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1.  Effects of Promoting Longer Term and Exclusive Breastfeeding on Cardiometabolic Risk Factors at Age 11.5 Years: A Cluster-Randomized, Controlled Trial 
Circulation  2013;129(3):321-329.
Background
The duration and exclusivity of breastfeeding in infancy have been inversely associated with future cardiometabolic risk. We investigated the effects of an experimental intervention to promote increased duration of exclusive breastfeeding on cardiometabolic risk factors in childhood.
Methods and results
We followed-up children in the Promotion of Breastfeeding Intervention Trial, a cluster-randomized trial of a breastfeeding promotion intervention based on the World Health Organization/United Nations Children’s Fund Baby-Friendly Hospital Initiative. 17,046 breastfeeding mother-infant pairs were enrolled in 1996/7 from 31 Belarussian maternity hospitals and affiliated polyclinics (16 intervention vs 15 control sites); 13,879 (81.4%) children were followed-up at 11.5 years, with 13,616 (79.9%) fasted and without diabetes. The outcomes were blood pressure; fasting insulin, adiponectin, glucose and apolipoprotein A1; and presence of metabolic syndrome. Analysis was by intention to treat, accounting for clustering within hospitals/clinics. The intervention substantially increased breastfeeding duration and exclusivity compared with the control arm (43% vs. 6% and 7.9% vs. 0.6% exclusively breastfed at 3 and 6 months, respectively). Cluster-adjusted mean differences at 11.5 years between experimental vs control groups were: 1.0mmHg (95% CI: −1.1, 3.1) for systolic and 0.8mmHg (−0.6, 2.3) for diastolic blood pressure; −0.1mmol/l (−0.2, 0.1) for glucose; 8% (−3%, 34%) for insulin; −0.33μ/ml (−1.5, 0.9) for adiponectin; and 0.0g/l (−0.1, 0.1) for ApoA1. The cluster-adjusted odds ratio for metabolic syndrome, comparing experimental vs control groups, was 1.21 (0.85, 1.72).
Conclusions
An intervention to improve breastfeeding duration and exclusivity among healthy term infants did not influence cardiometabolic risk factors in childhood.
Clinical Trial Registration Information
Current Controlled Trials: ISRCTN37687716 (http://www.controlled-trials.com/ISRCTN37687716); Clinicaltrials.gov. Identifier: NCT01561612.
doi:10.1161/CIRCULATIONAHA.113.005160
PMCID: PMC3946966  PMID: 24300437
Breastfeeding; lactation; blood pressure; fasting insulin; glucose; adiponectin; lipids; randomized controlled trial; childhood
2.  Gestational Glucose Tolerance and Cord Blood Leptin Levels Predict Slower Weight Gain in Early Infancy 
The Journal of pediatrics  2010;158(2):227-233.
Objective
To determine the extent to which known pre- and perinatal predictors of childhood obesity also predict weight gain in early infancy.
Study design
We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z-score (WFL-z) from 0 to 6 months.
Results
Mean (SD) change in WFL-z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z-score (-0.28 [95% C.I. -0.37, -0.19] per unit), cord blood leptin (-0.40 [95% C.I. -0.61, -0.19] per 10 ng/ml) and gestational diabetes (-0.50 [95% C.I. -0.88, -0.11] versus normal glucose tolerance) were each associated with slower gain in WFL-z from 0 to 6 months.
Conclusion
Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.
doi:10.1016/j.jpeds.2010.07.052
PMCID: PMC4270123  PMID: 20855080
obesity
3.  A qualitative study of gestational weight gain counseling and tracking 
Maternal and child health journal  2013;17(8):1508-1517.
Objectives
Excessive gestational weight gain (GWG) predicts adverse pregnancy outcomes and later obesity risk for both mother and child. Women who receive GWG advice from their obstetric clinicians are more likely to gain the recommended amount, but many clinicians do not counsel their patients on GWG, pointing to the need for new strategies. Electronic medical records (EMRs) are a useful tool for tracking weight and supporting guideline-concordant care, but their use for care related to GWG has not been evaluated.
Methods
We performed in-depth interviews with 16 obstetric clinicians from a multi-site group practice in Massachusetts that uses an EMR. We recorded, transcribed, coded, and analyzed the interviews using immersion-crystallization.
Results
Many respondents believed that GWG had “a lot” of influence on pregnancy and child health outcomes but that their patients did not consider it important. Most indicated that excessive GWG was a big or moderate problem in their practice, and that inadequate GWG was rarely a problem. All used an EMR feature that calculates total GWG at each visit. Many were enthusiastic about additional EMR-based supports, such as a reference for recommended GWG for each patient based on pre-pregnancy body mass index, a “growth chart” to plot actual and recommended GWG, and an alert to identify out-of-range gains, features which many felt would remind them to counsel patients about excessive weight gain.
Conclusion
Additional decision support tools within EMRs would be well received by many clinicians and may help improve the frequency and accuracy of GWG tracking and counseling.
doi:10.1007/s10995-012-1158-9
PMCID: PMC3574181  PMID: 23065312
Gestational weight gain; obstetrics; electronic medical record; counseling
4.  Sex-Specific Associations of Gestational Glucose Tolerance With Childhood Body Composition 
Diabetes Care  2013;36(10):3045-3053.
OBJECTIVE
To examine the associations of maternal gestational glucose tolerance with offspring body composition in late childhood.
RESEARCH DESIGN AND METHODS
Among 958 women in the prebirth cohort Project Viva, glucose tolerance was assessed in the second trimester by nonfasting 50-g 1-h glucose challenge test (GCT), followed if abnormal by fasting 100-g 3-h oral glucose tolerance test (OGTT). We categorized women as normoglycemic (83.3%) if GCT was ≤140 mg/dL, isolated hyperglycemia (9.1%) if GCT was abnormal but OGTT normal, intermediate glucose intolerance (IGI) (3.3%) if there was one abnormal value on OGTT, or gestational diabetes mellitus (GDM) (4.5%) if there were two or more abnormal OGTT values. Using multivariable linear regression, we examined adjusted associations of glucose tolerance with offspring overall (N = 958) and central (N = 760) adiposity and body composition using dual X-ray absorptiometry (DXA) measured at the school-age visit (95 ± 10 months).
