Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia

Pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables.

source: NEJM

Summary

Evolocumab in Pediatric Heterozygous Familial Hypercholesterolemia

[Posted 13/Oct/2020]

AUDIENCE: Pediatric, Cardiology, Internal Medicine

KEY FINDINGS: In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables. (Funded by Amgen; HAUSER-RCT ClinicalTrials.gov number, NCT02392559.)

BACKGROUND: Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin–kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known.

DETAILS: We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was –44.5% in the evolocumab group and –6.2% in the placebo group, for a difference of –38.3 percentage points (P<0.001). The absolute change in the LDL cholesterol level was –77.5 mg per deciliter (–2.0 mmol per liter) in the evolocumab group and –9.0 mg per deciliter (–0.2 mmol per liter) in the placebo group, for a difference of –68.6 mg per deciliter (–1.8 mmol per liter) (P<0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups.

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Copyright © 2020 Massachusetts Medical Society. All rights reserved.

Source: N Engl J Med. Published October 1, 2020. DOI: 10.1056/NEJMoa2019910


Gastrointestinal Hemorrhage: A Manifestation of the TBD

GI bleeding in patients with TBDs is associated with significant morbidity and is associated with vascular ectasias rather than varices.

source: J Pediatr.

Summary

Gastrointestinal Hemorrhage: A Manifestation of the Telomere Biology Disorders

[Posted 22/Sep/2020]

AUDIENCE: Pediatric, Gastroenterology, Genetics, Internal Medicine

KEY FINDINGS: GI bleeding in patients with TBDs is associated with significant morbidity and is associated with vascular ectasias rather than varices.

BACKGROUND: To describe the clinical features, therapeutic interventions, and patient outcomes of GI hemorrhage in individuals with telomere biology disorders which include dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome and Coats plus.

DETAILS: Clinical Care Consortium for Telomere Associated Ailments members were invited to contribute data on individuals with TBDs at their institutions who experienced GI bleeding. Patient demographic, laboratory, imaging, procedural and treatment information, and outcomes were extracted from the medical record. Sixteen patients who experienced GI hemorrhage were identified at 11 centers. Among 14 patients who had genetic testing, 8 had mutations in TINF2, 4 in CTC1 or STN1, and 1 each in TERC and RTEL1. Ten had a history of hematopoietic cell transplantation. The Coats plus and non-Coats plus patients had similar clinical features and courses. Angiodysplasia of the stomach and/or small bowel was described in 8 of the 12 patients who underwent endoscopy; only 4 had esophageal varices. A variety of medical interventions were trialed. No single intervention was uniformly associated with cessation of bleeding, although one patient had a sustained response to treatment with bevacizumab. Recurrence was common and the overall long-term outcome for affected patients was poor.

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Copyright © 2020 Elsevier Inc. All rights reserved.

Source: The Journal of Pediatrics. Published September 20, 2020. DOI:https://doi.org/10.1016/j.jpeds.2020.09.038


A Machine-Learning Algorithm for Neonatal Seizure Recognition

ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR.

source: The Lancet

Summary

A Machine-Learning Algorithm for Neonatal Seizure Recognition: A Multicentre, Randomised, Controlled Trial

[Posted 07/Sep/2020]

AUDIENCE: Pediatric, Neonatology, Neurology

KEY FINDINGS: ANSeR, a machine-learning algorithm, is safe and able to accurately detect neonatal seizures. Although the algorithm did not enhance identification of individual neonates with seizures beyond conventional EEG, recognition of seizure hours was improved with use of ANSeR. The benefit might be greater in less experienced centres, but further study is required.

BACKGROUND: Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR).

