Two case studies have been published recently in AJP Reports in which obese pregnant patients developed hemolytic disease of the fetus and newborn (HDFN) after receiving Rho(D) immune globulin (RhIG) treatment.
The authors stated these case studies show that obesity may cause RhIG treatment to be ineffective, leading to the development of HDFN.
28-year-old patient shows ‘hybrid allele’ in D gene
The first case study described a 28-year-old woman who underwent a cesarean section for her first pregnancy at a gestational age (GA) of 39 weeks, one day. Her prior medical history included exercise-induced asthma, depression and class III obesity. Regarding her obesity, the patient’s body mass index (BMI) was 41 kg/m2 prior to becoming pregnant, which rose to 44 kg/m2 during her pregnancy due to weight gain of 24 pounds.
At 28 weeks, five days GA, the patient received an intramuscular injection of RhIG to prevent the development of RhD alloimmunization, or Rh incompatibility. Based on typing and screening prior to the injection, her antibody screen was negative. At 37 weeks’, three days’ GA, her type and screen were anti-D–positive, which was deemed to be associated with the prior RhIG administration.
In the postpartum period, the mother underwent RhD genotyping. In this patient, genotyping of the RHD gene demonstrated a “hybrid allele” in the D gene. This situation was described as “exons 3 through 9 of RHD replaced by the corresponding exons of the RHCE gene.” In spite of this RHD/RHCE genetic “crossover” detected at the molecular level, the patient was RhD seronegative. In fact, she was considered to be as susceptible to the occurrence of anti-D alloimmunization as is any Rh-negative person.
Read more about HDFN testing and diagnosis
33-year-old patient positive for anti-D despite past negative screenings
The second case described a 33-year-old woman who underwent a vaginal delivery at 40 weeks’, two days’ GA. This was her third pregnancy, with the first leading to a stillbirth at 22 weeks and the second resulting in a vaginal delivery at term. The patient received appropriate RhIG prophylaxis in both prior pregnancies. The baby from her second pregnancy was Rh-positive.
She was diagnosed with class II obesity, with her BMIs ranging 33 kg/m2 to 39 kg/m2. Based on typing and screening performed in the first and second trimesters of this third pregnancy, she was negative for anti-D antibodies. She was treated with an IM injection of RhIG at 27 weeks’, 2 days’ GA, at which time her antibody screen was negative.
When she was admitted to the hospital at 40 weeks’, 2 days’ GA, her antibody screen was positive for anti-D. The infant showed no signs of anemia and was ultimately discharged home at two days of age.
Current recommendations for RhIG
Prior to the use of RhIG, the most common cause of HDFN was anti-D alloimmunization. Currently, it is recommended that all pregnant patients who test negative for the D antigen are treated with RhIG 300 µg at 28 weeks’ GA, along with the administration of RhIG within 72 hours of a potential exposure to Rh-positive fetal blood.
Although the pharmacokinetics of RhIG have been well evaluated, they remain to be elucidated in the population of pregnant patients with obesity. In fact, between 3 and 10 days following the administration of RhIG, a study reported that a wide range of plasma anti-D concentrations was observed among the recipients. Of note, lower anti-D levels were seen among those women with higher BMIs.
Although RhIG is usually administered via an intramuscular injection, the use of intravenous forms of the agent has been effective as well. To date, which route of administration—intramuscular or intravenous—is more favorable in women with obesity remains to be determined.
The authors concluded that “[O]besity is a risk factor for failure of RhIG . . . and could lead to an increase in HDFN.”
