Cohen Jacqueline M, Hernández-Díaz Sonia, Bateman Brian T, Park Yoonyoung, Desai Rishi J, Gray Kathryn J, Patorno Elisabetta, Mogun Helen, Huybrechts Krista F
Department of Epidemiology, Harvard T.H. Chan School of Public Health, the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, and the Department of Anesthesiology, Brigham and Women's Hospital and Harvard Medical School, and the Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, Massachusetts.
Obstet Gynecol. 2017 Dec;130(6):1192-1201. doi: 10.1097/AOG.0000000000002362.
To evaluate whether psychostimulants used to treat attention-deficit/hyperactivity disorder (ADHD) are associated with risk of adverse placental-associated pregnancy outcomes including preeclampsia, placental abruption, growth restriction, and preterm birth.
We designed a population-based cohort study in which we examined a cohort of pregnant women and their liveborn neonates enrolled in Medicaid from 2000 to 2010. Women who received amphetamine-dextroamphetamine or methylphenidate monotherapy in the first half of pregnancy were compared with unexposed women. We considered atomoxetine, a nonstimulant ADHD medication, as a negative control exposure. To assess whether the risk period extended to the latter half of pregnancy, women who continued stimulant monotherapy after 20 weeks of gestation were compared with those who discontinued. Risk ratios and 95% CIs were estimated with propensity score stratification to control for confounders.
Pregnancies exposed to amphetamine-dextroamphetamine (n=3,331), methylphenidate (n=1,515), and atomoxetine (n=453) monotherapy in early pregnancy were compared with 1,461,493 unexposed pregnancies. Among unexposed women, the risks of the outcomes were 3.7% for preeclampsia, 1.4% for placental abruption, 2.9% for small for gestational age, and 11.2% for preterm birth. The adjusted risk ratio for stimulant use was 1.29 for preeclampsia (95% CI 1.11-1.49), 1.13 for placental abruption (0.88-1.44), 0.91 for small for gestational age (0.77-1.07), and 1.06 for preterm birth (0.97-1.16). Compared with discontinuation (n=3,527), the adjusted risk ratio for continuation of stimulant use in the latter half of pregnancy (n=1,319) was 1.26 for preeclampsia (0.94-1.67), 1.08 for placental abruption (0.67-1.74), 1.37 for small for gestational age (0.97-1.93), and 1.30 for preterm birth (1.10-1.55). Atomoxetine was not associated with the outcomes studied.
Psychostimulant use during pregnancy was associated with a small increased relative risk of preeclampsia and preterm birth. The absolute increases in risks are small and, thus, women with significant ADHD should not be counseled to suspend their ADHD treatment based on these findings.
评估用于治疗注意力缺陷多动障碍（ADHD）的精神兴奋药是否与不良胎盘相关妊娠结局的风险相关，这些结局包括子痫前期、胎盘早剥、生长受限和早产。
我们设计了一项基于人群的队列研究，研究对象为2000年至2010年参加医疗补助计划的孕妇及其活产新生儿。将妊娠前半期接受苯丙胺-右旋苯丙胺或哌甲酯单一疗法的女性与未暴露的女性进行比较。我们将非刺激性ADHD药物托莫西汀作为阴性对照暴露。为了评估风险期是否延长至妊娠后半期，将妊娠20周后继续使用兴奋剂单一疗法的女性与停药的女性进行比较。采用倾向评分分层法估计风险比和95%可信区间，以控制混杂因素。
将妊娠早期暴露于苯丙胺-右旋苯丙胺（n = 3331）、哌甲酯（n = 1515）和托莫西汀（n = 453）单一疗法的妊娠与1461493例未暴露妊娠进行比较。在未暴露的女性中，子痫前期的风险为3.7%，胎盘早剥的风险为1.4%，小于胎龄儿的风险为2.9%，早产的风险为11.2%。使用兴奋剂的校正风险比，子痫前期为1.29（95%可信区间1.11 - 1.49），胎盘早剥为1.13（0.88 - 1.44），小于胎龄儿为0.91（0.77 - 1.07），早产为1.06（0.97 - 1.16）。与停药组（n = 3527）相比，妊娠后半期继续使用兴奋剂组（n = 1319）的校正风险比，子痫前期为1.26（0.94 - 1.67），胎盘早剥为1.08（0.67 - 1.74），小于胎龄儿为1.37（0.97 - 1.93），早产为1.30（1.10 - 1.55）。托莫西汀与所研究的结局无关。
孕期使用精神兴奋药与子痫前期和早产的相对风险小幅增加相关。风险的绝对增加量很小，因此，不应根据这些研究结果建议患有严重ADHD的女性暂停其ADHD治疗。
