Prenatal Selective Serotonin Reuptake Inhibitor Research Articles

Discussion around SSRIs and pregnancy still leans toward treatment

Last year a seminal study, “Prenatal antidepressant exposure and offspring brain morphologic trajectory” by Dojukan Koc, M.D., and colleagues was published in JAMA Psychiatry. The cohort study results suggested that there may be an association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and changed brain regions involved in emotional regulation in offspring; however, in some brain regions such as the amygdala, the changes disappeared by age 15. The Koc study included a total of 2,198 mother‐child dyads; compared to nonexposed controls, children prenatally exposed to SSRIs had less cerebral gray matter, and a steeper increase in amygdala volume and gyrus from 7 to 15 years of age. Changes in the amygdala and fusiform gyrus did not persist until early adolescence. Postnatal depression in the mother was associated with a reduced fusiform gyrus in the offspring; prenatal depression was aassociated with a smaller volume of the rostral anterior cingulate gyrus in the child. There was no association of SSRI use before pregnancy with brain outcomes in offspring. The Koc study was notable for its long follow‐up of brain growth, allowing for a focus on trajectory and not just a single image.

Citalopram exposure of hESCs during neuronal differentiation identifies dysregulated genes involved in neurodevelopment and depression.

Selective serotonin reuptake inhibitors (SSRIs), including citalopram, are widely used antidepressants during pregnancy. However, the effects of prenatal exposure to citalopram on neurodevelopment remain poorly understood. We aimed to investigate the impact of citalopram exposure on early neuronal differentiation of human embryonic stem cells using a multi-omics approach. Citalopram induced time- and dose-dependent effects on gene expression and DNA methylation of genes involved in neurodevelopmental processes or linked to depression, such as BDNF, GDF11, CCL2, STC1, DDIT4 and GAD2. Single-cell RNA-sequencing analysis revealed distinct clusters of stem cells, neuronal progenitors and neuroblasts, where exposure to citalopram subtly influenced progenitor subtypes. Pseudotemporal analysis showed enhanced neuronal differentiation. Our findings suggest that citalopram exposure during early neuronal differentiation influences gene expression patterns associated with neurodevelopment and depression, providing insights into its potential neurodevelopmental impact and highlighting the importance of further research to understand the long-term consequences of prenatal SSRI exposure.

Selective serotonin re-uptake inhibitors affect craniofacial structures in a mouse model.

Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.

Intrauterine Exposure to Antidepressants or Maternal Depressive Symptoms and Offspring Brain White Matter Trajectories From Late Childhood to Adolescence

BackgroundDuring pregnancy, both selective serotonin reuptake inhibitor (SSRI) exposure and maternal depression have been associated with poor offspring neurodevelopmental outcomes. In a population-based cohort, we investigated the association between intrauterine exposure to SSRIs and depressive symptoms and offspring white matter development from childhood to adolescence. MethodsSelf-reported SSRI use was verified by pharmacy records. In midpregnancy, women reported on depressive symptoms using the Brief Symptom Inventory. Using diffusion tensor imaging, offspring white matter microstructure, including whole-brain and tract-specific fractional anisotropy (FA) and mean diffusivity, was measured at 3 assessments between ages 7 to 15 years. The participants were divided into 4 groups: prenatal SSRI exposure (n = 37 with 60 scans), prenatal depression exposure (n = 229 with 367 scans), SSRI use before pregnancy (n = 72 with 95 scans), and reference (n = 2640 with 4030 scans). ResultsIntrauterine exposure to SSRIs and depressive symptoms were associated with lower FA in the whole-brain and the forceps minor at 7 years. Exposure to higher prenatal depressive symptom scores was associated with lower FA in the uncinate fasciculus, cingulum bundle, superior and inferior longitudinal fasciculi, and corticospinal tracts. From ages 7 to 15 years, children exposed to prenatal depressive symptoms showed a faster increase in FA in these white matter tracts. Prenatal SSRI exposure was not related to white matter microstructure growth over and above exposure to depressive symptoms. ConclusionsThese results suggest that prenatal exposure to maternal depressive symptoms was negatively associated with white matter microstructure in childhood, but these differences attenuated during development, suggesting catch-up growth.

Cohort study finds prenatal SSRI exposure linked to reduced brain volume

A population‐based cohort study has found that prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants was associated with reduced brain volume in children aged 7 to 15. The study did not examine whether any of the observed changes in the brain predisposed these young people to any impairments.

