What's new in pediatrics

Authors
Alison G Hoppin, MD
Melanie S Kim, MD
Elizabeth TePas, MD, MS
Mary M Torchia, MD
Carrie Armsby, MD, MPH

Disclosures: Alison G Hoppin, MD Nothing to disclose. Melanie S Kim, MD Nothing to disclose. Elizabeth TePas, MD, MS Nothing to disclose. Mary M Torchia, MD Nothing to disclose. Carrie Armsby, MD, MPH Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

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All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Sep 2015. | This topic last updated: Oct 06, 2015.

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

E-cigarette use and use of combustible tobacco products (August 2015)

Studies have associated e-cigarette use with an increased risk of conventional cigarette smoking among youth. A new prospective study was conducted in 2530 ninth-grade students who had never used a combustible tobacco product and compared students who had ever used e-cigarettes with never users [1]. Compared with never users, ever users of e-cigarettes were more likely to report use of any combustible tobacco product at both 6-month (31 versus 8 percent) and 12-month (25 versus 9 percent) follow-up. Additionally, after adjusting for other risk factors for smoking, baseline e-cigarette use was associated with a greater likelihood of use of any combustible tobacco product (OR 2.7), including conventional cigarettes, cigars, and hookahs. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)

Breastfeeding and childhood leukemia risk (July 2015)

Several studies have suggested that breastfeeding is associated with a modest reduction in childhood cancers. Now, a meta-analysis of case-control studies has found that breastfeeding for six months or more is associated with a 19 percent reduction in the risk of childhood leukemia [2]. A smaller protective effect also was detected for shorter durations of breastfeeding. Possible mechanisms for the observed association include enhancement of the immune system or modification of the infant's microbiome. (See "Infant benefits of breastfeeding", section on 'Cancer'.)

Improving uptake of long-acting reversible contraceptives (July 2015)

Long-acting reversible contraceptives (LARC), which include implants and intrauterine devices, are the most effective reversible methods to prevent pregnancy. Interventions that increase LARC use lower the rate of unintended pregnancy. In a trial of 1500 women who were randomly assigned to receive either standardized counseling for LARC or routine contraceptive counseling, standardized counseling resulted in increased LARC use and a reduction in unintended pregnancies (8 versus 15 percent) [3]. Introduction of affordable LARC methods in the state of Colorado from 2009 to 2013 was associated with an approximately 40 percent reduction in teen birth and abortion rates compared with previous years [4]. These data add further support to our suggestion to use LARC for women who desire reversible contraception. (See "Overview of contraception", section on 'Effectiveness'.)

Updated recommendations for pediatric head lice (May 2015)

Pediculosis capitis is a common condition that can lead to physical discomfort and social stigmatization. An update to the 2010 clinical report on head lice published by the American Academy of Pediatrics incorporates new therapies (spinosad and topical ivermectin), clarifies diagnosis and treatment protocols, and provides guidance for the management of children with pediculosis capitis in the school setting [5]. Examples of major points in the update include recommendations that no child should be excluded from school because of head lice or nits and that pyrethroids remain reasonable first-line therapies for primary treatment of pediculosis capitis in communities where resistance to pyrethroids is unproven. (See "Pediculosis capitis", section on 'Pediculicide selection'.)

Warning about use of non-prescription asthma treatments (April 2015)

The US Food and Drug Administration (FDA) released a consumer warning about the potential health risks of over-the-counter (OTC) homeopathic products for asthma [6]. The efficacy and safety of OTC products are not evaluated by the FDA. In addition, there is evidence that some non-prescription therapies, such as racemic epinephrine inhaler (sold as Asthmanefrin) and systemic ephedrine (sold as Bronkaid and Primatene tablets), are less effective than standard therapies for asthma and have a higher rate of side effects. Thus, OTC products are not recommended for the routine care of asthma, particularly acute asthma symptoms. These warnings are an important reminder for clinicians to ask their patients about use of OTC products. (See "Asthma in children younger than 12 years: Rescue treatment for acute symptoms", section on 'Nonstandard therapies' and "Alternative and experimental agents for the treatment of asthma", section on 'Risks associated with inhaled epinephrine' and "Alternative and experimental agents for the treatment of asthma", section on 'Homeopathic agents' and "Homeopathy", section on 'Specific diseases'.)

NEONATOLOGY

Conjunctival icterus and bilirubin levels in newborn infants (September 2015)

Based on currently available data, the presence and extent of jaundice has not been a consistently reliable method to predict total serum or plasma bilirubin (TB) concentration for neonatal hyperbilirubinemia. However, a recent observational study of 240 term or late preterm neonates reported that conjunctival icterus may be a useful clinical marker. In this study, all infants with conjunctival icterus had TB levels that were either in the high intermediate or high risk category for severe hyperbilirubinemia (defined as TB >25 mg/dL [428 micromol/L]) using the hour-specific Bhutani nomogram (figure 1) [7]. In addition, most infants with conjunctival icterus had TB >15 mg/dL (257 micromol/L). These results suggest that TB or transcutaneous bilirubin levels should be measured in an infant with conjunctival icterus as these infants are at risk for developing severe hyperbilirubinemia. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Jaundice'.)

