Search

Background: This study assessed associations between antenatal physical activity and the onset of spontaneous labor (SL). Methods: Data were taken from 541 participants in the third pregnancy, infection, and nutrition study who had no contraindications to antenatal physical activity. An interviewer-administered questionnaire assessed labor triggers, gestational age at birth, and physical activity within the week (24 h to 7 d) and the 24-hour period (0–24 h) prior to SL. A case-crossover design examined the association between physical activity (recreational, occupational, or any) and the risk of onset of SL within the subsequent 24 hours. Results: Overall, 21% (any), 26% (recreational), and 14% (occupational) of participants reported physical activity during the week; whereas 5% (any), 7% (recreational), and 3% (occupational) reported physical activity during the 24-hour period, prior to SL onset. Participants who reported any or occupational physical activity during the 24-hour period had a decreased likelihood of SL within the subsequent 24 hours, while participants who reported at least 30 minutes of recreational physical activity had an increased likelihood. Results remained consistent among early, full, or postterm participants. Conclusion: Recreational, but not occupational, physical activity at term may increase the likelihood of SL; however, the authors cannot rule out reverse causality.

BACKGROUND There is a lack of consensus in the literature about the association between meal patterning during pregnancy and birth outcomes. This study examined whether maternal meal patterning in the week before birth was associated with an increased likelihood of imminent spontaneous labor. METHODS Data came from 607 participants in the third phase of the Pregnancy, Infection, and Nutrition Study (PIN3). Data were collected through an interviewer-administered questionnaire after birth, before hospital discharge. Questions included the typical number of meals and snacks consumed daily, during both the week before labor onset and the 24-hour period before labor onset. A self-matched, case-crossover study design examined the association between skipping one or more meals and the likelihood of spontaneous labor onset within the subsequent 24 hours. RESULTS Among women who experienced spontaneous labor, 87.0% reported routinely eating three daily meals (breakfast, lunch, and dinner) during the week before their labor began, but only 71.2% reported eating three meals during the 24-hour period before their labor began. Compared with the week before their labor, the odds of imminent spontaneous labor were 5.43 times as high (95% CI: 3.41-8.65) within 24 hours of skipping 1 or more meals. The association between skipping 1 or more meals and the onset of spontaneous labor remained elevated for both pregnant individuals who birthed early (37

Prenatal organophosphorus pesticide (OPP) exposure has been associated with child attention-deficit/hyperactivity disorder (ADHD) in agricultural communities and those that are exposed to residentially applied insecticides. To examine this association in populations that are exposed primarily through diet, we estimate the associations between prenatal OPP exposure and preschool ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa), and describe modification by paraoxonase 1 (PON1) gene variants. We used participants from the MoBa Preschool ADHD Sub-study (n = 259 cases) and a random sample of MoBa sub-cohort participants (n = 547) with birth years from 2004 to 2008. Prenatal urinary dialkylphosphate (DAP) metabolites (total diethylphosphate [∑DEP] and total dimethylphosphate [∑DMP]) were measured by an ultra-performance liquid chromatography-time-of-flight system and summed by molar concentration. Maternal DNA was genotyped for coding variants of PON1 (Q192R and L55M). We used a multivariable logistic regression to calculate the odds ratios (OR) and 95% confidence intervals, adjusted for maternal education, parity, income dependency, age, marital status, ADHD-like symptoms, pesticide use, produce consumption, and season. We found no associations between DAP metabolite concentrations and preschool ADHD. The adjusted ORs for exposure quartiles 2–4 relative to 1 were slightly inverse. No monotonic trends were observed, and the estimates lacked precision, likely due to the small sample size and variation in the population. We found no evidence of modification by PON1 SNP variation or child sex. Maternal urinary DAP concentrations were not associated with preschool ADHD.

OBJECTIVE: To examine the association between neonatal jaundice and autism spectrum disorder (ASD) and non-ASD developmental disorder (DD). STUDY DESIGN: We analyzed data from the Study to Explore Early Development, a US multisite, case-control study conducted from 2007 to 2011. Developmental assessment classified children aged 2–5 years into: ASD (n= 636), DD (n= 777), or controls (POP; n= 926). Neonatal jaundice (n= 1054) was identified from medical records and maternal interviews. We examined associations between neonatal jaundice and ASD and DD using regression models to obtain adjusted odds ratios (aOR). RESULTS: Our results showed interaction between gestational age and neonatal jaundice. Neonatal jaundice was associated with ASD at 35–37 weeks (aOR = 1.83, 95%CI 1.05, 3.19), but not ≥38 weeks gestation (aOR = 0.97, 95%CI 0.76, 1.24). Similar results were observed with DD. CONCLUSIONS: Further exploration of timing and severity of neonatal jaundice and ASD/DD is warranted.

Previous studies have shown complications of pregnancy, often examined in aggregate, to be associated with autism spectrum disorder (ASD). Results for specific complications, such as maternal diabetes and hypertension, have not been uniformly consistent and should be investigated independently in relation to ASD in a large community-based sample. The Study to Explore Early Development (SEED), a US multisite case-control study, enrolled children born in 2003-2006 at 2-5 years of age. Children were classified into three groups based on confirmation of ASD (n = 698), non-ASD developmental delay (DD; n = 887), or controls drawn from the general population (POP; n = 979). Diagnoses of any diabetes or hypertensive disorder during pregnancy were identified from prenatal medical records and maternal self-report. Logistic regression models estimated adjusted odds ratios (aOR) and confidence intervals (CI) adjusting for maternal age, race/ethnicity, education, smoking during pregnancy, and study site. Models for hypertension were additionally adjusted for parity and plurality. Among 2,564 mothers, we identified 246 (9.6%) with any diabetes and 386 (15.1%) with any hypertension in pregnancy. After adjustment for covariates, any diabetes during pregnancy was not associated with ASD (aOR = 1.10 [95% CI 0.77, 1.56]), but any hypertension was associated with ASD (aOR = 1.69 [95% CI 1.26, 2.26]). Results were similar for DD, and any diabetes (aOR = 1.29 [95% CI 0.94, 1.78]) or any hypertension (aOR = 1.71 [95% CI 1.30, 2.25]). Some pregnancy complications, such as hypertension, may play a role in autism etiology and can possibly serve as a prompt for more vigilant ASD screening efforts. Autism Res 2019, 12: 967-975. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied if common complications in pregnancy are associated with autism spectrum disorder (ASD) in a large sample of mothers and children. Our results show an association between conditions marked by high blood pressure and ASD, but no association with conditions marked by high blood sugar and ASD. Associations were similar for children who had a developmental disorder that was not ASD, suggesting that this relationship may not be specific to ASD.

We examined language profiles of 2571 children, 30-68 months old, with autism spectrum disorder (ASD), other developmental disabilities (DD), and typical development from the general population (POP). Children were categorized as expressive dominant (ED), receptive dominant (RD), or nondominant (ND). Within each group, the ED profile was the least frequent. However, children in the ASD group were more likely to display an ED profile than those in the DD or POP groups, and these children were typically younger, had lower nonverbal cognitive skills, and displayed more severe social-affect symptoms of ASD compared to their peers with RD or ND profiles. These findings have research and clinical implications related to the focus of interventions targeting young children with ASD and other DDs.

OBJECTIVES: Population-based recruitment of a cohort of women who are currently pregnant or who may become pregnant in a given timeframe presents challenges unique to identifying pregnancy status or the likelihood of future pregnancy. Little is known about the performance of individual eligibility items on pregnancy screeners although they are critical to participant recruitment. This paper examined the patterns and respondent characteristics of key pregnancy screener items used in a large national study. METHODS: Cross-sectional analyses were conducted. Descriptive statistics and multivariable logistic regression models were used to examine nonresponse patterns to three questions (currently pregnant, trying to get pregnant and able to get pregnant). The questions were asked of 50,529 women in 17 locations across the U.S., as part of eligibility screening for the National Children’s Study Vanguard Study household-based recruitment. RESULTS: Most respondents were willing to provide information about current pregnancy, trying, and able to get pregnant: 99.3% of respondents answered all three questions and 97.4% provided meaningful answers. Nonresponse ranged from 0.3% to 2.5% for individual items. Multivariable logistic regression results identified small but statistically significant differences in nonresponse by respondent age, marital status, race/ethnicity-language, and household-based recruitment group. CONCLUSIONS FOR PRACTICE: The high levels of response to pregnancy-related items are impressive considering that the eligibility questions were fairly sensitive, were administered at households, and were not part of a respondent-initiated encounter.

