METHODS OF INTRAUTERINE FETAL STATE DIAGNOSIS. PLACENTA INSUFFICIENCY. FETAL DISTRESS.  FETAL GROWTH RETARDATION.

Prepared by N.Bahnij

FETAL MOVEMENTS

Passive unstimulated activity of the human fetus commences as early as 7 weeks of gestation and becomes more sophisticated and coordinated by the end of pregnancy (Vindla and James, 1995). Indeed,  beyond 8 menstrual weeks, fetal body movements are never absent for time periods exceeding 13 minutes (DeVries and co-workers, 1985). Between 20 and 30 weeks, general body movements become organized and the fetus starts to show rest–activity cycles (Soronkin and co-workers, 1982). In the third trimester, fetal movement maturation continues until about 36 weeks, when behavioral states are established in 80 percent of normal fetuses. Nijhuis and colleagues (1982) studied fetal heart rate patterns, general body movements, and eye movements and described four fetal behavioral states:

· State 1F is a quiescent state (quiet sleep), with narrow oscillatory bandwidth of the fetal heart rate.

· State 2F includes frequent gross body movements, continuous eye movements and wider oscillation of the fetal heart rate. This state is analogous to REM (rapid eye movement) or active sleep in the neonate.

· State 3F includes continuous eye movements in the absence of body movements and no accelerations of the heart rate. The existence of this state is disputed (Pillai and James, 1990a).

· State 4F is one of vigorous body movement with continuous eye movements and fetal heart rate accelerations. This state corresponds to the awake state in infants.

Fetuses spend most of their time in states 1F and 2F. For example, at 38 weeks’ gestational age, fetuses spend 75 percent of their time in states 1F and 2F (Nijuis and colleagues, 1982).

These behavioral states, particularly 1F and 2F, corresponding to quiet sleep and active sleep, have been used to develop an increasingly sophisticated understanding of fetal behavior. Oosterhof and co-workers (1993) studied fetal urine production in normal human pregnancies in relation to states 1F or 2F. Bladder volumes increased during quiet sleep (state 1F), defined by the narrow bandwidth fetal heart rate baseline. During state 2F, the fetal heart rate baseline bandwidth increased appreciably, and bladder volume was significantly diminished. The latter occurred due to fetal voiding as well as decreased urine production. These phenomena were interpreted to represent reduced renal blood flow during active sleep.

Rayburn (1982) defined reassuring maternally perceived fetal activity as an average of four or more movements per hour when counting was performed at least 1 hour per day. Three or fewer movements per hour for 2 consecutive days was defined to be abnormal. Fetal death occurred in 16 of 46 inactive fetuses, whereas death occurred in only 7 of 1115 active fetuses. Most of the inactive fetuses were chronically ill, as evidenced by growth restriction. Fetal death also occurred, albeit much less frequently, in fetuses exhibiting normal activity, as a result of umbilical cord entanglements, placental abruption, oligohydramnios, and uterine rupture. Rayburn concluded that normal activity was generally reassuring but that fetal inactivity required further assessment with methods described in the following sections.

FETAL Breathing

After decades of uncertainty as to whether the fetus normally breathes, Dawes and co-workers (1972) showed small inward and outward flows of tracheal fluid indicating fetal thoracic movement in sheep. These chest wall movements differed from those following birth in that they were discontinuous. Another interesting feature of fetal respiration was paradoxical chest wall movement. During inspiration, the chest wall paradoxically collapses and the abdomen protrudes (Johnson and co-authors, 1988). In the newborn or adult, the opposite occurs. One interpretation of the paradoxical respiratory motion might be coughing to clear amnionic fluid debris. Although the physiological basis for the breathing reflex is not completely understood, such exchange of amnionic fluid appears to be essential for normal lung development.

Two types of respiratory movements were identified: (1) gasps (or sighs), which occurred at a frequency of 1 to 4 per minute; and (2)  irregular bursts of breathing, occurring at rates up to 240 cycles per minute (Dawes, 1974). The latter rapid respiratory movements were associated with rapid eye movements. Badalian and co-workers (1993) studied the maturation of normal human fetal breathing using color flow and spectral Doppler analysis of fetal nasal fluid flow as an index of lung function. They suggested that fetal respiratory rate decreased in conjunction with increased inspiratory volume at about 33 to 36 weeks, coincidental with commencement of fetal lung maturation.

The potential for fetal breathing activity to be an important marker of fetal health appears to be unfulfilled because of the multiplicity of factors that affect breathing in normal fetuses. Most clinical applications have included assessment of other fetal biophysical indices, such as heart rate. More recently, as will be discussed, fetal breathing has become a component of the biophysical profile.

CONTRACTION STRESS TESTING

As amnionic fluid pressure increases with uterine contractions, myometrial pressure exceeds collapsing pressure for vessels coursing through uterine muscle, ultimately isolating the intervillous space. Brief periods of impaired oxygen exchange result, and if uteroplacental pathology is present, these elicit late fetal heart rate decelerations. Uterine contractions may also produce a pattern of variable decelerations due to cord compression suggesting oligohydramnios, which is often a concomitant of placental insufficiency (American College of Obstetricians and Gynecologists, 1994).

Ray and colleagues (1972) used this concept in 66 complicated pregnancies and developed what they termed the oxytocin challenge test, and later called the contraction stress test. Contractions were induced using intravenous oxytocin and the fetal heart rate response was recorded using a standard electronic fetal monitor. The criterion for a positive (abnormal) test was uniform repetitive fetal heart rate decelerations. These reflected the uterine contraction waveform and had an onset at or beyond the acme of a contraction. Such late decelerations could be due to uteroplacental insufficiency. The tests were generally repeated on a weekly basis, and the investigators concluded that negative (normal) contraction stress tests forecast fetal health. One disadvantage cited was that the average contraction stress test required 90 minutes to complete.

Freeman (1975) subsequently reported a much larger experience with 1500 contraction stress tests in 600 pregnancies at risk for placental insufficiency. Contractions lasting 40 to 60 seconds and occurring at least 3 per 10 minutes were arbitrarily defined as adequate uterine activity for a “challenge” or “stress.”  Spontaneous uterine contractions meeting these criteria were also considered acceptable. Testing was performed on a weekly basis, because only one fetal death was observed within a week of a normal test result. Freeman (1975) proposed combining contraction stress tests with 24-hour urinary estriol measurements, the former presumably a test of placental respiratory function and the latter an index of nutritive function. Importantly, both tests used in combination were considered superior to either alone, because false positives for either test were cross-checked.  A fourth of pregnancies with positive contraction stress tests tolerated subsequent labor, and these were considered false-positive (Freeman and co-workers, 1976). Others reported much higher false-positive rates, some as high as 75 percent (Gauthier and colleagues, 1979). Difficulties with the meaningfulness of positive contraction stress tests have prompted most investigators to perform these tests hoping for a normal (negative test) result, because this permits the clinician to avoid intervention.

Nipple stimulation in lieu of oxytocin induced uterine contractions has been reported to be usually successful for contraction stress testing (Huddleston and associates, 1984). One method recommended by the American College of Obstetricians and Gynecologists (1994) involves the woman rubbing one nipple through her clothing for 2 minutes or until a contraction begins. She is instructed to restart after 5 minutes if the first nipple stimulation did not induce three contractions in 10 minutes. Advantages include reduced cost and shortened testing times. Although Schellpfeffer and associates (1985) reported unpredictable uterine hyperstimulation with fetal distress, others did not find excessive nipple-stimulated induced uterine activity to be harmful (Frager and Miyazaki, 1987).

NONSTRESS TESTING

Freeman (1975) and Lee and colleagues (1975) introduced the nonstress test to describe fetal heart rate acceleration in response to fetal movement as a sign of fetal health. This test involved the use of Doppler-detected fetal heart rate acceleration coincident with fetal movements perceived by the mother. By the end of the 1970s, the contraction stress test was supplanted by the nonstress test as the primary method of testing fetal health. The nonstress test was much easier to perform and normal results were used to further discriminate false-positive contraction stress tests. Simplistically, the nonstress test is primarily a test of fetal condition, and it differs from the contraction stress test, which is a test of uteroplacental function. The nonstress test has become the most widely used primary testing method for assessment of fetal well-being.

PHYSIOLOGY OF FETAL HEART RATE ACCELERATION

Fetal heart rate is normally increased or decreased on a beat-to-beat basis by autonomic influences mediated by sympathetic or parasympathetic impulses from brainstem centers. Thus,  fetal heart rate acceleration is felt to be an indication of fetal autonomic function. Beat-to-beat variability is also under the control of the autonomic nervous system (Matsuura and colleagues, 1996). Consequently, pathological loss of acceleration may be seen in conjunction with significantly decreased beat-to-beat variability of the fetal heart rate (see p. 1015). Loss of such reactivity, however, is most commonly associated with sleep cycles (discussed earlier in the chapter), and may be due to central nervous system depression from medications. The nonstress test is based on the hypothesis that the heart rate of a fetus who is not acidotic as a result of hypoxia or neurological depression, will temporarily accelerate in response to fetal movement. Smith and colleagues (1988) observed a decrease in the number of accelerations in preterm human fetuses subsequently found to have lower umbilical artery blood PO2 values compared with those fetuses who had normal fetal heart rate characteristics. Thus, nonstress testing is considered to reflect fetal condition.

Gestational age also is a factor influencing acceleration or reactivity of fetal heart rate. Pillai and James (1990b) studied the development of fetal heart rate acceleration patterns during normal pregnancy. The percentage of body movements accompanied by acceleration and the amplitude of these accelerations increased with gestational age .

DEFINITION OF NORMAL NONSTRESS TESTS

 There have been many different definitions of  normal nonstress test results. Definitions vary as to the number, amplitude, and duration of acceleration, as well as the test duration itself. The definition currently recommended by the American College of Obstetricians and Gynecologists (1994) is two or more accelerations of 15 beats/min or more, each lasting 15 seconds or more and all occurring within 20 minutes of beginning the test. Shown in Figure 1  is an example of a nonstress test meeting these criteria for reactivity.

Fig. 1. Reactive nonstress test. Notice increase of fetal heart rate to more than 15 beats/min for longer than 15 seconds following fetal movements, indicated by the vertical marks on the lower part of the recording.

 It was also recommended that accelerations with or without fetal movements be accepted, and that a 40-minute or longer tracing (to account for fetal sleep cycles) should be performed before concluding that there was insufficient fetal reactivity. Miller and colleagues (1996) reviewed fetal outcomes after nonstress tests considered as non-reactive because there was only one, and not the required two accelerations, used to define a normal result. They concluded that one acceleration was just as reliable in predicting healthy fetal status as was two accelerations.

As initially devised, nonstress testing involved the detection of accelerations associated with documented fetal movement. Subsequent studies, however, demonstrated that appropriate accelerations are predictive of fetal well-being, regardless of the presence of maternally perceived fetal movement (Devoe and associates, 1994; Stanco and colleagues, 1993). Indeed, a recent investigation using Doppler-detected fetal body movements during nonstress testing suggest that this technique may allow the clinician to avoid the inappropriate diagnosis of fetal compromise when the nonstress test is nonreactive (Devoe and co-workers, 1994).

Although a normal number and amplitude of accelerations seems to reflect fetal well-being, “insufficient acceleration” does not invariably predict fetal compromise. Indeed,  some investigators have reported false-positive nonstress test rates in excess of 90 percent when fetal heart rate acceleration was considered insufficient (Devoe and colleagues, 1986). Because healthy fetuses may not move for periods of up to 75 minutes, Brown and Patrick (1981) considered that a longer duration of nonstress testing might increase the positive predictive value of an abnormal, or nonreactive test. They concluded that either the test became reactive during a period of time up to 80 minutes, or that the test remained nonreactive for 120 minutes indicating that the fetus was very ill.

These admittedly arbitrary normal standards for fetal reactivity aside, there are abnormal nonstress test patterns that reliably forecast severe fetal jeopardy. Hammacher and co-workers (1968) described not only acceleration in response to movement, but also antepartum cardiotocograms with what he termed a silent oscillatory pattern. This pattern consisted of a fetal heart rate baseline that oscillated less than 5 beats/min and pre-sumably indicated absent acceleration as well as beat-to-beat variability. Hammacher considered this pattern ominous. Rochard and co-workers (1976) found that absence of accelerations coupled with less than 6 beats/min baseline variability were associated with a 40 percent perinatal mortality. Likewise, Farahani and Fenton (1977) found a high correlation between tests showing less than 10 beats/min acceleration and serious perinatal pathology. Similarly, Visser and associates (1980) described a “terminal cardiotocogram,” which included (1) baseline oscillation of less than 5 beats/min (2) absent accelerations, and (3) late decelerations with spontaneous uterine contractions. These results were very similar to experiences from our own institution in which absence of accelerations during an 80-minute recording period in 27 pregnancies was associated consistently with evidence of uteroplacental pathology (Leveno and associates, 1983). This included fetal growth restriction (75 percent), oligohydramnios (80 percent), fetal acidosis (40 percent), meconium (30 percent), and placental infarction (93 percent). We concluded that inability of the fetus to accelerate its heart rate, when not due to maternal sedation, was an ominous finding.  Similarly, Devoe and co-workers (1985) concluded that nonstress tests that were nonreactive for 90 minutes were almost invariably (93 percent) associated with significant perinatal pathology. Figure 43–7  shows an example of a nonstress test with no heart rate acceleration that prompted an oxytocin challenge test. This latter test caused mild late decelerations consistent with placental insufficiency. The fetus could not be resuscitated.

BIOPHYSICAL PROFILE

Manning and colleagues (1980) proposed the combined use of five fetal biophysical variables as a more accurate means of assessing fetal health than any single variable used alone. They concluded that consideration of five variables could significantly reduce both false-positive and false-negative single test rates. Required equipment included a real-time ultrasound device and Doppler ultrasound to record fetal heart rate. Typically, these tests require 30 to 60 minutes of examiner time. The five biophysical variables assessed (Table 43–1 ) included (1) fetal heart rate acceleration, (2) fetal breathing, (3) fetal movements, (4) fetal tone, and (5) amnionic fluid volume. Normal variables were assigned a score of two each and abnormal variables a score of zero. Thus, the highest score possible for a normal fetus was 10.

Biophysical Variable	Score	Explanation
Fetal breathing movements (FBM)	Normal =  2	At least 1 FBM of at least 30 seconds duration in 30 minutes
	Abnormal = 0	No FBM of at least 30-seconds duration in 30 minutes
Gross body movement	Normal =  2	At least 3 discrete body /limb movements in 30 minutes
	Abnormal = 0	2 or less discrete body /limb movements in 30 minutes
Fetal tone	Normal =  2	At least 1 episode of active extension with return to flexion of fetal limbs/trunk or opening/closing of hand
	Abnormal = 0	Either slow extension with return to partial flexion or movement of limb in full extension or no fetal movement
Reactive fetal heart rate	Normal =  2	Reactive NST
	Abnormal = 0	Nonreactive NST
Qualitative amniotic fluid volume	Normal =  2	At least 1 pocket of amniotic fluid at least 1 cm in two perpendicular planes
	Abnormal = 0	No amniotic fluid or no pockets of fluid greater than 1 cm in two perpendicular planes

ULTRASONOGRAPHY

The impact of the use of ultrasonography on the practice of obstetrics has been profound. Given but one choice from the many biochemical and biophysical techniques that have been developed in more recent years to try to improve pregnancy outcome, sonography would seem the best. Methods for evaluating the health of the fetus that apply pulse-echo ultrasound are now employed widely for many reasons that will be summarized in this chapter and illustrated frequently throughout the book. Ultrasonic techniques that are now available, when performed carefully and interpreted accurately, can supply vital information about the status of the fetus, with no confirmed biological hazards from ultrasound (American College of Obstetricians and Gynecologists, 1993; American Institute of Ultrasound in Medicine, 1991).

UMB DOPPLER VELOCIMETRY

Ultrasound technology has evolved from only producing images of the pregnancy to now include methods for measurement of both maternal and fetal circulatory functions. The phenomenon of Doppler shift of ultrasonic echoes forms the technical basis for acquisition of information on the maternal–fetal hemodynamic circulations.

Johann Christian Doppler was an Austrian physicist who taught in Prague during the mid-1800s (White, 1982). He suggested that when a sound source (for example, red blood cells in fetal umbilical circulation) is moving relative to an observer (for example, an ultrasound transducer), the perceived pitch will vary from the true pitch. In accordance with the Doppler shift principle, echoes returning from moving structures are altered in frequency and the amount of shift is directly proportional to the velocity of the moving structure. The frequencies of echoes returning from structures moving toward the transducer are higher than the frequency originally transmitted by the transducer. In contrast, the frequencies of echoes returning from structures moving away from the transducer are lower. The primary uses of these Doppler echo shifts in obstetrics have been to detect and measure blood flow. The sound of moving blood cells within the vasculature generates an effective Doppler shift, which serves as the basis of Doppler velocimetry studies of maternal and fetal circulations. There are two methods of estimating circulatory hemodynamics: (1) direct measurement of the volume of blood flow and (2) indirect estimation of flow velocity using waveform analysis.

FETAL HEART RATE MONITORING

Continuous electronic fetal heart rate monitoring is a marvelous invention introduced into obstetrical practice during the late 1960s. No longer was the perception of fetal distress limited to heart sounds; the continuous graph paper portrayal of the fetal heart rate was potentially diagnostic in assessing pathophysiological events affecting the fetus. There were great expectations that:

(1) electronic fetal heart rate monitoring provided accurate information

(2) the information was of value in diagnosing fetal distress

(3) it would be possible to intervene to prevent fetal death or morbidity

and (4) continuous electronic fetal heart rate monitoring was superior to intermittent methods.

The first report to describe clinical application of electronic fetal monitoring in the United States was from Paul and Hon (1970). They described their experiences with 6 percent of 4561 deliveries at Yale–New Haven Hospital. Indications for monitoring included pregnancies at risk. They compared their findings with those from the Collaborative Perinatal Study and found no difference in the incidence of various Apgar scores. They concluded, however, that electronic monitoring was beneficial in complicated pregnancies because of finding a lesser number of depressed babies in the monitored group.

When first introduced, electronic fetal heart rate monitoring was used primarily in complicated pregnancies, but gradually it came to be used in most pregnancies. By 1978 it was estimated that nearly two thirds of American women were being monitored electronically during labor (Banta and Thacker, 1979). In 1993, 3,120,636 American women, comprising 78 percent of all live births, underwent electronic fetal monitoring (Ventura and colleagues, 1995).

INTERNAL ELECTRONIC FETAL HEART RATE MONITORING

The fetal heart rate may be measured by attaching a bipolar spiral electrode directly to the fetus.

 The wire spiral electrode penetrates the fetal scalp and the second pole is the metal wing on the electrode panel. Vaginal body fluids create a saline electrical bridge that completes the circuit and permits measurement of the voltage differences between the two poles. The electrical fetal cardiac signal (P wave, QRS complex, and T wave) is amplified and fed into a cardiotachometer for heart rate calculation.  The peak R-wave voltage is the portion of the fetal electrocardiogram most reliably detected. The two wires of the bipolar electrode are attached to a reference electrode on the maternal thigh to eliminate electrical interference. Shown in Figure 14–2  is an example of the method of fetal heart rate processing employed when a scalp electrode is used. Time (t) in milliseconds between fetal R waves is fed into a cardiotachometer, where a new fetal heart rate is set with the arrival of each new R wave. A premature atrial contraction is computed as a heart rate acceleration because the interval (t2) is shorter than the preceding one (t1). The phenomena of continuous R wave to R wave fetal heart rate computation is known as “beat to beat” variability. However, the physiological event being counted is not a mechanical event corresponding to a heartbeat but rather an electrical event.

