What's new in pediatrics

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

ORTHOPEDICS AND SPORTS MEDICINE

Running injuries in high school and collegiate athletes (March 2024)

Although running is the most common form of exercise, few high-quality reviews of running-related injuries have been published. A recent systematic review that included 24 prospective cohort studies (nearly 2000 adolescent and young adult competitive runners) found that female runners sustained more injuries than their male counterparts [1]. All runners, but particularly females, with risk factors for relative energy deficiency in sport (REDS) experienced higher injury rates; athletes with weak hip and thigh muscles were at increased risk of developing anterior knee pain (eg, patellofemoral pain). This study also confirmed known risk factors, such as a history of prior running-related injury. Overall, study quality and certainty of evidence were low to moderate. These findings reinforce the importance of sound nutrition and adjunct strength training to prevent running injuries. (See "Running injuries of the lower extremities: Risk factors and prevention", section on 'Sex and age'.)

Concussion and mental health disorders in children and adolescents (March 2024)

Ongoing research continues to examine the complex relationship between concussion and mental health disorders. In a recent case-control study of over 18,000 children (≤17 years old) with concussion and over 37,000 matched controls, concussion was associated with an increased risk for a new diagnosis of a behavior disorder at two and four years after injury [2]. For most diagnoses, the absolute numbers were low. Confidence in a causal relationship is limited by risk of confounding and reliance on an electronic medical record for establishing lack of baseline behavioral problems prior to injury. Whether pediatric concussion is an independent risk factor for new behavioral problems after recovery remains unclear. (See "Concussion in children and adolescents: Management", section on 'Mental health disorders'.)

Overuse injuries, overtraining, and burnout in children and adolescents (February 2024)

Greater numbers of children and adolescents now specialize in a single sport, thereby increasing the risk for overuse injuries, overtraining, and burnout. The American Academy of Pediatrics has issued a new clinical report that reviews the medical literature about these conditions and summarizes key findings pertaining to risk factors, clinical presentation, and prevention [3]. The report emphasizes the importance of achieving a healthy balance between stress and recovery. Specific recommendations include taking one to two days off from competition and sport-specific training each week and two to three months away from any specific sport each year. Discussions of endurance sports and weekend tournaments are included. (See "Overtraining syndrome in athletes", section on 'Special considerations in the young athlete'.)

Risk of reinjury following ACL repair (February 2024)

Despite advances in surgical techniques, the risk of reinjury following repair of a ruptured anterior cruciate ligament remains substantial, ranging from 5 to 15 percent depending on the patient's age and activities. According to a systematic review of 71 studies involving over 600,000 patients, factors associated with an increased risk for retear following surgery include male sex, younger age, preoperative high-grade knee laxity, return to a high activity level or sport, and concomitant medial collateral ligament injury [4]. The modifiable factors identified highlight the importance of following a rigorous rehabilitation program and allowing time for complete healing before returning to sport. (See "Anterior cruciate ligament injury", section on 'Risk of reinjury'.)

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

Same-day contraceptive start and pregnancy risk (May 2024)

Individuals who desire contraception often want to start the method on the same day as their office visit, but the risk of pregnancy for those >7 days from the onset of their last menstrual period has been a concern. However, in a prospective study of over 3500 individuals seeking hormonal contraception, first-cycle unintended pregnancy rates were low for both those with same-day starts >7 days from the onset of menses and those who waited to start the method within 7 days of onset of menses (0.4 and 0.1 percent, respectively), even though approximately 20 percent of same-day start participants had at least one episode of unprotected intercourse within the prior 14 days [5]. For individuals who prefer a same-day start and understand the potential need for follow-up pregnancy testing, hormonal contraceptives (any method) may be started on the same day as the visit with low overall pregnancy risk. (See "Contraception: Counseling and selection", section on 'Starting a method'.)

High-flow nasal cannula oxygen therapy in children with bronchiolitis (April 2024)

High-flow nasal cannula (HFNC) oxygen therapy is increasingly used for children with bronchiolitis and significant respiratory distress, but the clinical benefit has been questioned. In a meta-analysis of eight trials (over 2100 patients <2 years old with bronchiolitis) that compared oxygen therapy using HFNC with standard (low-flow) oxygen, the risk of escalation of therapy was lower with HFNC oxygen therapy; rates of adverse events were similar in the two groups (four studies, nearly 1800 patients, approximately 1 percent) [6]. Interpretation of these results is limited by significant heterogeneity and risk of bias. These findings suggest that HFNC oxygen therapy provides modest benefit for children with bronchiolitis without increasing adverse events. For children with bronchiolitis, we suggest HFNC in patients with severe respiratory distress; we advise against routine use of HFNC for children with hypoxemia and mild-to-moderate increased work of breathing. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'High-flow nasal cannula'.)

