Maternal immune markers during pregnancy and child neurodevelopmental outcomes at age 20 months in the Seychelles Child Development Study

Irwin, Jessica H.; McSorley, Emeir M.; Yeates, Alison J.; Mulhern, Maria S.; Strain, JJ; Watson, Gene E.; Grzesik, Katherine; Thurston, Sally W.; Love, Tanzy; Smith, Tristram; Broberg, Karin; Shamlaye, Conrad; Myers, Gary J.; Davidson, Philip W.; Wijngaarden, Edwin van

doi:10.1016/j.jneuroim.2019.577023

Cited by 11 publications

(10 citation statements)

References 34 publications

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“…Out of the inflammatory markers tested, beneficial associations were observed for pro-inflammatory markers TARC and IL-1β, and pro-lymphangiogenic VEGF-D, and adverse associations were seen for pro-inflammatory IL-2, anti-inflammatory IL-10, and anti-angiogenic sFlt-1 [103]. Despite these disagreements, the general impression from the literature is that activation of the maternal immune system, regardless of the cause, can indeed alter the prenatal environment by skewing the levels of certain cytokines, increasing foetal susceptibility to ASD.…”

Section: Maternal Immune Activation Alters Maternal Cytokine Profilesmentioning

confidence: 97%

“…Although a variety of different maternal cytokines have been implicated in ASD [101][102][103]105,106], for the purpose of this literature review, only IL-1β, IL-6 and IL-17 will be discussed, as the pathological mechanisms by which they exert their effects on the prenatal environment are the most well understood.…”

Section: Mechanisms By Which Cytokines Affect the Prenatal Environmentmentioning

confidence: 99%

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Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Ravaccia

Ghafourian

2020

Biomedicines

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Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders characterised by impairments in communication, social interaction, and the presence of restrictive and repetitive behaviours. Over the past decade, most of the research in ASD has focused on the contribution of genetics, with the identification of a variety of different genes and mutations. However, the vast heterogeneity in clinical presentations associated with this disorder suggests that environmental factors may be involved, acting as a “second hit” in already genetically susceptible individuals. To this regard, emerging evidence points towards a role for maternal immune system dysfunctions. This literature review considered evidence from epidemiological studies and aimed to discuss the pathological relevance of the maternal immune system in ASD by looking at the proposed mechanisms by which it alters the prenatal environment. In particular, this review focuses on the effects of maternal immune activation (MIA) by looking at foetal brain-reactive antibodies, cytokines and the microbiome. Despite the arguments presented here that strongly implicate MIA in the pathophysiology of ASD, further research is needed to fully understand the precise mechanisms by which they alter brain structure and behaviour. Overall, this review has not only shown the importance of the maternal immune system as a risk factor for ASD, but more importantly, has highlighted new promising pathways to target for the discovery of novel therapeutic interventions for the treatment of such a life-changing disorder.

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Section: Maternal Immune Activation Alters Maternal Cytokine Profilesmentioning

confidence: 97%

Section: Mechanisms By Which Cytokines Affect the Prenatal Environmentmentioning

confidence: 99%

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Ravaccia

Ghafourian

2020

Biomedicines

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“…High levels of IL-8 can lead to systemic inflammation which may disrupt the normal trafficking of neuronal processes, the formation of appropriate synaptic contacts and neural plasticity [ 4 , 6 , 13 , 36 ]. Accordingly, several studies have linked increased maternal inflammatory cytokines to increased risk of serious conditions including cerebral palsy, autism, schizophrenia, intellectual disability, depression and psychosis among offspring [ 1 , 4 , 6 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]. However, to our knowledge this is the first study to specifically link prenatal IL-8 to fine motor and problem-solving skills in early childhood.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have linked prenatal measures of inflammatory biomarkers with adverse neurodevelopmental outcomes in offspring including cognitive ability [ 9 ], neurodevelopmental delay [ 1 ], psychomotor development [ 10 ], autism [ 11 , 12 , 13 , 14 , 15 ], neurologic abnormalities [ 4 ], depression [ 16 ], psychosis [ 17 ] and schizophrenia [ 6 ]. Although directions of effect have not always been consistent across these studies, there is a strong biological rationale for the involvement of the dysregulation of maternal immune function and maternal inflammatory biomarkers in childhood neurodevelopment [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

