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Maternal early-pregnancy ferritin and offspring neurodevelopment: A prospective cohort study from gestation to school
Sara Sammallahti1, Henning Tiemeier1,2, Irwin K M Reiss3
1Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, Sophia Children's Hospital, Rotterdam, Netherlands.
Insights
High maternal ferritin during pregnancy is linked to lower child IQ and smaller brain volume. This suggests maternal iron status impacts offspring neurodevelopment.
Area of Science:
- Neuroscience
- Developmental Biology
- Public Health
Background:
- Iron is crucial for developing brain functions.
- Maternal iron deficiency during pregnancy is common, but high iron levels (ferritin) and their impact on offspring are less understood.
- Evidence linking maternal ferritin levels to child neurodevelopmental outcomes is limited.
Purpose of the Study:
- To investigate the association between maternal ferritin levels in early pregnancy and cognitive and motor abilities in offspring.
- To explore the relationship between maternal ferritin and offspring brain morphology.
Main Methods:
- Prospective study of Dutch mother-child dyads (Generation R Study).
- Maternal ferritin levels categorized as low, intermediate, or high.
- Child neurodevelopment assessed via cognitive tests (IQ, language) and motor tests (finger-tapping, balancing) at ages 4-12 years.
- Brain morphology analyzed using structural magnetic resonance imaging.
Main Results:
- High maternal ferritin was associated with a lower child IQ (2.54 points decrease) and smaller brain volume (16.02 cm³ decrease).
- Low maternal ferritin showed no association with cognitive abilities.
- Maternal ferritin levels were not linked to child motor outcomes.
Conclusions:
- Elevated maternal ferritin levels during pregnancy may negatively impact offspring cognitive development and brain structure.
- Maternal iron status during pregnancy is a potential factor influencing neurodevelopmental trajectories.
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.
