Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
Imprinting disorders in children born after ART: a Nordic study from the CoNARTaS group
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DOI：
10.1093/humrep/deaa039
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发表时间：
2020-05-01
影响因子：
6.1
通讯作者：
Lidegaard, O.
中科院分区：
文献类型：
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作者：
Henningsen, A. A.;Gissler, M.;Lidegaard, O.
研究问题：接受抗逆转录病毒治疗后怀孕的儿童出现印记障碍的风险是否增加？结论：我们发现抗逆转录病毒治疗儿童贝克威氏综合征的校正优势比（AOR）为2.84 [95% CI: 1.34-6.01]，而接受抗逆转录病毒治疗的儿童患praper - willi综合征、silverrussell综合征或Angelman综合征的风险并未增加。已知情况：早期的研究（大多数是小型研究）表明，ART与印痕障碍之间存在关联。研究设计、规模、持续时间：这是一项基于两国注册的队列研究。确定了丹麦（n = 45393，生于1994年至2014年）和芬兰（n = 29244，生于1990年至2014年）通过ART怀孕的所有儿童。在这两个国家同一时期出生的全部背景人口作为对照。计算ART患儿与自然受孕患儿的印迹障碍比值比。ART儿童的中位随访时间为8年9个月，NC儿童的中位随访时间为11年9个月。参与者/材料、环境、方法：从丹麦和芬兰的国家卫生登记处，我们分别确定了1994/1990年至2014年出生的所有被诊断为Prader-Willi综合征（n = 143）、silverrussell综合征（n = 69）、Beckwith-Wiedemann综合征（n = 105）和Angelman综合征（n = 72）的儿童。主要结果和偶然性的作用：我们共确定了388名被诊断为印迹障碍的儿童；其中16人是在抗逆转录病毒治疗后怀孕的。ART儿童与NC儿童相比，四种印迹障碍的总体AOR为1.35 [95% CI: 0.80-2.29]，但由于有8名ART儿童被诊断为Beckwith-Wiedemann综合征，因此这种特定印迹障碍的AOR为2.84 [95% CI: 1.34-6.01]。抗逆转录病毒治疗后怀孕的儿童患贝克维斯-魏德曼综合征的绝对风险仍然很低：每10万名新生儿中有10.7人。接受抗逆转录病毒治疗的儿童患Prader-Willi综合征、Silver-Russell综合征和Angelman综合征的风险没有增加。局限性和谨慎的原因：印迹障碍是罕见的事件，我们的结果是基于少数有印迹障碍的ART儿童。病因是复杂的，只是部分澄清，临床诊断是由广泛的表型谱的挑战。研究结果的更广泛意义：在现有的研究中，关于ART后怀孕的儿童的印迹障碍风险的结果是模糊的。这项研究补充说，抗逆转录病毒治疗儿童出现印记障碍的风险非常小，可能仅限于贝克威思-魏德曼综合征。
STUDY QUESTION: Is the risk of imprinting disorders increased in children conceived after ART?SUMMARY ANSWER: We found an adjusted odds ratio (AOR) of 2.84 [95% CI: 1.34-6.01] for Beckwith-Wiedemann syndrome in ART children, while the risk of Prader-Willi syndrome, Silver-Russell syndrome or Angelman syndrome was not increased in children conceived after ART.WHAT IS KNOWN ALREADY: Earlier studies, most of them small, have suggested an association between ART and imprinting disorders.STUDY DESIGN, SIZE, DURATION: This was a binational register-based cohort study. All children conceived by ART in Denmark (n = 45 393, born between 1994 and 2014) and in Finland (n = 29 244, born between 1990 and 2014) were identified. The full background populations born during the same time periods in the two countries were included as controls. Odds ratios of imprinting disorders in ART children compared with naturally conceived (NC) children were calculated. The median follow-up time was 8 years and 9 months for ART children and 11 years and 9 months for NC children.PARTICIPANTS/MATERIALS, SETTING, METHODS: From the national health registries in Denmark and Finland, we identified all children diagnosed with Prader-Willi syndrome (n = 143), Silver-Russell syndrome (n = 69), Beckwith-Wiedemann syndrome (n = 105) and Angelman syndrome (n = 72) born between 1994/1990 and 2014, respectively.MAIN RESULTS AND THE ROLE OF CHANCE: We identified a total of 388 children diagnosed with imprinting disorders; 16 of these were conceived after ART. The overall AOR for the four imprinting disorders in ART children compared with NC children was 1.35 [95% CI: 0.80-2.29], but since eight ART children were diagnosed with Beckwith-Wiedemann syndrome, the AOR for this specific imprinting disorder was 2.84 [95% CI: 1.34-6.01]. The absolute risk of Beckwith-Wiedemann syndrome in children conceived after ART was still low: 10.7 out of 100 000 newborns. The risks of Prader-Willi syndrome, Silver-Russell syndrome and Angelman syndrome were not increased in children conceived after ART.LIMITATIONS, REASONS FOR CAUTION: Imprinting disorders are rare events and our results are based on few ART children with imprinting disorders. The aetiology is complex and only partly clarified, and the clinical diagnoses are challenged by a broad phenotypic spectrum.WIDER IMPLICATIONS OF THE FINDINGS: In the existing studies, results on the risk of imprinting disorders in children conceived after ART are ambiguous. This study adds that the risk of imprinting disorders in ART children is very small and perhaps restricted to Beckwith-Wiedemann syndrome.