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ContextIn preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce.DesignWe evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression.ResultsHigher maternal androgen levels associated with lower BMIz at birth (β = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (β = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03).ConclusionOur findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

BackgroundPrevious studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring's brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex.MethodUsing a nested case-control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1β, IL-8, IL-6, tumor necrosis factor (TNF)-α and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ = 44; affective psychoses (AP) = 44] and 100 healthy controls from a pregnancy cohort followed for > 40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models.ResultsThere were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-α levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75 = 3.33, 95% confidence interval (CI) 1.13-9.82], and greater prevalence of low TNF-α levels (ConclusionsThe results underscore the importance of immunologic processes affecting fetal brain development and differential risk for psychoses depending on psychosis subtype and offspring sex.

Background: A previously conducted study of prenatal lead exposure and schizophrenia using delta-aminolevulinic acid, a biologic marker of Pb exposure, in archived maternal serum samples collected from subjects enrolled in the Childhood Health and Development Study (1959-1966) based in Oakland, California, suggested a possible association between prenatal Pb exposure and the development of schizophrenia in later life.Objectives: In the present study we extend these findings using samples collected from the New England cohort of the National Collaborative Perinatal Project (1959-1966) . Using similar methods, in this study we found results that suggest a comparable association in this cohort.Methods: We pooled matched sets of cases and controls from both the California and New England sites using a multilevel random-intercept logistic regression model, accounting for matching and site structure as well as adjusting for maternal age at delivery and maternal education.Results: The estimated odds ratio for schizophrenia associated with exposure corresponding to 15 µg/dL of blood Pb was 1.92 (95% confidence interval, 1.05-3.87 ; p = 0.03) .Conclusion: Although several limitations constrain generalizability, these results are consistent with previous findings and provide further evidence for the role of early environmental exposures in the development of adult-onset psychiatric disorders. [ABSTRACT FROM AUTHOR]

There remains considerable debate regarding the effects of maternal smoking during pregnancy on children's growth and development. Evidence that exposure to maternal smoking during pregnancy is associated with numerous adverse outcomes is contradicted by research suggesting that these associations are spurious. The authors investigated the relation between maternal smoking during pregnancy and 14 developmental outcomes of children from birth through age 7 years, using data from the Collaborative Perinatal Project (1959-1974; n = 52,919). In addition to adjusting for potential confounders measured contemporaneously with maternal smoking, the authors fitted conditional fixed-effects models among siblings that controlled for unmeasured confounders. Results from the conditional analyses indicated a birth weight difference of -85.63 g associated with smoking of >or=20 cigarettes daily during pregnancy (95% confidence interval: -131.91, -39.34) and 2.73 times' higher odds of being overweight at age 7 years (95% confidence interval: 1.30, 5.71). However, the associations between maternal smoking and 12 other outcomes studied (including Apgar score, intelligence, academic achievement, conduct problems, and asthma) were entirely eliminated after adjustment for measured and unmeasured confounders. The authors conclude that the hypothesized effects of maternal smoking during pregnancy on these outcomes either are not present or are not distinguishable from a broader range of familial factors associated with maternal smoking. [ABSTRACT FROM AUTHOR]

Objectives: 1) To investigate the comorbidity of verbal and nonverbal learning disability subtypes with several domains of behavior problems among 8-year-old children. 2) To determine whether receipt of an early intervention modified the association between childhood behavior problems and learning disabilities (LD). Methods: This is a secondary data analysis of the Infant Health and Development Program (IHDP), a randomized clinical trial of an early intervention provided between ages 0 and 3 involving 985 children born low birthweight and premature. The findings are based on a prospective follow-up of these children at 8 years of age. Results: Compared to children without verbal LD (VLD), those with VLD were twice as likely to exhibit clinical levels of total behavior problems and 89% more likely to exhibit externalizing behavior problems. Analysis of specific subscales of behavior revealed significant associations with anxious/depressed and withdrawn behaviors, as well as an increased likelihood of attention problems among children with VLD. No significant association was found between nonverbal LD (NVLD) and any type of behavior problem. Furthermore, there was a significant interaction between VLD and the intervention, in which the odds of internalizing behavior problems were greater among children with VLD. No interaction effect of the intervention occurred for any type of behavior problem among children with NVLD. Conclusions: These findings provide evidence that distinct differences exist for different learning disability subtypes with regards to behavioral outcomes and the effects of early intervention services among 8-year-old children. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We examined whether retail tobacco outlet density was related to youth cigarette smoking after control for a diverse range of neighborhood characteristics. METHODS: Data were gathered from 2116 respondents (aged 11 to 23 years) residing in 178 census tracts in Chicago, Ill. Propensity score stratification methods for continuous exposures were used to adjust for potentially confounding neighborhood characteristics, thus strengthening causal inferences. RESULTS: Retail tobacco outlets were disproportionately located in neighborhoods characterized by social and economic disadvantage. In a model that excluded neighborhood confounders, a marginally significant effect was found. Youths in areas at the highest 75th percentile in retail tobacco outlet density were 13% more likely (odds ratio [OR]=1.13; 95% confidence interval [CI]=0.99, 1.28) to have smoked in the past month compared with those living at the lowest 25th percentile. However, the relation became stronger and significant (OR=0.21; 95% CI=1.04, 1.41) after introduction of tract-level confounders and was statistically significant in the propensity score-adjusted model (OR = 1.20; 95% CI = 1.001, 1.44). Results did not differ significantly between minors and those legally permitted to smoke. CONCLUSIONS: Reductions in retail tobacco outlet density may reduce rates of youth smoking. [ABSTRACT FROM AUTHOR]

BACKGROUND: Despite an extensive literature, there have been widely divergent findings regarding the direction of the association between area socio-economic characteristics and area suicide rates, with high-quality studies finding either a direct relation (higher rates of suicide in higher socio-economic areas), an inverse relation (lower rates of suicide in higher socio-economic areas) or no association. METHOD: We performed a systematic review of the literature dating from 1897 to 2004 and identified 86 publications with 221 separate analyses that met our inclusion criteria. We examined the percent of direct, inverse and null findings stratified by key study characteristics including size of aggregated area, socio-economic measure used, region of study, control variables and study design. RESULTS: Analyses at the community level are significantly more likely to demonstrate lower rates of suicide among higher socio-economic areas than studies using larger areas of aggregation. Measures of area poverty and deprivation are most likely to be inversely associated with suicide rates and median income is least likely to be inversely associated with suicide rates. Analyses using measures of unemployment and education and occupation were equally likely to demonstrate inverse associations. Study results did not vary significantly by gender or by study design. CONCLUSIONS: The heterogeneity of associations is mostly accounted for by study design features that have largely been neglected in this literature. Enhanced attention to size of region and measurement strategies provide a clearer picture of how suicide rates vary by region. Resources for suicide prevention should be targeted to high poverty/deprivation and high unemployment areas. [ABSTRACT FROM AUTHOR]