Filtered sunlight phototherapy for neonatal hyperbilirubinemia (September 2015)

A recent Nigerian trial confirmed results from a previous observational study that filtered sunlight using commercial window tinting films (which selectively allow the transmission of blue light and removal of significant amounts of harmful ultraviolet and infrared light rays) is a safe and efficacious method for treating neonatal hyperbilirubinemia [8]. In this trial of 447 term and late preterm infants with an elevated total serum bilirubin (TSB), filtered sunlight therapy for at least five hours a day was as effective as conventional daytime phototherapy in treating neonatal hyperbilirubinemia without adverse effects. Of note, afternoon TSB were measured in all infants, and conventional nighttime phototherapy was provided to all infants from both groups if their afternoon TSB reached a targeted level for phototherapy. These data suggest filtered sunlight phototherapy for neonatal hyperbilirubinemia may be a reasonable option in resource-limited tropical regions with limited availability of conventional phototherapy. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Sunlight exposure'.)

Prolonged hypoxia and increased late mortality and morbidity for extremely premature infants (August 2015)

A meta-analysis of several large clinical trials of extremely premature (EP) infants (gestational age <28 weeks) demonstrated low target pulse oximetry levels of hemoglobin saturation (SpO₂) compared with high target SpO₂levels (85 to 89 versus 91 to 95 percent) were associated with increased mortality at hospital discharge but not mortality or morbidity at 24 months corrected age (CA). However, in a subsequent post hoc analysis of one of the included trials (Canadian Oxygen Trial), prolonged hypoxemic episodes during the first two to three months after birth were associated with late mortality or neurodevelopment impairment at 18 months CA [9]. Of note, this association was stronger for infants randomly assigned to the high SpO₂ group than for those in the low SpO₂ group. Nevertheless, based on currently available data, we continue to recommend an SpO₂ target range between 90 to 95 percent for EP infants. (See "Oxygen monitoring and therapy in the newborn", section on 'Clinical trials'.)

Acetaminophen alone not effective in reducing neonatal pain (August 2015)

Acetaminophen (paracetamol) has been used in the management of mild to moderate procedural and postoperative neonatal pain. However, a recent systematic review of randomized trials found that acetaminophen alone was not more effective than placebo in preventing or reducing pain associated with heel lance or eye examination in newborns [10]. As a result, we do not recommend using acetaminophen as the sole agent in newborns to reduce pain from painful procedures. (See "Prevention and treatment of neonatal pain", section on 'Lack of efficacy'.)

Universal versus selective screening for patent ductus arteriosus in preterm infants (July 2015)

It remains uncertain whether the outcome of preterm infants is improved by universal echocardiographic screening for patent ductus arteriosus (PDA) versus echocardiographic evaluation based on the presence of clinical signs of PDA. Support for universal screening was provided by a report from EPIPAGE 2, a French national prospective population-based cohort study of extremely premature infants (born at 24 to 28 weeks of gestation), that found screening for a PDA before day three of life versus no screening was associated with lower in-hospital mortality and a lower risk of pulmonary hemorrhage [11]. However, this study may be limited due to a potential bias that the non-screening group may have included a greater proportion of more severely affected infants. As a result, our clinical practice remains selective echocardiography based on the presence of clinical signs of PDA. (See "Management of patent ductus arteriosus in premature infants", section on 'Screening'.)

Effect of active resuscitation on survival at borderline viability (June 2015)

A major issue regarding the ability to predict neonatal outcome at borderline viability is the impact of initial management. Interpretation of outcome data should always take into account whether neonatal resuscitation was offered at delivery, because neonatal outcome varies depending on the degree of assistance offered to the infant, particularly for those born at or below 23 weeks of gestation. This was illustrated in a recent National Institute of Child Health and Human Development (NICHHD) study that included data from 24 hospitals and nearly 5000 infants [12]. In a multivariable analysis, differences in practice regarding the initiation of active treatment for infants born below 24 weeks of gestation accounted for three-quarters of the between-hospital variation in neonatal survival and survival without impairment. These findings emphasize the difficulty in determining the optimal management for infants at the limit of viability. (See "Limit of viability", section on 'Impact of initial management'.)

Endotracheal suctioning may not benefit nonvigorous neonates with meconium-stained amniotic fluid (May 2015)

Current guidelines recommend intubation and tracheal suctioning (endotracheal suctioning) of residual meconium for nonvigorous (depressed) infants (ie, absent or depressed respirations, decreased muscle tone, or heart rate less than 100 beats/minute) with meconium-stained amniotic fluid (MSAF), although supportive data are limited. In a recent randomized clinical trial of 122 nonvigorous term infants with MSAF in India, there was no additional benefit to endotracheal suctioning compared with no intubation and suctioning [13]. Specifically, there were no differences between the two groups in the incidence of meconium aspiration syndrome (33 versus 31 percent), need for mechanical ventilation (23 versus 25 percent), survival at nine months of age (70 versus 72 percent), and mental and motor developmental status at nine months of age. Although these results suggest that endotracheal suctioning may not be needed in all infants with MSAF regardless of the level of activity, additional confirmatory evidence with larger clinical trials is needed before we recommend a change in practice for nonvigorous infants with MSAF. (See "Prevention and management of meconium aspiration syndrome", section on 'Neonatal care'.)

