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Obstentrics_Williams. FIGURE 4-8 Let ventricular mass of normal-weight and overweight women across pregnancy compared with 12-week postpartum (nonpregnant) values. (Data from Stewart, 2016.) output is appropriate andthus cardiac unction during pregnancy is eudynamic. Of the metabolic changes that occur in the heart during pregnancy, the eiciency of cardiac work-which is the product ofcardiac output X mean arterial pressure-is estimated to rise by approximately 25 percent. The associated increase in oxygen consumption is primarily accomplished via increased coronary blood low rather than increased extraction (Liu, 2014).


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Obstentrics_Williams. When measured in the lateral recumbent position at rest, cardiac output increases signiicantly beginning in earlypregnancy. It continues to rise and remains elevated during the remainder ofpregnancy. In a supine woman, a large uterus rather consistently compresses veins and diminishes venous return from the lower body. It also may compress the aorta (Bieniarz, 1968). In response, cardiac illing may be reduced and cardiac output ..J= FIGURE 4-9 Relationship between let ventricular stroke work index (LVSWI), cardiac output, and pulmonary capillary wedge pressure (PCWP) in 10 normal pregnant women in the third trimester. (Data from Clark, 1989.) TABLE 4-4. Central Hemodynamic Changes in 10 Normal Nulliparous Women Near Term and 6.2 ± 1.0 4.3 ± 0.9 +43% 18.0 ± 1.5 20.8 ± 1.0 -14% 10.5 ± 2.7 14.5 ± 2.5 -28% 48 ± 6 41 ± 8 NSC aMeasured in lateral recumbent position. bChanges significant unless NSC = no significant change.


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Obstentrics_Williams. bChanges significant unless NSC = no significant change. COP = colloid osmotic pressure; PCWP = pulmonary capillary wedge pressure. Data from Clark, 1989. lessened. Speciically, cardiac MR imaging shows that when a woman rolls from her back onto her left side, cardiac output at 26 to 30 weeks' gestation rises by approximately 20 percent and at 32 to 34 weeks by 10 percent (Nelson, 2015). Consistent with this, Simpson and James (2005) found that fetal oxygen saturation is approximately 10 percent higher ifa laboring woman lies in a lateral recumbent position compared with supine. Upon standing, cardiac output falls to the same degree as in the nonpregnant woman (Easterling, 1988).


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Obstentrics_Williams. In multifetal pregnancies, compared with singletons, maternal cardiac output is augmented further by almost another 20 percent. Ghi and coworkers (2015) used transthoracic echocardiography to show that irst-trimester cardiac output with twins (mean 5.50 Umin) was more than 20 percent greater than postpartum values. Cardiac output values in the second (6.31 L/min) and third (6.29 Umin) trimesters were increased an additional 15 percent compared with irst-trimester output. Left atrial and left ventricular end-diastolic diameters are also longer with twins due to augmented preload (Kametas, 2003). The greater heart rate and inotropic contractility imply that cardiovascular reserve is reduced in multifetal gestations. During first-stage labor, cardiac output rises moderately. During the second stage, with vigorous expulsive eforts, it is appreciably greater. The pregnancy-induced increase is lost ater delivery, at times dependent on blood loss.


Obstentrics_Williams

Obstentrics_Williams. During the second stage, with vigorous expulsive eforts, it is appreciably greater. The pregnancy-induced increase is lost ater delivery, at times dependent on blood loss. Clark and associates (1989) conducted invasive studies to measure hemodynamic function late in pregnancy (Table 4-4). Right heart catheterization was performed in 10 healthy nulliparas at 35 to 38 weeks' gestation, 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 dropped signiicantly, as did colloid osmotic pressure. Pulmonary capillary wedge pressure and central venous pressure did not change appreciably. Thus, although cardiac output rises, left ventricular function as measured by stroke work index remains similar to the nonpregnant normal range (see Fig. 4-9). Put another way, normal pregnancy is not a continuous "high-output" state.


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Obstentrics_Williams. Changes in posture afect arterial blood pressure (Fig. 4-10). Brachial artery pressure when sitting is lower than that when in the lateral recumbent supine position (Bamber, 2003). Additionally, systolic blood pressure is lower in the lateral positions compared with either the flexed sitting or supine positions (Armstrong, 2011). Arterial pressure usually declines to a nadir at 24 to 26 weeks' gestation and rises thereafter. Diastolic pressure decreases more than systolic. FIGURE 4-10 Sequential changes (±SEM) in blood pressure throughout pregnancy in 69 women in supine (blue lines) and left lateral recumbent positions (red lines). PP = postpartum. (Adapted from Wilson, 1980.) Morris and associates (2015) studied measures of vas cular compliance before pregnancy, during pregnancy, and postpartum. Compared with healthy nonpregnant controls, stifness, measured using pulse wave velocity, were observed between the prepregnant and the postpartum time periods.


Obstentrics_Williams

Obstentrics_Williams. sibly help explain why the risk of preeclampsia is reduced in subsequent pregnancies. Antecubital venous pressure remains unchanged during pregnancy. In the supine position, however, femoral venous pressure rises steadily, from approximately 8 mm Hg early in pregnancy to 24 mm Hg at term. Venous blood flow in the legs is retarded during pregnancy except when the lateral recumbent position is assumed (Wright, 1950). his tendency toward blood stagnation in the lower extremities during later pregnancy is attriburable to occlusion of the pelvic veins and inferior vena cava by the enlarged uterus. he elevated venous pressure returns to normal when the pregnant woman lies on her side and immediately after delivery (McLennan, 1943). These alterations contribute to the dependent edema frequently experienced and to the development of varicose veins in the legs and vulva, as well as hemorrhoids. These changes also predispose to deep-vein thrombosis.


Obstentrics_Williams

Obstentrics_Williams. In approximately 10 percent of women, supine compression of the great vessels by the uterus causes signiicant arterial hypotension, sometimes referred to as the supine hypotensive syndrome (Kinsella, 1994). Also when supine, uterine arterial pressure-and thus uterine blood flow-is signiicantly lower than that in the brachial artery. Evidence to support whether this directly afects fetal heart rate patterns in uncomplicated low-risk pregnancies is conlicting (Armstrong, 2011; Ibrahim, 2015; Tamas, 2007). Similar changes can also be seen with hemorrhage or with spinal analgesia. • Renin, Angiotensin II, and Plasma Volume


Obstentrics_Williams

Obstentrics_Williams. • Renin, Angiotensin II, and Plasma Volume The renin-angiotensin-aldosterone axis is intimately involved in blood pressure control via sodium and water balance. All components of this system show increased levels in normal pregnancy. Renin is produced by both the maternal kidney and the placenta, and greater amounts of renin substrate (angiotensinogen) are produced by both maternal and fetal liver. Elevated angiotensinogen levels result, in part, from augmented estrogen production during normal pregnancy and are important in irst-trimester blood pressure maintenance (Lumbers, 2014).


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Obstentrics_Williams. Gant and associates (1973) reported that nulliparas who remained normotensive became and stayed refractory to the pressor efects of infused angiotensin II. Conversely, those who ultimately became hypertensive developed, but then lost, this refractoriness. The diminished vascular responsiveness to angiotensin II may be progesterone related. Normally, pregnant women lose their acquired vascular refractoriness to angiotensin II within 15 to 30 minutes after the placenta is delivered. Large amounts of intramuscular progesterone given during late labor delay this diminishing refractoriness.


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Obstentrics_Williams. Large amounts of intramuscular progesterone given during late labor delay this diminishing refractoriness. At least two species of these-atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP)-are secreted by cardiomyocytes in response to chamber-wall stretching. These peptides regulate blood volume by provoking natriuresis, diuresis, and vascular smooth-muscle relaxation. In nonpregnant and pregnant patients, levels of BNP and of amino-terminal pro-brain natriuretic peptide (Nt pro-BNP), as well as newer analytes such as suppressor of tumorigenicity 2 (ST2), may be useful in screening for depressed left ventricular systolic function and determining chronic heart failure prognosis (Ghashghaei, 2016).


