Zamstein Omri, Wainstock Tamar, Sheiner Eyal
The Obstetrics and Gynecology Division, Soroka University Medical Center, Ben-Gurion University of the Negev, P.O.B 151, Beer-Sheva, Israel.
School of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Arch Gynecol Obstet. 2025 Aug 26. doi: 10.1007/s00404-025-08160-x.
Significant effort has been made in recent years to identify environmental factors-particularly perinatal exposures-that contribute to the development of autism spectrum disorder (ASD), yet many proposed associations remain inconsistent and inconclusive. Given the common use of labor induction for both medical indications and maternal preference, we aimed to investigate its potential association with ASD development, while accounting for synergistic factors that may influence its onset.
A population-based cohort study was conducted at a tertiary referral center, focusing on singleton births. The study aimed to compare the occurrence of ASD in children, considering both hospital and community-based diagnoses, in relation to whether labor was induced (using mechanical cervical ripening or prostaglandins, with or without oxytocin) or began spontaneously. A Kaplan-Meier survival curve was employed to assess the cumulative incidence of ASD, and a Cox proportional hazards model was used to account for confounding variables.
Among 115,081 births, 13,071 (11.4%) were labor induced, with the remainder beginning spontaneously. Pregnancy complications, such as gestational diabetes mellitus, preeclampsia or eclampsia, and non-reassuring fetal heart rate patterns, were significantly more common in the labor induction group (p<0.001 for all). During follow-up, 767 children were diagnosed with ASD: 1.0% in the labor induction group and 0.6% in the spontaneous labor onset group (p<0.001). The Kaplan-Meier analysis showed a significantly higher cumulative hazard for ASD diagnosis in the labor induction group (log-rank p-value <0.001). However, after adjusting for maternal and perinatal factors such as maternal age, cesarean delivery, ethnicity, and gestational conditions, no significant association was found between labor induction and ASD risk (adjusted HR = 1.21, 95% CI 0.99-1.47, p = 0.063).
Labor induction was associated with a higher ASD incidence but not as an independent risk factor after adjusting for maternal and perinatal factors.
近年来，人们为确定环境因素，尤其是围产期暴露因素对自闭症谱系障碍（ASD）发展的影响付出了巨大努力，但许多提出的关联仍不一致且尚无定论。鉴于引产在医学指征和产妇意愿方面的普遍应用，我们旨在研究其与ASD发展的潜在关联，同时考虑可能影响其发病的协同因素。
在一家三级转诊中心进行了一项基于人群的队列研究，重点关注单胎分娩。该研究旨在比较经引产（使用机械性宫颈成熟或前列腺素，有无催产素）或自然发动分娩的儿童中ASD的发生率，同时考虑医院和社区诊断。采用Kaplan-Meier生存曲线评估ASD的累积发病率，并使用Cox比例风险模型来考虑混杂变量。
在115,081例分娩中，13,071例（11.4%）为引产，其余为自然发动分娩。妊娠并发症，如妊娠期糖尿病、先兆子痫或子痫以及胎心异常，在引产组中明显更为常见（所有p<0.001）。在随访期间，767名儿童被诊断为ASD：引产组为1.0%，自然发动分娩组为0.6%（p<0.001）。Kaplan-Meier分析显示，引产组ASD诊断的累积风险显著更高（对数秩p值<0.001）。然而，在调整了产妇年龄、剖宫产、种族和妊娠情况等产妇和围产期因素后，未发现引产与ASD风险之间存在显著关联（调整后HR = 1.21，95%CI 0.99-1.47，p = 0.063）。
引产与较高的ASD发病率相关，但在调整产妇和围产期因素后，它并非独立的风险因素。