Background Prenatal phthalate exposure has been linked with altered neurodevelopment, including externalizing behaviors and attention-deficit hyperactivity disorder (ADHD). However, the implicated metabolite, neurobehavioral endpoint, and child sex have not always been consistent across studies, possibly due to heterogeneity in neurodevelopmental instruments. The complex set of findings may be synthesized using executive function (EF), a construct of complex cognitive processes that facilitate ongoing goal-directed behaviors. Impaired EF can be presented with various phenotypes of poor neurodevelopment, differently across structured conditions, home/community, or preschool/school. We evaluated the relationship between prenatal phthalate exposure and comprehensive assessment of preschool EF. Methods Our study comprised 262 children with clinically significant/subthreshold ADHD symptoms and 78 typically developing children who were born between 2003 and 2008 and participated in the Preschool ADHD Substudy, which is nested within a population-based prospective cohort study, the Norwegian Mother, Father, and Child Cohort (MoBa). Twelve phthalate metabolites were measured from urine samples that their mothers had provided during pregnancy, at 17 weeks’ gestation. All children, at approximately 3.5-years, took part in a detailed clinical assessment that included parent-and teacher-rated inventories and administered tests. We used instruments that measured constructs related to EF, which include a parent-and teacher-reported Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P) and three performance-based tests: A Developmental NEuroPSYchological Assessment (NEPSY), Stanford-Binet intelligence test V (SB5), and the cookie delay task (CDT). The standard deviation change in test score per interquartile range (IQR) increase in phthalate metabolite was estimated with multivariable linear regression. We applied weighting in all models to account for the oversampling of children with clinically significant or subthreshold symptoms of ADHD. Additionally, we assessed modification by child sex and potential co-pollutant confounding. Results Elevated exposure to mono-benzyl phthalate (MBzP) during pregnancy was associated with poorer EF, across all domains and instruments, in both sex. For example, an IQR increase in MBzP was associated with poorer working memory rated by parent (1.23 [95% CI: 0.20, 2.26]) and teacher (1.13 [0.14, 2.13]) using BRIEF-P, and administered tests such as SB5 (no-verbal: 0.19 [0.09, 0.28]; verbal: 0.13 [0.01, 0.25]). Adverse associations were also observed for mono-n-butyl phthalate (MnBP) and mono-iso-butyl phthalate (MiBP), although results varied by instruments. EF domains reported by parents using BRIEF-P were most apparently implicated, with stronger associations among boys (e.g., MnBP and inhibition: 2.74 [1.77, 3.72]; MiBP and inhibition: 1.88 [0.84, 2.92]) than among girls (e.g., MnBP and inhibition: −0.63 [−2.08, 0.83], interaction p-value: 0.04; MiBP and inhibition: −0.15 [−1.04, 0.74], interaction p-value: 0.3). Differences by sex, however, were not found for the teacher-rated BRIEF-P or administered tests including NEPSY, SB5, and CDT. Conclusion and relevance Elevated mid-pregnancy MBzP, MiBP, and MnBP were associated with more adverse profiles of EF among preschool-aged children across a range of instruments and raters, with some associations found only among boys. Given our findings and accumulating evidence of the prenatal period as a critical window for phthalate exposure, there is a timely need to expand the current phthalate regulations focused on baby products to include pregnancy exposures.

To compare receipt of contraception and method effectiveness in the early postpartum period among women with and without a recent preterm birth (PTB). We used data from North Carolina birth certificates linked to Medicaid claims. We assessed contraceptive claims with dates of service within 90 days of delivery among a retrospective cohort of women who had a live birth covered by Medicaid between September 2011 and 2012 (n = 58,201). To estimate the odds of receipt of contraception by PTB status (24–36 weeks compared to 37–42 weeks [referent]), we used logistic regression and tested for interaction by parity. To estimate the relationship between PTB and method effectiveness based on the Center for Disease Control and Prevention Levels of Effectiveness of Family Planning Methods (most, moderate and least effective [referent]), we used multinomial logistic regression. Less than half of all women with a live birth covered by Medicaid in North Carolina had a contraceptive claim within 90 days postpartum. Women with a recent PTB had a lower prevalence of contraceptive receipt compared to women with a term birth (45.7% vs. 49.6%). Women who experienced a PTB had a lower odds of receiving contraception. When we stratified by parity, women with a PTB had a lower odds of contraceptive receipt among women with more than two births (0.79, 95% CI 0.74–0.85), but not among women with two births or fewer. One-fourth of women received a most effective method. Women with a preterm birth had a lower odds of receiving a most effective method (0.83, 95% CI 0.77–0.88) compared to women with a term birth. Contraceptive receipt was low among women with a live birth covered by Medicaid in North Carolina. To optimize contraceptive use among women at risk for subsequent preterm birth, family planning strategies that are responsive to women’s priorities and context, including a history of preterm birth, are needed. Access to free or affordable highly effective contraception is associated with reductions in preterm birth. Self-report data indicate that women with a very preterm birth (PTB) are less likely to use highly or moderately effective contraception postpartum compared to women delivering at later gestational ages. Using Medicaid claims data, we found that less than half of all women with a Medicaid covered delivery in North Carolina in 2011–2012 had a contraceptive claim within 90 days postpartum, and one fourth received a most effective method. Women with a PTB and more than two children were least likely to receive any method. Family planning strategies that are responsive to women’s priorities and context, including a history of preterm birth, are needed so that women may access their contraceptive method of choice in the postpartum period.

Background Contemporary human populations are exposed to elevated concentrations of organophosphate esters (OPEs) and phthalates. Some metabolites have been linked with altered thyroid function, however, inconsistencies exist across thyroid function biomarkers. Research on OPEs is sparse, particularly during pregnancy, when maintaining normal thyroid function is critical to maternal and fetal health. In this paper, we aimed to characterize relationships between OPEs and phthalates exposure and maternal thyroid function during pregnancy, using a cross-sectional investigation of pregnant women nested within the Norwegian Mother, Father, and Child Cohort (MoBa). Methods We included 473 pregnant women, who were euthyroid and provided bio-samples at 17 weeks' gestation (2004–2008). Four OPE and six phthalate metabolites were measured from urine; six thyroid function biomarkers were estimated from blood. Relationships between thyroid function biomarkers and log-transformed concentrations of OPE and phthalate metabolites were characterized using two approaches that both accounted for confounding by co-exposures: co-pollutant adjusted general linear model (GLM) and Bayesian Kernal Machine Regression (BKMR). Results We restricted our analysis to common-detect OPE and phthalate metabolites (>94%): diphenyl phosphate (DPHP), di-n-butyl phosphate (DNBP), and all phthalate metabolites. In GLM, pregnant women with summed di-isononyl phthalate metabolites (∑DiNP) concentrations in the 75th percentile had a 0.37 ng/μg lower total triiodothyronine (TT3): total thyroxine (TT4) ratio (95% credible interval: [−0.59, −0.15]) as compared to those in the 25th percentile, possibly due to small but diverging influences on TT3 (−1.99 ng/dL [−4.52, 0.53]) and TT4 (0.13 μg/dL [−0.01, 0.26]). Similar trends were observed for DNBP and inverse associations were observed for DPHP, monoethyl phthalate, mono-isobutyl phthalate, and mono-n-butyl phthalate. Most associations observed in co-pollutants adjusted GLMs were attenuated towards the null in BKMR, except for the case of ∑DiNP and TT3:TT4 ratio (−0.48 [−0.96, 0.003]). Conclusions Maternal thyroid function varied modestly with ∑DiNP, whereas results for DPHP varied by the type of statistical models.

Neurodevelopmental outcomes including behavior, executive functioning, and IQ exhibit complex correlational structures, although they are often treated as independent in etiologic studies. We performed a principal components analysis of the behavioral assessment system for children, the behavior rating inventory of executive functioning, and the Wechsler scales of intelligence in a prospective birth cohort, and estimated associations with early life characteristics. We identified seven factors: (1) impulsivity and externalizing, (2) executive functioning, (3) internalizing, (4) perceptual reasoning, (5) adaptability, (6) processing speed, and (7) verbal intelligence. Prenatal fish consumption, maternal education, preterm birth, and the home environment were important predictors of various neurodevelopmental factors. Although maternal smoking was associated with more adverse externalizing, executive functioning, and adaptive composite scores in our sample, of the orthogonally-rotated factors, smoking was only associated with the impulsivity and externalizing factor ( $$\hat{\beta}$$ − 0.82, 95% CI − 1.42, − 0.23). These differences may be due to correlations among outcomes that were accounted for by using a phenotypic approach. Dimension reduction may improve upon traditional approaches by accounting for correlations among neurodevelopmental traits.