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Obstentrics_Williams. During normal pregnancy, plasma ANP and BNP levels are maintained in the nonpregnant range despite greater plasma volume (Yurteri-Kaplan, 2012). In one study, median BNP levels were stable across pregnancy with values <20 pg/mL (Resnik, 2005). BNP levels are increased in severe preeclamp sia, and this may be caused by cardiac strain from increased afterload (Afshani, 2013). It would appear that ANP-induced ume expansion and in the elevated plasma aldosterone concen trations characteristic of normal pregnancy.


Obstentrics_Williams

Obstentrics_Williams. Elevated prostaglandin production during pregnancy is thought to have a central role in control of vascular tone, blood pressure, and sodium balance. Renal medullary prostaglandin E2 synthesis is markedly elevated during late pregnancy and is presumed to be natriuretic. Levels of prostacyclin (PGI2), the principal prostaglandin of endothelium, also rise during late pregnancy. PGI2 regulates blood pressure and platelet function. It helps maintain vasodilation during pregnancy, and its deiciency is associated with pathological vasoconstriction (Shah, 2015). Thus, the ratio of PGI2 to thromboxane in maternal urine and blood is considered important in preeclampsia pathogenesis (Majed, 2012).


Obstentrics_Williams

Obstentrics_Williams. Several endothelins are generated in pregnancy. Endothelin-1 is a potent vasoconstrictor produced in endothelial and vascular smooth muscle cells and regulates local vasomotor tone (George, 2011; Lankhorst, 2016). Its production is stimulated by angiotensin II, arginine vasopressin, and thrombin. Endothelins, in turn, stimulate secretion of ANP, aldosterone, and catecholamines. Vascular sensitivity to endothelin-1 is not altered during normal pregnancy. Pathologically elevated levels may playia role in preeclampsia (Saleh, 2016). This potent vasodilator is released by endothelial cells and may modiy vascular resistance during pregnancy. Moreover, nitric oxide is an important mediator of placental vascular tone and development (Krause, 2011; Kulandavelu, 2013). Abnormal nitric oxide synthesis has been linked to preeclampsia development (Laskowska, 2015; Vignini, 2016).


Obstentrics_Williams

Obstentrics_Williams. Of anatomic changes, the diaphragm rises approximately 4 cm during pregnancy (Fig. 4-11). he subcostal angle widens appreciably as the transverse diameter of the thoracic cage lengthens approximately 2 cm. The thoracic circumference increases about 6 cm, but not suiciently to prevent reduced residual lung volumes created by the elevated diaphragm. Even so, diaphragmatic excursion is greater in pregnant than in nonpregnant women.


Obstentrics_Williams

Obstentrics_Williams. Of physiological lung changes, unctional residual capaciy (PRe) decreases by approximately 20 to 30 percent or 400 to 700 mL during pregnancy (Fig. 4-12). his capacity is composed of expiratory reserve volume-which drops 15 to 20 percent or 200 to 300 mL-and residual volume-which decreases 20 to 25 percent or 200 to 400 mL. FRe and residual volume decline progressively across pregnancy due to diaphragm elevation. Signiicant reductions are observed by the sixth month. Inspiratory capaciy, the maximum volume that can be inhaled from FRe, rises by 5 to 10 percent or 200 to 350 mL during pregnancy. Total lung capaci-the combination of FRe and inspiratory capacity-is unchanged or decreases by less than 5 percent at term Decreased plasma osmolality also results in less respiratory depression (Moen, 2014). his provides an additional mechanism for the increased minute ventilation seen in pregnancy, and one that is not dependent on progesterone.


Obstentrics_Williams

Obstentrics_Williams. Regarding pulmonary function, peak expiratory low rates rise progressively as gestation advances (Grindheim, 2012). Lung compliance is unafected by pregnancy. Airway conductance is increased and total pulmonary resistance reduced, possibly as a result of progesterone. The maximum breathing capaciy andorced or timed vital capaciy are not altered appreciably. It is unclear whether the critical closing volume-the lung volume at which airways in the dependent parts of the lung begin to close during expiration-is higher in pregnancy (Hegewald, 2011). Pulmonary function with a singleton pregnancy does not signiicantly difer from that with twins (MAulife, 2002; Siddiqui, 2014). Importantly, the greater oxygen requirements and perhaps the increased critical closing volume imposed by pregnancy make respiratory diseases more serious.


Obstentrics_Williams

Obstentrics_Williams. Demir and colleagues (2015) studied nasal physiology in 85 pregnant women. Although the minimal cross-sectional area decreased between the irst and third trimesters, subjective reports ,/ 103.5° "" II , " \\ . (37 weeks) : (Hegewald, 2011). The respiratory rate is essentially unchanged, but tidal volume and resting minute ven as pregnancy advances. Kolar zyk and coworkers (2005) .. -� is-7 em .--_ - reported significantly greater mean tidal volumes-0.66 to 0.8 LI min-and resting minute ventilations-10.7 to 14.1 Llmin-compared with those of nonpregnant women. The elevated minute ventilation is caused by several factors. These include enhanced respira ,;, . ,----------.---.A..,, .I \IIII,\\ ..<: ::: --------------- toy drive primarily due to the stimulatory action of proges terone, low expiratory reserve


Obstentrics_Williams

Obstentrics_Williams. Chest wall measurements in nonpregnant (left) and pregnant women (right). The subcostal angle increases, as does the anteroposterior and transverse diameters of the chest wall and chest wall circumference. These changes compensate for the 4-cm elevation of the diaphragm volume, and compensated respiso that total lung capacity is not significantly reduced. (Redrawn from Hegewald MJ, Crapo RO: ratory alkalosis (Heenan, 2003). Respiratory physiology in pregnancy. Clin Chest Med 32(1 ):1,2011.) 5 4 TLC 2 FVC FAC RV Not pregnant Pregnant (7-9 mos.) 4 FVC 3 2 RV


Obstentrics_Williams

Obstentrics_Williams. FIGURE 4-1 2 Changes in lung volumes with pregnancy. The most significant changes are reduction in functional residual capacity (FRC) and its subcomponents, expiratory reserve volume (ERV) and residual volume (RV), as well as increases in inspiratory capacity (IC) and tidal volume (). (Redrawn from Hegewald MJ, Crapo RO: Respiratory physiology in pregnancy. Clin Chest Med 32(1):1,2011.) of nasal congestion or total nasal resistance did not signiicantly difer among trimesters or compared with nonpregnant controls.


Obstentrics_Williams

Obstentrics_Williams. he amount ofoxygen delivered into the lungs by the increased tidal volume clearly exceeds oxygen requirements imposed by pregnancy. Moreover, the total hemoglobin mass and, in turn, total oxygen-carrying capacity rise appreciably during normal pregnancy, as does cardiac output. Consequently, the maternal arteriovenous oxygen diference is diminished. Oxygen consumption grows approximately 20 percent during pregnancy, and it is approximately 10 percent higher in multifetal gestations (Ajjimaporn, 2014). During labor, oxygen consumption increases 40 to 60 percent (Bobrowski, 2010).


Obstentrics_Williams

Obstentrics_Williams. A greater awareness of a desire to breathe is common even early in pregnancy (Milne, 1978). his may be interpreted as dyspnea, which may suggest pulmonary or cardiac abnormalities when none exist. This physiological dyspnea, which should not interfere with normal physical activity, is thought to result from greater tidal volume that lowers the blood Peo2 slightly and paradoxically causes dyspnea. he increased respiratory efort during pregnancy, and in turn the reduction in the partial pressure ofcarbon dioxide in blood (Peo2), is likely induced in large part by progesterone and to a lesser degree by estrogen. Progesterone acts centrally, where it lowers the threshold and raises the sensitivity ofthe chemoreflex response to carbon dioxide (C02) 0ensen, 2005).


Obstentrics_Williams

Obstentrics_Williams. To compensate for the resulting respiratory alkalosis, plasma bicarbonate levels normally drop from 26 to 22 mmollL. Although blood pH is increased only minimally, it does shift the oxygen dissociation curve to the left. his shift increases the ainity of maternal hemoglobin for oxygen-the Bohr fectthereby lowering the oxygen-releasing capacity of maternal blood. This is ofset because the slight pH rise also stimulates an increase in 2,3-diphosphoglycerate in maternal erythrocytes. ): �:3 This shifts the curve back to the right (Tsai, 1982). hus, reduced Peo2 from maternal hyperventilation aids CO2 (waste) transfer from the fetus to the mother while also aiding oxygen release to the fetus.


