Systemic and Central Nervous System Changes During Pregnancy

This chapter includes an accompanying lecture presentation that has been prepared by the authors: .

Key Concepts

Maternal adaptation to pregnancy involves all organ systems and requires a panoply of physiologic alterations.
Particularly dramatic are homeostatic changes in the neuroendocrine, cardiovascular, immune, renal, and pulmonary systems.
Maternal adaptations are not strictly confined to the fetal-placental unit and are initially orchestrated by ovarian and placental hormone production.
Not all maternal adaptations to pregnancy fully reverse after delivery, and women who have been pregnant display long-term changes in metabolism and renal, cardiovascular, immune, and musculoskeletal function and corresponding changes in pituitary size.
In many women, fetal cells persist in maternal circulation or embed in maternal tissues including the brain and can persist indefinitely. This phenomenon is termed fetal microchimerism, and it has been linked to long-term changes in disease diathesis and immune alterations.

Introduction

To some extent every maternal organ system is altered in pregnancy. The impact of pregnancy on the endocrine system is profound and begins at implantation with the production of human chorionic gonadotropin (hCG) from the trophoblast. The impact of pregnancy on other organ systems are more gradual and may not appear until later in pregnancy. Although the vast majority of these changes are hormonally mediated, some organ systems are also affected by the enlarging uterus or secondarily by the physiologic increase in maternal blood volume. The placenta essentially functions as an enlarging arteriovenous malformation, and at term approximately 25% of the maternal blood volume transits the placenta per minute. Abnormal placentation (increta, accreta, percreta) often leads to intrapartum hemorrhage that can present with severe compromise of perfusion and hemostasis. It is critically important for the clinician to understand the cardiovascular and hemodynamic changes during gestation, which are gradual, and the profound and immediate intrapartum and immediate postpartum hemodynamics when caring for pregnant women, as many physical examination findings, laboratory results, and imaging studies may be judged as abnormal whereas in the pregnant patient such findings represent physiologic adaptations. Pregnancy is characterized by profound changes in the maternal hematologic, cardiovascular, pulmonary, metabolic, renal, immune, and endocrine systems designed to ensure a successful pregnancy and adequate fetal growth ( Table 48.1 ). In addition, the physical forces of the gravid uterus cause secondary changes in the maternal musculoskeletal system. Here we initially review the systemic physiologic and the underlying neuroendocrine changes that are relevant to the neurosurgeon challenged with treating a patient with a neurosurgical disorder who also happens to be pregnant.

TABLE 48.1

Physiologic Changes During Pregnancy

Data from Cunningham FG, Leveno KJ, Bloom SL, et al, eds. Williams Obstetrics. 25th ed. McGraw-Hill; 2018.

System	Changes
Hematologic	Systemic blood volume ↑	Plasma volume ↑	Red blood cell mass ↑	Hematocrit ↓
Cardiovascular	Heart rate ↑	Cardiac output ↑	Diastolic blood pressure ↓	Peripheral vascular resistance ↓
Renal	Glomerular filtration rate (GFR) ↑	Serum creatinine level ↓	Renal blood flow ↑	Serum osmolality ↓
Pulmonary	Vascular resistance ↓	Tidal volume ↑	Respiratory rate ↔	Respiratory reserve ↓
Gastrointestinal	Gastric emptying time ↑	Intestinal motility ↓	Gallbladder motility ↓	Gallbladder volume ↑

Before considering the various changes in the physiology of a pregnant woman, an obvious difference in treating neurosurgical disorders of the pregnant patient is that two lives are potentially at risk, and consequently the treating physicians may face medical and ethical challenges. When pregnancy threatens the life of mother, physicians should obviously determine input from the mother, but should be mindful of potential legal ramifications. Engagement of a medical ethics team may facilitate medical decision making and may bring into focus the medical priorities and options including termination.

Systemic Physiologic Changes in Pregnancy

Hematologic Changes

Pregnancy alters the balance within the coagulation system in favor of clotting so that a physiologic hypercoagulable state ensues in preparation for hemostasis following delivery. The pregnant and postpartum woman is predisposed to venous thrombosis beginning in the first trimester and lasting 12 weeks after delivery ( Box 48.1 ). Factors VIII, IX, and X are increased, as are fibrinogen levels (by up to 50%), whereas fibrinolytic activity and antithrombin and protein S levels are decreased. Endogenous anticoagulants (i.e., antithrombin and protein S) decrease to promote a prothrombotic state

Platelet count decreases during normal pregnancy. The diagnosis of thrombocytopenia in pregnancy occurs when the platelet count is less than 100 × 10 ⁹ cells per liter.
In vitro tests of coagulation (activated partial thromboplastin time [aPTT], prothrombin time [PT], and thrombin time [TT]) remain normal in the absence of anticoagulants or a coagulopathy.
Plasma volume increases throughout normal pregnancy, reaching a peak by the middle of the third trimester. Expansion in plasma volume is greater than the increase in red blood cell mass, which causes a decrease in hemoglobin concentration, hematocrit, and red blood cell count but no change in mean corpuscular volume (MCV) or mean corpuscular hemoglobin concentration (MCHC).

