Fetal femur length and risk of diabetes in adolescence: a prospective cohort study.

BACKGROUND: Diabetes is more apparent in adulthood but may be dormant in childhood and originates during early fetal development. In fetal biometry, femur length (FL) is crucial for assessing fetal growth and development. This study aimed to assess potential associations between fetal femur growth and prediabetic biomarkers in Bangladeshi children. METHODS: A cohort study embedded in a population-based maternal food and micronutrient supplementation (MINIMat) trial was conducted in Matlab, Bangladesh. The children in the cohort were followed up until 15 years of age. In the original trial, pregnancy was confirmed by ultrasound before 13 gestational weeks (GWs). Afterward, ultrasound assessments were performed at 14, 19, and 30 GWs. FL was measured from one end to the other, capturing a complete femoral image. The FL was standardized by GW, and a z-score was calculated. FBG and HbA1c levels were determined in plasma and whole blood, and the triglyceride-glucose index, a biomarker of insulin resistance, was calculated as Ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. Multivariable linear regression analysis using a generalized linear model was performed to estimate the effects of FL at 14, 19 and 30 GWs on prediabetic biomarkers at 9 and 15 years of age. Maternal micronutrient and food supplementation group, parity, child sex, and BMI at 9 years or 15 years were included as covariates. RESULTS: A total of 1.2% (6/515) of the participants had impaired fasting glucose during preadolescence, which increased to 3.5% (15/433) during adolescence. At 9 years, 6.3% (32/508) of the participants had elevated HbA1c%, which increased to 28% (120/431) at 15 years. Additionally, the TyG index increased from 9.5% (49/515) (during preadolescence) to 13% (56/433) (during adolescence). A one standard deviation decrease in FL at 14 and 19 GWs was associated with increased FBG (ß = - 0.44 [- 0.88, - 0.004], P = 0.048; ß = - 0.59 [- 1.12, - 0.05], P = 0.031) and HbA1c (ß = - 0.01; [- 0.03, -0.005], P = 0.007; ß = - 0.01 [- 0.03, - 0.003], P = 0.018) levels at 15 years. FL was not associated with diabetic biomarkers at 9 years. CONCLUSION: Mid-trimester impaired femur growth may be associated with elevated prediabetic biomarkers in Bangladeshi adolescents.

Systems for rating bodies of evidence used in systematic reviews of air pollution exposure and reproductive and children's health: a methodological survey.

BACKGROUND: Translating findings from systematic reviews assessing associations between environmental exposures and reproductive and children's health into policy recommendations requires valid and transparent evidence grading. METHODS: We aimed to evaluate systems for grading bodies of evidence used in systematic reviews of environmental exposures and reproductive/ children's health outcomes, by conducting a methodological survey of air pollution research, comprising a comprehensive search for and assessment of all relevant systematic reviews. To evaluate the frameworks used for rating the internal validity of primary studies and for grading bodies of evidence (multiple studies), we considered whether and how specific criteria or domains were operationalized to address reproductive/children's environmental health, e.g., whether the timing of exposure assessment was evaluated with regard to vulnerable developmental stages. RESULTS: Eighteen out of 177 (9.8%) systematic reviews used formal systems for rating the body of evidence; 15 distinct internal validity assessment tools for primary studies, and nine different grading systems for bodies of evidence were used, with multiple modifications applied to the cited approaches. The Newcastle Ottawa Scale (NOS) and the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework, neither developed specifically for this field, were the most commonly used approaches for rating individual studies and bodies of evidence, respectively. Overall, the identified approaches were highly heterogeneous in both their comprehensiveness and their applicability to reproductive/children's environmental health research. CONCLUSION: Establishing the wider use of more appropriate evidence grading methods is instrumental both for strengthening systematic review methodologies, and for the effective development and implementation of environmental public health policies, particularly for protecting pregnant persons and children.

Climate change and infectious disease surveillance in Nepal: qualitative study exploring social, cultural, political and institutional factors influencing disease surveillance.

