Rh Isoimmunization in Pregnancy

SWARAJ HOSPITAL & RESEARCH INSTITUTE

BOLANGIR, ODISHA  •  OBSTETRICS & GYNAECOLOGY CLINICAL PATHWAY SERIES

Clinician Reference Infographic

Rh Isoimmunization in Pregnancy — Screening, Prevention & Management

Rh isoimmunization occurs when an Rh-negative mother is exposed to Rh-positive fetal red cells and mounts an anti-D antibody response. In a future pregnancy with an Rh-positive fetus, these IgG antibodies cross the placenta and destroy fetal red cells, causing haemolytic disease of the fetus and newborn (HDFN) — ranging from mild neonatal jaundice to severe fetal anaemia and hydrops. The disease is now largely preventable with timely anti-D immunoglobulin — the challenge is not missing the window.

🩸 AT A GLANCE — WHO'S AT RISK

Risk Drivers

Rh-negative mother carrying an Rh-positive fetus (father Rh-positive or genotype unknown)

Any prior sensitizing event — miscarriage, ectopic, delivery, invasive procedure, trauma

Prior pregnancy or transfusion without adequate anti-D cover

First pregnancy is usually unaffected unless an earlier sensitizing event occurred

GREEN: Rh-negative, antibody screen negative, no sensitizing event — routine prophylaxis pathway

AMBER: Rh-negative with a sensitizing event — needs a directed dose of anti-D within 72 hours

RED: Antibody screen positive (isoimmunized) — refer for specialist fetal surveillance; prophylaxis no longer helps this pregnancy

🧪 ANTENATAL SCREENING & PREVENTION

Routine Pathway

Booking visit: blood group, Rh type, and antibody screen (indirect Coombs test) for every pregnant woman

~28 weeks: repeat antibody screen, then give routine antenatal anti-D prophylaxis (RAADP) if still negative and Rh-negative

After delivery: anti-D within 72 hours if the baby is confirmed Rh-positive, regardless of antenatal doses already given

Kleihauer–Betke test after a large bleed (e.g., abruption, trauma) to quantify fetomaternal haemorrhage and adjust the anti-D dose upward if needed

Standard Anti-D Dose

300 mcg (1500 IU) IM — the standard dose for RAADP, after delivery, and after most sensitizing events at or beyond 12 weeks' gestation; covers up to ~30 mL fetal whole blood (~15 mL fetal RBCs)

50 mcg (250 IU) IM — smaller dose used by some protocols for sensitizing events before 12 weeks' gestation

Exact dose still depends on gestation, event, and local protocol — when the Kleihauer–Betke test shows a large fetomaternal bleed, additional doses are needed beyond the standard vial. When in doubt, treat as a sensitizing event and give anti-D.

⏱️ SENSITIZING EVENTS — ACT WITHIN 72 HOURS

1

Miscarriage or threatened miscarriage beyond early first trimester

2

Ectopic pregnancy or molar pregnancy

3

Amniocentesis, CVS, cordocentesis, or other invasive procedure

4

Antepartum haemorrhage or abdominal trauma

5

External cephalic version (successful or attempted)

6

Intrauterine death

7

Delivery — if the baby is Rh-positive

🚨 IF ANTIBODY SCREEN IS POSITIVE — ESCALATE

Rising antibody titre, or titre above the lab's critical threshold

Raised MCA peak systolic velocity on Doppler (suggests fetal anaemia)

Ultrasound signs of hydrops — ascites, effusions, skin oedema, placentomegaly

History of a previously, severely affected fetus or neonate

Any of the above → refer promptly to maternal-fetal medicine

📈 MONITORING AN ISOIMMUNIZED PREGNANCY

Serial antibody titres — typically monthly — once the screen turns positive

If titre crosses the critical threshold: start MCA Doppler PSV surveillance, usually from 18–20 weeks, every 1–2 weeks

MCA-PSV > 1.5 MoM suggests moderate-to-severe fetal anaemia — proceed to fetal blood sampling ± intrauterine transfusion

Paternal / fetal Rh genotyping (including cell-free fetal DNA where available) helps clarify fetal risk if the father is heterozygous

Amniotic fluid bilirubin (ΔOD450) is largely historical — Doppler surveillance has replaced it in most modern practice.

👶 FETAL & NEONATAL MANAGEMENT

Intrauterine transfusion (IUT) via cordocentesis for significant fetal anaemia; repeated every 2–4 weeks as needed

Timing of delivery balances prematurity risk against progressive anaemia — often planned around 37–38 weeks, earlier if severe

At birth: cord blood for blood group, direct Coombs test (DCT), haemoglobin, and bilirubin

Neonatal care: phototherapy, exchange transfusion for severe hyperbilirubinaemia or hydrops, and top-up transfusions for late anaemia

Anti-D (Classic Rh)

Most common and best-studied cause of severe HDFN

Largely preventable with timely anti-D prophylaxis

Other Rh (c, E) & Kell

Not covered by anti-D immunoglobulin

Kell antibodies suppress fetal bone marrow directly — anaemia can be severe out of proportion to titre

ABO Incompatibility

Can occur in a first pregnancy; generally much milder than Rh disease

Direct Coombs often weakly positive; usually managed with phototherapy alone

Hydrops Fetalis

Severe end-stage of untreated fetal anaemia

Needs urgent tertiary-centre fetal medicine input

Critical Window

Give Anti-D Immunoglobulin

72

HOURS
FROM THE EVENT

Anti-D works by clearing fetal red cells from the maternal circulation before the mother's immune system recognizes and responds to them — timing is what makes it effective.

Standard dose: 300 mcg (1500 IU) IM for RAADP, postpartum, and most events ≥12 weeks; smaller 50 mcg (250 IU) doses are used by some protocols before 12 weeks

Give after any sensitizing event, and again after delivery if the baby is Rh-positive — even if a dose was already given antenatally

Run a Kleihauer–Betke test whenever a large fetomaternal bleed is suspected — a large bleed needs more than one standard dose

Document every dose and every event clearly — this record matters for every future pregnancy

Counsel the patient: she will need anti-D again in future pregnancies, regardless of how many doses she has already had

Reminder: anti-D prevents sensitization — it does nothing once the antibody screen is already positive. That pregnancy now needs surveillance, not prophylaxis.

Swaraj Hospital & Research Institute · Department of Obstetrics & Gynaecology, Bolangir, Odisha

Clinician-facing summary for structured teaching and triage; anti-D dosing and surveillance thresholds vary by protocol — follow local blood bank and transfusion medicine guidelines.