Obstentrics_Williams

Obstentrics_Williams. he urinary system undergoes several remarkable changes in pregnancy (Table 4-5). Kidney size grows approximately 1.0 cm (Cietak, 1985). Both theglomerulariltration rate (CPR) and renal plasma low increase early in pregnancy. he GFR rises as much as 25 percent by the second week after conception and 50 percent by the beginning of the second trimester. his hyperiltration results from two principal factors. First, hypervolemia-induced hemodilution lowers the protein concentration and oncotic pressure ofplasma entering the glomerular microcirculation. Second, renal plasma flow increases by approximately 80 percent before the end of the irst trimester (Conrad, 2014b; Odutayo, 2012). As shown in Figure 4-13, , 25 FIGURE 4-13 Percentage increment in glomerular filtration rate (GFR) and renal plasma flow (RPF) across gestation and in the puerperium. (Data from Odutayo, 201o2.) TABLE 4-5. Renal Changes in Normal Pregnancy


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Obstentrics_Williams. TABLE 4-5. Renal Changes in Normal Pregnancy Renal function Glomerular filtration rate and renal plasma flow increase ...50% Maintenance of Decreased bicarbonate threshold; acid-base progesterone stimulates respiratory center osmotic thresholds for AVP release and thirst decrease; hormonal disposal rates increase Size returns to normal postpartum Can be confused with obstructive uropathy; retained urine leads to collection errors; renal infections are more virulent; may be responsible for "distention syndrome"; elective pyelography should be deferred to at least 12 weeks postpartum Serum creatinine decreases during normal gestation; >0.8 mg/dL (> 72 �mol/L) creatinine already borderline; protein, amino acid, and glucose excretion all increase


Obstentrics_Williams

Obstentrics_Williams. Serum creatinine decreases during normal gestation; >0.8 mg/dL (> 72 �mol/L) creatinine already borderline; protein, amino acid, and glucose excretion all increase Serum bicarbonate decreased by 4-5 mEq/L; Pc02 decreased 10 mm Hg; a Pc02 of 40 mm Hg already represents CO2 retention 5 mEq/L) during normal gestation; increased placental metabolism of AVP may cause transient diabetes insipidus during pregnancy AVP = vasopressin; IVP = intravenous pyelography; Pc02= partial pressure carbon dioxide. Modified from Lindheimer, 2000. elevated GFR persists until term, even though renal plasma flow declines during late pregnancy. Primarily as a consequence of this elevated GFR, approximately 60 percent of nulliparas during the third trimester experience urinary frequency, and 80 percent experience nocturia (F rederice, 2013).


Obstentrics_Williams

Obstentrics_Williams. During the puerperium, a marked GFR persists during the first postpartum day, principally from the reduced glomerular capillary oncotic pressure. A reversal of the gestational hypervolemia and hemodilution, still evident on the first postpartum day, eventuates by the second week postpartum (Odutayo, 2012). Studies suggest that relaxin, discussed earlier (p. 52), may mediate both increased GFR and renal blood flow during pregnancy (Conrad, 2014a; Helal, 2012). Relaxin boosts renal nitric oxide production, which leads to renal vasodilation and lowered renal aferent and eferent arteriolar resistance. This augments renal blood flow and GFR (Bramham, 2016). Relaxin may also increase vascular gelatinase activity during pregnancy, which leads to renal vasodilation, glomerular hyperiltration, and reduced myogenic reactivity of small renal arteries (Odutayo, 2012).


Obstentrics_Williams

Obstentrics_Williams. As with blood pressure, maternal posture may considerably inluence several aspects of renal function. Late in pregnancy, the sodium excretion rate in the supine position averages less than half that in the lateral recumbent position. The efects of posture on GFR and renal plasma low vary. One unusual feature of the pregnancy-induced changes in renal excretion is the remarkably increased amounts of some nutrients lost in the urine. Amino acids and water-soluble vitamins are excreted in much greater amounts (Shibata, 2013).


Obstentrics_Williams

Obstentrics_Williams. Of renal function tests, serum creatinine levels decline during normal pregnancy from a mean of 0.7 to 0.5 mg/dL. Values of 0.9 mg/dL or reater sugest underying renal disease and prompt further evaluation. Creatinine clearance in pregnancy averages 30 percent higher than the 100 to 115 mLi min in nonpregnant women. his is a useful test to estimate renal function, provided that complete urine collection is made during an accurately timed period. If this is not done precisely, results are misleading (Lindheimer, 2000, 2010). During the day, pregnant women tend to accumulate water as dependent edema, and at night, while recumbent, they mobilize this fluid with diuresis. This reversal of the usual nonpregnant diurnal pattern of urinary flow causes nocturia, and urine is more dilute than in nonpregnant women. Failure of a pregnant woman to excrete concentrated urine after withholding fluids for approximately 18 hours does not necessarily signiy renal damage. In fact, the kidneys in these


Obstentrics_Williams

Obstentrics_Williams. women. Failure of a pregnant woman to excrete concentrated urine after withholding fluids for approximately 18 hours does not necessarily signiy renal damage. In fact, the kidneys in these circumstances function perfectly normally by excreting mobilized extracellular fluid of relatively low osmolality.


Obstentrics_Williams

Obstentrics_Williams. Glucosuria during pregnancy may not be abnormal. The appreciably increased GFR, together with impaired tubular reabsorptive capacity for filtered glucose, accounts for most cases of glucosuria. Chesley (1963) calculated that about a sixth of pregnant women will spill glucose in the urine. hat said, although common during pregnancy, when glucosuria is identiied, a search for diabetes mellitus is pursued. Hematuria frequently results from contamination during collection. If not, it most often suggests urinary tract disease or infection. Hematuria is common after diicult labor and delivery because of trauma to the bladder and urethra.


Obstentrics_Williams

Obstentrics_Williams. Proteinuria is typically deined in nonpregnant subjects as a protein excretion rate of more than 150 mg/ d. Because of the aforementioned hyperiltration and possible reduction of tubular reabsorption, proteinuria during pregnancy is usually considered signiicant once a protein excretion threshold total protein excretion by gestational age. Mean and 95-percent confidence limits are outlined. (Redrawn from Higby K, Suiter CR,


Obstentrics_Williams

Obstentrics_Williams. Phelps JY, et al: Normal values of urinary albumin and total protein excretion during pregnancy. Am J Obstet Gynecol 171 :984, 1994.) of at least 300 mg/d is reached (Odutayo, 2012). Higby and coworkers (1994) measured protein excretion in 270 normal women throughout pregnancy (Fig. 4-14). Mean 24-hour excretion for all three trimesters was 11i5 mg, and the upper 95-percent conidence limit was 260 mg/d without significant diferences by trimester. They showed that albumin excretion is minimal and ranges from 5 to 30 mg/d. Proteinuria increases with gestational age, which corresponds with the peak in CFR (see Fig. 4-13)(Odutayo, 2012).


Obstentrics_Williams

Obstentrics_Williams. Measuring Urine Protein. The three most commonly employed approaches for assessing proteinuria are the qualitative classic dipstick, the quantitative 24-hour collection, and the albumin/ creatinine or protein/creatinine ratio of a single voided urine specimen. he pitfalls of each approach have been reviewed by Conrad (20 14b) and Bramham (2016) and their colleagues. he principal problem with dipstick assessment is that it fails to account for renal concentration or dilution of urine. For example, with polyuria and extremely dilute urine, a negative or trace dipstick could actually be associated with excessive protein excretion.


Obstentrics_Williams

Obstentrics_Williams. he 24-hour urine collection is afected by urinaty tract dilatation, which is discussed in the next section. he dilated tract may lead to errors related both to retention-hundreds of milliliters of urine remaining in the dilated tract-and to timing-the remaining urine may have formed hours before the collection. To minimize these pitfalls, the patient is irst hydrated and positioned in lateral recumbency-the deinitive nonobstructive posture-for 45 to 60 minutes. After this, she is asked to void, and this specimen is discarded. Immediately following this void, her 24-hour collection begins. During the final hour of collection, the patient is again placed in the lateral recumbent position. But, at the end of this hour, the inal collected urine is incorporated into the total collected volume (Lindheimer, 2010).


