The OneLiner Archives

The OneLiner is a resident-generated, evidence-based monthly newsletter designed to keep readers up-to-date with recently published general pediatrics literature. We have collaborated with CHOP OPEN to generate an archive compiled of past OneLiners written by our residents. If you have any questions or would like to learn more about The OneLiner, please reach out to chopopensupport@chop.edu.

2024

  • February

    The One-Liner: The risk of death or moderate/severe bronchopulmonary dysplasia at 36 weeks was not significantly lower among extremely pre-term infants with a large patent ductus arteriosus who received early ibuprofen (within 72 hours of birth) as compared to infants who received placebo.  

    Gupta, Samir, et al. “Trial of Selective Early Treatment of Patent Ductus Arteriosus with  Ibuprofen | Nejm.” The New England Journal of Medicine, 25 Jan. 2024, www.nejm.org/doi/full/10.1056/NEJMoa2305582. 

    In extremely pre-term infants (born at less than 29 weeks), a large patent ductus arteriosus (PDA) that lasts beyond 3 days of age is associated with higher morbidity, mortality, and higher risk of bronchopulmonary dysplasia (BPD). Notably, the incidence of PDA is inversely proportional to gestational age at birth. Infants can be screened for large PDAs to determine if they would benefit from treatment, and at CHOP, clinical assessment of PDA guides whether infants receive an echocardiogram. Echocardiograms characterize PDAs based on restrictiveness of transductal flow, the pulmonary artery ratio, and signs of chamber dilation in the heart to stage the PDA. “Large” PDAs at CHOP receive pharmacological treatment, which consists of 3 doses of ibuprofen or indomethacin.   

    This multi-center, randomized, double-blind trial compared early treatment (within 72 hours of birth) of a large PDA (defined as diameter greater than or equal to 1.5 mm with pulsatile flow as a left to right shunt) with ibuprofen in extremely pre-term infants (born between 23 weeks, 0 days and 28 weeks, 6 days). Infants were randomized to 3 doses of Ibuprofen or 3 doses of placebo, and followed to 36 weeks post-menstrual age (PMA). The primary outcome was a composite of death or moderate/severe BPD at 36 weeks PMA. This outcome occurred in 69.2% of infants who received ibuprofen, and 63.5% of infants assigned to placebo. Notably, there was no statistically significant difference between the two arms, given that 13.6% of infants who received ibuprofen died, and 10.3% of infants who received placebo died. Of the infants who survived to 36 weeks PMA, moderate or severe BPD was present in 64.2% of ibuprofen group and 59.3% of placebo group. 

    Therefore, treatment with ibuprofen at <72 hours was not associated with a lower incidence of death or moderate/severe BPD at 36 weeks PMA as compared to placebo. This finding is consistent with other studies that have also not shown that early targeted treatment of PDA with ibuprofen is associated with a reduced incidence of death, BPD, or neurodisability. 

    The OneLiner: Sustaining a mild traumatic brain injury significantly increases the risk of developing a new affective or behavioral disorder up to 4 years after the incident, especially for children between 10-13 years of age.  

    Richard L. Delmonico, Lue-Yen Tucker, Brian R. Theodore, Michelle Camicia, Charles Filanosky, Juliet Haarbauer-Krupa; Mild Traumatic Brain Injuries and Risk for Affective and Behavioral Disorders. Pediatrics February 2024; 153 (2): e2023062340. 10.1542/peds.2023-062340 

    Sustaining a mild traumatic brain injury (mTBI), defined as causing 30 minutes or less of loss of consciousness with no documented traumatic intracranial lesions, is associated with an increased risk of developing an affective or behavioral disorder. This longitudinal cohort study compared the aforementioned psychiatric outcomes of approximately 18900 pediatric patients who acquired a mild TBI to a matched cohort of approximately 37800 pediatric patients without an mTBI. The study found that the mTBI group was 18% more likely to be diagnosed with a psychiatric disorder within 4 years, and patients within the 10-13 age group were found to have the highest risk for post-injury affective and behavioral disorders. This study demonstrates the importance of initial and ongoing screening for affective and behavioral disorders after mTBI in children and adolescents, as healthcare providers may be better able to identify persistent conditions that pose barriers to recovery. 

    The One-Liner: Exercise has been demonstrated to improve mental health in children and adolescents with neurodevelopmental disorders, and healthcare providers may optimize this association by targeting different mental health domains with different exercise interventions. 

    Liu C, Liang X, Sit CHP. Physical Activity and Mental Health in Children and Adolescents With Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis. JAMA Pediatr. 2024;178(3):247–257. doi:10.1001/jamapediatrics.2023.6251 

    Physical activity can improve mental health domains such as cognitive function, psychological well-being, internalizing, and externalizing problems, and this can be leveraged to benefit children and adolescents with neurodevelopmental disorders. This study investigated randomized and unrandomized trials that applied exercise interventions and appreciated at least 1 mental health outcome in pediatric patients with neurodevelopmental disorders. Overall, physical activity was found to improve overall mental health and the extent was dependent on factors such as frequency, total duration, and type of exercise. Notably, the type of neurodevelopmental disorder did not play the same role that the aforementioned factors did. As healthcare providers caring for patients with diverse neurodevelopmental and mental health needs, it is necessary to utilize exercise as a tool for both, while simultaneously improving physical health! 

    The One-Liner: The 2009 changes to WIC food package were highly cost-effective in preventing childhood obesity and improving socioeconomic inequities in childhood obesity prevalence, but further work needs to be done to improve the program’s reach to all qualifying families.  

    Erica L. Kenney, Matthew M. Lee, Jessica L. Barrett, Zachary J. Ward, Michael W. Long, Angie L. Cradock, David R. Williams, Steven L. Gortmaker; Cost-effectiveness of Improved WIC Food Package for Preventing Childhood Obesity. Pediatrics February 2024; 153 (2): e2023063182. 10.1542/peds.2023-063182 

    The 2009 changes to the WIC food package for children between the ages of 1 to 4 years aimed to prevent the development of childhood obesity by directing WIC benefits towards food items thought to reduce chronic disease risk while still supporting adequate nutrition. This resulted in the application of the benefit away from items such as juice, cheese, and eggs and towards healthier alternatives such as whole grains, low-fat milk, fruits, and vegetables. As a result, WIC recipients demonstrated increased fruit and vegetable consumption, decreased juice consumption, and reduced caloric intake. The authors conducted microsimulation models to estimate the cases of obesity prevented in 2019 and costs per quality-adjusted-life year gained. The WIC changes were found to lead to reductions in childhood obesity risk, predicted to prevent 62,700 cases of childhood obesity in the year 2019 alone, all among children living in households with low income. This led to narrowing of the gap in obesity prevalence between children experiencing poverty and children with family incomes at or above 350% of the federal poverty line by 4.5%. The study also found that if WIC had been able to reach all eligible children, the population health benefits would have more than doubled. More research and advocacy work are needed in expanding WIC’s reach and improving program retention, as the program’s public health benefits and cost-effectiveness have been well-demonstrated. 

  • March

    The One Liner: Omalizumab is an oral monoclonal antibody that has been shown to be an effective and safe treatment to increase reaction threshold to multiple common food allergens. 

    Wood, Robert A., et al. “Omalizumab for the Treatment of Multiple Food Allergies.” New England Journal of Medicine, 25 Feb. 2024, www.nejm.org/doi/full/10.1056/NEJMoa2312382. 

    Peanuts, and Eggs, and Cashews, oh my! 

    Food allergies are common and hinder both health and wellbeing. In pediatrics, food allergies necessitate immense caution, attention, and education at school and home to avoid accidental ingestions. And misery loves company: over 80% of individuals that have a food allergy have more than one. There is currently only one FDA-approved oral therapy for food allergies, but it is specific only against peanuts. A group of researchers are working on changing this with Omalizumab: a monoclonal antibody that binds to IgE, effectively blocking an immune response regardless of the antigenic trigger.  

    The OUtMATCH trial, or The Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy in Food Allergic Children and Adults, aims to assess Omalizumab’s utility in decreasing allergic response to multiple food allergens. The trial randomized 117 children between 1-17 years old who had allergies to peanuts and at least two other foods (milk, eggs, wheat, walnuts, cashews, or hazelnuts). Allergies were confirmed by skin-prick test, IgE level, and oral food challenge. Participants were randomized to receive a subcutaneous injection (Omalizumab or placebo) every 2-4 weeks for 16-20 weeks. Participants were told to avoid food allergens during this period and return after 20 weeks for repeat testing. The primary endpoint was no “dose-limiting symptoms” (as defined by the “Consortium for Food Allergy Research grading scale for acute allergic reaction”) to 600 milligrams of peanuts. Secondary endpoints included no “dose-limiting symptoms” to 1000 milligrams of cashews, milk, or eggs. Dosages were selected given that these are the amounts typically encountered during accidental exposure. 

    What did they find? 

    Overall, Omalizumab worked! Participants on Omalizumab could safely consume higher quantity of allergenic foods as compared to placebo. 67% of participants on Omalizumab had no dose-limiting symptoms with peanuts compared to 7% of placebo. Similar data was found with cashews (41% Omalizumab vs 3% placebo), eggs (67% Omalizumab vs 0% placebo), and milk (66% Omalizumab vs 10% placebo).  

    So, what does this mean? 

    These data present exciting and promising ways to revolutionize the experience of kids with multiple food allergens. Notably, based on these results alone, children would be protected only in emergency situations (such as accidental ingestions) and would still need to avoid these allergenic foods. However, these findings are just results from phase 1 of a 3-part trial. Phase 2 will continue the trial for one year to assess long-term efficacy of Omalizumab, and phase 3 will assess response to allergens in the diet after a year of oral Omalizumab therapy. Stay tuned for more!  

