A path model examination: maternal anxiety and parenting mediate the association between maternal adverse childhood experiences and children's internalizing behaviors.

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 (meanage = 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.

A study on the association of placental and maternal urinary phthalate metabolites.

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 (2nd, 3rd 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 ×102 nmol/l) and in placental tissue (GM 2.56 ×104 nmol/l). MEHP was the least abundant in urine (GM 5.32 ×101 nmol/l) and second most abundant in placental tissue (2.04 ×104 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.

Maternal early exposure to violence, psychopathology, and child adaptive functioning: pre- and postnatal programming.

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.

Prenatal urinary metabolites of polycyclic aromatic hydrocarbons and toddler cognition, language, and behavior.

BACKGROUND: Animal and epidemiological studies suggest that prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) may negatively impact toddler neurodevelopment. METHODS: We investigated this association in 835 mother-child pairs from CANDLE, a diverse pregnancy cohort in the mid-South region of the U.S. PAH metabolite concentrations were measured in mid-pregnancy maternal urine. Cognitive and Language composite scores at ages 2 and 3 years were derived from the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley-3). Behavior Problem and Competence scores at age 2 were derived from the Brief Infant and Toddler Social Emotional Assessment (BITSEA). We used multivariate linear or Poisson regression to estimate associations with continuous scores and relative risks (RR) of neurodevelopment delay or behavior problems per 2-fold increase in PAH, adjusted for maternal health, nutrition, and socioeconomic status. Secondary analyses investigated associations with PAH mixture using Weighted Quantile Sum Regression (WQS) with a permutation test extension. RESULTS: 1- hydroxypyrene was associated with elevated relative risk for Neurodevelopmental Delay at age 2 (RR = 1.20, 95% CI: 1.03,1.39). Contrary to hypotheses, 1-hydroxynaphthalene was associated with lower risk for Behavior Problems at age 2 (RR = 0.90, 95% CI: 0.83,0.98), and combined 1- and 9-hydroxyphenanthrene was associated with 0.52-point higher (95% CI: 0.11,0.93) Cognitive score at age 3. For PAH mixtures, a quintile increase in hydroxy-PAH mixture was associated with lower Language score at age 2 (ßwqs = -1.59; 95% CI: -2.84, -0.34; ppermutation = 0.07) and higher Cognitive score at age 3 (ßwqs = 0.96; 95% CI: 0.11, 1.82; ppermutation = 0.05). All other estimates were consistent with null associations. CONCLUSION: In this large southern U.S. population we observed some support for adverse associations between PAHs and neurodevelopment.

The Primary Results of the Treating Adult Smokers at Risk for Weight Gain with Interactive Technology (TARGIT) Study.

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.

The Recruitment Experience of a Randomized Clinical Trial to Aid Young Adult Smokers to Stop Smoking without Weight Gain with Interactive Technology.

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/m2, 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.

Longitudinal change in energy expenditure and effects on energy requirements of the elderly.

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.

Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.

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.

Fatty acid consumption and risk of fracture in the Women's Health Initiative.

BACKGROUND: Fatty acids (FAs) may be important dietary components that modulate osteoporotic fracture risk. OBJECTIVE: The objective was to examine FA intake in relation to osteoporotic fractures. DESIGN: The participants were postmenopausal women enrolled in the Women's Health Initiative (n = 137,486). Total fractures were identified by self-report; hip fractures were confirmed by medical record review. FA intake was estimated from baseline food-frequency questionnaires and standardized to total caloric intake. No data on omega-3 (n-3) FA supplements were available. Cox proportional hazard models were constructed to estimate risk of fracture. RESULTS: Higher saturated FA consumption was associated with higher hip fracture risk [quartile 4 multivariate-adjusted hazard ratio (HR): 1.31; 95% CI: 1.11, 1.55; P for trend = 0.001]. Lower total fracture risk was associated with a higher monounsaturated FA intake (quartile 3 HR: 0.94; 95% CI: 0.89, 0.98; P for trend = 0.050) and polyunsaturated FA intake (quartile 4 HR: 0.95; 95% CI: 0.90, 0.99; P for trend = 0.019). Unexpectedly, higher consumption of marine n-3 FAs was associated with greater total fracture risk (quartile 4 HR: 1.07; 95% CI: 1.02, 1.12; P for trend = 0.010), whereas a higher n-6 FA intake was associated with a lower total fracture risk (quartile 4 HR: 0.94; 95% CI: 0.89, 0.98; P for trend 0.009). CONCLUSIONS: These results suggest that saturated FA intake may significantly increase hip fracture risk, whereas monounsaturated and polyunsaturated FA intakes may decrease total fracture risk. In postmenopausal women with a low intake of marine n-3 FAs, a higher intake of n-6 FAs may modestly decrease total fracture risk. This trial was registered at clinicaltrials.gov as NCT00000611.

