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Cited by 81Craniofacial Disorders and TreatmentsThyroid Disorders and TreatmentsFetal and Pediatric Neurological Disorders

Maternal Thyroid Disease as a Risk Factor for Craniosynostosis

Rasmussen, Sonja A., Yazdy, Mahsa M., Carmichael, Suzan L., Jamieson, Denise J., Canfield, Mark A., Honein, Margaret A.·2007·Obstetrics & Gynecology
DOI 10.1097/01.aog.0000270157.88896.76
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Abstract

OBJECTIVE: To study the relationship between maternal thyroid disease and craniosynostosis using data from the National Birth Defects Prevention Study, a multisite, case-control study. METHODS: 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). RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: II.

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  • Race and ethnicity have been reported as modifiers of sagittal craniosynostosis (sCS) risk.

    “In addition, race and ethnicity have also been reported as modifiers of sCS risk. Several studies consistently report a higher prevalence among individuals of white race [29, 93], whereas lower risks have been observed in black (OR = 0.2), Hispanic (OR = 0.4), and other racial or ethnic groups (OR = 0.6) [56, 96].”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [93]

    The Results (page unavailable) report that mothers of infants with craniosynostosis were more likely than control mothers to be non-Hispanic white. This supports a racial or ethnic difference for craniosynostosis overall, but the paper does not report that difference specifically for sagittal craniosynostosis or give the quoted race-specific odds ratios. (LLM, conf=0.85)

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  • Maternal thyroid disease is linked to increased risk of CS, with reported ORs ranging from 1.3 to 2.11.

    “Maternal thyroid disease has also been linked to an increased risk of CS, with reported ORs ranging from 1.3 to 2.11 [56, 93], consistent with the well-established role of thyroid hormones in skeletal development.”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [93]

    The Results report an association between maternal thyroid disease and craniosynostosis, but the overall adjusted OR is 2.47, outside the stated range. The paper reports an OR of 2.11 only for sagittal craniosynostosis; it does not report 1.3 as an OR for the overall association (Results; page not specified in our copy). (LLM, conf=0.90)

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  • Advanced maternal age (>35 years) is highly correlated with sagittal suture fusion, with OR ranging from 2.01 to 2.32.

    “Firstly, advanced maternal age (> 35 years) has been found to highly correlate with sagittal suture fusion, with an OR ranging from 2.01 to 2.32 [2, 82, 93, 102], while young maternal age has a protective effect OR 0.6 [56].”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [93]

    The Results (page unavailable) say mothers of infants with craniosynostosis were more likely to be older, supporting an association with maternal age in general. They do not report an age-over-35 association specifically for sagittal suture fusion or an age-related OR of 2.01–2.32; the reported sagittal OR of 2.11 concerns maternal thyroid disease. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Several studies consistently report a higher prevalence of sCS among individuals of white race.

    “Several studies consistently report a higher prevalence among individuals of white race [29, 93]”

    From Genetics versus environment in the pathophysiology of sagittal synostosis (2026) · cites this paper as [93]

    The Results report that mothers of infants with craniosynostosis were more likely than control mothers to be non-Hispanic white; the accompanying table gives 72.9% versus 60.0%. The paper does not report this race comparison specifically for sCS, and this single study cannot establish that several studies consistently found it. (LLM, conf=0.82)

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Research works printed but not linked: 3

  1. [1]1. International Committee of Medical Journal Editors. Uniform requirements for manuscripts submitted to biomedical journals. Available at: http://www.icmje.org. Retrieved September 15, 2005.
  2. [2]2. DeAngelis CD, Drazen JM, Frizelle FA, Haug C, HoeyJ, Horton R, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. JAMA 2004;292:1363-4.
  3. [3]3. DeAngelis CD, Drazen JM, Frizelle FA, Haug C, HoeyJ, Horton R, et al. Is this clinical trial fully registered?: a statement from the International Committee of Medical Journal Editors. JAMA 2005;293:2927–9.

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Authors
Rasmussen, S. A., Yazdy, M. M., Carmichael, S. L., Jamieson, D. J., Canfield, M. A., & Honein, M. A.
Affiliations
  • Centers for Disease Control and Prevention (US)
  • March of Dimes (US)
ORCID
Venue
Obstetrics & Gynecology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2007-08
Volume
110
Issue
2
Pages
369-377
ISSN
0029-7844 (ISSN-L)
DOI
10.1097/01.aog.0000270157.88896.76
OpenAlex
W1974922370
Cited by
81
References
45
Citations by year
2026: 6 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 9 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 5 · 2012: 5
FWCI
1.25
Type
journal article
Language
en
Open access
closed
Locations
  • Obstetrics and Gynecology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Craniofacial Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
maternal thyroid disease, craniosynostosis, Graves' disease, congenital malformations, maternal age, pregnancy complications
MeSH terms
Adolescent, Adult, Craniosynostoses, Female, Humans, Male, Pregnancy, Pregnancy Complications, Risk Factors, Thyroid Diseases, United States, Odds Ratio, Case-Control Studies

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