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What's new in pediatrics

What's new in pediatrics
Literature review current through: Jan 2024.
This topic last updated: Jan 31, 2024.

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.


Return to sport following stress fracture (November 2023)

Evidence is limited regarding return to sport (RTS) following stress fracture. A new systematic review of 76 studies involving nearly 3000 cases,provides some guidance; most of the studies were retrospective and involved predominately male athletes [1]. The lowest overall rates for RTS were reported for injuries of the femoral neck (55 percent), talus (69 percent), anterior tibial shaft (76 percent), and tarsal navicular (83 percent). The longest average times for RTS were reported for stress fractures of the tarsal navicular (127 days), femoral neck (107 days), and medial malleolus (106 days). These figures are averages, and healing for individuals may vary substantially given the many factors involved, including location within the bone, radiologic grade, duration of symptoms, compliance with treatment, and underlying bone health. Nevertheless, these findings inform treatment decisions and anticipatory guidance for athletes. (See "Overview of stress fractures", section on 'Return to activity'.)

Heavy load resistance exercise for tendinopathy (November 2023)

Evidence supporting the effectiveness of resistance exercise for the treatment of chronic (overuse) tendinopathy is growing. A recent systematic review and meta-analysis of 110 studies with just under 4000 subjects assessed research primarily involving the rotator cuff, Achilles, lateral elbow, and patellar tendons [2]. While noting that resistance dose was not well documented in many studies, researchers found consistent evidence that rehabilitation programs using resistance loads in excess of body weight and performed less frequently (ie, less than daily) demonstrated greater efficacy. These findings are consistent with our approach to treatment. (See "Overview of the management of overuse (persistent) tendinopathy", section on 'Heavy-load resistance training'.)

Avulsion fractures of hip and pelvis in children (October 2023)

There are few large-scale studies of pelvic avulsion fractures in children. A retrospective review of over 700 children with pelvic or hip avulsion fractures from a single tertiary care hospital reported the average patient age was just over 14 years and nearly 80 percent were sustained by males [3]. The anterior-superior and inferior iliac spines and ischial tuberosity were the most common sites, accounting for over 80 percent of fractures. Most injuries were sustained while the patient was running or kicking during sport, most often football (soccer). The incidence of avulsion fracture rose substantially during the study period, 2005 to 2020. (See "Pelvic trauma: Initial evaluation and management", section on 'Epidemiology and mechanism'.)

6th International Conference on Concussion in Sport (August 2023)

Recently, a consensus statement and multiple systematic reviews and other studies were published based on work completed at the 6th International Conference on Concussion in Sport held in Amsterdam in late 2022 [4]. Highlights from the conference include evidence summaries emphasizing the effectiveness of policies to reduce the risk for sports-related concussion (SRC), including mouthguard use in ice hockey and limiting contact drills in American football, and updated clinical assessment tools. These tools include the sixth edition of the Sport Concussion Assessment Tool for adults and children (SCAT6 and Child SCAT6), designed for acute evaluations, and the new Sports Concussion Office Assessment Tool 6 for adults and children (SCOAT6 and Child SCOAT6). The conference affirmed the importance of physical activity and aerobic exercise that does not exacerbate symptoms as an early intervention. The conference consensus statement is consistent with our approach to the assessment and management of SRC. (See "Clinic-based evaluation of sports-related concussion in adolescents and adults", section on 'Introduction'.)


Cannabinoids and mental health in adolescents (December 2023)

Cannabis use is associated with an increased risk of mental health disorders. However, little is known about the effects of cannabidiol (CBD), a nonpsychoactive component of cannabis used for anorexia and childhood epilepsy, or of recreational synthetic cannabinoids. In a school-based survey from the United Kingdom that included over 6500 adolescents ages 13 to 14 years, reported use of cannabis, CBD, or synthetic cannabinoids were each associated with probable depression, anxiety disorder, or conduct disorder, as well as with auditory hallucinations [5]. For each disorder, the risk appeared greatest with synthetic cannabinoids. This study highlights the need for further investigation into the association between mental health effects in youth and the different types of cannabinoids. We advise adolescents (and younger children) to avoid cannabis consumption, including CBD. (See "Substance use disorder in adolescents: Epidemiology, clinical features, assessment, and diagnosis", section on 'Cannabis, cannabidiol, and synthetic cannabinoids'.)

