FEMALE PELVIS. FETUS AS OBJECT OF DELIVER. PHYSIOLOGY OF PREGNANCY. THE PERINATAL CARE OF THE FETUS. METHODS OF PREGNANT INSPECTION.. OBSTETRIC TERMINOLOGY.
Prepared by N. Bahnij
The Placenta and Fetal Membranes
The development of the human placenta is as uniquely intriguing as the embryology of the fetus. The placenta is a fascinating organ, especially when its function is considered. During its brief intrauterine existence, the fetus is dependent upon the placenta as its lung, liver, and kidneys. The organ serves these purposes until sufficient maturation of the fetus allows it to survive ex utero as an air-breathing organism.
Despite its unassailable role in human fetal development, study of the placenta has lagged behind that of the fetus. A number of anatomists and embryologists worked through the 1980s to provide some basic knowledge. It has not been until recently that clinicians have appreciated the plethora of knowledge that can be gained by microscopic study of the placenta. This latter enlightenment has transposed through the efforts of placental pathologists such as Benirschke, Driscoll, Fox, and Naeye. Their work, as well as that of many of their colleagues, has shown that careful examination of the placenta may frequently shed light on the etiopatho-genesis of a number of maternal-fetal disorders (Benirschke, 2000; Benirschke and Kauffman, 2000). Abnormal placentation, placental pathology, and their effects on pregnancy outcome, as well as adverse placental effects from maternal diseases, are considered in Chapters 31 and 32.
Boyd and Hamilton (1970) presented a marvelous account of the history of placental research. A summary of this history was presented in Chapter 5 (p. 95) of the 20th edition of Williams Obstetrics. The interested reader is referred to this summary or to the treatise of Boyd and Hamilton (1970).
FETAL TISSUES OF THE FETAL-MATERNAL COMMUNICATION SYSTEM
The two arms of the fetal-maternal communication system of human pregnancy were described in Chapters 2 and 4 (see Fig. 5-2). The extravillous and villous trophoblasts are the embryonic-fetal tissues of the anatomical interface of the placental arm; the avascular fetal membranes—the amnion and chorion laeve—are the fetal tissues of the anatomical interface of the paracrine arm of this system.
The placental arm of this system links the mother and fetus as follows: maternal blood (spurting out of the uteroplacental vessels) directly bathes the syncytiotrophoblast, the outer surface of the trophoblastic villi; fetal blood is contained within fetal capillaries, which traverse within the intravillous spaces of the villi. This is a hemochorioendothelial type of placenta. The paracrine arm of this system links the mother and fetus through the anatomical and biochemical juxtaposition of (extraembryonic) chorion laeve and (maternal uterine) decidua parietalis tissue.
Therefore, at all sites of direct cell-to-cell contact, maternal tissues (decidua and blood) are juxtaposed to extraembryonic cells (trophoblasts) and not to embryonic cells or fetal blood. This is an extraordinarily important arrangement for communication between fetus and mother and for maternal (immunological) acceptance of the conceptus.
The role of the placenta in nidation and in the transfer of nutrients from mother to embryo-fetus has longed fueled interest in this unique organ. Subsequently, the enormous diversity of form and function of the placenta was recognized as the incredible metabolic, endocrine, and immunological properties of its trophoblasts were discovered.
EARLY HUMAN DEVELOPMENT
The definitions that follow are taken from Moore (1973, 1988).
• Zygote: The cell that results from the fertilization of the ovum by a spermatozoan.
• Blastomeres: Mitotic division of the zygote (cleavage) yields daughter cells called blastomeres.
• Morula: The solid ball of cells formed by 16 or so blastomeres.
• Blastocyst: After the morula reaches the uterus, a fluid-filled cavity is formed, converting the morula to a blastocyst.
• Embryo: The embryo-forming cells, grouped together as an inner cell mass, give rise to the embryo, which usually is so designated when the bilaminar embryonic disc forms. The embryonic period extends until the end of the seventh week, at which time the major structures are present.
• Fetus: After the embryonic period, the developing conceptus is referred to as the fetus.
• Conceptus: This term is used to refer to all tissue products of conception—embryo (fetus), fetal membranes, and placenta. The conceptus includes all tissues, both embryonic and extraembryonic, that develop from the zygote.
FERTILIZATION OF THE OVUM AND CLEAVAGE OF THE ZYGOTE
Few, if any, naturally occurring phenomena are of greater importance to humankind than the union of egg and sperm. Fertilization occurs in the fallopian tube; and it is generally agreed that fertilization of the ovum must occur within minutes or no more than a few hours after ovulation. Consequently, spermatozoa must be present in the fallopian tube at the time of ovulation. Most all pregnancies occur when intercourse occurs during the 2 days preceding or on the day of ovulation. If intercourse takes place on the day after ovulation, pregnancy probably will not result.
Spermatozoa around ovum
After fertilization in the fallopian tube, the mature ovum becomes a zygote—a diploid cell with 46 chromosomes—that then undergoes segmentation, or cleavage, into blastomeres. The first typical mitotic division of the segmentation nucleus of the zygote results in the formation of two blastomeres (Fig. 5-1). The zygote undergoes slow cleavage for 3 days while still within the fallopian tube; fertilized human ova that are recovered from the uterine cavity may be composed of only 12 to 16 blastomeres. As the blastomeres continue to divide, a solid mulberry-like ball of cells, referred to as the morula, is produced. The morula enters the uterine cavity about 3 days after fertilization. The gradual accumulation of fluid between blastomeres within the morula results in the formation of the blastocyst (Fig. 5-2). The compact mass of cells at one pole of the blastocyst, called the inner cell mass, is destined to be the embryo. The outer mass of cells is destined to be the trophoblasts.
THE EARLY HUMAN ZYGOTE. Hertig and co-workers (1954) found in the two-cell zygote that the blastomeres and the polar body are free in the perivitelline fluid and are surrounded by a thick zona pellucida (Fig. 5-1A). In a 58-cell blastocyst, the outer cells which are progenitors of the trophoblasts can be distinguished from the inner cells that form the embryo (Fig. 5-2B). The 107-cell blastocyst was found to be no larger than the earlier cleavage stages, despite the accumulated fluid (Fig. 5-1C). It measured 0.153 by 0.155 mm in diameter before fixation and after the disappearance of the zona pellucida. The eight formative or embryo-producing cells were surrounded by 99 trophoblastic cells.
Just before implantation, the zona pellucida disappears and the blastocyst touches the endometrial surface; at this time of apposition, the blastocyst is composed of 107 to 256 cells. The blastocyst adheres to the endometrial epithelium, and implantation occurs most commonly on the endometrium of the upper part and on the posterior wall of the uterus. After gentle erosion between epithelial cells of the surface endometrium, the invading trophoblasts burrow deeper into the endometrium, and the blastocyst becomes totally encased within the endometrium, being covered over by the endometrium.
BIOLOGY OF THE TROPHOBLAST
Of all placental components, the trophoblast is the most variable in structure, function, and development. Its invasiveness provides for attachment of the blastocyst to the decidua of the uterine cavity; its role in nutrition of the conceptus is reflected in its name; and its function as an endocrine organ in human pregnancy is essential to maternal physiological adaptations and to the maintenance of pregnancy.
DIFFERENTIATION. Morphologically, trophoblasts are either cellular or syncytial, and may appear as uni-nuclear cells or multinuclear giant cells. At implantation, some of the innermost cytotrophoblasts or Langhans cells that are contiguous with and invading the endometrium, coalesce to become an amorphous, multinucleated, continuous membrane that is uninterrupted by intercellular spaces, the syncytium. There are no individual cells, only a continuous lining; therefore it is the singular "syncytiotrophoblast" or syncytium. The true syncytial nature of the human syncytiotrophoblast has been confirmed by electron microscopy. The mechanism of syncytial growth, however, was a mystery in view of the discrepancy between an increase in the number of nuclei in the syncytiotrophoblast and equivocal evidence (at best) of intrinsic nuclear replication. Mitotic figures are completely absent from the syncytium, being confined to the cytotrophoblasts.
FORMATION OF THE SYNCYTIUM. Ulloa-Aguirre and co-workers (1987) elegantly demonstrated the conversion of cytotrophoblasts to a morphologically and functionally characteristic syncytium in vitro. They established that at least part of this differentiation process involves the action of cyclic adenosine monophosphate (cAMP). Based on their methods of isolation and characterization of human cytotrophoblasts, others developed systems to evaluate blastocyst implantation in vitro (Kliman and associates, 1986; Ringler and Strauss, 1990). Isolated cytotrophoblasts, placed in serum-containing medium, migrate toward one another and form aggregates. Ultimately, the aggregates fuse and syncytium is produced during 3 to 4 days. The syncytium also is formed in the absence of serum, provided that extracellular matrix components are present to serve as a lattice for cytotrophoblast migration. The syncytium produced in vitro is covered by microvilli, as it is in vivo. Cytotrophoblast aggregation is dependent upon protein synthesis, and involves a calcium-dependent cell adhesion molecule, E-cadherin, for aggregation. Desmosomes develop between the cells; and as the cytotrophoblasts fuse, the expression of E-cadherin diminishes.
The cytotrophoblast is the germinal cell; the syncytium, or the secretory component, is derived from cytotrophoblasts. Therefore, the cytotrophoblasts are the cellular progenitors of the syncytiotrophoblast. Well-demarcated borders and a single, distinct nucleus characterize each cytotrophoblast; and there are frequent mitoses among the cytotrophoblasts. These characteristics are lacking, however, in the syncytium, in which the cytoplasm is amorphous, without cell borders, and the nuclei are multiple and diverse in size and shape. The absence of cell borders in the syncytium obliges transport across this structure. Hence, the control of transport is not dependent on the participation of individual cells.
Coutifaris and Coukos (1994) presented a succinct and informative review of the processes of human implantation. They point out that after apposition and adherence of the trophectoderm of the blastocyst to the endometrial epithelial cells, implantation commences by intrusion of cytotrophoblasts between endometrial epithelial cells. This process of trophoblast invasion is facilitated by degradation of the extracellular matrix of the endometrium/decidua, catalyzed by urokinase-type plasminogen activator, urokinase plasminogen activator receptor, and metalloproteinases that are produced by selected cytotrophoblasts at various stages of implantation/placentation. These functions of cytotrophoblasts invading the endometrium are indistinguishable from those of metastasizing malignant cells. As the cytotrophoblasts move through the decidua, selected populations of these cells bind to various extracellular matrix components of the decidual stromal cells. This facilitates migration and thence the establishment of placental anchors to the decidua.
IMMUNOLOGICAL ACCEPTANCE OF THE CONCEPTUS
Over the last half century, many attempts to explain the survival of the semiallogenic fetal graft have been proposed. One of the earliest explanations was based on the theory of antigenic immaturity of the embryo-fetus. This was disproved by Billingham (1964) who showed that transplantation (HLA) antigens are demonstrable very early in embryonic life. The trophoblasts are the only cells of the conceptus in direct contact with maternal tissues or blood and these tissues are genetically identical with fetal tissues. Another explanation was based on diminished immunological responsiveness of the pregnant woman. There is, however, no evidence for this to be other than an ancillary factor. In a third explanation, the uterus (decidua) is proposed as an immunologically privileged tissue site. Clearly, transplantation immunity can be evoked and expressed in the uterus as in other tissues. Therefore, the acceptance and the survival of the conceptus in the maternal uterus must be attributed to an immunological peculiarity of the trophoblasts, not the decidua.
CURRENT STATUS OF RESEARCH
It still is enigmatic that maternal tissues accept and tolerate the grafted conceptus. Moreover, the placenta likely expresses "novel" genes (Dizon-Townson and colleagues, 2000). Several novel aspects of the expression of the HLA system in trophoblasts, together with a unique set of lymphocytes, may provide an explanation for this.
IMPLANTATION AND INTEGRIN SWITCHING.
The attachment of the trophectoderm of the blastocyst to the endometrial surface by apposition and adherence and then the intrusion and invasion of the endometrium/decidua by cytotrophoblasts (implantation) appears to be dependent upon two factors:
1. Trophoblast elaboration of specific proteinases that degrade selected extracellular matrix proteins of the endometrium/decidua.
2. A coordinated and alternating process referred to as integrin switching, which facilitates migration and then attachment of trophoblasts in the decidua.
The integrins, one of four families of cell adhesion molecules (CAMs), are cell-surface receptors that mediate the adhesion of cells to extracellular matrix proteins (Frenette and Wagner, 1996). Great diversity of cell binding to a host of different extracellular matrix proteins is possible by way of the integrin system.
Recall that the decidual cell becomes completely encased by a pericellular (extracellular matrix) membrane. This "wall" around the decidual cell provides the scaffolding for the attachment of the extravillous trophoblasts, the anchoring cytotrophoblasts. These cells first elaborate selected proteinases that degrade the extracellular matrix of decidua. Thereafter, the expression of a specific group of integrins enables the docking of these cells. By alternating between these two processes and by "integrin switching," the movement of cytotrophoblasts into the decidua is aggressive, but regulated. Specific decidual localization of the cytotrophoblasts to establish attachment of the placenta to the wall of the uterine cavity results. Craven and colleagues (2000) have provided evidence that a similar process is operative for trophoblastic invasion of uterine veins.
ORGANIZATION OF PLACENTA
From the electron microscopic studies of Wislocki and Dempsey (1955), data were provided that permitted a functional interpretation of the fine structure of the placenta. There are prominent microvilli on the syncytial surface, corresponding to the "brush border" described by light microscopy Associated pinocytotic vacuoles and vesicles are related to the absorptive and secretory placental functions. The inner layer of the villi—the cytotrophoblasts—persists to term, although often compressed against the trophoblastic basal lamina, and retains its ultrastructural simplicity
Villi can first be distinguished easily in the human placenta on about the 12th day after fertilization. When a mesenchymal cord, presumably derived from cytotrophoblasts, invades the solid trophoblast column secondary villi are formed. After angiogenesis occurs from the mesenchymal cores in situ, the resulting villi are termed tertiary. Maternal venous sinuses are tapped early in the implantation process, but until the 14th or 15th day after fertilization, maternal arterial blood does not enter the intervillous space. By about the 17th day, fetal blood vessels are functional, and a placental circulation is established. The fetal-placental circulation is completed when the blood vessels of the embryo are connected with the chorionic blood vessels. Some villi, in which failure of angiogenesis results in a lack of circulation, become distended with fluid and form vesicles. A striking exaggeration of this process is characteristic of the development of hydatidiform mole
Proliferation of cellular cytotrophoblasts at the tips of the villi produces the trophoblastic cell columns, which are not invaded by fetal mesenchyme but are anchored to the decidua at the basal plate. Thus, the floor of the intervillous space (maternal-facing side) consists of cytotrophoblasts from the cell columns, the peripheral syncytium of the trophoblastic shell, and decidua of the basal plate. The floor of the chorionic plate, consisting of the two layers of trophoblasts externally and fibrous mesoderm internally, forms the roof of the intervillous space.