Obstentrics_Williams

Obstentrics_Williams. Last, the protein/creatinine ratio is a promising approach because data can be obtained quickly and collection errors are ,S 200 avoided. Disadvantageously, the amount of protein per unit of creatinine excreted during a 24-hour period is not constant, and the thresholds to deine abnormal vary. Nomograms for cated pregnancies have been developed (Waugh, 2003).


Obstentrics_Williams

Obstentrics_Williams. After the uterus completely rises out of the pelvis, it rests on the ureters. This laterally displaces and compresses them at the pelvic brim. Above this level, elevated intraureteral tonus results, and ureteral dilatation is impressive (Rubi, 1968). It is right sided in 86 percent of women (Fig. 4-15) (Schulman, 1975). This unequal dilatation may result from cushioning provided the left ureter by the sigmoid colon and perhaps from greater right ureteral compression exerted by the dextrorotated uterus. The right ovarian vein complex, which is remarkably dilated during pregnancy, lies obliquely over the right ureter and may also contribute to right ureteral dilatation. Progesterone likely has some additional efect. Van Wagenen and Jenkins (1939) described continued 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, however, seems more consistent with ureteral compression.


Obstentrics_Williams

Obstentrics_Williams. Ureteral elongation accompanies distention, and the ureter is frequently thrown into curves of varying size, the smaller of which may be sharply angulated. hese so-called kinks are FIGURE 4-15 Hydronephrosis. Plain film from the 15-minute image of an intravenous pyelogram (IVP). Moderate hydronephrosis on the right (arrows) and mild hydronephrosis on the left (arrowheads) are both normal for this 35-week gestation. poorly named, because the term connotes obstruction. hey are usually single or double curves that, when viewed in a radiograph taken in the same plane as the curve, may appear as acute angulations. Another exposure at right angles nearly always identiies them to be gentle curves. Despite these anatomical changes, complication rates associated with ureteroscopy in pregnant and nonpregnant patients do not difer signiicantly (Semins, 2014).


Obstentrics_Williams

Obstentrics_Williams. he bladder shows few significant anatomical changes before 12 weeks' gestation. Subsequently, however, increased uterine size, the hyperemia that afects all pelvic organs, and hyperplasia of bladder muscle and connective tissues elevate the trigone and thicken its intraureteric margin. Continuation of this process to term produces marked deepening and widening of the trigone. The bladder mucosa is unchanged other than an increase in the size and tortuosity of its blood vessels.


Obstentrics_Williams

Obstentrics_Williams. Bladder pressure in primigravidas increases from 8 cm H20 early in pregnancy to 20 cm H20 at term (Iosif, 1980). To compensate for reduced bladder capacity, absolute and functional urethral lengths increased by 6.7 and 4.8 mm, respectively. Concurrently, maximal intraurethral pressure rises from 70 to 93 cm H20, and thus continence is maintained. Still, at least half of women experience some degree of urinary incontinence by the third trimester (Abdullah, 20 16a). Indeed, this is always considered in the diferential diagnosis of ruptured membranes. Near term-particularly in nulliparas, in whom the presenting part often engages before labor-the entire base of the bladder is pushed ventral and cephalad. his converts the normally convex surface into a concavity. As a result, diiculties in diagnostic and therapeutic procedures are greatly accentuated. Moreover, pressure from the presenting part impairs blood and lymph drainage from the bladder base, often rendering the area edematous,


Obstentrics_Williams

Obstentrics_Williams. diagnostic and therapeutic procedures are greatly accentuated. Moreover, pressure from the presenting part impairs blood and lymph drainage from the bladder base, often rendering the area edematous, easily traumatized, and possibly more susceptible to infection.


Obstentrics_Williams

Obstentrics_Williams. As pregnancy progresses, the stomach and intestines are displaced cephalad by the enlarging uterus. Consequently, the physical findings in certain diseases are altered. he appendix, for instance, is usually displaced upward and somewhat laterally. At times, it may reach the right lank. Pyrosis (heartburn) is common during pregnancy and is most likely caused by reflux of acidic secretions into the lower esophagus. Although the altered stomach position probably contributes to its frequency, lower esophageal sphincter tone also is decreased. In addition, intraesophageal pressures are lower and intragastric pressures higher in pregnant women. Concurrently, esophageal peristalsis has lower wave speed and lower amplitude (Ulmsten, 1978).


Obstentrics_Williams

Obstentrics_Williams. Gastric empying time is unchanged during each trimester and compared with nonpregnant women (Macfie, 1991; Wong, 2002, 2007). During labor, however, and especially after administration of analgesics, gastric emptying time may be appreciably prolonged. As a result, one danger of general anesthesia for delivery is regurgitation and aspiration of either food-laden or highly acidic gastric contents. Hemorrhoids are common during pregnancy (Shin, 2015). hey are caused in large measure by constipation and elevated pressure in rectal veins below the level of the enlarged uterus. Liver size does not enlarge during human pregnancy. Hepatic arterial and portal venous blood flow, however, increase substantively (Clapp, 2000).


Obstentrics_Williams

Obstentrics_Williams. Liver size does not enlarge during human pregnancy. Hepatic arterial and portal venous blood flow, however, increase substantively (Clapp, 2000). Some laboratory test results of hepatic function are altered in normal pregnancy (Appendix, p. 1257). Total alkaline phosphatase activity almost doubles, but much of the rise is attributable to heat-stable placental alkaline phosphatase isozymes. Serum aspartate transaminase (AST) , alanine transaminase (AL T), 1-glutamyl transpeptidase (GGT), and bilirubin levels are slightly lower compared with nonpregnant values (Cattozzo, 2013; Ruiz-Extremera, 2005). The serum albumin concentration declines during pregnancy. By late pregnancy, albumin levels may be near 3.0 g/dL compared with approximately 4.3 g/dL in nonpregnant women (Mendenhall, 1970). Total body albumin levels rise, however, because of pregnancy-associated increased plasma volume. Serum globulin levels are also slightly higher.


Obstentrics_Williams

Obstentrics_Williams. Leucine aminopeptidase is a proteolytic liver enzyme whose serum levels may be increased with liver disease. Its activity is markedly elevated in pregnant women. he rise, however, results from a pregnancy-speciic enzyme(s) with distinct substrate speciicities (Song, 1968). Pregnancy-induced aminopeptidase has oxytocinase and vasopressinase activity that occasionally causes transient diabetes insipidus.


Obstentrics_Williams

Obstentrics_Williams. During normal pregnancy, gallbladder contractility is reduced and leads to greater residual volume (Braverman, 1980). Progesterone potentially impairs gallbladder contraction by inhibiting cholecystokinin-mediated smooth muscle stimulation, which is the primary regulator of gallbladder contraction. Impaired emptying, subsequent stasis, and the increased cholesterol saturation of bile in pregnancy contribute to the increased prevalence of cholesterol gallstones in multiparas. In one study, approximately 8 percent of women had gallbladder sludge or stones when imaged at 18 and/or 36 weeks' gestation (Ko, 2014). he pregnancy efects on maternal serum bile acid concentrations are still incompletely characterized. his is despite the long-acknowledged propensity for pregnancy to cause intrahepatic cholestasis and pruritus gravidarum from retained bile salts. Cholestasis of pregnancy is described in Chapter 55 (p. 1059).


Obstentrics_Williams

Obstentrics_Williams. During normal pregnancy, the pUUltary gland enlarges by approximately 135 percent (Gonzalez, 1988). This increase may suiciently compress the optic chiasma to reduce visual fields. Impaired vision from this is rare and usually due to macro ad enomas (Lee, 2014). Pituitary enlargement is primarily caused by estrogen-stimulated hypertrophy and hyperplasia of the lactotrophs (Feldt-Rasmussen, 2011). And, as discussed subse quently, maternal serum prolactin levels parallel the increasing size. Gonadotrophs decline in number, and corticotrophs and thyrotrophs remain constant. Somatotrophs are generally sup pressed due to negative feedback by the placental production of growth hormone.