RESULTS
Compared with that in the male offspring of normoglycemic mothers, DXA fat mass was higher in male offspring of GDM mothers (1.89 kg [95% CI 0.33–3.45]) but not in male offspring of mothers with IGI (0.06 kg [−1.45 to 1.57]). DXA trunk-to-peripheral fat mass, a measure of central adiposity, was also somewhat higher in male offspring of GDM mothers (0.04 [−0.01 to 0.09]). In girls, DXA fat mass was higher in offspring of mothers with IGI (2.23 kg [0.12–4.34]) but not GDM (−1.25 kg [−3.13 to 0.63]). We showed no association of gestational glucose tolerance with DXA lean mass.
CONCLUSIONS
In this study, only male offspring of GDM mothers manifested increased adiposity, whereas only female offspring of mothers with IGI did so. Sex differences in glycemic sensitivity may explain these findings.
doi:10.2337/dc13-0333
PMCID: PMC3781569  PMID: 23877978
5.  Infant feeding and childhood cognition at ages 3 and 7 years: effects of breastfeeding duration and exclusivity 
JAMA pediatrics  2013;167(9):836-844.
Importance
Breastfeeding may benefit child cognitive development, but few studies have quantified breastfeeding exclusivity or duration, nor has any study examined the role of maternal diet during lactation on child cognition.
Objectives
(1) To examine associations of breastfeeding duration and exclusivity with child cognition at 3 and 7 years; and (2) to examine the extent to which maternal fish intake during lactation modifies associations of infant feeding with later cognition
Design
Prospective cohort study
Setting
Project Viva, a U.S. pre-birth cohort that enrolled mothers from 1999-2002 and followed children to age 7 years
Participants
1312 Project Viva mothers and children
Main exposure
Duration of any breastfeeding to 12 months
Main outcome measures
Child receptive language assessed with the Peabody Picture Vocabulary Test (PPVT-III) age 3 years; Wide Range Assessment of Visual Motor Abilities (WRAVMA) at 3 and 7 years; and Kaufman Brief Intelligence Test (KBIT) and Wide Range Assessment of Memory and Learning (WRAML) at 7 years.
Results
Adjusting for sociodemographics, maternal intelligence, and home environment in linear regression, longer breastfeeding duration was associated with higher age 3 PPVT-III scores (0.21 points/month, 95% CI: 0.03, 0.38) and greater age 7 intelligence (0.35 verbal KBIT points/month, 95% CI: 0.16, 0.53; 0.29 non-verbal KBIT points/month, 95% CI: 0.05, 0.54). Breastfeeding duration was not associated with WRAML scores. Beneficial effects of breastfeeding on the WRAVMA at age 3 appeared greater for women who consumed ≥2 fish servings/week (0.24 points, 95% CI: 0.00, 0.47) vs. <2 servings/week (-0.01 points, 95% CI: -0.22, 0.20); interaction p-value 0.16.
Conclusions and relevance
Our results support a causal relationship of breastfeeding duration with receptive language and verbal and non-verbal intelligence later in life.
doi:10.1001/jamapediatrics.2013.455
PMCID: PMC3998659  PMID: 23896931
6.  The Association of Early Childhood Cognitive Development and Behavioural Difficulties with Pre-Adolescent Problematic Eating Attitudes 
PLoS ONE  2014;9(8):e104132.
Objectives
Few studies have prospectively investigated associations of child cognitive ability and behavioural difficulties with later eating attitudes. We investigated associations of intelligence quotient (IQ), academic performance and behavioural difficulties at 6.5 years with eating attitudes five years later.
Methods
We conducted an observational cohort study nested within the Promotion of Breastfeeding Intervention Trial, Belarus. Of 17,046 infants enrolled at birth, 13,751 (80.7%) completed the Children's Eating Attitude Test (ChEAT) at 11.5 years, most with information on IQ (n = 12,667), academic performance (n = 9,954) and behavioural difficulties (n = 11,098) at 6.5 years. The main outcome was a ChEAT score ≥85th percentile, indicative of problematic eating attitudes.
Results
Boys with higher IQ at 6.5 years reported fewer problematic eating attitudes, as assessed by ChEAT scores ≥85th percentile, at 11.5 years (OR per SD increase in full-scale IQ = 0.87; 0.79, 0.94). No such association was observed in girls (1.01; 0.93, 1.10) (p for sex-interaction = 0.016). In both boys and girls, teacher-assessed academic performance in non-verbal subjects was inversely associated with high ChEAT scores five years later (OR per unit increase in mathematics ability = 0.88; 0.82, 0.94; and OR per unit increase in ability for other non-verbal subjects = 0.86; 0.79, 0.94). Behavioural difficulties were positively associated with high ChEAT scores five years later (OR per SD increase in teacher-assessed rating = 1.13; 1.07, 1.19).
Conclusion
Lower IQ, worse non-verbal academic performance and behavioural problems at early school age are positively associated with risk of problematic eating attitudes in early adolescence.
doi:10.1371/journal.pone.0104132
PMCID: PMC4125275  PMID: 25102171
7.  Dietary Quality during Pregnancy Varies by Maternal Characteristics in Project Viva: A US Cohort 
Background
Maternal diet may influence outcomes of pregnancy and childhood, but data on correlates of food and nutrient intake during pregnancy are scarce.
Objective
To examine relationships between maternal characteristics and diet quality during the first trimester of pregnancy. Secondarily we examined associations of diet quality with pregnancy outcomes.
