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What's new in pediatrics

What's new in pediatrics
Authors:
Alison G Hoppin, MD
Elizabeth TePas, MD, MS
Mary M Torchia, MD
Carrie Armsby, MD, MPH
Laurie Wilkie, MD, MS
Literature review current through: May 2022. | This topic last updated: Jun 30, 2022.

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

Impact of screen time on recovery from concussion in adolescents and young adults (February 2022)

Observational studies suggest that cognitive exertion after sustaining a concussion (eg, reading, screen time, or taking standardized tests) may delay recovery and exacerbate symptoms. In a new randomized trial of 125 adolescents and young adults with acute head trauma who were diagnosed with a concussion during an emergency department evaluation, individuals permitted to have screen time as tolerated had a longer time to recovery compared with those assigned to abstain from screen time for 48 hours after injury (median 8 versus 3.5 days, respectively) [1]. Median screen time in the unrestricted group was approximately 10 hours over 2 days, compared with approximately 2 hours in the restricted group. High loss to follow-up and use of self-report to measure screen time limit interpretation of this study. However, these findings support our suggestion for reasonable cognitive rest with avoidance of mental activities that worsen symptoms after a concussion. (See "Concussion in children and adolescents: Management", section on 'Cognitive rest'.)

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

Firearms are the leading cause of death in children in the United States (June 2022)

Firearm injury (homicide, suicide, or unintentional) is a major cause of morbidity and mortality in the United States. In 2019, firearms surpassed motor vehicle crashes (MVC) as the leading cause of death in children and adolescents (age 1 to 19 years) [2-4]. This finding highlights the increasing numbers of firearm deaths, driven largely by homicides in adolescents, as well as the success of interventions to prevent MVC deaths such as car seats, booster seats, side airbags, rear facing cameras, and lane departure warnings. (See "Firearm injuries in children: Prevention", section on 'Firearm injuries'.)

Phentermine-topiramate for treatment of obesity in adolescents (June 2022)

Pharmacotherapy is occasionally used for adolescents with obesity as an adjunct to diet and physical activity interventions, but therapeutic options are limited. The combination of phentermine and topiramate was evaluated in a 56-week, randomized dose-ranging trial in 223 adolescents with obesity unresponsive to diet and exercise interventions [5]. For the higher dose of phentermine-topiramate (15 mg/92 mg), placebo-adjusted change in body mass index was -5.3 kg/m2 (95% CI -6.4 to -4.3) with a good safety profile. These outcomes are similar to those seen in larger studies in adults and suggest that phentermine-topiramate may be useful for management of obesity in selected adolescents, in combination with ongoing lifestyle intervention. Based on these findings, phentermine-topiramate has been approved by the US Food and Drug Administration for treatment of obesity in adolescents 12 years and older. (See "Prevention and management of childhood obesity in the primary care setting", section on 'Pharmacotherapy'.)

Screening for eating disorders (May 2022)

Although eating disorders (ED; eg, binge eating disorder, bulimia nervosa, anorexia nervosa) are associated with significant morbidity and mortality, the United States Preventive Services Task Force concluded that for asymptomatic individuals with a normal or high body mass index, the evidence is insufficient to determine the balance between the benefits and harms (unnecessary referrals, treatment, labeling, anxiety, stigma) of screening [6]. We suggest screening patients who are at increased risk for ED, such as those who manifest signs or symptoms of ED or who have a history of trauma (eg, experiencing or witnessing an event that may cause or threaten death, serious injury, or sexual violence). (See "Eating disorders: Overview of epidemiology, clinical features, and diagnosis", section on 'Screening'.)

COVID-19-associated croup in young children (May 2022)

Croup has increasingly been recognized as a manifestation of COVID-19 in young children, particularly during the Omicron surge. It is unclear whether the severity of illness or response to treatment differs between COVID-19-associated croup and other viral croup etiologies. The largest case series included 75 children with COVID-19-associated croup. Most patients were treated with dexamethasone (97 percent); 37 percent of patients received racemic epinephrine [7]. A large majority of patients (88 percent) responded well and were discharged from the emergency department. Among patients requiring hospitalization, most required repeated doses of racemic epinephrine and dexamethasone; four children required intensive care. No patients required invasive ventilation or died. These findings suggest that most patients with COVID-19-related croup can be successfully managed with standard croup therapies. (See "Croup: Clinical features, evaluation, and diagnosis", section on 'Etiology'.)