In early pregnancy, the villi are distributed over the entire periphery of the chorionic membrane. A blastocyst dislodged from the endometrium at this stage of development appears shaggy (Fig. 5-9). The villi in contact with the decidua basalis proliferate to form the leafy chorion, or chorion frondosum, the fetal component of the placenta; the villi in contact with the decidua capsularis cease to grow and degenerate to form the chorion laeve. The chorion laeve is generally more nearly translucent than the amnion even though rarely exceeding 1 mm in thickness. The chorion laeve contains ghost villi, and decidua clings to its surface.
Until near the end of the third month, the chorion laeve is separated from the amnion by the exocoelomic cavity. Thereafter, the amnion and chorion are in intimate contact. In the human, the chorion laeve and amnion form an avascular amniochorion, but these two structures are important sites of molecular transfer and metabolic activity. They constitute the paracrine arm of the fetal-maternal communication system.
Certain villi of the chor-ion frondosum extend from the chorionic plate to the decidua and serve as anchoring villi. Most villi, however, arboresce and end freely in the intervillous space without reaching the decidua (Fig. 5-10). As the placenta matures, the short, thick, early stem villi branch repeatedly, forming progressively finer subdivisions and greater numbers of increasingly small villi (Fig. 5-11). Each of the main stem (truncal) villi and their ramifications (rami) constitute a placental cotyledon (lobe). Each cotyledon is supplied with a branch (truncal) of the chorionic artery; and for each cotyledon, there is a vein, constituting a 1:1:1 ratio of artery to vein to cotyledon.
BREAKS IN THE PLACENTAL "BARRIER"
The placenta does not maintain absolute integrity of the fetal and maternal circulations. This is evidenced by numerous findings of the passage of cells between mother and fetus in both directions. This situation is best exemplified clinically by erythrocyte D-antigen isoimmunization and the occurrence of erythroblastosis fetalis (Chap. 39, p. 1061). Typically, a few fetal blood cells are found in maternal blood; but on extremely rare occasions, the fetus exsanguinates into the maternal circulation. Fetal leukocytes may replicate in the mother and leukocytes bearing a Y chromosome have been identified in women for up to 5 years after giving birth to a son (Ciaranfi and colleagues, 1977). Desai and Creger (1963) labeled maternal leukocytes and platelets with atabrine and found that the atabrine-labeled cells crossed the placenta from mother to fetus.
PLACENTAL SIZE AND WEIGHT
Crawford (1959) suggested that the total number of cotyledons remains the same throughout gestation. Individual cotyledons continue to grow, although less actively in the final weeks. Placental weights vary considerably, depending upon how the placenta is prepared. If the fetal membranes and most of the cord are left attached and adherent maternal blood clot is not removed, the weight may be greater by nearly 50 percent (Thomson and co-workers, 1969).
THE PLACENTA AT TERM
According to Boyd and Hamilton (1970), the placenta at term is, on average, 185 mm in diameter and 23 mm in thickness, with an average volume of 497 mL, and weight of 508 g; but these measurements vary widely. There are multiple shapes and forms of the human placenta and a variety of types of umbilical cord insertions, which are discussed in Chapter 32. Viewed from the maternal surface, the number of slightly elevated convex areas called lobes (or if small, lobules) varies from 10 to 38. These lobes are separated, albeit incompletely, by grooves of variable depth, the placental septa. The lobes are also referred to as cotyledons.
Maternal side of placenta
Fetal side of placenta
As the villi continue to branch and the terminal ramifications become more numerous and smaller, the volume and prominence of cytotrophoblasts decrease. As the syncytium thins and forms knots, the vessels become more prominent and lie closer to the surface. The stroma of the villi also exhibits changes associated with aging. In placentas of early pregnancy, the branching connective tissue cells are separated by an abundant loose intercellular matrix. Later, the stroma becomes denser and the cells more spindly and more closely packed.
Another change in the stroma involves the Hofbauer cells, which likely are fetal macrophages. These cells are nearly round with vesicular, often eccentric nuclei and very granular or vacuolated cytoplasm. These cells are characterized histochemically by intracytoplasmic lipid and are readily distinguished from plasma cells.
Certain of the histological changes that accompany placental growth and aging are suggestive of an increase in the efficiency of transport and exchange to meet increasing fetal metabolic requirements. Among these changes are a decrease in thickness of the syncytium, partial reduction of cytotrophoblastic cells, decrease in the stroma, and an increase in the number of capillaries and the approximation of these vessels to the syncytial surface. By 4 months, the apparent continuity of the cytotrophoblasts is broken, and the syncytium forms knots on the more numerous smaller villi. At term, the covering of the villi may be focally reduced to a thin layer of syncytium with minimal connective tissue; and the fetal capillaries seem to abut the trophoblast. The villous stroma, Hofbauer cells, and cytotrophoblasts are markedly reduced, and the villi appear filled with thin-walled capillaries.
Other changes, however, are suggestive of a decrease in the efficiency for placental exchange. These changes include thickening of the basement membranes of the trophoblast capillaries, obliteration of certain fetal vessels, and fibrin deposition on the surface of the villi in the basal and chorionic plates as well as elsewhere in the intervillous space.
The amnion at term is a tough and tenacious but pliable membrane. It is the innermost fetal membrane and is contiguous with the aminonic fluid. This particular avascular structure occupies a role of incredible importance in human pregnancy. In many obstetrical populations, preterm premature rupture of the fetal membranes is the single most common antecedent of preterm delivery. The amnion is the tissue that provides almost all of the tensile strength of the fetal membranes. Therefore, the development of the component(s) of the amnion that protects against rupture or tearing is vitally important to successful pregnancy outcome.
Bourne (1962) described five separate layers of amnion tissue. The inner surface, which is bathed by the amnionic fluid, is an uninterrupted, single layer of cuboidal epithelial cells, believed to be derived from embryonic ectoderm. This epithelium is attached firmly to a distinct basement membrane that is connected to the acellular compact layer, which is composed primarily of interstitial collagens I, III, and V. On the outer side of the compact layer, there is a row of fibroblast-like mesenchymal cells (which are widely dispersed at term). These cells are probably derived from mesoderm of the embryonic disc. There also are a few fetal macrophages in the amnion. The outermost layer of amnion is the relatively acellular zona spongiosa, which is contiguous with the second fetal membrane, the chorion laeve. The important "missing" elements of human amnion are smooth muscle cells, nerves, lymphatics, and importantly, blood vessels.
Early in the process of implantation, a space develops between the embryonic cell mass and adjacent trophoblasts (Fig. 5-5). Small cells that line this inner surface of trophoblasts have been called amniogenic cells, the precursors of the amnionic epithelium. The human amnion is first identifiable about the seventh or eighth day of embryo development. Initially, a minute vesicle (Fig. 5-5), the amnion, develops into a small sac that covers the dorsal surface of the embryo. As the amnion enlarges, it gradually engulfs the growing embryo, which prolapses into its cavity (Benirschke and Kaufman, 2000).
Distension of the amnionic sac eventually brings it into contact with the interior surface of the chorion laeve. Apposition of the mesoblasts of chorion laeve and amnion near the end of the first trimester then causes an obliteration of the extraembryonic coelom. The amnion and chorion laeve, though slightly adherent, are never intimately connected, and usually can be separated easily, even at term.
The amnion is clearly more than a simple avascular membrane that functions to contain amnionic fluid. It is metabolically active, involved in solute and water transport to maintain amnionic fluid homeostasis, and produces a variety of interesting bioactive compounds, including vasoactive peptides, growth factors, and cytokines.
The normally clear fluid that collects within the amnionic cavity increases in quantity as pregnancy progresses until near term, when there is a decrease in amnionic fluid volume in many normal pregnancies. An average volume of about 1000 mL is found at term, although this may vary widely from a few milliliters to many liters in abnormal conditions (oligohydramnios and polyhydramnios or hydramnios).
In early pregnancy, amnionic fluid is an ultrafiltrate of maternal plasma. By the beginning of the second trimester, it consists largely of extracellular fluid which diffuses through the fetal skin, and thus reflects the composition of fetal plasma (Gilbert and Brace, 1993). After 20 weeks, however, the cornification of fetal skin prevents this diffusion and amnionic fluid is composed largely of fetal urine. The fetal kidneys start producing urine at 12 weeks' gestation, and by 18 weeks are producing 7 to 14 mL per day. Fetal urine contains more urea, creatinine, and uric acid than plasma, as well as desquamated fetal cells, vernix, lanugo, and various secretions. Because these are hypotonic, the net effect is decreasing amionic fluid osmolality with advancing gestation. Pulmonary fluid contributes a small proportion of the amnionic volume, and fluid filtering through the placenta accounts for the rest.
The volume of amnionic fluid at each week of gestation is quite variable. In general, the volume increases by 10 mL per week at 8 weeks and increases up to 60 mL per week at 21 weeks, then declines gradually back to a steady state by 33 weeks (Brace and Wolf, 1989). The usual amnionic fluid volume thus increases from 50 mL at 12 weeks to 400 mL at midpregnancy and 1000 mL at term (Gillibrand, 1969).
Amnionic fluid serves to cushion the fetus, allowing musculoskeletal development and protecting it from trauma. It also maintains temperature and has a minimal nutritive function. Epidermal growth factor (EGF) and EGF6-like growth factors, such as transforming growth factor-a, are present in amnionic fluid. Ingestion of amnionic fluid into the lung and gastrointestinal tract may promote growth and differentiation of these tissues by inspiration and swallowing amnionic fluid. PTH-rP7 and endothelin-1 also are present in amnionic fluid, and it has been proposed that these peptides may be involved in fetal development. Both act as growth factors in selected cells, and PTH-rP promotes surfactant synthesis cells in type II pneumonocytes in vitro (Rubin and co-workers, 1994).
A more important function, however, is to promote the normal growth and development of the lungs and gastrointestinal tract. Animal studies have shown that pulmonary hypoplasia can be produced by draining off amnionic fluid, by banding the trachea to prevent "inhalation" of fluid into the lungs, by chronically draining pulmonary fluid through the trachea, and by physically preventing the prenatal chest excursions that mimic breathing (Adzick and associates, 1984; Alcorn and colleagues, 1977). Thus the formation of intrapulmonary fluid and, at least as important, the alternating egress and retention of fluid in the lungs by breathing movements, are essential to normal pulmonary development. Clinical implications of oligohydramnios and pulmonary hypoplasia are discussed in Chapter 31 (p. 822).
UMBILICAL CORD AND RELATED STRUCTURES
The yolk sac and the umbilical vesicle into which it develops are quite prominent early in pregnancy. At first, the embryo is a flattened disc interposed between amnion and yolk sac (Fig. 5-6). Because the dorsal surface grows faster than the ventral surface, in association with the elongation of the neural tube, the embryo bulges into the amnionic sac and the dorsal part of the yolk sac is incorporated into the body of the embryo to form the gut. The allantois projects into the base of the body stalk from the caudal wall of the yolk sac or, later, from the anterior wall of the hindgut.
As pregnancy advances, the yolk sac becomes smaller and its pedicle relatively longer. By about the middle of the third month, the expanding amnion obliterates the exocoelom, fuses with the chorion laeve, and covers the bulging placental disc and the lateral surface of the body stalk, which is then called the umbilical cord, or funis. Remnants of the exocoelom in the anterior portion of the cord may contain loops of intestine, which continue to develop outside the embryo. Although the loops are later withdrawn, the apex of the midgut loop retains its connection with the attenuated vitelline duct. The duct terminates in a crumpled, highly vascular sac 3 to 5 cm in diameter lying on the surface of the placenta between amnion and chorion or in the membranes just beyond the placental margin, where occasionally it may be identified at term.
The cord at term normally has two arteries and one vein. The right umbilical vein usually disappears early during fetal development, leaving only the original left vein. Sections of any portion of the cord frequently reveal, near the center, the small duct of the umbilical vesicle, lined by a single layer of flattened or cuboid epithelial cells. In sections just beyond the umbilicus, but never at the maternal end of the cord, another duct representing the allantoic remnant is occasionally found. The intra-abdominal portion of the duct of the umbilical vesicle, which extends from umbilicus to intestine, usually atrophies and disappears, but occasionally it remains patent, forming a Meckel diverticulum. The most common vascular anomaly is the absence of one umbilical artery.
STRUCTURE AND FUNCTION
The umbilical cord, or funis, extends from the fetal umbilicus to the fetal surface of the placenta or chorionic plate. Its exterior is dull white, moist, and covered by amnion, through which three umbilical vessels may be seen. Its diameter is 0.8 to 2.0 cm, with an average length of 55 cm and a range of 30 to 100 cm. Generally, cord length less than 30 cm is considered abnormally short (Benirschke and Kauffman, 2000). Folding and tortuosity of the vessels, which are longer than the cord itself, frequently create nodulations on the surface, or false knots, which are essentially varices. The extracellular matrix, which is a specialized connective tissue, consists of Wharton jelly (Figs. 5-18 and 5-19). After fixation, the umbilical vessels appear empty, but Figure 5-19 more accurately is representative of the situation in vivo, when the vessels are not emptied of blood. The two arteries are smaller in diameter than the vein. When fixed in their normally distended state, the umbilical arteries exhibit transverse intimal folds of Hoboken across part of their lumens (Chacko and Reynolds, 1954). The mesoderm of the cord, which is of allantoic origin, fuses with that of the amnion.
Blood flows from the umbilical vein by two routes—the ductus venosus, which empties directly into the inferior vena cava, and numerous smaller openings into the fetal hepatic circulation—and then into the inferior vena cava by the hepatic vein. The blood takes the path of least resistance through these alternate routes. Resistance in the ductus venosus is controlled by a sphincter situated at the origin of the ductus at the umbilical recess and innervated by a branch of the vagus nerve.
True umbilical knot
Anatomically, the umbilical cord can be regarded as a fetal membrane. The vessels contained in the cord are characterized by spiraling or twisting. The spiraling may occur in a clockwise (dextral) or anticlockwise (sinistral) direction. The anticlockwise spiral is present in 50 to 90 percent of cases. It is believed that the spiraling serves to attenuate "snarling," which occurs in all hollow cylinders subjected to torsion. Boyd and Hamilton (1970) note that these twists are not really spirals, but rather they are cylindrical helices in which a constant curva-ture is maintained equidistant from the central axis. Benirschke and Kauffman (2000) reported that 11 is the average number of helices in the cord.