Methods
As part of the ongoing US prospective cohort study Project Viva, we studied 1,777 women who completed a food frequency questionnaire during the first trimester of pregnancy. We used linear regression models to examine the relationships of maternal age, prepregnancy body mass index, parity, education, and race/ethnicity with dietary intake during pregnancy. We used the Alternate Healthy Eating Index, slightly modified for pregnancy (AHEI-P), to measure diet quality on a 90-point scale with each of the following nine components contributing 10 possible points: vegetables, fruit, ratio of white to red meat, fiber, trans fat, ratio of polyunsaturated to saturated fatty acids, and folate, calcium, and iron from foods.
Results
Mean AHEI-P score was 61±10 (minimum 33, maximum 89). After adjusting for all characteristics simultaneously, participants who were older (1.3 points per 5 years, 95% confidence interval [CI] [0.7 to 1.8]) had better AHEI-P scores. Participants who had higher body mass index (−0.9 points per 5 kg/m2, 95% CI [−1.3 to −0.4]), were less educated (−5.2 points for high school or less vs college graduate, 95% CI [−7.0 to −3.5]), and had more children (−1.5 points per child, 95% CI [−2.2 to −0.8]) had worse AHEI-P scores, but African-American and white participants had similar AHEI-P scores (1.3 points for African American vs white, 95% CI [−0.2 to 2.8]). Using multivariate adjusted models, each five points of first trimester AHEI-P was associated lower screening blood glucose level (β −.64 [95% CI −0.02 to −1.25]). In addition, each five points of second trimester AHEI-P was associated with a slightly lower risk of developing preeclampsia (odds ratio 0.87 [95% CI 0.76 to 1.00]), but we did not observe this association with first trimester AHEI-P (odds ratio 0.96 [95% CI 0.84 to 1.10]).
Conclusions
Pregnant women who were younger, less educated, had more children, and who had higher prepregnancy body mass index had poorer-quality diets. These results could be used to tailor nutrition education messages to pregnant women to avoid long-term sequelae from suboptimal maternal nutrition.
doi:10.1016/j.jada.2009.03.001
PMCID: PMC4098830  PMID: 19465182
8.  Choline Intake During Pregnancy and Child Cognition at Age 7 Years 
American Journal of Epidemiology  2012;177(12):1338-1347.
Animal models indicate that exposure to choline in utero improves visual memory through cholinergic transmission and/or epigenetic mechanisms. Among 895 mothers in Project Viva (eastern Massachusetts, 1999–2002 to 2008–2011), we estimated the associations between intakes of choline, vitamin B12, betaine, and folate during the first and second trimesters of pregnancy and offspring visual memory (measured by the Wide Range Assessment of Memory and Learning, Second Edition (WRAML2), Design and Picture Memory subtests) and intelligence (measured using the Kaufman Brief Intelligence Test, Second Edition (KBIT-2)) at age 7 years. Mean second-trimester intakes were 328 (standard deviation (SD), 63) mg/day for choline, 10.5 (SD, 5.1) µg/day for vitamin B12, 240 (SD, 104) mg/day for betaine, and 1,268 (SD, 381) µg/day for folate. Mean age 7 test scores were 17.2 (SD, 4.4) points on the WRAML 2 Design and Picture Memory subtests, 114.3 (SD, 13.9) points on the verbal KBIT-2, and 107.8 (SD, 16.5) points on the nonverbal KBIT-2. In a model adjusting for maternal characteristics, the other nutrients, and child's age and sex, the top quartile of second-trimester choline intake was associated with a child WRAML2 score 1.4 points higher (95% confidence interval: 0.5, 2.4) than the bottom quartile (P-trend = 0.003). Results for first-trimester intake were in the same direction but weaker. Intake of the other nutrients was not associated with the cognitive tests administered. Higher gestational choline intake was associated with modestly better child visual memory at age 7 years.
doi:10.1093/aje/kws395
PMCID: PMC3676149  PMID: 23425631
choline; cognition; folate; memory; pregnancy
9.  Weight gain in pregnancy and risk of maternal hyperglycemia 
OBJECTIVE
The purpose of this study was to examine associations of weight gain from prepregnancy to glycemic screening with glucose tolerance status.
STUDY DESIGN
Main outcomes were failed glycemic screening (1-hour glucose result ≥ 140 mg/dL) with either 1 high value on 3-hour oral glucose tolerance testing (impaired glucose tolerance in pregnancy) or ≥ 2 high values on 3-hour oral glucose tolerance testing (gestational diabetes mellitus). We performed multinomial logistic regression to determine the odds of these glucose intolerance outcomes by quartile of gestational weight gain among 1960 women in Project Viva.
RESULTS
Mean gestational weight gain was 10.2 ± 4.3 (SD) kg. Compared with the lowest quartile of weight gain, participants in the highest quartile had an increased odds of impaired glucose tolerance in pregnancy (adjusted odds ratio, 2.54; 95% confidence interval, 1.25–5.15), but not gestational diabetes mellitus (odds ratio, 0.93; 95% confidence interval, 0.50–1.70).
CONCLUSION
Higher weight gain predicted impaired glucose tolerance in pregnancy, but not gestational diabetes mellitus.
doi:10.1016/j.ajog.2009.01.039
PMCID: PMC4050656  PMID: 19371858
gestational diabetes mellitus; impaired glucose tolerance; obesity; pregnancy; weight gain
10.  Television Viewing in Infancy and Child Cognition at 3 Years of Age in a US Cohort 
Pediatrics  2009;123(3):e370-e375.
Objective
To examine the extent to which infant television viewing is associated with language and visual motor skills at 3 years of age.
Measures
We studied 872 children who were participants in Project Viva, a prospective cohort. The design used was a longitudinal survey, and the setting was a multisite group practice in Massachusetts. At 6 months, 1 year, and 2 years, mothers reported the number of hours their children watched television in a 24-hour period, from which we derived a weighted average of daily television viewing. We used multivariable regression analyses to predict the independent associations of television viewing between birth and 2 years with Peabody Picture Vocabulary Test III and Wide-Range Assessment of Visual Motor Abilities scores at 3 years of age.
