Maternal-Fetal Medicine

01 Placental & Fetal Physiology

Placental Development

The placenta develops from the trophoblast, which differentiates into the outer syncytiotrophoblast (multinucleated, hormone-producing, in direct contact with maternal blood) and the inner cytotrophoblast (proliferative stem cells). Placentation involves two waves of trophoblast invasion: the first wave (6-10 weeks) invades the decidua, and the critical second wave (16-20 weeks) invades the myometrial segments of the spiral arteries, transforming them from high-resistance muscular vessels into low-resistance, high-capacitance channels. Failure of this second wave of trophoblast invasion is the central pathophysiology of preeclampsia and fetal growth restriction.

The mature placenta weighs ~500 g at term and contains approximately 150 mL of maternal blood in the intervillous space at any time. Maternal blood enters via 80-100 spiral arteries and bathes the chorionic villi (the functional units of gas and nutrient exchange). The placental barrier consists of syncytiotrophoblast, cytotrophoblast (diminishes after 20 weeks), villous connective tissue, and fetal capillary endothelium. By the third trimester, the barrier thins to ~3.5 μm, facilitating efficient diffusion.

Placental Gas Exchange

Oxygen transfer across the placenta occurs by simple diffusion down a partial pressure gradient. Maternal arterial PaO2 is ~100 mmHg, intervillous space PO2 is ~30-35 mmHg, and umbilical vein PO2 is ~30 mmHg. Despite this low PO2, the fetus maintains adequate oxygen delivery through several compensatory mechanisms: fetal hemoglobin (HbF) has a left-shifted oxygen-hemoglobin dissociation curve (higher oxygen affinity, P50 ~19 mmHg vs adult ~27 mmHg), fetal hemoglobin concentration is higher (16-18 g/dL), fetal cardiac output per kg is higher than adult, and the double Bohr effect (CO2 transfer from fetal to maternal blood shifts the fetal curve leftward and maternal curve rightward, facilitating bidirectional exchange).

Carbon dioxide crosses the placenta ~20 times faster than oxygen (high diffusibility), also by simple diffusion. Glucose crosses via facilitated diffusion (GLUT transporters). Amino acids are transported by active transport. IgG crosses by receptor-mediated endocytosis (pinocytosis), primarily in the third trimester — this provides passive immunity to the neonate. IgM and IgA do not cross the placenta (if IgM is detected in neonatal blood, it indicates fetal infection).

Fetal Circulation

The fetal circulation contains three critical shunts that bypass the non-functioning lungs and liver:

At birth, the first breath causes a dramatic decrease in pulmonary vascular resistance and increase in systemic resistance (clamping the umbilical cord). Increased left atrial pressure functionally closes the foramen ovale. Rising PaO2 and declining prostaglandins cause the ductus arteriosus to constrict (functional closure by 12-24 hours; anatomic closure by 2-3 weeks). The ductus venosus closes and becomes the ligamentum venosum.

Amniotic Fluid Dynamics

Amniotic fluid volume increases progressively through pregnancy, peaking at ~800-1000 mL at 36-37 weeks, then declining slightly toward term. Production: Early pregnancy — transudate across fetal skin and amnion; after 16 weeks — predominantly fetal urine (by term, fetal urine output is ~800-1200 mL/day) with a smaller contribution from fetal lung fluid (~250 mL/day). Removal: Fetal swallowing (~500-1000 mL/day) and intramembranous absorption. This balance explains why oligohydramnios (AFI < 5 cm or MVP < 2 cm) occurs with renal agenesis, posterior urethral valves, and uteroplacental insufficiency (decreased fetal renal perfusion), while polyhydramnios (AFI > 24 cm or MVP > 8 cm) occurs with esophageal atresia, duodenal atresia, and fetal anemia (conditions that impair fetal swallowing or increase fetal urine output).

02 Obstetric Ultrasound

First Trimester Ultrasound

Dating: Crown-rump length (CRL) measured between 6-13+6 weeks is the most accurate parameter for determining gestational age (±5-7 days). If the CRL-based dating differs from LMP dating by > 5 days (in the first trimester) or > 7 days (second trimester), the ultrasound date should be used. A gestational sac is visible by transvaginal ultrasound (TVUS) at ~4.5-5 weeks, a yolk sac at ~5.5 weeks, and cardiac activity at 6-6.5 weeks (CRL ≥ 7 mm). Absence of cardiac activity with CRL ≥ 7 mm confirms nonviable pregnancy.

Nuchal translucency (NT): Measured between 11+0 and 13+6 weeks (CRL 45-84 mm). The NT is the sonolucent space between the skin and soft tissue overlying the fetal cervical spine. Normal NT is < 3.0 mm at the 95th percentile. Increased NT (≥ 3.0 mm) is associated with trisomy 21, trisomy 18, trisomy 13, Turner syndrome, congenital heart defects, skeletal dysplasias, and other structural anomalies. NT combined with maternal age, free β-hCG, and PAPP-A constitutes the first trimester combined screen (detection rate ~85-90% for trisomy 21, false positive rate ~5%).

Anatomy Scan — Systematic Approach

The standard detailed anatomy scan is performed at 18-22 weeks. A systematic survey includes:

Fetal Growth Parameters

Four standard biometric measurements are used to calculate estimated fetal weight (EFW): BPD (biparietal diameter — outer edge to inner edge), HC (head circumference), AC (abdominal circumference — at the level of the stomach and intrahepatic umbilical vein), and FL (femur length — ossified diaphysis only). The Hadlock formula (using BPD, HC, AC, FL) is the most widely used EFW formula, with an accuracy of ±15-20%. The AC is the single most sensitive parameter for detecting growth abnormalities — a small AC reflects decreased liver glycogen stores in growth-restricted fetuses.

Cervical Length Assessment

Transvaginal cervical length measurement is a key screening tool for preterm birth. Normal cervical length at 18-24 weeks is ≥ 25 mm. A short cervix (< 25 mm) in a singleton pregnancy at 16-24 weeks is an indication for vaginal progesterone. In women with prior spontaneous preterm birth, cervical length screening begins at 16 weeks and is repeated every 1-2 weeks until 24 weeks. Cervical length < 25 mm in a patient with a prior preterm birth is an indication for cerclage placement (ultrasound-indicated cerclage).

Doppler Ultrasonography

Doppler assessment is essential for surveillance of high-risk pregnancies, particularly fetal growth restriction:

03 Genetic Screening & Diagnosis

Cell-Free DNA / Non-Invasive Prenatal Testing (NIPT)

Cell-free DNA (cfDNA) screening analyzes placental-origin cell-free DNA fragments in the maternal circulation. Available from 10 weeks gestation. Performance characteristics:

Key limitations: cfDNA is a screening test, not a diagnostic test — all positive results require confirmation with diagnostic testing (amniocentesis or CVS). Factors that reduce accuracy: low fetal fraction (< 4%), early gestational age, maternal obesity, confined placental mosaicism, vanishing twin, maternal malignancy, maternal copy number variants. The cfDNA actually originates from the placenta (trophoblast), not the fetus — confined placental mosaicism is the most common cause of discordant results.

Traditional Serum Screening

First trimester combined screen (11-13+6 weeks): NT measurement + free β-hCG + PAPP-A. Detection rate for trisomy 21: 82-87%, FPR: 5%. Trisomy 21 pattern: increased NT, increased β-hCG, decreased PAPP-A. Trisomy 18 pattern: increased NT, decreased β-hCG, decreased PAPP-A.

Quad screen (15-22 weeks): AFP, hCG, unconjugated estriol (uE3), and inhibin A. Detection rate for trisomy 21: 81%, FPR: 5%. Trisomy 21 pattern: low AFP, high hCG, low uE3, high inhibin A ("ALAM" — AFP Low, All Markers abnormal). Open neural tube defects: elevated MSAFP (> 2.5 MoM). Trisomy 18: all four markers low.

Diagnostic Procedures

Chorionic villus sampling (CVS): Performed at 10-13 weeks. Obtains placental (trophoblast) tissue via transcervical or transabdominal approach. Advantage: earlier results allow earlier decision-making. Limitation: ~1-2% rate of confined placental mosaicism (CPM), which may necessitate follow-up amniocentesis. Procedure-related loss rate: ~1/455 (0.22%).

Amniocentesis: Performed at ≥ 15 weeks (typically 15-20 weeks). Obtains amniotic fluid containing fetal cells (primarily desquamated fetal skin and urogenital cells). Gold standard for karyotype. Procedure-related loss rate: ~1/900 (0.11%). Also used for fetal lung maturity testing, fetal infection workup, and ΔOD450 in alloimmunization.

Cordocentesis (percutaneous umbilical blood sampling / PUBS): Obtains fetal blood directly from the umbilical vein at the cord insertion into the placenta. Performed at ≥ 18 weeks. Indications: rapid karyotype (results in 48-72 hours), evaluation of fetal anemia (hematocrit), fetal infection (IgM), thrombocytopenia (platelet count). Highest risk procedure — loss rate ~1-2%. Also used therapeutically for intrauterine transfusion.

Genetic Testing Modalities

04 Risk Assessment & Antepartum Surveillance

Biophysical Profile (BPP)

The BPP is a composite assessment of fetal well-being that evaluates five parameters, each scored 0 or 2 (total 0-10):

Interpretation:

The amniotic fluid component reflects long-term placental function, while the other four reflect acute CNS function. In progressive hypoxemia, the components are lost in reverse order of their developmental appearance: NST reactivity (last to develop, first to be lost) → breathing movements → body movements → tone (first to develop, last to be lost). This pattern reflects the maturation of CNS centers — the more recently developed centers (FHR reactivity, medulla) are more sensitive to hypoxemia than the earlier-developing centers (tone, cortex/subcortex).

Non-Stress Test (NST)

The NST assesses fetal heart rate (FHR) patterns by external cardiotocography. A reactive NST requires ≥ 2 accelerations of ≥ 15 bpm above baseline lasting ≥ 15 seconds within a 20-minute window (for fetuses ≥ 32 weeks). Before 32 weeks, the criteria are ≥ 10 bpm for ≥ 10 seconds. A non-reactive NST lacks these accelerations and may indicate fetal sleep cycle (extend to 40 minutes), fetal compromise, or medication effects (opioids, magnesium, betamethasone). Variable decelerations on NST suggest cord compression; late decelerations suggest uteroplacental insufficiency.

