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Optimizing Neonatal Nutrition in Resource-Constrained Settings
Amy Sarah Ginsburg, MD, MPH1; Valerie Flaherman, MD, MPH2
doi : 10.1001/jamapediatrics.2020.5241
JAMA Pediatr. 2021;175(5):451-452
Neonates have high nutrient demands. Exclusive breastfeeding, an effective way to ensure child health and survival, is recommended for neonates within the first hour of birth and to be continued on demand for the first 6 months of life. However, exclusively breastfed neonates typically lose about 7% of their birth weight prior to beginning weight gain. Risk factors for inadequate neonatal growth may include low birth weight and weight loss greater than 5% at 4 days of age.1,2 Different phenotypes of low birth weight such as preterm birth and intrauterine growth restriction may differ in nutrition requirements and response. While initial weight loss is often transient and may not have subsequent consequences in the majority of healthy term neonates, it may have serious consequences for more vulnerable, at-risk neonates, including those with low birth weight or who were born preterm, particularly in resource-constrained settings in Africa and Asia.
Creating Practical Primary Care Supports for Parent-Child Relationships—Language, Literacy, and Love
Perri Klass, MD1,2; Dipesh Navsaria, MPH, MSLIS, MD3
doi : 10.1001/jamapediatrics.2020.5706
JAMA Pediatr. 2021;175(5):452-453
Young children learn and develop primarily through contingent interactions and strong foundational relationships; this is true of language and, more generally, cognitive and socioemotional development. Separate domains have great utility for screening, assessment, and referral, since isolated delays can point to specific diagnoses and therapies. In other respects it is difficult (and sometimes artificial) to separate cognitive from socioemotional, given the complex overlays of cause and effect and the essential role that interactions and language play throughout. Healthy mental, emotional, and behavioral development in young children reflects—and requires—secure attachment and stable foundational relationships with adult caregivers, including the emotional responsiveness and positive parenting behaviors that also result in the kinds of positive language-rich interactions that stimulate language and cognitive development. Now, with the coronavirus disease 2019 pandemic stressing families, strategies to strengthen and support those relationships and behaviors on a population scale are critical.
Contribution of Glucose Meter Error to Misclassification of Neonatal Glycemic Status
Mark Inman, MD1; Barry D. Kyle, PhD2; Martha E. Lyon, PhD2
doi : 10.1001/jamapediatrics.2020.5787
JAMA Pediatr. 2021;175(5):453-455
Glucose point-of-care testing in the neonatal intensive care unit, as the basis for informing clinical decision-making and treatment of neonatal hypoglycemia, has been extensively adopted as a preferred clinical tool, given its ease of use and minimal blood volume requirement to obtain a timely bedside glucose result. National guidelines for the evaluation and management of neonatal hypoglycemia have become widely disseminated and incorporated into North American clinical practice.1-3 Inherent to these guidelines is the use of glucose meters, often with a caveat that glucose point-of-care testing devices are designed for hyperglycemia detection, whereas hypoglycemia detection and its error rates have never been prioritized and require clinical laboratory confirmation of glucose meter results. Given the convenience of glucose point-of-care testing, we surmise that, in many institutions, it has become the first-line clinical tool for neonatal glycemic decision-making.
Why Is Avoidant-Restrictive Food Intake Disorder Relevant to the Pediatric Gastroenterologist?
Stephanie B. Oliveira, MD, CNSC1,2
doi : 10.1001/jamapediatrics.2020.5784
JAMA Pediatr. 2021;175(5):455-457
Avoidant-restrictive food intake disorder (ARFID) is a condition that falls under the umbrella of eating disorders. Patients with ARFID can present with signs and symptoms commonly seen in primary care and gastroenterology settings. Lack of knowledge about this condition has resulted in misdiagnosis and incorrect management. The lack of discussion on the topic in the pediatric gastroenterology literature is not because of low prevalence of ARFID in our population, but mostly the result of a lack of awareness and recognition of the condition.
JAMA Pediatrics—The Year in Review, 2020
Dimitri A. Christakis, MD, MPH1,2
doi : 10.1001/jamapediatrics.2021.0099
JAMA Pediatr. 2021;175(5):458-459
Should We Prioritize Deimplementation of Continuous Pulse Oximetry in Bronchiolitis Care?