    The OneLiner: Sharing a sleeping surface increases the risk of having more than 1 unsafe sleep risk factor, and increases the risk of Sudden Unexpected Infant Death. 

    Alexa B. Erck Lambert, Carrie K. Shapiro-Mendoza, Sharyn E. Parks, Carri Cottengim, Meghan Faulkner, Fern R. Hauck; Characteristics of Sudden Unexpected Infant Deaths on Shared and Nonshared Sleep Surfaces. Pediatrics March 2024; 153 (3): e2023061984. 10.1542/peds.2023-061984 

    Sudden Unexpected Infant Death (SUID) accounts for 3400 deaths of infants <1 year old in the US each year. This study utilized data from the CDC’s SUID Case Registry and reviewed more than 7,500 cases over a 10-year period from nearly half of the US. Of the SUID cases studied, 59.5% of infants were sharing a sleep surface at time of death. The study found that infants sharing sleep surfaces were more likely to have >1 unsafe sleep risk factor; notably, 31.3% of surface-sharing infants experienced the 3 major unsafe sleep practices (soft or loose bedding/objects, not in a crib, not supine). Additionally, 76% of cases of SUID involved >1 unsafe sleep practice, regardless of surface-sharing status. Breastfeeding was found to be a protective factor, while maternal smoking increased the risk for SUID tenfold. Due to the presence of multiple unsafe sleep practices in most cases of SUID, the study recommends comprehensive safe sleep counseling to all families to prevent sudden infant death, as opposed to only counseling on appropriate sleep surfaces.  

    The OneLiner: A dose-response relationship was observed between increased screen time at age 1 year and developmental delays at age 2 and 4 years in communication and problem-solving. 

    Takahashi I, Obara T, Ishikuro M, et al. Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delay at 2 and 4 Years. JAMA Pediatr. 2023;177(10):1039–1046. doi:10.1001/jamapediatrics.2023.3057 

    The AAP currently recommends a 1 hour of screen time limit for children aged 2-5 years. However, many children exceed this limit, especially after the height of the COVID pandemic. This study occurred in Japan and divided children into 4 groups ranging from screen time < 1 hour to > 4 hours per day. Developmental delays were assessed using the Japanese language version of the Ages and Stages Questionnaire. This study is unique because no previous study looked specifically at which domains of development were affected by screen time, or only looked at single measures as outcomes. Domains affected included communication, fine motor, problem-solving, personal skills, and social skills, with communication and problem-solving domains exhibiting dose-response relationships to screen time. Notably, some domains were impacted at age 2 and not at age 4. The study hypothesized that this could be due to self-improvement in these domains or reverse causation (developmental delays in these areas lengthen screen time). Additionally, this study found that mothers of children with higher screen times were more likely to be younger, first-time mothers, with a lower household income, with a lower education level, or experiencing or have experienced post-partum depression. This study demonstrates the importance of counseling about screen time to decrease the risk of developmental delay. 

     

    The OneLiner: 20% of US child passenger deaths involve an alcohol-impaired driver, and child endangerment laws designed to elicit enhanced DUI penalties while transporting a child have been increasingly shown to be ineffective. 

    Kyran Quinlan, Eduardo Romano, Tara Kelley-Baker; Child Passenger Deaths in Traffic Crashes Involving Alcohol-Impaired Drivers: 2011–2020. Pediatrics March 2024; 153 (3): e2023064159. 10.1542/peds.2023-064159 

    Approximately 20% of US child passenger deaths within the last 40 years have involved an alcohol-impaired driver. This study demonstrated that 64% of these children died while riding in the same vehicle as an impaired driver and found a negative correlation between the driver’s blood alcohol content (BAC) and child passenger seatbelt use. Child endangerment laws designed to elicit enhanced DUI penalties while transporting a child have not been effective. Physicians can protect child passengers by advocating for a wider use of measures to address alcohol-impaired driving, such as alcohol ignition interlock devices for drivers previously convicted of a DUI, lowering tolerable BAC limits, or rehabilitation programs for repeat offenders. 

     

  • April

    The OneLiner: There is no substantially increased risk of ASD after prenatal exposure to either topiramate or lamotrigine, however prenatal valproate exposure leads to a dose-dependent increased risk of autism spectrum disorder, cognitive impairment, and anatomic malformations.  

    Hernández-Díaz, Sonia, et al. “Risk of autism after prenatal topiramate, valproate, or lamotrigine exposure.” New England Journal of Medicine, vol. 390, no. 12, 21 Mar. 2024, pp. 1069–1079, https://doi.org/10.1056/nejmoa2309359. 

    Maternal use of valproate during pregnancy has been associated with increased risk of neurodevelopmental disorders, such as autism spectrum disorder (ASD), in children. Scientists have hypothesized that this may occur due to interference of valproate with neurotransmission critical for cell migration and differentiation. Valproate is oftentimes used for generalized epilepsy and is utilized by women of child-bearing potential only if their epilepsy has proven to be refractory to other medications. There is limited data regarding the risk of ASD associated with the maternal use of other anti-seizure medications, such as topiramate, hence the development of this study.  

    This study analyzed a population-based cohort of pregnant women and their children from two U.S. healthcare utilization databases from 2000-2020. Exposure to anti-seizure medications was defined based on filled prescriptions from gestational week 19 until delivery. Children who had been exposed to topiramate during the second half of pregnancy were compared with those unexposed to any anti-seizure medication during pregnancy. Valproate was used as a positive control, while lamotrigine was used as a negative control.  

    Amongst children not exposed to any anti-seizure medication, the cumulative incidence of ASD was 1.9%. For children born to mothers with epilepsy not exposed to any anti-seizure medication, the incidence of ASD was 4.2%. For children born to mothers who utilized lamotrigine during pregnancy, the incidence of ASD was 4.1%, while those with topiramate use during pregnancy demonstrated an incidence of 6.2%, and those with valproate use resulted in an incidence of 10.5%. 

    After adjustment for indication, there was no substantially increased risk of ASD after prenatal exposure to either topiramate or lamotrigine. There was a dose-dependent increased risk of ASD, cognitive impairments, and anatomic malformations associated with prenatal valproate exposure. Therefore, topiramate and lamotrigine remain viable options for anti-seizure medications throughout pregnancy. 

    The OneLiner: The 2022 hyperbilirubinemia guidelines have led to a significant decrease in phototherapy utilization and serum bilirubin measurements without increasing readmission rates and lengthening admission for phototherapy by only 1 hour. 

    Leela Sarathy, Joseph H. Chou, Giuseppina Romano-Clarke, Katherine A. Darci, Paul H. Lerou; Bilirubin Measurement and Phototherapy Use After the AAP 2022 Newborn Hyperbilirubinemia Guideline. Pediatrics April 2024; 153 (4): e2023063323. 10.1542/peds.2023-063323  

    Neonatal hyperbilirubinemia affects nearly 80% of infants and leads to a large burden on both families and the healthcare system at large. While untreated hyperbilirubinemia is associated with neurologic sequelae, phototherapy comes with its own harm to patients and families. Phototherapy leads to disruption of bonding and breastfeeding, increased parental anxiety, and additional lab draws for the infant. More recently, studies have also demonstrated higher rates of epilepsy in patients who received phototherapy. This study aimed to assess if the new 2022 AAP hyperbilirubinemia guidelines achieved the intended goal of reducing rates of phototherapy utilization, while continuing to keep infants safe. The study included >22,000 newborns from 8 hospitals and analyzed phototherapy utilization, serum bilirubin measurements, readmission rate, and length of admission. When comparing data pre- and post- guideline implementation, this study showed that the 2022 guidelines led to a statistically significant reduction in phototherapy utilization and serum bilirubin measurements. Additionally, there was no change in readmission rates for phototherapy and admissions with phototherapy utilization were extended by only 1 hour! 

    The OneLiner: Antidepressant dispensing rates were increasing prior to the onset of the COVID-19 pandemic, but afterwards, these rates accelerated 64% faster, with rates driven by increased dispensing for adolescent females and occurred despite a decrease in dispensing to adolescent males. 

    Arwa K. Nasir, Laeth S. Nasir; Antidepressant Prescriptions and Mental Health. PediatricsMarch 2024; 153 (3): e2023064677. 10.1542/peds.2023-064677 

    This study analyzed a database covering 92% of all antidepressant prescriptions dispensed from U.S. retail pharmacies between 2016-2022. Study authors identified adolescents (aged 12-17) and young adults (aged 18-25) and tracked their antidepressant (SSRIs, SNRIs, TCAs, etc.) dispense rate (number of antidepressant prescriptions dispensed per 100,000 people) from 2016-2022.  

    Overall, the study demonstrated that monthly antidepressant dispensing rates for U.S. adolescents and young adults increased by 66.3% between January 2016 and December 2022. This rate increased 63.5% faster after March 2020. Amongst adolescent females, dispensing rates increased 130% faster after March 2020, and amongst young adult females, rates increased 66% faster after March 2020. Meanwhile, amongst adolescent males, dispensing rates decreased sharply starting in March 2020, and did not recover by 2022. There was no significant change in dispensing rates for young adult males after March 2020. The authors speculate that the decrease in dispensing to male adolescents after March 2020 does not represent decreased need, but instead could reflect less care-seeking behavior or underuse relative to the level of need. 

