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1.
Obesity (Silver Spring) ; 28(10): 1984-1992, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32959518

RESUMO

OBJECTIVE: The purpose of this study was to test the extent to which pregnancy per- and polyfluoroalkyl substance (PFAS) concentrations were associated with gestational weight gain and postpartum weight changes. METHODS: This study was composed of 1,614 women recruited between 1999 and 2002 via the Project Viva cohort with pregnancy plasma concentrations of six PFAS, including perfluorooctanesulfonic acid, perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. Gestational weight gain was defined as the difference between last pregnancy weight and prepregnancy weight, 1-year postpartum weight retention as the difference between 1-year postpartum weight and prepregnancy weight, and 3-year postpartum weight change as the difference between 3-year postpartum weight and prepregnancy weight. RESULTS: During pregnancy, women gained 0.37 kg (95% CI: 0.11-0.62) more weight per doubling of 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid. At 1 year post partum, women retained 0.55 kg (95% CI: 0.07-1.04) more weight per doubling of PFOA. At 3 years post partum, women gained 0.91 kg (95% CI: 0.25-1.56) more weight per doubling in PFOA. Findings were similar after adjustment for all PFAS. Other PFAS were not associated with weight changes. Postpartum associations were stronger among women with higher prepregnancy BMI. Models were adjusted for demographics. CONCLUSIONS: Pregnancy PFAS were associated with greater gestational weight gain, weight retention, and weight gain years after pregnancy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32885485

RESUMO

BACKGROUND: Maternal abnormal glucose tolerance during pregnancy may adversely affect offspring cognition and behaviour, but few prospective studies investigated this association at multiple points throughout childhood. OBJECTIVES: We hypothesised that maternal abnormal glucose tolerance is associated with child cognitive and behavioural outcomes in early and mid-childhood. METHODS: We examined the associations of maternal abnormal glucose tolerance at 26-28 weeks of pregnancy with offspring cognitive and behavioural scores in 1421 children in the Project Viva pre-birth cohort. In early (mean 3.3 years) and mid-childhood (mean 7.9 years), we measured child cognition using validated instruments, the Kaufman Brief Intelligence Test, Wide Range Assessment of Memory and Learning, and the Wide Range Assessment of Visual Motor Abilities (WRAVMA); we assessed parent- and teacher-rated behavioural outcomes with the Strengths and Difficulties Questionnaire and the Behavioural Rating Inventory of Executive Function. We used linear regression models adjusted for potential confounders (maternal race/ethnicity, pre-pregnancy BMI, intelligence, age, parity, smoking status, education, and household income at enrolment, in addition to child's sex and age at assessment). RESULTS: Of 1421 mothers, 69 (4.9%) had gestational diabetes mellitus, 43 (3.0%) impaired glucose tolerance, 122 (8.6%) isolated hyperglycaemia, and 1187 (83.5%) normal glucose tolerance. Offspring born to women with gestational diabetes mellitus had lower total WRAVMA scores (-3.09 points; 95% CI -6.12, -0.05) in early childhood compared with offspring of women with normal glucose tolerance. None of the abnormal glucose tolerance categories during pregnancy were associated with any of the cognitive outcomes (verbal, non-verbal, and visual motor scores) or behavioural measures in mid-childhood. CONCLUSIONS: Children born to mothers who had gestational diabetes mellitus had slightly lower scores on one cognitive test in early childhood. We found no evidence to support that maternal abnormal glucose tolerance was associated with cognitive or behavioural development in mid-childhood.

