Altered lipid metabolism and the development of metabolic-associated fatty liver disease.

PURPOSE OF REVIEW: An increasing amount of research has underscored the significant role of lipoproteins in the pathogenesis of metabolic-associated fatty liver disease (MAFLD). This comprehensive review examines the intricate relationship between lipoprotein abnormalities and the development of MAFLD. RECENT FINDINGS: Atherogenic dyslipidemia seen in insulin resistance states play a significant role in initiating and exacerbating hepatic lipid accumulation. There are also specific genetic factors ( PNPLA3 , TM6SF2 , MBOAT7 , HSD17B13 , GCKR- P446L) and transcription factors (SREBP-2, FXR, and LXR9) that increase susceptibility to both lipoprotein disorders and MAFLD. Most monogenic primary lipid disorders do not cause hepatic steatosis unless accompanied by metabolic stress. Hepatic steatosis occurs in the presence of secondary systemic metabolic stress in conjunction with predisposing environmental factors that lead to insulin resistance. Identifying specific aberrant lipoprotein metabolic factors promoting hepatic fat accumulation and subsequently exacerbating steatohepatitis will shed light on potential targets for therapeutic interventions. SUMMARY: The clinical implications of interconnection between genetic factors and an insulin resistant environment that predisposes MAFLD is many fold. Potential therapeutic strategies in preventing or mitigating MAFLD progression include lifestyle modifications, pharmacological interventions, and emerging therapies targeting aberrant lipoprotein metabolism.

Children and Adolescents With Hybrid Diabetes: A Management Conundrum.

OBJECTIVE: Hybrid diabetes (HD); ie, insulin resistance with positive diabetes-associated autoantibodies (DAAs) is increasing in children. We aimed to compare the characteristics of children with HD with those with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) at diagnosis and after 2 years. METHODS: A retrospective review of patients aged 0 to 19 years, with C-peptide and 4 DAA measurements available, who were diangosed with new-onset diabetes from 2016 to 2020 were included in the analysis. RESULTS: Overall, 102 subjects were included, 32 with T1DM, 21 with HD, and 49 with T2DM. Amongst the groups (T1DM vs HD vs T2DM), there were differences in the proportion of non-Hispanic Whites (81.3% vs 47.6% vs 16.4%, P < .001), frequency of family history of T2DM (37.5% vs 100% vs 85.4%, P < .001), acanthosis nigricans (0% vs 42.9% vs 93.9%, P <.001), median body mass index z-score (-0.55 vs 1.8 vs 2.4, P <.001), and median C-peptide (0.4 ng/mL vs 0.9 ng/mL vs 2.4 ng/mL, P <.001). At 2 years, differences were seen in median body mass index z-scores (0.3 vs 1.9 vs 2.3, P <.001), mean HDL-cholesterol (58.0 mg/dL vs 48.2 mg/dL vs 39.5 mg/dL, P <.001), and the use of basal insulin (100% vs 100% vs 74.4%, P <.001). CONCLUSION: Phenotypic and metabolic differences were seen in youth with T1DM, HD, and T2DM at diagnosis and follow-up. At 2 years, all subjects with HD remained insulin dependent whereas some with T2DM were not, indicating the need for targeted interventions to address the etiopathogenesis.

Hyponatremia after craniotomy in children: a single-institution review.

PURPOSE: Hyponatremia after craniotomy can be associated with increased morbidity. However, the incidence of and factors associated with post-craniotomy hyponatremia in children are not known. METHODS: We performed a retrospective cohort study of patients aged 0-21 years who underwent craniotomy in 2017-2019 at a single center to determine the incidence of and to identify risk factors for hyponatremia after craniotomy. Indications for craniotomy included tumors (excluding craniopharyngioma), epilepsy, intracranial infection, trauma, craniofacial, suboccipital decompression for the treatment of Chiari malformation, and cerebrovascular disease. Hyponatremia was defined as a serum sodium level ≤ 135 mEq/L any time during the postoperative hospital stay. Statistical significance was defined a priori at p < 0.05. RESULTS: Postoperative hyponatremia occurred in 61 (25%) of 240 children. On univariate analysis, hyponatremia was associated with younger age (8.5 vs 6.3 years, p = 0.01), use of preoperative anti-epileptic drugs (p = 0.02), need for blood transfusion (p = 0.02), government/private insurance (p = 0.04), and pre-existing hydrocephalus, defined as the requirement for permanent cerebrospinal fluid (CSF) diversion (p = 0.04). On multivariate analysis, only hydrocephalus (OR 2.95, 95% CI 1.03-8.40) remained statistically significant. Hyponatremia most occurred on the first postoperative day, with normonatremia achieved in a median of 14 (IQR 9.8-24.3) h. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3 days, p < 0.01). CONCLUSION: Hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus as an independent risk factor for hyponatremia after craniotomy.

