Malaria prevention in pregnancy, birthweight, and neonatal
mortality: a meta-analysis of 32 national cross-sectional
datasets in Africa
mortality: a meta-analysis of 32 national cross-sectional
datasets in Africa
Thomas P Eisele, David A Larsen, Philip A Anglewicz, Joseph Keating, Josh Yukich, Adam Bennett, Paul Hutchinson, Richard W Steketee
Summary
Background Low birthweight is a signifi cant risk factor for neonatal and infant death. A prominent cause of low
birthweight is infection with Plasmodium falciparum during pregnancy. Antimalarial intermittent preventive therapy
in pregnancy (IPTp) and insecticide-treated mosquito nets (ITNs) signifi cantly reduce the risk of low birthweight in
regions of stable malaria transmission. We aimed to assess the eff ectiveness of malaria prevention in pregnancy
(IPTp or ITNs) at preventing low birthweight and neonatal mortality under routine programme conditions in malaria
endemic countries of Africa.
Methods We used a retrospective birth cohort from national cross-sectional datasets in 25 African countries from
2000–10. We used all available datasets from multiple indicator cluster surveys, demographic and health surveys,
malaria indicator surveys, and AIDS indicator surveys that were publically available as of 2011. We tried to limit
confounding bias through exact matching on potential confounding factors associated with both exposure to malaria
prevention (ITNs or IPTp with sulfadoxine–pyrimethamine) in pregnancy and birth outcomes, including local malaria
transmission, neonatal tetanus vaccination, maternal age and education, and household wealth. We used a logistic
regression model to test for associations between malaria prevention in pregnancy and low birthweight, and a Poisson
model for the outcome of neonatal mortality. Both models incorporated the matched strata as a random eff ect, while
accounting for additional potential confounding factors with fi xed eff ect covariates.
Findings We analysed 32 national cross-sectional datasets. Exposure of women in their fi rst or second pregnancy to full
malaria prevention with IPTp or ITNs was signifi cantly associated with decreased risk of neonatal mortality (protective
effi cacy [PE] 18%, 95% CI 4–30; incidence rate ratio [IRR] 0·820, 95% CI 0·698–0·962), compared with newborn
babies of mothers with no protection, after exact matching and controlling for potential confounding factors. Compared
with women with no protection, exposure of pregnant women during their fi rst two pregnancies to full malaria
prevention in pregnancy through IPTp or ITNs was signifi cantly associated with reduced odds of low birthweight
(PE 21%, 14–27; IRR 0·792, 0·732–0·857), as measured by a combination of weight and birth size perceived by the
mother, after exact matching and controlling for potential confounding factors.
Interpretation Malaria prevention in pregnancy is associated with substantial reductions in neonatal mortality and
low birthweight under routine malaria control programme conditions. Malaria control programmes should strive to
achieve full protection in pregnant women by both IPTp and ITNs to maximise their benefi ts. Despite an attempt to
mitigate bias and potential confounding by matching women on factors thought to be associated with access to
malaria prevention in pregnancy and birth outcomes, some level of confounding bias possibly remains.
Summary
Background Low birthweight is a signifi cant risk factor for neonatal and infant death. A prominent cause of low
birthweight is infection with Plasmodium falciparum during pregnancy. Antimalarial intermittent preventive therapy
in pregnancy (IPTp) and insecticide-treated mosquito nets (ITNs) signifi cantly reduce the risk of low birthweight in
regions of stable malaria transmission. We aimed to assess the eff ectiveness of malaria prevention in pregnancy
(IPTp or ITNs) at preventing low birthweight and neonatal mortality under routine programme conditions in malaria
endemic countries of Africa.
Methods We used a retrospective birth cohort from national cross-sectional datasets in 25 African countries from
2000–10. We used all available datasets from multiple indicator cluster surveys, demographic and health surveys,
malaria indicator surveys, and AIDS indicator surveys that were publically available as of 2011. We tried to limit
confounding bias through exact matching on potential confounding factors associated with both exposure to malaria
prevention (ITNs or IPTp with sulfadoxine–pyrimethamine) in pregnancy and birth outcomes, including local malaria
transmission, neonatal tetanus vaccination, maternal age and education, and household wealth. We used a logistic
regression model to test for associations between malaria prevention in pregnancy and low birthweight, and a Poisson
model for the outcome of neonatal mortality. Both models incorporated the matched strata as a random eff ect, while
accounting for additional potential confounding factors with fi xed eff ect covariates.
Findings We analysed 32 national cross-sectional datasets. Exposure of women in their fi rst or second pregnancy to full
malaria prevention with IPTp or ITNs was signifi cantly associated with decreased risk of neonatal mortality (protective
effi cacy [PE] 18%, 95% CI 4–30; incidence rate ratio [IRR] 0·820, 95% CI 0·698–0·962), compared with newborn
babies of mothers with no protection, after exact matching and controlling for potential confounding factors. Compared
with women with no protection, exposure of pregnant women during their fi rst two pregnancies to full malaria
prevention in pregnancy through IPTp or ITNs was signifi cantly associated with reduced odds of low birthweight
(PE 21%, 14–27; IRR 0·792, 0·732–0·857), as measured by a combination of weight and birth size perceived by the
mother, after exact matching and controlling for potential confounding factors.
Interpretation Malaria prevention in pregnancy is associated with substantial reductions in neonatal mortality and
low birthweight under routine malaria control programme conditions. Malaria control programmes should strive to
achieve full protection in pregnant women by both IPTp and ITNs to maximise their benefi ts. Despite an attempt to
mitigate bias and potential confounding by matching women on factors thought to be associated with access to
malaria prevention in pregnancy and birth outcomes, some level of confounding bias possibly remains.
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