The Effects of Malaria in Pregnancy on Neurocognitive Development in Children at 1 and 6 Years of Age in Benin: A Prospective Mother-Child Cohort

Abstract

Background: Malaria in pregnancy (MiP) contributes significantly to infant mortality rates in sub-Saharan Africa and has consequences on survivors, such as preterm birth and low birth weight. However, its impact on long-term neurocognitive development in children remains unknown.

Methods: Our prospective cohort included pregnant women and their live-born singletons from the Malaria in Pregnancy Preventive Alternative Drugs clinical trial. MiP was assessed using microscopy and real-time quantitative polymerase chain reaction (qPCR). Neurocognitive development in children was assessed using the Mullen Scales of Early Learning and the Kaufman Assessment Battery for Children, 2nd edition (KABC-II), at 1 and 6 years of age, respectively.

Results: Of 493 pregnant women, 196 (40%) were infected with malaria at least once: 121 (31%) with placental malaria diagnosed by qPCR. Multiple linear regression B-coefficients showed that impaired gross motor scores were associated with MiP at least once (-2.55; confidence interval [95% CI]: -5.15, 0.05), placental malaria by qPCR (-4.95; 95% CI: -7.65, -2.24), and high parasite density at delivery (-1.92; 95% CI: -3.86, 0.02) after adjustment. Malaria and high parasite density at the second antenatal care visit were associated with lower KABC-II Non-Verbal Index scores at 6 years (-2.57 [95% CI: -4.86, -0.28] and -1.91 [-3.51, -0.32]), respectively.

Conclusions: This prospective cohort study provides evidence that MiP, particularly late term, could have important negative consequences on child development at 1 and 6 years of age. Mechanisms behind this association must be further investigated and diagnostic methods in low-income countries should be strengthened to provide adequate treatment.

Clinical trials registration: NCT00811421.

Keywords: child development; malaria; neurocognition; pregnancy; sub-Saharan Africa.

Figure 1.

Population follow-up of women and children from pregnancy until 6 years of age. Abbreviations: APEC, Anemia in Pregnancy: Etiologies and Consequences; MiPPAD, Malaria in Pregnancy Preventive Alternative Drugs.

Figure 2.

Linear regression B-coefficients and confidence intervals of association between MiP and child neurocognitive development at 1 year of age. White diamond, unadjusted B-coefficients and 95% bootstrapped confidence intervals. Black diamond, adjusted B-coefficients and 95% bootstrapped confidence intervals; controlling for maternal age and education, gravidity, prepregnancy BMI, family possession score, HOME score, and child sex and age at time of neurocognitive assessment. Abbreviations: ANV, antenatal visit; BMI, body mass index; HOME, Home Observation for Measurement of the Environment; MiP, malaria in pregnancy; qPCR, quantitative polymerase chain reaction.

Figure 3.

Linear regression B-coefficients and confidence intervals of association between MiP and child neurocognitive development at 6 years of age. White diamond, unadjusted B-coefficients and 95% bootstrapped confidence intervals. Black diamond, adjusted B-coefficients and 95% bootstrapped confidence intervals; controlling for maternal age and education, gravidity, prepregnancy BMI, family possession score, HOME score, and child sex and age at time of neurocognitive assessment. Abbreviations: ANV, antenatal visit; BMI, body mass index; HOME, Home Observation for Measurement of the Environment; KABC-II, Kaufman Assessment Battery for Children, 2nd edition; MiP, malaria in pregnancy; qPCR, quantitative polymerase chain reaction.