Prenatal exposure to organophosphorus pesticides (OPs) has been associated with different neurodevelopmental outcomes across different cohorts. A phenotypic approach may address some of these differences by incorporating information across scales and accounting for the complex correlational structure of neurodevelopmental outcomes. Additionally, Bayesian hierarchical modeling can account for confounding by collinear co-exposures. We use this framework to examine associations between prenatal exposure to OPs and behavior, executive functioning, and IQ assessed at age 6-9 years in a cohort of 404 mother/infant pairs recruited during pregnancy. We derived phenotypes of neurodevelopment with a factor analysis, and estimated associations between OP metabolites and these phenotypes in Bayesian hierarchical models for exposure mixtures. We report seven factors: 1) Impulsivity and Externalizing, 2) Executive Functioning, 3) Internalizing, 4) Perceptual Reasoning, 5) Adaptability, 6) Processing Speed, and 7) Verbal Intelligence. These, along with the Working Memory Index, were standardized and scaled so that positive values reflected positive attributes and negative values represented adverse outcomes. Standardized dimethylphosphate metabolites were negatively associated with Internalizing factor scores (β^ - 0.13, 95% CI - 0.26, 0.00) but positively associated with Executive Functioning factor scores (β^ 0.18, 95% CI 0.04, 0.31). Standardized diethylphosphate metabolites were negatively associated with the Working Memory Index (β^ - 0.17, 95% CI - 0.33, - 0.03). Associations with factor scores were generally stronger and more precise than associations with individual instrument-specific items. Factor analysis of outcomes may provide some advantages in etiological studies of childhood neurodevelopment by incorporating information across scales to reduce dimensionality and improve precision.

Introduction Daily or weekly averages of physical activity and sedentary behavior could mask patterns of behavior throughout the week that independently affect cardiovascular health. We examined associations between day-to-day physical activity and sedentary behavior latent classes and cardiovascular disease (CVD) risk factors in U.S. youth. Methods Data were from 3984 youth ages 6-17 yr from the National Health and Nutrition Examination Survey (2003-2006) and from previously published accelerometry latent classes characterizing average counts per minute and percent of wear time in moderate-to-vigorous physical activity (MVPA) and sedentary behavior. Multiple linear regression was used to examine associations of the classes with waist circumference, systolic and diastolic blood pressure, HDL-C and LDL-C, triglycerides, glucose, and insulin. Results Participants spent 50.4% of the day in sedentary behavior and 5.3% of the day in moderate-to-vigorous physical activity. Average counts per minute were 516.4 for a 7-d period. Significant differences in CVD risk factors were between extreme classes with few differences observed in intermediate classes. Youth in latent class 4 (highest average counts per minute) had lower systolic blood pressure (-4.11 mm Hg, 95% confidence interval [CI] = -7.74 to -0.55), lower glucose (-4.25 mg·dL, 95% CI = -7.84 to -0.66]), and lower insulin (-6.83 μU·mL, 95% CI = -8.66 to -4.99]) compared with youth in class 1 (lowest average counts per minute). Waist circumference was lower for the least sedentary class (-2.54 cm, 95% CI = -4.90 to -0.19) compared with the most sedentary class. Some associations were attenuated when classes were adjusted for mean physical activity or sedentary level. Conclusions There is some indication that patterns, in addition to the total amount of physical activity and sedentary behavior, may be important for cardiovascular health in youth. Longitudinal studies are needed to examine associations between physical activity and sedentary behavior patterns and changes in CVD risk factors.

Background: Little is known about intergenerational differences in associations of urbanization-related lifestyle behaviors with cardiometabolic risk factors in children and their parents in rapidly urbanizing China.Objective: We tested the intergenerational differences in longitudinal associations of away-from-home eating, snacking, screen time, and leisure-time sports with high waist-to-height ratio (WHtR), elevated blood pressure (BP), elevated glycated hemoglobin (HbA1c), and elevated C-reactive protein (CRP) among Chinese children and their parents.Design: We studied children enrolled in the longitudinal China Health and Nutrition Survey (1991-2009, 7 surveys) aged 7-17 y in ≥2 surveys (average follow-up: 2.3 surveys out of a possible 4 surveys with the age restriction; n = 3875, including 1175 siblings) and their parents (2947 mothers, 2632 fathers) living in the same household. We used 3 consecutive interviewer-administered 24-h dietary recalls to derive a 3-d average for away-from-home eating (nonconsumer, >0 and 1 and ≤2, or >2 h/d) and leisure-time sports (any or none). Random-effects logistic regression was used to examine the associations of lagged (average: 3 y) behaviors with cardiometabolic risk factors (WHtR, BP, HbA1c, and CRP).Results: We detected intergenerational differences in associations between lagged behaviors and risk factors (P-interaction 2 compared with ≤1 h/d) was positively associated with parents' (OR: 2.58; 95% CI: 1.56, 4.28) and children's high WHtR (OR: 2.26; 95% CI: 1.06, 4.83).Conclusion: Parent-offspring differences in associations between lifestyle behaviors and cardiometabolic risk factors provide insight into intergenerational differences in cardiometabolic risk with urbanization.

Background While chronic kidney disease (CKD) is a growing public health concern in low- and middle-income countries, such as China, few studies have investigated the association between urbanization and the occurrence of CKD in those countries. Methods We investigated the association between urbanization and estimated glomerular filtration rate (eGFR), an important CKD risk marker. Data came from the China Health and Nutrition Survey wave 2009, in which we collected fasting serum, individual and household data along with community level urbanization data, which was used to derive a study-specific urbanization measure, in 218 communities across nine provinces. A total of 3644 men and 4154 women participants aged 18 years or older were included in the analysis. Reduced renal function was defined as eGFR of less than 60 mL/min/1.73 m2 measured using serum creatinine concentration (mg/dL). Results After adjusting for socio-demographic (e.g., age, education and household income), a sex-stratified multilevel logistic model revealed that living in a more urbanized community was associated with higher odds of reduced eGFR (odds ratio [OR] = 1.38 per one-standard deviation [SD] increase in the CHNS specific urbanization index, 95% confidence interval [CI] = 1.11–1.73 for men; OR = 1.35, 95% CI = 1.11–1.62 for women). After adjusting for behavioral variables (i.e., alcohol consumption, smoking, physical activity and diet), as well as obesity and cardiometabolic risk factors, the association was attenuated in men (OR = 1.25, 95% CI = 0.98–1.59), but remained statistically significant in women (OR = 1.24, 95% CI = 1.01–1.52). Conclusion Our findings suggest that living in an urban environment is linked with higher odds of reduced renal function independently of behavioral and cardiometabolic risk factors, which have been shown to increase along with urbanization. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0577-7) contains supplementary material, which is available to authorized users.

It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N = 47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.

Background: Organophosphate compounds are commonly used in residential furniture, electronics, and baby products as flame retardants and are also used in other consumer products as plasticizers. Although the levels of exposure biomarkers are generally higher among children and decrease with age, relatively little is known about the individual characteristics associated with higher levels of exposure. Here, we investigate urinary metabolites of several organophosphate flame retardants (PFRs) in a cohort of pregnant women to evaluate patterns of exposure. Methods: Pregnant North Carolina women (n = 349) provided information on their individual characteristics (e.g. age and body mass index (BMI)) as a part of the Pregnancy Infection and Nutrition Study (2002–2005). Women also provided second trimester urine samples in which six PFR metabolites were measured using mass spectrometry methods. Results: PFR metabolites were detected in every urine sample, with BDCIPP, DHPH, ip-PPP and BCIPHIPP detected in >80% of samples. Geometric mean concentrations were higher than what has been reported previously for similarly-timed cohorts. Women with higher pre-pregnancy BMI tended to have higher levels of urinary metabolites. For example, those classified as obese at the start of pregnancy had ip-PPP levels that were 1.52 times as high as normal weight range women (95% confidence interval: 1.23, 1.89). Women without previous children also tended to have higher urinary levels of DPHP, but lower levels of ip-PPP. In addition, we saw strong evidence of seasonal trends in metabolite concentrations (e.g. higher DPHP, BDCIPP, and BCIPHIPP in summer, and evidence of increasing ip-PPP between 2002 and 2005). Conclusions: Our results indicate ubiquitous exposure to PFRs among NC women in the early 2000s. Additionally, our work suggests that individual characteristics are related to exposure and that temporal variation, both seasonal and annual, may exist. Keywords: Organophosphate flame retardants (PFRs), Pregnancy, Exposure

PURPOSE: Studies suggest exposure to ambient particulate matter less than 2.5 μg/m(3) in aerodynamic diameter (PM(2.5)) may be associated with preterm birth (PTB), but few have evaluated how this is modified by ambient temperature. We investigated the relationship between PM(2.5) exposure during pregnancy and PTB in infants without birth defects (1999–2006) and enrolled in the National Birth Defects Prevention Study and how it is modified by concurrent temperature. METHODS: PTB was defined as spontaneous or iatrogenic delivery before 37 weeks. Exposure was assigned using inverse distance weighting with up to four monitors within 50 kilometers of maternal residence. To account for state-level variations, a Bayesian two-level hierarchal model was developed. RESULTS: PTB was associated with PM(2.5) during the third and fourth months of pregnancy (range: (odds ratio (95% confidence interval) = 1.00 (0.35, 2.15) to 1.49 (0.82, 2.68) and 1.31 (0.56, 2.91) to 1.62 (0.7, 3.32), respectively); no week of exposure conveyed greater risk. Temperature may modify this relationship; higher local average temperatures during pregnancy yielded stronger positive relationships between PM(2.5) and PTB compared to nonstratified results. CONCLUSIONS: Results add to literature on associations between PM(2.5) and PTB, underscoring the importance of considering co-exposures when estimating effects of PM(2.5) exposure during pregnancy.

