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1.  Staphylococcal Enterotoxin P Predicts Bacteremia in Hospitalized Patients Colonized With Methicillin-Resistant Staphylococcus aureus 
The Journal of Infectious Diseases  2013;209(4):571-577.
Background. Methicillin-resistant Staphylococcus aureus (MRSA) colonization predicts later infection, with both host and pathogen determinants of invasive disease.
Methods. This nested case-control study evaluates predictors of MRSA bacteremia in an 8–intensive care unit (ICU) prospective adult cohort from 1 September 2003 through 30 April 2005 with active MRSA surveillance and collection of ICU, post-ICU, and readmission MRSA isolates. We selected MRSA carriers who did (cases) and those who did not (controls) develop MRSA bacteremia. Generating assembled genome sequences, we evaluated 30 MRSA genes potentially associated with virulence and invasion. Using multivariable Cox proportional hazards regression, we assessed the association of these genes with MRSA bacteremia, controlling for host risk factors.
Results. We collected 1578 MRSA isolates from 520 patients. We analyzed host and pathogen factors for 33 cases and 121 controls. Predictors of MRSA bacteremia included a diagnosis of cancer, presence of a central venous catheter, hyperglycemia (glucose level, >200 mg/dL), and infection with a MRSA strain carrying the gene for staphylococcal enterotoxin P (sep). Receipt of an anti-MRSA medication had a significant protective effect.
Conclusions. In an analysis controlling for host factors, colonization with MRSA carrying sep increased the risk of MRSA bacteremia. Identification of risk-adjusted genetic determinants of virulence may help to improve prediction of invasive disease and suggest new targets for therapeutic intervention.
PMCID: PMC3903375  PMID: 24041793
Bacteremia; methicillin-resistant Staphylococcus aureus; epidemiology; hospital infections; microbial genetics
2.  Infant feeding and childhood cognition at ages 3 and 7 years: effects of breastfeeding duration and exclusivity 
JAMA pediatrics  2013;167(9):836-844.
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.
(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
Prospective cohort study
Project Viva, a U.S. pre-birth cohort that enrolled mothers from 1999-2002 and followed children to age 7 years
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.
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.
PMCID: PMC3998659  PMID: 23896931
3.  Dietary Quality during Pregnancy Varies by Maternal Characteristics in Project Viva: A US Cohort 
Maternal diet may influence outcomes of pregnancy and childhood, but data on correlates of food and nutrient intake during pregnancy are scarce.
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.
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.
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]).
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.
PMCID: PMC4098830  PMID: 19465182
4.  Weight gain in pregnancy and risk of maternal hyperglycemia 
The purpose of this study was to examine associations of weight gain from prepregnancy to glycemic screening with glucose tolerance status.
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.
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).
Higher weight gain predicted impaired glucose tolerance in pregnancy, but not gestational diabetes mellitus.
PMCID: PMC4050656  PMID: 19371858
gestational diabetes mellitus; impaired glucose tolerance; obesity; pregnancy; weight gain
5.  Racial/ethnic and immigrant differences in early childhood diet quality 
Public health nutrition  2013;17(6):1308-1317.
To examine racial/ethnic differences in diet in young children.
Among 723 white, 128 black, and 47 Hispanic 3-year-olds in Project Viva, we used negative binomial and linear regression to examine associations of race/ethnicity with foods and nutrients assessed by food frequency questionnaire.
Mean (SD) age was 38.3 (2.8) months; 464 (52%) were boys; 127 mothers (14%) were immigrants. Compared with whites, black and Hispanic children had higher intake of sugar-sweetened beverages (rate ratios [95%CI]; 3.35 [2.61,4.37] and 2.04 [1.39,3.14] respectively) and fast food (1.42 [1.19,1.70] and 1.35 [1.01,1.76]), and lower skim/1% milk (0.35 [0.28,0.43] and 0.36 [0.26,0.50]), and snack food (0.89 [0.81,0.95] and 0.85 [0.73,0.99]); lower intake of calcium (166 [−215,−117] and 115 [−192,−39] mg/day), and among blacks only, lower saturated fat (−0.67% of energy [−1.22,−0.11]) and higher polyunsaturated fat (0.42% [0.16,0.69]). Being born outside the US was associated with more healthful nutrient intakes.