    The OneLiner: A universal, free school meals policy implemented in low-income California public schools from 2018-2019 demonstrated a 2.4% decrease in obesity prevalence.  

    Anna M. Localio, Melissa A. Knox, Anirban Basu, Tom Lindman, Lina Pinero Walkinshaw, Jessica C. Jones-Smith; Universal Free School Meals Policy and Childhood Obesity. Pediatrics April 2024; 153 (4): e2023063749. 10.1542/peds.2023-063749 

    Community Eligibility Provision (CEP) is a universal, free school meals policy which allows for schools in low-income areas to provide free breakfast and lunch to all students. Participating schools also receive federal reimbursement, and by 2023, more than 40% of US public schools were participating in this program, benefiting nearly 20 million children.  

    The objective of this particular study was to estimate the association of CEP with childhood obesity, and the study population included 3531 low-income California public schools, where the baseline obesity prevalence was 25%. The study identified a net decrease of 2.4% in obesity prevalence in schools that adopted CEP as compared to nonparticipating schools from 2018-2019. This study contributes to growing knowledge regarding the positive impact of universal free school meals to address childhood obesity. Additionally, these policies have been demonstrated to both improve food insecurity and child academic performance, and contribute towards increasing disposable income for families. 

     

  • May

    The OneLiner: Different nutritional interventions did not lead to significant differences in body fat percentage or time to full enteral feeding in moderate-to-late preterm infants. 

    Alexander, Tanith, et al. “Nutritional support for moderate-to-late–preterm infants — a randomized trial.” New England Journal of Medicine, vol. 390, no. 16, 25 Apr. 2024, pp. 1493–1504, https://doi.org/10.1056/nejmoa2313942. 

     

    One of the most common and favorite populations of the NICU are the “feeder-growers,” usually moderate-to-late preterm infants, but sadly, this population is not commonly the focus of many research studies! The same is true for studies evaluating optimal nutrition strategies for the moderate-to-late preterm population. This multicenter, randomized trial involved 532 infants born at 32 weeks to 35 weeks 6 days’ gestation who had intravenous access and whose mothers intended to breastfeed. The study compared the effects of 3 interventions: parenteral nutrition (PN) or sugar solution until full feeding with milk was established, milk supplement given when maternal breast milk (MBM) was insufficient or exclusive MBM, and exposure or no exposure to the taste and smell of milk before each tube feeding. The goal for all infants was to reach full feeds of only mothers’ breast milk as quickly as possible.  

     

    The primary outcome for the parenteral nutrition and milk supplement interventions (first two groups) was body fat percentage (first two interventions). The primary outcome for the taste and smell intervention was time to full enteral feeding (last group). The body fat percentage at 4 months was similar among infants who received parenteral nutrition and those who received dextrose solution, as well as those who received milk supplement and those who received exclusive MBM. The time to enteral feeding was also similar among the infants who were exposed to taste and smell and those who were not. This work contributes to the small amount of existing data to guide practices in optimizing nutrition for this vulnerable population and helps frame conversations about nutrition with these families! 

     

    The One-Liner: CRP is a poor diagnostic indicator for early onset sepsis in neonates admitted to the NICU and removal of CRP from early onset sepsis diagnostic criteria was correlated with lower rates of early onset sepsis evaluation, antibiotic administration, and antibiotic prolongation in patients without early onset sepsis.  

    Dhudasia, Miren B., et al. “Diagnostic performance and patient outcomes with C-reactive protein use in early-onset sepsis evaluations.” The Journal of Pediatrics, vol. 256, 15 Dec. 2022, https://doi.org/10.1016/j.jpeds.2022.12.007. 

     

    While the gold standard to diagnose early-onset sepsis (EOS) is isolation of a pathogen from either a blood culture or cerebrospinal fluid culture, C-reactive protein (CRP) is an acute phase reactant oftentimes used as a biomarker in evaluation of neonatal EOS. This retrospective cohort study involved infants from 2 NICUs in the University of Pennsylvania Hospital System. The 2009-2014 cohort, in which CRP was routinely used in EOS evaluation, was compared to the 2018-2020 cohort, in which the practice was discontinued. Overall, the incorporation of CRP into EOS evaluation was associated with higher rates of diagnostic testing, such as blood cultures and lumbar punctures, and higher rates of antibiotic administration. Importantly, in comparing the two study populations, there was no change in time to detection of infection or antibiotic initiation, infection rates, transfer to higher level of care, or in-hospital mortality in the first week after birth.  

     

    The OneLiner: The use of CRISPR-Cas9 gene editing in patients with sickle cell disease significantly decreases VOE and hospitalizations for at least 12 months.
    Frangoul, Haydar, et al. “Exagamglogene autotemcel for severe sickle cell disease.” New England Journal of Medicine, vol. 390, no. 18, 9 May 2024, pp. 1649–1662, https://doi.org/10.1056/nejmoa2309676. 

    For our patients with sickle cell disease, elevated levels of fetal hemoglobin (HbF) are associated with reduced morbidity and mortality, given that HbF inhibits polymerization and prevents sickling of RBCs. Exagamglogene Autotemcel (exa-cel) is a novel cell therapy designed to reactivate fetal hemoglobin synthesis through the use of CRISPR-Cas9 gene editing. This Phase 3, open-label study focused on 30 patients with sickle cell disease who received the gene therapy, and an astounding 97% of these patients were free from vaso-occlusive episodes (VOE) for at least 12 months, and 100% were free from hospitalizations for VOE for at least 12 months! Given that patients underwent myeloablative conditioning prior to exa-cel administration, safety was a key focus within the study; however, no new malignancies were reported during this follow-up period.  

    The OneLiner: Recess is associated with increased physical activity, better in-school behavior, improved cognitive functioning, and lower stress, and pediatricians can partner with the community to help pass recess laws for our patients! 

    Pooja S. Tandon, Linnea Westerlind, Julie McCleery, King County Play Equity Coalition’s Advocacy Action Team; Advocacy for Equitable Recess in Washington State. Pediatrics May 2024; 153 (5): e2023064226. 10.1542/peds.2023-064226 

    Undoubtedly, one of the best aspects of elementary school is recess! Did you know that daily recess is officially recommended by the American Academy of Pediatrics?! Recess has been associated with increased physical activity, better in-school behavior, improved cognitive functioning, and lower stress. Given that more than 75% of U.S. children are not meeting physical activity guidelines, recess is key in helping to combat this! State laws can help promote equitable and high-quality recess, however, most states do not have recess laws. This case study focuses on a proposed 2023 Washington State bill that mandates at least 30 minutes of daily recess, which passed with the joint efforts of pediatricians, parents, teachers, community organizations, and the students! 

2023

  • November

    The One-Liner: Nirsevimab reduces medically attended RSV-associated lower respiratory tract infection and may reduce hospitalization for these infections in late-preterm and term infants (finally, something to help not only our preemie babies fight against RSV!)  
    Hammitt, Laura L., et al. “Nirsevimab for prevention of RSV in healthy late-preterm and term infants.” New England Journal of Medicine, vol. 386, no. 9, 2022, pp. 837–846, https://doi.org/10.1056/nejmoa2110275. 

    Why it’s important:  

    Palivizumab (remember the pale ghost from the RSV Sketchy?) has strict cutoffs: it is for babies who were born at or before 35 weeks and who are 6 months of age or less at the start of RSV season. However, most hospitalizations for RSV actually occur in healthy infants born at term! Enter Nirsevimab, which can be used as an intervention to prevent some of the burden of RSV in healthy, term infants. This study was a randomized, controlled, double-blinded trial that compared outcomes in patients receiving nirsevimab to placebo.  

    How does Nirsevimab work?  

    Nirsevimab is a recombinant human IgG1 kappa monoclonal antibody that binds the F1 and F2 subunit of the RSV fusion protein at a highly conserved epitope and prevents RSV from entering the host cell.  

    Outcomes  

    Medically attended RSV-associated lower respiratory tract infection was significantly lower in the nirsevimab treatment group compared to placebo, corresponding to an efficacy of 74.5% (P<0.001). Through 150 days after injection of either nirsevimab or placebo, the treatment group had fewer hospitalizations for RSV-associated lower respiratory tract infection with an efficacy of 62.1% (P = 0.07). Relatively lower efficacy estimates were observed in infants who were < 3 months of age and weighed less than < 5 kg. No serious adverse effect that occurred to participants in this study was thought to be related to nirsevimab or placebo; adverse events thought to be related to nirsevimab occurred in 1% of infants (most significant was a rash that self-resolved without intervention).  

    Strengths and Weaknesses of the Trial 

    The trial captured patients not just across the United States but across several different countries. Both investigators and parents/guardians were double-blinded to what infants were receiving. The study used intention to treat protocol. Overall, the study did not lose too many patients to follow-up (retained 91.7% of participants by 360 days). However, the study was funded by MedImmune/AstraZeneca and Sanofi, the companies who will manufacture, distribute, and profit from this new drug. The study also included few infants with underlying diseases, and further research must be done to see how the drug will impact this population. 

    The One-Liner: 30 minutes of outdoor cold air can decrease the severity of croup clinical symptoms, especially in children with moderate croup, offering a potential adjunct to steroids during the window of time (30 min) before the benefit of steroids hits.  
    Johan N. Siebert, Coralie Salomon, Ilaria Taddeo, Alain Gervaix, Christophe Combescure, Laurence Lacroix; Outdoor Cold Air Versus Room Temperature Exposure for Croup Symptoms: A Randomized Controlled Trial. Pediatrics September 2023; 152 (3): e2023061365. 10.1542/peds.2023-061365 

    Respiratory virus season is upon us, and croup or laryngotracheobronchitis, is one of the most common acute upper airway obstructive pathologies we see in children. There are robust data to support the use of steroids benefitting croup of any severity, with a one-time dose of oral dexamethasone as mainstay first-line treatment (CITE). Nebulized epinephrine (CITE) is often used as additional treatment in more severe cases. But what about non-pharmacologic therapies? We often hear of the anecdotal benefit of “cold night air” – is there any merit to it?  

