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Background: Children from families with low socioeconomic status (SES), as determined by income, experience several negative outcomes, such as higher rates of newborn mortality and behavioral issues. Moreover, associations between DNA methylation and low income or poverty status are evident beginning at birth, suggesting prenatal influences on offspring development. Recent evidence suggests neighborhood opportunities may protect against some of the health consequences of living in low income households. The goal of this study was to assess whether neighborhood opportunities moderate associations between household income (HI) and neonate developmental maturity as measured with DNA methylation., Methods: Umbilical cord blood DNA methylation data was available in 198 mother-neonate pairs from the larger CANDLE cohort. Gestational age acceleration was calculated using an epigenetic clock designed for neonates. Prenatal HI and neighborhood opportunities measured with the Childhood Opportunity Index (COI) were regressed on gestational age acceleration controlling for sex, race, and cellular composition., Results: Higher HI was associated with higher gestational age acceleration (B = .145, t = 4.969, p = 1.56x10-6, 95% CI [.087, .202]). Contrary to expectation, an interaction emerged showing higher neighborhood educational opportunity was associated with lower gestational age acceleration at birth for neonates with mothers living in moderate to high HI (B = -.048, t = -2.08, p = .03, 95% CI [-.092, -.002]). Female neonates showed higher gestational age acceleration at birth compared to males. However, within males, being born into neighborhoods with higher social and economic opportunity was associated with higher gestational age acceleration., Conclusion: Prenatal HI and neighborhood qualities may affect gestational age acceleration at birth. Therefore, policy makers should consider neighborhood qualities as one opportunity to mitigate prenatal developmental effects of HI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pilkay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Traffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression., Methods: Whole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO 2 exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO 2 or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10)., Results: In GAPPS, final-month NO 2 exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO 2 on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO 2 on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants)., Discussion: Overall, pregnancy NO 2 exposure and placental gene expression associations were primarily null, with exception of final month NO 2 exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2, CEBPA, and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation., Competing Interests: Declaration of competing interest All authors have read and approved the submission of the manuscript. The Institutional Review Boards of all participating institutions approved study protocols. Neither the authors nor the institutions with which they are affiliated have any direct or indirect financial interest in the subject matter of our research. All authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Phthalate exposure in pregnancy is typically estimated using maternal urinary phthalate metabolite levels. Our aim was to evaluate the association of urinary and placental tissue phthalates, and to explore the role of maternal and pregnancy characteristics that may bias estimates., Methods: Fifty pregnancies were selected from the CANDLE Study, recruited from 2006 to 2011 in Tennessee. Linear models were used to estimate associations of urinary phthalates (2 nd , 3 rd trimesters) and placental tissue phthalates (birth). Potential confounders and modifiers were evaluated in categories: temporality (time between urine and placenta sample), fetal sex, demographics, social advantage, reproductive history, medication use, nutrition and adiposity. Molar and quantile normalized phthalates were calculated to facilitate comparison of placental and urinary levels., Results: Metabolites detectable in >80% of both urine and placental samples were MEP, MnBP, MBzP, MECPP, MEOHP, MEHHP, and MEHP. MEP was most abundant in urine (geometric mean [GM] 7.00 ×10 2  nmol/l) and in placental tissue (GM 2.56 ×10 4  nmol/l). MEHP was the least abundant in urine (GM 5.32 ×10 1  nmol/l) and second most abundant in placental tissue (2.04 ×10 4  nmol/l). In aggregate, MEHP differed the most between urine and placenta (2.21 log units), and MEHHP differed the least (0.07 log units). MECPP was positively associated between urine and placenta (regression coefficient: 0.31 95% CI 0.09, 0.53). Other urine-placenta metabolite associations were modified by measures of social advantage, reproductive history, medication use, and adiposity., Conclusion: Phthalates were ubiquitous in 50 full-term placental samples, as has already been shown in maternal urine. MEP and MEHP were the most abundant. Measurement and comparison of urinary and placental phthalates can advance knowledge on phthalate toxicity in pregnancy and provide insight into the validity and accuracy of relying on maternal urinary concentrations to estimate placental exposures., Impact Statement: This is the first report of correlations/associations of urinary and placental tissue phthalates in human pregnancy. Epidemiologists have relied exclusively on maternal urinary phthalate metabolite concentrations to assess exposures in pregnant women and risk to their