Three year-old black and Hispanic (v. white) children had more sugar-sweetened beverages and fast food, and fewer bad fats, snacks, and lowfat dairy. Children of immigrants ate less fast food and bad fats and more fiber.
PMCID: PMC3883931  PMID: 23651520
race/ethnicity; preschool children; diet; maternal body mass index; perception of weight; acculturation
6.  Confounding by indication affects antimicrobial risk factors for methicillin-resistant Staphylococcus aureus but not vancomycin-resistant enterococci acquisition 
Observational studies rarely account for confounding by indication, whereby empiric antibiotics initiated for signs and symptoms of infection prior to the diagnosis of infection are then viewed as risk factors for infection. We evaluated whether confounding by indication impacts antimicrobial risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) acquisition.
We previously reported several predictors of MRSA and VRE acquisition in 967 intensive care unit (ICU) patients with no prior history of MRSA or VRE who had an initial negative screening culture followed by either a subsequent negative screening culture (controls) or positive screening or clinical culture (cases). Within and prior to this acquisition interval, we collected demographic, comorbidity, daily device and antibiotic utilization data. We now re-evaluate all antibiotics by medical record review for evidence of treatment for signs and symptoms ultimately attributable to MRSA or VRE. Generalized linear mixed models are used to assess variables associated with MRSA or VRE acquisition, accounting for clustering by ward. We find that exclusion of empiric antibiotics given for suspected infection affects 17% (113/661) of antibiotic prescriptions in 25% (60/244) of MRSA-positive patients but only 1% (5/491) of antibiotic prescriptions in 1% (3/227) of VRE-positive patients. In multivariate testing, fluoroquinolones are no longer associated with MRSA acquisition, and aminoglycosides are significantly protective (OR = 0.3, CI:0.1-0.7).
Neglecting treatment indication may cause common empiric antibiotics to appear spuriously associated with MRSA acquisition. This effect is absent for VRE, likely because empiric therapy is infrequent given the low prevalence of VRE.
PMCID: PMC4057914  PMID: 24932407
Antimicrobial predictors; MRSA; VRE; Confounding by indication
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.
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.
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)).
Infant weight change between birth and 6 months mediates associations of breastfeeding with BMI, but only partially with indicators of child adiposity.
PMCID: PMC3977954  PMID: 20979572
body mass index; breastfeeding; infant weight change; obesity; overweight
8.  A Randomized Controlled Trial to Improve Primary Care to Prevent and Manage Childhood Obesity: The High Five for Kids Study 
Archives of pediatrics & adolescent medicine  2011;165(8):10.1001/archpediatrics.2011.44.
To examine the effectiveness of a primary care-based obesity intervention over the first year (6 intervention contacts) of a planned 2 year study.
Cluster-randomized controlled trial.
10 pediatric practices; 5 Intervention and 5 Usual Care.
475 children ages 2 – 6 years with body mass index (BMI) ≥ 95th percentile or 85th- < 95th percentile if at least one parent was overweight; 445 (93%) had 1 year outcomes.
Intervention practices received primary care restructuring, and families received motivational interviewing by clinicians and educational modules targeting TV, fast food, and sugar sweetened beverages.
Outcome Measures
Change in BMI and obesity-related behaviors from baseline to 1 year.
Compared with usual care, intervention participants had a smaller, non-significant increase in BMI (−0.21 kg/m2; 95% CI: −0.50, 0.07; p=0.15), greater decreases in TV viewing (−0.36 hours/day; 95% CI: −0.64, −0.09; p=0.01) and had slightly greater decreases in fast food (−0.16 servings/week; 95% CI: −0.33, 0.01; p=0.07) and sugar sweetened beverages (−0.22 servings/day; 95% CI: −0.52, 0.08; p=0.15). In post-hoc analyses, we observed significant effects on BMI among females (−0.38 kg/m2; 95% CI: −0.73, −0.03; p=0.03) but not males (0.04 kg/m2; 95% CI: −0.55, 0.63; p=0.89) and among participants in households with annual incomes $50,000 or less (−0.93 kg/m2; 95% CI: −1.60, −0.25; p=0.01) but not in higher income households (0.02 kg/m2; 95% CI: −0.30, 0.33; p=0.92).
After 1 year, the High Five for Kids intervention was effective in reducing TV viewing but did not significantly reduce BMI.