 Electrical cardiac complexes detected by the fetal scalp electrode include those generated by the mother. The relative amplitude of maternal R waves is approximately one-fifth that of the fetus, which varies between 50 and 100 microvolts (Freeman and co-authors, 1991). However, spontaneous variations in fetal R-wave amplitude are not rare during labor (Lee and Hon, 1965). These are likely due to frequent changes in fetal position, thus changing the fetal cardiac axis and corresponding electrical vectors (Roche and Hon, 1965). Although the maternal electrocardiogram (ECG) signal is approximately five times stronger than the fetal ECG, its amplitude is diminished when it is recorded through the fetal scalp electrode. In a live fetus, this low maternal ECG signal is detected but masked by the “noise” of the fetal ECG. If the fetus is dead, the smaller maternal signal will be amplified by the automatic gain control circuitry in the fetal monitor and displayed as “fetal” heart rate (Freeman and co-authors, 1991).

EXTERNAL (INDIRECT) ELECTRONIC FETAL HEART RATE MONITORING

The necessity for membrane rupture and uterine invasion may be avoided by use of external detectors to monitor fetal heart action and uterine activity. External monitoring does not provide the precision of fetal heart measurement or the quantification of uterine pressure afforded by internal monitoring.

The fetal heart rate may be detected in a number of ways through the maternal abdominal wall. The easiest technique employs the ultrasound Doppler principle (Fig. 2).

 Fig. 2. Ultrasound Doppler principle used externally to measure fetal heart motions. Pulsations of the maternal aorta may also be detected and counted. (Adapted from Klavan and co-authors, Clinical concepts of fetal heart rate monitoring. Hewlitt-Packard Co, 1977. With permission.).

Ultrasonic waves undergo a shift in frequency as they are reflected from moving fetal heart valves and from blood ejected in pulsatile fashion during systole. The unit consists of a transducer that emits ultrasound and a sensor to detect a shift in frequency of the reflected sound. The transducer is placed on the maternal abdomen at a site where fetal heart action is best detected. A coupling gel must be applied because air conducts ultrasound poorly. The device is held in position by a belt. Care should be taken that maternal aortic pulsations are not confused with fetal cardiac motion.

Ultrasound Doppler signals are edited electronically before fetal heart rate data are printed onto the bedside monitor tracing paper. Reflected ultrasound signals from moving fetal heart valves are put through a microprocessor that compares incoming signals with the most recent previous signal. This process is called  autocorrelation, and is based on the premise that the fetal heart rate has regularity whereas “noise” is random and without regularity. Essentially, several fetal heart motions must be deemed electronically acceptable by the microprocessor before the fetal heart rate is printed. Such electronic manipulation has greatly improved the tracing quality of externally recorded fetal heart rate.

FETAL HEART RATE PATTERNS

Because the fetal heart rate is rarely fixed, but instead shows frequent periodic variations, standardized terminology was proposed to more precisely describe both baseline activity and periodic variations from the baseline (Freeman and co-authors, 1991). Despite this, definitions among clinicians are remarkably varied (Parer and Quilligan, 1996). It is important to recognize that interpretation of electronic fetal heart rate data is based upon the visual pattern of the heart rate as portrayed on chart recorder graph paper. Thus the choice of vertical and horizontal scaling directly affects the appearance of the fetal heart rate.  Typical scaling factors employed in the United States are 30 beats/min per vertical cm (range, 5 to 240 beats/min) and 3 cm/min chart recorder paper speed. For example (Fig. 3), fetal heart rate variation is falsely displayed at the slower 1cm/min paper speed when compared with the smoother baseline recorded at 3 cm/min. Thus, pattern recognition can be considerably distorted depending on the scaling factors used.

Fig. 3. Fetal heart rate obtained by scalp electrode and recorded at 1 cm/min compared with 3 cm/min chart recorder paper speed.

BASELINE FETAL HEART ACTIVITY

Baseline fetal heart activity refers to the modal characteristics that prevail apart from periodic accelerations or decelerations associated with uterine contractions. Descriptive characteristics of baseline fetal heart activity include rate, beat-to-beat variability, fetal arrhythmia, and distinct patterns such as sinusoidal or saltatory fetal heart rates.

RATE

With increasing fetal maturation, the mean heart rate decreases. This continues postnatally such that the average rate is 90 beats/min by age 8 (Behrman, 1992). Pillai and James (1990) longitudinally studied fetal heart rate characteristics in 43 normal human pregnancies  from 16 to 40 weeks. The baseline fetal heart rate decreased an average of 24 beats/min between 16 weeks and term, or approximately 1 beat/min per week. At 16 weeks the average baseline rate was about 160 beats/min, which decreased to 140 at 40 weeks. It is postulated that this normal gradual slowing of the fetal heart rate corresponds to maturation of parasympathetic (vagal) heart control (Renou and co-workers, 1969).

During the third trimester, the normal average baseline fetal heart rate is generally accepted to be between 120 and 160 beats/min. The average fetal heart rate is considered to be the result of tonic balance between accelerator and decelerator influences on pacemaker cells. In this concept, the sympathetic system is the accelerator influence, and the parasympathetic system is the decelerator factor mediated via vagal slowing of heart rate (Dawes, 1985). Heart rate is also under the control of arterial chemoreceptors such that both hypoxia and hypercapnia can modulate rate. More severe and prolonged hypoxia with a rising blood lactate level and severe metabolic acidemia, induces a prolonged fall of heart rate due to direct effects on the myocardium.

BRADYCARDIA

Bradycardia is a   baseline fetal heart rate under 120 beats/min that lasts 15 minutes or longer (Freeman and co-authors, 1991). However, a rate between 100 and 119 beats/min, in the absence of other changes, is usually not considered to represent fetal compromise. Such low but potentially normal baseline heart rates have also been attributed to head compression from occiput posterior or occiput transverse positions, particularly during second-stage labor (Young and Weinstein, 1976). Moderate bradycardias are defined as 80 to 100 beats/min, and  severe bradycardias are less than 80 beats/min, for 3 minutes or longer. Mild bradycardia without deceleration or acceleration is not necessarily evidence for fetal compromise. Umbilical arterial blood acidemia (pH less than 7.2) was identified by Gilstrap and co-workers (1987) in one third of 53 neonates with mild bradycardia of 90 to 119 beats/min during the last 10 minutes of the second stage of labor. None of these acidemic neonates required resuscitation. Gilstrap and associates also found umbilical arterial blood acidemia in 40 percent of 63 neonates with moderate to severe bradycardia, defined as less than 90 beats/min.

Other causes of fetal bradycardia include congenital heart block and serious fetal compromise. Figure 14–7  shows bradycardia in a fetus dying from placental abruption. Maternal hypothermia under general anesthesia for repair of a cerebral aneurysm or during maternal cardiopulmonary bypass for open-heart surgery can also cause fetal bradycardia (van Bull and colleagues, 1993). We have also observed sustained fetal bradycardia in the setting of severe pyelonephritis and maternal hypothermia (Hankins and Leicht, 1996). These infants are apparently not harmed by several hours of such bradycardia.

Other nonperiodic but sudden slowings of the fetal heart rate are often termed fetal “bradycardias.” Instead, these are probably best considered prolonged decelerations, which are subsequently discussed. Some causes include  uterine hyperactivity; paracervical or conduction analgesia; pelvic examination, presumably due to manual fetal head compression; cord prolapse; uterine rupture; placental abruption; maternal hypoperfusion (e.g., supine hypotension syndrome or hemorrhage due to trauma); and maternal hypoxia (e.g., eclampsia).

TACHYCARDIA

Tachycardia is considered by most as mild if the baseline rate is between 161 and 180 beats/min and  severe if 181 or more. The  most common explanation for fetal tachycardia is maternal fever from amnionitis, although fever from any source can increase baseline fetal heart rate. Such infections have also been observed to induce fetal tachycardia before overt maternal fever is diagnosed (Gilstrap and associates, 1987). Fetal tachycardia caused by maternal infection is typically not associated with fetal compromise unless there are associated periodic heart rate changes or fetal sepsis.

Other causes of fetal tachycardia include fetal compromise, cardiac arrhythmias, and administration of parasympathetic (atropine) or sympathomimetic (terbutaline) drugs to the mother. The key feature to distinguish fetal compromise in association with tachycardia seems to be concomitant heart rate decelerations. However, prompt relief of the compromising event, such as correction of maternal hypotension caused by epidural analgesia, can result in fetal recovery.

Beat-to-Beat Variability

Baseline fetal heart rate variability is an important index of cardiovascular function and appears to be regulated largely by the autonomic nervous system. The baseline rate normally exhibits an oscillating form, reflective of beat-to-beat changes in rate, which gives it varying degrees of irregularity or variability when printed on graph paper. Such deviations in heart rate are defined as baseline variability. Variability is further divided into short term and long term.

Short-term variability reflects the instantaneous change in fetal heart rate from one beat (or R wave) to the next. This variability is a measure of the time interval between cardiac systoles (Fig. 4).

Fig. 4. Schematic representation of short-term beat-to-beat variability measured by a fetal scalp electrode (t = time interval between successive fetal R waves). (From Klavan and co-authors, 1977.)

 It can most reliably be determined to be normally present only when electrocardiac cycles are measured directly with a scalp electrode. External Doppler ultrasound recording methods can create artifactual “normal” variability. Conversely, absence of variability during external Doppler fetal heart recording can suggest loss of beat-to-beat variability.

Long-term variability is used to describe the oscillatory changes that occur during the course of 1 minute and result in the waviness of the baseline. The normal frequency of such waves is three to five cycles per minute (Freeman and co-authors, 1991).

Decreased beat-to-beat variability is diagnosed when the fetal heart rate baseline is flat or nearly flat with absent short-term variability and fewer than two cyclic changes per minute of long-term variability. It should be recognized, however, that precise quantitative analysis of both short- and long-term variability presents a number of frustrating problems due to technical and scaling factors. For example, Parer and co-workers (1985) evaluated 22 mathematical formulas designed to quantify heart rate variability and most were unsatisfactory. Consequently, most clinical interpretation is based on visual analysis with subjective judgment of the smoothness or flatness of the baseline.

Several physiological and pathological processes can affect or interfere with beat-to-beat variability. Dawes and co-workers (1981) described increased beat-to-beat variability during fetal breathing. In healthy infants, short-term variability is attributable to respiratory sinus arrhythmia (Divon and co-workers, 1986). Moreover, this respiratory variability can be reduced by asphyxia. Fetal body movements affect variability. Granat and co-investigators (1979) observed that fetuses exhibited 40- to 80-minute cycles of movements thought to correspond to fetal wakefulness. Van Geijn and co-workers (1980) analyzed electroencephalographic data in healthy term infants and observed 30- to 70-minute sleep cycles corresponding to fetal physical inactivity. Pillai and James (1990) reported increased baseline variability with advancing gestation. Up to 30 weeks, baseline characteristics were similar during both fetal rest and activity. After 30 weeks, fetal inactivity was associated with diminished baseline variability and, conversely, variability was increased during fetal activity.

It is important to recognize that the baseline fetal heart rate becomes more physiologically fixed (less variable) as the rate increases. Conversely, there is more instability or variability of the baseline at lower heart rates. This phenomenon presumably reflects less cardiovascular physiological wandering as beat-to-beat intervals shorten due to increasing heart rate. It is generally believed that all of these physiological processes modulate variability via the autonomic nervous system (Renou and co-workers, 1969). That is, sympathetic and parasympathetic control of the sinoatrial node mediates moment-to-moment or beat-to-beat oscillation of the baseline heart rate.

Fig. 5. Diminished short- and long-term variability (2 waves or less per minute) due to uterine rupture caused by a motor vehicle accident. Umbilical artery blood pH was 6.7 and the 1735-g infant succumbed despite emergency cesarean delivery.

Although loss of variability and its ominous significance, such as shown in Figure 7, are concepts familiar to most obstetricians, mild degrees of fetal hypoxemia during human labor have been reported to increase variability, at least at the outset of the hypoxic episode (Huck and co-workers, 1977). According to Dawes (1985), it seems probable that the loss of variability (as shown in Fig. 8) is a result of metabolic acidemia that causes depression of the fetal brainstem or the heart itself.

 Thus, diminished beat-to-beat variability, when a reflection of compromised fetal condition, likely reflects acidemia rather than hypoxia.

A common cause of diminished beat-to-beat variability is analgesic drugs given during labor. A large variety of central nervous system depressant drugs can cause transient diminished beat-to-beat variability. Included are narcotics, barbiturates, phenothiazines (e.g., promethazine), tranquilizers (e.g., diazepam), and general anesthetics. Diminished beat-to-beat variability occurs regularly within 5 to 10 minutes following intravenous meperidine administration, and the effects may last up to 60 minutes or longer depending on the dosage given (Petrie, 1993). Butorphanol given intravenously diminishes fetal heart rate reactivity (Schucker and colleagues, 1996). Reduced fetal heart rate variability was observed by Viscomi and co-workers (1990) but not Hoffman and associates (1996) when fentanyl was administered epidurally for labor analgesia. Magnesium sulfate may decrease short-term variability for up to 60 minutes after administration (Atkinson and colleagues, 1994). Obviously, such drug-induced effects can greatly confuse interpretation of the fetal significance of diminished variability.

It is generally believed that reduced baseline heart rate variability is the single most reliable sign of fetal compromise. For example, Smith and co-workers (1988) performed a computerized analysis of beat-to-beat variability in growth-restricted fetuses before labor. They observed that diminished beat-to-beat variability (4.2 beats/min or less) that was maintained for 1 hour is diagnostic of developing acidemia and imminent fetal death. We have reported similar experiences (Leveno and co-workers, 1983). Snijders and colleagues (1992) also observed a relationship between significant fetal growth retardation and diminished baseline variability. They studied 13 fetuses over 25 days and observed that long-term fetal heart rate variation decreased gradually with time and fell below normal at about the same time decelerations due to placental insufficiency appeared. By contrast, during labor, Samueloff and associates (1994) evaluated fetal heart rate variability as a predictor of fetal outcome in 2200 consecutive deliveries and concluded that variability by itself cannot be used as the only indicator of fetal well-being. Indeed, they also concluded that good fetal heart rate variability should not be interpreted as necessarily reassuring.

In summary, beat-to-beat variability and its short- and long-term components are affected by a variety of physiological mechanisms. Variability has considerably different meaning depending on the clinical setting. The development of decreased variability in the absence of decelerations is unlikely to be due to fetal hypoxia (Davidson and co-workers, 1992).

CARDIAC ARRHYTHMIA

When fetal cardiac arrhythmias are first suspected using electronic monitoring, findings can include baseline bradycardia, tachycardia, or most commonly in our experience, abrupt baseline spiking. Intermittent baseline bradycardia is frequently due to congenital heart block (Ol’ah, 1991; Silver, 1992; Weber, 1994; and their associates).

Documentation of an arrhythmia can only be accomplished, practically speaking, when scalp electrodes are used. Most fetal monitors can be adapted to output the scalp electrode signals into an electrocardiographic recorder. However, only a single lead is obtained, thus severely restricting interpretation to analysis of rhythm and rate disturbances.

Most supraventricular arrhythmias are of little fetal significance during labor unless there is coexistent heart failure as evidenced by hydrops. Most supraventricular arrhythmias disappear in the immediate neonatal period, although some are associated with structural cardiac defects. Maxwell and associates (1988) reported 23 fetuses with supraventricular arrhythmias diagnosed before labor; 12 had supraventricular tachycardia, eight atrial flutter, and three a mixture of these two. No relation was found between the rate or type of arrhythmia and fetal heart failure. Outcome for hydropic fetuses was dependent on maturity at delivery and in utero cardioversion by maternal administration of digoxin, verapamil, or both. Spontaneous delivery was not injurious to nonhydropic fetuses; most hydropic fetuses were either delivered electively by cesarean delivery or required abdominal delivery for fetal distress. Special attention is called to the use of amiodarone for treatment of fetal supraventricular tachycardia in pregnancy. With a half-life of from 14 to 60 days, the drug potentially reduces both maternal and fetal thyroid function (DeCatte and colleagues, 1994).

The clinical significance of intrapartum fetal arrhythmias continues to be a complex problem. Most are of little consequence during labor when there is no evidence for fetal hydrops. However, such arrhythmias impair interpretation of intrapartum heart rate tracings. Ultrasonic survey of fetal anatomy as well as echocardiography may be useful, particularly when the arrhythmia is suspected antepartum. Some clinicians use fetal scalp sampling as an adjunct. Generally, in the absence of fetal hydrops, neonatal outcome is not measurably improved by pregnancy intervention. At Parkland Hospital, intrapartum fetal cardiac arrhythmias, especially in the presence of clear amnionic fluid, are managed conservatively. Deans and Steer (1994) have extensively reviewed interpretation of the fetal electrocardiogram during labor.

SINUSOIDAL Heart Rates

Discovery of sinusoidal heart rates is attributed to Kubli and co-workers (1972) and Manseau and colleagues (1972). A true sinusoidal pattern may be observed with serious fetal anemia (Fig.7), whether from D-isoimmunization, ruptured vasa previa, fetomaternal hemorrhage, or twin-to-twin transfusion. Insignificant sinusoidal patterns have been reported following administration of meperidine, morphine, alphaprodine, and butorphanol (Angel, 1984; Egley, 1991; Epstein, 1982; and their associates). The pattern has also been described with amnionitis, fetal distress, and umbilical cord occlusion (Murphy and associates, 1991). Young and co-workers (1980a) and Johnson and colleagues (1981) concluded that intrapartum sinusoidal fetal heart patterns were not generally associated with fetal compromise.

Fig. 7. Antepartum fetal heart tracing obtained using a Doppler transducer and showing a sinusoidal pattern that was intermittent. The fetus was severely anemic due to fetal–maternal hemorrhage as a consequence of maternal blunt abdominal trauma. Sine waves are occurring at a rate of 3 cycles/min.

Modanlou and Freeman (1982), based on their extensive review, proposed adoption of a strict definition: (1)  stable baseline heart rate of 120 to 160 beats/min with regular oscillations, (2) amplitude of 5 to 15 beats/min (rarely greater), (3) frequency of 2 to 5 cycles/min long-term variability, (4) fixed or flat short-term variability, (5) oscillation of the sinusoidal waveform above or below a baseline, and (6) absence of accelerations. Although these criteria were selected to define a sinusoidal pattern that is most likely ominous, they observed that the pattern associated with alphaprodine is indistinguishable. Other investigators have proposed a classification of sinusoidal heart rate patterns into mild (amplitude 5 to 15 beats/min), intermediate (16 to 24 beats/min), and major (25 or more beats/min) to quantify fetal risk (Murphy and colleagues, 1991; Neesham and co-workers, 1993).

