Exploring height outcomes with adjuvant aromatase inhibition in growth hormone-deficient male survivors of childhood cancer.

BACKGROUND: Aromatase inhibitors (AI) may improve height in short stature conditions; however, the effect in childhood cancer survivors (CCS) is unknown. We assessed final adult height (FAH) in CCS treated with AI and GH compared with those treated with GH alone. METHODS: Retrospective cohort study of GH-deficient male CCS treated between 2007 and 2023. FAH was noted as the height at the fusion of growth plates or 18 years of age. Multivariable linear regression was used to examine treatment association with FAH, adjusting for other risk factors. RESULTS: Ninety-two patients were included; 70 were treated with GH and 22 with combination AI/GH. The mean age at GH initiation did not differ between groups. The mean age at AI initiation was 13.7 ± 1.9 years. A greater proportion of patients in the AI/GH group were treated with stem cell transplantation, abdominal radiation, total body irradiation, and cis-retinoic acid (p < .01). Multivariable linear regression demonstrated no significant treatment association with FAH Z-score (ß = 0.04, 95% CI: -0.9 to 0.9). History of spinal radiation (ß = -0.93, 95% CI: -1.7 to -0.2), lower starting height Z-score (ß = -0.8, 95% CI: -1.2 to -0.4), and greater difference between bone age and chronological age (ß = -0.3, 95% CI: -0.5 to -0.07) were associated with lower FAH Z-score. CONCLUSIONS: Adjuvant AI was not associated with increased FAH in male CCS compared with GH monotherapy. Future work is needed to determine the optimal adjunctive treatment to maximize FAH for this population.

Selenomonas sputigena Interactions with Gingival Epithelial Cells That Promote Inflammation.

Increased prevalence and abundance of Selenomonas sputigena have been associated with periodontitis, a chronic inflammatory disease of tooth-supporting tissues, for more than 50 years. Over the past decade, molecular surveys of periodontal disease using 16S and shotgun metagenomic sequencing approaches have confirmed the disease association of classically recognized periodontal pathogens such as Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia while highlighting previously underappreciated organisms such as Filifactor alocis and S. sputigena. Despite abundant clinical association between S. sputigena and periodontal disease, we have little to no understanding of its pathogenic potential, and virulence mechanisms have not been studied. In this study, we sought to characterize the response of gingival epithelial cells to infection with S. sputigena. Here, we show that S. sputigena attaches to gingival keratinocytes and induces expression and secretion of cytokines and chemokines associated with inflammation and leukocyte recruitment. We demonstrate that S. sputigena induces signaling through Toll-like receptor 2 (TLR2) and TLR4 but evades activation of TLR5. Cytokines released from S. sputigena-infected keratinocytes induced monocyte and neutrophil chemotaxis. These results show that S. sputigena-host interactions have the potential to contribute to bacterially driven inflammation and tissue destruction, the hallmark of periodontitis. Characterization of previously unstudied pathogens may provide novel approaches to develop therapeutics to treat or prevent periodontal disease.

The impact of fear of hypoglycaemia on sleep in adolescents with type 1 diabetes.

AIMS: Fear of hypoglycaemia (FOH) can contribute to impaired sleep for adults with type 1 diabetes (T1D) and parents of children with T1D, although it is unknown how FOH may affect sleep for adolescents with T1D. This study examines the relationship between adolescent FOH and sleep and assessed the influences of continuous glucose monitor (CGM) and insulin pump use. METHODS: Adolescents ages 14-18 years with T1D completed questionnaires evaluating FOH (Child Hypoglycemia Fear Survey) and sleep (Pittsburgh Sleep Quality Index, PSQI). Analyses included linear and logistic regression, t-tests and Fisher's exact tests. RESULTS: Participants included 95 adolescents (52 female) with a median (IQR) age of 16.5 (15.3-17.7) years and a T1D duration of 5.7 (2.5-9.6) years. Analyses showed increased FOH-Worry subscale scores were associated with reduced sleep duration (ß = -0.03, p = 0.042, adjusting for BMI z-score, race and ethnicity) and increased sleep disturbances (OR = 1.1, p = 0.038, adjusting for race and ethnicity). Frequent CGM users had longer sleep duration (average 7.5 h) compared with infrequent or non-CGM users (average = 6.8 h; p = 0.029), and pump users had overall improved sleep health as determined by PSQI score (p = 0.019). Technology use did not have significant interactions in the relationships between FOH and sleep duration or sleep disturbances. CONCLUSIONS: Worrying about hypoglycaemia was associated with impaired sleep for adolescents with T1D. Diabetes technology users have some sleep improvements, but CGM and pump use do little to alter the relationship between FOH and sleep outcomes.