PMCID: PMC3881272  PMID: 21464376
9.  Racial/Ethnic Differences in Early Life Risk Factors for Childhood Obesity 
Pediatrics  2010;125(4):10.1542/peds.2009-2100.
By the preschool years, racial/ethnic disparities in obesity prevalence are already present.
To examine racial/ethnic differences in early life risk factors for childhood obesity.
Design, Setting, Participants
343 white, 355 black, and 128 Hispanic mother-child pairs in a prospective study.
Main Exposure
Mother’s report of child’s race/ethnicity.
Main Outcome Measures
Risk factors from the prenatal period through age 4 years known to be associated with child obesity.
In multivariable models, compared to their white counterparts, black and Hispanic children exhibited a range of risk factors related to child obesity. In pregnancy, these included higher rates of maternal depression (OR: 1.55 for blacks; 1.89 for Hispanics); in infancy more rapid weight gain (OR: 2.01 for blacks; 1.75 for Hispanics), more likely to introduce solid foods before 4 months of age (OR: 1.91 for blacks; 2.04 for Hispanics), higher rates of maternal restrictive feeding practices (OR: 2.59 for blacks; 3.35 for Hispanics), and after age 2 years, more televisions in their bedrooms (OR: 7.65 for blacks; 7.99 for Hispanics), higher intake of sugar-sweetened beverages (OR: 4.11 for blacks; 2.48 for Hispanics), and higher intake of fast food (OR: 1.65 for blacks; 3.14 for Hispanics). Blacks and Hispanics also had lower rates of exclusive breastfeeding and were less likely to sleep at least 12 hours/day in infancy.
Racial/ethnic differences in risk factors for obesity exist prenatally and in early childhood. Racial/ethnic disparities in childhood obesity may be determined by factors operating at the earliest stages of life.
PMCID: PMC3836212  PMID: 20194284
Obesity; Race/Ethnicity; Pregnancy; Infancy; Childhood; Prevention
10.  Associations of obesogenic behaviors in mothers and obese children participating in a randomized trial 
Obesity (Silver Spring, Md.)  2012;20(7):10.1038/oby.2012.43.
Relatively little research has assessed the association between obesogenic behaviors in parents and their children. The objective of the present analysis was to examine cross-sectional associations in television (TV)/video viewing, sugar-sweetened beverage intake, and fast food intake between mothers and their pre-school aged children. We studied baseline data among 428 participants in High Five for Kids, a randomized controlled trial of behavior change among overweight and obese children ages 2-6.9 years. The main exposures were whether mothers viewed TV/videos <1 hour/day, drank <1 serving/day of sugar-sweetened beverages, and ate fast food <1 time/week. The main outcomes were whether children met these goals for the same behaviors. Using multivariate logistic regression adjusted for maternal and child characteristics, we estimated odds ratios of children meeting the behavioral goals. The majority of mothers ate fast food <1 time/week (73%) and drank <1 serving/day of sugar-sweetened beverages (73%), while few mothers viewed <1 hour/day of TV/videos (31%). Most children met the fast food goal (68%), but not the goals for sugar-sweetened beverages (31%) or TV/video viewing (13%). In adjusted models, the odds ratios for a child meeting the goal were 3.2 (95% CI 1.7, 6.2) for TV/video viewing, 5.8 (95% CI 2.8, 12.0) for sugar-sweetened beverage intake, and 17.5 (95% CI 9.8, 31.2) for fast food intake if their mothers met the goal for the same behavior. Obesogenic behaviors of mothers and pre-school aged children were strongly associated. Our findings lend support to obesity prevention strategies that target parental behavior and the family environment.
PMCID: PMC3835375  PMID: 22349735
childhood obesity; maternal behavior; television; fast food; sugar-sweetened beverages
11.  Reducing Racial/Ethnic Disparities in Childhood Obesity: The Role of Early Life Risk Factors 
JAMA pediatrics  2013;167(8):10.1001/jamapediatrics.2013.85.
Many early life risk factors for childhood obesity are more prevalent among blacks and Hispanics than among whites and may explain the higher prevalence of obesity among racial/ethnic minority children.
To examine the extent to which racial/ethnic disparities in adiposity and overweight are explained by differences in pregnancy (gestational diabetes and depression), infancy (rapid infant weight gain, non-exclusive breastfeeding, early introduction of solid foods) and early childhood (sleeping less than 12 hours/day, presence of a television in the bedroom, any intake of sugar-sweetened beverages, and any intake of fast food) risk factors.