Association between obesity in adolescence and development of chronic kidney disease (April 2024)

Observational studies have suggested that adolescents with obesity are at increased risk for impaired kidney function. In a new study of 630,000 adolescents in Israel, high body mass index (BMI) in late adolescence was associated with development of chronic kidney disease in early adulthood, as measured by albuminuria [7]. For severe obesity, the adjusted hazard ratio for early chronic kidney disease was 9.4 for males and 4.3 for females. These findings support our suggestion to screen for impaired kidney function in patients with risk factors for chronic kidney disease, including severe obesity, hypertension, or type 2 diabetes. Screening consists of measuring urine albumin-to-creatinine ratio. (See "Overview of the health consequences of obesity in children and adolescents", section on 'Kidney'.)

Management of children with mild sleep-disordered breathing (February 2024)

For children with mild sleep-disordered breathing (SDB) and relevant symptoms, little evidence has been available to guide a choice between adenotonsillectomy and watchful waiting. In a randomized trial in 459 children 3 to <13 years with tonsillar hypertrophy and mild SDB (defined by habitual snoring with occasional episodes of obstruction with apnea per hour of sleep), executive function and attention were similar for individuals assigned to adenotonsillectomy compared with watchful waiting at 12 months follow-up [8]. However, children treated with adenotonsillectomy had greater decrease in snoring, obstruction with apnea or hypopnea, blood pressure, and caregiver-reported symptoms (sleep symptoms, behavioral problems, sleepiness) as well as increased quality of life. These findings support our suggestion to offer adenotonsillectomy to children with mild obstructive sleep apnea and relevant symptoms although watchful waiting is a reasonable alternative. (See "Management of obstructive sleep apnea in children", section on 'Adenotonsillectomy'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Possible infectious causes of IgA vasculitis (April 2024)

Although IgA vasculitis (IgAV; formerly Henoch-Schönlein purpura) is the most common cause of systemic vasculitis among children, its cause is unknown. A hospital-based surveillance system in France identified over 9000 children diagnosed with IgAV from 2015 to 2023 [9]. A time-series analysis indicated that the incidence of IgAV decreased by over 50 percent following the implementation of social distancing policies for the COVID-19 pandemic. Subsequently, after relaxation of social distancing and mask-wearing, there was a temporal association between the monthly incidence of IgAV and outbreaks of Streptococcus pneumoniae and Streptococcus pyogenes, but not other common pathogens. This study demonstrates a potential causal relationship between specific infections and IgA vasculitis, but these results need to be replicated in other patient populations. (See "IgA vasculitis (Henoch-Schönlein purpura): Clinical manifestations and diagnosis", section on 'Pathogenesis'.)

Association between gut bacteriophage abundance and asthma risk (April 2024)

The abundance and diversity of gut flora and their interaction with the immune system have been associated with a predisposition to childhood asthma. A recent study examined the role of the fecal virome, predominantly comprising temperate bacteriophages, in a Danish birth cohort of 647 one-year-old children who were subsequently longitudinally assessed for asthma [10]. The relative abundance of certain viral families was associated with subsequent asthma development, and the viromes in turn were associated with early life exposures (eg, siblings and season of birth). The association between virome and asthma was not mediated by the impact on gut bacteria, suggesting independent effects on the developing immune system. (See "Risk factors for asthma", section on 'Influence of microbiome'.)

Multisystem inflammatory syndrome in children incidence and severity (March 2024)

Although multisystem inflammatory syndrome in children (MIS-C) is increasingly rare as the overall COVID-19 burden declines, it continues to be associated with substantial morbidity. In 2023, 117 patients with MIS-C were reported to the Centers for Disease Control and Prevention, resulting in an estimated incidence of 0.11 cases per million person-months [11]. Of these patients, 50 percent required care in an intensive care unit, 34 percent experienced shock, and 27 percent experienced cardiac dysfunction; mortality was 2.6 percent (3 patients). More than 80 percent of patients were SARS-CoV2 vaccine eligible but had not been vaccinated; among 20 patients who had been vaccinated, 60 percent likely had waning immunity at the time of diagnosis. This study suggests that MIS-C severity remains high, but that SARS-CoV2 vaccination may provide some degree of protection. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis", section on 'Epidemiology'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Pharmacotherapy for ADHD and mortality risk (April 2024)

Attention deficit hyperactivity disorder (ADHD) is associated with higher mortality than in the general population; whether treatment modifies that risk is unclear. In an observational study of nearly 149,000 individuals with ADHD in Sweden (mean age 17 years), initiation of medication within three months of diagnosis was associated with lower all-cause mortality (hazard ratio [HR] 0.79) as well as lower mortality from unnatural causes (eg, suicide, unintentional injury, and accidental poisoning; HR 0.75) over the ensuing two years [12]. While the study could not control for unmeasured confounders that may have impacted mortality risk (eg, lifestyle factors, social support), these data generally lend further support for pharmacotherapy of ADHD. (See "Attention deficit hyperactivity disorder in adults: Treatment overview", section on 'Benefits of stimulant treatment'.)