Familial resemblance and diversity in bone mass and strength in the population are established during the first year of postnatal life.

Familial resemblance and diversity in bone structure and strength in adulthood are determined in part during growth. Whether these characteristics are established during gestation or shortly after birth is not known. Total-body, lumbar spine, and femoral neck size and mass and indices of tibial bending strength and distal radial compressive strength were measured using bone densitometry and quantitative computed tomography in 236 girls at 18.5 years of age. Among them, 219, 141, and 105 girls had crown-heel length (CHL) and weight recorded at birth and at 6 and 12 months of age, and then height and weight were recorded at 3, 5, 10, 13, and 15 years of age in 181, 176, 127, 111, and 228 girls, respectively. Of these girls, 101 and 93 girls also had bone structure assessed at 11 and 13 years of age, respectively. Similar bone measurements were made once in 78 mother-father pairs. CHL and weight at birth did not correlate or did so weakly with bone traits in girls at 18 years of age. By contrast, CHL at 6 months correlated with the height, bone traits, and strength at puberty and at 18 years of age (r = 0.24-0.56, p < .001) in girls and with their parents' height and bone traits (r = 0.15-0.37, p < .05). When the girls' CHL at 6 months was stratified into quartiles, the absolute and relative differences in bone traits observed at puberty (approximately 11.5 years) were maintained as these traits tracked during the ensuing 7 years. Similarly, weight at 6 months correlated with the girls' bone traits at puberty and 18 years of age (r = 0.22-0.55, p < .05). During puberty and at 18 years of age, the girls' bone traits correlated with the corresponding traits in their parents (r = 0.32-0.43, p < .01). It is concluded that familial resemblance in bone structural strength and the position of an individual's bone traits relative to others in adulthood are likely to be established during the first year of life. Thus susceptibility to bone fragility late in life has its antecedents established early in life.

Relations of dietary magnesium intake to biomarkers of inflammation and endothelial dysfunction in an ethnically diverse cohort of postmenopausal women.

OBJECTIVE: Although magnesium may favorably affect metabolic outcomes, few studies have investigated the role of magnesium intake in systemic inflammation and endothelial dysfunction in humans. RESEARCH DESIGN AND METHODS: Among 3,713 postmenopausal women aged 50-79 years in the Women's Health Initiative Observational Study and free of cardiovascular disease, cancer, and diabetes at baseline, we measured plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), turnor necrosis factor-alpha receptor 2 (TNF-alpha-R2), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin. Magnesium intake was assessed using a semiquantitative food frequency questionnaire. RESULTS: After adjustment for age, ethnicity, clinical center, time of blood draw, smoking, alcohol, physical activity, energy intake, BMI, and diabetes status, magnesium intake was inversely associated with hs-CRP (P for linear trend = 0.003), IL-6 (P < 0.0001), TNF-alpha-R2 (P = 0.0006), and sVCAM-1 (P = 0.06). Similar findings remained after further adjustment for dietary fiber, fruit, vegetables, folate, and saturated and trans fat intake. Multivariable-adjusted geometric means across increasing quintiles of magnesium intake were 3.08, 2.63, 2.31, 2.53, and 2.16 mg/l for hs-CRP (P = 0.005); 2.91, 2.63, 2.45, 2.27, and 2.26 pg/ml for IL-6 (P = 0.0005); and 707, 681, 673, 671, and 656 ng/ml for sVCAM-1 (P = 0.04). An increase of 100 mg/day magnesium was inversely associated with hs-CRP (-0.23 mg/l +/- 0.07; P = 0.002), IL-6 (-0.14 +/- 0.05 pg/ml; P = 0.004), TNF-alpha-R2 (-0.04 +/- 0.02 pg/ml; P = 0.06), and sVCAM-1 (-0.04 +/- 0.02 ng/ml; P = 0.07). No significant ethnic differences were observed. CONCLUSIONS: High magnesium intake is associated with lower concentrations of certain markers of systemic inflammation and endothelial dysfunction in postmenopausal women.

