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1.  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
2.  Timing of Solid Food Introduction and Risk of Obesity in Preschool-Aged Children 
Pediatrics  2011;127(3):e544-e551.
OBJECTIVE:
To examine the association between timing of introduction of solid foods during infancy and obesity at 3 years of age.
METHODS:
We studied 847 children in Project Viva, a prospective pre-birth cohort study. The primary outcome was obesity at 3 years of age (BMI for age and gender ≥95th percentile). The primary exposure was the timing of introduction of solid foods, categorized as <4, 4 to 5, and ≥6 months. We ran separate logistic regression models for infants who were breastfed for at least 4 months (“breastfed”) and infants who were never breastfed or stopped breastfeeding before the age of four months (“formula-fed”), adjusting for child and maternal characteristics, which included change in weight-for-age z score from 0 to 4 months–a marker of early infant growth.
RESULTS:
In the first 4 months of life, 568 infants (67%) were breastfed and 279 (32%) were formula-fed. At age 3 years, 75 children (9%) were obese. Among breastfed infants, the timing of solid food introduction was not associated with odds of obesity (odds ratio: 1.1 [95% confidence interval: 0.3–4.4]). Among formula-fed infants, introduction of solid foods before 4 months was associated with a sixfold increase in odds of obesity at age 3 years; the association was not explained by rapid early growth (odds ratio after adjustment: 6.3 [95% confidence interval: 2.3–6.9]).
CONCLUSIONS:
Among formula-fed infants or infants weaned before the age of 4 months, introduction of solid foods before the age of 4 months was associated with increased odds of obesity at age 3 years.
doi:10.1542/peds.2010-0740
PMCID: PMC3065143  PMID: 21300681
obesity; infant feeding; complementary foods
3.  Misdiagnosis of Overweight and Underweight Children Younger Than 2 Years of Age Due to Length Measurement Bias 
Context
Accurate determination of the length of very young children is important because weight-for-length standards are used to assess both under- and overweight. Clinical measurements of length, which usually involve a paper-and-pencil method, may often be inaccurate in children younger than 2 years.
Objective
To compare length measured by the conventional clinical paper-and-pencil method with length measured by the research standard recumbent length-board method in a sample of children under 2 years of age.
Methods
Research assistants measured 160 children 0 through 23 months of age using the recumbent length-board method, and clinical staff measured the same children using the paper-and-pencil method. To assess the relationship between the research and clinical length measurements, we used ordinary least squares regression.
Results
We found a strong linear relationship between the 2 measures of length (R2 = 0.98). The paper-and-pencil method systematically overestimated length in children under 2 years of age. A fitted regression equation estimated that the research standard length was 95.3% of the clinical measurement plus 1.88 cm. Over the entire age span, the mean (SD) difference between clinical and research measurements was 1.3 (1.5) cm.
Conclusions
Using the paper-and-pencil method can lead to underestimates of overweight and exaggerated estimates of thinness. To improve the accuracy of length measurement, medical providers should use standardized procedures with a recumbent length board to measure children under 2 years of age, at least for children whose initial paper-and-pencil measurement of length puts them at one extreme or the other.
PMCID: PMC1488725  PMID: 16614678
4.  Changes in dietary intake from the first to the second trimester of pregnancy 
Summary
Rifas-Shiman SL, Rich-Edwards JW, Willett WC, Kleinman KP, Oken E, Gillman MW. Changes in dietary intake from the first to the second trimester of pregnancy.
Maternal diet may influence outcomes of pregnancy and childhood. Diet in the first trimester may be more important to development and differentiation of various organs, whereas diet later in pregnancy may be important for overall fetal growth as well as for brain development. To our knowledge, no studies have examined individual-level changes in food and nutrient intake from the 1st to 2nd trimester of pregnancy. The objective of this study was to examine changes in dietary intake from the 1st to 2nd trimester of pregnancy. As part of the ongoing US prospective cohort study, Project Viva, we studied 1543 women who completed food-frequency questionnaires that assessed dietary intakes during the 1st and 2nd trimester of pregnancy. For both foods and energy-adjusted nutrients, we examined changes in dietary intake from 1st to 2nd trimester.