Infertility and autism spectrum disorder (December 2023)

Patients with infertility often ask about the impact of the disorder and its treatment on risk of autism spectrum disorder (ASD) in offspring. In a large population-based cohort study comparing ASD risk among children whose parents had subfertility (an infertility consultation without treatment), infertility treatment, or neither (unassisted conception), children in the subfertility and infertility treatment groups had a small increased risk of ASD compared with unassisted conception but the absolute risk was low (2.5 to 2.7 per 1000 person-years versus 1.9 per 1000 person-years with unassisted conception) [13]. The increased risk was similar in the subfertile and infertility treatment groups, suggesting that infertility treatment was not a major risk factor. Obstetrical and neonatal factors (eg, preterm birth) appeared to mediate a sizeable proportion of the increased risk for ASD. (See "Assisted reproductive technology: Infant and child outcomes", section on 'Confounders'.)

EMERGENCY MEDICINE

High-flow nasal cannula oxygen therapy in children with bronchiolitis (April 2024)

High-flow nasal cannula (HFNC) oxygen therapy is increasingly used for children with bronchiolitis and significant respiratory distress, but the clinical benefit has been questioned. In a meta-analysis of eight trials (over 2100 patients <2 years old with bronchiolitis) that compared oxygen therapy using HFNC with standard (low-flow) oxygen, the risk of escalation of therapy was lower with HFNC oxygen therapy; rates of adverse events were similar in the two groups (four studies, nearly 1800 patients, approximately 1 percent) [6]. Interpretation of these results is limited by significant heterogeneity and risk of bias. These findings suggest that HFNC oxygen therapy provides modest benefit for children with bronchiolitis without increasing adverse events. For children with bronchiolitis, we suggest HFNC in patients with severe respiratory distress; we advise against routine use of HFNC for children with hypoxemia and mild-to-moderate increased work of breathing. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'High-flow nasal cannula'.)

ENDOCRINOLOGY

Proposed formal diagnostic criteria for hypophosphatasia in children and adults (March 2024)

Hypophosphatasia is a rare form of osteomalacia caused by pathogenic variants in the tissue nonspecific alkaline phosphatase gene (ALPL). Missed or delayed diagnosis is common, in part due to lack of formal diagnostic criteria. An international working group has proposed diagnostic criteria for hypophosphatasia in both children and adults [14]. Two major criteria or one major and two minor criteria are considered sufficient for diagnosis. For both children and adults, major criteria include a pathogenic (or likely pathogenic) variant in ALPL and elevated natural substrate concentrations (eg, pyridoxal 5'-phosphate). Additional major criteria for adults are atypical femoral fracture and recurrent metatarsal fractures and, for children, early loss of primary teeth and radiographic evidence of rickets. These criteria highlight the variable phenotypic expression of hypophosphatasia and the importance of considering this diagnosis in individuals with metabolic bone disease. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults", section on 'Low alkaline phosphatase (hypophosphatasia)' and "Skeletal dysplasias: Specific disorders", section on 'Hypophosphatasia'.)

Janus kinase inhibition to preserve insulin secretion in early onset type 1 diabetes (January 2024)

In type 1 diabetes, the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been implicated in immune-mediated beta cell destruction. In a trial in 91 individuals (aged 10 to 30 years) with new-onset type 1 diabetes (diagnosed within 100 days), participants were randomly assigned to daily treatment with the oral JAK1/2 inhibitor baricitinib (n = 60) or placebo (n = 31) [15]. After 48 weeks of therapy, insulin secretion was greater with baricitinib compared with placebo (median stimulated mean C-peptide level 0.65 versus 0.43 nmol/L per minute, respectively). A1C, frequency of hypoglycemia, and the percentage of time spent in the target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]) were not significantly different between groups. JAK/STAT pathway inhibition is a promising strategy for preserving insulin secretion in new-onset type 1 diabetes. (See "Type 1 diabetes mellitus: Prevention and disease-modifying therapy", section on 'Cytokine-directed therapies'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Odevixibat for pruritus in Alagille syndrome (May 2024)

Severe pruritus is a common complication of cholestatic liver disease in Alagille syndrome. In a 24-week open-label trial in 35 children with Alagille syndrome and clinically significant pruritus, odevixibat, an ileal bile acid transport (IBAT) inhibitor, significantly reduced serum bile acids and pruritus [16]. A clinically meaningful improvement in scratching score was reported by 54 percent (19 of 35) of participants treated with odevixibat versus 18 percent (3 of 17) treated with placebo. Diarrhea was the most common treatment-emergent adverse effect and was generally mild. This trial was the basis for the US Food and Drug Administration's approval of odevixibat for the treatment of cholestatic pruritus in patients ≥12 months of age with Alagille syndrome and supports our suggestion to use odevixibat or maralixibat (another IBAT inhibitor) as a first- or second-line treatment for severe pruritus in this condition. (See "Alagille syndrome", section on 'Pruritus'.)