3.
Pediatr Obes ; : e12704, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32761791

RESUMO

BACKGROUND: Increased visceral adipose tissue (VAT) precedes development of insulin resistance and dyslipidemia in adults. The associations of abdominal adiposity derived from dual-energy X-ray absorptiometry (DXA), including VAT, subcutaneous abdominal adipose tissue (SAAT) and total abdominal adipose tissue (TAAT) with cardio-metabolic risk in adolescents are understudied. OBJECTIVES: We examined the cross-sectional associations of DXA-measured abdominal adiposity with cardio-metabolic risk and related markers in early adolescence (mean [SD] age 13.0 [0.7] years). METHODS: We collected data from 740 adolescents (374 girls and 366 boys) in Project Viva, a U.S. pre-birth cohort. We used DXA estimates of VAT, SAAT and TAAT area. We conducted overall and sex-stratified linear regression models, adjusting for age, sex (in overall models), race/ethnicity, puberty score and body mass index (BMI) z-score. RESULTS: Mean BMI z-score was 0.59 (1.28). After adjustment, greater VAT (per 1 SD score) was associated with higher metabolic risk z-score (ß 0.14 units; 95% CI 0.08, 0.20), higher log high-sensitivity C-reactive protein (ß 0.51 mg/L; 0.36, 0.66) and log leptin (ß 0.36 ng/mL; 0.27, 0.44), and lower log adiponectin (ß -0.08 ug/mL; -0.13, -0.02). SAAT and TAAT showed similar associations as VAT with comparable or greater effect sizes. CONCLUSION: In early adolescence, DXA-measured VAT, SAAT and TAAT are associated with cardio-metabolic risk and related markers, independent of current BMI. Among two adolescents with the same BMI, there is an associated higher cardio-metabolic risk in the adolescent with greater DXA-measured abdominal adiposity.

4.
Epidemiology ; 31(5): 677-680, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32618710

RESUMO

BACKGROUND: Manganese, an essential micronutrient, has been found in lower concentrations among women with preeclampsia in cross-sectional and case-control studies without establishment of a temporal relationship. METHODS: We evaluated the prospective association of manganese (in red blood cells) in first trimester of pregnancy with incidence of preeclampsia (ascertained by reviewing medical records) among 1,312 women in eastern Massachusetts (Project Viva, 1999-2002). We used log-binomial regression to examine the manganese-preeclampsia relationship, adjusting for maternal age, race/ethnicity, parity, prepregnancy body mass index, blood pressure, and hematocrit. RESULTS: The median (25th, 75th percentile) manganese concentrationin red blood cells was 16.2 ng/g (13.1, 20.4) and 48 (4%) women developed preeclampsia. We observed an inverse dose-response relationship between manganese and preeclampsia. Compared with women in the lowest tertile, women in the middle manganese tertile had 0.81 times the risk of preeclampsia (95% CI: 0.43, 1.5) and those in the highest tertile had 0.50 (95% CI: 0.25, 0.99) times the risk. CONCLUSIONS: Our results provide insight into a potentially modifiable way to prevent preeclampsia.

5.
J Clin Endocrinol Metab ; 105(9)2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32620010

RESUMO

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) are environmental chemicals linked to weight gain and type 2 diabetes. OBJECTIVE: We examined the extent to which PFAS plasma concentrations during pregnancy were associated with postpartum anthropometry and biomarkers. DESIGN, PATIENTS, AND MEASURES: We studied women recruited between 1999 and 2002 in the Project Viva prospective cohort with pregnancy plasma concentrations of PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and 2-(N-ethyl-perfluorooctane sulfonamide) acetic acid (EtFOSAA). Three-year postpartum anthropometry measurements were available from 786 to 801 women, blood pressure from 761 women, and blood biomarkers from 450 to 454 women. We used multivariable regression to evaluate the association of log2-transformed PFAS with postpartum anthropometry, blood pressure, and blood biomarkers (leptin, adiponectin, sex hormone binding globulin [SHBG], hemoglobin A1c, interleukin-6 [IL-6], C-reactive protein), adjusting for age, prepregnancy body mass index, marital status, race/ethnicity, education, income, smoking, parity, and breastfeeding history. RESULTS: Pregnancy concentrations of certain PFAS were associated with greater adiposity (eg, 0.4 cm [95% confidence interval [95%CI]: -0.1, 0.9] greater waist circumference per doubling in EtFOSAA; 0.2 cm [95%CI: -0.1, 0.5] greater mid-upper arm circumference per doubling in PFOA; 1.2 mm [95%CI: 0.1, 2.2] thicker sum of subscapular and triceps skinfolds per doubling in PFOS) and higher systolic blood pressure (eg, 1.2 mm Hg [95%CI: 0.3, 2.2] per doubling in PFOS) at 3 years postpartum. Higher EtFOSAA concentrations were also associated with 10.8% higher IL-6 (95%CI: 3.3, 18.9) and 6.1% lower SHBG (95%CI: 0.7, 11.2) per doubling. CONCLUSIONS: Pregnancy concentrations of EtFOSAA, PFOS, and PFOA were associated with adverse postpartum cardiometabolic markers.

