Exposure to heavy metals in utero and autism spectrum disorder at age 3: a meta-analysis of two longitudinal cohorts of siblings of children with autism.

BACKGROUND: Autism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized. METHODS: In Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (< 28 weeks and ≥ 28 weeks of gestation) were measured using inductively coupled plasma mass spectrometry. At age three, clinicians assessed ASD with DSM-5 criteria. In an exposure-wide association framework, using multivariable log binomial regression, we examined each metal for association with ASD status, adjusting for gestational age at urine sampling, child sex, age at pregnancy, race/ethnicity and education. We meta-analyzed across the two cohorts. RESULTS: In EARLI (n = 170) 17% of children were diagnosed with ASD, and 44% were classified as having non-neurotypical development (Non-TD). In MARBLES (n = 231), 21% were diagnosed with ASD, and 14% classified as Non-TD. During the first and second trimester period (< 28 weeks), having cadmium concentration over the level of detection was associated with 1.69 (1.08, 2.64) times higher risk of ASD, and 1.29 (0.95, 1.75)times higher risk of Non-TD. A doubling of first and second trimester cesium concentration was marginally associated with 1.89 (0.94, 3.80) times higher risk of ASD, and a doubling of third trimester cesium with 1.69 (0.97, 2.95) times higher risk of ASD. CONCLUSION: Exposure in utero to elevated levels of cadmium and cesium, as measured in urine collected during pregnancy, was associated with increased risk of developing ASD.

Urine manganese, cadmium, lead, arsenic, and selenium among autism spectrum disorder children in Kuala Lumpur.

Background: The development of autism spectrum disorder (ASD) may stem from exposure to environmental pollutants such as heavy metals. The primary objective of this study is to determine the role of heavy metals of concern such as manganese (Mn), cadmium (Cd), lead (Pb), arsenic (As), and essential trace element selenium (Se) among ASD children in Kuala Lumpur, Malaysia. Method: A total of 155 preschoolers in Kuala Lumpur between the ages 3 to 6 participated in an unmatched case-control study, comprising ASD children (n = 81) recruited from an early intervention program for autism, and 74 children without autism who were recruited from public preschools. Urine samples were collected at home, delivered to the study site, and transported to the environmental lab within 24 hours. Inductively coupled plasma mass spectrometry (ICP-MS) was applied to measure the concentration of heavy metals in the samples. Data were analysed using bivariate statistical tests (Chi-square and T-test) and logistic regression models. Result: This study demonstrated that Cd, Pb, and As urine levels were significantly greater in children without autism relative to those affected with ASD (p < 0.05). No significant difference was in the levels of Se (p = 0.659) and Mn (p = 0.875) between children with ASD and the control group. The majority of children in both groups have urine As, Pb, and Cd values lower than 15.1 µg/dL, 1.0 µg/dL, and 1.0 µg/dL, respectively which are the minimal risk values for noncarcinogenic detrimental human health effect due to the heavy metal's exposure . Factors associated with having an ASD child included being a firstborn, male, and higher parental education levels (adjusted odds ratios (aOR) > 1, p < 0.05). Conclusion: Preschoolers in this study demonstrated low levels of heavy metals in their urine samples, which was relatively lower in ASD children compared to the healthy matched controls. These findings may arise from the diminished capacity to excrete heavy metals, especially among ASD children, thereby causing further accumulation of heavy metals in the body. These findings, including the factors associated with having an ASD child, may be considered by healthcare professionals involved in child development care, for early ASD detection. Further assessment of heavy metals among ASD children in the country and interventional studies to develop effective methods of addressing exposure to heavy metals will be beneficial for future reference.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

[Autistic spectrum disorder in women : how does gender operate?] / Trouble du spectre de l'autisme au féminin : comment le genre opère-t-il ?