Some investigators have defined intrapartum sine-wave like baseline variation with periods of acceleration as pseudo-sinusoidal. Murphy and co-workers (1991) reported that pseudo-sinusoidal patterns were seen in 15 percent of monitored labors. Mild pseudo-sinusoidal patterns were associated with use of meperidine and epidural analgesia. Intermediate pseudo-sinusoidal patterns were linked to fetal sucking or transient episodes of fetal hypoxia caused by umbilical cord compression. In contrast, Egley and colleagues (1991) reported that 4 percent of fetuses demonstrated sinusoidal patterns transiently during normal labor. These authors observed patterns for up to 90 minutes in some cases and also in association with oxytocin and/or alphaprodine usage.

The case shown in Figure 10 is a sinusoidal pattern observed with fetal–maternal hemorrhage.

The pathophysiology of sinusoidal patterns is unclear, in part due to various definitions. There seems to be general agreement that antepartum sine wave baseline undulation portends severe fetal anemia; however, few D-isoimmunized fetuses develop this pattern (Nicolaides, 1989). Moreover, the sinusoidal pattern has been reported to develop or disappear after fetal transfusion (Del Valle and associates, 1992; Lowe and co-workers, 1984). Murata and co-investigators (1985) found that interruption of the vagus nerve was required to produce sinusoidal patterns in fetal lambs. The sinusoidal heart rate did not appear to be under the influence of the a- or b-sympathetic systems.

PERIODIC FETAL HEART RATE.

The periodic fetal heart rate refers to deviations from baseline that are related to uterine contractions. Acceleration refers to an increase in fetal heart rate above baseline and deceleration to a decrease below baseline rate. The most commonly used system in the United States is based on the timing of the deceleration in relation to contractions—thus, early, late, or variable in onset compared with the corresponding uterine contraction. The waveform of these decelerations is also significant for pattern recognition. In early and late decelerations, the slope of fetal heart rate change is gradual, resulting in a curvilinear and uniform or symmetrical waveform. With variable decelerations, the slope of fetal heart rate change is abrupt and erratic, giving the waveform a jagged appearance.

Another system now used less often for description of decelerations is based on the pathophysiological events considered most likely to cause the pattern. In this system, early decelerations are termed head compression, late decelerations are termed uteroplacental insufficiency, and variable decelerations become cord compression patterns. The nomenclature of type I (early), type II (late), and type III (variable) “dips” proposed by Caldeyro-Barcia and co-workers (1973) is not used much in the United States.

ACCELERATIONS

An acceleration is an  increase in the fetal heart rate of at least 15 beats/min, usually of 15 to 20 seconds duration. According to Freeman and co-authors (1991), accelerations occur most commonly antepartum, in early labor, and in association with variable decelerations. Proposed explanations for intrapartum acceleration include fetal movement, stimulation by uterine contractions, umbilical cord occlusion, and fetal stimulation during pelvic examination. Fetal scalp blood sampling and acoustic stimulation both incite fetal heart rate acceleration (Clark and co-workers, 1982). Finally, acceleration can also occur during labor without any apparent stimulus. Indeed, accelerations are common in labor and nearly always associated with fetal movement. These accelerations are virtually always reassuring and almost always confirm that the fetus is not acidotic at that time.

Accelerations seem to have the same physiological explanations as beat-to-beat variability in that they represent intact neurohormonal cardiovascular control mechanisms linked to fetal behavioral states. Krebs and co-workers (1982a) analyzed electronic heart rate tracings in nearly 2000 fetuses and found sporadic accelerations during labor in 99.8 percent. Accelerations during the first and/or last 30 minutes was a favorable sign for fetal well-being. The absence of fetal heart accelerations during labor, however, is not necessarily an unfavorablesign unless coincidental with other nonreassuring changes. There is about a 50 percent chance of acidosis in the fetus who fails to respond to stimulation in the presence of an otherwise nonreassuring pattern (Clark and colleagues, 1984; Smith and colleagues, 1986).

 Early deceleration of the fetal heart rate was first described by Hon (1958). He observed that there was a drop in heart rate with uterine contractions, and that this was related to cervical dilatation. He considered these physiological. Compressing the fetal head produced variable type decelerations in 18 of 19 attempts (Ball and Parer, 1992). Similar decelerations were elicited by locking of forceps and initiation of traction.

Freeman and co-authors (1991) defined early decelerations as those generally seen in active labor between 4 and 7 cm dilatation. In their definition, the degree of deceleration is generally proportional to the contraction strength and rarely falls below 100 to 110 beats/min or 20 to 30 beats/min below baseline. An example consistent with this definition is shown in Figure 11.  Such decelerations are uncommon during active labor and are not associated with baseline changes. Importantly, early decelerations are not associated with fetal hypoxia, acidemia, or low Apgar scores.

Fig. 8. Early fetal heart rate deceleration coinciding with spontaneous uterine contractions at 4 cm cervical dilatation. (Tracing courtesy of Scottie Brewster, RN.)

Head compression probably causes vagal nerve activation due to dural stimulation that mediates heart rate deceleration (Paul and co-workers, 1964).

A late deceleration is a symmetrical decrease in fetal heart rate beginning at or after the peak of the contraction and returning to baseline only after the contraction has ended (American College of Obstetrics and Gynecologists, 1995b). Late decelerations are uniform in shape and typically begin 30 seconds or more after the onset of the contraction. As shown in Figure 12, the nadir of deceleration is after the contraction acme, and the return to baseline is well after the contraction is over. Descent and return of the fetal heart rate are gradual and smooth.  The magnitude of late decelerations reportedly is rarely more than 30 to 40 beats/min below baseline, and typically not more than 10 to 20 beats/min in intensity. Late decelerations are usually not accompanied by accelerations.

Murata and co-workers (1982) also showed that a late deceleration was the first fetal heart rate consequence of uteroplacental induced hypoxia. During the course of progressive hypoxia that led to fetal death over 2 to 13 days, the fetuses invariably exhibited late decelerations before the development of acidemia. Variability of the baseline heart rate disappeared as acidemia developed.

The precise pathophysiological mechanisms whereby fetal hypoxia is translated into fetal heart rate effects are unclear. Harris and colleagues (1982) studied mechanisms of late decelerations in fetal lambs and concluded that there are two pathophysiological pathways: (1) chemoreceptor-mediated vagal reflex and (2) hypoxic myocardial depression. They observed that it often is noticed clinically that sudden maternal hypotension or uterine hyperstimulation with oxytocin in a previously normal fetus results in late decelerations with retention of beat-to-beat variability. They postulated that the chemoreceptor–vagal nerve reflex mechanism is involved in such circumstances. In contrast, with prolonged fetal hypoxia, late deceleration is mediated via direct myocardial depression, and baseline variability is absent.

Generally, any process that causes maternal hypotension, excessive uterine activity, or placental dysfunction can induce late decelerations. The two most common causes are hypotension from epidural analgesia and uterine hyperactivity due to oxytocin stimulation. Maternal diseases such as hypertension, diabetes, and collagen–vascular disorders can cause chronic placental dysfunction. A rare cause is severe chronic maternal anemia without hypovolemia. Placental abruption can cause acute and severe late decelerations (Fig. 9).

Fig.9. Late decelerations due to uteroplacental insufficiency resulting from placental abruption. Immediate cesarean delivery was performed. Umbilical artery pH was 7.05 and the PO2 was 11 mm Hg.

VARIABLE DECELERATIONS

The most common deceleration patterns encountered during labor are variable decelerations attributed to umbilical cord occlusion. Release of amnionic fluid and fetal descent during parturition are conducive to umbilical cord entrapment. One fourth of fetuses have one or more loops of cord wound around the neck. Similarly, short (less than 35 cm) and long (more than 80 cm) cords are found in 6 percent of births and are associated with variable decelerations (Rayburn and associates, 1981).

Ball and Parer (1992) concluded that variable decelerations are vagally mediated and that the vagal response may be due to chemoreceptor or baroreceptor activity or both. Partial or complete cord occlusion (baroreceptor) produces afterload increase, hypertension, and decreases in fetal arterial oxygen content (chemoreceptor), both of which result in vagal activity leading to deceleration. In fetal monkeys the baroreceptor reflexes appear to be operative during the first 15 to 20 seconds of umbilical cord occlusion followed by decline in PO2 at approximately 30 seconds, which then serves as a chemoreceptor stimulus (Mueller-Heubach and Battelli, 1982). Salafia and colleagues (1996) have suggested that cord vessel vasculitis may be caused by vasospasm induced by compression.

 Thus, variable decelerations represent fetal heart rate reflexes that reflect either blood pressure changes due to interruption of umbilical flow or changes in oxygenation. It is likely that most fetuses have experienced brief but recurrent periods of hypoxia due to umbilical cord compression during gestation. The frequency and inevitability of cord occlusion has undoubtedly provided the fetus with these physiological mechanisms as a means of coping. Hence, we have elected to term these reflexes “physiological” rather than pathophysiological. The great dilemma for the obstetrician in managing variable fetal heart rate decelerations is determining when variable decelerations are pathological. The American College of Obstetricians and Gynecologists (1995b) has  defined significant variable decelerations as those decreasing to less than 70 beats/min and lasting more than 60 seconds.

Other fetal heart rate patterns have been associated with umbilical cord compression. Saltatory baseline heart rate (Fig. 10) was first described by Hammacher and co-workers (1968) and linked to umbilical cord complications during labor. The pattern is considered due to rapidly recurring couplets of acceleration and deceleration causing relatively large oscillations of the baseline fetal heart rate. We also observed a relationship between cord occlusion and the saltatory pattern (Leveno and associates, 1984). In the absence of other fetal heart rate findings, these do not signal fetal compromise.

 Fig. 10. Saltatory fetal heart rate baseline showing rapidly recurring couplets of acceleration combined with deceleration.

Prolonged Deceleration

Prolonged decelerations are defined as isolated decelerations lasting more than 60 to 90 seconds (Freeman and co-authors, 1991). However, this description does not define the maximum duration. Put another way, when does a prolonged deceleration cease being a periodic heart rate change and become a rate bradycardia? Because baseline rate refers to a baseline lasting 15 minutes or longer, then prolonged decelerations would be those lasting more than 60 and 90 seconds and less than 15 minutes. Their incidence during first-stage labor is unclear; however, Melchior and Bernard (1985) described them in approximately one third of second-stage labors. The significance of the amplitude of prolonged decelerations is also unclear; presumably, guidelines for interpretation of baseline bradycardias should prevail.

 Prolonged decelerations are difficult to interpret because they are seen in many different clinical situations. Some of the more common causes include cervical examination, uterine hyperactivity, cord entanglement, and maternal supine hypotension. In a study by Tejani and associates (1975), the longest prolonged deceleration was 12 minutes. Only one of the fetuses was mildly acidemic (pH 7.18) measured by scalp sampling 20 minutes following recovery from the prolonged deceleration. They concluded that prolonged decelerations are temporary and are typically followed by fetal recovery.

Other causes of prolonged deceleration include epidural, spinal, or paracervical analgesia; maternal hypoperfusion or hypoxia due to any cause; placental abruption; umbilical cord knots or prolapse; maternal seizures including eclampsia and epilepsy; application of a fetal scalp electrode; impending birth; or even maternal valsalva maneuver.

The placenta is very effective in resuscitating the fetus if the original insult does not recur immediately. Occasionally, such self-limited prolonged decelerations are followed by loss of beat-to-beat variability, baseline tachycardia, and even a period of late decelerations; all of which resolve as the fetus recovers. Freeman and co-authors (1991) emphasize rightfully that the fetus may die during prolonged decelerations. Thus, management of prolonged decelerations can be extremely tenuous. Management of isolated prolonged decelerations is based on bedside clinical judgment, which will inevitably be imperfect given the unpredictability of these decelerations. Harsh “morning after” criticisms of such clinical judgments are frequently inappropriate.

FETAL SCALP BLOOD SAMPLING

Measurements of the pH of appropriately collected capillary blood may help to identify the fetus in serious distress. An illuminated endoscope is inserted through the sufficiently dilated cervix and ruptured membranes so as to press firmly against fetal skin, usually the scalp (Fig. 11).

 Fig. 11. The technique of fetal scalp sampling utilizing an amnioscope. The end of the endoscope is displaced from the fetal vertex approximately 2 cm to show disposable blade against the fetal scalp before incision. (From Hamilton and McKeown, 1974.)

The skin is wiped clean with a cotton swab and coated with a silicone gel to cause the blood to accumulate as discrete globules. An incision is made through the skin to a 2 mm depth with a special blade on an appropriately long handle. As a drop of blood forms on the surface, it is immediately collected into a heparinized glass capillary tube, and the pH of the blood is promptly measured. To date neither scalp electrodes nor fetal scalp pH sampling appear to increase the risk of perinatal transmission of HIV infection (Viscarello and associates, 1994).

The pH of fetal capillary scalp blood is usually lower than umbilical venous blood and approaches that of umbilical arterial blood. Zalar and Quilligan (1979) recommended the following protocol to try to confirm fetal distress: If the pH is greater than 7.25, labor is observed. If the pH is between 7.20 and 7.25, the pH measurement is repeated within 30 minutes. If the pH is less than 7.20, another scalp blood sample is collected immediately and the mother is taken to an operating room and prepared for surgery. Delivery is performed promptly if the low pH is confirmed. Otherwise, labor is allowed to continue and scalp blood samples are repeated periodically. The only benefits reported for scalp pH testing were estimates of fewer cesarean deliveries for fetal distress (Young and co-workers, 1980b). However, Goodwin and associates (1994), in a study of 112,000 deliveries, showed a fall in their scalp pH sampling rate from approximately 1.8 percent in the mid-1980s to 0.03 percent by 1992 with no increased delivery rate for fetal distress. They concluded that scalp pH sampling was unnecessary.

Scalp Stimulation.    Clark and associates (1984) have suggested that scalp stimulation is an alternative to scalp blood sampling. An Allis clamp was used to pinch the fetal scalp just prior to obtaining scalp blood for pH measurement. Acceleration of the heart rate in response to pinching was invariably associated with a normal scalp blood pH. Conversely, failure to provoke acceleration was not uniformly predictive of fetal acidemia. Spencer (1991) reported that of 69 cases in which the fetal heart rate accelerated with scalp stimulation, none had a pH less than 7.20. Without an acceleration, only 9 percent of fetuses had a pH less than 7.20.

Fetal Pulse Oximetry

Using technology similar to that of adult pulse oximetry, instrumentation has been developed that may allow assessment of fetal oxyhemoglobin saturation once the membranes are ruptured (Dildy and co-workers, 1994). A pod-like sensor is inserted through the cervix and positioned against the fetal scalp or face. Unfortunately, this device provides reliable signal information only about 50 percent of the period monitored (Jongsma and associates, 1996). Luttkus and colleagues (1995) concluded that although fetal pulse oximetry corresponds satisfactorily to results from fetal blood analysis, at present available sensors provide only intermittent measurement of oxygenation.

Complications from Electronic and Physicochemical Monitoring

There are potential dangers inherent in monitoring by direct application of a fetal electrode, measuring uterine pressure by an indwelling uterine catheter, or incising the fetal scalp to measure blood pH. A strong orientation toward universal use of internal monitoring is likely to predispose to early amniotomy and its potential dangers, including cord prolapse, infection, and possibly more cord compression because of less amnionic fluid.

Injury to the fetal scalp or breech by the electrode is rarely a major problem, although application at some other site—such as the eye in case of a face presentation—can prove serious. A fetal vessel in the placenta may be ruptured by catheter placement (Trudinger and Pryse-Davies, 1978). Severe cord compression has been described from entanglement with the catheter. Penetration of the placenta, causing hemorrhage and uterine perforation during catheter insertion, has led to serious morbidity, as well as spurious recordings that resulted in inappropriate management.

Both the fetus and the mother may be at increased risk for infection as the consequence of internal monitoring. Scalp wounds from the electrode may become infected and cause osteomyelitis (McGregor and McFarren, 1989). Faro and associates (1990) observed puerperal infection to be increased from 12 percent in women externally monitored compared with 18 percent when an internal apparatus was used.

Abnormalities of the Placenta, Umbilical Cord, and Membranes

INTRODUCTION Much of the ever-growing knowledge of primary placental pathology was stimulated by a nucleus of placental pathologists that includes, amongst others, Benirschke, Driscoll, Fox, Naeye, and Salafia. For a detailed account of these disorders, the reader is referred to the Fourth Edition of Pathology of the Human Placenta (Benirschke and Kaufmann, 2000).

PLACENTAL ABNORMALITIES In general, placental and fetal size and weight roughly correlate in a linear fashion. There is also evidence that fetal growth depends on placental weight, which is less with small-for-gestational age infants (Heinonen and colleagues, 2001). According to Mathews and associates (2004), this is not dependent on nutrients.

ABNORMAL SHAPE OR IMPLANTATION. There are a number of variations of placental shape or implantation, and some have significant clinical impact.

Multiple Placentas with a Single Fetus. The placenta occasionally is separated into lobes. When the division is incomplete and the vessels of fetal origin extend from one lobe to the other before uniting to form the umbilical cord, the condition is termed placenta bipartita or bilobata Fox (1978) cited its incidence to be at about 1 in every 350 deliveries. If the two or three distinct lobes are separated entirely, and the vessels remain distinct, the condition is designated placenta duplex or placenta triplex.

Succenturiate Lobes. This variation describes one or more small accessory lobes that develop in the membranes at a distance from the periphery of the main placenta, to which they usually have vascular connections of fetal origin. It is a smaller version of the bilobed placenta, and although its incidence has been cited by Benirschke and Kaufmann (2000) to be as high as 5 percent, we have encountered these very infrequently. The accessory lobe may sometimes be retained in the uterus after delivery and may cause serious hemorrhage. In some cases, an accompanying vasa previa may cause dangerous fetal hemorrhage at delivery.

Membranaceous Placenta. Very rarely, all of the fetal membranes are covered by functioning villi, and the placenta develops as a thin membranous structure occupying the entire periphery of the chorion. This finding is called placenta membranacea and also is referred to as placenta diffusa. Diagnosis often can be made using sonography. It may occasionally give rise to serious hemorrhage because of associated placenta previa or accreta.

Ring-Shaped Placenta. In fewer than 1 in 6000 deliveries, the placenta is annular in shape, and sometimes a complete ring of placental tissue is present. This development may be a variant of membranaceous placenta. Because of tissue atrophy in a portion of the ring, a horseshoe shape is more common. These abnormalities appear to be associated with a greater likelihood of antepartum and postpartum bleeding and fetal growth restriction.

Fenestrated Placenta. In this rare anomaly, the central portion of a discoidal placenta is missing. In some instances, there is an actual hole in the placenta, but more often the defect involves only villous tissue with the chorionic plate intact. Clinically, it may be mistakenly considered to indicate that a missing portion of placenta has been retained in the uterus.

Extrachorial Placentation. When the chorionic plate, which is on the fetal side of the placenta, is smaller than the basal plate, which is located on the maternal side, the placental periphery is uncovered and leads to the common designation of extrachorial placenta . If the fetal surface of such a placenta presents a central depression surrounded by a thickened, grayish-white ring, it is called a circumvallate placenta. The ring is composed of a double fold of amnion and chorion, with degenerated decidua and fibrin in between. Within the ring, the fetal surface presents the usual appearance, except that the large vessels terminate abruptly at the margin of the ring. When the ring does not have the central depression with the fold of membranes, the condition is described as a circummarginate placenta. There is an increased risk with circumvallate placentas of antepartum hemorrhage ¾ both from placental abruption and from fetal hemorrhage ¾ as well as of preterm delivery, perinatal mortality, and fetal malformations (Benirschke, 1974; Lademacher and co-workers, 1981). Adverse clinical outcomes with circummarginate placentas are less well defined.