Obstentrics_Williams

Obstentrics_Williams. Peak pituitary size may reach 12 mm in MR images in the irst days postpartum. he gland then involutes rapidly and sen, 2011). he incidence of pituitary prolactinomas is not increased during pregnancy (Scheithauer, 1990). When these tumors are large before pregnancy-a macroadenoma measur ing : 1 0 mm-then growth during pregnancy is more likely (Chap. 58, p. 1132). he maternal pituitary gland is not essential for pregnancy maintenance. Many women have undergone hypophysectomy, completed pregnancy successfully, and entered spontaneous labor while receiving compensatory glucocorticoids, thyroid hormone, and vasopressin.


Obstentrics_Williams

Obstentrics_Williams. During the first trimester, growth hormone is secreted predominantly from the maternal pituitary gland, and concentrations in serum and amnionic luid lie within the nonpregnant range of 0.5 to 7.5 ng/mL (Kletzky, 1985). As early as 6 weeks' gestation, growth hormone secreted from the placenta becomes detectable, and by approximately 20 weeks, the placenta is the principal source of growth hormone secretion (Perez-Ibave, 2014). Maternal serum values rise slowly from approximately 3.5 ng/mL at 10 weeks to plateau at about 14 ng/mL after 28 weeks. Growth hormone in amnionic fluid peaks at 14 to 15 weeks and slowly declines thereafter to reach baseline values after 36 weeks.


Obstentrics_Williams

Obstentrics_Williams. Placental growth hormone-which difers from pituitary growth hormone by 13 amino acid residues-is secreted by syncytiotrophoblast in a nonpulsatile fashion (Newbern, 2011). Its regulation and physiological efects are incompletely understood, but it inluences fetal growth via up regulation of insulin-like growth factor 1 (IGF-1). Higher levels have been linked with development of preeclampsia (MinaI, 2007; PerezIbave, 2014). Further, placental expression correlates positively with birthweight but negatively with fetal-growth restriction (Koutsaki, 201l). Maternal serum levels are associated with uterine artery resistance changes (Schiessl, 2007). hat said, fetal growth still progresses in the complete absence of this hormone. Although not absolutely essential, the hormone may act in concert with placental lactogen to regulate fetal growth (Newbern, 2011).


Obstentrics_Williams

Obstentrics_Williams. Maternal plasma prolactin levels increase markedly during normal pregnancy. Concentrations are usually tenfold greater at term-about 150 ng/mL-compared with those of nonpregnant women. Paradoxically, plasma concentrations drop after delivery even in women who are breastfeeding. During early lactation, pulsatile bursts of prolactin secretion are a response to suckling. The principal function of maternal prolactin is to ensure lac tation. Early in pregnancy, prolactin acts to initiate DNA syn thesis and mitosis of glandular epithelial cells and presecretory alveolar cells of the breast. Prolactin also augments the number of estrogen and prolactin receptors in these cells. Finally, pro lactin promotes mammary alveolar cell RNA synthesis, galac topoiesis, and production of casein, lactalbumin, lactose, and lipids (Andersen, 1982). A woman with isolated prolactin dei ciency failed to lactate after two pregnancies (Kauppila, 1987).


Obstentrics_Williams

Obstentrics_Williams. This establishes prolactin as a requisite for lactation but not for pregnancy. Grattan (2015) has reviewed the numerous physi ological roles of prolactin for facilitating maternal adaptations to pregnancy. A possible role is proposed for a prolactin frag ment in the genesis of peripartum cardiomyopathy (Chap. 49, p. 963) (Cunningham, 2012). Prolactin is present in amnionic fluid in high concen trations. Levels of up to 10,000 ng/mL are found at 20 to 26 weeks' gestation. Thereafter, levels decline and reach a nadir after 34 weeks. Uterine decidua is the synthesis site of prolactin found in amnionic luid. Although the exact function of amni onic luid prolactin is unknown, impaired water transfer from the fetus into the maternal compartment to thereby prevent fetal dehydration is one suggestion.


Obstentrics_Williams

Obstentrics_Williams. These two hormones are secreted from the posterior pituitary gland. The roles of oxytocin in parturition and lactation are discussed in Chapters 21 (p. 416) and 36 (p. 657), respectively. Brown and colleagues (2013) have reviewed the complex mechanisms that promote quiescence of oxytocin systems during pregnancy. Levels of antidiuretic hormone, also called vasopressin, do not change during pregnancy. hyrotropin-releasing hormone (TRH) is secreted by the hypothalamus and stimulates thyrotrope cells of the anterior pituitary to release thyroid-stimulating hormone (TSH), also called thyrotropin. TRH levels do not rise during normal pregnancy. However, TRH does cross the placenta and may serve to stimulate the fetal pituitary to secrete TSH (horpe-Beeston, 1991).


Obstentrics_Williams

Obstentrics_Williams. Serum TSH and hCG levels vary with gestational age (Fig. 4-16). As discussed in Chapter 5 (p. 98), the a-subunits of the two glycoproteins are identical, whereas the 3-subunits, although similar, difer in their amino acid sequence. As a result of this structural similarity, hCG has intrinsic thyrotropic activity, and thus, high serum hCG levels cause thyroid stimulation. Indeed, TSH levels in the irst trimester decline in more than 80 percent of pregnant women, however, they still remain in the normal range for nonpregnant women The thyroid gland boosts production of thyroid hormones by 40 to 100 percent to meet maternal and fetal needs (Moleti, 2014). To accomplish this, the thyroid gland undergoes moderate enlargement during pregnancy caused by glandular hyperplasia and greater vascularity. Mean thyroid volume increases from 12 mL in the first trimester to 15 mL at term (Glinoer, Week of pregnancy


Obstentrics_Williams

Obstentrics_Williams. Week of pregnancy FIGURE 4-16 Relative changes in maternal and fetal thyroid function across pregnancy. Maternal changes include a marked and early increase in hepatic production of thyroxine-binding globulin (TBG) and placental production of human chorionic gonadotropin (hCG). Increased TBG increases serum thyroxine (T4) concentrations. hCG has thyrotropin-like activity and stimulates maternal free T4 secretion. This transient hCG-induced increase in serum T4 levels inhibits maternal secretion of thyrotropin. Except for minimally increased free T4 levels when hCG peaks, these levels are essentially unchanged. Fetal levels of all serum thyroid analytes increase incrementally across pregnancy. Fetal triiodothyronine (T3) does not increase until late pregnancy. (Modified from Burrow, 1994.) 1990). That said, normal pregnancy does not typically cause significant thyromegaly, and thus any goiter warrants evaluation.


Obstentrics_Williams

Obstentrics_Williams. Early in the first trimester, levels of the principal carrier protein-thyroid-binding globulin (TBG)-rise, reach their zenith at about 20 weeks, and stabilize at approximately double baseline values for the remainder of pregnancy (see Fig. 4-16). he greater TBG concentrations result from both higher hepatic synthesis rates-due to estrogen stimulation-and lower metabolism rates due to greater TBG sialylation and glycosylation. These elevated TBG levels increase total serum thyroxine (T 4) and triiodothyronine (T 3) concentrations, but do not afect the physiologically important serum ree T4 and ree T3 levels. Specifically, total serum T4 levels rise sharply beginning between 6 and 9 weeks' gestation and reach a plateau at 18 weeks. Serum free T 4 levels rise only slightly and peak along with hCG levels, and then they return to normal.


Obstentrics_Williams

Obstentrics_Williams. Interestingly, T 4 and T 3 secretion is not similar for all pregnant women (G linoer, 1990). Approximately a third of women experience relative hypothyroxinemia, preferential T3 secretion, and higher, albeit normal, serum TSH levels. hus, thyroidal adjustments during normal pregnancy may vary considerably. The fetus relies on maternal T 4, which crosses the placenta in small quantities to maintain normal fetal thyroid function (Chap. 58, p. 1118). Recall that the fetal thyroid does not begin to concentrate iodine until 10 to 12 weeks' gestation. he synthesis and secretion of thyroid hormone by fetal pituitary TSH ensues at approximately 20 weeks. At birth, approximately 30 percent of the T 4 in umbilical cord blood is of maternal origin (Leung,i2012).