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, that affects both pediatric and adult populations and presents heterogeneously. The understanding of the clinical characteristics of ASD has expanded, in parallel with societal developments, including the integration of the notion of gender in medicine. It appears that individuals affected by this disorder, regardless of their age, are neither detected, diagnosed, nor followed or treated in the same manner depending on their gender. This article proposes to review current knowledge on ASD, its expression based on gender, factors influencing care, and the consequences for patients of exposure to gender bias.

Le trouble du spectre de l'autisme (TSA) est un trouble neurodéveloppemental fréquent. Il touche la population pédiatrique et adulte et se présente de manière hétérogène. La compréhension des caractéristiques clinique du TSA s'est étendue, en parallèle des évolutions sociétales, dont l'intégration de la notion de genre en médecine. Il apparaît que les personnes touchées par ce trouble, quel que soit leur âge, ne sont ni détectées, diagnostiquées, suivies ou traitées de manière identique selon leur genre. Cet article reprend les connaissances actuelles de l'expression du TSA en fonction du genre, et les conséquences pour les patient-e-s de l'exposition aux biais de genre.

Autism Spectrum Disorders: Etiology, Epidemiology, and Challenges for Public Health.

Autism spectrum disorder (ASD) is a growing public health problem. American psychiatrist Leo Kanner is considered the "father of autism." ASD encompasses a range of neurodevelopmental disorders that last throughout life. Symptoms of ASD include impairments in social skills, including specific repetitive behaviors, as well as abnormal sensory responses. The clinical symptoms of ASD vary among patients. Their severity also differs, both in the area of social communication and cognitive functioning. The etiology of ASD is still unclear, although a role is attributed to both genetic and environmental factors. According to the World Health Organization, 1/100 children have ASD, but these estimates vary depending on the methodology used. Nevertheless, early detection of ASD and initiation of appropriate therapy may be essential in the continued functioning of patients and their families. The purpose of this article is to provide an overview of current knowledge about autism spectrum disorders. We discuss factors associated with autism and the prevalence of ASD in various parts of the world, and identify the most common diseases comorbid with ASD, pointing to limitations in the quality of life of patients with ASD and their families.

Quantifying the relative importance of genetics and environment on the comorbidity between mental and cardiometabolic disorders using 17 million Scandinavians.

Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Newborn Dried Blood Spot Folate in Relation to Maternal Self-reported Folic Acid Intake, Autism Spectrum Disorder, and Developmental Delay.

BACKGROUND: Maternal folic acid intake has been associated with decreased risk for neurodevelopmental disorders including autism spectrum disorder (ASD). Genetic differences in folate metabolism could explain some inconsistencies. To our knowledge, newborn folate concentrations remain unexamined. METHODS: We measured folate in archived newborn dried blood spots of children from the CHARGE (Childhood Autism Risks from Genetics and the Environment) case-control study who were clinically confirmed at 24-60 months to have ASD (n = 380), developmental delay (n = 128), or typical development (n = 247). We quantified monthly folic acid intake from maternally-reported supplements and cereals consumed during pregnancy and 3 months prior. We assessed associations of newborn folate with maternal folic acid intake and with ASD or developmental delay using regression. We stratified estimates across maternal and child MTHFR genotypes. RESULTS: Among typically developing children, maternal folic acid intake in prepregnancy and each pregnancy month and prepregnancy prenatal vitamin intake were positively associated with newborn folate. Among children with ASD, prenatal vitamin intake in pregnancy months 2-9 was positively associated with newborn folate. Among children with developmental delay, maternal folic acid and prenatal vitamins during the first pregnancy month were positively associated with neonatal folate. Associations differed by MTHFR genotype. Overall, neonatal folate was not associated with ASD or developmental delay, though we observed associations with ASD in children with the MTHFR 677 TT genotype (odds ratio: 1.76, 95% CI = 1.19, 2.62; P for interaction = 0.08). CONCLUSION: Maternal prenatal folic acid intake was associated with neonatal folate at different times across neurodevelopmental groups. Neonatal folate was not associated with reduced ASD risk. MTHFR genotypes modulated these relationships.

