Child Health Study Research Articles

Joint effects of indoor air pollution and maternal psychosocial factors during pregnancy on trajectories of early childhood psychopathology.

Prenatal indoor air pollution and maternal psychosocial factors have been associated with adverse psychopathology. We used environmental-exposure mixture methodology to investigate joint effects of both exposure classes on child behavior trajectories. For 360 children from the South African Drakenstein Child Health Study, we created trajectories of Child Behavior Checklist scores (at 24, 42, and 60 months) using latent-class linear mixed effects models. Indoor air pollutants and psychosocial factors were measured during pregnancy (second trimester). After adjusting for confounding, single-exposure effects (per natural log-1 unit increase) were assessed using polytomous logistic regression models, joint effects using self-organizing maps, and principal component analysis. Three trajectories were chosen for both internalizing and externalizing problems, with "high" (externalizing) or "increasing" (internalizing) being the most adverse trajectories. High externalizing trajectory was associated with increased exposure to particulate matter of ≤ 10 microns in diameter (PM10) (odds ratio [OR] = 1.25; 95% CI, 1.01-1.55) and self-organizing maps exposure profile most associated with smoking (OR = 2.67; 95% CI, 1.14-6.27). Medium internalizing trajectory was associated with increased emotional intimate partner violence (OR = 2.66; 95% CI, 1.17-5.57), increasing trajectory with increased benzene (OR = 1.24; 95% CI, 1.02-1.51) and toluene (1.21; 95% CI, 1.02-1.44) and the principal component most correlated with benzene and toluene (OR = 1.25; 95% CI, 1.02-1.54). Prenatal exposure to environmental pollutants and psychosocial factors was associated with internalizing and externalizing child behavior trajectories. Understanding joint effects of adverse exposure mixtures will facilitate targeted interventions to prevent childhood psychopathology. This article is part of a Special Collection on Mental Health.

Language outcomes of preschool children who are HIV-exposed uninfected: An analysis of a South African cohort.

There are approximately 16 million children who are HIV-exposed and uninfected (CHEU) worldwide. Studies suggest that CHEU are at risk for developmental impairment in infancy, particularly in language domains. However, there is limited research examining neurocognitive function in CHEU older than 2 years, including important pre-school years. This study aimed to investigate associations between HIV exposure without infection and neurocognitive outcomes and to determine risk factors for neurodevelopment in CHEU at age 3-4 years. The Drakenstein Child Health Study is a South African population-based birth cohort which enrolled women in pregnancy with ongoing follow up. Neurocognitive outcomes were assessed in children at 3.5 years by trained assessors blinded to HIV status including general cognitive function, language, and memory, measured using the Kaufmann Assessment Battery for Children, Second Edition (KABC-II). Data were compared between CHEU and children who were HIV-unexposed uninfected (CHUU) using multivariable logistic and linear regression, including testing for effect modification; sex-stratified risk factor analyses were performed. A total of 497 children were included (97 [20%] CHEU; 400 [80%] CHUU; 50% male), with a mean age of 3.5 years (range 3.4-3.6). Groups had similar birth and household characteristics, although mothers of CHEU were older, on average. Overall, CHEU had lower expressive language scores compared to CHUU on unadjusted and adjusted analyses (effect size: -0.23 [95% CI -0.45, -0.01]). There were no group differences in general cognitive or memory function (p>0.05). On sex-stratified analyses, male CHEU were found to have higher odds of suboptimal cognitive development compared to male CHUU (aOR 2.28 [95% CI 1.06, 4.87], p = 0.034). Several other factors including birthweight, maternal education, maternal ART duration and HIV viral load during pregnancy were associated with cognition, memory, or expressive language outcomes in CHEU, dependent on child sex. The findings suggest that perinatal HIV exposure continues to be associated with impaired language development across the preschool years, highlighting the importance of targeting early interventions to optimise language outcomes. Further, the results suggest the importance of demographic, biological and HIV-related variables influencing developmental outcomes in CHEU. The greater risk of suboptimal cognitive development in male CHEU requires investigation around sex-specific mechanisms.

Joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation

It is hypothesized that air pollution and stress impact the central nervous system through neuroinflammatory pathways Despite this, the association between prenatal exposure to indoor air pollution and psychosocial factors on inflammatory markers in infancy has been underexplored in epidemiology studies. This study investigates the individual and joint effects of prenatal exposure to indoor air pollution and psychosocial factors on early life inflammation (interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)). We analyzed data from the South African Drakenstein Child Health Study (N = 225). Indoor air pollution and psychosocial factor measurements were taken in the 2nd trimester of pregnancy. Circulating inflammatory markers (IL-1β, Il-6, and TNF-α) were measured in serum in the infants at 6 weeks postnatal. Linear regression models were used to investigate associations between individual exposures and inflammatory markers. To investigate joint effects of environmental and psychosocial factors, Self-Organizing Maps (SOM) were used to create exposure profile clusters. These clusters were added to linear regression models to investigate the associations between exposure profiles and inflammatory markers. All models were adjusted for maternal age, maternal HIV status, and ancestry to control for confounding. Most indoor air pollutants were positively associated with inflammatory markers, particularly benzene and TNF-α in single pollutant models. No consistent patterns were found for psychosocial factors in single-exposure linear regression models. In joint effects analyses, the SOM profile with high indoor air pollution, low SES, and high maternal depressive symptoms were associated with higher inflammation. Indoor air pollutants were consistently associated with increased inflammation in both individual and joint effects models, particularly in combination with low SES and maternal depressive symptoms. The trend for individual psychosocial factors was not as clear, with mainly null associations. As we have observed pro- and anti-inflammatory effects, future research should investigate joint effects of these exposures on inflammation and their health effects.

An Upsurge of Measles Cases in Mali-a Consequence of Pandemic-associated Disruption in Routine Immunization.

Measles deaths highlight immunization program gaps. In the Child Health and Mortality Prevention Surveillance study in Mali, we observed a rise in under-5 measles-related deaths in 2022 that corresponded with increased measles cases at the same time and a decline in measles vaccine coverage in Mali in 2020.

Factors predicting mortality in hospitalised HIV-negative children with lower-chest-wall indrawing pneumonia and implications for management.

In 2012, the World Health Organization revised treatment guidelines for childhood pneumonia with lower chest wall indrawing (LCWI) but no 'danger signs', to recommend home-based treatment. We analysed data from children hospitalized with LCWI pneumonia in the Pneumonia Etiology Research for Child Health (PERCH) study to identify sub-groups with high odds of mortality, who might continue to benefit from hospital management but may not be admitted by staff implementing the 2012 guidelines. We compare the proportion of deaths identified using the criteria in the 2012 guidelines, and the proportion of deaths identified using an alternative set of criteria from our model. PERCH enrolled a cohort of 2189 HIV-negative children aged 2-59 months who were admitted to hospital with LCWI pneumonia (without obvious cyanosis, inability to feed, vomiting, convulsions, lethargy or head nodding) between 2011-2014 in Kenya, Zambia, South Africa, Mali, The Gambia, Bangladesh, and Thailand. We analysed risk factors for mortality among these cases using predictive logistic regression. Malnutrition was defined as mid-upper-arm circumference <125mm or weight-for-age z-score <-2. Among 2189 cases, 76 (3·6%) died. Mortality was associated with oxygen saturation <92% (aOR 3·33, 1·99-5·99), HIV negative but exposed status (4·59, 1·81-11·7), moderate or severe malnutrition (6·85, 3·22-14·6) and younger age (infants compared to children 12-59 months old, OR 2·03, 95%CI 1·05-3·93). At least one of three risk factors: hypoxaemia, HIV exposure, or malnutrition identified 807 children in this population, 40% of LCWI pneumonia cases and identified 86% of the children who died in hospital (65/76). Risk factors identified using the 2012 WHO treatment guidelines identified 66% of the children who died in hospital (n = 50/76). Although it focuses on treatment failure in hospital, this study supports the proposal for better risk stratification of children with LCWI pneumonia. Those who have hypoxaemia, any malnutrition or those who were born to HIV positive mothers, experience poorer outcomes than other children with LCWI pneumonia. Consistent identification of these risk factors should be prioritised and children with at least one of these risk factors should not be managed in the community.

