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Intervention Recommendations for Children With Autism in Light of a Changing Evidence Base
Micheal Sandbank, PhD1; Kristen Bottema-Beutel, PhD2; Tiffany Woynaroski, PhD, CCC-SLP3
doi : 10.1001/jamapediatrics.2020.4730
JAMA Pediatr. 2021;175(4):341-342
In the wake of a rapid transformation of the evidence base regarding autism interventions, the American Academy of Pediatrics (AAP) recently updated guidance on the identification, evaluation, and support of children with autism.1 This guidance is undoubtedly a useful resource for pediatricians serving this population. It does not, however, highlight some notable new evidence on the choice of intervention approach or provide specific recommendations regarding intervention intensity, although it does imply that more intensive services can generally be expected to yield greater improvements. At approximately the same time that AAP guidelines were updated, our team completed a systematic review and meta-analysis2 of all quasi-experimental and randomized studies (known to us) that evaluate any outcome of any intervention for young children (up to age 8 years) with autism. In this Viewpoint, we seek to augment the recent AAP statement by offering medical professionals a brief background on common intervention recommendations, a summary of recent findings, and corresponding additional guidance on intervention intensity and variety. While our recommendations align with several points made by the AAP working group, they diverge to some degree in their emphasis and description of the present evidence base on intervention approach and intensity for young children with autism.
The Complicated Legacy of Cassandra Callender Ethics, Decision-making, and the Role of Adolescents
Jonathan M. Marron, MD, MPH1,2; Elaine C. Meyer, PhD, RN, MBE2,3; Kerri O. Kennedy, MA, BSN, RN2,4
doi : 10.1001/jamapediatrics.2020.4812
JAMA Pediatr. 2021;175(4):343-344
On May 12, 2020, Cassandra Callender died at the age of 22 years. Pushed off the front pages by the latest news about coronavirus disease 2019 (COVID-19), her untimely death invites reexamination of her story and the lessons it provides. “Cassandra C,” as she was referenced in news reports to protect her identity as a 17-year-old, was diagnosed as having Hodgkin lymphoma in September 2014.1 Although believed to have a more than 80% chance of cure, she refused further treatment after receiving several cycles of chemotherapy in her home state of Connecticut. Her mother, who supported her decision, stated at the time, “My daughter does not want poison in her body.…She is very bright, very smart.…Does she know she will die? Yes. And do I know that? Yes.”1 The hospital contacted the Connecticut Department of Children and Families, who took legal custody of Cassandra, precipitating a lengthy, contentious legal battle.
COVID-19 Pandemic Health Disparities and Pediatric Health Care—The Promise of Telehealth
Deepa U. Menon, MBBS1,2; Harolyn M. E. Belcher, MD, MHS3,4
doi : 10.1001/jamapediatrics.2020.5097
JAMA Pediatr. 2021;175(4):345-346
Allocating Resources Across the Life Span During COVID-19—Integrating Neonates and Children Into Crisis Standards of Care Protocols
Monica E. Lemmon, MD1,2; Robert D. Truog, MD3,4; Peter A. Ubel, MD5,6
doi : 10.1001/jamapediatrics.2020.5215
JAMA Pediatr. 2021;175(4):347-348
Family Media Use Planning With Teens—Is It Time for Shared Decision-making?
Emily Kroshus, ScD, MPH1,2; Dimitri Christakis, MD, MPH1,2
doi : 10.1001/jamapediatrics.2020.5637
JAMA Pediatr. 2021;175(4):349-350
Managing screen use in an ever-evolving media landscape is a challenge for many families, particularly families with adolescents. Whereas with younger children, parents can more readily restrict access to screens and monitor screen use,1 adolescents are often in situations without direct parental oversight.2,3 The heightened role of screens in adolescent socialization and schoolwork further complicates the use of media-related strategies that require a high degree of parental control. Moreover, and consistent with self-determination theory,4 highly controlling parenting may thwart emergent adolescent needs for autonomy, limit the development of intrinsic motivation, and lead to noncompliance with parent-desired behaviors.5 Autonomy-supportive parenting is distinct from permissive or uninvolved parenting in that it includes a developmentally appropriate amount of parental involvement, with the goal of fostering increasing independence and self-regulation.6 Evidence suggests that autonomy-supportive parent communication about media use is associated with less media use concealment by adolescents.7 In sum, parent-identified and enforced rules alone are likely not sufficient for adolescents to gain the buy-in necessary for consistent implementation of limits on media use and may constrain the development of important self-determined motivation and skills necessary for self-regulation in the transition to independent living (eg, college).
Long-term Outcomes of Children After Fetal Surgery for Spina Bifida—Toward Sustainability
Martin Meuli, MD1,2,3; Ueli Moehrlen, MD1,2,3
doi : 10.1001/jamapediatrics.2020.5687
JAMA Pediatr. 2021;175(4):e205687
The study by Houtrow et al1 is an eagerly awaited new chapter of an intriguing story that began almost 70 years ago.In 1956, Cameron published a Lancet article to describe allegedly secondary tissue damage of the openly exposed spinal cord tissue of fetuses and newborn babies with spina bifida (SB) aperta (ie, myelomeningocele or myeloschisis).2 The lesion was characterized by neural tissue damage that was apparently acquired in utero or during birth. This observation did not yet elicit in-depth interpretations regarding the prenatal natural history of SB and possible therapeutic implications.
