Differences in maternal smoking across successive pregnancies - dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysis.

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

Plasma metabolite profiles in children with current asthma.

BACKGROUND: Identifying metabolomic profiles of children with asthma has the potential to increase understanding of asthma pathophysiology. OBJECTIVE: To identify differences in plasma metabolites between children with and without current asthma at mid-childhood. METHODS: We used untargeted mass spectrometry to measure plasma metabolites in 237 children (46 current asthma cases and 191 controls) in Project Viva, a birth cohort from eastern Massachusetts, USA. Current asthma was assessed at mid-childhood (mean age 8.0 years). The ability of a broad spectrum metabolic profile to distinguish between cases and controls was assessed using partial least squares discriminant analysis. We used logistic regression models to identify individual metabolites that were differentially abundant by case-control status. We tested significant metabolites for replication in 411 children from the VDAART clinical trial. RESULTS: There was no evidence of a systematic difference in the metabolome of children reporting current asthma vs. healthy controls according to partial least squares discriminant analysis. However, several metabolites were associated with odds of current asthma at a nominally significant threshold (P < .05), including a metabolite of nicotinamide (N1-Methyl-2-pyridone-5-carboxamide (Odds Ratio (OR) = 2.8 (95% CI 1.1-8.0)), a pyrimidine metabolite (5,6-dihydrothymine (OR = 0.4 (95% CI 0.2-0.9)), bile constituents (biliverdin (OR = 0.4 (95%CI 0.1-0.9), taurocholate (OR = 2.0 (95% CI 1.2-3.4)), two peptides likely derived from fibrinopeptide A (ORs from 1.6 to 1.7), and a gut microbiome metabolite (p-cresol sulphate OR = 0.5 (95% CI 0.2-0.9)). The associations for N1-Methyl-2-pyridone-5-carboxamide and p-cresol sulphate replicated in the independent VDAART population (one-sided P values = .03-.04). CONCLUSIONS AND CLINICAL RELEVANCE: Current asthma is nominally associated with altered levels of several metabolites, including metabolites in the nicotinamide pathway, and a bacterial metabolite derived from the gut microbiome.

Associations of prenatal and early life dietary inflammatory potential with childhood adiposity and cardiometabolic risk in Project Viva.

BACKGROUND: Limited information exists regarding the association between early-life diet and cardiometabolic risk. OBJECTIVES: Examine associations of dietary inflammatory index (DII) in pregnancy and early childhood (3-5 years) with adiposity, blood pressure and metabolic markers in mid-childhood (6-10 years). METHODS: Among 992 mother-child pairs from Project Viva, a pre-birth cohort, we examined associations of DII scores with outcomes using multivariable linear regression adjusted for child age and sex and maternal age, BMI, education, parity, smoking, race and income. RESULTS: Mean (SD) maternal DII in pregnancy was -2.6(1.4) units and in child DII in early childhood was 0.3(0.7). Mean mid-childhood BMI z-score was 0.40(0.98) units. In boys only, DII in early childhood was associated with higher BMIz (adjusted ß = 0.16 units per unit DII, 95%CI 0.02, 0.29), waist circumference (0.93 cm; -0.07, 1.92) and skin fold thicknesses (1.12 mm; 0.01, 2.23). Dietary inflammatory index in the highest quartiles during both pregnancy and in early childhood, compared to the lowest quartiles, was associated with higher waist circumference (2.4 cm; 0.14, 4.6) in all children, and BMIz in boys (0.78 units; 0.34, 1.22). Associations with BP and metabolic markers were null. CONCLUSIONS: A pro-inflammatory diet in pregnancy and early childhood may promote the development of adiposity.

Associations of maternal and cord blood adipokines with offspring adiposity in Project Viva: is there an interaction with child age?

