Assisted Reproductive Techniques and Risk of Beckwith-Wiedemann Syndrome

Pediatrics. 2017 Jul;140(1):e20164311. doi: 10.1542/peds.2016-4311. Epub 2017 Jun 20.

Abstract

Background and objectives: The emerging association of assisted reproductive techniques (ART) with imprinting disorders represents a major issue in the scientific debate on infertility treatment and human procreation. We studied the prevalence of Beckwith-Wiedemann syndrome (BWS) in children conceived through ART to define the specific associated relative risk.

Methods: Patients with BWS born in Piemonte, Italy, were identified and matched with the general demographic data and corresponding regional ART registry.

Results: Between 2005 and 2014, live births in Piemonte were 379 872, including 7884 from ART. Thirty-eight patients with BWS were born, 7 from ART and 31 naturally conceived. BWS birth prevalence in the ART group was significantly higher than that of the naturally conceived group (1:1126 vs 1:12 254, P < .001). The absolute live birth risk in the ART group was 887.9 per 1 000 000 vs 83.3 per 1 000 000 in the naturally conceived group, providing a relative risk of 10.7 (95% confidence interval 4.7-24.2). During the 1997-2014 period, 67 patients were diagnosed with BWS out of 663 834 newborns (1:9908 live births). Nine out of the 67 BWS patients were conceived through ART (13.4%), and 8 were molecularly tested, with 4 having an imprinting center 2 loss of methylation, 2 with 11p15.5 paternal uniparental disomy, and 2 negative results.

Conclusions: ART entails a 10-fold increased risk of BWS and could be implicated in the pathogenesis of genomic events besides methylation anomalies. These data highlight the need for awareness of ART-associated health risk.

MeSH terms

  • Beckwith-Wiedemann Syndrome / epidemiology*
  • Beckwith-Wiedemann Syndrome / etiology*
  • Humans
  • Infant, Newborn
  • Prevalence
  • Reproductive Techniques, Assisted / adverse effects*
  • Retrospective Studies
  • Risk Assessment