Breastfeeding versus formula-feeding and girls' pubertal development.

To examine the association of breastfeeding or its duration with timing of girls' pubertal onset, and the role of BMI as a mediator in these associations. A population of 1,237 socio-economically and ethnically diverse girls, ages 6-8 years, was recruited across three geographic locations (New York City, Cincinnati, and the San Francisco Bay Area) in a prospective study of predictors of pubertal maturation. Breastfeeding practices were assessed using self-administered questionnaire/interview with the primary caregiver. Girls were seen on at least annual basis to assess breast and pubic hair development. The association of breastfeeding with pubertal timing was estimated using parametric survival analysis while adjusting for body mass index, ethnicity, birth-weight, mother's education, mother's menarcheal age, and family income. Compared to formula fed girls, those who were mixed-fed or predominantly breastfed showed later onset of breast development [hazard ratios 0.90 (95 % CI 0.75, 1.09) and 0.74 (95 % CI 0.59, 0.94), respectively]. Duration of breastfeeding was also directly associated with age at onset of breast development (p trend = 0.008). Associations between breastfeeding and pubic hair onset were not significant. In stratified analysis, the association of breastfeeding and later breast onset was seen in Cincinnati girls only. The association between breast feeding and pubertal onset varied by study site. More research is needed about the environments within which breastfeeding takes place in order to better understand whether infant feeding practices are a potentially modifiable risk factor that may influence age at onset of breast development and subsequent risk for disease in adulthood.

Maternal hyperglycemia during pregnancy predicts adiposity of the offspring.

OBJECTIVE: To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity. RESEARCH DESIGN AND METHODS: We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls' adiposity, measured annually: (1) ≥85th age-specific percentile for BMI; (2) percent body fat (%BF); and (3) waist-to-height ratio (WHR). RESULTS: Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl's age, and girl's age at onset of puberty, having a mother with GDM increased a girl's risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28-9.92]; OR 3.13 [95% CI 1.08-9.09]; and OR 2.80 [95% CI 1.00-7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70-18.2]; Q4 %BF, OR 6.04 [95% CI 1.76-20.7]; and Q4 WHR, OR 3.60 [95% CI 1.35-9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity. CONCLUSIONS: Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.

KRAS testing and epidermal growth factor receptor inhibitor treatment for colorectal cancer in community settings.

BACKGROUND: In metastatic colorectal cancer (mCRC), mutations in the KRAS gene predict poor response to EGF receptor (EGFR) inhibitors. Clinical treatment guidelines now recommend KRAS testing if EGFR inhibitors are considered. Our study investigates the clinical uptake and utilization of KRAS testing. METHODS: We included 1,188 patients with mCRCs diagnosed from 2004 to 2009, from seven integrated health care delivery systems with a combined membership of 5.5 million. We used electronic medical records and targeted manual chart review to capture the complexity and breadth of real-world clinical oncology care. RESULTS: Overall, 428 patients (36%) received KRAS testing during their clinical care, and 266 (22%) were treated with EGFR inhibitors. Age at diagnosis (P = 0.0034), comorbid conditions (P = 0.0316), and survival time from diagnosis (P < 0.0001) influence KRAS testing and EGFR inhibitor prescribing. The proportion who received KRAS testing increased from 7% to 97% for those treated in 2006 and 2010, respectively, and 83% of all treated patients had a KRAS wild-type genotype. Most patients with a KRAS mutation (86%) were not treated with EGFR inhibitors. The interval between mCRC diagnosis and receipt of KRAS testing decreased from 26 months (2006) to 10 months (2009). CONCLUSIONS: These findings show rapid uptake and incorporation of this predictive biomarker into clinical oncology care. IMPACT: In this delivery setting, KRAS testing is widely used to guide treatment decisions with EGFR inhibitors in patients with mCRCs. An important future research goal is to evaluate utilization of KRAS testing in other delivery settings in the United States.

Father absence, body mass index, and pubertal timing in girls: differential effects by family income and ethnicity.

PURPOSE: Numerous studies show associations between father absence and girls' early puberty. However, most research has been retrospective, focused on menarche, and failed to consider body mass index (BMI), ethnicity, and income in the analyses. This study resolves these scientific gaps. METHODS: This was a prospective study of 444 girls aged 6-8 years and their caregivers (96% mothers). Data were collected annually in clinic, including weight, height, and Tanner stage for breast and pubic hair. Caregivers reported on father absence and demographics. This report focuses on the assessment of father absence at baseline and 2 years of follow-up for pubertal outcomes. Cox proportional hazards regression models were used to test whether father absence at baseline predicted pubertal onset by follow-up visit 2. BMI was assumed to be in the causal pathway. Differences by ethnicity and income were examined. RESULTS: Income and ethnicity moderated associations between father absence and pubertal onset when adjusting for BMI. Father absence predicted earlier onset of breast development only in higher-income families and onset of pubic hair development only in higher-income African Americans families. BMI was not related to father absence and therefore was not in the causal pathway. CONCLUSION: Among girls from higher-income families, father absence was linked to earlier puberty. This was particularly true for African Americans in terms of pubic hair development. These effects are not explained by body weight. Future research is needed to identify social and biophysiological mechanisms through which father absence, ethnicity, and income affect the pubertal onset.