Valganciclovir for treatment of symptomatic congenital CMV infections (April 2015)

Congenital cytomegalovirus (CMV) infection is a leading cause of hearing loss in children and can cause other serious long-term neurodevelopmental disabilities. An earlier study found that in infants with congenital CMV involving the central nervous system (CNS), six weeks of ganciclovir was associated with improved audiologic outcomes. Subsequent studies found that valganciclovir (the orally available prodrug of ganciclovir) achieved similar clinical effectiveness. A recent multicenter randomized controlled trial compared six months with six weeks of valganciclovir therapy in infants with symptomatic congenital CMV (including infants without neurologic involvement) [14]. Infants who received six months of therapy had improved hearing and language development at 24 months compared with those who received six weeks of therapy. Based on these findings we now treat all infants with symptomatic congenital CMV infection (not just those with isolated CNS infection) with six months of antiviral therapy. (See "Congenital cytomegalovirus infection: Management and outcome", section on 'Whom to treat'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Antibiotic use and development of juvenile idiopathic arthritis (August 2015)

A few studies have found a link between antibiotic use and the development of juvenile idiopathic arthritis (JIA). In one of these case-control studies, previous antibiotic prescriptions were compared in 152 children newly diagnosed with JIA and 1520 controls in the United Kingdom [15]. As with a previous study, this study found that any use of antibiotics was associated with a twofold increased risk of JIA. The risk was dose dependent and was greatest for antibiotic exposures that occurred within one year of diagnosis. The potential underlying mechanism is unknown, but alteration of the intestinal microbiome with subsequent immune dysregulation is postulated. Alternative explanations include the possibility that these patients develop more frequent infections due to some intrinsic abnormalities in the immune system that also predispose them to JIA. (See "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis", section on 'Antibiotics'.)

Predictors of the need for repeat epinephrine doses in anaphylaxis (August 2015)

Epinephrine is the first-line therapy for anaphylaxis, and retrospective studies suggest that up to one-third of patients may require a second dose. However, predictive factors for requiring more than one dose are not well defined. In a prospective cohort study of over 500 patients (all ages) treated for anaphylaxis in a tertiary care emergency department, 14 percent of those requiring any epinephrine required more than one dose [16]. Patients with a history of previous anaphylaxis, and those presenting with flushing, diaphoresis, or dyspnea, were more likely to require multiple doses of epinephrine to control symptoms. Anaphylaxis is an inherently unpredictable disorder, but this study provides some insight into predictors of a more complicated treatment course and may help clinicians managing such patients. (See "Anaphylaxis: Rapid recognition and treatment", section on 'Dosing and administration'.)

Ease of use of different epinephrine autoinjectors for anaphylaxis (July 2015)

Epinephrine autoinjectors can be life saving for patients with serious allergies, but even with specific training, many people have trouble using the various devices properly. A randomized trial of mothers of food-allergic children, tested in simulated anaphylaxis scenarios, suggested that the Auvi-Q device, a rectangular cassette that has audible instructions to guide the user through the injection process, was easier to use than non-audible pen devices [17]. When prescribing an epinephrine autoinjector, ease of use, cost, the need for multiple injectors, and patient facility with self-injection should all be considered. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Ease of use'.)

Dedicator of cytokinesis 2 deficiency (June 2015)

Dedicator of cytokinesis 2 (DOCK2) deficiency is a newly recognized combined immunodeficiency (CID). Biallelic (homozygous or compound heterozygous) mutations in the DOCK2 gene were identified through whole-exome sequencing in a group of unrelated patients with early-onset invasive bacterial and viral infections, lymphopenia, and defective T, B, and NK cell responses [18]. DOCK2 deficiency results in impaired activation of RAC1 that leads to defects in actin polymerization, lymphocyte proliferation and migration, natural killer cell degranulation, and response to viral infections in fibroblasts and peripheral blood mononuclear cells. Other CIDs that are the result of defects in actin regulation include Wiskott-Aldrich syndrome and DOCK8 deficiency. (See "Combined immunodeficiencies", section on 'Dedicator of cytokinesis 2 deficiency'.)

Low allergic cross-reactivity between penicillins and carbapenems (May 2015)

Carbapenems (eg, imipenem, meropenem) share a common beta-lactam ring with penicillins and hence the potential for allergic cross-reactivity, and some drug information systems list penicillin allergy as a contraindication to the use of carbapenems (figure 2). In the largest study to date, 212 patients with allergy to penicillins, confirmed by skin testing, were then tested with carbapenems [19]. All subjects were negative to carbapenem skin testing and tolerated graded challenges to three different carbapenems. Based on this and other series, the rate of reactivity to carbapenems in patients with confirmed penicillin allergy is estimated at <1 percent. This supports our current recommendations on administration of carbapenems to patients reporting immediate-type penicillin allergy: Perform penicillin skin testing when available. If negative, patients may safely receive penicillins and carbapenems. If penicillin skin testing is positive or not available, carbapenems may be administered via a graded challenge. (See "Penicillin-allergic patients: Use of cephalosporins, carbapenems, and monobactams", section on 'Carbapenems'.)