Results
Mean daily television viewing in infancy (birth to 2 years) was 1.2 (SD: 0.9) hours, less than has been found in other studies of this age group. Mean Peabody Picture Vocabulary Test III score at age 3 was 104.8 (SD: 14.2); mean standardized total Wide-Range Assessment of Visual Motor Abilities score at age 3 was 102.6 (SD: 11.2). After adjusting for maternal age, income, education, Peabody Picture Vocabulary Test III score, marital status, and parity, and child's age, gender, birth weight for gestational age, breastfeeding duration, race/ethnicity, primary language, and average daily sleep duration, we found that each additional hour of television viewing in infancy was not associated with Peabody Picture Vocabulary Test III or total standardized Wide-Range Assessment of Visual Motor Abilities scores at age 3.
Conclusion
Television viewing in infancy does not seem to be associated with language or visual motor skills at 3 years of age.
doi:10.1542/peds.2008-3221
PMCID: PMC4042392  PMID: 19254972
television viewing; infancy; media; cognition
11.  Fish intake during pregnancy and the risk of child asthma and allergic rhinitis -longitudinal evidence from the Danish National Birth Cohort 
The British journal of nutrition  2013;110(7):1313-1325.
Background
Maternal fish intake during pregnancy may influence risk of child asthma and allergic rhinitis, yet evidence is conflicting on its association with these outcomes.
Methods
We examined associations of maternal fish intake during pregnancy with child asthma and allergic rhinitis. Mothers in the Danish National Birth Cohort (N=28,936) reported their fish intake at 12 and 30 weeks of gestation. Using multivariate logistic regression, we examined associations of fish intake with child wheeze, asthma, and rhinitis assessed at several time points: ever wheeze, recurrent wheeze (>3 episodes), ever asthma and allergic rhinitis, and current asthma, assessed at 18 months (N~22,000) and 7 years (N~17,000) using self-report and registry data on hospitalizations and prescribed medications.
Results
Compared to consistently high fish intake during pregnancy (fish as a sandwich or hot meal >=2-3 times/week), never eating fish was associated with higher risk of child asthma diagnosis at 18 months (1·30, 95%CI: 1·05, 1·63, P=0.02), and ever asthma by hospitalization (1·46, 95%CI: 0·99, 2·13, P=0.05) and medication prescription (1·37, 95%CI: 1·10, 1·71, P=0·01). A dose-response was present for asthma at 18 months only (P for trend: 0·001). We found no associations with wheeze or recurrent wheeze at 18 months or with allergic rhinitis.
Conclusions
Our results suggest that high (vs. no) maternal fish intake during pregnancy is protective against both early and ever asthma in 7 year old children.
doi:10.1017/S000711451300038X
PMCID: PMC4035354  PMID: 23473120
fish; cohort study; asthma; allergic rhinitis
12.  Declines in Birth weight and Fetal Growth Independent of Gestational Length 
Obstetrics and gynecology  2013;121(1):51-58.
Objective
Birth weight is decreasing in the US and elsewhere, even among term singletons, although trends in most maternal characteristics should contribute to increased birth weight. Some studies have attributed this decline to the simultaneous decrease in gestational length.
Methods
Using data from Intermountain Healthcare, where a successful initiative reduced the number of early term (37–38 week) elective deliveries, we examined trends in birth weight, small-for-gestational-age (SGA), and large-for-gestational-age (LGA) among 219,694 singleton infants born July 2000 to December 2008 at 37–41 weeks gestation.
Results
Over the 8.5 years, births through scheduled deliveries at 37–38 weeks decreased (9.4% to 4.4%), but overall scheduled deliveries increased (29% to 34%) and mean gestational age at birth (39.1 weeks) did not change. Mean birth weight (3410g to 3383g) and LGA (9.0% to 7.4%) both decreased, whereas SGA increased (7.5% to 8.2%). In multivariable analyses adjusting for maternal and infant characteristics, birth weight decreased (36g; 95% CI: 31, 42), especially among infants born at 37–38 weeks (40g; 30, 49) or that had medical indications for urgent deliveries (48g; 34, 63). Odds of LGA decreased (0.84; 0.80, 0.88) and odds of SGA increased (1.14; 1.08, 1.20).
Conclusion
Even in a population where gestation length did not change, birth weight and fetal growth declined. Decrease in not only gestational length but in fetal growth as well is likely to be contributing to the widely observed recent decrease in birth weight.
PMCID: PMC3977951  PMID: 23262927
13.  IS THE ASSOCIATION OF BREASTFEEDING WITH CHILD OBESITY EXPLAINED BY INFANT WEIGHT CHANGE? 
Objective
Breastfeeding and infant weight change are both associated with adiposity. We examined the extent to which infant weight change mediates the association between breastfeeding and adiposity at age 3 years.
Methods
We studied 884 children in a prospective cohort study. We determined breastfeeding status at 6 months. Our primary outcomes at 3 years were body mass index (BMI) z score and the sum of subscapular and triceps skinfold thicknesses (SS + TR); we also assessed obesity. We defined infant weight change as change in weight-for-age z score between birth and 6 months. We performed multivariable regression analyses.
Results
At age 6 months, 25.0% of infants were fully breastfed. At age 3 years, mean (SD) BMI z score was 0.45 (1.03). In linear regression analyses adjusted for mother’s educational level, race/ethnicity, smoking, BMI, pregnancy weight gain and birth weight (adjusted for gestational age), the BMI z score of fully breastfed children was 0.17 (95% CI:−0.43, 0.09) units lower than never breastfed children. After additional adjustment for infant weight change, the estimate was attenuated (−0.03, 95% CI: −0.27, 0.20). Adjustment for infant weight change only modestly attenuated estimates for SS + TR (from −1.48 (95% CI: −2.52, −0.44) to −1.16 mm (95% CI: −2.18, −0.14)), and for the odds of being obese (from 0.21 (95% CI: 0.07, 0.68) to 0.29 (95% CI: 0.08, 1.05)).
