Serotonin Reuptake Inhibitor Exposure 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.

Effects of Selective Serotonin Reuptake Inhibitors Exposure in Stressed Pregnant Mice on the Anxiety Behavior of the Offspring

Background: Stress hurts problem-solving abilities, while anxiety disorders and depression are associated with unpleasant feelings and impaired daily functioning. Open field test (OFT) is used to assess anxiety-like behavior in animals by observing their exploratory behavior. Pregnant women are vulnerable to stress, which increases the risk of premature birth and low birth weight. Stress during pregnancy can also lead to preeclampsia and behavioural problems in newborns. Selective serotonin reuptake inhibitors (SSRIs), commonly used antidepressants during pregnancy, help manage mental disorders by increasing serotonin levels and regulating the endocrine system. They reduce glucocorticoid levels, thereby alleviating anxiety and stress in pregnant women. Objectives: This research investigates the correlation between the administration of SSRIs to stress-induced expectant mothers, the manifestation of depression-like behaviour, and the expression of glucocorticoid receptors in the offspring's hippocampus. Material and Methods: This study included four mouse groups: control without stress, control with offspring stress, stress model with footshock on dams and o ffspring, and stress with fluvoxamine treatment. Depressive and stress-related behaviors were measured using OFT. Results: OFT was used to assess the behaviour of offspring mice. Significant differences were observed in the number of crossings in the centre area and behaviour. The SSRI treatment showed potential anxiolytic effects, while stress led to reduced behaviour. These findings contribute to understanding anxiety-related responses and the effects of stress and SSRI treatment in animal models. Conclusions: OFT revealed significant differences in anxiety behaviour, specifically in the number of crossing centres, the centre area, and behaviour. SSRI treatment exhibited anxiolytic effects, while stress-decreased behaviour findings enhanced our understanding of anxiety responses and the impact of stress and SSRI treatment in animal models.

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.

Voltammetric Approach for Characterizing the Biophysical and Chemical Functionality of Human Induced Pluripotent Stem Cell-Derived Serotonin Neurons.

Depression is quickly becoming one of the world's most pressing public health crises, and there is an urgent need for better diagnostics and therapeutics. Behavioral models in animals and humans have not adequately addressed the diagnosis and treatment of depression, and biomarkers of mental illnesses remain ill-defined. It has been very difficult to identify biomarkers of depression because of in vivo measurement challenges. While our group has made important strides in developing in vivo tools to measure such biomarkers (e.g., serotonin) in mice using voltammetry, these tools cannot be easily applied for depression diagnosis and drug screening in humans due to the inaccessibility of the human brain. In this work, we take a chemical approach, ex vivo, to introduce a human-derived system to investigate brain serotonin. We utilize human induced pluripotent stem cells differentiated into serotonin neurons and establish a new ex vivo model of real-time serotonin neurotransmission measurements. We show that evoked serotonin release responds to stimulation intensity and tryptophan preloading, and that serotonin release and reuptake kinetics resemble those found in vivo in rodents. Finally, after selective serotonin reuptake inhibitor (SSRI) exposure, we find dose-dependent internalization of the serotonin reuptake transporters (a signature of the in vivo response to SSRI). Our new human-derived chemical model has great potential to provide an ex vivo chemical platform as a translational tool for in vivo neuropsychopharmacology.

Cortical Cross-Frequency Coupling Is Affected by in utero Exposure to Antidepressant Medication.

Up to five percent of human infants are exposed to maternal antidepressant medication by serotonin reuptake inhibitors (SRI) during pregnancy, yet the SRI effects on infants’ early neurodevelopment are not fully understood. Here, we studied how maternal SRI medication affects cortical frequency-specific and cross-frequency interactions estimated, respectively, by phase-phase correlations (PPC) and phase-amplitude coupling (PAC) in electroencephalographic (EEG) recordings. We examined the cortical activity in infants after fetal exposure to SRIs relative to a control group of infants without medical history of any kind. Our findings show that the sleep-related dynamics of PPC networks are selectively affected by in utero SRI exposure, however, those alterations do not correlate to later neurocognitive development as tested by neuropsychological evaluation at two years of age. In turn, phase-amplitude coupling was found to be suppressed in SRI infants across multiple distributed cortical regions and these effects were linked to their neurocognitive outcomes. Our results are compatible with the overall notion that in utero drug exposures may cause subtle, yet measurable changes in the brain structure and function. Our present findings are based on the measures of local and inter-areal neuronal interactions in the cortex which can be readily used across species, as well as between different scales of inspection: from the whole animals to in vitro preparations. Therefore, this work opens a framework to explore the cellular and molecular mechanisms underlying neurodevelopmental SRI effects at all translational levels.

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.

Early-life exposure to selective serotonin reuptake inhibitors: Long-term effects on pain and affective comorbidities.