Childhood Hypertriglyceridemia: Is It Time for a New Approach?

PURPOSE OF REVIEW: Hypertriglyceridemia (HTG) is widely prevalent in youth. There is an unmet need for effective medications in the management of HTG in youth. The purpose of this review is to summarize the approach to HTG in acute and chronic settings, and highlight emerging therapies targeted at specific genes, proteins, and enzymes to selectively alter triglyceride (TG) metabolism. RECENT FINDINGS: Genetic and lifestyle factors play a significant role in the pathophysiology of HTG. Severe elevation of TG poses a risk of acute pancreatitis, while mild-to-moderate HTG increases the risk for premature atherosclerotic cardiovascular disease (ASCVD) and, increasingly, has been linked with non-alcoholic fatty liver disease. Although a variety of therapeutic agents are in development, strict adherence to a heart healthy lifestyle, including dietary changes, remain the cornerstone of management for youth with HTG. In addition to lifestyle changes, pharmacological interventions, including fibrates, omega 3 fatty acids, and statins may be considered for management of moderate-to-severe HTG. In view of its association with premature cardiovascular disease (CVD), non-high-density-lipoprotein-C (non-HDL-C) is an important target for therapy in children with moderate HTG. Management of HTG is dependent on its etiology, concomitant symptoms, and degree of TG elevation. The last two decades have seen remarkable changes in drug development, specifically those that act through the lipoprotein lipase complex, including new targeted treatments such as inhibitors of apolipoprotein C3 and angiopoietin-like protein 3.

Pediatric Endocrinology: Perspectives of Pediatric Endocrinologists Regarding Career Choice and Recruitment of Trainees.

OBJECTIVES: To examine main factors that influence the decision to choose pediatric endocrinology as a career among pediatric endocrinologists and assess their work satisfaction or stress level and suggested strategies to increase interest in subspecialty training in pediatric endocrinology. METHODS: A workforce survey was distributed among 1470 members of the Pediatric Endocrine Society. RESULTS: The response rate was 37.4%, with 550 members responding. The most common reasons for the respondents choosing pediatric endocrinology were intellectual stimulation (79%), exposure to endocrinology during residency (57%) or medical school (43%), and ability to establish relationships with patients with chronic disorders (54%). Of the respondents, 97% considered intellectual stimulation as the most favorable aspect of the specialty, and 84% considered financial compensation as the most unfavorable aspect of pediatric endocrinology. Majority (77%) were satisfied or very satisfied with their work environment. The mean work-related stress score (0 [none] to 10 [worst]) was 5.7, standard deviation was 2.1, and median was 6 (Q1, Q3: 4, 7). Increased financial compensation for the services and loan payment or forgiveness option were the top strategies suggested to enhance interest among residents for training in the subspecialty. One third (37%) felt that reducing the duration of the fellowship to 2 years would increase interest in training in pediatric endocrinology. CONCLUSION: The pediatric endocrinologists reported overall excellent career satisfaction, indicating the potential to attract high-quality doctors to the specialty. Improving reimbursement and loan forgiveness were the top strategies suggested for increasing interest in subspecialty training in pediatric endocrinology.

Incidental Pituitary Cysts in Children: Does Growth Hormone Treatment Affect Cyst Size?

