Maternal thyroid disease and risk of birth defects in offspring: a population‐based case‐control study

Abstract

We investigated the relationship between maternal thyroid disease and the risk of birth defects in offspring using data from a large population-based, case-control study. Cases included 4904 stillborn and liveborn infants with major anomalies diagnosed in the first year of life and born to residents of metropolitan Atlanta between 1968 and 1980. Controls included 3027 normal babies, frequency-matched to cases by race, hospital of birth and quarter of birth. We compared mothers of cases and controls regarding history of physician-diagnosed hypothyroidism and hyperthyroidism before the infant's birth, age at diagnosis of thyroid condition, duration of illness, and intake of thyroid medications before and during pregnancy. Information obtained from maternal interviews was evaluated for concordance with hospital records. We adjusted for potentially confounding factors using conditional logistic regression analysis. Overall, there was no relationship between the risk of total birth defects and history of maternal hypothyroidism (odds ratio (OR) = 1.05, 95% C.I. 0.84-1.31), maternal hyperthyroidism (OR = 1.00, 95% C.I. 0.66-1.53), and intake of thyroid hormone and antithyroid drugs before and during pregnancy. In an analysis of 66 specific birth defects and defect groups, we found two statistically significant associations with hypothyroidism and three with hyperthyroidism which may reflect chance findings. In an evaluation of babies with multiple anomalies, we observed a two-fold increased risk with hypothyroidism but no discernible pattern of defects. The absolute risk of major birth defects in offspring of women with history of hypothyroidism can be estimated as 2.1%, a finding at odds with the 10-20% risk cited in the literature.

Etiological aspects of congenital diaphragmatic hernia: results of a case comparison study

“…Thyroid hormone is a well-known trophic factor for normal lung development and alveolar cell differentiation (DeMello et al 1989). Moreover, maternal hypothyroidism has been associated with an increased risk of a variety of birth defects in offspring (Potter 1980;Khoury et al 1989), but information on its role in CDH is lacking. The exact mechanism of teratogenesis is not known but evidence is accumulating that Nitrofen may interact with the embryonic nuclear receptors for thyroid hormone (Manson 1986).…”

Craniosynostosis: The Potential Contribution of Thyroid-Related Mechanisms

“…Observational Studies We are aware of only two observational studies (i.e., studies that include a comparison group of noncases) that have examined the association of maternal thyroid dysfunction with CS, and their results are mixed [38,39]. The first case-control study did not observe an increased risk of CS among offspring born to mothers who reported a history of thyroid disease, but the study had limited power (it included 63 CS cases, 4 of whom reported a history of thyroid disease), and exposure assessment occurred up to 15 years after delivery [38].…”

“…The first case-control study did not observe an increased risk of CS among offspring born to mothers who reported a history of thyroid disease, but the study had limited power (it included 63 CS cases, 4 of whom reported a history of thyroid disease), and exposure assessment occurred up to 15 years after delivery [38]. The second study was based on the National Birth Defects Prevention Study, a population-based case-control study [39].…”

Use of computer simulation to evaluate a putative cluster of genetic or teratologic outcomes: Adjustment for “multiple hypotheses” and application to a reported excess of Down's syndrome

“…(Other variables such as Hispanic ethnic status in the United States [Wilson et al, 1992] or other ethnic variation [Hook and Harlap, 1979], and a history of maternal thyroid problems [Khoury et al, 1989] may reflect other significant predisposing factors [Hook, 1994].) The recognition of clusters in space and/or time is therefore potentially important in providing clues to the existence of environmental influences on the frequency of the disorder.…”