Prenatal Antidepressant Exposure and Offspring Brain Morphologic Trajectory

Clinical decision-making on antidepressant treatment during pregnancy, particularly selective serotonin reuptake inhibitors (SSRIs), is challenging, as both prenatal SSRI exposure and maternal depressive symptoms may be associated with negative outcomes in offspring. To investigate the association between intrauterine SSRI exposure and maternal depressive symptoms and structural brain development in offspring from mid-childhood to early puberty. This prospective, population-based cohort study was embedded in the Generation R Study in Rotterdam, the Netherlands. All pregnant individuals with an expected delivery date between April 1, 2002, and January 31, 2006, were invited to participate. Data were analyzed from February 1 to September 30, 2022. Maternal-reported SSRI use verified by pharmacy records. In mid-pregnancy and 2 and 6 months after delivery, participants reported depressive symptoms using the Brief Symptom Inventory and were divided into 5 groups: SSRI use during pregnancy (n = 41; 80 scans), SSRI use only before pregnancy (n = 77; 126 scans), prenatal depressive symptoms without prenatal SSRI use (n = 257; 477 scans), postnatal depressive symptoms only (n = 74; 128 scans), and nonexposed control individuals (n = 2749; 4813 scans). The main outcome was brain morphometry in offspring, including global and cortical brain volumes, measured at 3 magnetic resonance imaging assessments from 7 to 15 years of age. The study included 3198 mother-child dyads. A total of 3198 mothers (100%) identified as women; mean (SD) age at intake was 31.1 (4.7) years. Children (1670 [52.2%] female) underwent brain imaging assessment from 7 to 15 years of age with 5624 total scans. Most brain gray matter volumes showed an inverted U-shaped trajectory. Compared with nonexposed controls, children prenatally exposed to SSRIs had less cerebral gray matter (β [SE], -20 212.2 [7285.6] mm3; P = .006), particularly within the corticolimbic circuit, which persisted up to 15 years of age. Children exposed to SSRIs prenatally showed a steeper increase in volumes of the amygdala (age interaction: β [SE], 43.3 [13.4] mm3; P = .006) and fusiform gyrus (age interaction: β [SE], 168.3 [51.4] mm3; P = .003) from 7 to 15 years of age. These volumetric differences in the amygdala and fusiform observed in childhood did not persist until early adolescence. Prenatal depression was associated with a smaller volume in the rostral anterior cingulate gyrus (β [SE], -166.3 [65.1] mm3; P = .006), and postnatal depression was associated with a reduced fusiform gyrus (β [SE], -480.5 [189.2] mm3; P = .002). No association of SSRI use before pregnancy with brain outcomes was observed. The results of this cohort study suggest that prenatal SSRI exposure may be associated with altered developmental trajectories of brain regions involved in emotional regulation in offspring. Further research on the functional implications of these findings is needed.

Early prenatal and late prenatal escitalopram exposure differentially impacts behavioral flexibility and anxiety-related behaviors in adulthood

Selective serotonin reuptake inhibitors (SSRIs) are medications commonly used by pregnant women. While SSRIs have been considered safe during pregnancy, there is limited understanding of the long-term consequences of prenatal SSRI exposure on adult behavioral processes. Recent human studies have demonstrated prenatal exposure to some SSRIs in humans may increase susceptibility to autism spectrum disorder (ASD) and developmental delays. While escitalopram is one of the most effective antidepressants, it is also one of the newer available SSRIs, resulting in less information on its safety profile during pregnancy. The current study administered escitalopram (0 or 10 mg/kg, s.c.) to nulliparous female Long-Evans rats for the first (G1–10) or last half (G11–20) of the gestational period. Young adult male and female offspring were subsequently tested on a battery of behavioral tasks consisting of probabilistic reversal learning task, open field conflict, marble burying and social approach tasks. Results demonstrate that escitalopram exposure during the first half of pregnancy resulted in reduced anxiety-like behavior (disinhibition) on the modified open field and enhanced flexibility on the probabilistic reversal learning task. Exposure to escitalopram later in pregnancy resulted in an increase in marble burying behavior, but no differences were found with the other measures. These results suggest that exposure to escitalopram during the first half of prenatal development can have long lasting changes on adult behavior demonstrating better behavioral flexibility and lower anxiety-like behavior compared to non-exposed controls.

Prenatal SSRI Exposure Increases the Risk of Autism in Rodents via Aggravated Oxidative Stress and Neurochemical Changes in the Brain.

