Department of Public Health and Pediatric Sciences, University of Torino, Torino, Italy.
NICU and Neonatology, Department of Gynecology and Obstetrics, S. Anna Hospital, Città della Salute e della Scienza di Torino, Torino, Italy.
Pediatrics. 2017 Jul;140(1). doi: 10.1542/peds.2016-4311. Epub 2017 Jun 20.
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.
Patients with BWS born in Piemonte, Italy, were identified and matched with the general demographic data and corresponding regional ART registry.
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, < .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.
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.
辅助生殖技术（ART）与印迹疾病的新兴关联是不孕治疗和人类生殖科学争论的主要问题。我们研究了通过 ART 受孕的儿童中 Beckwith-Wiedemann 综合征（BWS）的患病率，以确定特定的相对风险。
在意大利皮埃蒙特，我们确定了患有 BWS 的患者，并与一般人口统计学数据和相应的区域 ART 登记处进行了匹配。
在 2005 年至 2014 年期间，皮埃蒙特的活产儿为 379872 例，其中 7884 例来自 ART。共出生了 38 例 BWS 患儿，7 例来自 ART，31 例自然受孕。ART 组 BWS 的出生率明显高于自然受孕组（1:1126 比 1:12254，<0.001）。ART 组的绝对活产儿风险为每 100 万例 887.9 例，而自然受孕组为每 100 万例 83.3 例，相对风险为 10.7（95%置信区间 4.7-24.2）。在 1997 年至 2014 年期间，在 663834 名新生儿中诊断出 67 例 BWS（1:9908 活产儿）。67 例 BWS 患者中有 9 例通过 ART 受孕（13.4%），其中 8 例进行了分子检测，4 例存在印迹中心 2 甲基化缺失，2 例存在 11p15.5 父源单亲二体，2 例结果阴性。
ART 会使 BWS 的风险增加 10 倍，并且可能与除甲基化异常以外的基因组事件的发病机制有关。这些数据突出了对 ART 相关健康风险的认识的必要性。