Budesonide oral suspension for eosinophilic esophagitis (March 2024)

In patients with eosinophilic esophagitis (EoE), use of topical glucocorticoids has been limited by lack of regulatory approval and potentially inconsistent drug delivery. Budesonide oral suspension is a formulation that was recently approved by the US Food and Drug Administration for treating EoE in adults and pediatric patients ages 11 years and older [17,18]. Approval was informed by clinical trials showing that topical budesonide resulted in higher rates of histologic remission and symptomatic improvement compared with placebo. We anticipate using budesonide oral suspension as the preferred topical glucocorticoid for treating EoE. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Topical glucocorticoids'.)

Dupilumab for refractory eosinophilic esophagitis (February 2024)

Few data are available on the use of dupilumab (a monoclonal antibody) for treating refractory eosinophilic esophagitis. In a cohort study of 46 patients with refractory eosinophilic esophagitis, dupilumab therapy was associated with histologic remission (defined as <15 eosinophils/high-power field) in 37 patients (80 percent) and with symptomatic improvement in 42 patients (91 percent) after a median of six months [19]. These data support our approach of using dupilumab for patients with eosinophilic esophagitis who have not responded to other therapies (eg, topical glucocorticoids). (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Dupilumab'.)

GENETIC AND METABOLIC DISORDERS

Investigational gene therapy for autosomal recessive deafness (March 2024)

Gene therapies for single gene disorders are an area of active study. In two recent studies, children with autosomal recessive deafness 9, a type of congenital deafness, were treated with gene therapy to supply functional otoferlin, encoded by the OTOF gene, using an adeno-associated virus vector injected into cochlear cells [20,21]. Of eight treated children, seven had significant improvements in hearing. This therapy has not been approved by the US Food and Drug Administration. (See "Overview of gene therapy, gene editing, and gene silencing", section on 'Inherited single gene disorders'.)

N-acetyl-l-leucine (NALL) for Niemann-Pick disease type C (February 2024)

Niemann-Pick disease type C (NPD-C) is a rare lysosomal disease with a wide phenotypic spectrum; most patients have onset in childhood with cerebellar ataxia and slowly progressive neurologic deterioration. Investigational therapies include N-acetyl-l-leucine (NALL), a putative neuroprotective agent that improves cellular energy production and reduces neuroinflammation. In a recent placebo-controlled, 12-week crossover trial of 60 patients (age ≥4 years) with NPD-C, treatment with NALL was well tolerated and led to improved neurologic status on a scale that measures ataxia and other neurologic signs and symptoms [22]. While these results are promising, longer-term trials are needed to determine if NALL is beneficial for patients with NPD-C. (See "Overview of Niemann-Pick disease", section on 'Experimental therapies'.)

HEMATOLOGY AND ONCOLOGY

Emicizumab in infants with hemophilia A (April 2024)

Emicizumab is a monoclonal antibody that substitutes for the function of factor VIII; initial use has focused on older patients with factor VIII inhibitors. Now, two new studies report safety and efficacy in infants, most of whom did not have inhibitors. In HAVEN 7, there were no spontaneous bleeds or intracerebral bleeds [23]. In the second study, annualized bleeding rate decreased from 2 to 1 [24]. Neither study observed serious adverse events. Emicizumab is an attractive option due to its efficacy, lower rate of factor VIII exposure, and maintenance dosing schedule (subcutaneously once every other week), but use requires specialized knowledge of monitoring, risks, and treatment of breakthrough bleeding. (See "Hemophilia A and B: Routine management including prophylaxis", section on 'Emicizumab efficacy and adverse events'.)

Updates on congenital fibrinogen disorders (April 2024)

Congenital fibrinogen disorders are rare and remain underdiagnosed. New publications address the clinical manifestations of these disorders and provide obstetric guidance:

●A new report from the Rare Bleeding Disorders database described 123 patients with afibrinogenemia, hypofibrinogenemia, and dysfibrinogenemia and characterized bleeding and thrombotic manifestations [25]. (See "Disorders of fibrinogen", section on 'Clinical manifestations'.)

●New guidelines from the International Society on Thrombosis and Hemostasis (ISTH) provide target fibrinogen levels and advice for managing postpartum bleeding and thromboprophylaxis in individuals with congenital fibrin disorders [26]. (See "Disorders of fibrinogen", section on 'Conception and pregnancy'.)

