The impact of gravidity, symptomatology and timing of infection on placental malaria

Abstract

Background: Placental 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.

Methods: The 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.

Results: Of 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).

Conclusions: Total 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.

Keywords: Africa; Global health; Infectious disease; Obstetrics; Perinatal outcome; Plasmodium falciparum; Pregnancy; Primigravid.

Fig. 1

Flowchart of study participants. This figure displays the process for selecting study participants and the number of participants excluded in each category. SP sulfadoxine-pyrimethamine, LAMP loop-mediated isothermal amplification

Fig. 2

Number of placental malaria infections diagnosed by each method. The yellow circle holds women diagnosed by placental histopathology. The blue circle indicates diagnosis via placental blood microscopy, and the green circle represents diagnosis via placental blood LAMP

Fig. 3

Timing of infection by malaria status and gravidity. a Shows the number (label) and percent of the total cohort (y-axis) of women whose initial documented infection occurred within each gestational age category separated for individuals with no placental malaria (black) and placental malaria (grey). b presents these data on initial symptomatic infection among symptomatic women. c Presents data for primigravid women only, while d presents data for multigravid women only. p-values are two-way and calculated with Chi squared analysis

Fig. 4

Frequency of infection by malaria status and gravidity. a Shows the frequency of malaria infection by malaria status (no placental malaria versus placental malaria) for all women. b Shows these data for primigravid women, while c shows these data for multigravida women. Each triangle represents one woman. Mean and 95% CI are represented with error bars. p values are two-way and calculated with Chi squared analysis