Contraction Stress Test (CST)

The CST evaluates FHR response to uterine contractions (endogenous or oxytocin-induced). Requires ≥ 3 contractions in 10 minutes. Negative CST: No late decelerations — highly reassuring (negative predictive value > 99.8% for fetal death within 1 week). Positive CST: Late decelerations with ≥ 50% of contractions — indicates uteroplacental insufficiency. Contraindications: preterm labor risk, PPROM, placenta previa, prior classical uterine incision.

Modified BPP

The modified BPP combines NST (acute marker) with amniotic fluid index (chronic marker). If both are normal (reactive NST + AFI ≥ 5), the result is reassuring. This is the most commonly used surveillance method due to ease of performance and comparable predictive value to the full BPP.

Surveillance Frequency by Condition

05 Hypertensive Disorders of Pregnancy

Classification

Hypertensive disorders complicate 5-10% of pregnancies and are a leading cause of maternal morbidity and mortality. The ACOG classification divides them into four categories:

Preeclampsia — Diagnostic Criteria

Preeclampsia without severe features: BP ≥ 140/90 mmHg on two occasions at least 4 hours apart after 20 weeks + proteinuria (≥ 300 mg/24h, P:C ≥ 0.3, or dipstick ≥ 2+).

Preeclampsia with severe features (any one of the following):

• SBP ≥ 160 mmHg or DBP ≥ 110 mmHg on two occasions (minutes apart, allowing treatment)
• Platelet count < 100,000/μL
• Serum creatinine > 1.1 mg/dL or doubling of baseline
• Liver transaminases ≥ 2× upper limit of normal
• Pulmonary edema
• New-onset headache unresponsive to medication or visual disturbances

HELLP Syndrome

HELLP — Hemolysis, Elevated Liver enzymes, Low Platelets — is a severe variant of preeclampsia. It may occur without significant hypertension or proteinuria (15-20% of cases). Peak incidence: 28-36 weeks; 30% present postpartum.

Eclampsia

Eclampsia is the occurrence of generalized tonic-clonic seizures in a patient with preeclampsia that cannot be attributed to other causes. It occurs antepartum (38-53%), intrapartum (18-36%), or postpartum (11-44%). It can occur without preceding severe hypertension or proteinuria. Management: left lateral position, protect airway, magnesium sulfate (4-6 g IV loading dose over 15-20 minutes, then 1-2 g/hour maintenance), stabilize BP, deliver after stabilization.

Aspirin Prophylaxis for Preeclampsia Prevention

ACOG/USPSTF recommendation: Low-dose aspirin (81 mg/day) starting at 12-16 weeks (optimally before 16 weeks) through 36 weeks for women at high risk. High-risk criteria (one or more): prior preeclampsia, multifetal gestation, chronic hypertension, type 1 or type 2 diabetes, renal disease, autoimmune disease (SLE, APS). Moderate-risk criteria (two or more): nulliparity, obesity (BMI > 30), family history of preeclampsia, African American race, low socioeconomic status, age ≥ 35, prior adverse outcome (SGA, abruption, stillbirth). The ASPRE trial demonstrated that aspirin 150 mg nightly (starting 11-14 weeks, based on first-trimester combined screening) reduced preterm preeclampsia by 62%. Nighttime administration is preferred (targets the nocturnal platelet activation peak).

Acute Management of Severe HTN

Acute-onset severe hypertension (SBP ≥ 160 and/or DBP ≥ 110) requires urgent treatment within 30-60 minutes to prevent stroke, the leading cause of death in preeclampsia. First-line agents:

Magnesium Sulfate Protocol

Indication: Seizure prophylaxis in preeclampsia with severe features and treatment of eclampsia. Loading dose: 4-6 g IV over 15-20 minutes, followed by maintenance infusion of 1-2 g/hour. Continue for 24-48 hours postpartum. Monitor: deep tendon reflexes (lost at 7-10 mEq/L), respiratory rate (≥ 12/min), urine output (≥ 30 mL/hour). Therapeutic level: 4-7 mEq/L. Toxicity: respiratory depression (10-12 mEq/L), cardiac arrest (15-20 mEq/L). Antidote: calcium gluconate 1 g IV over 3 minutes.

Delivery Timing

Gestational hypertension or preeclampsia without severe features: deliver at 37+0 weeks (per HYPITAT/PHOENIX trials). Preeclampsia with severe features: deliver at 34+0 weeks (or at diagnosis if ≥ 34 weeks). Before 34 weeks with severe features: individualize — administer corticosteroids and deliver within 48 hours unless expectant management criteria are met (stable maternal/fetal status, inpatient setting). HELLP: deliver after maternal stabilization, regardless of gestational age if < 34 weeks (after steroids if feasible). Eclampsia: deliver after seizure control and maternal stabilization.

06 Diabetes in Pregnancy

Pregestational Diabetes (Type 1 & Type 2)

Pregestational diabetes complicates ~1% of pregnancies and is associated with significantly increased risks of congenital anomalies (3-5× baseline, especially cardiac — VSD, transposition; NTDs; caudal regression syndrome), macrosomia, preeclampsia, stillbirth, and neonatal hypoglycemia. Risk is directly related to periconceptional glycemic control — HbA1c < 6.5% before conception is the target (anomaly risk is near baseline at this level; risk doubles with HbA1c > 8% and increases 5-10× with HbA1c > 10%).

Periconceptional counseling: Folic acid 4 mg/day (not 0.4 mg — the higher dose for NTD prevention in high-risk patients), optimize HbA1c to < 6.5%, discontinue teratogenic medications (ACE inhibitors, ARBs, statins), assess for retinopathy, nephropathy, and cardiac disease before pregnancy.

Glucose targets in pregnancy (ACOG recommendations): fasting < 95 mg/dL, 1-hour postprandial < 140 mg/dL, 2-hour postprandial < 120 mg/dL. Insulin is the preferred pharmacotherapy — it does not cross the placenta. Insulin requirements typically increase by 50-100% during pregnancy due to progressive insulin resistance (mediated by human placental lactogen, cortisol, TNF-α). A drop in insulin requirements in the third trimester may indicate placental insufficiency and warrants increased surveillance.

White Classification of Diabetes in Pregnancy

Gestational Diabetes (GDM)

Gestational diabetes affects 6-9% of pregnancies. Universal screening is recommended at 24-28 weeks. Two approaches:

Management: Nutritional counseling (carbohydrate-controlled diet: 3 meals + 2-3 snacks, ~33-40% carbohydrate calories) and glucose monitoring (fasting + 1-hour or 2-hour postprandial, 4 times/day minimum). If targets are not met within 1-2 weeks, initiate pharmacotherapy. Insulin is first-line and the only FDA-approved agent for diabetes in pregnancy. Common regimens: basal insulin (NPH or detemir) for fasting hyperglycemia + rapid-acting insulin (lispro, aspart) for postprandial hyperglycemia. Metformin and glyburide are used off-label — metformin crosses the placenta (long-term effects on offspring under study, may have benefits for maternal weight and insulin requirements); glyburide is associated with higher rates of neonatal hypoglycemia and macrosomia compared to insulin and is increasingly falling out of favor after the MiTy and GEMS trials.

Fetal surveillance: A1 GDM (diet-controlled): no routine antepartum testing beyond growth scans (growth US at 28-32 weeks to assess for macrosomia). A2 GDM (medication-treated): initiate antepartum testing at 32 weeks (NST 1-2x/week). Pregestational diabetes: antepartum testing at 32 weeks (or earlier if poorly controlled or with vasculopathy); growth US every 3-4 weeks starting at 28 weeks. Delivery timing: A1 GDM: deliver at 39+0-40+6 weeks (expectant management to 40+6). A2 GDM: deliver at 39+0-39+6 weeks. Pregestational diabetes (well-controlled without vasculopathy): deliver at 37+0-39+6 weeks. Pregestational diabetes (poorly controlled or with vasculopathy): individualize delivery at 34+0-37+6 weeks. Early third-trimester fetal echocardiography is recommended for pregestational diabetes given the 3-5× increased risk of congenital heart defects.

07 Cardiac Disease in Pregnancy

Physiologic Cardiovascular Changes in Pregnancy

Normal pregnancy produces dramatic hemodynamic changes: blood volume increases by 40-50% (peaking at 32-34 weeks), cardiac output increases by 30-50% (increased HR by 10-20 bpm and increased stroke volume), systemic vascular resistance decreases by 20-30% (progesterone-mediated vasodilation), and blood pressure normally decreases in the first and second trimesters (nadir at 24-28 weeks) before returning to baseline at term. These changes make pregnancy a cardiovascular stress test — women with limited cardiac reserve may decompensate, particularly at 28-34 weeks (maximum volume loading) and during labor/delivery (autotransfusion of 300-500 mL with each contraction).

Modified WHO (mWHO) Risk Classification

Specific Cardiac Conditions

Mechanical heart valves: Require continuous anticoagulation throughout pregnancy. Options: dose-adjusted LMWH (anti-Xa 0.8-1.2 U/mL 4-6h post-dose) throughout pregnancy, warfarin throughout pregnancy (lowest fetal risk if dose ≤ 5 mg/day, but warfarin embryopathy risk 4-10% in first trimester at higher doses), or sequential regimen (LMWH in first trimester, warfarin second/early third trimester, switch to heparin near delivery). Warfarin offers the lowest thrombotic risk to the mother; LMWH offers the lowest teratogenic risk to the fetus. There is no perfect solution — shared decision-making is essential.

Peripartum cardiomyopathy (PPCM): New-onset HF with EF < 45% presenting in the last month of pregnancy through 5 months postpartum, with no other identifiable cause. Incidence ~1 in 1,000-4,000. Risk factors: African American race, multiparity, advanced maternal age, preeclampsia, tocolytic use. Treatment: standard HF therapy (diuretics, hydralazine/nitrates — avoid ACE inhibitors until postpartum, beta-blockers). Approximately 50% recover normal EF within 6 months. Bromocriptine shows promise. Subsequent pregnancy carries recurrence risk of 30-50% (higher if EF has not normalized).