Christine C. Cheston, MD1; Ronnye Rutledge, MD2; Heather E. Hsu, MD, MPH1
doi : 10.1001/jamapediatrics.2020.6157
JAMA Pediatr. 2021;175(5):459-461
Bronchiolitis, an acute viral infection of the lower respiratory tract, is a leading cause of hospitalizations among infants and toddlers.1 The Choosing Wisely campaign and the American Academy of Pediatrics clinical practice guidelines outline an evidence-based, supportive approach to bronchiolitis care, but adoption of these recommendations remains variable.2-4 In particular, a recent cross-sectional study4 of 56 North American hospitals found that guideline-concordant use of continuous pulse oximetry in hospitalized infants with bronchiolitis ranged from 2% to 92%. This variability may stem from the fact that the recommendation is based on evidence from retrospective, nonrandomized studies that found associations between use of continuous pulse oximetry and increased length of stay (LOS), higher costs, and patient harm. It therefore carries the worst evidence-quality grade (D) and weakest recommendation strength of any in the American Academy of Pediatrics guideline.
Rightsizing Treatment for Pneumonia in Children
Sharon V. Tsay, MD1; Adam L. Hersh, MD, PhD2; Katherine E. Fleming-Dutra, MD3
doi : 10.1001/jamapediatrics.2020.6743
JAMA Pediatr. 2021;175(5):462-463
Antibiotics are the double-edged swords we love to wield. They save lives, but they also cause harm with adverse drug events and the promotion of antibiotic resistance. Antibiotic stewardship is the effort to optimize the use of antibiotics to the right antibiotic at the right time and for the right duration. Stewardship encourages us to ask ourselves: can we decrease the biological costs of using these powerful tools, even a little, if we put them away earlier? Evidence has accumulated that we can give shorter courses of antibiotics, at least to adult patients, for many conditions, including for pneumonia, urinary tract infections, sinusitis, and cellulitis.1 This is welcome news to anyone who has taken antibiotics themselves or given their child an antibiotic and experienced diarrhea or a yeast infection; adverse events and effects are common, especially in children.2 However, in children, evidence regarding the efficacy of shorter antibiotic courses is lacking for most common conditions. At least in part because of this uncertainty, most antibiotic courses prescribed to children in the US for common infections, including pneumonia, are 10 days in duration.3 This may be owing in part to the lack of strong evidence to guide recommendations for duration of therapy for many infections.
Association of Eviction During Pregnancy With Birth Outcomes
Erika G. Cordova-Ramos, MD1,2; Robert Koenig, MBA2; Michael Silverstein, MD, MPH1
doi : 10.1001/jamapediatrics.2020.6556
JAMA Pediatr. 2021;175(5):464-465
In this issue of JAMA Pediatrics, Himmelstein and Desmond1 pose the question whether eviction during pregnancy is associated with adverse birth outcomes. The authors conduct a retrospective cohort study linking Georgia birth certificate data to the state’s eviction court records, thereby reconstructing the timing of eviction actions relative to childbirth. The authors compare birth outcomes of infants whose mothers were evicted during pregnancy (n?=?10?135) with those of infants whose mothers were evicted at other times (n?=?78?727). Their main findings are that eviction during pregnancy is associated with lower infant birth weight (mean difference, ?26.88 [95% CI, ?39.53 to ?14.24] g) and gestational age (mean difference, ?0.09 [95% CI, ?0.16 to ?0.03] weeks) and increased rates of low birth weight (0.88 [95% CI, 0.23-1.54] percentage points) and prematurity (1.14 [95% CI, 0.21-2.06] percentage points). The association of eviction with birth weight appears to be most significant during the second and third trimesters, and although the CIs appear to overlap across subgroups, eviction seems to affect birth weight to a greater degree among Black women than among White women.