fetuses. Even though it has not yet been confirmed empirically, it is widely assumed that urinary concentrations are strongly and positively correlated with placental and fetal levels. Our data suggest that may not be the case, and these associations may vary by phthalate metabolite and associations may be modified by measures of social advantage, reproductive history, medication use, and adiposity., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Children of mothers with adverse childhood experiences (ACEs) are at increased risk for developmental problems. However, the mechanisms through which a mother's experience of ACEs are transmitted to her offspring are understudied. The current study investigates potential modifiable mediators (maternal psychopathology and parenting) of the association between maternal ACEs and children's behavioral problems., Methods: We utilized data from a pregnancy cohort study ( N = 1030; CANDLE study) to investigate longitudinal associations between maternal ACEs, postpartum anxiety, observed parenting behavior, and child internalizing behaviors ( mean age = 4.31 years, s.d. age = 0.38) in a racially diverse (67% Black; 33% White/Other) sample. We used structural equation modeling to test for direct associations between maternal ACEs and children's internalizing behaviors, as well as indirect associations via two simple mediations (maternal anxiety and parenting), and one serial mediation (sequence of maternal anxiety to parenting)., Results: Simple mediation results indicated that maternal anxiety and cognitive growth fostering behaviors independently mediated the association between maternal ACEs and child internalizing. We observed no evidence of a serial mediation from ACEs to internalizing via the effects of maternal anxiety on parenting., Conclusions: This study supports and refines extant literature by confirming the intergenerational association between maternal ACEs and child internalizing behaviors in a large, diverse sample, and identifies potential modifiable mediators: maternal anxiety and parenting behaviors related to fostering cognitive development. Findings may inform interventions targeting mothers who have experienced ACEs and suggest that providing support around specific parenting behaviors and addressing maternal anxiety may reduce internalizing behaviors in children.

The association between prenatal phthalate exposure and late preterm birth (LPTB) is unclear. We examined singleton pregnancies (2006-2011) from a racially and socioeconomically diverse sample of women in the CANDLE cohort of the ECHO-PATHWAYS Consortium. Urine collected in the second and third trimester was analyzed for 14 phthalate metabolites. Multivariate logistic and linear regressions were performed for LPTB, defined as delivery 34-37 weeks, and gestational week, respectively. Models were controlled for socio-demographics, behavioral factors, clinical measurements, medical history, and phthalates in the other trimester. Effect modification by race and pregnancy stress, indicated by intimate partner violence (IPV), was investigated. We conducted a secondary analysis in women with spontaneous preterm labor. The rate of LPTB among 1408 women (61% Black, 32% White) was 6.7%. There was no evidence of decreased gestational age (GA) in association with any phthalate metabolite. Each two-fold increase in third trimester mono-benzyl phthalate (MBzP) was associated with 0.08 weeks longer gestational age (95% CI: 0.03, 0.12). When restricting to women with spontaneous labor, second trimester mono-n-butyl phthalate (MBP) was associated with 54% higher odds (95% CI: 2%, 132%) of LPTB. Associations were not modified by maternal race or IPV exposure. In conclusion, we observed mixed evidence concerning our hypothesis that prenatal phthalate exposure increases risk of LPTB, though secondary analyses suggest increased risk of spontaneous LPTB associated with MBP, which is consistent with a recent pooled analysis of 16 cohorts.

Background: The pre- and postnatal programming mechanisms, timing, and direction of effects linking maternal early exposure to violence (MEEV), psychopathology, and child adaptive functioning are understudied. Thus, the following hypotheses were tested: (H1) higher pre- and postnatal maternal psychopathology will predict lower adaptive functioning, (H2) lower adaptive functioning will predict higher subsequent maternal psychopathology, (H3) cumulative effects of MEEV on maternal psychopathology and adaptive functioning will be observed, and (H4) higher MEEV will predict lower adaptive functioning via maternal psychopathology both pre- and postnatally., Methods: Prospective pregnancy cohort study including 1503 mother-child dyads with associations between MEEV, psychopathology, and child adaptive functioning examined using cross-lagged panel analysis. Assessment occurred in the third trimester and annually across the first four years of life., Results: Higher pre- and postnatal maternal psychopathology predicted lower child adaptive functioning at 12 and 24 months, respectively. MEEV predicted maternal psychopathology cumulatively and offered a repeated prediction of adaptive functioning across the first two years of the child's life, operating predominantly through maternal psychopathology during pregnancy. Child effects on mothers were not observed., Conclusions: Like in socioemotional assessment, pediatric assessment of child adaptive functioning should consider the intergenerational transmission of MEEV., Impact: Associations between maternal early exposure to violence (MEEV), psychopathology, and child socioemotional development