CARDIOLOGY

Early cardiovascular disease in youth with depressive and bipolar disorders (October 2015)

The American Heart Association recently proposed that major depression and bipolar disorder in adolescents be positioned alongside other pediatric diseases that are considered moderate risk conditions for early cardiovascular disease (CVD), which include chronic inflammatory diseases (eg, systemic lupus erythematosus), HIV infection, and nephrotic syndrome [20]. There is growing evidence that major depression and bipolar disorder are associated with accelerated atherosclerosis and early CVD. In addition, traditional risk factors for CVD (eg, obesity, diabetes mellitus, sedentary lifestyle, and smoking) are more prevalent in youth with major depression and bipolar disorder. Although psychotropic medication may contribute to the elevated risk of cardiovascular disease, particularly in youths with bipolar disorder, it appears that the association between depression and cardiovascular disease is independent of medication effects. Management of youth with major depression and bipolar disorder should thus include monitoring and management of other CVD risk factors, including body mass index, blood pressure, lipids, and fasting glucose. (See "Diseases associated with atherosclerosis in childhood", section on 'Depressive and bipolar disorders'.)

DERMATOLOGY

Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)

Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region [21]. All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)

Pimecrolimus for atopic dermatitis in infants and young children (May 2015)

Topical calcineurin inhibitors have been approved in the United States as second-line therapies for the treatment of mild to moderate atopic dermatitis (AD) in adults and children ≥2 years. However, they have been used off-label as first-line treatment for AD in younger children and infants, in the absence of long-term studies evaluating their efficacy and safety. A five-year randomized, open-label trial evaluated the safety and long-term efficacy of pimecrolimus 1% cream compared with low or mid-potency topical corticosteroids in over 2400 infants with mild to moderate AD [22]. After five years, overall treatment success was achieved in approximately 90 percent of children in both groups. Growth, immune function, and cancer rates were similar in the two groups, as were overall rates of adverse events. However, episodes of bronchitis, infected eczema, impetigo, and nasopharyngitis were slightly more frequent in the pimecrolimus group, and the rates of cutaneous adverse events (eg, skin irritation, atrophy, telangiectasias) were not reported. Thus, the advantage of using pimecrolimus rather than low to mid-potency topical corticosteroids in this age group remains unclear. (See "Treatment of atopic dermatitis (eczema)", section on 'Off-label use in infants'.)

Serum potassium monitoring during spironolactone therapy for acne (March 2015)

Spironolactone is an androgen receptor antagonist that is effective for the treatment of acne in females. Although periodic monitoring of serum potassium levels is often performed during treatment with spironolactone, there is uncertainty about the need for monitoring in young, healthy acne patients. A large retrospective study comparing the rate of hyperkalemia during treatment with spironolactone with baseline rates of hyperkalemia in women with acne (ages 18 to 45) did not find increased rates of hyperkalemia during spironolactone therapy, suggesting that periodic monitoring of serum potassium in healthy women is not necessary [23]. These results cannot be applied to patients who may be at increased risk for hyperkalemia due to heart failure, renal disease, concomitant medical therapy, or other conditions. (See "Hormonal therapy for women with acne vulgaris", section on 'Side effects'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Genetic testing in autism spectrum disorder (September 2015)

Genetic testing is often performed in children with autism spectrum disorder (ASD) to provide information about prognosis and recurrence. The suggested evaluation has evolved with advances in molecular diagnostic techniques. In a population-based study, the yield of genetic diagnosis with whole-exome sequencing was similar to that with chromosomal microarray (CMA): 8.4 and 9.3 percent, respectively; and 15.8 percent when both tests were performed [24]. Genetic diagnosis was achieved more often in children with higher levels of dysmorphology, suggesting that severity of dysmorphology is predictive of genetic abnormalities [25]. Pending additional studies, we continue to suggest genetic testing by CMA and DNA analysis for fragile X syndrome for all children with ASD, whether or not they have dysmorphic features. (See "Autism spectrum disorder: Diagnosis", section on 'Genetic testing'.)

Course of ADHD during adulthood (June 2015)

While it is well established that 40 to 60 percent of children with attention deficit hyperactivity disorder (ADHD) go on to have significant ADHD-related problems as adults, little is known about the course of the disorder during adulthood. A recent, prospective follow-up study reported on the persistence of ADHD in a clinical sample of 344 Brazilian outpatients [26]. Participants met DSM-IV criteria for ADHD during childhood and as adults at the start of the study (mean age 34 years). Approximately one-third of participants did not meet diagnostic criteria for the disorder after an average of seven years, and 12 percent of the sample met criteria for full remission. The persistence of ADHD was associated with higher numbers of inattention and hyperactivity/impulsivity symptoms, and with co-occurring oppositional defiant disorder and social phobia. Despite expectations that adult ADHD might be nonremitting, these findings suggest that some adults with the disorder experience improvement over time. (See "Attention deficit hyperactivity disorder in adults: Epidemiology, pathogenesis, clinical features, course, assessment, and diagnosis", section on 'Course'.)

