Subclinical psychotic experiences (PLEs) are among the frequently reported mental health problems in children/adolescents. PLEs identified in cross sectional studies of children/adolescents are ...associated with current and future mental health problems. These associations are stronger for PLEs that persist over time. Hence, it could be useful to examine which children/adolescents with PLEs at a first assessment (baseline) are more likely to have PLEs at subsequent assessments.
We conducted a scoping review of studies that examined whether characteristics of children/adolescents (≤18 years) with PLEs at baseline predict whether PLEs are likely to be persistent or remittent at subsequent assessments. We included studies published between January 2002 and December 2017, conducted on general child/adolescent populations of ≥300 individuals, that provided data on PLEs for at least 2 time points, had available follow-up data for ≥50% of those assessed for PLEs at baseline and targeted for follow-up examination, and reported the differences between individuals with PLEs that persisted or remitted during the study period.
Six studies met our criteria. Each of them investigated a wide range of baseline characteristics but no predictor of persistence was replicated.
Our knowledge about which children/adolescents with PLEs at an initial assessment are likely to have persistent PLEs at subsequent assessments is sparse. A handful of predictors of persistent PLEs have been investigated so far, and none replicated. A better understanding of these predictors would be an important complement to investigations examining the evolution of PLEs and of mental health problems in children/adolescents.
IMPORTANCE Prenatal folic acid supplements reduce the risk of neural tube defects in children, but it has not been determined whether they protect against other neurodevelopmental disorders. ...OBJECTIVE To examine the association between maternal use of prenatal folic acid supplements and subsequent risk of autism spectrum disorders (ASDs) (autistic disorder, Asperger syndrome, pervasive developmental disorder–not otherwise specified PDD-NOS) in children. DESIGN, SETTING, AND PATIENTS The study sample of 85 176 children was derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa). The children were born in 2002-2008; by the end of follow-up on March 31, 2012, the age range was 3.3 through 10.2 years (mean, 6.4 years). The exposure of primary interest was use of folic acid from 4 weeks before to 8 weeks after the start of pregnancy, defined as the first day of the last menstrual period before conception. Relative risks of ASDs were estimated by odds ratios (ORs) with 95% CIs in a logistic regression analysis. Analyses were adjusted for maternal education level, year of birth, and parity. MAIN OUTCOME MEASURE Specialist-confirmed diagnosis of ASDs. RESULTS At the end of follow-up, 270 children in the study sample had been diagnosed with ASDs: 114 with autistic disorder, 56 with Asperger syndrome, and 100 with PDD-NOS. In children whose mothers took folic acid, 0.10% (64/61 042) had autistic disorder, compared with 0.21% (50/24 134) in those unexposed to folic acid. The adjusted OR for autistic disorder in children of folic acid users was 0.61 (95% CI, 0.41-0.90). No association was found with Asperger syndrome or PDD-NOS, but power was limited. Similar analyses for prenatal fish oil supplements showed no such association with autistic disorder, even though fish oil use was associated with the same maternal characteristics as folic acid use. CONCLUSIONS AND RELEVANCE Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation.
Epidemiological studies and work in animal models indicate that immune activation may be a risk factor for autism spectrum disorders (ASDs). We measured levels of 60 cytokines and growth factors in ...869 maternal mid-gestational (MMG) and 807 child cord blood (CB) plasma samples from 457 ASD (385 boys, 72 girls) and 497 control children (418 boys, 79 girls) from the Norwegian Autism Birth Cohort. We analyzed associations first using sex-stratified unadjusted and adjusted logistic regression models, and then employed machine learning strategies (LASSO + interactions, Random Forests, XGBoost classifiers) with cross-validation and randomly sampled test set evaluation to assess the utility of immune signatures as ASD biomarkers. We found prominent case-control differences in both boys and girls with alterations in a wide range of analytes in MMG and CB plasma including but not limited to IL1RA, TNFα, Serpin E1, VCAM1, VEGFD, EGF, CSF1, and CSF2. MMG findings were most striking, with particularly strong effect sizes in girls. Models did not change appreciably upon adjustment for maternal conditions, medication use, or emotional distress ratings. Findings were corroborated using machine learning approaches, with area under the receiver operating characteristic curve values in the test sets ranging from 0.771 to 0.965. Our results are consistent with gestational immunopathology in ASD, may provide insights into sex-specific differences, and have the potential to lead to biomarkers for early diagnosis.