is well documented. Much less is known about the pre- and postnatal programming mechanisms, timing, and direction of effects between MEEV, maternal psychopathology, and child adaptive functioning. Findings suggest associations of both prenatal and postnatal maternal psychopathology with child adaptive functioning, though the effects of MEEV were more strongly operative through the prenatal pathway. Pediatric assessment and interventions surrounding adaptive functioning should consider the potential role of MEEV in shaping children's health and development, in addition to potential consequences of pre- and postnatal maternal mental health., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: While strong evidence supports adverse maternal and offspring consequences of air pollution, mechanisms that involve the placenta, a key part of the intrauterine environment, are largely unknown. Previous studies of air pollution and placental gene expression were small candidate gene studies that rarely considered prenatal windows of exposure or the potential role of offspring sex. We examined overall and sex-specific associations of prenatal exposure to fine particulate matter (PM 2.5 ) with genome-wide placental gene expression., Methods: Participants with placenta samples, collected at birth, and childhood health outcomes from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle, WA) (n = 205) cohorts of the ECHO-PATHWAYS Consortium were included in this study. PM 2.5 exposures during trimesters 1, 2, 3, and the first and last months of pregnancy, were estimated using a spatiotemporal model. Cohort-specific linear adjusted models were fit for each exposure window and expression of >11,000 protein coding genes from paired end RNA sequencing data. Models with interaction terms were used to examine PM 2.5 -offspring sex interactions. False discovery rate (FDR < 0.10) was used to correct for multiple testing., Results: Mean PM 2.5 estimate was 10.5-10.7 μg/m 3 for CANDLE and 6.0-6.3 μg/m 3 for GAPPS participants. In CANDLE, expression of 13 (11 upregulated and 2 downregulated), 20 (11 upregulated and 9 downregulated) and 3 (2 upregulated and 1 downregulated) genes was associated with PM 2.5 in the first trimester, second trimester, and first month, respectively. While we did not find any statistically significant association, overall, between PM 2.5 and gene expression in GAPPS, we found offspring sex and first month PM 2.5 interaction for DDHD1 expression (positive association among males and inverse association among females). We did not observe PM 2.5 and offspring sex interactions in CANDLE., Conclusion: In CANDLE, but not GAPPS, we found that prenatal PM 2.5 exposure during the first half of pregnancy is associated with placental gene expression., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Given inconsistent evidence on preconception or prenatal tobacco use and offspring autism spectrum disorder (ASD), this study assessed associations of maternal smoking with ASD and ASD-related traits. Among 72 cohorts in the Environmental Influences on Child Health Outcomes consortium, 11 had ASD diagnosis and prenatal tobaccosmoking (n = 8648). and 7 had Social Responsiveness Scale (SRS) scores of ASD traits (n = 2399). Cohorts had diagnoses alone (6), traits alone (2), or both (5). Diagnoses drew from parent/caregiver report, review of records, or standardized instruments. Regression models estimated smoking-related odds ratios (ORs) for diagnoses and standardized mean differences for SRS scores. Cohort-specific ORs were meta-analyzed. Overall, maternal smoking was unassociated with child ASD (adjusted OR, 1.08; 95% confidence interval [CI], 0.72-1.61). However, heterogeneity across studies was strong: preterm cohorts showed reduced ASD risk for exposed children. After excluding preterm cohorts (biased by restrictions on causal intermediate and exposure opportunity) and small cohorts (very few ASD cases in either smoking category), the adjusted OR for ASD from maternal smoking was 1.44 (95% CI, 1.02-2.03). Children of smoking (versus non-smoking) mothers had more ASD traits (SRS T-score + 2.37 points, 95% CI, 0.73-4.01 points), with results homogeneous across cohorts. Maternal preconception/prenatal smoking was consistently associated with quantitative ASD traits and modestly associated with ASD diagnosis among sufficiently powered United States cohorts of non-preterm children. Limitations resulting from self-reported smoking and unmeasured confounders preclude definitive conclusions. Nevertheless, counseling on potential and known risks to the child from maternal smoking is warranted for pregnant women and pregnancy planners. LAY SUMMARY: Evidence on the association between maternal prenatal smoking and the child's risk for autism spectrum disorder has been conflicting, with some studies reporting harmful effects, and others finding reduced risks. Our analysis of children in the ECHO consortium found that maternal prenatal tobacco smoking is consistently associated with an increase in autism-related symptoms in the general population and modestly associated with elevated risk for a diagnosis of autism spectrum disorder when looking at a combined analysis from multiple studies that each included both pre- and full-term births. However, this study is not proof of a causal connection. Future studies to clarify the role of smoking in autism-like behaviors or autism diagnoses should collect more reliable data on smoking and measure other exposures or lifestyle factors that might have confounded our results., (© 2022 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals LLC.)

