TUCSON, ARIZ. — Maternal thyroid disease or its treatment may increase the risk of craniosynostosis in offspring by nearly threefold, preliminary results from an ongoing study suggest.
The finding is important because thyroid disease is the second most common endocrinopathy, after diabetes, in women of reproductive age, Dr. Sonja A. Rasmussen said at the annual meeting of the Teratology Society.
“Several case reports in the medical literature have linked craniosynostosis to postnatal hyperthyroidism and with maternal Graves' disease during pregnancy,” said Dr. Rasmussen of the division of birth defects at the Centers for Disease Control and Prevention, Atlanta.
“Congenital hypothyroidism is associated with delayed closure of the fontanelles. In addition, thyroid hormone is known to play a key role in normal bone metabolism, acting on both osteoblasts and osteoclasts. This information suggests that excess thyroid hormone might lead to premature cranial suture fusion,” she said.
To examine the relationship between maternal thyroid disease and craniosynostosis, Dr. Rasmussen and her associates used data from the National Birth Defects Prevention Study, an ongoing population-based case-control study of major birth defects. The data included maternal interviews and clinical information on 4,555 infants born between Oct. 1, 1997, and Dec. 31, 2002, in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, and Texas.
Maternal interviews were completed 6–24 months after estimated date of delivery. Infants born with a condition of known etiology, such as a chromosome abnormality or single gene condition, were excluded from the study.
Of the 4,555 infants, 433 had craniosynostosis verified by radiographic imaging and 4,122 live-born infants without major birth defects served as the control group.
Of the mothers of infants with craniosynostosis, 19 (4.4%) had maternal thyroid disease, compared with 67 (1.6%) of mothers in the control group. Odds ratio analysis revealed that mothers with thyroid disease were 2.8 times more likely to have an infant with craniosynostosis, compared with mothers in the control group.
The association remained the same from a statistical standpoint after the researchers adjusted for several potential confounding factors, including maternal age, education, race, smoking status, use of selective serotonin reuptake inhibitors, body mass index, and preexisting diabetes; infant sex, birth weight, and gestational age; and family history of craniosynostosis.
Odd ratios were increased for all types of craniosynostosis except for metopic. The highest odds ratio was for multiple sutures.
“There are several possible mechanisms for the findings we observed,” said Dr. Rasmussen. First, “mothers with hyperthyroidism may have received inadequate treatment, with passage of excess thyroid hormone across the placenta. Another possible mechanism is that a mother with hypothyroidism received overtreatment with exogenous thyroid hormone. Finally, the mother might have autoimmune thyroid disease that results in production of thyroid-stimulating antibodies that cross the placenta and stimulate the fetal thyroid to make excess thyroid hormone.”
Maternal thyroid disease was based on self-report, “so only limited information on the type of thyroid disease was available.” Dr. Rasmussen also noted that work-ups for genetic causes of craniosynostosis differed among the study sites. Some infants with genetic etiology might have been included.