Sleep problems in children with ADHD (March 2015)

Attention deficit hyperactivity disorder (ADHD) is associated with sleep problems, particularly initiating and maintaining sleep. A randomized trial suggests that ADHD symptoms improve with treatment of comorbid sleep problems [27]. Children with ADHD and a moderate to severe sleep disorder were assigned to usual care or two sleep consultations and a follow-up phone call with a trained clinician; most of the children were receiving ADHD medications (predominantly methylphenidate). At the three- and six-month follow-up, children in the intervention group had modest improvements in ADHD symptoms and teacher-reported behavior. These findings highlight the importance of treating coexisting sleep problems in children with ADHD. (See "Attention deficit hyperactivity disorder in children and adolescents: Overview of treatment and prognosis", section on 'Treatment of coexisting conditions'.)

EMERGENCY MEDICINE

Contrast regimens for children requiring abdominal and pelvic computed tomography after blunt trauma (September 2015)

In a multicenter, prospective observational study of over 5000 children with blunt trauma undergoing abdominal and pelvic computed tomography (CT) with intravenous (IV) contrast, of whom 1010 also received oral contrast, the sensitivity for identifying intraabdominal injury was not significantly different with or without oral contrast (99 versus 98 percent, respectively) [28]. Patients who received oral contrast had a significantly longer delay in undergoing CT (median 12 minutes) compared with children who received IV contrast alone. Thus, oral contrast does not improve detection of intraabdominal injury in children but delays time to imaging. We suggest that hemodynamically stable children undergoing CT of the abdomen and pelvis after blunt trauma receive IV contrast alone rather than IV and oral contrast. (See "Overview of blunt abdominal trauma in children", section on 'Use of contrast'.)

Timely administration of epinephrine improves survival following pediatric arrest (August 2015)

Epinephrine is recommended during cardiopulmonary resuscitation for children with asystole or pulseless electrical activity without ventricular fibrillation or tachycardia. In a retrospective review of registry data on 1558 children with inpatient arrest and a documented nonshockable initial rhythm, adjusted survival to discharge occurred in up to 37 percent of patients who received epinephrine one minute or less after arrest and decreased 5 percent for every additional minute delay in epinephrine administration [29]. Survival with favorable neurologic outcome at discharge occurred in approximately 16 percent of all patients and in adjusted analysis also decreased 5 percent for every additional minute of delay in epinephrine administration. Thus, timely administration of epinephrine is associated with improved outcomes after pediatric arrests with nonshockable cardiac rhythms. (See "Guidelines for pediatric advanced life support", section on 'Advanced management'.)

Oxyhemoglobin desaturation during rapid sequence intubation in children (June 2015)

Timing the laryngoscopy duration during a pediatric endotracheal intubation attempt and discontinuing it if intubation is unsuccessful within a specific time period (eg, 30 seconds) may prevent oxyhemoglobin desaturation. In an observational study that used video review of 114 children undergoing rapid sequence intubation in a pediatric emergency department, at least one episode of oxyhemoglobin desaturation (pulse oximetry <90 percent) occurred in 33 percent of patients [30]. Oxyhemoglobin desaturation was more common in children two years of age or younger compared with older children (59 versus 10 percent) and was strongly associated with the duration of laryngoscopy; 82 percent of patients experiencing desaturations had laryngoscopy durations of 30 seconds or longer. There was no association between the number of intubation attempts and episodes of desaturation. (See "Emergency endotracheal intubation in children", section on 'During laryngoscopy/intubation'.)

Post-resuscitation therapeutic hypothermia not better than targeted normothermia in children (May 2015)

Therapeutic hypothermia to maintain core body temperature below normal (typically 32 to 34°C) has been proposed after resuscitation from pediatric cardiac arrest based upon evidence for improved neurologic outcome in neonates and selected adults. In a multicenter trial involving children who were resuscitated from an out-of-hospital cardiac arrest, 260 patients (48 hours to 18 years of age) were randomized to either therapeutic hypothermia with a target core body temperature of 33°C or therapeutic normothermia to maintain a temperature of 36.8°C. One-year survival with good neurologic function was not significantly different in patients undergoing therapeutic hypothermia compared with therapeutic normothermia (20 versus 12 percent, respectively, relative likelihood 1.54, 95% CI 0.86-2.76) [31]. Of note, the number of patients randomized was insufficient to exclude an important benefit or harm from therapeutic hypothermia. Further study is needed to determine the role of therapeutic hypothermia after resuscitation from pediatric cardiac arrest; current practice is to provide targeted temperature management to prevent fever (core body temperature >38°C). (See "Guidelines for pediatric advanced life support", section on 'Early postresuscitation management'.)

Diagnostic accuracy of serial ultrasounds for pediatric appendicitis (April 2015)

In pediatric patients whose initial ultrasound is equivocal for the diagnosis of appendicitis and who have persistent findings, repeat physical examination and a second ultrasound has good diagnostic accuracy and can markedly reduce the use of computed tomography (CT). A prospective observational study of 294 children undergoing acute evaluation for abdominal pain (38 percent with appendicitis) evaluated a protocol stratifying children into three paths: serial physical examination, surgical consultation, and repeat ultrasound if the initial ultrasound was equivocal; discharge home if the initial ultrasound showed a normal appendix; and surgical consultation if the initial ultrasound was positive for appendicitis [32]. This strategy, consistent with our approach, achieved a sensitivity of 97 percent and a specificity of 91 percent; CT was performed in four patients. (See "Acute appendicitis in children: Diagnostic imaging", section on 'Imaging approach'.)