Marfan syndrome: Autosomal dominant FBN1 mutation. Risk of aortic root dissection increases during pregnancy, particularly in the third trimester and peripartum (hemodynamic stress, hormonal effects on connective tissue). Aortic root < 40 mm: pregnancy generally tolerated with close monitoring (echocardiography every 4-8 weeks). Aortic root 40-45 mm: higher risk, individualized counseling advised, consider genetic counseling (50% transmission to offspring). Aortic root > 45 mm: pregnancy contraindicated — prophylactic aortic root repair before pregnancy recommended. Beta-blockers (metoprolol, atenolol) should be continued throughout pregnancy to reduce the rate of aortic root dilation.

Eisenmenger syndrome: Pulmonary hypertension with right-to-left shunting. Maternal mortality 20-50%. Pregnancy is absolutely contraindicated. The physiologic decrease in systemic vascular resistance during pregnancy worsens right-to-left shunting, leading to progressive cyanosis, syncope, and sudden death. If pregnancy occurs, termination should be offered. If continued, intensive monitoring, pulmonary vasodilators (sildenafil, inhaled nitric oxide), and early delivery are needed.

Aortic stenosis: Mild-moderate AS is generally well tolerated. Severe symptomatic AS (valve area < 1.0 cm²) is high risk (mWHO III-IV). The inability to increase cardiac output across a fixed obstruction during the hemodynamic changes of pregnancy leads to heart failure, syncope, and arrhythmia. Ideally, severe AS should be corrected before pregnancy. If diagnosed during pregnancy: medical management with beta-blockers, avoid dehydration and vasodilation, consider percutaneous balloon valvuloplasty for critical cases.

08 Renal Disease in Pregnancy

Chronic Kidney Disease (CKD) in Pregnancy

Normal pregnancy increases GFR by ~50% — serum creatinine normally decreases to 0.4-0.6 mg/dL (a "normal" non-pregnant creatinine of 1.0 mg/dL represents significant renal impairment in pregnancy). The degree of baseline renal dysfunction predicts outcomes: mild CKD (creatinine < 1.4): generally favorable outcomes, 20% risk of preeclampsia; moderate CKD (creatinine 1.4-2.5): 40% risk of preeclampsia, 35% risk of preterm delivery, 20% risk of accelerated decline in renal function; severe CKD (creatinine > 2.5): poor fetal outcomes, high risk of preeclampsia (60-80%), often requires dialysis during pregnancy. Pregnancy is generally advised against with creatinine > 2.5 mg/dL.

Pregnancy After Renal Transplant

Pregnancy is reasonable ≥ 1-2 years post-transplant if: stable graft function (creatinine < 1.5), no recent rejection episodes, no active infections, minimal proteinuria, controlled BP, and immunosuppression at maintenance levels. Safe immunosuppressants include: azathioprine, cyclosporine, tacrolimus, and prednisone. Mycophenolate mofetil (CellCept) is absolutely contraindicated — teratogenic (cleft lip/palate, ear anomalies, heart defects) — must be stopped ≥ 6 weeks before conception and replaced with azathioprine.

Acute Kidney Injury in Pregnancy

The differential diagnosis of AKI in pregnancy is broad and includes pregnancy-specific etiologies:

09 Thrombophilia & Venous Thromboembolism

Inherited Thrombophilias

Pregnancy is a hypercoagulable state due to increased clotting factors (I, VII, VIII, X, vWF), decreased protein S, increased PAI-1 and PAI-2, and venous stasis. The risk of VTE is 4-5× higher in pregnancy and 20-80× higher in the postpartum period.

Antiphospholipid Syndrome (APS)

Sapporo (revised Sydney) criteria require at least one clinical AND one laboratory criterion:

Treatment in obstetric APS: Low-dose aspirin (81-162 mg, starting before 16 weeks) PLUS prophylactic-dose heparin (unfractionated or LMWH) throughout pregnancy and 6-12 weeks postpartum. For patients with prior thrombosis: therapeutic-dose anticoagulation. For triple-positive APS (all three antibodies positive): highest risk — therapeutic anticoagulation is recommended even without prior thrombosis by some experts.

Thromboprophylaxis Protocols

VTE Treatment in Pregnancy

LMWH is the drug of choice for treatment of VTE in pregnancy (enoxaparin 1 mg/kg q12h, adjusted-dose dalteparin, or tinzaparin). LMWH does not cross the placenta and has a more predictable pharmacokinetic profile than UFH. Anti-Xa levels should be monitored (target peak 0.6-1.0 U/mL 4-6 hours post-dose for therapeutic dosing). Dose adjustments are often needed as pregnancy progresses due to increased volume of distribution and renal clearance. Warfarin is contraindicated for VTE treatment in pregnancy — crosses the placenta, causes warfarin embryopathy (nasal hypoplasia, stippled epiphyses) in weeks 6-12 and CNS anomalies throughout pregnancy. DOACs (rivaroxaban, apixaban, etc.) are also contraindicated — they cross the placenta and animal studies show reproductive toxicity. IVC filters are reserved for patients with contraindications to anticoagulation or recurrent PE despite therapeutic anticoagulation.

Peripartum management: Hold LMWH 24 hours before planned delivery (12 hours for prophylactic dose). Neuraxial anesthesia requires ≥ 12 hours after prophylactic dose, ≥ 24 hours after therapeutic dose. Resume anticoagulation 6-12 hours after vaginal delivery, 12-24 hours after cesarean. Continue for ≥ 6 weeks postpartum (minimum total duration: 3 months for provoked VTE). Warfarin and LMWH are both safe with breastfeeding. Postpartum transition to warfarin (INR 2-3) is an option for patients who prefer oral therapy.

10 Autoimmune Disease in Pregnancy

Systemic Lupus Erythematosus (SLE)

SLE flares occur in ~40-60% of pregnancies (risk higher if disease is active at conception — ideally defer pregnancy until 6 months of quiescence). Key complications: preeclampsia (20-30%), fetal growth restriction, preterm delivery, and pregnancy loss. Distinguishing lupus nephritis flare from preeclampsia is critical and often challenging — complement levels (C3/C4 — decrease in lupus flare but are normally increased in pregnancy), anti-dsDNA titers (rise in flare), and urine sediment (active sediment with casts in lupus) help differentiate. Hydroxychloroquine should be continued throughout pregnancy — it reduces flares, preeclampsia risk, and neonatal lupus incidence.

Neonatal lupus: Caused by transplacental passage of maternal anti-Ro (SSA) and anti-La (SSB) antibodies. Manifestations: cutaneous lupus rash (photosensitive, resolves by 6-9 months as maternal antibodies clear), hematologic (cytopenias), hepatic, and congenital heart block (CHB — the most serious complication, incidence ~2% with positive antibodies, 18% recurrence with prior affected child). Complete CHB is irreversible and may require fetal/neonatal pacemaker. Surveillance: serial fetal echocardiography every 1-2 weeks from 16-26 weeks to detect PR prolongation before progression to complete block. Dexamethasone (crosses the placenta) may be used for incomplete block, though efficacy for preventing progression is debated.

Rheumatoid Arthritis

RA typically improves during pregnancy (70% of patients) due to the immunosuppressive effect of pregnancy, but flares are common postpartum (90% within 3 months). Safe medications: hydroxychloroquine, sulfasalazine, low-dose prednisone, azathioprine, TNF-α inhibitors (certolizumab preferred — does not cross placenta due to pegylated Fab fragment structure). Contraindicated: methotrexate (teratogenic — stop ≥ 3 months before conception), leflunomide (requires cholestyramine washout), JAK inhibitors, cyclophosphamide.

Inflammatory Bowel Disease (IBD)

Active IBD at conception is the strongest predictor of poor pregnancy outcomes. Maintain disease remission through pregnancy — most IBD medications are safe (5-ASA, azathioprine/6-MP, anti-TNF agents, corticosteroids). Methotrexate must be stopped before conception. Timing of biologic dosing is adjusted so the last dose is given 6-10 weeks before the expected delivery to minimize neonatal immunosuppression. Live vaccines are delayed in infants exposed to biologics in utero until 6-12 months of age.

11 Hematologic Disorders

Sickle Cell Disease

Sickle cell disease (HbSS, HbSC, HbS-β-thalassemia) in pregnancy is associated with increased risk of pain crises, acute chest syndrome, preeclampsia (2-4×), FGR, preterm delivery, VTE, and maternal mortality (0.5-2%). Management: continued folic acid supplementation (4 mg/day), serial growth ultrasounds, low-dose aspirin for preeclampsia prevention, prophylactic transfusion is controversial (TAPS study suggests benefit). Pain crises are managed with IV hydration, oxygen, and opioid analgesia (avoid NSAIDs after 20 weeks). Hydroxyurea is teratogenic and must be stopped before conception (limited data on inadvertent first-trimester exposure). Iron overload should be assessed and treated before pregnancy.

Immune Thrombocytopenic Purpura (ITP)

ITP results from autoantibodies (IgG) against platelet glycoproteins. These antibodies cross the placenta and can cause fetal/neonatal thrombocytopenia (but severe neonatal bleeding is rare — < 1% intracranial hemorrhage). Treatment: first-line is corticosteroids (prednisone 1 mg/kg) or IVIG (1 g/kg × 2 days) for platelet counts < 30,000 or in the third trimester to prepare for delivery. Target for vaginal delivery: platelets ≥ 50,000. Target for neuraxial anesthesia: platelets ≥ 70,000-80,000. Mode of delivery is based on obstetric indications — ITP alone is not an indication for cesarean delivery.

Von Willebrand Disease

The most common inherited bleeding disorder. VWF levels normally increase during pregnancy (may reach normal levels in type 1 by the third trimester). Management varies by type: Type 1 (most common — quantitative deficiency): VWF levels typically normalize by delivery, DDAVP may be used for mild bleeding. Type 2: qualitative defects — VWF factor concentrates preferred over DDAVP. Type 3: severe quantitative deficiency — VWF/FVIII concentrates for delivery and postpartum (risk of delayed postpartum hemorrhage as VWF levels decline rapidly after delivery). Levels should be checked at 28-34 weeks and targeted to ≥ 50 IU/dL for delivery.