Reported mean energy intake was similar for the 1st (2046 kcal) and 2nd (2137 kcal) trimesters. Foods and energy-adjusted nutrients from foods whose overall mean intakes increased more than 5% from 1st to 2nd trimester were skim or 1% dairy foods (22%), whole-fat dairy foods (15%), red and processed meat (11%), saturated fat (6%) and vitamin D (7%). Intake of caffeinated beverages (−30%) and alcoholic beverages (−88%) decreased more than 5%. Because mean multivitamin intake increased by 35% from the 1st to 2nd trimester, total micronutrient intake increased appreciably more than micronutrient intake from foods only. Correlations across trimesters ranged from 0.32 for vitamin B12 to 0.68 for fruit and vegetables.
In conclusion, for many outcomes of pregnancy and childhood, the incremental information obtained from assessing complete diet in both early and late pregnancy may not outweigh the burden to participants and investigators. However, investigators should assess caffeine, alcohol, and vitamin and supplement use in both the 1st and 2nd trimester, and consider doing so for foods and nutrients for which trimester-specific hypotheses are well substantiated.
doi:10.1111/j.1365-3016.2006.00691.x
PMCID: PMC1488723  PMID: 16420339
pregnancy; maternal diet; nutrients; dietary supplements; changes in pregnancy
5.  Associations of Prenatal Maternal Blood Mercury Concentrations with Early and Mid-Childhood Blood Pressure: A Prospective Study 
Environmental research  2014;133:327-333.
Background
Childhood blood pressure (BP) is an important determinant of adult cardiovascular disease. Prenatal exposure to methylmercury through maternal fish consumption has been reported to increase the BP of children years later.
Methods
Mother-child pairs were enrolled from Project Viva, a prospective cohort study in Massachusetts. From second trimester maternal blood samples, we measured erythrocyte mercury concentration. Systolic BP in children, measured up to 5 times per visit in early and mid-childhood (median ages 3.2 and 7.7 years), was the primary outcome. We used mixed-effect regression models to account for variation in the number of BP measurements and to average effects over both time points.
Results
Among 1,103 mother-child pairs, mean (SD) second trimester total erythrocyte mercury concentration was 4.0 (3.9) ng/g among mothers whose children were assessed in early childhood and 4.0 (4.0) ng/g for children assessed in mid-childhood. Mean (SD) offspring systolic BP was 92.1 (10.4) mm Hg in early childhood and 94.3 (8.4) mm Hg in mid-childhood. After adjusting for mother and infant characteristics, mean second trimester blood mercury concentration was not associated with child systolic BP (regression coefficient, 0.1 mm Hg; 95% CI, −1.3 to 1.5 for quartile 4 vs. quartile 1) at either time period. Further adjusting for second trimester maternal fish consumption, as well as docosahexaenoic acid and eicosapentaenoic acid consumption, did not substantially change the estimates.
Conclusions
The results of this study demonstrate an absence of association between childhood blood pressure and low-level mercury exposure typical of the general US population.
doi:10.1016/j.envres.2014.06.004
PMCID: PMC4364915  PMID: 25019468
mercury; prenatal exposure; blood pressure
6.  Chronic Sleep Curtailment and Adiposity 
Pediatrics  2014;133(6):1013-1022.
OBJECTIVES:
To examine the extent to which chronic sleep curtailment from infancy to mid-childhood is associated with total and central adiposity.
METHODS:
We studied 1046 children participating in a prospective cohort study. At age 6 months and yearly from age 1 to 7 years, mothers reported their children’s sleep duration in a usual 24-hour period. The main exposure was a sleep curtailment score from age 6 months to 7 years. The range of the total score was 0 to 13, where 0 indicated the maximal sleep curtailment and 13 indicated never having curtailed sleep. Outcomes in mid-childhood were BMI z score, dual X-ray absorptiometry total and trunk fat mass index (kg/m2), and waist and hip circumferences (cm).
RESULTS:
The mean (SD) sleep score was 10.2 (2.7); 4.4% scored a 0 to 4, indicating multiple exposures to sleep curtailment between age 6 months to 7 years, 12.3% scored 5 to 7, 14.1% scored 8 to 9, 28.8% scored 10 to 11, and 40.3% scored 12 to 13. In multivariable models, children who had a sleep score of 0 to 4 had a BMI z score that was 0.48 U (95% confidence interval, 0.13 to 0.83) higher than those who had a sleep score of 12 to 13. We observed similar associations of higher total and trunk fat mass index and waist and hip circumferences, and higher odds of obesity (odds ratio, 2.62; 95% confidence interval, 0.99 to 6.97) among children who had a score of 0 to 4 vs 12 to 13.