FETAL GROWTH AND DEVELOPMENT
The high purposes of obstetrics are to maintain the health of the pregnant woman and to ensure the optimal well-being of the newborn. To this end, contemporary obstetrical research focuses on the physiology and pathophysiology of the fetus, its development, and its environment.
An important direct result of this research is that the status of the fetus has been elevated to that of a patient who, in large measure, can be given the same meticulous care that obstetricians provide for pregnant women. In the course of these studies it has become apparent that the conceptus is the dynamic force in the pregnancy unit. In general, the maternal organism responds passively to signals emanating from embronic-fetal and extraembryonic tissues. The contributions of the conceptus to implantation, maternal recognition of pregnancy, immunological acceptance, endocrine function, nutrition, and parturition are enormous, and absolutely essential for successful pregnancy .
DETERMINATION OF GESTATIONAL AGE
Several different terms are used to define the duration of pregnancy, and thus fetal age, but these are somewhat confusing. Gestational age or menstrual age is the time elapsed since the first day of the last menstrual period, a time that actually precedes conception. This starting time, which is usually about 2 weeks before ovulation and fertilization and nearly 3 weeks before implantation of the blastocyst, has traditionally been used because most women know when their last period was but not when they last ovulated, although the increasing use of infertility therapy has changed this somewhat. Embryologists, however, describe embryo-fetal development in days or weeks from the time of ovulation (ovulation age) or conception (postconceptional age), the latter two being nearly identical.
Obstetricians customarily calculate gestational age as menstrual age of a given pregnancy. About 280 days, or 40 weeks, elapse on average between the first day of the last menstrual period and the birth of the fetus; 280 days correspond to 9 1/3 calendar months, or 10 units of 28 days each. The unit of 28 days has been referred to, commonly but imprecisely, as a lunar month of pregnancy; actually, the time from one new moon to the next is 29 1/2 days. A quick estimate of the due date of a pregnancy based on menstrual cycle can be made as follows: add 7 days to the first day of the last menstrual period and subtract 3 months. For example, if the first day of the last menses was June 8, the due date of this pregnancy is 06 08 + 7 (days) minus 3 (months) = 03 15, or March 15 of the following year. As noted in Chapter 41 (p. 116), however, many women now undergo first or early second trimester ultrasound examination to confirm gestational age, and the sonographic estimate is usually a few days later than that determined by the last period. To rectify this inconsistency—and to reduce the number of pregnancies diagnosed as postterm—some authorities suggest assuming that the average pregnancy is actually 283 days long instead of 280, and thus adding 10 days to the last menses instead of 7 (Olsen and Clausen, 1998).
The period of gestation can also be divided into three units of three calendar months each, or three trimesters, because important obstetrical milestones can be designated conveniently by trimesters. The possibility of spontaneous abortion, for example, is limited principally to the first trimester, whereas the likelihood of survival of the infant born preterm is increased greatly in pregnancies that reach the third trimester.
OVUM, ZYGOTE, AND BLASTOCYST
During the first 2 weeks after ovulation, several successive phases of development can be identified:
2. Fertilization of the ovum.
3. Formation of free blastocyst.
4. Implantation of the blastocyst .
Primitive chorionic villi are formed soon after implantation. With the development of chorionic villi, it is conventional to refer to the products of conception not as a fertilized ovum, or zygote, but as an embryo. The early stages of preplacental development, and formation of the placenta, are described in Chapter 5.
The embryonic period commences at the beginning of the third week after ovulation/fertilization, which coincides in time with the expected day that the next menstruation would have started. Most pregnancy tests that measure human chorionic gonadotropin (hCG) use are positive by this time (Chap. 2, p. 26), and the embryonic disc is well defined. The body stalk is differentiated; the chorionic sac is approximately 1 cm in diameter (Figs. 7-2 and 7-3). There is a true intervillous space that contains maternal blood and villous cores in which angioblastic chorionic mesoderm can be distinguished.
By the end of the fourth week after ovulation, the chorionic sac is 2 to 3 cm in diameter, and the embryo is about 4 to 5 mm in length (Fig. 7-4). Partitioning of the primitive heart begins in the middle of the fourth week. Arm and leg buds are present, and the amnion is beginning to unsheathe the body stalk, which thereafter becomes the umbilical cord.
At the end of the sixth week after fertilization, the embryo is 22 to 24 mm in length, and the head is quite large compared with the trunk. The heart is completely formed. Fingers and toes are present, and the arms bend at the elbows. The upper lip is complete and the external ears form definitive elevations on either side of the head.
The end of the embryonic period and the beginning of the fetal period is arbitrarily designated by most embryologists to occur 8 weeks after fertilization, or 10 weeks after the onset of the last menstrual period. At this time, the embryo-fetus is nearly 4 cm long. The major portion of lung development is yet to occur, but few other new major body structures are formed after this time. Development during the fetal period of gestation consists of growth and maturation of structures that were formed during the embryonic period.
12 GESTATIONAL WEEKS. By the end of the 12th week of pregnancy, when the uterus usually is just palpable above the symphysis pubis, the crown-rump length of the fetus is 6 to 7 cm (Fig. 7-5). Centers of ossification have appeared in most of the fetal bones, and the fingers and toes have become differentiated. Skin and nails have developed and scattered rudiments of hair appear; the external genitalia are beginning to show definitive signs of male or female gender. The fetus begins to make spontaneous movements.
16 GESTATIONAL WEEKS. By the end of the 16th week, the crown-rump length of the fetus is 12 cm, and the weight is 110 g. Gender can be correctly determined by experienced observers by inspection of the external genitalia by 14 (menstrual) weeks.
20 GESTATIONAL WEEKS. The end of the 20th week is the midpoint of pregnancy as estimated from the beginning of the last normal menstrual period. The fetus now weighs somewhat more than 300 g, and the weight begins to increase in a linear manner. The fetal skin has become less transparent, a downy lanugo covers its entire body, and some scalp hair has developed.
24 GESTATIONAL WEEKS. By the end of the 24th week, the fetus weighs about 630 g. The skin is characteristically wrinkled, and fat deposition begins. The head is still comparatively quite large; eyebrows and eyelashes are usually recognizable. The canalicular period of lung development, during which the bronchi and bronchioles enlarge and alveolar ducts develop, is nearly completed. A fetus born at this period will attempt to breathe, but most will die because the terminal sacs, required for gas exchange, have not yet formed.
28 GESTATIONAL WEEKS. By the end of the 28th week, a crown-rump length of about 25 cm is attained and the fetus weighs about 1100 g. The thin skin is red and covered with vernix caseosa. The pupillary membrane has just disappeared from the eyes. An infant born at this time moves the limbs quite energetically and cries weakly. The otherwise normal infant of this age has a 90 percent chance of intact survival.
32 GESTATIONAL WEEKS. At the end of 32 gestational weeks, the fetus has attained a crown-rump length of about 28 cm and a weight of about 1800 g. The surface of the skin is still red and wrinkled. Barring other complications, infants born at this period usually survive intact.
36 GESTATIONAL WEEKS. At the end of 36 weeks gestation, the average crown-rump length of the fetus is about 32 cm and the weight is about 2500 g. Because of the deposition of subcutaneous fat, the body has become more rotund, and the previous wrinkled appearance of the face has been lost. Infants born at this time have an excellent chance of survival with proper care.
40 GESTATIONAL WEEKS. Term is reached at 40 weeks from the onset of the last menstrual period. At this time, the fetus is fully developed, with the characteristic features of the newborn infant to be described here. The average crown-rump length of the fetus at term is about 36 cm, and the weight is approximately 3400 g, with variations to be discussed subsequently.
LENGTH OF FETUS. Because of the variability in the length of the legs and the difficulty of maintaining them in extension, measurements corresponding to the sitting height (crown-to-rump) are more accurate than those corresponding to the standing height. The average sitting height and weight of the fetus at the end of each lunar month were determined by Streeter (1920) from 704 specimens. These values are similar to those found more recently and shown in Table 7-1. Such values are approximate, but generally, length is a more accurate criterion of gestational age than weight.
WEIGHT OF THE NEWBORN. The average term infant in the United States at birth weighs about 3000 to 3600 g, depending upon race, parental economic status, size of the parents, parity of the mother, and altitude, with boys about 100 g (3 oz) heavier than girls. During the second half of pregnancy, the fetal weight increases in a linear manner with time until about the 37th week of gestation, and then the rate slows variably. The principal determinants of fetal growth late in pregnancy are related, in large part, to factors influenced by the socioeconomic status of the mother, such as diet, smoking, or substance abuse. In general, the greater the socioeconomic deprivation, the slower the rate of fetal growth late in pregnancy.
Birthweights over 5000 g occur occasionally (Chap. 29, p. 757), but many tales of huge babies vastly exceeding this figure are based on hearsay or inaccurate measurements at best. Presumably, the largest baby recorded in the medical literature is that described by Belcher (1916), a stillborn female weighing 11,340 g (25 lb). Term infants, however, frequently weigh less than 3200 g, and sometimes as little as 2250 g (5 lb) or even less. It was customary in the past, when the birthweight was 2500 g or less, to classify the infant as preterm even though in some cases the low birthweight was not the consequence of preterm birth but rather the result of restricted growth.
MATERNAL ADAPTATIONS TO PREGNANCY
The anatomical, physiological, and biochemical adaptations to pregnancy are profound. Many of these changes begin soon after fertilization and continue throughout gestation, and most of these remarkable adaptations occur in response to physiological stimuli provided by the fetus. Equally astounding is that the woman who was pregnant is returned almost completely to her pre-pregnancy state after delivery and lactation. The understanding of these adaptations to pregnancy remains a major goal of obstetrics, and without such knowledge, it is almost impossible to understand the disease processes that can threaten women during pregnancy and the puerperium.
Because of these physiological adaptations, in some cases there are marked aberrations that would be perceived as abnormal in the nonpregnant state. For example, cardiovascular changes normally include substantive increases in blood volume and cardiac output, with hemodynamic adaptations that accompany them. This "high-output state" resembles thyrotoxicosis and other abnormal states. At the same time, underlying heart disease may lead to cardiac failure with these burdens.
Thus, physiological adaptations of normal pregnancy can be misinterpreted as disease, but they also may unmask or worsen preexisting disease. A number of laboratory values may appear abnormal, for example, pregnancy hypervolemia is accompanied by plasma volume expansion out of proportion to red cell mass increase. The result is so-called "physiological anemia" that is a major misnomer. The impact of these marked physiological changes on underlying disease, and vice versa, are considered in some detail in Section XII, which deals with medical and surgical complications of pregnancy.
In the nonpregnant woman, the uterus is an almost-solid structure weighing about 70 g and with a cavity of 10 mL or less During pregnancy, the uterus is transformed into a relatively thin-walled muscular organ of sufficient capacity to accommodate the fetus, placenta, and amnionic fluid The total volume of the contents at term averages about 5 L but may be 20 L or more, so that by the end of pregnancy the uterus has achieved a 500 to 1000 times greater capacity than in the nonpregnant state There is a corresponding increase in uterine weight, and at term, the organ weighs approximately 1100 g
During pregnancy, uterine enlargement involves stretching and marked hypertrophy of muscle cells, whereas the production of new myocytes is limited. The myometrial smooth muscle cells are surrounded by an irregular array of collagen fibrils. The force of contraction is transmitted from the contractile proteins of the myocytes to the surrounding connective tissue through the collagen reticulum.
Accompanying the increase in size of muscle cells is an accumulation of fibrous tissue, particularly in the external muscle layer, together with a considerable increase in elastic tissue. The network that is formed adds materially to the strength of the uterine wall. Concomitantly, there is a great increase in size and number of blood vessels and lymphatics. The veins that drain the placental site are transformed into large uterine sinuses, and there is hypertrophy of the nerves exemplified by the increase in size of the Frankenhauser cervical ganglion.
During the first few months, uterine hypertrophy is probably stimulated chiefly by the action of estrogen and perhaps that of progesterone. It is apparent that early hypertrophy is not entirely in response to mechanical distention by the products of conception, because similar uterine changes are observed with ectopic pregnancy But after about 12 weeks, the increase in uterine size is in large part related in some manner to the effect of pressure exerted by the expanding prducts of conception.
During the first few months of pregnancy, the uterine walls become considerably thicker, but as gestation advances the walls gradually thin. At term, the walls of the corpus are only about 1.5 cm or less in thickness. Early in pregnancy, the uterus loses the firmness and resistance characteristic of the nonpregnant organ. In the later months, the uterus is changed into a muscular sac with thin, soft, readily indentable walls, demonstrable by the ease with which the fetus usually can be palpated.
Uterine enlargement is not symmetrical, and it is most marked in the fundus. The differential growth is readily apparent by observing the relative positions of the attachments of the fallopian tubes and ovarian and round ligaments. In the early months of pregnancy, these structures attach only slightly below the apex of the fundus, whereas in the later months, they are located slightly above the middle of the uterus (see Fig. 3-9, p. 41). The position of the placenta also influences the extent of uterine hypertrophy, because the portion of the uterus surrounding the placental site enlarges more rapidly than does the rest.
ARRANGEMENT OF THE MUSCLE CELLS.
The uterine musculature during pregnancy is arranged in three strata:
1. An external hoodlike layer, which arches over the fundus and extends into the various ligaments.
2. An internal layer, consisting of sphincter-like fibers around the orifices of the tubes and the internal os.
3. Lying between these two, a dense network of muscle fibers perforated in all directions by blood vessels.
The main portion of the uterine wall is formed by the middle layer, which consists of an interlacing network of muscle fibers between which extend the blood vessels. Each cell in this layer has a double curve, so that the interlacing of any two gives approximately the form of the figure eight. As a result of this arrangement, when the cells contract after delivery they constrict the penetrating blood vessels and thus act as ligatures.
The muscle cells composing the uterine wall in pregnancy, especially in its lower portion, overlap one another like shingles on a roof. One end of each fiber arises beneath the serosa of the uterus and extends obliquely downward and inward toward the decidua, forming a large number of muscular lamellae that are interconnected by short muscular processes.
UTERINE SIZE, SHAPE, AND POSITION.
For the first few weeks the uterus maintains its original pear shape, but as pregnancy advances the corpus and fundus assume a more globular form, becoming almost spherical by 12 weeks. Subsequently, the organ increases more rapidly in length than in width and assumes an ovoid shape. By the end of 12 weeks, the uterus has become too large to remain totally within the pelvis. As the uterus continues to enlarge, it contacts the anterior abdominal wall, displaces the intestines laterally and superiorly, and continues to rise, ultimately reaching almost to the liver. As the uterus rises, tension is exerted upon the broad ligaments and upon the round ligaments.
