Maternal early-pregnancy ferritin and offspring neurodevelopment: A prospective cohort study from gestation to school age.

Abstract

BackgroundIron plays a role in many key processes in the developing brain. During pregnancy, iron supplementation is widely recommended to prevent and treat iron deficiency; however, the prevalence of iron deficiency and the risk of iron overload vary greatly between populations. Evidence on the role of high levels of maternal ferritin, a storage iron marker during pregnancy in relation to offspring neurodevelopment is lacking.ObjectiveOur main objective was to examine if maternal ferritin levels during pregnancy are associated with child cognitive and motor abilities.MethodsWe included Dutch mother‐child dyads from the prospective population‐based Generation R Study, born in 2002–2006. We compared children whose mothers had high (standard deviation score >+1) or low (standard deviation score <−1) early‐pregnancy ferritin to children whose mothers had intermediate ferritin (reference group) using linear regression. Children underwent non‐verbal intelligence and language tests at 4–9 years (cognitive abilities), finger‐tapping and balancing tests at 8–12 years (motor abilities), and structural magnetic resonance imaging at 8–12 years (brain morphology). Covariates were child age, sex, maternal intelligence quotient estimate, age, body‐mass‐index, education, parity, smoking and alcohol use.ResultsOf the 2479 mother‐child dyads with data on maternal ferritin and at least one child neurodevelopmental outcome, 387 mothers had low (mean = 20.6 µg/L), 1700 intermediate (mean = 64.6 µg/L) and 392 high (mean = 170.3 µg/L) early‐pregnancy ferritin. High maternal ferritin was associated with 2.54 points (95% confidence interval ‐4.16, ‐0.92) lower child intelligence quotient and 16.02 cm3 (95% confidence interval ‐30.57, ‐1.48) smaller brain volume. Results remained similar after excluding mothers with high C‐reactive protein. Low maternal ferritin was not associated with child cognitive abilities. Maternal ferritin was unrelated to child motor outcomes.ConclusionHigh maternal ferritin during pregnancy was associated with poorer child cognitive abilities and smaller brain volume. Maternal iron status during pregnancy may be associated with offspring neurodevelopment.