OBJECTIVE: To evaluate the response of incidentally discovered pituitary cysts to growth hormone (GH) treatment. METHODS: A retrospective chart review was performed of children with pituitary cysts on magnetic resonance imaging (MRI) over a 5-year period. Records and images were reviewed, and the results were analyzed using descriptive statistics. Children with pituitary cysts who received GH treatment were compared with those without. RESULTS: We identified 109 children with pituitary cysts, 24 were treated with GH therapy. The average age was 8.5 ± 5.1 years. Children whose initial MRI scan was to evaluate growth hormone deficiency were more commonly male and non-Hispanic White compared with those with scans for other indications (male, 18 of 24 vs 35 of 85, P = .003; White, 23 of 24 vs 58 of 85, P = .004). Among patients who received GH treatment, 12 had follow-up MRI. Six had no change in cyst size and 6 had a decrease in cyst size. We observed no difference in the likelihood of cyst growth between those who received GH and those who did not (0 of 12 cysts with GH vs 1 of 15 cysts without GH showed growth at follow-up). No patient had neurologic deficits attributable to the pituitary cyst at any time. CONCLUSION: In a single-institution, retrospective study, we find no evidence of growth in pituitary cysts in response to GH therapy.

Chylomicronemia from GPIHBP1 autoantibodies.

Some cases of chylomicronemia are caused by autoantibodies against glycosylphosphatidylinositol-anchored HDL binding protein 1 (GPIHBP1), an endothelial cell protein that shuttles LPL to the capillary lumen. GPIHBP1 autoantibodies prevent binding and transport of LPL by GPIHBP1, thereby disrupting the lipolytic processing of triglyceride-rich lipoproteins. Here, we review the "GPIHBP1 autoantibody syndrome" and summarize clinical and laboratory findings in 22 patients. All patients had GPIHBP1 autoantibodies and chylomicronemia, but we did not find a correlation between triglyceride levels and autoantibody levels. Many of the patients had a history of pancreatitis, and most had clinical and/or serological evidence of autoimmune disease. IgA autoantibodies were present in all patients, and IgG4 autoantibodies were present in 19 of 22 patients. Patients with GPIHBP1 autoantibodies had low plasma LPL levels, consistent with impaired delivery of LPL into capillaries. Plasma levels of GPIHBP1, measured with a monoclonal antibody-based ELISA, were very low in 17 patients, reflecting the inability of the ELISA to detect GPIHBP1 in the presence of autoantibodies (immunoassay interference). However, GPIHBP1 levels were very high in five patients, indicating little capacity of their autoantibodies to interfere with the ELISA. Recently, several GPIHBP1 autoantibody syndrome patients were treated successfully with rituximab, resulting in the disappearance of GPIHBP1 autoantibodies and normalization of both plasma triglyceride and LPL levels. The GPIHBP1 autoantibody syndrome should be considered in any patient with newly acquired and unexplained chylomicronemia.

Dyslipidemia in Pediatric Type 2 Diabetes Mellitus.

PURPOSE OF REVIEW: Cardiovascular (CV) disease is a major cause of mortality in type 2 diabetes mellitus (T2D). Dyslipidemia is prevalent in children with T2D and is a known risk factor for CVD. In this review, we critically examine the epidemiology, pathophysiology, and recommendations for dyslipidemia management in pediatric T2D. RECENT FINDINGS: Dyslipidemia is multifactorial and related to poor glycemic control, insulin resistance, inflammation, and genetic susceptibility. Current guidelines recommend lipid screening after achieving glycemic control and annually thereafter. The desired lipid goals are low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) > 35 mg/dL, and triglycerides (TG) < 150 mg/dL. If LDL-C remains > 130 mg/dL after 6 months, statins are recommended with a treatment goal of < 100 mg/dL. If fasting TG are > 400 mg/dL or non-fasting TG are > 1000 mg/dL, fibrates are recommended. Although abnormal levels of atherogenic TG-rich lipoproteins, apolipoprotein B, and non-HDL-C are commonly present in pediatric T2D, their measurement is not currently considered in risk assessment or management.

Temporal trends in incidence of pediatric type 1 diabetes in Alabama: 2000-2017.

OBJECTIVE: The incidence of type 1 diabetes has increased in the United States and worldwide. We hypothesized that trends in the annual incidence rates of childhood-onset type 1 diabetes in the state of Alabama would be different by race and sex. METHODS: We performed a retrospective observational cohort study, analyzing children with type 1 diabetes (n = 3770) managed at the Children's Hospital of Alabama between 2000 and 2017. We compared crude incidence rates using negative binomial regression models and analyzed differences in annual trends of age-adjusted incidence by race and sex using joinpoint regression. RESULTS: The crude type 1 diabetes incidence rate was estimated at 16.7 per 100 000 children <19 years of age in Alabama. Between 2000 and 2007, there was an increase in age-adjusted incidence of type 1 diabetes with an annual percent change (APC) of 10% from 2000 to 2007 and a 1.7% APC decrease from 2007 to 2017. The age-adjusted incidence for Whites and Blacks increased with an average annual percentage change (AAPC) of 4.4% and 2.8%, respectively. A nearly 11% increasing trend in age-adjusted incidence was observed for both races, though the increase plateaued in 2006 for Whites and 2010 for Blacks. CONCLUSIONS: Following significantly increasing annual trends for both races, the age-adjusted rate remained statistically stable for Whites and decreased significantly for Blacks. Longer-sustained trend increases for Blacks resulted in type 1 diabetes incidence tripling compared to the doubling of the rate for Whites.

