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Anemia in early, but not late, pregnancy was negatively associated with infant neurodevelopment, according to a Swedish registry study.

Among more than 500,000 children, those whose mothers had anemia within the first 30 weeks of pregnancy had increased risk of autism spectrum disorder (odds ratio 1.44, 95% CI 1.13-1.84), intellectual disability (OR 2.20, 95% CI 1.61-3.01), and attention-deficit hyperactivity disorder (OR 1.37, 95% CI 1.14-1.64) after adjustment for covariates, reported Renee Gardner, PhD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues.

But cases of early anemia occurred in fewer than 1% of women in the study, and children whose mothers were affected by anemia after the first 30 weeks showed no special risk for neurodevelopmental disorders, the researchers wrote in .

"Even though there was a notable increase in risk for neurodevelopmental disorders in this case, this does not mean that every child born to a mother that experienced anemia in pregnancy will go on to have a neurodevelopmental disorder," Gardner stressed in an email, noting that these are "relatively rare disorders."

For example, just 3.1% of children born to women diagnosed with anemia early in pregnancy were diagnosed with an intellectual disability, compared to 1.3% whose mothers were not, she added.

Given that iron is necessary for proper neurodevelopment, it's not surprising that iron deficiency anemia would be linked to adverse neurodevelopmental outcomes, said Rebecca Schmidt, PhD, of the University of California Davis, who was not involved in this study.

What was surprising, however, was how specific the timing of the anemia association was to early pregnancy, Schmidt told 番茄社区 in an email.

This will be important for clinicians to note as more women who become pregnant are obese and thus prone to anemia, she said. It could also be a potential mediating factor explaining why and autism spectrum disorder, she added.

"It would have been interesting to have examined these associations stratified by maternal obesity and age, and child sex, as effect modification by these factors seems biologically plausible," she said. "However, numbers with outcomes and early anemia would have been limited."

For this study, Gardner and her team collected data from the Stockholm Youth Cohort and controlled for disposable income, parental education, whether mothers were born in Sweden or not, maternal body mass index, interpregnancy interval, multiple versus singleton births, and maternal hospitalization for infection.

In total, 532,232 children (51.3% male) born to 299,768 mothers were included. Overall, just 5.8% of mothers were diagnosed with anemia and as noted, the majority of these cases occurred after 30 weeks of pregnancy (91%).

In analyses accounting for overlap within neurodevelopmental disorders, intellectual disability without co-occurring autism spectrum disorder had the strongest association with early maternal anemia (OR 2.72, 95% CI 1.84-4.01), the authors reported.

Women were more likely to develop anemia if they were overweight, obese, older than 40, had a psychiatric history, had multiple births, and who were hospitalized for infection during pregnancy. Women were specifically more likely to develop early anemia if they were less educated, less wealthy, underweight, and younger.

Adverse outcomes during pregnancy accounted for a "modest proportion" of the association between maternal anemia and risk for neurodevelopmental disorders in a mediation analysis, with preterm birth accounting for one-third of the association between early anemia in pregnancy and risk for autism spectrum disorder (28%), ADHD (33%), and intellectual disability (32%), the authors reported.

"While it's possible that a lack of iron or other nutrients for a longer period of time during pregnancy directly influences the development of the brain on a molecular level, we also saw some evidence that the complications associated with earlier anemia, such as preterm birth and pre-eclampsia, could explain some of the increased risks that we observed," Gardner said.

They also conducted a sensitivity analysis to account for the possibility of shared genetic liability for neurodevelopmental disorders and found early anemia to be associated with increased risk for autism spectrum disorder (OR 2.25, 95% CI 1.24-4.11) and intellectual disability (OR 2.58, 95% CI 1.08-6.22), although there were a limited number of sibling pairs in this analysis, they reported.

The results could be affected by residual confounding: for example, other dietary deficiencies associated with anemia could influence the association, the authors noted. (Diet composition was not addressed in the study.) Also, many infections do not require hospitalization, so Gardner and colleagues could not account for all infections occurring during pregnancy, they added. Lastly, the timing and effectiveness of treatment for anemia that occurred in pregnancy were unknown.

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