title: Pharmacokinetics and Pharmacogenetics of Selective Serotonin Reuptake Inhibitors During Pregnancy: An Observational Study.
abstract: An involvement of selective serotonin reuptake inhibitors (SSRIs) in increasing the risk of malformations, neonatal withdrawal syndrome, has been suggested recently. Here, we aimed to investigate the contribution of individual pharmacogenetics of SSRI on infants' outcome. We also estimated the umbilical/maternal plasma SSRI concentration ratio in the pregnant women still on SSRI therapy at the time of delivery.
  
  
  
  Thirty-four pregnant women, referred to our hospital from January 2011 to July 2015, who were given SSRIs in the third trimester, and related children, were considered. The umbilical/maternal plasma SSRI concentration ratio was estimated in 15 mothers still on SSRI therapy at the time of delivery. For patients with pharmacokinetic analyses, blood samples were collected for pharmacogenetic analyses.
  
  
  
  Nineteen newborns presented clinical signs possibly related to drug toxicity. A high umbilical/maternal plasma ratio of SSRI was observed in 10 of the 15 evaluated newborns. Five mothers were intermediate metabolizers and 1 a poor metabolizer for the major CYP enzyme involved in pharmacokinetic pathway.
  
  
  
  Individualized psychopharmacologic treatment that takes into account the mother's exposure to SSRI concentrations and eventually her genetic background may become the standard of care to maximize drug benefit and minimize risks to the newborn.
authors.affiliation: *Department of Pediatrics, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital, Milan; †Unit of Clinical Pharmacology, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital, Milan; ‡Department of Gynecology and Obstetrics, ASST Fatebenefratelli-Sacco, L. Sacco Hospital, University Hospital, Milan; §Department of Pediatrics, ASST Fatebenefratelli-Sacco, Ospedale dei Bambini V. Buzzi, Milan; ¶Clinical Pharmacology Unit, Consiglio Nazionale delle Ricerche Institute of Neuroscience, Department of Biomedical and Clinical Sciences, L. Sacco University Hospital, Università degli Studi di Milano, Milan; and ‖E. Medea Scientific Institute, Bosisio Parini, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pogliani
authors.forename: Felicia S
authors.initials: FS
authors.lastname: Falvella
authors.forename: Dario
authors.initials: D
authors.lastname: Cattaneo
authors.forename: Paola
authors.initials: P
authors.lastname: Pileri
authors.forename: Anna F
authors.initials: AF
authors.lastname: Moscatiello
authors.forename: Stefania
authors.initials: S
authors.lastname: Cheli
authors.forename: Sara
authors.initials: S
authors.lastname: Baldelli
authors.forename: Valentina
authors.initials: V
authors.lastname: Fabiano
authors.forename: Irene
authors.initials: I
authors.lastname: Cetin
authors.forename: Emilio
authors.initials: E
authors.lastname: Clementi
authors.forename: Gianvincenzo
authors.initials: G
authors.lastname: Zuccotti
mesh_terms: D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure; D009035:Mothers; D009357:Neonatal Abstinence Syndrome / Q000097:blood* / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000378:metabolism; D011263:Pregnancy Trimester, Third / Q000097:blood / Q000378:metabolism; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000139:chemically induced* / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D017367:Selective Serotonin Reuptake Inhibitors