Heart

Some of the most profound physiologic changes of pregnancy take place in the cardiovascular system in order to maximize oxygen delivery to both the mother and fetus. The combination of displacement of the diaphragm and the effect of pregnancy on the shape of the rib cage displaces the heart upward and to the left. The heart also rotates along its long axis, thereby resulting in an increased cardiac silhouette on imaging studies. No change is evident in the cardiothoracic ratio. Other radiographic findings include an apparent straightening of the left-sided heart border and increased prominence of the pulmonary conus. It is therefore important to confirm the diagnosis of cardiomegaly with an echocardiogram and not simply to rely on radiographic imaging.

Eccentric cardiac hypertrophy is commonly noted in pregnancy. It is thought to result from expanded blood volume in the first half of pregnancy and progressively increasing afterload in later gestation. These changes, similar to those found in response to exercise, enable the pregnant woman’s heart to work more efficiently. Unlike the heart of an athlete that regresses rapidly with inactivity, the pregnant woman’s heart decreases in size less rapidly and takes up to 6 months to return to normal.

Cardiac Output

One of the most remarkable changes in pregnancy is the tremendous increase in cardiac output (CO). A review of 33 cross-sectional and 19 longitudinal studies revealed that CO increased significantly beginning in early pregnancy and peaked at an average of 30% to 50% above preconceptional values. In a longitudinal study using Doppler echocardiography, CO increased by 50% at 34 weeks from a prepregnancy value of 4.88 to 7.34 L/min ( Fig. 3-1 ). In twin gestations, CO incrementally increases an additional 20% above that of singleton pregnancies. By 5 weeks’ gestation, CO has already risen by more than 10%. By 12 weeks, the rise in output is 34% to 39% above nongravid levels, which accounts for about 75% of the total increase in CO during pregnancy. Although the literature is not clear regarding the exact point in gestation at which CO peaks, most studies point to a range between 25 and 30 weeks. The data on whether the CO continues to increase in the third trimester are very divergent, with equal numbers of good longitudinal studies showing a mild decrease, a slight increase, or no change. Thus little to no change is likely during this period. This apparent discrepancy appears to be explained by the small number of individuals in each study and the probability that the course of CO during the third trimester is determined by factors specific to the individual. For example, maternal CO in the third trimester is significantly correlated with fetal birthweight and maternal height and weight.

Increase in cardiac output, stroke volume, and heart rate from the nonpregnant state throughout pregnancy. PN, postnatal; P-P, prepregnancy.

(From Hunter S, Robson S. Adaptation of the maternal heart in pregnancy. Br Heart J. 1992;68:540.)

Most of the increase in cardiac output is directed to the uterus, placenta, and breasts. In the first trimester, as in the nongravid state, the uterus receives 2% to 3% of CO and the breasts 1%. The percentage of CO that goes to the kidneys (20%), skin (10%), brain (10%), and coronary arteries (5%) remains at similar nonpregnant percentages, but because of the overall increase in CO, this results in an increase in absolute blood flow of about 50%. By term, the uterus receives 17% (450 to 650 mL/min) and the breasts 2%, mostly at the expense of a reduction of the fraction of the CO going to the splanchnic bed and skeletal muscle. The absolute blood flow to the liver is not changed, but the overall percentage of CO is significantly decreased.

Cardiac output (CO) is the product of stroke volume (SV) and heart rate (HR; CO = SV × HR), both of which increase during pregnancy and contribute to the overall rise in CO. An initial rise in the HR occurs by 5 weeks’ gestation and continues until it peaks at 32 weeks’ gestation at 15 to 20 beats above the nongravid rate, an increase of 17%. The SV begins to rise by 8 weeks of gestation and reaches its maximum at about 20 weeks at 20% to 30% above nonpregnant values.

Cardiac output in pregnancy depends on maternal position. In a study in 10 normal gravid women in the third trimester, using pulmonary artery catheterization, CO was noted to be highest in the knee-chest and lateral recumbent positions at 6.9 and 6.6 L/min, respectively. CO decreased by 22% to 5.4 L/min in the standing position ( Fig. 3-2 ). The decrease in CO in the supine position, compared with the lateral recumbent position, is 10% to 30%. In both the standing and the supine positions, decreased CO results from a fall in SV secondary to decreased blood return to the heart. In the supine position, the enlarged uterus compresses the inferior vena cava (IVC), which reduces venous return; before 24 weeks, this effect is not observed. In late pregnancy, the IVC is completely occluded in the supine position, and venous return from the lower extremities occurs through the dilated paravertebral collateral circulation. It is worth noting that whereas the original studies of CO were done with invasive testing, the current accepted practice is to estimate CO in pregnancy using echocardiography.

