Département de Santé Publique, Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Trousseau, Centre de Référence sur les Agents Tératogènes (CRAT), Paris, F75012, France.
Department of Neonatology, Centre Hospitalier du Mans, Le Mans, 72037, France.
Eur J Epidemiol. 2024 Oct;39(10):1073-1096. doi: 10.1007/s10654-024-01156-y. Epub 2024 Oct 1.
Adverse neonatal outcomes following in utero antipsychotic exposure remain unclear. This systematic review and meta-analysis aimed to investigate associations between in utero first- and second-generation antipsychotic exposure and various neonatal outcomes. The primary outcome was small for gestational age. Secondary outcomes included other birth weight-related measures, prematurity and neonatal outcomes. MEDLINE, EMBASE, CENTRAL, ICTRP, and ClinicalTrials.gov were searched for on 8th July 2023. Two reviewers independently selected studies reporting associations between exposure and neonatal outcomes (all designs were eligible, no language or time restriction) and extracted data. ROBINS-I was used for risk of bias assessment. Meta-analyses were performed. Measures of association were odds ratios and mean differences. Thirty-one observational studies were included. Regarding small for gestational age < 10th percentile, meta-analysis was only performed for second-generation antipsychotics and showed no evidence for an association (OR 1.31 [95%CI 0.83; 2.07]; I²=46%; p=0.13, n = 4 studies). First-generation antipsychotics were associated with an increased risk of small for gestational age < 3rd percentile (OR 1.37 [95%CI 1.02; 1.83]; I²=60%; p=0.04, n = 5) and a lower mean birthweight (MD -135 g [95%CI -203; -66]; I²=53%; p=0.07, n = 5). Second-generation antipsychotics were associated with large for gestational age > 97th percentile (OR 1.56 [95%CI 1.31; 1.87]; I²=4%; p=0.37, n = 4) and Apgar score < 7 (OR 1.64 [95%CI 1.09; 2.47]; I²=47%; p=0.13, n = 4). Both types of antipsychotics were associated with increased risks of preterm birth and neonatal hospitalization. Despite potential confounding in the studies, this systematic review and meta-analysis showed that newborns of mothers using antipsychotics during pregnancy are potentially at risk of adverse neonatal outcomes. Data sources: MEDLINE, EMBASE, CENTRAL, ICTRP, ClinicalTrials.gov. Prospero Registration Number CRD42023401805.
胎儿暴露于抗精神病药物后新生儿结局不良仍不清楚。本系统评价和荟萃分析旨在调查胎儿第一代和第二代抗精神病药物暴露与各种新生儿结局之间的关系。主要结局是胎龄小于正常。次要结局包括其他与出生体重相关的指标、早产和新生儿结局。于 2023 年 7 月 8 日检索了 MEDLINE、EMBASE、CENTRAL、ICTRP 和 ClinicalTrials.gov 数据库。两名评审员独立筛选了报告暴露与新生儿结局之间关系的研究（所有设计均合格，无语言或时间限制）并提取数据。使用 ROBINS-I 评估偏倚风险。进行荟萃分析。关联测量指标为比值比和均数差。纳入了 31 项观察性研究。关于胎龄小于第 10 百分位数的小于胎龄儿，仅对第二代抗精神病药物进行了荟萃分析，结果表明没有关联（OR 1.31 [95%CI 0.83; 2.07]；I²=46%；p=0.13，n=4 项研究）。第一代抗精神病药物与胎龄小于第 3 百分位数的小于胎龄儿风险增加相关（OR 1.37 [95%CI 1.02; 1.83]；I²=60%；p=0.04，n=5）和出生体重较低（MD -135 g [95%CI -203; -66]；I²=53%；p=0.07，n=5）。第二代抗精神病药物与胎龄大于第 97 百分位数的大于胎龄儿相关（OR 1.56 [95%CI 1.31; 1.87]；I²=4%；p=0.37，n=4）和阿普加评分小于 7 分（OR 1.64 [95%CI 1.09; 2.47]；I²=47%；p=0.13，n=4）。两种类型的抗精神病药物都与早产和新生儿住院的风险增加相关。尽管研究中存在潜在混杂因素，但本系统评价和荟萃分析表明，母亲在怀孕期间使用抗精神病药物的新生儿可能存在不良新生儿结局的风险。数据来源：MEDLINE、EMBASE、CENTRAL、ICTRP、ClinicalTrials.gov。Prospéro 注册号 CRD42023401805。