Purpose Both substance use and depression are common in adolescence and often comorbid. Past research has produced conflicting results on whether there is a temporal relationship, and if so, in which direction it operates and how it may vary by sex. We examined the longitudinal associations between substance use frequency and depressive symptoms from adolescence into young adulthood and whether the associations were moderated by sex. Methods With data from Waves I, III, and IV of the National Longitudinal Study of Adolescent to Adult Health (n = 9,816), we used growth curve models to test if depressive symptoms predicted marijuana use or binge drinking frequency (Self-Medication Model) or if substance use frequency predicted depressive symptoms (Stress Model). Moderation by sex and age was tested for both potential pathways. Results Increases in adolescent depressive symptoms, compared to no symptoms, were associated with a steeper predicted increase in marijuana use frequency from adolescence to young adulthood. Increases in persistent binge drinking or marijuana use frequency had concurrent positive associations with depressive symptoms from adolescence to young adulthood, and these associations were significantly stronger for females compared to males. Conclusions The results not only support the Self-Medication Model for marijuana use but also provide modest support for the Stress Model, that substance use is associated with depressive symptoms, especially for females.

Background: Ecologic analyses, case–case comparisons, and animal experiments suggest positive associations between air pollution and tuberculosis. Objectives: We evaluated this hypothesis in a large sample, which yielded results that are applicable to the general population. Methods: We conducted a case–control study nested within a cohort of Kaiser Permanente of Northern California members. All active pulmonary tuberculosis (TB) cases newly diagnosed between 1996 and 2010 (n = 2,309) were matched to two controls (n = 4,604) by age, sex, and race/ethnicity on the index date corresponding with the case diagnosis date. Average individual-level concentrations of carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and particulate matter with aerodynamic diameter ≤ 2.5 μm (PM2.5) and 10 μm (PM10) for 2 years before diagnosis/entry into the study were estimated using measurements from the California Air Resources Board monitor closest to the participant’s residence. Results: In single-pollutant adjusted conditional logistic regression models, the pulmonary TB odds ratios (95% confidence intervals) for the highest quintile (vs. lowest) were 1.50 (95% CI: 1.15, 1.95) for CO and 1.42 (95% CI: 1.10, 1.84) for NO2. Corresponding estimates were higher among never [1.68 (95% CI: 1.26, 2.24)] than ever [1.19 (95% CI: 0.74, 1.92)] smokers for CO. In contrast, for NO2, estimates were higher among ever [1.81 (95% CI: 1.13, 2.91)] than never [1.29 (95% CI: 0.97, 1.71)] smokers. O3 was inversely associated for smokers [0.66 (95% CI: 0.43, 1.02)] and never smokers [0.65 (95% CI: 0.52, 0.81)]. No other consistent patterns were observed. Conclusions: In this first, to our knowledge, U.S. nested case–control study on air pollution and pulmonary TB, we observed positive associations with ambient CO and NO2, which require confirmation. Citation: Smith GS, Van Den Eeden SK, Garcia C, Shan J, Baxter R, Herring AH, Richardson DB, Van Rie A, Emch M, Gammon MD. 2016. Air pollution and pulmonary tuberculosis: a nested case-control study among members of a Northern California health plan. Environ Health Perspect 124:761–768; http://dx.doi.org/10.1289/ehp.1408166

Objective Evidence for optimal timing of delivery for some pregnancy complications at late preterm gestation is limited. The purpose of this study was to identify center variation of indicated late preterm births. Study design We performed an analysis of singleton late preterm and term births from a large U.S. retrospective obstetrical cohort. Births associated with spontaneous preterm labor, major congenital anomalies, chorioamnionitis, and emergency cesarean were excluded. We used modified Poisson fixed effects logistic regression with interaction terms to assess center variation of indicated late preterm births associated with four medical/obstetric comorbidities after adjusting for socio-demographics, comorbidities, and hospital/provider characteristics. Results We identified 150,055 births from 16 hospitals; 9,218 were indicated late preterm births. We found wide variation of indicated late preterm births across hospitals. The extent of center variation was greater for births associated with preterm premature rupture of membranes (risk ratio [RR] across sites: 0.45–3.05), hypertensive disorders of pregnancy (RR across sites: 0.36–1.27), and placenta previa/abruption (RR across sites: 0.48–1.82). We found less center variation for births associated with diabetes (RR across sites: 0.65–1.39). Conclusion Practice variation in the management of indicated late preterm deliveries might be a source of preventable late preterm birth.

Objective To assess the potential impact of missing data on body mass index (BMI) on the association between prepregnancy obesity and specific birth defects. Methods Data from the National Birth Defects Prevention Study (NBDPS) were analyzed. We assessed the factors associated with missing BMI data among mothers of infants without birth defects. Four analytic methods were then used to assess the impact of missing BMI data on the association between maternal prepregnancy obesity and three birth defects; spina bifida, gastroschisis, and cleft lip with/without cleft palate. The analytic methods were: (1) complete case analysis; (2) assignment of missing values to either obese or normal BMI; (3) multiple imputation; and (4) probabilistic sensitivity analysis. Logistic regression was used to estimate crude and adjusted odds ratios (aOR) and 95 % confidence intervals (CI). Results Of NBDPS control mothers 4.6 % were missing BMI data, and most of the missing values were attributable to missing height (~90 %). Missing BMI data was associated with birth outside of the US (aOR 8.6; 95 % CI 5.5, 13.4), interview in Spanish (aOR 2.4; 95 % CI 1.8, 3.2), Hispanic ethnicity (aOR 2.0; 95 % CI 1.2, 3.4), and

Objectives Obstetric ultrasound imaging requires the acquisition of a standard set of maternal and fetal images. Our objective was to evaluate the impact of implementation of a protocol-based ultrasound examination on the duration of ultrasound examinations, examination completion, and accuracy of documentation. Methods We conducted a case-cohort study. Obstetric ultrasound examinations performed in the first, second, and third trimesters were reviewed before and after implementation of a protocol-based ultrasound examination. The duration of the ultrasound examination, number of missing required images, and documentation of missing images were abstracted from an image archival system. To account for clustering by sonographer, 3 mixed effects models with a fixed effect for protocol and a random intercept for sonographer were used to evaluate the effect on the total time of the examination, number of missing images, and whether missing images were documented. Results A total of 100 ultrasound examinations were compared: 50 before and 50 after implementation of the protocol. Statistically significant differences between outcomes before and after protocol implementation were observed for all outcomes. After implementation of the protocol, the average duration of ultrasound examinations decreased by 7.62 minutes (95% confidence interval [CI], 3.57–11.68 minutes); the number of missing images was reduced by 5.81 per examination (95% CI, 4.24–7.39); and proper documentation of missing images increased by 40.24% (95% CI, 22.77%–57.71%). Conclusions Implementation of a software protocol–based ultrasound examination significantly improved the efficiency and accuracy of obstetric ultrasound examinations in this study.

Reliable and stable environmental audit instruments are needed to successfully identify the physical and social attributes that may influence physical activity. This study described the reliability and stability of the PIN3 environmental audit instrument in both urban and rural neighborhoods. Four randomly sampled road segments in and around a one-quarter mile buffer of participants’ residences from the Pregnancy, Infection, and Nutrition (PIN3) study were rated twice, approximately 2 weeks apart. One year later, 253 of the year 1 sampled roads were re-audited. The instrument included 43 measures that resulted in 73 item scores for calculation of percent overall agreement, kappa statistics, and log-linear models. For same-day reliability, 81% of items had moderate to outstanding kappa statistics (kappas ≥ 0.4). Two-week reliability was slightly lower, with 77% of items having moderate to outstanding agreement using kappa statistics. One-year stability had 68% of items showing moderate to outstanding agreement using kappa statistics. The reliability of the audit measures was largely consistent when comparing urban to rural locations, with only 8% of items exhibiting significant differences (α

Organophosphate esters (OPEs) are often used as flame retardants and plasticizers. Animal data suggest exposure to OPEs could impact children's growth and development, yet impacts on human birth outcomes are understudied. We evaluate impacts of OPE exposure on the timing of delivery and infant's birthweight in the Pregnancy Infection and Nutrition Study (PIN). North Carolina women enrolled in PIN in early pregnancy and participated in follow-up through delivery. Analyses were limited to mothers recruited from 2002 to 2005, whose children participated in additional follow-up in early childhood ( n = 349). Mothers collected urine samples in which OPE metabolites were assessed and birth outcomes were abstracted from medical records. Bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), isopropyl-phenyl phenyl phosphate (ip-PPP), bis(1-chloro-2-propyl) 1-hydroxy-2-propyl phosphate (BCIPHIPP) were detected in >80% of samples. Average birthweight and gestational age were 3326 g and 39.1 weeks, respectively. As data suggest that the mechanisms of action by which OPEs impact birth outcomes may be fetal sex dependent, we conducted sex-stratified statistical analyses. Women with the highest ip-PPP concentrations delivered girls 1 week earlier than women with lower levels (95% Confidence Interval (CI): −1.85, −0.15). Women with BDCIPP levels above the median had 3.99 (95% CI: 1.08, 14.78) times the odds of delivering their daughters preterm. Similarly, higher ip-PPP levels were associated with lower birthweight, but not after standardizing for gestational age. Among males, maternal ip-PPP was associated with decreased odds of preterm birth (OR = 0.21, 95% CI: 0.06, 0.68). DPHP and BCIPHIPP levels were not associated with outcomes in either sex. Results indicate that prenatal OPE exposure may impact timing of birth, though results are imprecise. Given widespread OPE exposure and the urgent need to identify and mitigate causes of preterm birth, further investigation is warranted.

