Question:

A 32-year-old primigravid woman at 20 weeks gestation comes to the office for a routine prenatal visit. She has no vaginal bleeding, leakage of fluid, or contractions. The patient had mild nausea that resolved at 14 weeks gestation. A fetal anatomical sonogram performed a week ago revealed no abnormalities. The patient has no chronic medical issues or previous surgeries. She is taking a daily prenatal vitamin and does not use tobacco, alcohol, or illicit drugs. The patient works in a laboratory as a biotechnology research assistant. She has blood group O, Rh(D) positive, and her husband has blood group AB, Rh(D) positive. On physical examination, the fundus is palpable at the umbilicus, and the fetal heart rate is 140/min. The patient is concerned about different blood groups and the risk of pregnancy complications. Which of the following is the most appropriate response to this patient?

"ABO antigens elicit only an IgM response, so you are not at risk with this pregnancy."

"Antibodies to ABO antigens are not hemolytic."

"Most newborns affected by ABO incompatibility will have only mild hemolytic disease."

"You are not at risk as the immune response is depressed during pregnancy."

"You are tolerant to your child's ABO antigens, so your newborn will not have hemolytic disease."

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Explanation:

ABO hemolytic disease
Risk factors	Infants with blood types A or B born to a mother with blood type O
Clinical features	Jaundice within 24 hours of birth Anemia ↑ Reticulocyte count Hyperbilirubinemia Positive Coombs test
Management	Serial bilirubin levels, oral hydration & phototherapy for most neonates Exchange transfusion for severe anemia/hyperbilirubinemia

This patient with blood group O, whose husband is blood group AB, will bear a child with either blood group A or B. In these situations of ABO incompatibility, signs of hemolytic disease are typically mild and apparent only in approximately one-third of infants. Affected infants are usually asymptomatic or mildly anemic at birth; within the first 24 hours of life they may develop jaundice (eg, hyperbilirubinemia), which typically responds to phototherapy.

A pregnant woman's immune system is not depressed overall; interaction between the innate (eg, neutrophils, macrophages) and adaptive (eg, antibodies) immune systems allows for an appropriate response at the fetal-maternal interface (Choice D). Exposure to the A and B antigens of the fetus does provoke an IgM response during pregnancy, but these antibodies are large pentamers that cannot cross the placenta (Choice E). However, patients with blood group O are exposed to A and B antigens early in life (from exposure to A- and B-like antigens present in food, bacteria, and viruses) and produce antibodies to these antigens. By the time a woman with blood group O becomes pregnant, she already has anti-A and anti-B IgG antibodies that cross the placenta; therefore, ABO incompatibility can affect a first pregnancy (Choice A).

(Choice B) Antibodies against A and B are hemolytic. However, in addition to red blood cells, A and B antigens are present on the cells of all other fetal tissues. The reaction of the anti-A and anti-B antibodies with the antigens on these other cells neutralizes the antibody response, leading to a much milder form of hemolytic disease.

Educational objective:
ABO incompatibility typically occurs between a mother with blood group O and an infant with blood group A or B, which can cause mild hemolytic disease of the newborn. Affected infants are usually asymptomatic at birth or have mild anemia, and may develop neonatal jaundice that typically responds to phototherapy.