Maternal plasma phospholipid polyunsaturated fatty acids in early pregnancy and thyroid function throughout pregnancy: a longitudinal study

BackgroundEvidence has indicated that polyunsaturated fatty acids (PUFAs)-enriched diet could reduce inflammation because of thyroid autoimmunity in vivo, and therefore, enhance thyroid function. ObjectivesWe investigated whether early pregnancy plasma phospholipid PUFAs could benefit maternal thyroid function across pregnancy, which is critical to fetal brain development and growth in pregnancy. MethodsWithin the National Institute of Child Health and Human Development Fetal Growth Studies–Singleton Cohort, we collected plasma samples longitudinally from 214 subjects [107 with gestational diabetes mellitus (GDM) matched with 107 controls] with a singleton pregnancy. We measured 11 PUFAs at early pregnancy (10–14 wk) and 5 thyroid biomarkers at 10–14, 15–26, 23–31, and 33–39 wk, including free thyroxine (fT4), free triiodothyronine (fT3), thyroid-stimulating hormone, antithyroid peroxidase, and antithyroglobulin. Associations of PUFAs with thyroid function biomarkers and relative risk (RR) of gestational hypothyroidism (GHT) during pregnancy were assessed using generalized linear mixed models and modified Poisson regression, respectively. ResultsAfter sample weighting because of subjects with GDM over-representing in the analytic sample with biomarkers, eicosapentaenoic acid (EPA) at early pregnancy was associated with a reduction of 0.24 pmol/L (95% confidence intervals: −0.31, −0.16) in fT3 across gestation per standard deviation (SD) increment, whereas docosahexaenoic acid (DHA) at early pregnancy was associated with an increment of 0.04 ng/dL (0.02, 0.05) in fT4 across gestation per SD increment. Furthermore, EPA and docosatetraenoic acid (DTA) were associated with lower risks of persistent GHT (EPA—RR: 0.13; 0.06, 0.28; DTA—RR: 0.24; 0.13, 0.44) per SD increment. All significant associations remained robust in sensitivity analysis and multiple testing. ConclusionsCertain plasma phospholipid PUFAs were associated with optimal levels of thyroid biomarkers and even lower risk of GHT throughout pregnancy, which might be potentially targeted for maternal thyroid regulation in early pregnancy. Clinical Trial RegistryThis trial was registered at https://beta.clinicaltrials.gov/study/NCT00912132?distance=50&term=NCT00912132&rank=1 as NCT00912132.

Leveraging big data for causal understanding in mental health: a research framework.

Over the past 30 years there have been numerous large-scale and longitudinal psychiatric research efforts to improve our understanding and treatment of mental health conditions. However, despite the huge effort by the research community and considerable funding, we still lack a causal understanding of most mental health disorders. Consequently, the majority of psychiatric diagnosis and treatment still operates at the level of symptomatic experience, rather than measuring or addressing root causes. This results in a trial-and-error approach that is a poor fit to underlying causality with poor clinical outcomes. Here we discuss how a research framework that originates from exploration of causal factors, rather than symptom groupings, applied to large scale multi-dimensional data can help address some of the current challenges facing mental health research and, in turn, clinical outcomes. Firstly, we describe some of the challenges and complexities underpinning the search for causal drivers of mental health conditions, focusing on current approaches to the assessment and diagnosis of psychiatric disorders, the many-to-many mappings between symptoms and causes, the search for biomarkers of heterogeneous symptom groups, and the multiple, dynamically interacting variables that influence our psychology. Secondly, we put forward a causal-orientated framework in the context of two large-scale datasets arising from the Adolescent Brain Cognitive Development (ABCD) study, the largest long-term study of brain development and child health in the United States, and the Global Mind Project which is the largest database in the world of mental health profiles along with life context information from 1.4 million people across the globe. Finally, we describe how analytical and machine learning approaches such as clustering and causal inference can be used on datasets such as these to help elucidate a more causal understanding of mental health conditions to enable diagnostic approaches and preventative solutions that tackle mental health challenges at their root cause.

Exposure to Airborne PM2.5 Water-Soluble Inorganic Ions Induces a Wide Array of Reproductive Toxicity.

