Background:
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. Methods: In this case-control study, cases (n = 42) were Caucasian women with a diagnosis of depression and/or anxiety, treated with
SSRIs for the whole pregnancy. Controls (n = 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 cases. Results: 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) (p = 0.01), had significantly lower mean Apgar scores at 1' (p = 0.006) and at 5' (p = 0.023) and worse Apgar distribution at 1' (p = 0.017) and at 5' (p = 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. 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. Preliminary pharmacogenetic analysis showed that the degree of CYPs alterations, that depends on polymorphisms, may influence neonatal outcomes.