What's new in pediatrics

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

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

ADHD medications and risk of cardiovascular events (February 2023)

The risk of cardiovascular (CV) events in patients receiving attention deficit hyperactivity disorder (ADHD) medications has been the focus of several large cohort studies. A recent meta-analysis of 19 observational studies including 3.9 million patients did not detect an association between ADHD medication use and the overall risk of adverse CV events [1]. In an analysis of nine studies that reported rates of sudden cardiac death (SCD), cardiac arrest, or tachyarrhythmia, the risk was slightly higher among individuals using ADHD medications, but the finding was not statistically significant. The absolute rates of SCD in these studies were very low. Based on these data, we suggest that children and adolescents who are starting ADHD medications be assessed with a complete history and physical examination. If this assessment does not suggest cardiac disease, no additional evaluation is necessary. (See "Cardiac evaluation of patients receiving pharmacotherapy for attention deficit hyperactivity disorder", section on 'General population'.)

Exercise in children and adolescents with depression (February 2023)

Prescribing exercise for depression in adults is supported by multiple trials. Physical activity also appears to benefit children and adolescents with depression. In a meta-analysis of 21 studies of more than 2400 youths (mostly randomized trials), a variety of aerobic exercise programs (generally prescribed as monotherapy) were associated with moderately improved depressive symptoms compared with usual care or no treatment [2]. However, after a mean follow-up of 21 weeks, improvement of depressive symptoms in the two groups was comparable. For children and adolescents with unipolar major depression, we suggest physical exercise as an adjunct treatment along with pharmacotherapy and/or psychotherapy. (See "Overview of prevention and treatment for pediatric depression", section on 'Adjunctive exercise'.)

Sleeve gastrectomy versus gastric bypass for adolescents with severe obesity (January 2023)

For metabolic weight loss surgery in adolescents, sleeve gastrectomy (SG) (figure 1) is increasingly used rather than Roux-en-Y gastric bypass (RYGB) (figure 2) based on short-term observational data that suggests similar weight loss but fewer complications with SG. In an observational study of 855 adolescents undergoing weight loss surgery with five-year follow-up, SG compared with RYGB was associated with reduced frequency of emergency department visits (53.3 versus 59.9 percent) and hospitalization (36.9 versus 52.1 percent) [3]. There was no significant difference in the frequency of complications (1.5 versus 2.1 percent) or reoperations (7.2 versus 7.7 percent), and outcomes for weight loss and obesity comorbidities were not reported. These findings support the trend towards preferential use of SG for weight loss surgery in adolescents pending further data on weight and comorbidity outcomes. (See "Surgical management of severe obesity in adolescents", section on 'Sleeve gastrectomy'.)

Time course of weight gain after adenotonsillectomy for OSA in children (January 2023)

Previous studies have shown a complex relationship between obstructive sleep apnea (OSA), adenotonsillectomy, and weight gain in children. In a randomized trial of early versus delayed adenotonsillectomy in 190 children ages three to five years with mild to moderate OSA, weight gain occurred in the first 12 months after surgery in both groups, but the early intervention group had no further increase in the second postoperative year [4]. These results suggest that postoperative weight gain is time limited and may not represent a new trajectory toward increased risk for obesity. Providers should be aware that children with OSA are at risk for weight gain, regardless of whether they receive adenotonsillectomy, and take steps to minimize or reverse this tendency where possible. (See "Adenotonsillectomy for obstructive sleep apnea in children", section on 'Weight gain'.)

Semaglutide for obesity in adolescents (November 2022, Modified January 2023)

Glucagon-like peptide (GLP-1) analogs are important options for treatment of type 2 diabetes and/or obesity in adults. In a 68-week randomized trial in 201 adolescents with obesity, patients assigned to weekly subcutaneous semaglutide, a GLP-1 analog, had substantial weight loss compared with lifestyle intervention alone (17.7 kg greater weight loss compared with placebo; 6 kg/m² greater decrease in body mass index [BMI]) [5]. Gastrointestinal adverse events were common in both groups but were generally mild and rarely led to treatment discontinuation. While head-to-head trials have not been performed in adolescents, indirect evidence suggests greater weight loss with semaglutide than the alternatives, including liraglutide and metformin. Based on these findings, we now suggest semaglutide over other agents for pharmacotherapy of obesity in selected adolescents. (See "Prevention and management of childhood obesity in the primary care setting", section on 'Pharmacotherapy'.)

Risk of drug overdose in young people prescribed benzodiazepines for sleep disorders (December 2022)

Prescription database studies indicate that benzodiazepines are commonly prescribed for insomnia, despite risks and the availability of safer options. In a recent cohort study in the United States that included over 90,000 children and young adults (age 10 to 29 years) with a sleep disorder who were prescribed a new insomnia medication, benzodiazepines were associated with increased risk of drug overdose in the next six months compared with alternative insomnia medications (trazodone, hydroxyzine, zolpidem, zaleplon, eszopiclone) [6]. Risk was highest among individuals who had also received an opioid prescription in the preceding three months. We do not prescribe benzodiazepines for insomnia in patients taking opioids or in those with a substance use disorder. (See "Pharmacotherapy for insomnia in adults", section on 'Shared warnings and precautions'.)