Water-soluble inorganic ions (WSIIs, primarily NH4+, SO42-, and NO3-) are major components in ambient PM2.5, but their reproductive toxicity remains largely unknown. An animal study was conducted where parental mice were exposed to PM2.5 WSIIs or clean air during preconception and the gestational period. After delivery, all maternal and offspring mice lived in a clean air environment. We assessed reproductive organs, gestation outcome, birth weight, and growth trajectory of the offspring mice. In parallel, we collected birth weight and placenta transcriptome data from 150 mother-infant pairs from the Rhode Island Child Health Study. We found that PM2.5 WSIIs induced a broad range of adverse reproductive outcomes in mice. PM2.5 NH4+, SO42-, and NO3- exposure reduced ovary weight by 24.22% (p = 0.005), 14.45% (p = 0.048), and 16.64% (p = 0.022) relative to the clean air controls. PM2.5 SO42- exposure reduced the weight of testicle by 5.24% (p = 0.025); further, mice in the PM2.5 SO42- exposure group had 1.81 (p = 0.027) fewer offspring than the control group. PM2.5 NH4+, SO42-, and NO3- exposure all led to lower birth than controls. In mice, 557 placenta genes were perturbed by exposure. Integrative analysis of mouse and human data suggested hypoxia response in placenta as an etiological mechanism underlying PM2.5 WSII exposure's reproductive toxicity.

Sex-Specific Pathways From Prenatal Maternal Inflammation to Adolescent Depressive Symptoms

Prenatal maternal inflammation has been associated with major depressive disorder in offspring in adulthood as well as with internalizing and externalizing symptoms in childhood; however, the association between prenatal inflammation and offspring depression in adolescence has yet to be examined. To determine whether maternal levels of inflammatory biomarkers during pregnancy are associated with depressive symptomatology in adolescent-aged offspring and to examine how gestational timing, offspring sex, and childhood psychiatric symptoms impact these associations. This was an observational study of a population-based birth cohort from the Child Health and Development Studies (CHDS), which recruited almost all mothers receiving obstetric care from the Kaiser Foundation Health Plan (KFHP) in Alameda County, California, between June 1959 and September 1966. Pregnancy data and blood sera were collected from mothers, and offspring psychiatric symptom data were collected in childhood (ages 9-11 years) and adolescence (ages 15-17 years). Mother-offspring dyads with available maternal prenatal inflammatory biomarkers during first and/or second trimesters and offspring depressive symptom data at adolescent follow-up were included. Data analyses took place between March 2020 and June 2023. Levels of inflammatory biomarkers (interleukin 6 [IL-6], IL-8, IL-1 receptor antagonist [IL-1RA], and soluble tumor necrosis factor receptor-II) assayed from maternal sera in the first and second trimesters of pregnancy. Self-reported depressive symptoms at adolescent follow-up. A total of 674 mothers (mean [SD] age, 28.1 [5.9] years) and their offspring (350 male and 325 female) were included in this study. Higher second trimester IL-6 was significantly associated with greater depressive symptoms in offspring during adolescence (b, 0.57; SE, 0.26); P = .03). Moderated mediation analyses showed that childhood externalizing symptoms significantly mediated the association between first trimester IL-6 and adolescent depressive symptoms in male offspring (b, 0.18; 95% CI, 0.02-0.47), while childhood internalizing symptoms mediated the association between second trimester IL-1RA and adolescent depressive symptoms in female offspring (b, 0.80; 95% CI, 0.19-1.75). In this study, prenatal maternal inflammation was associated with depressive symptoms in adolescent-aged offspring. The findings of the study suggest that pathways to adolescent depressive symptomatology from prenatal risk factors may differ based on both the timing of exposure to prenatal inflammation and offspring sex.

Revisiting implications of early family economic conditions for adolescent adaptations: An integrative cascade model.

Implications of family economic conditions (FECs) for child development have been extensively examined. What remains sparse is research spanning multiple life stages to delineate the far-reaching influences of early FECs for child subsequent development in different domains and how various family stress and investment processes jointly account for such association. To address these gaps, using data from 929 families in the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development (NICHD Early Child Care Research Network, 2001, 2005), this study examined how family income-to-needs ratio (FITNR) when children were 1-36 months old was associated with child language skills, social competence, externalizing, and internalizing problems at 6th grade. Parental investment and maternal/paternal depressive symptoms and sensitivity when children were 54 months old and in 3rd grade were tested as potential mediators. Results indicated that early FITNR shaped child cognitive, social, and behavioral adaptation in early adolescence indirectly through parental investment, depressive symptoms, and sensitive parenting in the preschool period and middle childhood. Parental investment, depressive symptoms, and sensitive parenting played such mediating roles above and beyond each other. Parental investment primarily accounted for the association between early FITNR and child later language skills, whereas parental depressive symptoms and sensitive parenting uniquely explained the associations between early FITNR and child subsequent internalizing symptoms, externalizing problems, social competence, and language skills. Theoretical/practical implications of such findings were discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Perceived Stress From Childhood to Adulthood and Cardiometabolic End Points in Young Adulthood: An 18-Year Prospective Study.

