FCPS Paediatrics TOACS · Interactive Station FETAL THERAPY

✅ Candidate's answer:
• Rh alloimmunization: Development of maternal IgG antibodies against Rh(D) antigen on fetal red blood cells. Occurs when an Rh-negative mother is exposed to Rh-positive fetal blood (usually at delivery, but also during pregnancy, abortion, invasive procedures, or trauma).
• This mother is sensitized (positive indirect Coombs). She had a previous hydropic infant – indicates severe disease.
• High risk for this pregnancy because:
- She has already developed a high anti-D antibody titer (1:256).
- The severity of HDFN tends to worsen with successive pregnancies (anamnestic response).
- The fetus is likely Rh-positive (father is Rh-positive).
- Risk of hydrops is very high without intervention.

✅ Candidate's answer:
• MCA-PSV is the non-invasive gold standard for detecting fetal anemia. It measures blood flow velocity in the fetal middle cerebral artery.
• Physiology: In fetal anemia, blood viscosity decreases → increased cardiac output and cerebral blood flow → increased MCA-PSV.
• Interpretation: MCA-PSV ≥1.5 multiples of the median (MoM) for gestational age indicates moderate-to-severe fetal anemia (sensitivity ~75-85% for moderate anemia, >95% for severe anemia).
• Timing: Start at 16-18 weeks (earlier if previous hydrops).
• Frequency: Weekly if antibodies are present and titers are high (≥1:16-32). More frequent if MCA-PSV is rising or close to threshold.
• If MCA-PSV is normal (<1.5 MoM), fetal anemia is unlikely; can continue monitoring.
• If MCA-PSV ≥1.5 MoM → proceed to PUBS/cordocentesis for confirmation.

✅ Candidate's answer:
• Next step: PUBS (percutaneous umbilical blood sampling) or cordocentesis – ultrasound-guided needle puncture of the umbilical vein at the placental cord insertion or free loop.
• Purpose: Measure fetal hemoglobin/hematocrit, blood type, Coombs test, and reticulocyte count.
• Findings: If fetal hematocrit is <30% (or hemoglobin <10 g/dL) at 20 weeks, the fetus has moderate-severe anemia.
• Immediate intervention: Intrauterine transfusion (IUT) can be performed through the same needle access.
• Risks of PUBS: Fetal bradycardia, cord hematoma, bleeding, chorioamnionitis, preterm rupture of membranes, fetal loss (~1-2% per procedure).
• Performed by an experienced operator in a tertiary fetal medicine center.

✅ Candidate's answer:
• IUT: Direct transfusion of packed red blood cells into the fetal umbilical vein (intravascular IUT) – the preferred method. (Intraperitoneal IUT is rarely used now).
• Blood product: Rh-negative, CMV-negative, irradiated, leukoreduced packed RBCs (hemoglobin ~15-18 g/dL, hematocrit 70-80%). Cross-matched against maternal serum.
• Volume calculation: Estimated fetal weight (kg) × (target increment in hematocrit %) × 2-3 mL/% (varies by institution). Typically 20-50 mL per transfusion depending on gestational age.
• Target post-transfusion hematocrit: 40-50% (normal for gestational age).
• Frequency: Repeat IUTs every 2-4 weeks (because transfused RBCs have a half-life of ~30 days vs fetal RBCs 60 days).
• Serial transfusions continue until delivery (usually at 32-36 weeks).
• Fetal monitoring during IUT: Continuous ultrasound, fetal heart rate monitoring. Risks: bradycardia, cord accident, chorioamnionitis, preterm labor, fetal demise (~1-2% per procedure).

✅ Candidate's answer:
• Timing of delivery: Usually between 32-36 weeks (sometimes earlier if complications arise, later if well-controlled).
- After 32 weeks, the risks of prematurity outweigh the benefits of continued IUTs.
- If the fetus has no hydrops and stable hematocrit, delivery at 34-36 weeks.
- If hydropic, delivery may be earlier (32-34 weeks) with NICU preparedness.
• Mode of delivery: Cesarean section is often preferred because:
- The fetus is often not in vertex presentation.
- Risk of fetal distress during labor is high.
- Need for immediate neonatal resuscitation and exchange transfusion.
- However, vaginal delivery is not absolutely contraindicated if fetal presentation is favorable and the mother is stable.
• Delivery should occur at a tertiary center with: Neonatology, transfusion medicine, exchange transfusion capability, and pediatric cardiology (for hydrops).

