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.

Vitamin D deficiency and its treatment in cystic fibrosis.

Vitamin D deficiency is a common finding in individuals with cystic fibrosis (CF), despite routine supplementation. Hypovitaminosis D is often the result of fat malabsorption, but other contributors include increased latitude, poor nutritional intake, decreased sun exposure, impaired hydroxylation of vitamin D, and non-adherence to the prescribed vitamin D regimen. Vitamin D is critical for calcium homeostasis and optimal skeletal health, and vitamin D deficiency in CF can lead to skeletal complications of osteopenia and osteoporosis. Over time, our understanding of treatment regimens for vitamin D deficiency in CF has evolved, leading to recommendations for higher doses of vitamin D to achieve target levels of circulating 25-hydroxyvitamin D. There is also some evidence that vitamin D deficiency may have non-skeletal consequences such as an increase in pulmonary exacerbations. The exact mechanisms involved in the non-skeletal complications of vitamin D deficiency are not clearly understood, but may involve the innate immune system. Future clinical studies are needed to help address whether vitamin D has a role in CF beyond skeletal health.

Assessment of the efferent auditory system in children with suspected auditory processing disorder: the Middle ear muscle reflex and contralateral inhibition of OAEs.

OBJECTIVE: To determine whether children aged 7 to 12 years with listening difficulties show objective evidence for efferent auditory function based on measurements of medial olivo-cochlear and middle ear muscle reflexes. DESIGN: Click-evoked otoacoustic emissions recorded with and without contralateral broadband noise and ipsilateral and contralateral tonal (1000, 2000 Hz) middle ear muscle reflex thresholds were examined. STUDY SAMPLE: 29 children diagnosed with suspected auditory processing disorder (APD) and a control group of 34 typically developing children participated in this study. RESULTS: Children with suspected APD had poorer performance on auditory processing tests than the control group. Middle ear muscle reflex thresholds were significantly higher at 2000 Hz in the suspected APD group for contralateral stimulation. MOC inhibition effects did not differ between APD and control groups. CONCLUSIONS: This research supports earlier studies showing altered acoustic reflexes in children with APD. No group differences were found for the MOC reflex measures, consistent with some earlier studies in children with APD.

Long-Term Parathyroid Hormone 1-34 Replacement Therapy in Children with Hypoparathyroidism.

OBJECTIVE: To determine whether multiple daily injections of parathyroid hormone (PTH) 1-34 are safe and effective as long-term therapy for children with hypoparathyroidism. STUDY DESIGN: Linear growth, bone accrual, renal function, and mineral homeostasis were studied in a long-term observational study of PTH 1-34 injection therapy in 14 children. METHODS: Subjects were 14 children with hypoparathyroidism attributable to autoimmune polyglandular syndrome type 1 (N = 5, ages 7-12 years) or calcium receptor mutation (N = 9, ages 7-16 years). Mean daily PTH 1-34 dose was 0.75 ± 0.15 µg/kg/day. Treatment duration was 6.9 ± 3.1 years (range 1.5-10 years). Patients were evaluated semiannually at the National Institutes of Health Clinical Center. RESULTS: Mean height velocity and lumbar spine, whole body, and femoral neck bone accretion velocities were normal throughout the study. In the first 2 years, distal one-third radius bone accrual velocity was reduced compared with normal children (P < .003). Serum alkaline phosphatase correlated with PTH 1-34 dose (P < .006) and remained normal (235.3 ± 104.8 [SD] U/L, N: 51-332 U/L). Mean serum and 24-hour urine calcium levels were 2.05 ± 0.11 mmol/L (N: 2.05-2.5 mmol/L) and 6.93 ± 1.3 mmol/24 hour (N: 1.25-7.5 mmol/24 hour), respectively-with fewer high urine calcium levels vs baseline during calcitriol and calcium treatment (P < .001). Nephrocalcinosis progressed in 5 of 12 subjects who had repeated renal imaging although renal function remained normal. CONCLUSIONS: Twice-daily or thrice-daily subcutaneous PTH 1-34 injections provided safe and effective replacement therapy for up to 10 years in children with hypoparathyroidism because of autoimmune polyglandular syndrome type 1 or calcium receptor mutation.

Vitamin D3 supplementation in obese, African-American, vitamin D deficient adolescents.