Placenta Accreta, Increta, and Percreta. These abnormalities are serious variations in which trophoblastic tissues invade the myometrium to varying depths. They are much more likely with placenta previa or with implantation over a prior uterine incision or perforation. Torrential hemorrhage is a frequent complication.

DEGENERATIVE PLACENTAL LESIONS. Degenerative lesions may result from trophoblast aging, or impairment of uteroplacental circulation with infarction. Deposition of calcium salts is heaviest on the maternal surface in the basal plate. Further deposition occurs along the septa, and both increase as pregnancy progresses. It is more extensive in smokers whose placentas also have reduced fetal capillary diameters (Larsen and co-workers, 2002). Extensive calcification is found in 10 to 15 percent of all placentas at term. This can be seen with sonography, and Spirt and colleagues (1982) reported that by 33 weeks more than half of placentas have some degree of calcification. It is difficult to correlate the degree of calcium deposition with pregnancy outcome (Benirschke and Kaufmann, 2000).

CIRCULATORY DISTURBANCES. Placental perfusion may be impaired by disruption of uterine vessels, placental vessels, or the intervillous space (Becroft and associates, 2004).

Placental Infarctions. These are the most common placental lesions, and their presence is a continuum from normal changes to extensive and pathological involvement. For example, Salafia and associates (2000) identified infarcts in 10 percent of 500 consecutive placentas from uncomplicated term pregnancies. Almost 90 percent were located at the placental margin and 90 percent were less than 1 cm. These types of limited infarctions result from occlusion of the maternal uteroplacental circulation and usually represent normal aging. Around the edge of nearly every term placenta there is a dense yellowish-white fibrous ring representing a zone of degeneration and necrosis, which is an incidental finding. Thus, although these infarcts are "normal," if they are numerous, placental insufficiency may develop. When they are thick, centrally located, and randomly distributed they may be associated with preeclampsia or lupus anticoagulant (Benirschke and Kaufmann, 2000; Many and colleagues, 2001). These conspicuous lesions arise after occlusion of the decidual artery interrupts blood flow to the intervillous space. Necrosis of villous tissue develops from ischemia. Histopathological features include fibrinoid degeneration of the trophoblast, calcification, and ischemic infarction. If decidual artery occlusion is followed by hemorrhage, then placental abruption results. Another type of infarct is found underneath the chorionic plate. These yellowish-white fibrous lesions are usually pyramidal shaped and range from 2 mm to 3 cm across the base. These subchorionic infarcts extend downward with their apices in the intervillous space. Similar lesions may be noted about the intercotyledonary septa. Occasionally these lesions meet and form a column of cartilage-like material extending from the maternal surface to the fetal surface. Less frequently, round or oval islands of similar tissue occupy the central portions of the placenta.

Maternal Floor Infarction. This uteroplacental vasculopathy differs from the previously described infarctions in that there are not large areas of villous infarction. Instead, fibrinoid deposition occurs within the decidua basalis and usually is confined to the placental floor. The fibrin, however, can extend into the intervillous space to envelop the villi, which then atrophy. According to Benirschke and Kaufmann (2000  there frequently is massive net-like fibrin deposition throughout the placenta. It is an uncommon lesion, and Adams-Chapman and colleagues (2002) identified it in 6 per 1000 deliveries. The etiopathogenesis of these lesions is not well defined, although in some cases it is associated with thrombophilia (Katz, 2002; Sebire, 2002, 2003; van der Molen, 2000; Ward, 2000, and all their colleagues). There is no doubt that maternal floor infarction is associated with fetal growth restriction, abortion, and stillbirths. It is not associated with preeclampsia or placental abruption. There also appears to be an increased incidence of central nervous system injury and neurodevelopmental sequelae in these infants (Adams-Chapman and associates, 2002).

Placental Vessel Thrombosis. When a stem artery from the fetal circulation in the placenta is occluded, it produces a sharply demarcated area of avascularity. Fox (1978) found such single-artery thrombosis in 5 percent of placentas from normal pregnancies and in 10 percent of those from diabetic women. He estimated that thrombosis of a single stem artery will deprive only 5 percent of the villi of their blood supply. Despite this, Benirschke and Kaufmann (2000) found these lesions to be frequently associated with fetal growth restriction and stillbirth.

HYPERTROPHIC LESIONS OF THE CHORIONIC VILLI. Striking enlargement of the chorionic villi is commonly seen in association with severe erythroblastosis and fetal hydrops. It also has been described in maternal diabetes, fetal congestive heart failure, and maternal-fetal syphilis (Sheffield and colleagues, 2002).

MICROSCOPIC PLACENTAL ABNORMALITIES. Beginning after 32 weeks, clumps of syncytial nuclei are found to project into the intervillous space. These projections are called syncytial knots and likely represent apoptosis, although some are artifacts of tangential sectioning of villi (Benirschke and Kaufmann, 2000). The number of cytotrophoblastic cells becomes progressively reduced as pregnancy advances. By term, such cells are few and inconspicuous. In some maternal or fetal disorders, numerous cytotrophoblastic cells are found in placentas. Some examples include gestational hypertension, diabetes, and erythroblastosis fetalis.

PLACENTAL INFLAMMATION. Changes that are now recognized as various forms of degeneration and necrosis were formerly described under the term placentitis. For example, small placental cysts with grumous contents were formerly thought to be abscesses. Nonetheless, especially in cases of preterm and prolonged membrane rupture, bacteria invade the fetal surface of the placenta. This occurrence is discussed in the section on chorioamnionitis (see p. 625).

TUMORS OF THE PLACENTA

Chorioangioma (Hemangioma). Various angiomatous tumors ranging widely in size have been described. Because of the resemblance of their components to the blood vessels and stroma of the chorionic villus, the term chorioangioma, or chorangioma, has been considered the most appropriate designation. These are the only benign tumors of the placenta (Benirschke and Kaufmann, 2000). They most likely are hamartomas of primitive chorionic mesenchyme and have an incidence of about 1 percent. Larger chorioangiomas may be suspected on the basis of certain sonographic findings. Small growths are usually asymptomatic, but large tumors may be associated with hydramnios or antepartum hemorrhage. Fetal death and malformations are uncommon complications, although there may be a correlation with low birthweight. Stiller and Skafish (1986) described a case with multiple placental chorioangiomas in which a blood group A fetus bled acutely into her O group mother. The mother showed evidence of acute hemolysis without anemia, and the fetus developed a sinusoidal heart rate pattern frequently seen with severe anemia. We have identified an unusual case of severe iron deficiency anemia in the neonate as the consequence of chronic fetal-to-maternal bleeding from multiple small chorioangiomas. Large tumors provide an arteriovenous shunt that can lead to fetal heart failure.

Tumors Metastatic to the Placenta. Malignant tumors rarely metastasize to the placenta. Of those that do, melanoma accounts for nearly one third of reported cases, and leukemias and lymphomas comprise another third (Dildy and associates, 1989; Read and Platzer, 1981). Tumor cells usually are confined within the intervillous space. In a fourth, the fetus will have metastases. Even so, malignant cells seldom proliferate to cause clinical disease (Altman and associates, 2003; Baergen and colleagues, 1997b).

Embolic Fetal Brain Tissue. Fetal brain tissue occasionally is seen embolized to the placenta or fetal lungs (Baergen and associates, 1997a; Gardiner, 1956). It usually has been described with "traumatic" deliveries. This phenomenon is not without precedent because brain tissue has been found in pulmonary veins following head trauma in older children and adults.

ABNORMALITIES OF THE MEMBRANES MECONIUM STAINING. The presence of meconium in amnionic fluid is relatively common ¾ it was identified in 12 percent of more than 175,000 liveborn infants by Wiswell and Bent (1993). Benirschke and Kaufmann (2000) described visible meconium-stained placentas in 18 percent of nearly 13,000 consecutive deliveries. The incidence of meconium staining at Parkland Hospital has been remarkably constant, and of almost 250,000 women delivered during the past 20 years, about 20 percent had meconium identified during labor or at delivery. From their review, Ghidini and Spong (2001) cited meconium staining in a median of 14 percent of pregnancies. Preterm fetuses seldom pass meconium. It is uncommon prior to 38 weeks, after which it increases to 25 to 30 percent after 42 weeks. Staining of the amnion can be obvious within 1 to 3 hours after meconium passage (Miller and colleagues, 1985). Although more prolonged exposure results in staining of the chorion, umbilical cord, and decidua, according to Benirschke and Kaufmann (2000), meconium passage cannot be timed or dated accurately. In its global sense, meconium passage is associated with increased perinatal morbidity and mortality. Fujikura and Klionsky (1975) identified meconium-stained membranes or fetuses in about 10 percent of 43,000 liveborn infants in the Collaborative Study of Cerebral Palsy. The neonatal mortality rate was 3.3 percent in the group with meconium-stained membranes compared with 1.7 percent in those without such staining. Nathan and co-workers (1994) reviewed perinatal outcomes at Parkland Hospital in more than 8000 women delivered in whom meconium was identified intrapartum. Outcomes were compared with those of more than 34,500 pregnancies with clear amnionic fluid. Perinatal mortality was increased significantly in the meconium group: 1.5 versus 0.3 per 1000. Severe fetal acidemia ¾ cord arterial pH less than 7.0 ¾ was significantly more common with meconium-stained fluid: 7 versus 3 per 1000. Moreover, cesarean delivery was doubled in the meconium group: 14 versus 7 percent. These global findings are not applicable to individual cases, but despite this, meconium has assumed great importance in many medicolegal pursuits. Benirschke and Kaufmann (2000) aptly conclude that the legal profession overemphasizes the importance of meconium passage without appreciating its complexity. Neonatal morbidity and mortality associated with meconium is characterized by the meconium aspiration syndrome, which develops in about 10 percent of exposed infants (Ghidini and Spong, 2001). Severe disease requires ventilatory assistance and has a mortality rate of about 10 percent. Although it is commonly held that meconium aspiration syndrome is primarily the result of aspiration of thick, tenacious meconium, Ghidini and Spong (2001) concluded from their review that thin meconium also was associated with respiratory insufficiency. One serious maternal risk is that meconium associated with amnionic fluid embolism greatly increases maternal mortality from cardiorespiratory failure and consumptive coagulopathy. Jazayeri and colleagues (2002) also have shown a fourfold risk of puerperal metritis with meconium-stained amnionic fluid.

CHORIOAMNIONITIS. Inflammation of the fetal membranes usually is a manifestation of intrauterine infection. It frequently is associated with prolonged membrane rupture and long labor. Grossly, infection is characterized by clouding of the membranes. There also may be a foul odor, depending on bacterial species and concentration. When mono- and polymorphonuclear leukocytes infiltrate the chorion, the resulting microscopical finding is designated chorioamnionitis. These cells are maternal in origin. Conversely, if leukocytes are found in amnionic fluid (amnionitis), or the umbilical cord (funisitis), the cells are fetal in origin (Goldenberg and co-workers, 2000). Before 20 weeks, almost all polymorphonuclear leukocytes are maternal in origin, but later the inflammatory response is both maternal and fetal (Sampson and colleagues, 1997). Microscopic evidence for inflammation of these structures is much more common in preterm deliveries. According to some investigators, these findings of inflammation may be nonspecific and are not always associated with other evidence of fetal or maternal infection. For example, Yamada and colleagues (2000) found that meconium-stained fluid is a chemoattractant for leukocytes. Conversely, Benirschke and Kaufmann (2000) believe that microscopic chorioamnionitis is always due to infection. Management of overt clinical chorioamnionitis is antimicrobial administration and expedient delivery .Occult chorioamnionitis, caused by a wide variety of microorganisms, frequently is cited as a possible explanation for many otherwise unexplained cases of ruptured membranes, preterm labor, or both. Often, however, it is impossible to verify which occurred first.

OTHER ABNORMALITIES. Small amnionic cysts lined by typical amnionic epithelium occasionally are formed. The common variety results from fusion of amnionic folds, with subsequent fluid retention. Amnion nodosum are tiny, light tan, creamy nodules in the amnion made up of vernix caseosa with hair, degenerated squames, and sebum. They result from oligohydramnios and are most commonly found in fetuses with renal agenesis, prolonged preterm ruptured membranes, or in the placenta of the donor fetus with twin-to-twin transfusion syndrome (Benirschke and Kaufmann, 2000). Amnionic bands are caused when disruption of the amnion leads to formation of bands or strings that entrap the fetus and impair growth and development of the involved structure. Fetal conditions that appear to be the consequence of this phenomenon, including intrauterine amputations.

UMBILICAL CORD ABNORMALITIES The cord develops in close association with the amnion. The cord serves a vital function, but it unfortunately is susceptible to entanglement, compression, and occlusion. Collins and Collins (2000) reported a 1- percent incidence of potentially harmful cord complications.

LENGTH. Cord length at term has appreciable variation, and extremes range from no cord (achordia) to lengths up to 300 cm. Short umbilical cords may be associated with adverse perinatal outcomes such as fetal growth restriction, congenital malformations, intrapartum distress, and a twofold risk of death (Krakowiak and associates, 2004). Excessively long cords are more likely to cause complications such as prolapse. In a study of more than 20,000 placentas, Baergen and colleagues (2001) reported a mean length of 37 cm. They defined excessively long cords to be more than two standard deviations, which was 70 cm or longer. In a retrospective analysis, they compared 926 fetuses with long cords with 200 controls who had normal-length cords. Pregnancies involving a fetus with a long cord were associated with maternal systemic disease and delivery complications. There were more cases of cord entanglement, fetal distress, fetal anomalies, and respiratory distress. Perinatal mortality was increased nearly threefold, albeit with borderline statistical significance. Determinants of cord length are intriguing. Animal studies and observational studies in human pregnancy support the concept that cord length is influenced positively by both the volume of amnionic fluid and fetal mobility. Heredity is a factor, and 9 percent of women with an excessively long cord in the study by Baergen and colleagues (2001) had such a finding in a subsequent pregnancy. Miller and associates (1981) identified the cord to be shortened appreciably when there had been either chronic fetal constraint from oligohydramnios or decreased fetal movement, such as with Down syndrome or limb dysfunction.

CORD COILING. In most cases, the umbilical vessels course through the cord in a spiraled manner. Several authors have observed a significant increase in various adverse outcomes in fetuses with hypocoiled cords. Some of these are meconium staining, preterm birth, and fetal distress (Strong and colleagues, 1993, 1994). Shen-Schwarz and associates (1996) reported an association between "absent" cord twisting and marginal and velamentous cord insertion. Rana and associates (1995) found a higher incidence of preterm delivery and cocaine abuse in women with hypercoiled cords.

SINGLE UMBILICAL ARTERY. Identification of a two-vessel cord is an important observation. About one fourth of all infants with only one umbilical artery have associated congenital anomalies. In a review of nearly 350,000 deliveries, Heifetz (1984) found an incidence of a single artery to be 0.63 percent in liveborns, 1.92 percent in neonates with perinatal death, and 3 percent in twins. The incidence is increased considerably in women with diabetes, epilepsy, preeclampsia, antepartum hemorrhage, oligohydramnios, and hydramnios (Leung and Robson, 1989). Two-vessel cords were identified in 1.5 percent of 879 fetuses aborted spontaneously (Byrne and Blanc, 1985). Over half of these had serious malformations, most associated with chromosomal abnormalities. In many cases, a single umbilical artery is detected by routine ultrasound screening. Hill and co-workers (2001) reported that the number of cord vessels could be quantified ultrasonically in almost 98 percent of cases studied between 17 and 36 weeks. The fetal prognosis depends on whether the two-vessel cord is associated with other abnormalities or whether it is an isolated finding. Coexistent fetal anomalies detected by ultrasound have been reported to be from 10 and 50 percent. Perinatal prognosis is better when a two-vessel umbilical cord is an isolated sonographic finding. In one study, Parilla and colleagues (1995) reported no adverse outcomes in 50 such fetuses. In another report, Budorick and co-workers (2001) found no abnormal karyotypes and only one echocardiographic abnormality in 31 fetuses with a two-vessel cord as an isolated finding. Gossett and associates (2002) reported that 74 such fetuses all had normal echocardiography. Conversely, Catanzarite (1995) described 46 fetuses with this isolated ultrasonographic finding, two of whom had lethal chromosomal abnormalities and a third, a tracheoesophageal fistula. When a two-vessel cord is a nonisolated finding, as many as half of fetuses are aneuploid (Budorick and associates, 2001). There are a number of associated anomalies, and Pavlopoulos and colleagues (1998) reported renal aplasia, limb-reduction defects, and atresia of hollow organs in such fetuses, suggesting a vascular etiology. Goldkrand and colleagues (1999) performed Doppler velocimetry in 45 fetuses with a two-vessel cord and 124 normal controls. Although velocity indices were all in the normal range, beginning at 26 weeks they were lower in affected fetuses than in those fetuses with normal cords. These investigators later measured blood flow and found that the single artery had volumetric blood flow equal to a normal cord with two arteries (Goldkrand and associates, 2001). They concluded that growth restriction did not occur in anatomically normal fetuses with a single artery. Raio and colleagues (1999) reported an association between a single artery and a reduction of Wharton jelly.

FOUR-VESSEL CORD. Careful inspection may disclose a venous remnant in 5 percent of cases (Fox, 1978). The significance is unknown.

ABNORMALITIES OF CORD INSERTION. The umbilical cord usually is inserted at or near the center of the fetal surface of the placenta.

Furcate Insertion. In this rare anomaly, the umbilical vessels separate from the cord substance before their insertion into the placenta. Because vessels lose cushioning, they are prone to twisting and thrombosis.

Marginal Insertion. Cord insertion at the placental margin is sometimes referred to as a Battledore placenta. It is found in about 7 percent of term placentas (Benirschke and Kaufmann, 2000). With the exception of the cord being pulled off during delivery of the placenta, it is of little clinical significance.

Velamentous Insertion. This insertion is of considerable importance. The umbilical vessels separate in the membranes at a distance from the placental margin, which they reach surrounded only by a fold of amnion. Benirschke and Kaufmann (2000) reviewed almost 195,000 deliveries and found an average incidence of 1.1 percent. Velamentous insertion occurs much more frequently with twins, and Feldman and associates (2002) identified it in 28 percent of triplets.