A growing body of evidence indicates that early‐life exposure to selective serotonin reuptake inhibitor has long‐term consequences on the offspring's pain in addition to affective disorders like anxiety disorder and major depression. Serotonin, besides its role in regulating pain and emotions, promotes neuronal network formation. The prefrontal cortex and the amygdala are two key brain regions involved in the modulation of pain and its affective comorbidities. Thus, the aim of this review is to understand how early‐life selective serotonin reuptake inhibitor exposure alters the developing prefrontal cortex and amygdala and thereby underlies the long‐term changes in pain and its affective comorbidities in later life. While there is still limited data on the effects of early‐life selective serotonin reuptake inhibitor exposure on pain, there is a substantial body of evidence on its affective comorbidities. From this perspective paper, four conclusions emerged. First, early‐life selective serotonin reuptake inhibitor exposure results in long‐term nociceptive effects, which needs to be consistently studied to clarify. Second, it results in enhanced depressive‐like behaviour and diminished exploratory behaviour in adult rodents. Third, early‐life selective serotonin reuptake inhibitor exposure alters serotonergic levels, transcription factors expression, and brain‐derived neurotrophic factor levels, resulting in hyperconnectivity within the amygdala and the prefrontal cortex. Finally, it affects antinociceptive inputs of the prefrontal cortex and the amygdala in the spinal cord. We conclude that early‐life selective serotonin reuptake inhibitor exposure affects the maturation of prefrontal cortex and amygdala circuits and thereby enhances their antinociceptive inputs in the spinal cord.

Severity of neonatal opioid withdrawal syndrome with prenatal exposure to serotonin reuptake inhibitors.

To evaluate the severity of neonatal opioid withdrawal syndrome (NOWS) in infants prenatally exposed to medications for opioid use disorder (MOUD) and serotonin reuptake inhibitors (SRI). A prospective cohort included 148 maternal-infant pairs categorized into MOUD (n = 127) and MOUD + SRI (n = 27) groups. NOWS severity was operationalized as the infant's need for pharmacologic treatment with opioids, duration of hospitalization, and duration of treatment. The association between prenatal SRI exposure and the need for pharmacologic treatment (logistic regression), time-to-discharge, and time-to-treatment discontinuation (Cox proportional hazards modeling) was examined after adjusting for the type of maternal MOUD, use of hydroxyzine, other opioids, benzodiazepines/sedatives, alcohol, tobacco, marijuana, gestational age, and breastfeeding. Infants in the MOUD + SRI group were more likely to receive pharmacologic treatment for NOWS (OR = 3.58; 95% CI: 1.31; 9.76) and had a longer hospitalization (median: 11 vs. 6 days; HR = 0.54; 95% CI: 0.33; 0.89) compared to the MOUD group. With respect to time-to-treatment discontinuation, no association was observed in infants who received treatment (HR = 0.59; 95% CI: 0.26, 1.32); however, significant differences were observed in the entire sample (HR = 0.55; 95% CI: 0.34, 0.89). Use of SRIs among pregnant women on MOUD might be associated with more severe NOWS. A potential drug-drug interaction between maternal SRIs and opioid medications that inhibit the reuptake of serotonin has been hypothesized but not carefully evaluated in clinical studies. Results of this prospective cohort indicate that the use of SRIs among pregnant women on MOUD is associated with more severe neonatal opioid withdrawal syndrome. This is the first prospective study which carefully examined effect modification between the type of maternal MOUD and SRI use on neonatal outcomes. This report lays the foundation for treatment optimization in pregnant women with co-occurring mental health and substance use disorders.

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 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.

Perinatal selective serotonin reuptake inhibitor (SSRI) and other antidepressant exposure effects on anxiety and depressive behaviors in offspring: A review of findings in humans and rodent models

The developmental impact of selective serotonin reuptake inhibitor (SSRI) and other antidepressant treatments during gestation and postpartum on anxiety and depression behaviors in offspring is unclear. This review focuses on how perinatal exposure to SSRI and other antidepressant may have long term consequences for these affective behaviors during early childhood and beyond. Outcomes vary and consideration is given to methodological factors related to how early SSRI exposure affects developments studied in rodent models such as: a) between pre- and early post-natal SSRI exposure, b) sex, c) experimental models of gestational maternal stress and d) impact of non-SSRI antidepressant medications. We will also review how multiple contextual factors (maternal caregiving and gene x environment interactions) may contribute to the effects of perinatal SSRI exposure and maternal mental illness on affective behaviors in children.

