Environmental Phenols and Growth in Infancy: The Infant Feeding and Early Development Study.

CONTEXT: Higher mean and rapid increases in body mass index (BMI) during infancy are associated with subsequent obesity and may be influenced by exposure to endocrine-disrupting chemicals such as phenols. OBJECTIVE: In a prospective US-based cohort conducted 2010-2014, we investigated associations between environmental phenol exposures and BMI in 199 infants. METHODS: We measured seven urinary phenols at ages 6-8 and 12 weeks and assessed BMI z-score at up to 12 study visits between birth and 36 weeks. We examined individual and joint associations of averaged early infancy phenols with level of BMI z-score using mean differences (ß [95% confidence intervals (CI)]) and with BMI z-score trajectories using relative risk ratios (RR [95% CI]). RESULTS: Benzophenone-3, methyl and propyl paraben, and all phenols jointly were positively associated with higher mean BMI z-score (0.07 [-0.05, 0.18], 0.10 [-0.08, 0.27], 0.08 [-0.09, 0.25], 0.17 [-0.08, 0.43], respectively). Relative to a Stable trajectory, benzophenone-3, 2,4-dichlorophenol, 2,5-dichlorophenol, and all phenols jointly were positively associated with risk of a Rapid Increase trajectory (1.46 [0.89, 2.39], 1.33 [0.88, 2.01], 1.66 [1.03, 2.68], 1.41 [0.71, 2.84], respectively). CONCLUSION: Early phenol exposure was associated with a higher mean and rapid increase in BMI z-score across infancy, signaling potential long-term cardiometabolic consequences of exposure.

A comparison of ultrasound-based testis volume with Prader orchidometry and stability of testis size relative to peers from birth to 28 weeks.

BACKGROUND: Testis volume, an indicator of the reproductive development during minipuberty, is commonly measured by Prader orchidometer, despite ultrasound being the gold standard. Data are lacking on the longitudinal relationship between these two measures and on the stability of boys' relative testis size across infancy. OBJECTIVES: To examine the relationship between ultrasound-based and orchidometer-based testis volume measurements and to assess the stability of relative testis size among individual boys in the study. MATERIALS AND METHODS: The Infant Feeding and Early Development study is a longitudinal cohort of healthy infants recruited from hospitals in the Philadelphia area during 2010-2013. We measured testis size from birth to 28 weeks in 147 infants using Prader orchidometry (nine study visits) and ultrasound (five study visits). We modeled testis growth, extracted predicted volumes for each boy on each day of the study, and ranked these volumes from smallest to largest. RESULTS: The average testis volume trajectory exhibited linear growth over the first 16 weeks followed by slower growth and then a plateau. Prader orchidometry overestimated testis size by almost 3-fold, compared to ultrasound. A range of ultrasound volumes corresponded to each bead size (e.g., bead size of 1 cm3 corresponded to an ultrasound-based volume between 0.11 and 0.87 cm3). Infants changed rankings of median of 22 positions (of 147) across the entire 6-month follow-up. Infants' ranks near birth were highly correlated with their ranks at the end of the study. DISCUSSION: Consistent with other studies, we found wide variability in testis size during infancy and that Prader orchidometry overestimates testis size. When compared to ultrasound, orchidometry only crudely estimates testis size in this age group. Ultrasound-based volumes generally showed stability in relative testis size across infancy. CONCLUSION: Accurate measurement of testis size is difficult using orchidometry in infants. This highlights the need for ultrasound for accurate measurement, with a one-time measurement likely sufficient to determine relative testis size across the first 6 months of infancy.

Environmental phenol exposures in 6- to 12-week-old infants: The Infant Feeding and Early Development (IFED) study.

