Reproductive
The Association Between Hemoglobinopathy Carrier States and Anemia During Pregnancy Kimi Van Wickle* Kimi Van Wickle Stephanie Engel Achille Massougbodji Florence Migot-Nabias Anais Merckx Michel Cot Florence Bodeau-Livinec
Hemoglobinopathy carrier states, the presence of one abnormal copy of a hemoglobin variant, have largely unknown clinical manifestations during pregnancy despite their widespread regional frequency in sub-Saharan Africa due to their protection against severe malaria. We included 895 mother-infant dyads from MiPPAD, a randomized control trial in Benin that followed pregnant women less than 28 weeks’ gestation through delivery, who received hemoglobin electrophoresis and had data collected on hemoglobin levels during antenatal visits and upon arrival for delivery. We investigated the extent to which trait status, including sickle cell trait and hemoglobin C trait, is associated with anemia over the course of pregnancy and at delivery and whether intrapartum malaria, as measured by placental parasitemia, mediates the association of carrier states with anemia at delivery (using gestational age-specific thresholds to account for physiologic hemodilution during pregnancy). We found that sickle cell trait, but not hemoglobin C trait, was associated with higher rates of anemia at delivery (OR = 1.59, 95%CI: 1.05, 2.40, p = 0.03). This relationship was exclusive to delivery and was not observed across the course of pregnancy (OR=1.05, 95%CI:0.80, 1,39, p = 0.70). Placental parasitemia did not substantially mediate the association between sickle cell trait and anemia at delivery: The odds of anemia amongst pregnant women with placental parasitemia did not differ by sickle cell trait status (OR = 1.00, 95%CI:0.99,1.01, p= 0.88). Likewise the odds of anemia through placental parasitemia among hemoglobin C trait carriers was not significant (OR = 1.08, 95%CI: 084, 1.40, p = 0.55). However, placental parasitemia was strongly associated with hemoglobin C trait (OR = 1.53, 95%CI: 1.09, 2.15, p = 0.01). Our findings demonstrate the distinct relationships that carrier traits have with anemia and malaria, two important predictors of maternal and neonatal outcomes, and suggest that sickle cell trait, but not hemoglobin C trait, is an important risk factor for maternal anemia with the highest risk period observed at delivery.