Effect of position change on cardiac output during pregnancy. * P < .05. K-C, knee-chest; L.LAT, left lateral; R.LAT, right lateral; SIT, sitting; ST, standing; SUP, supine.

(From Clark S, Cotton D, Pivarnik J, et al. Position change and central hemodynamic profile during normal third-trimester pregnancy and postpartum. Am J Obstet Gynecol. 1991;164:883.)

Despite decreased cardiac output, most supine women are not hypotensive or symptomatic because of the compensated rise in systemic vascular resistance (SVR). However, 5% to 10% of gravidas manifest supine hypotension with symptoms of dizziness, lightheadedness, nausea, and even syncope. The women who become symptomatic have a greater decrease in CO and blood pressure (BP) and a greater increase in HR when in the supine position than do asymptomatic women. Interestingly, with engagement of the fetal head, less of an effect on CO is seen. The ability to maintain a normal BP in the supine position may be lost during epidural or spinal anesthesia because of an inability to increase SVR. Clinically, the effects of maternal position on CO are especially important when the mother is clinically hypotensive or in the setting of a nonreassuring fetal heart rate tracing. The finding of a decreased CO in the standing position may give a physiologic basis for the finding of decreased birthweight in working women who stand for prolonged periods. In twin pregnancies, CO is notably 15% higher than in singleton pregnancies. This finding is corroborated with findings of increased left atrial diameter in twin pregnancies, indicating volume overload.

Arterial Blood Pressure and Systemic Vascular Resistance

Blood pressure is the product of cardiac output and systemic vascular resistance (BP = CO × SVR). Despite the significant increase in cardiac output, the maternal BP is decreased until later in pregnancy as a result of a decrease in SVR that reaches its nadir at midpregnancy and is followed by a gradual rise until term. Even at full term, SVR remains 21% lower than prepregnancy values in pregnancies not affected by gestational hypertension or preeclampsia. The most obvious cause for the decreased SVR is progesterone-mediated smooth muscle relaxation. However, the exact mechanism for the fall in SVR is poorly understood and likely involves vasorelaxation via the nitric oxide pathway and blunting of vascular responsiveness to vasoconstrictors such as angiotensin II and norepinephrine. As a result, despite the overall increase in the renin-angiotensin aldosterone system (RAAS), the normal gravida is refractory to the vasoconstrictive effects of angiotensin II. Gant and colleagues showed that nulliparous women who later develop preeclampsia retain their response to angiotensin II before the appearance of clinical signs of preeclampsia.

Decreases in maternal BP parallel the falling SVR, with initial decreased BP that manifests at 8 weeks’ gestation or earlier. Because BP fluctuates with menstruation and is decreased in the luteal phase, it seems reasonable that BP drops immediately in early pregnancy. The diastolic BP and the mean arterial pressure (MAP, [2 × diastolic BP + systolic BP]/3) decrease more than the systolic BP, which changes minimally. The overall decrease in diastolic BP and MAP is 5 to 10 mm Hg ( Fig. 3-3 ). The diastolic BP and the MAP reach their nadir at midpregnancy and return to prepregnancy levels by term. In most studies, they rarely exceed prepregnancy or postpartum values; however, some investigators have reported that at term, the BP is greater than that in matched nonpregnant controls. They have also found that in the third trimester, the BP is higher than prepregnant values. As noted previously, pregnancy-induced BP changes happen very early, possibly even before the patient realizes that she is pregnant, and therefore even early pregnancy BP assessments may not be consistent with prepregnancy values.

Blood pressure (BP) trends (sitting and lying) during pregnancy. Postnatal (PN) measures were performed 6 weeks postpartum.

(From MacGillivray I, Rose G, Rowe B. Blood pressure survey in pregnancy. Clin Sci. 1969;37:395.)

The position when the BP is taken and what Korotkoff sound is used to determine the diastolic BP are important. BP is lowest in the lateral recumbent position, and the BP of the superior arm in this position is 10 to 12 mm Hg lower than that in the inferior arm. In the ambulatory setting, BP should be measured in the sitting position, and the Korotkoff 5 sound should be used. This is the diastolic BP when the sound disappears, as opposed to the Korotkoff 4, when a muffling of the sound is apparent. In a study of 250 gravidas, the Korotkoff 4 sound could only be identified in 48% of patients, whereas the Korotkoff 5 sound could always be determined. The Korotkoff 4 should only be used when the Korotkoff 5 occurs at 0 mm Hg. Automated BP monitors have been compared with mercury sphygmomanometry during pregnancy, and although they tended to overestimate the diastolic BP, the overall results were similar in normotensive women. Of note in patients with suspected preeclampsia, automated monitors appear increasingly inaccurate at higher BPs.