CONCLUSIONS:
Chronic sleep curtailment from infancy to school age was associated with higher overall and central adiposity in mid-childhood.
doi:10.1542/peds.2013-3065
PMCID: PMC4035591  PMID: 24843068
sleep curtailment; adiposity; fat mass index; BMI; obesity; early childhood
7.  Peanut, milk, and wheat intake during pregnancy is associated with reduced allergy and asthma in children 
Background
Maternal diet during pregnancy may influence childhood allergy and asthma.
Objective
To examine the associations between maternal intake of common childhood food allergens during early pregnancy and childhood allergy and asthma.
Methods
We studied 1277 mother-child pairs from a United States pre-birth cohort unselected for any disease. Using food frequency questionnaires administered during the first and second trimesters, we assessed maternal intake of common childhood food allergens during pregnancy. In mid-childhood (mean age 7.9 years), we assessed food allergy, asthma, allergic rhinitis, and atopic dermatitis by questionnaire and serum specific IgE levels. We examined the associations between maternal diet during pregnancy and childhood allergy and asthma. We also examined the cross-sectional associations between specific food allergies, asthma, and atopic conditions in mid-childhood.
Results
Food allergy was common (5.6%) in mid-childhood, as was sensitization to at least one food allergen (28.0%). Higher maternal peanut intake (each additional z-score) during the first trimester was associated with 47% reduced odds of peanut allergic reaction (OR 0.53, 95%CI 0.30–0.94). Higher milk intake during the first trimester was associated with reduced asthma (OR 0.83, 95%CI 0.69–0.99) and allergic rhinitis (OR 0.85, 95%CI 0.74–0.97). Higher maternal wheat intake during the second trimester was associated with reduced atopic dermatitis (OR 0.64, 95%CI 0.46–0.90). Peanut, wheat, and soy allergy were each cross-sectionally associated with increased childhood asthma, atopic dermatitis, and allergic rhinitis (ORs 3.6 to 8.1).
Conclusion
Higher maternal intake of peanut, milk, and wheat during early pregnancy was associated with reduced odds of mid-childhood allergy and asthma.
doi:10.1016/j.jaci.2013.11.040
PMCID: PMC4004710  PMID: 24522094
maternal diet; pregnancy; food allergy; sensitization; asthma; allergic rhinitis; peanut; milk; wheat; childhood
8.  Television Viewing, Bedroom Television, and Sleep Duration From Infancy to Mid-Childhood 
Pediatrics  2014;133(5):e1163-e1171.
BACKGROUND:
Television and insufficient sleep are associated with poor mental and physical health. This study assessed associations of TV viewing and bedroom TV with sleep duration from infancy to midchildhood.
METHOD:
We studied 1864 children in Project Viva. Parents reported children’s average daily TV viewing and sleep (at 6 months and annually from 1–7 years) and the presence of a bedroom TV (annually 4–7 years). We used mixed effects models to assess associations of TV exposures with contemporaneous sleep, adjusting for child age, gender, race/ethnicity, maternal education, and income.
RESULTS:
Six hundred forty-three children (35%) were racial/ethnic minorities; 37% of households had incomes ≤$70 000. From 6 months to 7 years, mean (SD) sleep duration decreased from 12.2 (2.0) hours to 9.8 (0.9) hours per day; TV viewing increased from 0.9 (1.2) hours to 1.6 (1.0) hours per day. At 4 years, 17% had a bedroom TV, rising to 23% at 7 years. Each 1 hour per day increase in lifetime TV viewing was associated with 7 minutes per day (95% confidence interval [CI]: 4 to 10) shorter sleep. The association of bedroom TV varied by race/ethnicity; bedroom TV was associated with 31 minutes per day shorter sleep (95% CI: 16 to 45) among racial/ethnic minority children, but not among white, non-Hispanic children (8 fewer minutes per day [95% CI: −19 to 2]).