    Physicians and researchers at the University of Geneva in Switzerland conducted a randomized controlled trial asking this exact question. They randomized 118 children, ages 3 months to 10 years, in a pediatric ED with a Westley Croup Score (WCS), a clinical assessment tool to evaluate the degree of severity of croup, of > 2. Each child received a single dose of dexamethasone at triage and then were randomized to a study group while the steroid took effect (data suggest the benefits of dexamethasone are seen 30 minutes after administration). The intervention was exposure to outdoor cold air (< 10 C), while the control group was exposure to indoor air (kept at 24-25 C). Kids in the intervention group actually went outside the ED to breathe the cool Swiss air!  

    After 30 minutes, the child’s WCS was reassessed. The study found that 49.2% (29/59) of children in the outdoor group had a drop >= 2 in their WCS, while 23.7% (14/59) of children in the indoor group had a drop >=2, a statistically significant difference (risk difference 25.4%, p = 0.007)! Interestingly, the children with moderate-severity croup showed the greatest improvement with the cold air adjunct. So, next time you pull up the CHOP Croup Pathway or chat with parents in clinic, remember this study that transitioned anecdotal stories into science: that “cold night’s air” can offer an easy, affordable, non-pharmacologic adjunct intervention to croup. 

    The One-Liner: Pediatric ingestions of THC edibles have increased, and THC ingestions > 1.7 mg/kg can lead to incredible toxicity in children less than 6! 
    Lesley C. Pepin, Mark W. Simon, Shireen Banerji, Jan Leonard, Christopher O. Hoyte, George S. Wang; Toxic Tetrahydrocannabinol (THC) Dose in Pediatric Cannabis Edible Ingestions. Pediatrics September 2023; 152 (3): e2023061374. 10.1542/peds.2023-061374 

    Background: This was a retrospective study of children less than 6 years old presenting with edible ingestions of known THC dose in 1 hospital network from 2015 – 2022. Ingestions increased over this time period, and the study assessed trends in ingestion incidence, length of episode, and severity of toxicity. 

    Findings: 80 patients met inclusion criteria. THC dose ranged 0.2 to 69.1mg/kg. Gummies accounted for 61% of ingestions and half of children with ingestions were hospitalized. 74% had toxicity that was prolonged (defined as requiring more than 6 hours to return to baseline). 46% had toxicity characterized as severe (examples include shock requiring pressors, respiratory failure requiring intubation, seizure), with most severe episodes involving the neurologic system.  

    Moreover, each 1mg/kg higher ingestion of THC was associated with approximately 3 times higher odds of severe and/or prolonged toxicity. THC ingestions > 1.7-2.3mg/kg were predictive of both severe and prolonged toxicity (could be as small as two 10-mg edibles)! Although this 1.7mg/kg threshold that helps to predict severe and prolonged toxicity could vary in places that are not regulated (this study was conducted in Denver), this threshold can be helpful in both regulatory and clinical guidelines! 

    The One-Liner: Internalized racism poses a direct threat to the emotional health, racial self-identity, and self-esteem of Black children.  
    Antwon Chavis, DeOnna Johnson; Internalized Racism and Racial Self-Identity Formation in Black Children. Pediatrics August 2023; 152 (2): e2023061292. 10.1542/peds.2023-061292 

    This article discusses how the tripartite model of racism frames racism at 3 levels: institutionalized, interpersonal, and internalized racism. Subconscious normalization of systemic oppression may result from multiple aspects, including persistent economic marginalization and devaluation as well as frequent media misrepresentation. The concept of internalized racism was highlighted in the 1954 “Doll Study”, in which both Black and White children were asked to select dolls to play with and demonstrated an overwhelming preference towards the socially-privileged White phenotype. Black children are at increased risk of internalizing negative perceptions as they become old enough to experience and understand discrimination. This internalized racism poses a direct threat to emotional health, racial self-identity, and self-esteem of Black children. There has been a demonstrated positive correlation between racial discrimination and internalized negative beliefs. Pediatric healthcare providers must be prepared to: understand and discuss effects of exposure to racism (including understanding the historical and cultural context of internalized racial oppression), seek to examine one’s own intrinsic biases, and advocate alongside community partnerships to help address inequities in the health, justice, and educational systems.

  • December

    The OneLiner: This study comparing traditional urine culture to a reference standard of bacterial gene sequencing in urine demonstrated that a cutoff of 10,000 colony-forming units (CFU)/mL optimized the balance between sensitivity and specificity for children undergoing bladder catheterization for suspected UTI. 

    Nader Shaikh, Sojin Lee, Janina A. Krumbeck, Marcia Kurs-Lasky; Support for the Use of a New Cutoff to Define a Positive Urine Culture in Young Children. Pediatrics October 2023; 152 (4): e2023061931. 10.1542/peds.2023-061931 

    The details: The definition of a positive urine culture has been a subject of controversy for many decades and will usually involve a tradeoff between sensitivity and specificity at various cutoffs. This study utilized 16s rRNA sequencing (locates the highly preserved 16s rRNA gene) to identify the bacteria present in samples, thereby providing a culture-independent reference standard. Researchers using this reference standard defined UTI as both the relative abundance of any organism of at least 80% in the urine and elevated urinary inflammatory markers. 341 febrile children between 1 month and 3 years of age undergoing bladder catheterization for suspected UTI were enrolled in this study.  

    What did the results show? When using a cutoff of 10,000 colony-forming units (CFU)/mL, the sensitivity of urine culture was 98% and specificity was 99%, correctly identifying 45 of 46 patients with UTI. When using a cutoff of 50,000 CFU/mL, sensitivity was 80% and specificity was 99%, missing 9 of the 46 UTIs. This means that using 50,000 CFU/mL as the cutoff had a much lower sensitivity without having a higher specificity! Given this data, 10,000 CFU/mL was identified as an appropriate cutoff for children undergoing bladder catheterization for suspected UTI.  

    What does this mean for us? If implemented at CHOP, this would lower the threshold at which a UTI is defined. Like many other institutions, here at CHOP (per the UTI pathway), UTI symptoms such as dysuria, frequency, urgency, and hematuria and a catheterized sample only meets criteria for a definite UTI if >50,000 CFU/mL are identified. It might be time for us to rethink what defines a positive urine culture… 

     

    The OneLiner: ADHD medication errors increased by 299% between 2000-2021, are most common in children 6-12 years old and males, and are most likely to be due to inadvertently taking a medication twice or taking someone else’s medication. 

    Mikaela M. DeCoster, Henry A. Spiller, Jaahnavi Badeti, Marcel J. Casavant, Natalie I. Rine, Nichole L. Michaels, Motao Zhu, Gary A. Smith; Pediatric ADHD Medication Errors Reported to United States Poison Centers, 2000 to 2021. Pediatrics October 2023; 152 (4): e2023061942. 10.1542/peds.2023-061942 

    This study investigates trends of out-of-hospital ADHD medication errors among individuals <20 years old reported to US poison centers from 2000-2021. These medication errors, defined as unintentional deviation from a proper therapeutic regimen, increased by 299% during the study period. The exponential increase is likely attributable to increased ADHD diagnoses, and corresponding increased use of ADHD medications among children. Two-thirds of exposures involved children from 6-12 years old, three-fourths of exposures were among males, and half involved amphetamines and related compounds. 93% of exposures occurred in the home setting, 2.3% of exposures resulted in healthcare admission, and 4.2% of exposures resulted in a serious outcome. Interestingly, therapeutic errors involving guanfacine were more than 5 times as likely to be associated with admission to a healthcare facility and were more than twice as likely to be associated with a serious medical outcome. 53.9% of the therapeutic errors were attributed to inadvertently taking medication twice, 13.4% were attributed to inadvertently taking someone else’s medication, and 12.9% were due to the wrong medication being taken or given. Given that these therapeutic errors are preventable, it is vital that clinicians provide appropriate patient and caregiver education regarding medication dispensing and tracking systems. 

     

    The OneLiner: The strongest risk factor for late-onset sepsis in very low birth weight infants was found to be a gestational age of less than 27 weeks, and coagulase-negative staphylococci is the most commonly isolated pathogen. 

    Gil Klinger, Ruben Bromiker, Inna Zaslavsky-Paltiel, Sharon Klinger, Nir Sokolover, Liat Lerner-Geva, Brian Reichman, ISRAEL NEONATAL NETWORK; Late-Onset Sepsis in Very Low Birth Weight Infants. Pediatrics November 2023; 152 (5): e2023062223. 10.1542/peds.2023-062223 

    Late-onset sepsis, defined as sepsis occurring 72 hours or later after birth, is associated with increased morbidity and mortality in very low birth weight (VLBW) (<1500 grams) infants. This Israeli population-based study occurred between 1995-2019 with a study population of 31612 VLBW infants, and sought to determine risk factors associated with late-onset sepsis and investigate temporal trends in pathogen-specific rates. This study found that 23.5% of these infants experienced 1 or more episodes of late-onset sepsis, and the strongest risk factor was a gestational age of less than 27 weeks. Coagulase-negative staphylococci (CoNS) was consistently the most commonly isolated pathogen. Additionally, over a 25-year period, the pathogen-specific rates of late-onset sepsis among VLBW infants decreased approximately 2-fold for gram-positive and gram-negative bacterial infections, and 6-fold for fungal infections, which was attributed to quality improvement measures such as staff education of infection control, stronger adherence to aseptic techniques, and increased care of central lines. 

