Does maternal anemia affect fetal neurodevelopment?

A cohort study of more than a half million individuals suggests that maternal anemia in early pregnancy may have a negative impact on a fetus’s neurodevelopment. The findings underscore the importance of ob/gyns performing prenatal screening for iron status and offering nutritional counseling to women as part of antenatal care.

Published in JAMA Psychiatry, the results are by Swedish investigators, who hypothesized that maternal anemia during pregnancy was associated with increased risk of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD) and intellectual disability (ID). Some studies have suggested that giving prenatal iron supplements might protect against ASD in offspring whereas others have shown no consistent association.

The authors used health and population register data from the Stockholm Youth Cohort to evaluate 532,232 nonadoptive children born from January 1, 1987 to December 31, 2010 in Sweden, with follow-up in health registers until December 31, 2016. The main outcomes were registered diagnoses of ASD, ADHD or ID or co-occurring combinations of those disorders.

To assess for potential critical windows of fetal neurodevelopment, the researchers look at whether the anemia was first recorded at ≤ 30 weeks or > 30 weeks. They also compared risk of ASD, ADHD, and ID diagnoses in siblings exposed to anemia versus nonexposed siblings, with adjustment for factors such as sex, birth year, and interpregnancy interval. Covariates controlled for in the individuals exposed to anemia during gestation included size for gestational age, Apgar score, cesarean delivery, and gestational age at birth.

The authors found that prevalence of ASD, ADHD, and ID was significantly higher among children born to mothers diagnosed with anemia within the first 30 weeks of pregnancy (4.9% ASD, 9.3% ADHD, 3.1% ID) compared with mothers diagnosed with anemia later in pregnancy (3.8% ASD, 7.2% ADHD, 1.1% ID) or mothers not diagnosed with anemia (3.5% ASD, 7.1% ADHD, 1.3% ID). Anemia diagnosed during the first 30 weeks of pregnancy but not later was associated with increased risk of diagnosis of ASD (odds ratio [OR], 1.44; 95% CI, 1.13-1.84), ADHD (OR, 1.37; 95% CI, 1.14-1.64) and ID (OR, 2.20; 95% CI, 1.61-3.01) in offspring in models that controlled for socioeconomic, maternal, and pregnancy-related factors.

In the sibling comparison, a similar association was found with risk of ASD and early anemia diagnosis. The strongest association was found between anemia and ID without co-occurring ASD (OR, 2.72; 95% CI, 1.84-4.01) when the authors considered mutually exclusive diagnostic groups.

They researchers hypothesize that the association between maternal anemia in early pregnancy and offspring neurodevelopment disorders may be ascribable to iron deficiency in the developing brain. Iron, they said, is necessary for processes such as myelination and dendrite arborization and synthesis of monoamine neurotransmitters. “Given that iron deficiency and anemia are common among women of childbearing age,” the researchers concluded, “our findings appear to emphasize the importance of early screening for iron status and nutritional counseling in antenatal care.”