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Hum. Reprod. Advance Access originally published online on November 14, 2008
Human Reproduction 2009 24(2):360-366; doi:10.1093/humrep/den387
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Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology 2008

Assisted reproductive technology and major structural birth defects in the United States{dagger}

J. Reefhuis1,3, M.A. Honein1, L.A. Schieve1, A. Correa1, C.A. Hobbs2, S.A. Rasmussen1 and the National Birth Defects Prevention Study

1 National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, 1600 Clifton Road N.E., MS E-86, Atlanta, GA 30033, USA 2 University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA

3 Correspondence address. E-mail: nzr5{at}cdc.gov

BACKGROUND: With >1% of US births occurring following use of assisted reproductive technology (ART), it is critical to examine whether ART is associated with birth defects.

METHODS: We analyzed data from the National Birth Defects Prevention Study, a population-based, multicenter, case–control study of birth defects. We included mothers of fetuses or live-born infants with a major birth defect (case infants) and mothers who had live-born infants who did not have a major birth defect (control infants), delivered during the period October 1997–December 2003. We compared mothers who reported ART use (IVF or ICSI) with those who had unassisted conceptions. Multiple logistic regression was used to adjust for the following confounders: maternal race/ethnicity, maternal age, smoking and parity; we stratified by plurality.

RESULTS: ART was reported by 1.1% of all control mothers, and by 4.5% of control mothers 35 years or older. Among singleton births, ART was associated with septal heart defects (adjusted odds ratio [aOR] = 2.1, 95% confidence intervals [CI] 1.1–4.0), cleft lip with or without cleft palate (aOR = 2.4, 95% CI 1.2–5.1), esophageal atresia (aOR = 4.5, 95% CI 1.9–10.5) and anorectal atresia (aOR = 3.7, 95% CI 1.5–9.1). Among multiple births, ART was not significantly associated with any of the birth defects studied.

CONCLUSIONS: These findings suggest that some birth defects occur more often among infants conceived with ART. Although the mechanism is not clear, couples considering ART should be informed of all potential risks and benefits.

Key words: National Birth Defects Prevention Study/assisted reproductive technology/in vitro fertilization/birth defects/congenital anomalies


{dagger} This work was completed by U.S. government employees as part of their official duties, and thus is a U.S. government work, and remains in the public domain.

Submitted on June 3, 2008; resubmitted on September 24, 2008; accepted on October 2, 2008.


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