Background: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer. Objective: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003–2009). Methods: Non-Hispanic black (4,452) and white women (n=42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence. Results: A total of 2,326 women developed breast cancer during follow-up (average follow-up=5.4y). Among black women, none of the latent class hazard ratios was elevated, but there were

Background Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants, known human lung carcinogens, and potent mammary carcinogens in laboratory animals. However, the association between PAHs and breast cancer in women is unclear. Vehicular traffic is a major ambient source of PAH exposure. Objectives Our study aim was to evaluate the association between residential exposure to vehicular traffic and breast cancer incidence. Methods Residential histories of 1,508 participants with breast cancer (case participants) and 1,556 particpants with no breast cancer (control participants) were assessed in a population-based investigation conducted in 1996–1997. Traffic exposure estimates of benzo[a]pyrene (B[a]P), as a proxy for traffic-related PAHs, for the years 1960–1995 were reconstructed using a model previously shown to generate estimates consistent with measured soil PAHs, PAH–DNA adducts, and CO readings. Associations between vehicular traffic exposure estimates and breast cancer incidence were evaluated using unconditional logistic regression. Results The odds ratio (95% CI) was modestly elevated by 1.44 (0.78, 2.68) for the association between breast cancer and long-term 1960–1990 vehicular traffic estimates in the top 5%, compared with below the median. The association with recent 1995 traffic exposure was elevated by 1.14 (0.80, 1.64) for the top 5%, compared with below the median, which was stronger among women with low fruit/vegetable intake [1.46 (0.89, 2.40)], but not among those with high fruit/vegetable intake [0.92 (0.53, 1.60)]. Among the subset of women with information regarding traffic exposure and tumor hormone receptor subtype, the traffic–breast cancer association was higher for those with estrogen/progesterone-negative tumors [1.67 (0.91, 3.05) relative to control participants], but lower among all other tumor subtypes [0.80 (0.50, 1.27) compared with control participants]. Conclusions In our population-based study, we observed positive associations between vehicular traffic-related B[a]P exposure and breast cancer incidence among women with comparatively high long-term traffic B[a]P exposures, although effect estimates were imprecise. Citation Mordukhovich I, Beyea J, Herring AH, Hatch M, Stellman SD, Teitelbaum SL, Richardson DB, Millikan RC, Engel LS, Shantakumar S, Steck SE, Neugut AI, Rossner P Jr., Santella RM, Gammon MD. 2016. Vehicular traffic–related polycyclic aromatic hydrocarbon exposure and breast cancer incidence: the Long Island Breast Cancer Study Project (LIBCSP). Environ Health Perspect 124:30–38; http://dx.doi.org/10.1289/ehp.1307736

Background Emerging research suggests that young adult sexual minorities (identifying as lesbian, gay, or bisexual or engaging in same-sex attractions or behaviors) experience poorer health than their majority counterparts, but many measures of health inequity remain unexamined in population-based research. Purpose To describe a wide range of health status and healthcare access characteristics of sexual minorities in comparison with those of the majority population in a national sample of U.S. young adults. Methods Binary and multinomial logistic regression analyses of Wave IV data (2008) from the National Longitudinal Study of Adolescent Health (participants aged 24–32 years, n =13,088) were conducted. Health measures were self-rated health; diagnosis of any of several physical or mental illnesses or sexually transmitted infections; measured BMI; depression classified from self-reported symptoms; use of antidepressant and anxiolytic medication; uninsured; forgone care; and receipt of physical, dental, and psychological services. Analyses were conducted in 2012–2013. Results Sexual minority women had elevated odds of most adverse health conditions and lower odds of receiving a physical or dental examination. Sexual minority men had elevated odds of fewer adverse health conditions. Conclusions Young adult sexual minorities are at higher risk of poor physical and mental health. The results highlight the multidimensionality of sexual minority status and respond to calls for greater understanding of the health of this population.

Objective To determine if maternal major depression (MD), antidepressant use, or paternal MD are associated with pregnancy outcomes after non-IVF fertility treatments. Design Cohort study. Setting Clinics. Patient(s) Participants in two randomized trials: PPCOS II (clomiphene citrate versus letrozole for polycystic ovary syndrome), and AMIGOS (gonadotropins versus clomiphene citrate versus letrozole for unexplained infertility). Intervention(s) Female and male partners completed the Patient Health Questionnaire (PHQ-9). Female medication use was collected. PHQ-9 score ≥10 was used to define currently active MD. Main Outcome Measure(s) Primary outcome: live birth. Secondary outcomes: pregnancy, first-trimester miscarriage. Poisson regression models were used to determine relative risks after adjusting for age, race, income, months trying to conceive, smoking, and study (PPCOS II versus AMIGOS). Result(s) Data for 1,650 women and 1,608 men were included. Among women not using an antidepressant, the presence of currently active MD was not associated with poorer fertility outcomes (live birth, miscarriage), but rather was associated with a slightly increased likelihood of pregnancy. Maternal antidepressant use (n = 90) was associated with increased risk of miscarriage, and male partners with currently active MD were less likely to achieve conception. Conclusion(s) Currently active MD in the female partner does not negatively affect non-IVF treatment outcomes; however, currently active MD in the male partner may lower the likelihood of pregnancy. Maternal antidepressant use is associated with first-trimester pregnancy loss, which may depend upon the type of antidepressant. Clinical Trial Registration Numbers NCT00719186 and NCT01044862.

Background Prenatal alcohol exposure can affect neurodevelopment, but few studies have examined associations with autism spectrum disorder (ASD). Methods We assessed the association between maternal alcohol use and ASD in the Study to Explore Early Development, a multi-site case-control study of children born between September 2003 and August 2006 in the US Regression analyses included 684 children with research clinician-confirmed ASD, 869 children with non-ASD developmental delays or disorders (DDs), and 962 controls ascertained from the general population (POP). Maternal alcohol exposure during each month from 3 months prior to conception until delivery was assessed by self-report. Results Mothers of POP children were more likely to report any prenatal alcohol use than mothers of children with ASD or DD. In trimester one, 21.2% of mothers of POP children reported alcohol use compared with 18.1% and 18.2% of mothers of children with ASD or DD, respectively (adjusted OR for ASD vs. POP 0.8, 95% confidence interval 0.6, 1.1). During preconception and the first month of pregnancy, one to two drinks on average per week was inversely associated with ASD risk. Conclusions These results do not support an adverse association between low-level alcohol exposure and ASD, although these findings were based on retrospective self-reported alcohol use. Unmeasured confounding or exposure misclassification may explain inverse associations with one to two drinks per week. Pregnant or potentially pregnant women should continue to follow recommendations to avoid alcohol use because of other known effects on infant health and neurodevelopment.

The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women’s metabolism of As as indicated by greater proportions of MMAs and smaller proportions of DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gomez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 μmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels

To better understand the impact that nonresponse for specimen collection has on the validity of estimates of association, we examined associations between self-reported maternal periconceptional smoking, folic acid use, or pregestational diabetes mellitus and six birth defects among families who did and did not submit buccal cell samples for DNA following a telephone interview as part of the National Birth Defects Prevention Study (NBDPS). Analyses included control families with live born infants who had no birth defects (N = 9,465), families of infants with anorectal atresia or stenosis (N = 873), limb reduction defects (N = 1,037), gastroschisis (N = 1,090), neural tube defects (N = 1,764), orofacial clefts (N = 3,836), or septal heart defects (N = 4,157). Estimated dates of delivery were between 1997 and 2009. For each exposure and birth defect, odds ratios and 95% confidence intervals were calculated using logistic regression stratified by race-ethnicity and sample collection status. Tests for interaction were applied to identify potential differences between estimated measures of association based on sample collection status. Significant differences in estimated measures of association were observed in only four of 48 analyses with sufficient sample sizes. Despite lower than desired participation rates in buccal cell sample collection, this validation provides some reassurance that the estimates obtained for sample collectors and noncollectors are comparable. These findings support the validity of observed associations in gene-environment interaction studies for the selected exposures and birth defects among NBDPS participants who submitted DNA samples.

