Article

Maternal Thyroid Disease as a Risk Factor for Craniosynostosis

National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333, USA.
Obstetrics and Gynecology (Impact Factor: 4.37). 09/2007; 110(2 Pt 1):369-77. DOI: 10.1097/01.AOG.0000270157.88896.76
Source: PubMed

ABSTRACT To study the relationship between maternal thyroid disease and craniosynostosis using data from the National Birth Defects Prevention Study, a multisite, case-control study.
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).
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.
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.
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    • "First, we examined the association of maternal thyroid disease with craniosynostosis, given that our previous analysis of this study question only included data on births through 2002 [Rasmussen et al., 2007]. The current analysis was adjusted only for maternal age, as was done for the previous study. "
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    ABSTRACT: Thyroid disease is a common problem among women of reproductive age but often goes undiagnosed. Maternal thyroid disease has been associated with increased risk of craniosynostosis. We hypothesized that known risk factors for thyroid disease would be associated with risk of craniosynostosis among women not diagnosed with thyroid disease. Analyses included mothers of 1,067 cases and 8,494 population-based controls who were interviewed for the National Birth Defects Prevention Study. We used multivariable logistic regression to estimate adjusted odds ratios (AOR) and 95% confidence intervals (CI). After excluding women with diagnosed thyroid disease, younger maternal age (AOR 0.7, 95% CI 0.6-0.9, for <25 years versus 25-29), black or other race-ethnicity (AOR 0.3, 95% CI 0.2-0.4 and AOR 0.6, 95% CI 0.4-0.8, respectively, relative to non-Hispanic whites), fertility medications or procedures (AOR 1.5, 95% CI 1.2-2.0), and alcohol consumption (AOR 0.8, 95% CI 0.7-0.9) were associated with risk of craniosynostosis, based on confidence intervals that excluded 1.0. These associations with craniosynostosis are consistent with the direction of their association with thyroid dysfunction (i.e., younger age, black race-ethnicity and alcohol consumption are associated with reduced risk and fertility problems are associated with increased risk of thyroid disease). This study thus provides support for the hypothesis that risk factors associated with thyroid dysfunction are also associated with risk of craniosynostosis. Improved understanding of the potential association between maternal thyroid function and craniosynostosis among offspring is important given that craniosynostosis carries significant morbidity and that thyroid disease is under-diagnosed and potentially modifiable. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    American Journal of Medical Genetics Part A 02/2015; 167(4). DOI:10.1002/ajmg.a.36953 · 2.05 Impact Factor
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    • "Delays in neuropsychological development have been reported for 15e62% of patients (Oi and Matsumoto, 1987; Sidoti et al., 1996; Aryan et al., 2005; Engel et al., 2012). The aetiology of metopic synostosis remains unknown (Engel et al., 2012; van der Meulen, 2012), but it is often ascribed to either an intrinsic malformation of the frontal bones (Lajeunie et al., 1998; Rasmussen et al., 2007; Wilkie et al. 2007; Senarath-Yapa et al. 2012) fetal head constraints in the pelvic area during pregnancy (Graham and Smith, 1980; Smartt et al., 2005) or to a malformation of the frontal lobes leading to a reduction of stimuli for cranial growth (Moss, 1959; Senarath-Yapa et al. 2012). Surgical intervention is warranted in order to increase the volume of the underdeveloped anterior cranial fossa as well as to improve aesthetics (Panchal and Uttchin, 2003; Forrest and Hopper, 2013). "
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    Journal of Cranio-Maxillofacial Surgery 09/2014; 42(6). DOI:10.1016/j.jcms.2014.01.017 · 2.60 Impact Factor
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    • "This registry has been described previously (Miller, 2006). Information on factors that have been reported to or may be associated with craniosynostosis or thyroxine levels (maternal age, race or ethnicity, education, and parity and infant sex, birth weight, and gestational age) were also abstracted from the registry (Alderman et al., 1988; Rasmussen et al., 2007). All cases were evaluated by a clinical geneticist and classified as isolated (presence of no major birth defect other than a single-suture CS) or nonisolated defects (presence of multiple suture involvement, multiple major birth defects, or a known syndrome). "
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    ABSTRACT: BACKGROUND: Craniosynostosis (CS), a structural anomaly characterized by premature fusion of cranial sutures, occurs in 1 in 2000 live births. Associations of CS with the thyroid have been reported. Neonatal thyroid hormone (T4) is evaluated nationally at birth by the Newborn Screening Program (NBS). This study evaluated the relationship between NBS T4 levels and craniosynostosis. METHODS: Live-born singleton babies born in 2004 through 2007 were identified through the Texas Birth Defects Registry (499 cases) and Texas Bureau of Vital Statistics (3570 controls) and successfully linked to analyte data available in the Texas NBS Database. Cases were classified based on the absence of other major defects (isolated cases, n = 382) and suture(s) involved. Mean T4 levels were compared between controls and cases (overall and stratified by classification). T4 levels were stratified by quintiles to evaluate differences between cases and controls within quintiles. The diagnostic utility of NBS T4 was evaluated using receiver operator characteristic (ROC) curves. RESULTS: Mean T4 levels were lower in isolated cases (16.89 μg/dl) than in controls (17.77 μg/dl; p = 0.0004). This trend persisted for sagittal (16.69 μg/dl; p = 0.002) and metopic (16.83 μg/dl; p = 0.042) CS. When stratified by quintiles, 54% of isolated lambdoid CS were in the first quintile compared to controls (p = 0.012). ROC area under the curve (AUC) was approximately 0.55 for all classifications except lambdoid (AUC = 0.73). CONCLUSION: NBS T4 levels were slightly lower among cases with nearly half of all lambdoid CS having T4 levels in the lowest quintile. However, overall NBS T4 levels are not suitable for potential screening or diagnostic application. Birth Defects Research (Part A), 2012. © 2012 Wiley Periodicals, Inc.
    Birth Defects Research Part A Clinical and Molecular Teratology 12/2012; 94(12). DOI:10.1002/bdra.23077 · 2.21 Impact Factor
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