Venous Pressure

Venous pressure in the upper extremities remains unchanged in pregnancy but rises progressively in the lower extremities. Femoral venous pressure increases from values near 10 cm H ₂ O at 10 weeks’ gestation to 25 cm H ₂ O near term. From a clinical standpoint, this increase in pressure—in addition to the obstruction of the IVC by the expanding uterus—leads to the development of edema, varicose veins, and hemorrhoids and increases the risk for deep venous thrombosis (DVT).

Central Hemodynamic Assessment

Clark and colleagues studied 10 carefully selected normal women at 36 to 38 weeks’ gestation and again at 11 to 13 weeks’ postpartum with arterial lines and Swan-Ganz catheterization to characterize the central hemodynamics of term pregnancy ( Table 3-2 ). Newer, noninvasive methods of central hemodynamic monitoring are being developed and validated in the pregnant population. As described earlier, CO, HR, SVR, and pulmonary vascular resistance (PVR) change significantly with pregnancy. In addition, clinically significant decreases occur in colloidal oncotic pressure (COP) and in the COP–pulmonary capillary wedge pressure (PCWP) difference, which explains why gravid women have a greater propensity for developing pulmonary edema with changes in capillary permeability or elevations in cardiac preload. The COP can fall even further after delivery, to 17 mm Hg, and if the pregnancy is complicated by preeclampsia, it can reach levels as low as 14 mm Hg. When the PCWP is more than 4 mm Hg above the COP, the risk for pulmonary edema increases; therefore pregnant women can experience pulmonary edema at PCWPs of 18 to 20 mm Hg, which is significantly lower than the typical nonpregnant threshold of 24 mm Hg.

Normal Changes That Mimic Heart Disease

The physiologic adaptations of pregnancy lead to a number of changes in maternal signs and symptoms that can mimic cardiac disease and make it difficult to determine whether true disease is present. Dyspnea is common to both cardiac disease and pregnancy, but certain distinguishing features should be considered. First, the onset of pregnancy-related dyspnea usually occurs before 20 weeks, and 75% of women experience it by the third trimester. Unlike cardiac dyspnea, pregnancy-related dyspnea does not worsen significantly with advancing gestation. Second, physiologic dyspnea is usually mild, does not stop women from performing normal daily activities, and does not occur at rest. The mechanism for dyspnea of pregnancy is not well characterized but is thought to be secondary to the increased effort of inspiratory muscles. Other normal symptoms that can mimic cardiac disease include decreased exercise tolerance, fatigue, occasional orthopnea, syncope, and chest discomfort. Symptoms that should not be attributed to pregnancy and that need a more thorough investigation include hemoptysis, syncope or chest pain with exertion, progressive orthopnea, or paroxysmal nocturnal dyspnea. Normal physical findings that could be mistaken as evidence of cardiac disease include peripheral edema, mild tachycardia, jugular venous distension after midpregnancy, and lateral displacement of the left ventricular apex.

Pregnancy also alters normal heart sounds. At the end of the first trimester, both components of the first heart sound become louder, and exaggerated splitting is apparent. The second heart sound usually remains normal with only minimal changes. Up to 80% to 90% of gravidas demonstrate a third heart sound (S ₃ ) after midpregnancy because of rapid diastolic filling. Rarely, a fourth heart sound may be auscultated, but typically phonocardiography is needed to detect this. Systolic ejection murmurs along the left sternal border develop in 96% of pregnancies, and increased blood flow across the pulmonic and aortic valves is thought to be the cause. Most commonly, these are midsystolic and less than grade 3. Diastolic murmurs have been found in up to 18% of gravidas, but their presence is uncommon enough to warrant further evaluation. A continuous murmur in the second to fourth intercostal space may be heard in the second or third trimester owing to the so-called mammary souffle caused by increased blood flow in the breast ( Fig. 3-4 ).

Summary of the findings on auscultation of the heart in pregnancy. MC, mitral closure; TC, tricuspid closure; A2 and P2, aortic and pulmonary elements of the second heart sound.

(From Cutforth R, MacDonald C. Heart sounds and murmurs in pregnancy. Am Heart J. 1966;71:741.)

Troponin 1 and creatinine kinase-MB levels are tests used to assess myocardial injury in acute myocardial infarction. Uterine contractions can lead to significant increases in the creatinine kinase-MB level, but troponin levels are not affected by pregnancy or labor.

Effect of Labor and the Immediate Puerperium

The profound anatomic and functional changes in cardiac function reach a crescendo during the labor process. In addition to the dramatic rise in cardiac output with normal pregnancy, even greater increases in cardiac output occur with labor and in the immediate puerperium. In a Doppler echocardiography study of 15 uncomplicated cases without epidural anesthesia, the CO between contractions increased 12% during the first stage of labor ( Fig. 3-5 ). This increase in CO is caused primarily by an increased SV, but HR may also rise. By the end of the first stage of labor, the CO during contractions is 51% above baseline term pregnancy values (6.99 to 10.57 L/min). Increased CO is in part secondary to increased venous return from the 300- to 500-mL autotransfusion that occurs at the onset of each contraction as blood is expressed from the uterus. Paralleling increases in CO, the MAP also rises in the first stage of labor, from 82 to 91 mm Hg in early labor to 102 mm Hg by the beginning of the second stage. MAP also increases with uterine contractions.