Iron Deficiency Anemia

The most common cause of anemia in pregnancy. Physiologic anemia of pregnancy (dilutional, hemoglobin nadir ~10.5 g/dL at 28-34 weeks) must be distinguished from true iron deficiency (ferritin < 30 ng/mL, low serum iron, elevated TIBC). Iron requirements increase from 1 mg/day prepregnancy to 6-7 mg/day in the third trimester. Oral iron (ferrous sulfate 325 mg 1-2x/day, between meals with vitamin C) is first-line. IV iron (ferric carboxymaltose, iron sucrose) is indicated for intolerance of oral iron, severe anemia (Hb < 7-8 g/dL), or second/third trimester when rapid repletion is needed.

12 Infections in Pregnancy

TORCH Infections

The TORCH acronym encompasses the major perinatal infections: Toxoplasmosis, Other (syphilis, varicella, parvovirus B19), Rubella, Cytomegalovirus, Herpes simplex virus. Shared clinical features of congenital TORCH infection include: IUGR, hepatosplenomegaly, jaundice, thrombocytopenia, rash, and intracranial calcifications (pattern varies by pathogen).

Zika Virus

Zika virus is an arbovirus (Flaviviridae family) transmitted by Aedes mosquitoes and sexually. Maternal infection in pregnancy (especially first/second trimester) is associated with congenital Zika syndrome: severe microcephaly, intracranial calcifications (subcortical, distinct from periventricular pattern of CMV), macular scarring/focal pigmentary retinal mottling, congenital contractures (arthrogryposis), and marked early hypertonia. Most maternal infections are asymptomatic or mild (rash, conjunctivitis, arthralgia, low-grade fever). Vertical transmission rate: ~5-15% (risk of microcephaly ~5% with first-trimester infection). Diagnosis: serum and urine Zika RNA PCR, Zika IgM (cross-reactivity with dengue is common). No specific antiviral treatment or vaccine. Prevention: avoid travel to endemic areas, mosquito precautions, condom use for partners with Zika exposure for ≥ 3 months.

HIV in Pregnancy

Without intervention, vertical transmission is 25-30%. With combined antiretroviral therapy (cART), elective cesarean for viral load > 1,000 copies/mL, and avoidance of breastfeeding, transmission is reduced to < 1-2%. Universal screening at first prenatal visit. ART should be initiated or continued regardless of CD4 count. Intrapartum: IV zidovudine for women with viral load > 1,000. Scheduled cesarean at 38 weeks if viral load > 1,000 near delivery. If viral load < 1,000 and on cART: vaginal delivery is appropriate. Avoid invasive procedures (amniotomy, fetal scalp electrode, operative vaginal delivery) when possible.

Hepatitis B & C

Hepatitis B: Universal screening with HBsAg at first prenatal visit. Vertical transmission with HBeAg-positive mother: 70-90% without prophylaxis. Prevention: neonatal hepatitis B immunoglobulin (HBIG) + HBV vaccine within 12 hours of birth (reduces transmission to < 5%). Tenofovir in the third trimester for mothers with viral load > 200,000 IU/mL further reduces transmission. Breastfeeding is safe after neonatal immunoprophylaxis.

Hepatitis C: Vertical transmission 5-6% (higher with HIV coinfection — 10-20%, and with higher viral loads). No interventions are currently proven to reduce vertical transmission (no vaccine, no immunoglobulin). Direct-acting antivirals (DAAs — sofosbuvir/ledipasvir, glecaprevir/pibrentasvir) are not yet approved in pregnancy, although studies are ongoing (STORC trial). Mode of delivery does not affect transmission — cesarean is not protective. Avoid prolonged rupture of membranes (> 6 hours may increase risk) and fetal scalp electrode when possible. Breastfeeding is not contraindicated unless nipples are cracked or bleeding. Test infant with HCV RNA at ≥ 2 months (earliest) or anti-HCV at ≥ 18 months (maternal antibodies persist before this).

Varicella-Zoster Virus (VZV): Primary varicella (chickenpox) in pregnancy carries risk of maternal complications (varicella pneumonia — 10-20% mortality if untreated in pregnancy) and fetal effects: congenital varicella syndrome (maternal infection at 8-20 weeks — 0.4-2% risk — limb hypoplasia, cicatricial skin scarring, eye anomalies, cortical atrophy, microcephaly) and neonatal varicella (maternal rash onset 5 days before to 2 days after delivery — 17-30% attack rate, 7% mortality). Management: varicella-zoster immune globulin (VariZIG) within 10 days of exposure for susceptible pregnant women; acyclovir/valacyclovir for active infection. Vaccination is a live vaccine — contraindicated in pregnancy, but inadvertent administration has not shown teratogenicity. Ensure immunity before conception (two doses recommended).

Group B Streptococcus (GBS)

GBS colonizes 10-30% of pregnant women. Universal screening with vaginal-rectal culture at 36+0-37+6 weeks. Intrapartum antibiotic prophylaxis (IAP) indications: positive GBS culture, GBS bacteriuria in current pregnancy, prior infant with GBS disease, or unknown GBS status with risk factors (preterm labor < 37 weeks, ROM ≥ 18 hours, intrapartum fever ≥ 38.0°C). Preferred agent: penicillin G 5 million units IV loading then 2.5-3 million units q4h until delivery. Adequate prophylaxis requires ≥ 4 hours of antibiotic administration before delivery.

13 Fetal Growth Abnormalities

Fetal Growth Restriction (FGR)

Fetal growth restriction is defined as estimated fetal weight (EFW) < 10th percentile for gestational age. It affects 5-10% of pregnancies and is a leading cause of perinatal morbidity and mortality. Distinction from constitutionally small fetus is important — a growth-restricted fetus shows declining growth velocity and/or abnormal Doppler findings.

Doppler-Based Staging & Delivery Timing for Early-Onset FGR

Macrosomia

Macrosomia is defined as birth weight ≥ 4,000 g (some use ≥ 4,500 g). Risk factors: maternal diabetes (most important modifiable risk factor), obesity, excessive weight gain, post-dates, multiparity, male fetus. Complications: shoulder dystocia (risk ~1-3% at 4,000-4,499 g, 5-9% at 4,500-4,999 g, 20-50% at ≥ 5,000 g), brachial plexus injury, clavicle fracture, maternal perineal lacerations, postpartum hemorrhage. Planned cesarean is recommended for EFW ≥ 5,000 g in non-diabetic women and ≥ 4,500 g in diabetic women. Ultrasound estimation of fetal weight has an inherent error of ±15-20%, which limits the accuracy of macrosomia prediction.

14 Fetal Structural Anomalies

Central Nervous System Anomalies

Anencephaly: Failure of closure of the rostral neural tube. Absence of the cranial vault and cerebral hemispheres. Universally lethal. Diagnosed by first trimester (absent calvarium). Elevated MSAFP. Folic acid supplementation (0.4-4 mg/day) reduces NTD risk by 50-70%.

Spina bifida (myelomeningocele): Failure of closure of the caudal neural tube. Open spina bifida: meninges and neural tissue protrude through vertebral defect. Associated with Arnold-Chiari II malformation (cerebellar tonsillar herniation), hydrocephalus (90%), and lower extremity motor/sensory deficits. US signs: "lemon sign" (scalloping of frontal bones) and "banana sign" (cerebellar compression). Elevated MSAFP. Candidate for fetal surgery (see MOMS trial, Section 25).

Ventriculomegaly: Lateral ventricular atrial width ≥ 10 mm. Mild (10-12 mm): isolated mild ventriculomegaly has 85-90% normal outcome — follow serially and offer genetic testing. Moderate (13-15 mm): higher association with genetic abnormalities and structural defects. Severe (≥ 15 mm, hydrocephalus): significant risk of neurodevelopmental impairment, often associated with other anomalies. Workup: detailed anatomy scan, MRI (fetal MRI superior to US for CNS evaluation), microarray, CMV testing (TORCH).

Dandy-Walker malformation: Complete or partial agenesis of the cerebellar vermis with cystic dilation of the fourth ventricle and enlarged posterior fossa. Associated with hydrocephalus (80%), other CNS anomalies, cardiac defects, and chromosomal abnormalities (trisomy 18, trisomy 13). US: cystic posterior fossa mass with absent or hypoplastic vermis. Prognosis depends on associated anomalies — isolated Dandy-Walker has better prognosis than previously thought.

Holoprosencephaly: Failure of the prosencephalon (forebrain) to divide into two hemispheres. Spectrum: alobar (most severe — single midline ventricle, fused thalami, absent falx), semilobar, lobar. Strongly associated with trisomy 13, trisomy 18, and midline facial defects (cyclopia, proboscis, cleft lip/palate). "The face predicts the brain." Alobar form is lethal.

Cardiac Anomalies

Congenital heart defects are the most common structural anomalies (~8 per 1,000 live births). The four-chamber view on screening US detects only ~50% of CHD; adding outflow tract views and the three-vessel view increases detection to ~80-90%. Fetal echocardiography is indicated for: increased NT, family history of CHD, pregestational diabetes, fetal arrhythmia, extracardiac anomaly, abnormal screening views, and teratogen exposure.

Ventricular septal defect (VSD): Most common CHD. Membranous (70%), muscular (20%), inlet, or outlet. Small muscular VSDs often close spontaneously. Large VSDs cause heart failure if unrepaired. Hypoplastic left heart syndrome (HLHS): Underdevelopment of the left ventricle, mitral valve, aortic valve, and ascending aorta. Fatal without intervention. Requires staged surgical palliation (Norwood, Glenn, Fontan) or cardiac transplantation. The four-chamber view will show a small left ventricle.

Abdominal Wall Defects

Renal Anomalies

Hydronephrosis: The most common prenatal urinary anomaly (1-5% of pregnancies). Grading (SFU): mild (renal pelvis dilation only), moderate (calyceal dilation), severe (parenchymal thinning). Most mild-moderate cases resolve postnatally. Severe bilateral hydronephrosis with oligohydramnios: consider obstructive uropathy (posterior urethral valves in males). Bilateral renal agenesis (Potter sequence): Lethal — absent kidneys, severe oligohydramnios, pulmonary hypoplasia, limb/facial compression deformities. Posterior urethral valves: Most common cause of lower urinary tract obstruction in males. US: bilateral hydronephrosis, distended bladder, "keyhole sign." May be candidate for fetal vesicoamniotic shunting if early and progressive.

