产前尼古丁或大麻暴露与后代神经行为结果。
Prenatal Nicotine or Cannabis Exposure and Offspring Neurobehavioral Outcomes.
机构信息
Departments of Obstetrics and Gynecology, University of Utah Health, Salt Lake City, Utah, University of Texas-Southwestern, Dallas, Texas, Columbia University, New York, New York, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, University of Texas Medical Branch at Galveston, Galveston, Texas, University of Alabama at Birmingham, Birmingham, Alabama, Northwestern University, Chicago, Illinois, Brown University, Providence, Rhode Island, University of Texas-Houston, Houston, Texas, The Ohio State University, Columbus, Ohio, Case Western Reserve University, Cleveland, Ohio, and University of Pittsburgh, Pittsburgh, Pennsylvania; the Department of Pathology, University of Utah Health and ARUP Laboratories, Salt Lake City, Utah; the George Washington University Biostatistics Center, Washington, DC; and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
出版信息
Obstet Gynecol. 2022 Jan 1;139(1):21-30. doi: 10.1097/AOG.0000000000004632.
OBJECTIVE
To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes.
METHODS
We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment.
RESULTS
Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89).
CONCLUSIONS
Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT00388297.
目的
研究母体尿液中尼古丁或大麻代谢物的存在与儿童神经发育结果之间的关联。
方法
我们对两项平行的多中心随机对照试验进行了二次分析，这些试验针对的是妊娠 8-20 周的甲状腺素功能减退或亚临床甲状腺功能减退患者的治疗。所有在入组时具有母体尿液样本且对儿童进行神经发育测试的母婴对子均包括在内（N=1197）。暴露是尿液样本中尼古丁（可替宁）或大麻 11-去甲-9-羧基-Δ9-四氢大麻酚[THC-COOH]）或两者的代谢物呈阳性。主要结局是 60 个月时的儿童智商。次要结局包括认知、运动和语言、注意力、行为和社会能力，以及 12、24、36 和 48 个月时的差异技能评估。进行了分位数回归分析，并进行了混杂因素调整。
结果
在 1197 名孕妇中，99 名（8.3%）的可替宁样本呈阳性，47 名（3.9%）的 THC-COOH 样本呈阳性；33 名（2.8%）同时呈阳性。两组在自我报告的种族和民族、教育程度、婚姻状况、保险和甲状腺状况方面存在差异。可替宁暴露组和未暴露组儿童的中位数智商相似（90 对 95，调整后的中位数差异-2.47，95%CI-6.22 至 1.29），THC-COOH 暴露组和未暴露组儿童的中位数智商相似（89 对 95，调整后的中位数差异-1.35，95%CI-7.76 至 5.05）。在次要结局分析中，与未暴露于 THC-COOH 的儿童相比，暴露于 THC-COOH 的儿童在 48 个月时的注意力评分更高（57 对 49，调整后的中位数差异 6.0，95%CI 1.11-10.89）。
结论
产前尼古丁或大麻暴露均与智商差异无关。大麻暴露与儿童早期注意力评分下降有关。需要进行纵向研究，评估儿童神经发育结果与产前尼古丁和大麻暴露之间的关联，并重点关注暴露的时间和数量。
临床试验注册
ClinicalTrials.gov，NCT00388297。
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