Background: Malaria in pregnancy remains a significant public health challenge, particularly in sub-Saharan Africa (SSA), where it contributes to maternal anemia, low birthweight (LBW), preterm birth (PTB), and neonatal mortality. With increasing resistance to sulfadoxine-pyrimethamine (SP), the World Health Organization (WHO)-recommended intermittent preventive treatment during pregnancy (IPTp) strategy faces declining efficacy. Dihydroartemisinin-piperaquine (DHA-PQ) has emerged as a promising alternative, but its impact on broader perinatal outcomes remains unclear.

Objective: This systematic review and meta-analysis evaluate the comparative effectiveness of IPTp-DHA-PQ and IPTp-SP in preventing malaria-related adverse pregnancy outcomes, aiming to guide clinical practice and policy updates in malaria-endemic regions.

Methods: A systematic search of PubMed, EMBASE, Cochrane Library, and LILACS was conducted to identify randomized controlled trials (RCTs) comparing IPTp-DHA-PQ to IPTp-SP. Outcomes included placental malaria, Low birth weight (<2500 g), fetal loss (still birth and spontaneous abortion), Pre Term Birth (<37 weeks), neonatal death (0–28 days), and fetal anemia (Hb <11 g/dL) . Data were pooled using a random-effects meta-analysis, with odds ratios (OR) and 95% confidence intervals (CI) reported. Risk of bias was assessed using Cochrane methods, and heterogeneity was evaluated using the I² statistic.

Results: Seven RCTs involving 8,080 participants were included. DHA-PQ significantly reduced the incidence of placental malaria compared to SP (OR: 0.51, 95% CI: 0.30–0.87), demonstrating superior efficacy against malaria-specific endpoints. However, no significant differences were observed between DHA-PQ and SP for LBW, PTB, fetal loss, or neonatal deaths. Both regimens were well-tolerated, with minimal adverse effects reported.

Conclusions: DHA-PQ effectively prevents placental malaria, particularly in regions with high SP resistance, while showing comparable outcomes to SP for broader pregnancy complications. These findings support its use as an alternative to SP and highlight the need for integration into holistic antenatal care strategies to improve pregnancy outcomes in malaria-endemic regions, informing potential updates to WHO guidelines.

Keywords:
Malaria in pregnancy, IPTp, sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, adverse pregnancy outcomes, sub-Saharan Africa.