Renal Anomalies — Additional Detail

Multicystic dysplastic kidney (MCDK): Non-functioning kidney with multiple non-communicating cysts of varying sizes (largest at periphery). The most common cystic renal disease in the fetus. Unilateral MCDK has excellent prognosis (contralateral kidney compensates). Bilateral MCDK is lethal (no functioning renal tissue). Must be distinguished from hydronephrosis (which has communicating dilated calyces centered on a dilated pelvis) and autosomal recessive polycystic kidney disease (ARPKD — bilateral enlarged echogenic kidneys with oligohydramnios).

Congenital diaphragmatic hernia (CDH): While classified as a thoracic anomaly, CDH is a critical fetal surgical consideration. Incidence: 1 in 2,500. Left-sided in 80-85%. US: herniated abdominal viscera (stomach, bowel, liver) in the thorax with mediastinal shift. The key prognostic factor is pulmonary hypoplasia, quantified by lung-to-head ratio (LHR) and observed/expected LHR. O/E LHR < 25% with liver herniation: severe (survival ~15-20% with standard postnatal care). Fetoscopic endoluminal tracheal occlusion (FETO) via balloon placement may improve lung growth in severe cases — the TOTAL trial showed benefit in severe left CDH. Delivery should be at a center with ECMO capability.

Skeletal Dysplasias

Skeletal dysplasias are a heterogeneous group of > 450 conditions. Key US findings: shortened long bones (rhizomelic — proximal, mesomelic — middle, or acromelic — distal), fractures, bowing, absent mineralization, and abnormal thoracic dimensions. The femur length/abdominal circumference (FL/AC) ratio and femur length/biparietal diameter (FL/BPD) ratio help identify short-limbed conditions. A narrow thorax with a thoracic circumference < 5th percentile for GA predicts lethal pulmonary hypoplasia.

Thanatophoric dysplasia (most common lethal skeletal dysplasia): severe micromelia, narrow thorax, cloverleaf skull (type II), platyspondyly, FGFR3 mutation. Lethal due to pulmonary hypoplasia. Achondroplasia (most common non-lethal skeletal dysplasia): rhizomelic shortening, frontal bossing, trident hands, FGFR3 mutation (different from thanatophoric). Often not detectable until late second/third trimester because shortening becomes more pronounced as growth progresses. Osteogenesis imperfecta type II (lethal): multiple fractures in utero, decreased mineralization, crumpled/accordion-like long bones, blue sclerae. Type I and IV are non-lethal with variable severity.

15 Fetal Chromosomal & Genetic Conditions

Trisomy 21 (Down Syndrome)

Most common viable autosomal trisomy (1 in 700 live births). Risk increases with maternal age (1 in 1,250 at age 25; 1 in 350 at age 35; 1 in 100 at age 40). US markers: increased NT, absent or hypoplastic nasal bone, shortened humerus and femur, echogenic bowel, echogenic intracardiac focus, mild ventriculomegaly, mild pyelectasis, sandal gap, clinodactyly. Cardiac defects in 40-50% (AVSD most characteristic, also VSD, ASD, tetralogy of Fallot). Duodenal atresia (double bubble sign).

Trisomy 18 (Edwards Syndrome)

Incidence: 1 in 5,000-8,000. Median survival: 5-15 days. US findings: IUGR, clenched hands with overlapping fingers (index over third, fifth over fourth), strawberry-shaped skull, choroid plexus cysts, omphalocele, cardiac defects (VSD, ASD, DORV), single umbilical artery, rocker-bottom feet. Screening: all serum markers low on quad screen; cfDNA detection rate 97-99%.

Trisomy 13 (Patau Syndrome)

Incidence: 1 in 10,000-16,000. Median survival: 7-10 days. US findings: holoprosencephaly, midline facial defects (cleft lip/palate, cyclopia, proboscis), polydactyly, cardiac defects (80%), echogenic kidneys, omphalocele. Screening: cfDNA detection rate 92-99%.

Turner Syndrome (45,X)

Incidence: 1 in 2,500 female births (but ~99% of 45,X conceptions end in miscarriage). Prenatal US findings: cystic hygroma (large, septated, posterior cervical), hydrops, coarctation of the aorta, horseshoe kidney, short femur. Postnatal features: short stature, webbed neck, widely spaced nipples, ovarian failure, cardiac defects (bicuspid aortic valve 30%, coarctation 10%). cfDNA detection rate 90-95%.

Microarray Findings & Single Gene Disorders

Chromosomal microarray detects clinically significant copy number variants (CNVs) in ~6% of fetuses with structural anomalies and ~1.7% of structurally normal fetuses beyond what karyotype identifies. Common pathogenic CNVs: 22q11.2 deletion (DiGeorge — conotruncal cardiac defects, thymic hypoplasia, cleft palate), 1p36 deletion, 15q11-q13 deletion (Prader-Willi/Angelman), 7q11.23 deletion (Williams syndrome), 5p deletion (Cri-du-chat). For fetuses with anomalies and normal microarray, exome sequencing has a diagnostic yield of ~10-30%, particularly for skeletal dysplasias, multiple congenital anomalies, and hydrops of unknown etiology.

Consanguinity

Consanguineous unions (first cousins: coefficient of inbreeding = 1/16) increase the risk of autosomal recessive conditions by increasing the likelihood of homozygosity for deleterious alleles. Genetic counseling should include: expanded carrier screening, detailed anatomy scan, consideration of exome/genome sequencing if anomalies are detected. The absolute risk of birth defects in first-cousin unions is approximately 4-7% (vs 2-3% in the general population).

Carrier Screening

ACOG recommendations: All patients should be offered carrier screening. Options include: ethnicity-based screening (CF for Caucasians, sickle cell for African Americans, Tay-Sachs for Ashkenazi Jewish patients, thalassemia for Mediterranean/Southeast Asian descent) or expanded carrier screening (ECS) panels — which simultaneously screen for > 100-300 autosomal recessive conditions regardless of ethnicity. ECS has largely replaced ethnicity-based screening in many practices. If both partners are carriers for the same autosomal recessive condition, there is a 25% chance of an affected offspring per pregnancy. Genetic counseling, prenatal diagnosis (CVS/amniocentesis), and preimplantation genetic testing (PGT-M with IVF) should be offered.

Cystic fibrosis: Most common lethal autosomal recessive condition in Caucasians. Carrier frequency: 1 in 25 (Caucasian). > 2,000 known CFTR mutations; ΔF508 most common (~70% of CF alleles). If one partner is a carrier and the other tests negative, there is a residual carrier risk that depends on ethnicity and the number of mutations screened (for Caucasians, ~1 in 240 with a negative expanded panel).

Spinal muscular atrophy (SMA): Carrier frequency: ~1 in 40-60 across ethnicities. Caused by homozygous deletion of SMN1 gene. ~2% of carriers have two copies on one chromosome (duplication, making detection difficult). Universal carrier screening is now recommended (ACOG 2017). Treatment of affected neonates with nusinersen or onasemnogene has dramatically improved outcomes, making early detection particularly important.

16 Multiple Gestations

Chorionicity Determination

Determining chorionicity is the single most important step in managing twin pregnancies, ideally in the first trimester. Dichorionic-diamniotic (DCDA): "Lambda sign" (twin peak sign) — triangular projection of placental tissue extending between the membranes at the placental surface. Two separate placentas or thick dividing membrane. Monochorionic-diamniotic (MCDA): "T sign" — thin membrane inserts directly into the placental surface without an intervening wedge of tissue. Shared placenta. Monochorionic-monoamniotic (MCMA): No dividing membrane. All monochorionic twins share vascular anastomoses in the placenta, which are the basis for TTTS and other monochorionic-specific complications.

Monochorionic Twin Complications

Twin anemia-polycythemia sequence (TAPS): Chronic, slow transfusion through tiny (< 1 mm) anastomoses causing large inter-twin hemoglobin difference (> 8 g/dL at birth) without amniotic fluid discordance. Diagnosed prenatally by MCA-PSV discordance (donor > 1.5 MoM, recipient < 1.0 MoM). Can occur spontaneously (3-5% of MCDA) or post-laser (13-16%).

Twin reversed arterial perfusion (TRAP) sequence: One twin (the "pump twin") perfuses a nonviable acardiac twin through reversed arterial flow. The acardiac mass acts as a parasitic shunt. Risk to the pump twin: high-output cardiac failure and hydrops. Treatment: radiofrequency ablation or bipolar coagulation of the cord to the acardiac twin when the mass approaches the size of the pump twin or signs of cardiac failure develop.

Selective FGR in monochorionic twins: Growth discordance > 25% (larger twin as reference). Classified by UA Doppler in the smaller twin: Type 1 (positive end-diastolic flow — favorable), Type 2 (persistent AEDF/REDF — unfavorable), Type 3 (intermittent AEDF/REDF — unpredictable). Management ranges from surveillance (Type 1) to laser/selective reduction/delivery (Type 2/3 depending on gestational age).

Dichorionic Twin Management

DCDA twins have lower risks than MCDA twins but still have increased rates of preterm birth (50% deliver < 37 weeks), preeclampsia (13% vs 5% in singletons), FGR (especially discordant growth), and gestational diabetes compared to singletons. Surveillance: growth US every 4 weeks. Growth discordance > 20% (calculated as [larger EFW - smaller EFW] / larger EFW × 100) warrants increased surveillance and evaluation for FGR in the smaller twin.

Mode of delivery: Vaginal delivery is appropriate for DCDA and MCDA twins if the presenting twin (Twin A) is vertex, regardless of Twin B presentation, at centers experienced in breech extraction of the second twin. Cesarean is recommended for MCMA twins (cord entanglement risk during labor) and when Twin A is non-vertex.

17 Hydrops Fetalis

Definition & Classification

Hydrops fetalis is the pathologic accumulation of fluid in ≥ 2 fetal body compartments (ascites, pleural effusion, pericardial effusion, skin edema > 5 mm). Immune hydrops (10-15% of cases): caused by maternal red cell alloimmunization (anti-D, anti-Kell, anti-c) leading to fetal hemolytic anemia. Non-immune hydrops (85-90%): caused by a wide variety of etiologies — the differential is extensive.

