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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: Feb 2022. | This topic last updated: Mar 01, 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

Return to play following COVID illness (November 2021)

The American Academy of Pediatrics (AAP) has updated its interim guidance for clinicians managing children and adolescents who are returning to sport after recovering from COVID-19 illness [1]. According to the AAP, younger children recovering from mild illness may return to activity as tolerated. Children and adolescents 12 years and older recovering from mild illness should return to play in a graduated manner over a minimum of seven days. Before doing so, the child or adolescent must be free of any cardiorespiratory symptoms when performing normal activities of daily living. A more detailed evaluation and longer protocol for return to activity is needed following severe illness. We concur with the guidance and schedule outlined for a return to full play. (See "COVID-19: Return to play or strenuous activity following infection", section on 'Children and adolescents'.)

Myocarditis in athletes recovering from COVID-19 (October 2021)

Despite initial concerns about possible myocarditis in older adolescent and young adult athletes recovering from COVID-19, recent studies suggest that the risk of cardiac injury is low. In a prospective, multi-center cohort of over 3,000 US collegiate athletes diagnosed with COVID-19 and undergoing cardiac evaluation, possible cardiac injury was noted in 21 (0.7 percent), including 15 of 119 individuals who underwent cardiac magnetic resonance (CMR) imaging based on preliminary test findings (ECG, cardiac troponin, and/or echocardiography) and 6 of 198 individuals who underwent primary CMR screening [2]. During subsequent surveillance, only one adverse cardiac event occurred, most likely unrelated to COVID-19. These findings may not reflect the frequency of myocarditis after SARS-CoV-2 infection caused by subsequent variants such as the Delta variant. Nevertheless, they provide support for the current approach to cardiac evaluation and return to play in this population (algorithm 1). (See "COVID-19: Return to play or strenuous activity following infection", section on 'Cardiovascular complications in athletes'.)

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

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 20 pediatric hospitals in the United States during a period of Delta and Omicron variant circulation, infants <6 months of age were 61 percent less likely to be hospitalized with COVID-19 if their mothers became fully vaccinated with an mRNA COVID-19 vaccine during pregnancy [3]. Furthermore, 88 percent of the intensive care unit admissions for COVID-19 and the only death 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 [4]. In pregnant patients with COVID-19, unvaccinated individuals represented a significantly higher proportion of COVID-19-associated hospital admissions (77 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 [5]. This lends further support to vaccinating against HPV at a younger age. (See "Human papillomavirus vaccination", section on 'Cervical, vaginal, and vulvar disease'.)

Atenolol for complicated infantile hemangiomas (November 2021)

Evidence from small studies suggest that oral atenolol, a selective beta-1 blocker, may be as effective as propranolol for the treatment of complicated infantile hemangiomas, with the potential for a lower risk of serious adverse effects (eg, bronchospasm, bradycardia, hypoglycemia). In a randomized, open-label trial of nearly 400 infants with problematic hemangiomas treated with atenolol (1 mg/kg per day in a single dose) or propranolol (2 mg/kg per day in three divided doses), the rate of complete/nearly complete response at 96 weeks was similar in the two groups (80 versus 82 percent, respectively) [6]. Adverse events, including sleep disturbance, cold extremities, and bradycardia, were more frequent in the propranolol group than in the atenolol group (70 versus 44 percent). These findings indicate that atenolol has similar efficacy as propranolol for the treatment of complicated infantile hemangiomas with a better safety profile. Atenolol also has the advantage of once-daily administration. However, an oral formulation suitable for infants is not widely available. (See "Infantile hemangiomas: Management", section on 'Other beta blockers'.)

Breastfeeding and infant mortality (November 2021)

Prior studies show an association between breastfeeding and reduced infant mortality, particularly in resource-limited countries, but the association was less clear in high-resource countries. A new observational study of more than 3 million births in the United States found that breastfeeding initiation was significantly associated with reduced mortality during the late perinatal period (7 to 28 days) and the post-perinatal period (28 to 364 days) [7]. Significant effects were seen across different racial/ethnic groups, across all gestational age and birth weight groups, and for deaths due to infection, sudden unexpected infant death, and necrotizing enterocolitis. These findings support and expand the evidence for beneficial effects of breastfeeding for virtually all infants. (See "Infant benefits of breastfeeding", section on 'Mortality and hospitalization'.)