High blood lead levels in US children after eating cinnamon applesauce pouches (November 2023)

The Centers for Disease Control and Prevention have issued a health alert following reports of high blood lead levels from several states for a total of 22 children who were fed cinnamon-containing applesauce pouches that were subsequently found to contain extremely high concentrations of lead [6]. Children who have eaten a recalled product should undergo blood lead testing. Clinicians should advise parents, primary caregivers, and guardians to not buy specific cinnamon-containing apple puree or applesauce products named in the US Food and Drug Administration announcement and to discard any recalled products that they have purchased. (See "Childhood lead poisoning: Exposure and prevention", section on 'Food' and "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Laboratory evaluation' and "Childhood lead poisoning: Management".)

Long distance effect of wildfire smoke on asthma symptoms (October 2023)

Wildfire fine particulate matter (PM2.5) has been shown to affect respiratory health; however, previous work has focused on populations residing near and directly affected by wildfires. In June 2023, smoke from wildfires in Canada drifted hundreds of miles to New York City, resulting in increased ambient PM2.5. During smoke waves, emergency department visits for asthma in both pediatric and adult patients increased to 261 per day (reference during nonsmoke periods, 181.5 per day; incidence rate ratio 1.4) [7]. Wildfires have health effects far from their source and are particularly hazardous to those with underlying lung disease. (See "Climate emergencies", section on 'Changing wildfire exposure'.)


Baricitinib for refractory juvenile idiopathic arthritis (November 2023)

Janus kinase (JAK) inhibitors are one of several options for children with polyarticular juvenile idiopathic arthritis (pJIA) that is refractory to conventional therapy (eg, methotrexate with or without a biologic tumor necrosis factor inhibitor). In a phase 3, randomized trial of 220 children aged 2 to 17 years with JIA (66 percent with pJIA) who had inadequate response or intolerance to standard therapy, patients assigned to the investigational JAK inhibitor baricitinib had a longer time to disease flare compared with placebo [8]. During the study period, fewer patients receiving baricitinib had a flare compared with placebo (17 versus 51 percent, respectively), but more infections occurred in the baricitinib group than the placebo group. However, rates of serious adverse events were similar in both groups. Baricitinib compares favorably with tofacitinib, another JAK inhibitor used in refractory pJIA, but is not yet approved for this indication. (See "Polyarticular juvenile idiopathic arthritis: Treatment", section on 'Baricitinib'.)

Low awareness of meat allergy caused by "alpha-gal syndrome" (September 2023)

Allergy to galactose-alpha-1,3-galactose, a carbohydrate allergen found in all mammalian meat except that of primates, causes allergic reactions to meats like beef, pork, and lamb, as well as to an array of other products, medications, and medical devices made with mammalian tissues. This allergy, first reported in 2009 and termed "alpha-gal syndrome," develops following the bites of certain ticks and causes reactions that are uncharacteristically delayed (ie, several hours after ingestion). A common presentation is anaphylaxis developing in the middle of the night after a meat-containing evening meal. Although the prevalence is increasing worldwide, a web-based survey of 1,500 health care professionals in the United States revealed that 42 percent had never heard of the disorder [9]. This lack of awareness can delay diagnosis for decades. (See "Allergy to meats", section on 'In whom to suspect the diagnosis'.)

Newborn screening for severe combined immunodeficiency (August 2023)

Historically, best outcomes after hematopoietic cell transplantation (HCT) for severe combined immunodeficiency (SCID) occur in younger recipients without infection at the time of transplant. In a multicenter, longitudinal study, from 2010 to 2018, five-year overall survival after HCT was higher for children identified with SCID by newborn screening (93 percent) compared with those identified by family history or clinical presentation (80 and 85 percent, respectively) [10]. In multivariable analysis, younger age and absence of active infection at the time of HCT, both of which are improved by identification through newborn screening, were strongly associated with overall survival. Expanded use of newborn screening for SCID in public health programs worldwide could lead to additional improvement in survival after HCT wherever available. (See "Hematopoietic cell transplantation for severe combined immunodeficiencies", section on 'Newborn screening'.)


Infertility and autism spectrum disorder (December 2023)

Patients with infertility often ask about the impact of the disorder and its treatment on risk of autism spectrum disorder (ASD) in offspring. In a large population-based cohort study comparing ASD risk among children whose parents had subfertility (an infertility consultation without treatment), infertility treatment, or neither (unassisted conception), children in the subfertility and infertility treatment groups had a small increased risk of ASD compared with unassisted conception but the absolute risk was low (2.5 to 2.7 per 1000 person-years versus 1.9 per 1000 person-years with unassisted conception) [11]. The increased risk was similar in the subfertile and infertility treatment groups, suggesting that infertility treatment was not a major risk factor. Obstetrical and neonatal factors (eg, preterm birth) appeared to mediate a sizeable proportion of the increased risk for ASD. (See "Assisted reproductive technology: Infant and child outcomes", section on 'Confounders'.)