Causes of Non-Immune Hydrops

Workup

Systematic evaluation: Maternal — blood type and antibody screen (Coombs), Kleihauer-Betke (fetomaternal hemorrhage), TORCH serologies (parvovirus B19 IgM/IgG, CMV, toxoplasmosis, syphilis), hemoglobin electrophoresis (alpha-thalassemia carrier status), and metabolic screening. Fetal — detailed anatomy US and fetal echocardiography, MCA-PSV Doppler (fetal anemia), karyotype/microarray (± exome), and if indicated, cordocentesis (CBC, reticulocyte count, direct Coombs, viral PCR). MRI may be helpful for thoracic and CNS anomalies.

Management

Directed at the underlying cause when possible:

Prognosis depends heavily on etiology — chromosomal causes and severe structural defects have a poor prognosis (mortality > 90%). Treatable causes (anemia, arrhythmia) have much better outcomes. Idiopathic hydrops has an overall survival of ~50-60%. The gestational age at presentation also matters: hydrops before 20 weeks carries worse prognosis than later onset. Overall perinatal mortality for hydrops is 50-90% depending on the cause and gestational age at diagnosis.

18 Fetal Demise

Definition & Evaluation

Intrauterine fetal demise (IUFD) is defined as fetal death at ≥ 20 weeks gestation (or birth weight ≥ 350 g if gestational age is unknown). Incidence: ~6 per 1,000 births. Diagnosis: absent fetal cardiac activity on ultrasound. Common causes: placental insufficiency (abruption, FGR, preeclampsia), umbilical cord abnormalities, fetal anomalies/aneuploidy, infection, maternal medical disease, and unexplained (25-60%).

Management of IUFD

Delivery is recommended after diagnosis, though timing is individualized (most women prefer prompt delivery). Methods: induction of labor is preferred (vaginal delivery is appropriate at any gestational age). Cervical ripening with misoprostol: 200-400 μg vaginally q4-6h (< 28 weeks — higher doses may be used); 25-50 μg vaginally q4h (≥ 28 weeks, lower doses if prior uterine scar). Mifepristone 200 mg followed by misoprostol increases efficacy for second-trimester fetal demise. Mechanical dilation (balloon catheter) is an alternative. DIC may develop if IUFD is retained for > 3-4 weeks (consumptive coagulopathy from tissue thromboplastin release) — check fibrinogen, PT/INR, platelet count weekly if expectant management is chosen.

Recurrence Counseling

Recurrence risk of stillbirth in a subsequent pregnancy is approximately 2-10× the baseline risk (depending on cause). Modifiable risk factors should be addressed (optimize diabetes control, treat hypertension, aspirin for preeclampsia prevention, smoking cessation, weight management). Subsequent pregnancy management: early and serial growth ultrasounds (starting at 24-28 weeks, every 3-4 weeks), antepartum testing beginning at 32 weeks (or 1-2 weeks before the gestational age of the prior loss), low-dose aspirin if indicated, and delivery at 37-39 weeks (balancing prematurity risk against stillbirth risk). Psychosocial support is essential — subsequent pregnancies after stillbirth are associated with significant maternal anxiety, PTSD, and depression.

19 Preterm Birth & Cervical Insufficiency

Preterm Birth — Epidemiology & Risk Factors

Preterm birth (< 37 weeks) complicates ~10% of pregnancies and is the leading cause of neonatal morbidity and mortality. Risk factors: prior spontaneous preterm birth (strongest predictor — recurrence risk 15-50%), short cervical length, multiple gestation, uterine anomalies, prior cervical surgery (LEEP, cone biopsy), infection/inflammation, African American race, low BMI, tobacco use, short interpregnancy interval.

Cervical Length Screening

Universal transvaginal cervical length screening at 18-24 weeks is recommended by many professional organizations. Short cervix (< 25 mm) in a singleton without prior PTB: vaginal progesterone (200 mg suppository or 90 mg gel nightly until 36+6 weeks). Short cervix in a patient with prior PTB: ultrasound-indicated cerclage (if < 24 weeks) and progesterone.

Cerclage Types

Progesterone for Preterm Birth Prevention

Vaginal progesterone (200 mg suppository or 90 mg gel nightly): Indicated for short cervix (< 25 mm) at 18-24 weeks in singleton pregnancies regardless of prior PTB history. Reduces preterm birth by ~40% (Fonseca, Hassan, OPPTIMUM trials). 17-alpha hydroxyprogesterone caproate (17-OHPC, Makena): Previously given IM weekly from 16-36 weeks for prior spontaneous PTB. The PROLONG trial (2019) failed to confirm benefit, leading to FDA withdrawal of accelerated approval. Current practice is evolving — vaginal progesterone is increasingly preferred.

Periviable Counseling

Periviable birth (20-25+6 weeks) requires multidisciplinary counseling (MFM, neonatology, social work). Survival and intact survival by gestational age (approximate, varies by center): 22 weeks: 10-30% survival (significant morbidity); 23 weeks: 30-50%; 24 weeks: 50-70%; 25 weeks: 70-80%. Key considerations: antenatal corticosteroids (typically offered from 23-24 weeks, though some centers offer at 22 weeks), mode of delivery (cesarean for fetal indication at periviable GA is controversial), comfort care vs active resuscitation. Family wishes are paramount.

20 Preterm Premature Rupture of Membranes

Definition & Epidemiology

PPROM occurs in ~3% of pregnancies and accounts for approximately 30-40% of all preterm births. It is distinct from preterm labor (which presents with contractions and cervical change with intact membranes). Risk factors: prior PPROM (recurrence 13-32%), genital tract infection (BV, GBS, Chlamydia), short cervical length, smoking, polyhydramnios, multiple gestation, prior cervical surgery, amniocentesis, and cerclage.

Diagnosis

PPROM is rupture of membranes before 37 weeks and before the onset of labor. Diagnosis is confirmed by the classic triad: pooling of amniotic fluid in the posterior vaginal vault on sterile speculum exam, positive nitrazine test (amniotic fluid is alkaline, pH 7.1-7.3, turns nitrazine paper blue — false positives with blood, semen, BV, cervical mucus), and ferning of dried vaginal fluid on microscopy (arborization pattern of amniotic fluid crystallized on a glass slide). Newer immunoassay tests include AmniSure (placental alpha-macroglobulin-1, PAMG-1 — sensitivity 98.9%, specificity 99.1%) and ROM Plus (IGFBP-1 + AFP). These are especially useful in equivocal presentations. Avoid digital cervical exams — use sterile speculum exam only (digital exams decrease latency and increase infection risk). Assess for cord prolapse, collect GBS culture, and obtain cervical length by ultrasound if indicated.

Management by Gestational Age

Latency Antibiotics

Antibiotic prophylaxis extends the latency period and reduces neonatal infection. The ORACLE I regimen: ampicillin 2 g IV q6h + erythromycin 250 mg IV q6h for 48 hours, followed by amoxicillin 250 mg PO q8h + erythromycin 250 mg PO q8h for 5 days (total 7-day course). Alternative: ampicillin + azithromycin 1 g PO × 1 (increasingly used, simpler). Avoid amoxicillin-clavulanate (augmentin) — associated with increased risk of necrotizing enterocolitis in the neonate (ORACLE I trial finding).

GBS Prophylaxis in PPROM

If GBS status is positive or unknown: administer intrapartum GBS prophylaxis (penicillin G). If GBS culture is negative within the past 5 weeks and no other indication exists, GBS prophylaxis may be withheld. Re-culture at presentation with PPROM if status is unknown and results are pending.

21 Placenta Accreta Spectrum

Classification

Placenta accreta spectrum (PAS) describes abnormally adherent or invasive placentation resulting from defective decidua basalis. Risk increases dramatically with the number of prior cesarean deliveries, particularly with concurrent placenta previa.

Risk factors: Prior cesarean delivery (strongest risk factor), placenta previa, prior uterine surgery (myomectomy, D&C), advanced maternal age, multiparity, Asherman syndrome, IVF. Risk of PAS with placenta previa: no prior CD — 3%; 1 prior CD — 11%; 2 prior CDs — 40%; 3 prior CDs — 61%; ≥ 4 prior CDs — 67%.

Diagnosis

Ultrasound findings: Loss of the retroplacental clear zone, irregular placental lacunae ("Swiss cheese" appearance — most predictive US finding), myometrial thinning, disruption of the bladder-uterine interface, bridging vessels crossing the uterine-bladder interface. Color Doppler: turbulent flow in lacunae, hypervascularity at the bladder interface. MRI is complementary — most useful for posterior placentas and to assess depth/extent of invasion (especially percreta involving the bladder or parametrium). Sensitivity of US: 77-97%; MRI adds value primarily in equivocal cases.

Management

Planned cesarean hysterectomy at 34-36 weeks (after antenatal corticosteroids) at a center of excellence with a multidisciplinary team (MFM, gynecologic oncology, anesthesia, urology, interventional radiology, blood bank). No attempt at manual placental removal (dramatically increases hemorrhage). Massive transfusion protocol should be activated proactively. Average blood loss: 3,000-5,000 mL. Conservative management (leaving the placenta in situ) is reserved for select cases with patient desire for future fertility — requires close follow-up and carries risk of delayed hemorrhage, infection, DIC, and sepsis.

22 Obstetric Hemorrhage

Antepartum Hemorrhage

Placental abruption: Premature separation of a normally implanted placenta from the uterine wall. Risk factors: chronic HTN (most important), prior abruption (recurrence 5-17%), cocaine use, trauma, PPROM, advanced maternal age, smoking. Presentation: vaginal bleeding (80%), abdominal/back pain, uterine tenderness, contractions, non-reassuring fetal heart tracing. Concealed hemorrhage (20%) can present with hemodynamic instability without visible bleeding. US sensitivity for abruption is only 25-50% (a negative US does NOT rule out abruption). Severe abruption can trigger DIC (release of tissue thromboplastin). Management: stabilize, transfuse, deliver. If mild and preterm (< 34 weeks): consider expectant management with close surveillance after steroids.