Kelly

Lee-Sarwar

Chen

et al. 2022

IJMS

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Maternal infection and stress during the prenatal period have been associated with adverse neurodevelopmental outcomes in offspring, suggesting that biomarkers of increased inflammation in the mothers may associate with poorer developmental outcomes. In 491 mother–child pairs from the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we investigated the association between maternal levels of two inflammatory biomarkers; interleukin-8 (IL-8) and C-Reactive Protein (CRP) during early (10–18 wks) and late (32–38 wks) pregnancy with offspring scores in the five domains of the Ages and Stages Questionnaire, a validated screening tool for assessing early life development. We identified a robust association between early pregnancy IL-8 levels and decreased fine-motor (β: −0.919, 95%CI: −1.425, −0.414, p = 3.9 × 10−4) and problem-solving skills at age two (β: −1.221, 95%CI: −1.904, −0.414, p = 4.9 × 10−4). Associations between IL-8 with other domains of development and those for CRP did not survive correction for multiple testing. Similarly, while there was some evidence that the detrimental effects of early pregnancy IL-8 were strongest in boys and in those who were not breastfed, these interactions were not robust to correction for multiple testing. However, further research is required to determine if other maternal inflammatory biomarkers associate with offspring neurodevelopment and work should continue to focus on the management of factors leading to increases in IL-8 levels in pregnant women.

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“…The most commonly collected samples in the included studies were maternal venous blood, cord blood and urine. These are all simple to collect and have high ENID, 18 FOETAL, 17 RECIPAL, 15 AMANHI, 10 INTERBIO-21st, 19 NuPED, ZAPPS, 26 HeLTI, 22 MiPADD, 20 ENID, 18 FOETAL, 17 RECIPAL, 15 AMANHI, 10 NuPED, 16 ZAPPS, 26 HeLTI, 22 NuPED, 16 ZAPPS, 26 HeLTI, 22 PRECISE 9 6 (42.9%) IPTp +, 21 COSMIC, 27 MiPADD, 20 FOETAL, 17 COSMIC, 27 MiPADD, 20 FOETAL, 17 RECIPAL, 15 AMANHI, 10 INTERBIO-21st, 19 NuPED, 16 ZAPPS, 26 HeLTI, 22 --*Inclusive of studies planning to report on these variables/outcomes, but for which data collection is still ongoing. †Denominator based on number of studies collecting corresponding outcome.…”

Section: Summary Of Findingsmentioning

confidence: 99%

Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review

et al. 2020

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BackgroundTechnological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity.MethodsInclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included: scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were screened in a three-stage process based on title, abstract and full text by two independent reviewers. The review is registered on PROSPERO (CRD42019147483).ResultsFourteen SSA studies met the inclusion criteria from database searches (n=8), reference list searches (n=2) and expert input (n=4). Three studies have ongoing data collection. The most represented countries were South Africa and Mozambique (Southern Africa) (n=3), Benin (Western Africa) (n=4) and Tanzania (Eastern Africa) (n=4); including an estimated 31 763 women. Samples commonly collected were blood, cord blood and placenta. Seven studies collected neonatal samples. Common clinical outcomes included maternal and perinatal mortality, malaria and preterm birth.ConclusionsIncreasingly numerous pregnancy cohorts in SSA that include biobanking are generating a uniquely valuable resource for collaborative discovery science, and improved understanding of the high regional risks of maternal, fetal and neonatal morbidity and mortality. Future studies should align protocols and consider their added value and distinct contributions.

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Maternal immune markers during pregnancy and child neurodevelopmental outcomes at age 20 months in the Seychelles Child Development Study

Cited by 11 publications

References 34 publications

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Critical Role of the Maternal Immune System in the Pathogenesis of Autism Spectrum Disorder

Maternal Inflammatory Biomarkers during Pregnancy and Early Life Neurodevelopment in Offspring: Results from the VDAART Study

Pregnancy cohorts and biobanking in sub-Saharan Africa: a systematic review

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