Antenatal screening is a systematic, timed process — from booking history through trimester-specific tests. The combined test (11-14 wk) screens for aneuploidy, the anomaly scan (18-22 wk) checks fetal anatomy, and the OGTT (24-28 wk) catches GDM. The key is knowing which test at which gestation, and what to do with the result.
NIPT >99% sensitivity for T21 — but it is SCREENING, not diagnostic
FMF preeclampsia algorithm at 11-14 wk — aspirin 150 mg if high risk
Most common trap:
NIPT (cell-free fetal DNA) is a highly sensitive screening test, not a diagnostic test. A positive NIPT result must be confirmed by invasive testing (CVS or amniocentesis) before irreversible decisions are made.
Antenatal Screening
Let's walk through antenatal screening the way you'd actually plan it in clinic. You start at the booking visit — ideally before 10 weeks — and build a complete risk profile covering maternal age, parity, past obstetric history (previous miscarriages, preterm births, growth restriction, stillbirth, caesarean sections), medical history (hypertension, diabetes, epilepsy, cardiac disease, thromboembolism, autoimmune disorders), family history (genetic conditions, thrombophilia), and social history (smoking, alcohol, recreational drugs, domestic violence). Everything you gather here feeds directly into what screening tests you offer and when.
First-Trimester Screening
First-trimester screening for aneuploidy (combined test at 11-14 weeks) includes nuchal translucency (NT) measurement by ultrasound and maternal serum biomarkers — pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotrophin (beta-hCG).
The detection rate for trisomy 21 is 85-90% with a 5% false-positive rate. The addition of ductus venosus Doppler assessment and nasal bone evaluation improves detection further.
Cell-free fetal DNA (cffDNA) testing (non-invasive prenatal testing — NIPT) from maternal blood provides >99% sensitivity for trisomies 21, 18, and 13 with a <0.1% false-positive rate
, but it remains a screening test — a positive result requires confirmatory invasive testing (chorionic villus sampling — CVS at 11-14 weeks, or amniocentesis at >15 weeks).
Second-Trimester Screening
Second-trimester screening (quadruple test at 15-20 weeks) measures alpha-fetoprotein (AFP), beta-hCG, unconjugated oestriol (uE3), and inhibin A. This screen detects 80% of trisomy 21 cases with increased detection of open neural tube defects (elevated AFP). The anomaly ultrasound (18-22+6 weeks) systematically evaluates fetal anatomy — head (ventricles, choroid plexus, cavum septum pellucidum, cerebellum, cisterna magna, nuchal fold), face (lips, orbits, profile), chest (heart — four-chamber view, outflow tracts, three-vessel view), abdomen (stomach, kidneys, bladder, abdominal wall, diaphragm), spine, extremities, and placenta.
Invasive Diagnostic Testing
Invasive diagnostic testing is offered to women with increased risk following screening, advanced maternal age (>=35 years at delivery), previous aneuploidy, known parental chromosomal translocation, or ultrasound-detected structural anomalies. CVS (transabdominal or transcervical, 11-14 weeks) carries a procedure-related miscarriage risk of 0.5-1%. Amniocentesis (>15 weeks) carries a risk of 0.1-0.5%. Both provide fetal karyotype (46,XX or 46,XY), and chromosomal microarray analysis (CMA) can detect submicroscopic copy number variants not visible on conventional karyotyping. Whole exome sequencing (WES) is increasingly used for fetuses with structural anomalies and normal karyotype and CMA.
Screening Test
Timing
Components
Detection Rate (T21)
Combined test
11-14 weeks
NT, PAPP-A, free beta-hCG
85-90%
Quadruple test
15-20 weeks
AFP, hCG, uE3, Inhibin A
80%
NIPT (cffDNA)
From 10 weeks
cfDNA from maternal blood
>99%
Other Screening
Screening for gestational diabetes mellitus (GDM) is performed at 24-28 weeks using a 75 g oral glucose tolerance test (OGTT) with diagnostic thresholds (fasting >=5.1 mmol/L, 1-hour >=10.0 mmol/L, 2-hour >=8.5 mmol/L). The HAPO study demonstrated a linear relationship between maternal glucose levels and adverse outcomes.
