Maternal Changes in Pregnancy

• Maximum endometrial changes: ~7 days after ovulation. • Implantation window: 6–10 days after LH spike. • Pre-decidualization: 9–10 days after ovulation; decidual cells begin covering uterine surface. • Decidualization in pregnancy: Cells become modified with lipids and glycogen; form the maternal part of the placenta. • Glandular secretions contain growth factors, adhesion molecules, nutrients, vitamins, matrix proteins, and hormones to support implantation.

• Decidual cells: On the endometrial surface, fill with lipids and glycogen → become the maternal part of the placenta. • Syncytiotrophoblast: Forms by cell fusion, creating a multi-nucleated cytoplasmic mass that invades the endometrium. • Chorionic gonadotropin (hCG): Acts as an autocrine growth factor for the blastocyst

Day 7–8: * Syncytiotrophoblast erodes the endometrium. * Embryonic disc forms epiblast (future amnion) and hypoblast. * Epiblast develops the fluid-filled amniotic cavity. Day 12: * Implantation complete. * Extraembryonic mesoderm forms beneath the cytotrophoblast. Day 16: * Cytotrophoblast + associated mesoderm = chorion. * Chorionic villi extend into maternal tissue. * Lacunae filled with maternal blood mingle with villi, establishing early maternal-fetal circulation.

• The maternal-fetal interface is a specialized, dynamic zone of interaction between maternal uterine tissues (decidua) and fetal-derived placental tissues (trophoblasts). • It functions as a complex immunological, physiological, and physical barrier, enabling nutrient/gas exchange and fostering tolerance toward the foreign fetus while protecting against infections.

Source: Secreted by the syncytiotrophoblast; rapid rise is the basis of pregnancy tests. Function: * Prevents death of the corpus luteum, so the endometrium is maintained. * Corpus luteum continues producing estrogen and progesterone. Effect: Maternal systems undergo rapid changes in response to luteal and later placental steroids.

Synthesis: * Derived from fetal and maternal adrenal steroids. * Placenta lacks 17α-hydroxylase and 17,20-lyase, so some conversions require maternal/fetal contribution. Progesterone: Synthesized directly from cholesterol. Functions: * Decidualization (corpus luteum support) * Smooth muscle relaxation → uterine quiescence * Mineralocorticoid effect → cardiovascular adaptations * Breast development (glands & stroma) Estrogens (Estradiol E2, Estriol E3): Synthesized via aromatase. Functions: * Uterine hypertrophy * Cardiovascular changes * Increased clotting factor production → haemostasis * Breast development * Metabolic changes (insulin resistance)

Average total gain: 9–13 kg. Components: * Fetus & placenta: ~5 kg * Fat & protein: ~4.5 kg * Body water: ~1.5 kg (intravascular, interstitial, intracellular) * Breasts: ~1 kg * Uterus: 0.5–1 kg Timeline: * First 20 weeks: ~2 kg total * After 20 weeks: ~0.5 kg per week until 40 weeks Clinical notes: * Failure to gain or sudden weight change requires investigation. * Constant monitoring can cause anxiety.

BMR increase: * Mid-gestation: +350 kcal/day * Late gestation: +250 kcal/day * Energy use: ~75% for fetus & uterus, 25% for maternal respiration Energy storage: 9 kcal ≈ 1 g fat → 350 kcal ≈ 40 g fat Glucose: Maternal glucose rises to cross the placenta for fetal needs

First trimester Maternal reserves * Pancreatic cells increase in number raising circulating insulin so more glucose is taken up into tissues. Fasting serum glucose decreases. Second trimester Fetal reserves * Placental Lactogen causes insulin resistance, ie less glucose into stores and increase in serum glucose. Transfer of glucose to fetus. * Increased glucose level in blood during 2nd trimester. Glucose is transported across placenta as fetal energy source. Fetus stores some in liver.

