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: 5.18). 09/2007; 110(2 Pt 1):369-77. DOI: 10.1097/01.AOG.0000270157.88896.76
Source: PubMed


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.
    Full-text · Article · Feb 2015 · American Journal of Medical Genetics Part A
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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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    ABSTRACT: 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.
    Full-text · Article · Sep 2014 · Journal of Cranio-Maxillofacial Surgery
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    • "The Center for Disease Control National Birth Defects Prevention Study (CDC NBDPS) has identified maternal thyroid disease as a risk factor for craniosynostosis with an adjusted odds ratio of 2.47 [3]. Craniosynostosis is a pathological condition in which premature fusion of one or more of the calvarial sutures occurs before the cessation of brain growth. "
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    ABSTRACT: The incidence of craniosynostosis is one in every 1,800-2500 births. The gene-environment model proposes that if a genetic predisposition is coupled with environmental exposures, the effects can be multiplicative resulting in severely abnormal phenotypes. At present, very little is known about the role of gene-environment interactions in modulating craniosynostosis phenotypes, but prior evidence suggests a role for endocrine factors. Here we provide a report of the effects of thyroid hormone exposure on murine calvaria cells. Murine derived calvaria cells were exposed to critical doses of pharmaceutical thyroxine and analyzed after 3 and 7 days of treatment. Endpoint assays were designed to determine the effects of the hormone exposure on markers of osteogenesis and included, proliferation assay, quantitative ALP activity assay, targeted qPCR for mRNA expression of Runx2, Alp, Ocn, and Twist1, genechip array for 28,853 targets, and targeted osteogenic microarray with qPCR confirmations. Exposure to thyroxine stimulated the cells to express ALP in a dose dependent manner. There were no patterns of difference observed for proliferation. Targeted RNA expression data confirmed expression increases for Alp and Ocn at 7 days in culture. The genechip array suggests substantive expression differences for 46 gene targets and the targeted osteogenesis microarray indicated 23 targets with substantive differences. 11 gene targets were chosen for qPCR confirmation because of their known association with bone or craniosynostosis (Col2a1, Dmp1, Fgf1, 2, Igf1, Mmp9, Phex, Tnf, Htra1, Por, and Dcn). We confirmed substantive increases in mRNA for Phex, FGF1, 2, Tnf, Dmp1, Htra1, Por, Igf1 and Mmp9, and substantive decreases for Dcn. It appears thyroid hormone may exert its effects through increasing osteogenesis. Targets isolated suggest a possible interaction for those gene products associated with calvarial suture growth and homeostasis as well as craniosynostosis.
    Full-text · Article · Jul 2013 · PLoS ONE
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