Diagnosing Childhood Tuberculosis
Jeffrey R. Starke, MD1; Andrea T. Cruz, MD1
doi : 10.1001/jamapediatrics.2020.6078
JAMA Pediatr. 2021;175(5):e206078
Prior to 2012, there were no reliable estimates of the incidence of tuberculosis in the world’s children. Using the only available information, in 2013, the World Health Organization estimated there were approximately 500?000 annual cases and 89?000 deaths among children not living with HIV; there were no data to even estimate the mortality among children living with HIV.1 Throughout the next several years, modeling studies suggested that the rates of cases and mortality were much higher.2 Using these techniques, in 2019, the World Health Organization estimated there were 1.2 million annual cases and 230?000 annual deaths from tuberculosis in children younger than 15 years.3 One study estimated that 96% of the children who died never received treatment, mostly because they were never diagnosed.4
Intermittent vs Continuous Pulse Oximetry in Hospitalized Infants With Stabilized Bronchiolitis
Sanjay Mahant, MD, MSc1,2,3; Gita Wahi, MD4; Ann Bayliss, MD1,5
doi : 10.1001/jamapediatrics.2020.6141
JAMA Pediatr. 2021;175(5):466-474
Importance There is low level of evidence and substantial practice variation regarding the use of intermittent or continuous monitoring in infants hospitalized with bronchiolitis.
Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia
Jeffrey M. Pernica, MD1,2; Stuart Harman, MD2,3; April J. Kam, MD2,4
doi : 10.1001/jamapediatrics.2020.6735
JAMA Pediatr. 2021;175(5):475-482
Importance Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required.
Association Between Preterm-Birth Phenotypes and Differential Morbidity, Growth, and Neurodevelopment at Age 2 Years
Jose Villar, MD1,2; Mar?a C. Restrepo-Méndez, PhD1,2; Rose McGready, MD3,4; Fernando C. Barros, MD5; Cesar G. Victora, MD6; Shama Munim, MD7; Aris T. Papageorghiou, MD1,2; Roseline Ochieng, MMed8; Rachel Craik, BSc1; Hellen C. Barsosio, MD9,10; James A. Berkley, FRCPCH11; Maria Carvalho, MD8; Michelle Fernandes, MD1,12; Leila Cheikh Ismail, PhD1,13; Ann Lambert, PhD1,2; Shane A. Norris, PhD14; Eric O. Ohuma, PhD1,15; Alan Stein, FRCPsych16,17; Chrystelle O. O. Tshivuila-Matala, DPhil1,14,18; Krina T. Zondervan, DPhil1,19; Adele Winsey, PhD1; Francois Nosten, PhD3,4; Ricardo Uauy, MD20; Zulfiqar A. Bhutta, MD21; Stephen H. Kennedy, MD1,2
doi : 10.1001/jamapediatrics.2020.6087
JAMA Pediatr. 2021;175(5):483-493
Importance The etiologic complexities of preterm birth remain inadequately understood, which may impede the development of better preventative and treatment measures.
Association of Eviction With Adverse Birth Outcomes Among Women in Georgia, 2000 to 2016
Gracie Himmelstein, MA1,2; Matthew Desmond, PhD1,3
doi : 10.1001/jamapediatrics.2020.6550
JAMA Pediatr. 2021;175(5):494-500
Importance More than 2 million families face eviction annually, a number likely to increase due to the coronavirus disease 2019 pandemic. The association of eviction with newborns’ health remains to be examined.
Association of the Timing of School Closings and Behavioral Changes With the Evolution of the Coronavirus Disease 2019 Pandemic in the US
Frederick J. Zimmerman, PhD1; Nathaniel W. Anderson, BA1
doi : 10.1001/jamapediatrics.2020.6371
JAMA Pediatr. 2021;175(5):501-509
Importance The consequences of school closures for children’s health are profound, but existing evidence on their effectiveness in limiting severe acute respiratory syndrome coronavirus 2 transmission is unsettled.