Conclusion
Infant weight change between birth and 6 months mediates associations of breastfeeding with BMI, but only partially with indicators of child adiposity.
doi:10.3109/17477166.2010.524700
PMCID: PMC3977954  PMID: 20979572
body mass index; breastfeeding; infant weight change; obesity; overweight
14.  Air Pollution Exposure and Abnormal Glucose Tolerance during Pregnancy: The Project Viva Cohort 
Environmental Health Perspectives  2014;122(4):378-383.
Background: Exposure to fine particulate matter (PM with diameter ≤ 2.5 μm; PM2.5) has been linked to type 2 diabetes mellitus, but associations with hyperglycemia in pregnancy have not been well studied.
Methods: We studied Boston, Massachusetts–area pregnant women without known diabetes. We identified impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) during pregnancy from clinical glucose tolerance tests at median 28.1 weeks gestation. We used residential addresses to estimate second-trimester PM2.5 and black carbon exposure via a central monitoring site and spatiotemporal models. We estimated residential traffic density and roadway proximity as surrogates for exposure to traffic-related air pollution. We performed multinomial logistic regression analyses adjusted for sociodemographic covariates, and used multiple imputation to account for missing data.
Results: Of 2,093 women, 65 (3%) had IGT and 118 (6%) had GDM. Second-trimester spatiotemporal exposures ranged from 8.5 to 15.9 μg/m3 for PM2.5 and from 0.1 to 1.7 μg/m3 for black carbon. Traffic density was 0–30,860 vehicles/day × length of road (kilometers) within 100 m; 281 (13%) women lived ≤ 200 m from a major road. The prevalence of IGT was elevated in the highest (vs. lowest) quartile of exposure to spatiotemporal PM2.5 [odds ratio (OR) = 2.63; 95% CI: 1.15, 6.01] and traffic density (OR = 2.66; 95% CI: 1.24, 5.71). IGT also was positively associated with other exposure measures, although associations were not statistically significant. No pollutant exposures were positively associated with GDM.
Conclusions: Greater exposure to PM2.5 and other traffic-related pollutants during pregnancy was associated with IGT but not GDM. Air pollution may contribute to abnormal glycemia in pregnancy.
Citation: Fleisch AF, Gold DR, Rifas-Shiman SL, Koutrakis P, Schwartz JD, Kloog I, Melly S, Coull BA, Zanobetti A, Gillman MW, Oken E. 2014. Air pollution exposure and abnormal glucose tolerance during pregnancy: the Project Viva Cohort. Environ Health Perspect 122:378–383; http://dx.doi.org/10.1289/ehp.1307065
doi:10.1289/ehp.1307065
PMCID: PMC3984217  PMID: 24508979
15.  Second Trimester Estimated Fetal Weight and Fetal Weight Gain Predict Childhood Obesity 
The Journal of pediatrics  2012;161(5):864-870.
Objective
To determine the extent to which fetal weight during mid-pregnancy and fetal weight gain from mid-pregnancy to birth predict adiposity and blood pressure (BP) at age 3 years.
Study design
Among 438 children in the Project Viva cohort, we estimated fetal weight at 16–20 (median 18) weeks gestation using ultrasound biometry measures. We analyzed fetal weight gain as change in quartile of weight from the second trimester until birth, and we measured height, weight, subscapular and triceps skinfold thicknesses and BP at age 3.
Results
Mean (SD) estimated weight at 16–20 weeks was 234 (30) grams and birth weight was 3518 (420) grams. In adjusted models, weight estimated during the second trimester and at birth were associated with higher BMI z-scores at age 3 years (0.32 units [95% C.I. 0.04, 0.60] and 0.53 units [95% C.I. 0.24, 0.81] for the highest v. lowest quartile of weight). Infants with more rapid fetal weight gain and those who remained large from mid-pregnancy to birth had higher BMI z-scores (0.85 units [95% C.I. 0.30, 1.39] and 0.63 units [95% C.I. 0.17, 1.09], respectively) at age 3 than infants who remained small during fetal life. We did not find associations between our main predictors and sum or ratio of subscapular and triceps skinfold thicknesses or systolic BP.
Conclusion
More rapid fetal weight gain and persistently high fetal weight during the second half of gestation predicted higher BMI z-score at age 3 years. The rate of fetal weight gain throughout pregnancy may be important for future risk of adiposity in childhood.
doi:10.1016/j.jpeds.2012.04.065
PMCID: PMC3962288  PMID: 22682615
childhood blood pressure; cohort
16.  Effects of promoting increased duration and exclusivity of breastfeeding on adiposity and insulin-like growth factor-I at age 11.5 years: a randomized trial 
Importance
Evidence that increased duration and exclusivity of breastfeeding reduces child obesity risk is based on observational studies that are prone to confounding.
Objective
To investigate effects of an intervention to promote increased duration and exclusivity of breastfeeding on child adiposity and circulating insulin-like growth factor (IGF)-I (which regulates growth).
Design
Cluster-randomized controlled trial.
Setting
31 Belarusian maternity hospitals and their affiliated polyclinics, randomized to usual practices (n=15) or a breastfeeding promotion intervention (n=16).
Participants
17,046 breastfeeding mother-infant pairs enrolled in 1996/7, of whom 13,879 (81.4%) were followed-up between January 2008 and December 2010 at a median age of 11.5 years.
Intervention
Breastfeeding promotion intervention modeled on the WHO/UNICEF Baby Friendly Hospital Initiative.
