Neonatal Outcomes of Newborns Exposed to SSRI during Pregancy: a Pharmacokinetic and Pharmacogenetic Analysis

Background SSRI (Selective Serotonin Reuptake Inhibitors) are the most frequent drugs to treat depression during pregnancy (16% prevalence in Italy), but they have direct potential effects on the developing embryo including abortion, growth restriction, preterm birth, malformations and neonatal complications. The aim of our study was to investigate the contribution of pharmacokinetics and pharmacogenetics approach on infants outcome. Methods We performed a case-control study: cases (n. 43) were caucasian women with a diagnosis of depression and/or anxiety, in treatment with SSRI for the whole pregnancy. Controls (n. 86) were caucasian women without a psychiatric diagnosis and not exposed to SSRIs during pregnancy. Exclusion criteria for both groups were other psychotropic drugs, anti-epileptic drugs, drug of abuse or alcohol addiction, maternal or fetal infectious diseases, fetal/neonatal chromosomal genetic abnormalities. Maternal and fetal blood samples to measure drug concentrations and to analyse maternal genotyope, looking for polymorphisms in CYPs genes, were analyzed at delivery. Results The population was homogenous for demographic, anthropometric, socio-economic and obstetric variables except for smoking and mean haemoglobin values before delivery. Obstetric features, were comparable. Newborns exposed to SSRIs during fetal life were significantly more likely to be born of low birth weight (p=0.01) and had significantly lower mean Apgar scores at 1’ (p=0.006) and at 5’ (p=0.023) and worse Apgar-1’ distribution (p=0.006). Clinically these findings were associated to poor neonatal adaptation syndrome, respiratory distress syndrome or transient tachypnea of the newborn. PNAS accounted for 56% of newborns and was the most represented adverse outcome. The pharmacokinetic/pharmacogenetic analysis at delivery showed no striking differences in terms of frequency of obstetric or neonatal complications between those with compared to those without any polymorphism. But for each drug, the worst adverse outcome was observed in infants born to the mothers with the most altered CYPs activity. Conclusions 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. The pharmacokinetic/pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence the severity of outcomes, more than their frequency. Our hypothesis should be confirmed by larger studies, to have clinical implication