Abstract Exposure to adverse life events during pregnancy has been linked to increased risk of schizophrenia spectrum disorders (SSD) in offspring. Nevertheless, much of the previous work inferred ...maternal stress from severe life events rather than directly assessing maternal reports of stress. The present study aimed to examine maternal reports of stress during pregnancy and risk for offspring SSD. Participants were 95 SSD cases and 206 controls who were offspring from a large birth cohort study that followed pregnant women from 1959 to 1966. During pregnancy interviews, women were asked if anything worrisome had occurred recently. Interviews were qualitatively coded for stress-related themes, including reports of daily life stress, by two independent raters. None of the maternal psychosocial stress themes were significantly associated with increased odds of offspring SSD in analyses of the full sample. However, results indicated a significant daily life stress by infant sex interaction. Maternal daily life stress during pregnancy was associated with significantly increased odds of SSD among male offspring. Findings suggest sex-specific fetal sensitivity to maternal reported daily life stress during pregnancy on risk for SSD, with males appearing to be more vulnerable to the influences of maternal stress during pregnancy.
There is great interest in the role epigenetic variation induced by non-genetic exposures may play in the context of health and disease. In particular, DNA methylation has previously been shown to be ...highly dynamic during the earliest stages of development and is influenced by in utero exposures such as maternal smoking and medication. In this study we sought to identify the specific DNA methylation differences in blood associated with prenatal and birth factors, including birth weight, gestational age and maternal smoking. We quantified neonatal methylomic variation in 1263 infants using DNA isolated from a unique collection of archived blood spots taken shortly after birth (mean = 6.08 days; s.d. = 3.24 days). An epigenome-wide association study (EWAS) of gestational age and birth weight identified 4299 and 18 differentially methylated positions (DMPs) respectively, at an experiment-wide significance threshold of p < 1 × 10
. Our EWAS of maternal smoking during pregnancy identified 110 DMPs in neonatal blood, replicating previously reported genomic loci, including AHRR. Finally, we tested the hypothesis that DNA methylation mediates the relationship between maternal smoking and lower birth weight, finding evidence that methylomic variation at three DMPs may link exposure to outcome. These findings complement an expanding literature on the epigenomic consequences of prenatal exposures and obstetric factors, confirming a link between the maternal environment and gene regulation in neonates. This article is part of the theme issue 'Developing differences: early-life effects and evolutionary medicine'.
Maternal stress during pregnancy has been repeatedly linked to increased risk for schizophrenia; however, no study has examined maternal cortisol during pregnancy and risk for the disorder. Study ...aims were to determine whether prenatal cortisol was associated with risk for schizophrenia and risk for an intermediate phenotype—decreased fetal growth—previously linked to prenatal cortisol and schizophrenia. Timing of exposure and fetal sex also were examined given previous findings.
Participants were 64 cases diagnosed with schizophrenia spectrum disorders (SSD) and 117 controls from a prospective birth cohort study. Maternal cortisol was determined from stored sera from each trimester and psychiatric diagnoses were assessed from offspring using semi-structured interviews and medical records review.
Maternal cortisol during pregnancy was not associated with risk for offspring schizophrenia. There was a significant interaction between 3rd trimester cortisol and case status on fetal growth. Specifically, cases exposed to higher 3rd trimester maternal cortisol had significantly decreased fetal growth compared to controls. In addition, these findings were restricted to male offspring.
Our results indicate that higher prenatal cortisol is associated with an intermediate phenotype linked to schizophrenia, fetal growth, but only among male offspring who developed schizophrenia. Findings were consistent with evidence that schizophrenia genes may disrupt placental functioning specifically for male fetuses, as well as findings that males are more vulnerable to maternal cortisol during pregnancy. Finally, results suggest that examining fetal sex and intermediate phenotypes may be important in understanding the mechanisms involved in prenatal contributors to schizophrenia.
