Vanderbilt University, Nashville, Tennessee.
Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee.
JAMA Netw Open. 2024 Feb 5;7(2):e2355990. doi: 10.1001/jamanetworkopen.2023.55990.
Opioid exposure during pregnancy has been associated with preterm birth, but prior studies have not differentiated between spontaneous and indicated preterm birth or fully investigated these associations as functions of opioid dose.
To determine whether prescription opioid use during pregnancy is associated with spontaneous preterm birth and whether the association is dose-dependent.
DESIGN, SETTING, AND PARTICIPANTS: This case-control study examined a retrospective cohort of pregnant patients enrolled in Tennessee Medicaid. Enrollment files were linked to health care encounters, hospital discharge information, birth certificate data, and prescription fills. Eligible participants were pregnant people ages 15 to 44 years without opioid use disorder who experienced birth of a single fetus at 24 weeks gestation or greater between 2007 and 2019 with linked birth certificate data. Cases of spontaneous preterm birth were matched with up to 10 controls based on pregnancy start date, race, ethnicity, age at delivery within 2 years, and history of prior preterm birth. Cases and matched controls were continuously enrolled in TennCare for at least 90 days prior to the index date (case delivery date).
Total opioid MME filled during the 60 days prior to the index date.
The primary outcome was spontaneous preterm birth determined by a validated algorithm using birth certificate data. Conditional logistic regression was used to estimate the association between spontaneous preterm birth and total opioid morphine milligram equivalents (MME) dispensed, adjusting for parity, prepregnancy body mass index, education level, tobacco use, hepatitis infections, and pain indications.
A total of 25 391 cases (median [IQR] age, 23 [20-28] years; 127 Asian [0.5%], 9820 Black [38.7%], 664 Hispanic [2.6%]; 14 748 non-Hispanic White [58.1%]) with spontaneous preterm birth were identified and matched with 225 696 controls (median [IQR] age, 23 [20-27] years; 229 Asian [0.1%], 89 819 Black [39.8%], 3590 Hispanic [1.6%]; 132 002 non-Hispanic White [58.5%]) (251 087 patients total), with 18 702 patients (7.4%) filling an opioid prescription in the 60 days prior to the index date. Each doubling of nonzero opioid MME was associated with a 4% increase in the odds of spontaneous preterm birth compared with no opioid exposure (adjusted odds ratio, 1.04; 95% CI, 1.01-1.08).
In this case-control study, a positive association was found between total prescription opioid dose dispensed and the odds of spontaneous preterm birth. These findings support guidance to minimize opioid exposure during pregnancy and prescribe the lowest dose necessary.
孕期阿片类药物暴露与早产有关，但先前的研究并未区分自发性和指征性早产，也没有充分研究这些关联作为阿片类药物剂量的函数。
确定孕期处方类阿片类药物的使用是否与自发性早产有关，以及这种关联是否与剂量有关。
设计、地点和参与者：这项病例对照研究检查了田纳西州医疗补助计划中纳入的回顾性队列中的孕妇。登记档案与医疗保健遭遇、出院信息、出生证明数据和处方配药相链接。合格的参与者是年龄在 15 至 44 岁之间、无阿片类药物使用障碍的孕妇，在 2007 年至 2019 年间经历了妊娠 24 周或以上的单胎分娩，且有相关的出生证明数据。自发性早产病例与最多 10 名对照基于妊娠开始日期、种族、民族、分娩年龄在 2 年内、以及既往早产史进行匹配。病例和匹配的对照在指数日期（病例分娩日期）前至少连续 90 天持续参加 TennCare。
在指数日期前 60 天内开出的总阿片类药物 MME。
主要结局是通过使用出生证明数据的验证算法确定的自发性早产。条件逻辑回归用于估计自发性早产与总阿片类药物吗啡毫克当量（MME）之间的关联，调整了产次、孕前体重指数、教育水平、吸烟、肝炎感染和疼痛指征。
共确定了 25391 例（中位数[IQR]年龄，23[20-28]岁；127 例亚洲人[0.5%]，9820 名黑人[38.7%]，664 名西班牙裔[2.6%]；14748 名非西班牙裔白人[58.1%]）自发性早产病例，并与 225696 名对照（中位数[IQR]年龄，23[20-27]岁；229 例亚洲人[0.1%]，89819 名黑人[39.8%]，3590 名西班牙裔[1.6%]；132002 名非西班牙裔白人[58.5%]）（总计 251087 例患者）相匹配，其中 18702 例（7.4%）在指数日期前 60 天内开出了阿片类药物处方。与无阿片类药物暴露相比，每增加一倍的非零阿片类 MME，自发性早产的几率增加 4%（调整后的优势比，1.04；95%CI，1.01-1.08）。
在这项病例对照研究中，发现总处方类阿片类药物剂量与自发性早产的几率之间存在正相关。这些发现支持了减少孕期阿片类药物暴露和开具最低必要剂量的指导。
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