Prophylactic oral dextrose gel in at risk newborns does not improve neurodevelopmental outcomes (April 2022)

Oral dextrose gel (ODG) is an effective treatment for documented neonatal hypoglycemia. However, the benefits of prophylactic use in newborns with risk factors (eg, large or small for gestational age, late prematurity, or maternal diabetes) but without hypoglycemia are unclear. In a planned follow-up of almost 1200 infants from the multicenter randomized hPOD trial, neurodevelopmental outcomes at two years corrected age were similar for those who were assigned to ODG at one hour of age compared with placebo [8]. Based on these findings, we do not suggest prophylactic ODG for at-risk newborns. Instead, treatment should consist of early oral feeding (ie, within the first hour after birth), routine blood glucose monitoring, and use of ODG only if the newborn has documented hypoglycemia. (See "Management and outcome of neonatal hypoglycemia", section on 'Dextrose gel'.)

Long-term effectiveness of school-based prevention to reduce alcohol use in adolescents (April 2022)

Alcohol use is a leading cause of disease and injury among adolescents and young adults worldwide. Preventive strategies at school may be effective in the short term; however, little is known about their long-term effectiveness. A recent study evaluated 2190 students (mean age 13.3 years) who had participated in a prior randomized trial that compared various preventive strategies (universal web-based prevention, selective prevention for high-risk students, or a combination of the two) with health education as usual [9]. At seven-year follow-up, individuals from all three intervention groups had reduced odds of alcohol-related harms compared with the health education group. Results from this study support the concept that benefits of school-based interventions are sustained beyond secondary schools and into early adulthood. (See "Psychosocial interventions for substance use disorder in adolescents", section on 'School-based treatment'.)

COVID-19 vaccination in pregnancy improves infant outcomes (February 2022)

COVID-19 vaccination of pregnant women reduces serious maternal and pregnancy morbidity from infection. In an analysis of data from 30 pediatric hospitals in the United States during a period of Delta and Omicron variant circulation, infants <6 months of age were 52 percent less likely to be hospitalized with COVID-19 if their mothers became fully vaccinated with an mRNA COVID-19 vaccine during pregnancy [10]. Furthermore, 90 percent of the intensive care unit admissions for COVID-19 and the only two deaths occurred among infants of unvaccinated mothers. Thus, maternal vaccination also appears to protect infants in the first six months of life. (See "COVID-19: Overview of pregnancy issues", section on 'Safety and efficacy'.)

COVID-19 vaccination improves outcomes of infected pregnant patients (February 2022, Modified February 2022)

A recent population-based study of over 18,000 pregnant patients in Scotland provides the first evidence of more favorable pregnancy outcomes among those who have received COVID-19 vaccination [11]. In pregnant patients with COVID-19, unvaccinated individuals represented a significantly higher proportion of COVID-19-associated hospital admissions (90 percent), COVID-19-associated critical care admissions (98 percent), and perinatal deaths (100 percent of stillbirths and neonatal deaths). The perinatal death rate in the vaccinated cohort was similar to historical background rates and the rates in pregnant people without COVID-19. These findings further support universal recommendations for pregnant people to be up-to-date with COVID-19 vaccination. (See "COVID-19: Overview of pregnancy issues", section on 'Safety and efficacy'.)

Vaccination against human papillomavirus, especially at an early age, is associated with greater reductions in cervical cancer (December 2021)

Human papillomavirus (HPV) vaccination has been shown to decrease incidence of HPV infection and cervical intraepithelial neoplasia (CIN), but whether vaccinating females at an earlier age is associated with lower incidence of cervical cancer has not been well established. In a registry-based observational study of 13.7 million years of follow-up of females aged 20 to 30 years, females who received the bivalent HPV vaccine at a younger age had a greater relative reduction in the incidence of cervical cancer and CIN3 (34 percent for vaccination at age 16 to 18 years, 62 percent at age 14 to 16 years, and 87 percent at age 12 to 13 years) compared with the unvaccinated cohort [12]. This lends further support to vaccinating against HPV at a younger age. (See "Human papillomavirus vaccination", section on 'Cervical, vaginal, and vulvar disease'.)

NEONATOLOGY

Postnatal hydrocortisone does not reduce bronchopulmonary dysplasia in preterm neonates (April 2022)

Postnatal dexamethasone therapy reduces bronchopulmonary dysplasia (BPD) in preterm infants, but use is limited due to concerns that it increases the risk of neurodevelopmental impairment (NDI), particularly cerebral palsy. Hydrocortisone has been proposed as an alternative since it may have a lower risk of NDI, though its efficacy for reducing BPD remains uncertain. In a randomized trial comparing hydrocortisone with placebo in 800 preterm neonates who had been intubated for at least seven days, rates of BPD, hospital mortality, and moderate to severe NDI at two years were similar between groups [13]. Thus, we continue to recommend against the routine use of use of postnatal corticosteroid therapy, and we reserve dexamethasone for high-risk preterm infants (ie, those who remain ventilator dependent at two to four weeks after birth). (See "Prevention of bronchopulmonary dysplasia: Postnatal use of corticosteroids", section on 'Hydrocortisone'.)