BOX 48.1

Hematologic Changes

Pregnancy alters the balance within the coagulation system in favor of clotting so that a physiologic hypercoagulable state ensues in preparation for hemostasis following delivery.
The pregnant and postpartum woman is predisposed to venous thrombosis beginning in the first trimester and lasting until 12 weeks after delivery.

Cardiovascular System

Physical Examination

Because of profound changes in cardiovascular status during pregnancy as outlined in the following paragraphs, the cardiovascular examination findings may be misinterpreted as pathologic. For example, pulse may be bounding or collapsing, but it is usually increased as a result of peripheral vasodilation. An ejection systolic murmur is found in more than 90% of pregnant women. The murmur may be loud and audible all over the precordium. There may be ectopic beats and peripheral edema.

Electrocardiogram

Changes in the position of the heart secondary to the gravid uterus cause a left-axis shift of the QRS. Also frequently noted are atrial and ventricular ectopic beats, small Q waves and inverted T waves in lead III, and ST-segment depression and T-wave inversion in the inferior and lateral leads.

Heart

Cardiac output increases by 20% by the eighth week and can increase by 40% thereafter ( Box 48.2 ). This is achieved predominantly through an increase in stroke volume and to a lesser extent through an increase in heart rate. The maximum cardiac output is found at about 20 to 28 weeks’ gestation. The increase in cardiac output is secondary to the placenta functioning as a low-resistance, high-capacity shunt, and thus there is peripheral vasodilation and reduced systemic vascular resistance (SVR).

BOX 48.2

Cardiovascular System in Pregnancy

Heart

Cardiac output increases by 20% by the eighth week and can increase by 40% thereafter.
The maximum cardiac output is found at about 20–28 weeks’ gestation.
The increase in cardiac output is secondary to a peripheral vasodilation and a drop in systemic vascular resistance primarily due to placentation and smooth muscle relaxation.

Blood Pressure

Decreases in the first and second trimesters.
Increases to nonpregnant levels in the third trimester.

Intravascular Volumes

Maternal blood volume increases by 45%.
Pregnancy causes a hypervolemic, hypo-osmolar state with a 30%–50% increase in extracellular volume and 30%–40% increase in plasma volume.
Plasma volume increase maintains blood volume and blood pressure in the mother while augmenting uteroplacental perfusion.
Late third trimester plasma volumes are increased by more than 50%–60% but with a lower increase in red blood cell mass, and therefore plasma osmolality falls by 10 mOsm/kg.
The increases in plasma volume combined with the decrease in systemic vascular resistance result in arterial underfilling unique to pregnancy.

Positioning

Positioning affects BP and can lead to decreased cardiac output.
In the supine position, pressure of the gravid uterus on the inferior vena cava (IVC) causes a reduction in venous return to the heart and a consequent fall in stroke volume and cardiac output. Consequently, turning from the lateral to the supine position may result in a 25% reduction in cardiac output.
Pregnant women, especially in the third trimester, should therefore be cared for in the left or right lateral position.
If the expectant mother has to be kept on her back (e.g., during a craniotomy), the pelvis should be rotated so that the uterus drops to the side and off the IVC, thereby optimizing cardiac output and uteroplacental blood flow to avoid compromising the fetus.

Blood pressure decreases in the first and second trimesters (see Box 48.2 ) but increases to nonpregnant levels in the third trimester.

Positioning affects cardiac performance and systemic blood pressure (see Box 48.2 ). In the supine position, pressure of the gravid uterus on the inferior vena cava (IVC) causes a reduction in venous return to the heart and a consequent fall in stroke volume and cardiac output. Consequently, turning from the lateral to the supine position may result in a 25% reduction in cardiac output. Pregnant women, especially in the third trimester, should therefore be cared for in the left or right lateral position. If the expectant mother has to be kept on her back, the pelvis should be rotated so that the uterus drops to the side and off the IVC, thereby optimizing cardiac output and uteroplacental blood flow to avoid compromising the fetus.

Intravascular Volumes

Maternal blood volume (see Box 48.2 ) increases by 45%. In general, pregnancy causes a hypervolemic, hypo-osmolar state with a 30% to 50% increase in extracellular volume and 30% to 40% increase in plasma volume. Plasma volume increase maintains blood volume and blood pressure in the mother while augmenting uteroplacental perfusion. In the late third trimester, plasma volume increases by more than 50% to 60% but with a lower increase in red blood cell mass, and therefore plasma osmolality falls by 10 mOsm/kg. The increases in plasma volume combined with the decrease in SVR results in arterial underfilling unique to pregnancy.

During Labor

Cardiac output is further increased by 15% in the first stage and 50% in the second stage. Uterine contractions lead to an autotransfusion of 300 to 500 mL of blood. Pain and anxiety further elevate the heart rate and blood pressure. Cardiac output is increased between contractions and further during contractions.

After Delivery

Cardiac output increases 60% to 80% immediately owing to relief of the IVC obstruction and contraction of the uterus. Within an hour, cardiac output declines to prelabor values, but transfer of fluid from the extravascular space increases venous return and stroke volume. By 2 weeks, cardiac output returns to normal (prepregnancy) values, although some pathologic changes (e.g., hypertension in preeclampsia) may take much longer.

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