Prenatal IgE as a Risk Factor for the Development of Childhood Neurodevelopmental Disorders.
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ABSTRACT:
SUBMITTER: Straughen JK
PROVIDER: S-EPMC8160239 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions.
| S-EPMC3728489 | biostudies-other
Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).
2013-12-31 | E-GEOD-35222 | biostudies-arrayexpress
Project description:ImportanceGiven the critical role that iron plays in neurodevelopment, an association between prenatal iron deficiency and later risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and intellectual disability (ID), is plausible.ObjectiveTo test the a priori hypothesis that anemia diagnosed in mothers during pregnancy is associated with an increased risk of ASD, ADHD, and ID in offspring and that the magnitude of the risk varies with regard to the timing of anemia in pregnancy.Design, setting, and participantsThis cohort study used health and population register data from the Stockholm Youth Cohort to evaluate 532 232 nonadoptive children born from January 1, 1987, to December 31, 2010, in Sweden, with follow-up in health registers until December 31, 2016. Data analysis was performed from January 15, 2018, to June 20, 2018.ExposuresRegistered diagnoses of anemia during pregnancy. Gestational timing of the first recorded anemia diagnosis (≤30 weeks or >30 weeks) was considered to assess potential critical windows of development.Main outcomes and measuresRegistered diagnoses of ASD, ADHD, or ID or co-occurring combinations of these disorders.ResultsThe cohort included 532 232 individuals (272 884 [51.3%] male) between 6 and 29 years of age at the end of follow-up (mean [SD] age, 17.6 [7.1] years) and their 299 768 mothers. The prevalence of ASD, ADHD, and ID was higher among children born to mothers diagnosed with anemia within the first 30 weeks of pregnancy (4.9% ASD, 9.3% ADHD, and 3.1% ID) compared with mothers with anemia diagnosed later in pregnancy (3.8% ASD, 7.2% ADHD, and 1.1% ID) or mothers not diagnosed with anemia (3.5% ASD, 7.1% ADHD, and 1.3% ID). Anemia diagnosed during the first 30 weeks of pregnancy but not later was associated with increased risk of diagnosis of ASD (odds ratio [OR], 1.44; 95% CI, 1.13-1.84), ADHD (OR, 1.37; 95% CI, 1.14-1.64), and ID (OR, 2.20; 95% CI, 1.61-3.01) in offspring in models that included socioeconomic, maternal, and pregnancy-related factors. Early anemia diagnosis was similarly associated with risk of ASD (OR, 2.25; 95% CI, 1.24-4.11) and ID (OR, 2.59; 95% CI, 1.08-6.22) in a matched sibling comparison. Considering mutually exclusive diagnostic groups, we observed the strongest association between anemia and ID without co-occurring ASD (OR, 2.72; 95% CI, 1.84-4.01). Associations of these disorders with anemia diagnosed later in pregnancy were greatly diminished.Conclusions and relevanceIn contrast to maternal anemia diagnosed toward the end of pregnancy, anemia diagnosed earlier in pregnancy was associated with increased risk of the development of ASD, ADHD, and particularly ID in offspring. Given that iron deficiency and anemia are common among women of childbearing age, our findings emphasize the importance of early screening for iron status and nutritional counseling in antenatal care.
| S-EPMC6751782 | biostudies-literature
Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders.
