P-717 Trends in the incidence of major birth defects after Assisted Reproductive Technologies (ART) in Lombardy Region, Northern Italy
Authors: Galati G , Esposito G , Somigliana E , Muzii L , Franchi M , Corrao G , Parazzini F 
Published: June 2022

Abstract

Study question
Does the association between Assisted Reproductive Technologies (ART) and birth defects change over time?

Summary answer
The increased incidence of birth defects in ART pregnancies is not steady over time. A decline of this risk emerged in most recent years.

What is known already
The incidence of birth defects is increased in pregnancies after ART. The latest meta-analysis showed that infants born following IVF-ICSI have a 40% increased risk (Zhao et al., 2020). Even if infertile women are exposed to higher risk per se, some ART related factors may also contribute. To note, ART procedures are continuously evolving, and it cannot be excluded that the magnitude of the association of ART and birth defects may have changed in recent years. We failed to identify in the literature studies reporting on the trends of birth defects in IVF-ICSI pregnancies over time.

Study design, size, duration
This is a population-based study using the automated system of healthcare utilization databases from Lombardy, a region located in Northern Italy accounting for about 10 million inhabitants. We identified deliveries occurring between January 2014 and December 2020 from women beneficiaries of the public health system using the standard discharge form and the certificate of delivery assistance. We excluded cases with incomplete information and pregnancies obtained by intrauterine insemination or ovarian hyperstimulation alone.

Participants/materials, setting, methods
The rate of newborns affected by major defects was calculated among natural and IVF-ICSI pregnancies. A logistic regression model was used to adjust for maternal sociodemographic features (i.e., age, nationality, marital status, education, and employment). Data are presented as adjusted odd ratio (aOR) and corresponding 95% Confidence Interval (CI) of major defects among IVF-ICSI pregnancies compared to natural conceptions. Analyses were repeated for every calendar year.

Main results and the role of chance
A total of 508,421 live births were included, of whom 14,067 (2.8%) were achieved with IVF-ICSI. The proportion of non-spontaneous conceptions per year progressively increased over the years, being 2.1%, 2.3%, 2.6%, 2.8%, 3.2%, 3.4% and 3.2% in 2014, 2015, 2016, 2017, 2018, 2019, and 2020, respectively (p &lt; 0.0001). Overall, 13,080 birth defects were recorded, of whom 412 occurred among ART newborns (3.1%). The risk of birth defects is increased in women undergoing ART (aOR 1.13; 95%CI:1.02-1.25), but a decreasing trend over time was highlighted. Indeed, the aOR dropped from 1.40 (95%CI: 1.04-1.91) in 2014 to 0.7 (95%CI: 0.73-1.28) in 2020 (p &lt; 0.001). During the study period, a statistically significant reduction in multiple pregnancies (p-value for trend &lt;0.0001) and in the ratio of ICSI to conventional IVF (p-value for trend &lt;0.0001) was also observed, potentially explaining the positive trend observed for birth defects.

Limitations, reasons for caution
The diagnosis of malformation is based on information detected at the time of delivery, and not during the subsequent infant’s hospitalization, or later in lifetime. Further, we have no information on pregnancies terminated early. Finally, data was collected from registries and this modality may expose the findings to some inaccuracies.

Wider implications of the findings
The increased risk of birth defects in IVF-ICSI pregnancies is not steady over time. A decline of this risk emerged in our region. Policy changes in ART may explain this beneficial effect. Evidence obtained more than one decade ago may not be valid in the modern era of IVF.

Trial registration number
not applicable