We investigated how childhood-to-adulthood perceived stress patterns predict adult cardiometabolic risk. This study included 276 participants from the Southern California Children's Health Study (2003-2014), and a follow-up assessment (2018-2021). Perceived stress (Perceived Stress Scale) was initially reported by participants' parents for themselves during early childhood (mean age, 6.3 years), and later self-reported during adolescence (13.3 years) and young adulthood (23.6 years). Participants were grouped into 4 stress patterns: consistently high, decreasing, increasing, and consistently low. Cardiometabolic risk was assessed in young adulthood by carotid artery intima-media thickness, systolic and diastolic blood pressure, obesity, percent body fat, android/gynoid ratio, and glycated hemoglobin. A cardiometabolic risk score was generated by summing the clinically abnormal markers. Multivariable linear and logistic regression models were used to (1) examine the associations between Perceived Stress Scale at 3 time points and adult cardiometabolic risk, and (2) assess the impact of stress pattern on adult cardiometabolic risk. Findings suggested that in adulthood, higher Perceived Stress Scale score was associated with increased overall cardiometabolic risk (β=0.12 [95% CI, 0.01-0.22]), carotid artery intima-media thickness (β=0.01 [95% CI, 0.0003-0.02]), systolic blood pressure (β=1.27 [95% CI, 0.09-2.45]), and diastolic blood pressure (β=0.94 [95% CI, 0.13-1.75]). Individuals with a consistently high adolescence-to-adulthood stress patternhad greater overall cardiometabolic risk (β=0.31 [95% CI, 0.02-0.60]), android/gynoid ratio (β=0.07 [95% CI, 0.02-0.13]), percent body fat (β=2.59 [95% CI, 0.01-5.17]), and greater odds of obesity (odds ratio, 5.57 [95% CI, 1.62-19.10]) in adulthood, compared with those with a consistently low Perceived Stress Scale score. Consistently high perceived stress from adolescence to adulthood may contribute to greater cardiometabolic risk in young adulthood.

Risk and rates of hospitalisation in young children: A prospective study of a South African birth cohort.

Children in sub-Saharan Africa (SSA) are disproportionately affected by morbidity and mortality. There is also a growing vulnerable population of children who are HIV-exposed uninfected (HEU). Understanding reasons and risk factors for early-life child hospitalisation will help optimise interventions to improve health outcomes. We investigated hospitalisations from birth to two years in a South African birth cohort study. Mother-child pairs in the Drakenstein Child Health Study were followed from birth to two years with active surveillance for hospital admission and investigation of aetiology and outcome. Incidence, duration, cause, and factors associated with child hospitalisation were investigated, and compared between HEU and HIV-unexposed uninfected (HUU) children. Of 1136 children (247 HEU; 889 HUU), 314 (28%) children were hospitalised in 430 episodes despite >98% childhood vaccination coverage. The highest hospitalisation rate was from 0-6 months, decreasing thereafter; 20% (84/430) of hospitalisations occurred in neonates at birth. Amongst hospitalisations subsequent to discharge after birth, 83% (288/346) had an infectious cause; lower respiratory tract infection (LRTI) was the most common cause (49%;169/346) with respiratory syncytial virus (RSV) responsible for 31% of LRTIs; from 0-6 months, RSV-LRTI accounted for 22% (36/164) of all-cause hospitalisations. HIV exposure was associated with increased incidence rates of hospitalisation in infants (IRR 1.63 [95% CI 1.29-2.05]) and longer hospital admission (p = 0.004). Prematurity (HR 2.82 [95% CI 2.28-3.49]), delayed infant vaccinations (HR 1.43 [95% CI 1.12-1.82]), or raised maternal HIV viral load in HEU infants were risk factors for hospitalisation; breastfeeding was protective (HR 0.69 [95% CI 0.53-0.90]). In conclusion, children in SSA experience high rates of hospitalisation in early life. Infectious causes, especially RSV-LRTI, underly most hospital admissions. HEU children are at greater risk of hospitalisation in infancy compared to HUU children. Available strategies such as promoting breastfeeding, timely vaccination, and optimising antenatal maternal HIV care should be strengthened. New interventions to prevent RSV may have additional impact in reducing hospitalisation.

