Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes

James Kapisi,Atis Muehlenbachs,Patricia Awori,Diane V Havlir,Prasanna Jagannathan,Paul Natureeba,Stephanie L Gaw,Tamara D Clark,Richard Ssekitoleko,Peter Olwoch,John Ategeka,Gabrielle Rizzuto,Moses R Kamya,Miriam Nakalembe,Patience Nayebare,Abel Kakuru,Mary K Muhindo,Grant Dorsey

doi:10.1186/s12936-017-2040-4

Abstract

BackgroundMalaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes.MethodsThis is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes. HIV-uninfected pregnant women were enrolled at 12–20 weeks of gestation. Symptomatic malaria during pregnancy was measured using passive surveillance and monthly detection of asymptomatic parasitaemia using loop-mediated isothermal amplification (LAMP). Placental malaria was defined as either the presence of parasites in placental blood by microscopy, detection of parasites in placental blood by LAMP, or histopathologic evidence of parasites or pigment. Adverse birth outcomes assessed included low birth weight (LBW), preterm birth (PTB), and small for gestational age (SGA) infants.ResultsThe 282 women were divided into three groups representing increasing malaria burden during pregnancy. Fifty-two (18.4%) had no episodes of symptomatic malaria or asymptomatic parasitaemia during the pregnancy, 157 (55.7%) had low malaria burden (0–1 episodes of symptomatic malaria and < 50% of samples LAMP+), and 73 (25.9%) had high malaria burden during pregnancy (≥ 2 episodes of symptomatic malaria or ≥ 50% of samples LAMP+). Women with high malaria burden had increased risks of placental malaria by blood microscopy and LAMP [aRR 14.2 (1.80–111.6) and 4.06 (1.73–9.51), respectively], compared to the other two groups combined. Compared with women with no malaria exposure during pregnancy, the risk of placental malaria by histopathology was higher among low and high burden groups [aRR = 3.27 (1.32–8.12) and aRR = 7.07 (2.84–17.6), respectively]. Detection of placental parasites by any method was significantly associated with PTB [aRR 5.64 (1.46–21.8)], and with a trend towards increased risk for LBW and SGA irrespective of the level of malaria burden during pregnancy.ConclusionHigher malaria burden during pregnancy was associated with placental malaria and together with the detection of parasites in the placenta were associated with increased risk for adverse birth outcomes.Trial Registration Current Controlled Trials Identifier NCT02163447

Highlights

Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes
Asymptomatic parasitaemia during pregnancy was detected by loop-mediated isothermal amplification (LAMP) on dried blood spots (DBS) in 230/282 (81.6%) of women; 162/282 (57.4%) had asymptomatic parasitaemia with < 50% of their monthly DBS samples positive for malaria parasites and 68/282 (24.1%) had ≥ 50% of their DBS samples positive for malaria parasites
Three groups representing increasing malaria burden were defined as follows: (1) “none” = women who had no episodes of symptomatic malaria or asymptomatic parasitaemia during pregnancy; (2) “low” = women with 0–1 episode of symptomatic malaria and < 50% of DBS samples positive for parasites by LAMP during pregnancy; and (3) “high” = women who had ≥ 2 episodes of symptomatic malaria or ≥ 50%

Summary

Introduction

Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. Data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes. Malaria in pregnancy remains a major public health problem in many parts of sub-Saharan Africa partly because the coverage of malaria control measures is still low. Placental malaria is associated with adverse birth outcomes such as low birth weight (LBW) and preterm birth (PTB) [4, 5]. 20% of all LBW deliveries in Africa are attributable to malaria in pregnancy, leading to 75,000–200,000 infant deaths annually [2, 6]. Malaria in pregnancy is associated with approximately 36% of all preterm births in endemic regions [3]

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