Early environmental predictors for attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD) and their co-occurrence: The prospective ABIS-Study.

ADHD and ASD are highly heritable and show a high co-occurrence and persistence into adulthood. This study aimed to identify pre and perinatal risk factors, and early psychosocial exposures related to later diagnosis of ADHD, ASD, and their co-occurrence. 16,365 children born 1997-1999 and their families, involved in the prospective population-based ABIS study (All Babies in Southeast Sweden), were included in this sub-study. Pre and perinatal factors and early environmental psychosocial exposures were collected from parental-questionnaires at birth and 1-year follow-up. Diagnoses from birth up to 23 years of age were obtained from the Swedish National Diagnosis Register in 2020. The cumulative incidence of ADHD, ASD, and their co-occurrence in the ABIS-cohort Study were 4.6%, 1.7%, and 1.1%, respectively. Being male was associated with an increased risk for ADHD, ASD, and their co-occurrence (aOR 1.30, 1.56, and 1.91, respectively), while higher household income reduced it (aOR 0.82, 0.73, and 0.64). Serious life events during pregnancy (aOR 1.40) and maternal smoking (aOR 1.51) increased the risk of ADHD, while older maternal age (aOR 0.96), higher parental education (aOR 0.72 maternal and aOR 0.74 paternal) and longer exclusive breastfeeding (aOR 0.72) reduced it. Non-Swedish paternal nationality (aOR 0.40) and higher maternal education (aOR 0.74) were associated with a lower risk of ASD, while a family history of autoimmune diseases increased the risk of the co-occurrence of both disorders (aOR 1.62). Obtained results suggest that the etiology of ADHD, ASD, and their co-occurrence is independently associated with environmental psychosocial predictors. The co-occurrence seems to overlap the etiology of ADHD, in which psychosocial determinants have a larger role, however, it is also independently influenced by a family history of autoimmune diseases.

Sleep disturbances are associated with greater healthcare utilization in children with autism spectrum disorder.

BACKGROUND: Sleep disturbances are frequently reported in children with autism spectrum disorder (ASD) and are associated with the severity of co-occurring symptoms. This study's aim was to examine the extent of healthcare utilization and clinical outcomes associated with sleep disturbances in children with ASD. STUDY DESIGN: A retrospective, cross-sectional study of 541 children with ASD from the Azrieli National Center for Autism and Neurodevelopment Research (ANCAN) whose parents completed the Children's Sleep Habits Questionnaire (CSHQ). Children with a total CSHQ score ≥ 48 were defined as having sleep disturbances. Sociodemographic characteristics, ASD diagnostic measures, chronic co-occurring conditions, medication usage, hospitalizations, visits to the emergency room (ER), and visits to specialists were compared in ASD children with and without sleep disturbances. Multivariate logistic regression models were then used to assess the independent association of sleep disturbances with clinical characteristics and healthcare utilization. RESULTS: Of the 541 children with ASD, 257 (47.5%) had sleep disturbances. Children with sleep disturbances exhibited higher rates of multiple (≥ 3) co-occurring conditions (19.1% vs. 12.7%; p = 0.0414) and prescribed medications (45.5% vs. 32.7%; p = 0.0031) than other children. Finally, ASD children with sleep disturbances were 1.72 and 2.71 times more likely to visit the ER and be hospitalized than their counterparts (aOR = 1.72; 99%CI = 1.01-2.95; and aOR = 2.71; 99%CI = 1.10-6.67, respectively). CONCLUSIONS: Our findings suggest that sleep disturbances are associated with greater healthcare utilization among children with ASD. Further studies could examine whether treating sleep disturbances in children with ASD yields additional clinical benefits beyond improvements in sleep.

Anthropometric Profile, Overweight/Obesity Prevalence, and Socioeconomic Impact in Moroccan Children Aged 6-12 Years Old with Autism Spectrum Disorder.