DETAILS: This multicentre, randomised, two-arm, parallel, controlled trial was done in eight neonatal centres across Ireland, the Netherlands, Sweden, and the UK. Neonates with a corrected gestational age between 36 and 44 weeks with, or at significant risk of, seizures requiring EEG monitoring, received cEEG plus ANSeR linked to the EEG monitor displaying a seizure probability trend in real time (algorithm group) or cEEG monitoring alone (non-algorithm group). The primary outcome was diagnostic accuracy (sensitivity, specificity, and false detection rate) of health-care professionals to identify neonates with electrographic seizures and seizure hours with and without the support of the ANSeR algorithm. Neonates with data on the outcome of interest were included in the analysis. This study is registered with ClinicalTrials.gov, NCT02431780. Between Feb 13, 2015, and Feb 7, 2017, 132 neonates were randomly assigned to the algorithm group and 132 to the non-algorithm group. Six neonates were excluded (four from the algorithm group and two from the non-algorithm group). Electrographic seizures were present in 32 (25.0%) of 128 neonates in the algorithm group and 38 (29.2%) of 130 neonates in the non-algorithm group. For recognition of neonates with electrographic seizures, sensitivity was 81.3% (95% CI 66.7–93.3) in the algorithm group and 89.5% (78.4–97.5) in the non-algorithm group; specificity was 84.4% (95% CI 76.9–91.0) in the algorithm group and 89.1% (82.5–94.7) in the non-algorithm group; and the false detection rate was 36.6% (95% CI 22.7–52.1) in the algorithm group and 22.7% (11.6–35.9) in the non-algorithm group. We identified 659 h in which seizures occurred (seizure hours): 268 h in the algorithm versus 391 h in the non-algorithm group. The percentage of seizure hours correctly identified was higher in the algorithm group than in the non-algorithm group (177 [66.0%; 95% CI 53.8–77.3] of 268 h vs 177 [45.3%; 34.5–58.3] of 391 h; difference 20.8% [3.6–37.1]). No significant differences were seen in the percentage of neonates with seizures given at least one inappropriate antiseizure medication (37.5% [95% CI 25.0 to 56.3] vs 31.6% [21.1 to 47.4]; difference 5.9% [–14.0 to 26.3]).

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FUNDING: Wellcome Trust, Science Foundation Ireland, and Nihon Kohden.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Source: The Lancet Published August 27, 2020. DOI: https://doi.org/10.1016/S2352-4642(20)30239-X


Synchronized Inflations Generate Greater Gravity Dependent Lung Ventilation in Neonates

With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

source: J Pediatr.

Summary

Synchronized Inflations Generate Greater Gravity Dependent Lung Ventilation in Neonates

[Posted 21/Aug/2020]

AUDIENCE: Pediatric, Neonatology, Internal Medicine, Emergency Medicine

BACKGROUND: Objective of this tudy was to describe the regional distribution patterns of tidal ventilation within the lung during mechanical ventilation that is synchronous or asynchronous with an infant’s own breathing effort.

DETAILS: Intubated infants receiving synchronised mechanical ventilation at The Royal Children’s Hospital NICU were studied. During four 10-minute periods of routine care, regional distribution of tidal volume (VT; Electrical Impedance Tomography), delivered pressure and airway flow (Florian Respiratory Monitor) were measured for every inflation. Post hoc, each inflation was then classified as synchronous or asynchronous from video data of the ventilator screen, and the distribution of absolute V T and delivered ventilation characteristics determined. 2,749 inflations (2,462 synchronous) were analysed in 19 infants; mean (SD) age 28 (30) day, GA 35 (5) weeks. Synchronous inflations were associated with a shorter respiratory cycle (P = .004) and more homogenous VT (centre of ventilation) along the right (0%) to left (100%) lung plane; 45.3 (8.6)% vs 48.8 (9.4)% (uniform ventilation 46%). The gravity dependent center of ventilation was a mean (95% CI) 2.1 (-0.5, 4.6)% more toward the dependent lung during synchronous inflations. Tidal ventilation relative to anatomical lung size was more homogenous during synchronised inflations in the dependent lung.

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KEY FINDINGS: Synchronous mechanical ventilator lung inflations generate more gravity dependent lung ventilation and more uniform right to left ventilation than asynchronous inflations.

Copyright © 2020 Elsevier Inc. All rights reserved.