6.
Environ Int ; 142: 105849, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32593049

RESUMO

BACKGROUND: Recent studies suggest that greater exposure to natural vegetation, or "green space" is associated with lower diabetes risk, possibly through increasing physical activity. However, there is limited research on green space and insulin resistance in youth. We hypothesized greater green space at early-life sensitive time periods would be associated with lower insulin resistance in youth. METHODS: We used data from Project Viva (N = 460), a pre-birth cohort study that recruited pregnant women in eastern Massachusetts, 1999-2002, and followed offspring into adolescence. We defined residential green space exposure at infancy (median age - 1.1 years), early childhood (3.2 years), mid-childhood (7.7 years), and early adolescence (12.8 years), using 30 m resolution Landsat satellite imagery to estimate the Normalized Difference Vegetation Index [NDVI]. Our main outcome was early adolescence estimated insulin resistance (HOMA-IR). We used multiple imputation to account for missing data and multiple linear regression models adjusted for age, sex, race/ethnicity, parental education, household income, and neighborhood median household income. RESULTS: The highest green space tertile had the highest percentage of white participants (85%), college-educated mothers (87%) and fathers (85%), and households with income higher than US$70,000 (86%). Unadjusted models showed that participants living in the highest green space tertile at infancy had a 0.15 unit lower HOMA-IR (95% CI: -0.23, -0.06) in early adolescence, than those living in the lowest tertile. However, in adjusted models, we did not observe evidence of associations between green space from infancy to early adolescence and HOMA-IR in early adolescence, although some point estimates were in the hypothesized direction. For example, participants in the highest green space tertile in infancy had 0.03 units lower HOMA-IR (95%CI: -0.14, 0.08) than those living in the lowest tertile. CONCLUSIONS: Exposure to green space at early life sensitive time periods was not associated with HOMA-IR in youth. Early-life longitudinal studies across diverse populations are needed to confirm or refute our results.

7.
J Clin Endocrinol Metab ; 105(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32480407

RESUMO

CONTEXT: Per- and polyfluoroalkyl substances (PFAS) exposure may alter glucose homeostasis. Research on PFAS exposure and glucose tolerance during pregnancy is limited. OBJECTIVE: The objective of this work is to estimate associations between first-trimester plasma PFAS concentrations and glucose tolerance assessed in late second pregnancy trimester. DESIGN, SETTING, PARTICIPANTS, AND MAIN OUTCOME MEASURES: Pregnant women (n = 1540) enrolled in Project Viva in 1999 to 2002 provided first-trimester plasma samples analyzed for 8 PFAS. At approximately 28 weeks' gestation, women completed 1-hour nonfasting, 50-g oral glucose challenge tests (GCTs); if abnormal, women completed subsequent 3-hour oral glucose tolerance tests (OGTTs) to screen for gestational diabetes mellitus (GDM). We assessed both continuous GCT glucose levels and 4 categories of glucose tolerance (normal glycemia [reference], isolated hyperglycemia, impaired glucose tolerance, GDM). We used multinomial logistic regression to estimate associations of PFAS with glucose tolerance categories. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to assess individual and joint effects of PFAS on continuous GCT glucose levels, respectively. We evaluated effect modification by maternal age and race/ethnicity. RESULTS: PFAS were not associated with glucose tolerance categories. In BKMR analyses, we observed a positive association between ln-perfluorooctane sulfonate (PFOS) and glucose levels (Δ25th to 75th percentile: 6.2 mg/dL, 95% CI, 1.1-11.3) and an inverse-U shaped association between 2-(N-perfluorooctane sulfonamide) acetate and glucose levels. Individual linear regression results were similar. We found suggestive evidence that associations varied by age and racial/ethnic group. CONCLUSION: Certain PFAS may alter glucose homeostasis during pregnancy, but may not be associated with overt GDM.