New threshold for elevated blood lead in United States children (November 2021)

Detectable blood lead levels (BLLs) are associated with neurocognitive deficits in infants and children <6 years old, and targeted screening of at-risk children is recommended. The Centers for Disease Control and Prevention has lowered the blood lead level (BLL) threshold for action to 3.5 mcg/dL (0.17 micromol/L) from the previous level of 5.0 mcg/dL (0.24 micromol/L) [8,9]. At or above this threshold, specific interventions should be taken based upon the degree of BLL elevation (table 1). For children with BLLs below 3.5 mcg/dL, the limit of detection for lead varies by laboratory, and the actual blood lead value may be close to or above the threshold. Thus, some children may need to be retested depending upon age or other risk factors. (See "Childhood lead poisoning: Management", section on 'Approach'.)

Pediatric fatalities associated with over-the-counter cough and cold medications (November 2021)

Manufacturer labelling and US Food and Drug Administration recommendations strongly advise against the use of over-the-counter cough and cold medications (CCM) in young children. A new report describes fatalities identified by a United States surveillance system and associated with CCM ingestion in children <12 years of age from 2008 to 2016 [10]. During this period, there were 40 reported deaths; the majority occurred in children <2 years old and involved diphenhydramine. Root cause analysis determined that 13 deaths occurred after deliberate supratherapeutic administration by a caregiver with the goal of sedating or harming the child. Health care providers should continue to educate caregivers on the dangers of CCM in children and maintain a high index of suspicion for child abuse with a low threshold for toxicology testing in infants and young children with unexplained signs or symptoms compatible with drug toxicity. (See "Physical child abuse: Diagnostic evaluation and management", section on 'Toxicology'.)

Point-of-care lead testing kit recall (October 2021)

Certain lots of point-of-care capillary blood lead testing kits manufactured by Magellan Diagnostics, Inc (LeadCare II, LeadCare Plus, and LeadCare Ultra) and distributed after October 27, 2020 have been recalled by the manufacturer and the US Food and Drug Administration (FDA) because of a significant risk of falsely low results. Per the FDA, children and pregnant or breastfeeding individuals who had test results <3.5 mcg/dL (0.14 micromol/L) using either a recalled test kit or a test kit with an unknown lot number should be retested with a venous blood lead level, especially those with potential signs or symptoms of lead toxicity or who are at high risk for lead exposure [11,12]. Remaining recalled test kits should be quarantined and no longer used. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Lead levels'.)

Iron deficiency anemia in children and neurocognitive deficits (October 2021)

Observational studies from low- and middle-income countries show an association between iron deficiency anemia (IDA) and neurodevelopmental deficits. A new randomized trial in more than 3000 infants in rural Bangladesh (one-third with iron deficiency and one-fifth with IDA at baseline) evaluated the effect of iron supplementation (alone or with other micronutrients, compared with placebo) for three months starting in late infancy [13]. Iron supplementation effectively reduced the prevalence of IDA, but there were no significant differences between the three groups on neurocognitive tests or growth outcomes at study completion or nine months later, including in the subgroup with IDA. Thus, the association between IDA and neurocognitive development may not be causal, or the timing and duration of the iron supplementation in this study was insufficient to detect such an effect. Despite these results, IDA has other adverse health effects, and routine screening of young children is warranted. (See "Iron deficiency in infants and children <12 years: Screening, prevention, clinical manifestations, and diagnosis", section on 'Associated disorders and effects of treatment'.)

Severe consequences of feeding a homemade vegan infant formula (October 2021)

Case reports describe life-threatening consequences of feeding a homemade plant-based formula to infants. The infants presented with acute respiratory distress, severe life-threatening hypocalcemia, hypophosphatemia, and rickets, with or without hypothyroidism, and some experienced seizure or cardiac arrest [14,15]. The formulas were made by the parents, following a vegan or "alkaline diet" recipe that they perceived to be healthy, but that lacked essential vitamins and minerals, including vitamin D, calcium, and iodine. These reports support our recommendation to provide explicit nutritional guidance to families who follow a vegan diet, and advise them not to feed homemade formulas to infants [16]. (See "Vegetarian diets for children", section on 'Plant-based formulas and beverages'.)