Screening for anxiety in children and adolescents (December 2022)

Anxiety in children and adolescents interferes with social, emotional, and academic development. The United States Preventive Services Task Force (USPSTF) now recommends screening for anxiety in all individuals aged 8 to 18 years old [7]. This updated recommendation is supported by a meta-analysis that included 39 studies with 6065 subjects in that age range and showed moderate accuracy of screening tools and moderate benefit of treatment on symptom response and disease remission [8]. The harms associated with screening and subsequent treatment were minimal. Our approach is consistent with these recommendations. We use the Screen for Child Anxiety-Related Emotional Disorders (SCARED) tool, which is available in the public domain. (See "Anxiety disorders in children and adolescents: Assessment and diagnosis", section on 'Screening'.)

Synthetic ("tobacco-free") oral nicotine product use in teenagers (October 2022)

New synthetic nicotine products are available as gum, lozenges, gummies, and pouches. Features that may promote increased use among youth include availability in appealing flavors, readily concealed forms, and marketing messages such as "tobacco-free" that imply minimal harm. In a survey of 9th and 10th grade students in Southern California in late 2021, these products were the second-most common nicotine source (after e-cigarettes) and more common than combustible tobacco [9]. The US Food and Drug Administration has issued warning letters to manufacturers and retailers regarding illegal marketing of many of these products [10,11]. (See "Prevention of smoking and vaping initiation in children and adolescents", section on 'Oral nicotine products'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Revised CDC MIS-C case definition (February 2023)

The case definition for multisystem inflammatory syndrome in children (MIS-C) that was revised by the United States Council of State and Territorial Epidemiologists/Centers for Disease Control (CSTE/CDC) and implemented in 2023 aligns closely with the World Health Organization (WHO) MIS-C criteria [12-14]. Both definitions require fever, elevated inflammatory markers, at least two signs of multisystem involvement, evidence of SARS-CoV-2 infection or exposure, and exclusion of other potential causes. One important change is that the CTSE/CDC MIS-C case definition designates Kawasaki disease (KD) as an alternative diagnosis that should trigger reporting to the CDC KD passive surveillance system. (See "COVID-19: Multisystem inflammatory syndrome in children (MIS-C) clinical features, evaluation, and diagnosis", section on 'CDC and WHO case definitions'.)

Vaccination in children with autoimmune diseases (January 2023)

The European Alliance of Associations for Rheumatology/Paediatric Rheumatology European Society (EULAR/PRES) recently updated their recommendations for vaccination of children with autoimmune inflammatory rheumatic diseases such as juvenile idiopathic arthritis (JIA) [15]. These recommendations include several overarching principles, such as assessing vaccination status and indications/contraindications for additional vaccines yearly and administering vaccines when disease is quiescent or at least two weeks before starting immunosuppressive therapy, if possible. Vaccine-specific recommendations are also reviewed. As an example, data support administration of the measles-mumps-rubella (MMR) booster vaccine in children with JIA on methotrexate. Our approach is consistent with their guidance. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Immunizations'.)

New NF-kB-mediated autoinflammatory disease (ROSAH syndrome) (November 2022)

Retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache (ROSAH) syndrome is an autosomal dominant disorder caused by gain-of-function heterozygous missense variants in the alpha kinase 1 gene (ALPK1). A recent study confirmed that ROSAH is an autoinflammatory disorder mediated by enhanced nuclear factor kappa B (NF-kB) signaling [16]. In this small case series, immunomodulation with anticytokine therapy was associated with improved autoinflammatory disease manifestations including fatigue, headache, and arthralgia, and also intraocular inflammation in those who did not have advanced retinal disease. Additional studies are needed to determine the best choice of therapy and whether earlier treatment can prevent development of disease manifestations. (See "Autoinflammatory diseases mediated by NFkB and/or aberrant TNF activity", section on 'ALPK1 gain-of-function defects (ROSAH syndrome)'.)

Timing of cow's milk protein introduction in infants and risk of allergy (November 2022)

Current guidelines recommend introducing highly allergenic foods, including cow's milk (CM) protein, in infants who are exclusively breast fed, beginning around four to six months of age. A prospective cohort study in 1298 children that examined the timing of receipt of CM-based formula supplementation after delivery and first reported introduction of CM-based formula or other CM products found that introduction at <2 weeks of age followed by continued exposure was associated with the lowest subsequent risk of development of parent-reported adverse reactions to CM (IgE- or non-IgE mediated) between 2 to 13 years of age [17]. This and other accumulating data suggest that very early introduction and continued ingestion of CM protein in some form (other than liquid, whole CM) may reduce the risk of developing CM allergy, although further studies are needed. (See "Introducing highly allergenic foods to infants and children", section on 'Introduction in the general population'.)

COVID-19 and asthma control in children (November 2022)

Initial data suggested that COVID-19 did not increase asthma morbidity in children, contrary to that expected for a viral respiratory infection. However, asthma control may have improved during the early waves of the pandemic due to an overall decrease in viral respiratory infections. A comparison of nearly 62,000 children with asthma from 108 health care systems in the United States from March 2020 through February 2021 found that a SARS CoV-2 polymerase chain reaction-positive test was associated with increased rates of emergency department visits, hospitalizations, and use of short-acting beta agonist and oral glucocorticoids in the six months following the positive test compared with those who tested negative [18]. This reinforces the importance of patients continuing medications necessary to maintain optimal asthma control so as to better weather COVID-19 and other viral respiratory infections. (See "Asthma in children younger than 12 years: Management of persistent asthma with controller therapies", section on 'Advice related to Covid-19'.)