BACKGROUND: To explore the impacts of contextual issues encompassing social, cultural, political and institutional elements, on the operation of public health surveillance systems in Nepal concerning the monitoring of infectious diseases in the face of a changing climate. METHODS: Semi-structured interviews (n = 16) were conducted amongst key informants from the Department of Health Services, Health Information Management System, Department of Hydrology and Meteorology, World Health Organization, and experts working on infectious disease and climate change in Nepal, and data were analysed using thematic analysis technique. RESULTS: Analysis explicates how climate change is constructed as a contingent risk for infectious diseases transmission and public health systems, and treated less seriously than other 'salient' public health risks, having implications for how resources are allocated. Further, analysis suggests a weak alliance among different stakeholders, particularly policy makers and evidence generators, resulting in the continuation of traditional practices of infectious diseases surveillance without consideration of the impacts of climate change. CONCLUSIONS: We argue that along with strengthening systemic issues (epidemiological capacity, data quality and inter-sectoral collaboration), it is necessary to build a stronger political commitment to urgently address the influence of climate change as a present and exponential risk factor in the spread of infectious disease in Nepal.

Prenatal exposure to ambient air pollutants and congenital heart defects: An umbrella review.

BACKGROUND: Prenatal exposure to ambient air pollutants has been linked to congenital heart defects (CHD), but findings of existing systematic reviews have been mixed. OBJECTIVE: To assess the epidemiological evidence on associations between prenatal exposure to ambient air pollutants and CHD subtypes, based on a systematic overview of reviews ("umbrella review"). METHODS: We conducted a systematic search for reviews assessing associations between prenatal exposure to criteria air pollutants and CHD. The risk of bias was evaluated using the Risk of Bias in Systematic Reviews (ROBIS) tool. The certainty of the systematic review findings was graded using the Navigation Guide methodology. RESULTS: We identified eleven systematic reviews, including eight with meta-analyses, assessing in total 35 primary studies of prenatal exposure to criteria air pollutants and various CHD subtypes. The certainty of the findings of four meta-analyses indicating an increased risk for coarctation of the aorta associated with nitrogen dioxide exposure was rated as moderate. The certainty of findings indicating positive, inverse, or null associations for other pollutant-subtype combinations was rated as very low to low, based on low precision and high statistical heterogeneity of summary odds ratios (SOR), substantial inconsistencies between review findings, and methodological limitations of the systematic reviews. DISCUSSION: The inconsistent findings and high statistical heterogeneity of many SOR of the included systematic reviews may partly be traced to differences in methodological approaches, and the risk of bias across included reviews (e.g., inclusion criteria, systematic search strategies, synthesis methods) and primary studies (e.g., exposure assessment, diagnostic criteria). Adherence to appropriate systematic review guidelines for environmental health research, as well as rigorous evaluation of risk of bias in primary studies, are essential for future risk assessments and policy-making. Still, our findings suggest that prenatal exposure to ambient air pollutants may increase risks for at least some CHD subtypes.

Association between Childhood Maltreatment and Depressive and Anxiety Symptoms among Men Who Have Sex with Men in Los Angeles.

Adverse childhood experiences (ACEs) have been associated with poor mental health outcomes in adulthood. Childhood maltreatment is related to both depressive and anxiety symptoms. Our objective was to investigate these associations among low-income, mostly Black and Latino men who have sex with men (MSM), as these may be a particularly vulnerable population group. Data come from a longitudinal study of MSM with varied substance use behaviors (n = 321) collected between August 2014 and April 2022. Cumulative, childhood maltreatment ACEs, and the single ACE of childhood sexual abuse were investigated as potential predictors of self-reported depressive and anxiety symptoms in mixed-effects logistic and ordinal regression models. There was no evidence of a dose-response relationship between the number of ACEs and the predicted probability of depressive and anxiety symptoms. Compared to MSM reporting fewer than five ACEs, those with five or more ACEs had approximately double the odds ratio of reporting depressive (OR = 1.93; 95% CI: 1.04-3.60) and anxiety symptoms (OR = 2.21; 95% CI: 1.05-4.68). The dimension of childhood maltreatment had a more robust prediction of depressive symptoms than the dimension of household dysfunction across all models. The association between childhood sexual abuse history and depressive symptoms remained after adjustment for the other nine ACEs (OR = 2.27; 95% CI: 1.11-4.68). The ordinal logistic model suggested that cumulative ACEs more than triple the odds of being in a higher anxiety category (OR = 3.12; 95% CI: 1.58-6.14), with associations reported for childhood maltreatment ACEs (OR = 1.31; 95% CI: 1.06-1.66) and childhood sexual abuse (OR = 1.93; 95% CI: 0.89-4.21). Childhood maltreatment ACEs, particularly childhood sexual abuse, are salient predictors of depressive and anxiety symptoms among adult urban MSM. Mitigating the impact of childhood maltreatment requires understanding the additional burden of social distress often faced by MSM throughout the life course.