Risk of intracranial injury in young children with isolated linear skull fractures (April 2015)

Linear skull fractures account for approximately 75 percent of all skull fractures in children, and hospitalization for this condition is frequently performed. In a prospective, multicenter observational study of 350 children (median age 10 months) with isolated linear skull fractures and no additional injury identified on initial computed tomography, no patient required neurosurgical intervention on follow-up ranging from 7 to 90 days (95% CI 0 to 1 percent), although 201 patients were hospitalized after initial evaluation [33]. These findings suggest that neurologically normal children with isolated linear skull fractures have a low risk for intracranial injury requiring neurosurgical intervention and may safely undergo discharge home to a reliable caretaker after emergency department evaluation. (See "Skull fractures in children", section on 'Isolated skull fractures'.)

GENETICS AND PEDIATRIC METABOLISM

Down syndrome disintegrative disorder (September 2015)

It is not clear if Down syndrome disintegrative disorder is one disorder or several different disorders with similar presentations [34]. The etiology is not known, but autoimmunity is suspected. There are no established diagnosis or treatment recommendations for this clinical association, although some patients respond to psychiatric care. Further research is needed in this area. (See "Down syndrome: Clinical features and diagnosis", section on 'Behavioral and psychiatric disorders'.)

Medical food supplements for organic acidemias (August 2015)

Patients with organic acidemias such as methylmalonic acidemia (MMA) are treated with a low-protein diet that is supplemented with an amino acid mixture that excludes the problematic amino acids. However, excessive consumption of this "medical food" in patients with MMA, while uncommon, can result in increased leucine intake that causes depletion of the essential amino acids valine and isoleucine [35]. These amino acid deficiencies are associated with poor growth outcomes. Patients with cobalamin C (cblC) defects, which cause combined MMA and homocystinuria, should be treated carefully with the medical food used for MMA, since this medical food is devoid of methionine and is relatively high in leucine content. Use of this medical food in patients with cblC deficiency could potentially adversely affect brain growth and development [36]. Patients with these disorders should have plasma amino acid analysis performed on a regular basis to prevent these and other complications. (See "Organic acidemias", section on 'Treatment'.)

False positive Down syndrome screening tests (April 2015)

Noninvasive prenatal Down syndrome screening using cell free DNA results in lower false positive and false negative rates than conventional aneuploidy screening tests. In a recent study of Down syndrome screening in an unselected population including almost 16,000 women, the false positive rates of cell free DNA and conventional screening were 0.1 and 5 percent, respectively, and false negative rates were 0 and 21 percent, respectively [37]. False positive results can be due to factors such as maternal mosaicism, maternal tumors, maternal copy number variants, vanishing twins, confined placental mosaicism, or a failure of the complex bioinformatics necessary to generate a result [38-45]. Despite the low false positive rate with cell free DNA screening, confirmatory diagnostic testing (genetic amniocentesis or chorionic villus sampling) is mandatory after a screen positive result. (See "Noninvasive prenatal testing using cell-free nucleic acids in maternal blood", section on 'Trisomy 21, 18, 13'.)

HEMATOLOGY AND ONCOLOGY

Underuse of hydroxyurea in sickle cell disease (April 2015)

Hydroxyurea is a mainstay of therapy for individuals with sickle cell disease. Despite the clear clinical benefits, studies suggest that many patients do not receive this therapy. A large United States database review identified 2086 adults with sickle cell disease and frequent painful episodes, and found that only one-fourth were prescribed hydroxyurea [46]. These data highlight the underuse of appropriate therapy in sickle cell disease. Potential contributing factors include patient-, parent/family/caregiver-, provider-, and system-level barriers. (See "Hydroxyurea and other disease-modifying therapies in sickle cell disease", section on 'Indications'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)

In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age [47]. Changes for the 2015-2016 season include:

●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines

●A simplified dosing algorithm for children six months through eight years (algorithm 1)

●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 1)

(See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule' and "Seasonal influenza vaccination in adults", section on 'Overview'.)

Repeat testing for women treated for trichomoniasis (July 2015)

The risk of repeat infection following treatment for a sexually transmitted infection (STI) is high. In the United States, reinfection with Trichomonas vaginalis has been reported to occur in up to 17 percent of women following treatment for an initial infection. The 2015 Centers for Disease Control and Prevention (CDC) guidelines on the management of STIs recommend that women treated for confirmed T. vaginalis infection undergo repeat testing within three months of treatment, regardless of partner treatment status [48]. Prior guidelines had only listed retesting as a consideration. The preferred diagnostic test for repeat testing is a nucleic acid amplification test (NAAT) on a vaginal swab, which can be performed as soon as two weeks after treatment. Data are insufficient to support retesting men. (See "Trichomoniasis", section on 'Follow-up'.)