Vasa Previa. This finding is associated with velamentous insertion when some of the fetal vessels in the membranes cross the region of the cervical os below the presenting fetal part. Lee and co-workers (2000) attempted to view the internal cervical os with sonography in nearly 94,000 women studied in the second or third trimester. Vasa previa was identified in 18, for an incidence of 1 in about 5200 pregnancies. About half were associated with velamentous insertion and the rest divided between marginal cord insertions and bilobed or succenturiate-lobed placentas. Occasionally, the examiner will be able to palpate or directly visualize a tubular fetal vessel in the membranes overlying the presenting part. Because of a low sensitivity for imaging vasa previa with ultrasound, color Doppler examination is recommended when these are suspected (Harris and Alexander, 2000; Lee and associates, 2000; Nomiyama and colleagues, 1998). In a study of 155 cases by Oyelese and associates (2004), prenatal diagnosis was associated with increased survival ¾ 97 versus 44 percent. With vasa previa, there is considerable potential fetal danger because membrane rupture may be accompanied by tearing of a fetal vessel with exsanguination. In their review, Fung and Lau (1998) found that a low-lying placenta was a risk factor in 80 percent of cases. They also found that antenatal diagnosis was associated with decreased fetal mortality compared with discovery at delivery. Oyelese and colleagues (1999) recommended transvaginal ultrasound with color Doppler for women with risk factors. These included a bilobed, succenturiate, or low-lying placenta; multifetal pregnancy; or pregnancy resulting from in vitro fertilization. In a prospective study of 45 women with a third-trimester placenta previa, Megier and colleagues (1999) found that 3 of 20 previas located over the internal os also had a vasa previa. In an 8-year survey of more than 90,000 women who had grayscale ultrasonography, Lee and colleagues (2000) utilized endovaginal and Doppler studies to confirm vasa previa in women whose initial ultrasound showed an "echogenic parallel or circular line near the cervix". They were able to detect vasa previa in asymptomatic women as early as the midtrimester. Whenever there is hemorrhage antepartum or intrapartum, the possibility of vasa previa and a ruptured fetal vessel exists. Unfortunately, the amount of fetal blood that can be shed without killing the fetus is relatively small. Thus, in many cases, fetal death is virtually instantaneous. One approach to detecting fetal blood is to smear the blood on glass slides, stain the smears with Wright stain, and examine for nucleated red cells, which normally are present in cord blood but not maternal blood.

CORD ABNORMALITIES CAPABLE OF IMPEDING BLOOD FLOW. Several mechanical and vascular abnormalities of the umbilical cord are capable of impairing fetal-placental blood flow.

Knots. False knots, which result from kinking of the vessels to accommodate to the length of the cord, should be distinguished from true knots, which result from active fetal movements. In nearly 17,000 deliveries in the Collaborative Study on Cerebral Palsy, Spellacy and co-workers (1966) found an incidence of true knots of 1.1 percent. The incidence is especially high in monoamnionic twins. Venous stasis may lead to mural thrombosis and fetal hypoxia, causing death or neurological morbidity. Collins and Collins (2000) estimate a 6 percent incidence of stillbirths when true knots are found.

Loops. The cord frequently becomes coiled around portions of the fetus, usually the neck. This is more likely with longer cords. Several large studies have reported one loop of nuchal cord in 20 to 34 percent of deliveries; two loops in 2.5 to 5 percent; and three loops in 0.2 to 0.5 percent (Kan and Eastman, 1957; Sornes, 1995; Spellacy and associates, 1966). Fortunately, coiling of the cord around the neck is an uncommon cause of antepartum fetal death or neurological damage (Clapp and colleagues, 2003; Nelson and Grether, 1998). Such entwined cords, however, may cause intrapartum complications. As labor progresses and there is fetal descent, contractions may compress the cord vessels. This causes fetal heart rate decelerations that persist until the contraction ceases. In labor, 20 percent of fetuses with a nuchal cord have moderate or severe variable heart rate decelerations, and they also are more likely to have a lower umbilical artery pH (Hankins and colleagues, 1987).

TORSION AND STRICTURES. Torsion of the cord is rare. It results from fetal movements during which the cord normally becomes twisted. Occasionally, the torsion is so marked that fetal circulation is compromised. Cord stricture is more serious, and most infants with this finding are stillborn. The stricture is associated with an extreme focal deficiency in Wharton jelly. In monoamnionic twinning, a significant fraction of the high perinatal mortality rate is attributed to entwining of the umbilical cords before labor.

HEMATOMA. These accumulations of blood are associated with short cords, trauma, and entanglement (Benirschke and Kaufmann, 2000). They may result from the rupture of a varix, usually of the umbilical vein, with effusion of blood into the cord (Fig. 27-10). Hematomas also may be caused by umbilical vessel venipuncture.

CYSTS. Cord cysts occasionally are found along the course of the cord and are designated true and false, according to their origin. True cysts are quite small and may be derived from remnants of the umbilical vesicle or the allantois. False cysts, which may attain considerable size, result from liquefaction of Wharton jelly. Such cysts that are detected by sonography are difficult to identify precisely.

PATHOLOGICAL EXAMINATION The development of placental pathology as a discipline has renewed interest in placental examination. In many cases, expert evaluation will help to elucidate the etiopathogenesis of some perinatal outcomes. Although most authorities agree that routine placental examination by a pathologist is not indicated, there still is debate as to which placentas should be submitted. For example, the College of American Pathologists recommends routine examination for a comprehensive and imposing list of maternal, perinatal, and placental conditions (Langston and colleagues, 1997). Conversely, the American College of Obstetricians and Gynecologists (1993) concluded that there are insufficient data to support all of these recommendations. The major concerns are that pathological examination is costly and time consuming and would exhaust resources that could be better spent. Certainly, all agree that the placenta and cord ¾ including the number of vessels ¾ should be examined grossly following all deliveries. The decision to request pathological examination will depend on clinical and placental findings. The possible correlation(s) of specific placental findings with both short- and long-term neonatal outcomes is unclear at this time. Although it is our opinion that routine placental examination by a pathologist cannot be justified, there are some obstetrical and perinatal conditions in which placental findings are helpful. For example, when performed in conjunction with fetal autopsy, it may prove useful in determining the cause of stillbirth. Porter (2000) recommends formal pathological placental examination in the following circumstances:

(1) perinatal death,

(2) preterm delivery,

(3) fetal growth abnormalities,

(4) fetal malformations,

(5) hydrops,

(6) any other fetal disorders,

(7) multiple pregnancy,

(8) maternal disorders, and

(9) gross placental lesions.

The protocol used at Parkland Hospital is that the placenta is sent for pathological examination whenever the neonatal resuscitation team is called. The placenta also is examined in all cases of stillborn infants or if there are obvious abnormalities. Thus, the indications are similar to those of Porter (2000). The specimen is accompanied by a completed data sheet with pertinent clinical information.

FETAL HYPOXIA AND ASPHYXIA OF NEWBORN. FETAL DISTRESS AND FETAL DAMAGE. DEFINITION OF FETAL DISTRESS

 The words fetal distress are too broad and vague to be applied with any precision to clinical situations. For example, some element of fetal distress (danger) is almost universal at some time during normal human parturition. Uncertainty about the diagnosis of fetal distress based upon interpretation of fetal heart rate patterns has given rise to use of descriptions such as reassuring or nonreassuring. “Reassuring” suggests a restoration of confidence by a particular pattern, whereas “nonreassuring” suggests inability to remove doubt. These patterns during labor are dynamic, such that they can rapidly change from reassuring to nonreassuring and vice versa. In this situation, obstetricians essentially experience surges of both confidence and doubt. Put another way, most diagnoses of fetal distress using heart rate patterns occur when obstetricians lose confidence or cannot assuage doubts about fetal condition. These fetal assessments are entirely subjective clinical judgments inevitably subject to imperfection and must be recognized as such.

Why is diagnosis of fetal distress based on heart rate patterns so tenuous? One explanation is that these patterns are more a reflection of fetal physiology than pathology. Physiological control of heart rate includes a variety of interconnected mechanisms that depend on blood flow as well as oxygenation. Moreover, the activity of these control mechanisms is influenced by the preexisting state of fetal oxygenation, as seen, for example, with chronic placental insufficiency. Importantly, the fetus is tethered by an umbilical cord, where blood flow is constantly in jeopardy, which demands that the fetus have a strategy for survival. Moreover, normal labor is a process of increasing acidemia (Dildy and associates, 1994). Thus, normal parturition is a process of repeated fetal hypoxic events resulting in acidemia. Put another way, and assuming that  “asphyxia” can be defined as hypoxia leading to acidemia, then normal parturition is an asphyxiating event for the fetus.

DIAGNOSIS OF FETAL DISTRESS

    Diagnosis of fetal distress based upon fetal heart rate patterns is too often oversimplified. Fetal heart rate decelerations provide clues about in utero events; but do not define fetal damage. A critical dimension—duration of the in utero event—is essentially ignored in deliberations on fetal distress. There have been several research efforts aimed at quantifying the duration of abnormal heart rate patterns necessary to portend significant fetal effects. The most common, due to umbilical cord occlusion, requires considerable time to significantly affect the fetus in experimental animals. Watanabe and associates (1992) showed that sequential complete occlusion of the umbilical cord for 40 seconds followed by 80 seconds of release for 30 minutes in sheep resulted in only moderate fetal acidemia. Similarly, Clapp and colleagues (1988) partially occluded the umbilical cord for 1 minute every 3 minutes in fetal sheep and observed brain damage after 2 hours.

Myers and co-workers (1972) observed that more than 20 late decelerations were necessary in humans for a depressed Apgar score. Low and co-workers (1977), using profound fetal metabolic acidemia as an endpoint, reported that heart rate patterns could only be correlated with outcome during the last 2 hours of labor, and moreover, only in those 2-hour segments showing decelerations with more than 35 percent of uterine contractions. Fleischer and co-workers (1982) observed that abnormal heart rate patterns had to persist for 120 to 140 minutes before fetal acidemia increased significantly.

Significant fetal impact cannot be attributed to severely abnormal fetal heart rate deceleration patterns when these patterns are intermittent and of short duration. The prognostic significance of fetal heart rate changes is further increased by combining several patterns. For example, Gaziano (1979) observed that variable decelerations in conjunction with abnormal baseline rate (either tachycardia or bradycardia) and loss of variability more often predicted poor fetal condition compared with variable decelerations without baseline changes. Nelson and associates (1996) found that although multiple late decelerations and/or decreased beat-to-beat variability were associated with a 4- to 6-fold increased risk for cerebral palsy, these cases accounted for only 0.2 percent of all fetuses with such tracings during labor.

Inevitably, the timing and route of delivery are scrutinized in deliberations about fetal distress. It is generally assumed that cesarean delivery would have improved the infant outcome. Keegan and associates (1985) emphasized that prompt intervention—within 30 minutes of diagnosis of fetal distress—did not prevent newborn seizures. Moreover, Krebs and colleagues (1982b) observed that fetuses with abnormal heart rate patterns in the last portion of labor were in worse metabolic condition when delivered by cesarean delivery compared with those delivered vaginally. The most frequent cause of worrisome patterns is umbilical cord compression. Management of variable fetal heart decelerations, in the absence of baseline changes, is difficult because of the unpredictability of cord occlusion.

Interestingly, cesarean delivery itself, as well as the choice of anesthetic, can affect the fetal heart rate. Prolonged decelerations have been reported during abdominal wall scrubbing in 10 percent of cesarean deliveries (Petrikovsky and co-workers, 1988). Another 10 percent of fetuses exhibited decelerations as a result of the uterine incision provoking excessive contractility.

MECONIUM IN THE AMNIONIC FLUID

    Obstetrical teaching throughout this century has included the concept that meconium passage is a potential warning of fetal asphyxia. J. Whitridge Williams, writing in 1903, observed that “a characteristic sign of impending asphyxia is the escape of meconium.” He attributed meconium passage to “relaxation of the sphincter ani muscle induced by faulty aeration of the (fetal) blood.” Obstetricians, however, have also long realized that the detection of meconium during labor is problematic in the prediction of fetal distress or asphyxia. In their review, Katz and Bowes (1992) emphasized the prognostic uncertainty of meconium by referring to the topic as a “murky subject.” Indeed, although 12 to 22 percent of human labors are complicated by meconium, few such labors are linked to infant mortality. In a recent investigation from Parkland Hospital, meconium was found to be a “low-risk” obstetrical hazard because the perinatal mortality attributable to meconium was 1 death per 1000 live births (Nathan and co-workers, 1994).

Three theories have been suggested to explain fetal passage of meconium and may, in part, explain the tenuous connection between the detection of meconium and infant mortality. The pathological explanation proposes that fetuses pass meconium in response to hypoxia, and that meconium therefore signals fetal compromise (Walker, 1953). Alternatively, in utero passage of meconium may represent normal gastrointestinal tract maturation under neural control (Mathews and Warshaw, 1979). Third, meconium passage could also follow vagal stimulation from common but transient umbilical cord entrapment and resultant increased peristalsis (Hon and colleagues, 1961). Thus, fetal release of meconium could also represent physiological processes. Naeye (1995) has postulated that meconium, and perhaps bile acids, can cause constriction of umbilical and placental surface veins.

In a study by Ramin and co-authors (1996) that included almost 8000 pregnancies delivered at Parkland Hospital with meconium in the amnionic fluid, meconium aspiration syndrome was significantly associated with fetal acidemia at birth .

Other significant correlates of aspiration included indices of fetal jeopardy such as cesarean delivery, forceps to expedite delivery, and intrapartum heart rate abnormalities. Similarly, indices of condition at birth, to include depressed Apgar scores and need for assisted ventilation in the delivery room, also implicated fetal compromise during labor and/or delivery. Analysis of the type of fetal acidemia based on umbilical blood gases suggested that the fetal compromise associated with meconium aspiration syndrome was an acute event, because most acidemic fetuses had abnormally increased PCO2 rather than the pure metabolic acidemia.

Interestingly, hypercarbia in fetal lambs has been shown to induce fetal gasping and resultant increased amnionic fluid inhalation (Boddy and colleagues, 1974; Dawes and co-workers, 1972). Jovanovic and Nguyen (1989) later observed that meconium gasped into the fetal lungs caused aspiration syndrome only in asphyxiated animals. Ramin and co-authors (1996) hypothesized that the pathophysiology of meconium aspiration syndrome includes, but is not limited to, fetal hypercarbia, which stimulates fetal respiration leading to aspiration of meconium into the alveoli, and lung parenchymal damage secondary to acidemia-induced alveolar cell damage in the presence of meconium. The results of this study could thus be interpreted to implicate meconium as a fetal hazard when acidemia supervenes rather than a result of fetal compromise. In this pathophysiological scenario, meconium in amnionic fluid is a fetal environmental hazard rather than a marker of preexistent compromise.

 This proposed pathophysiological sequence is not exclusive, because it does not account for approximately half of cases of meconium aspiration syndrome in which the fetus was not acidemic at birth. It was concluded that the high incidence of meconium observed in the amnionic fluid of women during labor often represents fetal passage of gastrointestinal contents in conjunction with normal physiological processes. Such meconium, however, can become an environmental hazard when fetal acidemia supervenes. Importantly, fetal acidemia occurs acutely, and therefore meconium aspiration is unpredictable and likely unpreventable.

MANAGEMENT

     Management of significantly variant fetal heart rate patterns consists of correcting the potential fetal insult, if possible (American College of Obstetricians and Gynecologists, 1995b). Measures may include discontinuing oxytocin, moving the mother to a lateral position, increasing fluid infusions to improve intervillous perfusion, giving oxygen by mask at 8 to 10 L/min, and correcting hypotension associated with regional analgesia. Vaginal examination to rule out prolapsed cord or impending delivery may be helpful. As previously described, amnioinfusion has been used in selected instances of fetal distress due to umbilical cord occlusion fetal heart rate patterns. If these measures are not effective, preparations should be made for prompt delivery by the most expeditious route. Most evidence indicates that even such ideal management of abnormal fetal heart patterns will not always prevent fetal death or brain damage.

BENEFITS OF ELECTRONIC FETAL HEART RATE MONITORING

By the end of the 1970s, questions about the efficacy, safety, and costs of electronic monitoring were being voiced from the Office of Technology Assessment, Congress of the United States, and Centers for Disease Control. Banta and Thacker (1979) analyzed 158 reports and concluded that “the technical advances required in the demonstration that reliable recording could be done seems to have blinded most observers to the fact that this additional information will not necessarily produce better outcomes.” They attributed the apparent lack of benefit to the imprecision of electronic monitoring to diagnose fetal distress.  Moreover, increased usage was linked to more frequent cesarean delivery. They estimated that additional costs of childbirth in the United States, if half of labors had electronic monitoring, was approximately $400 million per year in 1979 dollars.

The National Institute of Child Health and Human Development appointed a task force that published its consensus report in 1979. After an exhaustive review of electronic monitoring literature, the group concluded that the evidence only suggested a trend toward improved infant outcome in complicated pregnancies. No evidence demonstrated improved outcome in uncomplicated pregnancies. They emphasized that few scientifically conducted investigations had been done to address perinatal benefits.

 Importantly, and largely ignored in the current obstetrical litigation crisis, the task force concluded that “courts of law should recognize intrapartum hypoxia as only one of the many potential factors involved in the development of handicaps and perinatal death, and current research and clinical data do not allow comprehensive definition of antepartum or intrapartum risk, nor means to reduce risk of adverse outcome.”

RANDOMIZED ELECTRONIC FETAL HEART RATE MONITORING STUDIES

    The first five randomized clinical trials of electronic monitoring involved 3100 pregnancies (Haverkamp, 1976, 1979; Kelso, 1978; Renou, 1976; Wood, 1981; and their many colleagues). Only complicated pregnancies were studied in three of these. In four studies, no perinatal benefits of electronic monitoring were found.

The National Maternity Hospital, Dublin, was the site of the largest randomized study of electronic monitoring (MacDonald and co-workers, 1985). Nearly 13,000 pregnancies were included. Most were uncomplicated; however, about one fourth had diabetes, preeclampsia, chronic hypertension, renal and cardiac disease, prior perinatal death, prior neurological abnormality, prior low birthweight, prolonged pregnancy, multiple gestation, breech presentation, or gestation less than 34 weeks. The incidence of forceps delivery was more frequent in the electronically monitored group, but cesarean delivery rates did not differ. No differences were found in the incidence of intrapartum stillbirths or neonatal deaths. Although the number of infants suffering seizures in the auscultation group was increased, there was an equal number of neurologically damaged infants in either group at follow-up.

Luthy and co-workers (1987) studied the effects of electronic monitoring on neurobehavioral development of low-birthweight infants. They studied the neurological outcomes of 212 live-born infants weighing 700 to 1750 g whose intrapartum management had been randomly assigned to either electronic monitoring or periodic fetal heart rate auscultation. Electronic monitoring was not associated with significantly improved neurological outcomes. Cerebral palsy was diagnosed in 13 percent of infants with electronic monitoring compared with 8 percent of those in whom auscultation had been used.

Vintzileos and associates (1993) used coin flipping to randomly assign women to electronic monitoring or to intermittent auscultation in a study performed in Athens, Greece. In contrast to other randomized trials, they showed a significant reduction in “perinatal deaths due to hypoxia.” This study has been severely criticized because of serious flaws in methodology and interpretation (Keirse, 1994). For example, uncontrolled selection of women for subsequent coin flipping to determine study group allocation is a classical example of a “randomization” method that can easily be subverted (Schulz, 1995). Keirse (1994) likened this report to the Trojan horse of the ancient Greeks when he wrote: “The symbolic feature of a Trojan horse, now as in ancient times, is that it encourages the weary and unsuspicious to draw incorrect and misleading inferences.” The Athens study has served as the basis for two other reports claiming the superiority of electronic fetal monitoring (Vintzileos and co-workers, 1995a, 1995b).