Prospective, pre-birth cohort study.
Multi-site group practice in Massachusetts.
1116 (63% white, 17% black, and 4% Hispanic) mother-child pairs.
Main Exposure
Mother’s report of child’s race/ethnicity.
Main Outcome Measures
Age- and sex-specific body mass index (BMI) z-score, total fat mass index (FMI) from dual-energy X-ray absorptiometry, and overweight/obesity defined as a BMI ≥ 85th percentile at age 7.
Black (0.48 units [95% CI: 0.31, 0.64]) and Hispanic (0.43 [0.12, 0.74]) children had higher BMI z-scores, as well as higher total FMI and overweight/obesity prevalence, than white children. After adjusting for socioeconomic confounders and parental BMI, differences in BMI z-score were attenuated for blacks (0.22 [0.05, 0.40]) and Hispanics (0.22 [−0.08, 0.52]). Adjustment for pregnancy risk factors did not substantially change these estimates. However, after further adjustment for infancy and childhood risk factors, we observed only minimal differences in BMI z-score for whites, blacks (0.07 [−0.11, 0.26]) and Hispanics (0.04 [−0.27, 0.35]). We observed similar attenuation of racial/ethnic differences in adiposity and overweight/obesity prevalence.
Conclusions and Relevance
Racial/ethnic disparities in childhood adiposity and obesity are determined by factors operating in infancy and early childhood. Efforts to reduce obesity disparities should focus on preventing early life risk factors.
PMCID: PMC3835398  PMID: 23733179
Obesity; Race/Ethnicity; Pregnancy; Infancy; Childhood; Prevention
12.  Vitamin D Deficiency in Pregnancy and Gestational Diabetes 
We examined the association of second trimester maternal plasma 25-hydroxyvitamin D (25[OH]D) during pregnancy with gestational diabetes mellitus(GDM).
Study Design
Among 1314 pregnant women participating in Project Viva, a birth cohort study, we measured 25(OH)D levels at 26–28 weeks’ gestation during GDM screening using a 1-hour 50g glucose challenge test.
We found 25(OH)D levels <25nmol/L in 44/1087(4.0%) women with normal glucose tolerance, 9/159(5.7%) women with impaired glucose tolerance and 9/68(13.2%) women with GDM. Analyses adjusted for sociodemographics, season, maternal BMI, gestational weight gain and dietary factors, suggested that women with 25(OH)D levels <25 vs. ≥25 nmol/L may have higher odds of GDM (2.2 [0.8, 5.5]). Glucose levels after the glucose challenge test were inversely associated with 25(OH)D levels(P <0.01).
Second trimester 25(OH)D levels were inversely associated with glucose levels after 1-hour 50g glucose challenge test and low 25(OH)D levels may be associated with increased risk of GDM.
PMCID: PMC3432741  PMID: 22717271
Vitamin D; Gestational Diabetes Mellitus; 25-hydroxyvitamin D; GDM; pregnancy
13.  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.
PMCID: PMC3732783  PMID: 22795497
Sleep; urbanicity; population density; infancy; built environment
14.  Health Care Transition in Patients With Type 1 Diabetes 
Diabetes Care  2012;35(8):1716-1722.
To examine characteristics of the transition from pediatric to adult care in emerging adults with type 1 diabetes and evaluate associations between transition characteristics and glycemic control.
We developed and mailed a survey to evaluate the transition process in emerging adults with type 1 diabetes, aged 22 to 30 years, receiving adult diabetes care at a single center. Current A1C data were obtained from the medical record.
The response rate was 53% (258 of 484 eligible). The mean transition age was 19.5 ± 2.9 years, and 34% reported a gap >6 months in establishing adult care. Common reasons for transition included feeling too old (44%), pediatric provider suggestion (41%), and college (33%). Less than half received an adult provider recommendation and <15% reported having a transition preparation visit or receiving written transition materials. The most recent A1C was 8.1 ± 1.3%. Respondents who felt mostly/completely prepared for transition had lower likelihood of a gap >6 months between pediatric and adult care (adjusted odds ratio 0.47 [95% CI 0.25–0.88]). In multivariate analysis, pretransition A1C (β = 0.49, P < 0.0001), current age (β = −0.07, P = 0.03), and education (β = −0.55, P = 0.01) significantly influenced current posttransition A1C. There was no independent association of transition preparation with posttransition A1C (β = −0.17, P = 0.28).