2013-12-31 | GSE35222 | GEO
Project description:Sleep disturbance is a common symptom of psychiatric and neurodevelopmental disorders and, especially in childhood, can be a precursor to various mental disorders. However, the genetic etiology of mental illness that contributes to sleep disturbance during childhood is poorly understood. We investigated whether the polygenic features of psychiatric and neurodevelopmental disorders are associated with sleep disturbance during childhood. We conducted polygenic risk score (PRS) analyses by utilizing large-scale genome-wide association studies (GWASs) (n = 46,350-500,199) of five major psychiatric and neurodevelopmental disorders (autism spectrum disorder, schizophrenia, attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), and bipolar disorder) and, additionally, anxiety disorders as base datasets. We used the data of 9- to 10-year-olds from the Adolescent Brain Cognitive Development study (n = 9683) as a target dataset. Sleep disturbance was assessed based on the Sleep Disturbance Scale for Children (SDSC) scores. The effects of PRSs for these psychiatric and neurodevelopmental disorders on the total scores and six subscale scores of the SDSC were investigated. Of the PRSs for the five psychiatric and neurodevelopmental disorders, the PRSs for ADHD and MDD positively correlated with sleep disturbance in children (ADHD: R2 = 0.0033, p = 6.19 × 10-5, MDD: R2 = 0.0042, p = 5.69 × 10-6). Regarding the six subscale scores of the SDSC, the PRSs for ADHD positively correlated with both disorders of initiating and maintaining sleep (R2 = 0.0028, p = 2.31 × 10-4) and excessive somnolence (R2 = 0.0023, p = 8.44 × 10-4). Furthermore, the PRSs for MDD primarily positively correlated with disorders of initiating and maintaining sleep (R2 = 0.0048, p = 1.26 × 10-6), followed by excessive somnolence (R2 = 0.0023, p = 7.74 × 10-4) and sleep hyperhidrosis (R2 = 0.0014, p = 9.55 × 10-3). Despite high genetic overlap between MDD and anxiety disorders, PRSs for anxiety disorders correlated with different types of sleep disturbances such as disorders of arousal or nightmares (R2 = 0.0013, p = 0.011). These findings suggest that greater genetic susceptibility to specific psychiatric and neurodevelopmental disorders, as represented by ADHD, MDD, and anxiety disorders, may contribute to greater sleep problems among children.
| S-EPMC7997961 | biostudies-literature
Project description:Prenatal exposure to maternal stress and depression has been identified as a risk factor for adverse behavioral and neurodevelopmental outcomes in early childhood. However, the molecular mechanisms through which maternal psychopathology shapes offspring development remain poorly understood. We analyzed transcriptome-wide gene expression profiles of 149 UCB samples from neonates born to mothers with prenatal PTSD (n=20), depression (n=31) and PTSD with comorbid depression (PTSD/Dep; n=13), compared to neonates born to carefully matched trauma exposed controls without meeting PTSD criteria (TE; n=23) and healthy mothers (n=62). We also evaluated physiological and developmental measures in these infants at birth, six months and twenty-four months. A multistep analytic approach was used that specifically sought to: 1) identify dysregulated genes, molecular pathways and discrete groups of co-regulated gene modules in UCB associated with prenatal maternal psychopathologies; and 2) to determine the impact of perinatal PTSD and depression on early childhood development outcomes.
2018-05-25 | GSE114852 | GEO
Project description:AimTo investigate neurodevelopmental outcome of children with open prenatal spina bifida aperta (SBA) repair.MethodPrenatal SBA repair was performed in 130 fetuses at the Zurich Center between 2010 and 2019. Seventy-seven children underwent 1 year assessment with the Griffiths Mental Developmental Scales (Griffiths) and 65 with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 2 years. Anatomical and functional level and ambulation status were assessed. Descriptive statistics and multiple linear regression analyses for risk factors were performed.ResultsThe Bayley-III cognition composite score in children with prenatal SBA repair was within normal limits but lower compared to population norms (mean=95.15, SD=14.683 vs norm=100, SD=15, p=0.01). Fine motor development (mean=9.58, SD=2.744, p=0.227) was typical while gross motor development was lower than the norm (mean=3.02, SD=2.758 vs norm=10, SD=3, p<0.001). Griffiths developmental quotient subscales correlated significantly with corresponding Bayley-III scores (all p<0.001, r=0.519-0.594). At 2 years, 50.8% could walk.InterpretationChildren with non-trial open prenatal SBA repair show favourable cognitive outcome in the low-average range at 1 and 2 years of age. While gross motor function remained delayed, fine motor function was age appropriate. The correlation between Griffiths and Bayley-III allows a prediction about neurodevelopmental outcome at the age of 1 year. What this paper adds Children with non-trial open prenatal spina bifida repair show favourable cognitive outcome. Gross motor function remains impaired, while fine motor function is age appropriate. At 2 years of age, 50.8% of children were walking. Neurodevelopmental testing correlated between 1 (Griffiths Mental Developmental Scales) and 2 (Bayley Scales of Infant and Toddler Development, Third Edition) years.