Risk criteria for predicting outcomes of brief resolved unexplained events (BRUE) in infants (September 2021)

The American Academy of Pediatrics has proposed criteria for predicting outcomes in infants presenting with a brief resolved unexplained event (BRUE) (table 2). In a large multicenter study of over 2000 infants evaluated for a possible BRUE, 87 percent had one or more high-risk characteristics [17]. The criteria were reasonably accurate for predicting a recurrent event in the emergency department or hospital (negative predictive value [NPV] 97 percent; positive predictive value [PPV] 14 percent) but less accurate for identifying the small minority with a serious underlying condition (NPV 97 percent; PPV 4 percent). The most common serious underlying causes were epilepsy/infantile spasms, airway abnormalities, and abusive head trauma. These observations suggest that the risk criteria have limited utility for identifying infants at high risk. (See "Acute events in infancy including brief resolved unexplained event (BRUE)", section on 'Evaluation of infants not meeting low-risk criteria'.)

Childhood obesity during the COVID-19 pandemic (September 2021)

In a retrospective cohort study of more than 190,000 children who had at least one body mass index measurement before and during the first year of the pandemic, obesity rates rose from pre-pandemic levels among all age groups. The increase by age groups was from 19 to 26 percent for 5- to 11-year-olds, from 19 to 23 percent for 12- to 15-year-olds, and from 18 to 20 percent for 16- to 17-year-olds [18]. Other studies report that the pandemic exacerbated risk factors for obesity including reduced physical activity, increased screen time, and access to unhealthy foods; studies also observed an increase in preexisting disparities in obesity rates between racial/ethnic and income groups [19,20]. (See "Definition, epidemiology, and etiology of obesity in children and adolescents", section on 'Trends'.)

NEONATOLOGY

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) [21]. Supporting evidence linking each of these practices with increased risk is reviewed in the guideline. We agree with this advice. (See "Management of normal labor and delivery", section on 'Alternative birthing practices that should be avoided'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

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 [22]. 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'.)

Evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines (November 2021)

An international panel of experts in allergy, infectious disease, and emergency medicine released recommendations for the evaluation and management of immediate allergic reactions to SARS-CoV-2 vaccines, based on a systematic review and meta-analysis [23]. These recommendations, which include not performing empiric testing in patients with past anaphylaxis to polyethylene glycol (PEG) or polysorbates, and referring patients who experienced anaphylaxis to the first dose of an mRNA vaccine to an allergist or completing vaccination with a different vaccine, are consistent with our approach. Most patients are able to complete the vaccination process. (See "COVID-19: Allergic reactions to SARS-CoV-2 vaccines", section on 'Immediate reactions to an initial dose'.)

DERMATOLOGY

Topical spinosad for scabies (September 2021)

Spinosad is an insecticide derived from fermentation of a soil actinobacterium and causes fatal neuronal excitation in insects, including the parasites responsible for scabies. In the combined results from two phase 3 randomized trials (551 adults and children with scabies), 78 percent of patients treated with a single application of spinosad 0.9% topical suspension achieved complete cure compared with only 40 percent of patients in the vehicle group [24]. Treatment was well tolerated. These findings support spinosad as a topical therapy for scabies and contributed to the US Food and Drug Administration (FDA) approval of spinosad for this indication. The efficacy of spinosad has not been directly compared with the currently preferred therapies (topical permethrin or oral ivermectin). (See "Scabies: Management".)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Intranasal oxytocin did not improve social interaction in children with ASD (October 2021)

Based upon limited evidence, some clinicians prescribe oxytocin to improve social interaction in children with autism spectrum disorder (ASD). However, in a placebo-controlled randomized trial in 290 children with ASD, social interaction or function did not improve for individuals assigned to 24 weeks of daily intranasal oxytocin as assessed by multiple social behavior scoring systems [25]. In subgroup analysis, the results were similar among participants with differing degrees of speech fluency and when analyzed according to baseline oxytocin levels. These findings do not support the use of oxytocin in children with ASD. (See "Autism spectrum disorder in children and adolescents: Pharmacologic interventions", section on 'Oxytocin'.)

