Pregnancy Physiology & Prenatal Development

Placental hormones

hCG. Human chorionic gonadotropin is secreted by the syncytiotrophoblast, peaks around 8–10 weeks, then declines. Acting like LH, it rescues the corpus luteum, which keeps producing progesterone until the placenta takes over by weeks 8–10. hCG shares its α subunit with LH, FSH and TSH; the β subunit is specific and is what pregnancy tests detect. Its TSH-like activity can cause transient gestational hyperthyroidism, and hCG is markedly elevated in molar pregnancy and choriocarcinoma.

Progesterone. Progesterone maintains the decidua (endometrium) and relaxes uterine smooth muscle to prevent contractions; its source shifts from the corpus luteum to the placenta by weeks 8–10. It also raises central respiratory drive and relaxes other smooth muscle, contributing to constipation and ureteral dilation. A fall in progesterone permits labor.

Estriol and the fetoplacental unit. The placenta cannot make androgens itself, so placental estrogen (mostly estriol) is built from fetal adrenal DHEA-S that the fetal liver hydroxylates and the placenta processes with sulfatase and aromatase. Because estriol needs a healthy fetus and placenta, rising estriol reflects fetal well-being. Estrogen also increases hepatic synthesis of thyroxine-binding globulin (total T₄ rises while free T₄ stays normal), SHBG, and clotting factors.

Human placental lactogen (hPL). Also called human chorionic somatomammotropin (hCS), hPL is made by the syncytiotrophoblast and rises through pregnancy in step with placental mass. It is diabetogenic: it induces maternal insulin resistance and lipolysis, diverting glucose and free fatty acids to the fetus, and it contributes to gestational diabetes when maternal β cells cannot compensate.

Maternal adaptations

Blood and circulation. Plasma volume outpaces red cell mass, so hemoglobin falls with a normal MCV: a dilutional, physiologic anemia. Cardiac output rises first through stroke volume and then through heart rate. Systemic vascular resistance falls, so blood pressure reaches a nadir in mid-pregnancy and normalizes by term. Late in pregnancy, lying supine lets the uterus compress the IVC and reduce venous return (supine hypotension), relieved by the left lateral position. Estrogen-driven increases in clotting factors make pregnancy hypercoagulable.

Kidneys. Higher renal plasma flow and GFR lower BUN and creatinine; a normal pregnancy creatinine is roughly 0.4–0.5 mg/dL, so a value that looks normal outside pregnancy may signal renal impairment. The increased filtered glucose load can exceed tubular reabsorption, causing benign glucosuria. RAAS is activated, but the vasculature is relatively resistant to angiotensin II. Dilated ureters let asymptomatic bacteriuria ascend more easily to pyelonephritis.

Lungs. Progesterone raises tidal volume and minute ventilation while respiratory rate is essentially unchanged, producing a compensated chronic respiratory alkalosis with renal bicarbonate loss. The low maternal PaCO₂ steepens the gradient that lets the fetus offload CO₂. The gravid uterus elevates the diaphragm and lowers functional residual capacity.

Fetal circulation and the transition at birth

Oxygenated blood enters through one vein. Blood from the placenta returns in the single umbilical vein, the most highly oxygenated fetal vessel (about 80% saturated). Two umbilical arteries, branches of the internal iliac arteries, return deoxygenated blood to the placenta; a single umbilical artery is associated with congenital anomalies.

The first breath. Lung expansion drops pulmonary vascular resistance, increasing pulmonary blood flow and left atrial return, while loss of placental flow lowers right atrial pressure; left atrial pressure now exceeds right, closing the foramen ovale. Rising O₂ tension and falling prostaglandins (the placenta was a major source) constrict the ductus arteriosus, which closes functionally in 1–2 days.

Controlling the ductus. Indomethacin (or ibuprofen) blocks prostaglandin synthesis and closes a patent ductus arteriosus, as in premature infants. PGE₁ (alprostadil) keeps it open when a newborn depends on ductal flow, as in transposition of the great arteries.

Fetal hemoglobin

Structure and O₂ affinity. Fetal hemoglobin (HbF) is α₂γ₂, whereas adult HbA is α₂β₂. γ Chains bind 2,3-BPG poorly, so HbF has higher O₂ affinity and a left-shifted dissociation curve; at the low PO₂ of the placenta it pulls O₂ away from maternal HbA.

Switching. HbF predominates until the switch to HbA, essentially complete by about 6 months after birth. That timing explains why β-chain disorders such as sickle cell disease and β-thalassemia major become symptomatic after the first several months, and why raising HbF with hydroxyurea helps in sickle cell disease.

Teratogen timing and the newborn

Windows of susceptibility. Weeks 1–2 (pre-implantation) are all-or-none: the embryo is either lost or recovers fully. Weeks 3–8, organogenesis, carry the greatest risk of major structural malformations. After week 8 (the fetal period), teratogens mainly cause growth restriction and functional defects.

Apgar score. Assigned at 1 and 5 minutes, it scores Appearance (color), Pulse (heart rate), Grimace (reflex irritability), Activity (tone) and Respiration, each 0–2, for a maximum of 10. A score of 7 or more is reassuring, 4–6 moderately abnormal, and 3 or less critically low. The score describes the infant's condition and response to resuscitation; it is not a predictor of an individual's long-term outcome, and resuscitation is never delayed to calculate it.

Heart rate is the single most important sign guiding neonatal resuscitation.