     

    The OneLiner: Homicide is the second leading cause of death among children aged 1-17, with females bearing the greatest burden of firearm homicides involving IPV and males disproportionately experiencing firearm homicides due to community violence. 

    Rebecca F. Wilson, Likang Xu, Carter J. Betz, Kameron J. Sheats, Janet M. Blair, Xin Yue, Brenda Nguyen, Katherine A. Fowler; Firearm Homicides of US Children Precipitated by Intimate Partner Violence: 2003–2020. Pediatrics December 2023; 152 (6): e2023063004. 10.1542/peds.2023-063004 

    This study provides needed insight into the role that intimate partner violence (IPV) plays in the overall scope of firearm violence perpetuated against children. Homicide is the second leading cause of death among children aged 1-17 years, and 75% of these deaths are due to firearm injuries. A staggering 15.5 million (29%) of US children are exposed to IPV at home annually. From 2003-2020, 11500+ child homicides were reported, and 49% were a result of firearms while 12% were related to IPV. Child corollary victims (children whose death was connected to IPV between others) composed 86% of these homicides, while 14% were teenagers killed by a current or former dating partner. Unsurprisingly, a disproportionate occurrence of firearm homicides of males were found to be due to community violence, whereas females bear the greatest burden of firearm homicides involving IPV. Given these staggering statistics, it is critical for our society to promote healthy intimate partner relationships from a young age. Moreover, we must advocate for violence interruption, strengthen economic support for families and youth, and address social and structural inequities at the root of youth firearm violence. 

2022

  • July

    The One-Liner: New guidelines for management of febrile neonates separate infants by age into 3 subgroups (8-21, 22-28 & 29-60 days), with new usage of inflammatory markers to determine the need for LP in infants >21 days old.  

    Robert H. Pantell, Kenneth B. Roberts, William G. Adams, Benard P. Dreyer, Nathan Kuppermann, Sean T. O’Leary, Kymika Okechukwu, Charles R. Woods, SUBCOMMITTEE ON FEBRILE INFANTS; Clinical Practice Guideline: Evaluation and Management of Well-Appearing Febrile Infants 8 to 60 Days Old. Pediatrics August 2021; 148 (2): e2021052228. 10.1542/peds.2021-052228 

    The new guidelines provide new recommendations based on age, broken down now into 3 groups: 8-21 days old, 22-28 days old and 29-60 days old. You’ll recall the previous breakdown was into 2 groups (0-28 & 29-56 days old). Inflammatory markers are also now being used to determine the need for lumbar puncture. The youngest kids (8-21 days old) still get the whole nine yards. 

    Initial prediction models defined age groupings somewhat arbitrarily. Recent studies have shown that infants 22-28 days old are at lower risk for invasive bacterial infection than infants 8-21 days old, but still at higher risk than older infants. 

    The bacteria causing neonatal bacterial infections has shifted from gram positive to gram negative predominance, with E. coli being the most common cause of bacteremia. This shift is due to increased GBS screening and improved food safety leading to less Listeria. Group B Strep remains the most common cause of meningitis. 

    The One-Liner: While more research needs to be done, this study showed that PHEN/TPM, when used as an adjunct to lifestyle therapy, can be a safe treatment option in adolescents with obesity. 

    Kelly AS, Bensignor MO, Hsia DS, et al. Phentermine/topiramate for the treatment of adolescent obesity. NEJM Evidence 2022;1(6). 

    While we’re all pros at the Obesity Screening Pathway, we don’t have too much to offer beyond lifestyle modifications. The combination of phentermine and topiramate has been approved for adults for over a decade. In a randomized, double-blind placebo control trial, adolescents with obesity were assigned to placebo, low and high doses of PHEN/TPM with primary end-point of percent change in BMI at 1 year. The study found that compared to placebo, both the low and high doses were shown to have significant reduction in BMI, waist circumference and increase in HDL. Adverse events were common in both placebo and study groups. This study was limited by a high drop-out rate (thought to be due to the COVID-19 pandemic). 

    The One-Liner: Non-operative management of appendicitis is here to stay. While most do well, look out for those with recurrence as they have a higher rate of post-op complications. 

    Susan C. Lipsett, Michael C. Monuteaux, Kristen H. Shanahan, Richard G. Bachur; Nonoperative Management of Uncomplicated Appendicitis. Pediatrics May 2022; 149 (5): e2021054693. 10.1542/peds.2021-054693 

    A recent study in the journal Pediatrics looked at over 100,000 children with appendicitis over a 9-year period to assess outcomes with non-operative management (NOM) of appendicitis. Non-operative management of non-perforated appendicitis in children is increasing. Patients undergoing NOM had higher rates of subsequent related emergency department visits (8.0% vs 5.1%, P < .001) and hospitalizations (4.2% vs 1.4%, P < .001) over a 12-month follow-up period. Although the majority of children who undergo NOM remain recurrence-free years later, they carry a substantial risk of perforation at the time of recurrence and may experience a higher rate of postoperative complications than children undergoing an immediate appendectomy. 

    The One Liner: Recent policy statement by the AAP reaffirms its position that the right to confidential care for adolescents considering abortion should be protected. 

    AMERICAN ACADEMY OF PEDIATRICS, COMMITTEE ON ADOLESCENCE; The Adolescent’s Right to Confidential Care When Considering Abortion. Pediatrics August 2022; 150 (3): e2022058780. 10.1542/peds.2022-058780 

    Unless you’ve been living under a rock, you’ve heard by now that the US Supreme Court overruled Roe vs. Wade, completely changing the landscape for reproductive health in America. Pediatricians across the country have raised concerns for what this means for our adolescent population. 

  • August

    The One-Liner: While the research behind SMART therapy is not new, the clinical application of combination therapy for moderate-to-severe persistent asthma has grown since the 2020 NHLBI guideline update. 

    Papi A, Chipps BE, Beasley R, et al. Albuterol–Budesonide fixed-dose combination rescue inhaler for asthma. New England Journal of Medicine 2022;386(22):2071–83. 

    The idea of combined inhaled corticosteroid and long-acting beta-agonists (LABA) is not a new one. The initial data was published in 1997 (aka when some of us were only 3 years old).  A little more recently, a 2006 Lancet article found that maintenance plus as-needed budesonide-formoterol reduced the risk of severe exacerbations and ED visits. In 2020, NHLBI released a guideline update that finally included SMART therapy. 

    Eligibility criteria include kids 5 years and up already on a daily low dose ICS or ICS/LABA. The children most likely to benefit from SMART are those with frequent exacerbations or albuterol use and those with difficulty adhering to 2 inhalers.  Combination inhalers include Dulera (mometasone/formoterol) and Symbicort (budesonide/formoterol). The combination inhaler should be used for both rescue and control, including before exercise. For kids less than 12 years, they should max out on 8 puffs daily, while those 12 years and up can do up to 12 puffs daily. 

    The MANDALA trial, a recently published multinational phase 3 double blind randomized trial, looked at the use of Albuterol-Budesonide as a rescue inhaler for patients with uncontrolled moderate-to-severe asthma already receiving inhaled glucocorticoid-containing maintenance therapy. Different from SMART therapy, this trial kept patients on their current controller medication and just changed their rescue medication (study arms: high dose combination, low dose combination, and albuterol). This study found that the risk of severe asthma exacerbation was 26% lower in the higher-dose combination group compared to albuterol alone without increasing the number of rescue doses needed. A limitation to keep in mind: while kids older than 4 years were included in the study, the number of pediatric patients was overall low and those 4 –11 years were only randomized to low-dose combination vs. Albuterol only given dosage concerns. 

    The One-Liner: While the 2013 AAP guidelines support the option of watchful waiting for management of uncomplicated, nonrecurrent acute otitis media (AOM), adoption of this has been limited and driven by clinician specialty and prescribing tendencies. 

    Nicole E. Smolinski, Patrick J. Antonelli, Almut G. Winterstein; Watchful Waiting for Acute Otitis Media. Pediatrics July 2022; 150 (1): e2021055613. 10.1542/peds.2021-055613 

    A retrospective cohort study in Pediatrics revealed that ~75% of cases of uncomplicated, nonrecurrent AOM received early antibiotics. The strongest predictor of this? Clinician specialty and previous prescribing tendencies, with otolaryngologists more likely to adopt watchful waiting than pediatricians. So why do we care? Antibiotic therapy for AOM contributes to the growth of antibiotic resistance, has adverse events, and yields limited benefit. In response to this, the AAP’s 2013 guideline provided explicit criteria for immediate treatment of AOM and gave the option of watchful waiting for non-severe cases. Despite this, adoption of watchful waiting for uncomplicated AOM remains limited and driven by clinician factors rather than patient factors. 

    The One-Liner: For children 2–23 months of age, duration of fever and history of UTI can replace race to determine the pre-test probability of UTI 

    Shaikh N, Lee MC, Stokes LR, et al. Reassessment of the Role of Race in Calculating the Risk for Urinary Tract Infection: A Systematic Review and Meta-analysis. JAMA Pediatr. 2022;176(6):569–575. doi:10.1001/jamapediatrics.2022.0700 

    This recently published meta-analysis in JAMA Pediatrics looked at 16 studies and over 17,000 patients to help answer the question: does race really matter for UTI risk? The authors replaced race with duration of fever and history of UTI in a previously studied prediction model and found similar accuracy, sensitivity, and specificity, prompting the exclusion of race in the latest version of the UTI prediction tool. 

