Abstract

Malaria infection in pregnancy is a major source of adverse obstetric outcomes in malaria-endemic areas. Our aim was to determine if placental malaria (PM) infection results in worse obstetric outcomes than non-placental malaria infection in pregnancy and to identify risk factors for placental infection. Nested case-control study from a prospective, double-blind randomized control trial of intermittent preventive therapy (IPTp) during pregnancy in Uganda. Women were enrolled from June to October 2014 at 12 to 20 weeks gestational age (GA) and followed through delivery. Malaria exposure was defined as symptomatic infection with confirmatory blood smear or laboratory evidence of malaria infection by loop-mediated isothermal amplification (LAMP), which was performed monthly and at delivery. PM was defined as presence of parasites or pigment on histopathology, parasites on placental blood smear, or positive placental blood LAMP. Cases included malaria-exposed pregnancies with PM. Controls were defined as malaria exposure without PM. Wilcoxon Rank Sum and Fisher exact tests were used to compare continuous and categorical variables respectively. Logistic regression was used for multivariate analysis. Of the 241 patients with malaria exposure in pregnancy, 134 (55.6%) had no evidence of PM and 107 (44.4%) had PM. Median GA at delivery was earlier in the PM group (39.3 ± 2.3wk vs. 40.0 ± 2.0wk, p<0.01) and there was increased incidence of low birth weight <2500g (18.9% versus 7.2%, p=0.01). There was no significant difference in mode of delivery, type of IPTp received, hematologic abnormalities at delivery, pregnancy loss, small for GA infants, or 5 min APGAR score <7. In multivariate analysis, odds of PM were significantly increased in primigravidas (OR 4.3, 95% CI 2.0-9.1, p<0.001) and in women who initiated IPTp after 16 weeks GA (OR 2.4, 95% CI 1.23-4.76, p=0.01). For every year increase in maternal age, the odds of PM decreased by 10% (OR 0.9, 95% CI 0.8-0.98, p=0.02). PM was associated with a 4-fold increase in preterm delivery (OR 4.7, 95% CI 1.28-17.5, p=0.02). PM is most likely to occur in primigravidas and young women and is associated with significantly increased risk of preterm delivery as compared to malaria without placental infection. Early initiation of IPTp prior to 16 weeks GA reduces the risk of PM.

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