Placenta previa: Placenta covering or within 2 cm of the internal cervical os. Incidence: 0.3-0.5%. Risk factors: prior cesarean, prior previa, multiparity, multiple gestation, advanced maternal age, smoking, IVF. Presents with painless vaginal bleeding (typically second/third trimester). Management: pelvic rest, serial US (many low-lying placentas "migrate" as the lower uterine segment develops — previa diagnosed at 20 weeks resolves in 90% by term). Persistent previa: cesarean delivery at 36-37 weeks (after steroids if < 37 weeks). Emergent delivery for life-threatening hemorrhage regardless of GA.

Vasa previa: Fetal vessels crossing or within 2 cm of the internal os, unprotected by the umbilical cord or placental tissue. Types: Type 1 — velamentous cord insertion with vessels traversing the lower segment; Type 2 — vessels connecting between lobes of a succenturiate or bilobed placenta. Risk of fetal exsanguination with rupture of membranes (fetal mortality > 50% if undiagnosed). Prenatal diagnosis is life-saving — US with color Doppler identifies the vessels. Management: antenatal corticosteroids, inpatient admission at 30-34 weeks, and planned cesarean delivery at 34-37 weeks (before labor/ROM). Sinusoidal FHR pattern with ROM and vaginal bleeding = vasa previa rupture until proven otherwise.

Postpartum Hemorrhage & DIC in Pregnancy

Postpartum hemorrhage (PPH) is defined as blood loss ≥ 1,000 mL or bleeding with hemodynamic instability regardless of mode of delivery (2017 ACOG revision). Causes follow the "4 T's": Tone (uterine atony — 70-80% of PPH), Trauma (lacerations, uterine rupture), Tissue (retained placenta), Thrombin (coagulopathy). Management escalation: bimanual uterine massage, uterotonics (oxytocin, methylergonovine, carboprost, misoprostol), intrauterine tamponade (balloon), uterine compression sutures (B-Lynch), uterine artery embolization, and hysterectomy as last resort.

DIC in pregnancy: Causes include massive abruption, amniotic fluid embolism, HELLP, AFLP, sepsis, and retained dead fetus. Amniotic fluid embolism (AFE) is a rare (1 in 40,000) catastrophic event: sudden cardiovascular collapse + DIC + respiratory failure during labor/delivery or immediately postpartum. Mortality: 20-60%. Treatment is supportive (aggressive resuscitation, blood products, vasopressors, immediate delivery if antepartum). No specific therapy exists. Lab findings in DIC: low fibrinogen (most sensitive marker in pregnancy — normal pregnancy fibrinogen is 400-600 mg/dL; a level < 200 mg/dL is highly abnormal), elevated D-dimer, prolonged PT/aPTT, low platelets, schistocytes on smear.

23 Alloimmunization

Rh Alloimmunization

Rh(D) alloimmunization occurs when an Rh-negative mother produces anti-D antibodies after exposure to Rh-positive fetal red blood cells (via fetomaternal hemorrhage at delivery, trauma, procedures, or spontaneous events). Anti-D antibodies cross the placenta and cause fetal hemolytic anemia (hemolytic disease of the fetus and newborn — HDFN). Anti-D prophylaxis (RhoGAM): 300 μg anti-D immunoglobulin IM at 28 weeks and within 72 hours of delivery (if neonate is Rh-positive). Additional doses for sensitizing events (amniocentesis, CVS, external cephalic version, abdominal trauma, vaginal bleeding). Kleihauer-Betke test to quantify fetomaternal hemorrhage — additional doses for large hemorrhages (> 30 mL fetal blood requires additional vials).

Monitoring the Alloimmunized Pregnancy

If anti-D antibody titer is ≥ 1:16 (critical titer, varies by lab), initiate serial MCA peak systolic velocity (MCA-PSV) monitoring every 1-2 weeks. MCA-PSV > 1.5 MoM for gestational age indicates moderate-severe fetal anemia with a sensitivity of ~100% and false positive rate of ~12%. This has replaced serial amniocentesis for ΔOD450 (Liley curve) as the primary surveillance method. If MCA-PSV is elevated, proceed to cordocentesis for fetal hematocrit — if anemic, perform intrauterine transfusion.

Kell Alloimmunization

Anti-Kell antibodies are the second most common cause of severe HDFN. Unlike anti-D (which causes hemolysis), anti-Kell antibodies suppress fetal erythropoiesis directly, leading to reticulocytopenia and anemia without proportionate hyperbilirubinemia. The critical titer is lower than for anti-D (often ≥ 1:8). MCA-PSV monitoring is the same. Maternal anti-Kell titers correlate poorly with disease severity — paternal/fetal Kell genotyping is critical (90% of Caucasians are Kell-negative, so the fetus may be unaffected).

Intrauterine Transfusion (IUT)

Intravascular IUT via cordocentesis (needle into the umbilical vein at the cord insertion under US guidance). Target hematocrit: 40-50%. Transfuse type O, Rh-negative, Kell-negative, CMV-negative, irradiated, leukocyte-reduced packed red blood cells. Typically needed every 2-4 weeks (interval based on expected decline in fetal hematocrit — approximately 1%/day). Delivery is usually planned at 34-37 weeks depending on the severity and need for ongoing transfusions. Complications: bradycardia (most common), bleeding, PPROM, fetal death (1-3% per procedure).

24 Amniocentesis & Chorionic Villus Sampling

Amniocentesis — Technique & Indications

Timing: ≥ 15 weeks (early amniocentesis at < 15 weeks is associated with increased talipes equinovarus and is not recommended). Technique: Under continuous ultrasound guidance, a 20-22 gauge spinal needle is inserted transabdominally into a pocket of amniotic fluid, avoiding the placenta and fetus. Approximately 20-30 mL of fluid is aspirated (1 mL per week of gestation as a guideline). The first 1-2 mL may be discarded to reduce maternal cell contamination.

Indications: Diagnostic genetic testing (after positive screening test, advanced maternal age, abnormal US findings, known carrier status), fetal lung maturity assessment (lamellar body count, L/S ratio — rarely needed in modern practice), evaluation of fetal infection (CMV, toxoplasmosis PCR), assessment of fetal hemolytic disease (ΔOD450), and therapeutic amnio-reduction (polyhydramnios, TTTS).

Risks: Procedure-related pregnancy loss: ~1 in 900 (0.11%) — this is above and beyond the background loss rate at the gestational age of the procedure. Other complications: transient vaginal bleeding or amniotic fluid leakage (1-2%, usually self-limited), chorioamnionitis (< 0.1%), needle injury to fetus (extremely rare with continuous US guidance), and Rh sensitization (administer RhoGAM 300 μg IM to all Rh-negative, unsensitized women after the procedure). Patients should be counseled about rest for 24 hours after the procedure and to report fever, persistent fluid leakage, vaginal bleeding, or contractions.

Amniocentesis for fetal lung maturity (FLM): Historically used at 32-39 weeks to guide delivery timing, but with modern neonatal care and evidence-based delivery timing guidelines, FLM testing is now rarely indicated. The lamellar body count (≥ 50,000/μL = mature), lecithin-sphingomyelin (L/S) ratio (≥ 2.0 = mature), and phosphatidylglycerol (PG present = mature) are the traditional markers. ACOG recommends against FLM testing to guide delivery timing when a clear clinical indication for delivery exists.

Chorionic Villus Sampling — Technique & Indications

Timing: 10-13+6 weeks. Technique: Transcervical (catheter through cervix to placenta under US guidance — preferred when placenta is posterior/low) or transabdominal (needle through abdominal wall — preferred when placenta is anterior/fundal). Approximately 15-30 mg of chorionic villi are obtained.

Advantages over amniocentesis: Earlier results (first trimester), allows earlier decision-making, DNA analysis does not require cell culture (direct preparation results in 24-48 hours for FISH). Limitations: 1-2% rate of confined placental mosaicism (CPM — abnormal cell line present in placenta but not fetus; if mosaicism is found, amniocentesis at ≥ 15 weeks is recommended to clarify). Cannot assess for neural tube defects (no AFP). Procedure-related loss: ~1 in 455 (0.22%). Do NOT perform before 10 weeks — risk of limb reduction defects.

25 Fetal Procedures & Surgery

Intrauterine Transfusion (IUT)

Detailed in Section 23 (Alloimmunization). Key points: intravascular approach (umbilical vein at cord insertion) under US guidance; peritoneal approach as backup if intravascular access is not possible. Type O, Rh-negative, Kell-negative, CMV-negative, irradiated, leukocyte-reduced pRBCs. Fetal paralysis (pancuronium) is often administered to facilitate the procedure.

Fetal Shunt Placement

Thoracoamniotic shunt: Indicated for large, isolated pleural effusions (chylothorax) causing mediastinal shift, hydrops, or pulmonary hypoplasia. A pigtail catheter is placed percutaneously under US guidance from the fetal pleural space into the amniotic cavity. Success rate: ~70% resolution of hydrops if etiology is primary chylothorax (vs secondary to other causes).

Vesicoamniotic shunt: Indicated for lower urinary tract obstruction (LUTO — typically posterior urethral valves) with progressive bilateral hydronephrosis, megacystis, and oligohydramnios threatening pulmonary development. A pigtail catheter is placed from the fetal bladder into the amniotic fluid. Patient selection is critical — vesicocentesis with fetal urine electrolytes and β2-microglobulin can help predict residual renal function (favorable: Na < 100, Cl < 90, osmolality < 200, β2-microglobulin < 6). The PLUTO trial was underpowered but suggested possible benefit.

Fetoscopic Laser Photocoagulation for TTTS

The Solomon technique is the current standard: after identifying and coagulating all visible arteriovenous anastomoses on the placental surface, a continuous line of coagulation is drawn along the vascular equator connecting all the ablated vessels (creating a complete "dichorionization"). This reduces the rate of TAPS and twin anemia recurrence compared to selective coagulation alone. Performed under fetoscopic visualization with a diode or Nd:YAG laser. Overall survival: ~70-80% at least one twin, ~50-60% both twins. Major complication: PPROM (30%), preterm delivery.