    The One-Liner: States with stricter gun legislation and universal background checks for firearm purchases had lower pediatric firearm-related mortality rates. This remains true even in areas with high gun ownership rates 

    Monika K. Goyal, Gia M. Badolato, Shilpa J. Patel, Sabah F. Iqbal, Kavita Parikh, Robert McCarter; State Gun Laws and Pediatric Firearm-Related Mortality. Pediatrics August 2019; 144 (2): e20183283. 10.1542/peds.2018-3283 

    Monika Goyal MD, MSCE (a former CHOP resident and fellow!) et al in their 2019 cross-sectional study evaluated the association between gun legislation and mortality. Data from the 2011-2015 Web-based Injury Statistics Query and Reporting System (WISQARS) which provides CDC data on fatal injuries in the US was compared with an objective rating score of state firearm legislation. Data was adjusted for sociodemographic variables associated with firearm related mortality and gun ownership rates. Results showed approximately 4,250 annual pediatric firearm related deaths. For every 10-point increase in the gun law score (higher numbers = stricter laws), mortality rates significantly decreased by 4%. Rates were >35% lower in states requiring universal background checks for firearm purchases. 

  • September

    The One-Liner: For healthy children < 24 months admitted for bronchiolitis, post discharge PCP follow-up should not be routinely scheduled.    

    Coon ER, Destino LA, Greene TH, Vukin E, Stoddard G, Schroeder AR. Comparison of As-Needed and Scheduled Posthospitalization Follow-up for Children Hospitalized for Bronchiolitis: The Bronchiolitis Follow-up Intervention Trial (BeneFIT) Randomized Clinical Trial. JAMA Pediatr. 2020 Sep 1;174(9):e201937. doi: 10.1001/jamapediatrics.2020.1937. Epub 2020 Sep 8. PMID: 32628250; PMCID: PMC7489830. 

    The Bronchiolitis Follow-up Intervention Trial (BeneFIT) was an open-label non-inferiority randomized control trial from 2018-2019 that compared scheduled vs. as needed follow-ups after bronchiolitis hospitalization. Only children < 24 months old without any chronic medical problems were enrolled. Just over 300 patients underwent randomization. While being discharged on home oxygen was an exclusion criterion, needing BiPAP/CPAP or even intubation did not preclude study participation.    

    There was no difference between the 2 groups for the primary outcome – 7-day parental anxiety score (measured using anxiety portion of the Hospital Anxiety and Depression Scale). There was also no difference between the 2 groups in time to symptom resolution after discharge or readmission rates. However, patients in the scheduled follow-up arm had more clinic visits and ambulatory testing (pulse oximetry). While not statistically significant, patients in the scheduled follow-up arm also had an absolute increase in receiving outpatient medications for their symptoms (yet symptom duration remained the same between the 2 groups!).   

    So, for otherwise healthy children < 24 months with this self-limiting condition (even if they needed the PICU during their admission!), we can decrease the burden on the health care system, while also sparing our care team assistants, outpatient schedulers, and resident colleagues by not recommending post-hospitalization follow-up! 

    The One-Liner: Early conversion to oral antibiotics in infants with bacteremic UTI decreased length of stay compared to infants treated with longer IV therapy. Recurrence was rare in both cases. 

    Olson J, Franz-O’Neal E, Cipriano FA, Ou Z, Presson AP, Thorell EA. Impact of Early Oral Antibiotic Therapy in Infants With Bacteremic Urinary Tract Infections. Hosp Pediatr. 2022 Jul 1;12(7):632-638. doi: 10.1542/hpeds.2021-006479. PMID: 35726551. 

    A 2022 retrospective cohort study published in Hospital Pediatrics looked at infants ≤ 90 days old with gram negative bacteremia and UTI to study the association of early convers ion to oral antibiotics on hospital length-of-stay and 30-day readmission or ED visits. Early oral conversion was defined as transition to oral antibiotics after ≤ 4 days of IV antibiotic therapy. Results showed that early oral conversion resulted in a 50% shorter length of stay (median LOS 2 days for early oral conversion vs 4 days for prolonged IV therapy). Both 30-day readmission and ED visits were minimal for each cohort. This supports prior studies by the AAP that recommend early oral conversion and earlier discharge for well-appearing, febrile neonates – so start prepping those discharges everyone! 

    The One-Liner: Those cute LGA babies are not without their risks. However, lowering the threshold for the diagnosis of gestational diabetes had no impact on the incidence of LGA infants. 

    Crowther CA, Samuel D, McCowan LME, Edlin R, Tran T, McKinlay CJ. Lower versus higher glycemic criteria for diagnosis of gestational diabetes. New England Journal of Medicine 2022;387(7):587–98. 

    In a randomized trial recently published in the NEJM, over 4,000 women were assigned to lower (fasting glucose >92) or higher (fasting glucose >99) cutoff for the diagnosis of gestational diabetes after the infamous OGTT. Non-singleton pregnancies as well as women with diabetes mellitus or a history of gestational diabetes were excluded from the study. Not surprisingly, those in the lower criteria cohort were 2.5x more likely to receive a diagnosis of gestational diabetes. Despite this, the study found no difference in incidence of large for gestational age (LGA) infants between the groups (8.8% in lower cohort, 8.9% in higher cohort). Secondary outcomes showed no significant difference in gestational age at birth, birth trauma, neonatal sepsis, or need for NICU stay between the groups. Get your glucose gel orders pended though, because hypoglycemia was detected and treated more frequently in the lower-glycemic criteria group – thought to be due to hospital protocols for these IDM babies and not necessarily symptomatic hypoglycemia. 

    The One-Liner: Significant discrepancies exist between well child visit adherence rates for children based on race and insurance status. 

    Abdus S, Selden TM. Well-Child Visit Adherence. JAMA Pediatr. 2022;176(11):1143–1145. doi:10.1001/jamapediatrics.2022.2954 

    A recent study in JAMA Pediatrics looked at national data on well child visit adherence and found that adherence rates have increased from 47.9% to 62.3% over a 10-year period. However, there was uneven adherence growth across race and ethnicity. While increased adherence rates were greatest among Hispanic children, overall adherence was still less than that of White non-Hispanic children. There was the least adherence growth among Black non-Hispanic children, further widening this gap. Uninsured children also had no significant increase in adherence rates compared to insured children. So, while rates of adherence overall are on the up and up, significant discrepancies continue to exist between well child visit adherence rates for children based on race and insurance status – identifying yet another area for improving access to care.

  • October

    The One-Liner: The AAP released new guidelines for hyperbilirubinemia management for infants > 35 weeks GA as evidence showed bilirubin neurotoxicity does not occur until concentrations well above the previous exchange transfusion thresholds. What does this mean for you? Well, this new evidence justified raising the phototherapy treatment thresholds too.   

    Alex R. Kemper, Thomas B. Newman, Jonathan L. Slaughter, M. Jeffrey Maisels, Jon F. Watchko, Stephen M. Downs, Randall W. Grout, David G. Bundy, Ann R. Stark, Debra L. Bogen, Alison Volpe Holmes, Lori B. Feldman-Winter, Vinod K. Bhutani, Steven R. Brown, Gabriela M. Maradiaga Panayotti, Kymika Okechukwu, Peter D. Rappo, Terri L. Russell; Clinical Practice Guideline Revision: Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation. Pediatrics August 2022; 150 (3): e2022058859. 10.1542/peds.2022-058859 

    Prevention of hyperbilirubinemia: When should you send a direct antiglobulin test (DAT)? For babies born to a birthing parent who have either a positive antibody screen, an unknown antibody screen, or are Rh-. Remember though if the mother was given RhoIG, this can result in DAT positivity but isn’t associated with increased risk of hemolysis. For babies who are DAT+, check bilirubin levels immediately, q4H x2, and q12H x3.  “Suboptimal intake hyperbilirubinemia” is the official new name for “breastfeeding jaundice”. The target remains at least 8 feeds in 24h. Whether or not to supplement with donor breast milk or formula is a decision to be made jointly with the parents. Supplementation with water is a no-go.    

    Risk Factors for hyperbilirubinemia: The updated guidelines eliminated East Asian race as a risk factor. Important risk factors to consider: lower gestational age (increased risk with each additional week <40 weeks GA), jaundice within first 24h, pre-discharge bilirubin close to phototherapy threshold, family history of inherited blood disorders (think G6PD), Trisomy  21, macrosomic IDM, scalp hematoma, or significant bruising, sibling/parent required phototherapy or exchange transfusion, high rate of rise (>0.3 mg/dL per hour within the first 24 hours or >0.2 mg/dL per hour after). Remember to check an infant DAT if there is a high rate of rise! 

    Treatment: When to check a serum bilirubin? If the transcutaneous bilirubin is within 3 of phototherapy level and/or if TcB is >15. The threshold for phototherapy is now higher. Don’t treat unless at threshold (other considerations: rate of rise and if baby is close to discharge). Neurotoxicity risk factors determine the appropriate curve (there are now 2 curves for w/ and w/o neurotoxicity risk). These include GA <38 weeks, isoimmune hemolytic disease (think DAT+), G6PD, other hemolytic disorder, sepsis, albumin < 3, significant clinical instability in the preceding 24h. Lower albumin levels increase the amount of unbound bili (hence, higher risk of permeating blood-brain barrier) so consider checking serum albumin level if escalating care.  

