Baum A L, Misri S
Fairfax Hospital, Georgetown University, Falls Church, Va., USA.
Harv Rev Psychiatry. 1996 Sep-Oct;4(3):117-25. doi: 10.3109/10673229609030534.
We explore the effects on the developing fetus and neonate of selective serotonin-reuptake inhibitors (SSRIs) during pregnancy and lactation, reviewing the relevant animal and human studies published in English from 1976 to the present. Medline was used to search the terms SSRI, fluoxetine, pregnancy, lactation, and teratogenesis. Animal studies were inconclusive: some found that fetal exposure to high doses of fluoxetine produced no congenital anomalies, while others linked the drug to abnormalities such as craniofacial malformations, alterations in serotonergic neurotransmitter systems, birth-related hematomas, and inhibition of the milk-ejection reflex. Human investigations indicated no relationship between in utero exposure to fluoxetine and teratogenic effects, although data are limited, and none have been collected regarding behavioral teratogenesis. However, we found a suggestion of an increased rate of miscarriage, an association with infants large for gestational age, one reported case of perinatal toxicity, and one case of an infant who was colicky while receiving breast milk from a mother taking fluoxetine. Based on these data, controlled prospective studies of exposure to SSRIs during pregnancy and lactation are needed, as is long-term evaluation for behavioral teratogenesis and enduring cognitive effects. Data are lacking on drug levels in breast milk and neonatal serum. Neonatal toxicity and the effect of SSRIs on labor and delivery, the mother-infant interaction, and lactation also merit further study. Clinically, a conservative approach is encouraged, minimizing the use of SSRIs in pregnancy, avoiding such drugs during the first trimester, tapering them prior to delivery, and discouraging breast-feeding during their use.
我们探讨了孕期和哺乳期使用选择性5-羟色胺再摄取抑制剂(SSRI)对发育中的胎儿和新生儿的影响,回顾了1976年至今以英文发表的相关动物和人体研究。利用医学在线数据库(Medline)检索了“SSRI”“氟西汀”“妊娠”“哺乳”和“致畸作用”等词条。动物研究尚无定论:一些研究发现,胎儿接触高剂量氟西汀未产生先天性异常,而另一些研究则将该药物与诸如颅面畸形、5-羟色胺能神经递质系统改变、分娩相关血肿以及对射乳反射的抑制等异常情况联系起来。人体研究表明,尽管数据有限且尚未收集到关于行为致畸作用的数据,但子宫内接触氟西汀与致畸作用之间并无关联。然而,我们发现有迹象表明流产率有所上升,与大于胎龄儿有关联,有一例围产期毒性报告病例,还有一例婴儿在接受服用氟西汀的母亲的母乳时出现腹绞痛。基于这些数据,需要对孕期和哺乳期接触SSRI进行对照前瞻性研究,同时也需要对行为致畸作用和持久的认知影响进行长期评估。目前缺乏关于母乳和新生儿血清中药物水平的数据。SSRI对新生儿的毒性以及对分娩、母婴互动和哺乳的影响也值得进一步研究。临床上,鼓励采取保守方法,尽量减少孕期使用SSRI,在孕早期避免使用此类药物,在分娩前逐渐减量,并在用药期间不鼓励母乳喂养。