Assisted Reproduction Linked To Higher Birth Defects

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Article Date: 18 Nov 2008 - 3:00 PST

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A nationwide US study found that babies conceived with Assisted Reproductive Technology (ART), such as in vitro fertilization (IVF) were between 2 and 4 times more likely to be born with certain defects than babies conceived naturally.

The study was conducted by researchers at the US Centers for Disease Control and Prevention (CDC) and was published early online in the journal Human Reproduction on 16 November.

Compared to babies conceived without ART, the CDC study found that among pregnancies that resulted in single births, ART was linked to twice the risk of certain heart defects, over twice the risk of cleft lip (with or without cleft palate) and more than four times the risk of some types of gastrointestinal defects.

Lead author Dr Jennita Reefhuis, an epidemiologist at the CDC's National Center on Birth Defects and Developmental Disabilities, said:

"Today, more than 1 per cent of infants are conceived through ART and this number may continue to increase."

"While the risk is low, it is still important for parents who are considering using ART to think about all of the potential risks and benefits of this technology."

Reefhuis and colleagues analyzed data from the National Birth Defects Prevention Study, a population-based, multicenter, case-control study designed to identify infants with major birth defects and evaluate any genetic and environmental factors that may be involved. The ongoing Study includes an annual birth population of over 480,000 and covers cases identified in registries of birth defects from eight states.

Case-controlled means that the researchers included mothers of fetuses or live-born infants who had a major birth defect (these were the cases) and mothers who had live-born babies who had no major birth defects (these were the controls). They counted the number of cases and controls delivered between October 1997 and December 2003 and compared the mothers who reported using ART with those whose conceptions were unassisted.

This gave data on 281 cases conceived with ART and 14,095 controls conceived without infertility treatments.

The researchers looked for reports of two types of ART: in vitro fertilization (IVF) and intra-cytoplasmic sperm injection (ICSI, a procedure used frequently as part of IVF, where the sperm is injected directly into the egg).

Using statistical tools like multiple logistic regression, they then compared the cases with the controls and adjusted for potential confounders like mother's racial/ethnic origin, mother's age, and smoking status.

The results showed that:

• 1.1 per cent of all the control mothers reported using ART.


• 4.5 per cent of the control mothers aged 35 and over reported using ART.


• Among single births, ART was linked with a 2.1 times higher rate of septal heart defects, a 2.4 times higher rate of cleft lip (with and without cleft palate), a 4.5 times higher rate of esophageal atresia (where the food pipe stops short of the stomach) and a 3.7 times higher rate of anorectal atresia (malformation of the rectum and/or anus).


• Among multiple births, ART was not significantly linked with any of the birth defects examined by the study.

The researchers concluded that:

"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."

Despite these findings, the absolute risk of any baby being born with a birth defect is still very low. In the US, 1 in every 950 babies is born with a cleft lip with or without cleft palate. The study showed that using ART doubled this risk to around 1 in every 425.

The investigators studied single births separately from multiple births because ART increases the likelihood of multiple births and multiple birth babies are more likely to be born with birth defects whether ART was used or not.

The results showed that ART only significantly increased the risk of birth defects among single birth babies and made no significant difference to multiple births. However, there may be an indirect effect in that it increases the likelihood of multiple births anyway.

The National Birth Defects Prevention Study uses data from birth defects research centers in Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas and Utah.

ART has been used in the US since 1981 to help women become pregnant. It is defined as any procedure where the eggs are removed from the ovaries, combined with sperm in the laboratory and then put back into the uterus (either of the original woman or another woman). Treatments that only handle sperm (as in artificial insemination) or stimulate ovulation without egg harvesting are not included.

The number of babies born with the help of ART has doubled between 1996 and 2004 in the US. In 2005 more than 134,000 procedures were performed resulting in around 52,000 babies born with the help of ART.

"Assisted reproductive technology and major structural birth defects in the United States."
J. Reefhuis , M.A. Honein , L.A. Schieve , A. Correa , C.A. Hobbs , S.A. Rasmussen , and the National Birth Defects Prevention Study.
Hum. Reprod. Advance Access published on November 16, 2008.
DOI 10.1093/humrep/den387.

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Sources: CDC, Journal Abstract.

Written by: Catharine Paddock, PhD
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