Perspectives of Pediatric Community Health Workers: Roles, Successes, and Challenges.

This multicenter qualitative study described the roles of 10 pediatric community health workers (CHWs) in their own words through exploration of the role features, successes, and challenges in pediatric health care settings across three urban U.S. cities (Philadelphia, New York City, and Cincinnati). Individual, semi-structured telephone interviews were conducted. Interviews described prominent features of the pediatric CHW role, which included taking a family-centered approach to goal setting and determining support needed, ensuring family goals stayed at the center of the work, and acting as a trusted figure for families to talk openly with. CHWs described their role as rewarding, believing in the work, and feeling a sense of fulfillment, and felt successful when families had positive outcomes, including when barriers were eliminated, resources were obtained, or independence was demonstrated by families. Challenges CHWs faced in their roles included establishing trust with families, managing the ever-changing family circumstances many families experience due to socioeconomic barriers, and managing limitations of protocol and restrictions within their roles. This study demonstrated numerous considerations for CHW practice in pediatric health care settings, in addition to considerations for pediatric-specific CHW program development and management. The primary policy implication of this study included a basis for increased funding for CHW programs in pediatric health care settings. This study also demonstrated a need for further research on the change CHWs effect within child and family systems outside of health care, such as schools and child welfare agencies.

Treponema denticola Induces Interleukin-36γ Expression in Human Oral Gingival Keratinocytes via the Parallel Activation of NF-κB and Mitogen-Activated Protein Kinase Pathways.

The oral epithelial barrier acts as both a physical barrier to the abundant oral microbiome and a sentry for the immune system that, in health, constrains the accumulation of the polymicrobial plaque biofilm. The immune homeostasis during gingivitis that is largely protective becomes dysregulated, unproductive, and destructive to gingival tissue as periodontal disease progresses to periodontitis. The progression to periodontitis is associated with the dysbiosis of the oral microbiome, with increasing prevalences and abundances of periodontal pathogens such as Treponema denticola. Despite the association of T. denticola with a chronic inflammatory disease, relatively little is known about gingival epithelial cell responses to T. denticola infection. Here, we characterized the transcriptome of gingival keratinocytes following T. denticola challenge and identified interleukin-36γ (IL-36γ) as the most differentially expressed cytokine. IL-36γ expression is regulated by p65 NF-κB and the activation of both the Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways downstream of Toll-like receptor 2 (TLR2). Finally, we demonstrate for the first time that mitogen- and stress-activated kinase 1 (MSK1) contributes to IL-36γ expression and may link the activation of MAPK and NF-κB signaling. These findings suggest that the interactions of T. denticola with the gingival epithelium lead to elevated IL-36γ expression, which may be a critical inducer and amplifier of gingival inflammation and subsequent alveolar bone loss.

Racial and Ethnic Disparities in the Investigation and Treatment of Growth Hormone Deficiency.