Prophylactic oral dextrose gel in at risk newborns does not improve neurodevelopmental outcomes (April 2022)

Oral dextrose gel (ODG) is an effective treatment for documented neonatal hypoglycemia. However, the benefits of prophylactic use in newborns with risk factors (eg, large or small for gestational age, late prematurity, or maternal diabetes) but without hypoglycemia are unclear. In a planned follow-up of almost 1200 infants from the multicenter randomized hPOD trial, neurodevelopmental outcomes at two years corrected age were similar for those who were assigned to ODG at one hour of age compared with placebo [8]. Based on these findings, we do not suggest prophylactic ODG for at-risk newborns. Instead, treatment should consist of early oral feeding (ie, within the first hour after birth), routine blood glucose monitoring, and use of ODG only if the newborn has documented hypoglycemia. (See "Management and outcome of neonatal hypoglycemia", section on 'Dextrose gel'.)

Alternative birthing practices to avoid (February 2022)

The American Academy of Pediatrics recently advised avoiding the following alternative birthing practices because they have been (or may be) associated with increased risks of neonatal morbidity and mortality and have no clear benefits: water birth, vaginal seeding, umbilical cord nonseverance, placentophagy, nonmedical deferral of hepatitis B vaccination and ocular prophylaxis, and delayed bathing of newborns exposed to active genital herpes simplex virus lesions or maternal history of bloodborne pathogens (eg, HIV, hepatitis B or C virus) [14]. Supporting evidence linking each of these practices with increased risk is reviewed in the guideline. We agree with this advice. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Alternative birthing practices that should be avoided'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Group A Streptococcus prophylaxis in patients with acute rheumatic heart disease (June 2022)

Patients with acute rheumatic fever (ARF) require antibiotic prophylaxis to prevent recurrent group A Streptococcus pharyngitis and progression of their cardiac disease. Benzathine penicillin G (BPG) given intramuscularly (IM) every 28 days is the preferred regimen for most patients (table 1). However, prior case series and case reports have described sudden death within minutes of IM BPG administration in patients with severe acute rheumatic heart disease; these events are now attributed to vasovagal syncope with coronary hypoperfusion rather than anaphylaxis. For patients with a history of ARF who have developed severe, symptomatic valvular disease, New York Heart Association class III or IV heart failure, or ventricular dysfunction (ejection fraction <50 percent), a new American Heart Association recommends prophylaxis with an oral antibiotic (eg, oral penicillin V) rather than IM BPG [15]. We agree with this recommendation. (See "Acute rheumatic fever: Treatment and prevention", section on 'Severe valvular disease'.)

Peanut oral immunotherapy in children less than four years of age (January 2022)

Data suggest the efficacy of peanut oral immunotherapy (OIT) increases as the age at treatment onset decreases. This finding was confirmed in a prespecified subset of children <4 years of age who were part of a trial of children with peanut allergy randomly assigned to peanut OIT (minimum daily maintenance dose target 250 mg, maximum 2000 mg) or placebo [16]. In these younger patients, desensitization after two years of maintenance therapy and sustained unresponsiveness (SU) after six months of avoidance was reported in 71 and 21 percent versus 2 and 2 percent in the treatment and placebo groups, respectively. Whether those with SU have developed permanent tolerance or whether additional children would develop SU after a longer course of maintenance therapy remains to be determined. (See "Oral immunotherapy for food allergy", section on 'Efficacy'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Evidence-informed milestone checklists for developmental surveillance (March 2022)

Parents and clinicians often use milestone checklists to identify children with developmental delays or disabilities. Limitations of existing checklists include inconsistency, lack of validation, lack of primary references, and uncertain thresholds for concern. The Centers for Disease Control and Prevention and the American Academy of Pediatrics compiled new checklists that are supported by normative data and well referenced (table 2) [17]. Among other criteria, they chose milestones that are achievable by ≥75 percent of children at ages corresponding to well-child visits; are easily observable in the natural setting by caregivers of different social, cultural, and ethnic backgrounds; and demonstrate progression with age. We recommend use of these evidence-informed checklists. (See "Developmental-behavioral surveillance and screening in primary care", section on 'Approach to surveillance'.)