8.
Environ Int ; 139: 105728, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32311629

RESUMO

BACKGROUND: Maternal and neonatal thyroid function is critical for growth and neurodevelopment. Exposure to individual per- and polyfluoroalkyl substances (PFAS) can alter circulating thyroid hormone levels, but few studies have investigated effects of combined exposure to multiple PFAS. OBJECTIVES: Estimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function. METHODS: The study population consisted of 726 mothers and 465 neonates from Project Viva, a Boston, Massachusetts area longitudinal pre-birth cohort. We measured six PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido)acetate (EtFOSAA), and 2-(N-methyl-perfluorooctane sulfonamido)acetate (MeFOSAA)] and thyroxine (T4), Free T4 Index (FT4I), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T4 in postpartum heel sticks. We estimated individual and joint effects of PFAS exposure with thyroid hormone levels using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), and evaluated potential non-linearity and interactions among PFAS using BKMR. RESULTS: Higher concentrations of the PFAS mixture were associated with significantly lower maternal FT4I, with MeFOSAA, EtFOSAA, PFOA, and PFHxS contributing most to the overall mixture effect in BKMR and WQS regression. In infants, higher concentrations of the PFAS mixture were associated with lower T4 levels, primarily in males, with PFHxS and MeFOSAA contributing most in WQS, and PFHxS contributing most in BKMR. The PFAS mixture was not associated with maternal T4 or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T4 levels (Δ25th to 75th percentile: 0.21 µg/dL; 95% credible interval: -0.03, 0.47) and ln-PFHxS was associated with a non-linear effect on TSH levels. CONCLUSIONS: These findings support the hypothesis that there may be combined effects of prenatal exposure to multiple PFAS on maternal and neonatal thyroid function, but the direction and magnitude of these effects may vary across individual PFAS.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32344059

RESUMO

BACKGROUND: Tocopherol isoforms may regulate child lung growth and spirometric measures. OBJECTIVE: Our aim was to determine the extent to which plasma α-tocopherol (α-T) or γ-tocopherol (γ-T) isoform levels in early childhood or in utero are associated with childhood lung function. METHODS: We included 622 participants in the Project Viva cohort who had lung function at a mid-childhood visit (age 6-10 years). Maternal and child tocopherol isoform levels were measured by HPLC at the second trimester and 3 years of age, respectively. Multivariable linear regression models (adjusted for mid-childhood body mass index z scores, maternal education, smoking in pregnancy, and prenatal particulate matter with diameter of <2.5 micrometers (PM2.5) particulate exposure) stratified by tertiles of child γ-T level were used to assess the association of α-T levels with FEV1 and forced vital capacity (FVC) percent predicted. Similarly, models stratified by child α-T tertile evaluated associations of γ-T levels with lung function. We performed similar analyses with maternal second trimester tocopherol isoform levels. RESULTS: The median maternal second trimester α-T level was 63 µM (interquartile range = 47-82). The median early-childhood level was 25 µM (interquartile range = 20-33 µM). In the lowest tertile of early-childhood γ-T, children with a higher α-T level (per 10 µM) had a higher mid-childhood FEV1 percent predicted (ß = 3.09; 95% CI = 0.58-5.59 and a higher FVC percent predicted (ß = 2.77; 95% CI = 0.47-5.06). This protective association of α-T was lost at higher γ-T levels. We did not see any consistent associations of second trimester levels of either α-T or γ-T with mid-childhood FEV1 or FVC. CONCLUSION: When γ-T levels were in the lowest tertile, a higher early-childhood α-T level was associated with better lung function at mid-childhood. Second trimester maternal plasma α-T concentration was 3-fold higher than in the adult nonpregnant female population.

10.
J Nutr ; 150(7): 1889-1898, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32321175

RESUMO

BACKGROUND: Postpartum weight trajectories and its implications on later cardiometabolic health are not entirely understood. OBJECTIVES: Our objectives were: 1) to characterize maternal weight trajectories from 1 to 24 mo postpartum, 2) to determine the association of prepregnancy BMI, gestational weight gain (GWG), and pregnancy behaviors with the trajectories, and 3) to evaluate the association of weight trajectories with BMI, waist circumference (WC), lipid profile, glucose, insulin resistance, blood pressure, and inflammatory markers at 3 y postpartum. METHODS: We studied 1359 mothers from the prospective cohort Project Viva. Using weights at 1, 6, 12, and 24 mo postpartum, we characterized weight trajectories using a latent class growth model. For objectives 2 and 3, we used multinomial logistic regression and multiple linear regression models, respectively. RESULTS: Around 85% of women fell into a trajectory of sustained weight loss (1-12 mo) + maintenance (12-24 mo) (reference), 5.7% followed a trajectory characterized by fast weight loss + slight gain, and 9.7% fell into a trajectory of little weight loss + slight gain. Prepregnancy overweight and obesity increased the odds of falling into the fast weight loss + slight gain trajectory, compared with the reference. Prepregnancy overweight [OR 1.57 (95% CI: 1.01, 2.46)] and a higher total GWG rate [3.69 (2.90, 4.68)] increased the odds of falling into the little weight loss + slight gain trajectory, whereas a higher Prudent dietary pattern score was protective [0.73 (0.54, 0.98)]. Women in this trajectory had higher BMI, WC, weight gain from prepregnancy, low-density lipoprotein cholesterol, and inflammatory markers at 3 y postpartum. CONCLUSIONS: Women following a trajectory of little weight loss + slight gain during the first 2 y postpartum had an adverse cardiometabolic profile 3 y after delivery. Targeting diet and GWG during pregnancy and facilitating postpartum weight loss could improve women's long-term health.