Background Limited evidence exists to inform physical activity (PA) and sedentary behavior guidelines for older people, especially women. Rigorous evidence on the amounts, intensities, and movement patterns associated with better health in later life is needed. Methods/Design The Objective PA and Cardiovascular Health (OPACH) Study is an ancillary study to the Women’s Health Initiative (WHI) Program that examines associations of accelerometer-assessed PA and sedentary behavior with cardiovascular and fall events. Between 2012 and 2014, 7048 women aged 63–99 were provided with an ActiGraph GT3X+ (Pensacola, Florida) triaxial accelerometer, a sleep log, and an OPACH PA Questionnaire; 6489 have accelerometer data. Most women were in their 70s (40%) or 80s (46%), while approximately 10% were in their 60s and 4% were age 90 years or older. Non-Hispanic Black or Hispanic/Latina women comprise half of the cohort. Follow-up includes 1-year of falls surveillance with monthly calendars and telephone interviews of fallers, and annual follow-up for outcomes with adjudication of incident cardiovascular disease (CVD) events through 2020. Over 63,600 months of calendar pages were returned by 5,776 women, who reported 5,980 falls. Telephone interviews were completed for 1,492 women to ascertain the circumstances, injuries and medical care associated with falling. The dataset contains extensive information on phenotypes related to healthy aging, including inflammatory and CVD biomarkers, breast and colon cancer, hip and other fractures, diabetes, and physical disability. Discussion This paper describes the study design, methods, and baseline data for a diverse cohort of postmenopausal women who wore accelerometers under free-living conditions as part of the OPACH Study. By using accelerometers to collect more precise and complete data on PA and sedentary behavior in a large cohort of older women, this study will contribute crucial new evidence about how much, how vigorous, and what patterns of PA are necessary to maintain optimal cardiovascular health and to avoid falls in later life. Clinical trials registration ClinicalTrials.gov identifier NCT00000611. Registered 27 October 1999. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4065-6) contains supplementary material, which is available to authorized users.

Introduction Latent class analysis provides a method for understanding patterns of physical activity and sedentary behavior. This study explored the association of accelerometer-assessed patterns of physical activity/sedentary behavior with all-cause mortality. Methods The sample included 4,510 U.S. National Health and Nutrition Examination Survey participants aged ≥40 years enrolled in 2003–2006 with mortality follow-up through 2011. Participants used a hip-worn accelerometer for 1 week that provided minute-by-minute information on physical activity/sedentary behavior. Accelerometry patterns were derived using latent class analysis. Cox proportional hazards models provided adjusted hazard ratios with 95% CIs. Analyses were conducted from 2014 to 2016. Results During an average of 6.6 years of follow-up, 513 deaths occurred. For average counts/minute, the more-active classes had a lower risk of mortality compared with the lowest (Class 1). Findings were generally similar for percentage of the day in minutes and bouts of moderate to vigorous physical activity, defined two ways. For percentage of the day in sedentary behavior, generally no associations were identified. However, the class with the highest percentage of the day in sedentary bouts (Class 1) had a higher risk of mortality (adjusted hazard ratio, 2.10; 95% CI=1.11, 3.97) versus the class with fewer sedentary bouts (Class 7). Conclusions In this national observational study, time spent in physical activity reduced the risk of all-cause mortality and time spent in sedentary bouts increased the risk of all-cause mortality, regardless of how both were accumulated. The latent class analysis contributed to understanding the impact of patterning of physical activity and sedentary behavior on mortality.

Background: Epidemiologic literature suggests that exposure to air pollutants is associated with fetal development. Objectives: We investigated maternal exposures to air pollutants during weeks 2–8 of pregnancy and their associations with congenital heart defects. Methods: Mothers from the National Birth Defects Prevention Study, a nine-state case–control study, were assigned 1-week and 7-week averages of daily maximum concentrations of carbon monoxide, nitrogen dioxide, ozone, and sulfur dioxide and 24-hr measurements of fine and coarse particulate matter using the closest air monitor within 50 km to their residence during early pregnancy. Depending on the pollutant, a maximum of 4,632 live-birth controls and 3,328 live-birth, fetal-death, or electively terminated cases had exposure data. Hierarchical regression models, adjusted for maternal demographics and tobacco and alcohol use, were constructed. Principal component analysis was used to assess these relationships in a multipollutant context. Results: Positive associations were observed between exposure to nitrogen dioxide and coarctation of the aorta and pulmonary valve stenosis. Exposure to fine particulate matter was positively associated with hypoplastic left heart syndrome but inversely associated with atrial septal defects. Examining individual exposure-weeks suggested associations between pollutants and defects that were not observed using the 7-week average. Associations between left ventricular outflow tract obstructions and nitrogen dioxide and between hypoplastic left heart syndrome and particulate matter were supported by findings from the multipollutant analyses, although estimates were attenuated at the highest exposure levels. Conclusions: Using daily maximum pollutant levels and exploring individual exposure-weeks revealed some positive associations between certain pollutants and defects and suggested potential windows of susceptibility during pregnancy. Citation: Stingone JA, Luben TJ, Daniels JL, Fuentes M, Richardson DB, Aylsworth AS, Herring AH, Anderka M, Botto L, Correa A, Gilboa SM, Langlois PH, Mosley B, Shaw GM, Siffel C, Olshan AF, National Birth Defects Prevention Study. 2014. Maternal exposure to criteria air pollutants and congenital heart defects in offspring: results from the National Birth Defects Prevention Study. Environ Health Perspect 122:863–872; http://dx.doi.org/10.1289/ehp.1307289

Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this group.Retrospective cohort study of infants 32 weeks gestation and 1,500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and fraction of inspired oxygen on the first day of each course of diuretic use were identified.About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6% to three diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per 1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia.Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support.

Genome-wide association studies (GWAS) and candidate gene analyses have led to the discovery of several dozen genetic polymorphisms associated with breast cancer susceptibility, many of which are considered well-established risk factors for the disease. Despite attempts to replicate these same variant-disease associations in African Americans, the evaluable populations are often too small to produce precise or consistent results. We estimated the associations between 83 previously identified single nucleotide polymorphisms (SNPs) and breast cancer among Carolina Breast Cancer Study (1993–2001) participants using maximum likelihood, Bayesian, and hierarchical methods. The selected SNPs were previous GWAS hits (n = 22), near-hits (n = 19), otherwise well-established risk loci (n = 5), or located in the same genes as selected variants (n = 37). We successfully replicated 18 GWAS-identified SNPs in whites (n = 2,352) and 10 in African Americans (n = 1,447). SNPs in the fibroblast growth factor receptor 2 gene (FGFR2) and the TOC high mobility group box family member 3 gene (TOX3) were strongly associated with breast cancer in both races. SNPs in the mitochondrial ribosomal protein S30 gene (MRPS30), mitogen-activated protein kinase kinase kinase 1 gene (MAP3K1), zinc finger, MIZ-type containing 1 gene (ZMIZ1), and H19, imprinted maternally expressed transcript gene (H19) were associated with breast cancer in whites, and SNPs in the estrogen receptor 1 gene (ESR1) and H19 gene were associated with breast cancer in African Americans. We provide precise and well-informed race-stratified odds ratios for key breast cancer–related SNPs. Our results demonstrate the utility of Bayesian methods in genetic epidemiology and provide support for their application in small, etiologically driven investigations.

We evaluate the use of three different exposure metrics to estimate maternal agricultural pesticide exposure during pregnancy. Using a geographic information system-based method of pesticide exposure estimation, we combine data on crop density and specific pesticide application amounts/dates to create the three exposure metrics. For illustration purposes, we create each metric for a North Carolina cohort of pregnant women, 2003-2005, and analyze the risk of congenital anomaly development with a focus on metric comparisons. Based on the results, and the need to balance data collection efforts/computational efficiency with accuracy, the metric which estimates total chemical exposure using application dates based on crop-specific earliest planting and latest harvesting information is preferred. Benefits and drawbacks of each metric are discussed and recommendations for extending the analysis to other states are provided.