The mechanisms underlying selective serotonin reuptake inhibitor (SSRI) use during pregnancy as a major autism risk factor are unclear. Here, brain neurochemical changes following fluoxetine exposure and in an autism model were compared to determine the effects on autism risk. The study was performed on neonatal male western albino rats which were divided into Groups one (control), two (propionic acid [PPA]-induced autism model), and three (prenatal SSRI-exposed newborn rats whose mothers were exposed to 5 mg/kg of fluoxetine over gestation days 10-20). SSRI (fluoxetine) induced significant neurochemical abnormalities in the rat brain by increasing lipid peroxide (MDA), Interferon-gamma (IFN-γ), and caspase-3 levels and by depleting Glutathione (GSH), Glutathione S-transferases (GST), Catalase, potassium (K+), and Creatine kinase (CK) levels, similarly to what has been discovered in the PPA model of autism when compared with control. Prenatal fluoxetine exposure plays a significant role in asset brain damage in newborns; further investigation of fluoxetine as an autism risk factor is thus warranted.

Associations between maternal depressive symptoms and selective serotonin reuptake inhibitor antidepressant treatment on internalising and anxiety behaviours in children: 12-year longitudinal study

Prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure is associated with increased internalising and anxious behaviours in young children; whether this continues into early adolescence is unknown. Also, it is not well established whether it is the in utero exposure to SSRIs or the underlying maternal mood that contributes more to these associations. To examine associations between maternal depressive symptoms, prenatal SSRI antidepressant treatment and internalising and anxiety behaviours from childhood into pre-adolescence. From a prospective longitudinal cohort, measures of maternal depressive symptoms and SSRI use and child outcomes (n = 191 births) were obtained from the second trimester to 12 years. Maternal reports of internalising and anxiety behaviours in children were obtained at 3, 6 and 12 years. Multilevel mixed-effects models revealed that maternal depressed mood at the third trimester assessment, not prenatal SSRI exposure, was associated with longitudinal patterns of higher levels of internalising and anxiety behaviours across childhood from 3 to 12 years of age. At each age, hierarchical regressions showed that maternal mood at the third trimester, compared with current maternal depression or prenatal SSRI exposure, explained a greater proportion of the variance in internalising and anxiety behaviours. Even with prenatal SSRI treatment, maternal depressed mood during the third trimester still had an enduring effect as it was associated with increased levels of internalising and anxiety behaviours across childhood and into early adolescence. Importantly, we found no evidence of a 'main effect' association between prenatal SSRI exposure and internalising and anxiety behaviours in children.

Prenatal stress and fluoxetine exposure in mice differentially affect repetitive behaviors and synaptic plasticity in adult male and female offspring

Autism spectrum disorder (ASD) is characterized by social communication impairments with restricted and repetitive behaviors (RRBs). The increase in prevalence of ASD and the heterogeneity of symptom severity may arise from a complex interaction of environmental and genetic factors that alter synaptic plasticity. Maternal stress during pregnancy, which is linked to depression, may be one risk factor for an ASD phenotype in offspring. Selective serotonin reuptake inhibitor (SSRI) treatment can be effective in alleviating maternal depression but prenatal SSRI exposure itself may be a risk factor for autism in offspring. The present study investigated in C57BL/6J pregnant mice whether restraint stress (G4–18) and/or treatment with the SSRI fluoxetine (G8–18) affects autism-related behaviors and hippocampal synaptic plasticity in male and female offspring. The findings indicate that restraint stress reduces preference for sucrose reward in pregnant dams that is reversed by fluoxetine. In adult male offspring, combined prenatal stress and SSRI exposure increased self-grooming and impaired spatial reversal learning. In adult female offspring, the prenatal experiences did not affect self-grooming, but restraint stress alone or SSRI exposure alone impaired spatial reversal learning. Prenatal stress reduced anxiety-related behavior in male and female offspring. Further, LTP induced by theta-burst stimulation of Schaffer-commissural afferents in field CA1 was significantly reduced in female offspring exposed to prenatal stress alone or combination with fluoxetine. Together, these findings suggest that exposure to prenatal stress, SSRI treatment or the combination differentially affects male and female offspring in autism-like behaviors and synaptic plasticity.