11.
Sleep Health ; 6(4): 463-468, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32331867

RESUMO

OBJECTIVE: To examine the association of maternal lifetime experiences of racial discrimination with infant sleep duration over the first 2 years of life. DESIGN: Prebirth cohort study. SETTING: Massachusetts, USA (baseline: 1999-2002). PARTICIPANTS: 552 mother-infant dyads in Project Viva, for whom the mother self-identified as being a woman of color. MEASUREMENTS: During pregnancy, mothers completed the Experiences of Discrimination survey that measured lifetime experiences of racial discrimination in eight domains. The main outcome was a weighted average of their infants' 24-hour sleep duration from 6 months to 2 years. RESULTS: 30% reported 0 domains of racial discrimination, 35% 1-2 domains, and 34% ≥3 domains. Any racial discrimination (≥1 vs. 0 domains) was higher among black (80%) versus Hispanic (58%) or Asian (53%) mothers and the United States versus foreign-born mothers (79% vs. 58%) and was associated with higher mean prepregnancy BMI (26.8 vs. 24.5 kg/m2). Children whose mothers reported ≥3 domains versus 0 domains had shorter sleep duration from 6 months to 2 years in unadjusted analysis (ß -18.6 min/d; 95% CI -37.3, 0.0), which was attenuated after adjusting for maternal race/ethnicity and nativity (-13.6 min/d; -33.7, 6.5). We found stronger associations of racial discrimination with offspring sleep at 6 months (-49.3 min/d; -85.3, -13.2) than for sleep at 1 year (-13.5 min/d; -47.2, 20.3) or 2 years (4.2 min/d; -21.5, 29.9). CONCLUSIONS: Maternal lifetime experiences of racial discrimination was associated with shorter offspring sleep duration at 6 months, but not with infant's sleep at 1 and 2 years of age.

12.
Nutrients ; 12(3)2020 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-32204442

RESUMO

Infancy is a time of plasticity in development of taste preference. Complementary feeding (CF) may be a "sensitive period" for learning new taste preferences and establishing healthy dietary behaviors that may track later in life. Among 1162 children in the U.S. prospective cohort study Project Viva, we aimed to identify patterns of CF behaviors around 1 year and examine associations with diet quality in early childhood (median age 3.1y). We identified patterns of CF using latent class analysis (LCA) and examined later diet quality based on scores on the Youth Healthy Eating Index (YHEI). We identified four distinct CF patterns (latent classes). Later YHEI scores were highest in the class characterized by "breast milk and delayed sweets and fruit juice" and lowest in the "picky eaters" class. The classes defined as "late flavor introduction and delayed sweets" and "early flavor introduction and more fruit juice" had similar, moderate scores. Our results suggest that CF patterns that increase food acceptance and discourage the innate preference for sweetness may have persistent influences on diet quality.