BACKGROUND: In addition to the inherent challenges of their condition, children with autism spectrum disorder (ASD) are also susceptible to the global obesity epidemic. However, concerning the prevalence of obesity within the Moroccan ASD pediatric population, data remain scarce. METHODS: A total of 258 children (boys = 195) aged 6 to 12 years old (mean = 9.4 ± 1.4) diagnosed with ASD participated in this study. Besides the body mass and height, four significant anthropometric markers for assessing obesity were examined: body mass index (BMI), body surface area (BSA), waist circumference (WC), and waist-to-height ratio (WHtR). Each anthropometric marker was categorized into one of three cardiometabolic risk levels based on the Z-scores and their corresponding percentiles. The distribution was as follows: low risk (≤84th percentile), high risk (85th-94th percentile), and very high risk (≥95th percentile). Subsequently, a multiple regression analysis was employed to develop an algorithm that generates a composite risk score. This score incorporates all the anthropometric variables simultaneously, while also weighting their individual contributions to the cardiometabolic risk. RESULTS: Children with ASD exhibit an anthropometric profile that markedly increases their susceptibility to cardiometabolic issues. While roughly 11% of the general Moroccan child population is overweight or obese, this figure soars to nearly 60% among children with ASD when considering the central adiposity markers. Furthermore, children from middle-class socioeconomic backgrounds display a more than threefold greater risk of developing overweight or obesity compared to their counterparts from lower socioeconomic backgrounds. CONCLUSIONS: This study has, for the first time, provided an up-to-date overview of the cardiometabolic risk in Moroccan children with ASD using traditional anthropometric measurements. The primary risk factor is clearly linked to central (abdominal) adiposity, which is recognized as the most deleterious. This study highlights the need to include general and central obesity markers. This study underscores the importance of incorporating both general and central adiposity markers for a more comprehensive assessment, and it emphasizes the need for closer monitoring within this high-risk population.

Cross-sectional analysis of the association between household food insecurity and mental health conditions in children aged 5-11 years in Canada.

BACKGROUND: Children living in food insecure households have poorer mental health outcomes compared with their food-secure peers; however, the relationship between the severity of food insecurity and diagnosed mental health conditions in young children remains unknown. This study examined the association between household food insecurity and reported diagnosed mental health conditions among children aged 5-11 years in Canada. METHODS: This study included 16 216 children aged 5-11 years living in Canada, from the 2019 Canadian Health Survey on Children and Youth. We measured household food insecurity using the Household Food Security Survey Module. We measured diagnosed mental health conditions by parent/caregiver report of health professional-diagnosed anxiety, depression, autism spectrum disorder or attention-deficit/hyperactive disorder. We developed a multivariable logistic regression model to assess the association between severities of food insecurity and mental health, controlling for potentially confounding variables. RESULTS: 17.0% of children lived in households reporting some level of food insecurity (5.4% marginal, 8.0% moderate and 3.6% severe). The prevalence of at least one diagnosed mental health condition in the same population was 10.9%. After adjusting for sociodemographic characteristics, children from marginal, moderate and severe food insecure households had a 1.39 (95% CI 0.99 to 1.97), 1.46 (95% CI 1.13 to 1.89) and 1.67 (95% CI 1.18 to 2.35) increased odds of having a diagnosed mental health condition, respectively. CONCLUSION: Household food insecurity is associated with an increased presence of diagnosed mental health conditions in children aged 5-11 years. This study adds to the body of research showing that social and economic inequities, including household food insecurity, negatively impact the health of children.

Gestational exposure to benzodiazepines or z-hypnotics and neurodevelopmental disorders in offspring: Systematic review and meta-analysis.

