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 : Our aim 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 parasitemia 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. We performed subgroup analysis 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 2-fold 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 Plasmodium 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 associated with placental malaria, whereas in multigravidas, parasitemias 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.

Placental Malaria

“…On the other hand, compared with primigravid women, multigravid women had higher levels of IL-27 and IL-28A that induce secretion of protective cytokines against malaria [ 24 ]. The influence of timing of infection changes according to gravidity, as primigravidas with early asymptomatic infection and contrarily multigravidas experiencing parasitemia later in pregnancy have higher rates of placental malaria [ 25 ]. Other than these, a study in Sudan proposed the carriage of female fetus as a novel risk factor for placental malaria [ 26 ].…”

“…Recent studies of pregnant women with and without placental malaria demonstrated that placental malaria had a significant association with low birth weight (< 2500 g) (relative risk (RR) 3.45, 95% CI 1.44–8.23, p = 0.005; adjusted relative risk (aRR) 3.42, p = 0.02), preterm birth (RR 7.52, 95% confidence interval (CI) 1.72–32.8, p = 0.007), small for gestational age (RR 2.30, 95% CI 1.10–4.80, p = 0.03; aRR 4.24, p < 0.001), stillbirth (odds ratio (OR) 1.95, 95% CI 1.48–2.57), and higher rates maternal anemia (aOR 2.22, 95% CI 1.02–4.84; p = 0.045) [ 16 •, 49 •, 50 •, 51 •], confirming that the pathological process occurring in the placenta is the likely source of these adverse obstetrical outcomes (Table 1 ). Longitudinal studies of malaria during pregnancy suggest that the total number of infections over pregnancy, and the parasitemia burden (measured by quantitative PCR), have the greatest association with placental malaria [ 25 , 52 ]. The impact on timing of infections during pregnancy on the development of placental malaria is dependent on maternal gravidity, with earlier infections having a greater impact in primigravidas compared with later infections in multigravidas [ 25 ].…”

“…Longitudinal studies of malaria during pregnancy suggest that the total number of infections over pregnancy, and the parasitemia burden (measured by quantitative PCR), have the greatest association with placental malaria [ 25 , 52 ]. The impact on timing of infections during pregnancy on the development of placental malaria is dependent on maternal gravidity, with earlier infections having a greater impact in primigravidas compared with later infections in multigravidas [ 25 ].…”

Risk Factors for Placental Malaria, Sulfadoxine-pyrimethamine Doses, and Birth Outcomes in a Rural to Urban Prospective Cohort Study on the Bandiagara Escarpment and Bamako, Mali

“…We replicated this nding for active and past PM infections only if maternal age and year of birth, which are associated with gravidity (SI Figure 2), were not included in the model (SI Table 1). It has been reported that the timing of malaria infection during pregnancy differentially impacts primigravid and multigravid women [33], but we cannot assess this possibility in our study as we did not collect data on the timing of infection.…”

Assessing the relationship between gravidity and placental malaria among pregnant women in a high transmission area in Ghana

“…Globally, malaria infection affects approximately 11 million pregnancies-predominantly in the sub-Saharan African region, and up to 100,000 infant deaths are attributed to PM every year [6]. In regions of low-transmission, levels of acquired immunity to malaria tend to be low, and all pregnant women are vulnerable to malaria, which is often symptomatic [1].…”