With the pregnant woman standing, the longitudinal axis of the uterus corresponds to an extension of the axis of the pelvic inlet. The abdominal wall supports the uterus and, unless it is quite relaxed, maintains this relation between the long axis of the uterus and the axis of the pelvic inlet. When the pregnant woman is supine, the uterus falls back to rest upon the vertebral column and the adjacent great vessels, especially the inferior vena cava and the aorta.
With ascent of the uterus from the pelvis, it usually undergoes rotation to the right, and this dextrorotation likely is caused by the rectosigmoid on the left side of the pelvis.
From the first trimester onward, the uterus undergoes irregular contractions, which are normally painless. In the second trimester, these contractions may be detected by bimanual examination. Because attention was first called to this phenomenon in 1872 by J. Braxton Hicks, the contractions have been known by his name. Such contractions appear unpredictably and sporadically, are usually nonrhythmic, and their intensity varies between approximately 5 and 25 mm Hg (Alvarez and Caldeyro-Barcia, 1950). Until the last month of gestation, Braxton Hicks contractions are infrequent, but increase during the last week or two. At this time, the contractions may develop as often as every 10 to 20 minutes and may also assume some degree of rhythmicity. Late in pregnancy, these contractions may cause some discomfort and account for so-called false labor
During pregnancy, there is pronounced softening and cyanosis of the cervix, often demonstrable as early as a month after conception. The factors responsible for these changes are increased vascularity and edema of the entire cervix, together with hypertrophy and hyperplasia of the cervical glands. Although the cervix contains a small amount of smooth muscle, its major component is connective tissue. The cervix will undergo a rearrangement of its collagen-rich connective tissue, producing a 12-fold reduction in mechanical strength by term (Rechberger and colleagues, 1988).
The glands of the cervix undergo such marked proliferation that by the end of pregnancy they occupy approximately half of the entire cervical mass, rather than a small fraction as in the nonpregnant state. Moreover, the septa separating the glandular spaces become progressively thinner, resulting in the formation of a structure resembling a honeycomb, the meshes of which are filled with tenacious mucus. Soon after conception, a clot of very thick mucus obstructs the cervical canal. At the onset of labor, if not before, this so-called mucus plug is expelled, resulting in a bloody show. The glands near the external os proliferate beneath the stratified squamous epithelium of the portio vaginalis. These are customarily red and velvety in appearance and are covered by columnar epithelium. These normal pregnancy-induced changes represent an extension, or eversion, of the proliferating columnar endocervical glands. This tissue tends to be friable and bleeds even with minor trauma, such as with taking Pap smears.
There is a change in the consistency of the cervical mucus during pregnancy. In the great majority of pregnant women, cervical mucus, spread and dried on a glass slide, is characterized by fragmentary crystallization, or beading, typical of the effect of progesterone. In some women, arborization of the crystals, or ferning, is observed.
During pregnancy, basal cells near the squamocolumnar junction histologically are likely to be prominent in size, shape, and staining qualities. These changes are considered to be estrogen induced. The frequency of less-than-optimal Pap smears is increased in the pregnant woman (Kost and associates, 1993).
In the later months of pregnancy, reddish, slightly depressed streaks commonly develop in the skin of the abdomen and sometimes in the skin over the breasts and thighs in about half of pregnant women In multiparous women, in addition to the reddish striae of the present pregnancy, glistening, silvery lines that represent the cicatrices of previous striae frequently are seen
Occasionally the muscles of the abdominal walls do not withstand the tension to which they are subjected, and the rectus muscles separate in the midline, creating a diastasis recti of varying extent. If severe, a considerable portion of the anterior uterine wall is covered by only a layer of skin, attenuated fascia, and peritoneum.
In many women, the midline of the abdominal skin becomes markedly pigmented, assuming a brownish-black color to form the linea nigra Occasionally, irregular brownish patches of varying size appear on the face and neck, giving rise to chloasma or melasma gravidarum (mask of pregnancy) There is also accentuation of pigment of the areolae and genital skin Fortunately, this usually disappears, or at least regresses considerably after delivery (Chap 54, p 1430) Oral contraceptives may cause similar pigmentation in these same women There is very little known of the nature of these pigmentary changes, although melanocyte-stimulating hormone, a polypeptide similar to corticotropin, has been shown to be elevated remarkably from the end of the second month of pregnancy until term (see also Chap 6) Estrogen and progesterone are reported to have some melanocyte-stimulating effects Vaughn Jones and Black (1999) attribute most changes to estrogen
In response to the rapidly growing fetus and placenta and their increasing demands, the pregnant woman undergoes metabolic changes that are numerous and intense. Certainly no other physiological event in postnatal life induces such profound metabolic alterations.
Most of the increase in weight during pregnancy is attributable to the uterus and its contents, the breasts, and increases in blood volume and extravascular extracellular fluid A smaller fraction of the increased weight is the result of metabolic alterations that result in an increase in cellular water and deposition of new fat and protein, so-called maternal reserves Hytten (1991) reported an average weight gain of 125 kg
Increased water retention is a normal physiological alteration of pregnancy. This is mediated, at least in part, by a fall in plasma osmolality of approximately 10 mOsm/kg induced by a resetting of osmotic thresholds for thirst and vasopressin secretion (Lindheimer and Davidson, 1995). As shown in Figure 8-3, this phenomenon is functioning by early pregnancy.
At term, the water content of the fetus, placenta, and amnionic fluid amounts to about 3.5 L. Another 3.0 L accumulates as a result of increases in the maternal blood volume and in the size of the uterus and the breasts. Thus, the minimum amount of extra water that the average women retains during normal pregnancy is about 6.5 L. Clearly demonstrable pitting edema of the ankles and legs is seen in a substantial proportion of pregnant women, especially at the end of the day. This accumulation of fluid, which may amount to a liter or so, is caused by an increase in venous pressure below the level of the uterus as a consequence of partial occlusion of the vena cava. A decrease in interstitial colloid osmotic pressure induced by normal pregnancy also favors edema late in pregnancy (Oian and co-workers, 1985).
Longitudinal studies of body composition have shown a progressive increase in total body water and fat mass during pregnancy. It has been known for decades that both initial maternal weight and the weight gained during pregnancy are highly associated with birthweight. It is unclear, however, what role maternal fat or water have in fetal growth. Recent studies in well-nourished term women suggest that maternal body water, rather than fat, contributes more significantly to infant birthweight (Lederman and associates, 1999; Mardones-Santander and associates, 1998).
The products of conception, as well as uterus and maternal blood, are relatively rich in protein rather than fat or carbohydrate. At term, the fetus and placenta together weigh about 4 kg and contain approximately 500 g of protein, or about half of the total pregnancy increase (Hytten and Leitch, 1971). The remaining 500 g is added to the uterus as contractile protein, to the breasts primarily in the glands, and to the maternal blood as hemoglobin and plasma proteins.
From nitrogen balance studies in pregnant women, it appears that actual nitrogen use is only 25 percent (Calloway, 1974). Therefore, daily requirements for protein intake during pregnancy are increased appreciably to correct for this. Equally important is the ingestion of adequate carbohydrates and fat. If these are not consumed in adequate amounts, energy requirements must be met by catabolism of maternal protein stores. Amino acids used for energy are not available for synthesis of maternal protein. With increasing intake of fat and carbohydrates as energy sources, less dietary protein is required to maintain positive nitrogen balance.
Normal pregnancy is characterized by mild fasting hypoglycemia, postprandial hyperglycemia, and hyperinsulinemia (Fig. 8-4). The fasting plasma glucose concentration falls somewhat, possibly due to increased plasma levels of insulin. This cannot be explained by a change in the metabolism of insulin because its half-life during pregnancy is not changed (Lind and associates, 1977).
The increased basal level of plasma insulin observed in normal pregnancy is associated with several unique responses to glucose ingestion. For example, after an oral glucose meal, there is both prolonged hyperglycemia and hyperinsulinemia in pregnant women, with a greater suppression of glucagon (Phelps and associates, 1981). The purpose of such a mechanism is likely to ensure a sustained or maintained postprandial supply of glucose to the fetus. This response is consistent with a pregnancy-induced state of peripheral resistance to insulin, which is suggested by three observations:
1. Increased insulin response to glucose.
2. Reduced peripheral uptake of glucose.
3. Suppressed glucagon response.
The mechanism(s) responsible for insulin resistance is not completely understood. Progesterone and estrogen may act, directly or indirectly, to mediate this resistance. Plasma levels of placental lactogen increase with gestation, and this protein hormone is characterized by growth hormone-like action that may result in increased lipolysis with liberation of free fatty acids (Freinkel, 1980). The increased concentration of circulating free fatty acids also may facilitate increased tissue resistance to insulin.
The mechanisms cited ensure that a continuous supply of glucose is available for transfer to the fetus. The pregnant woman, however, changes rapidly from a postprandial state characterized by elevated and sustained glucose levels to a fasting state characterized by decreased plasma glucose and amino acids such as alanine. There also are higher plasma concentrations of free fatty acids, triglycerides, and cholesterol in the pregnant woman during fasting (Fig. 8-5). Freinkel and colleagues (1985) have referred to this pregnancy-induced switch in fuels from glucose to lipids as accelerated starvation. Certainly, when fasting is prolonged in the pregnant woman, these alterations are exaggerated and ketonemia rapidly appears.
Hornnes and Kuhl (1980) measured glucagon and insulin responses to a standard glucose stimulus late in normal pregnancy and again in the same women postpartum. The peak insulin response to glucose infusion was increased fourfold in late pregnancy. In contrast, plasma glucagon concentrations were suppressed, and the degree was similar in late pregnancy and the puerperium. These results are consistent with the view that ß-cell sensitivity to a glucose challenge is increased significantly in normal pregnant women, but that the a-cell sensitivity to a glucose stimulus is unaltered.
The concentrations of lipids, lipoproteins, and apolipoproteins in plasma increase appreciably during pregnancy. Desoye and co-workers (1987) found that there were positive correlations between the concentrations of lipids shown in Figure 8-5 and those of estradiol, progesterone, and placental lactogen.
Plasma lipoprotein cholesterol levels also increase significantly. Low-density lipoprotein cholesterol (LDL-C) levels peak at approximately week 36, likely the consequence of the hepatic effects of estradiol and progesterone (Desoye and associates, 1987). High-density lipoprotein cholesterol (HDL-C) peaks at week 25, decreases until week 32, and remains constant for the remainder of pregnancy. The initial increase is believed to be caused by estrogen. High-density lipoprotein-2 and -3 cholesterol levels peak at approximately 28 weeks and remain unchanged throughout the remainder of pregnancy. Brizzi and colleagues (1999) have suggested that changes in the low-density lipoprotein (LDL) pattern during normal pregnancy might be used to identify those women who later in life may be predisposed to atherogenesis.
After delivery, the concentrations of these lipids, lipoproteins, and apolipoproteins decrease at different rates (Desoye and co-workers, 1987). Lactation increases the rate of decrease of many of these compounds (Darmady and Postle, 1982).
Hytten and Thomson (1968) and Pipe and co-workers (1979) concluded that storage of fat occurs primarily during midpregnancy. This fat is deposited mostly in central rather than peripheral sites. Later in pregnancy, as fetal nutritional demands increase remarkably, maternal fat storage decreases. Hytten and Thomson (1968) cited some evidence that progesterone may act to reset a lipostat in the hypothalamus, and at the end of pregnancy the lipostat returns to its previous nonpregnant level and the added fat is lost. Such a mechanism for energy storage, theoretically at least, might protect the mother and fetus during times of prolonged starvation or hard physical exertion.
The requirements for iron during pregnancy are considerable and often exceed the amounts available (p. 178). With respect to most other minerals, pregnancy induces little change in their metabolism other than their retention in amounts equivalent to those used for growth of fetal and, to a lesser extent, maternal tissues (Chaps. 7, p. 139 and 10, p. 235).
During pregnancy, calcium and magnesium plasma levels decline, the reduction probably reflecting for the most part the lowered plasma protein concentration and, in turn, the consequent decrease in the amount bound to protein. Bardicef and colleagues (1995), however, concluded that pregnancy is a state of magnesium depletion. They showed that total and ionized magnesium levels were significantly lower in normal pregnancy compared with nonpregnant women. Fogh-Andersen and Schultz-Larsen (1981) demonstrated a small but significant increase in free calcium ion concentration in late pregnancy by correcting for blood pH changes. Serum phosphate levels are within the nonpregnant range. The renal threshold for inorganic phosphate excretion is elevated in pregnancy due to increased calcitonin (Weiss and colleagues, 1998). Cole and co-workers (1987) reported that bone turnover was reduced during early pregnancy, returned toward normal during the third trimester, and increased in postpartum lactating women.
As discussed subsequently (p 186), minute ventilation increases during pregnancy and this causes a respiratory alkalosis by lowering the PCO2 of blood A moderate reduction in plasma bicarbonate from 26 to about 22 mmol/L partially compensates for this As a result, there is only a minimal increase in blood pH This increase shifts the oxygen dissociation curve to the left and increases the affinity of maternal hemoglobin for oxygen (Bohr effect), thereby decreasing the oxygen-releasing capacity of maternal blood Thus, the hyperventilation that results in a reduced maternal PCO2 facilitates transport of carbon dioxide from the fetus to the mother but appears to impair release of oxygen from maternal blood to the fetus The increase in blood pH, however, although minimal, stimulates an increase in 2, 3-diphosphoglycerate in maternal erythrocytes (Tsai and deLeeuw, 1982) This counteracts the Bohr effect by shifting the oxygen dissociation curve back to the right, facilitating oxygen release to the fetus
Despite large accumulations during pregnancy of sodium and potassium, the serum concentration of these electrolytes decreases During normal pregnancy, nearly 1000 mEq of sodium and 300 mEq of potassium are retained (Lindheimer and colleagues, 1987) Despite that their glomerular filtration is increased, sodium and potassium excretion are unchanged during pregnancy (Brown and colleagues, 1986, 1988) Thus, their fractional excretion is decreased, and it has been postulated that progesterone counteracts the natriuretic and kaliuretic effects of aldosterone
The maternal blood volume increases markedly during pregnancy In studies of normal women, the blood volumes at or very near term averaged about 40 to 45 percent above their nonpregnant levels (Pritchard, 1965; Whittaker and associates, 1996) The degree of expansion varies considerably, in some women there is only a modest increase, while in others the blood volume nearly doubles A fetus is not essential for the development of hypervolemia during pregnancy, for increases in blood volume have been demonstrated in some women with hydatidiform mole (Pritchard, 1965)
Pregnancy-induced hypervolemia has several important functions:
1. To meet the demands of the enlarged uterus with its greatly hypertrophied vascular system.
2. To protect the mother, and in turn the fetus, against the deleterious effects of impaired venous return in the supine and erect positions.