BACKGROUND: Exposure to phenols, endocrine-disrupting chemicals used in personal care and consumer products, is widespread. Data on infant exposures are limited despite heightened sensitivity to endocrine disruption during this developmental period. We aimed to describe distributions and predictors of urinary phenol concentrations among U.S. infants ages 6-12 weeks. METHODS: The Infant Feeding and Early Development (IFED) study is a prospective cohort study of healthy term infants enrolled during 2010-2013 in the Philadelphia region. We measured concentrations of seven phenols in 352 urine samples collected during the 6- or 8- and/or 12-week study visits from 199 infants. We used linear mixed models to estimate associations of maternal, sociodemographic, infant, and sample characteristics with natural-log transformed, creatinine-standardized phenol concentrations and present results as mean percent change from the reference level. RESULTS: Median concentrations (µg/L) were 311 for methylparaben, 10.3 for propylparaben, 3.6 for benzophenone-3, 2.1 for triclosan, 1.0 for 2,5-dichlorophenol, 0.7 for BPA, and 0.3 for 2,4-dichlorophenol. Geometric mean methylparaben concentrations were approximately 10 times higher than published estimates for U.S. children ages 3-5 and 6-11 years, while propylparaben concentrations were 3-4 times higher. Infants of Black mothers had higher concentrations of BPA (83%), methylparaben (121%), propylparaben (218%), and 2,5-dichorophenol (287%) and lower concentrations of benzophenone-3 (-77%) and triclosan (-53%) than infants of White mothers. Triclosan concentrations were higher in breastfed infants (176%) and lower in infants whose mothers had a high school education or less (-62%). Phenol concentrations were generally higher in summer samples. CONCLUSIONS: Widespread exposure to select environmental phenols among this cohort of healthy U.S. infants, including much higher paraben concentrations compared to those reported for U.S. children, supports the importance of expanding population-based biomonitoring programs to infants and toddlers. Future investigation of exposure sources is warranted to identify opportunities to minimize exposures during these sensitive periods of development.

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. METHODS: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. CONCLUSION: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Characterization of ovarian development in girls from birth to 9 months.

BACKGROUND: The minipuberty of infancy is a period of increased reproductive axis activity. Changes in reproductive hormone concentrations and organ size occur during this period, but longitudinal changes have not been well described. OBJECTIVES: The objective of this study was to characterize ovarian growth trajectories and ovarian follicle development during the first 9 months of life in a large longitudinal cohort of healthy girls. METHODS: Data from the Infant Feeding and Early Development Study, a longitudinal cohort study of oestrogen-responsive outcomes in healthy infants, were used to estimate ovarian growth trajectories and describe the presence of ovarian antral follicles in girls 0-9 months old. Ovarian ultrasound evaluations were performed on the infants within 72 hours of birth (newborn visit) and at 4, 8, 16, 24, and 32 weeks of age. Mixed-effects regression splines were used to characterize changes in ovarian volume during infancy and assess the association between the presence of ovarian follicles at the newborn visit and ovarian growth. RESULTS: This analysis included 163 girls with two or more ovarian ultrasounds in the study. Results from the estimated overall ovarian growth trajectory show that ovarian volume increases more than sixfold during the first 16 weeks after birth and then remains relatively stable in the later weeks of infancy. Among girls with observable ovaries at the newborn visit (n = 133), girls with at least one visible ovarian follicle showed more rapid initial ovarian growth compared with girls without visible follicles. CONCLUSIONS: Infant ovarian volume increased to a peak at 16 weeks, which was influenced by the number and size of developing follicles. This research contributes to future development of reference ranges for postnatal ovarian growth in healthy, term infants.

A Longitudinal Study of Estrogen-Responsive Tissues and Hormone Concentrations in Infants Fed Soy Formula.