Background: Childhood asthma is a common chronic disease that likely has prenatal origins. Gestational diabetes alters maternal physiology and may influence fetal risk for childhood-onset disease. However, the association between gestational diabetes and child asthma is not well characterized., Objective: To investigate the association between gestational diabetes and wheeze/asthma at approximately 4 years of age in a racially diverse US cohort., Methods: We studied mother-child dyads enrolled prenatally in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study. Gestational diabetes was determined by medical chart review. At approximately 4 years of age, we assessed child respiratory outcomes including parent report of physician-diagnosed asthma (ever), current wheeze (symptoms within the past 12 months), and current asthma (physician diagnosis and/or medication or symptoms within the past 12 months). We used the modified Poisson regression to assess associations between gestational diabetes and child respiratory outcomes, adjusting for maternal age, race, prenatal smoking, pre-pregnancy body mass index, parity, asthma history, socioeconomic status, and infant sex., Results: Among 1107 women, 66% were African American/Black. Six percent (n = 62) had gestational diabetes documented during pregnancy. Gestational diabetes was associated with increased risk of physician-diagnosed asthma (adjusted risk ratio (RR) [95% Confidence Interval]: 2.13 [1.35, 3.38]; prevalence: 14%), current wheeze (RR: 1.85 [1.23, 2.78]; prevalence: 19%), and current asthma (RR: 2.01 [1.30, 3.10]; prevalence: 16%)., Conclusions: Gestational diabetes was associated with increased risk of asthma and wheeze outcomes. Additional studies are needed to elucidate modifiable pathways underlying this association., (© 2021 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: The intrauterine environment may influence offspring blood pressure, with effects possibly extending into adulthood. The associations between prenatal nutrition and offspring blood pressure, alone or in combination with other sociodemographic or behavioral factors, are unclear., Objectives: To investigate the associations of maternal dietary patterns and plasma folate concentrations with blood pressure in children aged 4-6 years, and assess the potential effect modifications by child sex, maternal race, pre-pregnancy overweight or obesity, maternal smoking, and breastfeeding., Methods: Participants were 846 mother-child dyads from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. Maternal nutrition was characterized by the Healthy Eating Index 2010 (HEI) scores and plasma folate concentrations in pregnancy. We calculated the systolic blood pressure (SBP) and diastolic blood pressure percentiles, incorporating sex, age, and height, and categorized children as either having high blood pressure (HBP; ≥90th percentile) or normal blood pressure. Linear regressions were performed to quantify the associations between maternal nutrition and continuous blood pressure percentiles, and Poisson regressions were used to estimate the incidence rate ratio (IRR) of binary HBP. We examined the effect modifications using interaction models., Results: Mean HEI scores and folate concentrations were 60.0 (SD, 11.3) and 23.1 ng/mL (SD, 11.1), respectively. Based on measurements at 1 visit, 29.6% of the children were defined as having HBP. Maternal HEI scores and plasma folate concentrations were not associated with child blood pressure percentiles or HBP in the full cohort. Among mothers self-identified as white, there was an inverse relationship between maternal HEI score and child SBP percentile (β, -0.40; 95%CI: -0.75 to -0.06). A maternal HEI score above 59 was associated with a reduced risk of HBP in girls (IRR, 0.53; 95% CI: 0.32-0.88). No modified associations by pre-pregnancy overweight or obesity, maternal smoking, or breastfeeding were indicated., Conclusions: We found little evidence for effects of maternal nutrition during pregnancy on childhood blood pressure, but detected sex- and race-specific associations. The study contributes to the evolving scientific inquiry regarding developmental origins of disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Adequate maternal thyroid hormone (TH) is necessary for fetal brain development. The role of placental human chorionic gonadotropin (hCG) in ensuring the production of TH is less well understood. The objective of the study was to evaluate 1) associations of placental hCG and its subunits, and maternal TH in the second trimester, and 2) the single and joint effects of TH and placental hormones on cognitive development and communication at ages 1 and 3 years. Fifty individuals (5%) were selected from the CANDLE (Conditions Affecting Neurocognitive Development and Early Learning) pregnancy cohort in Memphis, Tennessee, with recruitment from 2006 to 2011, to equally represent male and female fetuses. Participants were 68% Black and 32% White. Hormones measured were maternal thyroid (thyrotropin [TSH] and free thyroxine [FT4]) and placental hormones (hCG, its hyperglycosylated form [hCG-h], and free α- [hCGα] and β-subunits [hCGβ]) in maternal serum (17-28 weeks). The primary outcome measurement was the Bayley Scales of Infant and Toddler Development. All forms of hCG were negatively associated with FT4 and not associated with TSH. hCGα was associated