OBJECTIVES: Higher leptin and lower adiponectin correlate with adult and childhood adiposity, but it is unclear how exposure to these adipokines during gestation relates to offspring growth. We aimed to investigate the relationships of maternal and cord adipokines with offspring adiposity across childhood to early adolescence, as well as interactions with child age. METHODS: In mother-child pairs in the Project Viva cohort, we measured adipokines in mothers at second trimester (n=1106) and in cord blood at birth (n=657). We measured offspring adiposity indices at early childhood (mean 3.3±s.d. 0.3 years), mid-childhood (7.9±0.8 years) and early adolescence (13.2±0.9 years). We analyzed associations of maternal and cord adipokines with offspring longitudinal adiposity using a linear mixed model adjusting for pre-pregnancy body mass index (BMI), gestational weight gain (GWG), and other confounders. RESULTS: Mothers with higher BMI and GWG had higher leptin. Offspring born to mothers with the highest vs lowest quartile of leptin had lower BMI z-score (-0.49 units, 95% confidence interval (CI):-0.72,-0.26), waist circumference (-2.6 cm, 95% CI: -3.7,-1.5) and sum of subscapular and triceps skinfolds (-2.8 mm, 95% CI: -4.1,-1.4) in early life. An interaction term between maternal leptin and child age was positive, suggesting that the associations between maternal leptin and child adiposity were not constant over time. Offspring born to mothers with lowest vs highest quartile of maternal adiponectin had lower early life adiposity (BMI z-score -0.27 units, 95% CI: -0.48,-0.05). Results were similar for cord leptin but not cord adiponectin. CONCLUSIONS: Our findings showed higher maternal and cord leptin, and lower maternal adiponectin are associated with lower offspring adiposity from childhood to early adolescence, independent of maternal BMI and GWG. However, the strength of these associations was not constant over time.

Adherence to the Mediterranean diet during pregnancy and offspring adiposity and cardiometabolic traits in childhood.

BACKGROUND: In adults, adherence to the Mediterranean diet has been inversely associated with cardiovascular risk, but the extent to which diet in pregnancy is associated with offspring adiposity is unclear. We aimed to investigate the association between adherence to Mediterranean diet in pregnancy and offspring cardiometabolic traits in two pregnancy cohorts. METHODS: We studied 997 mother-child pairs from Project Viva in Massachusetts, USA, and 569 pairs from the Rhea study in Crete, Greece. We estimated adherence to the Mediterranean diet with an a priori defined score (MDS) of nine foods and nutrients (0 to 9). We measured child weight, height, waist circumference, skin-fold thicknesses, blood pressure, and blood levels of lipids, c-reactive protein and adipokines in mid-childhood (median 7.7 years) in Viva, and in early childhood (median 4.2 years) in Rhea. We calculated cohort-specific effects and pooled effects estimates with random-effects models for cohort and child age. RESULTS: In Project Viva, the mean (SD, standard deviation) MDS was 2.7 (1.6); in Rhea it was 3.8 (1.7). In the pooled analysis, for each 3-point increment in the MDS, offspring BMI z-score was lower by 0.14 units (95% CI, -0.15 to -0.13), waist circumference by 0.39 cm (95% CI, -0.64 to -0.14), and the sum of skin-fold thicknesses by 0.63 mm (95% CI, -0.98 to -0.28). We also observed lower offspring systolic (-1.03 mmHg; 95% CI, -1.65 to -0.42) and diastolic blood pressure (-0.57 mmHg; 95% CI, -0.98 to -0.16). CONCLUSION: Greater adherence to Mediterranean diet during pregnancy may protect against excess offspring cardiometabolic risk.

Prenatal and early life exposure to traffic pollution and cardiometabolic health in childhood.

BACKGROUND: Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. METHODS: Among 1418 children in Project Viva, a Boston-area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics. RESULTS: Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1 kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived <50 m vs. ≥200 m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile. CONCLUSIONS: Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health.

Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

BACKGROUND: Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. METHODS: In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. RESULTS: Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL-1 (6.6) and cord blood adiponectin was 28.8 ng mL-1 (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted ß -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (ß -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (ß 2.28 ng mL-1 ; 95% CI 0.38, 4.17). CONCLUSIONS: Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin.

The effect of antenatal lifestyle advice for women who are overweight or obese on secondary measures of neonatal body composition: the LIMIT randomised trial.

OBJECTIVE: To evaluate the effect of providing antenatal dietary and lifestyle advice on neonatal anthropometry, and to determine the inter-observer variability in obtaining anthropometric measurements. DESIGN: Randomised controlled trial. SETTING: Public maternity hospitals across metropolitan Adelaide, South Australia. POPULATION: Pregnant women with a singleton gestation between 10(+0) and 20(+0) weeks, and body mass index (BMI) ≥25 kg/m(2). METHODS: Women were randomised to either Lifestyle Advice (comprehensive dietary and lifestyle intervention over the course of pregnancy including dietary, exercise and behavioural strategies, delivered by a research dietician and research assistants) or continued Standard Care. Analyses were conducted using intention-to-treat principles. MAIN OUTCOME MEASURES: Secondary outcome measures for the trial included assessment of infant body composition using body circumference and skinfold thickness measurements (SFTM), percentage body fat, and bio-impedance analysis of fat-free mass. RESULTS: Anthropometric measurements were obtained from 970 neonates (488 Lifestyle Advice Group, and 482 Standard Care Group). In 394 of these neonates (215 Lifestyle Advice Group, and 179 Standard Care Group) bio-impedance analysis was also obtained. There were no statistically significant differences identified between those neonates born to women receiving Lifestyle Advice and those receiving Standard Care, in terms of body circumference measures, SFTM, percentage body fat, fat mass, or fat-free mass. The intra-class correlation coefficient for SFTM was moderate to excellent (0.55-0.88). CONCLUSIONS: Among neonates born to women who are overweight or obese, anthropometric measures of body composition were not modified by an antenatal dietary and lifestyle intervention.

