Early Intravenous Immunoglobulin (IVIG) Therapy and Non Invasive Fetal Monitoring in Rh Alloimmunization (AI) and Pregnancy

Abstract

High titer (HT), ≥1:32, anti-E, anti-c and anti-D Rh antibodies can cause hemolytic disease of the newborn (HDN). Maternal IVIG therapy may reduce need for intrauterine and exchange transfusions in HDN. Minimal data exists regarding optimal timing of therapy initiation, dose and frequency and fetal outcomes. Late administration of IVIG therapy beyond gestational age of 16 weeks have not been shown to improve fetal outcome. We describe the clinical course of 3 pregnant women with Rh AI. Two women with high titer Rh AI were treated with early IVIG dose of 1 gm/kg/week. A third woman with low titer Rh AI did not receive IVIG. Fetal status was monitored non-invasively with weekly Fetal Doppler ultrasound measurement of peak systolic velocity (PSV) of the middle cerebral artery (MCA). Patient 1 was a 38 year old Caucasian female with high anti- D (> 1:500) and history of HDN; second baby required 3 exchange transfusions and third baby required 3 intrauterine transfusions during pregnancy and 2 exchange transfusions post delivery. IVIG weekly infusion was started on week 11. Amniocentesis done at week 21 showed that baby was Rh(D) positive and the Kleihauer-Bethke test was negative. Serial fetal MCA PSV done weekly till labor induction did not show evidence of significant fetal anemia. The IVIG infusions were completed on 33rd week and the patient delivered healthy baby by cesarean section on the 35th week. The baby did not receive any intra uterine or exchange transfusions.Patient 2 was a 37 year old caucasian woman with anti-c AI. The patient's husband is c antigen positive and she had seroconversion during her third pregnancy which manifested as positive antibody screen in a routine type and screen with her third delivery which was uneventful. She subsequently had a miscarriage of her fourth pregnancy at 9 weeks. Her peak anti –c titer was 1: 128. She received IVIG infusion from week 11 to week 33 with stable anti-c titer of 1: 64. Serial MCA PSV assesments did not reveal significant fetal anemia. She had a normal vaginal delivery on week 34 with a healthy baby not requiring any exchange transfusions. Patient 3 was a 41 year old caucasian woman with low titer anti-E AI (1:8). No IVIG was administered as her titers remained low during her pregnancy course. Her titers were monitored every 2 weeks; peak antibody titer was 1:8. Fetal anemia was ruled out with Serial MCA PSV assesments. She delivered a healthy baby by Ceserean section at 38 weeks, 4 days.Patient 1Patient 2Patient3Gravid statusG4 P2103G5 P3013G8, P4034Blood groupA-A+O+Antibody identificationAnti DAnti cAnti EH/o documented HDNYesNoNoNumber of doses of IVIG2323NAAge of Gestation IVIG started10 weeks11 weeksNACumulative dose of IVIG1580 gms1750 gmsNAPeak antibody titer10481288Serial Fetal Peak MCA velocityNormalNormalNormalIntra uterine/Exchange transfusionsnoneNoneNonePregnancy outcomenormal fetusnormal fetusnormal fetusIVIG adverse effectsHeadache, fatigueNoneN/APatient 1Weeks of gestationAnti D TiterIVIG –Cumulative No. of dosesMCA PSV (cm/s) MoM= Multiples of Median91:512121:10481171:5127201:5121021 (0.83 MoM)211:5121128 (1.04 MoM)221:5121221.3 (0.76 MoM)231:5121328.1 (0.96 MoM)241:5121422 (0.71 MoM)251:5121525 (0.77 MoM)261:5121632 (0.95 MoM)271:5121728 (0.79 MoM)281:5121835 (0.94 MoM)301:5122045 (1.11 MoM)321:5122261 (1.37 MoM)331:5122351.9 (1.1 MoM)Patient 2Weeks of gestationAnti c TiterIVIG – Cumulative number of dosesMCA PSV (cm/s) MoM= Multiples of Median111:1281141:644201:6410221:641122.3 (0.79 MoM)241:641323.7 (0.77 MoM)251:641422.7 (0.70 MoM)261:641530.1 (0.89 MoM)271:641634.3 (0.97 MoM)291:641837.9 (0.98 MoM)301:641933.3 (0.82 MoM)311:642027.9 (0.65 MoM)321:642128 (0.62 MoM)331:642259 (1.26 MoM)341:642335 (0.71 MoM)Patient 3Weeks of gestationAnti E TiterIVIG - Cumulative No. of dosesMCA PSV (cm/s) MoM= Multiples of Median121:80191:80261:80281:8040.6 (1.07 MoM)291:4039.7 (1.02 MoM)321:4042 (0.94 MoM341:4055 (1.12 MoM)Median – 1.29 MoM = No fetal anemia1.29 – 1.5 MoM = Mild anemia>1.5 MoM = Severe anemiaConclusion- Early initiation of weekly IVIg therapy at dose of 1 gm/kg at gestational age of 10 to 11 weeks in high titer (≥ 1:32) maternal Rh AI is well tolerated and can eliminate the need for invasive fetal monitoring, intrauterine transfusion and exchange transfusion.