Placental malaria: a systematic review and meta-analysis of global burden, risk factors, and maternal and foetal outcomes.

Background: Pregnant women in malaria-endemic countries are at risk of placental malaria (PM), which can lead to adverse outcomes for both mothers and children. Histology of placental tissue is the gold standard for diagnosing PM, as it can detect current and past infections. Prior reviews focussed on malaria in pregnancy generally; in this systematic review, we specifically examine PM due to Plasmodium falciparum, its associated risk factors, and its impact on maternal and foetal outcomes. Methods: We included studies performed since 2013, reflecting important updates in WHO policy recommendations for PM control efforts and resistance to sufadoxine-primethamine resistance over the past decade. After extracting relevant data, we calculated the pooled prevalence, odds ratios (ORs), and risk ratios. We assessed the quality of the included studies using the Newcastle-Ottawa scale. Results: The review included 50 studies, 45 of which were from sub-Saharan Africa (SSA), with 15 (33%) of them using histological diagnosis. Global PM prevalence was 17% (95% confidence interval (CI) = 12-21), rising to 23% (95% CI = 1-4) in histology-based studies. Prevalence was higher in SSA (19%; 95% CI = 14-24) than in other regions (4%; 95% CI = 1-9), with West Africa showing the highest rates. One study including only HIV-positive women reported a PM prevalence of 45% (95% CI = 38-52) compared to 17% (95% CI = 10-25) in HIV-negative women. One study on stillbirth showed an OR of 3.81 (95% CI = 1.22-11.94) and primigravidae had pooled ORs of 1.61 (95% CI = 0.91-2.84) compared to multigravidae. The ORs and CIs for congenital malaria, malaria in infancy, preterm birth, and low birth weight were wide, indicating imprecision. Conclusions: Our meta-analysis reveals a high PM burden in high- malaria transmission areas, especially among primigravidae and HIV-positive women. We note that PM remains high in SSA, with regional variation, with one in four pregnant women diagnosed by histological examination of the placenta, reflecting both current and past PM exposure. Reliance on non-histological methods may lead to underestimation of true PM prevalence. Due to wide confidence intervals and limited data, we could draw no conclusions on the impact of PM on maternal and foetal outcomes. Residual high heterogeneity reflects real-world diversity across populations, strengthening the generalisability of our findings.