    Once phototherapy is initiated, check a serum bilirubin level within 12 hours. Consider checking a level earlier based on neurotoxicity risk factors or if infant is < 24 HOL. Consider discontinuing phototherapy when the serum bilirubin level has decreased at least 2 below the hour-specific threshold at initiation of phototherapy. Risk factors for rebound hyperbilirubinemia: GA <38 weeks, <48 HOL at the start of phototherapy, hemolytic disease). These drive when to check levels after stopping phototherapy. 

    Escalation of care: We’ve covered a lot already, so we’ll keep this brief: call the NICU if within 2 of exchange level (make sure phototherapy is on in the meantime!). Labs to send: CBC, CMP (for albumin), type and screen. Check serum bilirubin q2H. Signs of bilirubin encephalopathy: hypertonia, arching, high-pitched cry, retrocollis, opisthotonos, recurrent apnea. 

    The One-Liner: While one study showed prevention of recurrent febrile seizures using acetaminophen, this systematic review demonstrates that the data is inconsistent and there is no evidence supporting the use of antipyretics for prevention of febrile seizures.   

    Hashimoto R, Suto M, Tsuji M, Sasaki H, Takehara K, Ishiguro A, Kubota M. Use of antipyretics for preventing febrile seizure recurrence in children: a systematic review and meta-analysis. Eur J Pediatr. 2021 Apr;180(4):987-997. doi: 10.1007/s00431-020-03845-8. Epub 2020 Oct 30. PMID: 33125519. 

    While multiple studies previously had shown that antipyretics had no major benefit in the prevention of recurrent febrile seizures, one study (Murata et al. 2018) found that antipyretics prevented recurrence of febrile seizures in the same fever episode (within 24 hours) compared to placebo. Hashimoto et al decided that the world deserves to know the truth and performed a systematic review of 8 studies investigating the efficacy of antipyretics in the prevention of febrile seizure recurrence in children. The Murata et al study is the only one to show possible seizure prevention with antipyretics. The review raised a few concerns, however, as this was a single-center trial with concern for insufficient blinding. 1 study showed no difference between ibuprofen and acetaminophen in preventing seizures in the same fever episode. 4 studies showed no evidence of efficacy of antipyretics in preventing seizures in distant fever episodes.  Therefore, the evidence is weak for antipyretic use for prevention of recurrent febrile seizures and more studies are needed to evaluate its efficacy. 

    The One-Liner: Home Oxygen Therapy may be beneficial for managing stable bronchiolitis in high-altitude settings, but we could likely just reduce the use of continuous pulse oximetry and oxygen thresholds for treatment and achieve the same outcomes. 

    Joanna Lawrence, Ramesh Walpola, Suzanne L. Boyce, Penelope A. Bryant, Anurag Sharma, Harriet Hiscock; Home Care for Bronchiolitis: A Systematic Review. Pediatrics October 2022; 150 (4): e2022056603. 10.1542/peds.2022-056603

    This systemic review investigates whether Hospital-At-Home (HAH) care would be feasible not just for patients with chronic conditions, but for those with acute respiratory illnesses too. The review highlighted 10 studies focusing on the impact of home oxygen therapy (HOT). While this model did generate some savings for the hospital, these studies neglected to account for the cost of home therapy. Moreover, the varying definitions of bronchiolitis across studies made it difficult to know whether oxygen was the appropriate treatment for some of these kids (the never-ending question of bronchiolitis vs, asthma in our two-year-olds). All in all, HOT may play a role in high-altitude settings where hypoxia occurs at a lower level of acuity and is a barrier to discharge for healthy infants. But, we could likely just reduce the use of continuous pulse oximetry and oxygen thresholds for treatment and still get these kids back home. 

    The One-Liner: Has anyone else ever been surprised that black infants with BPD supposedly have better in-hospital outcomes than white infants? A recent article in JAMA suggests that this effect may be more a measure of flawed methodology in health disparities research rather than a biological difference based on race.    

    Bamat NA, Vereen RJ, Montoya-Williams D. Disparities in Lung Disease of Prematurity—When Does Exposure to Racism Begin? JAMA Pediatr. 2022;176(9):845–847. doi:10.1001/jamapediatrics.2022.2671

    Racial disparities in neonatal outcomes are well documented, with the rate of black infant death more than double that of white infants.  However, most of the published literature on bronchopulmonary dysplasia (BPD), or chronic lung disease of prematurity, has suggested that this disease process seems to resist the typical trends with a negative association between black maternal race and both RDS and BPD. Published research also supports that as preterm children grow older, this trend seems to reverse with white infants experiencing better outcomes beyond the birth hospital.In this editorial from JAMA Pediatrics our very own NickBamat and colleagues call into question the possible “protective walls” of the NICU when assessing race and in-hospital outcomes beyond 36 weeks post menstrual age in infants with severe BPD.  Referencing an article by Lewis and colleagues in the August issue of JAMA, he reports that black maternal race was associated with an increased odds of death and 10-day increase in length of stay, noting this was the largest body of evidence to date to study an association between race and clinically important outcomes in severe BPD. He also warns that controlling for confounders (e.g. GA, sociodemographic factors, antenatal steroids) to reduce bias can also inadvertently bias the estimate of effect, as he demonstrates in several prior studies of RDS and BPD in black infants.  He raises the important question about when, where, and how exposure to racism begins in the lives of black preterm infants, noting that the NICU is likely not as protective of an environment as was once thought. His team calls for further research in this area to acknowledge that race as a variable represents a proxy for interpersonal and structural racism rather than an inherent genetic risk. 

  • November

    The One-Liner: the SCOUT-CAP randomized clinical trial showed that we can safely cut treatment duration in half (from 10 days to 5 days) for non-severe outpatient community acquired pneumonia. Prescribers, pharmacists, and parents rejoice!   

    Williams DJ, Creech CB, Walter EB, et al. Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia in Children: The SCOUT-CAP Randomized Clinical Trial. JAMA Pediatr.2022;176(3):253–261. doi:10.1001/jamapediatrics.2021.5547 

    The Short- vs Standard-Course Outpatient Antibiotic Therapy for Community-Acquired Pneumonia (or SCOUT-CAP, to save a breath) compared 5-day versus 10-day treatment courses of amoxicillin, amoxicillin-clavulanate, or cefdinir for treatment of CAP in outpatient, urgent care, or emergency room settings. Authors found no significant differences in clinical response, persistent symptoms, or antibiotic-associated adverse effects. (In fact, CHOP has already incorporated such research into the CAP Pathway – the “standard” 10-days isn’t even listed as a recommended duration anymore.) While previous studies have shown non-inferiority of shorter antibiotic courses, this is the first study of its kind to tackle side effects and resistance profiles associated with duration of treatment – and to demonstrate superiority of a shorter duration treatment. Authors used an 8-point desirability-of-outcome-ranking (DOOR) score at initial & follow up assessments looking at these parameters, with results that support a reduction of nearly 7.5 million antibiotic days in the US each year. Furthermore, fewer than 10% of children in the study had an inadequate clinical response to either treatment course – which shows that what we do works.  

    The shorter course strategy also yielded a lower number of antibiotic resistance genes (including beta-lactamase) from study participant oropharyngeal flora. While these findings were statistically significant, the clinical significance is questionable – does this actually translate to antibiotic resistance? Conversely, could a shorter treatment course leave behind untreated resistant bugs? All things to consider, however, any bit we can do to potentially avoid creating the next superbug + amoxicillin shortage is worthwhile.  

    Though this study focused on non-severe outpatient CAP in otherwise healthy children, the same principles may apply to other common pediatric infections. For example, the recommended duration of treatment for bread & butter otitis media in children >24 months has already been reduced from 10 days to 5-7 days based on similar studies. 

    The One-Liner: Procalcitonin continues to have high utility in the diagnosis of bacterial infection but should not be used alone to guide antimicrobial therapy. 

    Li P, Liu J, Liu J. Procalcitonin-guided antibiotic therapy for pediatrics with infective disease: A updated meta-analyses and trial sequential analysis. Front Cell Infect Microbiol. 2022 Sep 21;12:915463. doi: 10.3389/fcimb.2022.915463. PMID: 36211950; PMCID: PMC9532766.

    Procalcitonin (PCT) rises early and rapidly in bacterial infection with a half-life of 22 to 35 hours. As a result, levels of PCT can be used as good indicators for the early diagnosis of systemic bacterial infection and sepsis. However, their utility in guiding antibiotic duration remains less clear. Therefore, Li et al. sought to evaluate whether PCT could be used to guide antibiotic treatment through a systematic review and meta-analyses.   

    Through their analysis, Li et al. found that PCT guided therapy was associated with decreased antibiotic therapy length and thereby a decrease in antibiotic associated adverse events. However, guided therapy did not lead to decreased hospital stay or re-admission rate.    

    While their data is promising, it’s within a landscape of conflicting data. Nearly half of published RCTs showed no significant reductions in antibiotic exposure with PCT-guided management. This is likely secondary to progress in antibiotic stewardship or access to new infectious disease diagnostic tools. 

    The One-Liner: The majority of pumpkin carving injuries are hand lacerations in patients 19 years old and younger, and it is vital for healthcare providers to evaluate for tendon, vascular, and nerve injuries in this population 

    Johnson CA, LaRochelle L, Newton WN, Daly CA. Pumpkin carving knife injuries: National incidence and trends of Hand Injury. The American Journal of Emergency Medicine 2022;60:83–7. 