BACKGROUND: To examine the familial associations of overt and covert antisocial behavior within the diagnosis of conduct disorder (CD) in families ascertained by referred children with attention-deficit hyperactivity disorder (ADHD), and to test if these familial associations differed between male and female probands. METHOD: Subjects were clinically-referred male and female ADHD children (n = 273) and their first-degree biological relatives (n = 807). Scores for overt and covert conduct problems were calculated by summing the DSM-III-R conduct disorder symptoms, as derived from structured diagnostic interviews. Familial aggregation analyses were conducted with multivariate regression modeling methodology. RESULTS: Proband overt scores significantly predicted the overt scores of their relatives, and proband covert scores significantly predicted the covert scores of their relatives. There was no evidence of covert symptom scores predicting overt scores or vice versa. There was some evidence that the aggregation of covert symptoms was stronger in the families of female probands. CONCLUSIONS: These results provide preliminary evidence that overt and covert conduct disorder symptoms are independently transmitted through families and may represent distinct familial syndromes. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study examined the relationship between child sexual abuse (CSA) and subsequent onset of psychiatric disorders, accounting for other childhood adversities, CSA type, and chronicity of the abuse. METHODS: Retrospective reports of CSA, other adversities, and psychiatric disorders were obtained by the National Comorbidity Survey, a nationally representative survey of the United States (n = 5877). Reports were analyzed by multivariate methods. RESULTS: CSA was reported by 13.5% of women and 2.5% of men. When other childhood adversities were controlled for, significant associations were found between CSA and subsequent onset of 14 mood, anxiety, and substance use disorders among women and 5 among men. In a subsample of respondents reporting no other adversities, odds of depression and substance problems associated with CSA were higher. Among women, rape (vs molestation), knowing the perpetrator (vs strangers), and chronicity of CSA (vs isolated incidents) were associated with higher odds of some disorders. CONCLUSIONS: CSA usually occurs as part of a larger syndrome of childhood adversities. Nonetheless, CSA, whether alone or in a larger adversity cluster, is associated with substantial increased risk of subsequent psychopathology. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This article reviews the literature on racial, ethnic, and socioeconomic disparities in morbidity and mortality, focusing on substance use and abuse. OBSERVATIONS: In most populations and societies, people of higher social position live longer and remain healthier than those of lower position. Disparities in morbidity and mortality across ethnic groups also exist. Mortality rates for African Americans are about 1.6 times higher than those for white, with much higher disparities for certain causes, such as HIV/AIDS and diabetes. Disparities also exist in the level of substance use and abuse. CONCLUSION: Racial and ethnic differences in health and health behaviors, including substance use and abuse, may partly reflect biological differences, but it is more likely that they can be explained largely by socioeconomic differences, cultural factors, and prejudice and discrimination, both institutional and individual. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This article describes patterns of onset, persistence, and cessation of substance abuse among whites, blacks, and Hispanics that are masked in cross-sectional prevalence data. METHODS: The authors analyzed longitudinal data from a sample of 1,004 white, black, and Hispanic respondents from Chicago to investigate processes of onset, persistence, and cessation of substance abuse and dependence for two age cohorts, 15 and 18 at baseline and 17 and 20 at follow-up. RESULTS: The data show few racial or ethnic differences in the prevalence of alcohol and marijuana abuse and dependence at age 15. Rates of onset of alcohol abuse and dependence among whites between ages 15 and 17 were significantly higher than for blacks and Hispanics, and the rates of onset of marijuana abuse and dependence among blacks between ages 18 and 20 were significantly higher than for whites and Hispanics of the same age group. There were few significant differences among the three groups in the persistence rates of abuse and dependence. CONCLUSION: By age 20 the rates of marijuana abuse and dependence are significantly higher among blacks than among whites and Hispanics. [ABSTRACT FROM AUTHOR]

In this article, we tested a series of Item Response Theory (IRT) models to examine the individual and neighborhood variation in perceived risk along dimensions of substance use (alcohol, marijuana, and hard drugs) and usage patterns (light/experimental use, moderate use, heavy/regular use). Data were gathered from 2266 adolescents aged 9, 12, and 15 residing in 79 Chicago neighborhoods. Developmental patterns for age and amount of use were observed whereby older respondents rated alcohol and marijuana as less harmful compared to the younger respondents, but rated hard drugs as more harmful. Risk perceptions were found to be more closely tied to one's direct experience with drugs rather than a general constellation of beliefs. Neighborhood variation in risk perceptions was also observed for hard drugs and three patterns of use, controlling for characteristics of individual residents. Neighborhoods did not vary in risk perceptions toward alcohol use. Individual-level factors rather than characteristics of the neighborhoods explained the observed neighborhood variation in perceptions toward marijuana use. These findings illustrate the complex links between individual and contextual factors in the development of beliefs about the health risks associated with substance use. [ABSTRACT FROM AUTHOR]

Many young people do not meet recommended levels of participation in physical activity. Neighborhoods may play a role in supporting healthy behavior via social and physical environmental features. We examine whether neighborhood-levels of social cohesion, range of youth services and educational attainment were associated with participation in recreational programs and general physical activity among young people. Hierarchical regression analyses were carried out using data from 680 young people (ages 11-15 years at baseline) participating in the Project on Human Development in Chicago Neighborhoods. The participants' primary caregiver reported recreational program participation at baseline and self-reported general physical activity were assessed at follow-up 2-3 years later. Neighborhood-level characteristics were obtained from census data and via a community survey. Neighborhood social cohesion was inversely associated with participation in recreational programs at baseline, controlling for availability of neighborhood services for youth, neighborhood education status, race/ethnicity, individual-level parental education, overweight status, sex, and age. Residing in an area with greater social cohesion was directly associated with frequency of reported general physical activity, independent of previously reported participation in recreational programs and other neighborhood and individual-level covariates. The present findings suggest that neighborhood social cohesion influences participation in physical activity. [ABSTRACT FROM AUTHOR]

With an increasing aging population and Alzheimer's disease tsunami, it is critical to identify early antecedents of brain aging to target for intervention and prevention. Women and men develop and age differently, thus using a sex differences lens can contribute to identification of early risk biomarkers and resilience. There is growing evidence for fetal antecedents to adult memory impairments, potentially through disruption of maternal prenatal immune pathways. Here, we hypothesized that in utero exposure to maternal pro-inflammatory cytokines will have sex-dependent effects on specific brain circuitry regulating offspring's memory and immune function that will be retained across the lifespan. Using a unique prenatal cohort, we tested this in 204 adult offspring, equally divided by sex, who were exposed/unexposed to an adverse in utero maternal immune environment and followed into early midlife (~age 50). Functional magnetic resonance imaging results showed exposure to pro-inflammatory cytokines in utero (i.e., higher maternal IL-6 and TNF-α levels) was significantly associated with sex differences in brain activity and connectivity underlying memory circuitry and performance and with a hyperimmune state, 50 years later. In contrast, the anti-inflammatory cytokine, IL-10 alone, was not significantly associated with memory circuitry in midlife. Predictive validity of prenatal exposure was underscored by significant associations with age 7 academic achievement, also associated with age 50 memory performance. Results uniquely demonstrated that adverse levels of maternal in utero pro-inflammatory cytokines during a critical period of the sexual differentiation of the brain produced long-lasting effects on immune function and memory circuitry/function from childhood to midlife that were sex-dependent, brain region-specific, and, within women, reproductive stage-dependent., Competing Interests: Competing interests: JMG is on the scientific advisory board and has an equity interest in Cala Health (a neuromodulation company). JMG’s interests are managed by MGH and MassGeneral Brigham HealthCare in accordance with the conflict of interest policies. However, the work in the study presented here is unrelated thus there is no conflict of interest., (© 2024. The Author(s).)

