Brett Jonathan, Bruno Claudia, Varney Bianca, Havard Alys, Shand Antonia, Huybrechts Krista F, Zoega Helga
Faculty of Medicine and Health, St Vincent's Clinical School, University of New South Wales, Sydney, Australia.
Faculty of Medicine and Health, School of Population Health, University of New South Wales, Sydney, Australia.
Int J Epidemiol. 2025 Jun 11;54(4). doi: 10.1093/ije/dyaf137.
Analgesic opioid use in pregnancy could increase the risk of disorders related to placental malperfusion, but this relationship is incompletely characterized. We aimed to study the causal association between analgesic opioids in pregnancy and placental abruption, pre-eclampsia, preterm birth, and fetal growth restriction (FGR).
We conducted a population-based cohort study of pregnancies resulting in birth at ≥20 weeks of gestation between July 2013 and December 2019 in New South Wales, Australia. Linked data on pregnancy, births, medication dispensation, and health services were used. Opioid exposure was defined as at least one opioid dispensation from the last menstrual period to birth. We stratified analyses by exposure in early (≤20 weeks) and/or late (>20 weeks) pregnancy and opioid type by using non-exposed pregnancies as a comparator. We estimated risks by using Cox proportional-hazards models and time-varying exposure, adjusting for demographics, comorbidities, and other medications.
Among 509 971 births, 32 266 (6.3%) had an opioid dispensation. We observed modestly increased risks with any opioid exposure for placental abruption [adjusted hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.06-1.41] and preterm birth (adjusted HR 1.23, 95% CI 1.18-1.28), but not for pre-eclampsia (adjusted HR 1.06, 95% CI 0.99-1.13) or FGR (adjusted HR 0.95, 95% CI 0.88-1.02). Risks of abruption were the most elevated when exposure occurred in both early and late pregnancy (adjusted HR 1.76, 95% CI 1.30-2.40) and for preterm birth when exposure occurred in late-only pregnancy (adjusted HR 1.36, 95% CI 1.27-1.45). Monotherapy with both codeine and oxycodone was associated with elevated risks of abruption and preterm birth.
In this population-based cohort study, we observed modestly increased risks of preterm birth and placental abruption after analgesic opioid use in pregnancy, driven by codeine and oxycodone-the two most frequently used opioids.
孕期使用镇痛类阿片类药物可能会增加与胎盘灌注不良相关疾病的风险，但这种关系尚未完全明确。我们旨在研究孕期使用镇痛类阿片类药物与胎盘早剥、子痫前期、早产和胎儿生长受限（FGR）之间的因果关系。
我们对2013年7月至2019年12月在澳大利亚新南威尔士州妊娠≥20周并分娩的人群进行了一项队列研究。使用了妊娠、分娩、药物配给和医疗服务的关联数据。阿片类药物暴露定义为从末次月经到分娩至少有一次阿片类药物配给。我们以未暴露的妊娠作为对照，按妊娠早期（≤20周）和/或晚期（>20周）的暴露情况以及阿片类药物类型进行分层分析。我们使用Cox比例风险模型和随时间变化的暴露情况来估计风险，并对人口统计学、合并症和其他药物进行了调整。
在509971例分娩中，32266例（6.3%）有阿片类药物配给。我们观察到，任何阿片类药物暴露都会使胎盘早剥[调整后的风险比（HR）为1.22，95%置信区间（CI）为1.06 - 1.41]和早产（调整后的HR为1.23，95%CI为1.18 - 1.28）的风险略有增加，但子痫前期（调整后的HR为1.06，95%CI为0.99 - 1.13）或FGR（调整后的HR为0.95，95%CI为0.88 - 1.02）的风险没有增加。当妊娠早期和晚期都有暴露时，胎盘早剥的风险最高（调整后的HR为1.76，95%CI为1.
30 - 2.40）；仅在妊娠晚期暴露时，早产风险最高（调整后的HR为1.36，95%CI为1.27 - 1.45）。可待因和羟考酮单药治疗与胎盘早剥和早产风险升高有关。
在这项基于人群的队列研究中，我们观察到孕期使用镇痛类阿片类药物后，早产和胎盘早剥的风险略有增加，这主要由最常用的两种阿片类药物——可待因和羟考酮所致。