• Defined as transient glucose intolerance, which gets corrected after the end of the pregnancy • Occurs due to a predominance of anti-insulin hormones • Pregnancy leads to fasting hypo-glycaemia and post-prandial hyper-glycaemia • Linked with obesity and ethnicity • Can be controlled mostly by dietary adjustment

• Screening test: 75 g oral glucose tolerance test (OGTT). • Timing: 26–28 weeks of pregnancy, after an overnight fast. • Urine testing: Unreliable due to reduced renal threshold. • Blood glucose: Fasting and 2-hour post-glucose measured. • WHO thresholds: • Fasting: ≥ 5.6 mmol/L • 2-hour: ≥ 7.8 mmol/L

Maternal Effects: * Polyhydramnios (excess amniotic fluid) * Increased risk of infections * Preterm birth * Instrumental delivery (forceps or vacuum) * Later development of diabetes Fetal/Neonatal Effects: * Macrosomia (large baby) * Shoulder dystocia * Neonatal hypoglycaemia * Jaundice * Congenital abnormalities: not increased * Perinatal morbidity * Stillbirth

• Long-term risk: Higher chance of developing Type II diabetes later in life (acts like a stress test). • Treatment: • Mostly dietary management. • Sometimes requires Metformin or insulin for glucose control. • Drugs that stimulate insulin production are contraindicated in pregnancy. • Classification: Women needing insulin during pregnancy should be re-classified as Type II diabetes complicating pregnancy.

• Sodium & Blood Volume: • High estrogen and progesterone act like mineralocorticoids → retain sodium → increase blood volume. • RAAS Activation: • Placental renin + estrogen ↑ angiotensinogen → ↑ angiotensin II and aldosterone. • Despite high ANG II, vascular resistance decreases because progesterone reduces vasoconstriction sensitivity. • Connective tissue: Ligaments absorb water → become softer. • Fluid/osmoregulation: • Reset osmostat → decreased thirst threshold. • Oncotic pressure decreases (lower albumin).

• Mechanical changes: • Expanding uterus pushes the heart → alters ECG and heart sounds • Peripheral circulation: • Peripheral vasodilation (via nitric oxide, ↑ by estrogen/E2) • ↓ Total peripheral resistance (TPR) by 20–30% • Cardiac output (CO): • Increases (up to ~40% by 28 weeks) • Begins as early as 3 weeks • Due mainly to ↑ stroke volume + slight ↑ heart rate (8–10 bpm) • Blood pressure: • Decreases in 1st and 2nd trimesters • Clinical significance: • Increased cardiac workload can worsen pre-existing conditions (e.g., aortic valve disease, pulmonary hypertension)

• Increased cardiac output + steroid-induced vasodilation Reduced peripheral resistance → increased blood flow to: * Uterus * Placenta * Muscle * Kidneys * Skin Neo-angiogenesis: * Formation of new blood vessels (via VEGF/PLGF) * Extra skin capillaries → spider naevi and improved heat loss Overall state: * Low-pressure, high-volume circulation during pregnancy

• Supplementation advised up to 400μg/day until week 12 • Ideally 3 months before pregnancy. • Deficiency can lead to birth defects eg spina bifida (neural tube defects).

• Relaxin from corpus luteum/placenta stimulates formation of endothelin which mediates dilation of renal arteries by nitric oxide synthesis. • Progesterone and VEGF cause resistance to angiotensin II mediated vasoconstriction leading to further vasodilation and increased renal blood flow and increased GFR

Frequent urination is a common, often daily, symptom of pregnancy caused by hormonal shifts (hCG, progesterone), increased blood volume, and pressure from the growing uterus on the bladder.

Placental CRH: * Released into maternal and fetal circulation * Stimulates ACTH → ↑ cortisol (positive feedback loop) * Activates fetal HPA axis → ↑ DHEA production Cortisol effects: * Insulin resistance (metabolic changes) * Promotes fetal lung maturity * Has mineralocorticoid effects (via aldosterone) DHEA pathway: * Fetal DHEA → converted (aromatized) in placenta → estrogen Estrogen effects: * ↑ Estrogen:Progesterone ratio * ↑ Prostaglandin (PGE2) and oxytocin production Outcome: * Increased uterine blood flow * Uterine contractions * Cervical ripening → contributes to onset of labour