Parental Age and Childhood Risk for Cerebral Palsy in California.

OBJECTIVE: To investigate the associations between maternal or paternal age at the time of delivery and offspring's risk for cerebral palsy (CP) in California. STUDY DESIGN: We conducted a population-based, case-control study that included 8736 singleton CP cases and 90 250 singleton controls, matched by sex and birth year, selected from California birth certificate records from 1994 to 2010. We estimated OR and 95% CIs for CP diagnosis according to maternal and paternal age recorded on the birth certificates. Causal mediation analysis was performed to estimate direct and indirect effects of parental ages on CP with preterm delivery as a potential mediator. RESULTS: Children born to younger mothers (≤19 years) or older mothers (35-39 years; ≥40 years) had a greater risk of CP compared with children of mothers aged 25-29 years (ORs ranging from 1.13 to 1.59). Compared with paternal age 25-29 years, older paternal age (40-44 years; ≥45 years) also was associated with an increased risk for CP independent of maternal age. When analyzing jointly using both parents of ages 20-34 years as the reference, the greatest risk was estimated for older parents (≥35 years). Preterm birth was estimated to mediate 19%-34% of the total effects between maternal or paternal age and offspring CP risk. CONCLUSIONS: Young maternal age and an older age in either or both parents were associated with a greater risk of CP in their children. Although preterm birth was a mediator, additional factors related to parental age need further exploration to explain risk of CP.

Perceived social support moderates the association between household dysfunction adverse childhood experiences (ACEs) and self-reported drug use among men who have sex with men in Los Angeles, California.

BACKGROUND: Adverse childhood experiences (ACEs) have been shown to be associated with drug use in adulthood. The single ACE of household substance use history (part of the household dysfunction category) has frequently been associated with drug use. Resilience factors such as perceived social support appear to buffer the association between ACEs and drug use and may be particularly relevant for urban men who have sex with men (MSM). The current study of low-income mostly Black and Latino MSM aims to investigate whether the cumulative ACE score predicts self-reported drug use in a dose-response manner and whether this potential association differs by perceived social support. METHODS: Data was utilized from a longitudinal study of MSM (mean age=34; SD=7.1) with varied substance use behaviors (n = 321) collected between August 2014 and April 2022. Cumulative, household dysfunction ACEs, and the single ACE of household substance use history were investigated as predictors of self-reported drug use (methamphetamine, ecstasy, cocaine/crack, heroin/fentanyl, party drugs [GHB, special K, mushrooms, LSD/acid], other drugs [bath salts, PCP]) during the past six months in mixed-effects logistic regression models, with moderation analyses by perceived social support (measured by the Multidimensional Scale of Perceived Social Support) across all models using stratified analysis and one model of multiplicative interaction. RESULTS: There was no suggestion of a dose-response relationship between the number of ACEs and the predicted probability of self-reported drug use. Cumulative ACEs did not predict the outcome overall (aOR=1.99; 95% CI: 0.86-4.59), however, a positive association was estimated for individuals reporting lower levels of perceived social support (aOR=2.80; 95% CI: 0.97-8.06). The dimension of household dysfunction had a positive association with drug use (aOR=1.32; 95% CI: 1.00-1.74) whereas the dimension of childhood maltreatment did not. The association between household dysfunction and drug use was moderated by the perception of social support, with those reporting lower levels having greater odds of reporting drug use (aOR=2.94; 95% CI: 1.04-8.31). The association between household substance use history and self-reported drug use was similarly moderated by perceived social support in a multiplicative interaction model (p = .02). CONCLUSION: Perceived social support emerged as a potential buffering factor for any reported drug use, particularly for the single ACE of household substance use history. Given that the association between ACEs and drug use was weak among those with higher levels of perceived social support, promotion of social ties in the community may help reduce the burden of substance use among MSM exposed to ACEs.