Sleep problems in children with ADHD during the COVID-19 pandemic (September 2021)

Sleep disturbances are common in children with attention deficit hyperactivity disorder (ADHD), and home confinement associated with the COVID-19 pandemic has exacerbated prepandemic problems. In a survey study of nearly 1000 parents of children aged 5 to 18 years with ADHD, 60 to 70 percent of children had a change in bedtime during confinement, and the frequency of bedtimes later than 11 PM substantially increased [26]. Sleep duration changes were bidirectional, with more children sleeping less than 6 hours or between 10 and 11 hours per night. Management of sleep problems in children with ADHD begins with setting consistent sleep-wake schedules and treating behavioral contributors such as excess screen time near bedtime and anxiety (table 3A-B). (See "Sleep in children and adolescents with attention deficit hyperactivity disorder", section on 'Common sleep complaints'.)

EMERGENCY MEDICINE

Cannabis edible product ingestion in US children (October 2021)

Concentrated edible cannabis (marijuana) products are popular for recreational use. Exploratory ingestions of these products in young children can cause severe toxicity including seizures, apnea, and coma. In a report from the United States National Poison Data System, cannabis edible product ingestions have significantly increased in children <5 years old, with over twice the rate of exposures from states where adult cannabis use is legal [27]. These findings indicate an urgent need for education of adult cannabis users regarding the dangers that edible cannabis products pose to young children and for legislative efforts to prohibit cannabis product packaging and advertising that target children. (See "Cannabis (marijuana): Acute intoxication", section on 'Recreational use'.)

AAP clinical practice guidelines for febrile infants 8 to 60 days old (August 2021)

The American Academy of Pediatrics (AAP) has published multidisciplinary, consensus guidelines for the evaluation and management of well-appearing, healthy febrile infants 8 to 60 days old at low risk for invasive bacterial infection (bacteremia or meningitis) (algorithm 2 and algorithm 3 and algorithm 4) [28]. Key changes from prior guidelines include the use of inflammatory markers to identify infants 29 to 60 days old in whom lumbar puncture (LP) need not be performed and neonates 22 to 28 days old who may not require LP and a recommendation against sending a urine culture in infants with normal a normal urinalysis. Febrile infants 29 to 60 days of age with normal inflammatory markers and urinalysis may be managed at home by reliable caregivers as long as close follow-up is assured. These guidelines are consistent with our approach, although sending a urine culture on all febrile young infants is reasonable in facilities where contamination rates are low. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on '29 to 60 days old' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on '22 to 28 days old' and "The febrile infant (29 to 90 days of age): Management", section on 'Infants 29 to 60 days old'.)

ENDOCRINOLOGY

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 [29]. 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'.)

Serum sodium changes not associated with cerebral injury during treatment of diabetic ketoacidosis in children (November 2021)

Prior retrospective studies in children with diabetic ketoacidosis (DKA) reported associations between declines in serum sodium levels during treatment and risk of cerebral injury. In a new prospective study involving over 1200 episodes of DKA in children, the frequencies of mental status changes and clinical markers of cerebral injury were no different in children who had declines in glucose-corrected sodium concentrations during treatment compared with those who did not [30]. Declines in serum sodium were associated with higher serum sodium and chloride levels at presentation, previously diagnosed diabetes mellitus, and treatment with half normal saline (versus normal saline). These data suggest that serum sodium declines during DKA treatment largely reflect differences in fluid and sodium balance at presentation and are not a cause of cerebral injury. (See "Diabetic ketoacidosis in children: Cerebral injury (cerebral edema)", section on 'Initial theories based on osmotic change'.)

Exenatide for type 2 diabetes in adolescents (October 2021)

Extended-release exenatide, a glucagon-like peptide-1 (GLP-1) agonist, is a new treatment option for adolescents with type 2 diabetes mellitus (T2DM) who do not achieve glycemic targets with metformin monotherapy. In a randomized trial of 83 such patients, exenatide combined with lifestyle measures (diet and exercise) with or without standard pharmacologic intervention (primarily metformin and/or insulin) improved glycemic control at 24 weeks of therapy (change in hemoglobin A1C from baseline -0.36 versus +0.49 for placebo) (NCT01554618) [31]. Gastrointestinal symptoms were similar between treatment and control groups, and there were low rates of hypoglycemia. This trial was the basis for the US Food and Drug Administration's approval of exenatide for this age group. Extended-release exenatide is given by subcutaneous injection once weekly, compared with daily dosing for liraglutide or insulin. (See "Management of type 2 diabetes mellitus in children and adolescents", section on 'Trials of GLP-1 agonists'.)