Leisure time physical activity before and during mid-pregnancy and offspring adiposity in mid-childhood.

BACKGROUND: Effects of maternal leisure time physical activity (LTPA) on paediatric obesity are unknown. The objective of this study was to examine associations of maternal LTPA with offspring overall and central adiposity in mid-childhood. METHODS: We analysed data from 802 mother-child dyads from Project Viva, a prospective pre-birth cohort study. Women reported average weekly LTPA before and during mid-pregnancy. At age 7-10 years, we measured fat, truncal fat and lean mass with dual-energy X-ray absorptiometry. Using multivariable linear regression, we examined associations of maternal LTPA with offspring adiposity, adjusting for child age and sex, maternal race/ethnicity, education, age, pre-pregnancy body mass index, marital status and smoking status. RESULTS: Mean (standard deviation) of LTPA before and during mid-pregnancy were 9.5 (8.1) and 7.1 (7.0) h week(-1) . At mean age 7.8 (0.8) years, childhood fat, truncal fat and lean mass indices were 4.3 (1.8), 1.4 (0.8) and 12.9 (1.4) kg m(-2) . We did not find that higher maternal LTPA was associated with lower child adiposity outcomes. For example, compared with 0-3 h week(-1) of LTPA during mid-pregnancy, children of mothers with +8 h week(-1) had fat mass index 0.07 kg m(-2) (95% confidence interval: -0.22, 0.36). In analyses of within-person LTPA change from before to mid-pregnancy, compared with +2 h week(-1) decrease in LTPA, increased LTPA (2 ± h week(-1) ) was associated with a 0.09 kg m(-2) fat mass index (-0.25, 0.43). CONCLUSIONS: Contrary to our hypothesis, higher LTPA before and during mid-pregnancy, and the change between them, were not associated with lower adiposity in mid-childhood.

Associations of cord blood metabolites with early childhood obesity risk.

BACKGROUND/OBJECTIVE: Rapid postnatal weight gain is a potentially modifiable risk factor for obesity and metabolic syndrome. To identify markers of rapid infancy weight gain and childhood obesity, we analyzed the metabolome in cord blood from infants differing in their postnatal weight trajectories. METHODS: We performed a nested case-control study within Project Viva, a longitudinal cohort of mothers and children. We selected cases (n=26) based on top quartile of change in weight-for-age 0-6 months and body mass index (BMI) >85th percentile in mid-childhood (median 7.7 years). Controls (n=26) were age and sex matched, had normal postnatal weight gain (2nd or 3rd quartile of change in weight-for-age 0-6 months) and normal mid-childhood weight (BMI 25th-75th percentile). Cord blood metabolites were measured using untargeted liquid chromatography-mass spectrometry; individual metabolites and pathways differing between cases and controls were compared in categorical analyses. We adjusted metabolites for maternal age, maternal BMI and breastfeeding duration (linear regression), and assessed whether metabolites improved the ability to predict case-control status (logistic regression). RESULTS: Of 415 detected metabolites, 16 were altered in cases versus controls (t-test, nominal P<0.05). Three metabolites were related to tryptophan: serotonin, tryptophan betaine and tryptophyl leucine (46%, 48% and 26% lower in cases, respectively, P<0.05). Mean levels of two methyl donors, dimethylglycine and N-acetylmethionine, were also lower in cases (18% and 16%, respectively, P=0.01). Moreover, the glutamine:glutamate ratio was reduced by 33% (P<0.05) in cases. Levels of serotonin, tryptophyl leucine and N-acetylmethionine remained significantly different after adjustment for maternal BMI, age and breastfeeding. Adding metabolite levels to logistic regression models including only clinical covariates improved the ability to predict case versus control status. CONCLUSIONS: Several cord blood metabolites are associated with rapid postnatal weight gain. Whether these patterns are causally linked to childhood obesity is not clear from this cross-sectional analysis, but will require further study.