Neighborhood Contexts and Breast Cancer Among Asian American Women.

BACKGROUND: This study examines how neighborhood socioeconomic status (nSES) and ethnic composition are associated with breast cancer risk for Asian American women. METHODS: We linked individual level data from a population-based case-control study of breast cancer among Asian American women with neighborhood level data in the Greater San Francisco Bay Area (cases: n = 118, controls: n = 390). Multivariable logistic regression models examined the association between nSES, ethnic composition, and odds of having breast cancer. RESULTS: Asian American women living in neighborhoods with high nSES and high ethnic composition had the highest odds of breast cancer, compared to those living in neighborhoods with high nSES and low ethnic composition (OR = 0.34, 95% CI [0.16-0.75]) or in neighborhoods with low nSES and high ethnic composition (OR = 0.37, 95% CI [0.17-0.83]). DISCUSSION: Neighborhood socioeconomic and ethnic contexts are associated with breast cancer for Asian American women. We discuss explanations and avenues for future research.

Prenatal Exposure to Acetaminophen and Childhood Asthmatic Symptoms in a Population-Based Cohort in Los Angeles, California.

Acetaminophen is the most common over-the-counter pain and fever medication used by pregnant women. While European studies suggest acetaminophen exposure in pregnancy could affect childhood asthma development, findings are less consistent in other populations. We evaluated whether maternal prenatal acetaminophen use is associated with childhood asthmatic symptoms (asthma diagnosis, wheeze, dry cough) in a Los Angeles cohort of 1201 singleton births. We estimated risk ratio (RR) and 95% confidence interval (CI) for childhood asthmatic outcomes according to prenatal acetaminophen exposure. Effect modification by maternal race/ethnicity and psychosocial stress during pregnancy was evaluated. The risks for asthma diagnosis (RR = 1.39, 95% CI 0.96, 2.00), wheezing (RR = 1.25, 95% CI 1.01, 1.54) and dry cough (RR =1.35, 95% CI 1.06, 1.73) were higher in children born to mothers who ever used acetaminophen during pregnancy compared with non-users. Black/African American and Asian/Pacific Islander children showed a greater than two-fold risk for asthma diagnosis and wheezing associated with the exposure. High maternal psychosocial stress also modified the exposure-outcome relationships. Acetaminophen exposure during pregnancy was associated with childhood asthmatic symptoms among vulnerable subgroups in this cohort. A larger study that assessed prenatal acetaminophen exposure with other social/environmental stressors and clinically confirmed outcomes is needed.

Improved Water, Sanitation and Utilization of Maternal and Child Health Services in South Asia-An Analysis of Demographic Health Surveys.

Globally, many millions of people still lack access to safe drinking water and sanitation facilities. Here, we examined associations between household availability of improved drinking water and sanitation, respectively, and use of maternal and child health (MCH) services in South Asian countries. Demographic and Health Survey population-based data from Bangladesh, Nepal, India, and Pakistan were used, restricted to women with a child aged 0-36 months (n = 145,262). Types of households' water source and sanitation facilities were categorized based on the World Health Organization and UNICEF's definitions of "improved" and "unimproved". We applied logistic regressions to estimate odds ratios (OR) and 95% confidence intervals (CI) for improved water and sanitation, respectively, and reported antenatal care visits, having a skilled attendant at birth, and infant vaccination coverage, stratified by maternal education. Among lower educated women, access to improved water source was associated with greater ORs for presence of a skilled attendant at delivery and their children having up-to-date immunizations (OR: 1.29; 95% CI: 1.17, 1.42). Among lower and higher educated women, improved sanitation (vs. unimproved) was associated with greater ORs for having had adequate antenatal care visits (OR: 1.74; 95% CI: 1.62, 1.88; OR: 1.71; 95% CI: 1.62, 1.80), and similarly for having had a skilled attendant at birth, and children with up-to-date immunizations. Approaches addressing water/sanitation and MCH services across sectors could be a suggested public health strategy.

