Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta‐analysis of cohort studies

Kaplan, Yusuf Cem; Keskin-Arslan, Elif; Acar, Selin; Sözmen, Kaan

doi:10.1111/bcp.13382

Cited by 39 publications

(31 citation statements)

References 33 publications

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“…53,64 When maternal groups with psychiatric disorder but with no SSRI exposure during pregnancy were compared with unexposed groups, a higher incidence of ASD was observed in the former group (OR=1•81, 95% CI=1•44 to 2•29), supporting the idea that presence of a maternal psychiatric condition is an independent risk factor for ASD. 53 Meanwhile, when SSRIexposed groups were compared with unexposed groups with a history of affective disorder (setting in which the possibility of confounding by psychiatric disorder is minimized), the association with ASD was nonsignificant (OR=1•18, 95% CI=0•91 to 1•52). 64 Analyses restricted to sibling studies also showed a non-significant association (RR=0•96, 95% CI 0•65 to 1•42).…”

Section: Discussionmentioning

confidence: 79%

Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence

Kim

Son

et al. 2019

The Lancet Psychiatry

197

132

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Background Numerous studies have identified the potential risk factors and biomarkers for autism spectrum disorder (ASD). We aim to study the strength and validity of the suggested environmental risk factors or biomarkers of ASD. Methods We conducted an umbrella review and systematically appraised the relevant meta-analyses of observational studies (PROSPERO registration: CRD42018091704). We searched PubMed, Embase, and Cochrane Database of Systematic Reviews from inception to 10/17/2018 and screened the reference list of relevant articles. We obtained the summary effect, 95% confidence interval (CI), heterogeneity, and 95% prediction intervals. We examined small study effects and excess significance. We performed analyses under credibility ceilings. Findings A total of 46 eligible articles yielded data on 67 environmental risk factors (cases=544212, population=81708787) and 52 biomarkers (cases=15614, controls=15417). Evidence of association was convincing for greater maternal age (RR=1•31, 95% CI=1•18 to 1•45), maternal chronic hypertension (OR=1•48, 95% CI=1•29 to 1•70), maternal gestational hypertension (OR=1•37, 95% CI=1•21 to 1•54), maternal overweight (RR=1•28, 95% CI=1•19 to 1•36), preeclampsia (RR=1•32, 95% CI=1•20 to 1•45), pre-pregnancy maternal antidepressant exposure (RR=1•48, 95% CI=1•29 to 1•71), and selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy (OR=1•84, 95% CI=1•60 to 2•11). Only two associations, maternal overweight and SSRI during pregnancy, retained high level of evidence under subset sensitivity analyses. Evidence from biomarkers was limited. Interpretation Convincing evidence suggests that maternal factors such as age and features of metabolic syndrome are associated with risk of ASD. SSRI use during pregnancy was also convincingly associated with risk of ASD when exposed and non-exposed groups were compared. However, there is a possibility that the association is affected by other confounding factors, considering that pre-pregnancy maternal antidepressant exposure was also convincingly associated with higher risk of ASD. Findings from prior studies suggest that one possible confounding factor is underlying maternal psychiatric disorders.

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Section: Discussionmentioning

confidence: 79%

Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence

Kim

Son

et al. 2019

The Lancet Psychiatry

197

132

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“…These babies may experience long-term impacts on 5-HT neurotransmission [169], though extensive, longitudinal studies are needed to evaluate this possibility. Currently, the literature remains divided on whether maternal SSRI use is linked to an increased incidence of ASD in exposed offspring [147,[170][171][172][173][174][175][176][177][178] or not [179][180][181][182][183][184][185][186] (see Table 2 for summary).…”

