Social Science Research Institute and the Department of Biobehavioral Health, College of Health and Human Development, Pennsylvania State University, University Park, Pennsylvania; the Silberman School of Social Work, Hunter College, City University of New York, New York, New York; the Sandra Rosenbaum School of Social Work and Institute for Research on Poverty, College of Letters and Sciences, the La Follette School of Public Affairs, and the Department of Obstetrics and Gynecology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin; and the Chiles Center, College of Public Health, University of South Florida, Tampa, Florida.
Obstet Gynecol. 2023 Sep 1;142(3):603-611. doi: 10.1097/AOG.0000000000005289.
To evaluate the association between prenatal prescription opioid analgesic exposure (duration, timing) and neonatal opioid withdrawal syndrome (NOWS).
We conducted a retrospective cohort study of Wisconsin Medicaid-covered singleton live births from 2011 to 2019. The primary outcome was a NOWS diagnosis in the first 30 days of life. Opioid exposure was identified with any claim for prescription opioid analgesic fills during pregnancy. We measured exposure duration cumulatively in days (1-6, 7-29, 30-89, and 90 or more) and identified timing as early (first two trimesters only) or late (third trimester, regardless of earlier pregnancy use). We used logistic regression modeling to assess NOWS incidence by exposure duration and timing, with and without propensity score matching.
Overall, 31,456 (14.3%) of 220,570 neonates were exposed to prescription opioid analgesics prenatally. Among exposed neonates, 19,880 (63.2%) had 1-6 days of exposure, 7,694 (24.5%) had 7-29 days, 2,188 (7.0%) had 30-89 days, and 1,694 (5.4%) had 90 or more days of exposure; 15,032 (47.8%) had late exposure. Absolute NOWS incidence among neonates with 1-6 days of exposure was 7.29 per 1,000 neonates (95% CI 6.11-8.48), and incidence increased with longer exposure: 7-29 days (19.63, 95% CI 16.53-22.73); 30-89 days (58.96, 95% CI 49.08-68.84); and 90 or more days (177.10, 95% CI 158.90-195.29). Absolute NOWS incidence for early and late exposures were 11.26 per 1,000 neonates (95% CI 9.65-12.88) and 35.92 per 1,000 neonates (95% CI 32.95-38.90), respectively. When adjusting for confounders including timing of exposure, neonates exposed for 1-6 days had no increased odds of NOWS compared with unexposed neonates, whereas those exposed for 30 or more days had increased odds of NOWS (30-89 days: adjusted odds ratio [aOR] 2.15, 95% CI 1.22-3.79; 90 or more days: 2.80, 95% CI 1.36-5.76). Late exposure was associated with elevated odds of NOWS (aOR 1.57, 95% CI 1.25-1.96) when compared with unexposed after adjustment for exposure duration.
More than 30 days of prenatal prescription opioid exposure was associated with NOWS regardless of exposure timing. Third-trimester opioid exposure, irrespective of exposure duration, was associated with NOWS.
评估产前处方类阿片类药物暴露（持续时间、时间）与新生儿阿片戒断综合征（NOWS）之间的关联。
我们对 2011 年至 2019 年期间威斯康星州医疗补助覆盖的单胎活产进行了回顾性队列研究。主要结局是出生后 30 天内出现 NOWS 诊断。通过处方类阿片类药物的任何索赔来确定阿片类药物暴露。我们以天为单位（1-6 天、7-29 天、30-89 天和 90 天或以上）累计测量暴露持续时间，并确定早孕期（仅前两个三个月）或晚孕期（第三个三个月，无论早期妊娠是否使用）。我们使用逻辑回归模型，在不进行和进行倾向评分匹配的情况下，评估暴露持续时间和时间与 NOWS 发生率之间的关系。
总体而言，220570 名新生儿中有 31456 名（14.3%）在产前接触过处方类阿片类药物。在暴露的新生儿中，19880 名（63.2%）暴露 1-6 天，7694 名（24.5%）暴露 7-29 天，2188 名（7.0%）暴露 30-89 天，1694 名（5.4%）暴露 90 天或以上；15032 名（47.8%）有晚孕期暴露。暴露 1-6 天的新生儿中，NOWS 的绝对发病率为每 1000 名新生儿 7.29 例（95%CI 6.11-8.48），且随着暴露时间的延长，发病率增加：7-29 天（19.63，95%CI 16.53-22.73）；30-89 天（58.96，95%CI 49.08-68.84）；90 天或以上（177.10，95%CI 158.90-195.29）。早孕期和晚孕期暴露的绝对 NOWS 发病率分别为每 1000 名新生儿 11.26 例（95%CI 9.65-12.88）和 35.92 例（95%CI 32.95-38.90）。在调整了包括暴露时间在内的混杂因素后，与未暴露的新生儿相比，暴露 1-6 天的新生儿没有增加出现 NOWS 的几率，而暴露 30 天或以上的新生儿出现 NOWS 的几率增加（30-89 天：调整后的优势比[aOR]2.15，95%CI 1.22-3.79；90 天或以上：2.80，95%CI 1.36-5.76）。与未暴露的新生儿相比，晚孕期暴露（aOR 1.57，95%CI 1.25-1.96）在调整了暴露持续时间后与 NOWS 发生几率增加相关。
产前处方类阿片类药物暴露超过 30 天与 NOWS 有关，无论暴露时间如何。第三个三个月的阿片类药物暴露，无论暴露持续时间如何，均与 NOWS 相关。
