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Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation

Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effe...

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Autores principales: Campbell, Kayleigh S. J., Collier, Abby C., Irvine, Michael A., Brain, Ursula, Rurak, Dan W., Oberlander, Tim F., Lim, Kenneth I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415315/
https://www.ncbi.nlm.nih.gov/pubmed/34483982
http://dx.doi.org/10.3389/fpsyt.2021.680177
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author Campbell, Kayleigh S. J.
Collier, Abby C.
Irvine, Michael A.
Brain, Ursula
Rurak, Dan W.
Oberlander, Tim F.
Lim, Kenneth I.
author_facet Campbell, Kayleigh S. J.
Collier, Abby C.
Irvine, Michael A.
Brain, Ursula
Rurak, Dan W.
Oberlander, Tim F.
Lim, Kenneth I.
author_sort Campbell, Kayleigh S. J.
collection PubMed
description Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood. Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed (n = 31), SRI-Non-Depressed (n = 18), Depressed (unmedicated; n = 42), and Control (n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects. Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls. Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development.
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spelling pubmed-84153152021-09-04 Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation Campbell, Kayleigh S. J. Collier, Abby C. Irvine, Michael A. Brain, Ursula Rurak, Dan W. Oberlander, Tim F. Lim, Kenneth I. Front Psychiatry Psychiatry Background: Prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressants increases risk for adverse neurodevelopmental outcomes, yet little is known about whether effects are present before birth. In relation to maternal SRI pharmacokinetics, this study investigated chronic and acute effects of prenatal SRI exposure on third-trimester fetal heart rate variability (HRV), while evaluating confounding effects of maternal depressed mood. Methods: At 36-weeks' gestation, cardiotocograph measures of fetal HR and HRV were obtained from 148 pregnant women [four groups: SRI-Depressed (n = 31), SRI-Non-Depressed (n = 18), Depressed (unmedicated; n = 42), and Control (n = 57)] before, and ~5-h after, typical SRI dose. Maternal plasma drug concentrations were quantified at baseline (pre-dose) and four time-points post-dose. Mixed effects modeling investigated group differences between baseline/pre-dose and post-dose fetal HR outcomes. Post hoc analyses investigated sex differences and dose-dependent SRI effects. Results: Maternal SRI plasma concentrations were lowest during the baseline/pre-dose fetal assessment (trough) and increased to a peak at the post-dose assessment; concentration-time curves varied widely between individuals. No group differences in fetal HR or HRV were observed at baseline/pre-dose; however, following maternal SRI dose, short-term HRV decreased in both SRI-exposed fetal groups. In the SRI-Depressed group, these post-dose decreases were displayed by male fetuses, but not females. Further, episodes of high HRV decreased post-dose relative to baseline, but only among SRI-Non-Depressed group fetuses. Higher maternal SRI doses also predicted a greater number of fetal HR decelerations. Fetuses exposed to unmedicated maternal depressed mood did not differ from Controls. Conclusions: Prenatal SRI exposure had acute post-dose effects on fetal HRV in late gestation, which differed depending on maternal mood response to SRI pharmacotherapy. Importantly, fetal SRI effects were sex-specific among mothers with persistent depressive symptoms, as only male fetuses displayed acute HRV decreases. At trough (pre-dose), chronic fetal SRI effects were not identified; however, concurrent changes in maternal SRI plasma levels suggest that fetal drug exposure is inconsistent. Acute SRI-related changes in fetal HRV may reflect a pharmacologic mechanism, a transient impairment in autonomic functioning, or an early adaption to altered serotonergic signaling, which may differ between males and females. Replication is needed to determine significance with postnatal development. Frontiers Media S.A. 2021-08-16 /pmc/articles/PMC8415315/ /pubmed/34483982 http://dx.doi.org/10.3389/fpsyt.2021.680177 Text en Copyright © 2021 Campbell, Collier, Irvine, Brain, Rurak, Oberlander and Lim. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Campbell, Kayleigh S. J.
Collier, Abby C.
Irvine, Michael A.
Brain, Ursula
Rurak, Dan W.
Oberlander, Tim F.
Lim, Kenneth I.
Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title_full Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title_fullStr Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title_full_unstemmed Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title_short Maternal Serotonin Reuptake Inhibitor Antidepressants Have Acute Effects on Fetal Heart Rate Variability in Late Gestation
title_sort maternal serotonin reuptake inhibitor antidepressants have acute effects on fetal heart rate variability in late gestation
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415315/
https://www.ncbi.nlm.nih.gov/pubmed/34483982
http://dx.doi.org/10.3389/fpsyt.2021.680177
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