EMERGENCY MEDICINE

Nonoperative management of appendicitis in children (June 2022)

In a retrospective observational study of over 73,500 United States children treated for nonperforated appendicitis from 2011 to 2020, 14 percent were managed nonoperatively, with an increase from 3 to 33 percent during the study period [18]. Of children managed nonoperatively, the one- and five-year failure rates resulting in appendectomy were 19 and 23 percent, respectively, and the rate of perforation at the time of delayed surgery was higher than the rate in children who underwent early surgery (46 versus 38 percent). Appendectomy for early appendicitis remains the treatment of choice for most children diagnosed with appendicitis, although nonoperative management (NOM) appears to be increasing. NOM may be a safe option for older children with early appendicitis and imaging that shows an appendiceal diameter ≤1.1 cm and no appendicolith. (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)

Early physical activity in adolescents with acute concussion (February 2022)

In a multicenter, randomized trial of over 450 adolescents (mean age 13 years) with acute concussion, incremental resumption of physical activity within 72 hours after injury rather than waiting until symptoms resolved did not significantly reduce concussion symptoms two weeks after injury [19]. However, confidence intervals were wide, the rate of adherence was low in both groups, and a per protocol analysis in adherent patients suggested a benefit of physical activity. Smaller trials have supported a benefit of early initiation of physical activity after concussion. For children and adolescents with an acute concussion, we recommend physical rest for up to 48 hours after injury followed by stepwise resumption of physical activity (table 3). (See "Concussion in children and adolescents: Management", section on 'Physical rest'.)

ENDOCRINOLOGY

Idiopathic intracranial hypertension during treatment for precocious puberty (May 2022)

Two case reports describe idiopathic intracranial hypertension (IIH, pseudotumor cerebri) developing during gonadotropic-releasing hormone (GnRH) agonist therapy for precocious puberty [20,21]. Both patients developed papilledema soon after starting monthly injections. No other etiology was found and the IIH resolved after drug withdrawal and acetazolamide treatment. Based on reports like these, the US Food and Drug Administration has added a warning regarding IIH to GnRH agonist drug labels [22]. Children receiving GnRH agonist therapy warrant monitoring for signs or symptoms of IIH (eg, progressive headache, papilledema, or blurred vison). (See "Treatment of precocious puberty", section on 'Safety'.)

Closed-loop insulin pumps (artificial pancreas) for young children with type 1 diabetes (January 2022)

Hybrid closed-loop (HCL) insulin delivery systems (artificial pancreas) have established benefits in most age groups with type 1 diabetes (T1D), but their use in very young children has not been rigorously studied. A 16-week randomized crossover trial in 74 children two to seven years of age with well-controlled T1D compared a HCL system with a sensor-augmented insulin pump [23]. The HCL system increased percent of time in glycemic target range (71.6 versus 62.9 percent; mean adjusted difference 8.7 percentage points [95% CI 7.4-9.9]), with the greatest benefits during the night. The system also modestly decreased hemoglobin A1c and time spent in hyperglycemic range, but did not alter the overall time spent in the hypoglycemic range. One serious hypoglycemic event occurred, attributable to user error. These findings support the efficacy and safety of HCL systems for young children when used with age-appropriate settings and caregiver training. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Closed-loop insulin pumps'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Mild direct hyperbilirubinemia in newborns and later development of biliary atresia (June 2022)

Biliary atresia (BA) usually comes to medical attention after the first few weeks of life, when a young infant presents with jaundice and conjugated hyperbilirubinemia, defined as conjugated or direct bilirubin ≥1 mg/dL (17.1 micromol/L). In a new study of 346 infants who had direct bilirubin measured within the first three days of life, direct bilirubin >0.45 mg/dL (7.7 micromol/L) was a predictor of later diagnosis of BA (sensitivity 100 percent, specificity 15.4 percent), although confidence intervals were wide [24]. These findings suggest that mild elevations of serum conjugated or direct bilirubin in neonates may be predictors of later development of BA; such infants should be monitored and evaluated further to permit early diagnosis of BA. (See "Biliary atresia", section on 'Laboratory studies'.)

Outbreak of acute hepatitis in young children (June 2022)

In early 2022, an outbreak of acute hepatitis was identified among young children in several countries, including the United States. Preliminary analysis suggested a possible link with adenovirus type 41. However, analysis of data from four large administrative databases in the United States through March 2022 showed no overall increase in hospitalizations for hepatitis of unknown cause compared to before the COVID-19 pandemic and no increase in adenovirus types 40/41 positivity [25]. Thus, it is unclear whether the reported cases in the United States represent a novel cause of acute hepatitis or a previously existing phenomenon, and whether there is a relationship with adenovirus infection. (See "Acute liver failure in children: Etiology and evaluation", section on 'Outbreak 2022'.)

