title: Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications.
abstract: Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 non-exposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P<0.001). Birth weight was lower in exposed ls neonates (P=0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P<0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P<0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.
authors.affiliation: Early Human Experience Unit, Department of Pediatrics, Centre for Community Child Health Research, University of British Columbia, Vancouver, BC, Canada. toberlander@cw.bc.ca
authors.forename: T F
authors.initials: TF
authors.lastname: Oberlander
authors.forename: R J
authors.initials: RJ
authors.lastname: Bonaguro
authors.forename: S
authors.initials: S
authors.lastname: Misri
authors.forename: M
authors.initials: M
authors.lastname: Papsdorf
authors.forename: C J D
authors.initials: CJ
authors.lastname: Ross
authors.forename: E M
authors.initials: EM
authors.lastname: Simpson
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000328:Adult; D001008:Anxiety Disorders / Q000097:blood / Q000188:drug therapy; D001034:Apgar Score; D001724:Birth Weight / Q000187:drug effects*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy; D005260:Female; D005865:Gestational Age; D006801:Humans; D018730:Infant Behavior / Q000187:drug effects* / Q000502:physiology; D007231:Infant, Newborn; D008297:Male; D008431:Maternal-Fetal Exchange; D011110:Polymorphism, Genetic; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D012016:Reference Values; D018570:Risk Assessment; D050486:Serotonin Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics*; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; C493230:SLC6A4 protein, human