Hanan El Marroun, PhD, Department of Child and Adolescent Psychiatry, Sophia Children's Hospital and The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands; Tonya J. H. White, MD, PhD, Department of Child and Adolescent Psychiatry, Sophia Children's Hospital and Department of Radiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Noortje J. F. van der Knaap, MSc, Judith R. Homberg, PhD, Guillén Fernández, MD, PhD, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands; Nikita K. Schoemaker, MSc, Department of Child and Adolescent Psychiatry, Sophia Children's Hospital and The Generation R Study Group, Erasmus Medical Centre, Rotterdam, The Netherlands; Vincent W. V. Jaddoe, MD, PhD, The Generation R Study Group, Department of Epidemiology and Department of Pediatrics, Erasmus Medical Centre, Rotterdam, The Netherlands; Albert Hofman, MD, PhD, Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Frank C. Verhulst, MD, PhD, Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands; James J. Hudziak, MD, Department of Child and Adolescent Psychiatry, Erasmus Medical Centre, Sophia Children's Hospital, Rotterdam, The Netherlands, and University of Vermont, College of Medicine, Deptartment of Psychiatry, Burlington, Vermont, USA; Bruno H. C. Stricker, MD, PhD, Department of Epidemiology, Erasmus Medical Centre, Rotterdam and Inspectorate of Healthcare, The Hague, The Netherlands; Henning Tiemeier, MD, PhD, Department of Child and Adolescent Psychiatry, Sophia Children's Hospital, Department of Epidemiology and Department of Psychiatry, Erasmus Medical Centre, Rotterdam, The Netherlands.
Br J Psychiatry. 2014 Aug;205(2):95-102. doi: 10.1192/bjp.bp.113.127746. Epub 2014 Aug 1.
Selective serotonin reuptake inhibitors (SSRIs) are considered safe and are frequently used during pregnancy. However, two case-control studies suggested an association between prenatal SSRI exposure with childhood autism.
To prospectively determine whether intra-uterine SSSRI exposure is associated with childhood autistic symptoms in a population-based study.
A total of 376 children prenatally exposed to maternal depressive symptoms (no SSRI exposure), 69 children prenatally exposed to SSRIs and 5531 unexposed children were included. Child pervasive developmental and affective problems were assessed by parental report with the Child Behavior Checklist at ages 1.5, 3 and 6. At age 6, we assessed autistic traits using the Social Responsiveness Scale (n = 4264).
Prenatal exposure to maternal depressive symptoms without SSRIs was related to both pervasive developmental (odds ratio (OR) = 1.44, 95% CI 1.07-1.93) and affective problems (OR = 1.44, 95% CI 1.15-1.81). Compared with unexposed children, those prenatally exposed to SSRIs also were at higher risk for developing pervasive developmental problems (OR = 1.91, 95% CI 1.13-3.47), but not for affective problems. Children prenatally exposed to SSRIs also had more autistic traits (B = 0.15, 95% CI 0.08-0.22) compared with those exposed to depressive symptoms only.
Our results suggest an association between prenatal SSRI exposure and autistic traits in children. Prenatal depressive symptoms without SSRI use were also associated with autistic traits, albeit this was weaker and less specific. Long-term drug safety trials are needed before evidence-based recommendations are possible.
选择性 5-羟色胺再摄取抑制剂（SSRIs）被认为是安全的，并且在怀孕期间经常使用。然而，两项病例对照研究表明，产前 SSRI 暴露与儿童自闭症之间存在关联。
在一项基于人群的研究中，前瞻性确定宫内 SSRI 暴露是否与儿童自闭症症状有关。
共纳入 376 名母亲在怀孕期间患有抑郁症但未使用 SSRI（无 SSRI 暴露）的儿童、69 名母亲在怀孕期间使用 SSRI 的儿童和 5531 名未暴露的儿童。通过父母报告，使用儿童行为检查表在 1.5、3 和 6 岁时评估儿童的普遍发育和情感问题。在 6 岁时，我们使用社会反应量表（n=4264）评估自闭症特征。
无 SSRI 的母亲产前抑郁症状暴露与普遍发育（比值比（OR）=1.44，95%置信区间 1.07-1.93）和情感问题（OR=1.44，95%置信区间 1.15-1.81）有关。与未暴露的儿童相比，那些在子宫内暴露于 SSRIs 的儿童也有更高的发展为普遍发育问题的风险（OR=1.91，95%置信区间 1.13-3.47），但不是情感问题。与仅暴露于抑郁症状的儿童相比，暴露于 SSRIs 的儿童也具有更多的自闭症特征（B=0.15，95%置信区间 0.08-0.22）。
我们的结果表明，产前 SSRI 暴露与儿童自闭症特征之间存在关联。无 SSRI 药物使用的母亲产前抑郁症状也与自闭症特征有关，尽管这种关联较弱且不具有特异性。在提出循证建议之前，需要进行长期的药物安全性试验。