Urinary selective serotonin reuptake inhibitors across critical windows of pregnancy establishment: a prospective cohort study of fecundability and pregnancy loss

To prospectively investigate the association of selective serotonin reuptake inhibitor (SSRI) exposure through critical windows of pregnancy establishment with fecundability and pregnancy loss. Prospective cohort study using longitudinal urine measurements of common SSRIs while women are actively trying to conceive. Four clinical sites. A total of 1,228 women without uncontrolled depression/anxiety, attempting natural conception while participating in a randomized trial of preconception-initiated low-dose aspirin. Not applicable. Urinary SSRIs (fluoxetine, sertraline, escitalopram/citalopram) were measured while trying to conceive and, for women who became pregnant, at weeks 0, 4, and 8 of pregnancy. Fecundability odds ratios and incidence of pregnancy loss and live birth were estimated. A total of 172 women (14%) were exposed to SSRIs while trying to conceive. SSRI exposure was associated with 24% reduced fecundability, and accordingly, a nonsignificant 9% lower live birth incidence, with significantly lower live birth in fluoxetine-exposed women. SSRI exposure was not associated with subsequent pregnancy loss, whether exposure was before conception or at 0, 4, or 8 weeks of gestation, although estimates varied by specific SSRI drug. Women using SSRIs may have more difficulty becoming pregnant, and although SSRI exposure overall was not associated with pregnancy loss, fluoxetine deserves caution and future study. NCT00467363.

Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population-based cohort study.

The association between selective serotonin reuptake inhibitor (SSRI) exposure and cancer incidence has been investigated; however, no epidemiological study has investigated the association between exposure to individual SSRIs and kidney cancer incidence. The aim of this study is to examine whether SSRI use affected the risk of kidney cancer. We conducted a population-based retrospective cohort study using data from Taiwan's National Health Insurance Research Database. After adjusting for sex, age, urbanization level, comorbidity and medication use through propensity score matching, we identified 222 024 SSRI users and 221 361 SSRI nonusers. A robust Cox proportional hazards model was used to examine the associations between use of individual SSRIs and the risk of kidney cancer with 1- and 2-year induction periods. The result showed that SSRI users tended to be associated with a lower risk of kidney cancer with a 2-year induction period than nonusers; however, the association was not statistically significant (adjusted hazards ratio [aHR] = 0.88, 95% confidence interval [CI] = 0.77-1.01). We further examined the effects of individual SSRIs and observed a significantly lower risk of kidney cancer associated with the use of citalopram (aHR = 0.67, 95% CI = 0.47-0.96) and paroxetine (aHR = 0.75, 95% CI = 0.58-0.97) with the 2-year induction period. These findings support that SSRIs are associated with decreased kidney cancer risk and indicate that citalopram and paroxetine have protective effects in depressed patients with kidney cancer.

Selective Serotonin Reuptake Inhibitor Exposure Is Associated with Greater Risk of Recurrent Hemorrhagic Stroke

Selective Serotonin Reuptake Inhibitor Exposure Is Associated with Greater Risk of Recurrent Hemorrhagic Stroke

Association of Selective Serotonin Reuptake Inhibitor Use After Intracerebral Hemorrhage With Hemorrhage Recurrence and Depression Severity

Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat poststroke depression but are associated with increased incidence of first-ever intracerebral hemorrhage (ICH) in the general population. The decision to treat ICH survivors with SSRIs must therefore balance potential risks of ICH recurrence with presumed benefits on depressive symptoms. To determine whether SSRI use among survivors of primary ICH was associated with ICH recurrence and decreased severity of depressive symptoms. Longitudinal ICH cohort study at a tertiary care center enrolling from January 2006 to December 2017, with follow-up for a median of 53.2 months (interquartile range, 42.3-61.2 months). The study included 1279 consenting individuals (1049 White, 89 Black, 77 Hispanic, and 64 other race/ethnicity) of 1335 eligible patients presenting with primary ICH and who were discharged alive from initial hospitalization for stroke. We conducted univariable and multivariable analyses for ICH recurrence risk and depression severity, including subset analyses for patients with 1 or more of the following characteristics associated with high ICH recurrence risk: (1) lobar ICH; (2) presence of the apolipoprotein ε2/ε4 gene variants; (3) prior history of ICH/TIA/ischemic stroke; and (4) Black or Hispanic race/ethnicity. Mean age of study participants was 71.3 years, with 602 women (47%); of the 1279 participants, 1049 were White, 89 were Black, 77 were Hispanic, and 64 were other race/ethnicity. SSRI exposure was associated with both ICH recurrence (subhazard ratio [SHR], 1.31; 95% CI, 1.08-1.59) and resolution of post-ICH depression (SHR, 1.53; 95% CI, 1.12 2.09). Among those individuals at high risk for recurrent ICH, SSRIs were associated with further elevation in risk for ICH recurrence (SHR, 1.79; 95% CI, 1.22-2.64) compared with all other survivors of ICH (SHR, 1.20; 95% CI, 1.01-1.42; P = .008 for comparison of effect sizes). The association of SSRI with reduced depressive symptoms did not differ between high those at high risk for recurrent ICH and all other ICH survivors. Selective serotonin reuptake inhibitor exposure after ICH is associated with both improvement in depressive symptoms and increased risk of recurrent hemorrhagic stroke. Clinical history, neuroimaging data, and genetic biomarkers may help to identify survivors of ICH more likely to safely tolerate SSRI use.