A high index of suspicion for these disorders and multidisciplinary management are required.

New international guideline for PK deficiency (March 2024)

A new international expert guideline for diagnosis and treatment of pyruvate kinase (PK) deficiency has been published [27]. Key recommendations include testing in any individual with nonimmune hemolytic anemia after exclusion of hemoglobin and red blood cell (RBC) membrane disorders, acceptance of genetic testing alone for diagnosis, regular RBC transfusions for children <5 years with symptomatic anemia, monitoring for iron overload and its complications, use of mitapivat for symptomatic anemia in adults who are not receiving transfusions and do not have two nonmissense mutations, and discontinuing mitapivat for lack of efficacy. These guidelines are consistent with the advice in UpToDate. (See "Pyruvate kinase deficiency", section on 'Treatment'.)

Hemoglobin nadir in transfusion-dependent thalassemia (March 2024)

Thalassemia experts generally target a nadir hemoglobin of 9.5 to 10.5 in patients with transfusion-dependent thalassemia (TDT), but supporting evidence for this has been very limited. A new retrospective study evaluated outcomes in 779 patients with TDT and reported that higher pretransfusion hemoglobin (the nadir between regular transfusions) correlated with improved 10-year survival [28]. The survival benefit was not seen with ferritin >1000 ng/mL, emphasizing the importance of addressing iron overload. While several caveats apply to interpretation, this study supports our practice of targeting a nadir of 9.5 to 10.5 g/dL in TDT. (See "Management of thalassemia", section on 'Supporting evidence'.)

No benefit of routine thromboprophylaxis for children with ALL (January 2024)

Whether routine thromboprophylaxis reduces the risk of thrombotic complications in patients with acute lymphoblastic leukemia (ALL) has been debated. In a multicenter randomized trial of over 500 children and adolescents with newly diagnosed pre-B or T cell ALL, patients assigned to prophylactic anticoagulation with apixaban compared with standard care alone had similar rates of symptomatic venous thrombosis (1.6 versus 2.3 percent, respectively) and asymptomatic venous thrombosis (11 versus 15 percent) [29]. Nonmajor bleeding episodes (mostly epistaxis) occurred more frequently in the apixaban group (4 versus 1 percent). These data do not support the routine use of thromboprophylaxis in children with ALL, although it may be warranted in selected patients with additional risk factors for thrombosis. (See "Thromboembolism in children with cancer", section on 'Primary prevention'.)

Maintenance eflornithine in high-risk neuroblastoma (January 2024)

For patients with high-risk neuroblastoma (HRNBL), there is interest in investigating novel maintenance therapies such as eflornithine, an ornithine decarboxylase inhibitor. In an externally controlled analysis of almost 100 patients with HRNBL who completed multimodality treatment and maintenance immunotherapy, extended maintenance therapy with eflornithine was associated with improved overall survival (hazard ratio 0.38) [30]. Based on these data, the US Food and Drug Administration approved eflornithine as maintenance therapy in patients with HRNBL who achieve at least a partial response to prior systemic agents and complete maintenance immunotherapy. Since maintenance eflornithine is not standard across all institutions, this agent may be offered on a case-by-case basis. (See "Treatment and prognosis of neuroblastoma".)

Methemoglobinemia in infants due to contaminated hospital water supply (January 2024)

Methemoglobinemia is a potentially life-threatening condition in which heme iron becomes oxidized, preventing oxygen delivery. A report from a hospital in Japan described methemoglobinemia in 10 neonates who were fed infant formula prepared with tap water from the general hospital water supply [31]. The cause was identified as high levels of nitrites, and the source was traced to contamination by an anticorrosion agent from the heating system that entered the water supply due to a malfunctioning valve. All 10 survived, although 3 required methylene blue therapy. Infants are especially susceptible to methemoglobinemia because they have lower baseline levels of the enzyme that converts heme iron back to its normal state. (See "Methemoglobinemia", section on 'Nitrates and nitrites (from foods, drugs, preservatives, and chemicals)'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Pemivibart for prevention of COVID-19 in selected immunocompromised patients (April 2024)

Monoclonal antibodies have been used as adjunctive pre-exposure prophylaxis to reduce the risk of COVID-19 in individuals expected to have suboptimal response to vaccination, although emergence of variants that escape neutralization limit their utility. In March 2024 in the United States, the novel monoclonal antibody pemivibart received emergency use authorization (EUA) to prevent COVID-19 in individuals age 12 years or older (weighing at least 40 kg) who have moderate-to-severe immunocompromising conditions (table 1) [32]. Pemivibart is active against JN.1, the dominant SARS-CoV-2 variant. We suggest pemivibart in individuals at the highest risk for vaccine nonresponse (eg, those with hematologic malignancy or recent history of transplantation) as long as it remains active against the main circulating variants. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Limited role for monoclonal antibodies in selected patients'.)