Source: The Journal of Pediatrics. Published August 19, 2020. DOI:https://doi.org/10.1016/j.jpeds.2020.08.043


Apgar Score and Risk of Neonatal Death among Preterm Infants

In this study, Apgar scores at 5 and 10 minutes provided prognostic information about neonatal survival among preterm infants across gestational-age strata.

source: NEJM

Summary

Apgar Score and Risk of Neonatal Death among Preterm Infants

[Posted 17/Jul/2020]

AUDIENCE: Neonatology, Pediatric, Family Medicine

KEY FINDINGS: In this study, Apgar scores at 5 and 10 minutes provided prognostic information about neonatal survival among preterm infants across gestational-age strata.

BACKGROUND: Gestational age is the major determinant of neonatal death (death within the first 28 days of life) in preterm infants. The joint effect of gestational age and Apgar score on the risk of neonatal death is unknown.

DETAILS: Using data from the Swedish Medical Birth Register, we identified 113,300 preterm infants (22 weeks 0 days to 36 weeks 6 days of gestation) born from 1992 through 2016. In analyses stratified according to gestational age (22 to 24 weeks, 25 to 27 weeks, 28 to 31 weeks, 32 to 34 weeks, and 35 or 36 weeks), we estimated adjusted relative risks of neonatal death and absolute rate differences in neonatal mortality (i.e., the excess number of neonatal deaths per 100 births) according to the Apgar scores at 5 and 10 minutes and according to the change in the Apgar score between 5 minutes and 10 minutes. Scores range from 0 to 10, with higher scores indicating a better physical condition of the newborn. here were 1986 neonatal deaths (1.8%). The incidence of neonatal death ranged from 0.2% (at 36 weeks of gestation) to 76.5% (at 22 weeks of gestation). Lower Apgar scores were associated with higher relative risks of neonatal death and greater absolute rate differences in neonatal mortality in all gestational-age strata. For example, among infants born at 28 to 31 weeks, the adjusted absolute rate differences according to the 5-minute Apgar score, with those who had a score of 9 or 10 serving as the reference group, were 51.7 (95% confidence interval [CI], 38.1 to 65.4) for a score of 0 or 1, 25.5 (95% CI, 18.3 to 32.8) for a score of 2 or 3, 7.1 (95% CI, 5.1 to 9.1) for a score of 4 to 6, and 1.2 (95% CI, 0.5 to 1.9) for a score of 7 or 8. An increase in the Apgar score between 5 minutes and 10 minutes was associated with lower neonatal mortality than a stable Apgar score.

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FUNDING: Swedish Research Council for Health, Working Life, and Welfare and Karolinska Institutet.

Copyright © 2020 Massachusetts Medical Society. All rights reserved.

Source: N Engl J Med. N Engl J Med 2020; 383:49-57. Published July 2, 2020. DOI: 10.1056/NEJMoa1915075


Method of Blood Pressure Measurement in Neonates and Infants

With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

source: J Pediatr.

Summary

Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis

[Posted 25/Jun/2020]

AUDIENCE: Pediatric, Cardiology, Family Medicine, Emergency Medicine

KEY FINDINGS: Proper BP measurement is critical in neonates with naturally lower BP and attention to BP cuff size, location, and method of measurement are essential. With decreasing use of intra-arterial catheters for long-term BP monitoring in neonates, further studies are urgently needed to validate and develop oscillometric methodology with enhanced accuracy.

BACKGROUND: To determine the recommended blood pressure (BP) measurement methods in neonates after systematically analyzing the literature regarding proper BP cuff size and measurement location and method.

DETAILS: A literature search was conducted in MEDLINE, PubMed, Embase, Cochrane Library, and CINAHL from 1946 to 2017 on BP in neonates <3 months of age (PROSPERO ID CRD42018092886). Study data were extracted and analyzed with separate analysis of Bland-Altman studies comparing measurement methods. Of 3587 nonduplicate publications identified, 34 were appropriate for inclusion in the analysis. Four studies evaluating BP cuff size support a recommendation for a cuff width to arm circumference ratio of approximately 0.5. Studies investigating measurement location identified the upper arm as the most accurate and least variable location for oscillometric BP measurement. Analysis of studies using Bland-Altman methods for comparison of intra-arterial to oscillometric BP measurement show that the 2 methods correlate best for mean arterial pressure, whereas systolic BP by the oscillometric method tends to overestimate intra-arterial systolic BP. Compared with intra-arterial methods, systolic BP, diastolic BP, and mean arterial pressure by oscillometric methods are less accurate and precise, especially in neonates with a mean arterial pressure <30 mm Hg.

