Haemolytic disease of the fetus and newborn — formative SAQs

SAQ 1 — Prevention, surveillance and the fetal anaemia threshold (10 marks)

A 30-year-old Rh-negative woman at 20 weeks' gestation is found to have anti-D antibody on her booking antibody screen, with a titre of 1 in 32. She did not receive anti-D after a miscarriage two years ago. [1] [4]

Questions

1. Outline how this sensitisation could have been prevented, and state the evidence for antenatal and postnatal anti-D prophylaxis. (5 marks) [1]
2. Describe the antenatal surveillance strategy from this point, including the validated non-invasive test for fetal anaemia and its intervention threshold. (5 marks) [3] [4]

Model answer

Prevention (5). This woman was sensitised by fetomaternal haemorrhage at the time of her miscarriage, and the sensitisation would very likely have been prevented by anti-D immunoglobulin given after that event. Routine prevention rests on two Crowther Cochrane reviews: antenatal anti-D at 28 weeks to all Rh-negative women, and postnatal anti-D within 72 hours of delivering an Rh-positive infant, together suppress the maternal immune response to fetal RhD-positive cells and dramatically reduce RhD alloimmunisation. Anti-D is also indicated after any sensitising event in pregnancy — antepartum haemorrhage, trauma, miscarriage, ectopic pregnancy, and procedures such as external cephalic version or abdominal trauma — and ABO incompatibility between mother and fetus is naturally protective because maternal anti-A and anti-B clear fetal cells before they sensitise the Rh system. [1]

Surveillance (5). Once a clinically significant antibody is identified, the strategy is serial antibody titres or quantitative anti-D levels every two to four weeks, and when the titre or level reaches the laboratory-specific critical threshold, serial middle cerebral artery peak systolic velocity (MCA-PSV) Doppler from about 18 weeks, performed every one to two weeks. Mari's landmark NEJM study established that MCA-PSV above 1.5 multiples of the median for gestational age detects moderate-to-severe fetal anaemia non-invasively with high sensitivity, and the SMFM Clinical Guideline #8 codified this threshold, retiring serial amniocentesis with delta-OD450. When the MCA-PSV exceeds 1.5 multiples of the median or hydrops develops, fetal blood sampling is performed with preparation for intrauterine transfusion, in a tertiary maternal-fetal-medicine centre. [3] [4]

SAQ 2 — The postnatal management ladder (10 marks)

A term infant born to a known RhD-sensitised mother is jaundiced at 12 hours of age. The cord direct antiglobulin test is positive, the haemoglobin is 110 g per litre, and the serum bilirubin is rising rapidly and is approaching the phototherapy threshold. [5] [8]

Questions

1. Describe the stepwise postnatal management of this infant, including the thresholds that govern escalation and the dose of any adjunctive therapy. (5 marks) [5] [8]
2. Explain why jaundice in the first 24 hours demands investigation, and how the bilirubin is interpreted against the hour-specific nomogram in a haemolysing infant. (5 marks) [5]

Model answer

Management ladder (5). The postnatal ladder runs from intensive phototherapy through intravenous immunoglobulin to exchange transfusion. Intensive phototherapy with a high-irradiance narrow-band blue light source applied to maximal exposed surface area is started as the bilirubin approaches the phototherapy threshold for the infant's age, gestation and risk factors — and haemolysis is itself a risk factor that lowers the threshold. If haemolysis is confirmed and the bilirubin continues to rise toward the exchange threshold despite intensive phototherapy, intravenous immunoglobulin 0.5 to 1 g per kilogram over two to four hours is given as an adjunct to block Fc receptors on splenic macrophages and reduce extravascular haemolysis. Exchange transfusion is performed when the bilirubin is at the exchange threshold or the infant shows signs of acute bilirubin encephalopathy, simultaneously removing antibody-coated red cells, bilirubin and antibody. A late anaemia at two to eight weeks may need a top-up transfusion as the antibody is cleared. [5] [8]

First-24-hour jaundice (5). Jaundice in the first 24 hours of life is never physiological and must be investigated for haemolysis regardless of how well the infant looks. The workup is a serum bilirubin with fractionation, a direct antiglobulin test, a full blood count and film, and maternal and infant blood groups. The bilirubin is plotted against the infant's age in hours on an hour-specific nomogram to define the risk zone and the threshold for phototherapy or exchange transfusion, adjusted for gestational age and risk factors. In a haemolysing infant the rate of rise is often above 8 to 10 micromoles per litre per hour, and haemolysis lowers the intervention thresholds — so the trajectory in the first hours, not just the absolute value, drives the decision to escalate. [5]