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According to the World Health Organization (WHO), in 2018, an estimated 228 million malaria cases occurred worldwide with most cases occurring in sub-Saharan Africa. Scale-up of vector control tools coupled with increased access to diagnosis and effective treatment has resulted in a large decline in malaria prevalence in some areas, but other areas have seen little change. Although interventional studies demonstrate that preventing malaria during pregnancy can reduce the rate of low birth weight (i.e. child’s birth weight &lt;2500 g), it remains unknown whether natural changes in parasite transmission and malaria burden can improve birth outcomes. We conducted an observational study of the effect of changing malaria burden on low birth weight using data from 18,112 births in 19 countries in sub-Saharan African countries during the years 2000–2015. Specifically, we conducted a difference-in-differences study via a pair-of-pairs matching approach using the fact that some sub-Saharan areas experienced sharp drops in malaria prevalence and some experienced little change. A malaria prevalence decline from a high rate ( Plasmodium falciparum  parasite rate in children aged 2-up-to-10 (i.e. PfPR 2-10 ) &gt; 0.4) to a low rate (PfPR 2-10  &lt; 0.2) is estimated to reduce the rate of low birth weight by 1.48 percentage points (95% confidence interval: 3.70 percentage points reduction, 0.74 percentage points increase), which is a 17% reduction in the low birth weight rate compared to the average (8.6%) in our study population with observed birth weight records (1.48/8.6 ≈ 17%). When focusing on first pregnancies, a decline in malaria prevalence from high to low is estimated to have a greater impact on the low birth weight rate than for all births: 3.73 percentage points (95% confidence interval: 9.11 percentage points reduction, 1.64 percentage points increase). Although the confidence intervals cannot rule out the possibility of no effect at the 95% confidence level, the concurrence between our primary analysis, secondary analyses, and sensitivity analyses, and the magnitude of the effect size, contribute to the weight of the evidence suggesting that declining malaria burden can potentially substantially reduce the low birth weight rate at the community level in sub-Saharan Africa, particularly among firstborns. The novel statistical methodology developed in this article–a pair-of-pairs approach to a difference-in-differences study–could be useful for many settings in which different units are observed at different times. Ryan A. Simmons is supported by National Center for Advancing Translational Sciences (UL1TR002553). The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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Relationship between changing malaria burden and low birth weight in sub-Saharan Africa: A difference-in-differences study via a pair-of-pairs approach