Authors Examine the Association Between Assistive Reproductive Technology and Major Structural Birth Defects

December 11, 2008

"Our multicenter approach . . . has improved our capacity to evaluate the possible association between ART [assisted reproductive technology] and a number of specific [birth] defects, which individually are quite rare outcomes," state the authors of an article published in Human Reproduction online (ahead of print) on November 16, 2008. In the United States and worldwide, ART is increasingly being used to treat infertility. (ART may be defined as infertility treatments in which both oocytes and sperm are handled outside the body.) The proportion of U.S. births occurring following use of ART procedures is expected to rise. Two reviews published in 2005 address the association between ART and birth defects. However, the studies included in these reviews are limited by methodological problems. The study described in this article further examines possible associations between ART and major structural birth defects.

Data for the study were drawn from the National Birth Defects Prevention Study (NBDPS), an ongoing, multicenter, case-control study to investigate environmental and genetic risk factors for more than 30 selected major birth defects. Case infants (live-born infants with major birth defects) were identified through existing birth defects surveillance systems. Case and control infants (live-born infants without major birth defects) were limited to those born on or after October 1, 1997, and with an estimated delivery date on or before December 31, 2003. Case and control mothers completed a telephone interview in English or Spanish between 6 weeks and 2 years after the estimated delivery date. The main exposure of interest was use of ART. All analyses were stratified into singleton and multiple births because multiple births are strongly associated with both ART and birth defects.

The authors found that

* ART use was reported by 51 control mothers (1.1%) and 230 case mothers (2.4%).

* After adjusting for age, study center, parity, family income, and prematurity, there were statistically significant associations between singletons conceived with ART and the following birth defects: septal heart defects (OR 2.1), cleft lip with or without cleft palate (OR 2.4), esophageal atresia (OR 4.5), and anorectal atresia (OR 3.7).

* Compared with singletons, infants from multiple births were more likely to have major birth defects. However, there were no statistically significant associations with these birth defects among multiple births conceived with ART.

"Although the underlying mechanism of this effect could not be answered by this study, couples considering infertility treatments should be aware of all the possible benefits and risks posed for children conceived with these treatments," conclude the authors.

Reefhuis J, Honein MA, Schieve LA, et al. 2008. Assisted reproductive technology and major structural birth defects in the United States. Human Reproduction [published online ahead of print on November 16, 2008]. Free full-text available here (

Additional information is available from the following MCH Library resources:

- Assisted Reproductive Technologies (ART) and Families: Resource Brief

- Genetics: Resource Brief