Adipocytokines and incident diabetes mellitus in older adults: the independent effect of plasminogen activator inhibitor 1.

BACKGROUND: Adipose tissue produces "adipocytokines" of uncertain clinical significance. METHODS: We analyzed the relationships among adiposity, adipocytokines, glycemia, and incident diabetes mellitus in 2356 white and black adults aged 70 to 79 years in the Health, Aging, and Body Composition Study who did not have diabetes at baseline. We measured the levels of adipocytokines adiponectin, leptin, interleukin 6, tumor necrosis factor alpha, and plasminogen activator inhibitor 1. Regional fat area was determined by means of computed tomography. New diabetes was defined as a self-reported diagnosis of diabetes or as a fasting plasma glucose level of 126 mg/dL or greater (>/=7.0 mmol/L) at the second, fourth, or sixth annual examination. RESULTS: A total of 143 participants (14.1 cases per 1000 person-years) developed diabetes across 5 years. Visceral fat area (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.10-1.60 per standard deviation increase) and body mass index (white individuals: OR, 1.65; 95% CI, 1.26-2.15 per standard deviation increase; black individuals: OR, 1.22; 95% CI, 0.99-1.51 per standard deviation increase) independently predicted incident diabetes. Adiponectin, leptin, and plasminogen activator inhibitor 1 attenuated the relationship between adiposity and diabetes. After controlling for body mass index, visceral fat, fasting glucose, fasting insulin, high-density lipoprotein cholesterol, triglycerides, and hypertension at baseline, plasminogen activator inhibitor 1 was the only adipocytokine independently associated with increased odds of diabetes (OR, 1.35; 95% CI, 1.01-1.81). Fasting glucose level at baseline remained a strong predictor of incident diabetes, whereas associations with body mass index and visceral fat were attenuated. CONCLUSIONS: Adipocytokines and glycemia partially account for the relationship between adiposity and risk of type 2 diabetes due to adiposity. Plasminogen activator inhibitor 1 may be a useful predictor of diabetes in addition to measurements of body fat.

Adipocytokines attenuate the association between visceral adiposity and diabetes in older adults.

OBJECTIVE: To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes. RESEARCH DESIGN AND METHODS: A nested case-control study from the Health, Aging, and Body Composition (Health ABC) study. We measured four adipocytokines: adiponectin, interleukin (IL)-6, tumor necrosis factor-alpha, and plasminogen activator inhibitor 1 (PAI-1). Regional fat area was determined by computed tomography scan. The 519 case subjects had diabetes defined by fasting plasma glucose level > or =126 mg/dl or by use of diabetes medications. The 519 control subjects had normal glucose tolerance and were matched by sex, race, and study site. Sex-specific logistic models were adjusted for age, race, site, total adiposity, smoking, and physical activity. RESULTS: Higher adiponectin levels were associated with lower risk of diabetes (P < 0.001). Visceral fat was the only adiposity measure associated with diabetes after adjusting for BMI (odds ratio 3.0 [2.1-4.3] in women and 1.3 [1.0-1.6] in men, P < 0.001 between-sex comparison). Adipocytokines attenuated the association between visceral fat and diabetes for both sexes but more strongly in men (women 2.3 [1.5-3.3], men 1.1 [0.9-1.4]). In men, adiponectin, IL-6, and PAI-1 remained independently associated with diabetes after adjusting for fat depots; in women, adiponectin was the only independently associated adipocytokine. Controlling for insulin, HDL, triglycerides, and blood pressure did not change these results. CONCLUSIONS: Adiponectin is associated with lower odds of diabetes in older men and women. Whereas several adipocytokines explained the relationship between visceral adiposity and diabetes in men, only adiponectin partially mediated this association among women.