OBJECTIVES: Obese, African-American (AA) adolescents are at increased risk for vitamin D deficiency. The primary objective of this pilot study was to examine the effect of vitamin D supplementation upon 25-hydroxy vitamin D (25OHD) levels in obese, AA adolescents. METHODS: A randomized, double-blinded, controlled pilot study included 26 obese (BMI ≥ 95%ile), vitamin D deficient (25OHD < 20 ng/mL), pubertal AA adolescents (ages 12-17). Subjects received cholecalciferol 1000 IU or 5000 IU daily for 3 months. Serum 25OHD, vitamin D binding protein, parathyroid hormone, and cardiometabolic risk markers were obtained at baseline and post-treatment. RESULTS: Of 39 subjects enrolled, 26 (67%) were vitamin D deficient (mean 25OHD 12.0 ±â€¯3.8 ng/mL) at baseline and were randomized, with 22 completing the study. Sex, age, season, pubertal stage, BMI, insulin resistance (HOMA-IR) and 25OHD were similar at baseline between the 1000 IU and 5000 IU groups. Post-treatment, 25OHD increased less in the 1000 IU group (5.6 ng/mL, p = 0.03) vs. the 5000 IU group (15.6 ng/mL, p = 0.002). 83% of the 5000 IU group and 30% of the 1000 IU group reached post-treatment 25OHD ≥ 20 ng/mL (p = 0.01); 50% of the 5000 IU group, but no subject from the 1000 IU group, achieved 25OHD ≥ 30 ng/mL (p = 0.009). We detected no group differences in mineral metabolites or cardiometabolic risk markers following supplementation. CONCLUSIONS: Cholecalciferol dosing in excess of the current Institute of Medicine dietary reference intakes was required to achieve 25OHD levels ≥20 ng/mL in obese, AA adolescents. Supplementation of 5000 IU may be required to achieve the desired goal.

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.

A meta-analysis of water quality and aquatic macrophyte responses in 18 lakes treated with lanthanum modified bentonite (Phoslock(®)).

Lanthanum (La) modified bentonite is being increasingly used as a geo-engineering tool for the control of phosphorus (P) release from lake bed sediments to overlying waters. However, little is known about its effectiveness in controlling P across a wide range of lake conditions or of its potential to promote rapid ecological recovery. We combined data from 18 treated lakes to examine the lake population responses in the 24 months following La-bentonite application (range of La-bentonite loads: 1.4-6.7 tonnes ha(-1)) in concentrations of surface water total phosphorus (TP; data available from 15 lakes), soluble reactive phosphorus (SRP; 14 lakes), and chlorophyll a (15 lakes), and in Secchi disk depths (15 lakes), aquatic macrophyte species numbers (6 lakes) and aquatic macrophyte maximum colonisation depths (4 lakes) across the treated lakes. Data availability varied across the lakes and variables, and in general monitoring was more frequent closer to the application dates. Median annual TP concentrations decreased significantly across the lakes, following the La-bentonite applications (from 0.08 mg L(-1) in the 24 months pre-application to 0.03 mg L(-1) in the 24 months post-application), particularly in autumn (0.08 mg L(-1) to 0.03 mg L(-1)) and winter (0.08 mg L(-1) to 0.02 mg L(-1)). Significant decreases in SRP concentrations over annual (0.019 mg L(-1) to 0.005 mg L(-1)), summer (0.018 mg L(-1) to 0.004 mg L(-1)), autumn (0.019 mg L(-1) to 0.005 mg L(-1)) and winter (0.033 mg L(-1) to 0.005 mg L(-1)) periods were also reported. P concentrations following La-bentonite application varied across the lakes and were correlated positively with dissolved organic carbon concentrations. Relatively weak, but significant responses were reported for summer chlorophyll a concentrations and Secchi disk depths following La-bentonite applications, the 75th percentile values decreasing from 119 µg L(-1) to 74 µg L(-1) and increasing from 398 cm to 506 cm, respectively. Aquatic macrophyte species numbers and maximum colonisation depths increased following La-bentonite application from a median of 5.5 species to 7.0 species and a median of 1.8 m to 2.5 m, respectively. The aquatic macrophyte responses varied significantly between lakes. La-bentonite application resulted in a general improvement in water quality leading to an improvement in the aquatic macrophyte community within 24 months. However, because, the responses were highly site-specific, we stress the need for comprehensive pre- and post-application assessments of processes driving ecological structure and function in candidate lakes to inform future use of this and similar products.

Allowing for asymmetric distributions when comparing auditory processing test percentage scores with normative data.

BACKGROUND: Raw percentage scores can be transformed to age-specific Z scores, despite the asymmetric distribution of normative data using a process that is applicable to any percentage (or proportion)-based result. PURPOSE: Normative values are generated for the commonly used dichotic digit and frequency pattern behavioral tests of auditory processing. STUDY SAMPLE: A total of 180 normal-hearing children aged 7 yr 0 mo to 12 yr 2 mo took part in this study. RESEARCH DESIGN: A transformation and regression method is incorporated that allows for the asymmetric distribution of normative results and the development of the response across the 7-12-yr-age range. DATA COLLECTION AND ANALYSIS: Percentage correct scores were determined for each ear in the dichotic digit and frequency pattern tests, delivered at 50 dB HL. The scores were arcsine transformed, then regressed against using an exponential equation, providing an age specific estimated mean score. The residual error of the regression was then used to estimate age specific variance. RESULTS AND CONCLUSIONS: The ability to express results along an age continuum (while accounting for the asymmetric distribution and significant developmental influences) as a standard unit across all ages enables a simplified expression of performance ability on a task.

Metabolic bone disease screening practices among U.S. neonatologists.

