Prenatal SSRI antidepressant use and maternal internalizing symptoms during pregnancy and postpartum: Exploring effects on infant temperament trajectories for boys and girls

Erickson, Nora L.; Hancock, Gregory R.; Oberlander, Tim F.; Brain, Ursula; Grunau, Ruth E.; Gartstein, Maria A.

doi:10.1016/j.jad.2019.08.003

Cited by 14 publications

(10 citation statements)

References 101 publications

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“…In humans, sex differences in antidepressant efficacy, as well as the underlying risk of depression, are observed in adults (LeGates et al., 2019); yet infant studies on prenatal SSRI exposure reporting sex‐specific outcomes remain extremely limited. Among the few studies to date, sex differences in infant temperament trajectories and early motor development have been associated with prenatal SSRI exposure (Erickson et al., 2019; Pedersen et al., 2010). Although most infant studies adjust for sex as a covariate in analyses, very few have assessed potential moderating effects of sex on antidepressant‐related outcomes.…”

Section: Introductionmentioning

confidence: 99%

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

Campbell

Williams

Björnson

et al. 2021

Developmental Psychobiology

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Prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants may influence white matter (WM) development, as previous studies report widespread microstructural alterations and reduced interhemispheric connectivity in SSRI‐exposed infants. In rodents, perinatal SSRIs had sex‐specific disruptions in corpus callosum (CC) axon architecture and connectivity; yet it is unknown whether SSRI‐related brain outcomes in humans are sex specific. In this study, the neonate CC was selected as a region‐of‐interest to investigate whether prenatal SSRI exposure has sex‐specific effects on early WM microstructure. On postnatal day 7, diffusion tensor imaging was used to assess WM microstructure in SSRI‐exposed (n = 24; 12 male) and nonexposed (n = 48; 28 male) term‐born neonates. Fractional anisotropy was extracted from CC voxels and a multivariate discriminant analysis was used to identify latent patterns differing between neonates grouped by SSRI‐exposure and sex. Analysis revealed localized variations in CC fractional anisotropy that significantly discriminated neonate groups and correctly predicted group membership with an 82% accuracy. Such effects were identified across three dimensions, representing sex differences in SSRI‐exposed neonates (genu, splenium), SSRI‐related effects independent of sex (genu‐to‐rostral body), and sex differences in nonexposed neonates (isthmus‐splenium, posterior midbody). Our findings suggest that CC microstructure may have a sex‐specific, localized, developmental sensitivity to prenatal SSRI exposure.

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Section: Introductionmentioning

confidence: 99%

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

Campbell

Williams

Björnson

et al. 2021

Developmental Psychobiology

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“…For example, hippocampal neurogenesis and plasticity appear to have a particular sex-specific sensitivity to SRIs and maternal stress (101); interestingly, hippocampal-brainstem connectivity has critical integrative roles in vagal modulation of cardiovascular function (102). In humans, studies reporting sexspecific infant or child outcomes following prenatal SRI exposure are extremely scarce; however, Erickson et al report that male and female infant temperament trajectories from 3-10 months are differentially associated with prenatal SRI exposure and maternal internalizing symptoms (103), and recently, we identified sexspecific alterations in brain microstructure in neonates with prenatal SRI exposure (104). Moreover, sex differences may influence pharmacologic factors contributing to the extent and effect of SRI exposure on the fetus, such placental functioning (23), metabolic enzyme activity and synaptic transmission (105).…”

Section: Acute Sri Effects On Fetal Hr Variability Are Sex-specificmentioning

confidence: 99%

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

et al. 2021

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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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“…In one study, patterns of stress and anxiety during pregnancy, rather than levels of these variables at any single time, predicted the risk of preterm birth (Glynn, Schetter, Hobel, & Sandman, 2008), suggesting that additional attention to trajectories of maternal pregnancy experiences could be fruitful. As described earlier, including both prenatal and postnatal time points (e.g., Erickson et al, 2019) are also essential for investigating the unique or interactive effects of environmental experience before and after birth.…”

Section: Opportunities and Directions For Researchmentioning

confidence: 99%

Applying Interdisciplinary Frameworks to Study Prenatal Influences on Child Development

Camerota

Willoughby

2020

Child Dev Perspectives

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Modern developmental science is informed by several shared principles and adopts a lifespan approach that goes from infancy to senescence. Increasingly, disciplines outside psychology are adopting research frameworks (e.g., fetal origins, developmental origins of health and disease, first 1000 days) that prioritize prenatal experience as a driver of children's long‐term health and developmental outcomes. Despite originating in medical literatures, these new frameworks share many of the core tenets of modern developmental theories. However, they also raise new questions and provoke a broader consideration of developmental influences, outcomes, and contexts. In this article, we describe these frameworks and consider how they align with, differ from, and inform modern developmental science.

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Prenatal SSRI antidepressant use and maternal internalizing symptoms during pregnancy and postpartum: Exploring effects on infant temperament trajectories for boys and girls

Cited by 14 publications

References 101 publications

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure

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

Applying Interdisciplinary Frameworks to Study Prenatal Influences on Child Development

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