13.
Paediatr Perinat Epidemiol ; 34(3): 366-375, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32162715

RESUMO

BACKGROUND: There is great interest in understanding whether interventions on sugar-sweetened beverage (SSB) consumption through pregnancy and early childhood affect adolescent body mass index (BMI). Without data from randomised trials, unbiased estimation of such effects might be achieved with observational data given sufficient and appropriate adjustment for both baseline and time-varying confounders. OBJECTIVES: To illustrate the use of inverse probability (IP) weighting of marginal structural models (MSM) for estimating the effects of SSB consumption through pregnancy and early childhood on the mean early adolescent BMI z-score. METHODS: Our baseline sample consisted of 1584 pregnant women from a pre-birth cohort. We defined 6 intervention intervals: early pregnancy, late pregnancy, 3, 4, 5, and 6 years. We fitted a MSM via a weighted linear regression with IP exposure and censoring weights to estimate the mean difference in BMI z-score under interventions: "maintain SSB consumption below (vs above) 0.5 servings/day in all intervals." RESULTS: The estimated difference in mean BMI z-score under interventions maintaining SSB consumption at or below (vs above) 0.5 servings/day from pregnancy to 6 years was -0.94 (95% confidence interval [CI] -1.52, -0.08). The effect estimate in pregnancy, while fixing the exposure range in childhood, was -0.05 (95% CI -0.34, 0.23), and in early childhood, while fixing the range in pregnancy was -0.89 (95% CI -1.46, -0.11). The effect estimates were largely unchanged under sensitivity analyses to different implementation choices except for the choice of time interval length. CONCLUSIONS: Under assumptions that include no unmeasured confounding and selection bias, and no model misspecification, results of this IP weighting application are in line with a lower mean BMI z-score in early adolescence under interventions ensuring lower, vs greater, SSB consumption in early life. This application provides a resource for researchers working with longitudinal birth cohort studies and interested in similar causal questions.

14.
Genome Med ; 12(1): 25, 2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32114984

RESUMO

BACKGROUND: Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. METHODS: We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. RESULTS: We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P < 1.06 × 10- 7, of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. CONCLUSIONS: We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.

15.
PLoS One ; 15(2): e0228769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32017807

RESUMO

BACKGROUND: Hair cortisol concentration (HCC) is an increasingly used measure of systemic cortisol concentration. However, determinants of HCC in children and adolescents are unclear because few prospective studies have been conducted to date. STUDY DESIGN: We followed 725 children in Project Viva, a pre-birth cohort study of mothers and children, who provided hair samples at mid-childhood (median age: 7.7 years) or early adolescence (median age: 12.9 years). We examined associations of various factors measured from pregnancy to mid-childhood with HCC in mid-childhood and early adolescence, as well as change in HCC between these time points (ΔHCC). RESULTS: There were 426 children with HCC measurements in both mid-childhood and early adolescence, 173 children with measures only in mid-childhood, and 126 with measures only in early adolescence. HCC was lower in mid-childhood (median 1.0pg/mg [interquartile range, IQR: 0.5, 2.4]) than early adolescence (2.2pg/mg [1.1, 4.4]). In multivariable-adjusted regression models, female sex (ß = -0.41, 95% CI: -0.67, -0.15) and birth weight-for-gestational age z-score (ß = -0.19, 95% CI: -0.33, -0.04) were associated with lower mid-childhood HCC, while prenatal smoking was associated with higher mid-childhood HCC (ß = 0.53, 95% CI: 0.04, 1.01). In early adolescence, child age (ß = 0.34 per year, 95% CI: 0.21, 0.46) female sex (ß = 0.33, 95% CI: 0.10, 0.57), and maternal pre-pregnancy body mass index (ß = 0.15 per 5-kg/m2, 95% CI: 0.01, 0.29) were positively associated with HCC. Child anthropometric measures and biomarker concentrations were not associated with HCC. CONCLUSION: Maternal pre-pregnancy BMI, maternal prenatal smoking, and low birth weight were associated with higher mid-childhood and adolescent HCC. However, few postnatal characteristics were associated with HCC.


Assuntos
Cabelo/metabolismo , Hidrocortisona/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Adolescente , Criança , Feminino , Humanos , Masculino , Gravidez , Fumar/efeitos adversos
16.
Paediatr Perinat Epidemiol ; 34(3): 267-277, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31965601

RESUMO

BACKGROUND: Over-the-counter analgesic use during pregnancy, particularly acetaminophen, may be associated with negative developmental outcomes in children. OBJECTIVE: Estimate associations of prenatal and early-life exposure to acetaminophen in early childhood with cognitive, motor, and language skills in two birth cohorts. METHODS: The American Project Viva cohort (1217 mother-child pairs enrolled 1999-2002) assessed cognition at approximately 3 years using the Peabody Picture Vocabulary Test and the Wide Range Achievement of Visual Motor Abilities (WRAVMA). The Brazilian 2015 Pelotas Birth Cohort (3818 mother-child pairs) assessed cognition at 2 years using the INTERGROWTH-21st Neurodevelopment Assessment. We used linear regression to estimate associations of acetaminophen use during pregnancy (Project Viva and Pelotas) and infancy (Project Viva) with children's cognitive scores adjusted for maternal age, pre-pregnancy body mass index, education, parity, race/ethnicity, smoking and alcohol use during pregnancy, depression during pregnancy, antibiotic and ibuprofen use during pregnancy, household income, and child's sex. RESULTS: In Project Viva, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was associated with lower WRAVMA drawing scores (ß -1.51, 95% CI -2.92, -0.10). However, in Pelotas, exposure to acetaminophen in both the 1st and 2nd trimester of pregnancy was not associated with INTER-NDA motor scores (ß 0.02; 95% CI -0.05, 0.09) and was associated with higher INTER-NDA total scores (ß 0.08, 95% CI 0.01, 0.16). Other comparisons did not show evidence for any associations. CONCLUSIONS: Inconsistencies and lack of specificity of the findings did not clarify the research question considering that we still have a large variability and uncertainty to define the risk or safety in the use of acetaminophen related to cognition in early childhood. More studies using better exposure assessment and better confounding variables are needed to clarify these associations.