    BOO! Did you know that 44% of Halloween-related injuries result from pumpkin carving?! You’ve ghost to be kidding me! This spooktacular study utilizes haunting information from the National Electronic Injury Surveillance System (NEISS) to gauge incidence and trends for hand injuries related to carving pumpkins. Researchers identified 20,570 pumpkin-related knife injuries in patients who presented to approximately 100 Emergency Departments across the country from 2012-2021. A majority of these injuries were due to lacerations (97.2%) and puncture wounds (1.3%) to the hand (87.6%), forearm (5.3%), and wrist (2.9%). Moreover, these spooky incidents resulted in 250 tendon injuries, 20 arterial injuries, and 16 infections. And even more terrifying, 51% of those injured were 19 years-old and younger! While an overwhelming majority of patients were discharged from the ED, it is vital for healthcare providers to consider tendon injury, vascular injury, and nerve injury in any patient with a pumpkin-related knife injury. Some tips for our little goblins and gremlins? Leave the actual pumpkin carving to adults, who should use pumpkin-carving knives! 

    The One-Liner: The Child Opportunity Index may become an increasingly utilized measure of the complex interplay of many structural factors that impact childhood health and health outcomes. 

    Sunitha V. Kaiser, Matthew Hall, Jessica L. Bettenhausen, Marion R. Sills, Jennifer A. Hoffmann, Clemens Noelke, Rustin B. Morse, Michelle A. Lopez, Kavita Parikh; Neighborhood Child Opportunity and Emergency Department Utilization. PediatricsOctober 2022; 150 (4): e2021056098. 10.1542/peds.2021-056098 

    The Child Opportunity Index (COI) is a complex, multi-dimensional composite measure used to estimate structural influences on children’s health and development, focusing on historically inequitable features of neighborhoods, including access to and quality of education, health and environment, and social and economic factors. Previous studies of COI in large metropolitan areas have found that lower scores are significantly associated with increased use of urgent care, emergency departments, and hospitals for medical care. This retrospective cohort study was designed to examine this association at a national level using data from 27 states (most in the South and Midwest) and analyzed over 6 million ED visits between 2018-2019. Perhaps unsurprisingly, very-low COI scores were associated with higher frequency of ED utilization, more Low Resource Utilization (LRI) ED visits (think URIs, rashes, and other complaints often better evaluated in primary care settings), and lower rates of inpatient admission from the ED. Children with these very-low COI scores were younger, Hispanic and non-Hispanic black children, on governmental insurance, and from lower income households.   This study sought to use a more complete measure of the multiple dimensions at play in a child’s health and development in order to better identify specific drivers leading to patterns in health care access and utilization. These results will hopefully help standardize some of the great work being done around social determinants of health and help inform health policy and ongoing healthcare interventions.

  • December

    The One-Liner: For a low-risk BRUE, clinicians are strongly recommended to provide education to and engage in shared decision-making with the family. Additional testing can be done on a case-by-case basis. 

    Joel S. Tieder, Joshua L. Bonkowsky, Ruth A. Etzel, Wayne H. Franklin, David A. Gremse, Bruce Herman, Eliot S. Katz, Leonard R. Krilov, J. Lawrence Merritt, Chuck Norlin, Jack Percelay, Robert E. Sapién, Richard N. Shiffman, Michael B.H. Smith, for the SUBCOMMITTEE ON APPARENT LIFE THREATENING EVENTS; Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants. Pediatrics May 2016; 137 (5): e20160590. 10.1542/peds.2016-0590 

    Telling a parent that their child had a brief, resolved, unexplained event (BRUE) sure sounds better than an apparent, life-threatening event (ALTE), doesn’t it?! The AAP thinks so too, which is one of the reasons they strongly advocated for replacing this outdated term in their 2016 BRUE AAP Guidelines. So, what should you do if a child less than 1 year-old presents for their initial medical assessment following a brief, resolved event? If they have any additional symptoms (such as a cough or respiratory difficulties) or abnormal vital signs (fever), this event is automatically not a BRUE! 

    For well-appearing patients, look for cyanosis/pallor, abnormal breathing, hypertonia/hypotonia, altered responsiveness for the diagnosis of BRUE. From there you can classify the BRUE as lower risk or higher risk. For low-risk criteria remember: age >60 days, >32 weeks gestational age and corrected to at least term, no CPR by a trained medical provider, duration (less than 1 minute), first event. 

    If the patient checks off all of those boxes, then the 2016 BRUE AAP Guidelines are for you! Per these new guidelines, as a provider, you SHOULD offer CPR training resources to caregivers, educate caregivers about BRUEs, and engage in shared decision-making with families. You SHOULD NOT obtain: CBC, electrolytes, blood culture, LP, chest x-ray, EEG, echocardiogram or metabolic labs! AKA most tests. Don’t send them home with a monitor and don’t start any medications. Based on clinical suspicion you can obtain pertussis testing, 12-lead ECG and continuous monitoring while the patient is being evaluated. 

    The One-Liner: Adolescent acute care visits can be used for age-appropriate immunizations without delaying subsequent well child visits. 

    Alexander G. Fiks, Chloe Hannan, Russell Localio, Mary Kate Kelly, Alisa J. Stephens-Shields, Robert W. Grundmeier, Laura P. Shone, Jennifer Steffes, Abigail Breck, Margaret Wright, Cynthia M. Rand, Christina Albertin, Sharon G. Humiston, Greta McFarland, Dianna E. Abney, Peter G. Szilagyi; HPV Vaccinations at Acute Visits and Subsequent Adolescent Preventive Visits. Pediatrics November 2022; 150 (5): e2022058188. 10.1542/peds.2022-058188 

    A study recently published in Pediatrics (authored by Karabots preceptor Alex Fiks!) looked at HPV vaccinations at acute care visits and whether this led to a delay in well-child care. The study looked at 17,000 adolescents across 37 primary care practices participating in the STOP-HPV NIH funded clinical trial between 2015 and 2018. They found a mean of 2 acute care visits between consecutive well visits. A quarter of patients ages 13-17 received a subsequent HPV vaccine at an acute visit with a much smaller number received the initial HPV vaccine. While those ages 11-12 had a delay of 0.5 months to next well-visit, vaccinating at acute visits for those 13-17 years was not associated with a statistically significant delay in well-child care. Despite large sample size in a non-COVID era, results may not be entirely generalizable as these practices had overall higher HPV vaccination rates than the national average. 

    The One-Liner: Early screen time was not directly associated with worse concussion symptoms at 30 days. 

    Molly Cairncross, Keith Owen Yeates, Ken Tang, Sheri Madigan, Miriam H. Beauchamp, William Craig, Quynh Doan, Roger Zemek, Kristina Kowalski, Noah D. Silverberg; on behalf of the Pediatric Emergency Research Canada A-CAP study team, Early Postinjury Screen Time and Concussion Recovery. Pediatrics November 2022; 150 (5): e2022056835. 10.1542/peds.2022-056835 

    A secondary analysis of a prospective longitudinal cohort study (A-CAP) compared patients with concussions to those with orthopedic injuries (control group). Authors looked at both post-concussion symptoms as well as early screen time (defined as 7-10 days postinjury) through self-reported questionnaires. This study found that greater screen time was not consistently associated with increased post-concussion symptoms. Both low and high screen time were associated with more severe symptoms in the concussion group compared to control during the first 30 days postinjury. Other risk factors and health behaviors had stronger associations with symptom severity. While more research needs to be done, moderation might be the key here. 

    The One-Liner: Ceftriaxone may be safer to use than we once thought, several more studies will be needed to determine the exact settings in which it is safe. Ceftriaxone should not be used in neonates with risk for hypocalcemia or need for calcium-containing solutions since this antibiotic can result in calcium-ceftriaxone deposits in neonatal vasculature. 

    Amin SB. Bilirubin-Displacing Effect of Ceftriaxone in Infants With Unconjugated Hyperbilirubinemia Born at Term. J Pediatr. 2023 Mar;254:91-95. doi: 10.1016/j.jpeds.2022.10.030. Epub 2022 Nov 3. PMID: 36336007. 

    Ceftriaxone is used with caution in infants due to concerns of bilirubin displacement from albumin theoretically leading to worsened unconjugated hyperbilirubinemia. Using a prospective within-subject study design, Amin S. sought to determine the effects of ceftriaxone on free bilirubin in infants with unconjugated hyperbilirubinemia. Using a rather small sample size of 27 infants < 7 days old receiving IV ceftriaxone in the setting of sepsis, Amin measured total serum bilirubin just prior to ceftriaxone infusion and 15 minutes following infusion. Exclusion criteria included: failed BAERS, previously receiving phototherapy, TORCH infections. This study found that ceftriaxone did not cause statistically significant displacement of free bilirubin at peak ceftriaxone plasma concentrations. Overall, this study suggested ceftriaxone is possibly safe to use in infants; however, given the small patient population and the exclusion of certain infections in this study, the clinical applicability is limited. 

    The One-Liner: While directed towards all physicians, this NEJM perspective is especially important to us as pediatricians as the loss of governmental support for gender-affirming care will hurt our marginalized adolescents the most.  

    McNamara M, Lepore C, Alstott A. Protecting transgender health and challenging science denialism in policy. New England Journal of Medicine 2022;387(21):1919–21. 

    A recent perspective published in the NEJM on protecting transgender health described a “virulent brand of science denialism” emerging within the US legal system. The authors cite laws in Texas, Alabama and Arkansas that make unsupported claims about cardiovascular disease and cancer associated with gender-affirming medications. They also highlight the known mental health benefits of gender-affirming care that making randomized, controlled trials in this case impossible.