Allergen immunotherapy for atopic dermatitis (October 2022)

Allergen immunotherapy (AIT) is a well-established treatment for allergic rhinoconjunctivitis and asthma, but studies of its utility for atopic dermatitis (AD) are mixed. In a new meta-analysis, the addition of AIT (either subcutaneous or sublingual, mostly using house dust mites as the allergen) or placebo was evaluated in 23 randomized trials that enrolled nearly 2000 children and adults with AD who were not controlled with standard therapy (either topical corticosteroids or calcineurin inhibitors) [19]. Patients receiving add-on AIT more often experienced a clinically important decrease in AD severity and improvement in quality of life. Thus, add-on AIT may be beneficial for patients who have eczema that is not controlled with conventional therapies and proven sensitization to house dust mites. AIT may be especially helpful for patients with concomitant allergic rhinoconjunctivitis or asthma. (See "Treatment of atopic dermatitis (eczema)".)

CARDIOLOGY

Newborn pulse oximetry screening for congenital heart disease (February 2023)

Delayed postnatal diagnosis of critical congenital heart disease (CHD) is associated with increased risk of morbidity and mortality. Universal newborn pulse oximetry screening (POS) is thought to improve timely detection of critical CHD and reduce adverse consequences of delayed presentation. A recent study found that CHD-related emergency hospitalizations within the first three months after birth were lower in states that had implemented mandatory newborn POS compared with the preimplementation era and states without mandatory screening [20]. This association supports our suggestion for routine POS in all newborns. (See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Early detection of critical CHD'.)

Long-term risk of ventricular septal defect (January 2023)

Limited data are available on long-term outcomes in adults with congenital ventricular septal defects (VSDs). In a population-based cohort study comparing 8000 patients with VSDs with over 80,000 matched controls for a median of more than 20 years, the risks of heart failure, arrhythmia, infectious endocarditis, and pulmonary hypertension were elevated in patients with unrepaired or surgically repaired VSDs [21]. Among patients with unrepaired VSDs, the risk of morbidity accelerated after age 40 years, and at a younger age in patients with repaired VSDs. These findings underscore the importance of long-term clinical follow-up in adults with VSDs. (See "Management and prognosis of congenital ventricular septal defect in adults", section on 'Long-term prognosis'.)

DERMATOLOGY

Laboratory monitoring for isotretinoin therapy (September 2022)

Reduced monitoring of liver function and lipid tests in healthy patients receiving isotretinoin has been proposed based upon data that suggest low utility of monthly testing. A Delphi consensus study in which acne experts responded to a series of surveys found at least 70 percent consensus for checking alanine aminotransferase (ALT) and triglyceride levels within one month prior to isotretinoin therapy and after reaching the peak isotretinoin dose [22]. There was also consensus that several other laboratory tests were not necessary, such as complete blood count panels, basal metabolic panels, and select liver function and lipid tests. Although these findings align with the trend towards reduced laboratory monitoring for healthy patients taking isotretinoin, no consensus was achieved for some commonly obtained tests, and additional study is necessary to confirm the best approach to monitoring. Additionally, individual patient characteristics may warrant a different approach to laboratory testing. (See "Oral isotretinoin therapy for acne vulgaris", section on 'Evidence'.)

EMERGENCY MEDICINE

Ultrasound in patients with suspected peritonsillar abscess (February 2023)

In patients with peritonsillar infection, physical examination may not accurately distinguish peritonsillar abscess (PTA) from peritonsillar cellulitis. In a meta-analysis of 17 studies (812 patients, mostly adults), ultrasound (US) was able to distinguish PTA from peritonsillar cellulitis with a pooled sensitivity of 86 percent and specificity of 76 percent [23]. Subgroup analysis suggested improved diagnostic characteristics for radiologist-performed US. These findings support our suggestion for US by an experienced clinician, if available, to distinguish PTA from peritonsillar cellulitis. (See "Peritonsillar cellulitis and abscess", section on 'Imaging'.)

HFNC oxygen therapy for mild to moderate acute hypoxemic respiratory failure in children (February 2023)

Evidence is limited regarding the role of high-flow nasal cannula (HFNC) oxygen therapy for children with mild to moderate acute hypoxemic respiratory failure (AHRF). In the multicenter PARIS-2 trial, over 1500 children hospitalized with AHRF defined as increased work of breathing, respiratory rate ≥35 per minute, and oxygen requirement to maintain pulse oximetry over 90 to 92 percent were randomized to HFNC or standard oxygen therapy; wheezing was present in approximately three-quarters of patients. Patients assigned to HFNC oxygen therapy, compared with standard oxygen therapy, had longer length of stay (1.77 versus 1.50 days) and more ICU admissions (12.5 versus 6.9 percent) [24]. Adverse events were low in both groups. These findings do not support the routine use of oxygen delivery by HFNC in young children with mild to moderate AHRF. (See "High-flow nasal cannula oxygen therapy in children", section on 'Indications'.)