Obstentrics_Williams

Obstentrics_Williams. Normal suppression of TSH during pregnancy may lead to a misdiagnosis of subclinical hyperthyroidism. Of greater concern is the potential failure to identiy women with early hypothyroidism because of suppressed TSH concentrations. To mitigate the likelihood of such misdiagnoses, Dashe and coworkers (2005) conducted a population-based study at Parkland Hospital to develop gestational-age-specific TSH normal curves for both singleton and twin pregnancies (Fig. 4-17). Similarly, Ashoor and associates (2010) established normal ranges for maternal TSH, free T4, and free T3 at 11 to 13 weeks' gestation. hese complex alterations of thyroid regulation do not appear to alter maternal thyroid status as measured by metabolic studies. lthough basal metabolic rate increases progressively by as much as 25 percent during normal pregnancy, most 4.0 0.4


Obstentrics_Williams

Obstentrics_Williams. FIGURE 4-17 Gestational age-specific thyroid-stimulating hormone (TSH) nomogram derived from 13,599 singleton pregnancies. The nonpregnant reference values of 4.0 and 0.4 mUll are represented as solid black lines. Upper shaded area represents the 28 percent of singleton pregnancies with TSH values above the 97.5th percentile threshold that would not have been identified as abnormal based on the assay reference value of 4.0 mUll. lower shaded area represents singleton pregnancies that would have been (falsely) identified as having TSH suppression based on the assay reference value of 0.4 mUll. (Data from Dashe, 2005.) of this greater oxygen consumption can be attributed to fetal metabolic activity. If fetal body surface area is considered along with that of the mother, the predicted and observed basal metabolic rates are similar to those in nonpregnant women.


Obstentrics_Williams

Obstentrics_Williams. Iodine requirements increase during normal pregnancy (Chap. 58, p. 1127). In women with low or marginal intake, deiciency may manifest as low T4 and higher TSH levels. Importantly, more than a third of the world population lives in areas where iodine intake is marginal. For the fetus, early exposure to thyroid hormone is essential for the nervous system, and despite public health programs to supplement iodine, severe iodine deiciency resulting in cretinism afects more than 2 million people globally (Syed, 2015).


Obstentrics_Williams

Obstentrics_Williams. In one longitudinal investigation of 20 women, all markers of bone turnover rose during normal pregnancy and failed to reach baseline levels by 12 months postpartum (More, 2003). Investigators concluded that the calcium needed for fetal growth and lactation may be drawn at least in part from the maternal skeleton. he factors afecting bone turnover yield a net result favoring fetal skeletal formation at the expense of the mother, such that pregnancy is a vulnerable period for osteoporosis (Sanz-Salvador, 2015). hat said, prevention is diicult due to a paucity of identiiable risk factors. Acute or chronic declines in plasma calcium or acute drops in magnesium levels stimulate parathyroid hormone (PTH) release. Conversely, greater calcium and magnesium levels suppress PTH levels. he action of this hormone on bone resorption, intestinal absorption, and kidney reabsorption is to raise extracellular luid calcium concentrations and lower phosphate levels.


Obstentrics_Williams

Obstentrics_Williams. Fetal skeleton mineralization requires approximately 30 g of calcium, primarily during the third trimester (Sanz-Salvador, 2015). Although this amounts to only 3 percent of the total calcium held within the maternal skeleton, the provision of calcium still challenges the mother. In most circumstances, augmented maternal calcium absorption provides the additional calcium. During pregnancy, the amount of calcium absorbed rises gradually and reaches approximately 400 mg/ d in the third trimester. Greater calcium absorption appears to be mediated by elevated maternal 1,25-dihydroxyvitamin D concentrations. This occurs despite decreased PTH levels during early pregnancy, which is the normal stimulus for active vitamin D production within the kidney. Indeed, PTH plasma concentrations decline during the irst trimester and then rise progressively throughout the remainder of pregnancy (Pitkin, 1979).


Obstentrics_Williams

Obstentrics_Williams. he increased production of active vitamin D is likely due to placental production of either PTH or a PTH-related protein (PTH-rP). Outside pregnancy and lactation, PTH-rP is usually detectable only in serum of women with hypercalcemia due to malignancy. During pregnancy, however, PTH-rP concentrations increase signiicantly. his protein is synthesized in both fetal tissues and maternal breasts. he C cells that secrete calcitonin are located predominantly in the perifollicular areas of the thyroid gland. Calcitonin opposes actions of PTH and vitamin D and protects the matenal skeleton during times of calcium stress. Pregnancy and lactation cause profound maternal calcium stress, ostensibly for the sake of the fetus. Indeed, fetal calcitonin levels are at least twofold higher than maternal levels (Ohata, 2016). And although maternal levels fall during pregnancy, they generally rise postpartum (M011er, 2013).


Obstentrics_Williams

Obstentrics_Williams. Calcium and magnesium promote the biosynthesis and secretion of calcitonin. Various gastric hormones-gastrin, pentagastrin, glucagon, and pancreozymin-and food ingestion also increase calcitonin plasma levels. In normal pregnancy, unlike their fetal counterparts, the maternal adrenal glands undergo little, if any, morphological change. The serum concentration of circulating cortisol rises, but much of it is bound by transcortin, the cortisol-binding globulin. The adrenal secretion rate of this principal glucocorticoid is not elevated, and probably it is lower than in the nonpregnant state. he metabolic clearance rate of cortisol, however, is diminished during pregnancy because its half-life is nearly doubled compared with that for nonpregnant women (Migeon, 1957). Administration of estrogen, including most oral contraceptives, causes changes in serum cortisol levels and transcortin similar to those of pregnancy Qung, 201i1).


Obstentrics_Williams

Obstentrics_Williams. During early pregnancy, the levels of circulating adrenocorticotropic hormone (A CTH) , also known as corticotropin, are dramatically reduced. As pregnancy progresses, ACTH and free cortisol levels rise equally and strikingly (Fig. 4-18). This ,50


Obstentrics_Williams

Obstentrics_Williams. FIGURE 4-18 Serial increases in serum cortisol (blue line) and adrenocorticotropic hormone (ACTH) (red line) across normal pregnancy. (Data from Carr, 1981o.) apparent paradox is not understood completely. Some suggest that greater free cortisol levels in pregnancy result from a "resetting" of the maternal feedback mechanism to higher thresholds (Nolten, 1981). his might result from tissue reractoriness to cortisol. Others assert that these incongruities stem from an antagonistic action of progesterone on mineralocorticoids (Keller-Wood, 2001). Thus, in response to elevated progesterone levels during pregnancy, an elevated free cortisol is needed to maintain homeostasis. Other theories include possible roles for higher free cortisol in preparation for the stress of pregnancy, delivery, and lactation. This pattern might also influence postpartum behavior and parenting roles (Conde, 2014).


Obstentrics_Williams

Obstentrics_Williams. As early as 15 weeks' gestation, the maternal adrenal glands secrete considerably increased amounts of aldosterone, the principal mineralocorticoid. By the third trimester, approximately 1 mg/d is released. If sodium intake is restricted, aldosterone secretion is even further elevated (Watanabe, 1963). Concurrently, levels of renin and angiotensin II substrate normally rise, especially during the latter half of pregnancy. his scenario promotes greater plasma levels of angiotensin II, which acts on the zona glomerulosa of the maternal adrenal glands and accounts for the markedly elevated aldosterone secretion. Some suggest the increased aldosterone secretion during normal pregnancy afords protection against the natriuretic efect of progesterone and atrial natriuretic peptide. Gennari-Moser and colleagues (2011) provide evidence that aldosterone, as well as cortisol, may modulate trophoblast growth and placental size.


Obstentrics_Williams

Obstentrics_Williams. Maternal plasma levels of this potent mineralocorticosteroid progressively increase during pregnancy. Indeed, plasma levels of deoxycorticosterone rise to near 1500 pg/mL by term, a more than 15-fold increase (Parker, 1980). his marked elevation does not derive from adrenal secretion but instead represents augmented kidney production resulting from estrogen stimulation. The levels of deoxycorticosterone and its sulfate in fetal blood are appreciably higher than those in maternal blood, which suggests transfer of fetal deoxycorticosterone into the maternal compartment.


