Department of Obstetrics and Gynecology, Faculty of Medicine, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
Pediatr Res. 2019 Jun;85(7):1032-1040. doi: 10.1038/s41390-019-0309-8. Epub 2019 Feb 9.
Approximately 1/3 of newborns exposed antenatally to selective serotonin reuptake inhibitors (SSRIs) exhibit poor neonatal adaptation. Although several potential mechanisms have been proposed, the actual mechanism has not been elucidated.
We investigated outcomes in neonatal lambs exposed prenatally or postnatally to fluoxetine (FX). Daily FX injections (50 mg) were given intravenously (i.v.) to five pregnant ewes via implanted catheters beginning at 131-132 days gestation (term = 147 days) for 2 weeks. In another group, lambs with implanted vascular catheters had sterile water (n = 9) or FX (1 mg/kg, n = 12) injected i.v. on ~postnatal day (PND) 4.
Prenatal FX-exposed lambs (n = 7) were hyperactive during PND 4 to 14 and their heart rate variability (HRV) was significantly lower than in control lambs (n = 7) on PND 2. In contrast, arterial pressure, heart rate, electrocardiogram, arterial blood gases, pH, glucose, lactate, cortisol, and sleep-activity cycles were not altered following postnatal FX injection.
This abnormal postnatal hyperactivity with antenatal FX exposure may reflect increased maturity in terms of locomotory activity. The results suggest that altered brain development may be involved in the poor neonatal adaptation in human infants exposed to FX in utero.
大约有 1/3 的新生儿在产前接触选择性 5-羟色胺再摄取抑制剂（SSRIs）后表现出不良的新生儿适应能力。尽管已经提出了几种潜在的机制，但实际的机制尚未阐明。
我们研究了产前或产后暴露于氟西汀（FX）的新生羔羊的结局。从妊娠 131-132 天（足月= 147 天）开始，通过植入的导管每天向五只怀孕母羊静脉内（i.v.）注射 50mg 的 FX，持续 2 周。在另一组中，植入血管导管的羔羊在大约出生后第 4 天静脉内注射无菌水（n=9）或 FX（1mg/kg，n=12）。
产前 FX 暴露的羔羊（n=7）在出生后第 4 天至第 14 天表现出过度活跃，其心率变异性（HRV）明显低于对照组羔羊（n=7）在出生后第 2 天。相比之下，动脉压、心率、心电图、动脉血气、pH 值、血糖、乳酸、皮质醇和睡眠-活动周期在出生后注射 FX 后并未改变。
这种与产前 FX 暴露相关的异常产后过度活跃可能反映了在运动活动方面的成熟度增加。结果表明，大脑发育的改变可能与人类婴儿在子宫内暴露于 FX 后不良的新生儿适应有关。