CONCLUSIONS:
More TV viewing, and, among racial/ethnic minority children, the presence of a bedroom TV, were associated with shorter sleep from infancy to midchildhood.
doi:10.1542/peds.2013-3998
PMCID: PMC4006444  PMID: 24733878
television; sleep duration; sleep hygiene; childhood
9.  Vitamin D Status and Hypertensive Disorders in Pregnancy 
Annals of epidemiology  2014;24(5):399-403.e1.
Purpose
Several studies have reported increased risk of preeclampsia when 25-hyrdoxyvitamin D (25[OH]D) levels are low. The extent to which 25(OH)D may lower risk for hypertensive disorder during pregnancy remains unclear.
Methods
Among women enrolled in the Project Viva prenatal cohort in Massachusetts, we examined associations of 25(OH)D levels obtained at 16.4 –36.9 weeks of gestation (mean 27.9 weeks) with hypertensive disorders of pregnancy, including preeclampsia (56/1591, 3.5%) and gestational hypertension (109/1591, 6.9%).
Results
We did not detect an association between plasma 25(OH)D concentration (mean 58, SD 22 nmol/L) and preeclampsia. For each 25 nmol/L increase in 25(OH)D, the adjusted odds ratio for preeclampsia was 1.14 (95% confidence interval: 0.77, 1.67). By contrast and contrary to hypothesis, higher 25(OH)D concentrations were associated with higher odds of gestational hypertension: adjusted odds ratio for gestational hypertension was 1.32 (95% confidence interval: 1.01, 1.72) per each 25nmol/L increment in 25(OH)D. Vitamin D intake patterns suggest this association was not because of reverse causation. While the elevated hypertension risk may be due to chance, randomized trials of vitamin D supplementation during pregnancy should monitor for gestational hypertension.
Conclusions
These data do not support the hypothesis that higher 25(OH)D levels lower the overall risk of hypertensive disorders of pregnancy.
doi:10.1016/j.annepidem.2014.02.001
PMCID: PMC4011985  PMID: 24631523
Pregnancy; Pre-Eclampsia; Hypertension; Pregnancy-Induced; Vitamin D; 25-hydroxyvitamin D
10.  Participant characteristics and intervention processes associated with reductions in television viewing in the High Five for Kids study 
Preventive medicine  2014;62:64-70.
Objective
To evaluate the High Five for Kids intervention effect on television (TV) within subgroups, examine participant characteristics associated with process measures and assess perceived helpfulness of TV intervention components.
Method
High Five (RCT of 445 overweight/obese 2–7 year-olds in Massachusetts [2006–2008]) reduced TV by 0.36 hours/day. 1-year effects on TV, stratified by subgroup, were assessed using linear regression. Among intervention participants (n=253), associations of intervention component helpfulness with TV reduction were examined using linear regression and associations of participant characteristics with processes linked to TV reduction (choosing TV and completing intervention visits) were examined using logistic regression.
Results
High Five reduced TV across subgroups. Parents of Latino (v. white) children had lower odds of completing >=2 study visits (OR 0.39 [95%CI: 0.18, 0.84]). Parents of black (v. white) children had higher odds of choosing TV (OR: 2.23 [95% CI: 1.08, 4.59]), as did parents of obese (v. overweight) children and children watching >=2 hours/day (v. <2) at baseline. Greater perceived helpfulness was associated with greater TV reduction.
Conclusion
Clinic-based motivational interviewing reduces TV in children. Low cost education approaches (e.g., printed materials) may be well-received. Parents of children at higher obesity risk could be more motivated to reduce TV.
doi:10.1016/j.ypmed.2014.02.005
PMCID: PMC4106410  PMID: 24518002
11.  Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age1–3 
Background
Vitamin D deficiency and asthma are common at higher latitudes. Although vitamin D has important immunologic effects, its relation with asthma is unknown.
Objective
We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of recurrent wheeze in children at 3 y of age.
Design
The participants were 1194 mother-child pairs in Project Viva—a prospective prebirth cohort study in Massachusetts. We assessed the maternal intake of vitamin D during pregnancy from a validated food-frequency questionnaire. The primary outcome was recurrent wheeze, ie, a positive asthma predictive index (≥2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma).