Precautions for individuals with COVID-19 in the community (April 2024)

In March 2024, the United States Centers for Disease Control and Prevention updated guidance for precautions for people with COVID-19 in the community [33]. Such individuals should stay at home until their symptoms are improving and they have been afebrile for 24 hours without the use of antipyretics. They can subsequently resume normal activities but are encouraged to use other precautions (eg, masking, social distancing, good ventilation) for an additional five days to further reduce the risk of transmission to others. These measures are particularly important when around persons who are at increased risk for severe disease (eg, advanced age, immunocompromise, cardiopulmonary disease). (See "COVID-19: Infection prevention for persons with SARS-CoV-2 infection".)

Nirsevimab effectiveness in infants (March 2024)

During the 2023-24 respiratory syncytial virus (RSV) season, infants could receive the monoclonal antibody nirsevimab for the first time to protect against RSV-related hospitalization. In a case-control study of almost 700 infants <8 months old who were hospitalized in the United States for an acute respiratory illness during this RSV season, almost 60 percent tested positive for RSV; almost all of these patients had not received nirsevimab [34]. Among infants who tested negative for RSV, 18 percent had received nirsevimab. Estimated effectiveness against RSV-associated hospitalization among nirsevimab recipients was 90 percent. These data provide additional support for recommendations to administer nirsevimab to all infants <8 months old upon entering their first RSV season and to all newborns during the RSV season unless the birthing parent received RSV vaccination during pregnancy. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

Nirsevimab to prevent severe respiratory syncytial virus in infants (January 2024)

Nirsevimab is a new antibody that prevents severe respiratory syncytial virus (RSV) infection in infants. In a trial conducted in France, Germany, and the United Kingdom, more than 8000 otherwise healthy infants ≤12 months, born at ≥29 weeks' gestation, and entering their first RSV season were assigned to receive one dose of nirsevimab or no intervention [35]. The group who received nirsevimab had fewer hospitalizations for RSV-associated lower respiratory tract infection (0.3 versus 1.5 percent, efficacy 83.2 percent, 95% CI 67.8-92.0) and fewer infants with an oxygen saturation <90 percent (0.1 versus 0.5 percent, efficacy 75.7 percent, 95% CI 32.8-92.9). These findings further support the use of nirsevimab for RSV immunoprophylaxis in infants. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

NEONATOLOGY

Neurodevelopmental effects of donor versus birth parent milk (March 2024)

For very low birth weight infants, feeding fortified human milk from the birth parent rather than preterm formula appears to have beneficial effects on cognitive development and significantly reduces the risk of necrotizing enterocolitis (NEC); whether cognitive benefits are seen with donor milk is unclear. In a randomized trial of 483 extremely preterm infants without access to birth parent milk that compared fortified donor milk with preterm formula during the birth hospitalization, individuals assigned to donor milk had similar cognitive development outcomes at approximately two years of age but had a lower risk of NEC during hospitalization (adjusted risk difference -5 percent) [36]. Despite the lack of benefit on cognitive outcomes, these findings support our suggestion to use fortified donor milk rather than preterm formula for very low birth weight infants without access to birth parent milk. (See "Human milk feeding and fortification of human milk for premature infants", section on 'Use of donor milk'.)

No benefit of early treatment of PDA in extremely preterm neonates (January 2024)

The optimal timing for intervention in extremely preterm (EPT) neonates with patent ductus arteriosus (PDA) is debated; some centers favor early pharmacologic treatment while others favor expectant supportive care initially. In a multicenter, placebo-controlled trial involving >650 EPT neonates with large PDA, early treatment with ibuprofen resulted in higher rates of PDA closure by three weeks of age, but it did not reduce mortality, moderate or severe bronchopulmonary dysplasia, or other neonatal morbidities [37]. Based on these findings and results from prior clinical trials, we suggest expectant supportive care for PDA rather than early pharmacologic therapy.(See "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome", section on 'Comparison of approaches'.)

Delayed cord clamping in preterm births (December 2023)

Increasing evidence supports delaying cord clamping in preterm births. In an individual participant data meta-analysis of randomized trials of delayed versus immediate cord clamping at births <37 weeks (over 3200 infants), delaying cord clamping for >30 seconds reduced infant death before discharge (6 versus 8 percent) [38]. In a companion network meta-analysis evaluating the optimal duration of delay, a long delay (≥120 seconds) significantly reduced death before discharge compared with immediate clamping; reductions also occurred with delays of 15 to <120 seconds but were not statistically significant [39]. For preterm births that do not require resuscitation, we recommend delayed rather than immediate cord clamping. We delay cord clamping for at least 30 to 60 seconds as approximately 75 percent of blood available for placenta-to-fetus transfusion is transfused in the first minute after birth. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Preterm infants'.)

