Physiologic Adaptations to Pregnancy

Blood Volume Expansion

Optimal cardiac function requires a balance between preload, afterload, heart rate, and contractility. During pregnancy, there is a dramatic increase in blood volume, which equates to an increase in cardiac preload. Starting at 6 to 8 weeks of gestation, maternal blood volume increases by up to 50% above nonpregnant values. This increase may be enhanced by multiple gestation, or it may be blunted in pregnancies complicated by fetal growth restriction, hypertension, or preeclampsia. The increase in plasma volume is greater than the increase in red cell mass (∼18%), leading to a lowered hematocrit, sometimes described as “the physiologic anemia” of pregnancy. Evidence suggests that the decreased blood viscosity facilitates placental perfusion and lowers the workload of the heart, and the absence of this “physiologic anemia” may lead to higher rates of stillbirth and fetal growth restriction. The increased plasma volume is partly caused by changes in the maternal hypothalamus–pituitary–adrenal axis, which lowers the threshold for renin, aldosterone, and antidiuretic hormone release, leading to retention of both sodium and water. Additionally, the increased vascular capacitance caused by the smooth muscle–relaxing effect of progesterone and other vasodilators allows for the increased systemic release of these hormones without concomitant negative feedback. Water retention is greater than sodium retention, explaining the mild reduction in sodium concentration that occurs in pregnant women (135–138 mEq/L compared with 135–145 mEq/L in nonpregnant women). These changes peak near the beginning of the third trimester.

Edema of Pregnancy

During normal pregnancy, total body water increases by 6 to 8 L. An estimated 4 to 6 L of this increase is extracellular, with 2 to 3 L being interstitial. Additionally, colloid osmotic pressure decreases, and capillary hydrostatic pressure increases. The hormonal changes of pregnancy also lead to increased water in the ground substance of connective tissue. Thus, it is not surprising that up to 80% of women with normal pregnancies manifest peripheral edema, particularly in the third trimester. Obese women, older women, and multiparous women all tend to develop more pronounced edema. In about half of women, the edema is limited to the lower extremities. In the other half, it is more generalized, involving the hands and the face. The edema can be sporadic or persistent, with both types occurring with approximately equal frequency.

The edema of pregnancy is not necessarily a negative occurrence. Women with edema tend to have babies of slightly greater birthweight, although the babies are not edematous. They have a lower incidence of low-birthweight babies and a slightly reduced rate of perinatal mortality compared with women who do not develop edema.

The increased plasma volume results in the development of normal physical examination findings unique to pregnancy, and an understanding of these will help to identify true perturbations in the cardiovascular system. Although the development of mild or moderate peripheral edema is common among women in the late second and third trimesters, the severe or earlier development of edema may indicate a failure of the cardiovascular system to tolerate the increase in plasma volume. Women with diminished systolic cardiac function or severely regurgitant valvular disease may manifest early and severe peripheral edema. Similarly, the increased blood flow through the heart may cause a functional heart murmur often described as a “systolic flow murmur.” It is often characterized as a systolic crescendo–decrescendo murmur of a grade 1 or 2, loudest with auscultation over the left-second intercostal space. An additional sound also may be heard bilaterally along the mid-clavicular line and represents the “mammary soufflé” associated with increased blood volume perfusing the breasts. Diastolic murmurs, harsh or loud murmurs, clicks, and rubs are abnormal and warrant a cardiac work-up.

Certain laboratory, imaging, and electrocardiogram findings are associated with the increased plasma volume seen in pregnancy. Hemoglobin concentration declines an average of 1.5 to 2.0 g/dL, such that the Centers for Disease Control and Prevention has defined true anemia during pregnancy as a hemoglobin less than 11.0 g/dL during the first and third trimesters and less than 10.5 g/dL during the second trimester. Chest x-ray findings may include enlargement of the cardiac silhouette and great vessels, and echocardiography may identify increased chamber dimensions and mild valve regurgitation. Coinciding with the increased cardiac chamber sizes, the nature of the electrical circuitry within the heart changes subtly. The electrocardiogram changes include mild sinus tachycardia, left-axis deviation, mild ST segment changes, and the development of small Q waves and T-wave inversions (especially in leads III and AVF). Findings outside of these expected physiologic changes suggest the presence of underlying disease or intolerance to the increase in plasma volume.

Increased Cardiac Output

In part because of the increased preload and the operation of Starling’s law, which states that contractility of the heart will increase as it is stretched by increased volume, cardiac output increases by 30% to 50% in a normal pregnancy. The increase in stroke volume is coupled with an increase in heart rate during pregnancy, which also contributes to increased cardiac output. The heart rate increases progressively throughout pregnancy and reaches a maximum of 20% to 25% over prepregnancy values in the third trimester. The increased heart rate is largely caused by an increase in sympathetic tone and a decrease in parasympathetic tone. The combination of the increases in stroke volume and heart rate results in a progressively increasing cardiac output that begins in the first trimester and peaks by 28 to 32 weeks’ gestation. The increases in heart rate and cardiac output are greater, 5.2 L/min versus 5.6 L/min, during subsequent pregnancies than during the first. The maternal cardiac output can change with body position. Various body positions and postures may cause the gravid uterus to obstruct the vena cava, resulting in diminished venous return and significant reductions in cardiac output ( Fig. 1.1 ).