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods . Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for International Journal of Clinical and Health Psychology and was not involved in the editorial review or the decision to publish this article., (© 2024 The Author(s).)

Background: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS., Objectives: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes., Methods: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods., Results: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: β = -0.323, P = 0.006; PFHxS: β = -0.292, P = 0.015; PFOA: β = -0.233, P = 0.03; PFHpS: β = -0.239, P = 0.023; PFNA: β = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: β = -0.168, P = 0.020; PFHxA: β = -0.148, P = 0.018)., Conclusions: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Braun was compensated for serving as an expert witness on behalf of plaintiffs in litigation related to PFAS-contaminated drinking water., (Copyright © 2023. Published by Elsevier Inc.)

Few population studies have sufficient follow-up period to examine early-life exposures with later life diseases. A critical question is whether involuntary exposure to tobacco smoke from conception to adulthood increases the risk of cardiometabolic diseases (CMD) in midlife. In the Collaborative Perinatal Project, serum-validated maternal smoking during pregnancy (MSP) was assessed in the 1960s. At a mean age of 39 years, 1623 offspring were followed-up for the age at first physician-diagnoses of any CMDs, including diabetes, heart disease, hypertension, or hyperlipidemia. Detailed information on their exposure to environmental tobacco smoke (ETS) in childhood and adolescence was collected with a validated questionnaire. Cox regression was used to examine associations of in utero exposure to MSP and exposure to ETS from birth to 18 years with lifetime incidence of CMD, adjusting for potential confounders. We calculated midlife cumulative incidences of hyperlipidemia (25.2%), hypertension (14.9%), diabetes (3.9%), and heart disease (1.5%). Lifetime risk of hypertension increased by the 2 nd -trimester exposure to MSP (adjusted hazard ratio: 1.29, 95% confidence interval: 1.01-1.65), ETS in childhood (1.11, 0.99-1.23) and adolescence (1.22, 1.04-1.44). Lifetime risk of diabetes increased by joint exposures to MSP and ETS in childhood (1.23, 1.01-1.50) or adolescence (1.47, 1.02-2.10). These associations were stronger in males than females, in never-daily smokers than lifetime ever smokers. In conclusion, early-life involuntary exposure to tobacco smoke increases midlife risk of hypertension and diabetes in midlife.

Background: Evidence of a biologically plausible association between maternal smoking during pregnancy (MSP) and the risk of depression is discounted by null findings from two sibling studies. However, valid causal inference from sibling studies is subject to challenges inherent to human studies of MSP and biases particular to this design. We addressed these challenges in the first sibling study of MSP and depression conducted among adults past the peak age for the onset of depression, utilizing a prospectively collected and biologically validated measure of MSP and accounting for non-shared as well as mediating factors., Methods: We fit GEE binomial regression models to correct for dependence in the risk of depression across pregnancies of the same mother. We also fit marginal structural models (MSM) to estimate the controlled direct effect of MSP on depression that is not mediated by the offspring's smoking status. Both models allow the estimation of within- and between-sibling risk ratios., Results: The adjusted within-sibling risk ratios (RR W ) from both models (GEE: RR W = 1.97, CI 1.16-3.32; MSM: RR W = 2.08, CI 1.04-4.17) evinced an independent association between MSP and risk of depression. The overall effects from a standard model evinced lower associations (GEE: RR T = 1.12, CI 0.98-1.28; MSM: RR T = 1.18, CI 1.01-1.37)., Conclusions: Based on within-sibling information free of unmeasured shared confounders and accounting for a range of unshared factors, we found an effect of MSP on the offspring's risk of depression. Our findings, should they be replicated in future studies, highlight the importance of considering challenges inherent to human studies of MSP and affective disorders.

For the past 40 years, our team has conducted a unique program of research investigating the prenatal risks for schizophrenia and related adult psychiatric disorders. The New England Family Study is a long-term prospective cohort study of over 16,000 individuals followed from the prenatal period for over 50 years. This chapter summarizes several major phases and findings from this work, highlighting recent results on maternal prenatal bacterial infections and brain imaging. Implications regarding the causes and potential prevention of major psychotic disorders are discussed., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Introduction: Child abuse is associated with adult obesity. Yet, it is unknown how the developmental timing and combination of abuse types affect this risk. This report examined how distinct child and adolescent abuse patterns were associated with incident obesity in young adulthood., Methods: Data came from 7,273 participants in the Growing Up Today Study, a prospective cohort study in the U.S. with 14 waves from 1996 to 2016 (data were analyzed during 2020-2021). An abuse group variable was empirically derived using latent class analysis with indicators for child (before age 11 years) and adolescent (ages 11-17 years) physical, sexual, and emotional abuse. Risk ratios for obesity developing during ages 18-30 years were estimated using modified Poisson models. Associations of abuse groups with BMI across ages 18-30 years were then examined using mixed-effects models. All models were stratified by sex., Results: Among women, groups characterized by abuse had higher BMIs entering young adulthood and greater changes in BMI per year across young adulthood. Groups characterized by multiple abuse types and abuse sustained across childhood and adolescence had approximately twice the risk of obesity as that of women in a no/low abuse group. Associations were substantially weaker among men, and only a group characterized by physical and emotional abuse in childhood and adolescence had an elevated obesity risk (risk ratio=1.38; 95% CI=1.04, 1.83)., Conclusions: Obesity risk in young adulthood varied by distinct abuse groups for women and less strongly for men. Women who experience complex abuse patterns have the greatest risk of developing obesity in young adulthood., (Copyright © 2022 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

The understanding of the impact of prenatal exposure to metal mixtures on birth weight is limited. We aimed to identify metal mixture components associated with birth weight and to determine additional pairwise interactions between metals showing such associations. Concentrations of 18 metals were measured using inductively coupled plasma mass spectrometry in urine samples collected in the 3rd trimester from a prenatal cohort (discovery; n = 1849) and the Healthy Baby Cohort (replication; n = 7255) in Wuhan, China. In the discovery set, we used two penalized regression models, i.e., elastic net regression for main effects and a lasso for hierarchical interactions, to identify important mixture components associated with birth weight, which were then replicated. We observed that 8 of the 18 measured metals were retained by elastic net regression, with five metals (vanadium, manganese, iron, cesium, and barium) showing negative associations with Z-scores for birth weight and three metals (cobalt, zinc, and strontium) showing positive associations. In replication set, associations remained significant for vanadium ( β  = -0.035; 95% confidence interval [CI], -0.059 to -0.010), cobalt ( β  = 0.073; 95% CI, 0.049 to 0.097), and zinc ( β  = 0.040; 95% CI, 0.016 to 0.065) after Bonferroni correction. We additionally identified and replicated a single pairwise interaction between iron and copper exposure on birth weight ( P  < 0.001). Using a two-stage analysis, we identified and replicated individual metals and additional pairwise interactions-associated birth weight. The approach could be used in other studies estimating the effect of complex mixtures on human health., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. The authors have no conflict of interest to declare. JMB’s institution was financially compensated for his services as an expert witness for plaintiffs in litigation related to PFAS-contaminated drinking water; these funds were not paid to JMB directly., (© 2022 The Authors.)