Ultrasound guidance for lumbar puncture in children (August 2023)

Previous studies suggest that ultrasound guidance for lumbar puncture (LP) in children increases the chance of success. In a meta-analysis of seven randomized trials (over 700 infants and children), overall LP success rate was higher with ultrasound guidance compared with the use of external landmarks and palpation alone, but the difference was not significant [12]. Subgroup analysis of five studies (over 520 children) demonstrated significantly higher first attempt success in infants undergoing ultrasound guidance, but not in older children. The overall quality of the evidence was considered low. Based on these findings, when performed by a trained provider, ultrasound guidance prior to LP may be useful in infants. Ultrasound guidance in older children is also reasonable, but evidence of benefit in these patients is lacking. (See "Lumbar puncture in children", section on 'Ultrasound guidance'.)

Invasive bacterial illness in febrile young infants with COVID-19 (July 2023)

Evidence is limited for the risk of invasive bacterial illness (IBI) in febrile young infants <60 days old with SARS-CoV-2 infection. In one cohort study of 163 well-appearing febrile infants ≤60 days old (36 neonates) who were diagnosed with COVID-19 by multiplex viral panel testing, none had IBI compared with 0.5 percent of 448 infants with other viral infection (none had meningitis) and 1.3 percent of 320 infants with no viral infection on testing (one with meningitis) [13]. For well-appearing febrile infants ≤60 days old with a positive test for SARS-CoV-2, the risk of IBI appears to be low. For well-appearing infants 29 to 60 days, we suggest, at minimum, urinalysis and urine culture. It is also reasonable to obtain additional studies according to the American Academy of Pediatric Clinical Practice Guideline (algorithm 1). Evidence is insufficient to change the recommended evaluation for well-appearing neonates. (See "The febrile infant (29 to 90 days of age): Outpatient evaluation", section on 'COVID-19' and "The febrile neonate (28 days of age or younger): Outpatient evaluation and initial management", section on 'Well-appearing'.)


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

In type 1 diabetes, the janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been implicated in immune-mediated beta cell destruction. In a trial in 91 individuals (aged 10 to 30 years) with new-onset type 1 diabetes (diagnosed within 100 days), participants were randomly assigned to daily treatment with the oral JAK1/2 inhibitor baricitinib (n = 60) or placebo (n = 31) [14]. After 48 weeks of therapy, insulin secretion was greater with baricitinib compared with placebo (median stimulated mean C-peptide level 0.65 versus 0.43 nmol/L per minute, respectively). A1C, frequency of hypoglycemia, and the percentage of time spent in the target glucose range (70 to 180 mg/dL [3.9 to 10 mmol/L]) were not significantly different between groups. JAK/STAT pathway inhibition is a promising strategy for preserving insulin secretion in new-onset type 1 diabetes. (See "Type 1 diabetes mellitus: Prevention and disease-modifying therapy", section on 'Cytokine-directed therapies'.)

Investigational once-weekly basal insulin therapy (insulin icodec) for the treatment of adults with type 1 diabetes (November 2023)

Ultra-long-acting insulin icodec is an investigational basal insulin therapy that requires only once-weekly dosing. In a trial in 655 adults with type 1 diabetes (mean A1C approximately 7.6 percent), participants were randomly assigned to basal insulin therapy with once-weekly insulin icodec or once-daily insulin degludec [15]. After 26 weeks, the mean reduction in A1C was similar in the icodec and degludec groups (-0.47 and -0.51 percentage points, respectively). However, insulin icodec led to a nearly twofold higher combined rate of clinically significant (<54 mg/dL [<3 mmol/L]) or severe hypoglycemia (2836 versus 1495 events with insulin degludec). Additional studies are needed to determine whether risk of hypoglycemia will limit the use of ultra-long-acting insulin in individuals with type 1 diabetes. (See "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.)


Testing for hepatitis C virus infection in infants with perinatal exposure (November 2023)

Perinatally acquired hepatitis C virus (HCV) infection in the United States has increased sharply since 2010. New guidance from the Centers for Disease Control and Prevention recommends early testing for infants with perinatal exposure to HCV (algorithm 2) [16]:

● Test for HCV RNA during early infancy after two months of age, and ideally before six months of age.