Sustained-release formulation of recombinant human growth hormone for use in children (August 2021)

Lonapegsomatropin is a new sustained-release formulation of recombinant human growth hormone (rhGH) for the treatment of growth hormone deficiency in children. In a 52-week randomized trial in 161 prepubertal children with growth hormone deficiency, lonapegsomatropin given once weekly achieved a higher annualized height velocity compared with equivalent doses of aqueous rhGH (somatropin) administered daily (11.2 versus 10.3 cm/year) while reducing treatment burden [32]. These findings were the basis of the approval of lonapegsomatropin by the US Food and Drug Administration for children one year and older with growth hormone deficiency. (See "Treatment of growth hormone deficiency in children", section on 'Formulations of growth hormone'.)

Incidence of chronic complications of type 2 diabetes in youth (August 2021)

Chronic complications are common among youth with type 2 diabetes mellitus (T2DM) and tend to progress more rapidly than in adults. A long-term follow up study described a high cumulative incidence 15 years after the diagnosis of T2DM for hypertension (67 percent); diabetic kidney disease (55 percent); dyslipidemia (52 percent); retinopathy (51 percent); and nerve disease (32 percent) [33]. These findings support our recommendations for intensive glycemic control, weight management, and monitoring and management of complications for youth with T2DM. (See "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus", section on 'Summary and recommendations'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Morbidity of high-powered magnet ingestion (February 2022)

The incidence of high-powered magnet ingestions has increased markedly in the United States after marketing restrictions were overturned in 2016. The morbidity of these ingestions is described in a new multicenter study of 574 children with magnet ingestions in which 57 children (9.6 percent) had a life-threatening complication, including intestinal perforation, fistula, obstruction, bleeding, infection, or volvulus [34]. 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 [35,36]. 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) [37]. 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) [38]. 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'.)

New guidelines for tuberous sclerosis complex (October 2021)

The guidelines for the diagnosis and management of tuberous sclerosis complex (TSC) were recently updated in an international consensus conference [39]. Compared with the prior 2012 guidelines, changes include two revisions to the diagnostic criteria and several surveillance and treatment updates. The guidelines now recommend routine baseline electroencephalogram (EEG) and avoidance of contrast agents with brain MRI unless there is an enlarging lesion or clinical suspicion for subependymal giant cell tumors. Greater attention is placed on TSC-associated neuropsychiatric disorders (TAND), and everolimus and a formulation of cannabidiol are now included in therapy options. Management should be coordinated by a multidisciplinary team with expertise in TSC. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis" and "Gene test interpretation: TSC1 and TSC2 (tuberous sclerosis complex genes)" and "Tuberous sclerosis complex: Management and prognosis".)

Updated diagnostic criteria for neurofibromatosis type 1 (September 2021)

Updated diagnostic criteria for neurofibromatosis type 1 (NF1) have been released by an international consensus conference (table 4) [40]. The criteria incorporate genetic testing as well as several new clinical features (eg, choroidal abnormalities, anterolateral bowing of the tibia, long bone pseudoarthrosis). The document also includes new diagnostic criteria for Legius syndrome (table 5), which has phenotypic overlap with NF1 in young patients with pigmentary findings, and criteria for mosaic forms of both conditions. (See "Neurofibromatosis type 1 (NF1): Pathogenesis, clinical features, and diagnosis", section on 'Diagnostic criteria'.)

HEMATOLOGY AND ONCOLOGY

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) [41]. 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 [42]. 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 [43]. 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 [44]. 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'.)