Parkland Hospital Experience: Selective versus Universal Monitoring.    In July 1982, an investigation began at Parkland Hospital to ascertain whether all women in labor should undergo electronic monitoring (Leveno and co-workers, 1986). In alternating months, universal electronic monitoring was rotated with selective heart rate monitoring, which was the prevailing practice. During the 3-year investigation, 17,410 fetuses were managed with selective monitoring practices. These were compared with 17,641 fetuses managed using universal electronic monitoring. No significant differences were found in any perinatal outcomes. There was a significant small increase in the frequency of cesarean delivery for fetal distress associated with universal electronic monitoring. Thus, increased application of electronic monitoring at Parkland Hospital did not improve perinatal results, but it increased the frequency of cesarean delivery for fetal distress.

SUMMARY OF RANDOMIZED STUDIES

    Thacker and co-authors (1995) identified 12 published randomized clinical trials of electronic fetal monitoring from 1966 to 1994. Total pregnancies included in these studies was 58,624. They concluded that the benefits once claimed for electronic fetal monitoring are clearly more modest than believed, and appear to be primarily in the prevention of neonatal seizures. Long-term implications of this outcome, however, appear less serious than once believed. Abnormal neurological consequences were not consistently higher among children monitored by auscultation compared with electronic methods. They concurred with the current position of the American College of Obstetricians and Gynecologists (1995b) on intrapartum fetal surveillance.

 Why Unfulfilled Expectations?    There are several fallacious assumptions behind expectations of improved perinatal outcome with electronic monitoring. One assumption is that fetal distress is a slowly developing phenomenon and that electronic monitoring makes possible early detection of the compromised fetus. This assumption is illogical; how can all fetuses die slowly? Another presumption is that all fetal damage develops in the hospital. Only recently has attention focused on the reality that many damaged fetuses suffered insults before arrival to labor units. The very term “fetal monitor” implies that this inanimate technology in some fashion “monitors.” The assumption is made that if a dead or damaged infant is delivered, the tracing strip must provide some clue, because this device was monitoring fetal condition. Last, and despite contrary evidence, many have hypothesized that fetal distress cannot be detected reliably without electronic instrumentation. All of these assumptions led to great expectations and fostered the belief that all dead or damaged neonates are preventable. These unwarranted expectations have greatly fueled the current litigation crisis in obstetrics. Indeed, Symonds (1994) reported that 70 percent of all liability claims related to fetal brain damage are based on reputed abnormalities in the electronic fetal monitor tracing.

           Too many fetuses demonstrate fetal heart rate abnormalities during labor to permit accurate detection of those who are actually compromised. Indeed, most “fetal distress” does not represent an overtly compromised fetus. Fetal heart rate abnormalities are quite common in labor. Importantly, debate continues about interpretation of many heart rate patterns. For example, Keith and co-workers (1995) asked each of 17 experts to review 50 tracings on two occasions, at least 1 month apart. About 20 percent changed their own interpretations, and approximately 25 percent did not agree with the interpretations of their colleagues. Ironically, this state of affairs for electronic monitoring does not differ from that of Benson and co-workers (1968) in their report on auscultation: “Naivete and wishful thinking inspired our hope for a simple rule-of-thumb estimate of fetal distress. Obviously, the problem is much too complex for such an easy appraisal.”

Current Recommendations

    The methods most commonly used for intrapartum fetal heart rate monitoring include auscultation with a fetal stethoscope or a Doppler ultrasound device, or continuous electronic monitoring of the heart rate and uterine contractions. There is no scientific evidence that has identified the most effective method, including frequency or duration of fetal surveillance, that ensures optimum results.   Intermittent auscultation or continuous electronic monitoring are considered acceptable methods of intrapartum surveillance in both low- and high-risk pregnancies. The recommended interval between checking the heart rate, however, is longer in the uncomplicated pregnancy. When auscultation is used, it is recommended that it be performed after a contraction and for 60 seconds. It is also recommended that a 1 to 1 nurse–patient ratio be used if auscultation is employed. Thus, the number of nurses available for labor and delivery may preclude use of intermittent auscultation.

Intrapartum Surveillance of Uterine Activity

Analysis of electronically measured uterine activity permits some generalities concerning the relationship of certain patterns of uterine contractions to labor outcome. There is considerable normal variation, however, and caution must be exercised before judging true labor or its absence solely from study of a monitor tracing. Uterine muscle efficiency to effect delivery varies greatly. To use an analogy, 100-meter sprinters all have the same muscle groups yet cross the finish line at different times.

Measurements of intrauterine pressure, that is, amnionic fluid pressure, Internal Uterine Pressure Monitoring

Between and during contractions, are made by a fluid-filled plastic catheter positioned so that the distal tip is located in amnionic fluid above the presenting part. First, a plastic catheter guide that contains the distal portion of the catheter is inserted just through the cervical os, and the fluid-filled catheter is then gently pushed beyond the guide into the uterine cavity. To minimize risk to the placenta from the catheter tip, when the site of placental implantation is known, the tip of the catheter inserter should be positioned so that the catheter is likely to be inserted away from the placental site. The opposite end of the catheter, filled with saline, is connected to a strain-gauge pressure sensor adjusted to the same level as the catheter tip in the uterus. The amplified electrical signal produced in the strain gauge by variations in pressure within the fluid system is recorded on a calibrated moving paper strip, simultaneously with the recording of the fetal heart rate. Free communication between amnionic fluid and fluid in the catheter is essential. If the catheter tip becomes obstructed, it can usually be cleared by injecting a small volume of saline through the catheter. Alternatively, intrauterine pressure catheters are now available that have the pressure sensor in the tip of the catheter, which obviates the need for the fluid column.

External Monitoring

Uterine contractions can be measured by a displacement transducer placed on the abdomen close to the fundus. The transducer button (“plunger”) is held against the abdominal wall and, as the uterus contracts, the button moves in proportion to the strength of the contraction. This movement is converted into a measurable electrical signal that indicates the relative intensity of the contraction—it does not give an accurate measure of intensity. If carefully supervised, however, external monitoring can give a good indication of the onset, peak, and end of the contraction.

Patterns of Uterine Activity

Caldeyro-Barcia and Poseiro (1960) from Montevideo, Uruguay, were pioneers who have done much to elucidate the patterns of spontaneous uterine activity throughout pregnancy. Their investigations were made possible by the development of electronic means of recording and quantifying uterine contractions before and during labor. Contractile waves of uterine activity were usually measured using intra-amnionic pressure catheters, but early in their studies as many as four simultaneous intramyometrial microballoons were also used to record uterine pressure. They also introduced the concept of  Montevideo units to define uterine activity. By this definition, uterine performance is the product of the intensity—increased uterine pressure above baseline tone—of a contraction in mm Hg multiplied by contraction frequency per 10 minutes. For example, three contractions in 10 minutes, each of 50 mm Hg intensity, would equal 150 Montevideo units. Their unique studies provided useful insights for understanding normal labor.

During the first 30 weeks, uterine activity measured in Montevideo units is comparatively quiescent . Uterine contractions are seldom greater than 20 mm Hg, and these have been equated with those first described in 1872 by John Braxton Hicks. Uterine activity increases gradually after 30 weeks, and it is noteworthy that these Braxton Hicks contractions also increase in intensity and frequency. Further increases in uterine activity are typical of the last weeks of pregnancy, termed prelabor. During prelabor, the cervix ripens, presumably as a consequence of increasing uterine contractions .

According to Caldeyro-Barcia and Poseiro (1960), clinical labor usually commences when uterine activity reaches values between 80 and 120 Montevideo units. This translates into approximately three contractions of 40 mm Hg every 10 minutes, or 120 Montevideo units.

    Importantly, there is no clear-cut division between prelabor and labor, but rather a gradual and progressive transition.During first-stage labor, uterine contractions increase progressively in intensity from about 25 mm Hg at commencement of labor to 50 mm Hg at the end. At the same time, frequency increases from three to five contractions per 10 minutes, and uterine baseline tone from 8 to 12 mm Hg. Uterine activity further increases during second-stage labor, aided by maternal abdominal muscles during bearing down . Indeed, contractions of 80 to 100 mm Hg are typical, and occur as frequently as five to six per 10 minutes. Interestingly, the duration of uterine contractions (60 to 80 seconds) does not increase appreciably from early active labor (3 to 4 cm dilatation) extending through the second-stage (Pontonnier and colleagues, 1975). Presumably, this constancy of duration serves a fetal respiratory gas-exchange function. That is, functional fetal “breath holding” during a uterine contraction, which results in isolation of the intervillous space where respiratory gas exchange occurs, has a 60- to 80-second limit that remains relatively constant.

Caldeyro-Barcia and Poseiro (1960) also observed empirically that  uterine contractions are clinically palpable only after their intensity exceeds 10 mm Hg. Moreover, until their intensity reaches 40 mm Hg, the uterine wall can readily be depressed by the finger. At greater intensity, it then becomes so hard that it resists easy depression. Uterine contractions are usually not associated with pain until their intensity exceeds 15 mm Hg, presumably because this is the minimum pressure required for distending the lower uterine segment and cervix. It follows that Braxton Hicks contractions exceeding 15 mm Hg may be perceived as uncomfortable because distension of the uterus, cervix, and birth canal is generally thought to elicit discomfort.

Hendricks (1968) observed that “the clinician makes great demands upon the uterus. He expects it to remain well relaxed during pregnancy, to contract effectively but intermittently during labor, and then to remain in a state of almost constant contraction for several hours postpartum.”  As also described by Caldeyro-Barcia and Poseiro (1960), uterine activity progressively and gradually increases from prelabor through late labor.  Indeed, the pattern of uterine activity is one of gradual subsidence or reverse of that leading up to delivery. It is therefore not surprising that the uterus that performs poorly before delivery is also prone to atony and puerperal hemorrhage.

Origin and Propagation of Uterine Contractions

The uterus, unlike the heart, has not been extensively studied in terms of its nonhormonal physiological mechanisms of function. The normal contractile wave of labor originates near the uterine end of one of the fallopian tubes; thus these areas act as “pacemakers” . The right pacemaker usually predominates over the left and starts the great majority of contractile waves.  The contraction spreads from the pacemaker area throughout the uterus at 2 cm/sec, depolarizing the whole organ within 15 seconds. This depolarization wave propagates downward toward the cervix. Intensity is greatest in the fundus, and it diminishes in the lower uterus. This phenomenon is thought to reflect reductions of myometrial thickness from the fundus to the cervix. Presumably, this descending gradient of pressure serves to direct fetal descent toward the cervix and efface the cervix. Importantly, all parts of the uterus are synchronized and reach their peak pressure almost simultaneously.

The pacemaker theory also serves to explain the varying intensity of adjacent coupled contractions shown in lines A and B of Figure .

 Such coupling is termed incoordination by Caldeyro-Barcia and Poseiro (1960). A contractile wave begins in one cornual-region pacemaker, but does not synchronously depolarize the entire uterus. As a result, another contraction begins in the contralateral pacemaker and produces the second contractile wave of the couplet. These small contractions alternating with larger ones appear to be typical of early labor, and indeed, labor may progress with such uterine activity but at a slower pace. They also observed that labor would progress slowly if regular contractions were hypotonic—that is, contraction intensity less than 25 mm Hg or frequency less than two contractions per 10 minutes. Similar observations were made by Seitchik (1981) in a computer-aided analysis comparing women in active labor with those with arrested labor. Normal labor was characterized by a minimum of three contractions that averaged greater than 25 mm Hg and less than 4-minute intervals between contractions. Less than this amount of uterine activity was associated with arrest of active labor. He cautioned that the prospective diagnosis of hypotonic labor based simply on a few uterine pressures cannot be accomplished reliably. He did report, however, that modest dosages of oxytocin—usually 8 mU/min or less—restored uterine contractions in women with hypocontractile patterns.

Caldeyro-Barcia and Poseiro (1960) attempted to quantify uterine work necessary to dilate the cervix from 2 cm to complete. Labor was induced by infusing oxytocin in parous women, and the total uterine contraction pressure in mm Hg necessary to accomplish complete dilatation was summed. They found that between 4000 and 8000 mm Hg of total pressure was required. If the contractions had an average intensity of 50 mm Hg, then 80 to 160 contractions were necessary. Moreover, if the contraction frequency ranged from four to five per 10 minutes, then the duration of the first stage would be between 3 and 6 hours. Calculations such as these apply to many normal labors and, although applicable to some pregnancies, the extreme biological variation of normal labor defies efforts to mathematically describe it for the purpose of determining departure from normal.

Hauth and co-workers (1986) quantified uterine contraction pressures in 109 women at term who received oxytocin for labor induction or augmentation. Most of these  women with successfully stimulated labor achieved 200 to 225 Montevideo units, and 40 percent had up to 300 Montevideo units to effect delivery. They suggested that these levels of uterine activity should be sought before consideration of cesarean delivery for presumed dystocia; a recommendation endorsed by the American College of Obstetricians and Gynecologists (1995a).

FETAL GROWTH DISORDERS

Each year, about 20 percent of the almost 4 million infants in the United States are born at the low and high extremes of fetal growth. Low-birthweight infants make up just less than half of these 700,000 births and include preterm infants as well as those whose growth has been impaired in utero. Although the majority of these infants are preterm, the National Institutes of Health estimated that approximately 40,000 are at term, having suffered abnormal fetal growth (Frigoletto, 1986). In 1997, 8 percent of infants weighed less than 2500 g at birth, and 10 percent weighed more than 4000 g (Ventura and colleagues, 1999). Between 1981 and 2001, the percentage of low-birthweight infants (less than 2500 g) and very-low-birthweight infants (less than 1500 g) increased by 13 percent and 24 percent, respectively (Martin and colleagues, 2002). Macrosomia, defined as birthweight of 4000 g or greater, occurred in 1 out of every 10 births in the United States in 1997. However, the incidence of macrosomia has been declining since 1991 after peaking at about 11 percent in the 1980s (Ventura and colleagues, 1999).

NORMAL FETAL GROWTH Human fetal growth is characterized by sequential patterns of tissue and organ growth, differentiation, and maturation that are determined by maternal provision of substrate, placental transfer of these substrates, and fetal growth potential governed by the genome. Steer (1998) has summarized the potential effects of evolutionary pressures on human fetal growth. During the past 3.5 million years, the human species has become adapted to an upright posture, and the pelvis has evolved to facilitate walking. During the past 500,000 years, human brain volume has increased from about 750 mL (Homo erectus) to about 1000 to 1800 mL (Homo sapiens). The head has to pass through the pelvis during parturition; thus, an increasing conflict between the need to walk — requiring a narrow pelvis — and the need to think — requiring a large brain — has developed. This leads to difficulty in labor because of dystocia. The difficulty posed by a large-sized head or brain and small pelvic capacity has been resolved to some extent by an evolutionary modification known as neoteny, whereby humans are born increasingly early. For example, if humans were born with the same level of functional maturity as the chimpanzee, human gestation would last 17 months. The human species may be resolving this dilemma in another way — by acquiring the ability to restrict growth late in pregnancy. This characteristic "tail off" of growth from 38 weeks onward as seen in human pregnancies is not evident in other mammals. Thus, the ability to "growth restrict " may be adaptive rather than pathological. Lin and Santolaya-Forgas (1998) have divided cell growth into three consecutive phases. The initial phase of hyperplasia is during the first 16 weeks and is characterized by a rapid increase in cell number. The second phase, which extends up to 32 weeks, includes both cellular hyperplasia and hypertrophy. After 32 weeks, fetal growth is by cellular hypertrophy, and it is during this phase that most fetal fat and glycogen deposition takes place. The corresponding fetal growth rates during these three phases are 5 g/day at 15 weeks, 15 to 20 g/day at 24 weeks, and 30 to 35 g/day at 34 weeks (Williams and co-authors, 1982). There is considerable biological variation in the velocity of fetal growth determined by sonography in the last half of gestation. Although many factors have been implicated in the process of fetal growth, the precise cellular and molecular mechanisms by which normal fetal growth occurs are not well understood. In early fetal life the major determinant of growth is the fetal genome, but later in pregnancy environmental, nutritional, and hormonal influences become increasingly important (Holmes and colleagues, 1998). For example, there is considerable evidence that insulin and insulin-like growth factor-I (IGF-I) and IGF-II have a role in the regulation of fetal growth and weight gain (Verhaeghe and colleagues, 1993). Insulin is secreted by fetal pancreatic cells primarily during the second half of gestation and is believed to stimulate somatic growth and adiposity. The IGFs are produced by virtually all fetal organs beginning early in development. They are potent stimulators of cell division and differentiation. Verhaeghe and colleagues (1993) have found that fetal serum levels of IGF-I, IGF-II, and insulin are all related to fetal growth and weight gain. In cord serum, IGF-I correlates best with birthweight. Moreover, a polymorphism in the IGF-I gene may be associated with low birthweight (Vaessen and colleagues, 2002). Since the discovery of the obesity gene and its protein product, leptin, which is synthesized in adipose tissue, there has been interest in maternal and fetal serum leptin levels. Fetal concentrations increase during the first two trimesters, and they correlate with birthweight (Sivan, 1998; Tamura, 1998; Tovi, 2005a,b, and all their colleagues). This relationship is controversial in growth-restricted fetuses (Grisaru-Granovsky and colleagues, 2003). Fetal growth is also dependent on an adequate supply of nutrients. Indeed, Williams (1903) aptly commented in the first edition of this textbook that "the increase in size of the foetus affords conclusive evidence that materials in solution must, pass from the maternal to the foetal circulation...." Glucose transfer has been extensively studied during pregnancy. Both excessive and diminished maternal glucose availability to the fetus affect fetal growth. Excessive glycemia produces macrosomia, whereas diminished glucose levels have been associated with fetal growth restriction. Indeed, the macrosomic infant of the mildly diabetic mother is the prototypical example of the effects of excessive maternal glucose supply. Characteristics of these infants include fetal hyperinsulinism and elevated umbilical cord levels of IGF-I and IGF-II (Roth and colleagues, 1996). There is less information concerning the physiology of maternal-fetal transfer of other nutrients such as amino acids and lipids. Ronzoni and colleagues (1999) studied maternal-fetal concentrations of amino acids in 26 normal pregnancies at the time of cesarean delivery. An increase in maternal amino acid levels led to an increase in fetal levels. In growth-restricted fetuses, amino acid disturbance similar to the biochemical changes seen in postnatal protein-starvation states has been detected (Economides and colleagues, 1989b). Jones and colleagues (1999) studied 38 growth-restricted infants and found impaired utilization of circulating triglycerides consistent with peripheral adipose depletion.

FETAL GROWTH RESTRICTION Low-birthweight infants who are small-for-gestational age are designated as suffering from fetal growth restriction. The term fetal growth retardation has been discarded because "retardation" implies abnormal mental function. It is estimated that 3 to 10 percent of infants are growth restricted (Divon and Hsu, 1992). In 1961, Warkany and co-workers reported normal values for infant weights, lengths, and head circumferences that served to define fetal growth restriction. Gruenwald (1963) reported that approximately one third of infants born weighing less than 2500 g were mature and that their small size could be explained by chronic placental insufficiency. These observations generated the concept that birthweight was governed not only by gestational length but also by fetal growth rate. It also has been suggested that fetal size is largely determined in the first trimester (Dickey and Gasser, 1993; Gluckman and Liggins, 1984). Smith and colleagues (1998) compared outcomes of 4229 pregnancies with the difference between measured and expected crown-rump length measured ultrasonically in the first trimester. Suboptimal first-trimester growth was associated with fetal growth restriction as well as preterm delivery between 24 and 32 weeks. It may be that a suboptimal environment in the first weeks of gestation limits fetal growth for the remainder of pregnancy and that such an environment may precipitate extremely preterm delivery.