Advances in developmental psychology, child psychiatry, and allied disciplines have pointed to events and experiences in the early years as the origin of many adult mental health challenges. Yet, children's mental health services still largely lack a developmental or prevention-focused orientation, with most referrals to mental health professionals occurring late, once problems are well established. An early childhood mental health system rooted in the principles of life-course health development would take a very different approach to designing, testing, and implementing prevention and intervention strategies directed toward early child mental health. Priorities for such a system include supporting healthy family environments, parent-child and family relationships, parents' emotional/behavioral health, and family routines as a means of providing the best possible neurobiological foundation for mental health across the life span. The system would include proactive, trauma-informed, multidisciplinary care, with integrated mental health and social services support embedded in pediatric primary care settings. Novel intervention approaches in need of further research include 2-generational dyadic interventions designed to improve the mental health of parents and children, mental health-oriented telemedicine, and contingency management (CM) strategies. Integral to this Life Course Health Development reformulation is a commitment by all organizations supporting children to primordial and primary prevention strategies to reduce racial and socioeconomic disparities in all settings. We contend that it is the family, not the individual child, that ought to be the identified target of these redesigned approaches, delivered through a transformed pediatric system with anticipated benefits for multiple health outcomes across the life course., (Copyright © 2022 by the American Academy of Pediatrics.)

Background: Child maltreatment may be an important risk factor for eating disorder (ED) behaviors. However, most previous research has been limited to clinical, female, and cross-sectional samples, and has not adequately accounted for complex abuse patterns., Objective: To determine whether women and men with distinct patterns of child and adolescent maltreatment have higher risks of developing ED behaviors in young adulthood than individuals with a low probability of maltreatment., Participants and Setting: Data came from 7010 U.S. women and men (95% White) in the Growing Up Today Study, a prospective, community-based cohort study (14 waves between 1996 and 2016)., Methods: We used a previously created maltreatment variable that was empirically derived using latent class analysis. Maltreatment groups were characterized as: "no/low abuse," "child physical abuse," "adolescent emotional abuse," "child and adolescent physical and emotional abuse," and "child and adolescent sexual abuse." We estimated risk ratios for ED behaviors developing in young adulthood using the modified Poisson approach with generalized estimating equations. We stratified models by sex., Results: Groups characterized by maltreatment had elevated risks of incident ED behaviors compared with the "no/low abuse" group among both women and men. For women, risks tended to be strongest among the "child and adolescent sexual abuse" group. For men, risks tended to be strongest among the "child and adolescent physical and emotional abuse" group. Risks were particularly strong for purging behaviors., Conclusion: Risk of incident ED behaviors in young adulthood varied by distinct maltreatment groups. Detecting maltreatment early may help prevent EDs and subsequent maltreatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background and Aims: Adult telomere length (TL) is substantially determined by birth TL, but associations of birth TL with cardiovascular disease (CVD) are unknown., Methods: We included 144 adult offspring born in 1959-1966 from the Collaborative Perinatal Project, a US birth cohort. Birth TL was measured from banked cord blood with quantitative polymerase chain reaction. Atherosclerotic lesions were predicted by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) score that was based on blood pressure, lipids, hemoglobin A1c, and body weight at the midlife follow-up in 2003-2008 (average age: 42 years). Information on midlife CVD risk factors including the age at first diagnoses of hypertension, hypercholesterolemia, and diabetes was also collected. We used linear and logistic regression models to analyze associations of birth TL with the continuous PDAY score and categorical CVD risk factors, respectively, adjusting for prenatal confounders., Results: At midlife follow-up, 31.2% and 18.7% of participants had ever been diagnosed with hypercholesterolemia and hypertension, respectively, and 8.3% met the criteria for metabolic syndrome. Short birth TL (Quartile 1, Q1) was associated with a higher PDAY score (adjusted β: 1.78, 95% CI: 0.31, 3.25), increased odds of hypercholesterolemia (adjusted odds ratio [OR]: 3.23, 95% CI: 1.28, 8.18) and the presence of any cardiometabolic abnormalities (adjusted OR: 2.54, 95% CI: 1.00, 6.48) as compared to longer birth TL (Q2-Q4) after adjusting for prenatal confounders., Conclusions: People born with short TL may be at increased risk of predicted midlife atherosclerotic lesions and hypercholesterolemia. Future studies with larger sample sizes and CVD morbidities are warranted to replicate our findings., (Copyright © 2021. Published by Elsevier B.V.)

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan., Competing Interests: Competing interest statement: J.M.G. is on the scientific advisory board for, and has equity interest in, Cala Health (a neuromodulation company). J.M.G.’s interests are managed by Massachusetts General Hospital and Mass General Brigham HealthCare in accordance with their conflict of interest policies. However, the work in the study presented here was conducted prior to that relationship, so there is no conflict of interest.

Background: According to the stress inoculation hypothesis, successfully navigating life stressors may improve one's ability to cope with subsequent stressors, thereby increasing psychiatric resilience., Aims: Among individuals with no baseline history of post-traumatic stress disorder (PTSD) and/or major depressive disorder (MDD), to determine whether a history of a stressful life event protected participants against the development of PTSD and/or MDD after a natural disaster., Method: Analyses utilised data from a multiwave, prospective cohort study of adult Chilean primary care attendees (years 2003-2011; n = 1160). At baseline, participants completed the Composite International Diagnostic Interview (CIDI), a comprehensive psychiatric diagnostic instrument, and the List of Threatening Experiences, a 12-item questionnaire that measures major stressful life events. During the study (2010), the sixth most powerful earthquake on record struck Chile. One year later (2011), the CIDI was re-administered to assess post-disaster PTSD and/or MDD., Results: Marginal structural logistic regressions indicated that for every one-unit increase in the number of pre-disaster stressors, the odds of developing post-disaster PTSD or MDD increased (OR = 1.21, 95% CI 1.08-1.37, and OR = 1.16, 95% CI 1.06-1.27 respectively). When categorising pre-disaster stressors, individuals with four or more stressors (compared with no stressors) had higher odds of developing post-disaster PTSD (OR = 2.77, 95% CI 1.52-5.04), and a dose-response relationship between pre-disaster stressors and post-disaster MDD was found., Conclusions: In contrast to the stress inoculation hypothesis, results indicated that experiencing multiple stressors increased the vulnerability to developing PTSD and/or MDD after a natural disaster. Increased knowledge regarding the individual variations of these disorders is essential to inform targeted mental health interventions after a natural disaster, especially in under-studied populations.

Objective: This study examined the extent to which maternal immune activity during pregnancy is associated with childhood adiposity, and if so, whether associations at birth differ from those in infancy and childhood. Sex-specific associations were also examined., Methods: Participants were 1,366 singleton pregnancies from the Collaborative Perinatal Project (1959-1966). Interleukin-1β (IL-1β), IL-6, TNF-α, IL-8, and IL-10 in maternal sera were assayed repeatedly during pregnancy. Children's BMI was calculated repeatedly from birth through age 8 and derived age- and sex-normalized BMI z scores (BMIz). Linear mixed models were used to estimate the cumulative concentration of each cytokine in the second and third trimesters and then related this concentration to child BMIz., Results: Children exposed to higher IL-1β, IL-6, IL-8, and IL-10 concentrations had lower BMIz at birth but higher BMIz during childhood. Higher concentrations of IL-8 and IL-1β were also associated with higher BMIz during infancy (B per log increase in IL-8 = 0.04; 95% CI: 0.02 to 0.07; B per log increase in IL-1β = 0.03; 95% CI: 0.001 to 0.06). The associations between TNF-α and BMIz were in opposing directions in boys (B = -0.13; 95% CI: -0.31 to 0.04) and girls (B = 0.14; 95% CI: 0.02 to 0.26) during childhood., Conclusions: Maternal prenatal inflammation contributes to the age- and sex-specific programming of obesity risk in childhood., (© 2020 The Obesity Society.)