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Copyright © 2020 Elsevier Inc. All rights reserved.

Source: The Journal of Pediatrics. Published June 01, 2020. DOI:https://doi.org/10.1016/j.jpeds.2020.02.072


FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease

FDA approved Koselugo (selumetinib) for the treatment of pediatric patients, with NF1, a genetic disorder of the nervous system causing tumors to grow on nerves.

source: FDA

Summary

FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease

[Posted 14/Apr/2020]

AUDIENCE: Pediatric, Oncology, Neurology, Dermatology, Internal Medicine

KEY FINDINGS: Today, the U.S. Food and Drug Administration approved Koselugo (selumetinib) for the treatment of pediatric patients, 2 years of age and older, with neurofibromatosis type 1 (NF1), a genetic disorder of the nervous system causing tumors to grow on nerves. Koselugo is the first drug approved by the FDA to treat this debilitating, progressive and often disfiguring rare disease that typically begins early in life.

"Everyone's daily lives have been disrupted during the COVID-19 pandemic, and in this critical time we want patients to know that the FDA remains committed to making patients with rare tumors and life threatening diseases, and their unique needs, a top priority. We continue to expedite product development for these patients," said Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Oncologic Diseases in the FDA's Center for Drug Evaluation and Research.

Koselugo is approved specifically for patients who have symptomatic, inoperable plexiform neurofibromas (PN), which are tumors involving the nerve sheaths (coating around nerve fibers) and can grow anywhere in the body, including the face, extremities, areas around the spine and deep in the body where they may affect organs. Koselugo is a kinase inhibitor, meaning it functions by blocking a key enzyme, which results in helping to stop the tumor cells from growing.

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NF1 is a rare, progressive condition caused by a mutation or flaw in a particular gene. NF1 is usually diagnosed in early childhood and appears in an estimated 1 out of every 3,000 infants. It is characterized by changes in skin coloring (pigmentation), neurologic and skeletal impairments and risk for development of benign and malignant tumors throughout life. Between 30% and 50% of patients born with NF1 develop one or more PNs.

"We are committed to regulatory flexibility and providing extensive guidance to industry in an effort to bring drugs forward that fulfill unmet medical needs. Koselugo represents this commitment," noted Pazdur. "For the first time, pediatric patients now have an FDA-approved drug to treat plexiform neurofibroma, a rare tumor associated with NF1."

The FDA approved Koselugo based on a clinical trial conducted by the National Cancer Institute of pediatric patients who had NF1 and inoperable PN (defined as a PN that could not be completely removed without risk for substantial morbidity to the patient). The efficacy results were from 50 of the patients who received the recommended dose and had routine evaluations of changes in tumor size and tumor-related morbidities during the trial. Patients received Koselugo 25 mg/m2 orally twice a day until disease progression or until they experienced unacceptable adverse reactions. The clinical trial measured the overall response rate (ORR), defined as the percentage of patients with a complete response and those who experienced more than a 20% reduction in PN volume on MRI that was confirmed on a subsequent MRI within 3-6 months. The ORR was 66% and all patients had a partial response, meaning that no patients had complete disappearance of the tumor. Of these patients, 82% had a response lasting 12 months or longer.

Other clinical outcomes for patients during Koselugo treatment including changes in PN-related disfigurement, symptoms and functional impairments. Although the sample sizes of patients assessed for each PN-related morbidity (such as disfigurement, pain, strength and mobility problems, airway compression, visual impairment and bladder or bowel dysfunction) were small, there appeared to be a trend of improvement in PN-related symptoms or functional deficits during treatment.