Main outcome measures
Body mass index (BMI), fat and fat-free mass indices (FMI and FFMI), percent body fat, waist circumference, triceps and subscapular skinfold thicknesses, overweight and obesity, and whole-blood IGF-I. Primary analysis was based on modified intention-to-treat (without imputation), accounting for clustering within hospitals/clinics.
Results
The experimental intervention substantially increased breastfeeding duration and exclusivity (43% vs. 6% and 7.9% vs. 0.6% exclusively breastfed at 3 and 6 months, respectively) versus the control intervention. Cluster-adjusted mean differences in outcomes at 11.5 years between experimental vs. control groups were: 0.19 kg/m2 (95% 4 CI: −0.09, 0.46) for BMI; 0.12 kg/m2 (−0.03, 0.28) for FMI; 0.04 kg/m2 (−0.11, 0.18) for FFMI; 0.47% (−0.11, 1.05) for % body fat; 0.30 cm (−1.41, 2.01) for waist circumference; −0.07 mm (−1.71, 1.57) for triceps and −0.02 mm (−0.79, 0.75) for subscapular skinfold thicknesses; and −0.02 standard deviations (−0.12, 0.08) for IGF-I. The cluster-adjusted odds ratio for overweight / obesity (BMI ≥85th percentile vs <85th percentile) was 1.18 (1.01, 1.39) and for obesity (BMI ≥95th vs <85th percentile) was 1.17 (0.97, 1.41).
Conclusions and relevance
Among healthy term infants in Belarus, an intervention that succeeded in improving the duration and exclusivity of breastfeeding did not prevent overweight or obesity, nor did it affect IGF-I levels, at age 11.5 years. Breastfeeding has many advantages, but population strategies to increase the duration and exclusivity of breastfeeding are unlikely to curb the obesity epidemic.
doi:10.1001/jama.2013.167
PMCID: PMC3752893  PMID: 23483175
Breast feeding; lactation; adiposity; body mass index; randomized controlled trial; insulin-like growth factor-1; childhood
17.  Associations of postnatal weight and length/height gain with wheeze, asthma and atopy: The PROBIT Study 
Background
It has been hypothesised that postnatal weight and length/height gain are variously related to wheeze, asthma and atopy, however supporting evidence is limited and inconsistent.
Methods
Weights and lengths/heights of 12,171 term-infants were measured from birth to 12 months and at 6.5 years, and extracted from polyclinic records prospectively obtained between 12 and 60 months. Atopic phenotypes were ascertained at 6.5 years with the International Study of Asthma and Allergy in Childhood questionnaire and skin-prick tests. Logistic regression models investigated whether rates of weight and length/height gain from infancy to mid-childhood were associated with atopy phenotypes that have occurred ever or in the last 12 months.
Results
After controlling for confounders and prior weight and length/height gain, all weight gain variables except birthweight were positively associated with ever having wheezed (p<0.1). A one SD increase in weight gain rate between 0–3 months was associated with a 12% increase (2%–23%) in allergic rhinitis ever. No other consistent patterns of association were found for weight gain or length/height gain rate between 0–60 months with atopic outcomes at 6.5 years. In contrast, all atopy outcomes except for ever having asthma were associated with current weight and height, even after controlling for prior growth.
Conclusion
Current height and weight are more strongly associated with the development of atopic phenotypes in childhood than patterns of infant and early childhood growth, which may well reflect reverse causality (atopy effects on growth) or residual confounding by an unknown common cause of growth and atopy.
doi:10.1111/pai.12049
PMCID: PMC3711479  PMID: 23374010
wheeze; asthma; atopy; postnatal growth; weight gain; length gain
18.  Delivery by caesarean section and risk of obesity in preschool age children: a prospective cohort study 
Archives of disease in childhood  2012;97(7):610-616.
Objective
To examine whether delivery by caesarean section is a risk factor for childhood obesity.
Design
Prospective pre-birth cohort study (Project Viva).
Setting
Eight outpatient multi-specialty practices based in the Boston, Massachusetts area.
Participants
We recruited women during early pregnancy between 1999 and 2002, and followed their children after birth. We included 1255 children with body composition measured at 3 years of age.
Main outcome measures
Body mass index (BMI) z-score, obesity (BMI for age and sex ≥ 95th percentile), and sum of triceps + subscapular skinfold thicknesses, at 3 years of age.
Results
284 children (22.6 percent) were delivered by caesarean section. At age 3, 15.7% of children delivered by caesarean section were obese, compared with 7.5% of children born vaginally. In multivariable logistic and linear regression models adjusting for maternal pre-pregnancy BMI, birth weight, and other covariates, birth by caesarean section was associated with a higher odds of obesity at age 3 (OR 2.10, 95%CI 1.36 to 3.23), higher mean BMI z-score (0.20 units, 95% CI 0.07 to 0.33), and higher sum of triceps + subscapular skinfold thicknesses (0.94 mm, 95% CI 0.36 to 1.51).
Conclusions
Infants delivered by caesarean section may be at increased risk of childhood obesity. Further studies are needed to confirm our findings and to explore mechanisms underlying this association.
doi:10.1136/archdischild-2011-301141
PMCID: PMC3784307  PMID: 22623615
19.  Determinants of excessive gestational weight gain in urban, low-income women 
Background
Factors influencing excessive weight gain in pregnancy have not been well studied among urban, low-income women.
Methods
Prospective cohort study of 94 prenatal care patients at a large university hospital in Philadelphia, examining associations of modifiable mid-pregnancy behaviors and non-modifiable or early pregnancy factors with excessive gestational weight gain. Data were collected through questionnaires and medical record abstraction in 2009-2011.
