Assisted Reproduction Safety and Risks

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

Boulet SL, Kirby RS, Reefhuis J, Zhang Y, Sunderam S, Cohen B, Bernson D, Copeland G, Bailey MA, Jamieson DJ, Kissin DM

Published June 6, 2016 JAMA pediatrics
DOI 10.1001/jamapediatrics.2015.4934 PMID 27043648 PMC PMC4899282

RRM Academy Synopsis

Certain birth defects were more common in infants conceived with ART

Birth defects of certain types were more common among infants conceived with ART in this cohort study of 4 618 076 live births in Florida, Massachusetts, and Michigan. The adjusted risk ratio for one or more selected nonchromosomal defects was 1.28.

Study at a glance, cohort study of 4 618 076 live births: Some birth defects were more common in infants conceived with ART
Study at a glance, cohort study of 4 618 076 live births: Some birth defects were more common in infants conceived with ART. Source: Boulet SL et al., 2016, PMID 27043648.

Key Findings

  • The association held after accounting for the mother's characteristics and birth year, with an adjusted risk ratio (aRR) of 1.28 (95% CI, 1.15 to 1.42) for selected nonchromosomal defects.
  • Adjusted risk ratios were 1.93 (95% CI, 1.40–2.67) for tracheoesophageal fistula/esophageal atresia, 2.03 (1.51–2.74) for rectal and large intestinal atresia/stenosis, and 2.18 (1.39–3.43) for reduction deformity of the lower limbs.
  • In multiple births, ART was significantly associated with only one defect group, with an aRR of 2.39 (95% CI, 1.38–4.12): rectal and large intestinal atresia/stenosis.
  • After fresh embryo transfer, ovulation disorder (aRR, 1.53; 95% CI, 1.13–2.06) and, among singletons, assisted hatching (aRR, 1.55; 95% CI, 1.10–2.19) were marginally associated with nonchromosomal defects.
  • Across the three states, 64 861 of 4 618 076 live-born infants (1.4%) were conceived with ART between 2000 and 2010.

Interpretation

This cohort study compared infants conceived with and without ART. The researchers matched national ART surveillance data to birth certificates and birth defects registries in three states. The authors could not evaluate underlying reduced fertility, which they name as a possible explanation for the link. The data excluded defects among fetal deaths and terminations, and the states differed in how they found cases. Maternal body mass index was unavailable for Massachusetts and for part of the study period in Florida and Michigan, so the authors could not adjust for it. Among ART births, no procedure showed a significant association with nonchromosomal defects after adjusting for multiple comparisons.

RRM Context

The authors suggest that factors related to reduced fertility may explain the link between ART and birth defects. Restorative reproductive medicine seeks the cause of reduced fertility in both partners and treats it. IVF bypasses that cause without establishing why conception fails.

Abstract

Use of assisted reproductive technology (ART) has been associated with increased risks for birth defects. Variations in birth defect risks according to type of ART procedure have been noted, but findings are inconsistent. To examine the prevalence of birth defects among liveborn infants conceived with and without ART and to evaluate risks associated with certain ART procedures among ART-conceived infants. Used linked ART surveillance, birth certificates, and birth defects registry data for 3 states (Florida, Massachusetts, and Michigan). Methods for ascertaining birth defect cases varied by state. Resident live births during 2000 to 2010 were included, and the analysis was conducted between Feburary 2015 and August 2015. Use of ART among all live births and use of certain ART procedures among ART births. Prevalence of selected chromosomal and nonchromosomal birth defects that are usually diagnosed at or immediately after birth. Of the 4 618 076 liveborn infants between 2000 and 2010, 64 861 (1.4%) were conceived using ART. Overall, the prevalence of 1 or more of the selected nonchromosomal defects was 58.59 per 10 000 for ART infants (n = 389) vs 47.50 per 10 000 for non-ART infants (n = 22 036). The association remained significant after adjusting for maternal characteristics and year of birth (adjusted risk ratio [aRR], 1.28; 95% CI, 1.15-1.42). Similar differences were observed for singleton ART births vs their non-ART counterparts (63.69 per 10 000 [n = 218] vs 47.17 per 10 000 [n = 21 251]; aRR, 1.38; 95% CI, 1.21-1.59). Among multiple births, the prevalence of rectal and large intestinal atresia/stenosis was higher for ART births compared with non-ART births (aRR, 2.39; 95% CI, 1.38-4.12). Among ART births conceived after fresh embryo transfer, infants born to mothers with ovulation disorders had a higher prevalence of nonchromosomal birth defects (aRR, 1.53; 95% CI, 1.13-2.06) than those born to mothers without the diagnosis, and use of assisted hatching was associated with birth defects among singleton births (aRR, 1.55; 95% CI, 1.10-2.19). Multiplicity-adjusted P values for these associations were greater than .05. Infants conceived after ART had a higher prevalence of certain birth defects. Assisted hatching and diagnosis of ovulation disorder were marginally associated with increased risks for nonchromosomal birth defects; however, these associations may be caused by other underlying factors.

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Assisted Reproduction › Safety and Risks › Birth Defects
Sheree L Boulet, Russell S Kirby, Jennita Reefhuis, Yujia Zhang, Saswati Sunderam, Bruce Cohen, Dana Bernson, Glenn Copeland, Marie A Bailey, Denise J Jamieson, Dmitry M Kissin
S Boulet, R Kirby, J Reefhuis, Y Zhang, S Sunderam, B Cohen, D Bernson, G Copeland, M Bailey, D Jamieson, D Kissin
PMID 27043648 27043648 DOI 10.1001/jamapediatrics.2015.4934 10.1001/jamapediatrics.2015.4934 Boulet et al. 2016, Boulet 2016