with cognitive development at age 1 year and jointly interacted with TSH to predict cognitive development at age 3 years. This pilot study added insight into the thyrotropic actions of hCG in the second trimester, and into the significance of this mechanism for brain development. More research is warranted to elucidate differences between hCGα, hCGβ, and hCG-h in relation to TH regulation and child brain function., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Maternal psychosocial stress increases the risk of adverse birth and postnatal outcomes for the mother and child, but the role of maternal exposure to childhood traumatic events (CTE) and multi-domain psychosocial stressors for the level and rise of placental Corticotrophin-Releasing Hormone (pCRH) across pregnancy has been understudied. In a sociodemographically and racially diverse sample of 1303 women (64% Black, 36% White/others) with low-medical risk pregnancies at enrollment from Shelby County, Tennessee, USA, blood samples were drawn twice, corresponding roughly to second and third trimester, and extracted prior to conducting radioimmune assays for pCRH. Mothers reported CTE (physical abuse, sexual abuse, or family violence, in childhood), adulthood traumatic events, and interpersonal violence during pregnancy. Neighborhood crime/deprivation was derived using geospatially-linked objective databases. General linear and mixed models tested associations between stress exposure variables and pCRH levels and rate of rise, adjusting for obstetric/clinical/health related factors. Maternal CTE did not predict pCRH levels at time 1, but positively predicted levels at time 2, and the rate of rise in pCRH across pregnancy. Race did not moderate this association. No additional maternal stress exposures across adulthood or during pregnancy predicted pCRH outcomes. Findings indicate that childhood violence or abuse exposure can become biologically embedded in a manner predicting later prenatal physiology relevant for maternal and offspring health, and that such embedding may be specific to childhood, but not adulthood, stress. Findings also highlight the placental-fetal unit as a mechanistic pathway through which intergenerational transmission of the adverse effects of childhood adversities may occur., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Importance: Inequities in social environments are likely associated with a large portion of racial disparities in childhood cognitive performance. Identification of the specific exposures associated with cognitive development is needed to inform prevention efforts., Objective: To identify modifiable factors associated with childhood cognitive performance., Design, Setting, and Participants: This longitudinal pregnancy cohort study included 1503 mother-child dyads who were enrolled in the University of Tennessee Health Science Center-Conditions Affecting Neurodevelopment and Learning in Early Life study between December 1, 2006, and July 31, 2011, and assessed annually until the children were aged 4 to 6 years. The analytic sample comprised 1055 mother-child dyads. A total of 155 prenatal, perinatal, and postnatal exposures were included to evaluate environment-wide associations. Participants comprised a community-based sample of pregnant women who were recruited between 16 weeks and 28 weeks of gestation from 4 hospitals in Shelby County, Tennessee. Women with high-risk pregnancies were excluded. Data were analyzed from June 1, 2018, to April 15, 2019., Exposures: Individual and neighborhood socioeconomic position, family structure, maternal mental health, nutrition, delivery complications, birth outcomes, and parenting behaviors., Main Outcomes and Measures: Child's full-scale IQ measured by the Stanford-Binet Intelligence Scales, Fifth Edition, at age 4 to 6 years., Results: Of 1055 children included in the analytic sample, 532 (50.4%) were female. Among mothers, the mean (SD) age was 26.0 (5.6) years; 676 mothers (64.1%) were Black, and 623 mothers (59.0%) had an educational level of high school or less. Twenty-four factors were retained in the least absolute shrinkage and selection operator regression analysis and full models adjusted for potential confounding. Associations were noted between child cognitive performance and parental education and breastfeeding; for each increase of 1.0 SD in exposure, positive associations were found with cognitive growth fostering from observed parent-child interactions (β = 1.12; 95% CI, 0.24-2.00) and maternal reading ability (β = 1.42; 95% CI, 0.16-2.68), and negative associations were found with parenting stress (β = -1.04; 95% CI, -1.86 to -0.21). A moderate increase in these beneficial exposures was associated with a notable improvement in estimated cognitive test scores using marginal means (0.5% of an SD). Black children experienced fewer beneficial cognitive performance exposures; in a model including all 24 exposures and covariates, no racial disparity was observed in cognitive performance (95% CIs for race included the null)., Conclusions and Relevance: The prospective analysis identified multiple beneficial and modifiable cognitive performance exposures that were associated with mean differences in cognitive performance by race. The findings from this observational study may help guide experimental studies focused on reducing racial disparities in childhood cognitive performance.