Direct oral anticoagulants for venous thromboembolism in children ≥2 years (August 2021)

In 2021, the US Food and Drug Administration approved two direct oral anticoagulants (DOACs), dabigatran and rivaroxaban, for treatment of venous thrombosis and thromboembolism (VTE) in children [45,46]. These regulatory approvals were based upon two large multicenter pediatric trials demonstrating that dabigatran and rivaroxaban have similar efficacy and bleeding risk compared with low molecular weight heparin (LMWH) and warfarin [47,48]. Adolescents made up most of the trial populations, and children <2 years were underrepresented. DOACs are an attractive option since they are orally administered and do not require drug monitoring. We now suggest one of the approved DOACs (dabigatran or rivaroxaban) for treatment of VTE in adolescents, after at least five days of initial parenteral therapy. For children ages 2 to 11 years, either a DOAC or LMWH is acceptable. For infants and children <2 years, the efficacy and safety of DOACs remain uncertain, and we continue to suggest LMWH. (See "Venous thrombosis and thromboembolism (VTE) in children: Treatment, prevention, and outcome", section on 'Direct oral anticoagulants'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

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 'How often are children with COVID-19 hospitalized?'.)

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 [50]. 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'.)

Dose and duration of amoxicillin for community-acquired pneumonia (CAP) in young children (November 2021)

In a 2 x 2 factorial multicenter randomized trial, investigators randomly assigned nearly 600 children (median age 2.5 years) with clinically diagnosed CAP who were discharged from the emergency department to standard- or high-dose amoxicillin administered twice daily and to three or seven days of therapy [51]. Repeat antibiotics for respiratory infection within 28 days were required in 12.5 to 12.9 percent of children in the four groups with no significant differences by antibiotic dose or duration. None of the participants were colonized with penicillin-resistant pneumococci. These results support standard-dose amoxicillin (35 to 50 mg/kg per day) in areas with low levels of penicillin resistance, twice-daily administration, and, in children with mild disease and adequate follow-up, antibiotic duration for <7 days. However, they are not generalizable to other antibiotics, older children, or children who are hospitalized. Pending confirmation of these findings, our preferred regimen for immunized children one to five years of age with suspected bacterial pneumonia is amoxicillin 90 to 100 mg/kg per day divided into two or three doses for at least five days. (See "Community-acquired pneumonia in children: Outpatient treatment", section on 'Duration' and "Community-acquired pneumonia in children: Outpatient treatment", section on 'Suspected bacterial etiology'.)

COVID-19 vaccination in children 5 years and older (November 2021)

In October 2021, the US Food and Drug Administration authorized BNT162b2 (Pfizer vaccine) for individuals 5 to 11 years old based on data from randomized trials in over 2000 children in this age group, which demonstrated 91 percent vaccine efficacy against symptomatic COVID-19 and immunogenicity similar to that in adolescents and young adults [52]. There were no cases of vaccine-associated myocarditis in the trials; although the precise risk is uncertain, it 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 to children ages 5 to 11 years. Clinicians should be aware that the dose and formulation used for children are different than those for adolescents and adults. (See "COVID-19: Vaccines", section on 'Summary and recommendations'.)

Updated sexually transmitted infections guidelines from CDC (October 2021)

In 2021, the United States Centers for Disease Control and Prevention (CDC) updated its guidelines on management of sexually transmitted infections [53]. Important changes include preferences for doxycycline over azithromycin for Chlamydia trachomatis infections and nongonococcal urethritis, routine anaerobic coverage for pelvic inflammatory disease, and a moxifloxacin-based regimen for Mycoplasma genitalium. The guidelines also affirmed previous recommendations to use a 500 mg dose of intramuscular ceftriaxone for gonococcal infections. Our approaches to sexually transmitted infections are largely consistent with these updated guidelines. (See "Pelvic inflammatory disease: Treatment in adults and adolescents" and "Mycoplasma genitalium infection in males and females" and "Treatment of uncomplicated Neisseria gonorrhoeae infections" and "Treatment of Chlamydia trachomatis infection", section on 'Doxycycline as preferred agent'.)

Updated ACIP guidance on influenza vaccination in the United States (September 2021)

In August 2021, the United States Advisory Committee on Immunization Practices (ACIP) issued recommendations for prevention of seasonal influenza [54]. During the 2021-22 influenza season, the following vaccine types are expected to be available: inactivated influenza vaccines (IIV4s), recombinant influenza vaccine (RIV4), and live attenuated influenza vaccine (LAIV4) (table 6 and table 7); all vaccines are expected to be quadrivalent. For the IIV4s produced from cell culture, the approved age indication has been expanded from ≥4 years to ≥6 months of age [55,56]. Influenza vaccination may be co-administered with COVID-19 vaccination, at different anatomic sites. We agree with the ACIP guidance. (See "Seasonal influenza vaccination in adults", section on 'Available formulations' and "Seasonal influenza in children: Prevention with vaccines", section on 'Influenza vaccines'.)

