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PEDIATRICS Vol. 111 No. 5 May 2003, pp. 1163-1166

Fertility Treatments and Craniosynostosis: California, Georgia, and Iowa, 1993–1997

Jennita Reefhuis, PhD^*, Margaret A. Honein, PhD, Gary M. Shaw, DrPH and Paul A. Romitti, PhD^||

^* Epidemiology Program Office and National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia
California Birth Defects Monitoring Program, Oakland, California
^|| Department of Epidemiology, University of Iowa, Iowa City, Iowa

--> Objective. Craniosynostosis, a malformation caused by premature closure of 1 or more cranial sutures, is a rare birth defect usually of unknown cause; however, it is often associated with advanced maternal age. Because fertility treatments are also associated with increased maternal age, this study investigated the possible association between fertility treatments and craniosynostosis.

Methods. Data from the Birth Defect Risk Factor Surveillance study were used, which included infants who were delivered from 1993 through 1997 in California, Georgia, and Iowa. Cases were defined as infants who had nonfamilial, nonsyndromic craniosynostosis and were ascertained through existing birth defect surveillance systems. Controls, infants without birth defects, were selected from the same regions and time period.

Results. Mothers of 99 case infants and 777 control infants from the 3 study locations participated in this study by completing a telephone interview. Unadjusted analyses showed associations with craniosynostosis for mothers who had used clomiphene citrate (odds ratio[OR]: 3.8; 95% confidence interval [CI]: 1.1–12.3), artificial insemination (OR: 4.2; 95% CI: 0.8–9.4), or assisted reproductive techniques (OR: 4.2; 95% CI: 0.5–27.3).

Conclusions. This is the first study that has found associations between fertility treatments and craniosynostosis. However, the numbers are small; therefore, the results should be viewed with caution.

Key Words: abnormalities • craniosynostoses • pregnancy • fertility agents • assisted reproductive techniques • artificial insemination • fertilization in vitro • registries

Abbreviations: MACDP, Metropolitan Atlanta Congenital Defects Program • OVST, ovulation stimulation • AI, artificial insemination • ART, assisted reproductive techniques • CC, clomiphene citrate • BDRFS, Birth Defect Risk Factor Surveillance • CT, computed tomography • OR, odds ratio

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Received for publication Oct 2, 2002; Accepted Dec 4, 2002.

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