3. To safeguard the mother against the adverse effects of blood loss associated with parturition.
Maternal blood volume starts to increase during the first trimester, expands most rapidly during the second trimester, and then rises at a much slower rate during the third trimester to plateau during the last several weeks of pregnancy.
Increased blood volume results from an increase in both plasma and erythrocytes. Although more plasma than erythrocytes is usually added to the maternal circulation, the increase in volume of erythrocytes is considerable, averaging about 450 mL, or an increase of about 33 percent (Pritchard and Adams, 1960). The importance of this increase in creating a demand for iron is discussed on page 178.
Moderate erythroid hyperplasia is present in the bone marrow, and the reticulocyte count is elevated slightly during normal pregnancy. This is almost certainly related to the increase in maternal plasma erythropoietin levels (Chap. 49, p. 1310). These levels increase after 20 weeks, corresponding to when erythrocyte production is most marked (Harstad and co-workers, 1992).
ATRIAL NATRIURETIC PEPTIDES. This group of biologically active peptides is synthesized and secreted by atrial myocytes. Three separate forms (a, ß, ?) have been isolated (Kangawa and co-workers, 1985). Atrial natriuretic peptide produces significant natriuresis and diuresis. It increases renal blood flow and glomerular filtration rate and decreases renin secretion. The actual mechanism(s) responsible for the natriuresis remains unclear, with evidence consistent for both a hemodynamically induced natriuresis and an inhibitory effect upon tubular sodium reabsorption (Wakitani and colleagues, 1985). Atrial natriuretic peptides also have been shown to reduce basal release of aldosterone from zona glomerulosa cells and to blunt corticotropin and angiotensin II-stimulated release of aldosterone as well (Atarashi and associates, 1984). Renin secretion is also inhibited by this peptide. Finally, atrial natriuretic peptides have a direct vasorelaxant action upon vascular smooth muscle stimulated by angiotesin II or norepinephrine.
Castro and associates (1994) summarized several studies done to evaluate plasma levels of atrial natriuretic peptide in normal and hypertensive pregnancy. The mean level rose by 40 percent over nonpregnant values by the third trimester and by 150 percent during the first week postpartum. These investigators hypothesized that atrial stretch receptors sense the expanded blood volume of pregnancy as normal to moderately increased. The marked rise in peptide levels during the first week postpartum is consistent with known hemodynamic changes and suggests that the hormone is involved in postpartum diuresis.
By comparison, Thomsen and colleagues (1994) investigated 10 healthy primigravid twin pregnancies and reported that all atrial natriuretic peptide levels during pregnancy were lower than values at 12 weeks postpartum. At 20, 28, and 32 weeks, plasma peptide levels were lower in twin than in singleton pregnancies. These observations may serve to explain in part the relatively increased plasma volume characteristic of women with twins compared with those with singleton fetuses.
HEMOGLOBIN CONCENTRATION AND HEMATOCRIT.
In spite of augmented erythropoiesis, hemoglobin concentration and the hematocrit decrease slightly during normal pregnancy. As a result, whole blood viscosity decreases (Huisman and colleagues, 1987). Hemoglobin concentration at term averages 12.5 m/dL and in 6 percent of women it is below 11.0 g/dL (see Fig. 49-1 and Table 49-1). Thus, in most women, a hemoglobin concentration below 11.0 g/dL, especially late in pregnancy, should be considered abnormal and usually due to iron deficiency rather than to hypervolemia of pregnancy.
IRON METABOLISM IRON STORES. Although the total body iron content averages about 4 g in men, in healthy young women of average size, it is probably half that amount. Commonly, iron stores of normal young women are only about 300 mg (Pritchard and Mason, 1964). As in men, heme iron in myoglobin and enzymes and transferrin-bound circulating iron together total only a few hundred milligrams. The total iron content of normal adult women ranges from 2.0 to 2.5 g.
IRON REQUIREMENTS. The iron requirements of normal pregnancy total about 1000 mg. About 300 mg are actively transferred to the fetus and placenta and about 200 mg are lost through various normal routes of excretion. These are obligatory losses and occur even when the mother is iron deficient. The average increase in the total volume of circulating erythrocytes of about 450 mL during pregnancy, when iron is available, uses another 500 mg of iron, because 1 mL of normal erythrocytes contains 1.1 mg of iron. Practically all of the iron for these purposes is used during the latter half of pregnancy. Therefore, the iron requirement becomes quite large during the second half of pregnancy, averaging 6 to 7 mg/day (Pritchard and Scott, 1970). Because this amount is not available from body stores in most women, the desired increase in maternal erythrocyte volume and hemoglobin mass will not develop unless exogenous iron is made available in adequate amounts. In the absence of supplemental iron, the hemoglobin concentration and hematocrit fall appreciably as the maternal blood volume increases. Hemoglobin production in the fetus, however, will not be impaired, because the placenta obtains iron from the mother in amounts sufficient for the fetus to establish normal hemoglobin levels even when the mother has severe iron-deficiency anemia.
The amount of iron absorbed from diet, together with that mobilized from stores, is usually insufficient to meet the demands imposed by pregnancy. This is true even though gastrointestinal tract iron absorption appears to be moderately increased during pregnancy (Hahn and associates, 1951). If the pregnant woman who is not anemic is not given supplemental iron, serum iron and ferritin concentrations decline during the second half of pregnancy (Fig. 8-7). The somewhat unexpected early pregnancy increases in serum iron and ferritin are thought to be due to minimal iron demands during the first trimester as well as to a positive iron balance because of amenorrhea. These values, summarized in Table 8-2, show that standard deviations for a given mean value are quite large. For example, in pregnant women with overt anemia and not given supplemental iron, serum ferritin levels can vary from 7 to 22 ng/mL during the third trimester. Also shown in Figure 8-7 is the increase in iron-binding capacity (transferrin) that occurs even when iron deficiency has been eliminated by oral iron supplementation.
BLOOD LOSS. Not all the iron added to the maternal circulation in the form of hemoglobin is necessarily lost from the mother. During normal vaginal delivery and through the next few days, only about half of the erythrocytes added to the maternal circulation during pregnancy are lost from the majority of women. These losses are by way of the placental implantation site, the placenta itself, the episiotomy or lacerations, and in the lochia. On the average, an amount of maternal erythrocytes corresponding to about 500 to 600 mL of predelivery blood is lost during and after vaginal delivery of a single fetus (Pritchard, 1965; Ueland, 1976). The average blood loss associated with cesarean delivery or with the vaginal delivery of twins is about 1000 mL, or nearly twice that lost with the delivery of a single fetus.
IMMUNOLOGICAL AND LEUKOCYTE FUNCTIONS
Pregnancy has been assumed to be associated with suppression of a variety of humoral and cellularly mediated immunological functions in order to accommodate the "foreign" semiallogeneic fetal graft (Chap 2, p 20) In fact, humoral antibody titers against several viruses—for example, herpes simplex, measles, and influenza A—decrease during pregnancy The decrease in titers, however, is accounted for by the hemodilutional effect of pregnancy The prevalence of a variety of autoantibodies is unchanged (Patton and colleagues, 1987) Furthermore, a-interferon, which is present in almost all fetal tissues and fluids, is most often absent in normally pregnant women (Chard and co-workers, 1986) There is evidence, as yet unexplained, that polymorphonuclear leukocyte chemotaxis and adherence functions are depressed beginning in the second trimester and continuing throughout pregnancy (Krause and associates, 1987) It is possible that these depressed leukocyte functions of pregnant women account in part for the improvement observed in some with autoimmune diseases and the possibly increased susceptibility to certain infections Thus, both function and absolute numbers of leukocytes appear to be important factors when considering the leukocytosis of normal pregnancy
The leukocyte count varies considerably during normal pregnancy. Usually it ranges from 5000 to 12,000/uL. During labor and the early puerperium it may become markedly elevated, attaining levels of 25,000 or even more; however, the concentration averages 14,000 to 16,000/uL (Taylor and co-workers, 1981). The cause for the marked increase is not known, but the same response occurs during and after strenuous exercise. It probably represents the reappearance in the circulation of leukocytes previously shunted out of the active circulation. During pregnancy there is a neutrophilia that consists predominantly of mature forms; however, an occasional myelocyte is found.
During pregnancy and the puerperium there are remarkable changes involving the heart and the circulation. The most important changes in cardiac function occur in the first eight weeks of pregnancy (McLaughlin and Roberts, 1999). Cardiac output is increased as early as the fifth week of pregnancy and this initial increase is a function of reduced systemic vascular resistance and an increase in heart rate. Between weeks 10 and 20, notable increases in plasma volume occur such that preload is increased. Ventricular performance during pregnancy is influenced by both the decrease in systemic vascular resistance and changes in pulsatile arterial flow. Vascular capacity increases, in part, due to an increase in vascular compliance. As discussed in the following section, multiple factors contribute to these changes in overall hemodynamic function, allowing the cardiovascular system to adjust to the physiological demands of the fetus while maintaining maternal cardiovascular integrity. These changes during the last half of pregnancy are graphically summarized in Figure 8-8, which also shows the important effects of maternal posture on hemodynamic events during pregnancy.
The resting pulse rate increases about 10 bpm during pregnancy (Stein and co-workers, 1999) As the diaphragm becomes progressively elevated, the heart is displaced to the left and upward, while at the same time it is rotated somewhat on its long axis As a result, the apex of the heart is moved somewhat laterally from its position in the normal nonpregnant state, and an increase in the size of the cardiac silhouette is found in radiographs (Fig 8-9) The extent of these changes is influenced by the size and position of the uterus, toughness of the abdominal muscles, and configurations of the abdomen and thorax Furthermore, normally pregnant women have some degree of benign pericardial effusion which may increase the cardiac silhouette (Enein and colleagues, 1987) Variability of these factors makes it difficult to identify precisely moderate degrees of cardiomegaly by simple x-ray studies
Katz and co-workers (1978) studied left ventricular performance during pregnancy and the puerperium using echocardiography. Both left ventricular wall mass and end-diastolic dimensions increased during pregnancy, as did heart rate, calculated stroke volume, and cardiac output. The changes in stroke volume were directly proportional to end-diastolic volume, implying, at least, that there is little change in the inotropic state of the myocardium during normal pregnancy. Sadaniantz and associates (1996) reported that these changes are not cumulative in subsequent pregnancies. In multifetal pregnancies, however, cardiac output is increased predominantly by increased inotropic effect (Veille and co-workers, 1985). The increased heart rate and inotropic contractility imply that cardiovascular reserve is reduced.
During pregnancy, some of the cardiac sounds may be altered. Cutforth and MacDonald (1966) obtained phonocardiograms at varying stages of pregnancy in 50 normal women and documented the following changes:
1. An exaggerated splitting of the first heart sound with increased loudness of both components; no definite changes in the aortic and pulmonary elements of the second sound; and a loud, easily heard third sound.
2. A systolic murmur in 90 percent of pregnant women, intensified during inspiration in some or expiration in others, and disappearing very shortly after delivery; a soft diastolic murmur transiently in 20 percent; and continuous murmurs arising from the breast vasculature in 10 percent.
Normal pregnancy induces no characteristic changes in the electrocardiogram, other than slight deviation of the electrical axis to the left as a result of the altered position of the heart.
CARDIAC OUTPUT. During normal pregnancy, arterial blood pressure and vascular resistance decrease while blood volume, maternal weight, and basal metabolic rate increase. Each of these events would be expected to affect cardiac output. It is now evident that cardiac output at rest, when measured in the lateral recumbent position, increases significantly beginning in early pregnancy (Duvekot and colleagues, 1993; Mabie and co-workers, 1994). It continues to increase and remains elevated during the remainder of pregnancy (Fig. 8-10). Typically, cardiac output in late pregnancy is appreciably higher when the woman is in the lateral recumbent position than when she is supine, because in the supine position the large uterus often impedes cardiac venous return. Ueland and Hansen (1969), for example, found cardiac output to increase 1100 mL (20 percent) when the pregnant woman was moved from her back onto her side. When she assumes the standing position after sitting, cardiac output in the pregnant woman falls to the same degree as in the nonpregnant woman (Easterling and associates, 1988).
During the first stage of labor, cardiac output increases moderately, and during the second stage, with vigorous expulsive efforts, it is appreciably greater (Fig. 8-10). After the substantively augmented cardiac output in the immediate puerperium, most of the pregnancy-induced increase is lost very soon after delivery.
HEMODYNAMIC VALUES FOR LATE PREGNANCY.
Clark and colleagues (1989) conducted studies of maternal cardiovascular hemodynamics that serve to define normal values late in pregnancy (Table 8-3). Right heart catheterization was performed in 10 healthy nulliparous women at 35 to 38 weeks, and again at 11 to 13 weeks postpartum. Late pregnancy was associated with the expected increases in heart rate, stroke volume, and cardiac output. Systemic vascular and pulmonary vascular resistance both decreased significantly, as did colloid osmotic pressure. Pulmonary capillary wedge pressure and central venous pressure did not change appreciably between late pregnancy and the puerperium. These investigators concluded that normal late pregnancy is not associated with hyperdynamic left ventricular function as determined by Starling function curves
The diaphragm rises about 4 cm during pregnancy (see Fig. 8-9). The subcostal angle widens appreciably as the transverse diameter of the thoracic cage increases about 2 cm. The thoracic circumference increases about 6 cm, but not sufficiently to prevent a reduction in the residual volume of air in the lungs created by the elevated diaphragm. Diaphragmatic excursion is actually greater during pregnancy than when nonpregnant.
A remarkable number of changes are observed in the urinary system as a result of pregnancy (Table 8-5) Kidney size increases slightly during pregnancy Bailey and Rolleston (1971), for example, found that the kidney was 15 cm longer during the early puerperium than when measured 6 months later The glomerular filtration rate (GFR) and renal plasma flow (RPF) increase early in pregnancy, the former as much as 50 percent by the beginning of the second trimester, and the latter not quite so much (Chesley, 1963; Dunlop, 1981) As shown in Figure 8-13, elevated glomerular filtration has been found by most investigators to persist to term, and this is despite that renal plasma flow decrease during late pregnancy Kallikrein, a tissue protease synthesized in cells of the distal renal tubule, is increased in several conditions associated with increased glomular perfusion in nonpregnant individuals Platts and colleagues (2000) studied urinary kallikrein excretion rates during human pregnancy and found increased excretion at 18 and 34 weeks which returned to nonpregnant levels at term The significance of these normal fluctuations in renal kallikrein excretion rates during pregnancy remains unknown
Most studies of renal function conducted during pregnancy have been performed while the subjects were supine, a position that late in pregnancy may produce marked systemic hemodynamic changes that lead to alterations in several aspects of renal function. Late in pregnancy, for instance, urinary flow and sodium excretion average less than half the excretion rate in the supine position compared with the lateral recumbent position.