✅ Candidate's answer:
• Immediate postnatal management:
1️⃣ Cord blood: Hemoglobin/hematocrit, bilirubin, blood type, direct Coombs test (DAT), reticulocyte count.
2️⃣ Phototherapy – may need intensive phototherapy from birth.
3️⃣ IVIG (0.5-1 g/kg) – reduces hemolysis and may prevent exchange transfusion.
4️⃣ Exchange transfusion – if bilirubin rises rapidly or reaches exchange threshold (lower than standard nomograms because IUT recipients have lower hemoglobin).
5️⃣ Top-up transfusions – may need in the first few weeks due to late anemia (from ongoing hemolysis and bone marrow suppression).
6️⃣ Erythropoietin (EPO) – may reduce need for later transfusions (controversial).
• Special considerations for IUT recipients:
- They have mixed blood (fetal + donor adult RBCs) → DAT may be weakly positive or negative.
- Bilirubin levels may peak earlier (day 2-3) and be higher.
- They often have thrombocytopenia and neutropenia (due to bone marrow suppression).
- They are at risk for late anemia (4-6 weeks of age) – monitor hemoglobin weekly.

✅ Candidate's answer:
• Hydrops fetalis: Pathological accumulation of fluid in ≥2 fetal compartments (ascites, pleural effusion, pericardial effusion, skin edema >5 mm) ± placentomegaly (>4-6 cm), polyhydramnios.
• Immune hydrops (Rh disease): Caused by severe fetal anemia.
- Anemia → high-output cardiac failure (due to decreased viscosity, increased cardiac output).
- Hypoxia → increased capillary permeability, impaired hepatic protein synthesis (hypoalbuminemia).
- Albumin loss → decreased oncotic pressure → fluid shifts into third spaces (ascites, pleural effusions, skin edema).
- Placentomegaly → fluid overload in mother (mirror syndrome).
• Without IUT, hydrops carries >80% mortality.
• This mother’s previous infant had hydrops – hence severe disease.

✅ Candidate's answer:
• Nonimmune hydrops (NIH): Hydrops in the absence of red cell alloimmunization (negative indirect Coombs in mother, negative DAT in infant). Accounts for >85% of hydrops cases.
• Most common causes (broad differential):
1️⃣ Cardiovascular: Structural heart disease, tachyarrhythmias (SVT, atrial flutter), cardiomyopathy.
2️⃣ Chromosomal/genetic: Turner syndrome (45,X), trisomies (21,18,13), Noonan syndrome.
3️⃣ Infectious: Parvovirus B19 (most common infectious cause), CMV, syphilis, toxoplasmosis, HSV.
4️⃣ Hematologic: Alpha-thalassemia major (Hb Bart's), other hemolytic anemias.
5️⃣ Pulmonary/thoracic: Congenital diaphragmatic hernia, cystic lung lesions, chylothorax.
6️⃣ Lymphatic: Lymphangiectasia, Noonan syndrome.
7️⃣ Metabolic/storage disorders.
8️⃣ Twin-twin transfusion syndrome (TTTS).
• Differentiation: Maternal indirect Coombs test and fetal/neonatal DAT. If positive → immune hydrops. If negative → NIH.
• This case is immune hydrops (positive indirect Coombs).

✅ Candidate's answer:
• IVIG (1 g/kg/week) may be used in severe, refractory Rh alloimmunization (e.g., previous hydrops, very early onset anemia, failed IUTs, or in pregnancies where IUT is technically difficult).
• Mechanism: IVIG may downregulate maternal anti-D antibody production or block Fc receptors on placental trophoblasts, reducing transplacental passage of antibodies.
• Evidence: Limited but some case series suggest IVIG delays the need for IUT and reduces the severity of fetal anemia.
• Used as an adjunct (not a replacement) to IUT.
• Plasmapheresis (maternal plasma exchange) is an even more aggressive therapy, rarely used (severe, very early disease).
• This mother (previous hydrops) may be a candidate for IVIG in addition to IUT.