Maternal immune activity during pregnancy has been associated with risk for psychiatric disorders in offspring, but less is known about its implications for children's emotional and behavioral development. This study examined whether concentrations of five cytokines assayed from prenatal serum were associated with socioeconomic status (SES) and racial disparities in their offspring's self-regulation abilities. Participants included 1628 women in the Collaborative Perinatal Project (CPP). Seven behavioral items conceptually related to self-regulation were rated by CPP psychologists when children were 4 years old. Concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, and IL-10 were assessed. Covariates included child sex and mother's age, psychiatric disorders, and medical conditions during pregnancy. There were significant SES differences in child self-regulation, with higher SES children scoring higher on self-regulation (β = 0.18, 95% CI [0.11, 0.25]), but no racial differences. The concentration of IL-8 in maternal serum was associated with higher child self-regulation, β = 0.09, 95% CI [0.02, 0.16]. In mediation analyses, variation in maternal IL-8 contributed to the association between family SES and child self-regulation (β = 0.02, 95% CI [0.003, 0.030]), explaining about one-tenth of the SES disparities. This study suggests pregnancy as an early sensitive period and maternal immune activity as an important context for child development., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Individuals can have vastly different maltreatment experiences depending on the types, developmental timing, and duration of abuse. Women and men may be differentially affected by distinct abuse patterns., Objective: To examine whether maltreatment subgroups could be identified based on the types, developmental timing, and duration of abuse, and to determine their prevalence among a large, community-based sample. We also examined sex differences in associations of maltreatment subgroups with adverse health outcomes., Participants and Setting: Data came from 9310 women and men (95 % White) in the United States who responded to the Growing Up Today Study questionnaire in 2007 (aged 19-27 years)., Methods: Participants reported on physical, sexual, and emotional abuse occurring in childhood (before age 11 years) and adolescence (ages 11-17 years). We conducted latent class (LC) analyses using indicators for child and adolescent abuse. We examined associations of LCs with health outcomes using sex-stratified log-binomial models with generalized estimated equations., Results: We identified five LCs characterized by: 1) no/low abuse (59 %), 2) child physical abuse (16 %), 3) adolescent emotional abuse (9%), 4) child and adolescent physical and emotional abuse (16 %), and 5) child and adolescent sexual abuse (1%). LCs were uniquely associated adult health outcomes among both women and men. Associations of LCs with eating disorder behaviors appeared stronger for men than women., Conclusions: Individuals experience distinct patterns of maltreatment based on the types, developmental timing, and duration of abuse. These patterns are uniquely associated with adverse health outcomes in adulthood, and can be identified using LCA., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Studies have shown adverse effects of a disadvantaged childhood on adult health-promoting behaviors and related outcomes. Optimism and social support have been linked to greater likelihood of engaging in healthy behavior, but it is unclear whether these positive psychosocial factors may buffer harmful effects of early adversity. This study aims to determine if optimism and social support in adulthood can modify effects of childhood disadvantage on health behavior-related outcomes., Methods: Longitudinal data were analyzed from a subset of participants in a US birth cohort established in 1959-1966 (ns of 681-840, per outcome). An index of childhood social disadvantage was derived from adverse socioeconomic and family stability factors reported by mothers at child's birth and age 7 years. Health behavior-related outcomes were self-reported when participants were of mean age 47 years. Multivariable adjusted robust Poisson regressions were performed., Results: Regardless of level of childhood social disadvantage, we found higher levels of optimism and social support were both associated with higher probabilities of being a non-smoker (relative risk [RR] optimism  = 1.17, 95% confidence interval [CI] = 1.09-1.26; RR social support  = 1.24, 95%CI = 1.11-1.39), having a healthy diet (RR optimism  = 1.25, 95%CI = 1.10-1.43; RR social support  = 1.27, 95%CI = 1.04-1.56), and a healthy body mass index (RR optimism  = 1.18, 95%CI = 1.00-1.40; RR social support  = 1.29, 95%CI = 1.00-1.66). Interactions link higher optimism or social support with lower risk of smoking among those with moderate childhood disadvantage., Conclusions: Overall, these findings are consistent with the possibility that positive psychosocial resources contribute to maintaining a healthy lifestyle in mid-adulthood and may buffer effects of childhood social disadvantage.

Background: Schizophrenia has been associated with pregnancy and birth complications and fetal exposure to inflammation is thought to be a common underlying mechanism. However, whether the risk is specific to particular phases of pregnancy is unclear. The aim of this study was to characterise and compare longitudinal patterns of maternal serum concentrations of cytokines across pregnancy between offspring who were later ascertained to have a psychotic disorder, non-psychotic siblings of these cases, and unrelated, non-psychotic individuals who served as controls., Methods: The National Collaborative Perinatal Project was a large-scale prospective longitudinal study that assessed the effects of perinatal factors on infant and child development. At sites across the USA, over 50 000 pregnant women were enrolled during prenatal clinical visits between 1959 and 1965. The present study draws from the Philadelphia cohort, which includes 9236 surviving offspring of 6753 pregnant women. Psychotic disorder diagnoses in adulthood were assessed with review of medical records and were confirmed with a validation study. Concentrations of TNFα, IL-1β, IL-5, IL-6, IL-8, IL-10, and IL-17a were assessed using a multiplex bead assay in archived maternal serum samples collected across prenatal visits and birth. We characterized cytokine patterns with linear mixed models., Findings: Our final sample comprised 90 cases, 79 siblings (of 40 cases), and 273 matched controls. Concentrations of proinflammatory cytokines TNFα, IL-1β, and IL-6 were significantly higher in maternal serum of offspring who later developed psychosis compared with maternal serum of matched controls. These differences were greatest in the first half of pregnancy (7-20 weeks), with no difference observed during the second half of pregnancy., Interpretation: Our results suggest that exposure to high maternal proinflammatory cytokine concentrations in early pregnancy might play a part in psychosis. These findings place the timing of risk associated with maternal inflammation much earlier in prenatal development than previously documented in humans and provide insight into a potential developmental pathway to the disorder., Funding: National Institute of Mental Health (P50) Silvio O Conte Center at Johns Hopkins, Stanley Foundation, March of Dimes, Yale University, National Science Foundation, and National Institute of Child Health and Human Development/Division of Intramural Population Health Research., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Previous studies suggest that prenatal immune challenges may elevate the risk of schizophrenia and related psychoses in offspring, yet there has been limited research focused on maternal bacterial infection. The authors hypothesized that maternal bacterial infection during pregnancy increases offspring risk of psychotic disorders in adulthood, and that the magnitude of this association varies as a function of severity of infectious exposure and offspring sex., Methods: The authors analyzed prospectively collected data from 15,421 pregnancies among women enrolled between 1959 and 1966 at two study sites through the Collaborative Perinatal Project. The sample included 116 offspring with confirmed psychotic disorders. The authors estimated associations between maternal bacterial infection during pregnancy and psychosis risk over the subsequent 40 years, stratified by offspring sex and presence of reported parental mental illness, with adjustment for covariates., Results: Maternal bacterial infection during pregnancy was strongly associated with psychosis in offspring (adjusted odds ratio=1.8, 95% CI=1.2-2.7) and varied by severity of infection and offspring sex. The effect of multisystemic bacterial infection (adjusted odds ratio=2.9, 95% CI=1.3-5.9) was nearly twice that of less severe localized bacterial infection (adjusted odds ratio=1.6, 95% CI=1.1-2.3). Males were significantly more likely than females to develop psychosis after maternal exposure to any bacterial infection during pregnancy., Conclusions: The study findings suggest that maternal bacterial infection during pregnancy is associated with an elevated risk for psychotic disorders in offspring and that the association varies by infection severity and offspring sex. These findings call for additional investigation and, if the findings are replicated, public health and clinical efforts that focus on preventing and managing bacterial infection in pregnant women.