Screening for preeclampsia at 11-14 weeks using the FMF algorithm (maternal factors, mean arterial pressure, uterine artery Doppler PI, PAPP-A, and PlGF) identifies women at high risk who benefit from aspirin 150 mg nightly from <16 weeks to prevent preterm preeclampsia.
PGI Chandigarh 2022: A 32-year-old primigravida at 12 weeks gestation undergoes first-trimester screening. Nuchal translucency is 3.5 mm. What is the next best step?
Answer: Offer invasive testing (CVS) for fetal karyotype. NT >3.5 mm is abnormal regardless of background risk. If combined test results are high risk (>1:150), invasive diagnosis is warranted.
NIPT (cell-free fetal DNA) is a highly sensitive screening test, not a diagnostic test. A positive NIPT result must be confirmed by invasive testing (CVS or amniocentesis) before irreversible decisions are made.
First-trimester combined test (11-14 wks): NT + PAPP-A + free beta-hCG — T21 detection 85-90%
Quadruple test (15-20 wks): AFP, hCG, uE3, Inhibin A — T21 detection 80%
NIPT (from 10 wks): cffDNA — >99% sensitivity for T21; screening, not diagnostic
CVS (11-14 wks): Transcervical or transabdominal — procedure-related loss 0.5-1%
Amniocentesis (>15 wks): Loss risk 0.1-0.5%
Cell types and genetic material obtained from chorionic villus sampling and amniocentesis for prenatal diagnosis.
Physiological Changes in Pregnancy
Overview
Pregnancy induces profound physiological adaptations across every organ system, driven primarily by hormonal changes (oestrogen, progesterone, human placental lactogen, relaxin) and mechanical effects of the gravid uterus. Understanding these changes is essential for distinguishing normal pregnancy from pathology and for managing medical conditions in pregnancy.
Cardiovascular Adaptations
Plasma volume increases by 40-50% (from 2600 mL to 3700 mL at term), while red blood cell mass increases by only 20-30%, resulting in physiological anaemia of pregnancy (haemoglobin nadir of 10-11 g/dL at 28-32 weeks).
Cardiac output increases by 30-50%, peaking at 28-32 weeks due to increased stroke volume (early pregnancy) and heart rate (later pregnancy, increasing by 10-20 bpm). Systemic vascular resistance decreases by 25-40% due to progesterone-mediated vasodilation and the low-resistance uteroplacental circulation, resulting in a physiological drop in blood pressure (nadir at 16-20 weeks), returning to non-pregnant levels by term.
Respiratory Changes
Progesterone increases respiratory centre sensitivity to CO2, lowering arterial PCO2 to 28-32 mmHg and increasing minute ventilation by 40-50%.
Tidal volume increases by 30-40%, while respiratory rate remains unchanged. Functional residual capacity (FRC) decreases by 20% due to diaphragmatic elevation from the gravid uterus, making pregnant women more susceptible to hypoxaemia during periods of hypoventilation (e.g., during induction of anaesthesia). Oxygen consumption increases by 20-30% to meet the demands of the fetoplacental unit.
Renal Changes
Renal plasma flow increases by 60-80% and glomerular filtration rate (GFR) by 50%, resulting in decreased serum creatinine (40-50 μmol/L is normal in pregnancy), decreased urea, and increased clearance of many drugs. Glycosuria is common due to decreased renal tubular reabsorption of glucose. The ureters are dilated (physiological hydronephrosis of pregnancy) due to progesterone-induced smooth muscle relaxation and mechanical compression at the pelvic brim (more pronounced on the right due to the dextrorotation of the gravid uterus and the protective effect of the sigmoid colon on the left).
Haematological Changes
Plasma volume expansion results in physiological dilutional anaemia. White blood cell count rises to 9-15 x 10^9/L (predominantly neutrophils). Platelet count may decline slightly (gestational thrombocytopenia — 5-8% of pregnancies, counts 100-150 x 10^9/L). The coagulation system shifts toward a prothrombotic state — increased fibrinogen (50% rise), factors VII, VIII, IX, X, and von Willebrand factor, decreased protein S activity, and acquired resistance to activated protein C.