Novel Variant Findings and Challenges Associated With the Clinical Integration of Genomic TestingAn Interim Report of the Genomic Medicine for Ill Neonates and Infants (GEMINI) Study
Jill L. Maron, MD, MPH1; Stephen F. Kingsmore, MD2; Kristen Wigby, MD2,3; Shimul Chowdhury, PhD2; David Dimmock, MD2; Brenda Poindexter, MD, MS4; Kristen Suhrie, MD5,6; Jerry Vockley, MD, PhD7; Thomas Diacovo, MD7; Bruce D. Gelb, MD8; Annemarie Stroustrup, MD, MPH9; Cynthia M. Powell, MD10; Andrea Trembath, MD, MPH10; Matthew Gallen, MPH11; Thomas E. Mullen, PhD11; Pranoot Tanpaiboon, MD11; Dallas Reed, MD12,13; Anne Kurfiss, MPH13; Jonathan M. Davis, MD13,14
doi : 10.1001/jamapediatrics.2020.5906
JAMA Pediatr. 2021;175(5):e205906
Importance A targeted genomic sequencing platform focused on diseases presenting in the first year of life may minimize financial and ethical challenges associated with rapid whole-genomic sequencing.
Sensitive and Feasible Specimen Collection and Testing Strategies for Diagnosing Tuberculosis in Young Children
Rinn Song, MD, MD(Res), MPH, MSc1,2,3; Eleanor S. Click, MD, PhD4; Kimberly D. McCarthy, MM4; Charles M. Heilig, PhD4; Walter Mchembere, MPH5; Jonathan P. Smith, PhD, MPH6,7; Mark Fajans, MPH4; Susan K. Musau, MPPM5; Elisha Okeyo, MBChB5; Albert Okumu, MCHD5; James Orwa, MSc5; Dickson Gethi, BSc5; Lazarus Odeny, MSc5; Scott H. Lee, PhD4; Carlos M. Perez-Velez, MD8,9; Colleen A. Wright, MD, PhD10; Kevin P. Cain, MD11
doi : 10.1001/jamapediatrics.2020.6069
JAMA Pediatr. 2021;175(5):e206069
Importance Criterion-standard specimens for tuberculosis diagnosis in young children, gastric aspirate (GA) and induced sputum, are invasive and rarely collected in resource-limited settings. A far less invasive approach to tuberculosis diagnostic testing in children younger than 5 years as sensitive as current reference standards is important to identify.
Bridging the Gap Between Intensivists and Primary Care Clinicians in Extracorporeal Membrane Oxygenation for Respiratory Failure in Children
Ryan P. Barbaro, MD, MSc1,2; Daniel Brodie, MD3,4; Graeme MacLaren, MBBS, MSc5,6
doi : 10.1001/jamapediatrics.2020.5921
JAMA Pediatr. 2021;175(5):510-517
Importance Extracorporeal membrane oxygenation (ECMO) is a form of advanced life support that may be used in children with refractory respiratory or cardiac failure. While it is required infrequently, in the US, ECMO is used to support childhood respiratory failure as often as children receive kidney or heart transplants. ECMO is complex, resource intensive, and potentially lifesaving, but it is also associated with risks of short-term complications and long-term adverse effects, most importantly with neurodevelopmental outcomes that are relevant to all pediatric clinicians, even those remote from the child’s critical illness.
Talking to Children About Race and Racism
Adrienne H. Mott Young, MD1; Donna M. Parker, MD1; Frieda P. Ansoanuur, MD2; Isaac Werner, BS3; Yana S. Banks, MD1
doi : 10.1001/jamapediatrics.2020.7130
JAMA Pediatr. 2021;175(5):544
Diabetic Ketoacidosis at the Time of Diagnosis of Type 1 Diabetes in Children
Meranda Nakhla, MD, MSc1; David Cuthbertson, MS2; Dorothy J. Becker, MD3; Daniéle Pacaud, MD4; Johnny Ludvigsson, MD, PhD5,6; Mikael Knip, MD, PhD7,8; Laurent Legault, MD1
doi : 10.1001/jamapediatrics.2020.5512
JAMA Pediatr. 2021;175(5):518-520
Type 1 diabetes (T1D) is one of the most common chronic diseases of childhood. If left untreated, diabetic ketoacidosis (DKA), a largely preventable life-threatening complication, will occur. Currently, 19% of Canadian children and 40% of US children will present with DKA at the time of diagnosis of T1D.1,2 Because symptoms of T1D exist before the onset of DKA, 1 risk factor for DKA is a delay in the diagnosis and treatment of T1D. Other risk factors include younger age (<5 years) and lower socioeconomic status (SES).1
Association of High-Density Lipoprotein Cholesterol With Sex Steroid Treatment in Transgender and Gender-Diverse Youth
Kate Millington, MD1; Courtney Finlayson, MD1; Johanna Olson-Kennedy, MD2; Robert Garofalo, MD3; Stephen M. Rosenthal, MD4; Yee-Ming Chan, MD, PhD5
doi : 10.1001/jamapediatrics.2020.5620
JAMA Pediatr. 2021;175(5):520-521
Mortality and morbidity from cardiovascular disease differ between men and women, and sex differences in lipid profiles may contribute to this difference. Starting at puberty, male individuals have more atherogenic cholesterol profiles, including lower high-density lipoprotein cholesterol (HDL-C) levels, than female individuals.1 The degree to which sex hormones vs sex chromosomes and other factors contribute to this difference is unknown. The gender-affirming treatment of transgender and gender-diverse youth provides a unique opportunity to study the association of sex steroids with cholesterol in different sex-chromosome contexts.
