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.

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.

Glargine co-administration with intravenous insulin in pediatric diabetic ketoacidosis is safe and facilitates transition to a subcutaneous regimen.

BACKGROUND: Diabetes ketoacidosis (DKA) is a common presentation and complication of type 1 diabetes (T1D). While intravenous insulin is typically used to treat acute metabolic abnormalities, the transition from intravenous to subcutaneous treatment can present a challenge. We hypothesize that co-administration of glargine, a subcutaneous long-acting insulin analog, during insulin infusion may facilitate a flexible and safe transition from intravenous to subcutaneous therapy. OBJECTIVE: To determine if the practice of administering subcutaneous glargine during intravenous insulin is associated with an increased risk of hypoglycemia, hypokalemia, or other complications in children with DKA. METHODS: Retrospective chart review of patients aged 2 to 21 years, presenting to our center with DKA between April 2012 and June 2014. Patients were divided into two groups: those co-administered subcutaneous glargine with intravenous insulin for over 4 hours (G+); and patients with less than 2 hours of overlap (G-). RESULTS: We reviewed 149 DKA admissions (55 G+, 94 G-) from 129 unique patients. There was a similar incidence of hypoglycemia between groups (25% G+ vs 20% G-, P = 0.46). Hypokalemia (<3.5 mmol/L) occurred more frequently in the G+ group (OR = 3.4, 95% CI 1.7-7.0, P = 0.001). Cerebral edema occurred in 2/55 (3.6%) of the G- group and none of the G+ subjects. CONCLUSION: Co-administration of glargine early in the course of DKA treatment is well tolerated and convenient for discharge planning; however, this approach is associated with an increased risk of hypokalemia.

Fear of hypoglycemia in parents of children with type 1 diabetes.

AIM: The aim of this study is to determine if parental hypoglycaemia fear is associated with worse glycaemic control and increased resource utilisation and to identify risk factors for increased hypoglycaemia fear. METHODS: Parents of children with diabetes completed a modified Hypoglycaemia Fear Survey. Demographic data, phone contacts and mean glycosylated haemoglobin A1c (HbA1c) were also recorded over a 1 year study period. RESULTS: A total of 106 parents participated. Mean patient age was 11.1 years, and duration of diabetes was 4.8 years. Fifty-two per cent were male, and 48% were on insulin pump therapy. Fear of hypoglycaemia was highest among parents of 6- to 11-year-olds. Parents of children with HbA1c less than 7.5% had less hypoglycaemia fear. Previous seizures and increased frequency of phone calls to the diabetes team were not associated with increased fear. CONCLUSION: Fear of hypoglycaemia is associated with worse glycaemic control. It is highest among parents of 6- to 11-year-olds but is not affected by previous severe hypoglycaemia or associated with increased contact with the diabetes team.

T-piece gas flow palpation as a clinical indicator of endotracheal intubation in neonates.

We aimed to determine if providers could detect simulated spontaneous respirations of an intubated neonate by palpating gas flow changes at the positive end expiratory pressure valve of a T-piece resuscitation device in an in vitro setting. We also aimed to demonstrate whether the sensitivity of this methodology was related to the exhaled tidal volumes and/or the gas flow settings on the resuscitation device. A T-piece resuscitator (Neopuff®) circuit was connected to a neonatal silicon test lung. Expiratory tidal volumes of 5, 10 and 15 ml were provided via the test lung, with the Neopuff® set at gas flow rates of 5, 10 and 15 L/min. Physician volunteers were asked to identify whether they could detect expiratory gas from the test lung at the circuit T-piece with the volar surface of their wrist, at different tidal volumes and gas flows. Ten doctors detected 315 of 450 expirations; 95, 73 and 42 % of tidal volumes of 15, 10 and 5 ml, respectively, were detected with an overall positive predictive value of 98.7 %. Detection of exhalations was similar at different gas flow rates for each tidal volume. No exhalations were detected at zero gas flow. We concluded that T-piece gas flow palpation may be a useful and previously unreported clinical sign, which may help to reassure clinicians that they have successfully intubated the trachea. As with any clinical sign, it should not be considered in isolation but within the context of the clinical picture.

Perfusion index in the very preterm infant.