Background: Multiple sclerosis (MS) is the most common chronic neurologic disease of young adults, placing a heavy burden on patients, families, and the healthcare system. Ongoing surveillance of the incidence and prevalence of MS is critical for health policy and research, but feasible options are limited in the United States and many other countries. We investigated the feasibility of monitoring the prevalence of MS using a large national telephone survey of the adult US population., Methods: We developed questions to estimate the lifetime prevalence and age of onset of MS using the US-based Behavioral Risk Factor Surveillance System (BRFSS) and piloted these questions in 4 states (MN, RI, MD, and TX). There was a total of 45,198 respondents aged 18 years and above. Analyses investigated individual state and combined prevalence estimates along with health-related comorbidities and limitations. MS prevalence estimates from the BRFSS were compared to estimates from multi-source administrative claims and traditional population-based methods., Results: The estimated lifetime prevalence of self-reported MS (per 100,000 adults) was 682 (95% CI 528-836); 384 (95% CI 239-529) among males and 957 (95% CI 694-1,220) among females. Estimates were consistent across the 4 states but much higher than recently published estimates using population-based administrative claims data. This was observed for both national results and for MS prevalence estimates from other studies within specific states (MN, RI, and TX). Prevalence estimates for Caucasian, African American, and Hispanic respondents were 824, 741, and 349 per 100,000 respectively. Age and sex distributions were consistent with prior epidemiologic reports. Comorbidity and functional limitations were more pronounced among female than male respondents., Conclusions: While yielding higher overall MS prevalence estimates compared to recent studies, this large-scale self-report telephone method yielded relative prevalence estimates (e.g., prevalence patterns of MS by sex, age, and race-ethnicity) that were generally comparable to other surveillance approaches. With certain caveats, population-based telephone surveys may eventually offer the ability to investigate novel disease correlates and are relatively feasible, and affordable. Further work is needed to create a valid question set and methodology for case ascertainment before this approach could be adopted to accurately estimate MS prevalence., (© 2020 S. Karger AG, Basel.)

Background: Previous epidemiologic studies have reported adverse neurodevelopmental sequelae following prenatal infectious exposure, yet long-term effects estimated from these observational studies are often subject to biases due to confounding and loss to follow-up., Objectives: We demonstrate the joint use of inverse probability (IP) treatment and censoring weights when evaluating neurotoxic effects of prenatal bacterial infection., Methods: We applied IP weighting for both treatment and censoring to estimate the effects of maternal bacterial infection during pregnancy on mean intelligence quotient (IQ) scores measured at age 7 using the Wechsler Intelligence Scale for Children. Participants were members of a population-based pregnancy cohort recruited in the Boston and Providence sites of the Collaborative Perinatal Project between 1959 and 1966 (n = 11 984). We calculated average treatment effects (ATE) and average treatment effects on the treated (ATT) using IP weights estimated via generalized boosted models., Results: ATE- and ATT-weighted mean IQ scores were lowest among offspring exposed to multi-systemic bacterial infection during pregnancy and highest for those unexposed. The effects of prenatal bacterial infection were greater among male offspring, particularly on performance IQ scores. Offspring who were exposed to multi-systemic bacterial infection in the third trimester displayed the largest reduction in mean full-scale, verbal, and performance IQ scores at age 7 compared to those unexposed or exposed in earlier trimesters., Conclusions: We find that prenatal bacterial infection is associated with cognitive impairments at age 7. Associations are strongest for more severe infections, that occur in the third trimester, and among males. Public health intervention targeting bacterial infection in pregnant women may help enhance the cognitive development of offspring., (© 2019 John Wiley & Sons Ltd.)

Background: Bisphenol A (BPA) is an endocrine disruptor that affects fetal growth in experimental studies. Bisphenol F (BPF) and bisphenol S (BPS), which have been substituted for BPA in some consumer products, have also shown endocrine-disrupting effects in experimental models. However, the effects of BPF and BPS on fetal growth in humans are unknown., Objectives: Our goal was to investigate trimester-specific associations of urinary concentrations of BPA, BPF, and BPS with size at birth., Methods: The present study included 845 pregnant women from Wuhan, China (2013-2015), who provided one urine sample in each of the first, second, and third trimesters. Linear regressions with generalized estimating equations were applied to estimate trimester-specific associations of urinary bisphenol concentrations with birth weight, birth length, and ponderal index. Linear mixed-effects models were used to identify potential critical windows of susceptibility to bisphenols by comparing the exposure patterns of newborns in the 10th percentile of each birth anthropometric measurement to that of those in the 90th percentile., Results: Medians (25th-75th percentiles) of urinary concentrations of BPA, BPF, and BPS were 1.40 (0.19-3.85), 0.65 (0.34-1.39), and 0.38 (0.13-1.11) ng/mL, respectively. Urinary BPA concentrations in different trimesters were inversely, but not significantly, associated with birth weight and ponderal index. Urinary concentrations of BPF and BPS during some trimesters were associated with significantly lower birth weight, birth length, or ponderal index, with significant trend p -values ( p trend < 0.05 ) across quartiles of BPF and BPS concentrations. The observed associations were unchanged after additionally adjusting for other bisphenols. In addition, newborns in the 10th percentile of each birth anthropometry measure had higher BPF and BPS exposures during pregnancy than newborns in the 90th percentile of each outcome., Conclusions: Prenatal exposure to BPF and BPS was inversely associated with size at birth in this cohort. Replication in other populations is needed. https://doi.org/10.1289/EHP4664.

