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

Background: Iron 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. Objective: Our main objective was to examine if maternal ferritin levels during pregnancy are associated with child cognitive and motor abilities. Methods: We 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. Results: Of 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. Conclusion: High 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.