Objective In adulthood, excess BMI is associated with cardiovascular disease (CVD); it is unknown whether risk differs by BMI trajectories from adolescence to adulthood. Design and Methods The National Longitudinal Study of Adolescent Health, a nationally representative, longitudinal adolescent cohort (mean age: 16.9 years) followed into adulthood (mean age: 28.8 years) [n = 13,984 individuals (41,982 observations)] was examined. Separate logistic regression models for diabetes, hypertension, and inflammation were used to examine odds of risk factors at given adult BMI according to varying BMI trajectories from adolescence to adulthood. Results CVD risk factor prevalence at follow-up ranged from 5.5% (diabetes) to 26.4% (hypertension) and 31.3% (inflammation); risk differed across BMI trajectories. For example, relative to men aged 27 years (BMI = 23 kg/m2 maintained over full study period), odds for diabetes were comparatively higher for men of the same age and BMI ≈ 30 kg/m2 with ≈8 BMI unit gain between 15 and 20 years (OR = 2.35; 95% CI, 1.51, 3.66) or in those who maintained BMI ≈ 30 kg/m2 across the study period (OR = 2.33; 1.92, 2.83) relative to the same ≈8 BMI unit gain, but between 20 and 27 years (OR = 1.44; 1.10, 1.87). Conclusions Specific periods and patterns of weight gain in the transition from adolescence to adulthood might be critical for CVD preventive efforts.

The emergence of partnered sexual behavior represents an important developmental transition. However, little is known about individuals who remain sexually inexperienced well into adulthood. We used data from 2,857 individuals who participated in Waves I, III, and IV of the National Longitudinal Study of Adolescent Health (Add Health) and reported no sexual activity (i.e., oral-genital, vaginal, or anal sex) by age 18 to identify, using discrete-time survival models, adolescent sociodemographic, biosocial, and behavioral characteristics that predicted adult sexual inexperience. The mean age of participants at Wave IV was 28.5 years (SD = 1.92). Over 1 out of 8 participants who did not initiate sexual activity during adolescence remained abstinent as young adults. Sexual non-attraction significantly predicted sexual inexperience among both males (aOR = 0.5) and females (aOR = 0.6). Males also had lower odds of initiating sexual activity after age 18 if they were non-Hispanic Asian, reported later than average pubertal development, or were rated as physically unattractive (aORs = 0.6–0.7). Females who were overweight, had lower cognitive performance, or reported frequent religious attendance had lower odds of sexual experience (aORs = 0.7–0.8) while those who were rated by the interviewers as very attractive or whose parents had lower educational attainment had higher odds of sexual experience (aORs = 1.4–1.8). Our findings underscore the heterogeneity of this unique population and suggest that there are a number of different pathways that may lead to either voluntary or involuntary adult sexual inexperience. Understanding the meaning of sexual inexperience in young adulthood may have important implications for the study of sexuality development across the life course.

Studying empirically derived dietary patterns is useful in understanding dietary practice. We classified women by their dietary patterns using latent class analysis of 66 foods and studied the association of these patterns with neural tube defects (NTDs) and congenital heart defects (CHDs) in the U.S. National Birth Defects Prevention Study (1997-2005). Logistic regression models used data from 1,047 with an NTD, 6,641 with a CHD, and 6,123 controls that were adjusted for maternal characteristics and tested the effect modification of multivitamin supplement use. Four latent dietary patterns were identified: prudent, Western, low-calorie Western, and Mexican. Among participants who did not use supplements, those in the Mexican, Western, and low-calorie Western classes were significantly more likely (odds ratios of 1.6, 1.5, and 1.4, respectively) to have offspring born with NTDs than were those in the prudent class after adjustment of for dietary folic acid intake. In contrast, among supplement users, there was no difference in the incidence of NTDs between classes. Associations between dietary class and CHD subgroups were not modified by supplement use except for tetralogy of Fallot; among supplement users, those in the Western class were twice as likely (95% confidence interval: 1.4, 2.8) as the prudent class to have offspring with tetralogy of Fallot. Women who adhered to a Western diet were 1.2 (95% confidence interval: 1.03, 1.35) times more likely to have an infant with septal heart defect than were women who adhered to a prudent diet. A prudent dietary pattern, even with folate fortification, may decrease the risk of NTDs and some heart defects.

Background While the household context is important for lifestyle behavior interventions, few studies have examined parent–child associations for diet and physical activity (PA) changes over time in a rapidly urbanizing country. We aimed to investigate changes in diet, screen time, and PA behaviors over time in children and their parents living in the same household, and examine the parent–child association for these behaviors. Methods We studied dietary, screen time, and PA behaviors in 5,201 parent–child pairs (children aged 7-17y) using longitudinal data from the China Health and Nutrition Survey (1991, 1993, 1997, 2000, 2004, 2006, and 2009). We collected three-day 24-h recall diet data to generate percentages of energy from animal-source foods, away-from-home eating, and snacking from 1991–2009, which are known urbanization-related behaviors. We used a seven-day PA recall to collect screen time (hours/week) and leisure-time sports participation (yes/no) since 2004. We examined the changes in children’s and parents’ behaviors over time using random-effects negative binomial regression for diet and screen time, and random-effects logistic regression for leisure-time sports. We then regressed each of the behaviors of offspring on each of their parents’ same behaviors to examine the parent–child association, using the same set of models. Results We observed increases in energy from animal-source foods, eating away-from-home, and snacking, as well as screen time and leisure-time sports in parents and children over time, with different rates of change between children and their parents for some behaviors. We found positive parent–child associations for diet, screen time, and PA. When parental intakes increased by 10 % energy from each dietary behavior, children’s increase in intakes ranged from 0.44 to 1.59 % total energy for animal-source foods, 0.17 % to 0.45 % for away-from-home eating, and 2.13 % to 7.21 % for snacking. Children were also more likely to participate in leisure-time sports if their parents participated in leisure-time sports. Conclusion Our findings support household-based health behavior interventions targeting both children and their parents. However, generation-specific intervention strategies may be needed for children and adults, especially for dietary behaviors, which changed differentially in children versus parents in this rapidly modernizing population. Electronic supplementary material The online version of this article (doi:10.1186/s12966-016-0445-z) contains supplementary material, which is available to authorized users.

Background Recent longitudinal work suggests that weight change is an important risk factor for inflammation across the full range of BMI . However, few studies have examined whether the risk of inflammation differs by patterns of weight gain over time. Using latent class trajectory analysis, we test whether patterns of weight gain are associated with elevated high‐sensitivity C‐reactive protein (hs‐ CRP 2–10 mg/L). Methods and Results Data come from China Health and Nutrition Survey ( CHNS ) participants (n=5536), aged 18 at baseline to 66 years in 2009, with measured weight over 18 years. Latent class trajectory analysis was used to identify weight‐change trajectories in 6 age and sex strata. Multivariable general linear mixed‐effects models fit with a logit link were used to assess the risk of elevated hs‐ CRP across weight trajectory classes. Models were fit within age and sex strata, controlling for baseline weight, adult height, and smoking, and included random intercepts to account for community‐level correlation. Steeper weight‐gain trajectories were associated with greater risk of elevated hs‐ CRP compared to more moderate weight‐gain trajectories in men and women. Initially high weight gain followed by weight loss was associated with lower risk of elevated hs‐ CRP in women aged 18 to 40. Conclusions Latent class trajectory analysis identified heterogeneity in adult weight change associated with differential risk of inflammation independently of baseline weight and smoking. These results suggest that trajectories of weight gain are an important clinical concern and may identify those at risk for inflammation and the development of cardiometabolic disease.

Background Applying latent class analysis (LCA) to accelerometry can help elucidated underlying patterns. This study described the patterns of accelerometer-determined sedentary behavior and physical activity among youth by applying LCA to a nationally representative United States (US) sample. Methods Using 2003–2006 National Health and Nutrition Examination Survey data, 3998 youths 6–17 years wore an ActiGraph 7164 accelerometer for one week, providing > =3 days of wear for > =8 h/day from 6:00 am-midnight. Cutpoints defined sedentary behavior ( = 2296 counts/minute), and vigorous activity (> = 4012 counts/minute). To account for wear time differences, outcomes were expressed as percent of day in a given intensity. LCA was used to classify daily (Monday through Sunday) patterns of average counts/minute, sedentary behavior, light activity, MVPA, and vigorous activity separately. The latent classes were explored overall and by age (6–11, 12–14, 15–17 years), gender, and whether or not youth attended school during measurement. Estimates were weighted to account for the sampling frame. Results For average counts/minute/day, four classes emerged from least to most active: 40.9 % of population (mean 323.5 counts/minute/day), 40.3 % (559.6 counts/minute/day), 16.5 % (810.0 counts/minute/day), and 2.3 % (1132.9 counts/minute/day). For percent of sedentary behavior, four classes emerged: 13.5 % of population (mean 544.6 min/day), 30.1 % (455.1 min/day), 38.5 % (357.7 min/day), and 18.0 % (259.2 min/day). For percent of light activity, four classes emerged: 12.3 % of population (mean 222.6 min/day), 29.3 % (301.7 min/day), 41.8 % (384.0 min/day), and 16.6 % (455.5 min/day). For percent of MVPA, four classes emerged: 59.9 % of population (mean 25.0 min/day), 33.3 % (60.9 min/day), 3.1 % (89.0 min/day), and 3.6 % (109.3 min/day). For percent of vigorous activity, three classes emerged: 76.8 % of population (mean 7.1 min/day), 18.5 % (23.9 min/day), and 4.7 % (47.4 min/day). Classes were developed by age, gender, and school attendance since some patterns differed when stratifying by these factors. Conclusion The models supported patterns for average intensity, sedentary behavior, light activity, MVPA, and vigorous activity. These latent class derived patterns can be used in other youth studies to explore correlates or outcomes and to target sedentary behavior or physical activity interventions. Electronic supplementary material The online version of this article (doi:10.1186/s12966-016-0382-x) contains supplementary material, which is available to authorized users.