Parental occupation and childhood germ cell tumors: a case-control study in Denmark, 1968-2016.

PURPOSE: To examine associations between parental occupation and childhood germ cell tumors (GCTs) in offspring while distinguishing by common histologic subtype (i.e., yolk sac tumor and teratoma). METHODS: This population-based case-control study included childhood GCT cases in Denmark diagnosed 1968-2015 (< 16 years old at diagnosis) and sex and birth year-matched controls. Demographic information and parental employment histories were obtained from Danish registries. Parental occupation was assessed by industry; job-exposure matrices were used to examine specific occupational exposures (i.e., potentially carcinogenic organic solvents and social contact). Conditional multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: Overall, 178 childhood GCT cases (50 yolk sac tumors; 65 teratomas) and 4,355 controls were included for analysis. Maternal employment in education during pregnancy was associated with offspring GCTs (OR 2.45, 95% CI 1.23-4.90), especially yolk sac tumors (OR 5.27, 95% CI 1.94-14.28). High levels of both maternal and paternal occupational social contact were also associated with offspring yolk sac tumors across all exposure periods (ORs 2.30-4.63). No signals were observed for paternal occupational solvent exposure, while imprecise associations were estimated for maternal exposure (e.g., dichloromethane exposure during pregnancy, OR 1.51, 95% CI 0.77-2.95). CONCLUSION: Our findings suggest that parental occupation is associated with offspring GCTs, with most consistent evidence supporting an association between maternal employment in education or other high social contact jobs and offspring yolk sac tumors.

A longitudinal study of rural Bangladeshi children with long-term arsenic and cadmium exposures and biomarkers of cardiometabolic diseases.

There is growing interest in understanding the contribution of environmental toxicant exposure in early life to development of cardiometabolic diseases (CMD) in adulthood. We aimed to assess associations of early life exposure to arsenic and cadmium with biomarkers of CMD in children in rural Bangladesh. From a longitudinal mother-child cohort in Matlab, Bangladesh, we followed up 540 pairs. Exposure to arsenic (U-As) and cadmium (U-Cd) was assessed by concentrations in urine from mothers at gestational week 8 (GW8) and children at ages 4.5 and 9 years. Blood pressure and anthropometric indices were measured at 4.5 and 9 years. Metabolic markers (lipids, glucose, hemoglobin A1c, adipokines, estimated glomerular filtration rate (eGFR) were determined in plasma/blood of 9 years old children. In linear regression models, adjusted for child sex, age, height-for-age z score (HAZ), BMI-for-age z score (BAZ), socioeconomic status (SES) and maternal education, each doubling of maternal and early childhood U-Cd was associated with 0.73 and 0.82 mmHg increase in systolic blood pressure (SBP) respectively. Both early and concurrent childhood U-Cd was associated with diastolic (D)BP (ß = 0.80 at 4.5 years; ß = 0.75 at 9 years). Each doubling of U-Cd at 9 years was associated with decrements of 4.98 mg/dL of total cholesterol (TC), 1.75 mg/dL high-density lipoprotein (HDL), 3.85 mg/dL low-density lipoprotein (LDL), 0.43 mg/dL glucose and 4.29 units eGFR. Each doubling of maternal U-Cd was associated with a decrement of 1.23 mg/dL HDL. Both maternal and childhood U-As were associated with decrement in TC and HDL. Multiple comparisons were checked with family-wise error rate Bonferroni-type-approach. The negative associations of arsenic and cadmium with biomarkers of CMD in preadolescent children indicated influence of both metal(loid)s on fat and carbohydrate metabolism, while cadmium additionally influenced kidney function and BP. Thus, fewer outcomes were associated with U-As compared to U-Cd at preadolescence.