Contemporary transition practices may help prevent gaps between pediatric and adult care but do not appear to promote improvements in A1C. More robust preparation strategies and handoffs between pediatric and adult care should be evaluated.
PMCID: PMC3402251  PMID: 22699289
15.  Correlations among adiposity measures in school-aged children 
BMC Pediatrics  2013;13:99.
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.
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.
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).
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.
PMCID: PMC3693882  PMID: 23799991
Adiposity; Obesity; DXA; BMI
16.  Decreasing Prevalence of Obesity Among Young Children in Massachusetts From 2004 to 2008 
Pediatrics  2012;129(5):823-831.
To examine whether the obesity prevalence is increasing, level, or decreasing among young US children (aged <6 years) in the past decade; and to compare regional data to those of 2 national databases.
We analyzed data from 108 762 well-child visits (36 827 children) at a multisite pediatric practice in eastern Massachusetts during 1999–2008. By using the Centers for Disease Control and Prevention 2000 gender-specific growth charts, we defined obesity as weight-for-length ≥95th percentile for children aged <24 months and BMI ≥95th percentile for children aged 24 to <72 months. By using multivariable logistic regression, we estimated gender-specific obesity trends in 2 separate periods, 1999–2003 and 2004–2008, adjusting for age group, race/ethnicity, health insurance, and practice site.
From 1999 to 2003, the obesity prevalence was fairly stable among both boys and girls. From 2004 to 2008, the obesity prevalence substantially decreased among both boys and girls. The decline in obesity prevalence during 2004–2008 was more pronounced among children insured by non-Medicaid health plans than among those insured by Medicaid.
Among children aged <6 years at this multisite pediatric practice, obesity prevalence decreased during 2004–2008, which is in line with national data showing no increase in prevalence during this time period. The smaller decrease among Medicaid-insured children may portend widening of socioeconomic disparities in childhood obesity.
PMCID: PMC3340588  PMID: 22529276
obesity; BMI; child; infant; prevalence; trends; epidemiology
17.  Pneumococcal Carriage and Antibiotic Resistance in Young Children before 13-Valent Conjugate Vaccine 
We sought to measure trends in Streptococcus pneumoniae (SP) carriage and antibiotic resistance in young children in Massachusetts communities after widespread adoption of heptavalent pneumococcal conjugate vaccine (PCV7) and before the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13).
We conducted a cross-sectional study including collection of questionnaire data and nasopharyngeal specimens among children <7 years in primary care practices from 8 Massachusetts communities during the winter season of 2008–9 and compared with to similar studies performed in 2001, 2003–4, and 2006–7. Antimicrobial susceptibility testing and serotyping were performed on pneumococcal isolates, and risk factors for colonization in recent seasons (2006–07 and 2008–09) were evaluated.
We collected nasopharyngeal specimens from 1,011 children, 290 (29%) of whom were colonized with pneumococcus. Non-PCV7 serotypes accounted for 98% of pneumococcal isolates, most commonly 19A (14%), 6C (11%), and 15B/C (11%). In 2008–09, newly-targeted PCV13 serotypes accounted for 20% of carriage isolates and 41% of penicillin non-susceptible S. pneumoniae (PNSP). In multivariate models, younger age, child care, young siblings, and upper respiratory illness remained predictors of pneumococcal carriage, despite near-complete serotype replacement. Only young age and child care were significantly associated with PNSP carriage.
Serotype replacement post-PCV7 is essentially complete and has been sustained in young children, with the relatively virulent 19A being the most common serotype. Predictors of carriage remained similar despite serotype replacement. PCV13 may reduce 19A and decrease antibiotic-resistant strains, but monitoring for new serotype replacement is warranted.
PMCID: PMC3288953  PMID: 22173142
Streptococcus pneumoniae; pneumococcal conjugate vaccine; antibiotic resistance; serotype; colonization
18.  Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood 
Epigenetics  2012;7(3):253-260.
Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.
PMCID: PMC3335948  PMID: 22430801
DNA methylation; pregnancy; cord blood; maternal diet; cadmium
19.  in silico Surveillance: evaluating outbreak detection with simulation models 
Detecting outbreaks is a crucial task for public health officials, yet gaps remain in the systematic evaluation of outbreak detection protocols. The authors’ objectives were to design, implement, and test a flexible methodology for generating detailed synthetic surveillance data that provides realistic geographical and temporal clustering of cases and use to evaluate outbreak detection protocols.