Do community-level predictors of pneumococcal carriage continue to play a role in the conjugate vaccine era?

This paper examined whether previously identified community-level factors (high proportion of crowded households and/or persons below the poverty level) remained associated with childhood pneumococcal carriage in the heptavalent pneumococcal conjugate vaccine (PCV7) era. Using logistic regression, individual factors were used to develop base models to which community-level factors were added to evaluate impact on pneumococcal carriage within two paediatric study cohorts from Massachusetts (urban Boston, outside Boston). Six years after introduction of universal childhood PCV7 vaccination, we found no consistent evidence that census tract characteristics (e.g. population size and density, age and race distribution, percent participating in group childcare, parental education, percent lacking in-unit plumbing, poverty, and community stability) affected odds of pneumococcal carriage when added to individual predictors (e.g. younger age, current respiratory tract infections, and attendance in group childcare). How community-level factors influence pneumococcal carriage continues to change in the era of increasing immunization coverage.

Maternal experiences of racial discrimination and child weight status in the first 3 years of life.

Among US racial/ethnic minority women, we examined associations between maternal experiences of racial discrimination and child growth in the first 3 years of life. We analyzed data from Project Viva, a pre-birth cohort study. We restricted analyses to 539 mother-infant pairs; 294 were Black, 127 Hispanic, 110 Asian and 8 from additional racial/ethnic groups. During pregnancy, mothers completed the Experiences of Discrimination survey that measured lifetime experiences of racial discrimination in diverse domains. We categorized responses as 0, 1-2 or ≥3 domains. Main outcomes were birth weight for gestational age z-score; weight for age (WFA) z-score at 6 months of age; and at 3 years of age, body mass index (BMI) z-score. In multivariable analyses, we adjusted for maternal race/ethnicity, nativity, education, age, pre-pregnancy BMI, household income and child sex and age. Among this cohort of mostly (58.2%) US-born and economically non-impoverished mothers, 33% reported 0 domains of discrimination, 33% reported discrimination in 1-2 domains and 35% reported discrimination in ≥3 domains. Compared with children whose mothers reported no discrimination, those whose mothers reported ≥3 domains had lower birth weight for gestational age z-score (ß -0.25; 95% CI: -0.45, -0.04), lower 6 month WFA z-score (ß -0.34; 95% CI: -0.65, -0.03) and lower 3-year BMI z-score (ß -0.33; 95% CI: -0.66, 0.00). In conclusion, we found that among this cohort of US racial/ethnic minority women, mothers' report of experiencing lifetime discrimination in ⩾ 3 domains was associated with lower fetal growth, weight at 6 months and 3-year BMI among their offspring.

Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination.

As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94 distinct sequence types (STs), including 19 that had not been previously recorded, and a xpt allele containing a large insertion. Comparison with a similar sample collected in 2007 revealed no significant overall difference in the ST composition (p=0.51) suggesting that the population has reached a new equilibrium following the introduction of 7 valent vaccination in 2000. Within serotypes, a large and statistically significant increase (p=0.014 Fisher's Exact test) was noted in the prevalence of the major multiresistant clone ST 320, which is apparently outcompeting ST 199 among serotype 19A strains. This sample will be used as a baseline to study the future evolution of the pneumococcal population in Massachusetts following introduction of vaccines with higher valency.

Does maternal feeding restriction lead to childhood obesity in a prospective cohort study?

BACKGROUND: Some studies show that greater parental control over children's eating habits predicts later obesity, but it is unclear whether parents are reacting to infants who are already overweight. OBJECTIVE: To examine the longitudinal association between maternal feeding restriction at age 1 and body mass index (BMI) at age 3 and the extent to which the association is explained by weight for length (WFL) at age 1. METHODS: We studied 837 mother-infant pairs from a prospective cohort study. The main exposure was maternal feeding restriction at age 1, defined as agreeing or strongly agreeing with the following question: "I have to be careful not to feed my child too much." We ran multivariable linear regression models before and after adjusting for WFL at age 1. All models were adjusted for parental and child sociodemographic characteristics. RESULTS: 100 (12.0%) mothers reported feeding restriction at age 1. Mean (SD) WFL z-score at age 1 was 0.32 (1.01), and BMI z-score at age 3 was 0.43 (1.01). Maternal feeding restriction at age 1 was associated with higher BMI z-score at age 3 before (ß 0.26 (95% CI 0.05 to 0.48)) but not after (ß 0.00 (95% CI -0.17 to 0.18)) adjusting for WFL z-score at age 1. Each unit of WFL z-score at age 1 was associated with an increment of 0.57 BMI z-score units at age 3 (95% CI 0.51 to 0.62). CONCLUSIONS: We found that maternal feeding restriction was associated with children having a higher BMI at age 3 before, but not after, adjusting for WFL at age 1. One potential reason may be that parents restrict the food intake of infants who are already overweight.

