Background

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).

Methods

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.

Results

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.

Conclusions

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.

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.

OBJECTIVE

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.

METHODS

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).

RESULTS

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.

CONCLUSION

GDM and IGT during pregnancy are associated with persistent metabolic dysfunction at 3 years postpartum, independent of other clinical risk factors.

OBJECTIVE:

To identify sensitive periods of postnatal growth for preterm infants relative to neurodevelopment at 18 months' corrected age.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

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.

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.

OBJECTIVE

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

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.

CONCLUSIONS

In this prospective cohort study, we found a direct relationship between the duration of lactation and both ghrelin and PYY at 3 years postpartum.

Background

Modeling childhood body mass index (BMI) trajectories, versus estimating change in BMI between specific ages, may improve prediction of later body-size-related outcomes. Prior studies of BMI trajectories are limited by restricted age periods and insufficient use of trajectory information.

Methods

Among 3,289 children seen at 81,550 pediatric well-child visits from infancy to 18 years between 1980 and 2008, we fit individual BMI trajectories using mixed effect models with fractional polynomial functions. From each child's fitted trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and velocity and area under curve between 1 week, infancy peak, adiposity rebound, and 18 years.

Results

Among boys, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1) and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity rebound were positively correlated (r = 0.76). Blacks had earlier adiposity rebound and greater velocity from adiposity rebound to 18 years of age than whites. Higher birth weight z-score predicted earlier adiposity rebound and higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ by birth year or type of health insurance, after adjusting for other socio-demographics and birth weight z-score.

Conclusions

Childhood BMI trajectory characteristics are informative in describing childhood body mass changes and can be estimated conveniently. Future research should evaluate associations of these novel BMI trajectory characteristics with adult outcomes.

Defining the propensity of Streptoccocus pneumoniae (SP) serotypes to invade sterile body sites following nasopharyngeal (NP) acquisition has the potential to inform about how much invasive pneumococcal disease (IPD) may occur in a typical population with a given distribution of carriage serotypes. Data from enhanced surveillance for IPD in Massachusetts children ≤7 years in 2003/04, 2006/07 and 2008/09 seasons and surveillance of SP NP carriage during the corresponding respiratory seasons in 16 Massachusetts communities in 2003/04 and 8 of the 16 communities in both 2006/07 and 2008/09 were used to compute a serotype specific “invasive capacity (IC)” by dividing the incidence of IPD due to serotype x by the carriage prevalence of that same serotype in children of the same age. A total of 206 IPD and 806 NP isolates of SP were collected during the study period. An approximate 50-fold variation in the point estimates between the serotypes having the highest (18C, 33F, 7F, 19A, 3 and 22F) and lowest (6C, 23A, 35F, 11A, 35B, 19F, 15A, and 15BC) IC was observed. Point estimates of IC for most of the common serotypes currently colonizing children in Massachusetts were low and likely explain the continued reduction in IPD from the pre-PCV era in the absence of specific protection against these serotypes. Invasive capacity differs among serotypes and as new pneumococcal conjugate vaccines are introduced, ongoing surveillance will be essential to monitor whether serotypes with high invasive capacity emerge (e.g. 33F, 22F) as successful colonizers resulting in increased IPD incidence due to replacement serotypes.

OBJECTIVE

To estimate changes over time in birth weight for gestational age and in gestational length among term singleton neonates born from 1990 to 2005.

METHODS

We used data from the U.S. National Center for Health Statistics for 36,827,828 singleton neonates born at 37–41 weeks of gestation, 1990–2005. We examined trends in birth weight, birth weight for gestational age, large and small for gestational age, and gestational length in the overall population and in a low-risk subgroup defined by maternal age, race or ethnicity, education, marital status, smoking, gestational weight gain, delivery route, and obstetric care characteristics.

RESULTS

In 2005, compared with 1990, we observed decreases in birth weight (−52 g in the overall population, −79 g in a homogenous low-risk subgroup) and large for gestational age birth (−1.4% overall, −2.2% in the homogenous subgroup) that were steeper after 1999 and persisted in regression analyses adjusted for maternal and neonate characteristics, gestational length, cesarean delivery, and induction of labor. Decreases in mean gestational length (−0.34 weeks overall) were similar regardless of route of delivery or induction of labor.

CONCLUSION

Recent decreases in fetal growth among U.S., term, singleton neonates were not explained by trends in maternal and neonatal characteristics, changes in obstetric practices, or concurrent decreases in gestational length.