A detailed representation of the Boston area was constructed, based on data about individuals, locations, and activity patterns. Influenza-like illness (ILI) transmission was simulated, producing 100 years of in silico ILI data. Six different surveillance systems were designed and developed using gathered cases from the simulated disease data. Performance was measured by inserting test outbreaks into the surveillance streams and analyzing the likelihood and timeliness of detection.
Detection of outbreaks varied from 21% to 95%. Increased coverage did not linearly improve detection probability for all surveillance systems. Relaxing the decision threshold for signaling outbreaks greatly increased false-positives, improved outbreak detection slightly, and led to earlier outbreak detection.
Geographical distribution can be more important than coverage level. Detailed simulations of infectious disease transmission can be configured to represent nearly any conceivable scenario. They are a powerful tool for evaluating the performance of surveillance systems and methods used for outbreak detection.
PMCID: PMC3691709  PMID: 23343523
Surveillance; Simulation; Outbreak detection; Evaluation; Agent-based model; Influenza-like illness
20.  Estimation of Newborn Risk for Child or Adolescent Obesity: Lessons from Longitudinal Birth Cohorts 
PLoS ONE  2012;7(11):e49919.
Prevention of obesity should start as early as possible after birth. We aimed to build clinically useful equations estimating the risk of later obesity in newborns, as a first step towards focused early prevention against the global obesity epidemic.
We analyzed the lifetime Northern Finland Birth Cohort 1986 (NFBC1986) (N = 4,032) to draw predictive equations for childhood and adolescent obesity from traditional risk factors (parental BMI, birth weight, maternal gestational weight gain, behaviour and social indicators), and a genetic score built from 39 BMI/obesity-associated polymorphisms. We performed validation analyses in a retrospective cohort of 1,503 Italian children and in a prospective cohort of 1,032 U.S. children.
In the NFBC1986, the cumulative accuracy of traditional risk factors predicting childhood obesity, adolescent obesity, and childhood obesity persistent into adolescence was good: AUROC = 0·78[0·74–0.82], 0·75[0·71–0·79] and 0·85[0·80–0·90] respectively (all p<0·001). Adding the genetic score produced discrimination improvements ≤1%. The NFBC1986 equation for childhood obesity remained acceptably accurate when applied to the Italian and the U.S. cohort (AUROC = 0·70[0·63–0·77] and 0·73[0·67–0·80] respectively) and the two additional equations for childhood obesity newly drawn from the Italian and the U.S. datasets showed good accuracy in respective cohorts (AUROC = 0·74[0·69–0·79] and 0·79[0·73–0·84]) (all p<0·001). The three equations for childhood obesity were converted into simple Excel risk calculators for potential clinical use.
This study provides the first example of handy tools for predicting childhood obesity in newborns by means of easily recorded information, while it shows that currently known genetic variants have very little usefulness for such prediction.
PMCID: PMC3509134  PMID: 23209618
21.  Gestational Glucose Tolerance and Maternal Metabolic Profile at 3 Years Postpartum 
Obstetrics and Gynecology  2011;118(5):1065-1073.
To estimate the independent effect of gestational impaired glucose tolerance, defined as a single abnormal oral glucose tolerance test (OGTT) value, on metabolic dysfunction at 3 years postpartum.
We used multiple linear regression to measure associations between glucose testing during pregnancy and metabolic markers at 3 years postpartum in Project Viva, a prospective cohort study of maternal and infant health. We compared metabolic measures at 3 years postpartum among four groups: normal glucose challenge test (less than 140 mg/dL, n=461); abnormal glucose challenge test but normal glucose tolerance test (GTT) (n=39); impaired glucose tolerance (IGT) (a single abnormal GTT value, n=21); and gestational diabetes mellitus (GDM) (n=16).