INTRODUCTION: Benzodiazepine (BDZP) and/or z-hypnotic dispensing during pregnancy has increased globally, as have rates of autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This systematic review and meta-analysis aimed to estimate the association between gestational exposure to BDZP and/or z-hypnotics and diagnosis of ASD or ADHD in offspring. METHODS: We searched MEDLINE, EMBASE, and SCOPUS from inception till December 2023 for relevant English-language articles. Outcomes of interest were risk of ASD and ADHD, two independent primary outcomes, in children exposed anytime during pregnancy to BDZP and/or z-hypnotics versus those unexposed. Secondary outcomes were trimester-wise analyses. Using a random effects model, we pooled the overall and trimester-wise hazard ratios (HRs), with 95% confidence intervals (CIs), separately for risk of ASD and ADHD. RESULTS: We found six eligible retrospective cohort studies and no case-control studies. There was no increased risk of ASD associated with anytime gestational BDZP and/or z-hypnotic exposure (primary outcome, HR, 1.10; 95% CI, 0.81-1.50; 4 studies; n = 3,783,417; 80,270 exposed, 3,703,147 unexposed) nor after first trimester exposure (HR, 1.15; 95% CI, 0.83-1.58; 3 studies; n = 1,539,335; 70,737 exposed, 1,468,598 unexposed) or later trimester exposures. A very small but significantly increased risk of ADHD was noted with anytime gestational exposure to these drugs (primary outcome, HR, 1.07; 95% CI, 1.03-1.12; 4 studies; n = 2,000,777; 78,912 exposed, 1,921,865 unexposed) and also with (only) second trimester exposure (HR, 1.07; 95% CI, 1.03-1.12; 3 studies; n = 1,539,281; 33,355 exposed, 1,505,926 unexposed). Findings were consistent in sensitivity analyses. CONCLUSION: Gestational exposure to benzodiazepines or z-hypnotics was not associated with an increased risk of ASD and with only a marginally increased risk of ADHD in offspring. Given the likelihood of confounding by indication and by unmeasured variables in the original studies, our findings should reassure women who need these medications for severe anxiety or insomnia during pregnancy.

Unpacking the prevalence: A warning against overstating the recently narrowed gap for Black autistic youth.

Recent findings from the Centers for Disease Control and Prevention's (CDC) Autism and Developmental Disabilities Monitoring (ADDM) Network's 2020 prevalence report indicate that disparities in autism diagnoses between Black and White youth have narrowed, reflecting improved screening, awareness, and access to services (Maenner et al., 2023. Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C.: 2002), 72, 1-14.). Claims of reducing disparities beyond prevalence rates, however, are not fully supported, as indicated by the reality that Black youth whose screenings indicate autistic traits are still not being referred for full evaluation or early intervention services at the same rate as their White peers (Major et al., 2020. Autism, 24, 1629-1638; Smith et al., 2020. Pediatrics, 145, S35-S46.). Black 8-year-olds identified as autistic still experience disparate educational placements (Waitoller et al., 2010. The Journal of Special Education. 44, 29-49.) where services may not be autism-specific or have Individual Education Plan goals only focused on "behavior problems" (Severini et al., 2018. Journal of Autism and Developmental Disorders, 48, 3261-3272.), are served in the most restrictive environments (Skiba et al., 2006. Exceptional Children, 72, 411-424.) and lack consistent augmentative and alternative communication support (Pope et al., 2022. American Journal of Speech-Language Pathology, 31, 2159-2174.). Additionally, ADMM researchers report consistent disparities in the identification of co-occurring intellectual disability where Black autistic children have significantly more co-occurrences than White autistic children. The purpose of this commentary is to first examine the assertion that the narrowed gap indicates, "…improved…access to services among historically underserved groups," (p. 9) (Maenner et al., 2023. Morbidity and Mortality Weekly Report. Surveillance Summaries (Washington, D.C.: 2002), 72, 1-14.). We will then recommend strategies to address the ongoing disparities.

Prevalence of comorbidity of autism and ADHD and associated characteristics in school population: EPINED study.