Results
The mean (±SD) total vitamin D intake during pregnancy was 548 ± 167 IU/d. By age 3 y, 186 children (16%) had recurrent wheeze. Compared with mothers in the lowest quartile of daily intake (median: 356 IU), those in the highest quartile (724 IU) had a lower risk of having a child with recurrent wheeze [odds ratio (OR): 0.39; 95% CI: 0.25, 0.62; P for trend <0.001]. A 100-IU increase in vitamin D intake was associated with lower risk (OR: 0.81; 95% CI: 0.74, 0.89), regardless of whether vitamin D was from the diet (OR: 0.81; 95% CI: 0.69, 0.96) or supplements (OR: 0.82; 95% CI: 0.73, 0.92). Adjustment for 12 potential confounders, including maternal intake of other dietary factors, did not change the results.
Conclusion
In the northeastern United States, a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood.
PMCID: PMC4406411  PMID: 17344501
Vitamin D; pregnancy; dietary intake; childhood wheeze; asthma
12.  To What Extent Is the Protective Effect of Breastfeeding on Future Overweight Explained by Decreased Maternal Feeding Restriction? 
Pediatrics  2006;118(6):2341-2348.
OBJECTIVE
Previous studies have found that breastfeeding may protect infants against future overweight. One proposed mechanism is that breastfeeding, as opposed to bottle feeding, promotes maternal feeding styles that are less controlling and more responsive to infant cues of hunger and satiety, thereby allowing infants greater self-regulation of energy intake. The objective of this study was to determine the extent to which the protective effect of breastfeeding on future overweight is explained by decreased maternal feeding restriction.
PATIENTS AND METHODS
We studied 1012 mother-infant pairs in Project Viva, an ongoing prospective cohort study of pregnant mothers and their children. The main exposure was breastfeeding duration, assessed at 1 year postpartum. At 3 years of age, the main outcomes were age- and gender-specific BMI z score and the sum of subscapular and triceps skinfold thicknesses, with overweight defined as a BMI ≥95th percentile. We defined maternal restriction of infant’s access to food as strongly agreeing or agreeing, with the following question from the Child Feeding Questionnaire: “I have to be careful not to feed my child too much.” To examine the association between breastfeeding duration and our outcomes, we used multivariate linear and logistic models, adjusting for several potential confounders. In subsequent models, we also adjusted for maternal restriction of infant’s access to food.
RESULTS
The mean duration of breastfeeding was 6.5 months, and 12% of women strongly agreed or agreed with the restriction question. At age 3, mean for BMI z score was 0.47. Each 3-month increment in breastfeeding duration was associated with a reduction of 0.045 BMI z score. After adjusting for maternal restriction, the estimate was −0.039, a 13% attenuation.
CONCLUSION
The protective effect of breastfeeding on future overweight seems to be explained only partially by decreased maternal feeding restriction.
doi:10.1542/peds.2006-1814
PMCID: PMC4406417  PMID: 17142517
breastfeeding; body mass index; BMI; infant feeding; maternal feeding restriction
13.  Prenatal Air Pollution Exposure and Newborn Blood Pressure 
Environmental Health Perspectives  2015;123(4):353-359.
Background
Air pollution exposure has been associated with increased blood pressure in adults.
Objective:
We examined associations of antenatal exposure to ambient air pollution with newborn systolic blood pressure (SBP).
Methods:
We studied 1,131 mother–infant pairs in a Boston, Massachusetts, area pre-birth cohort. We calculated average exposures by trimester and during the 2 to 90 days before birth for temporally resolved fine particulate matter (≤ 2.5 μm; PM2.5), black carbon (BC), nitrogen oxides, nitrogen dioxide, ozone (O3), and carbon monoxide measured at stationary monitoring sites, and for spatiotemporally resolved estimates of PM2.5 and BC at the residence level. We measured SBP at a mean age of 30 ± 18 hr with an automated device. We used mixed-effects models to examine associations between air pollutant exposures and SBP, taking into account measurement circumstances; child’s birth weight; mother’s age, race/ethnicity, socioeconomic position, and third-trimester BP; and time trend. Estimates represent differences in SBP associated with an interquartile range (IQR) increase in each pollutant.