Updated CDC guidelines on the management of sexually transmitted infections (June 2015)

The US Centers for Disease Control and Prevention (CDC) updated its guidelines on the management of sexually transmitted infections in June 2015 [49]. Major revisions include a lower threshold for the diagnosis of urethritis based on microscopy of a urethral specimen, a new emphasis on the role of Mycoplasma genitalium in persistent urethritis and cervicitis, preference for nucleic acid amplification-based testing for the diagnosis of Trichomonas vaginalis, and a recommendation to retest women after treatment for T. vaginalis to evaluate for reinfection. New screening recommendations include annual hepatitis C virus (HCV) testing for HIV-infected men who have sex with men and T. vaginalis testing for HIV-infected women annually and when pregnant. (See "Urethritis in adult men", section on 'Diagnostic criteria' and "Mycoplasma genitalium infection in men and women", section on 'Nongonococcal urethritis' and "Trichomoniasis", section on 'Follow-up' and "Primary care of the HIV-infected adult", section on 'Sexually transmitted infections'.)

Prevalence and clinical presentation of Borrelia miyamotoi infection (June 2015)

Borrelia miyamotoi is an emerging zoonotic pathogen that is transmitted by the same genus of ticks (eg, Ixodes scapularis, Ixodes pacificus) that transmits Borrelia burgdorferi (the agent of Lyme disease), Anaplasma phagocytophilum, and Babesia species. In one case series, B. miyamotoi was identified using polymerase chain reaction (PCR) in approximately 1 percent of specimens from 11,515 patients in the northeastern United States who presented with an acute febrile episode from April through November in 2013 and 2014 [50]. Clinical information was available for 51 patients with B. miyamotoi infection; the majority had marked headache, myalgia, arthralgia, malaise, and/or fatigue, and 24 percent were hospitalized. Diagnostic testing is not widely available, but doxycycline, which is used to treat many other tick-borne infections, is also effective against B. miyamotoi. (See "Borrelia miyamotoi infection", section on 'Clinical manifestations'.)

US ACIP recommendations for serogroup B meningococcal vaccination (June 2015)

In late 2014 and early 2015, the US Food and Drug Administration approved two serogroup B meningococcal vaccines (Trumenba, MenB-FHbp and Bexsero, MenB-4C). In June 2015, the Advisory Committee on Immunization Practices (ACIP) issued recommendations for serogroup B meningococcal vaccine for high-risk individuals aged 10 years or older; these include individuals with persistent complement component deficiencies, individuals with anatomic or functional asplenia, microbiologists routinely exposed to N. meningitidis isolates, and individuals at increased risk because of a serogroup B meningococcal disease outbreak [51]. These indications overlap with those for the quadrivalent meningococcal conjugate vaccine and are summarized in the table (table 2). Among patients with none of the above risk factors, the ACIP advises discussion between doctors and patients regarding vaccination against serogroup B meningococcus; routine vaccination has not been recommended [52]. (See "Meningococcal vaccines", section on 'Use in United States'.)

Antimicrobial-resistant Shigella infections in the United States (June 2015)

Antimicrobial resistance in Shigella is an increasing problem in the United States. Fluoroquinolones are typically the antibiotic class of choice in adults, and azithromycin is often used if fluoroquinolone resistance is suspected or documented. Clusters of ciprofloxacin-resistant cases, likely introduced by international travelers with subsequent domestic spread, have been reported throughout the country, and isolates with decreased susceptibility to azithromycin have caused outbreaks and sporadic cases, predominantly among men who have sex with men (MSM) [53,54]. Scattered infections with extremely drug-resistant isolates that are ciprofloxacin-resistant and have decreased susceptibility to azithromycin have also been reported [55]. These reports highlight the importance of obtaining susceptibility testing to ensure adequate efficacy of the chosen antimicrobial when managing shigellosis and emphasizing prevention measures, primarily hygiene practices around food preparation or consumption and oral or anal sex. (See "Shigella infection: Treatment and prevention in adults", section on 'Antimicrobial resistance' and "Shigella infection: Treatment and prevention in children", section on 'Antibiotic resistance'.)

Reduced HPV vaccination rate among women who have sex with women (May 2015)

Prior research has suggested that women who have sex with women (WSW) may be less likely to initiate human papillomavirus (HPV) vaccination than their age-matched heterosexual peers. One possible reason for this discrepancy is that both WSW and their healthcare providers may erroneously believe that WSW are not at risk for HPV infection or cervical cancer. In one study of over 12,000 United States women from 2006 to 2010, of women who were aware of the HPV vaccine, only 8 percent of lesbian women had initiated vaccination compared with 28 percent of heterosexual women and 32 percent of bisexual women [56]. This study highlights the need for healthcare providers to discuss HPV vaccination with all patients. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists recommend vaccination for females and males ages 11 or 12 years of age, up to age 26. (See "Medical care of women who have sex with women", section on 'Prevention of sexually transmitted diseases'.)

Effectiveness of pertussis vaccine in infants (May 2015)

Infants younger than 12 months have the highest incidence of pertussis and pertussis-related complications, including death. In a large case control study, having received ≥1 dose of pertussis vaccine was associated with a 72 percent reduction in the risk of death and a 31 percent reduction in the risk of hospitalization in infants ≥6 weeks of age (the minimum age for the first dose of pertussis vaccine) [57]. However, 64 percent of the deaths occurred in infants younger than six weeks. These findings highlight the importance of timely pertussis immunization for infants, as well as maternal immunization during pregnancy and immunization of the infant's close contacts, as recommended by the Global Pertussis Initiative [58]. (See "Diphtheria, tetanus, and pertussis immunization in infants and children 0 through 6 years of age", section on 'Efficacy and effectiveness' and "Immunizations during pregnancy", section on 'Tetanus, diphtheria, and pertussis vaccination' and "Bordetella pertussis infection in adolescents and adults: Treatment and prevention", section on 'Tdap booster'.)