Trauma and related fear exert significant influence on mental and physical health throughout the lifespan and are associated with intergenerational patterns of development, health, and behavior. DNA methylation and gene expression are involved in our developmental adaptations to our experiences and can be influenced by social interventions. Patterns of DNA methylation and expression of a gene involved in neurodevelopment and psychiatric risk ( BDNF ) have been linked with childhood trauma. Given the intergenerational patterns of health and behavior, and previous links between childhood trauma and BDNF methylation and expression, this study investigated the potential for maternal history of traumatic experiences to influence development in her newborn, via changes in her newborn's BDNF methylation and expression. We found that mothers' trauma history was associated with epigenetic regulation of BDNF in their newborns. Moreover, the association between maternal trauma and BDNF methylation and expression patterns were moderated by newborn sex. Male newborns showed increased BDNF expression with maternal exposure to child abuse ( p  = .001), and increased BDNF methylation with greater maternal fear ( p  = .001). Female newborns showed reduced BDNF expression with greater maternal fear ( p  = .004). Practitioners strive to identify prevention and intervention avenues that will reduce the harmful effects of trauma. Future research should consider the potential for maternal historical trauma experiences to influence offspring DNA methylation and gene expression in a manner that could alter development and inform novel prevention strategies., Competing Interests: The authors declare there are no competing interests., (©2020 Pilkay et al.)

Background: Findings on prenatal polyunsaturated fatty acid (PUFA) intake and child wheeze and asthma have been inconsistent., Objective: We sought to examine associations between prenatal PUFA status and child wheeze/asthma and modifying effects of maternal asthma/atopy, child sex, and maternal race., Methods: Analyses included 1019 mother-child dyads with omega-3 (n-3) and omega-3 (n-6) PUFAs measured in second-trimester plasma; n-6/n-3 ratios were calculated. Child wheeze/asthma outcomes ascertained at age 4 to 6 years included ever physician-diagnosed asthma, current wheeze (symptoms past 12 months), current asthma (diagnosis and medication and/or symptoms past 12 months), and current diagnosed asthma. Each PUFA indicator and outcome was analyzed in separate models using modified Poisson regression with interaction terms., Results: In quartile (Q) analyses, higher n-6 PUFAs were associated with increased risk of ever (risk ratio [RR] high vs low [RR Q4 vs Q1], 1.70; 95% CI, 1.07-2.71) and current (RR Q4 vs Q1, 1.70; 95% CI, 1.07-2.71) diagnosed asthma, whereas n-3 PUFAs were associated with lower risk (RR Q4 vs Q1, 0.59; 95% CI, 0.33-1.03) of current diagnosed asthma (P trend  < .05 for all). Higher n-6 PUFAs were associated with a higher risk of all respiratory outcomes among children born to women with asthma (P interaction  < .05 for all outcomes). A significant 3-way interaction between child sex, maternal asthma, and n-6/n-3 PUFA indicated that male children born to women with asthma and a higher ratio had the highest risk across wheeze/asthma outcomes (P interaction  < .05)., Conclusions: Associations between prenatal PUFA status and childhood wheeze/asthma were modified by maternal history of asthma and child sex., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objectives Viral bronchiolitis is the most common cause of infant hospitalization. Folic acid supplementation is important during the periconceptional period to prevent neural tube defects. An area of investigation is whether higher prenatal folate is a risk factor for childhood respiratory illnesses. We investigated the association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Methods We conducted a retrospective cohort analysis in a subset of mother-infant dyads (n = 676) enrolled in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood study and Tennessee Medicaid. Maternal folate status was determined using 2nd trimester (16-28 weeks) plasma samples. Bronchiolitis diagnosis in the first year of life was ascertained using International Classification of Diagnosis-9 codes from Medicaid administrative data. We used multivariable logistic regression to assess the adjusted association of prenatal folate levels and infant bronchiolitis outcome. Results Half of the women in this lower-income and predominately African-American (84%) study population had high levels of folate (median 2nd trimester level 19.2 ng/mL) and 21% of infants had at least one bronchiolitis healthcare visit. A relationship initially positive then reversing between maternal plasma folate and infant bronchiolitis was observed that did not reach statistical significance (p overall  = .112, p nonlinear effect  = .088). Additional adjustment for dietary methyl donor intake did not significantly alter the association. Conclusions for Practice Results did not confirm a statistically significant association between maternal 2nd trimester plasma folate levels and infant bronchiolitis. Further work is needed to investigate the role of folate, particularly higher levels, in association with early childhood respiratory illnesses.