Video laryngoscopy for emergency endotracheal intubation in children (January 2023)

Laryngeal exposure with visualization of the glottis is a key determinant of success or failure for emergency endotracheal intubation (ETI) in children. In a prospective cohort study of over 1400 children undergoing ETI in pediatric emergency departments, use of video laryngoscopy (VL) with standard geometry blades, when compared with traditional direct laryngoscopy (DL), was associated with higher odds of first-attempt success and decreased odds of severe adverse airway outcomes such as aspiration, severe hypoxia, unrecognized esophageal intubation, hypotension, or cardiac arrest [25]. Based on these and other data, we suggest routine use of VL, if readily available, for emergency intubation in children. However, some experienced clinicians continue to prefer DL based upon their expertise. (See "Emergency endotracheal intubation in children", section on 'Laryngoscopy'.)

Pediatric early warning scores in hospitalized children (January 2023)

Pediatric early warning scores (PEWS) are used to identify hospitalized children whose condition may be worsening and to prompt rapid assessment and specific intervention. The effect of PEWS was reviewed as part of the 2022 International Liaison Committee on Resuscitation (ILCOR) consensus recommendations [26]. In the single randomized trial of PEWS in 21 pediatric hospitals, fewer clinical deterioration events (eg, endotracheal intubation, fluid resuscitation, or CPR) occurred in hospitals using PEWS compared with those that did not, and there was a nonsignificant trend towards lower mortality. Meta-analysis of nine cohort studies found similar results, with nonsignificant differences in mortality and other endpoints favoring use of PEWS. Although the overall quality of the evidence is low, we agree with the ILCOR consensus and suggest use of PEWS in all hospitalized children. (See "Pediatric advanced life support (PALS)", section on 'Pediatric early warning scores'.)

Xylazine adulteration of illicit drugs (December 2022)

Xylazine is an alpha-2 agonist and a chemical analogue of clonidine that is used in veterinary medicine for sedation and analgesia. In humans, xylazine overdose has caused major toxicity consisting of coma, apnea, bradycardia, and hypotension as well as severe, necrotic skin ulcerations after repeated parenteral use. Xylazine is increasingly found as an adulterant in illicit drugs, especially heroin and fentanyl, with rising reports of serious side effects. As a result, the US Food and Drug Administration has issued an alert to health care professionals and a letter to stakeholders [27]. Xylazine poisoning is on the differential diagnosis for patients with suspected opioid overdose that does not respond to naloxone administration. Treatment consists of supportive care. There is no rapid diagnostic testing for xylazine poisoning or safe antidote. (See "Clonidine and related imidazoline poisoning", section on 'Imidazoline agents'.)

Administration of vasoactive therapy by peripheral IV in children with shock (October 2022)

For children with shock who require vasoactive therapy, central venous access is preferred. However, delivery of vasoactive therapy by peripheral intravenous (PIV) access may be used during initial resuscitation while central venous access is obtained. In a recent retrospective cohort study of over 750 critically ill children receiving vasoactive infusions for shock, of 231 children who initially received vasoactive therapy by PIV (93 patients with septic shock), extravasation occurred in 4 patients (1.7 percent, all hand vein sites) with no long-term complications; 46 percent of these patients ultimately did not require central venous access and had full recovery [28]. These findings confirm prior data that the delivery of dilute vasoactive medications by the most proximal peripheral vein in selected children with shock is safe. The decision and timing of central venous catheter placement depends on the expected severity and trajectory of shock, as well as other clinical needs that may require central venous access. (See "Septic shock in children: Rapid recognition and initial resuscitation (first hour)", section on 'Indications for vasoactive agents'.)

Risk of meningitis in febrile young infants with a positive urinalysis (October 2022)

Existing American Academy of Pediatrics guidelines suggest that cerebrospinal fluid (CSF) studies be obtained in otherwise low-risk febrile young infants (29 to 60 days old) with elevated blood inflammatory markers (IMs) (table 1), independent of urinalysis (UA) results. However, prior studies have found that for these infants, the risk of meningitis is low. In a secondary analysis of a prospective cohort study of nearly 700 well-appearing, previously healthy, febrile young infants (29 to 60 days old) with a positive UA, none had bacterial meningitis, including the 204 individuals with elevated procalcitonin or absolute neutrophil count [29]. Based on these findings, for otherwise low-risk febrile young infants 29 to 60 days old with elevated IMs and a positive UA, we no longer suggest obtaining CSF studies. Our practice is unchanged with regard to febrile infants in this age group who have elevated IMs and a negative UA (CSF recommended) or normal IMs and a positive UA (CSF not recommended). (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on '29 to 60 days old'.)

Severe complications of button battery ingestion in children (October 2022)

Button battery (BB) ingestion with esophageal impaction in children is a true emergency that can cause life-threatening complications. In a systematic review of 361 pediatric cases of BB ingestion resulting in severe complications (95 percent with esophageal impaction), death occurred in 19 percent of patients [30]. Hemorrhage from vascular injuries, primarily aortoesophageal fistulae, was the most common cause of death. Among patients with vascular injuries, those who died had a longer duration of impaction than those who survived (median 144 versus 11 hours, respectively). These findings highlight the importance of timely recognition of BB ingestion with esophageal impaction and emergency BB removal. (See "Button and cylindrical battery ingestion: Clinical features, diagnosis, and initial management", section on 'Complications'.)

