Oberlander T F, Bonaguro R J, Misri S, Papsdorf M, Ross C J D, Simpson E M
Early Human Experience Unit, Department of Pediatrics, Centre for Community Child Health Research, University of British Columbia, Vancouver, BC, Canada.
Mol Psychiatry. 2008 Jan;13(1):65-73. doi: 10.1038/sj.mp.4002007. Epub 2007 May 22.
Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P<0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.
据报道,产前接触5-羟色胺再摄取抑制剂(SRI)抗抑郁药物的新生儿中,高达30%会出现阿氏评分降低、出生体重减轻、呼吸窘迫风险增加、易激惹和肌张力增加。在成年人中,这些药物的作用可能与5-羟色胺转运体(SLC6A4)启动子的基因型有关。在本研究中,我们调查了SLC6A4基因型是否会影响产前接触SRI的新生儿出现不良结局的风险。测定了37例产前接触SRI的新生儿的新生儿结局,包括阿氏评分、出生体重、出生时的孕周、新生儿适应不良症状以及SLC6A4基因型,并与47例未接触的新生儿进行比较。在接触药物的新生儿中观察到5分钟阿氏评分降低,且ss基因型对此有调节作用(P<0.001)。接触药物的ls基因型新生儿出生体重较低(P=0.008)。与未接触药物的新生儿相比,ll基因型的接触药物新生儿出现呼吸道症状(呼吸窘迫和呼吸急促)的风险更高(P<0.05),而ss基因型的接触药物新生儿出现神经运动症状的风险增加(P<0.026)。在控制孕期母亲情绪、孕期药物暴露时长、出生时的孕周和剖宫产率后,这些关系依然存在。产前接触SRI与不良新生儿结局相关,且这些影响受婴儿SLC6A4基因型调节。多态性与特定结局之间的关系在新生儿期有所不同,这表明除了明显的基因-药物相互作用外,多种机制导致了产前接触SRI后出现不良新生儿结局。