Background and Objective: Maternal trauma can have intergenerational consequences but little is known about whether maternal traumas affect key biological domains associated with mental health in their offspring. The objective of this study was to examine maternal lifetime history of traumatic events through mid-gestation in relation to offspring cortisol production in early childhood., Methods: The sample was comprised of 660 children (49.9% Black, 44.4% White) from a longitudinal study of mother-offspring dyads in Shelby County, Tennessee, followed from mid-gestation to child age 4 years (enrolled 2006-2011). Maternal lifetime history of traumatic life events were assessed mid-gestation using the Traumatic Life Events Questionnaire. Total cortisol output among offspring was measured using hair cortisol concentrations at ages 1 to 4 years., Results: Associations of maternal trauma history with child hair cortisol varied by child's age. No association was observed at age 1 or 2. In adjusted regression models, at ages 3 and 4, offspring of mothers in the third (β = 0.99, P < .01), fourth (β=0.72, P < .05), and fifth (β=0.83, P < .01) quintiles of trauma exposure history had elevated (natural log) hair cortisol concentrations, relative to mothers in the lowest quintile (P-trend = 0.003). The associations were not attenuated after adjustment for theorized pathways, including premature birth, maternal postpartum depression, and maternal parenting stress., Conclusions: Maternal lifetime trauma exposures are associated with offspring hair cortisol concentrations. Future research is needed to determine intermediary mechanisms and functional significance of elevated hair cortisol concentration in young children., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To evaluate whether a behavioral weight management program combined with a smoking cessation program delivered via interactive technology could prevent postcessation weight gain., Methods: Three hundred and thirty young adult smokers, age 18 to 35 years, were randomized to a smoking cessation program alone (comparison group), which included behavioral counseling and nicotine replacement, or to a behavioral weight management program adapted from the Look AHEAD trial plus the same smoking cessation program (intervention group)., Results: The Treating Adult Smokers at Risk for Weight Gain with Interactive Technology study randomized 164 participants to the comparison group and 166 participants to the intervention group. On average, the participants gained 0.91 kg after 24 months in the trial (comparison group + 1.45 kg and intervention group + 0.32; P = 0.157). The only variable systematically affecting weight change over time was smoking abstinence, in which those who were abstinent, on average, gained 0.14 kg more per month compared with those who continued to smoke (P < 0.001). In exploratory analyses, the intervention participants who were abstinent at 6 months had numerically smaller weight gains compared with abstinent participants in the comparison group, but these differences were not statistically significant., Conclusions: Providing an intensive weight gain prevention program combined with a smoking cessation program via interactive technology was not associated with greater long-term weight gain prevention., (© 2017 The Obesity Society.)

Multiple recruitment strategies are often needed to recruit an adequate number of participants, especially hard to reach groups. Technology-based recruitment methods hold promise as a more robust form of reaching and enrolling historically hard to reach young adults. The TARGIT study is a randomized two-arm clinical trial in young adults using interactive technology testing an efficacious proactive telephone Quitline versus the Quitline plus a behavioral weight management intervention focusing on smoking cessation and weight change. All randomized participants in the TARGIT study were required to be a young adult smoker (18-35 years), who reported smoking at least 10 cigarettes per day, had a BMI < 40 kg/m 2, and were willing to stop smoking and not gain weight. Traditional recruitment methods were compared to technology-based strategies using standard descriptive statistics based on counts and proportions to describe the recruitment process from initial pre-screening (PS) to randomization into TARGIT. Participants at PS were majority Black (59.80%), female (52.66%), normal or over weight (combined 62.42%), 29.5 years old, and smoked 18.4 cigarettes per day. There were differences in men and women with respect to reasons for ineligibility during PS (p < 0.001; ignoring gender specific pregnancy-related ineligibility). TARGIT experienced a disproportionate loss of minorities during recruitment as well as a prolonged recruitment period due to either study ineligibility or not completing screening activities. Recruitment into longer term behavioral change intervention trials can be challenging and multiple methods are often required to recruit hard to reach groups.