ENDOCRINOLOGY

International consensus guidelines for the use of automated insulin delivery systems in type 1 diabetes (March 2023)

In individuals with type 1 diabetes, automated insulin delivery (AID; hybrid closed-loop) systems improve glycemia. AID therapy is now widely available, but formal guidance for implementing AID systems in clinical practice has been limited. An international panel convened by the Advanced Technologies & Treatments for Diabetes (ATTD) Congress has issued guidelines for the use of AID systems in diabetes management [31]. These guidelines provide recommendations for identifying candidates for AID therapy, providing requisite education and training for users, and selecting initial insulin delivery settings. They also emphasize the importance of creating structured and individualized treatment plans and reducing disparities in access to AID therapy. Adequate resources and infrastructure are critical for individuals with type 1 diabetes to derive benefit from AID systems. These guidelines are largely consistent with the UpToDate approach for the optimization of AID therapy in diabetes care. (See "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Patient selection'.)

Automated insulin delivery systems for young children with type 1 diabetes (March 2023)

Increasing evidence supports the benefits of automated insulin delivery systems groups for young children with type 1 diabetes. In a 13-week randomized trial in 102 children two to five years old that compared glycemic outcomes for a hybrid closed loop (HCL) system with standard type 1 diabetes care (continuous insulin pump or multiple daily injections with continuous glucose monitoring), patients assigned to the HCL system had substantially increased time in target range (approximately three more hours daily) with the greatest improvement at night [32]. Episodes of hyperglycemia (including one episode of diabetic ketoacidosis) were more common in the HCL group and were primarily related to infusion set failure. Severe hypoglycemia was uncommon in both groups. These findings and experience with other HCL devices in young children support our suggestion for a HCL system, if available, rather than insulin pumps for most pediatric patients with type 1 diabetes, including young children. Education of parents/primary caregivers regarding recognition and management of infusion set failures is essential to their safe use. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)'.)

Immunotherapy to delay type 1 diabetes (December 2022)

Immunotherapies have been investigated extensively as a means of preserving pancreatic beta cell function and thereby delaying or preventing progression to type 1 diabetes in high-risk individuals. Teplizumab is the first disease-modifying immunotherapy for type 1 diabetes to receive regulatory approval in the United States [33]. Teplizumab, administered as a single 14-day course of daily intravenous infusions, delays the diagnosis of type 1 diabetes by a median of two years in individuals at high risk for developing the disease (ie, abnormal glucose tolerance and presence of at least two diabetes autoantibodies). Adverse effects include transient lymphopenia, rash, anemia, and fever. The clinical use of teplizumab remains uncertain and will require additional data regarding its benefits and risks, as well as the development of clearly delineated strategies for identifying optimal candidates for treatment. (See "Prevention of type 1 diabetes mellitus", section on 'Teplizumab'.)

Completely automated insulin delivery systems for type 1 diabetes (October 2022)

For patients with type 1 diabetes (T1D), completely automated insulin delivery systems promise enhanced glycemic management without the substantial time and training required for use of partially automated systems. In a 13-week unblinded trial in which 219 patients with T1D (ages 6 to 79 years, A1C 5.5 to 13.1 percent) were randomly assigned to a fully automated insulin delivery system or standard care (any mode of insulin delivery coupled with continuous glucose monitoring), the fully automated system led to a greater reduction in A1C (mean adjusted difference in A1C -0.5 percent) [34]. Participants assigned to fully automated insulin delivery also had a higher percentage of time spent in the target glucose range without increased frequency of hypoglycemia. Completely automated insulin delivery systems may enable expanded use of continuous insulin therapy among patients with T1D. (See "Insulin therapy for children and adolescents with type 1 diabetes mellitus", section on 'Automated insulin delivery (hybrid closed-loop insulin pumps)' and "Continuous subcutaneous insulin infusion (insulin pump)", section on 'Insulin only, fully automated system'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Dupilumab for eosinophilic esophagitis (January 2023)

Therapeutic options for eosinophilic esophagitis (EoE) are expanding. In a two-part trial in patients with EoE that had not responded to proton pump inhibitor therapy, weekly dupilumab resulted in higher rates of histologic improvement after 24 weeks relative to placebo (part A [weekly dupilumab]: 60 versus 5 percent, and part B [dupilumab every 2 weeks]: 59 versus 6 percent) [35]. Dupilumab also improved dysphagia symptom scores. Based on these findings, the US Food and Drug Administration approved dupilumab for EoE in patients ≥12 years of age who weigh ≥40 kg [36]. Future studies will help to inform the role of dupilumab in EoE management. (See "Treatment of eosinophilic esophagitis (EoE)", section on 'Options for nonresponders'.)

GENETIC AND METABOLIC DISORDERS

Risk of progression to dementia in Down syndrome (October 2022)

Down syndrome (DS) is now considered a genetically determined form of Alzheimer disease (AD), with an estimated age of onset (53.8 years) and age of death (58.4 years) similar to that seen in autosomal dominant AD [37]. In one series of 632 adults with DS and varying levels of cognitive disability (436 asymptomatic, 69 with prodromal AD, and 127 with AD dementia) followed for five years, progression to AD dementia was seen in 17.1 percent of asymptomatic patients and was age dependent (0.6 percent for age <40 years, 21.1 percent for 40 to 44 years, 41.4 for 45 to 49 years, and 57.5 for ≥50 years) [38]. Patients with DS should be monitored closely for cognitive decline, particularly after age 40 years. (See "Down syndrome: Management", section on 'Alzheimer disease'.)