Changes in cardiac output during normal labor.

(From Hunter S, Robson S. Adaptation of the maternal heart in pregnancy. Br Heart J 1992;68:540.)

Much of the increase in CO and MAP is due to pain and anxiety. With epidural anesthesia, the baseline increase in CO is reduced, but the rise observed with contractions persists. Maternal posture also influences hemodynamics during labor. Changing position from supine to lateral recumbent increases CO. This change is greater than the increase seen before labor and suggests that during labor, CO may be more dependent on preload. Therefore it is important to avoid the supine position in laboring women and to give a sufficient fluid bolus before an epidural to maintain an adequate preload.

In the immediate postpartum period (10 to 30 min after delivery) , with a further rise in cardiac output of 10% to 20%, CO reaches its maximum. This increase is accompanied by a fall in the maternal HR that is likely secondary to increased SV. Traditionally, this rise was thought to be the result of uterine autotransfusion as described earlier with contractions, but the validity of this concept is uncertain. In both vaginal and elective cesarean deliveries, the maximal increase in the CO occurs 10 to 30 min after delivery and returns to the prelabor baseline 1 hour after delivery. The increase was 37% with epidural anesthesia and 28% with general anesthesia. Over the next 2 to 4 postpartum weeks, the cardiac hemodynamic parameters return to near-preconceptional levels.

Cardiac Rhythm

The effect of pregnancy on cardiac rhythm is limited to an increase in HR and a significant increase in isolated atrial and ventricular contractions. In a Holter monitor study, 110 pregnant women referred for evaluation of symptoms of palpitations, dizziness, or syncope were compared with 52 healthy pregnant women. Symptomatic women had similar rates of isolated sinus tachycardia (9%), isolated premature atrial complexes (56%), and premature ventricular contractions (PVCs; 49%) but increased rates of frequent PVCs greater than 10/hour (22% vs. 2%, P = .03). A subset of patients with frequent premature atrial complexes or PVCs had comparative Holter studies performed postpartum that revealed an 85% decrease in arrhythmia frequency ( P < .05). This dramatic decline, with patients acting as their own controls, supports the arrhythmogenic effect of pregnancy. In a study of 30 healthy women placed on Holter monitors during labor, a similarly high incidence of benign arrhythmias was found (93%). Reassuringly, the prevalence of concerning arrhythmias was no higher than expected. An unexpected finding was a 35% rate of asymptomatic bradycardia, defined as an HR of less than 60 beats/min in the immediate postpartum period. Other studies have shown that women with preexisting tachyarrhythmias have an increased incidence of these rate abnormalities during pregnancy. Whether labor increases the rate of arrhythmias in women with cardiac disease has not been thoroughly studied, but multiple case reports suggest labor may increase arrhythmias in these women.

Plasma Volume and Red Cell Mass

Maternal blood volume begins to increase at about 6 weeks’ gestation. Thereafter, it rises progressively until 30 to 34 weeks and then plateaus until delivery. The average expansion of blood volume is 40% to 50% (range 20% to 100%). Women with multiple pregnancies have a larger increase in blood volume than those with singletons. Likewise, volume expansion correlates with infant birthweight, but it is not clear whether this is a cause or an effect. The increase in blood volume results from a combined expansion of both plasma volume and red blood cell (RBC) mass. The plasma volume begins to increase by 6 weeks and expands at a steady pace until it plateaus at 30 weeks’ gestation; the overall increase is about 50% (1200 to 1300 mL). The exact etiology of the expansion of the blood volume is unknown, but the hormonal changes of gestation and the increase in nitric oxide (NO) play important roles.

Erythrocyte mass also begins to expand at about 10 weeks’ gestation. Although the initial slope of this increase is slower than that of the plasma volume, erythrocyte mass continues to grow progressively until term without plateauing. Without iron supplementation, RBC mass increases about 18% by term, from a mean nonpregnant level of 1400 mL up to 1650 mL. Supplemental iron increases RBC mass accumulation to 400 to 450 mL, or 30%, and a corresponding improvement is seen in hemoglobin levels. Because plasma volume increases more than the RBC mass, maternal hematocrit falls. This so-called physiologic anemia of pregnancy reaches a nadir at 30 to 34 weeks. Because the RBC mass continues to increase after 30 weeks when the plasma volume expansion has plateaued, the hematocrit may rise somewhat after 30 weeks ( Fig. 3-6 ). The mean and fifth-percentile hemoglobin concentrations for normal iron-supplemented pregnant women are outlined in Table 3-3 . A hemoglobin level that reaches its nadir at 9 to 11 g/dL has been associated with the lowest rate of perinatal mortality, whereas values below or above this range have been linked to an increased perinatal mortality.