Preterm, low-birth-weight neonates are predisposed to metabolic bone disease (MBD). This survey aimed to assess screening, diagnostic, and treatment practices in U.S. level IIIB/IIIC neonatal intensive care units (NICUs). A 29-question anonymous online survey was e-mailed to American Academy of Pediatrics Perinatal Section members. 338 neonatologists, representing 246 IIIB/IIIC NICUs, responded. 86% reported MBD screening. Screening was primarily based on gestational age (71%), with thresholds <26 to <36 weeks. Other criteria included birth weight (64%), total parenteral nutrition duration (48%), X-ray findings (56%), diuretic use (41%), and exclusive breast-feeding (9.6%). Almost universally, diagnosis was based on elevated alkaline phosphatase, most commonly >500 U/L (58.6%). 52% used X-ray for diagnosis. Treatment included human milk fortification (83%), vitamin D (67%), calcium (65%), and phosphorus (65%) supplementation. Our survey confirms widespread awareness of MBD but highlights lack of consensus regarding definition, screening, and treatment. Further research is needed to develop and optimize strategies to prevent, recognize, and manage MBD.

State of nutrition support teams.

The incidence of malnutrition in hospitalized patients is relatively high (up to 55%) despite breakthroughs in nutrition support therapies. These patients have increased morbidity and mortality, extended hospital stays, and care that is associated with higher costs. These patients are often poorly managed due to inadequate nutrition assessment and poor medical knowledge and practice in the field of nutrition. Nutrition support teams (NSTs) are interdisciplinary support teams with specialty training in nutrition that are often comprised of physicians, dietitians, nurses, and pharmacists. Their role includes nutrition assessment, determination of nutrition needs, recommendations for appropriate nutrition therapy, and management of nutrition support therapy. Studies have demonstrated significant improvements in patient nutrition status and improved clinical outcomes as well as reductions in costs when patients were appropriately managed by a multispecialty NST vs individual caregivers. Despite this, there has been steady decline in the number of formal NST in recent years (65% of hospitals in 1995 to 42% in 2008) as hospitals and other healthcare organizations look for ways to cut costs. Given the importance of nutrition status on clinical outcomes and overall healthcare costs, a number of institutions have introduced and sustained strong nutrition training and support programs and teams, demonstrating both clinical and economic benefit. The benefits of NST, training and implementation strategies, and tips for justifying these clinically and economically beneficial groups to healthcare organizations and governing bodies are discussed in this review.

A novel method for reproducibly measuring the effects of interventions to improve emotional climate, indices of team skills and communication, and threat to patient outcome in a high-volume thoracic surgery center.

OBJECTIVE: To create and test a reproducible method for measuring emotional climate, surgical team skills, and threats to patient outcome by conducting an observational study to assess the impact of a surgical team skills and communication improvement intervention on these measurements. DESIGN: Observational study. SETTING: Operating rooms in a high-volume thoracic surgery center from September 5, 2007, through June 30, 2008. PARTICIPANTS: Thoracic surgery operating room teams. INTERVENTIONS: Two 90-minute team skills training sessions focused on findings from a standardized safety culture survey administered to all participants and highlighting positive and problematic aspects of team skills, communication, and leadership. The sessions created an interactive forum to educate team members on the importance of communication and to role-play optimal interactive and communication strategies. MAIN OUTCOME MEASURES: Calculated indices of emotional climate, team skills, and threat to patient outcome. RESULTS: The calculated communication and team skills score improved from the preintervention to postintervention periods, but the improvement extinguished during the 3 months after the intervention (P < .001). The calculated threat-to-outcome score improved following the team training intervention and remained statistically improved 3 months later (P < .001). CONCLUSIONS: Using a new method for measuring emotional climate, teamwork, and threats to patient outcome, we were able to determine that a teamwork training intervention can improve a calculated score of team skills and communication and decrease a calculated score of threats to patient outcome. However, the effect is only durable for threats to patient outcome.

Electrophysiological and speech perception measures of auditory processing in experienced adult cochlear implant users.

OBJECTIVE: This study determined the relationship between auditory evoked potential measures and speech perception in experienced adult cochlear implant (CI) users and compared the CI evoked potential results to those of a group of age- and sex-matched control subjects. METHODS: CI subjects all used the Nucleus CI-22 implant. Middle latency response (MLR), obligatory cortical potentials (CAEP), mismatch negativity (MMN) and P3a auditory evoked potentials were recorded. Speech perception was evaluated using word and sentence tests. RESULTS: Duration of deafness correlated with speech scores with poor scores reflecting greater years of deafness. Na amplitude correlated negatively with duration of deafness, with small amplitudes reflecting greater duration of deafness. Overall, N1 amplitude was smaller in CI than control subjects. Earlier P2 latencies were associated with shorter durations of deafness and higher speech scores. In general, MMN was absent or degraded in CI subjects with poor speech scores. CONCLUSIONS: Auditory evoked potentials are related to speech perception ability and provide objective evidence of central auditory processing differences across experienced CI users. SIGNIFICANCE: Since auditory evoked potentials relate to CI performance, they may be a useful tool for objectively evaluating the efficacy of speech processing strategies and/or auditory training approaches in both adults and children with cochlear implants.