● After 18 months of age, test any infant who has not previously been tested by measuring anti-HCV antibodies, with reflexive testing for HCV RNA.

A negative HCV RNA result at any time point after two months of age virtually excludes HCV infection and further testing is not required. Children with a positive HCV RNA test before three years of age should have repeat testing for HCV RNA before initiating antiviral therapy to determine whether they have spontaneously cleared the infection. This new guidance is consistent with our previous recommendations for early testing for infants with perinatal exposure to HCV. (See "Hepatitis C virus infection in children", section on 'How to test'.)

Gene therapy for Crigler-Najjar syndrome (September 2023)

Gene therapy for Crigler-Najjar syndrome is directed at restoring sufficient UGT1A1 activity to maintain serum bilirubin in a safe range. In an open-label study of five young adults with Crigler-Najjar syndrome and severe hyperbilirubinemia managed with daily phototherapy (two with adjunctive phenobarbital), gene therapy was administered at one of two doses [17]. For the three participants in the high-dose cohort, the mean total bilirubin concentrations declined from 20.5 mg/dL (351 micromol/L) with phototherapy to 8.7 mg/dL (149 micromol/L) without phototherapy by 80 weeks. There were transient increases in liver enzymes, managed with immunosuppressive therapy, and no serious adverse events. Further studies are needed to determine the indications, optimal protocol, and long-term efficacy and safety of gene therapy. (See "Crigler-Najjar syndrome", section on 'Investigational therapies'.)


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

Whether routine thromboprophylaxis reduces the risk of thrombotic complications in patients with acute lymphoblastic leukemia (ALL) has been debated. In a multicenter randomized trial of over 500 children and adolescents with newly diagnosed pre-B or T cell ALL, patients assigned to prophylactic anticoagulation with apixaban compared with standard care alone had similar rates of symptomatic venous thrombosis (1.6 versus 2.3 percent, respectively) and asymptomatic venous thrombosis (11 versus 15 percent) [18]. Nonmajor bleeding episodes (mostly epistaxis) occurred more frequently in the apixaban group (4 versus 1 percent). These data do not support the routine use of thromboprophylaxis in children with ALL, although it may be warranted in selected patients with additional risk factors for thrombosis. (See "Thromboembolism in children with cancer", section on 'Primary prevention'.)

Maintenance eflornithine in high-risk neuroblastoma (January 2024)

For patients with high-risk neuroblastoma (HRNBL), there is interest in investigating novel maintenance therapies such as eflornithine, an ornithine decarboxylase inhibitor. In an externally controlled analysis of almost 100 patients with HRNBL who completed multimodality treatment and maintenance immunotherapy, extended maintenance therapy with eflornithine was associated with improved overall survival (hazard ratio 0.38) [19]. Based on these data, the US Food and Drug Administration approved eflornithine as maintenance therapy in patients with HRNBL who achieve at least a partial response to prior systemic agents and complete maintenance immunotherapy. Since maintenance eflornithine is not standard across all institutions, this agent may be offered on a case-by-case basis. (See "Treatment and prognosis of neuroblastoma", section on 'Eflornithine'.)

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

Methemoglobinemia is a potentially life-threatening condition in which heme iron becomes oxidized, preventing oxygen delivery. A report from a hospital in Japan described methemoglobinemia in 10 neonates who were fed infant formula prepared with tap water from the general hospital water supply [20]. The cause was identified as high levels of nitrites, and the source was traced to contamination by an anticorrosion agent from the heating system that entered the water supply due to a malfunctioning valve. All 10 survived, although 3 required methylene blue therapy. Infants are especially susceptible to methemoglobinemia because they have lower baseline levels of the enzyme that converts heme iron back to its normal state. (See "Methemoglobinemia", section on 'Nitrates and nitrites (from foods, drugs, preservatives, and chemicals)'.)

Severe hepatopathy in children with Wilms tumor (November 2023)

For children with Wilms tumor who develop severe hepatopathy (SH) due to chemotherapy and/or radiation therapy, there are limited studies on restarting therapy. In an observational study of almost 9000 patients treated for Wilms tumor with chemotherapy, the incidence of SH was less than 1 percent [21]. Among the 71 patients who developed SH, a majority (85 percent) were able to either continue or restart chemotherapy, typically at reduced doses. These data suggest that most patients with Wilms tumor who develop SH during treatment may be able to safely restart chemotherapy. (See "Treatment and prognosis of Wilms tumor", section on 'Late effects'.)