LEVEL OF EVIDENCE

III

Introduction

Harboring sensitive strains may prevent acquisition of resistant pathogens by competing for colonization of ecological niches. Competition may be relevant to decolonization strategies that eliminate sensitive strains and may predispose to acquiring resistant strains in high-endemic settings. We evaluated the impact of colonization with methicillin-sensitive Staphylococcus aureus (MSSA) and vancomycin-sensitive enterococci (VSE) on acquisition of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), respectively, when controlling for other risk factors.

Methods

We conducted a nested case-control study of patients admitted to eight ICUs performing admission and weekly bilateral nares and rectal screening for MRSA and VRE, respectively. Analyses were identical for both pathogens. For MRSA, patients were identified who had a negative nares screen and no prior history of MRSA. We evaluated predictors of MRSA acquisition, defined as a subsequent MRSA-positive clinical or screening culture, compared to those with a subsequent MRSA-negative nares screen within the same hospitalization. Medical records were reviewed for the presence of MSSA on the initial MRSA-negative nares screen, demographic and comorbidity information, medical devices, procedures, antibiotic utilization, and daily exposure to MRSA-positive patients in the same ward. Generalized linear mixed models were used to assess predictors of acquisition.

Results

In multivariate models, MSSA carriage protected against subsequent MRSA acquisition (OR = 0.52, CI: 0.29, 0.95), even when controlling for other risk factors. MRSA predictors included intubation (OR = 4.65, CI: 1.77, 12.26), fluoroquinolone exposure (OR = 1.91, CI: 1.20, 3.04), and increased time from ICU admission to initial negative swab (OR = 15.59, CI: 8.40, 28.94). In contrast, VSE carriage did not protect against VRE acquisition (OR = 1.37, CI: 0.54, 3.48), whereas hemodialysis (OR = 2.60, CI: 1.19, 5.70), low albumin (OR = 2.07, CI: 1.12, 3.83), fluoroquinolones (OR = 1.90, CI: 1.14, 3.17), third-generation cephalosporins (OR = 1.89, CI: 1.15, 3.10), and increased time from ICU admission to initial negative swab (OR = 15.13, CI: 7.86, 29.14) were predictive.

Conclusions

MSSA carriage reduced the odds of MRSA acquisition by 50% in ICUs. In contrast, VSE colonization was not protective against VRE acquisition. Studies are needed to evaluate whether decolonization of MSSA ICU carriers increases the risk of acquiring MRSA when discharging patients to high-endemic MRSA healthcare settings. This may be particularly important for populations in whom MRSA infection may be more frequent and severe than MSSA infections, such as ICU patients.

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this “serotype replacement” will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined.

Objective

To identify shared risk and protective factors for purging, binge eating, and overweight in a large sample of adolescents.

Design

Prospective cohort study.

Setting

Self-report questionnaires.

Participants

Females (n = 6022) and males (n= 4518), aged 11 to 17 years in 1998, in the ongoing Growing Up Today Study (GUTS). Main exposures were putative risk and protective factors within the psychological, behavioral, and socio-environmental domains.

Main outcome measures

Using laxatives or vomiting (purging), binge eating, and overweight. Due to the low prevalence of purging, we did not examine shared risk or protective factors for this behavior among males.

Results

In 1998, 219 (3.7%) females and 30 (0.7%) males reported purging behaviors, 426 (7.1%) females and 90 (2.0%) males reporting binge eating, and 1019 (17.4%) females and 1040 (24.6%) males were overweight. Over the 3-year follow-up period (1999-2001), 331 (7.8%) females initiated purging behaviors, 503 (11.8 %) females and 132 (4.5%) males initiated binge eating behaviors, and 424 (10.0 %) females and 382 (13.6 %) males became overweight. Concern for weight was significantly directly associated with all three weight-related problems among both males and females. Among females, dieting, parental weight-related teasing, and family meal frequency had a shared effect on the weight-related problems examined.

Conclusions

Factors within the psychological, behavioral, and socio-environmental domains may have a shared effect on purging, binge eating, and overweight. Further research is needed to determine if an intervention designed to address these shared risk and protective factors is effective in simultaneously reducing these weight-related problems.

Objective

Insufficient sleep in children is associated with adverse health effects. We examined the associations of early life risk factors with infant sleep duration.

Methods

We studied 1676 mother-infant pairs in a pre-birth cohort study. Main outcomes were mothers’ report of their infants’ average 24-hour sleep duration at 6 months, 1 year, and 2 years of age.