Background: Very little is known about the longitudinal changes in energy requirements in late life. The purposes of this study were to: (1) determine the energy requirements in late life and how they changed during a 7 year time-span, (2) determine whether changes in fat free mass (FFM) were related to changes in resting metabolic rate (RMR), and (3) determine the accuracy of predicted total energy expenditure (TEE) to measured TEE., Methods: TEE was assessed via doubly labeled water (DLW) technique in older adults in both 1999 (n = 302; age: 74 ± 2.9 yrs) and again in 2006 (n = 87 age: 82 ± 3.1 yrs). RMR was measured with indirect calorimetry, and body composition was assessed with dual-energy x-ray absorptiometry., Results: The energy requirements in the 9th decade of life were 2208 ± 376 kcal/d for men and 1814 ± 337 kcal/d for women. This was a significant decrease from the energy requirements in the 8th decade of life in men (2482 ± 476 kcal/d vs. 2208 ± 376 kcal/d) but not in women (1892 ± 271 kcal/d vs. 1814 ± 337 kcal/d). In addition to TEE, RMR, and activity EE (AEE) also decreased in men, but not women, while FFM decreased in both men and women. The changes in FFM were correlated with changes in RMR for men (r = 0.49, p < 0.05) but not for women (r = -0.08, ns). Measured TEE was similar to Dietary Reference Intake (DRI) predicted TEE for men (2208 ± 56 vs. 2305 ± 35 kcal/d) and women (1814 ± 42 vs. 1781 ± 20 kcal/d). However, measured TEE was different than the World Health Organization (WHO) predicted TEE in men (2208 ± 56 vs. 2915 ± 31 kcal/d (p < 0.05)) and women (1814 ± 42 vs. 2315 ± 21 kcal/d (p < 0.05))., Conclusions: TEE, RMR and AEE decreased in men, but not women, from the 8th to 9th decade of life. The DRI equation to predict TEE was comparable to measured TEE, while the WHO equation over-predicted TEE in our elderly population.

Objective: The objective of this study was to investigate whether differences in admixture in African-American (AFA) and Hispanic-American (HA) adult women are associated with adiposity and adipose distribution., Design: The proportion of European, sub-Saharan African and Amerindian admixture was estimated for AFA and HA women in the Women's Heath Initiative using 92 ancestry informative markers. Analyses assessed the relationship between admixture and adiposity indices., Subjects: The subjects included 11 712 AFA and 5088 HA self-identified post-menopausal women., Results: There was a significant positive association between body mass index (BMI) and African admixture when BMI was considered as a continuous variable, and age, education, physical activity, parity, family income and smoking were included covariates (P<10(-4)). A dichotomous model (upper and lower BMI quartiles) showed that African admixture was associated with a high odds ratio (OR=3.27 (for 100% admixture compared with 0% admixture), 95% confidence interval 2.08-5.15). For HA, there was no association between BMI and admixture. In contrast, when waist-to-hip ratio (WHR) was used as a measure of adipose distribution, there was no significant association between WHR and admixture in AFA but there was a strong association in HA (P<10(-4); OR Amerindian admixture=5.93, confidence interval=3.52-9.97)., Conclusion: These studies show that: (1) African admixture is associated with BMI in AFA women; (2) Amerindian admixture is associated with WHR but not BMI in HA women; and (3) it may be important to consider different measurements of adiposity and adipose distribution in different ethnic population groups.

Body fat distribution, particularly centralized obesity, is associated with metabolic risk above and beyond total adiposity. We performed genome-wide association of abdominal adipose depots quantified using computed tomography (CT) to uncover novel loci for body fat distribution among participants of European ancestry. Subcutaneous and visceral fat were quantified in 5,560 women and 4,997 men from 4 population-based studies. Genome-wide genotyping was performed using standard arrays and imputed to ~2.5 million Hapmap SNPs. Each study performed a genome-wide association analysis of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), VAT adjusted for body mass index, and VAT/SAT ratio (a metric of the propensity to store fat viscerally as compared to subcutaneously) in the overall sample and in women and men separately. A weighted z-score meta-analysis was conducted. For the VAT/SAT ratio, our most significant p-value was rs11118316 at LYPLAL1 gene (p = 3.1 × 10E-09), previously identified in association with waist-hip ratio. For SAT, the most significant SNP was in the FTO gene (p = 5.9 × 10E-08). Given the known gender differences in body fat distribution, we performed sex-specific analyses. Our most significant finding was for VAT in women, rs1659258 near THNSL2 (p = 1.6 × 10-08), but not men (p = 0.75). Validation of this SNP in the GIANT consortium data demonstrated a similar sex-specific pattern, with observed significance in women (p = 0.006) but not men (p = 0.24) for BMI and waist circumference (p = 0.04 [women], p = 0.49 [men]). Finally, we interrogated our data for the 14 recently published loci for body fat distribution (measured by waist-hip ratio adjusted for BMI); associations were observed at 7 of these loci. In contrast, we observed associations at only 7/32 loci previously identified in association with BMI; the majority of overlap was observed with SAT. Genome-wide association for visceral and subcutaneous fat revealed a SNP for VAT in women. More refined phenotypes for body composition and fat distribution can detect new loci not previously uncovered in large-scale GWAS of anthropometric traits., Competing Interests: DMG is an employee of Merck. The remaining authors have declared that no other competing interests exist.