Blood volume changes during pregnancy . RBC, red blood cell.

(From Scott DE. Anemia in pregnancy. Obstet Gynecol Annu. 1972;1:219-244.)

In pregnancy, erythropoietin levels increase twofold to threefold, starting at 16 weeks, and they may be responsible for the moderate erythroid hyperplasia found in the bone marrow and for the mild elevations in the reticulocyte count. The increased blood volume is protective given the possibility of hemorrhage during pregnancy or at delivery. The larger blood volume also helps fill the expanded vascular system created by vasodilation and by the large, low-resistance vascular pool within the uteroplacental unit, thereby preventing hypotension.

Vaginal delivery of a singleton infant at term is associated with a mean blood loss of 500 mL; an uncomplicated cesarean delivery, about 1000 mL; and a cesarean hysterectomy, 1500 mL. In a normal delivery, almost all of the blood loss occurs in the first hour. Pritchard and colleagues found that over the subsequent 72 hours, only 80 mL of blood is lost. Gravid women respond to blood loss in a different fashion than in the nonpregnant state. In pregnancy, the blood volume drops after postpartum bleeding, but no reexpansion to the prelabor level occurs, and less of a change is seen in the hematocrit. Indeed, instead of volume redistribution, an overall diuresis of the expanded water volume occurs postpartum. After delivery with average blood loss, the hematocrit drops moderately for 3 to 4 days, followed by an increase. By days 5 to 7, the postpartum hematocrit is similar to the prelabor hematocrit. If the postpartum hematocrit is lower than the prelabor hematocrit, either the blood loss was greater than appreciated, or the hypervolemia of pregnancy was less than normal, as in preeclampsia.

Iron Metabolism

Iron absorption from the duodenum is limited to its ferrous (divalent) state, the form found in iron supplements. Ferric (trivalent) iron from vegetable food sources must first be converted to the divalent state by the enzyme ferric reductase. If body iron stores are normal, only about 10% of ingested iron is absorbed, most of which remains in the mucosal cells or enterocytes until sloughing leads to excretion in the feces (1 mg/day). Under conditions of increased iron needs, such as during pregnancy, the fraction of iron absorbed increases. After absorption, iron is released from the enterocytes into the circulation, where it is carried bound to transferrin to the liver, spleen, muscle, and bone marrow. In those sites, iron is freed from transferrin and is incorporated into hemoglobin (75% of iron) and myoglobin or is stored as ferritin and hemosiderin. Menstruating women have about half the iron stores of men, with total body iron of 2 to 2.5 g and iron stores of only 300 mg. Before pregnancy, 8% to 10% of women in Western nations have an iron deficiency.

The iron requirements of gestation are about 1000 mg. This includes 500 mg used to increase the maternal RBC mass (1 mL of erythrocytes contains 1.1 mg iron), 300 mg transported to the fetus, and 200 mg to compensate for the normal daily iron losses by the mother. Thus the normal expectant woman needs to absorb an average of 3.5 mg/day of iron. In actuality, the iron requirements are not constant but increase remarkably during the pregnancy from 0.8 mg/day in the first trimester to 6 to 7 mg/day in the third trimester. The fetus receives its iron through active transport via transferrin receptors located on the apical surface of the placental syncytiotrophoblast. Holotransferrin is then endocytosed, and the iron is released and follows a similar pattern to reach the fetal circulation. In the setting of maternal iron deficiency, the number of placental transferrin receptors increases so that more iron is taken up by the placenta; however, the capacity of this compensatory mechanism can be inadequate and can result in fetal iron deficiency. Maternal iron deficiency anemia has also been associated with adverse pregnancy outcomes, such as low birthweight infants and preterm birth. For a review on the use of supplemental iron in pregnancy, see Chapter 44 .