OBJECTIVE: To determine if the racial/ethnic inequity in growth hormone (GH) use is due to differences in GH stimulation testing and/or prescribing patterns in children referred for endocrine evaluation of short stature. STUDY DESIGN: Retrospective chart review was performed including children aged 2-16 years, height z-score of ≤-1.5, and of non-Hispanic White (NHW), non-Hispanic Black (NHB), or Hispanic race/ethnicity, referred for endocrine growth evaluation between January 2012 and December 2019. RESULTS: This study included 7425 children (5905 NHW, 800 NHB, and 720 Hispanic). GH stimulation testing was performed in 992, and 576 were prescribed GH. NHW children were 1.4 (95% CI, 1.04-1.8) times more likely than NHB children and 1.7 (95% CI, 1.2-2.2) times more likely than Hispanic children to undergo GH stimulation testing. GH-treated NHB children had (1) a lower median peak GH concentration when compared with NHW (P = .02) and Hispanic (P = .08) children (NHB 4.7 ng/mL [95% CI, 1.2-8.3 ng/mL] ng/mL, NHW 7.2 ng/mL [95% CI, 4.9-9.7 ng/mL], Hispanic 7.1 ng/mL [95% CI, 4.3-11.9 ng/mL]); (2) lower median height z-scores than NHW (P = .01) but not Hispanic children (P = .5); and (3) a greater height deficit from midparental height when compared with NHW (P = .01) and Hispanic (P = .002) children. CONCLUSIONS: Racial and ethnic disparities exist in the evaluation and treatment of children with disordered growth. This likely results from both overinvestigation of NHW children as well as underinvestigation and undertreatment of children from minority communities. The evaluation and treatment of children with short stature should be determined by clinical concern alone, but this is not current practice.

Safety and Efficacy of Glucagon-Like Peptide-1 Receptor Agonists in Children and Adolescents with Obesity: A Meta-Analysis.

OBJECTIVES: To determine the weight, body mass index (BMI), cardiometabolic, and gastrointestinal effects of glucagon-like peptide-1 (GLP-1) receptor agonists in children with obesity. STUDY DESIGN: Web of Science, PubMed/MEDLINE, and Scopus databases from 01/01/1994-01/01/2021 for randomized control trials examining the weight, BMI, cardiometabolic, or gastrointestinal effects of GLP-1 receptor agonists in children and adolescents with obesity. Data were extracted by 2 independent surveyors and a random effects model was applied to meta-analyze generic inverse variance outcomes. Primary outcomes were related to weight and cardiometabolic profile, and secondary outcomes of interest were gastrointestinal-related treatment-emergent adverse events. RESULTS: Nine studies involving 574 participants were identified, of which 3 involved exenatide and 6 involved liraglutide. GLP-1 receptor agonists use caused a modest reduction in body weight (mean difference [MD] -1.50 [-2.50,-0.50] kg, I2 64%), BMI (MD -1.24 [-1.71,-0.77] kg/m2, I2 0%), and BMI z score (MD -0.14 [-0.23,-0.06], I2 43%). Glycemic control was improved in children with proven insulin resistance (glycated hemoglobin A1c MD -1.05 [-1.93,-0.18] %, I2 76%). Although no lipid profile improvements were noted, a modest decrease in systolic blood pressure was detected (MD -2.30 [-4.11,-0.49] mm Hg; I2 0%). Finally, analysis of gastrointestinal-related treatment-emergent adverse events revealed an increased risk of nausea (risk ratio 2.11 [1.44, 3.09]; I2 0%), without significant increases in other gastrointestinal symptoms. CONCLUSIONS: This meta-analysis indicates that GLP-1 receptor agonists are safe and effective in modestly reducing weight, BMI, glycated hemoglobin A1c, and systolic blood pressure in children and adolescents with obesity in a clinical setting, albeit with increased rates of nausea. PROSPERO ID: CRD42020195869.

Further delineation of a recognizable type of syndromic short stature caused by biallelic SEMA3A loss-of-function variants.

The semaphorin protein family is a diverse set of extracellular signaling proteins that perform fundamental roles in the development and operation of numerous biological systems, notably the nervous, musculoskeletal, cardiovascular, endocrine, and reproductive systems. Recently, recessive loss-of-function (LoF) variants in SEMA3A (semaphorin 3A) have been shown to result in a recognizable syndrome characterized by short stature, skeletal abnormalities, congenital heart defects, and variable additional anomalies. Here, we describe the clinical and molecular characterization of a female patient presenting with skeletal dysplasia, hypogonadotropic hypogonadism (HH), and anosmia who harbors a nonsense variant c.1633C>T (p.Arg555*) and a deletion of exons 15, 16, and 17 in SEMA3A in the compound heterozygous state. These variants were identified through next-generation sequencing analysis of a panel of 26 genes known to be associated with HH/Kallmann syndrome. Our findings further substantiate the notion that biallelic LoF SEMA3A variants cause a syndromic form of short stature and expand the phenotypic spectrum associated with this condition to include features of Kallmann syndrome.