Metabolomics analysis of maternal serum exposed to high air pollution during pregnancy and risk of autism spectrum disorder in offspring.

BACKGROUND: Previously, numerous epidemiologic studies reported an association between autism spectrum disorder (ASD) and exposure to air pollution during pregnancy. However, there have been no metabolomics studies investigating the impact of pregnancy pollution exposure to ASD risk in offspring. OBJECTIVES: To identify differences in maternal metabolism that may reflect a biological response to exposure to high air pollution in pregnancies of offspring who later did or did not develop ASD. METHODS: We obtained stored mid-pregnancy serum from 214 mothers who lived in California's Central Valley and experienced the highest levels of air pollution during early pregnancy. We estimated each woman's average traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 µm) during the first trimester using the California Line Source Dispersion Model, version 4 (CALINE4). By utilizing liquid chromatography-high resolution mass spectrometry, we identified the metabolic profiles of maternal serum for 116 mothers with offspring who later developed ASD and 98 control mothers. Partial least squares discriminant analysis (PLS-DA) was employed to select metabolic features associated with air pollution exposure or autism risk in offspring. We also conducted extensive pathway enrichment analysis to elucidate potential ASD-related changes in the metabolome of pregnant women. RESULTS: We extracted 4022 and 4945 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for potential confounders, we identified 167 and 222 discriminative features (HILIC and C18, respectively). Pathway enrichment analysis to discriminate metabolic features associated with ASD risk indicated various metabolic pathway perturbations linked to the tricarboxylic acid (TCA) cycle and mitochondrial function, including carnitine shuttle, amino acid metabolism, bile acid metabolism, and vitamin A metabolism. CONCLUSION: Using high resolution metabolomics, we identified several metabolic pathways disturbed in mothers with ASD offspring among women experiencing high exposure to traffic-related air pollution during pregnancy that were associated with mitochondrial dysfunction. These findings provide us with a better understanding of metabolic disturbances involved in the development of ASD under adverse environmental conditions.

Maternal Prenatal Smoking and Autism Spectrum Disorder in Offspring: A California Statewide Cohort and Sibling Study.

We examined associations between maternal smoking and autism spectrum disorder (ASD) in children in a statewide population-based cohort and sibling-comparison design using California birth records (n = 2,015,104) with information on maternal smoking, demographic factors, and pregnancy (2007-2010). ASD cases (n = 11,722) were identified through California Department of Developmental Services records with diagnoses based on the Diagnostic and Statistical Manual of Mental Disorders-IV-TR. We estimated odds ratios for ASD with and without intellectual disability in the full cohort using logistic regression and in a sibling comparison using conditional logistic regression. In the full cohort, the adjusted odds ratio for ASD and maternal smoking 3 months before/during pregnancy compared with nonsmoking was 1.15 (95% confidence interval (CI): 1.04, 1.26), and it was similar in cases with (odds ratio = 1.12, 95% CI: 0.84, 1.49) and without intellectual disability (odds ratio = 1.15, 95% CI: 1.04, 1.27). Heavy prenatal smoking (≥20 cigarettes/day in any trimester) was related to an odds ratio of 1.55 (95% CI: 1.21, 1.98). In the sibling comparison, the odds ratio for heavy smoking was similarly elevated but the confidence interval was wide. Our findings are consistent with an increased risk for ASD in offspring of mothers who smoked ≥20 cigarettes/day during pregnancy; associations with lighter smoking were weaker.

Ambient Exposure to Agricultural Pesticides during Pregnancy and Risk of Cerebral Palsy: A Population-Based Study in California.