HEMATOLOGY AND ONCOLOGY

Hydroxyurea in sickle cell disease (February 2023)

A 2014 guideline recommends hydroxyurea for all infants, children, and adolescents with sickle cell disease and all adults with frequent vaso-occlusive complications, supported by decades of experience and strong evidence of reduced complications and improved survival [39]. A new study documented increased hydroxyurea use from 7 percent in 2004 to 22 percent in 2019 [40]. While demonstrating improvement, these findings suggest that persistent barriers to use remain. Strategies are needed to increase uptake of this effective therapy. (See "Hydroxyurea use in sickle cell disease", section on 'Eliminating barriers to appropriate therapy'.)

Improved survival for transfusion-dependent thalassemia (February 2023)

Survival for transfusion-dependent thalassemia (TDT) continues to improve with advances in managing iron overload and other complications. A new longitudinal cohort of 700 individuals with TDT managed by specialized centers in Italy reported improved survival in those born after 1985 (survival to age 30 in 93 percent, versus 84 percent in earlier birth cohorts) [41]. Heart disease remains a major risk factor for – and cause of – death. Outcomes in other centers are poorer, emphasizing the need for multidisciplinary specialized centers in caring for individuals with TDT [42]. (See "Management of thalassemia", section on 'Prognosis'.)

Preoperative chemotherapy in bilateral Wilms tumor (November 2022)

Studies are investigating the strategy of preoperative chemotherapy followed by kidney parenchymal-sparing resection for patients with bilateral Wilms tumor. In long-term follow-up of a single arm, prospective study in almost 200 patients with bilateral Wilms tumor, this strategy was associated with a four-year overall survival rate of 95 percent [43]. It was greater for those with low-risk disease, intermediate-risk disease, and blastemal-type tumors than for those with high-risk diffuse anaplasia (>90 versus 72 percent). Fewer than 3 percent of patients required bilateral nephrectomy. For patients with bilateral Wilms tumor, we continue to suggest preoperative chemotherapy followed by kidney parenchymal-sparing resection rather than more extensive bilateral kidney resection. (See "Treatment and prognosis of Wilms tumor", section on 'Bilateral kidney involvement'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Meningitis B vaccination in young children (February 2023)

Indications for meningitis B vaccination vary by country and depend on the epidemiology of invasive meningococcal disease. In a case-control study from Spain that evaluated children <5 years of age, complete vaccination with the MenB-4C serogroup B meningococcal vaccine series was 71 percent effective against invasive serogroup B meningococcal disease; receipt of ≥1 dose was 64 percent effective [44]. The MenB-4C vaccine also provided protection against non–serogroup B invasive disease. The findings of this study may inform immunization programs for at-risk children and children from areas with a high prevalence of serogroup group B meningococcal disease. (See "Meningococcal vaccination in children and adults", section on 'Immunogenicity and effectiveness'.)

Feeding and antiretroviral prophylaxis for infants born to mothers with HIV (February 2023)

The United States Department of Health and Human Services (DHHS) issued updated guidelines on breastfeeding and antiretroviral prophylaxis for infants born to mothers with HIV [45]:

●Patients who are virologically suppressed and have been on ART consistently through at least the third trimester and at delivery can now consider breastfeeding after discussing the risks and benefits with their clinician. The guidelines continue to strongly recommend against breastfeeding for individuals without virologic suppression.

●Formula-fed infants who are at very low risk of HIV acquisition (full-term and born to mothers who maintained viral suppression on at least 10 consecutive weeks of ART during pregnancy and delivery without adherence concerns) can receive only 2 weeks of zidovudine instead of the previously recommended 4 to 6 weeks. For breastfed infants who are at low risk of HIV acquisition at birth, the guidelines recommend six weeks of zidovudine.

We are in agreement with these recommendations. (See "Intrapartum and postpartum management of pregnant women with HIV and infant prophylaxis in resource-rich settings", section on 'Breastfeeding'.)

Novel oral type 2 poliovirus vaccine (nOPV2) in newborn infants (January 2023)

In 2020, the World Health Organization (WHO) authorized emergency use of a novel oral poliovirus vaccine (nOPV2) to prevent outbreaks of polio caused by type 2 vaccine-derived strains; however, data in individuals <18 weeks had previously been limited. In a randomized, placebo-controlled trial of 330 healthy newborn infants with no prior poliovirus vaccination, nOPV2 was safe, well tolerated, and immunogenic (99 percent had protective antibody levels after two doses) [46]. Shedding of vaccine-derived virus in stool was low and of short duration, suggesting that sustained transmission of nOPV2 is unlikely. Many countries, including the United States, use injectable vaccines composed of inactivated poliovirus that cannot cause infection. However, for those countries that still use oral vaccines, these data are reassuring and support continued use of nOPV2 in infants. (See "Poliovirus vaccination", section on 'Monovalent OPV vaccines and nOPV2'.)

Increasing invasive group A streptococcal infections among children in Europe (December 2022)

Several European countries, including England, France, Ireland, the Netherlands, and Sweden, have reported an increased rate of invasive group A streptococcal (GAS) infections among children <10 years old during the fall and winter of 2022 to 2023 compared with prior years [47,48]. This increase parallels a >3-fold rise in reported cases of scarlet fever and may reflect an early GAS season coinciding with an increase in circulating respiratory viruses. No increase in antibiotic resistance has been observed among isolated GAS strains. Enhanced surveillance activities have been implemented in the affected areas and public health organizations are emphasizing the importance of early recognition and prompt treatment of GAS infections, particularly scarlet fever. (See "Invasive group A streptococcal infections in children", section on 'Incidence'.)