Platelets

Before the introduction of automated analyzers, studies of platelet counts during pregnancy reported conflicting results. Even with the availability of automated cell counters, the data on the change in platelet count during pregnancy are still somewhat unclear. Pitkin and colleagues measured platelet counts in 23 women every 4 weeks and found that the counts dropped from 322 ± 75 × 10 ³ /mm ³ in the first trimester to 278 ± 75 × 10 ³ /mm ³ in the third trimester. More recent studies confirm a decline in the platelet count during gestation possibly caused by increased destruction or hemodilution. In addition to the mild decrease in the mean platelet count, Burrows and Kelton demonstrated that in the third trimester, about 8% of gravidas develop gestational thrombocytopenia with platelet counts between 70,000 and 150,000/mm ³ . Gestational thrombocytopenia is not associated with an increase in pregnancy complications, and platelet counts return to normal by 1 to 2 weeks postpartum (see Chapter 44 ). Many features of gestational thrombocytopenia are similar to those of mild immune thrombocytopenia, so the etiology may be immunologic. Another hypothesis is that gestational thrombocytopenia is due to exaggerated platelet consumption, similar to that seen in normal pregnancy. Consistent with these findings, Boehlen and associates compared platelet counts during the third trimester of pregnancy with those in nonpregnant controls and showed a shift to a lower mean platelet count and an overall shift to the left of the “platelet curve” in the pregnant women ( Fig. 3-7 ). This study found that only 2.5% of nonpregnant women have platelet counts less than 150,000/mm ³ , the traditional value used outside of pregnancy as the cutoff for normal, versus 11.5% of gravid women. A platelet count of less than 116,000/mm ³ occurred in 2.5% of gravid women; therefore these investigators recommended using this value as the lower limit for normal in the third trimester. In addition, they suggested that workups for the etiology of decreased platelet count were unneeded at values above this level.

Histogram of platelet count of pregnant women in the third trimester ( n = 6770) compared with nonpregnant women ( n = 287).

(From Boehlen F, Hohlfield P, Extermann P. Platelet count at term pregnancy: a reappraisal of the threshold. Obstet Gynecol. 2000;95:29.)

The normal decrease in platelet count is associated with an increase in platelet aggregability. This is evidenced by decreased platelet-function analyzer (PFA-100) values, which signify a decreased time for a platelet plug to occlude an aperture in a collagen membrane and measures the ability of platelets to occlude a vascular breach. Thus while the number of platelets decreases, platelet function increases to maintain hemostasis.

Leukocytes

The peripheral white blood cell (WBC) count rises progressively during pregnancy. During the first trimester, the mean WBC count is 8000/mm ³ with a normal range of 5110 to 9900/mm ³ . During the second and third trimesters, the mean is 8500/mm ³ with a range of 5600 to 12,200/mm ³ . In labor, the count may rise to 20,000 to 30,000/mm ³ , and counts are highly correlated with labor progression as determined by cervical dilation. Because of the normal increase of WBCs in labor, the WBC count should not be used clinically in determining the presence of infection. The increase in the WBC count is largely due to increases in circulating segmented neutrophils and granulocytes, whose absolute number is nearly doubled at term. The reason for the increased leukocytosis is unclear, but it may be caused by the elevated estrogen and cortisol levels. Leukocyte levels return to normal within 1 to 2 weeks of delivery.

Coagulation System

Pregnancy places women at a fivefold to sixfold increased risk for thromboembolic disease (see Chapter 45 ). This greater risk is caused by increased venous stasis, vessel wall injury, and changes in the coagulation cascade that lead to hypercoagulability. The increase in venous stasis in the lower extremities is due to compression of the IVC and the pelvic veins by the enlarging uterus. The hypercoagulability is caused by an increase in several procoagulants, a decrease in the natural inhibitors of coagulation, and a reduction in fibrinolytic activity. These physiologic changes provide defense against peripartum hemorrhage.

Most of the procoagulant factors from the coagulation cascade are markedly increased, including factors I, VII, VIII, IX, and X. Factors II, V, and XII are unchanged or mildly increased, and levels of factors XI and XIII decline. Plasma fibrinogen (factor I) levels begin to increase in the first trimester and peak in the third trimester at levels 50% higher than before pregnancy. The rise in fibrinogen is associated with an increase in the erythrocyte sedimentation rate. In addition, pregnancy causes a decrease in the fibrinolytic system with reduced levels of available circulating plasminogen activator, a twofold to threefold increase in plasminogen activator inhibitor 1 (PAI-1), and a 25-fold increase in PAI-2. The placenta produces PAI-1 and is the primary source of PAI-2.

Pregnancy has been shown to cause a progressive and significant decrease in the levels of total and free protein S from early in pregnancy, but it has no effect on the levels of protein C and antithrombin III. The activated protein C (APC)/sensitivity (S) ratio, the ratio of the clotting time in the presence and the absence of APC, declines during pregnancy. The APC/S ratio is considered abnormal if it is less than 2.6. In a study of 239 women, the APC/S ratio decreased from a mean of 3.12 in the first trimester to 2.63 by the third trimester. By the third trimester, 38% of women were found to have an acquired APC resistance, with APC/S ratio values below 2.6. Whether the changes in the protein-S level and the APC/S ratio are responsible for some of the hypercoagulability of pregnancy is unknown. If a workup for thrombophilias is performed during gestation, the clinician should use caution when attempting to interpret these levels if they are abnormal. Ideally the clinician should order DNA testing for the Leiden mutation instead of testing for APC. For protein-S screening during pregnancy, the free protein-S antigen level should be tested, with normal levels in the second and third trimesters being identified as greater than 30% and 24%, respectively.