Use of palivizumab during increased interseasonal activity of respiratory syncytial virus (RSV) (August 2021)

During the coronavirus disease 2019 (COVID-19) pandemic, increased interseasonal activity of RSV has resulted in more hospitalizations and emergency department visits for infants in some regions. The American Academy of Pediatrics suggests administration of palivizumab for RSV prophylaxis in eligible infants outside of the typically recommended schedule if they live in regions with interseasonal RSV activity similar to that in a typical fall-winter season [57]. In the United States, information about state-level RSV activity is available from the Centers for Disease Control and Prevention. Health departments in the United Kingdom began offering palivizumab to eligible infants in July and have extended the number of doses from five to seven [58]. Eligibility criteria for palivizumab treatment vary geographically. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Increased interseasonal activity during COVID-19 pandemic'.)

NEUROLOGY

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 [59]. 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'.)

New guidelines for tuberous sclerosis complex (October 2021)

The guidelines for the diagnosis and management of tuberous sclerosis complex (TSC) were recently updated in an international consensus conference [39]. Compared with the prior 2012 guidelines, changes include two revisions to the diagnostic criteria and several surveillance and treatment updates. The guidelines now recommend routine baseline electroencephalogram (EEG) and avoidance of contrast agents with brain MRI unless there is an enlarging lesion or clinical suspicion for subependymal giant cell tumors. Greater attention is placed on TSC-associated neuropsychiatric disorders (TAND), and everolimus and a formulation of cannabidiol are now included in therapy options. Management should be coordinated by a multidisciplinary team with expertise in TSC. (See "Tuberous sclerosis complex: Genetics, clinical features, and diagnosis" and "Gene test interpretation: TSC1 and TSC2 (tuberous sclerosis complex genes)" and "Tuberous sclerosis complex: Management and prognosis".)

PULMONOLOGY

Duration of IV antibiotics for acute pulmonary exacerbation of CF (November 2021)

The optimal duration of intravenous (IV) antibiotics in patients with cystic fibrosis (CF) is unknown. In a randomized study of adults with CF and an acute pulmonary exacerbation, 277 patients with early robust response were randomized to a 10- or 14-day course of antibiotics, and 705 slower responders were randomized to a 14- or 21-day course [60]. Within both groups, mean FEV1 change from baseline, improvements in symptoms score, rates of treatment failure, and drug-induced toxicity were similar regardless of the duration of antibiotics. These findings are likely applicable to children with CF and support our suggestion for a 10-day course of IV antibiotics for patients with an early robust response to therapy, and a 14-day course for those with a slower response to therapy. A longer course of antibiotics may be warranted for patients requiring intensive care and those who experience a CF exacerbation despite a recent course of IV antibiotics. (See "Cystic fibrosis: Treatment of acute pulmonary exacerbations", section on 'Duration of treatment'.)

Triple- versus dual- or mono-therapy with CFTR modulators for cystic fibrosis (September 2021)

Elexacaftor-tezacaftor-ivacaftor (triple cystic fibrosis transmembrane modulator [CFTR]) therapy is indicated for patients who are F508del homo- or heterozygotes. Individuals who are F508del heterozygotes may already be receiving tezacaftor-ivacaftor (dual therapy) or ivacaftor (monotherapy); the benefit of triple CFTR therapy in these patients is unclear. In a trial of more than 250 children (F508del heterozygotes ≥12 years of age), triple therapy for eight weeks improved respiratory symptoms, pulmonary function, and sweat chloride compared with active controls receiving either dual therapy (patients with F508del-residual function genotypes) or monotherapy (patients with F508del-gating genotypes) [61]. We suggest triple CFTR modulator therapy rather than dual or monotherapy for CF patients with genotypes that make them eligible for either one of these treatments. (See "Cystic fibrosis: Treatment with CFTR modulators", section on 'Efficacy'.)

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Topic 2841 Version 10977.0

References

1 : https://services.aap.org/en/pages/2019-novel-coronavirus-covid-19-infections/clinical-guidance/covid-19-interim-guidance-return-to-sports/ (Accessed on March 01, 2022).