NEPHROLOGY AND UROLOGY

Single versus divided doses of oral corticosteroids for nephrotic syndrome (March 2024)

Prednisone or prednisolone is the initial treatment of choice for children with idiopathic nephrotic syndrome (NS). In a randomized trial in 60 children with a first episode of NS, a single daily dose and divided-dose therapy both induced remission within six weeks in all participants [40]. Suppression of the hypothalamic-pituitary-adrenal axis after six weeks of therapy was more common in children treated with divided-dose therapy (100 percent) compared with those treated with single-dose therapy (83 percent). These findings support our practice of using single daily doses of prednisone for this condition. (See "Treatment of idiopathic nephrotic syndrome in children", section on 'Initial steroid course'.)

Serial amnioinfusions for bilateral renal agenesis (January 2024)

Bilateral renal agenesis (BRA) is incompatible with extrauterine life because prolonged oligohydramnios results in pulmonary hypoplasia, leading to postnatal respiratory failure. A prospective study (RAFT) assessed use of serial amnioinfusions to treat 18 cases of BRA diagnosed at <26 weeks of gestation [41]. Of the 17 live births, 14 survived ≥14 days and had placement of dialysis access, but only 6 survived to hospital discharge. Of the 4 children alive at 9 to 24 months of age, 3 had experienced a stroke and none had undergone transplant. These findings show that serial amnioinfusions for BRA mitigates pulmonary hypoplasia and increases short-term survival and access to dialysis; however, long-term outcome remains poor with no survival to transplantation. Serial amnioinfusions remain investigational and should be offered only as institutional review board-approved research. (See "Renal agenesis: Prenatal diagnosis", section on 'Investigative role of therapeutic amnioinfusion'.)

NEUROLOGY

Givinostat for Duchenne muscular dystrophy (April 2024)

The histone deacetylase inhibitor givinostat was recently approved by the US Food and Drug Administration for the treatment of Duchenne muscular dystrophy (DMD) in patients six years of age and older. Approval was based on results from a small randomized trial, which suggest that givinostat may slow DMD progression [42]. Benefit was found on only one outcome (the four-stair climb test), as shown by a smaller performance decline from baseline to 72 weeks for the givinostat group compared with placebo (1.25 versus 3.03 seconds); statistical significance was marginal. Adverse effects of givinostat include gastrointestinal disturbances, thrombocytopenia, elevated triglycerides, fever, and potential QTc interval prolongation. While givinostat may be used in combination with glucocorticoid therapy and genetic therapies, its role in the treatment of DMD remains to be defined, and further data are needed to confirm benefit. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Givinostat'.)

Intrathecal gene therapy for giant axonal neuropathy (April 2024)

Giant axonal neuropathy (GAN) is a severe, hereditary neurodegenerative disorder of childhood characterized by a motor and sensory polyneuropathy with ataxia. In a small dose-escalation study in 14 children with GAN, intrathecal administration of an adeno-associated virus-based gigaxonin-containing transgene was associated with slowing of functional decline at 6 to 24 months compared with the pretreatment baseline, and electrodiagnostic studies improved in some patients [43]. Cerebrospinal fluid pleocytosis was observed in nearly all patients within six months after gene transfer but was asymptomatic and self-limited with immunosuppression; two deaths at 8 and 60 months after treatment were deemed possibly related to disease progression and unlikely related to the transgene. These promising results support the possibility of future disease-modifying therapy for GAN, pending further safety and efficacy assessments. (See "Overview of hereditary neuropathies", section on 'Giant axonal neuropathy'.)

Benign acute childhood myositis (January 2024)

Benign acute childhood myositis (BACM) is a self-limited syndrome associated with calf pain and creatinine kinase elevation, often following infection with influenza. In a retrospective study of 65 patients with BACM, the median age was 6.6 years and 66 percent of patients were male [44]. The most common symptoms were bilateral calf pain, refusal to walk, and diffuse weakness. The median creatinine kinase was 1827 U/L, which normalized after an average of seven days. Early recognition of this syndrome allows the clinician to avoid an unnecessary evaluation for other muscle diseases. (See "Overview of viral myositis", section on 'Benign acute childhood myositis'.)

Vamorolone for Duchenne muscular dystrophy (December 2023)

Glucocorticoid treatment with prednisone or deflazacort for Duchenne muscular dystrophy (DMD) is associated with improved motor function, but adverse effects include weight gain, slowing of growth, and bone loss. Vamorolone, a novel steroid, was designed to reduce adverse effects of glucocorticoid therapy for DMD. In the VISION-DMD trial, vamorolone treatment led to improvement on several motor outcomes compared with placebo, while efficacy was similar compared with prednisone [45]. Prednisone treatment (but not vamorolone) led to growth deceleration and bone biomarker abnormalities. Based on these findings, the US Food and Drug Administration approved vamorolone for children age ≥2 years with DMD [46]. We suggest glucocorticoid treatment for children with DMD and anticipate using vamorolone as an alternative to prednisone and deflazacort. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Benefits of glucocorticoid therapy'.)