Autism and attention deficit hyperactivity disorder (ADHD) comorbidity in the school population have been understudied. This study estimates its prevalence considering both parents' and teachers' reports and clinical diagnosis. Sociodemographic, clinical, and cognitive data were compared by diagnostic groups: autism, ADHD, autism and ADHD, subthreshold autism spectrum disorder (ASD), subthreshold ADHD, and children without neurodevelopmental conditions. Following a two-phase design, 3727 parents and teachers (1802 preschoolers, 1925 school-age children) participated in the first phase. Subsequently, 781 participants underwent individual assessment for DSM-5 diagnoses. The estimated prevalence of the comorbid diagnosis was 0.51% (0.28%-0.74%), with significant sex differences (0.16% girls, 0.89% boys). The cooccurrence of symptoms of autism and ADHD reported by parents or teachers was 3.2% and 2.6%, respectively. ADHD comorbidity was observed in 32.8% of autistic children and 31.4% of those with subthreshold ASD. ASD comorbidity was observed in 9.8% of children with ADHD and 5.7% of those with subthreshold ADHD. Comorbidity was reported by at least one informant in 95% of children. Only 15.8% of children with autism and ADHD had been previously diagnosed with both conditions. Early detection and accurate comorbidity diagnosis are crucial to address the clinical and socio-educational needs of these children.

Association between exposure to antibiotics during pregnancy or early infancy and risk of autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children: population based cohort study.

OBJECTIVE: To evaluate the association between antibiotic use during pregnancy or early infancy and the risk of neurodevelopmental disorders in children. DESIGN: Nationwide population based cohort study and sibling analysis. SETTING: Korea's National Health Insurance Service mother-child linked database, 2008-21. PARTICIPANTS: All children live born between 2009 and 2020, followed up until 2021 to compare those with and without antibiotic exposure during pregnancy or early infancy (first six months of life). MAIN OUTCOMES MEASURES: Autism spectrum disorder, intellectual disorder, language disorder, and epilepsy in children. After 1:1 propensity score matching based on many potential confounders, hazard ratios with 95% confidence interval were estimated using Cox proportional hazard models. A sibling analysis additionally accounted for unmeasured familial factors. RESULTS: After propensity score matching, 1 961 744 children were identified for the pregnancy analysis and 1 609 774 children were identified for the early infancy analysis. Although antibiotic exposure during pregnancy was associated with increased risks of all four neurodevelopmental disorders in the overall cohort, these estimates were attenuated towards the null in the sibling analyses (hazard ratio for autism spectrum disorder 1.06, 95% confidence interval 1.01 to 1.12; intellectual disorder 1.00, 0.93 to 1.07; language disorder 1.05, 1.02 to 1.09; and epilepsy 1.03, 0.98 to 1.08). Likewise, no association was observed between antibiotic exposure during early infancy and autism spectrum disorder (hazard ratio 1.00, 0.96 to 1.03), intellectual disorder (1.07, 0.98 to 1.15), and language disorder (1.04, 1.00 to 1.08) in the sibling analyses; however, a small increased risk of epilepsy was observed (1.13, 1.09 to 1.18). The results generally remained consistent across several subgroup and sensitivity analyses, except for slightly elevated risks observed among children who used antibiotics during very early life and those who used antibiotics for more than 15 days. CONCLUSIONS: In this large cohort study, antibiotic exposure during pregnancy or early infancy was not associated with an increased risk of autism spectrum disorder, intellectual disorder, or language disorder in children. However, elevated risks were observed in several subgroups such as children using antibiotics during very early life and those with long term antibiotic use, which warrants attention and further investigation. Moreover, antibiotic use during infancy was modestly associated with epilepsy, even after control for indications and familial factors. When prescribing antibiotics to pregnant women and infants, clinicians should carefully balance the benefits of use against potential risks.

A case-control study on pre-, peri-, and neonatal risk factors associated with autism spectrum disorder among Armenian children.

