Are Babies Born via ART More Likely to Have Birth Defects?

Peter Kovacs, MD, PhD


June 17, 2016

Assisted Reproductive Technology and Birth Defects Among Liveborn Infants in Florida, Massachusetts, and Michigan, 2000-2010

Boulet SL, Kirby RS, Reefhuis J, et al; States Monitoring Assisted Reproductive Technology (SMART) Collaborative
JAMA Pediatr. 2016;170-e154934


The issue of neonatal health has been part of the conversation surrounding in vitro fertilization (IVF) ever since the first successful treatment in 1978. Since the late 1980s, assisted reproductive technology (ART) has been rapidly developing, and it is estimated that more than 5 million children have been born via IVF. In the developed world, up to 5% of children are conceived through IVF-intracytoplasmic sperm injection treatments.[1]

With the large and increasing number of children being born after ART, it is even more important to evaluate the outcome of these pregnancies. Infertile patients who require ART cannot be randomly assigned to treatment vs no treatment in order to study the frequency of birth defects. Therefore, cohort and case-controlled studies can be used to assess the risk ART may carry. It is important to control for as many confounding variables as possible during the analysis to learn the impact of ART itself.

The Study

The authors studied the frequency of birth defects among liveborn infants in three states over a 10-year period and evaluated the impact of ART use. Various linked databases were used for data collection. The prevalence of chromosomal (chromosomes 13, 18, and 21) and nonchromosomal birth defects of specific organ systems were compared. Maternal age, race, education, parity, history of diabetes, hypertension, smoking status, plurality of pregnancy, infant sex, birth weight, and gestational age at delivery were adjusted for during the analysis. Subgroup analysis was carried out for types of ART procedures.

There were 4,553,215 non-ART liveborn infants and 64,861 ART liveborn infants identified in the study period. ART mothers were more likely to be over age 30 years, non-Hispanic white, nulliparous, and have a higher degree of education. They were less likely to be smokers but were more often affected by diabetes and hypertension. Multifetal deliveries, preterm delivery, low birth weight, and very low birth weight were more common in ART pregnancies.

Overall, the risk for birth defects was higher among ART infants (adjusted relative risk [aRR], 1.28; 95% confidence interval [CI], 1.15-1.42). When specific organ systems were analyzed separately, the risks for esophageal atresia, transesophageal fistula, rectal/large intestine atresia, and lower limb reduction deformity were higher in ART infants.

The risk for nonchromosomal birth defects was increased among singleton ART liveborn neonates (aRR, 1.36; 95% CI, 1.21-1.59). When organ systems were analyzed separately, the deformities affecting the gastrointestinal tract remained significantly more common. When multiple pregnancies were analyzed separately, there was no increased risk for birth defects among ART infants. Chromosomal birth defects were more common in ART births among women under age 35 years but were less common among women over age 35 years.

The authors did not find an association between the different types of ART procedures (fresh vs frozen cycles, donor vs own sperm, based on day of transfer), except for an increased risk for congenital anomalies after assisted hatching (aRR, 1.32; 95% CI, 1.02-1.71).


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