Common side effects for patients taking Koselugo were vomiting, rash, abdominal pain, diarrhea, nausea, dry skin, fatigue, musculoskeletal pain (pain in the body affecting bones, muscles, ligaments, tendons and nerves), fever, acneiform rash (acne), stomatitis (inflammation of the mouth and lips), headache, paronychia (infection in the skin that surrounds a toenail or fingernail) and pruritus (itching).

Koselugo can also cause serious side effects including heart failure (manifested as ejection fraction decrease, or when the muscle of the left ventricle of the heart is not pumping as well as normal) and ocular toxicity (acute and chronic damage to the eye) including retinal vein occlusion, retinal pigment epithelial detachment and impaired vision. Patients should have cardiac and ophthalmic assessments performed prior to initiating Koselugo and at regular intervals during treatment. Koselugo can also cause increased creatinine phosphokinase (CPK). CPK is an enzyme found in the heart, brain and skeletal muscles. When muscle tissue is damaged, CPK leaks into a person’s blood. CPK elevation in a patient receiving Koselugo should prompt an evaluation for rhabdomyolysis (breakdown of skeletal muscle due to direct or indirect muscle injury). Koselugo should be withheld, dosage reduced or dosage permanently discontinued based on the severity of adverse reactions. Further, Koselugo contains Vitamin E, and patients are at an increased risk of bleeding if their daily intake of Vitamin E exceeds the recommended or safe limits.

Based on findings from animal studies, Koselugo may cause harm to a newborn baby when administered to a pregnant woman. The FDA advises health care professionals to tell females of reproductive age, and males with female partners of reproductive potential, to use effective contraception during treatment with Koselugo, and for one week after the last dose.

The FDA granted this application Priority Review and Breakthrough Therapy designation. Koselugo also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases, and Rare Pediatric Disease Designation for the treatment of pediatric NF1. The application is awarded a Rare Pediatric Disease Priority Review Voucher.

The FDA granted approval of Koselugo to AstraZeneca Pharmaceuticals LP.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Copyright © 2020 FDA. All rights reserved.

Source: FDA Approves First Therapy for Children with Debilitating and Disfiguring Rare Disease FDA Published April 10, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-therapy-children-debilitating-and-disfiguring-rare-disease


Risk Factors for RBCTs in Children Undergoing Cardiac Catheterization

Length of procedure, blood loss, and oxygen saturations are additional risk factors associated with RBCT.

source: J Pediatr.

Summary

Risk Factors for Red Blood Cell Transfusions in Children Undergoing Cardiac Catheterization

[Posted 20/Feb/2020]

AUDIENCE: Pediatric, Cardiology, Family Medicine, Internal Medicine

KEY FINDINGS: Hospitalized infants with single ventricle or complex 2-ventricle anatomy are at highest risk of RBCT. Length of procedure, blood loss, and oxygen saturations are additional risk factors associated with RBCT. Operators should consider these factors when planning pediatric cardiac catheterizations, particularly when exposure to RBCT is undesirable.

BACKGROUND: To identify risk factors associated with risk of red blood cell transfusions (RBCTs) following pediatric cardiac catheterizations.

DETAILS: A review was performed of all pediatric cardiac catheterizations from 2012 to 2017. The primary endpoint was RBCT within 72 hours of pediatric cardiac catheterization. Patient and procedural factors were reviewed. Generalized linear modelling was performed to describe interactions among relevant risk factors. In total, 831 RBCTs occurred within 72 hours of 6028 pediatric cardiac catheterizations (13.8%). Univariate analysis revealed that the prevalence of RBCT was highest among infants (37.6% incidence of RBCT) and among those with higher estimated blood loss as a percent of blood volume (P = .03). Among infants, multivariate analysis revealed that weight (OR 0.72; 95% CI 0.63-0.81), complex 2-ventricle (OR 3.14, 95% CI 2.18-4.57), and single ventricle status (OR 5.21, 95% CI 3.42-8.01) were associated with risk of RBCT. Inpatient infants from intensive care (OR 4.74; 95% CI 3.49-6.49) or stepdown units (OR 2.33; 95% CI 1.58-3.46) were at higher risk. Length of procedure (OR 2.57; 95% CI 2.03-3.26) and oxygen saturation (OR 0.98; 95% CI 0.97-0.99; P < .01) were also associated with RBCTs.

