Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis

Manzari, Nicla; Matvienko‐Sikar, Karen; Baldoni, Franco; O’Keeffe, Gerard W.; Khashan, Ali S.

doi:10.1007/s00127-019-01745-3

Cited by 119 publications

(86 citation statements)

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“…Thus, results may differ from countries with universal healthcare access and no economic barriers to obtaining diagnosis and services 27 . Maternal depressive disorders and stress were significantly associated with ASD, and subgroup analyses suggested an association between maternal stress and bereavement in the third trimester and increased risk of ASD 28,29 .…”

Section: Resultsmentioning

confidence: 95%

“…Exposure to smoking in the first trimester appeared to increase the odds of TS and ADHD in the child, and exposure to maternal asthma in the first and second trimester is associated with childhood ASD. In contrast, the immune stress from maternal bacterial infections and negative life events seems greatest in the third trimester for both ASD and ADHD 28,34,38,61 . Evaluating the presence and timing of adverse or traumatic life events and assessments of related stress are not included in population databases and would need dedicated questionnaires or interviews, which are difficult to perform on a large scale.…”

Section: Discussionmentioning

confidence: 95%

“…The dose, type, intensity and timing of the immune response during pregnancy, likely influences fetal neurobehavior through impacts on specific developmental time course of different brain cells, regions and their underlying neural mechanisms 4,71 . Attempts to determine an association between timing of exposure to risk factors with childhood neurodevelopmental problems in epidemiology studies have been difficult 28,34,38,51,61 . Exposure to smoking in the first trimester appeared to increase the odds of TS and ADHD in the child, and exposure to maternal asthma in the first and second trimester is associated with childhood ASD.…”

Section: Discussionmentioning

confidence: 99%

“…SES socioeconomic status, Preg pregnancy, CC case-control, CO cohort, RR relative risk, OR odds ratio, HR hazard ratio, IRR incidence risk ratio. ADHD in children; subjective self-report of stress but not objectively evaluated stress had increased association (OR 2.44 [1.23-4.85] 28 ).…”

Section: Maternal Inflammatory States and Attention Deficit Hyperactimentioning

confidence: 99%

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Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

et al. 2021

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Inflammation is increasingly recognized as a cause or consequence of common problems of humanity including obesity, stress, depression, pollution and disease states such as autoimmunity, asthma, and infection. Maternal immune activation (MIA), triggered by both acute and systemic chronic inflammation, is hypothesized to be one of the mechanisms implicated in the pathogenesis of neurodevelopmental disorders (NDD). Although there is substantial preclinical evidence to support the MIA hypothesis, the human evidence is disparate. We performed a systematic review on human studies examining associations between maternal inflammatory states and offspring NDDs (autism spectrum disorder- ASD, attention deficit hyperactivity disorder-ADHD, Tourette syndrome-TS). 32 meta-analyses and 26 additional individual studies were identified. Maternal states associated with ASD include obesity, gestational diabetes mellitus, pre-eclampsia, pollution, stress, depression, autoimmune diseases, and infection. Maternal states associated with ADHD include obesity, pre-eclampsia, smoking, low socioeconomic status (SES), stress, autoimmune disease, and asthma. Maternal states associated with TS include low SES, depression, and autoimmune diseases. Diverse maternal inflammatory states in pregnancy are associated with common offspring NDDs. Given the increased prevalence of NDDs, there is urgent need to explore relative and cumulative maternal risk factors and disease mechanisms. Defining preventable risk factors in high-risk pregnancies could mitigate the expression and severity of NDDs.

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Section: Resultsmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Maternal Inflammatory States and Attention Deficit Hyperactimentioning

confidence: 99%

See 2 more Smart Citations

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

et al. 2021

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“…It is well documented that adverse experiences during the prenatal period are risk factors for the pathogenesis of affective disorders in later life (reviewed in: Manzari, Matvienko‐Sikar, Baldoni, O'Keeffe, & Khashan, 2019; van den Bergh, Dahnke, & Mennes, 2018). Pathophysiology of depression has repeatedly been linked to impaired functioning of the serotonergic system (reviewed in: Köhler, Cierpinsky, Kronenberg, & Adli, 2016; Paul & Lowry, 2013).…”

Section: Introductionmentioning

confidence: 99%

Prenatal stress‐related alterations in synaptic transmission and 5‐HT₇ receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT₇ receptor antagonist SB 269970