EXIT Procedure (Ex Utero Intrapartum Treatment)

The EXIT procedure maintains uteroplacental circulation during a partially delivered fetus to secure the airway before cord clamping. Indications: giant cervical teratoma, congenital high airway obstruction syndrome (CHAOS), large cervical lymphatic malformation, or any condition expected to cause complete airway obstruction at birth. The fetus is partially delivered via hysterotomy, the airway is secured (direct laryngoscopy, bronchoscopy, or tracheostomy) while placental gas exchange continues, and then the cord is clamped. Requires deep maternal general anesthesia (high-dose volatile agents for uterine relaxation).

Fetal Endoscopic Tracheal Occlusion (FETO) for CDH

For severe congenital diaphragmatic hernia (observed/expected LHR < 25% with liver herniation), FETO involves fetoscopic placement of a balloon in the fetal trachea at 27-29 weeks to occlude outflow, trapping lung fluid and promoting pulmonary growth. The balloon is removed at 34 weeks (or at the time of delivery) to allow resumption of fetal breathing movements. The TOTAL trial (NEJM 2021) demonstrated improved survival in severe left CDH (40% vs 15%) but increased the rate of preterm delivery. FETO is offered at specialized fetal therapy centers and remains a consideration for the most severe cases where expected survival with postnatal management alone is < 20%.

Fetal Surgery — Myelomeningocele Repair

The MOMS trial (Management of Myelomeningocele Study, 2011, NEJM) was the landmark RCT comparing prenatal repair (open hysterotomy at 19-25+6 weeks) vs standard postnatal repair. Results: prenatal repair reduced the need for VP shunt (40% vs 82%), improved motor function (42% vs 21% walking independently at 30 months), and reversed hindbrain herniation (Chiari II). Risks of prenatal repair: preterm delivery (79% before 37 weeks, mean 34 weeks), uterine dehiscence/thinning (35%), oligohydramnios, and maternal morbidity from hysterotomy. All subsequent pregnancies require cesarean delivery. Fetoscopic repair is under investigation and may reduce maternal morbidity.

26 Cervical Ripening & Induction in High-Risk Pregnancy

Cervical Ripening Methods

Prostaglandins: Misoprostol (PGE1 analog) — 25 μg intravaginally q3-6h (most effective ripening agent; contraindicated with prior uterine scar due to uterine rupture risk ~1-5%). Dinoprostone (PGE2) — 10 mg vaginal insert (Cervidil, retrievable) or 0.5 mg intracervical gel (Prepidil). Mechanical methods: Foley catheter (single or double balloon, inflated to 60-80 mL, placed transcervically through the internal os) — safe in prior cesarean (does not increase uterine rupture risk). Mechanical + pharmacologic combination may reduce time to delivery.

Oxytocin Induction

Oxytocin is initiated after cervical ripening or with a favorable cervix (Bishop score ≥ 6). Low-dose protocols: start 1-2 mU/min, increase by 1-2 mU/min every 30-40 minutes (maximum typically 20-40 mU/min). High-dose protocols: start 4-6 mU/min, increase by 4-6 mU/min every 15-30 minutes. Target: adequate contractions (3 in 10 minutes lasting 60-90 seconds). Tachysystole (> 5 contractions in 10 minutes averaged over 30 minutes) requires dose reduction or discontinuation, repositioning, and consideration of tocolysis (terbutaline 0.25 mg SC) if accompanied by FHR abnormalities.

Special considerations in high-risk induction: Prior cesarean with low transverse incision: cervical ripening with Foley catheter is acceptable (mechanical methods do not increase uterine rupture risk); misoprostol is contraindicated (uterine rupture risk ~1-5%); oxytocin augmentation is acceptable with close monitoring (rupture risk ~0.5-0.8% with TOLAC/VBAC). Fetal growth restriction: higher sensitivity to oxytocin; start at lowest dose. Preeclampsia with severe features: magnesium sulfate should be running concurrently; monitor fluid balance closely to avoid pulmonary edema (restrict total IV fluids to 80-100 mL/hour).

Delivery Timing by Condition

27 Antenatal Corticosteroids & Magnesium Neuroprotection

Antenatal Corticosteroids

Indication: Women at risk of preterm delivery within 7 days between 24+0 and 33+6 weeks of gestation (some centers extend to 23 weeks). Regimen: Betamethasone 12 mg IM q24h × 2 doses (preferred — shown in the 1994 NIH Consensus and Crowley meta-analysis to reduce RDS, IVH, NEC, and neonatal death), OR dexamethasone 6 mg IM q12h × 4 doses.

Rescue course: A single rescue course of betamethasone may be administered if ≥ 14 days have elapsed since the first course, the patient remains at risk of delivery within 7 days, and GA < 34 weeks. Repeated courses beyond the rescue course are not recommended (associated with decreased birth weight and head circumference).

Late Preterm Steroids (ALPS Trial)

The ALPS trial (Antenatal Late Preterm Steroids, 2016, NEJM) demonstrated that betamethasone administered at 34+0-36+5 weeks to women at high risk of preterm delivery reduced neonatal respiratory morbidity (RDS, TTN, need for surfactant or respiratory support: 11.6% vs 14.4%, NNT ~36). However, it also increased neonatal hypoglycemia (24% vs 15%). Current practice: consider late preterm steroids for patients at high risk of delivery within 7 days at 34+0-36+5 weeks, particularly if no prior corticosteroid course. The A-PLUS trial is evaluating whether restricting late preterm steroids to those at highest risk improves the risk-benefit profile.

Magnesium Sulfate for Fetal Neuroprotection

Indication: Imminent preterm delivery at < 32 weeks of gestation. Mechanism: Reduces risk of cerebral palsy by ~30-40% (NNT ~63 to prevent one case of CP). Evidence from three major trials: MagNET, ACTOMgSO4, BEAM. Dose: 4-6 g IV loading over 20-30 minutes, followed by 1-2 g/hour maintenance until delivery (or for up to 12 hours if delivery does not occur). The same dosing is used for neuroprotection as for seizure prophylaxis, but the indications are different (neuroprotection is for fetal benefit at < 32 weeks; seizure prophylaxis is for maternal benefit in preeclampsia at any GA).

28 Classification Systems

ACOG Preeclampsia Criteria

See Section 5 for complete diagnostic criteria. Key threshold: BP ≥ 140/90 + proteinuria (≥ 300 mg/24h or P:C ≥ 0.3) or BP ≥ 140/90 + any severe feature (without proteinuria). Severe features: SBP ≥ 160/DBP ≥ 110, platelets < 100K, creatinine > 1.1, liver transaminases ≥ 2× ULN, pulmonary edema, cerebral/visual symptoms.

Mississippi Classification of HELLP Syndrome

Class 1: Platelets ≤ 50,000 + LDH ≥ 600 + AST/ALT ≥ 70. Class 2: Platelets 50,001-100,000 + LDH ≥ 600 + AST/ALT ≥ 70. Class 3: Platelets 100,001-150,000 + LDH ≥ 600 + AST/ALT ≥ 40. Class 1 carries the highest risk of maternal morbidity (DIC, renal failure, hepatic rupture).

White Classification of Diabetes in Pregnancy

See Section 6 for complete table. A1/A2 = gestational; B through T = pregestational with increasing severity of vascular disease.

Modified WHO Cardiac Risk Classification

See Section 7 for complete table. mWHO I: no increased risk. mWHO II: small increase. mWHO II-III: moderate. mWHO III: significant. mWHO IV: pregnancy contraindicated.

Quintero Staging of TTTS

See Section 16 for complete staging. Stage I: polyhydramnios/oligohydramnios only. Stage II: absent donor bladder. Stage III: abnormal Doppler. Stage IV: hydrops. Stage V: demise.

Biophysical Profile Scoring

See Section 4. Five components, each scored 0 or 2 (total 0-10): NST, fetal breathing, fetal movement, fetal tone, amniotic fluid. Score ≥ 8 = reassuring; ≤ 4 = abnormal.

Doppler Staging for Fetal Growth Restriction

See Section 13 for complete staging. Stage I: elevated UA PI. Stage II: AEDF. Stage III: REDF or elevated DV PI. Stage IV: reversed DV a-wave or spontaneous decelerations.

Bishop Score

Bishop score ≥ 6: favorable cervix — proceed directly to oxytocin. Bishop score < 6: unfavorable — cervical ripening required before induction. A modified Bishop score (omitting effacement) is sometimes used with similar predictive value. The Bishop score's primary utility is predicting the likelihood of successful induction and the duration of labor — it does not determine whether induction is indicated.

Swansea Criteria for Acute Fatty Liver of Pregnancy

AFLP is diagnosed when ≥ 6 of the following are present (in the absence of another explanation): vomiting, abdominal pain, polydipsia/polyuria, encephalopathy, elevated bilirubin (> 0.8 mg/dL), hypoglycemia (< 72 mg/dL), elevated uric acid (> 5.7 mg/dL), leukocytosis (> 11,000), ascites or bright liver on US, elevated transaminases (AST/ALT > 42), elevated ammonia (> 47 μmol/L), renal impairment (creatinine > 1.7 mg/dL), coagulopathy (PT > 14 s or aPTT > 34 s), and microvesicular steatosis on liver biopsy. Key distinguishing features from HELLP: hypoglycemia (most specific), coagulopathy (low fibrinogen, prolonged PT — more prominent than in HELLP), and encephalopathy. Treatment is delivery. Screen neonate for LCHAD deficiency (long-chain 3-hydroxyacyl-CoA dehydrogenase — recurrence risk 25% if present, as AFLP is associated with fetal LCHAD deficiency through accumulation of toxic fatty acid intermediates).

29 Medications Master Table

Antihypertensives

Magnesium Sulfate

Tocolytics

Corticosteroids

Anticoagulants

RhoGAM (Anti-D Immunoglobulin)

30 Imaging & Diagnostics Reference

Ultrasound Parameters by Gestational Age

Doppler Indices — Normal Values

MRI in Pregnancy

Fetal MRI (without gadolinium) is safe at any gestational age (no evidence of teratogenicity at 1.5 or 3.0 Tesla) and is most useful for:

Gadolinium is contraindicated in pregnancy — it crosses the placenta, is excreted into amniotic fluid by the fetal kidneys, and has been associated with increased risk of rheumatologic/inflammatory conditions and stillbirth in one large retrospective cohort study (Ray et al., JAMA 2016). Non-contrast MRI is the standard for fetal imaging.

Genetic Testing Comparison

31 Abbreviations Master List

32 Landmark Trials