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Copyright © 2020 Elsevier Inc. All rights reserved.

Source: The Journal of Pediatrics. Published February 2020. DOI: https://doi.org/10.1016/j.jpeds.2019.10.033


Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia

Healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold was noninferior to a traditional threshold.

source: NEJM

Summary

Lower versus Traditional Treatment Threshold for Neonatal Hypoglycemia

[Posted 10/Feb/2020]

AUDIENCE: Neonatology, Endocrinology, Pediatric, Hematology

KEY FINDINGS: In otherwise healthy newborns with asymptomatic moderate hypoglycemia, a lower glucose treatment threshold (36 mg per deciliter) was noninferior to a traditional threshold (47 mg per deciliter) with regard to psychomotor development at 18 months.

BACKGROUND: Worldwide, many newborns who are preterm, small or large for gestational age, or born to mothers with diabetes are screened for hypoglycemia, with a goal of preventing brain injury. However, there is no consensus on a treatment threshold that is safe but also avoids overtreatment.

DETAILS: In a multicenter, randomized, noninferiority trial involving 689 otherwise healthy newborns born at 35 weeks of gestation or later and identified as being at risk for hypoglycemia, we compared two threshold values for treatment of asymptomatic moderate hypoglycemia. We sought to determine whether a management strategy that used a lower threshold (treatment administered at a glucose concentration of <36 mg per deciliter [2.0 mmol per liter]) would be noninferior to a traditional threshold (treatment at a glucose concentration of <47 mg per deciliter [2.6 mmol per liter]) with respect to psychomotor development at 18 months, assessed with the Bayley Scales of Infant and Toddler Development, third edition, Dutch version (Bayley-III-NL; scores range from 50 to 150 [mean {±SD}, 100±15]), with higher scores indicating more advanced development and 7.5 points (one half the SD) representing a clinically important difference). The lower threshold would be considered noninferior if scores were less than 7.5 points lower than scores in the traditional-threshold group. Bayley-III-NL scores were assessed in 287 of the 348 children (82.5%) in the lower-threshold group and in 295 of the 341 children (86.5%) in the traditional-threshold group. Cognitive and motor outcome scores were similar in the two groups (mean scores [±SE], 102.9±0.7 [cognitive] and 104.6±0.7 [motor] in the lower-threshold group and 102.2±0.7 [cognitive] and 104.9±0.7 [motor] in the traditional-threshold group). The prespecified inferiority limit was not crossed. The mean glucose concentration was 57±0.4 mg per deciliter (3.2±0.02 mmol per liter) in the lower-threshold group and 61±0.5 mg per deciliter (3.4±0.03 mmol per liter) in the traditional-threshold group. Fewer and less severe hypoglycemic episodes occurred in the traditional-threshold group, but that group had more invasive diagnostic and treatment interventions. Serious adverse events in the lower-threshold group included convulsions (during normoglycemia) in one newborn and one death.

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FUNDING: Netherlands Organization for Health Research and Development; HypoEXIT Current Controlled Trials number, ISRCTN79705768.

Copyright © 2020 Massachusetts Medical Society. All rights reserved.

Source: N Engl J Med. Published February 6, 2020. DOI: 10.1056/NEJMoa1905593


Children with CHD Need to Keep Moving

Physical activity needs to be promoted in overweight or obese patients, patients with complex CHD severity.

source: J Pediatr.

Summary

Children with Congenital Heart Disease Are Active but Need to Keep Moving: A Cross-Sectional Study Using Wrist-Worn Physical Activity Trackers

[Posted 10/Feb/2020]

AUDIENCE: Pediatric, Cardiology, Family Medicine, Internal Medicine

KEY FINDINGS: Even though the majority is sufficiently active, physical activity needs to be promoted in overweight or obese patients, patients with complex CHD severity, and in particular in those with total cavopulmonary connection.