Cumulative Stress Across the Life Course and Biological Aging in Adulthood.

Psychosocial stressors have been linked with accelerated biological aging in adults; however, few studies have examined stressors across the life course in relation to biological aging. In 359 individuals (57% White, 34% Black) from the Child Health and Development Studies Disparities study, economic (income, education, financial strain), social (parent-child relations, caretaker responsibilities) and traumatic (death of a sibling or child, violence exposure) stressors were assessed at multiple time points (birth and ages 9, 15, and 50 years). Experiences of major discrimination were assessed at age 50. Life period stress scores were then assessed as childhood (birth-age 15 years) and adulthood (age 50 years). At age 50 years, participants provided blood samples, and DNA methylation was assessed with the EPIC BeadChip. Epigenetic age was estimated using six epigenetic clocks (Horvath, Hannum, Skin and Blood age, PhenoAge, GrimAge, Dunedin Pace of Aging). Age acceleration was determined using residuals from regressing chronologic age on each of the epigenetic age metrics. Telomere length was assessed using the quantitative polymerase chain reaction-based methods. In linear regression models adjusted for race and gender, total life stress, and childhood and adult stress independently predicted accelerated aging based on GrimAge and faster pace of aging based on the DunedinPace. Associations were attenuated after adjusting for smoking status. In sex-stratified analyses, greater childhood stress was associated with accelerated epigenetic aging among women but not men. No associations were noted with telomere length. We found that cumulative stressors across the life course were associated with accelerated epigenetic age, with differences by sex (e.g., accelerated among women). Further research of this association in large and diverse samples is needed.

Body mass index, internalizing behavior and executive function: examining trait-state effects from age 2 to 15.

This study aimed to examine the reciprocal relation between body mass index and internalizing behavior from age 2 to 15, and also the predictive role of executive function. This study included a subset sample of 640 children (47% were male) from the National Institute of Child Health and Development Study of Early Child Care and Youth Development. A refined random-intercept cross-lagged model was employed to analyze: (1) the reciprocal relation between children's body mass index and internalizing behavior assessed in eight waves from age 2 to 15; (2) the predictive role of executive functioning in both children's body mass index and internalizing behavior. Trait-level body mass index-to-internalizing behavior association was not found; a significant state-level prediction from body mass index in 5th grade to internalizing behavior in 6th grade was found. Executive function was significantly associated with trait-level body mass index, trait-level internalizing behaviors, and state-level internalizing behaviors. The findings suggest that deficits in children's executive functioning may be a shared risk associated with both high body mass index and internalizing behaviors. From an intervention perspective, this study highlighted the importance of targeting executive function to intervene in children's obesity or internalizing behaviors.

COVID-19 pandemic impact on adolescent mental health: a reassessment accounting for development

Current prospective reports suggest a pandemic-related increase in adolescent mental health problems. We examine whether age-related change over 11–14 years accounts for this increase. Mothers and adolescents in a UK-based birth cohort (Wirral Child Health and Development Study; WCHADS; N = 737) reported on adolescent depression and behavioural problems pre-pandemic (December 2019–March 2020), mid-pandemic (June 2020–March 2021) and late pandemic (July 2021–March 2022). Analysis used repeated measures models for over-dispersed Poisson counts with an adolescent-specific intercept with age as a time-varying covariate. Maturational curves for girls, but not for boys, showed a significant increase in self-reported depression symptoms over ages 11–14 years. Behavioural problems decreased for both. After adjusting for age-related change, girls’ depression increased by only 13% at mid-pandemic and returned to near pre-pandemic level at late pandemic (mid versus late – 12%), whereas boys’ depression increased by 31% and remained elevated (mid versus late 1%). Age-adjusted behavioural problems increased for both (girls 40%, boys 41%) and worsened from mid- to late pandemic (girls 33%, boys 18%). Initial reports of a pandemic-related increase in depression in young adolescent girls could be explained by a natural maturational rise. In contrast, maturational decreases in boys’ depression and both boys’ and girls’ behavioural problems may mask an effect of the pandemic.

