31851
Prenatal Anemia and Neurodevelopmental Disorders in the Stockholm Youth Cohort: A Population-Based Cohort Study
Autism spectrum disorders (ASD) often co-occur with attention deficit hyperactivity disorder (ADHD) and intellectual disability (ID), potentially as a result of shared etiologies. Given the critical role iron plays in development, a causal association between prenatal iron deficiency and later risk for neurodevelopmental disorders like ASD, ADHD, and ID is plausible.
Objectives:
The objective of this study was to assess the relationship between anemia diagnosed in mothers during pregnancy and risk of ASD, ADHD, and ID in offspring.
Methods:
Swedish health and population registry data from the Stockholm Youth Cohort (SYC) were used. 532 232 children born 1987 – 2010 were included. To assess potential critical windows of development, timing of anemia diagnosis was considered, categorized as occurring £30 or >30 weeks of gestation. We considered three potentially over-lapping outcomes (any ASD, any ADHD, and any ID) and five mutually-exclusive outcomes: ASD only (no ADHD or ID); ADHD only (no ASD or ID); ID without ASD (no ASD; not excluding ADHD); ASD with ID (not excluding ADHD); and ASD with ADHD (no ID). To model the associations between maternal anemia and offspring risk of these outcomes, we used generalized estimating equation (GEE) models with logit link clustered on maternal identification number to account for the clustering of siblings born to the same mother in our dataset. Since associations between maternal anemia and offspring risk of neurodevelopmental disorders may be confounded by unobserved factors such as shared genetic liability, we conducted a matched sibling analysis for risk of any ASD, any ADHD and any ID diagnoses using a conditional logistic regression model.
Results:
Anemia diagnosed £30 weeks of pregnancy was associated with increased risk for diagnosis of any ASD (OR 1.44, 95% CI 1.13-1.84), any ADHD (1.37, 1.14-1.64) and any ID (2.20, 1.61-3.01) in offspring, in models including socioeconomic, maternal and pregnancy-related factors. Early anemia diagnosis was similarly associated with risk for both ASD (2.25, 1.24-4.11) and ID (2.59, 1.08-6.22) in a matched sibling comparison. Considering mutually exclusive diagnostic groups, we observed the strongest association between anemia and ID without co-occurring ASD (2.72, 1.84-4.01). Risk for ASD with ID was also associated with anemia diagnosed early in pregnancy (1.74, 1.06-2.86), while the associations for ASD with ADHD (1.38, 0.94-2.03) and ASD only (1.35, 0.92-2.00) were weaker and confidence intervals included one. Associations of these disorders with anemia diagnosed later in pregnancy were greatly diminished compared to the associations with anemia diagnosed earlier in pregnancy.
Conclusions: In contrast to maternal anemia diagnosed towards the end of pregnancy, anemia diagnosed earlier in pregnancy increased the risk for the development of ASD, ADHD, and particularly ID in offspring. Our findings regarding the timing of exposure to anemia indicate that exposure to anemia earlier in gestation may be more detrimental with regard to neurodevelopment of the child, emphasizing the clinical importance of early screening for iron status in antenatal care.