Most coagulation testing is unaffected by pregnancy. The prothrombin time (PT), activated partial thromboplastin time (PTT), and thrombin time all fall slightly but remain within the limits of normal nonpregnant values, whereas the bleeding time and whole blood clotting times are unchanged. Testing for von Willebrand disease is affected in pregnancy because levels of factor VIII, von Willebrand factor activity and antigen, and ristocetin cofactor all increase. Levels of coagulation factors normalize 2 weeks postpartum.

Researchers have found evidence to support the theory that during pregnancy, a state of low-level intravascular coagulation occurs. Low concentrations of fibrin degradation products (markers of fibrinolysis), elevated levels of fibrinopeptide A (a marker for increased clotting), and increased levels of platelet factor 4 and β-thromboglobulin (markers of increased platelet activity) have been found in maternal blood. The most likely cause for these findings involves localized physiologic changes needed for maintenance of the uterine-placental interface.

The complex array of procoagulative changes can be further illustrated via emerging point-of-care analyses, such as thromboelastography and rotational thromboelastography. Briefly, these assays provide a visual and numeric representation of the rate of clot formation and the stability of the clot, which allows a detailed analysis of the expected hypercoagulable state and, if indicated, targets for transfusion. Use of these tests in pregnancy requires caution, however, because physiologic values vary in pregnancy compared with a nonpregnant state; these changes reflect a procoagulative state. Reference ranges for pregnancy are shown in Table 3-4 .

Upper Respiratory Tract

During pregnancy, the mucosa of the nasopharynx becomes hyperemic and edematous with hypersecretion of mucus due to increased estrogen. These changes often lead to marked nasal stuffiness and decreased nasal patency; 27% of women at 12 weeks’ gestation report nasal congestion and rhinitis, and this increases to 42% at 36 weeks’ gestation. This decreased patency can lead to anesthesia complications; in fact, the Mallampati score is demonstrably increased (see Chapter 16 ). Epistaxis is also common and may rarely require surgery. Additionally, the placement of nasogastric tubes may cause excessive bleeding if adequate lubrication is not used. Polyposis of the nose and nasal sinuses develops in some individuals but regresses postpartum. Because of these changes, many gravid women complain of chronic cold symptoms. However, the temptation to use nasal decongestants should be avoided because of the risk for hypertension and rebound congestion.

Mechanical Changes

The configuration of the thoracic cage changes early in pregnancy, much earlier than can be accounted for by mechanical pressure from the enlarging uterus. Relaxation of the ligamentous attachments between the ribs and sternum may be responsible. The subcostal angle increases from 68 to 103 degrees, the transverse diameter of the chest expands by 2 cm, and the chest circumference expands by 5 to 7 cm. As gestation progresses, the level of the diaphragm rises 4 cm; however, diaphragmatic excursion is not impeded and actually increases 1 to 2 cm. This increased diaphragmatic excursion is the effect of progesterone, which acts at the level of the central chemoreceptors to increase diaphragmatic effort and results in greater negative inspiratory pressures. Respiratory muscle function is not affected by pregnancy, and maximal inspiratory and expiratory pressures are unchanged.

Lung Volume and Pulmonary Function

The described alterations in chest wall configuration and in the diaphragm lead to changes in static lung volumes. In a review of studies with at least 15 subjects, compared with nonpregnant controls, Crapo found significant changes ( Fig. 3-8 , Table 3-5 ). The elevation of the diaphragm decreases the volume of the lungs in the resting state, thereby reducing total lung capacity (TLC) and the functional residual capacity (FRC). The FRC can be subdivided into expiratory reserve volume (ERV) and residual volume (RV), and both decrease.

Lung volumes in nonpregnant and pregnant women. ERV, expiratory reserve; FRC, functional residual capacity; IC, inspiratory capacity; IRV, inspiratory reserve; RV, residual volume; TLC, total lung capacity; TV, tidal volume; VC, vital capacity.

(From Cruickshank DP, Wigton TR, Hays PM. Maternal physiology in pregnancy. In Gabbe SG, Niebyl JR, Simpson JL, eds. Obstetrics: Normal and Problem Pregnancies, 3rd ed. New York: Churchill Livingstone; 1996, p 94.)

