Maternal thyroid disease as a risk factor for craniosynostosis.

OBJECTIVE: To study the relationship between maternal thyroid disease and craniosynostosis using data from the National Birth Defects Prevention Study, a multisite, case-control study.
METHODS: Case infants (n=431) were identified through population-based birth defects surveillance systems at eight sites and had craniosynostosis verified by radiographic imaging. Control infants (n=4,094) consisted of a random sample of live births with no major birth defects from the same population as the case infants. Information on thyroid disease was based on self-report: mothers who reported either a thyroid disorder or use of a medication to treat a thyroid disorder during pregnancy were considered to have thyroid disease. Using an unconditional logistic regression model, we considered potential confounding factors (maternal age, race or ethnicity, smoking, body mass index, preexisting diabetes, plurality, gravidity, family history, infant sex).
RESULTS: Among case mothers, 19 (4.4%) were classified as having thyroid disease, compared with 65 (1.6%) of control mothers. Maternal thyroid disease was associated with craniosynostosis after controlling for maternal age (adjusted odds ratio 2.47, 95% confidence interval 1.46-4.18), the only factor that remained significant in the final model.
CONCLUSION: These data provide additional evidence that maternal thyroid disease (most likely Graves' disease) or its treatment is associated with craniosynostosis. Given the frequency of maternal thyroid disease, this association warrants further investigation. LEVEL OF EVIDENCE: II.