PharmacoEpidemiology and Drug Safety Research Group, Department of Pharmacy, and PharmaTox Strategic Research Initiative, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.
Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
JAMA Netw Open. 2022 Jul 1;5(7):e2222425. doi: 10.1001/jamanetworkopen.2022.22425.
Few studies have examined the neurodevelopmental consequences of prenatal exposure to opioid analgesics. Therefore, it is necessary to gain knowledge to inform clinical decisions for pregnant women with moderate to severe pain.
To investigate fifth-grade scholastic skills in children with prenatal exposure to opioid analgesics.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted based on data from the Norwegian Mother, Father, and Child Cohort (1999-2008). These data were linked to the Medical Birth Registry of Norway, and data from Statistics Norway included 64 256 live-born singletons, born to 54 568 mothers who reported pain during pregnancy, were analyzed. The study was conducted from July 1 to December 15, 2021.
Self-reported exposure to opioid analgesics during pregnancy, characterized in terms of any exposure, the exposure timing, and the exposure duration.
Scores from 3 national tests for children in fifth grade. The tests measured scholastic skills in literacy, numeracy, and the English language. Test scores were standardized to z scores. Differences in z scores were compared between children of mothers exposed to opioid analgesics during pregnancy and children of mothers with only prepregnancy opioid exposure.
Of the 64 256 children included, 32 521 were boys (50.6%), and 1483 children (2.3%) were exposed to an opioid analgesic at least once during gestation. All test scores were similar between children with any exposure to opioid analgesics in utero and children with only prepregnancy exposure. Children exposed in the first trimester and those exposed in two or three 4-week intervals during pregnancy scored lower than children of mothers with only prepregnancy exposures on tests in literacy (weighted β [wβ], -0.13; 95% CI, -0.25 to -0.01 and wβ, -0.19; 95% CI, -0.35 to -0.04) and numeracy (wβ, -0.14; 95% CI, -0.25 to -0.04 and wβ, -0.19; 95% CI, -0.34 to -0.05). These differences were small and may not be clinically relevant.
In this large birth cohort, prenatal exposure to opioid analgesics had no substantial negative association with fifth-grade scholastic skills. However, adequate pain management in pregnancy may be addressed on an individual patient level, bearing in mind the benefits and risks of different analgesic therapies.
很少有研究调查过产前暴露于阿片类镇痛药对神经发育的影响。因此，有必要获得知识，为有中度至重度疼痛的孕妇做出临床决策。
调查有产前阿片类药物暴露史的儿童的五年级学习技能。
设计、地点和参与者：本队列研究基于挪威母亲、父亲和儿童队列（1999-2008 年）的数据。这些数据与挪威医学出生登记处相关联，来自挪威统计局的数据包括 64256 名活产单胎，这些孩子的母亲在怀孕期间报告有疼痛，分析了这些数据。研究于 2021 年 7 月 1 日至 12 月 15 日进行。
报告的怀孕期间暴露于阿片类镇痛药，从任何暴露、暴露时间和暴露持续时间方面进行描述。
五年级儿童的 3 项全国性测试的分数。这些测试衡量了读写、计算和英语语言方面的学业技能。测试分数被标准化为 z 分数。与仅在妊娠前暴露于阿片类药物的母亲的孩子相比，妊娠期间至少暴露于阿片类药物一次的孩子的 z 分数差异。
在纳入的 64256 名儿童中，32521 名为男孩（50.6%），1483 名儿童（2.3%）在宫内至少暴露于一种阿片类镇痛药。所有测试分数在宫内有任何阿片类药物暴露的儿童和仅在妊娠前暴露的儿童之间相似。在妊娠早期暴露的儿童和在妊娠期间暴露于两个或三个 4 周间隔的儿童在读写（加权β[wβ]，-0.13；95%CI，-0.25 至 -0.01 和 wβ，-0.19；95%CI，-0.35 至 -0.04）和计算（wβ，-0.14；95%CI，-0.25 至 -0.04 和 wβ，-0.19；95%CI，-0.34 至 -0.05）测试中得分低于仅在妊娠前暴露的儿童。这些差异很小，可能没有临床意义。
在这个大型出生队列中，产前暴露于阿片类镇痛药与五年级学业成绩之间没有明显的负相关。然而，在考虑到不同镇痛疗法的益处和风险的情况下，可以在个体患者层面上解决妊娠期间的充分疼痛管理问题。
