Background

Increasing numbers of reproductive-aged women are using attention-deficit/hyperactivity disorder (ADHD) medications. Findings from studies exploring the safety of these medications during pregnancy are mixed, and it is unclear whether associations reflect causal effects or could be partially or fully explained by other factors that differ between exposed and unexposed offspring.

Objectives

The aim of this systematic review was to evaluate the adverse pregnancy-related and offspring outcomes associated with exposure to prescribed ADHD medication during pregnancy with a focus on how studies to date have handled the influence of confounding.

Methods

We searched PubMed, Embase, PsycINFO, and Web of Science up to 1 July 2019 without any restrictions on language or date of publication. We included all observational studies (e.g., cohort studies, case–control studies, case–crossover studies, cross-sectional studies, and registry-based studies) with pregnant women of any age or from any setting who were prescribed ADHD medications and evaluated any outcome, including both short- and long-term maternal and offspring outcomes. Two independent authors then used the Newcastle–Ottawa Scale to rate the quality of the included studies.

Results

Eight cohort studies that estimated adverse pregnancy-related and offspring outcomes associated with exposure to ADHD medication during pregnancy were included in the qualitative review. The included studies had substantial methodological differences in data sources, type of medications examined, definitions of studied pregnancy-related and offspring outcomes, types of control groups, and confounding adjustment. There was no convincing evidence for teratogenic effects according to the relative risk of pregnancy-related and offspring outcomes, and the observed differences in absolute risks were overall small in magnitude. Adjustment for confounding was inadequate in most studies, and none of the included studies adjusted for ADHD severity in the mothers.

Conclusion

The current evidence does not suggest that the use of ADHD medication during pregnancy results in significant adverse consequences for mother or offspring. However, the data are too limited to make an unequivocal recommendation. Therefore, physicians should consider whether the advantages of using ADHD medication outweigh the potential risks for the developing fetus according to each woman’s specific circumstances. Future research should attempt to triangulate research findings based on a combination of different designs that differ in their underlying strengths and limitations and should investigate specific confounding factors, the potential impact of timing of exposure, and potential long-term outcomes in the offspring.

中文翻译：

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妊娠期多动症处方药物与妊娠相关及后代结局的关联：系统评价。

背景

越来越多的育龄妇女正在使用注意力缺陷/多动症 (ADHD) 药物。探索怀孕期间这些药物的安全性的研究结果好坏参半，目前尚不清楚这种关联是否反映了因果效应，或者可以部分或完全由暴露和未暴露后代之间不同的其他因素解释。

目标

本系统评价的目的是评估与妊娠期间服用处方多动症药物相关的不良妊娠相关结局和后代结局，重点关注迄今为止的研究如何处理混杂因素的影响。

方法

我们检索了截至 2019 年 7 月 1 日的 PubMed、Embase、PsycINFO 和 Web of Science，对语言或出版日期没有任何限制。我们纳入了所有观察性研究（例如，队列研究、病例对照研究、病例交叉研究、横断面研究和基于登记的研究），对象是任何年龄或来自任何环境、服用 ADHD 药物的孕妇，并评估了结局，包括短期和长期的孕产妇和后代结局。然后，两位独立作者使用纽卡斯尔-渥太华量表来评估纳入研究的质量。

结果

定性评价中纳入了八项队列研究，这些研究估计了与妊娠期间接触多动症药物相关的不良妊娠相关和后代结局。纳入的研究在数据来源、检查的药物类型、研究的妊娠相关和后代结局的定义、对照组的类型以及混杂调整方面存在显着的方法学差异。根据妊娠相关和后代结局的相对风险，没有令人信服的证据表明有致畸作用，并且观察到的绝对风险差异总体上很小。大多数研究中对混杂因素的调整不足，并且纳入的研究均未针对母亲的 ADHD 严重程度进行调整。

结论

目前的证据并不表明怀孕期间使用多动症药物会给母亲或后代带来严重的不良后果。然而，数据太有限，无法提出明确的建议。因此，医生应根据每位女性的具体情况，考虑使用多动症药物的好处是否大于对胎儿发育的潜在风险。未来的研究应尝试根据不同设计的组合对研究结果进行三角测量，这些设计的潜在优势和局限性各不相同，并应调查具体的混杂因素、暴露时间的潜在影响以及后代的潜在长期结果。