| S-EPMC8596420 | biostudies-literature
Project description:Prenatal maternal infection and anxiety have been linked, in separate lines of study, with child neurodevelopment. We extend and integrate these lines of study in a large prospective longitudinal cohort study of child neurodevelopment. Data are based on the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort; prenatal maternal anxiety was assessed from self-report questionnaire; prenatal infection was derived from reports of several conditions in pregnancy (n = 7,042). Child neurodevelopment at approximately 8 years of age was assessed by in-person testing, reports of social and communication problems associated with autism, and psychiatric evaluation. Covariates included psychosocial, demographic, and perinatal/obstetric risks. Prenatal infection was associated with increased likelihood of co-occurring prenatal risk, including anxiety. Regression analyses indicated that both prenatal infection and prenatal anxiety predicted child social and communication problems; the predictions were largely independent of each other. Comparable effects were also found for the prediction of symptoms of attention problems and anxiety symptoms. These results provide the first evidence for the independent effects of prenatal infection and anxiety on a broad set of neurodevelopmental and behavioral and emotional symptoms in children, suggesting the involvement of multiple mechanisms in the prenatal programming of child neurodevelopment. The results further underscore the importance of promoting prenatal physical and mental health for child health outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
| S-EPMC9069845 | biostudies-literature
Project description:Insulin-Like Growth Factor 1 (IGF-1) is a neurotrophic polypeptide with crucial roles to play in Central Nervous System (CNS) growth, development and maturation. Following interrogation of the neurobiology underlying several neurodevelopmental disorders and Autism Spectrum Disorders (ASD), both recombinant IGF-1 (mecasermin) and related derivatives, such as (1-3)IGF-1, have emerged as potential therapeutic approaches. Clinical pilot studies and early reports have supported the safety/preliminary efficacy of IGF-1 and related compounds in the treatment of Rett Syndrome, with evidence mounting for its use in Phelan McDermid Syndrome and Fragile X Syndrome. In ASD, clinical trials are ongoing. Here, we review the role of IGF-1 in the molecular etiologies of these conditions in addition to the accumulating evidence from early clinical studies highlighting the possibility of IGF-1 and related compounds as potential treatments for these childhood-onset neurodevelopmental disorders.
| S-EPMC5043261 | biostudies-literature
Project description:OBJECTIVE:To investigate the relationship between prenatal geophagy, maternal prenatal haematological indices, malaria, helminth infections and cognitive and motor development among offspring. METHODS:At least a year after delivery, 552 of 863 HIV-negative mothers with singleton births who completed a clinical trial comparing the efficacy of sulfadoxine-pyrimethamine and mefloquine during pregnancy in Allada, Benin, responded to a nutrition questionnaire including their geophagous habits during pregnancy. During the clinical trial, helminth infection, malaria, haemoglobin and ferritin concentrations were assessed at 1st and 2nd antenatal care visits (ANV) and at delivery. After the first ANV, women were administered daily iron and folic acid supplements until three what? post-delivery. Singleton children were assessed for cognitive function at age 1 year using the Mullen Scales of Early Learning. RESULTS:The prevalence of geophagy during pregnancy was 31.9%. Pregnant women reporting geophagy were more likely to be anaemic (AOR = 1.9, 95% CI [1.1, 3.4]) at their first ANV if they reported geophagy at the first trimester. Overall, prenatal geophagy was not associated with maternal haematological indices, malaria or helminth infections, but geophagy during the third trimester and throughout pregnancy was associated with poor motor function (AOR = -3.8, 95% CI [-6.9, -0.6]) and increased odds of geophagous behaviour in early childhood, respectively. CONCLUSIONS:Prenatal geophagy is not associated with haematological indices in the presence of micronutrient supplementation. However, it may be associated with poor child motor function and infant geophagy. Geophagy should be screened early in pregnancy.
| S-EPMC6103800 | biostudies-literature