The risk of birth defects after assisted reproduction

Aim of this study was to investigate the association between congenital malformations and type of conception (spontaneous or medically assisted).

This is a population based study using data from the regional data base of Lombardy, a Northern Italian Region with a population of about 10 million inhabitants. Included in the study were 277,043 neonates born in Lombardy during the study period 2010-2012. Adjusted and unadjusted odds ratios (OR), and corresponding 95% confidence intervals (CI), of congenital abnormalities were calculated using unconditional multiple logistic regression.

A total of 7057 births (2.5%) were reported after non spontaneous conception. Overall, the frequency of birth defects was 4.4% among births after spontaneous conception and 6.7% among births after non spontaneous ones (OR = 1.67, 95%CI = 1.5-1.9). The association disappeared after taking into account the confounding effect of maternal age and factors associated with non spontaneous conception. The crude OR of abnormalities was higher than unity for any defect (OR = 1.67, 95%CI = 1.5-1.9), multiple defects (OR = 1.76, 95%CI = 1.3-2.3), cardiovascular (OR = 2.05, 95%CI = 1.8-2.4), musculoskeletal (OR = 2.05, 95%CI = 1.7-2.5) and metabolic system abnormalities (OR = 1.97, 95%CI = 1.1-3.5). Almost all these associations, however, disappeared after taking into account potential confounding with the exception of musculoskeletal defects (adjusted OR = 1.31, 95%CI = 1.1-1.6). In this case also, if adjustment for multiple comparison is taking into account, results did not reach statistical significance.

The results of this analysis confirm the recently emerging view that the increased frequency of birth defects observed after ART/medically induced ovulation only is largely due to confounders.