Although posture clearly affects sodium and water excretion in late pregnancy, its impact on glomerular filtration and renal plasma flow is much more variable. For example, Chesley and Sloan (1964) found both to be reduced when the pregnant woman was in the supine position, whereas Dunlop (1976) identified inconsequential reduction. Pritchard (1955) detected decreases while supine compared with lateral recumbency in some, but not most of women studied in late pregnancy. Ezimokhai and associates (1981) reported that the late pregnancy decrease in renal plasma flow is not due simply to a positional effect.
LOSS OF NUTRIENTS. One unusual feature of the pregnancy-induced changes in renal excretion is the remarkably increased amounts of various nutrients in the urine. Amino acids and water-soluble vitamins are lost in the urine of pregnant women in much greater amounts than in nonpregnant women (Hytten and Leitch, 1971).
TESTS OF RENAL FUNCTION. During pregnancy the plasma concentrations of creatinine and urea normally decrease as a consequence of their increased glomerular filtration. At times, the urea concentration may be so low as to suggest impaired hepatic synthesis, which sometimes occurs with severe liver disease.
Creatinine clearance is a useful test to estimate renal function in pregnancy provided that complete urine collection is made over an accurately timed period. Urine concentration tests may give results that are misleading (Davison and colleagues, 1981). During the day, pregnant women tend to accumulate water in the form of dependent edema; and at night, while recumbent, they mobilize this fluid and excrete it via the kidneys. This reversal of the usual nonpregnant diurnal pattern of urinary flow causes nocturia, and the urine is more dilute than in the nonpregnant state. Failure of a pregnant woman to excrete concentrated urine after withholding fluids for approximately 18 hours does not signify renal damage. In fact, the kidney in these circumstances functions perfectly normally by excreting mobilized extracellular fluid of relatively low osmolality.
URINALYSIS. Glucosuria during pregnancy is not necessarily abnormal. The appreciable increase in glomerular filtration, together with impaired tubular reabsorptive capacity for filtered glucose, accounts in most cases for the glucosuria (Davison and Hytten, 1975). Chesley (1963) calculated that for these reasons alone about one sixth of all pregnant women should spill glucose in the urine. Even though glucosuria is common during pregnancy, the possibility of diabetes mellitus should not be ignored when it is identified.
Proteinuria is normally not evident during pregnancy except occasionally in slight amounts during or soon after vigorous labor. Higby and associates (1994) measured protein excretion in 270 normal women throughout pregnancy. Their mean 24-hour excretion was 115 mg, and the upper 95 percent confidence limit was 260 mg/day. There were no significant differences by trimester (Fig. 8-14). They also showed that albumin excretion is minimal and ranges from 5 to 30 mg/day. Lopez-Espinoza and colleagues (1986) measured serial albumin excretion using a sensitive radioimmunoassay in 14 healthy pregnant women. There was a slight rise from a median of 7 to 18 mg/24 hours from early to late pregnancy, however, albuminuria was not detected using conventional testing methods.
Hematuria, if not the result of contamination during collection, is compatible with a diagnosis of urinary tract disease (Chap. 47, p. 1259). Difficult labor and delivery, of course, can cause hematuria because of trauma to the lower urinary tract.
HYDRONEPHROSIS AND HYDROURETER. After the uterus rises completely out of the pelvis, it rests upon the ureters, compressing them at the pelvic brim. Increased intraureteral tonus above this level compared with that of the pelvic portion of the ureter has been identified (Rubi and Sala, 1968). Schulman and Herlinger (1975) found ureteral dilatation to be greater on the right side in 86 percent of pregnant women studied (Fig. 8-15). The unequal degrees of dilatation may result from a cushioning provided the left ureter by the sigmoid colon and perhaps from greater compression of the right ureter as the consequence of dextrorotation of the uterus. The right ovarian vein complex, which is remarkably dilated during pregnancy, lies obliquely over the right ureter and may contribute significantly to right ureteral dilatation.
Another possible mechanism causing hydronephrosis and hydroureter is from an effect of progesterone. Major support for this concept was provided by Van Wagenen and Jenkins (1939), who described further ureteral dilatation after removal of the monkey fetus but with the placenta left in situ. The relatively abrupt onset of dilatation in women at midpregnancy is more consistent with ureteral compression from an enlarging uterus rather than a hormonal effect.
Elongation accompanies distention of the ureter, which is frequently thrown into curves of varying size, the smaller of which may be sharply angulated. These so-called kinks are poorly named, because the term connotes obstruction. They are usually single or double curves, which when viewed in the radiograph taken in the same plane as the curve, appear as more or less acute angulations of the ureter (Fig. 8-15). Another exposure at right angles nearly always identifies them to be more gentle curves rather than kinks. The ureter undergoes not only elongation but frequently lateral displacement by the pressure of the enlarged uterus.
Thorp and colleagues (1999) studied 123 pregnant women throughout pregnancy and the puerperium and found that pregnancy was associated with an increase in urinary incontinence When women were asked to compare urinary tract function week by week throughout their pregnancies, they reported a steady deterioration in perceived bladder function Indeed, objective measures of urinary frequency and total daily urinary output increased throughout pregnancy
There are few significant anatomical changes in the bladder before 12 weeks. From that time onward, however, the increased size of the uterus, together with the hyperemia that affects all pelvic organs, and the hyperplasia of the muscle and connective tissues, elevates the bladder trigone and causes thickening of its posterior, or intraureteric, margin. Continuation of this process to the end of pregnancy produces marked deepening and widening of the trigone. The bladder mucosa undergoes no change other than an increase in the size and tortuosity of its blood vessels.
Using urethrocystometry, Iosif and colleagues (1980) found that bladder pressure in primigravidas increased from 8 cm H2O early in pregnancy to 20 cm H2O at term. To compensate for reduced bladder capacity, absolute and functional urethral lengths increased by 6.7 and 4.8 mm, respectively. Finally, to preserve continence, maximal intraurethral pressure increased from 70 to 93 cm H2O. Still, the majority of women will experience their initial episode of urinary incontinence during pregnancy. Indeed, loss of urine is always high in the differential diagnosis of the woman presenting with a question of ruptured membranes.
Toward the end of pregnancy, particularly in nulliparas in whom the presenting part often engages before labor, the entire base of the bladder is pushed forward and upward, converting the normal convex surface into a concavity. As a result, difficulties in diagnostic and therapeutic procedures are greatly increased. In addition, the pressure of the presenting part impairs the drainage of blood and lymph from the base of the bladder, often rendering the area edematous, easily traumatized, and probably more susceptible to infection. Both urethral pressure and length have been shown to be decreased in women following vaginal but not abdominal delivery (Van Geelen and co-workers, 1982). These investigators suggest that a weakness of the urethral sphincter mechanism due to pregnancy or delivery may play a role in the pathogenesis of urinary stress incontinence.
Normally there is little residual urine in nulliparas, but occasionally it develops in the multipara with relaxed vaginal walls and a cystocele. Incompetence of the ureterovesical valve may supervene, with the consequent probability of vesicoureteral reflux of urine.
As pregnancy progresses, the stomach and intestines are displaced by the enlarging uterus. As the result of the positional changes in these viscera, the physical findings in certain diseases are altered. The appendix, for instance, is usually displaced upward and somewhat laterally as the uterus enlarges, and at times it may reach the right flank.
Gastric emptying and intestinal transit times are delayed in pregnancy because of hormonal or mechanical factors. For example, this may be the result of progeste-rone or decreased levels of motilin, a hormonal peptide known to have smooth-muscle stimulating effects (Christofides and associates, 1982). Macfie and colleagues (1991) studied gastric emptying times using acetaminophen absorption and found these to be unchanged during each trimester and compared with nonpregnant women. During labor, however, and especially after administration of analgesic agents, gastric-emptying time is typically prolonged appreciably. A major danger of general anesthesia for delivery is regurgitation and aspiration of either food-laden or highly acidic gastric contents (Chap. 15, p. 366).
Pyrosis (heartburn) is common during pregnancy and is most likely caused by reflux of acidic secretions into the lower esophagus (Chap. 48, p. 1276). The altered position of the stomach probably contributes to its frequent occurrence; however, lower esophageal sphincter tone is also decreased. Intraesophageal pressures are lower and intragastric pressures higher in pregnant women. At the same time, esophageal peristalsis has lower wave speed and lower amplitude (Ulmsten and Sundstrom, 1978).
The gums may become hyperemic and softened during pregnancy and may bleed when mildly traumatized, as with a toothbrush. A focal, highly vascular swelling of the gums, the so-called epulis of pregnancy, develops occasionally but typically regresses spontaneously after delivery. Most evidence indicates that pregnancy does not incite tooth decay.
Hemorrhoids are fairly common during pregnancy. They are caused in large measure by constipation and the elevated pressure in veins below the level of the enlarged uterus.
Although the liver in some animals increases remarkably in size during pregnancy, there is no evidence for such an increase during human pregnancy (Combes and Adams, 1971) Histological evaluation of liver biopsies, including examination with the electron microscope, have shown no distinct changes in liver morphology in normal pregnant women (Ingerslev and Teilum, 1946)
Some of the laboratory tests used to evaluate hepatic function yield appreciably different results during normal pregnancy. Moreover, some of those changes are similar to those in patients with liver disease. Total alkaline phosphatase activity in serum almost doubles during normal pregnancy, but much of the increase is attributable to heat-stable placental alkaline phosphatase isozymes. Serum aspartate transaninase (AST), alanine transaminase (ALT), gamma glutamyl transferase (GGT), and bilirubin levels are slightly lower during pregnancy
Mendenhall (1970) reconfirmed decreased plasma albumin concentration, showing it to average 3.0 g/dL late in pregnancy compared with 4.3 g/dL in nonpregnant women. Total albumin is increased, however, because of a greater volume of distribution. The reduction in albumin concentrations, combined with a normal slight increase in plasma globulins, results in a decrease in the albumin-to-globulin ratio similar to that seen in certain hepatic diseases.
Plasma cholinesterase activity is reduced during normal pregnancy. The magnitude of the decrease is about the same as the decrease in the concentration of albumin (Kambam and associates, 1988; Pritchard, 1955). Leucine aminopeptidase activity is markedly elevated in serum from pregnant women. The increase results from the appearance of a pregnancy-specific enzyme (or enzymes) with distinct substrate specificities (Song and Kappas, 1968). Pregnancy-induced aminopeptidase has oxytocinase and vasopressinase activity.
There is considerable alteration of gallbladder function during pregnancy Braverman and co-workers (1980), using ultrasonography, found impaired gallbladder contraction and high residual volume It has been suggested that progesterone impairs gallbladder contraction by inhibiting cholecystokinin-mediated smooth muscle stimulation, the primary regulator of gallbladder contraction Impaired gallbladder contraction leads to stasis, and this, associated with the increased cholesterol saturation of pregnancy, at least partially explains the increased prevalence of cholesterol stones in women who have been pregnant many times
The effects of pregnancy on maternal bile acid serum concentrations have been incompletely characterized despite the long-acknowledged propensity for pregnancy to cause intrahepatic cholestasis and pruritus gravidarum from retained bile salts (Chap. 48, p. 1283 and Chap. 54, p. 1431). Cholestasis has been linked to high circulating levels of estrogen, which inhibit intraductal transport of bile acids (Simon and colleagues, 1996). Leslie and associates (2000), however, compared circulating estrogen levels in normal pregnant women with those of women with cholestasis. They found the latter group to have significantly lower plasma estrogen levels as well as impaired fetal production of dehydro-epiandrosterone (DHEA), which is the precursor to placental estrogen production. The significance of this recent finding is unclear.
THE BONY PELVIS
In both women and men the pelvis forms the bony ring through which body weight is transmitted to the lower extremities, but in women it has a special form that adapts it to childbearing. The pelvis is composed of four bones: the sacrum, coccyx, and two innominate bones. Each innominate bone is formed by the fusion of the ilium, ischium, and pubis. The innominate bones are joined to the sacrum at the sacroiliac synchondroses and to one another at the symphysis pubis.
The false pelvis lies above the linea terminalis and the true pelvis below this anatomical boundary (Fig. 3-20). The false pelvis is bounded posteriorly by the lumbar vertebrae and laterally by the iliac fossae, and in front the boundary is formed by the lower portion of the anterior abdominal wall.
The true pelvis is the portion important in childbearing. It is bounded above by the promontory and alae of the sacrum, the linea terminalis, and the upper margins of the pubic bones, and below by the pelvic outlet. The cavity of the true pelvis can be described as an obliquely truncated, bent cylinder with its greatest height posteriorly, because its anterior wall at the symphysis pubis measures about 5 cm and its posterior wall about 10 cm . With the woman upright, the upper portion of the pelvic canal is directed downward and backward, and its lower course curves and becomes directed downward and forward.
The walls of the true pelvis are partly bony and partly ligamentous. The posterior boundary is the anterior surface of the sacrum, and the lateral limits are formed by the inner surface of the ischial bones and the sacrosciatic notches and ligaments. In front the true pelvis is bounded by the pubic bones, the ascending superior rami of the ischial bones, and the obturator foramina.
The sidewalls of the true pelvis of the normal adult woman converge somewhat; therefore, if the planes of the ischial bones were extended downward, they would meet near the knee. Extending from the middle of the posterior margin of each ischium are the ischial spines. The ischial spines are of great obstetrical importance because the distance between them usually represents the shortest diameter of the pelvic cavity. They also serve as valuable landmarks in assessing the level to which the presenting part of the fetus has descended into the true pelvis
The sacrum forms the posterior wall of the pelvic cavity. Its upper anterior margin corresponds to the body of the first sacral vertebra and is designated as the promontory. The promontory may be felt on vaginal examination in small pelves and can provide a landmark for clinical pelvimetry. Normally the sacrum has a marked vertical and a less pronounced horizontal concavity, which in abnormal pelves may undergo important variations. A straight line drawn from the promontory to the tip of the sacrum usually measures 10 cm, whereas the distance along the concavity averages 12 cm.
The descending inferior rami of the pubic bones unite at an angle of 90 to 100 degrees to form a rounded arch under which the fetal head must pass.
SYMPHYSIS PUBIS. Anteriorly, the pelvic bones are joined together by the symphysis pubis. This structure consists of fibrocartilage and the superior and inferior pubic ligaments; the latter is frequently designated the arcuate ligament of the pubis (Fig. 3-23). The symphysis has a certain degree of mobility, which increases during pregnancy. This fact was demonstrated by Budin (1897), who reported that if a finger was inserted into the vagina of a pregnant woman and she then walked, the ends of the pubic bones could be felt moving up and down with each step.