Prenatal Selective Serotonin Reuptake Inhibitor Exposure, Depression, and Brain Morphology in Middle Childhood: Results From the ABCD Study

BackgroundPrenatal selective serotonin reuptake inhibitor (SSRI) exposure has been inconsistently linked to depression, and little is known about neural correlates. We examined whether prenatal SSRI exposure is associated with depressive symptoms and brain structure during middle childhood. MethodsPrenatal SSRI exposure (retrospective caregiver report), depressive symptoms (caregiver-reported Child Behavior Checklist), and brain structure (magnetic resonance imaging–derived subcortical volume; cortical thickness and surface area) were assessed in children (analytic ns = 5420–7528; 235 with prenatal SSRI exposure; 9–10 years of age) who completed the baseline Adolescent Brain Cognitive Development Study session. Linear mixed-effects models nested data. Covariates included familial, pregnancy, and child variables. Matrix spectral decomposition adjusted for multiple testing. ResultsPrenatal SSRI exposure was not independently associated with depression after accounting for recent maternal depressive symptoms. Prenatal SSRI exposure was associated with greater left superior parietal surface area (b = 145.3 mm2, p = .00038) and lateral occipital cortical thickness (b = 0.0272 mm, p = .0000079); neither was associated with child depressive symptoms. Child depression was associated with smaller global brain structure. ConclusionsOur findings, combined with adverse outcomes of exposure to maternal depression and the utility of SSRIs for treating depression, suggest that risk for depression during middle childhood should not discourage SSRI use during pregnancy. Associations between prenatal SSRI exposure and brain structure were small in magnitude and not associated with depression. It will be important for future work to examine associations between prenatal SSRI exposure and depression through young adulthood, when risk for depression increases.

Interactions between maternal fluoxetine exposure, the maternal gut microbiome and fetal neurodevelopment in mice

Selective serotonin reuptake inhibitors (SSRIs) are the most widely used treatment by women experiencing depression during pregnancy. However, the effects of maternal SSRI use on early offspring development remain poorly understood. Recent studies suggest that SSRIs can modify the gut microbiota and interact directly with particular gut bacteria, raising the question of whether the gut microbiome impacts host responses to SSRIs. In this study, we investigate effects of prenatal SSRI exposure on fetal neurodevelopment and further evaluate potential modulatory influences of the maternal gut microbiome. We demonstrate that maternal treatment with the SSRI fluoxetine induces widespread alterations in the fetal brain transcriptome during midgestation, including increases in the expression of genes relevant to synaptic organization and neuronal signaling and decreases in the expression of genes related to DNA replication and mitosis. Notably, maternal fluoxetine treatment from E7.5 to E14.5 has no overt effects on the composition of the maternal gut microbiota. However, maternal pretreatment with antibiotics to deplete the gut microbiome substantially modifies transcriptional responses of the fetal brain to maternal fluoxetine treatment. In particular, maternal fluoxetine treatment elevates localized expression of the opioid binding protein/cell adhesion molecule like gene Opcml in the fetal thalamus and lateral ganglionic eminence, which is prevented by maternal antibiotic treatment. Together, these findings reveal that maternal fluoxetine treatment alters gene expression in the fetal brain through pathways that are impacted, at least in part, by the presence of the maternal gut microbiota.

Prenatal antidepressant exposure and sex differences in neonatal corpus callosum microstructure.

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.

Developmental Fluoxetine Exposure Alters Behavior and Neuropeptide Receptors in the Prairie Vole.

Developmental exposure to selective serotonin reuptake inhibitor (SSRI) increases the risk of Autism Spectrum Disorder (ASD), however, the underlying neurobiology of this effect is not fully understood. Here we used the socially monogamous prairie vole as a translational model of developmental SSRI exposure. Paired female prairie voles (n = 20) were treated with 5 mg/kg subcutaneous fluoxetine (FLX) or saline (SAL) daily from birth of the second litter until the day of birth of the 4th litter. This design created three cohorts of FLX exposure: postnatal exposure in litter 2, both prenatal and postnatal exposure in litter 3, and prenatal exposure in litter 4. Post-weaning, subjects underwent behavioral testing to detect changes in sociality, repetitive behavior, pair-bond formation, and anxiety-like behavior. Quantitative receptor autoradiography was performed for oxytocin, vasopressin 1a, and serotonin 1a receptor density in a subset of brains. We observed increased anxiety-like behavior and reduced sociality in developmentally FLX exposed adults. FLX exposure decreased oxytocin receptor binding in the nucleus accumbens core and central amygdala, and vasopressin 1a receptor binding in the medial amygdala. FLX exposure did not affect serotonin 1A receptor binding in any areas examined. Changes to oxytocin and vasopressin receptors may underlie the behavioral changes observed and have translational implications for the mechanism of the increased risk of ASD subsequent to prenatal SSRI exposure.

Effects of maternal depression and prenatal SSRI exposure on executive functions and susceptibility to household chaos in 6-year-old children: prospective cohort study.

