A Curious Case of Anti-D Antibody Titer

Jennifer G. Hensley, CNM, WHNP, EdD; Katherine P. Coughlin, CNM, MSN; Laura L. Klein, MD


J Midwifery Womens Health. 2009;54(6):497-502. 

In This Article

Abstract and Introduction


RhD alloimmunization remains a threat to 1% of the 10% of RhD-negative women in the United States who are giving birth to RhD-positive fetuses despite routine antenatal and postpartum administration of RhoD immune globulin (RhIG). This report examines the clinical course of an RhD-negative woman who developed a high anti-D antibody titer during her pregnancy while carrying an RhD-positive female fetus yet had a negative antibody screen at the time she gave birth. Although she delivered a healthy newborn unaffected by hemolytic disease, subsequent pregnancies will be treated as though she is RhD alloimmunized. The discussion below includes possible causes for the abrupt rise in this woman's anti-D antibody titer, a review of the complex Rh system and cellular anamnestic response, and current fetal surveillance for hemolytic disease of the fetus and newborn.


C.M., a 39-year-old gravida 2, para 0010, presented for an initial prenatal visit at 8 and 2/7 weeks' gestation by last menstrual period and transvaginal ultrasound crown-rump length. Conception was achieved after a course of metformin and clomiphene, which was given because she had a history of polycystic ovarian syndrome. Her first pregnancy resulted in a spontaneous abortion at 6 weeks' gestation, after which she received 50 mcg of RhoD immune globulin (RhIG) because she is Rh-negative. Initial prenatal laboratory values drawn at the first prenatal visit for this pregnancy revealed her blood as type A, RhD-negative, with a negative antibody screen. Sequential serum screening for Down syndrome was offered and accepted; the results were negative for trisomy 21 markers. A routine 20-week ultrasound revealed a female fetus.

During a routine return obstetric visit at 28 weeks' gestation, C.M. received 300 mcg of RhIG intramuscularly as prophylaxis against RhD alloimmunization. It was a busy clinic day, and her antibody screen was drawn 40 minutes after the injection. This serum sample was positive for anti-D antibody; the titer was 1:8. A Kleihauer-Betke test was 0.001, the equivalent of 0.065 mL of fetal red blood cells (RBCs) in the maternal circulation. The anti-D antibody titer peaked at 1:32 within 24 hours, remained as such for 2 weeks, then leveled off at 1:16 from weeks 3 through 9. At 36 and 3/7weeks' gestation, her antibody screen reverted to negative. All anti-D antibody titers were drawn and run at the same laboratory.

The 'critical' anti-D antibody titer for the laboratory where her blood was drawn was 1:16 (the threshold at which that particular laboratory determined that the titer may result in fetal hydrops). Because her titer was 1:32, RhD alloimmunization was presumed. Her certified nurse-midwife (CNM) and obstetrician-gynecologist referred her to a maternal-fetal medicine (MFM) specialist for the evaluation of hemolytic disease of the fetus and newborn. Return and follow-up obstetric visits included care by the CNM, obstetrician-gynecologist, and MFM specialist.

Paternal blood, determined by molecular DNA, was homozygous for RhD-positivity (DD); therefore, the female fetus was RhD-positive (Dd). Surveillance of fetal well-being began at 28 weeks' gestation and included every 1- to 2-week middle cerebral artery Doppler studies of peak systolic velocity for investigation of fetal anemia, twice weekly nonstress tests (NSTs) with amniotic fluid indices (AFIs) or weekly biophysical profiles (BPPs), and ultrasonographic assessment for interval fetal growth every 3 to 4 weeks.

At 35 weeks' gestation, the time at which middle cerebral artery Doppler studies of peak systolic velocity yield higher false positive results, the measurements became "equivocal" (i.e., slightly > 1.5 multiples of the median). Simultaneously, the ultrasound for interval growth revealed fetal growth restriction (FGR). Although C.M. had a total weight gain of 40 lbs, she had some risk factors for FGR that were not related to RhD alloimmunization. These risk factors included life-long smoking, which she stopped during the pregnancy, assisted reproduction, and advanced maternal age. An amniocentesis for fetal lung maturity revealed immature lungs by fluorescence polarization (FPOL), and measurement of the bilirubin level in the amniotic fluid corresponded to the "indeterminate" zone on the Queenan curve, which suggested the possibility of mild fetal anemia. A reassuring BPP score was 10 of 10. After informed consent, C.M. elected to continue the pregnancy to ensure fetal lung and hepatic maturity. Fetal surveillance continued with NST/AFI and BPP. A repeat amniocentesis at 36 and 3/7 weeks' gestation revealed fetal lung maturity by FPOL.

C.M. subsequently underwent an induction of labor at 36 and 3/7 weeks' gestation with misoprostol for cervical ripening followed by intravenous oxytocin. Interestingly, her antibody screen drawn on admission was negative. C.M. had a spontaneous vaginal birth. Her daughter was 4 lbs 13 oz (1694 g), which was small for gestational age; Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Cord blood was tested, and the direct agglutination test (DAT or direct Coomb test) was negative, blood type A, RhD-positive. The total bilirubin level was 2.1 mg/dL, and a hematocrit was 45% (which was the lower limit of normal for this laboratory). There was no evidence of hemolytic disease of the fetus and newborn or early newborn hyperbilirubinemia. After birth, the maternal-fetal screen (or rosette test) was negative. C.M. was given 300 mcg of RhIG postpartum before she was discharged. Two years later, her antibody screen remains negative. For the 18 weeks before the birth of her daughter, C.M. worried about the well-being of her fetus. What can be done to help C.M. during future pregnancies?


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