SACROILIAC JOINTS. Posteriorly the pelvic bones are joined by the articulations between the sacrum and the iliac portion of the innominate bones (sacroiliac joints). These joints also have a certain degree of mobility.
RELAXATION OF THE PELVIC JOINTS. During pregnancy, relaxation of these joints likely results from hormonal changes. Abramson and co-workers (1934) observed that relaxation of the symphysis pubis commenced in women in the first half of pregnancy and increased during the last 3 months. These investigators reported that regression of relaxation began immediately after parturition and was completed within 3 to 5 months. The symphysis pubis also increases in width during pregnancy (more in multiparas than in primigravidas), and returns to normal soon after delivery. By careful radiographic studies, Borell and Fernstrom (1957) demonstrated that the rather marked mobility of the pelvis of women at term was caused by an upward gliding movement of the sacroiliac joint. The displacement, which is greatest in the dorsal lithotomy position, may increase the diameter of the outlet by 1.5 to 2.0 cm. This is the main justification for placing a woman in this position for a vaginal delivery. It should be noted, however, that the increase in the diameter of the pelvic outlet occurs only if the sacrum is allowed to rotate posteriorly, that is, only if the sacrum is not forced anteriorly by the weight of the maternal pelvis against the delivery table or bed (Russell, 1969, 1982). This is likely the reason that the McRoberts maneuver often is successful in releasing an obstructed shoulder in a case of shoulder dystocia (Chap. 19, p. 461). Gardosi and co-workers (1989) reported in a randomized controlled trial that a modified squatting position in the second stage of labor resulted in a shorter second stage and fewer perineal lacerations. However, there was an increase in labial lacerations. The authors attributed the "success" of the method to increasing the interspinous diameter and the diameter of the pelvic outlet (Russell, 1969, 1982) as well as to improving the "pushing efforts" of the laboring woman. Although these observations are unconfirmed, such a squatting position is assumed by many primitive women as the usual position for birth (Gardosi and associates, 1989; Russell, 1982).
PLANES AND DIAMETERS OF THE PELVIS
Because of its complex shape, it is difficult to describe the exact location of an object within the pelvis. For convenience, therefore, the pelvis is described as having four imaginary planes:
1. The plane of the pelvic inlet
2. The plane of the midpelvis (least pelvic dimensions).
3. The plane of greatest pelvic dimensions.
4. The plane of the pelvic outlet
Because this last plane has no obstetrical significance, it is not considered further.
PELVIC INLET. The pelvic inlet (superior strait) is bounded posteriorly by the promontory and alae of the sacrum, laterally by the linea terminalis, and anteriorly by the horizontal rami of the pubic bones and symphysis pubis. The configuration of the inlet of the human female pelvis typically is more nearly round than ovoid. Caldwell and co-workers (1934) identified radiographically a nearly round or gynecoid pelvic inlet in approximately 50 percent of the pelves of white women.
Four diameters of the pelvic inlet are usually described: anteroposterior, transverse, and two obliques. The obstetrically important anteroposterior diameter is the shortest distance between the promontory of the sacrum and the symphysis pubis, and is designated the obstetrical conjugate. Normally, the obstetrical conjugate measures 10 cm or more, but it may be considerably shortened in abnormal pelves.
The transverse diameter is constructed at right angles to the obstetrical conjugate and represents the greatest distance between the linea terminalis on either side. It usually intersects the obstetrical conjugate at a point about 4 cm in front of the promontory. The segment of the obstetrical conjugate from the intersection of these two lines to the promontory is designated the posterior sagittal diameter of the inlet.
Each of the oblique diameters extends from one of the sacroiliac synchondroses to the iliopectineal eminence on the opposite side of the pelvis. They average just under 13 cm and are designated right and left, according to whether they originate at the right or left sacroiliac synchondrosis.
The anteroposterior diameter of the pelvic inlet that has been identified as the true conjugate does not represent the shortest distance between the promontory of the sacrum and symphysis pubis. The shortest distance is the obstetrical conjugate, which is the shortest anteroposterior diameter through which the head must pass in descending through the pelvic inlet.
The obstetrical conjugate cannot be measured directly with the examining fingers; therefore, various instruments have been designed in an effort to obtain such a measurement. Unfortunately, none of these instruments has proven to be reliable. For clinical purposes, it is sufficient to estimate the length of the obstetrical conjugate indirectly. This is accomplished by measuring the distance from the lower margin of the symphysis to promontory of the sacrum, that is, the diagonal conjugate), and subtracting 1.5 to 2 cm from the result, according to the height and inclination of the symphysis pubis
MIDPELVIS. The midpelvis at the level of the ischial spines (midplane, or plane of least pelvic dimensions) is of particular importance following engagement of the fetal head in obstructed labor. The interspinous diameter, 10 cm or somewhat more, is usually the smallest diameter of the pelvis. The anteroposterior diameter, through the level of the ischial spines, normally measures at least 11.5 cm. The posterior component (posterior sagittal diameter), between the sacrum and the line created by the interspinous diameter, is usually at least 4.5 cm.
PELVIC OUTLET. The outlet of the pelvis consists of two approximately triangular areas not in the same plane but having a common base, which is a line drawn between the two ischial tuberosities (Fig. 3-26). The apex of the posterior triangle is at the tip of the sacrum, and the lateral boundaries are the sacrosciatic ligaments and the ischial tuberosities. The anterior triangle is formed by the area under the pubic arch. Three diameters of the pelvic outlet usually are described: the anteroposterior, transverse, and posterior sagittal. The anteroposterior diameter (9.5 to 11.5 cm) extends from the lower margin of the symphysis pubis to the tip of the sacrum. The transverse diameter (11 cm) is the distance between the inner edges of the ischial tuberosities. The posterior sagittal diameter extends from the tip of the sacrum to a right-angle intersection with a line between the ischial tuberosities. The normal posterior sagittal diameter of the outlet usually exceeds 7.5 cm
In obstructed labors caused by a narrowing of the midpelvis or pelvic outlet, the prognosis for vaginal delivery often depends on the length of the posterior sagittal diameter of the pelvic outlet.
In the past, x-ray pelvimetry was used frequently in women with suspected cephalopelvic disproportion or fetal malpresentation. Pelvic radiography also was used as an aid in understanding the general architecture and configuration of the pelvis, as well as its size. Caldwell and Moloy (1933, 1934) developed a classification of the pelvis that is still used. The classification is based upon the shape of the pelvis, and familiarity with the classification helps the physician to understand the mechanisms of labor in normally and abnormally shaped pelves.
PELVIC SIZE AND ITS CLINICAL ESTIMATION
PELVIC INLET MEASUREMENTS DIAGONAL CONJUGATE. In many abnormal pelves, the anteroposterior diameter of the pelvic inlet (the obstetrical conjugate) is considerably shortened. It is important therefore to determine its length, but this measurement can be obtained only by radiographic techniques. The distance from the sacral promontory to the lower margin of the symphysis pubis (the diagonal conjugate), however, can be measured clinically. The examiner introduces two fingers into the vagina; before measuring the diagonal conjugate, the mobility of the coccyx is evaluated and the anterior surface of the sacrum is palpated. The mobility of the coccyx is tested by palpating it with the fingers in the vagina and attempting to move it to and fro. The anterior surface of the sacrum is then palpated from below upward, and its vertical and lateral curvatures are noted. In normal pelves only the last three sacral vertebrae can be felt without indenting the perineum, whereas in markedly contracted pelves the entire anterior surface of the sacrum usually is readily accessible. Occasionally, the mobility of the coccyx and the anatomical features of the lower sacrum may be defined more easily by rectal examination.
Except in extreme degrees of pelvic contraction, in order to reach the promontory of the sacrum, the examiner's elbow must be depressed and, unless the examiner's fingers are unusually long, the perineum forcibly indented by the knuckles of the examiner's third and fourth fingers. The index and the second fingers, held firmly together, are carried up and over the anterior surface of the sacrum. By sharply depressing the wrist, the promontory may be felt by the tip of the second finger as a projecting bony margin. With the finger closely applied to the most prominent portion of the upper sacrum, the vaginal hand is elevated until it contacts the pubic arch; and the immediately adjacent point on the index finger is marked. The hand is withdrawn, and the distance between the mark and the tip of the second finger is measured. The diagonal conjugate is determined, and the obstetrical conjugate is computed by subtracting 1.5 to 2.0 cm, depending upon the height and inclination of the symphysis pubis. If the diagonal conjugate is greater than 11.5 cm, it is justifiable to assume that the pelvic inlet is of adequate size for vaginal delivery of a normal-sized fetus.
Transverse contraction of the inlet can be measured only by imaging pelvimetry. Such a contraction is possible even in the presence of an adequate anteroposterior diameter.
ENGAGEMENT. This refers to the descent of the biparietal plane of the fetal head to a level below that of the pelvic inlet (Figs. 3-30 and 3-31). When the biparietal, or largest, diameter of the normally flexed fetal head has passed through the inlet, the head is engaged. Although engagement of the fetal head usually is regarded as a phenomenon of labor, in nulliparas it commonly occurs during the last few weeks of pregnancy. When it does so, it is confirmatory evidence that the pelvic inlet is adequate for that fetal head. With engagement, the fetal head serves as an internal pelvimeter to demonstrate that the pelvic inlet is ample for that fetus.
Whether the head is engaged may be ascertained by rectal or vaginal examination or by abdominal palpation. After gaining experience with vaginal examination, it becomes relatively easy to locate the station of the lowermost part of the fetal head in relation to the level of the ischial spines. If the lowest part of the occiput is at or below the level of the spines, the head usually, but not always, is engaged, because the distance from the plane of the pelvic inlet to the level of the ischial spines is approximately 5 cm in most pelves, and the distance from the biparietal plane of the unmolded fetal head to the vertex is about 3 to 4 cm. Under these circumstances, the vertex cannot possibly reach the level of the spines unless the biparietal diameter has passed the inlet, or unless there has been considerable elongation of the fetal head because of molding and formation of a caput succedaneum.
Engagement may be ascertained less satisfactorily by abdominal examination. If the biparietal plane of a term-sized infant has descended through the inlet, the examining fingers cannot reach the lowermost part of the head. Thus, when pushed downward over the lower abdomen, the examining fingers will slide over that portion of the head proximal to the biparietal plane (nape of the neck) and diverge. Conversely, if the head is not engaged, the examining fingers can easily palpate the lower part of the head and will converge
Fixation of the fetal head is its descent through the pelvic inlet to a depth that prevents its free movement in any direction when pushed by both hands placed over the lower abdomen. Fixation is not necessarily synonymous with engagement. Although a head that is freely movable on abdominal examination cannot be engaged, fixation of the head is sometimes seen when the biparietal plane is still 1 cm or more above the pelvic inlet, especially if the head is molded appreciably.
Although engagement is conclusive evidence of an adequate pelvic inlet for that fetal head, its absence is by no means always indicative of pelvic contraction.
PELVIC OUTLET MEASUREMENTS. An important dimension of the pelvic outlet that is accessible for clinical measurement is the diameter between the ischial tuberosities, variously called the biischial diameter, intertuberous diameter, and transverse diameter of the outlet. A measurement of over 8 cm is considered normal. The measurement of the transverse diameter of the outlet can be estimated by placing a closed fist against the perineum between the ischial tuberosities, after first measuring the width of the closed fist. Usually the closed fist is wider than 8 cm. The shape of the subpubic arch also can be evaluated at the same time by palpating the pubic rami from the subpubic region toward the ischial tuberosities.
MIDPELVIS ESTIMATION. Clinical estimation of midpelvis capacity by any direct form of measurement is not possible. If the ischial spines are quite prominent, the sidewalls are felt to converge, and the concavity of the sacrum is very shallow; if the biischial diameter of the outlet is less than 8 cm, then suspicion is aroused about a contraction in this region.
From an obstetrical viewpoint, the size of the fetal head is important because an essential feature of labor is the adaptation between the fetal head and the maternal bony pelvis. Only a comparatively small part of the head at term is represented by the face; the rest is composed of the firm skull, which is made up of two frontal, two parietal, and two temporal bones, along with the upper portion of the occipital bone and the wings of the sphenoid.
These bones are not united rigidly, but rather are separated by membranous spaces, called sutures The most important sutures are the frontal, between the two frontal bones; the sagittal, between the two parietal bones; the two coronal, between the frontal and parietal bones; and the two lambdoid, between the posterior margins of the parietal bones and upper margin of the occipital bone. With a vertex presentation, all of the sutures are palpable during labor except the temporal sutures, which are situated on either side between the inferior margin of the parietal and upper margin of the temporal bones, covered by soft parts, and cannot be felt in the living fetus.
Where several sutures meet, an irregular space forms, which is enclosed by a membrane and designated as a fontanel (Fig. 7-6). The three most clinically important fontanels are the greater, the lesser, and the temporal fontanels. The greater or anterior fontanel is a lozenge-shaped space that is situated at the junction of the sagittal and the coronal sutures. The lesser or posterior fontanel is represented by a small triangular area at the intersection of the sagittal and lambdoid sutures. Both can be palpated readily during labor. The localization of these fontanels gives important information concerning the presentation and position of the fetus. The temporal, or casserian fontanels, situated at the junction of the lambdoid and temporal sutures, have no diagnostic significance.
It is customary to measure certain critical diameters and circumferences of newborn head (Fig. 7-7).
The diameters most frequently used, and the average lengths thereof, are as follows:
1. The occipitofrontal (11.5 cm), which follows a line extending from a point just above the root of the nose to the most prominent portion of the occipital bone.
2. The biparietal (9.5 cm), the greatest transverse diameter of the head, which extends from one parietal boss to the other.
3. The bitemporal (8.0 cm), the greatest distance between the two temporal sutures.
4. The occipitomental (12.5 cm), from the chin to the most prominent portion of the occiput.
5. The suboccipitobregmatic (9.5 cm), which follows a line drawn from the middle of the large fontanel to the undersurface of the occipital bone just where it joins the neck ).
The greatest circumference of the head, which corresponds to the plane of the occipitofrontal diameter, averages 34.5 cm, a size too large to fit through the pelvis without flexion. The smallest circumference, corresponding to the plane of the suboccipitobregmatic diameter, is 32 cm. As a rule, white infants have larger heads than nonwhite infants; boys, somewhat larger than girls; and the infants of multiparas, larger heads than those of nulliparas. The bones of the cranium are normally connected only by a thin layer of fibrous tissue which allows considerable shifting or sliding of each bone to accommodate the size and shape of the maternal pelvis. This intrapartum process is termed molding. Because of the varying mobility of the bones of the skull and varying presentations of the fetal head relative to the pelvis, a variety of newborn head shapes are possible. The head position and degree of skull ossification result in a spectrum of cranial plasticity from minimal to great and, in some cases, undoubtedly contributes to fetopelvic disproportion, a leading indication for cesarean delivery (Chap. 18, p. 440).