Association of Headache With School Functioning Among Children and Adolescents in the United States
Scott B. Turner, DNP1; Christina L. Szperka, MD, MSCE2,3; Andrew D. Hershey, MD, PhD4,5; Emily F. Law, PhD6; Tonya M. Palermo, PhD6; Cornelius B. Groenewald, MB ChB7
doi : 10.1001/jamapediatrics.2020.5680
JAMA Pediatr. 2021;175(5):522-524
Headaches are among the world’s leading causes of disability for children and adults.1 Clinical samples of youth with headache report frequent school absences, poorer school performance, and lower quality of life than youth with other chronic conditions.2 However, little is known about the association of headache with school functioning at the population level.
Association of Salary Differences Between Medical Specialties With Sex Distribution
Terrill Bravender, MD, MPH1; Ellen Selkie, MD, MPH1; Julie Sturza, MPH1; Donna M. Martin, MD, PhD1; Kent A. Griffith, MPH, MS2; Niko Kaciroti, PhD3; Reshma Jagsi, MD, DPhil4
doi : 10.1001/jamapediatrics.2020.5683
JAMA Pediatr. 2021;175(5):524-525
Sex-based differences in physician compensation persist. Female physicians tend to make less money than their male colleagues in their first jobs1 and as faculty members.2-4 Various explanations have been proposed; however, concerns such as predictable hours, length of workday, and frequency of after-hours duties did not account for salary differences,1 whereas specialty explained about half of observed salary differences between women and men.1,4 Prior studies have not detailed whether specialties with higher representation of women have lower compensation in general. We sought to create a physician salary model based on the proportion of women in each specialty, hypothesizing that more women in a specialty would be associated with lower salaries for both men and women.
Pediatric Clinical Classification System for Use in Inpatient Settings
Peter J. Gill, MD, DPhil1,2; Mohammed Rashidul Anwar, MBBS, MSc2; Thaksha Thavam, MSc2; Matt Hall, PhD3; Jonathan Rodean, MPP3; Sanjay Mahant, MD, MSc1,2
doi : 10.1001/jamapediatrics.2020.6007
JAMA Pediatr. 2021;175(5):525-527
The transition from the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) to the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) system in 2015 in the United States limits the use of previously developed ICD-9-CM clinical classification systems to evaluate health care use, costs, variation, and trends. The ICD-10-CM Healthcare Cost and Utilization Project (HCUP) Clinical Classifications Software (CCS)1 aggregates more than 70?000 ICD-10-CM diagnosis codes into categories. However, it lacks categories for important inpatient pediatric conditions (eg, bronchiolitis, mental health2), thereby limiting its use. Therefore, we developed the open source Pediatric Clinical Classification System (PECCS), which categorizes all ICD-10-CM diagnosis codes into mutually exclusive, clinically meaningful conditions for use in inpatient settings. To assess the ability of the PECCS to identify pediatric categories, we compared detection of conditions in the PECCS with the HCUP-CCS (Agency for Healthcare Research and Quality) using a national pediatric hospitalization database.