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

Nirsevimab is a new antibody that prevents severe respiratory syncytial virus (RSV) infection in infants. In a trial conducted in France, Germany, and the United Kingdom, more than 8000 otherwise healthy infants ≤12 months, born at ≥29 weeks' gestation, and entering their first RSV season were assigned to receive one dose of nirsevimab or no intervention [22]. The group who received nirsevimab had fewer hospitalizations for RSV-associated lower respiratory tract infection (0.3 versus 1.5 percent, efficacy 83.2 percent, 95% CI 67.8-92.0) and fewer infants with an oxygen saturation <90 percent (0.1 versus 0.5 percent, efficacy 75.7 percent, 95% CI 32.8-92.9). These findings further support the use of nirsevimab for RSV immunoprophylaxis in infants. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

R21/Matrix-M vaccine to prevent malaria in children (November 2023)

In October 2023, the World Health Organization (WHO) approved the R21/Matrix-M vaccine for prevention of malaria in children [23]. In a placebo-controlled randomized trial of 4800 children (age 5 to 36 months) in four African countries, 12-month efficacy of a three-dose vaccine series against clinical malaria was 75 percent at sites with seasonal transmission and 68 percent at sites with year-round transmission; these data are under peer review prior to publication [24]. The vaccine was well tolerated. Injection site pain and fever were the most frequent adverse events. Together with the RTS,S/AS01 vaccine (recommended by the WHO in 2021), this approval is expected to facilitate sufficient vaccine supply to benefit all children living in areas where malaria is a public health risk. (See "Malaria: Epidemiology, prevention, and control", section on 'R21/Matrix-M vaccine'.)

Updated guidance for pneumococcal vaccination in children in the Unites States (October 2023)

The Centers for Disease Control and Prevention (CDC) has provided updated guidance for pneumococcal vaccination, endorsing use of either the 15-valent or 20-valent pneumococcal conjugate vaccine (PCV15 or PCV20) for routine vaccination in infancy and childhood [25]. The primary vaccine schedule otherwise remains unchanged. For infants who previously received the 13-valent vaccine (PCV13), the series may be completed with PCV15 or PCV20; restarting the series is not necessary. Children with high-risk conditions(table 11) may require additional pneumococcal vaccination with either PCV20 or the polysaccharide vaccine (PPSV23) after age two years if their primary series did not include at least one dose of PCV20. We agree with the updated CDC guidance. Guidelines for pneumococcal vaccination in other countries may differ. (See "Pneumococcal vaccination in children", section on 'In the United States'.)

Immunoprophylaxis for severe respiratory syncytial virus in infants (October 2023)

Nirsevimab is a new monoclonal antibody that targets the prefusion conformation of the respiratory syncytial virus (RSV) F glycoprotein [26]. It has a longer half-life than palivizumab, an existing antibody that requires five monthly injections to provide immunoprophylaxis against severe RSV infection. The efficacy and safety of nirsevimab were demonstrated in two randomized placebo-controlled trials, one involving 1490 infants ≥35 weeks' gestation and the other involving >1400 preterm infants (29 to <35 weeks' gestation) [27,28]. In both trials, a single intramuscular dose of nirsevimab lowered rates of RSV-related medical evaluation and hospital admissions for RSV. In line with American Academy of Pediatrics and United States Centers for Disease Control and Prevention guidance, we now recommend that infants <8 months old receive one dose of nirsevimab during their first RSV season if the birthing parent did not receive RSV vaccination between 32 and 36 weeks of gestation and at least 14 days prior to delivery. Palivizumab may be used in high-risk infants if nirsevimab is not available. (See "Respiratory syncytial virus infection: Prevention in infants and children", section on 'Immunoprophylaxis'.)

ACIP recommendations for 2023-24 seasonal influenza vaccination (September 2023)

The Advisory Committee on Immunization Practices (ACIP) issued new recommendations for seasonal influenza vaccination in August 2023 (table 2) [29]. The antigenic composition has been updated. In addition, the ACIP now states that egg allergy alone no longer necessitates additional safety measures for influenza vaccination, including with egg-based vaccines, beyond those recommended for any recipient of any vaccine, regardless of severity of previous reaction to egg. All vaccines should be administered in settings where personnel and equipment needed for prompt recognition and treatment of acute hypersensitivity reactions are available. This is consistent with our previous guidance. (See "Seasonal influenza vaccination in adults", section on 'Antigenic composition'.)