Adjusting for age, race, parity, parental history of diabetes, and maternal BMI at 3 years postpartum, we found women with GDM had lower adiponectin (11.2 ng/mL vs. 20.7 ng/mL) and higher homeostatic model assessment – insulin resistance (3.1 vs. 1.3) and waist circumference (91.3 cm vs. 86.2 cm) compared with women with IGT or normal glucose tolerance. Women in both the IGT and GDM groups had lower high-density lipoprotein (GDM: 44.7 mg/dL; IGT: 45.4/dL vs normal glucose tolerance 55.8 mg/dL) and higher triglycerides (GDM: 136.1 mg/dL; IGT: 140.1 mg/dL, vs. normal glucose tolerance: 78.3), compared with women in the normal glucose tolerance group. We found the highest values for Hemoglobin A1c (GDM: 5.1%; IGT 5.3%, normal glucose tolerance 5.1%) and high-sensitivity c reactive protein (GDM 1.4 mg/dL IGT: 2.2 mg/dL; NGT 1.0 mg/dL) among women with IGT.
GDM and IGT during pregnancy are associated with persistent metabolic dysfunction at 3 years postpartum, independent of other clinical risk factors.
PMCID: PMC3268071  PMID: 22015874
22.  Infant Growth Before and After Term: Effects on Neurodevelopment in Preterm Infants 
Pediatrics  2011;128(4):e899-e906.
To identify sensitive periods of postnatal growth for preterm infants relative to neurodevelopment at 18 months' corrected age.
We studied 613 infants born at <33 weeks' gestation who participated in the DHA for Improvement of Neurodevelopmental Outcome trial. We calculated linear slopes of growth in weight, length, BMI, and head circumference from 1 week of age to term (40 weeks' postmenstrual age), term to 4 months, and 4 to 12 months, and we estimated their associations with Bayley Scales of Infant Development, 2nd Edition, Mental (MDI) and Psychomotor (PDI) Development Indexes in linear regression.
The median gestational age was 30 (range: 2–33) weeks. Mean ± SD MDI was 94 ± 16, and PDI was 93 ± 16. From 1 week to term, greater weight gain (2.4 MDI points per z score [95% confidence interval (CI): 0.8–3.9]; 2.7 PDI points [95% CI: 1.2–.2]), BMI gain (1.7 MDI points [95% CI: 0.4–3.1]; 2.5 PDI points [95% CI: 1.2–3.9]), and head growth (1.4 MDI points [95% CI: −0.0–2.8]; 2.5 PDI points [95% CI: 1.2–3.9]) were associated with higher scores. From term to 4 months, greater weight gain (1.7 points [95% CI: 0.2–3.1]) and linear growth (2.0 points [95% CI: 0.7–3.2]), but not BMI gain, were associated with higher PDI. From 4 to 12 months, none of the growth measures was associated with MDI or PDI score.
In preterm infants, greater weight and BMI gain to term were associated with better neurodevelopmental outcomes. After term, greater weight gain was also associated with better outcomes, but increasing weight out of proportion to length did not confer additional benefit.
PMCID: PMC3182845  PMID: 21949135
growth; motor development; cognitive development; preterm infants
23.  Associations of LINE-1 DNA Methylation with Preterm Birth in a Prospective Cohort Study 
Preterm birth affects over 12% of all infants born in the US yet the biology of early delivery remains unclear, including whether epigenetic mechanisms are involved. We examined associations of maternal and umbilical cord blood long interspersed nuclear element-1 (LINE-1) DNA methylation with length of gestation and odds of preterm birth in singleton pregnancies in Project Viva. In white blood cells from maternal blood during 1st trimester (n=914) and 2nd trimester (n=922), and from venous cord blood at delivery (n=557), we measured LINE-1 by pyrosequencing (expressed as %5 methyl cytosines within the LINE-1 region analyzed [%5mC]). We ran linear regression models to analyze differences in gestation length, and logistic models for odds of preterm birth (<37 v. ≥37 weeks gestation), across quartiles of LINE-1. Mean(SD) LINE-1 levels were 84.3(0.6), 84.5(0.4), and 84.6(0.7) %5mC for 1st trimester, 2nd trimester and cord blood, respectively. Mean(SD) gestational age was 39.5(1.8) weeks, and 6.5% of infants were born preterm. After adjustment for maternal age, race/ethnicity, BMI, education, smoking status, and fetal sex, women with the highest vs. lowest quartile of 1st trimester LINE-1 had longer gestations (0.45 weeks [95% CI 0.12, 0.78]) and lower odds of preterm birth (OR 0.40 [0.17, 0.94]), whereas associations with cord blood LINE-1 were in the opposite direction (−0.45 weeks, −0.83, −0.08) and (OR 4.55 [1.18, 17.5]). In conclusion, higher early pregnancy LINE-1 predicts lower risk of preterm birth. In contrast, preterm birth is associated with lower LINE-1 in cord blood.