Viral Loads of SARS-CoV-2 in Young Children
Heather Finlay-Morreale, MD1
doi : 10.1001/jamapediatrics.2020.5532
JAMA Pediatr. 2021;175(5):527-528
To the Editor I am writing about the article “Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19)”1 published on July 30, 2020, in JAMA Pediatrics. I have serious concerns about the validity of their suggestion that individuals younger than 5 years may have more coronavirus disease 2019 (COVID-19) RNA. From a review of the Figure in this article,1 for children younger than 5 years, the authors plot 3 outliers among a total number of 46 participants. This is 6.5%. Had they included these outliers, I suspect they would not be able to make their suggestion that children younger than 5 years may have more COVID-19 RNA. Good data analysis does not allow scientists to simply discount data as outliers so that a significant outcome can be suggested. I would have preferred to see a graph with dots for all data points and then indications for the mean and the error bars. Further, the error bars are sufficiently wide and overlapping that I suspect there is not much difference between all the groups. Their suggestion that children younger than 5 years may have more COVID-19 RNA is being cited and amplified as fact over conventional and social media. This can influence important choices about daycare and schools, and I have serious concerns about how the authors analyzed their data.
Viral Loads of SARS-CoV-2 in Young Children
Alexandro Guterres, PhD1
doi : 10.1001/jamapediatrics.2020.5539
JAMA Pediatr. 2021;175(5):528
To the Editor Reliable data for profiles of viral load are needed and important to guide antiviral treatment, infection control, and vaccination. In their interesting article in JAMA Pediatrics, Heald-Sargent and colleagues1 describe that levels of viral nucleic acid in nasopharyngeal swabs are significantly greater in children younger than 5 years compared with older children. The authors report that children younger than 5 years (n?=?46), children aged 5 to 17 years (n?=?51), and adults aged 18 to 65 years (n?=?48) had median cutoff cycle threshold (Ct) values of 11 for older children and adults and 6.5 for children younger than 5 years.
Viral Loads of SARS-CoV-2 in Young Children
Amy B. Karger, MD, PhD1; Patricia Ferrieri, MD1; Andrew C. Nelson, MD, PhD1
doi : 10.1001/jamapediatrics.2020.5542
JAMA Pediatr. 2021;175(5):528-529
To the Editor Heald-Sargent et al1 report significantly higher cycle threshold (Ct) values in children younger than 5 years and conclude that they “can potentially be important drivers of SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] spread” and raise “concern for SARS-CoV-2 amplification in this population as public health restrictions are eased.”1 In drawing these conclusions, the authors do not account for numerous limitations associated with Ct value determination and fail to place their findings in the context of existing data on transmission in younger children.
Viral Loads of SARS-CoV-2 in Young Children
Julie C. Dunning Hotopp, PhD1
doi : 10.1001/jamapediatrics.2020.5545
JAMA Pediatr. 2021;175(5):529
To the Editor I have concerns about the methodology, which influences the results and conclusions, reported in a recent article on coronavirus disease 2019 samples that has garnered attention because of its implications for important public health decisions. In “Age-Related Differences in Nasopharyngeal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Levels in Patients With Mild to Moderate Coronavirus Disease 2019 (COVID-19),” Heald-Sargent et al1 compare cycle threshold (Ct) values for different cohorts of patients with coronavirus disease 2019 grouped by age. Most of the data appear to be for Ct values that were less than 11. The median Ct was 6.5 for children younger than 5 years, meaning half of the samples had a Ct value of 6.5 or less. Looking at the range in the plots, it appears some data points may have had a Ct near 3. Yet, Ct values typically are not quantitative in these ranges, and the authors did not include or refer to a standard curve to demonstrate that the values were quantitative in this range. Other related studies2,3 use Ct values in a range that is typically found to be more quantitative (Ct >14), which can be achieved by diluting the samples prior to testing. Given this problem, the conclusion that the virus is higher in children may not be supported by these data. The article seemingly still demonstrates that the virus can be found at high levels in these samples from these age groups, at least for many of these samples.