Results

Infants slept mean (SD) durations of 12.2 (2.0) hours/day at 6 months, 12.8 (1.6) hours/day at 1 year, and 11.9 (1.3) hours/day at 2 years. In multivariable regression models, maternal antenatal depression, introduction of solids < 4 months, and infant TV/video viewing were associated with shorter sleep durations at both 1 and 2 years of age. Estimates were 0.36 fewer hours/day of sleep for maternal antenatal depression, 0.39 fewer hours/day of sleep if infant was introduced to solids < 4 months, and 0.11 fewer hours/day of sleep for each 1-hour of TV viewed per week. Attendance at child care outside the home was associated with 0.18 fewer hours/day of sleep at age 2 years. At 2 years of age, black, Hispanic, and Asian infants slept 0.40, 0.82, and 0.95 fewer hours per day, respectively, than white infants.

Conclusions

Maternal depression during pregnancy, early introduction of solid foods, infant TV viewing, and attendance of child care were associated with shorter infant sleep duration. Racial/ethnic minority children slept fewer hours in the first two years of life than white children. Our results suggest that various risk factors, some potentially modifiable, are worthy of clinical consideration when addressing infant sleep duration.

Abstract

Objective

Lactation has been associated with reduced risk of type 2 diabetes and the metabolic syndrome in mothers. We examined the relation between breastfeeding duration and metabolic markers at 3 years postpartum.

Methods

We used linear regression to relate duration of lactation to maternal glucose and lipid metabolism, inflammatory markers, and anthropometry at 3 years postpartum among 570 participants with 3-year blood samples (175 fasting) in Project Viva, a cohort study of mothers and children.

Results

Among the participants, 88% had initiated breastfeeding, and 26% had breastfed ≥12 months. In multivariate analyses, we observed no consistent trends relating duration of lactation to maternal metabolism at 3 years postpartum. Women who exclusively breastfed for >6 months had lower postpartum weight retention at 3 years than women with shorter durations of exclusive breastfeeding (multivariate adjusted predicted mean −0.5, −3.6–2.6 kg vs. 4.8, 2.0–7.6 kg for those who never exclusively breastfed, partial F p = 0.03).

Conclusions

In this prospective cohort study, we did not observe a dose-response relationship between duration of lactation and metabolic risk at 3 years postpartum.

BACKGROUND

The majority of infants in the United States are in non-parental child care, yet little is known about the effect of child care on development of obesity.

OBJECTIVE

To examine the relationship between child care attendance from birth to 6 months and adiposity at 1 and 3 years of age.

METHODS

We studied 1138 children from a prospective cohort of pregnant women and their offspring. The main exposure was time in child care from birth to 6 months of age, overall and by type of care: (1) child care center; (2) someone else’s home; and (3) child’s own home by nonparent. The main outcomes were weight-for-length (WFL) z score at 1 year and BMI z score at 3 years of age.

RESULTS

A total of 649 (57%) infants attended child care; 17% were cared for in a center, 27% in someone else’s home, and 21% in their own home by a nonparent. After adjustment for confounders, overall time in child care was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age but not skinfold thicknesses. Center and own home care were not associated with the outcomes, but care in someone else’s home was associated with an increase in both the 1- and 3-year outcomes.

CONCLUSION

Child care in the first 6 months of life, especially in someone else’s home, was associated with an increased WFL z score at 1 year and BMI z score at 3 years of age.

Background

The spatial and space-time scan statistics are commonly applied for the detection of geographical disease clusters. Monte Carlo hypothesis testing is typically used to test whether the geographical clusters are statistically significant as there is no known way to calculate the null distribution analytically. In Monte Carlo hypothesis testing, simulated random data are generated multiple times under the null hypothesis, and the p-value is r/(R + 1), where R is the number of simulated random replicates of the data and r is the rank of the test statistic from the real data compared to the same test statistics calculated from each of the random data sets. A drawback to this powerful technique is that each additional digit of p-value precision requires ten times as many replicated datasets, and the additional processing can lead to excessive run times.