Clinical Characteristics and Sequelae of Severe Hypertriglyceridemia in Pediatrics.

OBJECTIVE: Severe hypertriglyceridemia (HTG) (i.e., plasma triglycerides [TGs] >1,000 mg/dL) in children is a rare but pernicious and understudied condition. Our objective was to evaluate the etiology, characteristics, and sequelae of severe pediatric HTG. METHODS: This was a retrospective electronic medical record review of pediatric patients with severe HTG at a tertiary referral Children's hospital over a 17-year period. RESULTS: There were a total of 124 patients with severe HTG. The etiology varied: hemato-oncologic (n = 48), diabetes and insulin resistance-related (n = 46), total parenteral nutrition (TPN)-related (n = 6), renal (n = 12), and miscellaneous (n = 12). There was considerable variability in the number of days for the plasma TGs to decrease to <1,000 mg/dL (147.7 ± 567.3 days) and to further decrease to <500 mg/dL (136.84 ± 230.9 days). Patients with diabetes required the longest time to improve their plasma TGs (165.8 ± 305.7 days) compared to other groups. There were 11 cases of pancreatitis, comorbid with diabetes (n = 5), hemato-oncologic conditions (n = 3), and TPN (n = 3). Sixty-seven patients (54%) had persistent HTG. CONCLUSION: Severe HTG in pediatrics is commonly due to secondary causes. Patients with diabetes tend to have a longer course of dyslipidemia. A substantial number of patients had persistent dyslipidemia, indicating underlying genetic susceptibility to HTG that is phenotypically expressed consequent to a secondary metabolic insult. ABBREVIATIONS: DKA = diabetic ketoacidosis; EMR = electronic medical record; GSD = glycogen storage disorder; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; HTG = hypertriglyceridemia; ICD-9 = International Classification of Diseases-Ninth Revision; IV = intravenous; LCHAD = long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency; LPL = lipoprotein lipase; NPO = nothing by mouth; PCOS = polycystic ovary syndrome; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; TG = triglyceride; TPN = total parenteral nutrition; VLDL = very-low-density lipoprotein.

Effect of Prenatal versus Postnatal Vitamin D Deficiency on Pulmonary Structure and Function in Mice.

Epidemiologic studies have linked gestational vitamin D deficiency to respiratory diseases, although mechanisms have not been defined. We hypothesized that antenatal vitamin D deficiency would impair airway development and alveolarization in a mouse model. We studied the effect of antenatal vitamin D deficiency by inducing it in pregnant mice and then compared lung development and function in their offspring to littermate controls. Postnatal vitamin D deficiency and sufficiency models from each group were also studied. We developed a novel tracheal ultrasound imaging technique to measure tracheal diameter in vivo. Histological analysis estimated tracheal cartilage total area and thickness. We found that vitamin D-deficient pups had reduced tracheal diameter with decreased tracheal cartilage minimal width. Vitamin D deficiency increased airway resistance and reduced lung compliance, and led to alveolar simplification. Postnatal vitamin D supplementation improved lung function and radial alveolar count, a parameter of alveolar development, but did not correct tracheal narrowing. We conclude that antenatal vitamin D deficiency impairs airway and alveolar development and limits lung function. Reduced tracheal diameter, cartilage irregularity, and alveolar simplification in vitamin D-deficient mice may contribute to increased airways resistance and diminished lung compliance. Vitamin D supplementation after birth improved lung function and, potentially, alveolar simplification, but did not improve defective tracheal structure. This mouse model offers insight into the mechanisms of vitamin D deficiency-associated lung disease and provides an in vivo model for investigating preclinical preventive and therapeutic strategies.

Approach to Hypertriglyceridemia in the Pediatric Population.