Maternal depressed mood during pregnancy may shape a child's adaptation to their environment and engagement in goal-directed behaviour such as executive functions. Whether everyday household context also alters executive functions in children with prenatal selective serotonin reuptake inhibitor (SSRI) antidepressant exposure remains to be determined. To examine the impact of prenatal depressed maternal mood and SSRI exposure on child executive functions and to determine whether these exposures shape a susceptibility to household chaos. A prospective cohort study of mothers and their children (118 mother-children dyads (47 SSRI-exposed, 71 non-exposed)) followed from the second trimester to 6 years. Regression models examined relationships between maternal depressed mood and household chaos on maternal report of child executive functions. Competitive-confirmatory regression models examined whether children were susceptible to household chaos or were positively influenced by less chaos. Prenatal SSRI exposure, third-trimester maternal depressed mood and household chaos in a three-way interaction were associated with executive functions within a model of differential susceptibility. When household chaos was low, children of non-prenatally depressed mothers had better executive function than children of prenatally depressed mothers, regardless of whether the mothers were SSRI-treated. However, when household chaos was high, SSRI-exposed children of mothers who were not depressed during pregnancy had poorer executive functions at 6 years of age compared with SSRI-exposed children whose mothers were symptomatic during pregnancy. The impact of household chaos depended on whether mothers were prenatally depressed and whether mothers were SSRI-treated.

Maternal use of selective serotonin reuptake inhibitors (SSRI) during pregnancy-neonatal outcomes in correlation with placental histopathology.

We investigated the association between prenatal selective serotonin reuptake inhibitors (SSRI) exposure and pregnancy-outcomes with correlation to placental-histopathology. Included were pregnancies with maternal SSRI use throughout pregnancy (SSRI-group) and the control group was matched with pregnancies unexposed to SSRI. Placental lesions were classified according to the "Amsterdam" criteria. Adverse neonatal outcome was defined as ≥1 early neonatal-complications. SSRI group had lower birthweights (p < 0.001), higher rates of meconium (p = 0.009), NICU admissions (p < 0.001), and adverse neonatal-outcome (p < 0.001). SSRI placentas had lower birthweight-to-placental-weight ratio (p = 0.02) and higher rates of fetal vascular malperfusion (FVM) lesions (p = 0.03). Using multivariable analyses: GA < 37 weeks (aOR = 2.1, 95%CI 1.7-4.6) and SSRI (aOR = 1.7, 95%CI 1.3-3.9) were independently associated with adverse neonatal outcome while GA < 37 weeks (aOR = 1.6, 95%CI 1.2-3.4), SSRI (aOR = 1.3, 95%CI 1.1-2.6), and smoking (aOR = 1.2, 95%CI 1.1-4.0) were independently associated with FVM lesions. SSRI use during pregnancy was independently associated with adverse neonatal outcome and placental FVM.

332: Maternal use of SSRIs during pregnancy - neonatal outcomes in correlation with placental histopathology

The association between maternal Selective Serotonin Reuptake Inhibitors (SSRIs) exposure during pregnancy and adverse pregnancy outcomes is controversial. We aimed to investigate the association between prenatal SSRIs exposure and pregnancy outcomes with correlation to placental histopathology. The study group included all singleton pregnancies with maternal SSRIs use throughout pregnancy (SSRIs group) that had a full placental histopathology-report. The control group was matched in a 1:1 ratio with unexposed pregnancies matched by year, mode of delivery, gestational-age, and maternal age. Pregnancy and placental reports of both groups were reviewed. Placental lesions were classified according to the current “Amsterdam” criteria. Adverse neonatal outcome was defined as ≥1 early neonatal complications. Multivariable regression analyses were performed to identify independent associations with adverse neonatal outcome and with specific placental lesions. Included were 82 cases of maternal SSRIs use and 82 matched controls. The SSRIs group had higher rates of smoking (p< 0.001), lower birthweights (2948±599 vs. 3331±647 gr, p< 0.001), higher rates of meconium (p=0.009), NICU admissions (p< 0.001), and composite adverse neonatal outcome (32.9% vs. 8.5%, p< 0.001). Placentas from the SSRIs group were characterized by lower birth-weight/placental-weight ratio (p=0.02) and higher rates of fetal vascular malperfusion (FVM) lesions (23.1% vs. 9.7%, p=0.03). Using multivariable regression analysess (table) GA < 37 weeks (aOR=2.1 95% CI 1.7-4.6), and SSRI use (aOR=1.7 95% CI 1.3-3.9) were independently associated with composite adverse neonatal outcome, while GA < 37 weeks (aOR=1.6 95% CI 1.2-3.4), SSRI use (aOR=1.3 95% CI 1.1-2.6), and smoking (aOR= 1.2 95% CI 1.1-4.0) were independently associated with FVM lesions. Maternal SSRIs use during pregnancy was independently associated with adverse neonatal outcome and placental FVM lesions. Prospective studies are needed to further study this association.

