Rhesus Iso Immunization

Rhesus iso-immunization Management Dr. P. A. Awoyesuku Dept. of Obs & Gynae UPTH

Introduction Major cause of perinatal mortality and a complete mystery before the 1940s Haemolytic disease continues to occur despite well organized prophylaxis programmes Care now given by specialized fetal medicine units Perinatal mortality has therefore decreased 100-fold in the last 3 decades Fetal disease varies from clinically insignificant to intrauterine fetal death (IUFD) as early as 17 weeks Management has improved in western countries as a result of technical advances in the last decade

History / Diagnosis Help to predict severity of haemolytic disease –

MATERNAL BLOOD TYPE / ANTIBODY SCREEN Husband’s blood type Husband’s zygosity Mother’s antibody status Antibody type – IgM or IgG

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PREVIOUS EPISODES OF SENSITIZATION Ectopic pregnancy (<1%) Spontaneous aborton >6/52 (3-4%) Inadequate rhogam dosage Previous Rh - +ve blood transfusion (90-95%) Previous full term delivery (14-17%) Sensitization in-utero (Grandmother theory)

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PREVIOUSLY AFFECTED FETUSES Determine severity of haemolytic disease Information about delivery –

Gestational age

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Type of delivery / events

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Type of therapy

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Knowledge of previous titres

Antibody titre monitoring Help to predict severity of haemolytic disease in current pregnancy in 62% + Amniocentesis and Ultrasound in 89% Most laboratories use indirect antiglobulin (Coomb’s) test and titre – 1:16 – carries 10% risk – 1:32 -

carries 25%

– 1:64 – 50% – 1:128 – 75%

Auto analyser should be used in preference to titres as they are more quantitative – <4 IU/mL no severe disease, repeat 2-4 weekly

Functional bioassays e.g. antibody-dependent cell-mediated (ADDC) test now available and show benefit over quantitative tests

Amniocentesis When anti-D level is >4 IU/mL but <10 IU/mL, monitoring is by amniotic fluid bilirubin determinations which reflect degree of haemolysis Spectrophotometry is employed to measure the optical density (OD) reading at 450nm wavelength – ΔOD450 The optical density is plotted on the standard Liley’s chart with Whitfield action line modification Timing of amniocentesis depends on antibody titre and history of previously affected fetuses First amniocentesis is generally performed 10 weeks prior to time of expected ominous event Repeat at 1 – 4 week interval Downward trend after 2nd or 3rd amniocentesis is good prognostic sign If no downward trend, the ΔOD450 trend line on Liley’s curve is extrapolated until it crosses the action line –

If this occurs <34weeks, fetal blood sampling is undertaken

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If after 34 weeks delivery is recommended at the time of intersection

NB: recently limit of 4Iu/mL has been challenged and an absolute level of ≥15 IU/mL has been proposed as threshold for prenatal intervention

Liley’s chart

Percutaneous umbilical blood sampling (Cordocentesis) Can be performed under direct visualizaton (Fetoscopy) or indirect visualization (Ultrasound directed needle aspiration) Provides information about fetal Hb/PCV, Blood group, direct Coomb’s titer, bilirubin level, reticulocyte count Fetal PCV preferable in 2nd trimester to Liley’s curve in estimating degree of fetal anaemia ( Liley’s curve more predictive in 3rd than 2nd trimester)

Ultrasound scan (USS) Now mainstay of fetal monitoring and timing of first intervention if anti-D level is ≥ 10 IU/mL With anti-D levels > 4IU/mL fetus should be scanned weekly from 18 weeks Partner homozygous or fetus Rhesus positive – continue weekly USS till you detect either fetal skin/scalp oedema, ascites, pericardial or pleural effusion Other USS features – – – – –

Polyhydramnios Fetal hepatosplenomegaly Cardiomegaly Placental hypertrophy Abnormal fetal posture (Buddha stance)

Treatment by fetal transfusion When ΔOD450 falls in the highest zone after 34 weeks patient should be delivered If < 34 weeks, an intrauterine transfusion is performed since the risk of transfusion is less than risk of prematurity Transfusion may be started as early as 18 weeks Blood can be administered either peritoneally or intravascularly Blood compatible with mothers blood is used; after the serum is depleted to a PCV of 90-95% Fetal transfusions are managed as out-patient procedures If sampled fetal PCV is below gestational reference range, fetus is usually transfused to a target PCV of 50-55% Second transfusion is always given 2 weeks after the first, which allows assessment of rate of fall in PCV and change in percentage of fetal cells left in fetal circulation These 2 factors determine timing of subsequent transfusions, usually given at 3-4 week intervals Since RDS is common in these fetuses, transfusions at ≥ 28 weeks should be preceeded by betamethasone in case emergency delivery becomes necessary

Timing of delivery The last transfusion is given around 32-33 weeks and the fetus is delivered 3 weeks later before it becomes too anaemic Delivery should be vaginal unless there is an obstetric indication for cs Trans placental passage of fetal RBCs increase after 37 weeks and worsens antibody status so there is little point in delaying delivery after this GA Caesarean section is usually the best alternative for deliveries before 34 weeks

Prevention A 300mg dose of Rhesus immune globulin covers fetomaternal haemorrhage of 30ml so 350mg should be given If an appropriate dose has been given, there should be a positive indirect Coomb’s test (excess free antibody) measured a day after the dose Failure of prophylaxis – Dose too small – Dose too late >72 hours – Patient already immunized but antibody titre too low for laboratory recognition – Defective immune globulin given

Indications for prophylaxis

– At 28/52 to a Rhesus –ve non-immunized woman whose husband is Rhesus +ve – Postpartum if the woman remains unimmunized and delivers a Rhesus +ve fetus – Following amniocentesis or chorionic villus sampling – Following evacuation of a molar pregnancy or termination of pregnancy – Following an ectopic pregnancy – Following abruptio placenta or undiagnosed uterine bleeding