Palivizumab for prevention of hospitalization during the 2022-2023 RSV season (November 2022)

During the COVID-19 pandemic, interseasonal respiratory syncytial virus (RSV) activity increased in some regions, resulting in increased pediatric hospitalizations. In regions with interseasonal activity similar to that in a typical fall-winter season, expert groups supported administration of palivizumab to eligible children outside of the typically recommended schedule. If regional RSV activity persists at high levels through the fall and winter of the 2022-2023 RSV season, the American Academy of Pediatrics supports administration of more than five consecutive doses of palivizumab to eligible children who initiated palivizumab earlier than typically recommended [49]. Information about state-level RSV activity in the United States is available from the Centers for Disease Control and Prevention. We agree with this endorsement. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Increased interseasonal activity during COVID-19 pandemic'.)

Expanded ACIP recommendations for oral cholera vaccine (October 2022)

CVD 103-HgR (Vaxchora) is a single-dose, live attenuated oral cholera vaccine derived from Vibrio cholerae serotype O1; it was licensed by the US Food and Drug Administration and recommended by the Advisory Committee on Immunization Practices (ACIP) in 2016 for adults age 18 to 64 years traveling to areas of active cholera transmission. In 2022, the ACIP expanded the age group to include individuals age 2 to 17 years who meet these criteria [50]. Thus far, assessment of CVD 103-HgR vaccine benefit in children has been based on safety and immunogenicity data rather than direct assessment of vaccine efficacy. We are in agreement with this guidance. (See "Cholera: Clinical features, diagnosis, treatment, and prevention", section on 'For travelers to high-risk areas'.)

Updated recommendations for pneumococcal vaccination in children and adolescents (September 2022)

Updated guidance from the Advisory Committee on Immunization Practices (ACIP) permits interchangeable use of the recently licensed 15-valent pneumococcal conjugate vaccine (PCV15) and 13-valent PCV (PCV13) for routine infant immunization and immunization of high-risk children and adolescents (table 2) [51]. PCV15 contains the 13 serotypes included in PCV13 plus serotypes 22F and 33F (table 3), which accounted for 15 to 23 percent of invasive pneumococcal disease cases in children <18 years in the United States during 2018 to 2019. In prelicensure randomized trials, PCV15 demonstrated immunogenicity and safety similar to those of PCV13. We agree with the ACIP recommendations for PCV15. Clinical trials of the 20-valent PCV in children are ongoing. (See "Pneumococcal vaccination in children", section on 'Conjugate vaccines'.)

NEONATOLOGY

Initial target for parenteral protein intake in extremely low birthweight infants (December 2022)

Recommended targets for parenteral amino acid (AA) intake in premature infants are between 2.5 and 3.5 g/kg/day, but the optimal target for extremely low birthweight infants (ELBW, birthweight <1000 g) is unknown. A new randomized trial in nearly 500 ELBW infants compared outcomes for infants with high (AA 3.4 g/kg/day) versus low intake (AA 2.6 g/kg/day) for the first five days of life [52]. At two years of age, the infants who received the higher AA dose were more likely to have moderate to severe neurodisability compared with those who received lower doses (16.5 versus 8.6 percent; adjusted relative risk [aRR] 1.95, 95% CI 1.09-3.48). There were no differences in mild neurodevelopmental impairment or in most other components of the Bayley III. These results are the basis for our suggested target of 2.5 g/kg/day of AA in parenteral nutrition for ELBW infants during the first week of life. (See "Parenteral nutrition in premature infants", section on 'Amino acids'.)

DHA supplementation for very low birth weight infants (November 2022)

The long-term effect of enteral supplementation with docosahexaenoic acid (DHA) on cognitive outcomes in low birth weight premature infants has been inconsistent. In a continuation of an earlier trial in 480 premature infants <29 weeks gestation assigned to DHA (60 mg/kg per day) or placebo at the initiation of enteral feeding, scores for full-scale intelligence quotient (IQ) at five years of corrected age were higher for the DHA-supplemented group (mean difference 3.5 points [95% CI 0.4-6.5], a 4-point difference is clinically relevant) [53]. Based on these findings and benefits identified for other comorbidities of prematurity in other studies, we suggest that premature infants receiving human milk also receive supplementation with DHA. Our approach is to add a human milk fortifier that contains these nutrients to breast milk. (See "Long-chain polyunsaturated fatty acids (LCPUFA) for preterm and term infants", section on 'Very low birth weight infants'.)

Updated guidance on neonatal hyperbilirubinemia (October 2022)

The American Academy of Pediatrics (AAP) has updated its clinical practice guidance on management of hyperbilirubinemia in term and late preterm newborns ≥35 weeks of gestation [54]. Key changes from earlier guidelines include:

●Initial newborn screening can be performed either with a laboratory test (ie, total serum bilirubin [TSB]) or transcutaneous bilirubin (TcB) device; abnormal TcB results require confirmation with TSB

●Guidance for follow-up after newborn bilirubin screening has been updated (table 4)

●Higher treatment TSB thresholds are used for initiating phototherapy (figure 3A-B) and exchange transfusion (figure 4A-B)

●New guidance is provided for "escalation of care" to rapidly address dangerously high bilirubin concentrations (algorithm 1)

We generally agree with the updated AAP guidance. Importantly, since the new treatment thresholds are higher than in previous guidelines, delays in starting phototherapy are more likely to result in dangerously high TSB levels. Thus, when treatment is indicated, it should begin promptly. (See "Screening for hyperbilirubinemia in term and late preterm newborns" and "Initial management of unconjugated hyperbilirubinemia in term and late preterm newborns" and "Escalation of care for term and late preterm newborn infants with unconjugated hyperbilirubinemia".)