Rationale: In 2017, the American College of Cardiology (ACC)/American Heart Association (AHA) released a new hypertension guideline for nonpregnant adults, using lower blood pressure values to identify hypertension. However, the impact of this new guideline on the diagnosis of gestational hypertension and the associated maternal and neonatal risks are unknown., Objective: To estimate the impact of adopting the 2017 ACC/AHA guideline on detecting gestational blood pressure elevations and the relationship with maternal and neonatal risk in the perinatal period using a retrospective cohort design., Methods and Results: This study included 16 345 women from China. Systolic and diastolic blood pressures of each woman were measured at up to 22 prenatal care visits across different stages of pregnancy. Logistic and linear regressions were used to estimate associations of blood pressure categories with the risk of preterm delivery, early-term delivery, and small for gestational age, and indicators of maternal liver, renal, and coagulation functions during pregnancy. We identified 4100 (25.1%) women with gestational hypertension using the 2017 ACC/AHA guideline, compared with 4.2% using the former definition. Gestational hypertension, but not elevated blood pressure (subclinical blood pressure elevation), was significantly associated with altered indicators of liver, renal, and coagulation functions during pregnancy for mothers and increased risk of adverse birth outcomes for newborns; adjusted odds ratios (95% CIs) for gestational hypertension stage 2 were 2.23 (1.18-4.24) for preterm delivery, 2.05 (1.67-2.53) for early-term delivery, and 1.43 (1.13-1.81) for small for gestational age., Conclusions: Adopting the 2017 ACC/AHA guideline would result in a substantial increase in the prevalence of gestational hypertension; subclinical blood pressure elevations during late pregnancy were not associated with increased maternal and neonatal risk in this cohort. Therefore, the 2017 ACC/AHA guideline may improve the detection of high blood pressure during pregnancy and the efforts to reduce maternal and neonatal risk. Replications in other populations are required.

Objective: To generate a national multiple sclerosis (MS) prevalence estimate for the United States by applying a validated algorithm to multiple administrative health claims (AHC) datasets., Methods: A validated algorithm was applied to private, military, and public AHC datasets to identify adult cases of MS between 2008 and 2010. In each dataset, we determined the 3-year cumulative prevalence overall and stratified by age, sex, and census region. We applied insurance-specific and stratum-specific estimates to the 2010 US Census data and pooled the findings to calculate the 2010 prevalence of MS in the United States cumulated over 3 years. We also estimated the 2010 prevalence cumulated over 10 years using 2 models and extrapolated our estimate to 2017., Results: The estimated 2010 prevalence of MS in the US adult population cumulated over 10 years was 309.2 per 100,000 (95% confidence interval [CI] 308.1-310.1), representing 727,344 cases. During the same time period, the MS prevalence was 450.1 per 100,000 (95% CI 448.1-451.6) for women and 159.7 (95% CI 158.7-160.6) for men (female:male ratio 2.8). The estimated 2010 prevalence of MS was highest in the 55- to 64-year age group. A US north-south decreasing prevalence gradient was identified. The estimated MS prevalence is also presented for 2017., Conclusion: The estimated US national MS prevalence for 2010 is the highest reported to date and provides evidence that the north-south gradient persists. Our rigorous algorithm-based approach to estimating prevalence is efficient and has the potential to be used for other chronic neurologic conditions., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Background: Early exposure to socioeconomic disadvantage is associated with obesity. Here we investigated how early, and conducted mediation analyses to identify behavioural factors in adulthood that could explain why., Methods: Among 931 participants in the New England Family Study, we investigated the associations of family socioeconomic disadvantage measured before birth and at age 7 years with the following measures of adiposity in mid-adulthood (mean age = 44.4 years): body mass index (BMI), waist circumference and, among 400 participants, body composition from dual-energy X-ray absorption scans., Results: In linear regressions adjusting for age, sex, race and childhood BMI Z-score, participants in the highest tertile of socioeconomic disadvantage at birth had 2.6 additional BMI units in adulthood [95% confidence interval (CI) = 1.26, 3.96], 5.62 cm waist circumference (95% CI = 2.69, 8.55), 0.73 kg of android fat mass (95% CI = 0.25, 1.21), and 7.65 higher Fat Mass Index (95% CI = 2.22, 13.09). Conditional on disadvantage at birth, socioeconomic disadvantage at age 7 years was not associated with adult adiposity. In mediation analyses, 10-20% of these associations were explained by educational attainment and 5-10% were explained by depressive symptoms., Conclusions: Infancy may be a sensitive period for exposure to socioeconomic disadvantage, as exposure in the earliest years of life confers a larger risk for overall and central adiposity in mid-adulthood than exposure during childhood. Intervention on these two adult risk factors for adiposity would, if all model assumptions were satisfied, only remediate up to one-fifth of the excess adult adiposity among individuals born into socioeconomically disadvantaged households., (Published by Oxford University Press on behalf of the International Epidemiological Association 2018. This work is written by US Government employees and is in the public domain in the US.)

Background: Prenatal overexposure to manganese (Mn), an essential micronutrient, is related to impaired fetal growth and development. Fetuses appear to be highly sensitive to Mn during short periods of gestation. However, little is known about the critical windows of susceptibility to Mn for humans., Objectives: Our objective was to estimate trimester-specific associations of exposure to Mn with size at birth., Methods: Urine samples of 3,022 women were collected repeatedly in the first, second, and third trimesters in Wuhan, China. Urinary concentrations of Mn and other toxic metals were measured using an inductively coupled plasma mass spectrometry. Trimester-specific associations of specific gravity–adjusted urinary Mn concentrations with birth weight, birth length, and ponderal index were estimated using multivariable linear regressions with generalized estimating equations. Linear mixed models were applied to evaluate the windows of susceptibility to Mn exposure by comparing the pattern of Mn exposure among newborns with restricted size at birth to those without., Results: When compared with the third quintile of urinary Mn concentrations, both higher and lower quintiles of urinary Mn concentrations in the second and third trimesters were related to reduced birth weight, birth length, and ponderal index. But the observed associations for higher quintiles were stronger and more likely to be statistically significant [e.g., for women who were in the fifth quintile of Mn concentration in the third trimester, the reduction in birth weight was [Formula: see text] (95% CI: [Formula: see text], [Formula: see text]) g and in birth length was [Formula: see text] (95% CI: [Formula: see text], 0.00) cm]. Moreover, newborns with restricted size at birth, compared with those without, had higher levels of Mn exposure in the second and third trimesters., Conclusions: This prospective prenatal cohort study revealed an association of exposure to Mn during pregnancy, especially late pregnancy, with restricted size at birth. Replications are needed. https://doi.org/10.1289/EHP3423.

Context: Growing preclinical evidence suggests that hormonal programming by androgens in utero may contribute to cardiovascular disease risk in adult offspring. However, the effect of prenatal androgens on cardiometabolic outcomes in the human population, especially their potential differential impact on male vs female offspring, has not been well studied., Design: Adult offspring (n = 274) of mothers enrolled in the New England birth cohorts of the Collaborative Perinatal Project were assessed at ages 39 to 50. Androgen bioactivity was measured in maternal serum during the third trimester using a receptor-mediated luciferase expression bioassay. Metabolic syndrome (MetS) using Adult Treatment Panel III criteria was assessed in adult offspring. Bioactive androgens were analyzed as quartiles, with the lowest quartile (Q1) defined as the reference. Generalized estimating equations were used to evaluate the relationship of maternal bioactive androgens on offspring MetS risk overall and by sex, controlling for potential confounders and intrafamilial correlation., Results: Mean age and body mass index of adult offspring were 44.7 ± 2.6 years and 29.7 ± 6.7 kg/m2, respectively. Participants born to mothers with the highest quartile (Q4) compared with Q1 of bioactive androgens had higher risk for MetS [adjusted odds ratio (aOR): 2.53(1.07 to 6.02)]. Stratified by sex, this association was found to be significant among women [Q4 vs Q1; aOR: 4.06 (1.10 to 14.93)] but not men [Q4 vs Q1; aOR: 1.67 (0.53 to 5.26)]. Women born to mothers with the highest levels of maternal bioactive androgens also demonstrated a 4.84-fold increased odds for having hypertension [Q4 vs Q1; aOR: 4.84 (1.12 to 20.85)]., Conclusion: Higher levels of maternal androgens were associated with increased risk for incident MetS in adult offspring, an effect that was significant in women but not men.