Although cardiac remodeling occurs during pregnancy, such that left ventricular wall thickness increases by about 28% and left ventricular mass increases by 52%, the contractility of the cardiomyocytes themselves does not increase. Rather, systemic and pulmonary resistance diminishes, contributing to the important rise in cardiac output. Diminished resistance is partly caused by increases in the serum concentration of progesterone, nitric oxide (NO), and prostaglandins. NO and prostaglandins, such as prostacyclin (PGI ₂ ), are vasodilators with direct relaxing effects on the endothelium. Somewhat counterintuitively, the maternal circulation also demonstrates increases in blood levels of both renin and angiotensin. However, there appears to be a decreased responsiveness to the pressor effects of these hormones, such that, despite their elevated serum concentrations in pregnancy, systemic vascular resistance diminishes.

Changes in left atrial function have been evaluated using two-dimensional speckle tracking. These studies demonstrate that whereas left atrial reservoir and booster pump functions increase in pregnancy, left atrial conduit function decreases.

Vascular resistance reaches its lowest point at 20 to 24 weeks’ gestation. The decrease in vascular resistance leads to physiologic hypotension. After the nadir is reached, vascular resistance increases, approaching prepregnancy values by term. Thus, blood pressure falls throughout the first and early second trimesters but increases in concert with the changes in vascular resistance toward term—often returning to prepregnancy values or even slightly higher.

Increases in cardiac output, coupled with a redistribution of blood flow to the organs most vital for optimal maternal and fetal health ( Fig. 1.2 ), provide additional oxygen uptake, heat dissipation, and excretion of metabolic waste. Uterine blood flow increases 10-fold throughout gestation, and the percentage of total cardiac output received increases from 2% before pregnancy to 10% at term. Pulmonary blood flow increases by approximately 30% by term, but no change in pulmonary artery pressure is seen. Blood flow to the brain increases by about 10%. Skin perfusion doubles in the second and third trimesters to provide improved heat exchange. By the second trimester, renal blood flow has increased by roughly 30% with a concomitant rise in the glomerular filtration rate (GFR) for the purposes of clearing metabolic wastes. As pregnancy progresses, it increases further to as much as 50% to 60%. An increase in distribution of cardiac output to the breasts occurs during pregnancy in anticipation of lactation and the need to provide nourishment to the newborn.

The increased cardiac demand and redistribution of cardiac output result in several common symptoms that can be considered normal for pregnancy. As early as the first trimester, patients may experience mild shortness of breath and occasional palpitations lasting a few seconds. They may find it more difficult to tolerate exercise, and their breathing may become more labored when climbing several flights of stairs. Other common symptoms are skin flushing and the sensation of feeling warm. However, chest pain is not common and should never be considered normal for pregnancy. Palpitations that last minutes rather than seconds also should be considered pathologic. In addition, the inability of a nonobese woman to climb one flight of stairs without marked shortness of breath warrants concern.

Hemodynamic Changes During Labor

During labor and delivery, the contraction of uterine muscle expels blood from the veins and venules within the uterus, resulting in a cyclic increase in blood volume of 300 to 500 mL with each contraction, the “autotransfusion effect.” Uterine contractions also may change the shape of the uterus, decreasing the pressure placed on the inferior vena cava and improving venous return. As a result, stroke volume is augmented, and cardiac output increases approximately 30% during labor. In addition, the increased cardiac output may be attributed to an increase in heart rate associated with the catecholamine surge from pain and anxiety. Regional analgesia has been shown to blunt the expected rise in cardiac output, perhaps partly caused by the reduced catecholamine surge from pain partly caused by the reduced venous return that occurs because of the vasodilation of the lower body. Depending on the woman’s level of anxiety and pain as well as her position, blood pressure may increase by up to 15% with uterine contractions.

Delivery is associated with a significant loss of maternal blood volume. Routine vaginal and cesarean delivery may result in losses of up to 10% and 30%, respectively, of maternal blood volume. Nevertheless, cardiac output continues to increase in the first hour or two after delivery because of the reduced vena caval compression and the autotransfusion effect from the involuted uterus. Over the subsequent 2 to 6 weeks, cardiac output returns to prelabor values. Heart rate and blood pressure increases are quite variable, depending on multiple factors, including pain levels and type of anesthesia.

Labor and delivery represent periods of heightened risk for women unable to accommodate the increased venous return and cardiac output, including women with mitral stenosis or left ventricular systolic dysfunction.

During the peripartum period, all women have an increased risk of aortic dissection or rupture. In the 6 months before delivery and for 3 months postpartum, the risk is increased by a factor of 4. This is of particular concern for women with aortopathies (e.g., Marfan syndrome, Loeys-Dietz syndrome, and the vascular type of Ehlers-Danlos syndrome), who are already at risk for aortic dissection. It is intuitive that the hemodynamic changes of pregnancy, including increased heart rate and stroke volume, would increase stress on the aorta, but many other factors likely contribute as well. The compression of the gravid uterus on the aorta increases outflow resistance. Pregnancy also causes many hormonal changes that affect the walls of the blood vessels, and these may result in a weakening of the blood vessel wall that predisposes it to aortic rupture and dissection. In women with aortopathies, any signs or symptoms suggesting cardiac compromise—shortness of breath, chest pain or pressure, upper back pain, oxygen desaturation, narrowing pulse pressure, or tachycardia and hypotension—warrant a thorough cardiovascular evaluation.