The effect was seen only in singleton births, possibly because multiple births are already at increased risk for birth defects, according to Jennita Reefhuis, Ph.D., of the CDC's National Center on Birth Defects and Developmental Disabilities, and colleagues.
The defects included septal heart defects, cleft lip with or without cleft palate, esophageal atresia, and anorectal atresia.
The case-control analysis came from the National Birth Defects Prevention Study, a CDC-sponsored multicenter look at environmental and genetic risk factors for more than 30 major birth defects, Dr. Reefhuis and colleagues wrote in the December issue of Human Reproduction.
"Today, more than 1% of infants are conceived through (assisted reproductive technology) and this number may continue to increase," Dr. Reefhuis said.
"While the risk is low," Dr. Reefhuis said, "it is still important for parents who are considering using assisted reproductive technology to think about all of the potential risks and benefits of this technology."
The study identified case infants through birth defect surveillance centers in 10 states, and control infants were randomly selected from the same source populations as the case babies.
To pick out risk factors, including assisted reproductive technology, mothers were interviewed by telephone between six months and two years after the date of delivery. Babies born on or after Oct. 1, 1997, and on or before Dec. 31, 2003, were included in the analysis.
The researchers limited their analysis to defects seen in at least three births, which left 9,584 case and 4,792 control mothers. A total of 683 case infants had more than one defect and were included in more than one category.
Assisted reproductive technology was used by 51 of the control mothers and 230 of the case mothers, or 1.1% versus 2.4%.
Among singleton births, multivariate analysis found that assisted reproductive technology was associated with an increased risk of:
- Septal heart defects, with an adjusted odds ratio of 2.1 and a 95% confidence interval from 1.1 to 4.0.
- Cleft lip with or without cleft palate, with an adjusted odds ratio of 2.4 and a 95% confidence interval from 1.2 to 5.1.
- Esophageal atresia, with an adjusted odds ratio of 4.5 and a 95% confidence interval from 1.9 to10.5.
- Anorectal atresia, with an adjusted odds ratio of 3.7 and a 95% confidence interval from 1.5to 9.1.
Within the septal heart defects, the risk of atrial septal defects secundum or not otherwise was tripled (odds ratio of 3.0 with a 95% confidence interval from 1.5 to 6.1) and the risk of ventricular plus atrial septal defects was nearly tripled (odds ratio of 2.8 with a 95% confidence interval from 1.2 to 7.0).
The researchers found no elevated risk of any defect among babies born in multiple births.
The underlying biological mechanism is "unclear," the researchers said, calling for further studies.
The study was limited by difficulty distinguishing between the effects of underlying subfertility and the infertility treatments used, the researchers said. Thus, they wrote "subfertile women might have a higher risk of having a child with a birth defect regardless of whether infertility treatments are used."
Because of this limitation, they noted, "until further studies have corroborated our ï¬ndings or clariï¬ed the basis for these ï¬ndings, the practical application of our results is limited."
Also, Dr. Reefhuis and colleagues noted, there was potential for exposure misclassification, since assisted reproductive technology use was based on maternal report and not validated by medical records.
Although the study is interesting, it's not clear what it says about assisted reproductive technologies, said Elizabeth Ginsburg, M.D., of Brigham and Women's Hospital in Boston.
"We don't know what it means," said Dr. Ginsburg, who is president of the Society for Assisted Reproductive Technology.
She said the study essentially compared infertile women who used assisted reproductive technologies with women who got pregnant spontaneously, so it's "very hard to make any conclusions."
Dr. Ginsburg said previous studies have shown similar results but others have shown no effect, perhaps because of different surveillance methods or different populations with different genetics.
It may also be the case that infants born after assisted reproductive technologies are managed differently by pediatricians, which might contribute to the findings.
From the standpoint of patients, nothing in the study dictates any change, she said, because specialists already highlight the risks, including the possibility of birth defects.
"I'll be doing nothing different," she said.
|The study was sponsored by the CDC. Dr. Reefhuis is an employee of the agency.|
Zalman S. Agus, MD Emeritus Professor
University of Pennsylvania School of Medicine
Human ReproductionSource Reference: Reefhuis J et al "Assisted reproductive technology and major structural birth defects in the United States" Hum Reprod 2008; DOI: 10.1093/humrep/den387.