Results:
Higher mean PM2.5 and BC exposures during the third trimester were associated with higher SBP (e.g., 1.0 mmHg; 95% CI: 0.1, 1.8 for a 0.32-μg/m3 increase in mean 90-day residential BC). In contrast, O3 was negatively associated with SBP (e.g., –2.3 mmHg; 95% CI: –4.4, –0.2 for a 13.5-ppb increase during the 90 days before birth).
Conclusions:
Exposures to PM2.5 and BC in late pregnancy were positively associated with newborn SBP, whereas O3 was negatively associated with SBP. Longitudinal follow-up will enable us to assess the implications of these findings for health during later childhood and adulthood.
Citation:
van Rossem L, Rifas-Shiman SL, Melly SJ, Kloog I, Luttmann-Gibson H, Zanobetti A, Coull BA, Schwartz JD, Mittleman MA, Oken E, Gillman MW, Koutrakis P, Gold DR. 2015. Prenatal air pollution exposure and newborn blood pressure. Environ Health Perspect 123:353–359; http://dx.doi.org/10.1289/ehp.1307419
doi:10.1289/ehp.1307419
PMCID: PMC4384198  PMID: 25625652
14.  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
15.  Association between television viewing and poor diet quality in young children 
Objective
To examine the association between television/video (TV) viewing and markers of diet quality among 3-year-old children.
Methods
We studied 613 boys and 590 girls, age 3 years old, who were participants in Project Viva. Each mother reported the number of hours her child watched TV on an average weekday and weekend day in the past month, from which we calculated a weighted mean. The main outcomes were intakes of selected foods and nutrients from a validated food frequency questionnaire. In linear regression models we adjusted for mother’s sociodemographic information, parental body mass index (BMI), and child’s age, sex, race/ethnicity, BMI z-score, sleep duration, and breast feeding duration.
Results
Mean (standard deviation, SD) age of subjects was 3.2 (0.2) years; 372 children (31%) were non-white and 151 (13%) had a household income <$40 000, and 330 mothers (28%) had completed less than a college degree. Mean (SD) TV viewing was 1.7 (1.0) hours per day. For each 1-hour increment of TV viewing per day, we found higher intakes of sugar-sweetened beverages (0.06 servings/day [95% CI 0.03, 0.10]), fast food (0.32 servings/month [95% CI 0.16, 0.49]), red and processed meat (0.06 servings/day [95% CI 0.02, 0.09]), total energy intake (48.7 kcal/day [95% CI 18.7, 78.6]), and percent energy intake from trans fat (0.05 [95% CI 0.03, 0.07]). We found lower intakes of fruit and vegetables (−0.18 servings/day [95% CI −0.32, −0.05]), calcium (−24.6 mg/day [95% CI −41.0, −8.1]), and dietary fiber (−0.44 g/day [95% CI −0.65, −0.22]).
Conclusions
Among 3-year-olds, more TV viewing is associated with adverse dietary practices. Interventions to reduce TV viewing in this age group may lead to improved diet quality.
doi:10.1080/17477160801915935
PMCID: PMC4249761  PMID: 19086298
Cross-sectional; diet quality; fast food; preschool children; television
16.  Characteristics of Walkable Built Environments and BMI z-Scores in Children: Evidence from a Large Electronic Health Record Database 
Environmental Health Perspectives  2014;122(12):1359-1365.
Background: Childhood obesity remains a prominent public health problem. Walkable built environments may prevent excess weight gain.
Objectives: We examined the association of walkable built environment characteristics with body mass index (BMI) z-score among a large sample of children and adolescents.
Methods: We used geocoded residential address data from electronic health records of 49,770 children and adolescents 4 to < 19 years of age seen at the 14 pediatric practices of Harvard Vanguard Medical Associates from August 2011 through August 2012. We used eight geographic information system (GIS) variables to characterize walkable built environments. Outcomes were BMI z-score at the most recent visit and BMI z-score change from the earliest available (2008–2011) to the most recent (2011–2012) visit. Multivariable models were adjusted for child age, sex, race/ethnicity, and neighborhood median household income.
Results: In multivariable cross-sectional models, living in closer proximity to recreational open space was associated with lower BMI z-score. For example, children who lived in closest proximity (quartile 1) to the nearest recreational open space had a lower BMI z-score (β = –0.06; 95% CI: –0.08, –0.03) compared with those living farthest away (quartile 4; reference). Living in neighborhoods with fewer recreational open spaces and less residential density, traffic density, sidewalk completeness, and intersection density were associated with higher cross-sectional BMI z-score and with an increase in BMI z-score over time.