Alcohol use and its consequences have often been associated with depression, particularly among female college students. Interpretation of this association has been challenging due to potential reverse causation. The current study sought to clarify the temporality of these relationships. We examined: (1) the association between alcohol consumption and onset depression among female college students, and (2) the association between drinking consequences and onset depression among drinkers only. We used a prospective longitudinal design. Participants were first-year female college students who completed a baseline survey at study entry, and monthly assessments of alcohol consumption, drinking consequences, and depression symptoms. Cox proportional hazards regression with time-varying covariates were constructed among the full sample (N = 412) and the drinkers only sample (N = 335). Adjusted hazard ratios accounted for known risk factors for depression such as race/ethnicity, academic challenge, not getting along with one's roommate, sexual victimization prior to college, marijuana use, and socioeconomic status. For each additional average drink per week, adjusting for all covariates, there was no (95% CI: -4%, +4%) increased risk of onset depression. For each additional alcohol consequence, adjusting for all covariates, there was a 19% (95% CI: 5%, 34%) increased risk of onset depression. This significant relationship remained after adjusting for quantity of alcohol consumption. Quantity of alcohol consumed did not predict incident depression. However, experiencing alcohol consequences, regardless of consumption, did increase the risk of incident depression. College substance use and mental health interventions should aim to reduce not only alcohol consumption, but also alcohol-related consequences., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Identification of windows of heightened vulnerability to environmental factors has substantial public health implications. Prenatal exposure to vanadium has been linked to adverse birth outcomes; however, critical windows for such exposure during fetal growth remain unknown. We aimed to assess trimester-specific associations of vanadium exposure with ultrasound measures of fetal growth and birth size in a Chinese longitudinal cohort., Methods: The present study was embedded in our ongoing prospective prenatal cohort study at the Wuhan Women and Children Medical Care Center (Wuhan, Hubei, China). Pregnant women were eligible for inclusion if they provided signed informed consent and were less than 16 weeks pregnant with a single gestation, and agreed to take in-person interviews, undergo ultrasound examinations, and provide blood and urine samples. We collected urine samples and measured urinary vanadium concentrations using inductively coupled plasma mass spectrometry. We calculated SD scores for ultrasound-measured biparietal diameter, head circumference, occipitofrontal diameter, abdominal circumference, femur length, and estimated fetal weight at 16, 24, and 31 weeks of gestation. We applied linear regressions with generalised estimating equations to estimate associations of urinary vanadium concentrations in each trimester with ultrasound-measured fetal growth parameters or neonatal size at birth., Findings: As of Oct 12, 2016, we recruited 3075 women who were non-smokers and non-drinkers during pregnancy, provided up to three urine samples during the first, second, and third trimesters, and gave birth to live singletons without birth defects. We excluded women who did not provide information on ultrasound measurements (n=20) or who only had one ultrasound measurement of fetal crown-rump length at the first trimester (n=14). We excluded another 16 women because they had missing values for confounding variables, leaving 3025 women retained in the study. Every doubling of urinary vanadium concentration in the first trimester was associated with a significant increase in femur length (adjusted percentage change 6·4%, 95% CI 0·7 to 12·1) at 16 weeks of gestation and reductions in biparietal diameter (-4·2%, -8·2 to -0·1), head circumference (-6·0%, -10·1 to -1·9), occipitofrontal diameter (-5·7%, -9·9 to -1·5), and abdominal circumference (-5·3%, -9·4 to -1·2) at 31 weeks of gestation. Every doubling of urinary vanadium concentration in the second trimester was significantly associated with reductions in SD scores for head circumference (-7·2%, -14·1 to -0·3) and abdominal circumference (-6·9%, -13·8 to -0·1) at 31 weeks of gestation. The highest quartile of urinary vanadium concentration (>1·18 μg/L) in the first trimester, when compared with the lowest quartile (≤0·60 μg/L), was associated with a mean decrease in birthweight of 12·6 g (95% CI 2·5-22·8; p trend =0·0055) and a mean decrease in ponderal index of 0·07 kg/m 3 (0·01-0·12; p trend =0·0053). Moreover, newborns with restricted birth size had higher vanadium exposure in the first and third trimesters., Interpretation: Vanadium might be toxic to humans and impair fetal growth. The first, early second, and late third trimesters could be critical windows for heightened vulnerability to vanadium for fetal growth. Our findings require further investigation in other populations., Funding: National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Huazhong University of Science and Technology., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear., Methods: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations., Results: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day., Conclusions: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors., (© 2018 World Obesity Federation.)

Background/objectives: A number of meta-analyses suggest an association between any maternal smoking in pregnancy and offspring overweight obesity. Whether there is a dose-response relationship across number of cigarettes and whether this differs by sex remains unclear., Subject/methods: Studies reporting number of cigarettes smoked during pregnancy and offspring BMI published up to May 2015 were searched. An individual patient data meta-analysis of association between the number of cigarettes smoked during pregnancy and offspring overweight (defined according to the International Obesity Task Force reference) was computed using a generalized additive mixed model with non-linear effects and adjustment for confounders (maternal weight status, breastfeeding, and maternal education) and stratification for sex., Results: Of 26 identified studies, 16 authors provided data on a total of 238,340 mother-child-pairs. A linear positive association was observed between the number of cigarettes smoked and offspring overweight for up to 15 cigarettes per day with an OR increase per cigarette of 1.03, 95% CI = [1.02-1.03]. The OR flattened with higher cigarette use. Associations were similar in males and females. Sensitivity analyses supported these results., Conclusions: A linear dose-response relationship of maternal smoking was observed in the range of 1-15 cigarettes per day equally in boys and girls with no further risk increase for doses above 15 cigarettes.

Aim: The objective of this study was to identify potential epigenetic mediating pathways linking early life social disadvantage (ELSD) to adulthood BMI., Methods: Sex-specific epigenome-wide two-stage mediation analyses were conducted in blood and adipose tissue, and mediation estimates were obtained using cross-product mediation analysis. Pathway analyses were conducted using GREAT software (Bejerano Lab, CA, USA)., Results: Candidate mediation CpG sites were identified in adipose tissue, but not blood, and were sex-specific. Significant mediation sites in females included CpG loci in genes: PKHG1, BCAR3, ADAM5P, PIEZO1, FGFRL1, FASN and DPP9, among others. Pathway analyses revealed evidence of enrichment for processes associated with TFG-β signaling and immunologic signatures. In males, significant mediation loci included sites in MAP3K5 and RPTOR, which have previously been associated with adipogenesis, inflammation and insulin resistance., Conclusion: Our findings provide supportive evidence for the mediating role of epigenetic mechanisms in the effect of early life social disadvantage on adulthood BMI.