Acute encephalopathy with biphasic seizures and late reduced diffusion (November 2023)

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a parainfectious syndrome characterized by presentation with febrile status epilepticus (FSE) followed by a brief seizure-free period before recurrence of seizures in clusters. In a retrospective study from Japan of 55 patients presenting with FSE, the development of AESD in 11 patients was associated with longer time from seizure onset to hospital arrival, presence of hypoxia, and later treatment with antiseizure medications [47]. These findings suggest that shortening the seizure duration by early effective treatment and preventing hypoxia during ambulance transportation might reduce the risk of AESD. (See "Clinical features and evaluation of febrile seizures", section on 'Acute encephalopathy with biphasic seizures and late reduced diffusion'.)

Expert panel on epilepsy with eyelid myoclonia (November 2023)

Epilepsy with eyelid myoclonia (EEM; Jeavons syndrome) is a female-predominant generalized epilepsy syndrome with onset from 3 to 12 years of age characterized by eyelid myoclonia, photosensitivity, and eye closure-induced seizures or paroxysms on electroencephalography (EEG). Recently, an international expert panel found a strong consensus that EEM is often underdiagnosed, that a correct diagnosis can only be made with EEG including photic stimulation, and that an earlier age at onset is associated with an increased risk of intellectual disability and drug-resistant epilepsy [48]. Management generally involves reducing exposure to provoking factors (eg, visual stimuli, various sources of natural and artificial light) and use of antiseizure medication such as levetiracetam or valproate [49]. (See "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)'.)

PULMONOLOGY

SCCM guidelines on the management of hyperglycemia in critically ill patients (May 2024)

The Society of Critical Care Medicine (SCCM) has issued new guidelines for the management of hyperglycemia in critically ill adults and children [50,51]. Compared with the 2012 guidelines, emphasis was placed on the use of management protocols (with decision support tools) that avoid hypoglycemia and liberalization of blood glucose targets (eg, 7.8 to 11.1 mmol/L [140 to 200 mg/dL]) with frequent monitoring (≤1 hourly). We agree with the new SCCM recommendations. While we use a lower upper limit for blood glucose (180 mg/dL [10 mmol/L]) than that recommended by the SCCM, it is unlikely to be clinically meaningful. (See "Glycemic control in critically ill adult and pediatric patients", section on 'Our approach'.)

Revised diagnostic criteria for allergic bronchopulmonary aspergillosis (May 2024)

Allergic bronchopulmonary aspergillosis (ABPA), a complex hypersensitivity reaction to airway colonization with Aspergillus fumigatus, can be hard to distinguish from difficult-to-treat asthma or cystic fibrosis. The International Society for Human and Animal Mycology (ISHAM) working group for ABPA recently published revised diagnostic criteria (table 2) that make some key changes to improve the sensitivity and specificity of the diagnosis [52]:

●Total serum immunoglobulin (Ig) E levels of ≥500 international units/mL are sufficient for the diagnosis, rather than the previously higher threshold of 1000 international units/mL.

●Elevated Aspergillus IgG levels by enzyme immunoassay or lateral flow assay are more sensitive for detecting sensitivity to Aspergillus antigens and should be used preferentially over Aspergillus serum precipitins.

We agree with the revised ISHAM diagnostic approach. (See "Clinical manifestations and diagnosis of allergic bronchopulmonary aspergillosis", section on 'Diagnostic criteria'.)

High-flow nasal cannula oxygen therapy in children with bronchiolitis (April 2024)

High-flow nasal cannula (HFNC) oxygen therapy is increasingly used for children with bronchiolitis and significant respiratory distress, but the clinical benefit has been questioned. In a meta-analysis of eight trials (over 2100 patients <2 years old with bronchiolitis) that compared oxygen therapy using HFNC with standard (low-flow) oxygen, the risk of escalation of therapy was lower with HFNC oxygen therapy; rates of adverse events were similar in the two groups (four studies, nearly 1800 patients, approximately 1 percent) [6]. Interpretation of these results is limited by significant heterogeneity and risk of bias. These findings suggest that HFNC oxygen therapy provides modest benefit for children with bronchiolitis without increasing adverse events. For children with bronchiolitis, we suggest HFNC in patients with severe respiratory distress; we advise against routine use of HFNC for children with hypoxemia and mild-to-moderate increased work of breathing. (See "Bronchiolitis in infants and children: Treatment, outcome, and prevention", section on 'High-flow nasal cannula'.)