Some spirometric measurements to assess bronchial flow are unchanged in pregnancy, whereas others are altered. Historically, it has been well accepted that the forced expiratory volume in 1 second (FEV ₁ ) does not change, which suggests that the airway function remains stable. However, FEV ₁ may indeed decrease across pregnancy under certain circumstances, such as high altitude. Different studies have observed varied effects on the peak expiratory flow. In a longitudinal study of the peak flow in 38 women from the first trimester until 6 weeks postpartum, peak flows had a statistically significant decrease as gestation progressed, but the amount of the decrease was of questionable clinical significance. Likewise, a small decline in the peak flow was found in the supine position versus the standing or sitting position. In a similar study of 80 women, peak expiratory flow (PEF) was found to increase progressively after 14 to 16 weeks. Notably, these values were also significantly higher at any time point during pregnancy in parous compared with nulliparous women, which may suggest that this change is permanent. An additional finding of this study was that no differences in forced vital capacity (FVC), FEV ₁ , or PEF were noted based on overweight status or excess gestational weight gain. In summary, both spirometry and peak flowmeters can be used to diagnose and manage respiratory illness, but the clinician should ensure that measurements are performed in the same maternal position .

Gas Exchange

Increasing progesterone levels drive a state of chronic hyperventilation, as reflected by a 30% to 50% increase in tidal volume by 8 weeks’ gestation. In turn, increased tidal volume results in an overall parallel rise in minute ventilation, despite a stable respiratory rate (minute ventilation = tidal volume × respiratory rate). The rise in minute ventilation, combined with a decrease in FRC, leads to a larger than expected increase in alveolar ventilation (50% to 70%). Chronic mild hyperventilation results in increased alveolar oxygen (PaO ₂ ) and decreased arterial carbon dioxide (PaCO ₂ ) from normal levels ( Table 3-6 ). The drop in the PaCO ₂ is especially critical because it drives a more favorable CO ₂ gradient between the fetus and mother, which facilitates CO ₂ transfer. The low maternal PaCO ₂ results in a chronic respiratory alkalosis. Partial renal compensation occurs through increased excretion of bicarbonate, which helps maintain the pH between 7.4 and 7.45 and lowers the serum bicarbonate levels. Early in pregnancy, the arterial oxygen (PaO ₂ ) increases (106 to 108 mm Hg) as the PaCO ₂ decreases, but by the third trimester, a slight decrease in the PaO ₂ (101 to 104 mm Hg) occurs as a result of the enlarging uterus. This decrease in the PaO ₂ late in pregnancy is even more pronounced in the supine position; one study found a further drop of 5 to 10 mm Hg and an increase in the alveolar-to-arterial gradient to 26 mm Hg. Up to 25% of women may exhibit a PaO ₂ of less than 90 mm Hg. The mean PaO ₂ is lower in the supine position than in the sitting position.

As the minute ventilation increases, a simultaneous but smaller increase in oxygen uptake and consumption occurs. Most investigators have found maternal oxygen consumption to be 20% to 40% above nonpregnant levels. This increase occurs as a result of the oxygen requirements of the fetus and placenta and the increased oxygen requirement of maternal organs. With exercise or during labor, an even greater rise in both minute ventilation and oxygen consumption takes place. During a contraction, oxygen consumption can triple. As a result of the increased oxygen consumption, and because the FRC is decreased, a lowering of the maternal oxygen reserve occurs. Therefore the pregnant patient is more susceptible to the effects of apnea, such as during intubation, when a more rapid onset of hypoxia, hypercapnia, and respiratory acidosis is seen. Indeed, the desaturation time after thorough preoxygenation is shortened from 9 minutes in the nonpregnant state to 3 minutes in pregnancy.

Sleep

Pregnancy causes both an increase in sleep disorders and significant changes in sleep profile and pattern that persist into the postpartum period. Pregnancy causes such significant changes that the American Academy of Sleep Medicine has described a specific pregnancy-associated sleep disorder: diagnostic criteria include a complaint of either insomnia or excessive sleepiness with onset during pregnancy . Sleep disturbances are associated with poor health outcomes in the general population, and emerging evidence suggests that abnormal sleep patterns in pregnancy may contribute to certain complications, such as hypertensive disorders and fetal growth restriction. It is well known that hormones and physical discomfort affect sleep ( Table 3-7 ). With the dramatic change in hormone levels and the significant mechanical effects that make women more uncomfortable, it is not difficult to understand why sleep is profoundly affected. Multiple authors have investigated the changes in sleep during pregnancy using questionnaires, sleep logs, and polysomnographic studies. From these studies, investigators have shown that most pregnant women (66% to 94%) report alterations in sleep that lead to the subjective perception of poor sleep quality. Sleep disturbances begin as early as the first trimester and worsen as the pregnancy progresses. During the third trimester, multiple discomforts occur that can impair sleep: urinary frequency, backache, general abdominal discomfort and contractions, leg cramps, restless legs syndrome (RLS), heartburn, and fetal movement. Interestingly, no changes are seen in melatonin levels, which modulate the body’s circadian pacemaker.

Stay updated, free articles. Join our Telegram channel

Join