AIM: Perfusion Index (PI) is a quantifiable measurement of peripheral perfusion and may be a useful adjunct to the assessment of circulatory status in the newborn. (i) To assess reproducibility of PI and (ii) To determine whether there is a difference between simultaneously obtained limb measurements of PI in newborns <32 weeks GA in the transitional period. METHODS: Perfusion Index was measured in newborns <32 weeks during the first 48 h of life. To examine reproducibility, the pulse oximetry probe was replaced on the same limb consecutively by the same operator. Upper and lower limbs were then simultaneously evaluated over a 5-min period. Heart rate, blood pressure, birth weight, ventilation requirement, inotrope use, lactate, PCO2 and CRIB-II score were also recorded. RESULTS: Thirty infants were assessed. Intraclass correlation coefficient for reproducibility in the same limb was high (r value = 0.982 p < 0.001). Measurements obtained in the right upper limb were consistently higher than either lower limb. The median (IQR) PI for the entire cohort was 0.70 (0.29-1.35). No correlation existed between gestational age, birth weight, CRIB scores, systolic and diastolic blood pressure, mean blood pressure and median PI values. CONCLUSION: Perfusion Index measurement is reproducible, and values are highest in the right upper limb. Wide differences between right upper and lower limb readings are most likely related to transitional circulatory changes.

Measuring growth hormone and insulin-like growth factor-I in infants: what is normal?

The role of growth hormone (GH) and insulinlike growth factor-I (IGF-I) change through early childhood. Whereas poor growth is a later presenting feature, infants with isolated GH deficiency have a normal birth weight and length, and often present with hypoglycemia. IGF-I plays an important role antenatally and post-natally in somatic and brain growth. In order to evaluate the GH/IGF-I axis in infancy, an understanding of the normal physiology is required. Measurements of GH and IGF-I in this population should be interpreted in the context of the assays used, as well as their limitations. In this review, we summarize our current understanding of normal GH and IGF-I secretion in children under 18 months of age, and describe variations in the reported assay-specific measurements.

A disappearing neonatal skin lesion.

A preterm baby girl was noted at birth to have a firm, raised, non-tender skin lesion located over her right hip. She developed three similar smaller lesions on her ear, buttock and right knee. All lesions had resolved by 2 months of age.

The Neopuff's PEEP valve is flow sensitive.

AIM: The current recommendation in setting up the Neopuff is to use a gas flow of 5-15 L/min. We investigated if the sensitivity of the positive end expiratory pressure (PEEP) valve varies at different flow rates within this range. METHODS: Five Neopuffs were set up to provide a PEEP of 5 cm H(2) O. The number of clockwise revolutions to complete occlusion of the PEEP valve and the mean and range of pressures at each quarter clockwise revolution were recorded at gas flow rates between 5 and 15 L/min. RESULTS: At 5, 10 and 15 L/min, 0.5, 1.7 and 3.4 full clockwise rotations were required to completely occlude the PEEP valve, and pressures rose from 5 to 11.4, 18.4 and 21.5 cm H(2) O, respectively. At a flow rate of 5 L/min, half a rotation of the PEEP dial resulted in a rise in PEEP from 5 to 11.4cm H(2) O. At 10 L/min, half a rotation resulted in a rise from 5 to 7.7cm H(2) O, and at 15 L/min PEEP rose from 5 to 6.8cm H(2) O. CONCLUSION: Users of the Neopuff should be aware that the PEEP valve is more sensitive at lower flow rates and that half a rotation of the dial at 5 L/min gas flow can more than double the PEEP.

Provocative growth hormone testing in children: how did we get here and where do we go now?

OBJECTIVES: Provocative growth hormone (GH) tests are widely used for diagnosing pediatric GH deficiency (GHD). A thorough understanding of the evidence behind commonly used interpretations and the limitations of these tests is important for improving clinical practice. CONTENT: To place current practice into a historical context, the supporting evidence behind the use of provocative GH tests is presented. By reviewing GH measurement techniques and examining the early data supporting the most common tests and later studies that compared provocative agents to establish reference ranges, the low sensitivity and specificity of these tests become readily apparent. Studies that assess the effects of patient factors, such as obesity and sex steroids, on GH testing further bring the appropriateness of commonly used cutoffs for diagnosing GHD into question. SUMMARY AND OUTLOOK: Despite the widely recognized poor performance of provocative GH tests in distinguishing GH sufficiency from deficiency, limited progress has been made in improving them. New diagnostic modalities are needed, but until they become available, clinicians can improve the clinical application of provocative GH tests by taking into account the multiple factors that influence their results.

Infants Diagnosed with Athyreosis on Scintigraphy May Have a Gland Present on Ultrasound and Have Transient Congenital Hypothyroidism.

Scintigraphy using technetium-99m (99mTc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of 99mTc uptake. AIMS: We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using 99mTc and to describe the clinical characteristics and natural history in these infants. METHODS: The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. RESULTS: Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. CONCLUSION: Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.

Growth Hormone Stimulation Testing Patterns Contribute to Sex Differences in Pediatric Growth Hormone Treatment.

