OBSTETRICS
By Mohammed Hassan
“The moment a child is born, the mother is also born. She never
existed before. The woman existed, but the mother, never. A
mother is something absolutely new.” - Rajneesh
Telegram Account: @MHJM_3
Telegram Channel: @IUCOM
Rh Incompatibility
Overview:
• Human red blood cells carry many antigens on their surfaces. The most important of these antigens belong to the ABO
system and the rhesus (Rh) system. The D antigen is the most important antigen of the rhesus system. People with the
rhesus D (RhD) antigen are referred to as RhD positive, and those without it as RhD negative. A baby inherits its blood
type from both parents. Therefore a mother who is RhD negative can carry a baby who is RhD positive.
• During pregnancy, small amounts of fetal blood can enter the maternal circulation (an event called feto–maternal
haemorrhage or FMH). The presence of fetal RhD-positive cells in her circulation can cause a mother who is RhD
negative to mount an immune response, producing a template for the production of antibodies as well as small
amounts of antibodies against the RhD antigen (anti-D antibodies). This process is called sensitisation or
alloimmunisation.
• Sensitisation, often occurring in the third trimester or childbirth, can result from procedures (e.g., amniocentesis),
trauma, or spontaneous FMH. Risk is higher with ABO-compatible fetuses and decreases in subsequent pregnancies.
Once sensitised, the mother remains so permanently. While harmless to the mother, sensitisation can cause severe
complications in future RhD-positive pregnancies. Maternal anti-D antibodies attack fetal red blood cells, leading to
anemia, hydrops, or fetal death. Postnatally, high bilirubin levels can cause jaundice (HDN) and kernicterus, resulting
in cerebral palsy, deafness, or developmental delays.
• The prevalence of D-rhesus negativity is 15% in the UK Caucasian population, but lower in all other ethnic groups.
Approximately 55% of UK Caucasian males are heterozygous for the D antigen; therefore, around two-thirds of rhesus-
negative mothers would be expected to carry a rhesus-positive fetus. Rhesus disease is most common in countries
where anti-D prophylaxis is not widespread, such as the Middle East and Russia.
• The occurrence of HDFN as a result of rhesus isoimmunization involves three key stages:
1) Rhesus-negative mother must conceive a baby who has inherited the rhesus-positive phenotype from the father.
2) Fetal cells must gain access to the maternal circulation in a sufficient volume to provoke a maternal antibody
response.
3) Maternal antibodies must cross the placenta and cause immune destruction of red cells in the fetus
Pathophysiology:
Clinical Features & Diagnosis:
Clinical Prenatal • Hydrops fetalis (expected in cases of Rh incompatibility and in nonimmune hydrops fetalis)
Features
Postnatal • Neonatal anemia (Hb < 10 g/dL ,hematocrit < 30%, in the first week of life. Anemia is caused by
the rapid breakdown of antigen-antibody complexes, including maternal antibodies and fetal
RBCs in the spleen. The breakdown time is faster than the time required to produce additional
RBCs).
• Hepatosplenomegaly (Increased destruction of erythrocytes in the spleen leads to a
compensatory increase in hematopoiesis in the liver).
• Neonatal jaundice:
❖ Usually present at birth or manifests within the first 24 hours of life
❖ In Rh incompatibility, unconjugated bilirubin levels may be dangerously high, causing
kernicterus.
• Hypoxia (Via increased RBC destruction and acidosis).
• Prematurity
• Scattered petechiae (rare but associated with poor prognosis)
Diagnosis Prenatal • Ultrasound: to determine hydrops fetalis:
❖ Fetal pleural or pericardial effusions
❖ Fetal ascites
❖ Fetal subcutaneous or nuchal edema
❖ Placental edema
• Doppler sonography of fetal blood vessels: Increased flow rate indicates fetal anemia.
Postnatal • If the newborn has signs of hemolysis, conduct a Coombs test (either direct or indirect):
❖ Rh incompatibility: positive
❖ ABO incompatibility: weak positive or negative
Prevention – Non Sensitized Women:
• Isoimmunization occurs when a D-negative woman is exposed to D-positive fetal red cells, leading to maternal
alloantibody formation. Anti-D immunoglobulin (Ig) works by “mopping up” fetal cells before the maternal immune
system is triggered. Sensitization can occur after clinically obvious events (e.g. miscarriage, trauma, procedures) but
also after silent fetomaternal haemorrhage (FMH) without any warning signs. Therefore, routine prophylaxis is
offered to all non-sensitized D-negative women.
• Routine Antenatal Prophylaxis (RAADP):
❖ The UK recommendation states that all D-negative, non-sensitized women should be offered RAADP.
❖ The regimens include a single-dose option of 1500 IU at 28–30 weeks or a two-dose option of 500 IU at 28 and 34
weeks.
❖ Before administering Anti-D, an antibody screen at 28 weeks is required. It is important to note that RAADP
supplements but does not replace Anti-D for sensitizing events.
❖ If Anti-D is detected during testing, it should be confirmed whether it is immune or passive. If unclear, prophylaxis
should continue.
• Postpartum Prophylaxis:
❖ Postpartum prophylaxis is indicated for all D-negative, non-sensitized women delivering a D-positive or unknown
infant. Testing includes cord blood for ABO & RhD typing and maternal blood for FMH (Kleihauer test). A minimum
dose of 500 IU Anti-D should be given within 72 hours of delivery.