Influence of social determinants of health barriers to family management of type 1 diabetes in Black single parent families: A mixed methods study.

OBJECTIVE: US disparities in pediatric type 1 diabetes treatment and outcomes are increasing disproportionately among Black youth and compounded for youth from single parent homes. Despite worsened outcomes, Black youth from single parent homes and their caregivers are underrepresented in pediatric type 1 diabetes research. The purpose of this study was to understand the social determinants of health (SDOH) barriers that may contribute to health disparities and family management in Black youth with type 1 diabetes from single parent homes. RESEARCH DESIGN AND METHODS: A three-phase mixed methods study with self-identified Black single parents of youth with type 1 diabetes from an urban US pediatric diabetes center was conducted. Focus groups and interviews informed development of a parent-generated survey of SDOH barriers to diabetes management. Survey results are presented. RESULTS: A resulting 71 item parent-generated survey was administered to 105 parents. Among all items, most problematic SDOH barriers included lack of social support, managing parent/child diabetes-related stress, difficulties accessing diabetes supplies, pain management, cost of food and diabetes camp, need to take time off from work, lack of skilled school staff, school absences and unsafe neighborhoods. Structural racism related to child welfare reporting, and police targeting were also notable concerns. CONCLUSIONS: There is a critical need for clinical, community, and policy-related research and interventions, designed to reduce type 1 diabetes racial health disparities by addressing the impacts of SDOH as drivers of family management outcomes among Black youth from single parent families.

Racial disparities in treatment and outcomes of children with type 1 diabetes.

OBJECTIVE: The aim of this study was to assess racial disparities in treatments and outcomes between Non-Hispanic black (NHB), Hispanic and Non-Hispanic white (NHW) children with type 1 diabetes (T1D). METHODS: We reviewed electronic health records of children (<18 years) attending a large, pediatric tertiary care diabetes center in the United States between October 1, 2018, and December 31, 2019. Health care utilization (appointment attendance, ED visits, hospitalizations), technology use (insulin pumps, continuous glucose monitors [CGM]) and hemoglobin A1c (HbA1c) were examined for each race/ethnicity and stratified by insurance type (private/government) as a proxy for socioeconomic status (SES). RESULTS: Of 1331 children (47% female) with a median (IQR) age of 14.2 (11.5, 16.3) years and T1D duration of 5.8 (3.8, 9) years; 1026 (77%) were NHW, 198 (15%) NHB, and 107 (8%) Hispanic. Government insurance was used by 358 (27%) children, representing 60% of NHB and 53% of Hispanic, but only 18% of NHW children. NHB children had higher HbA1c, more ED visits and hospitalizations, and were less likely to be treated with insulin pumps or CGM than NHW children (P < .001 for all). There were no racial disparities with regard to the number of appointments attended. CONCLUSIONS: Racial disparities in technology use and diabetes outcomes persist in children with T1D, regardless of insurance status. To ensure equitable care, pediatric healthcare providers should remain cognizant of racial disparities in diabetes treatment. The impact of provider and patient factors should be explored when studying the etiology of these health disparities.

The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

PURPOSE: Clinicians and researchers must contextualize a patient's genetic variants against population-based references with detailed phenotyping. We sought to establish globally scalable technology, policy, and procedures for sharing biosamples and associated genomic and phenotypic data on broadly consented cohorts, across sites of care. METHODS: Three of the nation's leading children's hospitals launched the Genomic Research and Innovation Network (GRIN), with federated information technology infrastructure, harmonized biobanking protocols, and material transfer agreements. Pilot studies in epilepsy and short stature were completed to design and test the collaboration model. RESULTS: Harmonized, broadly consented institutional review board (IRB) protocols were approved and used for biobank enrollment, creating ever-expanding, compatible biobanks. An open source federated query infrastructure was established over genotype-phenotype databases at the three hospitals. Investigators securely access the GRIN platform for prep to research queries, receiving aggregate counts of patients with particular phenotypes or genotypes in each biobank. With proper approvals, de-identified data is exported to a shared analytic workspace. Investigators at all sites enthusiastically collaborated on the pilot studies, resulting in multiple publications. Investigators have also begun to successfully utilize the infrastructure for grant applications. CONCLUSIONS: The GRIN collaboration establishes the technology, policy, and procedures for a scalable genomic research network.