INTRODUCTION: Males are twice as likely as females to receive pediatric growth hormone (GH) treatment in the USA, despite similar distributions of height z (HtZ)-scores in both sexes. Male predominance in evaluation and subspecialty referral for short stature contributes to this observation. This study investigates whether sex differences in GH stimulation testing and subsequent GH prescription further contribute to male predominance in GH treatment. METHODS: Retrospective chart review was conducted of all individuals, aged 2-16 years, evaluated for short stature or poor growth at a single large tertiary referral center between 2012 and 2019. Multiple logistic regression models were constructed to analyze sex differences. RESULTS: Of 10,125 children referred for evaluation, a smaller proportion were female (35%). More males (13.1%) than females (10.6%) underwent GH stimulation testing (p < 0.001) and did so at heights closer to average (median HtZ-score -2.2 [interquartile range, IQR -2.6, -1.8] vs. -2.5 [IQR -3.0, -2.0], respectively; p < 0.001). The proportion of GH prescriptions by sex was similar by stimulated peak GH level. Predictor variables in regression modeling differed by sex: commercial insurance predicted GH stimulation testing and GH prescription for males only, whereas lower HtZ-score predicted GH prescription for females only. CONCLUSIONS: Sex differences in rates of GH stimulation testing but not subsequent GH prescription based on response to GH stimulation testing seem to contribute to male predominance in pediatric GH treatment. That HtZ-score predicted GH prescription in females but not males raises questions about the extent to which sex bias - from children, parents, and/or physicians - as opposed to objective growth data, influence medical decision-making in the evaluation and treatment of short stature.

Recombinant human parathyroid hormone (1-84) is effective in CASR-associated hypoparathyroidism.

INTRODUCTION: Gain-of-function mutations in the CASR gene cause Autosomal Dominant Hypocalcemia Type 1 (ADH1), the most common genetic cause of isolated hypoparathyroidism. Subjects have increased calcium sensitivity in the renal tubule, leading to increased urinary calcium excretion, nephrocalcinosis and nephrolithiasis when compared with other causes of hypoparathyroidism. The traditional approach to treatment includes activated vitamin D but this further increases urinary calcium excretion. METHODS: In this case series, we describe the use of recombinant human parathyroid hormone (rhPTH)1-84 to treat subjects with ADH1, with improved control of serum and urinary calcium levels. RESULTS: We describe two children and one adult with ADH1 due to heterozygous CASR mutations who were treated with rhPTH(1-84). Case 1 was a 9.4-year-old female whose 24-h urinary calcium decreased from 7.5 to 3.9 mg/kg at 1 year. Calcitriol and calcium supplementation were discontinued after titration of rhPTH(1-84). Case 2 was a 9.5-year-old male whose 24-h urinary calcium decreased from 11.7 to 1.7 mg/kg at 1 year, and calcitriol was also discontinued. Case 3 was a 24-year-old female whose treatment was switched from multi-dose teriparatide to daily rhPTH(1-84). All three subjects achieved or maintained target serum levels of calcium and normal or improved urinary calcium levels with daily rhPTH(1-84) monotherapy. CONCLUSIONS: We have described three subjects with ADH1 who were treated effectively with rhPTH(1-84). In all cases, hypercalciuria improved by comparison to treatment with conventional therapy consisting of calcium supplementation and calcitriol.

Leg length and sitting height reference data and charts for children in the United States.

Population-specific reference data are required to interpret growth measurements in children. Sitting height and leg length (standing height minus sitting height) measurements are indicators of proportionality and can be used to evaluate children with disordered growth. NHANES III recorded sitting height and standing height measurements in a strategic random sample of the United States population from 1988 to 1994, and we have previously published reference charts for sitting height to standing height ratio in this population. In this study, we have developed separate sitting height and leg length reference charts for Non-Hispanic Black, Non-Hispanic White, and Mexican-American children in the United States. In addition, we provide mean (SD) and LMS data to support the use of these reference charts in clinical care.

CYP3A4 Induction by Rifampin: An Alternative Pathway for Vitamin D Inactivation in Patients With CYP24A1 Mutations.

Context: The P450 enzyme CYP24A1 is the principal inactivator of vitamin D metabolites. Biallelic loss-of-function mutations in CYP24A1 are associated with elevated serum levels of 1,25-dihydroxyvitamin D3 with consequent hypercalcemia and hypercalciuria and represent the most common form of idiopathic infantile hypercalcemia (IIH). Current management strategies for this condition include a low-calcium diet, reduced dietary vitamin D intake, and limited sunlight exposure. CYP3A4 is a P450 enzyme that inactivates many drugs and xenobiotics and may represent an alternative pathway for inactivation of vitamin D metabolites. Objective: Our goal was to determine if rifampin, a potent inducer of CYP3A4, can normalize mineral metabolism in patients with IIH due to mutations in CYP24A1. Methods: We treated two patients with IIH with daily rifampin (10 mg/kg/d, up to a maximum of 600 mg). Serum calcium, phosphorus, parathyroid hormone (PTH), liver, and adrenal function and vitamin D metabolites, as well as urinary calcium excretion, were monitored during treatment of up to 13 months. Results: Prior to treatment, both patients had hypercalcemia, hypercalciuria, and nephrocalcinosis with elevated serum 1,25-dihydroxyvitamin D3 and suppressed serum PTH. Daily treatment with rifampin was well tolerated and led to normalization or improvement in all clinical and biochemical parameters. Conclusion: These observations suggest that rifampin-induced overexpression of CYP3A4 provides an alternative pathway for inactivation of vitamin D metabolites in patients who lack CYP24A1 function.