Morbidity of high-powered magnet ingestion (February 2022)

The incidence of high-powered neodymium (rare earth) magnet ingestions has increased markedly in the United States after marketing restrictions were overturned in 2016. In a new multicenter retrospective cohort study of 574 children with high-powered magnet ingestions, 57 children (9.6 percent) had a life-threatening complication, including intestinal perforation, fistula, obstruction, bleeding, infection, or volvulus [26]. All cases with these complications involved two or more magnets, and almost all were small magnets (<5 cm). These findings show the substantial morbidity of high-powered magnet ingestion and call for further measures to limit their availability to children. (See "Foreign bodies of the esophagus and gastrointestinal tract in children", section on 'Magnets'.)

Maralixibat for cholestatic pruritus in Alagille syndrome (January 2022)

Alagille syndrome is a genetic disorder characterized by chronic cholestatic liver disease and often complicated by severe refractory pruritus. In a randomized trial in 29 children with Alagille syndrome, maralixibat, an inhibitor of intestinal bile acid transport, reduced mean serum bile acids and improved pruritus symptoms, quality of life, linear growth and xanthomas, and was well tolerated [27,28]. Whether maralixibat attenuates the progression of liver disease has not been established. Treatment effects were generally maintained in the open-label extension (mean duration 2.6 years). These findings were the basis for approval of maralixibat by the US Food and Drug Administration for cholestatic pruritus in Alagille syndrome. (See "Causes of cholestasis in neonates and young infants", section on 'Alagille syndrome'.)

Inflammatory bowel disease and response to COVID-19 vaccination (January 2022)

Data on the immunogenicity of COVID-19 vaccines in patients with inflammatory bowel disease (IBD) are emerging. In a study of nearly 600 adults with IBD who received mRNA SARS-CoV-2 vaccination, 99 percent who were tested two weeks after the second vaccine dose had detectable antibodies, regardless of medication regimen (ie, biologic therapy, small molecule therapy, immunomodulator therapy, and/or glucocorticoids) [29]. For patients with IBD, this study demonstrates high rates of initial humoral response, provides reassurance for those on immunosuppressive medications, and supports our recommendation for vaccination. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'COVID-19 vaccination'.)

GENETIC AND METABOLIC DISORDERS

Ex vivo gene therapy for metachromatic leukodystrophy (January 2022)

Ex vivo gene therapy is a new treatment approach for metachromatic leukodystrophy (MLD), which is caused by pathogenic variants in the arylsulfatase A (ARSA) gene. A new study reported promising results in 26 children with pre- or early-symptomatic MLD who received an autologous hematopoietic stem cell transplant using stem cells transduced with an ARSA gene therapy construct (arsa-cel) [30]. Participants had improvement or stabilization of motor skills compared with an untreated cohort; most treated patients showed normal cognitive development, and a subset showed improvement in peripheral nerve conduction velocity. Interim analysis of this study led to approval of this therapy in the European Union and United Kingdom. However, autologous transplant using gene therapy has not been compared with allogeneic transplant; short- and long-term complications of gene therapy remain a concern; and the initial cost of gene therapy is greater. Allogeneic transplant remains the standard of care for individuals with presymptomatic or minimally symptomatic MLD who have an available donor. (See "Metachromatic leukodystrophy", section on 'Ex vivo gene therapy'.)

HEMATOLOGY AND ONCOLOGY

New juvenile hemochromatosis gene (April 2022)

A recent report has identified a new cause of juvenile hemochromatosis in three children with neurologic abnormalities and iron overload [31]. Each child had a pathogenic variant in the PIGA gene, which encodes the first enzyme in the pathway that adds a glycophosphatidylinositol (GPI) anchor to certain plasma membrane proteins to maintain their cell surface attachment. The hemojuvelin protein is GPI-anchored, suggesting a possible mechanism of iron overload; the mechanism of the neurologic findings remains unexplained. (See "HFE and other hemochromatosis genes", section on 'PIGA'.)