Aerosolized measles vaccine inferior to subcutaneous vaccine with respect to seropositivity rate (April 2015)

Measles vaccine is usually given by subcutaneous injection; an aerosolized vaccine could be administered by individuals with less training and would not require sterile needles or syringes. In a study including 2004 infants aged 9.0 to 11.9 months in India randomized to receive measles vaccine either by aerosol inhalation or subcutaneous injection, aerosolized vaccine was found to be immunogenic but inferior to the subcutaneous vaccine with respect to seropositivity rate [59]. Follow-up was completed for 1560 children (775 children in the aerosolized vaccine group and 785 children in the subcutaneous vaccine group); seropositivity rates at day 91 were 85.4 and 94.6 percent, respectively. Subcutaneous administration of the measles vaccine remains the standard of care. (See "Prevention and treatment of measles", section on 'Types of vaccines'.)

NEPHROLOGY AND UROLOGY

Hypotonic versus isotonic parenteral maintenance fluids in hospitalized children (April 2015)

Previous systematic reviews have demonstrated that the use of parenteral hypotonic solution for maintenance fluid therapy in hospitalized children increased the risk of hyponatremia compared with isotonic solution. The largest clinical trial to date of 690 hospitalized children, which was subsequently published, reconfirmed that the administration of hypotonic (sodium concentration of 77 mEq/L) versus isotonic maintenance fluid (sodium concentration of 140 mEq/L) increased the risk of developing hyponatremia [60]. As a result, in hospitalized children requiring parenteral fluid therapy, we recommend that isotonic solution be used as maintenance therapy. (See "Maintenance fluid therapy in children", section on 'Hospitalized children'.)

NEUROLOGY

Etiologic evaluation in children with infantile spasms (April 2015)

Infantile spasms (IS) is a rare form of epilepsy with a wide range of underlying etiologies. Approximately two-thirds of patients will have an etiologic diagnosis established after clinical examination and brain magnetic resonance imaging (MRI); metabolic and genetic testing can establish an etiology in an additional 10 to 15 percent of patients. This was demonstrated by a prospective multicenter study of 251 patients with newly diagnosed IS, in which 55 percent of patients had an obvious cause for IS identified by an initial evaluation that included MRI [61]. In the remaining patients, array comparative genomic hybridization and epilepsy gene panel testing had the highest diagnostic yield; these and other tests established a diagnosis in 23 additional patients. These results support our practice of performing metabolic and genetic testing in patients with IS who do not have a cause identified by the initial evaluation. (See "Clinical features and diagnosis of infantile spasms", section on 'Metabolic and genetic testing'.)

PULMONOLOGY

Lumacaftor-ivacaftor for patients with cystic fibrosis and homozygous for the F508del mutation (August 2015)

Lumacaftor-ivacaftor is a combination of two cystic fibrosis transmembrane conductance regulator (CFTR) modulators that was approved by the US Food and Drug Administration in July 2015. The approval was based on two randomized trials with 1100 homozygous F508del subjects ages 12 years and older [62]. Compared with placebo, the groups receiving lumacaftor-ivacaftor for 24 weeks had small but statistically significant improvements in percent predicted FEV1 and body mass index (BMI), and reduced frequency of pulmonary exacerbations. Adverse effects included chest discomfort and dyspnea and were more common in subjects with worse baseline lung function. The improvement in absolute FEV1 from baseline compared with placebo (2.6 to 4 percentage points) is similar in magnitude to that achieved by treatments with inhaled dornase alfa or tobramycin. We suggest use of lumacaftor-ivacaftor for F508del homozygotes because it has modest short-term benefits and is tolerated by most patients. However, the expense of the drug and drug-drug interactions should be considered when deciding on its use. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Efficacy'.)

Outcomes of infants with inconclusive newborn screening for cystic fibrosis (July 2015)

CFTR-related metabolic syndrome (CRMS) describes infants with an equivocal diagnosis following newborn screening for cystic fibrosis (CF). These infants usually have elevated levels of immunoreactive trypsinogen, but inconclusive results of subsequent sweat and DNA testing. The natural history of infants with CRMS is unclear. Now, a small study of infants with an initial diagnosis of CRMS reports that 48 percent were later diagnosed with CF, most within the first year of life [63]. Affected individuals had a somewhat milder CF phenotype compared with infants who were diagnosed with CF by newborn screening. These findings highlight the importance of longitudinal clinical and laboratory follow-up of infants with CRMS. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'CFTR-related metabolic syndrome'.)

Ivacaftor for children two years and older with cystic fibrosis (March 2015)

Ivacaftor is a drug that restores the functioning of the mutant protein in patients with G551D or nine similar cystic fibrosis transmembrane regulator (CFTR) mutations. It has been recommended for children six years and older with one of these specific mutations. Now, ivacaftor has been approved by the US Food and Drug Administration for use in children two years and older [64]. The approval was based upon a small open-label trial in children two to less than six years, which demonstrated that the safety of ivacaftor was similar to that in older age groups. (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'CFTR modulators'.)

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