Sowa

Hess

2020

Eur J of Neuroscience

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Early life adversity exerts a detrimental influence on developing brain neuronal networks and its consequences may include mental health disorders. In rats, prenatal stress may lead to anxiety and depressive-like behavior in the offspring. Several lines of evidence implicated an involvement of prenatal stress in alterations of the brain serotonergic system functions, but the effects of prenatal stress on its core, the dorsal raphe nucleus (DRN), still remain incompletely understood. The present study was aimed at finding whether prenatal stress induces modifications in the glutamatergic and GABAergic inputs to DRN projection cells and whether it affects DRN 5-HT 7 receptors, which modulate activity of these synapses. Prenatal stress resulted in an increase in basal frequency of spontaneous excitatory postsynaptic currents (sEP-SCs) and in a decrease in basal frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) recorded from putative projection neurons in DRN slices ex vivo. While there were no changes in the excitability of DRN projection neurons, the 5-HT 7 receptor-mediated reduction in the sEPSC frequency and rise in the sIPSC frequency, seen in control rats, were largely absent in slices obtained from prenatally stressed rats. Repeated administration of SB 269970, a 5-HT 7 receptor antagonist, resulted in a reversal of prenatal stress-induced alterations in 5-HT 7 receptor-mediated effects on the sEPSC/sIPSC frequency. Moreover, the treatment reversed prenatal stress-induced alterations in basal excitatory transmission and partially reversed the effect of stress on basal inhibitory transmission in the DRN. How to cite this article: Sowa J, Hess G. Prenatal stress-related alterations in synaptic transmission and 5-HT 7 receptor-mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5-HT 7 receptor antagonist SB 269970.

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Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic

Firestein,

Manessis,

Warmingham

et al. 2024

JAMA Netw Open

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ImportanceStress and viral illness during pregnancy are associated with neurodevelopmental conditions in offspring. Autism screening positivity for children born during the pandemic remains unknown.ObjectiveTo examine associations between prenatal exposure to the pandemic milieu and maternal SARS-CoV-2 infection with rates of positive Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R) screenings.Design, Setting, and ParticipantsData for this cohort study were drawn from the COVID-19 Mother Baby Outcomes (COMBO) Initiative. M-CHAT-R scores obtained from children aged 16 to 30 months during routine clinical care at Columbia University Irving Medical Center in New York City were abstracted from electronic health records (EHRs) for children born between January 2018 and September 2021 (COMBO-EHR cohort). Separately, the M-CHAT-R was administered at 18 months for children born between February 2020 and September 2021 through a prospective longitudinal study (COMBO-RSCH cohort). Prenatal pandemic exposure (birth after March 1, 2020) and maternal SARS-CoV-2 status during pregnancy was determined through EHRs. Data were analyzed from March 2022 to June 2024.ExposuresPrenatal exposures to the pandemic milieu and maternal SARS-CoV-2 infection.Main Outcomes and MeasuresThe primary outcome was rate of positive M-CHAT-R screenings. For all primary analyses, unadjusted χ2 tests and adjusted logistic regression models were performed.ResultsThe COMBO-EHR cohort included 1664 children (442 born before the pandemic and 1222 born during the pandemic; 997 SARS-CoV-2 unexposed, 130 SARS-CoV-2 exposed, and 95 with unknown SARS-CoV-2 exposure status), of whom 266 (16.0%) were Black, 991 (59.6%) were Hispanic, 400 (24.0%) were White, 1245 (74.8%) were insured through Medicaid, 880 (52.9%) were male, and 204 (12.3%) were born prematurely. The COMBO-RSCH cohort included 385 children (74 born before the pandemic and 311 born during the pandemic; 201 SARS-CoV-2 unexposed, 101 SARS-CoV-2 exposed, and 9 with unknown SARS-CoV-2 exposure status), of whom 39 (10.1%) were Black, 168 (43.6%) were Hispanic, 157 (40.8%) were White, 161 (41.8%) were insured through Medicaid, 222 (57.7%) were male, and 38 (9.9%) were born prematurely. Prenatal pandemic exposure was not associated with a higher positive M-CHAT-R screening rate in either the COMBO-EHR or COMBO-RSCH cohort. Prenatal exposure to maternal SARS-CoV-2 infection was associated with a lower rate of M-CHAT-R positivity in the COMBO-EHR cohort (12.3% [16 children] vs 24.0% [239 children]; adjusted odds ratio, 0.40; 95% CI, 0.22-0.68; P = .001), but no association was found in the COMBO-RSCH cohort (12.9% [13 children] vs 19.9% [40 children]; adjusted odds ratio, 0.51; 95% CI, 0.24-1.04; P = .07).Conclusions and RelevanceIn this cohort study of 2 groups of children with prenatal pandemic exposure and/or exposure to maternal SARS-CoV-2 infection, neither exposure was associated with greater M-CHAT-R positivity.

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Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis

Cited by 119 publications

References 59 publications

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Prenatal stress‐related alterations in synaptic transmission and 5‐HT₇ receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT₇ receptor antagonist SB 269970

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic

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Prenatal maternal stress and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis

Cited by 119 publications

References 59 publications

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review

Prenatal stress‐related alterations in synaptic transmission and 5‐HT7 receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT7 receptor antagonist SB 269970

Positive Autism Screening Rates in Toddlers Born During the COVID-19 Pandemic

Contact Info

Product

Resources

About

Prenatal stress‐related alterations in synaptic transmission and 5‐HT₇ receptor‐mediated effects in the rat dorsal raphe nucleus are ameliorated by the 5‐HT₇ receptor antagonist SB 269970