Updated COVID-19 mRNA vaccine recommendations (September 2023)

The US Food and Drug Administration and Centers for Disease Control and Prevention have updated COVID-19 vaccine authorizations and recommendations [30,31]. Available COVID-19 vaccines have been updated to target Omicron variant XBB.1.5 (Moderna COVID-19 vaccine 2023-2024 formula, Pfizer COVID-19 vaccine 2023-2024 formula, and Novavax 2023-2024 formula); bivalent vaccines are no longer available. An updated 2023-2024 formula vaccine is recommended for all individuals aged six months and older. Immunocompetent individuals five years and older should receive one updated vaccine, regardless of prior vaccination history. For individuals who are four years or younger or have an immunocompromising condition (table 3), the number of recommended updated vaccines depends on their vaccination history. Our approach to COVID-19 vaccination is consistent with these recommendations. (See "COVID-19: Vaccines", section on 'Indications and vaccine selection' and "COVID-19: Vaccines", section on 'Benefits of vaccination'.)

Short course of oral antibiotics to treat UTI in children (August 2023)

In children with urinary tract infection (UTI) without suspected kidney involvement, there is controversy about the duration of antibiotic therapy. In a blinded randomized trial of more than 650 children (ages 2 months to 10 years) who were clinically improved by day 5 of oral antibiotics and were assigned to discontinue antibiotics versus complete a 10-day antibiotic course, the rate of treatment failure in those who were assigned to short-course therapy was low, although it was more common than in those assigned to a 10-day course (4.2 versus 0.6 percent, respectively) [32]. In children whose UTI symptoms are improving at day 5 of treatment, we suggest no further antibiotics. (See "Urinary tract infections in infants older than one month and children less than two years: Acute management, imaging, and prognosis", section on 'Preferred empiric oral regimens'.)

Nasopharyngeal culture in children with acute sinusitis (August 2023)

Children with acute bacterial sinusitis are generally treated empirically with antibiotics or observed for resolution of symptoms without obtaining nasopharyngeal swab for culture. In a trial that included 510 children ages 2 to 12 years who were randomly assigned to receive amoxicillin-clavulanate or placebo after obtaining nasopharyngeal swab for culture, antibiotics were beneficial only in the group who had positive cultures [33]. However, because current options for detecting pathogens require several days to get results, we continue to offer empiric antibiotics without testing; the development of rapid tests could allow a change in practice. (See "Acute bacterial rhinosinusitis in children: Microbiology and management", section on 'When to initiate antibiotics'.)


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

The optimal timing for intervention in extremely preterm (EPT) neonates with patent ductus arteriosus (PDA) is debated; some centers favor early pharmacologic treatment while others favor expectant supportive care initially. In a multicenter, placebo-controlled trial involving >650 EPT neonates with large PDA, early treatment with ibuprofen resulted in higher rates of PDA closure by three weeks of age, but it did not reduce mortality, moderate or severe bronchopulmonary dysplasia, or other neonatal morbidities [34]. Based on these findings and results from prior clinical trials, we suggest expectant supportive care for PDA rather than early pharmacologic therapy.(See "Patent ductus arteriosus (PDA) in preterm infants: Management and outcome", section on 'Comparison of approaches'.)

Delayed cord clamping in preterm births (December 2023)

Increasing evidence supports delaying cord clamping in preterm births. In an individual participant data meta-analysis of randomized trials of delayed versus immediate cord clamping at births <37 weeks (over 3200 infants), delaying cord clamping for >30 seconds reduced infant death before discharge (6 versus 8 percent) [35]. In a companion network meta-analysis evaluating the optimal duration of delay, a long delay (≥120 seconds) significantly reduced death before discharge compared with immediate clamping; reductions also occurred with delays of 15 to <120 seconds but were not statistically significant [36]. For preterm births that do not require resuscitation, we recommend delayed rather than immediate cord clamping. We delay cord clamping for at least 30 to 60 seconds as approximately 75 percent of blood available for placenta-to-fetus transfusion is transfused in the first minute after birth. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Preterm infants'.)

Long-term neurodevelopmental outcomes for preterm infants receiving minimally invasive surfactant (November 2023)

The technique of administering surfactant via thin intratracheal catheter (called minimally invasive surfactant therapy [MIST]) to preterm neonates with respiratory distress syndrome reduces the risk of bronchopulmonary dysplasia (BPD), but the long-term impact is uncertain. In a recent follow-up report of a multicenter international trial, infants who received MIST had lower rates of hospitalization for respiratory illness at two years but similar neurodevelopmental outcomes compared with those in the control group [37]. These findings and results from prior trials suggest that MIST improves short- and long-term pulmonary outcomes (ie, reduced need for intubation, reduced incidence of BPD, and reduced respiratory illnesses during the first two years). However, these benefits may not translate into meaningful improvements in long-term neurodevelopmental outcomes. Nevertheless, we continue to use MIST in appropriate candidates given the demonstrated pulmonary benefits. (See "Respiratory distress syndrome (RDS) in preterm infants: Management", section on 'Minimally invasive surfactant therapy (MIST)'.)