Viral Loads of SARS-CoV-2 in Young Children
Arnaud G. L’Huillier, MD1; Stéphanie Baggio, PhD2; Isabella Eckerle, MD3
doi : 10.1001/jamapediatrics.2020.5548
JAMA Pediatr. 2021;175(5):529-530
To the Editor Heald-Sargent et al1 recently reported that preschool- and school-aged children have higher and similar severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA loads than adults, respectively, concluding that children could have an active role in transmission of SARS-CoV-2 to others.1
Viral Loads of SARS-CoV-2 in Young Children—Reply
Taylor Heald-Sargent, MD, PhD1; William J. Muller, MD, PhD1,2; Larry K. Kociolek, MD, MSCI1,2
doi : 10.1001/jamapediatrics.2020.5551
JAMA Pediatr. 2021;175(5):530-531
In Reply Thank you for the opportunity to respond to several Letters that facilitate thoughtful discussion of our recently published article.1 Three Letters raised concerns about our reported cycle threshold (Ct) values. Ct values from different platforms are known to be assay specific, making cross-comparison difficult. The assay used in our study has significantly lower Ct values in comparison with other assays.2 However, there are abundant data3 to support use of Ct values as a proxy for level of viral RNA in a sample, including for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The assay used in our study includes an internal control (nonviral) sequence with every sample, and every run included a control sample with 1000 SARS-CoV-2 RNA copies per well. Serial dilutions of samples confirmed an estimate of 3.3 Ct value changes for every logarithm difference in RNA levels, allowing estimation of viral load from Ct data. Thus, a Ct value of 15 or less on our platform correlates with greater than 100?000 copies per milliliter, a viral load associated with culture-competent SARS-CoV-2.4 While an association between viral load and days from symptom onset would be expected, we did not identify a strong correlation between sample Ct and symptom duration in any of the groups, supporting the validity of our age-based comparisons. We acknowledge that our study demonstrates a wide spectrum of Ct values within and across groups, like many research studies in a diverse population of patients. However, the statistical analyses applied are appropriate and include the full spectrum of collected data (ie, no outliers were discounted from our analyses). Strong statistical significance was demonstrated.
Estimates From Heterogeneous Studies of Opioid-Related Morbidity
Kao-Ping Chua, MD, PhD1; Chad M. Brummett, MD2; Amy Bohnert, PhD2
doi : 10.1001/jamapediatrics.2020.5617
JAMA Pediatr. 2021;175(5):531-532
To the Editor We congratulate Quinn et al1 for their important study demonstrating an association between prescription opioid initiation and increased risk of substance-related morbidity among adolescents and young adults.1 Their use of multiple rigorous designs to address confounding greatly increases internal validity.
Estimates From Heterogeneous Studies of Opioid-Related Morbidity
Patrick D. Quinn, PhD1; Kurt Kroenke, MD2; Brian M. D’Onofrio, PhD3
doi : 10.1001/jamapediatrics.2020.5625
JAMA Pediatr. 2021;175(5):532-533
In Reply We thank Chua et al for their thoughtful comments on our article.1 We concur with much of their Letter and begin with 3 points of agreement.
Mandatory Coronavirus Disease 2019 Vaccine for Children?
Rafael Dal-Ré, MD, PhD, MPH1
doi : 10.1001/jamapediatrics.2020.6010
JAMA Pediatr. 2021;175(5):533-534
Mandatory Coronavirus Disease 2019 Vaccine for Children?—Reply
Douglas J. Opel, MD, MPH1,2; Douglas S. Diekema, MD, MPH1,2; Lainie Friedman Ross, MD, PhD3,4
doi : 10.1001/jamapediatrics.2020.6013
JAMA Pediatr. 2021;175(5):534
Early High-Dose Gluten Intake to Prevent Celiac Disease: Data Do Not Allow Conclusions
Sibylle Koletzko, MD1; M. Luisa Mearin, MD2
doi : 10.1001/jamapediatrics.2020.6516
JAMA Pediatr. 2021;175(5):534-535
To the Editor A secondary analysis of the Enquiring About Tolerance (EAT) trial concludes that high gluten intake from age 4 months reduces later celiac disease (CD).1 Of 1303 enrolled participants, 77% were tested for transglutaminase type 2 (TG2) at age 3 years. Celiac disease was reported in 7 of 516 children (1.4%) in the standard introduction group and 0 of 488 children in the early introduction group. We are concerned that the small sample size and methodological limitations may have influenced case findings.