Associations of maternal prenatal dietary intake of n-3 and n-6 fatty acids with maternal and umbilical cord blood levels.

Maternal n-3 and n-6 polyunsaturated fatty acid (PUFA) status may influence birth outcomes and child health. We assessed second trimester maternal diet with food frequency questionnaires (FFQs) (n=1666), mid-pregnancy maternal erythrocyte PUFA concentrations (n=1550), and umbilical cord plasma PUFA concentrations (n=449). Mean (SD) maternal intake of total n-3 PUFA was 1.17 g/d (0.43), docosahexaenoic and eicosapentaenoic acids (DHA+EPA) 0.16 g/d (0.17), and total n-6 PUFA 12.25 g/d (3.25). Mean maternal erythrocyte and cord plasma PUFA concentrations were 7.0% and 5.2% (total n-3), 5.0% and 4.6% (DHA+EPA), and 27.9% and 31.4% (total n-6). Mid-pregnancy diet-blood and blood-blood correlations were strongest for DHA+EPA (r=0.38 for diet with maternal blood, r=0.34 for diet with cord blood, r=0.36 for maternal blood with cord blood), and less strong for n-6 PUFA. The FFQ is a reliable measure of elongated PUFA intake, although inter-individual variation is present.

Association between the serum anion gap and blood pressure among patients at Harvard Vanguard Medical Associates.

Animal and human data suggest a link between endogenous acid production with elevations in blood pressure and the development of hypertension; increases in endogenous organic acid production can lead to a higher anion gap. We studied the cross-sectional association between the serum anion gap and blood pressure among 1057 non-diabetic patients who were not taking antihypertensive drugs, and who received their care at a multisite, multispecialty group practice in eastern Massachusetts. Using linear regression controlling for age, sex, race, BMI, estimated GFR and presence of impaired fasting glucose, every 1 mEq l(-1) higher serum anion gap was associated with a 0.27 mm Hg (P=0.08) higher systolic, 0.20 mm Hg (P=0.05) higher diastolic and 0.22 mm Hg (P=0.04) higher mean arterial pressure; these results suggest that endogenous acid production may raise the risk of hypertension.

Reducing antibiotic use in children: a randomized trial in 12 practices.

OBJECTIVE: To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old. METHODS: Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996-1997) and intervention (1997-1998) years. The primary analysis (for children 3 to <36 months and 36 to <72 months) assessed the impact of the intervention among children during the intervention year, controlling for covariates including patient age and baseline prescription rate. Confirmatory analyses at the practice level were also performed. RESULTS: The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to <36 months old decreased 0.41 antibiotics per person-year (18.6%) in intervention compared with 0.33 (11.5%) in control practices. Among children 36 to <72 months old, the rate decreased by 0.21 antibiotics per person-year (15%) in intervention and 0.17 (9.8%) in control practices. Multivariate analysis showed an adjusted intervention effect of 16% in the younger and 12% in the older age groups. The direction and approximate magnitude of effect were confirmed in practice-level analyses. CONCLUSIONS: A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

Comparing physical activity questionnaires for youth: seasonal vs annual format.

BACKGROUND: In large cohort studies of older children, self-report is the only practical way to assess physical activity. Assessing usual activity over the entire year is desirable, but children and adolescents may overestimate activities with high seasonal variability. Use of questionnaires in which individuals report each activity by season may improve accuracy. METHODS: A total of 6782 girls and 5110 boys, aged 9-14 years in 1996, completed self-administered activity questionnaires in 1996 and in 1997. In 1996, participants reported the average time spent in each of 17 activities during the previous 12 months; in 1997, we also asked for the average time spent in the previous year, but within each of the four seasons. RESULTS: Girls reported a median of 12.8 hours/week total activity in 1996 and 10.4 hours/week in 1997. For boys, the estimates were 15.5 hours/week and 13.4 hours/week, respectively. Girls and boys within 1-year age strata (e.g., comparison of 10-year olds in 1996 with 10-year olds in 1997) reported an average of 3.7 and 3.1 fewer hours per week, respectively, on the 1997 seasonal format versus the 1996 annual format questionnaire. In longitudinal analyses, the difference between the annual and the seasonal estimates was greater if participants did the activity in fewer seasons in 1997. CONCLUSIONS: In comparison to an annual format questionnaire, a seasonal format questionnaire may improve accuracy of self-report of physical activity by reducing over-reporting of activities in which pre-adolescents and adolescents engage in fewer seasons.