Hypertriglyceridemia is increasingly identified in children and adolescents, owing to improved screening and higher prevalence of childhood obesity. Hypertriglyceridemia can result from either increased triglyceride (TG) production or reduced TG clearance. The etiologic origin can be primary (genetic) or secondary, but it is often multifactorial. Management is challenging because of the interplay of genetic and secondary causes and lack of evidence-based guidelines. Lifestyle changes and dietary interventions are most important, especially in hypertriglyceridemia associated with obesity. Dietary restriction of fat remains the mainstay of management in primary hypertriglyceridemia. When fasting TG concentration is increased above 500 mg/dL (5.65 mmol/L), fibrates may be used to prevent pancreatitis. Omega-3 fatty acids are often used as an adjunctive therapy. When the fasting TG concentration is less than 500 mg/dL (5.65 mmol/L) and if the non-high-density lipoprotein cholesterol level is above 145 mg/dL (3.76 mmol/L), statin treatment can be considered.

Bone Mineral Content as a Driver of Energy Expenditure in Prepubertal and Early Pubertal Boys.

OBJECTIVE: To examine the associations of bone and bone-secreted factors with measures of energy metabolism in prepubertal and early pubertal boys. STUDY DESIGN: Participants in this cross-sectional, observational study included 37 (69% black, 31% white) boys, aged 7-12 years (Tanner stage

Fibroblast growth factor-21, body composition, and insulin resistance in pre-pubertal and early pubertal males and females.

OBJECTIVE: Accumulating evidence derived primarily from animal models suggests that fibroblast growth factor-21 (FGF-21) may affect the musculoskeletal system via effects on the capacity of tissues to respond to insulin. A proportion of musculoskeletal properties and underpinnings of promoting/preventing insulin resistance are established early in the pubertal transition. Thus, the objective of this study was to test the hypothesis that insulin resistance and/or obesity will promote greater FGF-21 concentration which will be inversely associated with musculoskeletal parameters [lean mass and bone mineral content (BMC)] in pre-/early pubertal children. Given the sexual dimorphic nature of musculoskeletal development of fat mass accrual, differences by obesity status and sex were also investigated. DESIGN: Cross-sectional. PATIENTS: Children ages 7-12 years (n = 69, 38% male, 48% non-Hispanic black, 45% obese). MEASUREMENTS: Fasting FGF-21, glucose and insulin measures were obtained. An estimate of insulin resistance was derived using the homoeostatic model assessment of insulin resistance (HOMA-IR). Body composition (BMC, lean mass and fat mass) was assessed by DXA. Multivariate regression analysis was used to evaluate the influence of FGF-21 on BMC, lean mass and HOMA-IR as dependent variables. Obesity status was established based on BMI z-score. RESULTS: FGF-21 concentrations did not differ by obesity status or by sex. There was an inverse association between FGF-21 and BMC among nonobese individuals (P = 0·01) and an inverse association between FGF-21 and lean mass among females (P = 0·02), which were both independent of fat mass. FGF-21 was inversely associated with HOMA-IR in males, but not females (P = 0·04). CONCLUSIONS: The existence of relationships of FGF-21 with musculoskeletal parameters and insulin resistance raises the possibility of crosstalk between these systems. These findings suggest that circulating FGF-21 may differ in its association with bone, lean mass and insulin resistance depending on sex and weight status.

Diabetes Status and Race are Associated with Cardiovascular Risk Markers in Obese Adolescents.