Antenatal corticosteroids for anticipated preterm birth before 23 weeks (October 2022)

The value of antenatal corticosteroids (ACS) in pregnancies between 21 and 23 weeks of gestation is controversial. In an observational cohort study including over 400 infants born at 22^0/7 to 23^6/7 weeks of gestation, administration of a complete course of ACS was associated with higher survival to discharge compared with no ACS (54 versus 36 percent); however, most survivors had major morbidity when evaluated at 36 weeks postmenstrual age (survival without major morbidity: 27 percent with ACS, 10 percent without ACS) [55]. Shared decision-making (parents, obstetrical and neonatal staff) is particularly important at this gestational age when parents are faced with a decision affecting their child's survival and quality of life. (See "Antenatal corticosteroid therapy for reduction of neonatal respiratory morbidity and mortality from preterm delivery", section on '22+0 to 22+6 weeks'.)

NEUROLOGY

Diagnostic criteria for myelin oligodendrocyte glycoprotein antibody-associated disease (March 2023)

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an inflammatory disorder of the central nervous system characterized by attacks of immune-mediated demyelination predominantly targeting the optic nerves, brain, and spinal cord. New diagnostic criteria for MOGAD proposed by an expert international consensus panel require the following [56]:

●One of six core clinical demyelinating events (ie, optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, cerebral monofocal or polyfocal deficits, brainstem or cerebellar deficits, or cerebral cortical encephalitis)

●A positive MOG-immunoglobulin G (IgG) antibody test

●The exclusion of a better diagnosis

The new MOGAD criteria include supportive features that argue for the diagnosis if the MOG-IgG titer is not clearly positive and red flag features that argue against the diagnosis. These criteria are intended to improve the identification of people with MOGAD and distinguish it from other disorders with overlapping clinical features, including multiple sclerosis and aquaporin 4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder. (See "Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD): Clinical features and diagnosis", section on 'Diagnostic criteria'.)

Cerebral palsy and maternal injury during pregnancy (January 2023)

The underlying causes of cerebral palsy (CP) are often unknown, though several perinatal risk factors have been identified (eg, prematurity, hypoxic-ischemic injury, intrauterine infections). In a large cohort study that included over 2 million children, those with in utero exposure to accidental maternal injury requiring emergency department or inpatient care had a higher prevalence of CP compared with unexposed children (3.6 versus 2.5 per 1000 children, respectively) [57]. CP risk correlated with severity of maternal injury. These findings highlight the importance of prevention efforts to reduce the risk of severe injury during pregnancy (correct use of seat belts and airbags). (See "Cerebral palsy: Epidemiology, etiology, and prevention", section on 'Antenatal infection or injury'.)

Gene therapy for early childhood cerebral adrenoleukodystrophy (November 2022)

Standard treatment for the early childhood cerebral form of adrenoleukodystrophy (ALD), caused by pathogenic variants in the ABCD1 gene, is allogenic hematopoietic cell transplantation (HCT), if the child has a human leukocyte antigen (HLA)-matched donor. Recently, the US Food and Drug Administration (FDA) approved elivaldogene autotemcel, a novel ex vivo lentiviral gene therapy consisting of autologous HCT using stem cells transfected with manufactured ABCD1 complementary DNA [58]. The approval was based upon published and unpublished data showing that survival at nine months following treatment appeared to be better in patients treated with either HLA-matched allogenic HCT or elivaldogene autotemcel compared with HLA-mismatched allogenic HCT [59]. No patient treated with elivaldogene autotemcel developed graft-versus-host disease, which can complicate allogenic HCT. These results suggest that elivaldogene autotemcel may have comparable efficacy for early cerebral ALD compared with allogeneic HCT and may be safer, particularly when compared with HLA-mismatched allogenic HCT. However, given the relatively short follow-up, the results should be regarded as preliminary. The FDA label carries a boxed warning about the risk of hematologic malignancy and life-threatening myelodysplastic syndrome. (See "X-linked adrenoleukodystrophy and adrenomyeloneuropathy", section on 'Autologous HCT with ex vivo gene therapy'.)

Mechanisms causing disability accrual in multiple sclerosis (October 2022)

An analysis of the large Novartis-Oxford multiple sclerosis data set evaluated the two main mechanisms leading to accrual of disability in multiple sclerosis (MS), which are relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) [60]. The study found that RAW contributed to disability progression primarily in the early stages of MS. PIRA was also present early in the course of all MS phenotypes (relapsing and progressive) and became the main driver of disability in the later stages. Early use of disease-modifying therapy (DMT) delayed disability progression by several years. These findings help to clarify the relative contributions of RAW and PIRA to disability accrual in MS and support the importance of starting DMT early in the course of MS. (See "Clinical presentation, course, and prognosis of multiple sclerosis in adults", section on 'Relapsing versus progressive disease'.)