Results

We propose a new method for obtaining more precise p-values with a given number of replicates. The collection of test statistics from the random replicates is used to estimate the true distribution of the test statistic under the null hypothesis by fitting a continuous distribution to these observations. The choice of distribution is critical, and for the spatial and space-time scan statistics, the extreme value Gumbel distribution performs very well while the gamma, normal and lognormal distributions perform poorly. From the fitted Gumbel distribution, we show that it is possible to estimate the analytical p-value with great precision even when the test statistic is far out in the tail beyond any of the test statistics observed in the simulated replicates. In addition, Gumbel-based rejection probabilities have smaller variability than Monte Carlo-based rejection probabilities, suggesting that the proposed approach may result in greater power than the true Monte Carlo hypothesis test for a given number of replicates.

Conclusions

For large data sets, it is often advantageous to replace computer intensive Monte Carlo hypothesis testing with this new method of fitting a Gumbel distribution to random data sets generated under the null, in order to reduce computation time and obtain much more precise p-values and slightly higher statistical power.

Shorter sleep duration is linked to obesity, coronary artery disease, and diabetes. Whether sleep deprivation during the postpartum period affects maternal postpartum weight retention remains unknown. This study examined the association of sleep at 6 months postpartum with substantial postpartum weight retention (SPPWR), defined as 5 kg or more above pregravid weight at 1 year postpartum. The authors selected 940 participants in Project Viva who enrolled during early pregnancy from 1999 to 2002. Logistic regression models estimated odds ratios of SPPWR for sleep categories, controlling for sociodemographic, prenatal, and behavioral attributes. Of the 940 women, 124 (13%) developed SPPWR. Sleep distributions were as follows: 114 (12%) women slept ≥5 hours/day, 280 (30%) slept 6 hours/day, 321 (34%) slept 7 hours/day, and 225 (24%) slept≤8 hours/day. Adjusted odds ratios of SPPWR were 3.13 (95% confidence interval (CI): 1.42, 6.94) for ≤5 hours/day, 0.99 (95% CI: 0.50, 1.97) for 6 hours/day, and 0.94 (95% CI: 0.50, 1.78) for ≥8 hours/day versus 7 hours/day (p = 0.012). The adjusted odds ratio for SPPWR of 2.05 (95% CI: 1.11, 3.78) was twofold greater (p = 0.02) for a decrease in versus no change in sleep at 1 year postpartum. Sleeping ≤5 hours/day at 6 months postpartum was strongly associated with retaining ≥5 kg at 1 year postpartum. Interventions to prevent postpartum obesity should consider strategies to attain optimal maternal sleep duration.

The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial is a randomized, controlled, single-masked trial designed to determine whether cognitive training interventions (memory, reasoning, and speed of information processing), which have previously been found to be successful at improving mental abilities under laboratory or small-scale field conditions, can affect cognitively based measures of daily functioning. Enrollment began during 1998; 2-year follow-up will be completed by January 2002. Primary outcomes focus on measures of cognitively demanding everyday functioning, including financial management, food preparation, medication use, and driving. Secondary outcomes include health-related quality of life, mobility, and health-service utilization. Trial participants (n = 2832) are aged 65 and over, and at entry into the trial, did not have significant cognitive, physical, or functional decline. Because of its size and the carefully developed rigor, ACTIVE may serve as a guide for future behavioral medicine trials of this nature.

The objective of this study was to model recall and learning on the Auditory Verbal Learning Test using latent growth curve techniques. Participants were older adults recruited for the ACTIVE cognitive intervention pilot. A series of nested models revealed that an approximately logarithmic growth curve model provided optimal fit to the data. Although recall and learning factors were statistically uncorrelated, a fitted multivariate model suggested that initial recall was significantly associated with demographic characteristics but unrelated to health factors and cognitive abilities. Individual differences in learning were related to race/ethnicity, speed of processing, verbal knowledge, and global cognitive function level. These results suggest that failing to recognize initial recall and learning as distinct constructs clouds the interpretation of supraspan memory tasks.

The authors investigated the rate of gestational weight gain associated with the lowest combined risk of 5 short- and longer-term maternal and child health outcomes for 2,012 mother-child pairs recruited in 1999–2002 into Project Viva, a prebirth cohort study in Massachusetts. Within each maternal prepregnancy body mass index (BMI, kg/m2) stratum, they performed a logistic regression analysis predicting all 5 outcomes, from which they determined the rate of gain at which average predicted prevalence of the adverse outcomes was the lowest. The mean rate of total gestational weight gain was 0.39 kg/week (standard deviation, 0.14). The prevalence of small for gestational age was 6%, large for gestational age was 14%, preterm delivery was 7%, substantial postpartum weight retention was 16%, and child obesity was 10%. The lowest predicted outcome prevalence occurred with a 0.28-kg/week gain for women whose BMI was 18.5–24.9, a 0.03-kg/week loss for a BMI of 25.0–29.9, and a 0.19-kg/week loss for a BMI of ≥30.0 kg/m2—the lowest observed weight changes in overweight and obese women. For normal-weight and overweight women, lowest-risk gains varied modestly with adjustment for maternal characteristics and with different outcome weightings. For obese women, the lowest-risk weight change was weight loss in all models. Recommendations for gestational weight gain for obese women should be revised.