Conclusions: Overall, built environment characteristics that may increase walkability were associated with lower BMI z-scores in a large sample of children. Modifying existing built environments to make them more walkable may reduce childhood obesity.
Citation: Duncan DT, Sharifi M, Melly SJ, Marshall R, Sequist TD, Rifas-Shiman SL, Taveras EM. 2014. Characteristics of walkable built environments and BMI z-scores in children: evidence from a large electronic health record database. Environ Health Perspect 122:1359–1365; http://dx.doi.org/10.1289/ehp.1307704
doi:10.1289/ehp.1307704
PMCID: PMC4256697  PMID: 25248212
17.  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
18.  Diagnostic accuracy of the bronchodilator response in children 
Background
The bronchodilator response (BDR) reflects the reversibility of airflow obstruction and is recommended as an adjunctive test to diagnose asthma. The validity of the commonly used definition of BDR, a 12% or greater change in FEV1 from baseline, has been questioned in childhood.
Objectives
We sought to examine the diagnostic accuracy of the BDR test by using 3 large pediatric cohorts.
Methods
Cases include 1041 children with mild-to-moderate asthma from the Childhood Asthma Management Program.
Control subjects (nonasthmatic and nonwheezing) were chosen from Project Viva and Home Allergens, 2 population-based pediatric cohorts. Receiver operating characteristic curves were constructed, and areas under the curve were calculated for different BDR cutoffs.
Results
A total of 1041 cases (59.7% male; mean age, 8.9 ± 2.1 years) and 250 control subjects (46.8% male; mean age, 8.7 ± 1.7 years) were analyzed, with mean BDRs of 10.7% ± 10.2% and 2.7% ± 8.4%, respectively. The BDR test differentiated asthmatic patients from nonasthmatic patients with a moderate accuracy (area under the curve, 73.3%).
Despite good specificity, a cutoff of 12% was associated with poor sensitivity (35.6%). A cutoff of less than 8% performed significantly better than a cutoff of 12% (P = .03, 8% vs 12%).
Conclusions
Our findings highlight the poor sensitivity associated with the commonly used 12% cutoff for BDR. Although our data show that a threshold of less than 8% performs better than 12%, given the variability of this test in children, we conclude that it might be not be appropriate to choose a specific BDR cutoff as a criterion for the diagnosis of asthma.
doi:10.1016/j.jaci.2013.03.031
PMCID: PMC3759549  PMID: 23683464
Asthma; bronchodilator response; diagnosis
19.  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
20.  Associations of Parental Control of Feeding with Eating in the Absence of Hunger and Food Sneaking, Hiding, and Hoarding 
Childhood Obesity  2013;9(4):346-349.
Abstract
Background
Overweight children as young as 5 years old exhibit disturbances in eating behaviors.
Methods
Using follow-up data from 419 participants in High Five for Kids, a randomized controlled trial of overweight children, the prevalence of (1) eating in the absence of hunger and (2) food sneaking, hiding, and hoarding was estimated and cross-sectional associations of parental control of feeding and these behaviors were examined using covariate-adjusted logistic regression models.
Results
At follow-up, mean [standard deviation (SD)] age of the children was 7.1 (1.2) years; 49% were female; 16% were healthy weight, 35% were overweight, and 49% were obese. On the basis of parental report, 16.5% of children were eating in the absence of hunger and 27.2% were sneaking, hiding, or hoarding food; 57.5% of parents endorsed parental control of feeding. In adjusted models, children exposed to parental control of feeding were more likely to eat in the absence of hunger [odds ratio (OR) 3.37, 95% confidence interval (CI) 1.66, 6.86], but not to sneak, hide, or hoard food (OR 1.43, 95% CI 0.87, 2.36).
Conclusions
Disturbances in eating behaviors are common among overweight children. Future research should be dedicated to identifying strategies that normalize eating behaviors and prevent excess weight gain among overweight children.
doi:10.1089/chi.2012.0149
PMCID: PMC3728724  PMID: 23806073
21.  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
22.  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
23.  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
24.  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
25.  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

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