Obstentrics_Williams

Obstentrics_Williams. In balance, androgenic aCtiVlty rises during pregnancy, and both maternal plasma levels of androstenedione and testosterone are increased. This inding is not totally explained by alterations in their metabolic clearance. Both androgens are converted to estradiol in the placenta, which increases their clearance rates. Conversely, greater plasma sex hormone-binding globulin levels in gravidas retard testosterone clearance. Thus, the production rates of maternal testosterone and androstenedione during human pregnancy are increased. he source of this higher C19-steroid production is unknown, but it likely originates in the ovary. Interestingly, little or no testosterone in maternal plasma enters the fetal circulation as testosterone. Even when massive testosterone levels are found in the circulation of pregnant women, as with androgen-secreting tumors, testosterone concentrations in umbilical cord blood are likely to be undetectable. his results from the near complete trophoblastic


Obstentrics_Williams

Obstentrics_Williams. circulation of pregnant women, as with androgen-secreting tumors, testosterone concentrations in umbilical cord blood are likely to be undetectable. his results from the near complete trophoblastic conversion of testosterone to 173-estradiol.


Obstentrics_Williams

Obstentrics_Williams. Maternal serum and urine levels of dehydroepiandrosterone suate are lower during normal pregnancy. his stems from a greater metabolic clearance through extensive maternal hepatic 16.-hydroxylation and placental conversion to estrogen (Chap. 5, p. 103).


Obstentrics_Williams

Obstentrics_Williams. Progressive lordosis is a characteristic feature of normal pregnancy. Compensating for the anterior position of the enlarging uterus, lordosis shifts the center of gravity back over the lower extremities. The sacroiliac, sacrococcygeal, and pubic joints have increased mobility during pregnancy. However, as discussed earlier (p. 52), increased joint laxity and associated discomfort during pregnancy do not correlate with increased maternal serum levels of estradiol, progesterone, or relaxin (Aldabe, 2012; Marnach, 2003; V0llestad, 2012). Most relaxation takes place in the first half of pregnancy. It may contribute to maternal posture alterations and in turn create lower back discomfort. s discussed in Chapter 36 (p. 661), although some symphyseal separation likely accompanies many deliveries, those greater than 1 cm may cause significant pain (Shnaekel, 2015).


Obstentrics_Williams

Obstentrics_Williams. Aching, numbness, and weakness also occasionally are experienced in the upper extremities. his may result from the marked lordosis and associated anterior neck flexion and shoulder girdle slumping, which produce traction on the ulnar and median nerves (Crisp, 1964). he latter may give rise to symptoms mistaken for the carpal tunnel syndrome (Chap. 60, p. 1167). Joint strengthening begins immediately following delivery and is usually complete within 3 to 5 months. Pelvic dimensions measured by MR imaging up to 3 months after delivery are not significantly diferent from prep regnancy measurements (Huerta-Enochian, 2006).


Obstentrics_Williams

Obstentrics_Williams. Central nervous system changes are relatively few and mostly subtle. Women often report problems with attention, concentration, and memory throughout pregnancy and the early puerperium. Systematic studies of memory in pregnancy, however, are limited and often anecdotal. Keenan and associates (1998) longitudinally investigated memory in pregnant women and a matched control group. hey found pregnancy-related memory decline that was limited to the third trimester. his decline was not attributable to depression, anxiety, sleep deprivation, or other physical changes associated with pregnancy. It was transient and quickly resolved following delivery. Others have found poorer verbal recall and processing speed and worse spatial recognition memory in pregnancy (Farrar, 2014; Henry, 2012).


Obstentrics_Williams

Obstentrics_Williams. Zeeman and coworkers (2003) used MR imaging to measure cerebral blood low across pregnancy. They found that mean blood flow in the middle and posterior cerebral arteries declined progressively from 147 and 56 mLimin when nonpregnant to 118 and 44 mLlmin late in pregnancy, respectively. Mechanisms and signiicance of the decline are unknown. Pregnancy does notiafect cerebrovascular autoregulation (Bergersen, 2006; Cipolla, 2014).


Obstentrics_Williams

Obstentrics_Williams. Intraocular pressure drops during pregnancy and is attributed partly to greater vitreous outlow. Corneal sensitivity is decreased, and the greatest changes are late in gestation. Most pregnant women demonstrate a measurable but slight increase in corneal thickness, thought to be due to edema. Consequently, they may have diiculty with previously comfortable contact lenses. Brownish-red opacities on the posterior surface of the cornea-Krukenberg spindles-are observed with a higher than expected frequency during pregnancy. Hormonal efects similar to those observed for skin lesions are believed to cause this increased pigmentation. Other than transient loss of accommodation reported with both pregnancy and lactation, visual function is unafected by pregnancy. These changes during pregnancy and pathological eye aberrations were reviewed by Grant and Chung (2013).


Obstentrics_Williams

Obstentrics_Williams. Beginning as early as 12 weeks' gestation and extending through the first 2 months postpartum, women have diiculty with falling asleep, frequent awakenings, fewer hours of night sleep, and reduced sleep eiciency (Pavlova, 2011). Abdullah and colleagues (2016b) concluded that sleep apnea is more common in pregnancy, especially in obese patients. he greatest disruption of sleep is encountered postpartum and may contribute to postpartum blues or to frank depression auulia Paavonen, 2017). Abdullah B, Ayub SH, Mohd Zahid AZ, et al: Urinary incontinence in primigravida: the neglected pregnancy predicament. Eur ] Obstet Gynecol Reprod Bioi 198:110, 2016a Abdullah HR, Nagappa M, Siddiqui N, Chung F: Diagnosis and treatment of obstructive sleep apnea during pregnancy. Curr Opin Anaesthesiol 29:317, 2016b


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Obstentrics_Williams. Abdullah HR, Nagappa M, Siddiqui N, Chung F: Diagnosis and treatment of obstructive sleep apnea during pregnancy. Curr Opin Anaesthesiol 29:317, 2016b Abeysekera MV, Morris ]A, Davis GK, et al: Alterations in energy homeostasis to favour adipose tissue gain: a longitudinal study in healthy pregnant women. Aust N Z] Obstet Gynaecol 56:42, 2016 Afshani N, Moustaqim-Barrette A, Biccard BM, et al: Utiliry of B-rype natriuretic peptides in preeclampsia: a systematic review. Int ] Obstet Anesth 22:96,r2013 Aguin T], Sobel ]0: Vulvovaginal candidiasis in pregnancy. Curr Infect Dis Rep 17:462,r2015 Ajjimaporn A, Somprasit C, Chaunchaiyakul R: A cross-sectional study of resting cardio-respiratory and metabolic changes in pregnant women. ] Phys Ther Sci 26:779, 2014 Aldabe 0, Ribeiro DC, Milosavljevic S, et al: Pregnancy-related pelvic girdle pain and its relationship with relaxin levels during pregnancy: a systematic review. Eur Spine] 21:1769, 2012


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Obstentrics_Williams. Aldabe 0, Ribeiro DC, Milosavljevic S, et al: Pregnancy-related pelvic girdle pain and its relationship with relaxin levels during pregnancy: a systematic review. Eur Spine] 21:1769, 2012 Alvarez H, Caldeyro-Barcia R: Contractiliry of the human uterus recorded by new methods. Surg Gynecol Obstet 91: 1, 1950 Amoah C, Yassin A, Cockayne E, et al: Hyperreactio luteinalis in pregnancy. Fertil Steril 95(7):2429.e1, 2011 Andersen ]R: Prolactin in amniotic luid and maternal serum during uncomplicated human pregnancy. Dan Med Bull 29:266, 1982 Anderson BL, Mendez-Figueroa H, Dahlke], et al: Pregnancy-induced changes in immune protection of the genital tracr: deining normal. Am ] Obstet GynecoIr208(4):321.e1,r2013 Angelidis G, Dafopoulos K, Messini CI, et al: Ghrelin: new insights into female reproductive system-associated disorders and pregnancy. Reprod Sci 19:903, 2012