Use of selective serotonin reuptake inhibitors, other antidepressant medication, and risk of cataract: a case-control study based on Swiss claims data.

Three previous studies reported controversial results regarding selective serotonin reuptake inhibitor (SSRI) exposure and cataract development. We therefore aimed to assess risk of cataract associated with previous exposure to SSRI using data from a large health insurance in Switzerland. In a case-control study, we analyzed individuals insured by the Helsana Group, a large Swiss health insurance provider. We matched patients aged 40 years or older with cataract extraction (i.e., a proxy for a cataract diagnosis) in 2014 or 2015 to four control patients, on age, sex, date of cataract extraction, and area of residence. Exposure of interest was the number of SSRI claims prior to cataract extraction. We conducted conditional logistic regression analyses to calculate odds ratios (OR) with 95% confidence intervals (CI). We adjusted our analyses for the presence of hypertension, diabetes, glaucoma, systemic steroid use, and use of other antidepressant drugs. We identified 13,773 cataract cases and 51,625 matched controls. Compared with non-use, long-term use of SSRI (≥ 20 claims) was not associated with an altered risk of cataract (adjusted OR 0.93, 95% CI 0.84-1.04). The analysis of the individual drug substances also yielded no statistically significant association between drug exposure and the risk of cataract. According to our study, use of SSRI does not change the risk of cataract in the overall population.

In Utero Antidepressants and Neurodevelopmental Outcomes in Kindergarteners.

To determine if in utero selective serotonin reuptake inhibitor (SSRI) or selective serotonin norepinephrine inhibitor (SNRI) exposure is associated with developmental vulnerability in kindergarten among children whose mothers were diagnosed with prenatal mood or anxiety disorder. Linkable administrative data were used to create a population-based cohort of 266 479 mother-child dyads of children born in Manitoba, Canada, between 1996 and 2014, with follow-up through 2015. The sample was restricted to mothers who had a mood or anxiety disorder diagnosis between 90 days before conception (N = 13 818). Exposed women had ≥2 SSRI or SNRI dispensations during pregnancy (n = 2055); unexposed mothers did not have a dispensation of an SSRI or SNRI during pregnancy (n = 10 017). The Early Development Instrument (EDI) was used to assess developmental health in kindergarten children. The EDI is a 104-component kindergarten teacher-administered questionnaire, encompassing 5 developmental domains. Of the 3048 children included in the study who met inclusion criteria and had an EDI, 21.43% of children in the exposed group were assessed as vulnerable on 2 or more domains versus 16.16% of children in the unexposed group (adjusted odds ratio = 1.43; 95% confidence interval 1.08-1.90). Children in the exposed group also had a significant risk of being vulnerable in language and/or cognition (adjusted odds ratio = 1.40; 95% confidence interval 1.03-1.90). Exposure to SSRIs or SNRIs during pregnancy was associated with an increased risk of developmental vulnerability and an increased risk of deficits in language and/or cognition. Replication of results is necessary before clinical implications can be reached.

Dose-effect of maternal serotonin reuptake inhibitor use during pregnancy on birth outcomes: A prospective cohort study

BackgroundWhile antidepressant use during pregnancy is increasingly common, there is concern about the possible effects of in-utero antidepressant exposure on the child. Our objective was to examine whether there is a dose-effect of maternal serotonin reuptake inhibitors (SRI) during pregnancy on birth outcomes. MethodsWomen between 12 and 16 weeks of gestation, who were using an SRI, were eligible for participation in this nation-wide prospective observational cohort study. Recruitment took place between April 2015 and February 2018 (n = 145). SRI exposure and psychopathology symptoms were assessed throughout pregnancy. Exposure was defined as SRI standardized dose at 36 weeks of gestation and mean SRI standardized dose over total pregnancy. Multivariable linear and logistic regression were used to examine the associations with birth weight, gestational age at birth, and being small for gestational age. ResultsMaternal SRI dose at 36 weeks of gestation was significantly associated with birth weight (adjusted ß = -180.7, 95%CI -301.1;-60.2, p-value < 0.01) as was mean SRI standardized dose during total pregnancy (adjusted ß = -187.3, 95%CI -322.0;-52.6, p-value < 0.01). No significant associations between maternal SRI dose and gestational age or being small for gestational age were observed. LimitationsAlthough prospective, we cannot make full causal inferences given that we did not randomize women to different dosages. ConclusionThese findings suggest that careful dosing of SRI use during pregnancy may prevent a negative impact on birth weight and indicate the need for further investigation of causality.

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.