Correction: The Genomics Research and Innovation Network: creating an interoperable, federated, genomics learning system.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Sitting Height to Standing Height Ratio Reference Charts for Children in the United States.

OBJECTIVE: To create reference charts for sitting height to standing height ratio (SitHt/Ht) for children in the US, and to describe the trajectory of SitHt/Ht during puberty. STUDY DESIGN: This was a cross-sectional study using data from the 1988-1994 National Health and Nutrition Examination Survey III, a strategic random sample of the US population. Comparison between non-Hispanic White (NHW), non-Hispanic Black (NHB) and Mexican American groups was performed by ANOVA to determine if a single population reference chart could be used. ANOVA was used to compare SitHt/Ht in pre-, early, and late puberty. RESULTS: NHANES III recorded sitting height and standing height measurements in 9569 children aged 2-18 years of NHW (n = 2715), NHB (n = 3336), and Mexican American (n = 3518) ancestry. NHB children had lower SitHt/Ht than NHW and Mexican American children throughout childhood (P < .001). In both sexes, the SitHt/Ht decreased from prepuberty to early puberty and increased in late puberty. Sex-specific percentile charts of SitHt/Ht vs age were generated for NHB and for NHW and Mexican American youth combined. CONCLUSIONS: SitHt/Ht assessment can detect disproportionate short stature in children with skeletal dysplasia, but age-, sex-, and population-specific reference charts are required to interpret this measurement. NHB children in the US have significantly lower SitHt/Ht than other children, which adds complexity to interpretation. We recommend the use of standardized ancestry-specific reference charts in screening for skeletal dysplasias and have developed such charts in this study.

Insulin Pump Use in Children with Type 1 Diabetes: Over a Decade of Disparities.

PURPOSE: Racial disparities have been shown in outcomes and treatment of children with type 1 diabetes (T1D). The purpose of this study was to examine temporal trends in insulin pump use among non-Hispanic white (NHW), non-Hispanic black (NHB) and Hispanic children attending a large urban diabetes center. . This study was a retrospective chart review of insulin pump usage by race (NHW/ NHB) in 2005, and race/ethnicity (NHW/NHB/Hispanic) in 2011-2019. Demographic data (age, sex, diabetes duration, SES) and most recent hemoglobin A1c were also abstracted in 2011-2019. RESULTS: In 2005, NHW children were twice as likely to use an insulin pump as NHB children. From 2011 to 2019, the odds ratio increased to 2.5 for NHW compared to NHB children. The odds of Hispanic children using insulin pumps were also higher than NHB. Insurance status (government versus private), a surrogate for SES, had very little influence on these trends, with NHW children consistently more likely than NHB children to be treated with insulin pumps in 2011, 2013, 2017, 2019 (p < 0.001). CONCLUSIONS: We have demonstrated that racial disparities in insulin pump use have persisted over the past 15 years, and are not determined by SES. This inequity in diabetes treatment may be playing a role in the poorer glycemic control and higher rates of diabetes complications in NHB children. PRACTICE IMPLICATIONS: Healthcare providers should be cognizant of racial and ethnic disparities in the treatment of children with T1D. Standardized treatment protocols may reduce unconscious bias in prescribing.

Optimal Timing of Repeat Newborn Screening for Congenital Hypothyroidism in Preterm Infants to Detect Delayed Thyroid-Stimulating Hormone Elevation.