DEFINITION. In 1963, Lubchenco and co-workers from Denver published detailed comparisons of gestational ages with birthweights in an effort to derive norms for expected fetal size at a given gestational week. Battaglia and Lubchenco (1967) then classified small-for-gestational-age (SGA) infants as those whose weights were below the 10th percentile for their gestational age. Such infants were shown to be at increased risk for neonatal death. For example, the neonatal mortality rate of SGA infants born at 38 weeks was 1 percent compared with that of 0.2 percent in those with appropriate birthweights. Many infants with birthweights less than the 10th percentile are not pathologically growth restricted but are small simply because of normal biological factors. Indeed, Manning and Hohler (1991) and Gardosi and colleagues (1992) concluded that 25 to 60 percent of SGA infants were, in fact, appropriately grown when maternal ethnic group, parity, weight, and height were considered. Because of these disparities, other classifications were proposed. Seeds (1984) suggested a definition based on birthweight below the fifth percentile. Usher and McLean (1969) proposed that fetal growth standards should be based on mean weightsfor- age with normal limits defined by ±2 standard deviations. This definition would limit SGA infants to 3 percent of births instead of 10 percent. Clinically, this definition is very meaningful. Most poor outcomes are in infants below the third percentile. In a study of 122,754 pregnancies delivered at Parkland Hospital, McIntire and colleagues (1999) also showed that mortality and morbidity were significantly increased among term infants whose birthweights were at or below the third percentile.

Normal Infant Birthweight. Normative data for fetal growth based on birthweight have evolved considerably following the pioneering work done by Lubchenco and co-workers (1963). Their data were derived exclusively from births to white and Hispanic women who resided at high altitudes. Such infants are smaller than those born at sea level. For example, term infants average 3400 g at sea level, 3200 g at 5000 feet, and 2900 g at 10,000 feet. Other researchers have developed fetal growth curves using various populations and geographic locations throughout the United States (Brenner and colleagues, 1976; Ott, 1993; Overpeck and colleagues, 1999; Williams, 1975). Each of these curves was based on specific ethnic or regional groups; therefore, they are not representative of the entire population. To address this, fetal growth graphs were derived on a nationwide basis in both the United States and Canada (Alexander and colleagues, 1996; Arbuckle and colleagues, 1993). Data from over 3.1 million mothers with singleton liveborn infants in the United States during 1991 were used to derive the growth curve. In general, the previously published fetal growth curve data underestimated birthweights when compared with national data. Importantly, there are significant ethnic or racial variations in neonatal mortality rates within the national neonatal mortality rate as well as within birthweight and gestational age categories (Alexander and colleagues, 1999, 2003).

Birthweight Versus Growth. Most of what is known about normal and abnormal human fetal growth is actually based on birthweight standards, which is the end point of fetal growth. These standards do not reveal the rate of fetal growth. Indeed, such birthweight curves reveal compromised growth only at the extreme of impaired growth. Thus, they cannot be used to identify the fetus who fails to achieve an expected or potential size but whose birthweight outlies the 10th percentile. Birthweight percentile is an incomplete measure of growth failure. Infants who are of apparently appropriate birthweight, but who "cross centiles," may be exhibiting signs of malnutrition because they have not achieved their full genetic potential (Owen and colleagues, 1996, 2003). The rate or velocity of human fetal growth depends on serial ultrasonic fetal anthropometry. Reports suggest that a diminished growth velocity is related to perinatal morbidity (Owen and co-workers, 1997; Owen and Khan, 1998).

Metabolic Abnormalities. Fetal blood sampling from the umbilical vein for karyotyping of severely growth-restricted fetuses has permitted remarkable insights into the pathophysiology of fetal growth. In 38 growth-restricted fetuses, Soothill and colleagues (1987) found that the severity of hypoxia correlated significantly with hypercapnia, acidosis, lactic acidemia, hypoglycemia, and erythroblastosis. Subsequently, Economides and Nicolaides (1989a) found that the major cause of hypoglycemia in SGA fetuses was reduced supply rather than increased fetal consumption or diminished fetal glucose production. Economides and co-workers (1989c) found that these fetuses also had hypoinsulinemia and hypoglycemia. The degree of fetal growth restriction, however, did not correlate with plasma insulin, suggesting that it is not the primary determinant of poor fetal growth. In children with kwashiorkor, the ratio of nonessential to essential amino acids is increased, presumably because of decreased intake of essential amino acids. Economides and colleagues (1989b) measured the glycine/valine ratio in cord blood from growth-restricted fetuses and found ratios similar to those observed in children with protein deprivation and kwashiorkor. Moreover, protein deprivation correlated with fetal hypoxemia. Economides and associates (1990) measured plasma triglyceride concentrations in small fetuses and infants and compared those with the concentrations of appropriately grown fetuses. Growth-restricted fetuses demonstrated hypertriglyceridemia that was correlated with the degree of fetal hypoxemia. They hypothesized that hypoglycemic, growth-restricted fetuses mobilize adipose tissue, and that the hypertriglyceridemia is the result of lipolysis of fetal fat stores. Elevated plasma concentrations of interleukin-10, placental atrial natriuretic peptide, and endothelin-1, as well as a defect in epidermal growth factor function, have also been described in growth-restricted fetuses (Varner and colleagues, 1996). These findings suggest a possible role for abnormal immune activation and abnormal placentation in the genesis of growth-restricted fetuses (Gabriel, 1994; Heyborne, 1994; Kingdom, 1994; McQueen, 1993; Neerhof, 1995, and all their associates). In animals, chronic reduction in nitric oxide, an endothelium-derived, locally acting vasorelaxant, has also been shown to result in diminished fetal growth (Diket and associates, 1994).

MORBIDITY AND MORTALITY. Fetal growth restriction is associated with substantive perinatal morbidity and mortality. Fetal demise, birth asphyxia, meconium aspiration, and neonatal hypoglycemia and hypothermia are all increased, as is the prevalence of abnormal neurological development (Paz and associates, 1995; Piper and colleagues, 1996). This is true for both term and preterm infants (Minior and Divon, 1998). Finally, the risk of longterm mortality in preterm growth-restricted infants is significantly increased compared with that of appropriately grown preterm infants (Kok and colleagues, 1998). Postnatal growth and development of the growth-restricted fetus depends on the cause of restriction, nutrition in infancy, and the social environment (Kliegman, 1997). Infants with growth restriction due to congenital, viral, chromosomal, or maternal size typically remain small throughout life. If growth restriction is due to placental insufficiency, infants must often have catchup growth to approach their inherited growth potential. Similarly, the neurodevelopmental outcome of the growth-restricted fetus is influenced by both pre- and postnatal environments. Infants born to families of higher socioeconomic status demonstrate fewer developmental problems than those born to indigent families.

ACCELERATED MATURATION. There have been numerous reports describing accelerated fetal pulmonary maturation in complicated pregnancies associated with growth restriction (Perelman and colleagues, 1985). One explanation for this phenomenon is that the fetus responds to a stressed environment by increasing adrenal glucocorticoid production, which leads to earlier or accelerated fetal lung maturation (Laatikainen and associates, 1988). Although this concept pervades modern perinatal thinking, there is scant verification for it. Owen and associates (1990) analyzed perinatal outcomes in 178 women delivered primarily because of hypertension. They compared these with those of 159 women delivered because of spontaneous preterm labor or ruptured membranes. They concluded that a "stressed" pregnancy, which often resulted in SGA infants, did not confer an appreciable survival advantage. Similar findings were reported by Friedman and colleagues (1995) in women with severe preeclampsia. Two studies from Parkland Hospital substantiate that fetal growth restriction accrues no apparent advantages to the preterm infant (McIntire and colleagues, 1999; Tyson and colleagues, 1995). Moreover, Smulian and colleagues (2000) reported that growth-restricted infants had higher 1-year infant mortality compared with infants from normal pregnancies.

SYMMETRICAL VERSUS ASYMMETRICAL GROWTH RESTRICTION. Campbell and Thoms (1977) described the use of the sonographically determined head-to-abdomen circumference ratio (HC/AC) to differentiate growth-restricted fetuses. Those that were symmetrical were proportionately small, and those that were asymmetrical had disproportionately lagging abdominal growth. These authors constructed an HC/AC ratio nomogram from approximately 500 normal fetuses. Although asymmetrical fetuses were "preferentially protected from the full effects of the growth-retarding stimulus," they more likely were associated with pregnancies complicated by severe preeclampsia, fetal distress, operative intervention, and lower Apgar scores than their symmetrical counterparts. It is compelling to relate the type of growth restriction to the onset or etiology of a particular insult. An early insult could theoretically result in a relative decrease in cell number as well as cell size, which might be caused by chemical exposure, viral infection, or inherent cellular development abnormality due to aneuploidy. The resultant proportionate reduction in these cases of both head and body size has been termed symmetrical growth restriction. On the other hand, a late pregnancy insult such as placental insufficiency from hypertension theoretically could primarily affect cell size. Placental insufficiency may result in diminished glucose transfer and hepatic storage, thus, fetal abdominal circumference — which reflects liver size — would be reduced. This sequence of events can theoretically result in asymmetrical growth restriction. This concept has been challenged (Roberts and co-authors, 1999). Such somatic growth restriction is proposed to result from preferential shunting of oxygen and nutrients to the brain, which allows normal brain and head growth. Because the fetal brain is normally relatively large and the liver relatively small, the ratio of brain weight to liver weight over the last 12 weeks — usually about 3 to 1 — may be increased to 5 to 1 or more in severely growth-restricted infants. Although these generalizations about the potential pathophysiology of symmetrical versus asymmetrical growth restriction are interesting from a conceptual standpoint, there is considerable evidence that fetal growth patterns are more complex. Nicolaides and co-authors (1991) found that fetuses with aneuploidy typically had disproportionately large head sizes and thus were asymmetrically growth restricted. Similarly, most preterm infants with growth restriction due to preeclampsia and associated uteroplacental insufficiency demonstrate symmetrical growth impairment (Salafia and co-authors, 1995). Crane and Kopta (1980) analyzed several anthropometric measurements in growth-restricted newborns and concluded that the concept of brain sparing could not be used to identify the cause(s) of fetal growth restriction. Dashe and colleagues (2000) analyzed 8722 consecutive liveborn singletons who underwent an ultrasound examination within 4 weeks of delivery. Although only 20 percent of growth-restricted fetuses demonstrated sonographic head-to-abdomen asymmetry, these fetuses were at increased risk for intrapartum and neonatal complications. Symmetrically growth-restricted fetuses were not at increased risk for adverse outcomes when compared with those appropriately grown. The researchers concluded that asymmetrical fetal growth restriction represented significantly disordered growth, whereas symmetrical growth restriction more likely represented normal, genetically determined small stature.

RISK FACTORS Constitutionally Small Mothers. Small women typically have smaller infants. If a woman begins pregnancy weighing less than 100 pounds, the risk of delivering an SGA infant is increased at least twofold (Simpson and colleagues, 1975). Moreover, intergenerational effects on birthweight are transmitted through the maternal line (Emanuel and associates, 1992). There is also evidence that reduced intrauterine growth of the mother is a risk factor for reduced intrauterine growth of her offspring (Klebanoff and co-authors, 1997). Whether the phenomenon of a small mother giving birth to a small infant is nature or nurture is unclear. Brooks and coauthors (1995) analyzed 62 births after ovum donation to examine the relative influence of the donor versus the recipient on birthweight. They concluded that the environment provided by the donor mother was more important than the genetic contribution to birthweight.

Poor Maternal Nutrition. In the woman of average or low body mass index (BMI), poor weight gain throughout pregnancy may be associated with fetal growth restriction (Simpson and colleagues, 1975). Lack of weight gain in the second trimester especially correlates with decreased birthweight (Abrams and Selvin, 1995). If the mother is large and otherwise healthy, however, below-average maternal weight gain without maternal disease is unlikely to be associated with appreciable fetal growth restriction. Marked restriction of weight gain after midpregnancy should not be encouraged. Even so, it appears that caloric restriction to less than 1500 kcal/day adversely affects fetal growth only minimally (Lechtig and co-workers, 1975). The best documented effect of famine on fetal growth was in the "hunger winter" of 1944 in Holland. The German Army restricted dietary intake to 600 kcal/day for civilians, including pregnant women. The famine persisted for 28 weeks. Although this resulted in an average birthweight decrease of only 250 g, fetal mortality rates increased significantly (Stein and colleagues, 1975).

Social Deprivation. The effect of social deprivation on birthweight is interconnected to the effects of associated lifestyle factors such as smoking, alcohol or other substance abuse, and poor nutrition. In a study of 7493 British women, Wilcox and associates (1995) found that the most socially deprived mothers had the smallest infants. Similarly, Dejin-Karlsson and colleagues (2000) prospectively studied a cohort of Swedish women and found that lack of psychosocial resources increased the risk of growth-restricted infants. Indeed, more than 100 years ago, Williams (1903) wrote in the first edition of this textbook: "The social condition of the mother and the comforts by which she is surrounded also exert a marked influence on the child's weight, heavier children being more common in the upper walks of life."

Fetal Infections. Viral, bacterial, protozoan, and spirochetal infections have been implicated in up to 5 percent of cases of fetal growth restriction (Klein and Remington, 1995). The best known of these are infections caused by rubella and cytomegalovirus (Lin and Evans, 1984; Stagno and associates, 1977). Mechanisms affecting fetal growth appear to be different with these two viral infections. Cytomegalovirus is associated with direct cytolysis and loss of functional cells. Rubella infection causes vascular insufficiency by damaging the endothelium of small vessels. Rubella also reduces cell division (Pollack and Divon, 1992). Hepatitis A and B are associated with preterm delivery but may also adversely affect fetal growth (Waterson, 1979). Listeriosis, tuberculosis, and syphilis have been reported to cause fetal growth restriction. Paradoxically, with syphilis, the placenta is almost always increased in weight and size due to edema and perivascular inflammation (Varner and Galask, 1984). Toxoplasmosis is the protozoan infection most often associated with compromised fetal growth, but congenital malaria may produce the same result (Varner and Galask, 1984).

Congenital Malformations. In a study of over 13,000 infants with major structural anomalies, 22 percent had accompanying growth restriction (Khoury and associates, 1988). In general, the more severe the malformation, the more likely the fetus is to be SGA. This is especially evident in fetuses with chromosomal abnormalities or those with serious cardiovascular malformations.

Chromosomal Aneuploidies. Placentas of fetuses with autosomal trisomies have a reduced number of small muscular arteries in the tertiary stem villi (Rochelson and associates, 1990). Depending on which chromosome is extra, there may be associated growth restriction. In trisomy 21, fetal growth restriction is generally mild (Thelander and Pryor, 1966). Whether there is a lag in crown-rump length is controversial (Golbus 1978; Stephens and Shepard, 1980). However, after the first trimester, all long-bone growth lags behind that of normal fetuses (Fitzsimmons and colleagues, 1990). Both shortened femur length and hypoplasia of the middle phalanx occur with increased frequency in trisomy 21. By contrast, fetal growth in trisomy 18 is virtually always significantly affected. In one series, 10 of 11 newborns weighed less than 2500 g (Moerman and associates, 1982). Growth failure has been documented as early as the first trimester. By the second trimester, long-bone measurements typically fall below the third percentile for age, and the upper extremity is even more severely affected (Droste and co-workers, 1990). Visceral organ growth is also abnormal (Droste, 1992). Fetuses with trisomy 13 have some degree of growth restriction but generally not as severely as those with trisomy 18. Trisomy 16 is the most common trisomy in spontaneous miscarriage and is usually lethal in the nonmosaic state (Lindor and associates, 1993). Patches of trisomy 16 (or others) in the placenta — confined placental mosaicism — can cause placental insufficiency that may account for many cases of previously unexplained fetal growth restriction (Kalousek and colleagues, 1993; Towner and colleagues, 2001). It is emphasized that in these pregnancies, the chromosomal abnormality is confined to the placenta. Significant fetal growth restriction is not seen with Turner syndrome (45,X) or Klinefelter syndrome (47,XXY) (Droste, 1992).

Disorders of Cartilage and Bone. Numerous inherited syndromes such as osteogenesis imperfecta and various chondrodystrophies are associated with fetal growth restriction.

Teratogens. Any teratogen is capable of adversely affecting fetal growth. Examples include anticonvulsants and antineoplastic agents. In addition, cigarette smoking, opiates and related drugs, alcohol, and cocaine may cause growth restriction, either primarily or by decreasing maternal food intake.

Vascular Disease. Especially when complicated by superimposed preeclampsia, chronic vascular disease commonly causes growth restriction. Preeclampsia may cause fetal growth failure and is an indicator of its severity, especially when the onset is before 37 weeks (Gainer, 2005; Odegard, 2000; Xiong, 1999, and all their colleagues).

Renal Disease. Chronic renal insufficiency is often associated with underlying hypertension and vascular disease. Chronic nephropathies are commonly accompanied by restricted fetal growth (Cunningham and colleagues, 1990; Stettler and Cunningham, 1992).

Chronic Hypoxia. When exposed to a chronically hypoxic environment, some fetuses have significantly reduced birthweight. As discussed earlier, fetuses of women who reside at high altitude usually weigh less than those born to women who live at a lower altitude (Krampl, 2002; Lichty and colleagues, 1957). Severe hypoxia from maternal cyanotic heart disease frequently is associated with severely growth-restricted fetuses (Patton and co-workers, 1990). Anemia. In most cases, maternal anemia does not cause fetal growth restriction. Exceptions include sickle cell disease and some other inherited anemias. Conversely, curtailed maternal blood volume expansion has been linked to fetal growth restriction (Duvekot and colleagues, 1995).

Placental and Cord Abnormalities. A number of placental abnormalities may cause fetal growth restriction. They include chronic placental abruption, extensive infarction, chorioangioma, marginal or velamentous cord insertion, circumvallate placenta, or placenta previa. Growth failure in these cases is often presumed to be due to uteroplacental insufficiency. Some women with otherwise unexplained fetal growth restriction and a grossly normal placenta have reduced uteroplacental blood flow when compared with normally grown fetuses (Kotini and colleagues, 2003; Lunell and Nylund, 1992; Papageorghiou and colleagues, 2001). Similar reductions have also been reported in growth-restricted fetuses with congenital malformations. These results suggest that maternal blood flow may in part be regulated by the fetus (Howard, 1987; Rankin and McLaughlin, 1979). Interestingly, there is no evidence that macrosomic infants have increased uteroplacental blood flow.

Multiple Fetuses. Pregnancy with two or more fetuses is more likely to be complicated by diminished growth of one or more fetuses when compared with normal singletons.

Antiphospholipid Antibody Syndrome. Two classes of antiphospholipid antibodies — anticardiolipin antibodies and lupus anticoagulant — have been associated with fetal growth restriction (Lockwood and Rand, 1994). Pregnancy outcome in women with these antibodies is often poor and may involve early-onset preeclampsia and fetal demise (Levine and associates, 2002; Lockwood, 2002). Specifically, these antibodies may be found in women with repetitive second-trimester fetal loss or early-onset fetal growth restriction, especially when accompanied by early and severe hypertensive disease. Not all researchers have reported these adverse outcomes. Infante-Rivard and colleagues (2002) did not find an association between maternal or newborn thrombophilia polymorphisms and risk of fetal growth restriction. Pathophysiological mechanisms in the fetus appear to be caused by maternal platelet aggregation and placental thrombosis.

