Corti Silvia, Pileri Paola, Mazzocco Martina I, Mandò Chiara, Moscatiello Anna F, Cattaneo Dario, Cheli Stefania, Baldelli Sara, Pogliani Laura, Clementi Emilio, Cetin Irene
Department of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, Italy.
Clinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Milan, Milan, Italy.
Front Pediatr. 2019 Jul 26;7:309. doi: 10.3389/fped.2019.00309. eCollection 2019.
SSRIs (Selective Serotonin Reuptake Inhibitors) are the most useful drugs to treat depression during pregnancy. Intrauterine exposure to SSRIs may increase the risk of growth restriction, preterm birth and neonatal complications. However, advantages in treating depression seem to exceed potential drug side effects in respect un-treated depression. SSRIs undergo extensive hepatic first-pass metabolism with the involvement of several cytochrome P450 (CYPs) enzymes. Genetic polymorphisms may influence the expression and activity of CYPs genes. The first aim of this study was to evaluate neonatal outcomes in depressed mothers exposed to SSRIs during pregnancy. SSRIs pharmacogenetics was also evaluated in a subset of mothers and fetuses. In this case-control study, ( = 42) were Caucasian women with a diagnosis of depression and/or anxiety, treated with SSRIs for the whole pregnancy. ( = 85) were Caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptics, drug of abuse, alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples were obtained at delivery to analyze genotype in 33 . The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean hemoglobin values before delivery. Obstetric features were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be Low Birth Weight (LBW) (birth weight <2,500 g) ( = 0.01), had significantly lower mean Apgar scores at 1' ( = 0.006) and at 5' ( = 0.023) and worse Apgar distribution at 1' ( = 0.017) and at 5' ( = 0.013). Fifty-six percent of newborns presented one or more symptoms consistent with poor neonatal adaptation syndrome (PNAS). Pharmacogenetic analysis at delivery did not show significant differences in the frequencies of obstetric or neonatal complications in relation to polymorphisms. We found that newborns exposed to SSRIs are at increased risk of poor neonatal outcomes in terms of low birth weight, low Apgar scores and, clinically, poor neonatal adaptation syndrome. Preliminary pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence neonatal outcomes.
选择性5-羟色胺再摄取抑制剂(SSRIs)是孕期治疗抑郁症最有效的药物。子宫内接触SSRIs可能会增加生长受限、早产和新生儿并发症的风险。然而,就未治疗的抑郁症而言,治疗抑郁症的益处似乎超过了潜在的药物副作用。SSRIs会经历广泛的肝脏首过代谢,涉及多种细胞色素P450(CYPs)酶。基因多态性可能会影响CYPs基因的表达和活性。本研究的首要目的是评估孕期接触SSRIs的抑郁症母亲的新生儿结局。还对一部分母亲和胎儿进行了SSRIs药物遗传学评估。在这项病例对照研究中,42名白种女性被诊断为抑郁症和/或焦虑症,整个孕期都接受SSRIs治疗。85名白种女性没有精神疾病诊断,孕期未接触SSRIs。两组的排除标准均为其他精神药物、抗癫痫药、滥用药物、酒精成瘾、母婴传染病、胎儿/新生儿染色体遗传异常。分娩时采集母婴血样,对33名进行基因分型分析。除了吸烟和分娩前平均血红蛋白值外,两组在人口统计学、人体测量学、社会经济和产科变量方面具有同质性。产科特征具有可比性。胎儿期接触SSRIs的新生儿出生体重低(出生体重<2500g)的可能性显著更高(P=0.01),出生后1分钟(P=0.006)和5分钟(P=0.023)时的平均阿氏评分显著更低,出生后1分钟(P=0.017)和5分钟(P=0.013)时的阿氏评分分布更差。56%的新生儿出现一种或多种与新生儿适应不良综合征(PNAS)一致的症状。分娩时的药物遗传学分析未显示与多态性相关的产科或新生儿并发症发生率有显著差异。我们发现,胎儿期接触SSRIs的新生儿在低出生体重、低阿氏评分以及临床上的新生儿适应不良综合征方面出现不良新生儿结局的风险增加。初步药物遗传学分析表明,取决于多态性的CYPs改变程度可能会影响新生儿结局。