Findings
The majority of women were African-American (83%) and all (100%) received Medicaid. Nearly two-thirds (60%) were overweight or obese in early pregnancy and 41% experienced excessive gain. In multivariable logistic regression analyses, significant predictors of excessive gestational weight gain included high early pregnancy body mass index (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 1.43, 12.34 for overweight/obese vs. normal weight), nulliparity (OR: 3.35, 95% CI: 1.17, 9.62 for nulliparity vs. multiparity), and clinician advice discordant with Institute of Medicine guidelines (OR: 5.88, 95% CI: 1.04, 33.32 for discordant vs. concordant advice). Watching under two hours of television daily (OR: 0.18, 95% CI: 0.03, 1.03) and engaging in regular physical activity during pregnancy (OR: 0.35, 95% CI: 0.11, 1.09) were suggestive of a reduced risk of excessive gain.
Conclusions
In this sample of urban, low-income women, high early pregnancy body mass index, nulliparity, and discordant clinician advice were directly associated with excessive gestational weight gain, with a trend toward decreased risk for viewing fewer hours of television and engaging in regular physical activity. Intervening on these targets may optimize gestational weight gain and promote long-term maternal health.
doi:10.1016/j.whi.2012.05.004
PMCID: PMC3433591  PMID: 22818249
20.  The Association of Urbanicity with Infant Sleep Duration 
Health & place  2012;18(5):1000-1005.
Short sleep duration is associated with multiple adverse child outcomes. We examined associations of the built environment with infant sleep duration among 1226 participants in a pre-birth cohort. From residential addresses, we used a geographic information system to determine urbanicity, population density, and closeness to major roadways. The main outcome was mother’s report of her infant’s average daily sleep duration at 1 year of age. We ranked urbanicity and population density as quintiles, categorized distance to major roads into 8 categories, and used linear regression adjusted for socio-demographic characteristics, smoking during pregnancy, gestational age, fetal growth, and television viewing at 1 year. In this sample, mean (SD) sleep duration at age 1 year was 12.8 (1.6) hours/day. In multivariable adjusted analyses, children living in the highest quintile of urbanicity slept −19.2 minutes/day (95% CI: −37.0, −1.50) less than those living in the lowest quintile. Neither population density nor closeness to major roadways was associated with infant sleep duration after multivariable adjustment. Our findings suggest that living in more urban environments may be associated with reduced infant sleep.
doi:10.1016/j.healthplace.2012.06.007
PMCID: PMC3732783  PMID: 22795497
Sleep; urbanicity; population density; infancy; built environment
21.  Filter Paper Blood Spot Enzyme Linked Immunoassay for Adiponectin and Application in the Evaluation of Determinants of Child Insulin Sensitivity 
PLoS ONE  2013;8(8):e71315.
Background
Adiponectin is an adipocyte-derived hormone that acts as a marker of insulin sensitivity. Bloodspot sampling by fingerstick onto filter paper may increase the feasibility of large-scale studies of the determinants of insulin sensitivity. We first describe the validation of an enzyme-linked immunoassay (ELISA) for quantifying adiponectin from dried blood spots and then demonstrate its application in a large trial (PROBIT).
Methods
We quantified adiponectin from 3-mm diameter discs (≈3 µL of blood) punched from dried blood spots obtained from: i) whole blood standards (validation); and ii) PROBIT trial samples (application) in which paediatricians collected blood spots from 13,879 children aged 11.5 years from 31 sites across Belarus. We examined the distribution of bloodspot adiponectin by demographic and anthropometric factors, fasting insulin and glucose.
Results
In the validation study, mean intra-assay coefficients of variation (n = 162) were 15%, 13% and 10% for ‘low’ (6.78 µg/ml), ‘medium’ (18.18 µg/ml) and 'high’ (33.13 µg/ml) internal quality control (IQC) samples, respectively; the respective inter-assay values (n = 40) were 23%, 21% and 14%. The correlation coefficient between 50 paired whole bloodspot versus plasma samples, collected simultaneously, was 0.87 (95% CI: 0.78 to 0.93). Recovery of known quantities of adiponectin (between 4.5 to 36 µg/ml) was 100.3–133%. Bloodspot adiponectin was stable for at least 30 months at −80°C. In PROBIT, we successfully quantified fasting adiponectin from dried blood spots in 13,329 of 13,879 (96%) children. Mean adiponectin (standard deviation) concentrations were 17.34 µg/ml (7.54) in boys and 18.41 µg/ml (7.92) in girls and were inversely associated with body mass index, fat mass, triceps and subscapular skin-fold thickness, waist circumference, height and fasting glucose.
Conclusions
Bloodspot ELISA is suitable for measuring adiponectin in very small volumes of blood collected on filter paper and can be applied to large-scale studies.
doi:10.1371/journal.pone.0071315
PMCID: PMC3731301  PMID: 23936498
22.  Age of Achievement of Gross Motor Milestones in Infancy and Adiposity at Age 3 Years 
Maternal and Child Health Journal  2012;16(5):1015-1020.
Early life physical activity may help prevent obesity but is difficult to measure. The purpose of this study was to examine associations of age of achievement of gross motor milestones in infancy with adiposity at age 3 years. Seven forty one mother/infant dyads participated in a longitudinal study in Massachusetts. Exposures were age of attainment of 4 gross motor milestones—rolling over, sitting up, crawling, and walking. Outcomes were 3-year sum of subscapular and triceps skinfold thickness (SS + TR) for overall adiposity, their ratio (SS:TR) for central adiposity, and body mass index (BMI) z-score. We used linear regression models adjusted for confounders to examine motor milestone achievement and later adiposity. Rolling over (0.04, 95% CI: 0.008, 0.07) and sitting up (0.02, 95% CI: 0.001, 0.05) at ≥6 months were associated with increased SS:TR compared with attainment before 6 months. Walking at ≥15 months was associated with 0.98 mm higher SS + TR (95% CI: 0.05, 1.91) compared with walking before 12 months. Age at crawling was not associated with the outcomes. None of the milestones were associated with BMI z-score. Age of motor milestone achievement was only a modest predictor of adiposity. Later rolling over and sitting up were associated with greater central adiposity, and later age at walking was associated with greater overall adiposity at age 3 years. Although we controlled for birth weight and 6-month weight-for-length in our models, more detailed assessment of early adiposity prior to achievement of motor milestones is needed to help determine causality.