Serial amnioinfusions for bilateral renal agenesis (January 2024)

Bilateral renal agenesis (BRA) is incompatible with extrauterine life because prolonged oligohydramnios results in pulmonary hypoplasia, leading to postnatal respiratory failure. A prospective study (RAFT) assessed use of serial amnioinfusions to treat 18 cases of BRA diagnosed at <26 weeks of gestation [38]. Of the 17 live births, 14 survived ≥14 days and had placement of dialysis access, but only 6 survived to hospital discharge. Of the 4 children alive at 9 to 24 months of age, 3 had experienced a stroke and none had undergone transplant. These findings show that serial amnioinfusions for BRA mitigates pulmonary hypoplasia and increases short-term survival and access to dialysis; however, long-term outcome remains poor with no survival to transplantation. Serial amnioinfusions remain investigational and should be offered only as institutional review board-approved research. (See "Renal agenesis: Prenatal diagnosis", section on 'Investigative role of therapeutic amnioinfusion'.)

Nedosiran for primary hyperoxaluria type 1 (October 2023)

For children with primary hyperoxaluria type 1 (PH1), a rare inborn error of glyoxylate metabolism, treatment with lumasiran, an RNA interference agent (RNAi), in combination with standard care (hyperhydration, crystallization inhibitors, and/or pyridoxine supplements), reduces urinary oxalate excretion and progression to kidney failure. In a randomized trial that included 18 children and adults with PH1, subcutaneous injection of nedosiran, a new RNAi, significantly decreased urinary oxalate excretion and achieved sustained normal or near-normal excretion levels compared with placebo with no significant safety concerns [39,40]. Based upon these findings, nedosiran has been approved for treatment of PH1 by the US Food and Drug Administration. For patients with PH1, we recommend RNAi therapy (either nedosiran or lumasiran) in addition to other measures to reduce kidney calcium oxalate deposition. (See "Primary hyperoxaluria", section on 'Additional therapies for primary hyperoxaluria type 1'.)

Antibiotic prophylaxis for children with high-grade vesicoureteral reflux (October 2023)

The management of vesicoureteral reflux (VUR) varies. Children with high-grade VUR (grade III to V (figure 1)) typically receive antibiotic prophylaxis to prevent urinary tract infection (UTI). In a recent randomized, open-label trial in over 290 young infants (mean age 3 months, about 75 percent uncircumcised males) with high-grade VUR and no prior UTI, antibiotic prophylaxis (primarily amoxicillin-clavulanate) over two years reduced the proportion of patients with a first symptomatic UTI compared with placebo (21 versus 36 percent, hazard ratio 0.55) [41]. Antibiotic resistance was more common in urine cultures obtained from children receiving prophylaxis. These findings confirm the benefit of antibiotic prophylaxis in young infants with high-grade VUR and no prior UTI. (See "Management of vesicoureteral reflux", section on 'Evidence'.)


Vamorolone for Duchenne muscular dystrophy (December 2023)

Glucocorticoid treatment with prednisone or deflazacort for Duchenne muscular dystrophy (DMD) is associated with improved motor function, but adverse effects include weight gain, slowing of growth, and bone loss. Vamorolone, a novel steroid, was designed to reduce adverse effects of glucocorticoid therapy for DMD. In the VISION-DMD trial, vamorolone treatment led to improvement on several motor outcomes compared with placebo, while efficacy was similar compared with prednisone [42]. Prednisone treatment (but not vamorolone) led to growth deceleration and bone biomarker abnormalities. Based on these findings, the US Food and Drug Administration approved vamorolone for children age ≥2 years with DMD [43]. We suggest glucocorticoid treatment for children with DMD and anticipate using vamorolone as an alternative to prednisone and deflazacort. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Benefits of glucocorticoid therapy'.)