OBJECTIVES

The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7).

METHODS

Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000–2001 and 2003–2004 and in 8 communities in 2006–2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates.

RESULTS

We collected 678, 988, and 972 specimens during the sampling periods in 2000–2001, 2003–2004, and 2006–2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006–2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted.

CONCLUSIONS

The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

Background

Syndromic surveillance systems can potentially be used to detect a bioterrorist attack earlier than traditional surveillance, by virtue of their near real-time analysis of relevant data. Receiver operator characteristic (ROC) curve analysis using the area under the curve (AUC) as a comparison metric has been recommended as a practical evaluation tool for syndromic surveillance systems, yet traditional ROC curves do not account for timeliness of detection or subsequent time-dependent health outcomes.

Methods

Using a decision-analytic approach, we predicted outcomes, measured in lives, quality adjusted life years (QALYs), and costs, for a series of simulated bioterrorist attacks. We then evaluated seven detection algorithms applied to syndromic surveillance data using outcomes-weighted ROC curves compared to simple ROC curves and timeliness-weighted ROC curves. We performed sensitivity analyses by varying the model inputs between best and worst case scenarios and by applying different methods of AUC calculation.

Results

The decision analytic model results indicate that if a surveillance system was successful in detecting an attack, and measures were immediately taken to deliver treatment to the population, the lives, QALYs and dollars lost could be reduced considerably. The ROC curve analysis shows that the incorporation of outcomes into the evaluation metric has an important effect on the apparent performance of the surveillance systems. The relative order of performance is also heavily dependent on the choice of AUC calculation method.

Conclusions

This study demonstrates the importance of accounting for mortality, morbidity and costs in the evaluation of syndromic surveillance systems. Incorporating these outcomes into the ROC curve analysis allows for more accurate identification of the optimal method for signaling a possible bioterrorist attack. In addition, the parameters used to construct an ROC curve should be given careful consideration.

Susan Huang and colleagues describe an automated statistical software, WHONET-SaTScan, its application in a hospital, and the potential it has to identify hospital infection clusters that had escaped routine detection.

Background

Detection of outbreaks of hospital-acquired infections is often based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. These rules typically focus on only a few pathogens, and they do not account for the pathogens' underlying prevalence, the normal random variation in rates, and clusters that may occur beyond a single ward, such as those associated with specialty services. Ideally, outbreak detection programs should evaluate many pathogens, using a wide array of data sources.

Methods and Findings

We applied a space-time permutation scan statistic to microbiology data from patients admitted to a 750-bed academic medical center in 2002–2006, using WHONET-SaTScan laboratory information software from the World Health Organization (WHO) Collaborating Centre for Surveillance of Antimicrobial Resistance. We evaluated patients' first isolates for each potential pathogenic species. In order to evaluate hospital-associated infections, only pathogens first isolated >2 d after admission were included. Clusters were sought daily across the entire hospital, as well as in hospital wards, specialty services, and using similar antimicrobial susceptibility profiles. We assessed clusters that had a likelihood of occurring by chance less than once per year. For methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE), WHONET-SaTScan–generated clusters were compared to those previously identified by the Infection Control program, which were based on a rule-based criterion of three occurrences in two weeks in the same ward. Two hospital epidemiologists independently classified each cluster's importance. From 2002 to 2006, WHONET-SaTScan found 59 clusters involving 2–27 patients (median 4). Clusters were identified by antimicrobial resistance profile (41%), wards (29%), service (13%), and hospital-wide assessments (17%). WHONET-SaTScan rapidly detected the two previously known gram-negative pathogen clusters. Compared to rule-based thresholds, WHONET-SaTScan considered only one of 73 previously designated MRSA clusters and 0 of 87 VRE clusters as episodes statistically unlikely to have occurred by chance. WHONET-SaTScan identified six MRSA and four VRE clusters that were previously unknown. Epidemiologists considered more than 95% of the 59 detected clusters to merit consideration, with 27% warranting active investigation or intervention.