Early High-Dose Gluten Intake to Prevent Celiac Disease: Data Do Not Allow Conclusions—Reply
Gideon Lack, MB, BCh1; Kirsty Logan, PhD1
doi : 10.1001/jamapediatrics.2020.6519
JAMA Pediatr. 2021;175(5):535-536
In Reply We thank Koletzko and Mearin for their considered critique of our recently published article in JAMA Pediatrics. Overall, we agree with the authors’ conclusion that our study does not provide conclusive evidence of a preventive effect of early high-dose gluten introduction on celiac disease (CD) in childhood, and we make several statements to that effect in the article.1 However, the results remain a vital contribution to the body of evidence in this area, especially when currently there are no preventive strategies for this chronic disease. There are specific points raised by Koletzko and Mearin that we endeavor to respond to below.
Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder
Allison Lee, MD, MS1; Jean Guglielminotti, MD, PhD1; Ruth Landau, MD1,2
doi : 10.1001/jamapediatrics.2020.6686
JAMA Pediatr. 2021;175(5):536
To the Editor We have strenuous concerns about the conclusions of Qiu et al,1 implying a causal link between maternal labor epidural analgesia (LEA) and an increased risk of autism spectrum disorder (ASD) in children, based on their analysis of a retrospective cohort of women who underwent vaginal delivery between 2008 and 2015 in Kaiser Permanente Southern California hospitals. Autism spectrum disorder is a major public health concern attributed primarily to genetic and environmental risk factors2 but, as the authors mention, has a purported association with general anesthesia for cesarean delivery (CD) and CD itself.3 The ASD incidence was lower than prior reports, possibly suggesting missing cases based on very early screening and loss to follow-up. Information regarding LEA management was omitted; however, the authors speculated that transplacental transfer of epidurally administered local anesthetics may be causal factors. Contemporary practice consists of minimal local anesthetics doses at levels insufficient to cause fetal neurotoxicity.4 Longer labors may reflect inherently more complicated pregnancies, and the incidence of ASD according to duration of labor among the no-LEA group is glaringly absent.
Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder
Adina R. Kern-Goldberger, MD, MPH1; Heather H. Burris, MD, MPH2; Lisa D. Levine, MD, MSCE1
doi : 10.1001/jamapediatrics.2020.6692
JAMA Pediatr. 2021;175(5):536-537
To the Editor We read with interest the work by Qiu et al1 investigating a potential association between intrapartum epidural analgesia and autism spectrum disorder (ASD) in offspring. We understand the urgency of uncovering the etiology of ASD given the rising rates in recent years, and we acknowledge the challenges of conducting clinical trials in this field. However, methodologic concerns and lack of biologic plausibility preclude conclusions of a causal relationship between epidural anesthesia and ASD.
Methodologic Concerns With Concluding a Link Between Epidural and Autism Spectrum Disorder—Reply
Chunyuan Qiu, MD, MS1; Vimal Desai, MD1; Anny H. Xiang, PhD2
doi : 10.1001/jamapediatrics.2020.6695
JAMA Pediatr. 2021;175(5):537-538
In Reply We appreciate the valuable perspectives and the thoughtful scrutiny that has been stimulated by our study,1 including those brought forward by Kern-Goldberger et al and Lee et al. Our study was not an experimental or mechanistic study and as such, we explicitly stated that our findings “cannot be interpreted as a demonstration of a causal link between LEA [labor epidural analgesia] exposure and subsequent development of ASD.”1 We are concerned about the assertions about biologic plausibility because that depends on the current state of knowledge. The lack of plausibility today does not preclude biological plausibility tomorrow; rather, this newly discovered association provides impetus for more biologic research. Thus, we called for further research to both “confirm our study findings and to investigate the probable mechanistic association.”1
Errors in Byline and Author Contributions
doi : 10.1001/jamapediatrics.2021.0206
JAMA Pediatr. 2021;175(5):538
Error in Methods Section and Figure
doi : 10.1001/jamapediatrics.2021.0272
JAMA Pediatr. 2021;175(5):538
Clarifications of Terms and for Interpreting Incidence Rate Ratios
doi : 10.1001/jamapediatrics.2021.0493
JAMA Pediatr. 2021;175(5):538
JAMA Pediatrics Peer Reviewers in 2020
doi : 10.1001/jamapediatrics.2021.0129
JAMA Pediatr. 2021;175(5):e210129