Purpose Both substance use and depression are common in adolescence and often comorbid. Past research has produced conflicting results on whether there is a temporal relationship and if so, in which direction it operates and how it may vary by sex. The purpose of this paper is to explore the longitudinal, potentially bidirectional, relationships between high-frequency substance use and depressive symptoms from adolescence into young adulthood for males and females. Methods Using data from the National Longitudinal Study of Adolescent to Adult Health we investigated longitudinal associations between high frequency substance use (alcohol, cigarettes, and marijuana) and depressive symptoms. The linear mixed effects models were stratified by sex and used a lagged measure of the dependent variable to test temporal relationships. A random intercept was used for respondent ID. Results Increases in depressive symptoms were significantly associated with a later increase of about a half day in marijuana use frequency for males and nearly a two day increase in smoking frequency for females. Conversely, increases in smoking frequency were significantly associated with approximately a 0.6-point increase for females and 0.4-point increase for males in depressive symptoms at a later wave. Conclusions Results indicate a bidirectional relationship between smoking and depressive symptoms for females. For males, there was evidence supporting self-medication with marijuana and for smoking being associated with later increases in depressive symptoms. Results inform how substance use and depression screening, prevention and treatment efforts should be paired and targeted for males and females.

Phthalates are hypothesized to cause obesity, but few studies have assessed whether prenatal phthalate exposures are related to childhood body mass index (BMI).We included 707 children from three prospective cohort studies enrolled in the US between 1998 and 2006 who had maternal urinary phthalate metabolite concentrations measured during pregnancy, and measures of weight and height at ages 4 to 7 years. We calculated age- and sex-standardized BMI z scores and classified children with BMI percentiles ≥85 as overweight/obese. We used mixed effects regression models to estimate associations between a 1 standard deviation increase in natural log phthalate metabolite concentrations and BMI z scores and overweight/obesity. We estimated associations in multiple metabolite models adjusted for confounders, and evaluated heterogeneity of associations by child's sex, race/ethnicity, and cohort.Mono-3-carboxypropyl phthalate concentrations were positively associated with overweight/obese status in children (odds ratio [95% credible interval] = 2.1 [1.2, 4.0]) but not with BMI z scores (β = -0.02 [-0.15, 0.11]). We did not observe evidence of obesogenic effects for other metabolites. However, monoethyl phthalate and summed di-(2-ethylhexyl) phthalate metabolites (∑DEHP) concentrations were inversely associated with BMI z scores among girls (monoethyl phthalate beta = -0.14 [-0.28, 0.00]; ∑DEHP beta = -0.12 [-0.27, 0.02]).Maternal urinary mono-3-carboxypropyl phthalate, a nonspecific metabolite of several phthalates, was positively associated with childhood overweight/obesity. Metabolites of diethyl phthalate and DEHP were associated with lower BMI in girls but not in boys, suggesting that prenatal exposures may have sexually dimorphic effects on physical development.

The US physical activity (PA) recommendations were based primarily on studies in which self-reported data were used. Studies that include accelerometer-assessed PA and sedentary behavior can contribute to these recommendations. In the present study, we explored the associations of PA and sedentary behavior with all-cause and cardiovascular disease (CVD) mortality in a nationally representative sample. Among the 2003–2006 National Health and Nutrition Examination Survey cohort, 3,809 adults 40 years of age or older wore an accelerometer for 1 week and self-reported their PA levels. Mortality data were verified through 2011, with an average of 6.7 years of follow-up. We used Cox proportional hazards models to obtain adjusted hazard ratios and 95% confidence intervals. After excluding the first 2 years, there were 337 deaths (32% or 107 of which were attributable to CVD). Having higher accelerometer-assessed average counts per minute was associated with lower all-cause mortality risk: When compared with the first quartile, the adjusted hazard ratio was 0.37 (95% confidence interval: 0.23, 0.59) for the fourth quartile, 0.39 (95% confidence interval: 0.27, 0.57) for the third quartile, and 0.60 (95% confidence interval: 0.45, 0.80) second quartile. Results were similar for CVD mortality. Lower all-cause and CVD mortality risks were also generally observed for persons with higher accelerometer-assessed moderate and moderate-to-vigorous PA levels and for self-reported moderate-to-vigorous leisure, household and total activities, as well as for meeting PA recommendations. Accelerometer-assessed sedentary behavior was generally not associated with all-cause or CVD mortality in fully adjusted models. These findings support the national PA recommendations to reduce mortality.

Early life exposure to endocrine disrupting chemicals may alter adipogenesis and energy balance leading to changes in obesity risk. Several studies have evaluated the association of prenatal bisphenol A exposure with childhood body size but only one study of male infants has examined other environmental phenols. Therefore, we assessed associations between prenatal exposure to environmental phenols and fat mass in a prospective birth cohort. We quantified four phenol biomarkers in third trimester maternal spot urine samples in a cohort of women enrolled in New York City between 1998 and 2002 and evaluated fat mass in their children using a Tanita scale between ages 4 and 9 years (173 children with 351 total observations). We estimated associations of standard deviation differences in natural log creatinine-standardized phenol biomarker concentrations with percent fat mass using linear mixed effects regression models. We did not observe associations of bisphenol A or triclosan with childhood percent fat mass. In unadjusted models, maternal urinary concentrations of 2,5-dichlorophenol were associated with greater percent fat mass and benzophenone-3 was associated with lower percent fat mass among children. After adjustment, phenol biomarkers were not associated with percent fat mass. However, the association between benzophenone-3 and percent fat mass was modified by child's sex: benzophenone-3 concentrations were inversely associated with percent fat mass in girls (beta = −1.51, 95% CI = −3.06, 0.01) but not boys (beta = −0.20, 95% CI = −1.69, 1.26). Although we did not observe strong evidence that prenatal environmental phenols exposures influence the development of childhood adiposity, the potential antiadipogenic effect of benzophenone-3 in girls may warrant further investigation. Keywords: Phenols, Pediatric obesity, Endocrine disruptors, Environmental exposure

CONTEXT Identifying young adult outcomes associated with adolescent sexual behavior, including patterns of first oral, vaginal and anal sex, is critical to promoting healthy sexual development. METHODS Associations between patterns of emerging sexual behavior, defined using latent class analysis, and young adult sexual and reproductive health were examined among 9,441 respondents to Waves 1 (1994–1995), 3 (2001–2002) and 4 (2008) of the National Longitudinal Study of Adolescent Health. Logistic regression analyses examined associations between class membership and young adult outcomes, and tested for interactions by race and ethnicity. RESULTS Compared with respondents who initiated vaginal sex first and reported other sexual behaviors within two years, those who initiated oral and vaginal sex during the same year had similar odds of having had an STD diagnosis ever or in the last year, of having had concurrent sexual partnerships in the last year and of having exchanged sex for money. However, respondents who postponed sexual activity had reduced odds of each outcome (odds ratios, 0.2–0.4); those who initiated vaginal sex and reported only one type of sexual behavior had reduced odds of reporting STD diagnoses and concurrent partnerships (0.4–0.6). Respondents who reported early initiation of sexual activity combined with anal sex experience during adolescence had elevated odds of having had concurrent partnerships (1.6). The data suggest racial and ethnic disparities even when patterns of emerging sexual behavior were the same. CONCLUSIONS Patterns of early sexual behavior considered high-risk may not predict poor sexual and reproductive health in young adulthood.

Background:Correlates of prenatal physical activity can inform interventions, but are not well-understood.Methods:Participants in the Pregnancy, Infection, and Nutrition 3 Study were recruited before 20 weeks gestation. Women self-reported frequency, duration, and mode of moderate and vigorous physical activities. We used logistic regression to identify correlates of any physical activity (≥10 minutes/week of any mode), any recreational activity (≥10 minutes/week), and high volume recreational activity (either ≥150 minutes/week of moderate or ≥75 minutes/week of vigorous). Our analysis included 1752 women at 19-weeks gestation and 1722 at 29 weeks.Results:Higher education, white race, and enjoyment of physical activity were positively correlated with all 3 outcomes. Any recreational activity was negatively associated with parity, body mass index, and history of miscarriage. The associations of history of miscarriage and body mass index differed at 19 weeks compared with 29 weeks. Single marital status, health professional physical activity advice, and time for activity were associated with high volume recreational activity only.Conclusions:Correlates of physical activity differed by mode and volume of activity and by gestational age. This suggests that researchers planning physical activity interventions should consider the mode and amount of activity and the gestational age of the participants.