2 : SARS-CoV-2 Cardiac Involvement in Young Competitive Athletes.

3 : Effectiveness of Maternal Vaccination with mRNA COVID-19 Vaccine During Pregnancy Against COVID-19-Associated Hospitalization in Infants Aged<6 Months - 17 States, July 2021-January 2022.

4 : SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland.

5 : The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study.

6 : Efficacy and Safety of Propranolol vs Atenolol in Infants With Problematic Infantile Hemangiomas: A Randomized Clinical Trial.

7 : Breastfeeding and Post-perinatal Infant Deaths in the United States, A National Prospective Cohort Analysis

8 : Breastfeeding and Post-perinatal Infant Deaths in the United States, A National Prospective Cohort Analysis

9 : Breastfeeding and Post-perinatal Infant Deaths in the United States, A National Prospective Cohort Analysis

10 : Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

11 : Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

12 : Pediatric Fatalities Associated With Over-the-Counter Cough and Cold Medications.

13 : Benefits and Risks of Iron Interventions in Infants in Rural Bangladesh.

14 : Notes from the Field: Vitamin D-Deficient Rickets and Severe Hypocalcemia in Infants Fed Homemade Alkaline Diet Formula - Three States, August 2020-February 2021.

15 : Recipe for Disaster: Homemade Formula Leading to Severe Complications in 2 Infants.

16 : Recipe for Disaster: Homemade Formula Leading to Severe Complications in 2 Infants.

17 : Risk Factors and Outcomes After a Brief Resolved Unexplained Event: A Multicenter Study.

18 : Changes in Body Mass Index Among Children and Adolescents During the COVID-19 Pandemic.

19 : COVID-19 and Changes in Child Obesity.

20 : Reducing risk of childhood obesity in the wake of covid-19.

21 : Risks of Infectious Diseases in Newborns Exposed to Alternative Perinatal Practices

22 : Efficacy and safety of oral immunotherapy in children aged 1-3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study.

23 : The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

24 : Spinosad at 0.9% in the treatment of scabies: Efficacy results from 2 multicenter, randomized, double-blind, vehicle-controlled studies.

25 : Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder.

26 : The impact of lockdown on sleep patterns of children and adolescents with ADHD.

27 : Edible Cannabis Exposures Among Children: 2017-2019.

28 : Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old.

29 : Randomized Trial of Closed-Loop Control in Very Young Children with Type 1 Diabetes.

30 : Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.

31 : Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.

32 : Weekly Lonapegsomatropin in Treatment-Naïve Children With Growth Hormone Deficiency: The Phase 3 heiGHt Trial.

33 : Long-Term Complications in Youth-Onset Type 2 Diabetes.

34 : High-Powered Magnet Exposures in Children: A Multi-Center Cohort Study.

35 : Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study.

36 : Placebo-Controlled Randomized Trial of an Intestinal Bile Salt Transport Inhibitor for Pruritus in Alagille Syndrome.

37 : Antibody Responses After SARS-CoV-2 mRNA Vaccination in Adults With Inflammatory Bowel Disease.

38 : Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access.

39 : Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations.

40 : Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation.

41 : Effect of Anticoagulant Therapy for 6 Weeks vs 3 Months on Recurrence and Bleeding Events in Patients Younger Than 21 Years of Age With Provoked Venous Thromboembolism: The Kids-DOTT Randomized Clinical Trial.

42 : Consensus statement for the perinatal management of patients withαthalassemia major.

43 : Betibeglogene Autotemcel Gene Therapy for Non-β0/β0 Genotypeβ-Thalassemia.

44 : Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.

45 : Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.

46 : Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.

47 : Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial.

48 : Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial.

49 : Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, July 2021-January 2022.

50 : Hospitalizations of Children and Adolescents with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, July 2021-January 2022.

51 : Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial.

52 : Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial.

53 : Sexually Transmitted Infections Treatment Guidelines, 2021.

54 : Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices, United States, 2021-22 Influenza Season.

55 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

56 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

57 : Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children.

58 : RSV: The year the respiratory infection "took its gloves off".

59 : Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

60 : A Randomized Clinical Trial of Antimicrobial Duration for Cystic Fibrosis Pulmonary Exacerbation Treatment.

61 : Triple Therapy for Cystic Fibrosis Phe508del-Gating and -Residual Function Genotypes.