Duration of anticoagulation for low-risk provoked venous thromboembolism in pediatric patients (February 2022)

The optimal duration of anticoagulant therapy for children with venous thromboembolism (VTE) is uncertain. Usual practice has been to treat for three months based largely upon evidence from adult studies. However, a recent clinical trial suggests that six weeks of therapy is sufficient for most pediatric patients with low-risk provoked VTE (ie, attributable to a transient risk factor) [32]. The trial enrolled 417 children with provoked VTE (catheter-associated in 50 percent; infection-related in 30 percent; surgery- or trauma-related in 20 percent) who were randomly assigned to six weeks or three months of anticoagulant therapy. At one year, rates of VTE recurrence were similarly low in both groups (1.1 and 1.6 percent, respectively). Based upon these findings, we now suggest a six-week course of treatment for pediatric patients with provoked VTE who met all of the following low-risk criteria:

No prior history of VTE

The VTE is not severe or life-threatening

The provoking risk factor resolves within six weeks

The thrombus resolves or is nonocclusive within six weeks

For patients with provoked VTE who do not meet these criteria, we continue to suggest three months of therapy. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Provoked VTE'.)

New consensus for managing alpha thalassemia major (January 2022)

Alpha thalassemia major (ATM; deletion of all four alpha globin genes) was once considered incompatible with life, but advances in prenatal and postnatal care have resulted in viability and good quality of life for an increasing number of individuals. A new consensus document outlines management principles for ATM, which include prenatal screening, confirmation of the diagnosis early in the pregnancy, nondirective counseling, and, for those who choose to continue the pregnancy with fetal therapy, intrauterine transfusions (IUTs) started as early as technically possible [33]. Delivery should occur in a facility that can provide high-level critical care. Some neonates may need aggressive resuscitation at birth, although this is generally unnecessary after serial IUTs. Education about options for future pregnancy should be provided. (See "Alpha thalassemia major: Prenatal and postnatal management".)

Gene therapy for thalassemia (December 2021)

Earlier studies of gene therapy for thalassemia determined that therapy is most effective when used for individuals with transfusion-dependent beta thalassemia who had some beta globin production (non-beta0/beta0 genotypes). A new gene therapy study restricted to this population has observed encouraging results, with transfusion independence in 20 of 22 evaluable patients (91 percent), including 6 of 7 children <12 years of age [34]. Hematopoietic stem cell transplantation with myeloablative chemotherapy is required. (See "Management of thalassemia", section on 'Gene therapy and other stem cell modifications'.)

Gene therapy for sickle cell disease (December 2021)

The largest study of gene therapy for sickle cell disease has been published, including data from 35 patients with a median follow-up of over 17 months [35]. The gene therapy construct uses an anti-sickling variant of beta globin, introduced into autologous hematopoietic stem and progenitor cells that are delivered by autologous hematopoietic stem cell transplant. After transplant, vaso-occlusive events decreased from a mean of 3.5 to 0 annually, and median hemoglobin increased from 8.5 to ≥11 g/dL. Transplant toxicities were as expected; one individual with underlying pulmonary hypertension and hypertrophic cardiomyopathy died after 20 months. Other gene therapy and gene editing approaches are under study. (See "Investigational therapies for sickle cell disease", section on 'Anti-sickling beta globin gene'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Shortened regimen for children with nonsevere, smear-negative TB (June 2022)

The prolonged treatment duration for tuberculosis (TB) is burdensome. The SHINE trial (Shorter Treatment for Minimal TB in Children) evaluated a shorter course among 1204 children <16 years old with nonsevere, smear-negative, presumed drug-susceptible TB [36]. All participants received an intensive phase (eight weeks of isoniazid, rifampin, and pyrazinamide, with or without ethambutol) then were randomly assigned to complete a total of four versus six months of therapy with isoniazid and rifampin. Rates of the primary outcome (treatment failure, loss to follow-up during treatment, or death by 72 weeks) were similar in both groups (3 percent each). Based on these findings, we suggest the shortened four-month regimen for selected children aged 3 to 16 years with nonsevere, smear-negative pulmonary TB. (See "Tuberculosis disease in children", section on 'Shortened (four-month) regimen for nonsevere, smear-negative disease'.)

Duration of therapy for uncomplicated community-acquired pneumonia in children in resource-rich settings (June 2022)

In infants and children four months and older with uncomplicated community-acquired pneumonia (CAP), the usual duration of antimicrobial therapy is seven days. In a meta-analysis of four randomized trials (>1500 participants) comparing 3 to 5 days with 7 to 10 days of outpatient antibiotic therapy for uncomplicated CAP in children in resource-rich settings, the rates of retreatment (approximately 8 percent) and hospitalization (0 percent) after one month were similar between groups, as were rates of adverse events [37]. Study participants had a mean age of <37 months, and 80 percent of participants had respiratory viruses in the only trial that tested for them. The results are not generalizable to older children who are more likely to have bacterial pathogens or to hospitalized children. We continue to treat uncomplicated CAP for at least five days. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Duration'.)