Quantitative determination of polycyclic aromatic hydrocarbons in the blood by high-performance liquid chromatography with fluorimetric detection for the tasks of socio-hygienic monitoring

Introduction. The polycyclic aromatic hydrocarbons (PAH) refer to the group of priority environmental pollutants that enter the human body by inhalation, orally, through the skin, causing a long-term impact on metabolic processes, chronic and oncological diseases. To assess the impact of polycyclic aromatic hydrocarbons on the health of the population, it is actual to evaluate their content in human biological media. &#x0D; The purpose of the study is to develop and apply a methodology for determining the polycyclic aromatic hydrocarbons (naphthalene, 2-methylnaphthalene, anthracene, the 9-methylanthracene, pyrene and benz (a) pyrene) in the blood by a method of highly efficient liquid chromatography with fluoremetric detection (HPLC-FDD) for social and hygienic monitoring problems. &#x0D; Materials and methods. The object of research was biological media (blood samples). Studies on the development of the technique were carried out on the Shimadzu liquid chromatograph with a fluoremetric detector RF-20A. The approximation of the technique was carried out within the framework of deeper studies of children health in residents in territories with various exposure levels.&#x0D; Results. The conditions for sample production and parameters of the chromatographic analysis of blood PAH by the HPLC / FDD method were established. The degree of extraction of PAH from the blood by the method of liquid extraction was 77-100%. The analysis of blood PAH showed average group concentrations to be reliably higher (p &lt;0.05) in the biological media in children living in the zone of influence of emissions of industrial enterprises. Priority compounds detected in the blood of the students are pyrene, naphthalene, 2-methylnaphthalene, &#x0D; Limitations are due to the period of selection of biological media of the different age groups in the territories of the Russian Federation with various levels of exposure. The expansion of the list of the populations can become a direction of further research on assessing the impact of polycyclic aromatic hydrocarbons on human health. &#x0D; Conclusion. The developed methodology can be used in hygienic studies for assessing the risk of conditions of exposure to polycyclic aromatic hydrocarbons for health of residents in the territories with different anthropogenic loads.

Exposure to perfluoroalkyl substances and longitudinal changes in bone mineral density in adolescents and young adults: A multi-cohort study

BackgroundPer- and polyfluoroalkyl substances (PFAS) may impair bone development in adolescence, which impacts life-long bone health. No previous studies have examined prospective associations of individual PFAS and their mixture with bone mineral density (BMD) changes in Hispanic young persons, a population at high risk of osteoporosis in adulthood. ObjectivesTo examine associations of individual PFAS and PFAS mixtures with longitudinal changes in BMD in an adolescent Hispanic cohort and examine generalizability of findings in a mixed-ethnicity young adult cohort (58.4% Hispanic). MethodsOverweight/obese adolescents from the Study of Latino Adolescents at Risk of Type 2 Diabetes (SOLAR; n = 304; mean follow-up = 1.4 years) and young adults from the Southern California Children's Health Study (CHS; n = 137; mean follow-up = 4.1 years) were included in this study. Plasma PFAS were measured at baseline and dual x-ray absorptiometry scans were performed at baseline and follow-up to measure BMD. We estimated longitudinal associations between BMD and five PFAS via separate covariate-adjusted linear mixed effects models, and between BMD and the PFAS mixture via quantile g-computation. ResultsIn SOLAR adolescents, baseline plasma perfluorooctanesulfonic acid (PFOS) was associated with longitudinal changes in BMD. Each doubling of PFOS was associated with an average −0.003 g/cm2 difference in change in trunk BMD per year over follow-up (95% CI: −0.005, −0.0002). Associations with PFOS persisted in CHS young adults, where each doubling of plasma PFOS was associated with an average −0.032 g/cm2 difference in total BMD at baseline (95% CI -0.062, −0.003), though longitudinal associations were non-significant. We did not find associations of other PFAS with BMD; associations of the PFAS mixture with BMD outcomes were primarily negative though non-significant. DiscussionPFOS exposure was associated with lower BMD in adolescence and young adulthood, important periods for bone development, which may have implications on future bone health and risk of osteoporosis in adulthood.

Comparing the reliability and validity of youth-reported checklists and standardized interviews for categorical measurement of emotional and behavioral problems.