Extrauterine Pregnancy. If the placenta is implanted outside the uterus, the fetus is usually growth restricted. Also, some uterine malformations have been linked to impaired fetal growth.

IDENTIFICATION OF FETAL GROWTH RESTRICTION. Early establishment of gestational age, attention to maternal weight gain, and careful measurement of uterine fundal growth throughout pregnancy identify many cases of abnormal fetal growth in low-risk women. Risk factors, including a previously growth-restricted fetus, increases the possibility of recurrence. In women with significant risk factors, consideration should be given to serial sonography. Although frequency of examinations varies depending on clinical circumstances, an initial dating examination, ideally in the first trimester followed by a second examination at 32 to 34 weeks, or when clinically indicated, should serve to identify many cases of growth restriction. Even so, definitive diagnosis frequently cannot be made until delivery. Identification of the inappropriately growing fetus remains a challenge. However, there are both simple clinical techniques and more complex technologies that may prove useful in helping to exclude and diagnose fetal growth restriction.

Uterine Fundal Height. Carefully performed serial fundal height measurements are a simple, safe, inexpensive, and reasonably accurate screening method to detect SGA fetuses (Gardosi and Francis, 1999). As a screening tool, its principal drawback is imprecision. For example, Jensen and Larsen (1991) and Walraven and colleagues (1995) found that this method helped correctly identify only 40 percent of such infants. Thus, SGA fetuses were both overlooked and overdiagnosed. Despite this, these results do not diminish the importance of carefully performed fundal measurements as a simple screening method. The method used by most for fundal height measurement was described by Jimenez and colleagues (1983). Briefly, this consists of a tape calibrated in centimeters applied over the abdominal curvature from the upper edge of the symphysis to the upper edge of the uterine fundus, which is identified by palpation or percussion. The tape is applied with the markings away from the examiner to avoid bias. Between 18 and 30 weeks, the uterine fundal height in centimeters coincides with weeks of gestation. If the measurement is more than 2 to 3 cm from the expected height, inappropriate fetal growth may be suspected.

Ultrasonic Measurements. Central to the debate over whether all pregnancies should routinely undergo ultrasonic evaluation is the potential for diagnosis of growth restriction (Ewigman and colleagues, 1993). Typically, such routine screening incorporates an initial ultrasound examination at 16 to 20 weeks to establish gestational age and identify anomalies. This is repeated at 32 to 34 weeks to evaluate fetal growth. Ironically, Gardosi and Geirsson (1998) found that accurate gestational dating at the initial examination resulted in a lower diagnosis rate of fetal growth restriction. The optimal ultrasonic method of estimating fetal size, and therefore growth restriction, was reviewed by Manning (1995). Combining head, abdomen, and femur dimensions should in theory enhance the accuracy of predictions of fetal size. Unfortunately, any potential improvement is apparently lost by the cumulative error inherent in measurement of each individual fetal dimension. As a result, abdominal circumference measurements have been accepted by most experts as the most reliable index of fetal size (Manning, 1995; Smith and colleagues, 1997; Snijders and Nicolaides, 1994). In these studies, the estimated fetal weight calculated with abdominal circumference measurements was almost always within 10 percent of the actual birthweight. Abdominal circumference measured directly in the newborn was also shown to be an important anatomical marker of growth restriction (Deter and colleagues, 1995). The elegant observations on the metabolic effects of fetal growth restriction, performed at Kings College Hospital and described earlier, were determined in fetuses whose ultrasonically determined abdominal circumference was less than the fifth percentile (Snijders and Nicolaides, 1994). Ssuch small circumferences are linked to decreased Po2 and pH. These observations emphasize that ultrasonic measurements of the abdominal circumference can meaningfully signify pathological growth restriction. Unfortunately, the use of ultrasound for detection of fetal growth restriction does not preclude missed diagnoses. Dashe and colleagues (2000) studied 8400 live births at Parkland Hospital in which fetal ultrasound had been performed within 4 weeks of delivery. They reported that 30 percent of growth-restricted fetuses were not detected. In a study of 1000 high-risk fetuses, Larsen and colleagues (1992) performed serial ultrasound beginning at 28 weeks and every 3 weeks thereafter. They found that reporting the results to the clinicians significantly increased the diagnosis of SGA fetuses. Although elective deliveries in this group were also increased, there was no overall improvement in neonatal outcome. An association between pathological fetal growth restriction and oligohydramnios has long been recognized The smaller the pocket of amnionic fluid, the greater the perinatal mortality. One likely explanation for oligohydramnios is diminished fetal urine production caused by hypoxia and diminished renal blood flow (Nicolaides and associates, 1990).

Doppler Velocimetry. Abnormal umbilical artery Doppler velocimetry — characterized by absent or reversed end-diastolic flow — has been uniquely associated with fetal growth restriction. The use of Doppler velocimetry in the management of fetal growth restriction has been recommended as a possible adjunct to techniques such as nonstress testing or a biophysical profile (American College of Obstetricians and Gynecologists, 2000b).

MANAGEMENT. Once fetal growth restriction is suspected, efforts should be made to confirm the diagnosis, assess fetal condition, and evaluate for anomalies. Although cordocentesis allows rapid karyotyping for detection of a lethal aneuploidy and thus may simplify management, the American College of Obstetricians and Gynecologists (2000b) has concluded that there are not enough data to warrant cord blood sampling in this situation. The timing of delivery is crucial, and the risks of fetal death versus the hazards of preterm delivery must be assessed as reported in the Growth Restriction Intervention Trial (GRIT) by Thornton and colleagues, 2004.

Growth Restriction Near Term. Prompt delivery is likely best for the fetus at or near term who is considered growth restricted. In fact, most clinicians recommend delivery at 34 weeks or beyond if there is clinically significant oligohydramnios. With a reassuring fetal heart rate pattern, vaginal delivery may be attempted. Some of these fetuses do not tolerate labor, and cesarean delivery is necessary. Uncertainty about the diagnosis should preclude intervention until fetal lung maturity is assured.

Growth Restriction Remote from Term. When growth restriction is diagnosed in an anatomically normal fetus prior to 34 weeks, and amnionic fluid volume and fetal surveillance are normal, observation is recommended. Screening for toxoplasmosis, rubella, cytomegalovirus, herpes, and other infections is recommended by some clinicians, however, we have not found this to be productive. As long as fetal growth continues and fetal evaluation remains normal, pregnancy is allowed to continue until fetal maturity. In some cases, amniocentesis may be helpful to assess pulmonary maturity. Although the onset of oligohydramnios is highly suggestive of fetal growth failure, importantly, normal amnionic fluid volume does not preclude growth restriction. Owen and colleagues (2001) reported that 4- and 6-week evaluation intervals were superior to 2-week intervals for predicting growth restriction. Depending on the gestational age of the fetus when fetal growth restriction is first suspected, this interval may be impractical clinically, and sonography is typically repeated more frequently. With growth restriction remote from term, no specific treatment ameliorates the condition. There is no evidence that bed rest results in accelerated growth or improved outcome. Despite this, many clinicians advise a program of modified rest. Nutrient supplementation, attempts at plasma volume expansion, oxygen therapy, antihypertensive drugs, heparin, and aspirin have all been shown to be ineffective (American College of Obstetricians and Gynecologists, 2000b). In most cases of growth restriction diagnosed prior to term, neither a precise etiology nor a specific therapy is apparent. Management decisions hinge on an assessment of the relative risks of fetal death with expectant management versus the risks from preterm delivery. Although reassuring fetal testing may allow observation with continued maturation of the preterm growth-restricted fetus, there is concern regarding long-term neurological outcome (Blair and Stanley, 1992; Thornton and colleagues, 2004). Some authorities challenge that various tests of fetal well-being are unnecessary to reduce risks for stillbirth. Weiner and colleagues (1996) performed nonstress tests, biophysical profiles, and umbilical artery velocimetry within 3 days of delivery in 135 fetuses confirmed at birth to have growth restriction. Other than metabolic acidosis at delivery, which was predicted by absent or reversed end-diastolic umbilical blood flow, morbidity and mortality were determined primarily by gestational age and birthweight and not by abnormal fetal testing. Importantly, there is no convincing evidence that such testing schemes reduce the risk of long-term neurological deficits (American College of Obstetricians and Gynecologists, 2000a). A review of the status of Doppler velicometry to aid in delivery timing was provided by Baschat (2004). The optimal management of the preterm growth-restricted fetus remains problematic.

LABOR AND DELIVERY. Fetal growth restriction is commonly the result of placental insufficiency due to faulty maternal perfusion, ablation of functional placenta, or both. If present, these conditions are likely aggravated by labor. The incidence of cesarean delivery is increased. The infant may need expert assistance in making a successful transition at birth. The risk of being born hypoxic and of having aspirated meconium is increased. Care for the newborn should be provided immediately by someone who can skillfully clear the airway below the vocal cords and ventilate the infant as needed. The severely growth-restricted newborn is particularly susceptible to hypothermia and may also develop other metabolic derangements such as hypoglycemia, polycythemia, and hyperviscosity. In addition, low-birthweight infants are at increased risk for motor and other neurological disabilities. Risk is highest at the lowest extremes of birthweight (Nelson and Grether, 1997).

LONG-TERM SEQUELAE. In his book Fetal and Infant Origins of Adult Disease, Barker (1992) hypothesizes that adult mortality and morbidity are related to fetal and infant health. In the context of fetal growth restriction, there are numerous reports of a relationship between suboptimal fetal nutrition and an increased risk of subsequent adult hypertension and atherosclerosis. However, recent reports challenge this hypothesis (Hubinette and colleagues, 2001; Huxley and coworkers, 2002). In another study, Smith and colleagues (2001) found that pregnancy complications resulting in lowbirthweight infants were associated with increased risk of subsequent ischemic heart disease in the mother. This suggests that common genetic risk factors might explain the link between low birthweight and risk of heart disease in both the developing fetus and the mother.

MACROSOMIA The term macrosomia is used rather imprecisely to describe a very large fetus or neonate. Although there is general agreement among obstetricians that newborns weighing less than 4000 g are not excessively large, a similar consensus has not been reached for the definition of macrosomia. Indeed, the term macrosomia does not appear in the New Shorter Oxford English Dictionary (1993), although Stedman's Medical Dictionary (1995) offers the definition of "abnormally large size of the body." The key word is "abnormal." What is the threshold for the upper limit of normal human fetal growth above which birthweight is abnormal? Which criteria should be used to define "abnormal"? Specifically, should the threshold for abnormally high birthweight be simply mathematically derived or should it include features of adverse pregnancy outcome? Given that the major hazard of excessive fetal growth is birth injury due to shoulder dystocia, should the definition include the risk of brachial plexus injury? This approach would not entirely suffice to diagnose excessive growth because shoulder dystocia would not be expected in an overgrown but preterm and thus physically small infant. Newborn weight rarely exceeds 11 pounds (5000 g), and excessively large infants are a curiosity. The birth of a 16-pound (7300 g) infant in the United States in 1979 was widely publicized. Two of the largest newborn weights ever recorded were those of a nearly 24-pound (10,800 g) infant described by Beach in 1879 (Barnes, 1957), and a 25-pound stillborn. Among over 216,000 singleton infants who were delivered at Parkland Hospital between 1988 and 2002, only two weighed 6000 g or more for an incidence of less than 1 in 100,000 births. One infant weighed 6025 g (13 lb 4 oz) and the other 6500 g (14 lb 5 oz). The incidence of excessively large infants has increased during the 20th century. For example, according to Williams (1903), the incidence of birthweight over 5000 g was 1 to 2 per 10,000 births at the beginning of the 20th century. This compares with 15 per 10,000 at Parkland Hospital from 1988 through 2002. The latter mothers had a mean BMI of 37.8 kg/cm2,and 20 percent were diabetic.

DEFINITION. Precise definitions of macrosomia on which all authorities agree do not exist. However, there are several definitions in general clinical use. In one scheme, macrosomia is viewed as those weights that exceed certain percentiles for populations. Another common scheme includes use of empirical birthweights.

Birthweight Distribution. Commonly, macrosomia is defined based on mathematical distributions of birthweight. Those infants exceeding the 90th percentile for a given gestational week are usually used as the threshold for macrosomia. For example, the 90th percentile at 39 weeks is 4000 g. If, however, birthweights two standard deviations above the mean are used, the threshold would be between the 97th and 99th percentile — substantially larger infants when compared with the 90th percentile. Specifically, the birthweight threshold at 39 weeks would be approximately 4500 g for the 97th percentile rather than 4000 g for the 90th percentile.

Empirical Birthweight. Absolute birthweight exceeding a specific threshold is another commonly used definition of macrosomia. Newborn weight exceeding 4000 g, or 8 lb 13 oz, is a frequently used threshold. Others use 4250 g or even 4500 g which is almost 10 lb. Birthweights of 4500 g or more are rare. Over a 12-year period at Parkland Hospital, during which time there were over 216,000 singleton births, only 1.25 percent of newborns weighed 4500 g or more. We are of the view that the upper limit of fetal growth, above which growth can be deemed abnormal, is likely two standard deviations above the mean, representing perhaps 3 percent of births. At 40 weeks such a threshold would correspond to approximately 4500 g. This definition of excessive growth is clearly more restrictive than using the upper 10 percent to define macrosomia. The American College of Obstetricians and Gynecologists (2000b) concluded that the term "macrosomia" was an appropriate designation for fetuses who, at birth, weigh 4500 g or more.

RISK FACTORS. Maternal diabetes is an important risk factor for development of fetal macrosomia The incidence of maternal diabetes increases as birthweight above 4000 g increases. However, it should be emphasized that maternal diabetes is associated with only a small percentage of such large infants. In macrosomic fetuses of diabetic women, there is a greater shoulder circumference and a greater shoulder circumference-to-head circumference ratio. Consequent to this is a greater risk of shoulder dystocia compared with that of similar weight fetuses of nondiabetic women (Modenlau and colleagues, 1982; Neiger, 1992; Sachs, 1993). Among macrosomic fetuses of similar weight, the presence of a relatively greater proportion of body fat is associated independently with an increased risk of labor dystocia and cesarean delivery (Bernstein and Catalano, 1994). Although known risk factors for macrosomia were identified by Boyd and associates (1983) in only 40 percent of women who deliver macrosomic infants, several factors favor the likelihood of a large fetus:

1. Large size of parents, especially the mother who is obese. The risk of fetal macrosomia is 30 percent if maternal weight is more than 300 pounds.

2. Multiparity.

3. Prolonged gestation.

4. Increased maternal age.

5. Male fetus.

6. Previous infant weighing more than 4000 g.

7. Race and ethnicity. These factors are additive. Among women who are simultaneously diabetic, obese, and postterm, the incidence of fetal macrosomia ranges from 5 to 15 percent (Arias, 1987; Chervenak, 1992).

DIAGNOSIS. Because there are no current methods to estimate excessive fetal size accurately, the diagnosis of macrosomia cannot be definitely made until delivery. Inaccuracy in clinical estimates of fetal weight by physical examination is often attributable, at least in part, to maternal obesity. Numerous attempts have been made to improve the accuracy of fetal weight estimations obtained by ultrasonography. A number of formulas have been proposed to estimate fetal weight using ultrasonic measurements of the head, femur, and abdomen. The estimates provided by these computations, although reasonably accurate for predicting the weight of small, preterm fetuses, are less valid in predicting the weight of very large fetuses. For example an infant predicted to weigh 4000 g can actually weigh considerably more or less than predicted. Rouse and co-authors (1996) reviewed 13 studies completed between 1985 and 1995 to assess ultrasonic prediction of macrosomic fetuses. They found only fair sensitivity (60 percent) in the accurate diagnosis of macrosomia but higher specificity (90 percent) in excluding excessive fetal size. A formula has not been derived that gives estimates of fetal macrosomia with sufficiently accurate predictive value to be useful in constructing clinical management decisions (American College of Obstetricians and Gynecologists, 2000a). Not surprisingly, Adashek and colleagues (1996) found that women who underwent ultrasonic evaluation in the last 4 weeks of pregnancy were at significantly increased risk for cesarean delivery if the estimated fetal size exceeded 4000 g. We can only conclude that the estimation of fetal weight from ultrasonic measurements is not reliable. Certainly its routine use to identify macrosomia cannot be recommended. Indeed, the findings of several studies are indicative that clinical estimates of fetal weight are as reliable as, or even superior to, those made from ultrasonic measurements (Sherman and colleagues, 1998).

CONTROVERSIES

"Prophylactic" Labor Induction. Some clinicians have proposed labor induction when fetal macrosomia is diagnosed in nondiabetic women. This obviates further fetal growth and thereby reduces potential delivery complications. Such prophylactic induction should theoretically reduce the risk of shoulder dystocia as well as that of cesarean delivery by preempting further fetal growth. Gonen and colleagues (1997) randomized 273 nondiabetic women with ultrasonic fetal weight estimates of 4000 to 4500 g to either induction or expectant management. Labor induction did not decrease the rate of cesarean delivery or shoulder dystocia. Similar results were reported by Leaphart and colleagues (1997) with the added finding that induction unnecessarily increased the rate of cesarean delivery. We agree with the American College of Obstetricians and Gynecologists (2000b) that current evidence does not support a policy for early induction for suspected macrosomia.

Elective Cesarean Delivery. Rouse and colleagues (1996, 1999) analyzed the potential effects of a policy of elective cesarean delivery for ultrasonically diagnosed fetal macrosomia compared with standard obstetrical management. They concluded that for women who are not diabetic, a policy of elective cesarean delivery was medically and economically unsound. Conversely, in diabetic women with macrosomic fetuses, such a policy of elective cesarean delivery was tenable. Conway and Langer (1998) described a protocol of routine cesarean delivery for ultrasonic estimates of 4250 g or greater in diabetic women that significantly reduced the rate of shoulder dystocia from 2.4 to 1.1 percent.

Prevention of Shoulder Dystocia. A major concern in the delivery of macrosomic infants is shoulder dystocia and attendant risks of permanent brachial plexus palsy. Such dystocia occurs when the maternal pelvis is of sufficient size to permit delivery of the fetal head but not large enough to allow delivery of the larger-diameter fetal shoulders. In this circumstance, the anterior shoulder becomes impacted against the maternal symphysis pubis. Even with expert obstetrical assistance at delivery, stretching and injury of the brachial plexus of the affected shoulder may be inevitable. According to the American College of Obstetricians and Gynecologists (1997), fewer than 10 percent of all shoulder dystocia cases result in a persistent brachial plexus injury. Planned cesarean delivery on the basis of suspected macrosomia is an unreasonable strategy in the general population. Ecker and colleagues (1997) analyzed 80 cases of brachial plexus injury in 77,616 consecutive infants born at Brigham and Women's Hospital. They concluded that an excessive number of otherwise unnecessary cesarean deliveries would be needed to prevent a single brachial plexus injury in infants born to women without diabetes. Conversely, planned cesarean delivery may be a reasonable strategy for diabetic women with an estimated fetal weight exceeding 4250 to 4500 g.