We aimed to investigate the role of pre-, peri- and neonatal risk factors in the development of autism spectrum disorder (ASD) among Armenian children with the goal of detecting and addressing modifiable risk factors to reduce ASD incidence. For this purpose a retrospective case-control study using a random proportional sample of Armenian children with ASD to assess associations between various factors and ASD was conducted. The study was approved by the local ethical committee, and parental written consent was obtained. A total of 168 children with ASD and 329 controls were included in the analysis. Multivariable logistic regression analysis revealed that male gender, maternal weight gain, use of MgB6, self-reported stress during the pregnancy, pregnancy with complications, as well as use of labor-inducing drugs were associated with a significant increase in the odds of ASD, whereas Duphaston use during pregnancy, the longer interpregnancy interval and birth height were associated with decreased odds of ASD. These findings are pertinent as many identified factors may be preventable or modifiable, underscoring the importance of timely and appropriate public health strategies aimed at disease prevention in pregnant women to reduce ASD incidence.

Prevalence of autism spectrum disorder in mainland china over the past 6 years: a systematic review and meta-analysis.

BACKGROUND: Coupled with its rising prevalence, Autism spectrum disorder (ASD) has become a globally recognized public health concern. Nevertheless, large-scale, multicenter studies that analyze the epidemiology of ASD in China are relatively scarce. METHODS: Literature searches were conducted in PubMed/Medline, Embase, the Cochrane Library, Wanfang Data Knowledge Service Platform, China Biology Medicine database (CBM), China Science and Technology Journal Database (CSTJ), and China National Knowledge Infrastructure (CNKI) to retrieve studies published before April 8, 2023, related to ASD prevalence among children aged 0 to 14 years in mainland China. Meta-analysis was conducted using RevMan 5.2 and Stata 14.0. RESULTS: Twenty-one articles were included. The ASD prevalence among children in mainland China has been 0.7% (95% confidence interval(CI): 0.006-0.008) since 2017. The prevalence of ASD among boys was 1.0% (95% CI: 0.008-0.011), which was significantly higher than that among girls at 0.2% (95% CI: 0.002-0.003), with a statistically significant difference (OR = 3.198, 95% CI: 2.489-4.109, P = 0.000). Among the included studies, 18 reported an ASD prevalence of 0.8% (95% CI: 0.007-0.010), while 3 studies reported an autistic disorder (AD) prevalence of 0.7% (95% CI: 0.006-0.008). The prevalence of autism among urban children was 23.9% (95% CI: 0.149-0.328), and in rural areas, it was 0.7% (95% CI: 0.002-0.013), with no statistically significant difference (OR = 1.342, 95% CI: 0.258-6.975, P = 0.727). Regression analysis showed that factors such as region (P = 0.000), age (P = 0.000), study period (P = 0.000), sample size (P = 0.000), sampling method (P = 0.002), population source (P = 0.000), disease type (P = 0.000), quality score of the study (P = 0.000), and diagnostic criteria (P = 0.000) might have contributed to the heterogeneity in ASD prevalence. CONCLUSION: The prevalence of ASD in China from 2017 to 2023 was 7/1000, showing an upward trend compared to that before 2017 (26.50/10,000). The male-to-female prevalence ratio was 5:1.The overall prevalence remained significantly lower than that reported in foreign countries.

Autism Spectrum Disorder Diagnoses and Congenital Cytomegalovirus.

OBJECTIVE: To examine the association between congenital cytomegalovirus (cCMV) and autism spectrum disorder (ASD) administrative diagnoses in US children. METHODS: Cohort study using 2014 to 2020 Medicaid claims data. We used diagnosis codes to identify cCMV (exposure), ASD (outcome), and covariates among children enrolled from birth through ≥4 to <7 years. Covariates include central nervous system (CNS) anomaly or injury diagnosis codes, including brain anomaly, microcephaly within 45 days of birth, cerebral palsy, epilepsy, or chorioretinitis. We used Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals, overall and stratified by sex, birth weight and gestational age outcome (low birth weight or preterm birth), and presence of CNS anomaly or injury. RESULTS: Among 2 989 659 children, we identified 1044 (3.5 per 10 000) children with cCMV and 74 872 (25.0 per 1000) children with ASD. Of those with cCMV, 49% also had CNS anomaly or injury diagnosis codes. Children with cCMV were more likely to have ASD diagnoses (hazard ratio: 2.5; 95% confidence interval: 2.0-3.2, adjusting for birth year, sex, and region). This association differed by sex and absence of CNS anomaly or injury but not birth outcome. CONCLUSIONS: Children with (versus without) cCMV diagnoses in Medicaid claims data, most of whom likely had symptomatic cCMV, were more likely to have ASD diagnoses. Future research investigating ASD risk among cohorts identified through universal cCMV screening may help elucidate these observed associations.