Early identification of autism spectrum disorder (ASD) is regarded as crucial for swift access to early intervention and, subsequently, better outcomes later in life. However, current instruments ...miss large proportions of children who later go on to be diagnosed with ASD, raising a question of what these instruments measure. The present study utilized data from the Norwegian Mother, Father, and Child Cohort Study and the Autism Birth Cohort study to explore the subsequent developmental and diagnostic characteristics of children raising developmental concern on the six-critical discriminative item criterion of the M-CHAT (DFA6) at 18 months of age (N = 834). The DFA6 identified 28.8% of children diagnosed with ASD (N = 163), but 4.4% with language disorder (N = 188) and 81.3% with intellectual disability (N = 32) without ASD. Scoring in the «at-risk» range was associated with lower IQ, impaired functional language, and greater severity of autism symptoms whether children had ASD or not.
The Autism Epidemic: Fact or Artifact? Wazana, Ashley; Bresnahan, Michaeline; Kline, Jennie
Journal of the American Academy of Child and Adolescent Psychiatry,
06/2007, Letnik:
46, Številka:
6
Journal Article
Recenzirano
Objective: We provide an illustration of how changes in methodological factors may produce variations in the frequency of autistic disorder (AD) over time and project how much of the observed ...increase in the frequency of AD may be explained by methodological factors. Method: Using a prediction analysis, we calculate how broadening diagnostic criteria, younger age at diagnosis, and improved efficiency of case ascertainment could produce temporal trends in the incidence and prevalence of AD, measured by calendar year and by year of birth, in a hypothetical population of children 0 to 18 across the years 1950 to 2020. Results: Time trend studies report an increase as large as 11.0-fold over a 13-year period for AD. Conservative changes in the three methodological factors produced increases in the frequency of AD ranging from 2.1- to 28.8-fold. Measures of frequency by year of birth show the largest magnitude of increase; predicted prevalence by calendar year and to age 4 by year of birth are influenced by changes in the distribution of age at diagnosis, but 1-year incidence and prevalence to age 12 are not. Discussion: Methodological factors may explain the observed increases in AD over time. To increase confidence in reports of time trends, we recommend particular frequency measures and study circumstances. (Contains 2 tables and 1 figure.)
Maternal infections during pregnancy are associated with risk of neurodevelopmental disorders, including autism spectrum disorders (ASDs). Proposed pathogenetic mechanisms include fetal infection, ...placental inflammation, and maternal cytokines or antibodies that cross the placenta. The Autism Birth Cohort comprises mothers, fathers, and offspring recruited in Norway in 1999 to 2008. Through questionnaire screening, referrals, and linkages to a national patient registry, 442 mothers of children with ASD were identified, and 464 frequency-matched controls were selected. Immunoglobulin G (IgG) antibodies to
, rubella virus, cytomegalovirus (CMV), herpes simplex virus 1 (HSV-1), and HSV-2 in plasma collected at midpregnancy and after delivery were measured by multiplexed immunoassays. High levels of HSV-2 IgG antibodies in maternal midpregnancy plasma were associated with increased risk of ASD in male offspring (an increase in HSV-2 IgG levels from 240 to 640 arbitrary units/ml was associated with an odds ratio of 2.07; 95% confidence interval, 1.06 to 4.06;
= 0.03) when adjusted for parity and child's birth year. No association was found between ASD and the presence of IgG antibodies to
, rubella virus, CMV, or HSV-1. Additional studies are needed to test for replicability of risk and specificity of the sex effect and to examine risk associated with other infections.
The cause (or causes) of most cases of autism spectrum disorder is unknown. Evidence from epidemiological studies and work in animal models of neurodevelopmental disorders suggest that both genetic and environmental factors may be implicated. The latter include gestational infection and immune activation. In our cohort, high levels of antibodies to herpes simplex virus 2 at midpregnancy were associated with an elevated risk of autism spectrum disorder in male offspring. These findings provide support for the hypothesis that gestational infection may contribute to the pathogenesis of autism spectrum disorder and have the potential to drive new efforts to monitor women more closely for cryptic gestational infection and to implement suppressive therapy during pregnancy.
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