PMCID: PMC3377352  PMID: 22720130
Preterm; epigenetics; LINE-1; DNA methylation
24.  Lifetime maternal experiences of abuse and risk of pre-natal depression in two demographically distinct populations in Boston 
Background To investigate lifetime history of interpersonal abuse and risk of pre-natal depression in socio-economically distinct populations in the same city.
Methods We examined associations of physical and sexual abuse with the risk of pre-natal depression in two cohorts in the Boston area, including 2128 participants recruited from a large urban- and suburban-managed care organization (Project Viva) and 1509 participants recruited primarily from urban community health centres (Project ACCESS). Protocols for the studies were designed in parallel to allow us to merge data to enhance ethnic and socio-economic diversity in the combined sample. In mid-pregnancy, the Personal Safety Questionnaire and Edinburgh Postnatal Depression Scale (EPDS) were administered in both cohorts. An EPDS score ≥13 indicated probable pre-natal depression. Logistic regression was used to estimate the odds ratio (OR) of pre-natal depression associated with lifetime abuse history.
Results Project ACCESS participants were twice as likely as Project Viva participants to report symptoms consistent with pre-natal depression: 22% of Project ACCESS participants had EPDS scores ≥13, compared with 11% of Project Viva participants. Fifty-seven percent of women in ACCESS and 46% in Viva reported lifetime physical and/or sexual abuse. In merged analysis, women reporting lifetime physical or sexual abuse had an OR for mid-pregnancy depression of 1.63 [95% confidence interval (95% CI): 1.29–2.07], adjusted for age and race/ethnicity. Lifetime histories of physical abuse [OR 1.48 (95% CI 1.15–1.90)] and sexual abuse [OR 1.68 (95% CI 1.24–2.28)] were independently associated with pre-natal depression. When child/teen, pre-pregnancy adult and pregnancy life periods were considered simultaneously, abuse in childhood was independently associated with an OR of 1.23 (95% CI 1.00–1.59), pre-pregnancy adult abuse with an OR of 1.70 (95% CI 1.31–2.21) and abuse during pregnancy with an OR of 1.77 (95% CI 1.14–2.74). Further adjustment for childhood socio-economic position made no material difference, and there were no clear interactions between abuse and adult socio-economic position.
Conclusions Physical and sexual abuse histories were positively associated with pre-natal depression in two economically and ethnically distinct populations. Stronger associations with recent abuse may indicate that the association of abuse with depression wanes with time or may result from less accurate recall of remote events.
PMCID: PMC3066428  PMID: 21169318
Depression; pregnancy; violence; pre-natal care; adult survivors of child abuse; partner abuse; spouse abuse
25.  Duration of Lactation and Maternal Adipokines at 3 Years Postpartum 
Diabetes  2011;60(4):1277-1285.
Lactation has been associated with reduced maternal risk of type 2 diabetes, the metabolic syndrome, and cardiovascular disease. We examined the relationship between breastfeeding duration and maternal adipokines at 3 years postpartum.
We used linear regression to relate the duration of lactation to maternal leptin, adiponectin, ghrelin, and peptide YY (PYY) at 3 years postpartum among 570 participants with 3-year postpartum blood samples (178 fasting), prospectively collected lactation history, and no intervening pregnancy in Project Viva, a cohort study of mothers and children.
A total of 88% of mothers had initiated breastfeeding, 26% had breastfed ≥12 months, and 42% had exclusively breastfed for ≥3 months. In multivariate analyses, we found that duration of total breastfeeding was directly related to PYY and ghrelin, and exclusive breastfeeding duration was directly related to ghrelin (predicted mean for never exclusively breastfeeding: 790.6 pg/mL vs. ≥6 months of exclusive breastfeeding: 1,008.1 pg/mL; P < 0.01) at 3 years postpartum, adjusting for pregravid BMI, gestational weight gain, family history of diabetes, parity, smoking status, and age. We found a nonlinear pattern of association between exclusive breastfeeding duration and adiponectin in multivariate-adjusted models.
In this prospective cohort study, we found a direct relationship between the duration of lactation and both ghrelin and PYY at 3 years postpartum.
PMCID: PMC3064101  PMID: 21350085

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