The effect of maternal malaria during pregnancy on birth size, early childhood growth and blood pressure in Nigerian children

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Abstract

Background: In Nigeria, there is an escalating incidence of hypertension, its complications and other cardiovascular risks, likely to have their origins in early life. Malaria is still hyperendemic, with pregnant women at increased risk, with associated consequences of maternal anemia and high rates of delivering low birth-weight babies. Aims and Hypothesis: In this study, we have tested the hypothesis that malaria in pregnancy will not only enhance the risk of small birth size and poor infant growth, but will also generate higher blood pressures in infancy and beyond. We also tested the hypothesis that metabolic markers in pregnant mothers affected by malaria would relate to infant birth size. Thus the aims of this project were: 1) to define relationships between the type of malaria exposure and birth size, 2) to characterize the association between maternal and cord metabolic biomarkers and birth size on the background of prenatal malaria exposure and 3) to examine the effect prenatal malaria exposure on first year growth and whether higher blood pressure (BP) is generated.Methods: Healthy pregnant women were recruited and followed at Adeoyo Maternity Hospital, Ibadan. Anthropometric, BP, and biomarkers (lipids, glucose, insulin and TNFα) measurements were obtained in the mothers at booking. Birth size and growth at 3 and 12 months along with biomarkers (as above) and IGF-I measures in cord blood were assessed in the infants. Blood films for malaria parasites were taken throughout pregnancy including delivery and in all babies. Women were grouped to distinguish between the timing of malaria parasitaemia (either during pregnancy only or during pregnancy and at delivery) and the severity of malaria infection (low vs high parasite load). At birth, 436 mother-baby pairs were measured. 467 maternal samples were obtained for metabolic profile and 187 cord blood samples. 318 babies were all followed from birth to 3 and 12 months. Results: Malaria parasitaemia was found in 48% of the women, associated with younger maternal age, being primigravid and a lower haematocrit. Babies of mothers with high parasitaemia through pregnancy had the smallest birth growth parameters compared with those without malaria (weight, length, and head circumference were smaller by 300g, 1.1cm and 0.7cm respectively, all p≤0.005) but their systolic BP (SBP) and diastolic BP (DBP) adjusted for weight were higher than those with low parasitaemia by 1.7 and 1.4 mmHg/kg respectively. SBPs were lowest in babies of mothers with malaria at delivery implying an acute effect on the babies’ circulation. Mothers with malaria had significantly lower lipids (except triglycerides) but higher TNFa, effect not seen in cord blood. Cord IGF-I was significantly lower in babies whose mothers had malaria. Significant determinants of birth size were maternal total cholesterol, LDL- cholesterol, insulin, malarial status and cord insulin and IGF-I. Babies exposed to maternal malaria remained smaller at 1 year, most marked in boys, whose SBP adjusted for weight at 3 and 12 months was higher than those not exposed. Change in SBP over the first year was greater in boys than girls while the change in girls was greater in those exposed to maternal malaria than those not exposed (18.7 vs 12.7 mmHg, 95% CI 1-11, p=0.02). 11% of boys (>twice expected) had BP >95th percentile (hypertensive, US criteria) of whom 68% had maternal malaria exposure. Gender, maternal malaria exposure and weight change were all independently associated with increased change in BP to 1 year.Conclusion: Intrauterine exposure to malaria appears not only to have an important impact on birth size but also gender-dependent effects on growth and changes in infant BP. These findings have potential implications for cardiovascular health in sub-Saharan Africa and may contribute to the global burden of hypertension.

Keyword(s)

prenatal malaria exposure, birth size, early growth, blood pressure ; • cord IGF-I, cord insulin, maternal lipids in pregnancy, change in blood pressure over first year of life

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