Prenatal selective serotonin reuptake inhibitors and therapeutic hypothermia for suspected hypoxic ischemic encephalopathy.

To evaluate the association between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and postnatal therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Matched case-control study of singleton deliveries at a tertiary hospital from 2010 to 2016. Cases were infants treated with therapeutic hypothermia for suspected hypoxic ischemic encephalopathy. Controls were noncase infants, matched on gestational age, maternal age, obstetric provider group, and hospital shift. Prenatal SSRI exposure occurred in 18.4% of cases compared with 4.1% of controls (aOR: 5.9, 95% CI: 1.8-19.7). Among all cases, 36.8% had evidence of hypoxic ischemic encephalopathy on postnatal MRI. In addition, 28.6% of SSRI-exposed cases and 38.7% of SSRI-unexposed cases had MRI confirmation of hypoxic ischemic encephalopathy, respectively. Future research to disentangle signs of SSRI exposure from true hypoxic ischemic encephalopathy may facilitate targeting therapeutic hypothermia stewardship toward infants more likely to benefit.

Hub distribution of the brain functional networks of newborns prenatally exposed to maternal depression and SSRI antidepressants

Prenatal maternal depression (PMD) and selective serotonin reuptake inhibitor (SSRI) antidepressants are associated with increased developmental risk in infants. Reports suggest that PMD is associated with hyperconnectivity of the insula and the amygdala, while SSRI exposure is associated with hyperconnectivity of the auditory network in the infant brain. However, associations between functional brain organization and PMD and/or SSRI exposure are not well understood. We examined the relation between PMD or SSRI exposure and neonatal brain functional organization. Infants of control (n = 17), depressed SSRI-treated (n = 20) and depressed-only (HAM-D ≥ 8) (n = 16) women, underwent resting-state functional magnetic resonance imaging at postnatal Day 6. At 6 months, temperament was assessed using Infant Behavioral Questionnaire (IBQ). We applied GTA and partial least square regression (PLSR) to the resting-state time series to assess group differences in modularity, and connector and provincial hubs. Modularity was similar across all groups. The depressed-only group showed higher connector hub values in the left anterior cingulate, insula, and caudate as well as higher provincial hub values in the amygdala compared to the control group. The SSRI group showed higher provincial hub values in Heschl's gyrus relative to the depressed-only group. PLSR showed that newborns' hub values predicted 10% of the variability in infant temperament at 6 months, suggesting different developmental patterns between groups. Prenatal exposures to maternal depression and SSRIs have differential impacts on neonatal functional brain organization. Hub values at 6 days predict variance in temperament between infant groups at 6 months of age.

Impact of Prenatal Selective Serotonin Reuptake Inhibitor Antidepressant Exposure and Maternal Mood on Physical Activity, Dietary Intake, and Markers of Adiposity at Age 6 Years.

This study assessed associations between maternal depressive symptoms, prenatal maternal antidepressant treatment, maternal estimates of child physical activity (PA), dietary total intake, and markers of adiposity. Mothers and their children (N = 116) were part of a longitudinal cohort study examining the effects of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants and maternal depression (SSRI exposed, n = 42; nonexposed, n = 74). Maternal depression symptoms were assessed prenatally and postnatally. At 6 years, PA was assessed using maternal report, 3-day dietary total intakes were obtained using objective records of intake, portion sizes, and product brand names, and birth weight, weight, height, and waist circumference (WC) at age 6 years were also collected. Body mass index (BMI) and WC z-scores standardized for sex and age were computed as markers of adiposity. Children with SSRI exposure had lower levels of PA than children without SSRI exposure. Total dietary energy intakes did not vary between exposure groups. SSRI exposure was not associated with BMI or WC z-scores of the children. Importantly, although lower birth weight was observed in SSRI-exposed children, differences did not remain, accounting for gestational age. Although SSRI exposure was associated with lower estimates of PA, such exposure was not associated with markers of adiposity or total diet energy intake at age 6 years. The implications across subsequent measures in childhood remain to be determined.