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.
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Acknowledgements
This research was funded by March of Dimes Foundation (USA) (No. 12-FY01-30), the Canadian Institutes of Health Research (CIHR No. MOP 54490 and 57837) and HELP, UBC (Human Early Learning Partnership). TFO is supported by a HELP, Senior Career Award and has the R Howard Webster Professorship in Child Development (UBC, Faculty of Graduate Studies). CJDR is supported by CIHR and Michael Smith Foundation for Health Research Fellowships. This work was also supported by a grant from the CIHR and Canada Research Chair in Genetics and Behaviour to EMS. We are grateful to the mothers and their infants who participated and contributed to this work, as well as to Colleen Fitzgerald and Ursula Brain for their contributions organizing and facilitating this research program. We also gratefully acknowledge the thoughtful comments provided by Ursula Brain and Tracey Weir and the manuscript reviewers from Molecular Psychiatry.
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Oberlander, T., Bonaguro, R., Misri, S. et al. Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications. Mol Psychiatry 13, 65–73 (2008). https://doi.org/10.1038/sj.mp.4002007
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DOI: https://doi.org/10.1038/sj.mp.4002007
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