Section: Exposure To Selective Serotonin Reuptake Inhibitors During Pmentioning

confidence: 99%

Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder

Garbarino¹,

Gilman

Daws

et al. 2019

Pharmacological Research

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A variety of human and animal studies support the hypothesis that serotonin (5-hydroxytryptamine or 5-HT) system dysfunction is a contributing factor to the development of autism in some patients. However, many questions remain about how developmental manipulation of various components that influence 5-HT signaling (5-HT synthesis, transport, metabolism) persistently impair social behaviors. This review will summarize key aspects of central 5-HT function important for normal brain development, and review evidence implicating perinatal disruptions in 5-HT signaling in the pathophysiology of autism spectrum disorder. We discuss the importance, and relative dearth, of studies that explore the possible correlation to autism in the interactions between important intrinsic and extrinsic factors that may disrupt 5-HT homeostasis during development. In particular, we focus on exposure to 5-HT transport altering mechanisms such as selective serotonin-reuptake inhibitors or genetic polymorphisms in primary or auxiliary transporters of 5-HT, and how they relate to neurological stores of serotonin and its precursors. A deeper understanding of the many mechanisms by which 5-HT signaling can be disrupted, alone and in concert, may contribute to an improved understanding of the etiologies and heterogeneous nature of this disorder. We postulate that extreme bidirectional perturbations of these factors during development likely compound or synergize to facilitate enduring neurochemical changes resulting in insufficient or excessive 5-HT signaling, that could underlie the persistent behavioral characteristics of autism spectrum disorder.

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“…The meta‐analyses on ASD have reported pooled adjusted point estimates (i.e. odds, hazard, or relative risk ratios) ranging from approximately 1.0–2.5 (Table ; Andalib et al., ; Brown, Hussain‐Shamsy, Lunsky, Dennis, & Vigod, ; Kaplan, Keskin‐Arslan, Acar, & Sozmen, ; Kaplan, Keskin‐Arslan, Acar, & Sozmen, ; Kobayashi, Matsuyama, Takeuchi, & Ito, ; Man et al., ; Mezzacappa et al., ; Morales et al., ; Zhou, Li, Ou, & Li, ).The meta‐analyses on ADHD have generally reported pooled point estimates (i.e. odds or relative risk ratios) of about 1.5 (Table ; Jiang, Peng, Zhang, & Ruan, ; Man et al., ; Morales et al., ).…”

Section: Observational Studiesmentioning

confidence: 99%

Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

Sujan

Öberg

Quinn

et al. 2018

Child Psychology Psychiatry

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Children of women treated with antidepressants during pregnancy are more likely to develop neurodevelopmental problems than are unexposed children. Associations between prenatal antidepressant exposure and neurodevelopmental problems could reflect a causal effect or could be partially or fully explained by other factors that differ between exposed and unexposed offspring, including having mothers with conditions requiring antidepressant treatment (e.g. depression), environmental risk factors, and/or genetic risk factors shared across disorders. This translational review aims to provide a brief overview of findings from rodent experiments and critically evaluate observational studies in humans to assess the extent to which associations between prenatal antidepressant exposure and neurodevelopmental problems are due to causal mechanisms versus other influences. We focus our review on two important neurodevelopmental outcomesautism spectrum disorder (ASD) and attention-deficit/ hyperactivity disorder (ADHD). In general, rodent studies have reported adverse effects of perinatal antidepressant exposure on neurodevelopment. Between-species differences raise questions about the generalizability of these findings to humans. Indeed, converging evidence from studies using multiple designs and approaches suggest that observed associations between prenatal antidepressant exposure and neurodevelopmental problems in humans are largely due to confounding factors. We also provide specific recommendations for future research. Animal research should explicitly evaluate the impact of timing of exposure and dosage of medications, as well as better map outcome measures in rodents to human neurodevelopmental problems. Observational studies should investigate specific confounding factors, specific antidepressant drugs and classes, the potential impact of timing of exposure, and a wider range of other potential offspring outcomes. The findings summarized in this review may help women and their doctors make informed decisions about antidepressant use during pregnancy by providing reassurance that use of these medications during pregnancy is unlikely to substantially increase the risk of ASD and ADHD.

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Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta‐analysis of cohort studies

Cited by 39 publications

References 33 publications

Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence

Environmental risk factors and biomarkers for autism spectrum disorder: an umbrella review of the evidence

Extreme enhancement or depletion of serotonin transporter function and serotonin availability in autism spectrum disorder

Annual Research Review: Maternal antidepressant use during pregnancy and offspring neurodevelopmental problems – a critical review and recommendations for future research

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