Late Presentation of Fulminant Necrotizing Enterocolitis in a Child with Hyperinsulinism on Octreotide Therapy.

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in infants and children. In cases of diazoxide-unresponsive HI, alternative medical and surgical approaches may be required to reduce the risk of hypoglycemia. Octreotide, a somatostatin analog, often has a role in the management of these children, but a dose-dependent reduction in splanchnic blood flow is a recognized complication. Necrotizing enterocolitis (NEC) has been reported within the first few weeks of initiating predominantly high doses of octreotide. We describe the case of an infant with Beckwith-Wiedemann syndrome and diazoxide-unresponsive HI, who had persistent hypoglycemia after two pancreatectomy surgeries. She developed NEC 2 months after beginning octreotide therapy at a relatively low dose of 8 µg/kg/day. This complication has occurred later, and at a lower dose, than has previously been described. We review the case and identify the known and suspected multifactorial risk factors for NEC that may contribute to the development of this complication in patients with HI.

Ketotic hypercalcemia: a case series and description of a novel entity.

CONTEXT: The ketogenic diet is increasingly used in refractory epilepsy and is associated with clinically significant effects on bone and mineral metabolism. Although hypercalciuria and loss of bone mineral density are common in patients on the ketogenic diet, hypercalcemia has not previously been described. OBJECTIVE: The aim of the study was to describe three children who developed hypercalcemia while on the ketogenic diet. DESIGN: A retrospective chart review of three children on the ketogenic with severe hypercalcemia was conducted. RESULTS: We describe three children on the ketogenic diet for refractory seizures who presented with hypercalcemia. Case 1 was a 5.5-year-old male with an undiagnosed, rapidly progressive seizure disorder associated with developmental regression. Case 2 was a 2.5-year-old male with a chromosomal deletion of 2q24.3, and case 3 was a 4.6-year-old male with cerebral cortex dysplasia. Patients had been on a ketogenic diet for 6 to 12 months before presentation. Daily intake of calcium and vitamin D was not excessive, and all three patients were not acidotic because they were taking supplemental bicarbonate. Each child had elevated serum levels of calcium and normal serum phosphate levels, moderately elevated urinary calcium excretion, and low levels of serum alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D. All patients responded to calcitonin. CONCLUSIONS: Hypercalcemia is an uncommon complication of the ketogenic diet, and these children may represent the severe end of a clinical spectrum of disordered mineral metabolism. The mechanism for hypercalcemia is unknown but is consistent with excess bone resorption and impaired calcium excretion.

Smartphone technology enhances newborn intubation knowledge and performance amongst paediatric trainees.

OBJECTIVE: Smartphones are widely used by physicians, but their effectiveness in improving teaching of clinical skills is not known. The aim of this study was to determine if pre procedural use of a smartphone neonatal intubation instructional application (NeoTube) improves trainee knowledge and enhances procedural skills performance in newborn intubation. DESIGN: Neonatal Resuscitation Program certified trainees in paediatrics and neonatology completed a knowledge based questionnaire on neonatal intubation, and were recorded intubating a term newborn manikin model. They then used the NeoTube iPhone application for 15 min, before completing the questionnaire and intubation again. Video recordings were later reviewed by two independent assessors, blinded to whether it was pre or post NeoTube use. RESULTS: 20 paediatric trainees (12 fellows and 8 residents) participated in this study. Comparing pre and post-viewing of the application, Questionnaire Scores (median (range)) increased from 18.5 (8-28) to 31 (24-35) (P<0.001), with calculation scores increasing from 6 (0-11) to 11 (6-12) (P<0.001), Skill Scores increased from 11 (9-15) to 12.5 (9-16) (P=0.016), and the duration of intubation attempt decreased from 39 to 31 s (P=0.044) following utilisation of the application. There was a significant positive correlation with duration of specialist training for procedure performance post viewing, but not pre viewing of the application. CONCLUSIONS: Bedside use of smartphones can enhance both knowledge of newborn intubation and improves procedural performance, including reducing the time to successfully intubate. Smartphones may have a useful role in bringing procedural skills training closer to the bedside.