❖ If FMH exceeds 4 mL, additional Anti-D dosing is required, calculated as 125 IU/mL if given intramuscularly or 100
IU/mL if given intravenously.
❖ Special cases include intrauterine death (IUD), where ≥500 IU Anti-D should be given at diagnosis without waiting
for delivery.
❖ In cases of intraoperative cell salvage with reinfusion in a D-positive or unknown case, ≥1500 IU Anti-D should be
administered after reinfusion, followed by FMH testing at 30–45 minutes.
Prevention – Sensitizing Events:
• Sensitizing Events: Anti-D Ig should be given as soon as possible, ideally within 72 hours of the event. If delayed,
administration up to 10 days may still provide some protection.
1) Miscarriage, ectopic pregnancy, molar pregnancy, termination of pregnancy , delivery (vaginal, instrumental, or C-section).
2) APH, trauma, external cephalic version, Intrauterine death/stillbirth.
3) Invasive procedures: CVS, amniocentesis, cordocentesis, in-utero transfusion, surgery.
4) Intraoperative cell salvage.
• <12 weeks:
❖ 250 IU Anti-D is only indicated in the following situations: ectopic pregnancy (regardless of management), molar pregnancy,
termination (medical or surgical), recurrent or heavy bleeding, or bleeding associated with pain.
❖ Anti-D is not required in cases of spontaneous miscarriage (complete, with no instrumentation) or mild, self-limiting vaginal
bleeding.
❖ FMH testing is not required in these cases.
• 12 - 20 weeks:
❖ 250 IU Anti-D, given within 72 hours of a sensitizing event.
❖ A FMH testing must be performed to allow calculation of additional Anti-D if needed.
❖ In cases of recurrent bleeding, administer 250 IU every 6 weeks.
• > 20 weeks:
❖ 500 IU Anti-D, given within 72 hours of the event.
❖ FMH testing is mandatory to guide the need for further Anti-D.
❖ For recurrent or ongoing bleeding, repeat 500 IU every 6 weeks and perform FMH testing every 2 weeks if bleeding is
intermittent. Any new bleeding event should be treated as a separate incident, and Anti-D should be repeated regardless of
prior doses.
Prevention – Sensitized Woman:
• Once a pregnant woman who is D-rhesus negative has been sensitized to the D-rhesus antigen, no amount of anti-D will ever
turn the clock back. In a subsequent pregnancy, close surveillance is required. Rhesus disease gets worse with successive
pregnancies, so it is important to note the severity of the disease in previous pregnancies. The management depends on the
clinical scenario.
• Risk assessment begins with consideration of paternal and fetal status. If the father is confirmed to be D-negative, there is no
risk that the fetus will inherit the D antigen, and therefore the pregnancy is safe from haemolytic disease. If the father is D-
positive, the possibility of heterozygosity must be borne in mind, since in that situation there is a 50% chance that the fetus will
be D-positive.
• While paternal phenotype is often helpful, issues of paternity and false prediction must be considered. Non-invasive fetal blood
group genotyping using cell-free fetal DNA extracted from maternal plasma between 16 and 25 weeks has revolutionised risk
assessment. This test allows accurate determination of the fetal RhD type and is now recommended in the UK to guide
subsequent surveillance and to avoid unnecessary prophylaxis.
• Once alloimmunisation is confirmed, maternal antibody levels must be monitored throughout pregnancy. Screening is
performed at booking and then repeated every two to four weeks thereafter. The preferred method of quantification is in
international units per millilitre (IU/mL), which provides more reliable correlation with clinical outcome than simple titre
dilutions. Rising antibody levels indicate an increasing risk of fetal anaemia and necessitate fetal assessment.
• Historically, fetal surveillance relied on invasive procedures such as amniocentesis with measurement of amniotic fluid bilirubin.
This approach has now been replaced by middle cerebral artery (MCA) Doppler velocimetry. An increased peak systolic velocity
(PSV) correlates strongly with fetal anaemia, with reported sensitivity approaching 100% and a false-positive rate of about 12%.
A fetus with a raised MCA PSV is at significant risk of anaemia and should be managed in, or in consultation with, a tertiary
fetal medicine centre.
• Management of fetal anaemia depends on both gestation and severity. From 36 to 37 weeks onwards, delivery is usually the
safest option if neonatal expertise is available. For fetuses too premature for delivery, intrauterine transfusion (IUT) is the
treatment of choice, restoring haemoglobin and preventing hydrops or intrauterine death. Transfused blood must be D-negative,
cross-matched with maternal samples, concentrated, white-cell depleted, irradiated, and screened for infection. The umbilical
vein at the placental insertion is the preferred access route, although the intrahepatic vein, peritoneal cavity, or rarely the fetal
heart may be used.
• At delivery, planning is vital. A neonatologist should be present if the fetus has been anaemic or received IUTs. Cord blood must
be tested for blood group and direct antiglobulin test (DAT), and exchange transfusion may be needed for severe neonatal
anaemia or jaundice.
• Recent advances include routine use of cell-free fetal DNA to determine RhD status. This allows selective administration of anti-D
prophylaxis only to women carrying a D-positive fetus, preventing unnecessary injections in the 40% of D-negative women
carrying a D-negative child. This approach, already established in parts of Europe, is now being introduced in the UK.
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