17.
Matern Child Health J ; 24(4): 503-513, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31897929

RESUMO

OBJECTIVE: Examine the associations of maternal thyroid hormones, maternal dietary information, and newborn T4 levels with cognitive outcomes in mid-childhood. METHODS: We studied 921 children born 1999-2003 at gestational age ≥ 34 weeks, who were participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We examined maternal dietary information, maternal thyroid hormone levels, and neonatal levels of T4. Research staff performed cognitive testing in mid-childhood (median age 7.7 years). RESULTS: We included 514 women with measured first trimester thyroid hormone concentrations (mean 10.2 weeks); 15% of women had a thyroid stimulating hormone (TSH) level ≥ 2.5 mU/L, and 71% were college graduates. Newborn T4 was collected from 375 infants (mean 17.6 µg/dl; SD 4.0), on day 2 (mean 1.9 days; SD 0.7) as part of the newborn screening program. Mean (SD) verbal and nonverbal IQ, memory, and motor scores of children were 113.2 (14.3), 107.1 (16.7), 17.1 (4.4), and 92.5 (16.6) points, respectively. In multivariable analysis, first trimester maternal thyroid function (total T3, total T4, free T4, thyroid stimulating hormone (TSH) or total thyroid peroxidase (TPO) antibody levels) or newborn T4 were not associated with any of the cognitive outcomes in mid-childhood after adjustment for sociodemographic and perinatal variables. CONCLUSIONS FOR PRACTICE: Maternal or neonatal thyroid hormone levels were not associated with cognitive outcomes in mid-childhood in this population with generally normal thyroid function. As we studied a highly educated cohort residing in an iodine-sufficient area, findings may not be generalizable.


Assuntos
Desenvolvimento Infantil , Cognição/fisiologia , Testes de Função Tireóidea/estatística & dados numéricos , Tiroxina/análise , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Massachusetts , Estudos Prospectivos , Testes de Função Tireóidea/métodos , Tiroxina/sangue , Estados Unidos
19.
Pediatr Pulmonol ; 55(2): 503-509, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31805224

RESUMO

Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation that is well-characterized in allergic disease states. However, FeNO is also involved in nonallergic inflammatory and pulmonary vascular mechanisms or responses to environmental stimuli. We sought to determine the extent to which obesity or sedentary lifestyle is associated with FeNO in adolescents not selected on the basis of allergic disease. In Project Viva, a prebirth cohort study, we measured body mass index (BMI), skinfold thicknesses, waist circumference, body fat, hours watching television, hours of physical activity, and heart rate after exercise among 929 adolescents (median age, 12.9). We measured FeNO twice and averaged these as a continuous, log-transformed outcome. We performed linear regression models, adjusted for child age, sex, height, and race/ethnicity, maternal education and smoking during pregnancy, household income and smoking, and neighbourhood characteristics. In secondary analysis, we additionally adjusted for asthma. More than 2 hours spent watching TV was associated with 10% lower FeNO (95% confidence interval [CI]: -20, 0%). Higher body fat percentage was also associated with lower FeNO. After additional adjustment for asthma, teens who are underweight (BMI <5th %tile, 3%) had 22% lower FeNO (95%CI: -40, 2%) and teens who are overweight (BMI ≥85th %ile, 28%) had 13% lower FeNO (95%CI: -23, -2%). Each of these associations of lifestyle and body weight with lower FeNO were greater in magnitude after adjusting for asthma. In summary, sedentary lifestyle, high and low BMI were all associated with lower FeNO in this adolescent cohort.

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