BACKGROUND: To compare daily physical activity of children with congenital heart disease (CHD) with healthy peers measured using wearables bracelets in a large cohort. Additionally, subjectively estimated and objectively measured physical activity was compared.

DETAILS: From September 2017 to May 2019, 162 children (11.8 ± 3.2 years; 60 girls) with various CHD participated in a self-estimated and wearable-based physical activity assessment. Step-count and moderate-to-vigorous physical activity were recorded with the Garmin vivofit jr. for 7 consecutive days and compared with a reference cohort (RC) of 96 healthy children (10.9 ± 3.8 years; 49 girls). Children with CHD were active and 123 (75.9%) achieved 60 minutes physical activity on a weekly average according to the World Health Organization criteria as 81 (84.3%) of the healthy peers did (P = .217). After correction for age, sex, and seasonal effects, only slightly lower step count (CHD: 10,206 ± 3178 steps vs RC: 11,142 ± 3136 steps; P = .040) but no lower moderate-to-vigorous physical activity (CHD: 80.5 ± 25.6 minutes/day vs RC: 81.5 ± 25.3 minutes/day; P = .767) occurred comparing CHD with RC. In children with CHD higher age (P = .004), overweight or obesity (P = .016), complex severity (P = .046), and total cavopulmonary connection (P = .027) were associated with not meeting World Health Organization criteria. Subjective estimation of daily moderate-to-vigorous physical activity was fairly correct in half of all children with CHD.

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Copyright © 2020 Elsevier Inc. All rights reserved.

Source: The Journal of Pediatrics. Published February 2020. DOI: https://doi.org/10.1016/j.jpeds.2019.09.077


Brain Injury in Infants with Critical CHD

The high prevalence of brain injury in critical CHD is a clinical concern.

source: J Pediatr.

Summary

Brain Injury in Infants with Critical Congenital Heart Disease: Insights from Two Clinical Cohorts with Different Practice Approaches

[Posted 5/Feb/2020]

AUDIENCE: Pediatric, Neurology, Cardiology, Family Medicine, Internal Medicine

KEY FINDINGS: Brain injury is common in clinical cohorts of infants with critical CHD and related to practice approaches. This study confirms that the high prevalence of brain injury in critical CHD is a clinical concern and does not simply reflect the inclusion criteria of published research studies.

BACKGROUND: To determine prevalence and risk factors for brain injury in infants with critical congenital heart disease (CHD) from 2 sites with different practice approaches who were scanned clinically.

DETAILS: Prospective, longitudinal cohort study (2016-2017) performed at Hospital for Sick Children Toronto (HSC) and Wilhelmina Children's Hospital Utrecht (WKZ), including 124 infants with cardiac surgery <=60 days (HSC = 77; WKZ = 47). Magnetic resonance imaging was performed per clinical protocol, preoperatively (n = 100) and postoperatively (n = 120). Images were reviewed for multifocal (watershed, white matter injury) and focal ischemic injury (stroke, single white matter lesion). The prevalence of ischemic injury was 69% at HSC and 60% at WKZ (P = .20). Preoperative multifocal injury was associated with low cardiac output syndrome (OR, 4.6), which was equally present at HSC and WKZ (20% vs 28%; P = .38). Compared with WKZ, HSC had a higher prevalence of balloon-atrioseptostomy in transposition of the great arteries (83% vs 53%; P = .01) and more frequent preoperative focal injury (27% vs 6%; P = .06). Postoperatively, 30% of new multifocal injury could be attributed to postoperative low cardiac output syndrome, which was equally present at HSC and WKZ (38% vs 28%; P = .33). Postoperative focal injury was associated with intraoperative selective cerebral perfusion in CHD with arch obstruction at both sites (OR, 2.7). Compared with HSC, WKZ had more arch obstructions (62% vs 35%; P < .01) and a higher prevalence of new focal injury (36% vs 16%; P = .01).

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Source: The Journal of Pediatrics Published December, 2019. DOI: https://doi.org/10.1016/j.jpeds.2019.07.017


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