[Tooth decay and autism spectrum disorders in children: is there a connection?] / Karies zubov i rasstroistva autisticheskogo spektra u detei: est' li svyaz'?

OBJECTIVE: The study of caries lesions of children 7 and 12 years old with different degrees of severity of autism and concomitant intellectual disabilities, in comparison with a control group of neurotypical patients of similar age. MATERIALS AND METHODS: The main study group included children with ASD ages 7 and 12 (n=214), and the comparison group included neurotypical children of the same age (n=140). To assess the incidence of dental caries, indicators of the prevalence and intensity of the process were used. RESULTS: The prevalence of dental caries in children with ASD is lower than in the comparison group or comparable. The average caries prevalence was found in the 7- and 12-year-old groups in children with mild autism without concomitant intellectual deficits (80.89±3.40 and 76.65±4.24, respectively). In children with severe and extremely severe autism, regardless of the presence of intellectual disability, the prevalence of dental caries was high in both age groups, which is comparable with the same indicator and age of neurotypical children. Moreover, both age groups of neurotypical children were also comparable in caries prevalence (89.67±1.65 and 90.32±1.20 respectively). Caries intensity did not seem to be related to years of autistic disorder (significantly lower in the group of 12-year-old children with ASD, compared to 7-year-olds). Caries intensity in children with ASD increased with increasing severity of autism and concomitant intellectual disability. CONCLUSION: Further comprehensive studies in terms of included variables are needed to identify contributing factors (impact of family socioeconomic opportunities, increased parental care, etc.).

Intrapartum exposure to synthetic oxytocin, maternal BMI, and neurodevelopmental outcomes in children within the ECHO consortium.

BACKGROUND: Synthetic oxytocin (sOT) is frequently administered during parturition. Studies have raised concerns that fetal exposure to sOT may be associated with altered brain development and risk of neurodevelopmental disorders. In a large and diverse sample of children with data about intrapartum sOT exposure and subsequent diagnoses of two prevalent neurodevelopmental disorders, i.e., attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), we tested the following hypotheses: (1) Intrapartum sOT exposure is associated with increased odds of child ADHD or ASD; (2) associations differ across sex; (3) associations between intrapartum sOT exposure and ADHD or ASD are accentuated in offspring of mothers with pre-pregnancy obesity. METHODS: The study sample comprised 12,503 participants from 44 cohort sites included in the Environmental Influences on Child Health Outcomes (ECHO) consortium. Mixed-effects logistic regression analyses were used to estimate the association between intrapartum sOT exposure and offspring ADHD or ASD (in separate models). Maternal obesity (pre-pregnancy BMI ≥ 30 kg/m2) and child sex were evaluated for effect modification. RESULTS: Intrapartum sOT exposure was present in 48% of participants. sOT exposure was not associated with increased odds of ASD (adjusted odds ratio [aOR] 0.86; 95% confidence interval [CI], 0.71-1.03) or ADHD (aOR 0.89; 95% CI, 0.76-1.04). Associations did not differ by child sex. Among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of offspring ADHD (aOR 0.72; 95% CI, 0.55-0.96). No association was found among mothers without obesity (aOR 0.97; 95% CI, 0.80-1.18). CONCLUSIONS: In a large, diverse sample, we found no evidence of an association between intrapartum exposure to sOT and odds of ADHD or ASD in either male or female offspring. Contrary to our hypothesis, among mothers with pre-pregnancy obesity, sOT exposure was associated with lower odds of child ADHD diagnosis.