Risk of overweight among adolescents who were breastfed as infants.

CONTEXT: Overweight during adolescence predicts short- and long-term morbidity as well as obesity in adulthood. The prevalence of overweight among adolescents is high and continues to increase. Physiological and behavioral mechanisms and preliminary epidemiologic data suggest that breastfeeding could lower the risk of subsequent obesity in adolescence. OBJECTIVE: To examine the extent to which overweight status among adolescents is associated with the type of infant feeding (breast milk vs infant formula) and duration of breastfeeding. DESIGN, SETTING, AND SUBJECTS: Survey of 8186 girls and 7155 boys, aged 9 to 14 years, who are participants in the Growing Up Today Study, a nationwide cohort study of diet, activity, and growth. In the fall of 1996 we mailed a questionnaire to each of the subjects, and in the spring of 1997, we mailed a supplemental questionnaire to their mothers, who are participants in the Nurses' Health Study II. MAIN OUTCOME MEASURE: Overweight status defined as body mass index exceeding the 95th percentile for age and sex from US national data. RESULTS: In the first 6 months of life, 9553 subjects (62%) were only or mostly fed breast milk, and 4744 (31%) were only or mostly fed infant formula. A total of 7186 subjects (48%) were breastfed for at least 7 months while 4613 (31%) were breastfed for 3 months or less. At ages 9 to 14 years, 404 girls (5%) and 635 boys (9%) were overweight. Among subjects who had been only or mostly fed breast milk, compared with those only or mostly fed formula, the odds ratio (OR) for being overweight was 0.78 (95% confidence interval [CI], 0.66-0.91), after adjustment for age, sex, sexual maturity, energy intake, time watching television, physical activity, mother's body mass index, and other variables reflecting social, economic, and lifestyle factors. Compared with subjects who had been breastfed for 3 months or less, those who had been breastfed for at least 7 months had an adjusted OR for being overweight of 0.80 (95% CI, 0.67-0.96). Timing of introduction of solid foods, infant formula, or cow's milk was not related to risk of being overweight. CONCLUSION: Infants who were fed breast milk more than infant formula, or who were breastfed for longer periods, had a lower risk of being overweight during older childhood and adolescence.

PrimeScreen, a brief dietary screening tool: reproducibility and comparability with both a longer food frequency questionnaire and biomarkers.

OBJECTIVE: Diet is an important determinant of health outcomes, but physicians have few ways to identify persons with suboptimal diets. The purposes of this study were to examine the reproducibility of a short dietary assessment questionnaire (PrimeScreen) and to compare its results with those of a longer food frequency questionnaire and with plasma levels of selected nutrients. DESIGN: Each subject completed two PrimeScreen questionnaires at an interval of 2 weeks and one full length, 131-item, semiquantitative food frequency questionnaire (SFFQ), and had a sample of blood drawn. We compared the PrimeScreen with two reference standards, the SFFQ and plasma levels of selected nutrients. SETTING: A large managed care organization in New England. SUBJECTS: A total of 160 men and women, aged 19-65 years, participated. RESULTS: For foods and food groups, the mean correlation coefficient (r) was 0.70 for reproducibility and 0.61 for comparability with the SFFQ. For nutrients, the mean r was 0.74 for reproducibility and 0.60 for comparability with the SFFQ. No substantial differences were evident by sex, race, body mass index, occupation or education. Correlation coefficients for the comparison of vitamin E, beta-carotene and lutein/zeaxanthin intakes from the PrimeScreen with plasma levels were 0.33, 0.43 and 0.43, respectively. These values were similar to those comparing the SFFQ with plasma levels. The median time to complete PrimeScreen was 5 min; 87% of participants required fewer than 10 min. CONCLUSIONS: A quick way to assess quality of diet among adults, PrimeScreen has adequate reproducibility and its results compare well with a longer food frequency questionnaire and biomarkers.