FETAL BRAIN. There is a steady gestational age-related change in the appearance and function of the fetal brain (Fig. 7-8). It is therefore possible to identify fetal age rather precisely from its external appearance (Dolman, 1977). Myelination of the ventral roots of the cerebrospinal nerves and brainstem begins at approximately 6 months, but the major portion of myelination occurs after birth. The lack of myelin and the incomplete ossification of the fetal skull permit the structure of the brain to be seen with ultrasound throughout gestation.
LIE, PRESENTATION, ATTITUDE, AND POSITION
By convention, fetal orientation is described with respect to fetal lie, presentation, attitude, and position. These can be established clinically by abdominal palpation, vaginal examination, and auscultation, or by technical means using sonography or x-ray. Clinical assessment is less accurate, or even sometimes impossible to perform and interpret in obese women.
The lie is the relation of the long axis of the fetus to that of the mother, and is either longitudinal or transverse.
Occasionally, the fetal and the maternal axes may cross at a 45-degree angle, forming an oblique lie, which is unstable and always becomes longitudinal or transverse during the course of labor. Longitudinal lies are present in over 99 percent of labors at term. Predisposing factors for transverse lies include multiparity, placenta previa, hydramnios, and uterine anomalies (Gemer and Segal, 1994).
The presenting part is that portion of the body of the fetus that is either foremost within the birth canal or in closest proximity to it.
The presenting part can be felt through the cervix on vaginal examination. The presenting part determines the presentation. Accordingly, in longitudinal lies, the pre-senting part is either the fetal head or breech, creating cephalic and breech presentations, respectively. When the fetus lies with the long axis transversely, the shoulder is the presenting part. Thus, a shoulder presentation is felt through the cervix on vaginal examination.
CEPHALIC PRESENTATION. These are classified according to the relation of the head to the body of the fetus (Fig. 12-1). Ordinarily the head is flexed sharply so that the chin is in contact with the thorax. In this circumstance, the occipital fontanel is the presenting part, and such a presentation is usually referred to as a vertex or occiput presentation. Actually, the vertex lies just in front of the occipital fontanel, and the occiput just behind the fontanel, as illustrated in Figure 7-7 (p. 136). Much less commonly, the fetal neck may be sharply extended so that the occiput and back come in contact and the face is foremost in the birth canal—face presentation. The fetal head may assume a position between these extremes, partially flexed in some cases, with the anterior (large) fontanel, or bregma, presenting (sinciput presentation), or partially extended in other cases, with the brow presenting (brow presentation). These latter two presentations are usually transient. As labor progresses, sinciput and brow presentations are almost always converted into vertex or face presentations by flexion or extension, respectively.
BREECH PRESENTATION. When the fetus presents as a breech, there are three general configurations. When the thighs are flexed and the legs extended over the anterior surfaces of the body, this is termed a frank breech presentation (Fig. 12-2). If the thighs are flexed on the abdomen and the legs upon the thighs, this is a complete breech presentation (Fig. 12-3). If one or both feet, or one or both knees, are lowermost, then there is an incomplete, or footling, breech presentation (Fig. 12-4).
FETAL ATTITUDE OR POSTURE
In the later months of pregnancy the fetus assumes a characteristic posture described as attitude or habitus As a rule, the fetus forms an ovoid mass that corresponds roughly to the shape of the uterine cavity. The fetus becomes folded or bent upon itself in such a manner that the back becomes markedly convex; the head is sharply flexed so that the chin is almost in contact with the chest; the thighs are flexed over the abdomen; the legs are bent at the knees; and the arches of the feet rest upon the anterior surfaces of the legs. In all cephalic presentations, the arms are usually crossed over the thorax or become parallel to the sides, and the umbilical cord lies in the space between them and the lower extremities. This characteristic posture results from the mode of growth of the fetus and its accommodation to the uterine cavity.
Abnormal exceptions to this attitude occur as the fetal head becomes progressively more extended from the vertex to the face presentation. This results in a progressive change in fetal attitude from a convex (flexed) to a concave (extended) contour of the vertebral column.
Position refers to the relation of an arbitrarily chosen portion of the fetal presenting part to the right or left side of the maternal birth canal. Accordingly, with each presentation there may be two positions, right or left. The fetal occiput, chin (mentum), and sacrum are the determining points in vertex, face, and breech presentations, respectively
VARIETIES OF PRESENTATION AND POSITION
For still more accurate orientation, the relation of a given portion of the presenting part to the anterior, transverse, or posterior portion of the maternal pelvis is considered. Because there are two positions, it follows that there must be three varieties for each position (either right or left), and six varieties for each presentation (three right and three left). Because the presenting part may be in either the left or right position, there are left and right occipital, left and right mental, and left and right sacral presentations, abbreviated as LO and RO, LM and RM, and LS and RS, respectively. Because the presenting part in each of the two positions may be directed anteriorly (A), transversely (T), or posteriorly (P), there are six varieties of each of these three presentations. Thus, in an occiput presentation, the presentation, position, and variety may be abbreviated in clockwise fashion as:
In shoulder presentations, the acromion (scapula) is the portion of the fetus arbitrarily chosen for orientation with the maternal pelvis. One example of the terminology sometimes employed for the purpose is illustrated in Figure 12-9. The acromion or back of the fetus may be directed either posteriorly or anteriorly and superiorly or inferiorly (Chap. 19, p. 455). Because it is impossible to differentiate exactly the several varieties of shoulder presentation by clinical examination, and because such differentiation serves no practical purpose, it is customary to refer to all transverse lies simply as shoulder presentations. Another term used is transverse lie, with back up or back down.
FREQUENCY OF THE VARIOUS PRESENTATIONS AND POSITIONS
At or near term the incidence of the various presentations is approximately as follows: vertex, 96 percent; breech, 3.5 percent; face, 0.3 percent; and shoulder, 0.4 percent. About two thirds of all vertex presentations are in the left occiput position, and a third in the right.
Although the incidence of breech presentation is only a little over 3 percent at term (see Table 19-1), it is much greater earlier in pregnancy. Scheer and Nubar (1976), using ultrasonography, found the incidence of breech presentation to be 14 percent between 29 and 32 weeks' gestation. Subsequently, the breech converted spontaneously to vertex in increasingly higher percentages as term approached.
There are several explanations of why the term fetus usually presents by the vertex. The most logical is because the uterus is piriform shaped. Although the fetal head at term is slightly larger than the breech, the entire podalic pole of the fetus—that is, the breech and its flexed extremities—is bulkier and more movable than the cephalic pole. The cephalic pole is comprised of the fetal head only.
Until about 32 weeks, the amnionic cavity is large compared with the fetal mass, and there is no crowding of the fetus by the uterine walls. At approximately this time, however, the ratio of amnionic fluid volume to fetal mass becomes altered by relative diminution of amnionic fluid and by increasing fetal size. As a result, the uterine walls are apposed more closely to the fetal parts. The fetal lie then is more nearly dependent upon the piriform shape of the uterus. The fetus, if presenting by the breech, often changes polarity in order to make use of the roomier fundus for its bulkier and more movable podalic pole. The high incidence of breech presentation in hydrocephalic fetuses is in accord with this theory, because in this circumstance the cephalic pole of the fetus is larger than the podalic pole.
The cause of breech presentation may be some circumstance that prevents the normal version from taking place, for example, a septum that protrudes into the uterine cavity. A peculiarity of fetal attitude, particularly extension of the vertebral column as seen in frank breeches, may also prevent the fetus from turning. If the placenta implants in the lower uterine segment, normal intrauterine anatomy is distorted. Also, any condition contributing to an abnormality of fetal muscle tone or movement may predispose to persistent breech presentations.
DIAGNOSIS OF FETAL PRESENTATION AND POSITION
Several methods can be used to diagnose fetal presentation and position. These include abdominal palpation, vaginal examination, combined examination, auscultation, and in certain doubtful cases, imaging studies such as ultrasonography, computerized tomographic scans (CT), or magnetic resonance imaging (MRI) studies.
ABDOMINAL PALPATION—LEOPOLD MANEUVERS
Abdominal examination should be conducted systematically employing the four maneuvers described by Leopold and Sporlin in 1894. The mother should be supine and comfortably positioned with her abdomen bared. During the first three maneuvers, the examiner stands at the side of the bed that is most convenient and faces the patient; the examiner reverses this position and faces her feet for the last maneuver. These maneuvers may be difficult if not impossible to perform and interpret if the patient is obese or if the placenta is anteriorly implanted.
FIRST MANEUVER. After outlining the contour of the uterus and ascertaining how nearly the fundus approaches the xiphoid cartilage, the examiner gently palpates the fundus with the tips of the fingers of both hands in order to define which fetal pole is present in the fundus. The breech gives the sensation of a large, nodular body, whereas the head feels hard and round and is more freely movable and ballottable.
SECOND MANEUVER. After determination of the pole that lies in the fundus, the palms are placed on either side of the abdomen, and gentle but deep pressure is exerted. On one side, a hard, resistant structure is felt, the back; and on the other, numerous small, irregular and mobile parts are felt, the fetal extremities. In women with a thin abdominal wall, the fetal extremities can often be differentiated, but in heavier women, only these irregular nodulations may be felt. In the presence of obesity or considerable amnionic fluid, the back is felt more easily by exerting deep pressure with one hand while counter-palpating with the other. By next noting whether the back is directed anteriorly, transversely, or posteriorly, a more accurate picture of the orientation of the fetus is obtained.
THIRD MANEUVER. Using the thumb and fingers of one hand, the lower portion of the maternal abdomen is grasped just above the symphysis pubis. If the presenting part is not engaged, a movable body will be felt, usually the head. The differentiation between head and breech is made as in the first maneuver. If the presenting part is not engaged, all that remains to be defined is the attitude of the head. If by careful palpation it can be shown that the cephalic prominence is on the same side as the small parts, the head must be flexed, and therefore the vertex is the presenting part. When the cephalic prominence of the fetus is on the same side as the back, the head must be extended. If the presenting part is deeply engaged, however, the findings from this maneuver are simply indicative that the lower fetal pole is fixed in the pelvis; the details are then defined by the last (fourth) maneuver.
FOURTH MANEUVER. The examiner faces the mother's feet and, with the tips of the first three fingers of each hand, exerts deep pressure in the direction of the axis of the pelvic inlet. If the head presents, one hand is arrested sooner than the other by a rounded body, the cephalic prominence, while the other hand descends more deeply into the pelvis. In vertex presentations, the prominence is on the same side as the small parts; and in face presentations, on the same side as the back. The ease with which the prominence is felt is indicative of the extent to which descent has occurred. In many instances, when the head has descended into the pelvis, the anterior shoulder may be differentiated readily by the third maneuver. In breech presentations, the information obtained from this maneuver is less precise.
Abdominal palpation can be performed throughout the latter months of pregnancy and during and between the contractions of labor. The findings provide information about the presentation and position of the fetus and the extent to which the presenting part has descended into the pelvis. For example, so long as the cephalic prominence is readily palpable, the vertex has not descended to the level of the ischial spines. The degree of cephalopelvic disproportion, moreover, can be gauged by evaluating the extent to which the anterior portion of the fetal head overrides the symphysis pubis. With experience, it is possible to estimate the size of the fetus, and even to map out the presentation of the second fetus in a twin gestation. According to Lydon-Rochelle and colleagues (1993), experienced clinicians accurately identify fetal malpresentation using Leopold maneuvers with a high sensitivity (88 percent), specificity (94 percent), positive predictive value (74 percent), and negative predictive value (97 percent).
Before labor, the diagnosis of fetal presentation and position by vaginal examination is often inconclusive, because the presenting part must be palpated through a closed cervix and lower uterine segment. With the onset of labor and after cervical dilatation, important information may be obtained. In vertex presentations, the position and variety are recognized by differentiation of the various sutures and fontanels. Face presentations are identified by the differentiation of the portions of the face. Breech presentations are identified by palpation of the sacrum and maternal ischial tuberosities.
In attempting to determine presentation and position by vaginal examination, it is advisable to pursue a definite routine, comprised of four maneuvers:
1. After the woman is prepared appropriately, two fingers of either gloved hand are introduced into the vagina and carried up to the presenting part. The differentiation of vertex, face, and breech is then accomplished readily.
2. If the vertex is presenting, the fingers are introduced into the posterior aspect of the vagina. The fingers are then swept forward over the fetal head toward the maternal symphysis . During this movement, the fingers necessarily cross the fetal sagittal suture. When it is felt, its course is outlined, with small and large fontanels at the opposite ends.
3. The positions of the two fontanels then are ascertained. The fingers are passed to the most anterior extension of the sagittal suture, and the fontanel encountered there is examined carefully and identified; then by a circular motion, the fingers are passed around the side of the head until the other fontanel is felt and differentiated .
4. The station, or extent to which the presenting part has descended into the pelvis, can also be established at this time .
Using these maneuvers, the various sutures and fontanels are located readily, and the possibility of error is lessened considerably. In face and breech presentations, errors are minimized, because the various parts are distinguished more readily.
While auscultation alone does not provide reliable information concerning fetal presentation and position, auscultatory findings sometimes reinforce results obtained by palpation. Ordinarily, fetal heart sounds are transmitted through the convex portion of the fetus that lies in intimate contact with the uterine wall. Therefore, fetal heart sounds are heard best through the fetal back in vertex and breech presentations, and through the fetal thorax in face presentations. The region of the abdomen in which fetal heart sounds are heard most clearly varies according to the presentation and the extent to which the presenting part has descended. In cephalic presentations, fetal heart sounds are best heard midway between the maternal umbilicus and the anterior superior spine of her ilium. In breech presentations, fetal heart tones are usually heard at or slightly above the umbilicus. In occipitoanterior positions, heart sounds usually are heard best a short distance from the midline; in the transverse varieties, they are heard more laterally; and in the posterior varieties, they are best heard well back in the flank.
Improvements in ultrasonic techniques have provided another diagnostic aid of particular value in doubtful cases. In obese women or in women whose abdominal walls are rigid, a sonographic examination may provide information to solve many diagnostic problems and lead to early recognition of a breech or shoulder presentation that might otherwise have escaped detection until late in labor. Employing ultrasonography, the fetal head and body can be located without the potential hazards of radiation. In some clinical situations, the information obtained radiographically far exceeds the minimal risk from a single x-ray exposure