These changes, combined with venous stasis from uterine compression and vascular injury at delivery, increase the risk of venous thromboembolism by 4-5 fold in pregnancy and 20-fold postpartum.
Endocrine Changes
The placenta functions as a major endocrine organ, producing human chorionic gonadotrophin (hCG — peaks at 8-10 weeks, maintains the corpus luteum), human placental lactogen (hPL — anti-insulin effects contributing to the diabetogenic state of pregnancy), progesterone (maintains uterine quiescence, thickens cervical mucus plug), and oestrogen (stimulates uterine growth, breast development). The thyroid gland increases in size with increased thyroxine-binding globulin (TBG), making total T4 and T3 elevated, but free hormone levels remain normal. The pituitary enlarges (physiological hyperplasia of lactotrophs), and the adrenal axis shows increased cortisol production with blunted feedback sensitivity.
Musculoskeletal and Gastrointestinal Changes
Relaxin causes ligamentous laxity, particularly at the sacroiliac joints and pubic symphysis, contributing to pelvic girdle pain. The gravid uterus displaces the stomach and intestines upward, leading to gastro-oesophageal reflux (progesterone also reduces LOS tone). Gastric emptying is delayed during labour (but not significantly in pregnancy), which has implications for anaesthetic risk (Mendelson's syndrome from aspiration of acidic gastric contents). Gallbladder motility is reduced, increasing the risk of gallstone formation (the "sludge" of pregnancy).
AIIMS Nov 2021: Which cardiovascular change is NOT seen in normal pregnancy?
A. Increased plasma volume by 40-50%
B. Increased cardiac output by 30-50%
C. Increased systemic vascular resistance
D. Decreased blood pressure in mid-pregnancy
Answer: C. Systemic vascular resistance decreases by 25-40% due to progesterone-mediated vasodilation and the low-resistance uteroplacental circulation.
A 28-year-old primigravida at 30 weeks has haemoglobin 10.2 g/dL. She is asymptomatic with normal vitals. Peripheral smear shows mild anisocytosis. What is the most likely explanation? Physiological anaemia of pregnancy — plasma volume increases 40-50% while RBC mass increases only 20-30%, causing dilutional anaemia with nadir at 28-32 weeks. Iron supplementation is not needed if ferritin is normal.
Cellular structure of the placenta showing the syncytiotrophoblast and cytotrophoblast layers.
Antenatal Complications: Preeclampsia and Gestational Diabetes
Preeclampsia
Preeclampsia is a multisystem disorder of pregnancy characterised by new-onset hypertension (>=140/90 mmHg) after 20 weeks gestation with proteinuria (>=300 mg/24 hours or protein:creatinine ratio >=30 mg/mmol) or other end-organ dysfunction (renal insufficiency, hepatic involvement, neurological complications, haematological disturbances, or uteroplacental dysfunction).
It affects 3-5% of pregnancies and remains a leading cause of maternal and perinatal morbidity and mortality worldwide.
Pathophysiology
The pathophysiology is centred on abnormal placentation — inadequate trophoblast invasion of the spiral arteries fails to convert them from high-resistance muscular vessels to low-resistance high-capacitance vessels. This results in placental ischaemia, oxidative stress, and release of anti-angiogenic factors (soluble fms-like tyrosine kinase 1 — sFlt-1, soluble endoglin — sEng) into the maternal circulation. These factors antagonise pro-angiogenic factors (vascular endothelial growth factor — VEGF, placental growth factor — PlGF), causing systemic endothelial dysfunction, vasospasm, and the clinical syndrome of hypertension, proteinuria, and multiorgan involvement.
The sFlt-1:PlGF ratio has diagnostic and predictive value — a ratio >85 before 34 weeks is highly predictive of preterm preeclampsia.
Risk Factors and Prevention
Risk factors: Previous preeclampsia, first pregnancy, multiple pregnancy, maternal age >=40, BMI >=35, pre-existing hypertension, diabetes, renal disease, autoimmune disorders (SLE, antiphospholipid syndrome), and family history.
