Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure

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...

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Main Authors: Silvia Corti, Paola Pileri, Martina I. Mazzocco, Chiara Mandò, Anna F. Moscatiello, Dario Cattaneo, Stefania Cheli, Sara Baldelli, Laura Pogliani, Emilio Clementi, Irene Cetin
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-07-01
Series:Frontiers in Pediatrics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fped.2019.00309/full
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author Silvia Corti
Paola Pileri
Martina I. Mazzocco
Chiara Mandò
Anna F. Moscatiello
Dario Cattaneo
Stefania Cheli
Sara Baldelli
Laura Pogliani
Emilio Clementi
Emilio Clementi
Irene Cetin
author_facet Silvia Corti
Paola Pileri
Martina I. Mazzocco
Chiara Mandò
Anna F. Moscatiello
Dario Cattaneo
Stefania Cheli
Sara Baldelli
Laura Pogliani
Emilio Clementi
Emilio Clementi
Irene Cetin
author_sort Silvia Corti
collection DOAJ
description 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.
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spelling doaj.art-c9b46de9bd884b6f84606d84cd97d5f22022-12-21T23:59:53ZengFrontiers Media S.A.Frontiers in Pediatrics2296-23602019-07-01710.3389/fped.2019.00309441335Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug ExposureSilvia Corti0Paola Pileri1Martina I. Mazzocco2Chiara Mandò3Anna F. Moscatiello4Dario Cattaneo5Stefania Cheli6Sara Baldelli7Laura Pogliani8Emilio Clementi9Emilio Clementi10Irene Cetin11Department of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyClinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Milan, Milan, ItalyClinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Milan, Milan, ItalyClinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Milan, Milan, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyClinical Pharmacology Unit, Department of Biomedical and Clinical Sciences, Consiglio Nazionale delle Ricerche Institute of Neuroscience, University of Milan, Milan, ItalyIRCCS E. Medea Institute, Bosisio Parini, ItalyDepartment of Mother and Child, ASST Fatebenefratelli-Sacco, University of Milan, Milan, ItalyBackground: 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.https://www.frontiersin.org/article/10.3389/fped.2019.00309/fullSSRIpharmacogeneticspoor neonatal adaptation syndromenewbornspregnancydepression
spellingShingle Silvia Corti
Paola Pileri
Martina I. Mazzocco
Chiara Mandò
Anna F. Moscatiello
Dario Cattaneo
Stefania Cheli
Sara Baldelli
Laura Pogliani
Emilio Clementi
Emilio Clementi
Irene Cetin
Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
Frontiers in Pediatrics
SSRI
pharmacogenetics
poor neonatal adaptation syndrome
newborns
pregnancy
depression
title Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
title_full Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
title_fullStr Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
title_full_unstemmed Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
title_short Neonatal Outcomes in Maternal Depression in Relation to Intrauterine Drug Exposure
title_sort neonatal outcomes in maternal depression in relation to intrauterine drug exposure
topic SSRI
pharmacogenetics
poor neonatal adaptation syndrome
newborns
pregnancy
depression
url https://www.frontiersin.org/article/10.3389/fped.2019.00309/full
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