Maternal Thyroid Disease as a Risk Factor for Craniosynostosis
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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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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ABSTRACT: Background Fronto-supraorbital bar advancement in the treatment for trigonocephaly is associated with extensive intraoperative blood loss and compensatory erythrocyte transfusions. Since both are related to the length of surgery, efforts have been focused on optimizing preoperative preparations. The utilization of three-dimensional skull models in surgical planning allows for familiarization with the patient’s anatomy, the optimization of osteotomies, the preparation of bone grafts and the selection of fixation plates. Methods Stereolithographic skull models were used in the surgical planning for five patients with non-syndromic trigonocephaly treated in Wilhelmina Children’s Hospital in 2012. A comparison group was composed of six patients with non-syndromic trigonocephaly treated by the same surgical team. Once all patients had received surgery, a retrospective chart review was performed to identify the volumes of perioperative blood loss and erythrocyte transfusions and the length of the procedure. Furthermore, the educational value of the models was assessed in a round table discussion with the surgical team and residents. Results In the model group patients were transfused a mean 24 ml/kg (27% of Estimated Blood Volume [EBV]) compared to 16 ml/kg (18% of EBV) in the comparison group (P=0.359) for a mean perioperative blood loss of 53 ml/kg (60% of EBV) in the model group against 40 ml/kg (41% of EBV) in the comparison group (P=0.792). The mean length of surgery in the model groups was 256 minutes versus 252 minutes in the comparison group (P=0.995). Evaluation of educational purposes demonstrated that the models had a role in the instruction of residents and communication to parents, but did not improve the insight of experienced surgeons. Conclusion The usage of stereolithographic skull models in the treatment of non-syndromic trigonocephaly does not reduce the mean volume of perioperative erythrocyte transfusions, the mean volume of perioperative blood loss nor the mean length of the surgical procedure. Nonetheless, the models do facilitate the education of the patient’s parents as well as support the training of residents.Journal of Cranio-Maxillofacial Surgery 09/2014; DOI:10.1016/j.jcms.2014.01.017 · 2.60 Impact Factor
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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