OBJECTIVES: To evaluate the timing of a delayed rise in thyroid-stimulating hormone (TSH) levels in preterm infants with congenital hypothyroidism, and to determine whether cases of congenital hypothyroidism would be missed by using current consensus guidelines of repeat screening at approximately 2 weeks of age or 2 weeks after the first screening. STUDY DESIGN: The study was performed over a 13-year period (January 2004-December 2016). Whole-blood TSH samples were collected between 72 and 120 hours after birth. Repeat samples were collected weekly in preterm infants until the infant was term-corrected (37 weeks' gestation). Patients were followed up to determine whether congenital hypothyroidism was permanent or transient. RESULTS: Twenty-seven (50.9%) preterm infants born at <33 weeks of gestation who were diagnosed with congenital hypothyroidism had delayed TSH elevation and would not have been detected on first newborn screen. Twelve of these infants (40.7%) with delayed TSH elevation had decompensated hypothyroidism at diagnosis (free thyroxine [FT4] <10 pmol/L), and 4 had severe congenital hypothyroidism (FT4 <5.5 pmol/L) at diagnosis. If screening had been repeated only at 2 weeks of life, 13 infants (48%) with delayed TSH elevation would not have been identified. Of the 27 infants with delayed TSH elevation, 6 (22%) have permanent congenital hypothyroidism, and another 12 will be reevaluated at age 3 years. CONCLUSION: Repeat screening for congenital hypothyroidism in preterm infants is necessary to avoid missing cases of congenital hypothyroidism with delayed TSH elevation. Repeat screening once at 2 weeks of life will miss infants with delayed TSH elevation and decompensated permanent congenital hypothyroidism.

Body Mass Index Is a Better Indicator of Body Composition than Weight-for-Length at Age 1 Month.

OBJECTIVE: To assess whether body mass index (BMI) provides a better assessment of measured adiposity at age 1 month compared with weight-for-length (WFL). STUDY DESIGN: Participants were healthy term-born infants in the Infant Growth and Microbiome (n = 146) and the Baby Peas (n = 147) studies. Length, weight, and body composition by air displacement plethysmography were measured at 1 month. World Health Organization-based WFL and BMI z-scores were calculated. Within-cohort z-scores of percent fat-Z, fat mass-Z, fat mass/length2-Z, fat mass/length3-Z, fat-free mass-Z, and fat-free mass/length2-Z were calculated. Correlation and multiple linear regression (adjusted for birth weight) analyses tested the associations between body composition outcomes and BMI-Z vs WFL-Z. Quantile regression was used to test the stability of these associations across the distribution of body compositions. RESULTS: The sample was 52% female and 56% African American. Accounting for birth weight, both BMI-Z and WFL-Z were strongly associated with fat mass-Z (coefficients 0.56 and 0.35, respectively), FM/L2-Z (0.73 and 0.51), and FM/L3-Z (0.79 and 0.58), with stronger associations for BMI-Z compared with WFL-Z (P < .05). Even after accounting statistically for birth weight, BMI-Z was persistently more strongly associated than WFL-Z with body composition outcomes across the distribution of body composition outcomes. CONCLUSIONS: We demonstrate in 2 distinct cohorts that BMI is a better indicator of adiposity in early infancy compared with WFL. Our findings support the preferred use of BMI for growth and nutritional status assessment in infancy.

Novel Preparations of Glucagon for the Prevention and Treatment of Hypoglycemia.

PURPOSE OF REVIEW: New more stable formulations of glucagon have recently become available, and these provide an opportunity to expand the clinical roles of this hormone in the prevention and management of insulin-induced hypoglycemia. This is applicable in type 1 diabetes, hyperinsulinism, and alimentary hypoglycemia. The aim of this review is to describe these new formulations of glucagon and to provide an overview of current and future therapeutic opportunities that these may provide. RECENT FINDINGS: Four main categories of glucagon formulation have been studied: intranasal glucagon, biochaperone glucagon, dasiglucagon, and non-aqueous soluble glucagon. All four have demonstrated similar glycemic responses to standard glucagon formulations when administered during hypoglycemia. In addition, potential roles of these formulations in the management of congenital hyperinsulinism, alimentary hypoglycemia, and exercise-induced hypoglycemia in type 1 diabetes have been described. As our experience with newer glucagon preparations increases, the role of glucagon is likely to expand beyond the emergency use that this medication has been limited to in the past. The innovations described in this review likely represent early examples of a pending large repertoire of indications for stable glucagon.

The relationship between IGF-I and -II concentrations and body composition at birth and over the first 2 months.