Self-completed checklists measuring youth mental health problems produce dimensional scale scores and can be converted to categorical classifications representing the presence/absence of psychopathology. We test whether categorical classifications from scale scores are equivalent psychometrically to categorical classifications of the same problems obtained by lay-administered standardized structured diagnostic interviews. The sample of n = 325 youth aged 12-18 (44% male) and their parent/caregivers come from combined test-retest reliability studies conducted in Ontario, Canada, from 2011 to 2015. Ontario Child Health Study Emotional Behavioural Scales-Brief Version (OCHS-EBS-B)scores converted to categorical classifications of emotional and behavioral problems were compared with interview classifications. We test hypotheses of statistical equivalence and inferiority, using a confidence interval approach to detect if differences lie within the smallest effect size of interest of ±0.18. We compare categorical classifications on: (1) test-retest reliability (ҡ), (2) content validity (between-instrument agreement), and (3) construct validity (strength of association with three mental health-related constructs). Average test-retest reliabilities were 0.695 (checklists) and 0.670 (interviews). The reliability of checklist emotional problem classifications was not inferior to interview classifications and the difference in reliability between instruments for behavioral problems was small (-0.036). Average between-instrument agreement was ҡ = 0.586 (observed) and ҡ = 0.841 (corrected for attenuation due to measurement error) indicating high content overlap. Statistical equivalence criteria were met in 5 of 6 construct validity comparisons. Categorical classifications of emotional and behavioral problems from youth-reported checklists are, on balance, equivalent to interview classifications. Checklists represent a simple, brief, inexpensive alternative to interviews.

Placental accelerated aging in antenatal depression

Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging. This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery. The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment. There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses. Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction.

Burden of diarrhea and antibiotic use among children in low-resource settings preventable by Shigella vaccination: A simulation study.

Shigella is a leading cause of diarrhea and dysentery in children in low-resource settings, which is frequently treated with antibiotics. The primary goal of a Shigella vaccine would be to reduce mortality and morbidity associated with Shigella diarrhea. However, ancillary benefits could include reducing antibiotic use and antibiotic exposures for bystander pathogens carried at the time of treatment, specifically for fluoroquinolones and macrolides (F/M), which are the recommended drug classes to treat dysentery. The aim of the study was to quantify the reduction in Shigella attributable diarrhea, all diarrhea, and antibiotic use in the first 2 years of life that could be prevented by a Shigella vaccine. We used data from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) study, a birth cohort study that followed 1,715 children with twice weekly surveillance for enteric infections, illnesses, and antibiotic use for the first 2 years of life from November 2009 to February 2014 at 8 sites. We estimated the impact of 2 one-dose (6 or 9 months) and 3 two-dose (6 and 9 months, 9 and 12 months, and 12 and 15 months) Shigella vaccines on diarrheal episodes, overall antibiotic use, and F/M use. Further, we considered additional protection through indirect and boosting effects. We used Monte Carlo simulations to estimate the absolute and relative reductions in the incidence of diarrhea and antibiotic use comparing each vaccination scenario to no vaccination. We analyzed 9,392 diarrhea episodes and 15,697 antibiotic courses among 1,715 children in the MAL-ED birth cohort study. There were 273.8 diarrhea episodes, 30.6 shigellosis episodes, and 457.6 antibiotic courses per 100 child-years. A Shigella vaccine with a mean vaccine efficacy of 60% against severe disease given at 9 and 12 months prevented 10.6 (95% CI [9.5, 11.5]) Shigella diarrhea episodes of any severity per 100 child-years (relative 34.5% reduction), 3.0 (95% CI [2.5, 3.5]) F/M courses for Shigella treatment per 100 child-years (relative 35.8% reduction), and 5.6 (95% CI [5.0, 6.3]) antibiotic courses of any drug class for Shigella treatment per 100 child-years (relative 34.5% reduction). This translated to a relative 3.8% reduction in all diarrhea, a relative 2.8% reduction in all F/M courses, a relative 3.1% reduction in F/M exposures to bystander pathogens, and a relative 0.9% reduction in all antibiotic courses. These results reflect Shigella incidence and antibiotic use patterns at the 8 MAL-ED sites and may not be generalizable to all low-resource settings. Our simulation results suggest that a Shigella vaccine meeting WHO targets for efficacy could prevent about a third of Shigella diarrhea episodes, antibiotic use to treat shigellosis, and bystander exposures due to shigellosis treatment. However, the reductions in overall diarrhea episodes and antibiotic use are expected to be modest (<5%).