Conclusions

Automated statistical software identified hospital clusters that had escaped routine detection. It also classified many previously identified clusters as events likely to occur because of normal random fluctuations. This automated method has the potential to provide valuable real-time guidance both by identifying otherwise unrecognized outbreaks and by preventing the unnecessary implementation of resource-intensive infection control measures that interfere with regular patient care.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

Admission to a hospital is often a life-saving necessity—individuals injured in a road accident, for example, may need immediate medical and surgical attention if they are to survive. Unfortunately, many patients acquire infections, some of which are life-threatening, during their stay in a hospital. The World Health Organization has estimated that, globally, 8.7% of hospital patients develop hospital-acquired infections (infections that are identified more than two days after admission to hospital). In the US alone, 2 million people develop a hospital-acquired infection every year, often an infection of a surgical wound, or a urinary tract or lung infection. Infections are common among hospital patients because increasing age or underlying illnesses can reduce immunity to infection and because many medical and surgical procedures bypass the body's natural protective barriers. In addition, poor infection control practices can facilitate the transmission of bacteria—including meticillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE)—and other infectious agents (pathogens) between patients.

Why Was This Study Done?

Sometimes, the number of cases of hospital-acquired infections increases unexpectedly or a new infection emerges. Such clusters account for relatively few health care–associated infections, but, because they may arise from the transmission of a pathogen within a hospital, they need to be rapidly identified and measures implemented (for example, isolation of affected patients) to stop transmission if an outbreak is confirmed. Currently, the detection of clusters of hospital-acquired infections is based on simple rules, such as the occurrence of three new cases of a single pathogen in two weeks on the same ward. This rule-based approach relies on the human eye to detect infection clusters within microbiology data (information collected on the pathogens isolated from patients), it focuses on a few pathogens, and it does not consider the random variation in infection rates or the possibility that clusters might be associated with shared facilities rather than with individual wards. In this study, the researchers test whether an automated statistical system can detect outbreaks of hospital-acquired infections quickly and accurately.

What Did the Researchers Do and Find?

The researchers combined two software packages used to track diseases in populations to create the WHONET-SaTScan cluster detection tool. They then compared the clusters of hospital-acquired infection identified by the new tool in microbiology data from a 750-bed US academic medical center with those generated by the hospital's infection control program, which was largely based on the simple rule described above. WHONET-SaTScan found 59 clusters of infection that occurred between 2002 and 2006, about three-quarters of which were identified by characteristics other than a ward-based location. Nearly half the cluster alerts were generated on the basis of shared antibiotic susceptibility patterns. Although WHONET-SaTScan identified all the clusters previously identified by the hospital's infection control program, it classified most of these clusters as likely to be the result of normal random variations in infection rates rather than the result of “true” outbreaks. By contrast, the hospital's infection control department only identified three of the 59 statistically significant clusters identified by WHONET-SaTScan. Furthermore, the new tool identified six previously unknown MRSA outbreaks and four previously unknown VRE outbreaks. Finally, two hospital epidemiologists (scientists who study diseases in populations) classified 95% of the clusters detected by WHONET-SaTScan as worthy of consideration by the hospital infection control team and a quarter of the clusters as warranting active investigation or intervention.

What Do These Findings Mean?

These findings suggest that automated statistical software should be able to detect clusters of hospital-acquired infections that would escape detection using routine rule-based systems. Importantly, they also suggest that an automated system would be able to discount a large number of supposed outbreaks identified by rule-based systems. These findings need to be confirmed in other settings and in prospective studies in which the outcomes of clusters detected with WHONET-SaTScan are carefully analyzed. For now, however, these findings suggest that automated statistical tools could provide hospital infection control experts with valuable real-time guidance by identifying outbreaks that would be missed by routine detection methods and by preventing the implementation of intensive and costly infection control measures in situations where they are unnecessary.

Additional Information

Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000238.

The World Health Organization's Prevention of Hospital-Acquired Infections, A Practical Guide contains detailed information on all aspects of hospital-acquired infections

MedlinePlus provides links to information on infection control in hospitals (in English and Spanish)

The US Centers for Disease Control and Prevention also provides information on infectious diseases in health care settings (in English and Spanish)

The WHONET/Baclink software and the SatScan software, the two components of WHONET-SaTScan are both available on the internet (the WHONET-SaTScan cluster detection tool is freely available as part of the version of WHONET/BacLink released June 2009)