Prevention with low-dose aspirin (150 mg nocte) from 12-16 weeks reduces the risk of preterm preeclampsia by 60-80% in high-risk women (ASPRE trial).
Management of Established Preeclampsia
Antihypertensive therapy (labetalol 200-800 mg twice daily, nifedipine MR 20-60 mg daily, or methyldopa 500-2000 mg daily in three divided doses) to maintain BP 130-155/80-105 mmHg.
Magnesium sulphate (4 g IV loading dose, then 1 g/hour IV for 24 hours) for seizure prophylaxis in severe preeclampsia (the Magpie trial demonstrated a 58% reduction in eclampsia).
Corticosteroids (betamethasone 12 mg IM, two doses 24 hours apart) for fetal lung maturation if delivery is anticipated before 34 weeks. Timely delivery is the definitive treatment — the decision between immediate delivery (for maternal or fetal compromise at >=34 weeks or at any gestation with uncontrollable severe hypertension, eclampsia, pulmonary oedema, or placental abruption) and expectant management (for preterm gestation without severe features) requires careful risk-benefit assessment.
Preeclampsia Diagnosis
↓
Assess severity
↓
Mild (BP 140-159/90-109, no severe features)
→ Outpatient monitoring, antihypertensives, delivery ≥37 weeks
Severe (BP ≥160/110, severe features)
→ Admission, MgSO4, antihypertensives, corticosteroids if <34 weeks
↓
Maternal/fetal compromise?
↓ Yes ↓ No
Deliver Expectant management (if <34 weeks)
with close monitoring
Gestational Diabetes Mellitus
Gestational diabetes mellitus (GDM) affects 7-15% of pregnancies.
The HAPO study demonstrated a continuous linear relationship between maternal glucose levels and adverse outcomes, including macrosomia (birth weight >90th percentile), large-for-gestational-age (LGA) infants, neonatal hypoglycaemia, primary caesarean section, and preeclampsia. Management involves medical nutrition therapy (30-40% carbohydrate, controlled glycaemic index), self-monitoring of blood glucose (target fasting <5.3 mmol/L, 1-hour postprandial <7.8 mmol/L, 2-hour postprandial <6.4 mmol/L), and pharmacological therapy if targets are not achieved within 1-2 weeks.
Metformin is increasingly used as first-line pharmacotherapy (more than 50% achieve adequate control), with insulin (NPH or detemir) as the second-line or add-on therapy.
Glyburide is not recommended due to higher rates of macrosomia and neonatal hypoglycaemia compared to insulin.
Postpartum follow-up with OGTT at 6-12 weeks is essential as 30-50% of women with GDM develop type 2 diabetes within 10 years.
Preeclampsia: sFlt-1:PlGF ratio >85 = high risk of preterm preeclampsia
Aspirin 150 mg nocte from 12-16 weeks reduces preterm preeclampsia by 60-80%
MgSO4: 4g IV load + 1g/h for 24h — 58% reduction in eclampsia (Magpie trial)
GDM: Metformin first-line; Insulin if targets not met; avoid glyburide
Postpartum OGTT at 6-12 weeks: 30-50% develop T2DM within 10 years
DNB Dec 2022: A 26-year-old primigravida at 34 weeks presents with BP 160/110 mmHg, proteinuria 2+, and severe headache. What is the single most important pharmacological intervention to prevent progression to eclampsia?
Answer: Magnesium sulphate — 4 g IV loading dose over 5-10 minutes, followed by 1 g/hour IV infusion for 24 hours. The Magpie trial demonstrated a 58% relative risk reduction in eclampsia with MgSO4 versus placebo.
Feature
Gestational Hypertension
Preeclampsia
BP criteria
≥140/90 mmHg
≥140/90 mmHg
Proteinuria
Absent
≥300 mg/24h or PCR ≥30 mg/mmol
End-organ dysfunction
None
Renal, hepatic, neurological, or haematological involvement
Delivery timing
37-40 weeks
Depends on severity and gestational age
Placental histopathology in preeclampsia showing inadequate trophoblast invasion and spiral artery remodelling failure.
