Abstract
BackgroundPlacental malaria is associated with increased risk of adverse perinatal outcomes. While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria.MethodsThe aim of this study was to investigate the relationship between the development of placental malaria and gravidity, timing of infection, and presence of symptoms. This is a secondary analysis of data from a double-blind randomized control trial of intermittent preventive therapy during pregnancy in Uganda. Women were enrolled from 12 to 20 weeks gestation and followed through delivery. Exposure to malaria parasites was defined as symptomatic (fever with positive blood smear) or asymptomatic (based on molecular detection of parasitaemia done routinely every 4 weeks). The primary outcome was placental malaria diagnosed by histopathology, placental blood smear, and/or placental blood loop-mediated isothermal amplification. Multivariate analyses were performed using logistic regression models. Subgroup analysis was performed based on the presence of symptomatic malaria, gravidity, and timing of infection.ResultsOf the 228 patients with documented maternal infection with malaria parasites during pregnancy, 101 (44.3%) had placental malaria. Primigravidity was strongly associated with placental malaria (aOR 8.90, 95% CI 4.34–18.2, p < 0.001), and each episode of malaria was associated with over a twofold increase in placental malaria (aOR 2.35, 95% CI 1.69–3.26, p < 0.001). Among multigravid women, the odds of placental malaria increased by 14% with each advancing week of gestation at first documented infection (aOR 1.14, 95% CI 1.02–1.27, p = 0.02). When stratified by the presence of symptoms, primigravidity was only associated with placental malaria in asymptomatic women, who had a 12-fold increase in the odds of placental malaria (aOR 12.19, 95% CI 5.23–28.43, p < 0.001).ConclusionsTotal number of P. falciparum infections in pregnancy is a significant predictor of placental malaria. The importance of timing of infection on the development of placental malaria varies based on gravidity. In primigravidas, earlier asymptomatic infections were more frequently identified in those with placental malaria, whereas in multigravidas, parasitaemias detected later in gestation were associated with placental malaria. Earlier initiation of an effective intermittent preventive therapy may help to prevent placental malaria and improve birth outcomes, particularly in primigravid women.
Highlights
Placental malaria is associated with increased risk of adverse perinatal outcomes
A prior analysis of this study cohort found that placental malaria was more likely in women with high malaria burden (defined as ≥ 2 episodes of symptomatic malaria or ≥ 50% positive loop-mediated isothermal amplification (LAMP) samples) and was associated with increased rates of preterm birth and a trend towards higher rates of small for gestational age (SGA) neonates [10]
Primigravidity was strongly associated with placental malaria in women whose initial documented infection occurred prior to 14 weeks, as well as in women whose first infection occurred between 14 and 19.9 weeks
Summary
While primigravidity has been reported as a risk factor for placental malaria, little is known regarding the relationship between gravidity, symptomatology and timing of Plasmodium falciparum infection and the development of placental malaria. Infection with malaria parasites during pregnancy is associated with increased risk of maternal and neonatal morbidity and mortality. Placental malaria has been associated with increased risks of adverse obstetric outcomes including maternal anaemia, preterm delivery, fetal growth restriction, low birth weight, and maternal and neonatal mortality [5,6,7]. Previous studies have shown that primigravidity is a risk factor for placental malaria and resulting obstetric morbidity [8, 9]. Little is known about whether the effect of gravidity on placental malaria varies by timing and symptomatology of P. falciparum. The main objective of this study was to assess whether the impact of gravidity on placental malaria varies by the presence of symptoms and/or timing of infection
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