Objective To investigate the potential association between prenatal opioid exposure and the risk of neuropsychiatric disorders in children. Design Nationwide birth cohort study. Setting From 1 January 2009 to 31 December 2020, birth cohort data of pregnant women in South Korea linked to their liveborn infants from the National Health Insurance Service of South Korea were collected. Participants All 3 251 594 infants (paired mothers, n=2 369 322; age 32.1 years (standard deviation 4.2)) in South Korea from the start of 2010 to the end of 2017, with follow-up from the date of birth until the date of death or 31 December 2020, were included. Main outcome measures Diagnosis of neuropsychiatric disorders in liveborn infants with mental and behaviour disorders (International Classification of Diseases 10th edition codes F00-99). Follow-up continued until the first diagnosis of neuropsychiatric disorder, 31 December 2020 (end of the study period), or the date of death, whichever occurred first. Eight cohorts were created: three cohorts (full unmatched, propensity score matched, and child screening cohorts) were formed, all of which were paired with sibling comparison cohorts, in addition to two more propensity score groups. Multiple subgroup analyses were performed. Results Of the 3 128 571 infants included (from 2 299 664 mothers), we identified 2 912 559 (51.3% male, 48.7% female) infants with no prenatal opioid exposure and 216 012 (51.2% male, 48.8% female) infants with prenatal opioid exposure. The risk of neuropsychiatric disorders in the child with prenatal opioid exposure was 1.07 (95% confidence interval 1.05 to 1.10) for fully adjusted hazard ratio in the matched cohort, but no significant association was noted in the sibling comparison cohort (hazard ratio 1.00 (0.93 to 1.07)). Prenatal opioid exposure during the first trimester (1.11 (1.07 to 1.15)), higher opioid doses (1.15 (1.09 to 1.21)), and long term opioid use of 60 days or more (1.95 (1.24 to 3.06)) were associated with an increased risk of neuropsychiatric disorders in the child. Prenatal opioid exposure modestly increased the risk of severe neuropsychiatric disorders (1.30 (1.15 to 1.46)), mood disorders, attention deficit hyperactivity disorder, and intellectual disability in the child. Conclusions Opioid use during pregnancy was not associated with a substantial increase in the risk of neuropsychiatric disorders in the offspring. A slightly increased risk of neuropsychiatric disorders was observed, but this should not be considered clinically meaningful given the observational nature of the study, and limited to high opioid dose, more than one opioid used, longer duration of exposure, opioid exposure during early pregnancy, and only to some neuropsychiatric disorders. Data are available on reasonable request. The study protocol and statistical code are available from DKY (yonkkang@gmail.com). The dataset is available from the National Health Insurance Service of Korea through a data use agreement.

中文翻译：

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产前阿片类药物暴露和儿童随后发生神经精神疾病的风险：韩国全国出生队列研究


目的 探讨产前阿片类药物暴露与儿童神经精神疾病风险之间的潜在关联。设计全国出生队列研究。背景 从2009年1月1日至2020年12月31日，韩国国民健康保险局收集了韩国孕妇与其活产婴儿相关的出生队列数据。研究对象 2010 年初至 2017 年底韩国所有 3 251 594 名婴儿（配对母亲，n=2 369 322；年龄 32.1 岁（标准差 4.2）），随访时间为出生之日至出生日期死亡日期或 2020 年 12 月 31 日也包括在内。主要结果指标 患有精神和行为障碍的活产婴儿的神经精神疾病的诊断（国际疾病分类第 10 版代码 F00-99）。随访一直持续到 2020 年 12 月 31 日（研究期结束）首次诊断出神经精神疾病或死亡日期（以先发生者为准）。创建了八个队列：形成了三个队列（完全不匹配、倾向评分匹配和儿童筛查队列），所有这些队列都与兄弟姐妹比较队列配对，此外还有另外两个倾向评分组。进行了多个亚组分析。结果 在纳入的 3 128 571 名婴儿（来自 2 299 664 名母亲）中，我们确定了 2 912 559 名婴儿（51.3% 男性，48.7% 女性）没有产前阿片类药物暴露，216 012 名婴儿（51.2% 男性，48.8% 女性）患有产前阿片类药物暴露。产前阿片类药物暴露。对于匹配队列中完全调整的风险比，产前阿片类药物暴露的儿童发生神经精神疾病的风险为 1.07（95% 置信区间 1.05 至 1.10），但在兄弟姐妹比较队列中没有发现显着关联（风险比 1.00（0 。93 至 1.07))。妊娠早期的产前阿片类药物暴露（1.11（1.07至1.15））、较高的阿片类药物剂量（1.15（1.09至1.21））以及60天或以上的长期阿片类药物使用（1.95（1.24至3.06））与儿童患神经精神疾病的风险增加。产前阿片类药物暴露会适度增加儿童严重神经精神疾病（1.30（1.15至1.46））、情绪障碍、注意力缺陷多动障碍和智力障碍的风险。结论 怀孕期间使用阿片类药物与后代神经精神疾病风险的大幅增加无关。观察到神经精神疾病的风险略有增加，但考虑到研究的观察性质，这不应被认为具有临床意义，并且仅限于高阿片类药物剂量、使用超过一种阿片类药物、较长的暴露时间、妊娠早期阿片类药物暴露、并且仅针对某些神经精神疾病。可根据合理要求提供数据。研究方案和统计代码可从 DKY (yonkkang@gmail.com) 获取。该数据集可通过数据使用协议从韩国国民健康保险公团获取。