Cerebral palsy (CP) is the most common neuro-motor disability in young children. Disruptions of maternal hormone function during pregnancy have been linked to CP risk. We investigated whether prenatal exposure to pesticide compounds with endocrine-disrupting action affect CP risk. We conducted a case-control study of 3905 CP cases and 39,377 controls born between 1998 and 2010 in California to mothers who lived in proximity (within 2 km) to any agricultural pesticide application recorded in the California Pesticide Use Reporting (PUR) system. We focused on 23 pesticides considered endocrine disruptors that are frequently used, and we found that exposure to any of the 23 pesticides in the first trimester was associated with elevated CP risks in female offspring (OR = 1.19; 95% CI: 1.05-1.35) but not males (OR = 0.99; 95% CI: 0.89-1.09) compared to the unexposed offspring. Positive associations were estimated for 15 pesticides suspected to affect the estrogen and 7 pesticides suspected to affect the thyroid hormone system. Our study suggests that first trimester exposure to pesticides that are suspected endocrine disruptors are associated with CP risk in female offspring. Pesticide exposures in early pregnancy may have sex-specific influences on the neuro-motor development of the fetus by interfering with endocrine systems.

Untargeted Metabolomics Screen of Mid-pregnancy Maternal Serum and Autism in Offspring.

Discovering pathophysiologic networks in a blood-based approach may help to generate valuable tools for early treatment or preventive measures in autism. To date targeted or untargeted metabolomics approaches to identify metabolic features and pathways affecting fetal neurodevelopment have rarely been applied to pregnancy samples, that is, an early period potentially relevant for the development of autism spectrum disorders (ASD). We conducted a population-based study relying on autism diagnoses retrieved from California Department of Developmental Services record. After linking cases to and sampling controls from birth certificates, we retrieved stored maternal mid-pregnancy serum samples collected as part of the California Prenatal Screening Program from the California Biobank for children born 2004 to 2010 in the central valley of California. We retrieved serum for 52 mothers whose children developed autism and 62 population controls originally selected from all eligible children matched by birth year and child's sex. Also, we required that these mothers were relatively low or unexposed to air pollution and select pesticides during early pregnancy. We identified differences in metabolite levels in several metabolic pathways, including glycosphingolipid biosynthesis and metabolism, N-glycan and pyrimidine metabolism, bile acid pathways and, importantly, C21-steroid hormone biosynthesis and metabolism. Disturbances in these pathways have been shown to be relevant for neurodevelopment in rare genetic syndromes or implicated in previous studies of autism. This study provides new insight into maternal mid-pregnancy metabolic features possibly related to the development of autism and an incentive to explore whether these pathways and metabolites are useful for early diagnosis, treatment, or prevention. LAY SUMMARY: This study found that in mid-pregnancy the blood of mothers who give birth to a child that develops autism has some characteristic features that are different from those of blood samples taken from control mothers. These features are related to biologic mechanisms that can affect fetal brain development. In the future, these insights may help identify biomarkers for early autism diagnosis and treatment or preventive measures. Autism Res 2020, 13: 1258-1269. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Occupational livestock or animal dust exposure and offspring cancer risk in Denmark, 1968-2016.

OBJECTIVE: To examine associations with occupational livestock or other animal dust exposure and offspring cancer risk. METHODS: In this population-based case-control study of Danish children aged < 17 years old, 5078 childhood cancer cases diagnosed 1968-2016 were matched to cancer-free controls by birth year and sex (n = 123,228). Occupational livestock or animal dust exposure was identified using a job-exposure matrix. We employed multivariable conditional logistic regression models to estimate associations with offspring cancer for births 1968-2016 and 1989-2016, with the latter timeframe reflecting a period of presumed higher exposure due to changes in Danish farming practices. Sensitivity analyses considered place of birth (urban areas vs. rural areas and small towns). RESULTS: For births 1968-2016, paternal exposure from offspring birth to cancer diagnosis was associated with central nervous system tumors (adjusted odds ratio [OR] = 1.30, 95% confidence interval [CI] 1.04-1.63) and germ cell tumors (OR = 1.82, 95% CI 1.05-3.27), while maternal pregnancy exposure was associated with astrocytoma (OR = 1.89, 95% CI 1.00-3.57). For births 1989-2016, paternal exposure from offspring birth to cancer diagnosis was negatively associated with acute lymphoid leukemia (OR = 0.58, 95% CI 0.33-1.00). For births in rural areas only, maternal exposure from offspring birth to cancer diagnosis was positively associated with acute myeloid leukemia (OR = 2.16, 95% CI 1.09-4.29). CONCLUSIONS: This study suggests that paternal occupational animal exposure is associated with offspring germ cell tumors, and maternal pregnancy exposure with astrocytomas. Our results are mixed with respect to leukemia subtypes.