Purpose: Chemicals with hormonelike activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Estrogen-responsive postnatal development was compared in infants exclusively fed soy formula, cow-milk formula, and breast milk. Methods: We enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014; 283 were exclusively fed soy formula (n = 102), cow-milk formula (n = 111), or breast milk (n = 70) throughout the study (birth to 28 or 36 weeks for boys and girls, respectively). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, and serum estradiol and follicle-stimulating hormone levels. We estimated MI, organ-growth, and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal-cell MI trended higher (P = 0.01) and uterine volume decreased more slowly (P = 0.01) in soy-fed girls compared with cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk vs soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal-cell MI, uterine volume, and girls' estradiol and boys' breast-bud diameter trajectories. Conclusions: Relative to girls fed cow-milk formula, those fed soy formula demonstrated tissue- and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Studies are needed to further evaluate the effects of soy on child development.

Size of testes, ovaries, uterus and breast buds by ultrasound in healthy full-term neonates ages 0-3 days.

BACKGROUND: Hormonally sensitive organs in the neonate can change size within days of birth as circulating maternal estrogen wanes. Although several reports document the size of these organs through infancy, few focus attention on the near-birth period. Clinical and research evaluation of hormonal and genitourinary disorders would benefit from reference size standards. OBJECTIVE: We describe the size of the uterus, ovaries, testes and breast buds in healthy term neonates. MATERIALS AND METHODS: As part of the Infant Feeding and Early Development (IFED) study, we sonographically measured the largest diameter of these organs in sagittal, transverse and anterior-posterior planes for 194 female and 204 male newborns up to 3 days old. We calculated mean, median and percentiles for longest axis length and for volume calculated from measured diameters. We evaluated size differences by laterality, gender and race and compared our observations against published values. RESULTS: Mean length and mean volume were as follows: uterus, 4.2 cm and 10.0 cm3; ovary, 1.0 cm and 0.2 cm3; testis, 1.1 cm and 0.3 cm3 (0.4 cm3 Lambert volume); female breast bud, 1.2 cm and 0.7 cm3; male breast bud, 1.1 cm and 0.6 cm3. Breast buds were larger in females than males. Laterality differences were typically below the precision of clinical measurement. No significant race differences were detected. CONCLUSION: Using data from our large cohort together with published values, we provide guidelines for evaluating the size of reproductive organs within the first 3 days of age. Discrepancies between our results and published values are likely attributable to technique.

Student public commitment in a school-based diabetes prevention project: impact on physical health and health behavior.

BACKGROUND: As concern about youth obesity continues to mount, there is increasing consideration of widespread policy changes to support improved nutritional and enhanced physical activity offerings in schools. A critical element in the success of such programs may be to involve students as spokespeople for the program. Making such a public commitment to healthy lifestyle program targets (improved nutrition and enhanced physical activity) may potentiate healthy behavior changes among such students and provide a model for their peers. This paper examines whether student's "public commitment"--voluntary participation as a peer communicator or in student-generated media opportunities--in a school-based intervention to prevent diabetes and reduce obesity predicted improved study outcomes including reduced obesity and improved health behaviors. METHODS: Secondary analysis of data from a 3-year randomized controlled trial conducted in 42 middle schools examining the impact of a multi-component school-based program on body mass index (BMI) and student health behaviors. A total of 4603 students were assessed at the beginning of sixth grade and the end of eighth grade. Process evaluation data were collected throughout the course of the intervention. All analyses were adjusted for students' baseline values. For this paper, the students in the schools randomized to receive the intervention were further divided into two groups: those who participated in public commitment activities and those who did not. Students from comparable schools randomized to the assessment condition constituted the control group. RESULTS: We found a lower percentage of obesity (greater than or equal to the 95th percentile for BMI) at the end of the study among the group participating in public commitment activities compared to the control group (21.5% vs. 26.6%, p = 0.02). The difference in obesity rates at the end of the study was even greater among the subgroup of students who were overweight or obese at baseline; 44.6% for the "public commitment" group, versus 53.2% for the control group (p = 0.01). There was no difference in obesity rates between the group not participating in public commitment activities and the control group (26.4% vs. 26.6%). CONCLUSIONS: Participating in public commitment activities during the HEALTHY study may have potentiated the changes promoted by the behavioral, nutrition, and physical activity intervention components. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT00458029.