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Obstentrics_Williams. Angelidis G, Dafopoulos K, Messini CI, et al: Ghrelin: new insights into female reproductive system-associated disorders and pregnancy. Reprod Sci 19:903, 2012 Angueira AR, Ludvik AE, Reddy TE, et al: New insights into gestational glucose metabolism: lessons learned from 21st century approaches. Diabetes 64:327,r2015 Armstrong S, Fernando R, Columb M, et al: Cardiac index in term pregnant women in the sitting, lateral, and supine positions: an observational, crossover study. Anesth Analg 113:318,r2011 Ashoor G, Kametas NA, Akolekar R, et al: Maternal thyroid function at 11-13 weeks of gestation. Fetal Diagn her 27(3): 156, 2010 Assali NS, Dilts PV, Pend M, et al: Physiology of the placenta. In Assali NS (ed): Biology of Gestation, Vol I. The Maternal Organism. New York, Academic Press, 1968 Assali NS, Douglas A, Baird W: Measurement of uterine blood low and uterine metabolism. IV. Results in normal pregnancy. Am] Obstet Gynecol 66(2):248, 1953


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Obstentrics_Williams. Assali NS, Douglas A, Baird W: Measurement of uterine blood low and uterine metabolism. IV. Results in normal pregnancy. Am] Obstet Gynecol 66(2):248, 1953 Astern ]M, Collier AC, Kendal-Wright CE: Pre-B cell colony enhancing factor (PBEF/NAMPT/Visfatin) and vascular endothelial growth factor (VEGF) cooperate to increase the permeabiliry of the human placental amnion. Placenta 34:42, 2013 Bamber ]H, Dresner M: Aortocaval compression in pregnancy: the efect of changing the degree and direction of lateral tilt on maternal cardiac output. Anesth Analg 97:256, 2003 Bao W, Baecker A, Song Y, et al: Adipokine levels during the irst or early second trimester of pregnancy and subsequent risk of gestational diabetes mellitus: a systematic review. Metabolism 64:756, 2015 Bardicef M, Bardicef 0, Sorokin Y, et al: Extracellular and intracellular magnesium depletion in pregnancy and gestational diabetes. Am ] Obstet Gynecol 172:1009,r1995


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Obstentrics_Williams. Bardicef M, Bardicef 0, Sorokin Y, et al: Extracellular and intracellular magnesium depletion in pregnancy and gestational diabetes. Am ] Obstet Gynecol 172:1009,r1995 Baronr], Shwarzman, Sheiner E, et al: Blood low Doppler velocimetry measured during active labor. Arch Gynecol Obstet 291:837,2015 Bastholm SK, Samson MH, Becher N, et al: Trefoil factor peptide 3 is positively correlated with the viscoelastic properties of the cervical mucus plug. Acta Obstet Gynecol Scand 96(1):47, 2017 Bergersen TK, Hartgill W, Pirhonen]: Cerebrovascular response to normal pregnancy: a longitudinal study. Am] Physiol Heart Circ Physiolr290: 1856,r2006 Berggren EK, Presley L, Amini SB, et al: Are the metabolic changes of pregnancy reversible in the first year postpartum? Diabetologia 58:1561,r2015 Bernstein 1M, Ziegler W, Badger G]: Plasma volume expansion in early pregnancy. Obstet Gynecol 97:669, 2001


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Obstentrics_Williams. Bernstein 1M, Ziegler W, Badger G]: Plasma volume expansion in early pregnancy. Obstet Gynecol 97:669, 2001 Bieniarz ], Branda A, Maqueda E, et al: Aortocaval compression by the uterus in late pregnancy, 3. Unreliabiliry of the sphygmomanometric method in estimating uterine artery pressure. Am ] Obstet Gynecol 102: 11 06, 1968 Bloom SL, Uppot R, Roberts 0]: Case 32-2010: a pregnant woman with abdominal pain and fluid in the peritoneal caviry. N Engl ] Med 363(17):1657,r2010 Bobrowski A: Pulmonary physiology in pregnancy. Clin Obstet Gynecol 53(2):286, 2010 Boehlen F, Hohlfeld P, Extermann P, et al: Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol 95:29, 2000 Bramham K, Hladunewich A, Jim B, et al: Pregnancy and kidney disease. NephSAP Neprology Self-Assessment Program 15(2):115,r2016 Braverman DZ, Johnson ML, Kern F ]r: Efects of pregnancy and contraceptive steroids on gallbladder function. N Engl] Med 302:362, 1980


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Obstentrics_Williams. NephSAP Neprology Self-Assessment Program 15(2):115,r2016 Braverman DZ, Johnson ML, Kern F ]r: Efects of pregnancy and contraceptive steroids on gallbladder function. N Engl] Med 302:362, 1980 Brifa ]F, McAinch A], Romano T, et al: Leptin in pregnancy and development: a contributor to adulthood disease? Am ] Physiol Endocrinol Metab 308:E335,r2015 Brown CH, Bains ]S, Ludwig M, et al: Physiological regulation of magnocellular neurosecretory cell activiry: integration of intrinsic, local and aferent mechanisms.r] NeuroendocrinoIr25:678, 2013 Brown A, Gallery EDM, Ross MR, et al: Sodium excretion in normal and hypertensive pregnancy: a prospective study. Am] Obstet Gynecol 159:297, 1988 Brown A, Sinosich M], Saunders OM, et al: Potassium regulation and progesterone-aldosterone interrelationships in human pregnancy: a prospective study. Am] Obstet Gynecol 155:349, 1986


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Obstentrics_Williams. Brown A, Sinosich M], Saunders OM, et al: Potassium regulation and progesterone-aldosterone interrelationships in human pregnancy: a prospective study. Am] Obstet Gynecol 155:349, 1986 Browne ]C, Veall N: The maternal placental blood low in normotensive and hypertensive women.r] Obstet Gynaecol Br Emp 60(2):141,r1953 Burns R, Azizi F, Hedayati M, et al: Is placental iodine content related to dietary iodine intake? Clin Endocrinol 75(2):261, 2011 Burrow GN, Fisher DA, Larsen PR: Maternal and fetal thyroid function. N Engl] Med 331:1072,r1994 Camaschella C: Iron deiciency anemia. N Engl] Med 372: 1832, 2015 Carr BR, Parker CR ]r, Madden ]0, et al: Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am ] Obstet GynecoIr139:416,r1981


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Obstentrics_Williams. Carr BR, Parker CR ]r, Madden ]0, et al: Maternal plasma adrenocorticotropin and cortisol relationships throughout human pregnancy. Am ] Obstet GynecoIr139:416,r1981 Cattozzo G, Calonaci A, lbeni e, et al: Reference values for alanine aminotransferase, a-amylase, aspartate aminotransferase, l-glutamyltransferase and lactate dehydrogenase measured according to the IFCC standardization during uncomplicated pregnancy. Clin Chen Lab Med 51:e239, 2013 Cavoretto P, Giorgione V, Sigismondi e, et al: Hyperreactio luteinalis: timely diagnosis minimizes the risk of oophorectomy and alerts clinicians to the associated risk of placental insuiciency. Eur J Obstet Gynecol Reprod Bioi 176:10,r2014 Chehab FF: 20 years ofleptin: leptin and reproduction: past milestones, present undertakings, and future endeavors. J Endocrinol 223:T37, 2014 Chesley LC: Renal function during pregnancy. In Carey HM (ed): Modern Trends in Human Reproductive Physiology. London, Butterworth, 1963


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Obstentrics_Williams. Chesley LC: Renal function during pregnancy. In Carey HM (ed): Modern Trends in Human Reproductive Physiology. London, Butterworth, 1963 Chong MF, Chia AR, Colega M, et al: Maternal protein intake during pregnancy is not associated with ofspring birth weight in a multiethnic Asian population. J Nutr 145:1303,r2015 Cietak A, Newton JR: Serial quantitative maternal nephrosonography in pregnancy. Br J Radiol 58:405, 1985 Cipolla MJ, Zeeman GG, Cunningham FG: Cerebrovascular (patho)physiology in preeclampsia/eclampsia. In Taylor RN, Roberts JM, Cunningham FG (eds): Chesley's Hypertensive Disorders in Pregnancy, 4th ed. Amsterdam, Academic Press, 2014 Clapp JF III, Stepanchak W, Tomaselli J, et al: Portal vein blood Bow-efects of pregnancy, gravity, and exercise. Am J Obstet Gynecol 183: 167,r2000 Clark SL, Cotton DB, Lee W, et al: Central hemodynamic assessment of nor mal term pregnancy. Am J Obstet Gynecol 161:1439, 1989


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