OBJECTIVE: The objective of this study was to evaluate differences in cardiovascular disease (CVD) risk markers in obese adolescents based on diabetes status and race in order to improve risk-reduction intervention strategies. METHODS: This was a retrospective, cross-sectional study of obese adolescents, age 10 to 21 years, who were evaluated at Children's of Alabama between 2000 and 2012. Subjects were classified by glycated hemoglobin (HbA1c) as having normoglycemia, prediabetes, or type 2 diabetes mellitus (T2DM). RESULTS: There were a total of 491 African American (AA) or Caucasian American (CA) subjects. Body mass index was not different between HbA1c and racial groups. Compared to subjects with normoglycemia or prediabetes, subjects with T2DM had higher levels of total cholesterol (TC) (178.6 ± 43.8 mg/dL vs. 161.5 ± 32.5 mg/dL vs. 162.4 ± 30.6 mg/dL; P<.0001) and low-density-lipoprotein cholesterol (107.4 ± 39.2 mg/dL vs. 97.0 ± 31.0 mg/dL vs. 97.5 ± 26.9 mg/dL; P = .0073). Compared with AA subjects, CA subjects had lower high-density-lipoprotein cholesterol (HDL-C) levels (40.4 ± 10.4 mg/dL vs. 44.3 ± 11.9 mg/dL; P = .0005) and higher non-HDL-C levels (129.6 ± 36.2 mg/dL vs. 122.5 ± 37.5 mg/dL; P = .0490). Of the characteristics studied, HbA1c had the most significant positive association with dyslipidemia and was strongly correlated with both TC (ß, 4.21; P<.0001) and non-HDL-C (ß, 4.3; P<.0001). CONCLUSION: Obese adolescents with T2DM have more abnormal lipoprotein profiles than those with normoglycemia or prediabetes. Obese CA adolescents have more abnormal lipids than obese AA adolescents. HbA1c was the characteristic most highly associated with abnormal lipoprotein profiles in our subjects. Our results show that CVD risk markers in obese adolescents vary by race and HbA1c concentration.

DIABETES AND PREDIABETES ARE SIGNIFICANTLY HIGHER IN MORBIDLY OBESE CHILDREN COMPARED WITH OBESE CHILDREN.

OBJECTIVE: The objective of this study was to examine the prevalence and characteristics of comorbidities in obese and morbidly obese children with a comparison between the 2 sets of children. METHODS: This was a retrospective electronic chart review of obese and morbidly obese children and adolescents as defined by body mass index. We evaluated medical history of comorbid conditions, medication use, and cardiovascular risk markers, including blood pressure, lipid profile, and glycosylated hemoglobin. RESULTS: There were 1,111 subjects (African American = 635; non-Hispanic white = 364; Hispanic = 36; others = 86), of which 274 were obese and 837 were morbidly obese children with a mean age of 12.7 ± 3.37 years. Morbidly obese children had a higher prevalence of prediabetes (19.5% of obese versus 27.3% of morbidly obese; P<.0001) and type 2 diabetes (39.8% of obese versus 52.4% of morbidly obese; P<.0001). Use of medications for treatment of asthma was significantly higher in the morbidly obese group compared with the obese group (21% versus 14%; P = .01). CONCLUSION: Morbidly obese children have a higher prevalence of diabetes, prediabetes, and use of asthma medications compared with obese children.

Rising tide: The global surge of type 2 diabetes in children and adolescents demands action now.

Childhood-onset obesity has emerged as a major public healthcare challenge across the globe, fueled by an obesogenic environment and influenced by both genetic and epigenetic predispositions. This has led to an exponential rise in the incidence of type 2 diabetes mellitus in children and adolescents. The looming wave of diabetes-related complications in early adulthood is anticipated to strain the healthcare budgets in most countries. Unless there is a collective global effort to curb the devastation caused by the situation, the impact is poised to be pro-found. A multifaceted research effort, governmental legislation, and effective social action are crucial in attaining this goal. This article delves into the current epidemiological landscape, explores evidence concerning potential risks and consequences, delves into the pathobiology of childhood obesity, and discusses the latest evidence-based management strategies for diabesity.

Invited Mini Review Metabolic Bone Disease of Prematurity: Overview and Practice Recommendations.

Metabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex-utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum calcium, phosphorus, and alkaline phosphatase to identify infants at risk. If these labs are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of phosphate can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines.

Precocious Puberty and GnRH analogs: Current treatment practices and perspectives amongst US pediatric endocrinologists.

INTRODUCTION: GnRHas are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs & Therapeutics subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the United States. The survey consisted of four main subsections: 1. Description of clinical practice; 2. Self-assessment of knowledge base of pediatric and adult GnRHa formulations; 3. Current practice for treating CPP; and 4. Utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the three-month preparation, and the histrelin implant (Supprelin®) (61.9%, 71.7%, and 34.5%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) and 22.9% and six-month subcutaneous leuprolide (Fensolvi®). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44.4%), but in practice, respondents reported a higher percentage of patients were treated with 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (65.5%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter-acting GnRHas, which are prescribed in greater numbers than newer, longer-acting formulations. There is lack of consensus on the need for CNS imaging in girls presenting with CPP between 6-8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers, while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.