BACKGROUND: Insulin-like growth factor (IGF)-I and -II play an important role in prenatal growth. During the first 2 months from birth, body fat doubles, and rapid weight gain during this time increases future risk of cardiometabolic disease. The aim of this study was to determine whether IGF measurements at birth associate with body composition and the trajectory of its changes in the first 2 months. METHODS: Umbilical cord IGF-I and -II concentrations were measured in term infants. Air displacement plethysmography was performed at birth and 2 months. Fat mass (FM) and fat-free mass (FFM) were corrected for infant length (L) to FM/L3 and FFM/L2, respectively. RESULTS: In 601 (317 male) infants, IGF-I concentrations at birth were associated with FM/L3 and FFM/L2 Z-scores at birth (R2 = 0.05 and 0.04, respectively, P < 0.001), and IGF-II concentrations were associated with FFM/L2 Z-scores at birth (R2 = 0.01, P = 0.02). Lower IGF-I concentrations were weakly associated with increases in FM/L3 Z-scores over the first 2 months (R2 = 0.01, P = 0.003). CONCLUSION: IGF-I concentrations at birth are associated with adiposity and lean mass at birth and inversely with the trajectory of FM accumulation over the first 2 months. IGF-I measurements only account for a small amount of the variance in these measures.

A structured 1-year education program for children with newly diagnosed type 1 diabetes improves early glycemic control.

BACKGROUND: The diagnosis of type 1 diabetes (T1D) brings significant medical, psychosocial, and educational challenges for the child, family, and medical team. We developed a structured certified diabetes educator (CDE) led program spanning the year after diagnosis with the goal of supporting families as their understanding of this chronic disease and its management evolves. OBJECTIVE: The aim of this study was to determine the effect of this program upon hemoglobin A1c (HbA1c), and how this effect is mitigated by socioeconomic status (SES). METHODS: Patients enrolled in the type 1 year 1 (T1Y1) program were assigned a CDE who provided intensive coaching, tailored to family lifestyle, and readiness to assume independence. We identified all patients diagnosed with T1D in the 2 years before (controls) and after (T1Y1 group) the start of the T1Y1 program on January 7, 2014. RESULTS: There were 675 patients diagnosed with T1D between July 2012 and June 2016 (284 controls, 391 T1Y1). HbA1c was significantly lower in the T1Y1 group at 6 (6.7% vs. 7.1%, P < 0.001), 12 (7.3% vs. 7.8%, P < 0.001) and 18 (7.6% vs. 7.9%, P = 0.01) months, but not 24 (7.8% vs. 8%, P = 0.14) months after diagnosis. This effect was not observed in patients with lower SES. CONCLUSION: Additional structured education and support in the year after diagnosis can improve short-term outcomes in children with T1D, but this effect may not persist after discontinuing intensive coaching. Families of lower SES did not benefit from this approach.

Newborn Screening in the US May Miss Mild Persistent Hypothyroidism.

OBJECTIVE: To determine if newborn screening (NBS) programs for congenital hypothyroidism in the US use thyroid-stimulating hormone (TSH) cutoffs that are age adjusted to account for the physiologic 4-fold reduction in TSH concentrations over the first few days of life. STUDY DESIGN: All NBS programs in the US were contacted and asked to provide information on their NBS protocols, TSH cutoffs, and whether these cutoffs were age adjusted. RESULTS: Of 51 NBS programs, 28 request a repeat specimen if the initial eluted serum TSH concentration is mildly increased (between the cutoff and a median upper limit of 50 mU/L), whereas 14 programs perform a routine second screen in all infants. Although these specimens are typically collected between 1 week and 1 month of life, 16 of the 28 programs with a discretionary second test and 8 of 14 programs with a routine second test do not have age-adjusted TSH cutoffs after the first 48 hours of life. CONCLUSIONS: There is variation in NBS practices for screening for congenital hypothyroidism across the US, and many programs do not adjust the TSH cutoff beyond the first 2 days of life. Samples are processed when received from older infants, often to retest borderline initial results. This approach will miss congenital hypothyroidism in infants with persistent mild TSH elevations. We recommend that all NBS programs provide age-adjusted TSH cutoffs, and suggest developing a standard approach to screening for congenital hypothyroidism in the US.