doi:10.1007/s10995-011-0828-3
PMCID: PMC3321389  PMID: 21643834
Infant; Motor development; Obesity; Physical activity
23.  Maternal intake of methyl-donor nutrients and child cognition at 3 years of age 
SUMMARY
Methyl-donor nutrients are substrates for methylation reactions involved in neurodevelopment processes. The role of maternal intake of these nutrients on cognitive performance of the offspring is poorly understood. We examined the associations of maternal intake of folate, vitamin B12, choline, betaine, and methionine during the first and second trimesters of pregnancy, with tests of cognitive performance in the offspring at 3 y of age using data from 1210 participants in Project Viva, a prospective pre-birth cohort study in Massachusetts. We assessed nutrient intake with the use of food frequency questionnaires. Children’s cognition at age 3 y was evaluated with the Peabody Picture Vocabulary Test III (PPVT-III) and visual-motor skills with the Wide Range Assessment of Visual Motor Abilities (WRAVMA) test. In multivariable models adjusting for potential sociobehavioral and nutritional confounders, for each 600 µg/d increment in total folate intake during the first trimester, PPVT-III score at age 3 y was 1.6 points [95% CI: 0.1, 3.1; P = 0.04] higher. There was a weak inverse association between vitamin B12 intake during the second trimester and PPVT-III scores [−0.4 points per 2.6 µg/d; 95% CI: −0.8, −0.1; P = 0.01]. We did not find associations between choline, betaine, or methionine and cognitive outcomes at this age. Results of this study suggest that higher intake of folate in early pregnancy is associated with higher scores on the PPVT-III, a test of receptive language that predicts overall intelligence, at age 3 y.
doi:10.1111/j.1365-3016.2012.01264.x
PMCID: PMC3375854  PMID: 22686384
folate; vitamin B12; choline; methionine; pregnancy; cognition; children
24.  Correlations among adiposity measures in school-aged children 
BMC Pediatrics  2013;13:99.
Background
Given that it is not feasible to use dual x-ray absorptiometry (DXA) or other reference methods to measure adiposity in all pediatric clinical and research settings, it is important to identify reasonable alternatives. Therefore, we sought to determine the extent to which other adiposity measures were correlated with DXA fat mass in school-aged children.
Methods
In 1110 children aged 6.5-10.9 years in the pre-birth cohort Project Viva, we calculated Spearman correlation coefficients between DXA (n=875) and other adiposity measures including body mass index (BMI), skinfold thickness, circumferences, and bioimpedance. We also computed correlations between lean body mass measures.
Results
50.0% of the children were female and 36.5% were non-white. Mean (SD) BMI was 17.2 (3.1) and total fat mass by DXA was 7.5 (3.9) kg. DXA total fat mass was highly correlated with BMI (rs=0.83), bioimpedance total fat (rs=0.87), and sum of skinfolds (rs=0.90), and DXA trunk fat was highly correlated with waist circumference (rs=0.79). Correlations of BMI with other adiposity indices were high, e.g., with waist circumference (rs=0.86) and sum of subscapular plus triceps skinfolds (rs=0.79). DXA fat-free mass and bioimpedance fat-free mass were highly correlated (rs=0.94).
Conclusions
In school-aged children, BMI, sum of skinfolds, and other adiposity measures were strongly correlated with DXA fat mass. Although these measurement methods have limitations, BMI and skinfolds are adequate surrogate measures of relative adiposity in children when DXA is not practical.
doi:10.1186/1471-2431-13-99
PMCID: PMC3693882  PMID: 23799991
Adiposity; Obesity; DXA; BMI
25.  A pilot randomized controlled trial to promote healthful fish consumption during pregnancy: The Food for Thought Study 
Nutrition Journal  2013;12:33.
Background
Nutritionists advise pregnant women to eat fish to obtain adequate docosahexaenoic acid (DHA), an essential nutrient important for optimal brain development. However, concern exists that this advice will lead to excess intake of methylmercury, a developmental neurotoxicant.
Objective
Conduct a pilot intervention to increase consumption of high-DHA, low-mercury fish in pregnancy.
Methods
In April-October 2010 we recruited 61 women in the greater Boston, MA area at 12–22 weeks gestation who consumed <=2 fish servings/month, and obtained outcome data from 55. We randomized participants to 3 arms: Advice to consume low-mercury/high-DHA fish (n=18); Advice + grocery store gift cards (GC) to purchase fish (n=17); or Control messages (n=20). At baseline and 12-week follow-up we estimated intake of fish, DHA and mercury using a 1-month fish intake food frequency questionnaire, and measured plasma DHA and blood and hair total mercury.
Results
Baseline characteristics and mean (range) intakes of fish [21 (0–125) g/day] and DHA from fish [91 (0–554) mg/d] were similar in all 3 arms. From baseline to follow-up, intake of fish [Advice: 12 g/day (95% CI: -5, 29), Advice+GC: 22 g/day (5, 39)] and DHA [Advice: 70 mg/d (3, 137), Advice+GC: 161 mg/d (93, 229)] increased in both intervention groups, compared with controls. At follow-up, no control women consumed >= 200mg/d of DHA from fish, compared with 33% in the Advice arm (p=0.005) and 53% in the Advice+GC arm (p=0.0002). We did not detect any differences in mercury intake or in biomarker levels of mercury and DHA between groups.
Conclusions
An educational intervention increased consumption of fish and DHA but not mercury. Future studies are needed to determine intervention effects on pregnancy and childhood health outcomes.
Trial registration
Registered on clinicaltrials.gov as NCT01126762
doi:10.1186/1475-2891-12-33
PMCID: PMC3616846  PMID: 23496848
Fish; Pregnancy; Nutrition; Mercury; Omega-3 fatty acid; Docosahexaenoic acid (DHA)

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