COVID-19 vaccination in children 6 months and older (June 2022)

As of June 2022, the US Food and Drug Administration (FDA) has authorized BNT162b2 (Pfizer COVID-19 vaccine) and mRNA-1273 (Moderna COVID-19 vaccine) for use in children 6 months and older. Trials in children 6 months to 11 years have demonstrated that these vaccines, given at lower doses, elicit neutralizing immune responses comparable to those in adolescents and adults following standard doses [38-40]. Vaccination also reduces the risk of symptomatic COVID-19 in these populations, although the estimates of effect vary, in part because of different variants prevalent during the trials. There were no cases of vaccine-associated myocarditis in the trials; the precise risk is uncertain but is expected to be lower than that seen in older individuals. We agree with recommendations from the Centers for Disease Control and Prevention to give BNT162b2 or mRNA-1273 to children ages 6 months to 11 years. Clinicians should be aware that the dose and formulation used for children are different than those for adolescents and adults (table 4). (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)

Second COVID-19 vaccine booster dose for selected individuals (April 2022, Modified May 2022)

In the United States, the Food and Drug Administration authorized and the Centers for Disease Control and Prevention (CDC) recommends a second booster dose of an mRNA COVID-19 vaccine (given at least four months after the first) for individuals who are >50 years old or are ≥12 years old and have certain immunocompromising conditions (table 1) [41,42]. The CDC also indicates that a second booster dose with an mRNA vaccine is an option for any individual who received Ad26.COV2.S (Janssen/Johnson and Johnson) for both the primary and booster doses. Vaccine effectiveness following a primary series and single booster dose appears to wane, and observational studies suggest that a second booster dose is associated with increased protection against severe COVID-19 and death [43,44]. (See "COVID-19: Vaccines", section on 'Role of booster vaccinations/waning efficacy'.)

Remdesivir approved for treatment of COVID-19 in children age 28 days and older (April 2022)

In April 2022, the US Food and Drug Administration (FDA) expanded approval for remdesivir treatment of COVID-19 to include children ≥28 days of age who weigh ≥3 kg [45,46]. Indications include hospitalization and, for outpatients, mild to moderate COVID-19 with a high risk of progression to severe disease. The FDA based approval on clinical trials in adults and a single-arm, open-label study in 53 hospitalized children ≥28 days of age, in which remdesivir was associated with improvement in clinical status. We make decisions about the use of remdesivir in children with SARS-CoV-2 infection on a case-by-case basis. (See "COVID-19: Management in children", section on 'SARS-CoV-2 antiviral therapy for select patients'.)

Nirsevimab for prevention of RSV in healthy infants (April 2022)

Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is a leading cause of hospitalization in infants. Most RSV LRTI hospitalizations occur in infants ineligible for palivizumab prophylaxis. In a multinational, placebo-controlled, randomized trial in nearly 1500 healthy infants born at ≥35 weeks gestation, a single injection of nirsevimab lowered rates of RSV infection requiring inpatient or outpatient medical attention within 150 days (1.2 versus 5 percent; efficacy of 75 percent) [47]. Although hospitalization rates were similar (0.6 and 1.6 percent), investigators paused enrollment before the target of 3000 participants due to effects of the COVID-19 pandemic on the circulation of RSV. Nirsevimab is not licensed for clinical use while awaiting additional safety and efficacy data. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Nirsevimab'.)

Clinical presentation of COVID-19 cases due to Delta and Omicron variant (April 2022)

Symptoms of upper respiratory tract infection (URI) are the most common manifestations of nonsevere COVID-19, although the relative frequency of each symptom may vary by viral variant. In an observational study evaluating the reported clinical symptoms of over 63,000 confirmed COVID-19 cases between two time periods (during Delta variant predominance and Omicron variant predominance), nasal congestion, headache, sneezing, and sore throat were the most common presenting symptoms [48]. Sore throat was more common and alteration or loss of smell was less common during the time period of Omicron predominance. As new variants emerge, the predominant URI symptoms of COVID-19 may continue to change. (See "COVID-19: Clinical features", section on 'Initial presentation'.)

Omicron variant associated with increased COVID-19 hospitalizations in children (March 2022)

With predominance of the Omicron (B.1.1.529) SARS-CoV-2 variant in the United States, weekly COVID-19 hospitalization rates among children reached an all-time high in January 2022 (7.1 per 100,000 population) [49]. Hospitalization rates were particularly high (15.6 per 100,000 population) in children age 0 to 4 years, who are not eligible for vaccination. Despite increased rates of hospitalization, the proportion of children and adolescents requiring intensive care or invasive mechanical ventilation was lower with Omicron than earlier circulating strains. Greater proportions of unvaccinated than fully vaccinated adolescents had COVID-19 as the primary reason for hospitalization (70 versus 41 percent) and required intensive care (30 versus 16 percent), highlighting the benefits of vaccination. (See "COVID-19: Clinical manifestations and diagnosis in children", section on 'Hospitalization and death'.)