✅ Candidate's answer:
• Rh immune globulin (RhIg, RhoGAM) – 300 mcg IM: Passive antibody that binds to fetal Rh-positive RBCs in maternal circulation, preventing maternal immune response.
• Indications for RhIg (standard protocol):
1️⃣ At 28 weeks of gestation (routine antenatal prophylaxis).
2️⃣ Within 72 hours of delivery of an Rh-positive infant.
3️⃣ After miscarriage, abortion, ectopic pregnancy, or threatened miscarriage (≥12 weeks: 300 mcg; <12 weeks: 50 mcg).
4️⃣ After invasive procedures (amniocentesis, chorionic villus sampling, PUBS).
5️⃣ After abdominal trauma or external cephalic version.
• This mother did not receive RhIg after her first Rh-positive infant, or received it late/missed a dose. She should have received a dose at 28 weeks and after delivery of her first infant.
• Once sensitized (positive indirect Coombs), RhIg is NO longer effective for that pregnancy. This pregnancy is already affected – management is IUT, not prevention.

✅ Candidate's answer:
• Historically, amniocentesis for ΔOD450 (change in optical density at 450 nm) using the Liley curve was used to predict fetal anemia. This is now obsolete and has been replaced by non-invasive MCA-PSV Doppler.
• Why obsolete?
- Invasive (risk of miscarriage, infection, preterm rupture).
- Less accurate for mild-to-moderate anemia.
- Cannot be used to guide IUT in real-time.
- Does not provide direct assessment of fetal hematocrit.
- MCA-PSV is more sensitive, safer, and can be repeated weekly.
• Current role: Amniocentesis may still be used for fetal lung maturity assessment prior to delivery (but rarely needed), or for genetic testing. Not for anemia surveillance.

✅ Candidate's answer:
• Survival with IUT: Overall survival is >90% for hydropic fetuses and >95% for non-hydropic fetuses.
• However, the earlier the disease (e.g., hydrops at 20 weeks), the lower the survival (<80% in some series).
• Neurodevelopmental impairment (NDI) after IUT:
- 5-15% risk of moderate-to-severe NDI (cerebral palsy, hearing loss, cognitive delay).
- Risk factors: Hydrops, early gestational age at first IUT, severe anemia, complications of IUT (bradycardia, acidosis).
- Surveillance: Cranial ultrasound, neurodevelopmental follow-up, hearing screens.
- This mother’s previous infant had mild sequelae – possible.
• Need for long-term follow-up for all survivors.

✅ Candidate's structured answer:
• “I understand you are very worried because your previous baby had hydrops. This pregnancy is at high risk for the same problem, but we have very effective treatments that were not available decades ago.”
• “First, we will monitor the baby using a special ultrasound called MCA-PSV Doppler – a painless test that measures blood flow in the baby’s brain. We will do this weekly starting at 16-18 weeks.”
• “If the MCA-PSV shows that the baby is becoming anemic, the next step is a procedure called cordocentesis or PUBS – a needle inserted into the umbilical cord to measure the baby’s blood count. If the baby is anemic, we will give an intrauterine transfusion (IUT) of Rh-negative blood through the same needle.”
• “IUTs can save the baby’s life. Most babies with severe anemia who receive IUTs survive (>90%). However, there are risks: the procedure carries a 1-2% risk of fetal loss, infection, or preterm labor. The benefits usually outweigh the risks.”
• “You will need to deliver at a specialized center with a NICU. After birth, the baby may need more transfusions, phototherapy, and possibly exchange transfusion.”
• “With close monitoring and treatment, the chance of this baby surviving without major disability is high. We will work with the fetal medicine team, neonatology, and you to give this baby the best possible chance. You are not alone.”

✅ Candidate's answer:
• Mirror syndrome (also called Ballantyne syndrome or triple edema): The mother mirrors the fetal hydrops, developing edema, hypertension, proteinuria, and pulmonary edema – resembling preeclampsia.
• Pathophysiology: Severe fetal hydrops (especially from Rh disease or parvovirus) → massive placentomegaly → activation of the renin-angiotensin system in the mother → maternal edema and hypertension.
• Occurs in ~20-30% of severe fetal hydrops cases.
• Management: The only definitive treatment is delivery of the fetus and placenta. IUTs may temporarily improve the condition. Maternal symptoms resolve after delivery.
• This mother is at risk for mirror syndrome if the fetus develops hydrops. She should be monitored for hypertension, edema, weight gain, and proteinuria.