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

Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a parainfectious syndrome characterized by presentation with febrile status epilepticus (FSE) followed by a brief seizure-free period before recurrence of seizures in clusters. In a retrospective study from Japan of 55 patients presenting with FSE, the development of AESD in 11 patients was associated with longer time from seizure onset to hospital arrival, presence of hypoxia, and later treatment with antiseizure medications [44]. These findings suggest that shortening the seizure duration by early effective treatment and preventing hypoxia during ambulance transportation might reduce the risk of AESD. (See "Clinical features and evaluation of febrile seizures", section on 'Acute encephalopathy with biphasic seizures and late reduced diffusion'.)

Expert panel on epilepsy with eyelid myoclonia (November 2023)

Epilepsy with eyelid myoclonia (EEM; Jeavons syndrome) is a female-predominant generalized epilepsy syndrome with onset from 3 to 12 years of age characterized by eyelid myoclonia, photosensitivity, and eye closure-induced seizures or paroxysms on electroencephalography (EEG). Recently, an international expert panel found a strong consensus that EEM is often underdiagnosed, that a correct diagnosis can only be made with EEG including photic stimulation, and that an earlier age at onset is associated with an increased risk of intellectual disability and drug-resistant epilepsy [45]. Management generally involves reducing exposure to provoking factors (eg, visual stimuli, various sources of natural and artificial light) and use of antiseizure medication such as levetiracetam or valproate [46]. (See "Photosensitive epilepsies", section on 'Epilepsy with eyelid myoclonia (Jeavons syndrome)'.)

New guidelines for the treatment of neonatal seizures (October 2023)

New guidelines from the International League Against Epilepsy (ILAE) recommend phenobarbital as first-line antiseizure medication (ASM) therapy for treating most etiologies of neonatal seizures [47]. The one exception is that sodium channel blockers (phenytoin/fosphenytoin or carbamazepine) are considered a first-line therapy for neonates with a channelopathy. Phenytoin, levetiracetam, midazolam, and lidocaine are considered second-line ASMs for infants who continue to have seizures despite first-line therapy. Our approach is in accordance with the ILAE guidelines. (See "Treatment of neonatal seizures", section on 'Phenobarbital for most etiologies'.)

Fatal immune reaction after gene therapy for Duchenne muscular dystrophy (September 2023)

Recombinant adeno-associated virus (rAAV) vectors used to deliver gene therapy can be associated with a risk of severe immune reactions. This was illustrated by a report of a 27-year-old patient with advanced Duchenne muscular dystrophy (DMD) and impaired cardiopulmonary function who was treated with a high dose of rAAV containing a CRISPR-based transgene designed to upregulate dystrophin [48]. After treatment, he developed worsening cardiac dysfunction, acute respiratory distress syndrome, and fatal cardiac arrest. Laboratory and postmortem studies suggested his death was due to an innate immune reaction. Further research to develop safer approaches and identify high-risk patients may help to mitigate the acute toxic effects of rAAV gene therapy. (See "Overview of gene therapy, gene editing, and gene silencing", section on 'Potential concerns with gene therapy' and "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Risk of immune reactions with AAV vectors'.)

Management of spinal deformities in children with NF1 (September 2023)

New consensus-based guidelines on the management of spinal deformities, including scoliosis in children with neurofibromatosis type 1 (NF1), have been published [49]. The guidelines recommend screening for spine deformity by physical examination at diagnosis and yearly thereafter. To limit radiation exposure in the pediatric population, diagnostic spine imaging is suggested only if clinical suspicion for a spinal abnormality arises from patient history or physical examination. Spinal tumor burden must be assessed preoperatively in any patient with NF1 undergoing surgery for scoliosis because instrumentation that impedes visualization of spinal tumors by magnetic resonance imaging is not recommended when spinal tumor burden is high. (See "Neurofibromatosis type 1 (NF1): Management and prognosis", section on 'Scoliosis'.)

Gene therapy for Duchenne muscular dystrophy (August 2023)

Delandistrogene moxeparvovec is a microdystrophin transgene delivered by an adeno-associated virus vector. The drug received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of ambulatory males, ages four through five years, with Duchenne muscular dystrophy (DMD) who have a pathogenic variant in the DMD gene [50]. FDA approval was based upon the surrogate outcome of increased dystrophin production, as shown in a placebo-controlled trial of 41 patients with DMD [51]. There was no improvement in functional outcome with delandistrogene moxeparvovec treatment compared with placebo, but a subgroup analysis suggested possible improvement with active treatment for the four- to five-year age group. Despite lack of proven benefit, we anticipate that most eligible patients and their families will request treatment. (See "Duchenne and Becker muscular dystrophy: Glucocorticoid and disease-modifying treatment", section on 'Delandistrogene moxeparvovec'.)

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