ACIP recommendations on dengue vaccination (February 2022)

Dengue is endemic to tropical regions of the world, including the US territories of Puerto Rico, American Samoa, the US Virgin Islands, the Federated States of Micronesia, and the Republic of Palau. In December 2021, the CDC Advisory Committee on Immunization Practices (ACIP) recommended the dengue vaccine CYD-TDV (Dengvaxia) for children aged 9 to 16 who live in those US territories and have serologic evidence of prior infection [50]. Serology for dengue must be performed prior to vaccination. In trials, breakthrough infection after vaccination was more likely to be severe in individuals who were seronegative at baseline, and thus such individuals should not receive the vaccine. It is not approved for travelers visiting dengue-endemic areas. (See "Dengue virus infection: Prevention and treatment", section on 'CYD-TDV (Dengvaxia)'.)

COVID-19: Updated CDC recommendations for isolation and quarantine in the community (January 2022)

In December 2021, the United States Centers for Disease Control and Prevention (CDC) updated recommendations on home isolation for individuals with SARS-CoV-2 infection and post-exposure precautions in the community [51]. For select immunocompetent patients with infection (eg, those who are asymptomatic; those with mild, improving infection), the duration of isolation was reduced from 10 to 5 days, followed by strict mask-wearing when around others for another 5 days. Following exposure, people should monitor for symptoms and wear masks when around others for 10 days; those not up-to-date on vaccination should quarantine at home for the first 5 days. Additional details on the role of testing and other restrictions during the post-infection or post-exposure period, as well as updated recommendations for quarantine and isolation for healthcare personnel can be found on the CDC website. (See "COVID-19: Epidemiology, virology, and prevention", section on 'Testing and quarantine' and "COVID-19: Infection prevention for persons with SARS-CoV-2 infection", section on 'In the community setting'.)

NEUROLOGY

Fenfluramine for seizures associated with Lennox-Gastaut syndrome (April 2022)

Lennox-Gastaut syndrome (LGS) is associated with severe seizures in childhood and a poor neurologic prognosis. Evidence supporting the benefit of fenfluramine comes from a trial of 263 patients with LGS, in which the median reduction in seizure frequency was greater with high-dose fenfluramine compared with placebo (-23.7 versus -8.7 percent) [52,53]. Most patients in the trial were taking one or more concomitant antiseizure medications. Based upon these results, fenfluramine was approved by the by the US Food and Drug Administration for the treatment of seizures associated with LGS in patients two years of age and older [54]. Fenfluramine will likely be used as an adjunct antiseizure mediation in patients with LGS who have refractory seizures. Due to the risk of cardiac valve injury and pulmonary hypertension, fenfluramine is available only through a risk evaluation and mitigation strategy program. (See "Epilepsy syndromes in children", section on 'Treatment of LGS'.)

Antiseizure medication withdrawal in seizure-free patients (February 2022)

A recent practice advisory from the American Academy of Neurology (AAN) evaluated antiseizure medication (ASM) withdrawal in seizure-free adults and children [55]. For adults who have been seizure free over a period of 24 to 60 months, the AAN concluded that it is unknown if electroencephalography (EEG) or imaging studies inform the decision to withdraw ASMs. The evidence review did not suggest an increased risk of status epilepticus or death after ASM withdrawal. For children, the AAN recommended consideration of ASM withdrawal for children who are seizure free for at least 18 to 24 months in the absence of an epileptiform EEG or an electroclinical epilepsy syndrome. (See "Overview of the management of epilepsy in adults", section on 'Recommendations of others' and "Seizures and epilepsy in children: Initial treatment and monitoring", section on 'Recommendations of others'.)

Rise in functional tics in adolescents and young adults (January 2022)

An increase in functional tics has been observed during the COVID-19 pandemic. Cases have been referred to as "TikTok tics," as affected individuals have commonly viewed online videos depicting tic-like behaviors [56]. Most patients are females between 15 and 25 years of age. Symptom onset is usually acute, with complex vocal and motor tics involving large-amplitude arm movements, self-injury, and a wide range of odd words or phrases, often with obscenities. The stresses of the pandemic are believed to be contributing, and comorbid depression and anxiety disorders are common. (See "Functional movement disorders", section on 'Functional tics'.)

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References