Intimate partner violence and childhood illnesses in Cambodia: a cross-sectional study.

BACKGROUND: Around a quarter of Cambodian women reported being victim to intimate partner violence (IPV) from their current partner. Children's exposure to familial IPV impacts psychosocial well-being and emerging research indicates associations with physical health. OBJECTIVE: Investigate associations between maternal experience of IPV and common childhood illnesses in Cambodia. DESIGN, SETTING, PARTICIPANTS: Analysis of the Cambodia Demographic and Health Survey (2000, 2005, 2014) using logistic regression, including 5025 children under 5 years of age whose mothers responded to questions about experience of emotional, physical and sexual violence by current partner. MAIN OUTCOME MEASURES: Report of diarrhoea, acute respiratory infection (ARI) or fever, respectively, in children in the two weeks preceding the survey. RESULTS: Children of mothers with experience of any type of IPV had estimated elevated odds of diarrhoea (adjusted OR (aOR)=1.65, 95% CI 1.39 to 1.97), estimated odds of ARI (aOR=1.78, 95% CI 1.47 to 2.16) and estimated odds of fever (aOR=1.51, 95% CI 1.31 to 1.76) compared with children of mothers without reported IPV experience. Exposure to any form of IPV corresponded to an estimated 2.65 times higher odds (95% CI 2.01 to 3.51) for reporting having both diarrhoea and ARI. CONCLUSIONS: Our findings support the notion that children's susceptibility to diarrhoea, ARI and fever may be affected by mothers' experience of IPV, including emotional violence. Maternal and child health programmes should train healthcare professionals to identify domestic violence and children at risk, and link victims to appropriate health and legal services.

Maternal serum metabolome and traffic-related air pollution exposure in pregnancy.

BACKGROUND: Maternal exposure to traffic-related air pollution during pregnancy has been shown to increase the risk of adverse birth outcomes and neurodevelopmental disorders. By utilizing high-resolution metabolomics (HRM), we investigated perturbations of the maternal serum metabolome in response to traffic-related air pollution to identify biological mechanisms. METHODS: We retrieved stored mid-pregnancy serum samples from 160 mothers who lived in the Central Valley of California known for high air particulate levels. We estimated prenatal traffic-related air pollution exposure (carbon monoxide, nitric oxides, and particulate matter <2.5 µm) during first-trimester using the California Line Source Dispersion Model, version 4 (CALINE4) based on residential addresses recorded at birth. We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) to select metabolic features associated with air pollution exposure. Pathway analyses were employed to identify biologic pathways related to air pollution exposure. As potential confounders we included maternal age, maternal race/ethnicity, and maternal education. RESULTS: In total we extracted 4038 and 4957 metabolic features from maternal serum samples in hydrophilic interaction (HILIC) chromatography (positive ion mode) and C18 (negative ion mode) columns, respectively. After controlling for confounding factors, PLS-DA (Variable Importance in Projection (VIP) ≥2) yielded 181 and 251 metabolic features (HILIC and C18, respectively) that discriminated between the high (n = 98) and low exposed (n = 62). Pathway enrichment analysis for discriminatory features associated with air pollution indicated that in maternal serum oxidative stress and inflammation related pathways were altered, including linoleate, leukotriene, and prostaglandin pathways. CONCLUSION: The metabolomic features and pathways we found to be associated with air pollution exposure suggest that maternal exposure during pregnancy induces oxidative stress and inflammation pathways previously implicated in pregnancy complications and adverse outcomes.