Effect of a Family Media Use Plan on Media Rule Engagement Among Adolescents
Megan A. Moreno, MD, MSEd, MPH1,2; Kole S. Binger, BS1; Qianqian Zhao, MS3; Jens C. Eickhoff, PhD3
doi : 10.1001/jamapediatrics.2020.5629
JAMA Pediatr. 2021;175(4):351-358
Importance The American Academy of Pediatrics recommends that all families use a family media use plan to select and engage with media rules. To date, the effectiveness of this tool in promoting adolescent media rule engagement is unknown.
Effect of Enteral Lipid Supplement on Severe Retinopathy of Prematurity
Ann Hellstr?m, MD, PhD1; Anders K. Nilsson, PhD1; Dirk Wackernagel, MD2; Aldina Pivodic, MSc1; Mireille Vanpee, MD, PhD3; Ulrika Sj?bom, MSCs1,4; Gunnel Hellgren, PhD1,5; Boubou Hallberg, MD, PhD6; Magnus Domell?f, MD, PhD7; Susanna Klevebro, MD, PhD1,8; William Hellstr?m, MD9; Mats Andersson, PhD1; Anna-My Lund, RD10; Chatarina L?fqvist, PhD1,4; Anders Elfvin, MD, PhD9,10; Karin S?vman, MD, PhD9,10; Ingrid Hansen-Pupp, MD, PhD11; Anna-Lena H?rd, MD, PhD1; Lois E. H. Smith, MD, PhD12; David Ley, MD, PhD11
doi : 10.1001/jamapediatrics.2020.5653
JAMA Pediatr. 2021;175(4):359-367
Importance Lack of arachidonic acid (AA) and docosahexaenoic acid (DHA) after extremely preterm birth may contribute to preterm morbidity, including retinopathy of prematurity (ROP).
Maternal Oxygen Supplementation Compared With Room Air for Intrauterine Resuscitation
Nandini Raghuraman, MD, MS1; Lorene A. Temming, MD, MSCI2; Michelle M. Doering, MLIS3; Carolyn R. Stoll, MPH, MSW4; Arvind Palanisamy, MD5; Molly J. Stout, MD, MSCI1; Graham A. Colditz, MD, DrPH4; Alison G. Cahill, MD, MSCI6; Methodius G. Tuuli, MD, MPH, MBA7
doi : 10.1001/jamapediatrics.2020.5351
JAMA Pediatr. 2021;175(4):368-376
Importance Supplemental oxygen is commonly administered to pregnant women at the time of delivery to prevent fetal hypoxia and acidemia. There is mixed evidence on the utility of this practice.
Association of Cannabis Use With Self-harm and Mortality Risk Among Youths With Mood Disorders
Cynthia A. Fontanella, PhD1; Danielle L. Steelesmith, PhD1; Guy Brock, PhD2; Jeffrey A. Bridge, PhD3; John V. Campo, MD4; Mary A. Fristad, PhD1
doi : 10.1001/jamapediatrics.2020.5494
JAMA Pediatr. 2021;175(4):377-384
Importance Cannabis use and cannabis use disorder (CUD) are common among youths and young adults with mood disorders, but the association of CUD with self-harm, suicide, and overall mortality risk is poorly understood in this already vulnerable population.
Population vs Individual Prediction of Poor Health From Results of Adverse Childhood Experiences Screening
Jessie R. Baldwin, PhD1,2; Avshalom Caspi, PhD2,3,4,5; Alan J. Meehan, PhD2; Antony Ambler, MSc6; Louise Arseneault, PhD2; Helen L. Fisher, PhD2,7; HonaLee Harrington, BA3; Timothy Matthews, PhD2; Candice L. Odgers, PhD5,8; Richie Poulton, PhD9; Sandhya Ramrakha, PhD9; Terrie E. Moffitt, PhD2,3,4,5; Andrea Danese, MD, PhD2,10,11
doi : 10.1001/jamapediatrics.2020.5602
JAMA Pediatr. 2021;175(4):385-393
Importance Adverse childhood experiences (ACEs) are well-established risk factors for health problems in a population. However, it is not known whether screening for ACEs can accurately identify individuals who develop later health problems.
Association Between Proton Pump Inhibitor Use and Risk of Asthma in Children
Yun-Han Wang, MSc, BPharm1; Viktor Wintzell, MSc1; Jonas F. Ludvigsson, MD, PhD2,3,4,5; Henrik Svanstr?m, PhD1,6; Bj?rn Pasternak, MD, PhD1,6
doi : 10.1001/jamapediatrics.2020.5710
JAMA Pediatr. 2021;175(4):394-403
Importance The use of proton pump inhibitors (PPIs) in children has increased substantially in recent years, concurrently with emerging concerns that these drugs may increase the risk of asthma. Whether PPI use in the broad pediatric population is associated with increased risk of asthma is not known.
Prenatal Repair and Physical Functioning Among Children With Myelomeningocele
Amy J. Houtrow, MD, PhD, MPH1,2; Cora MacPherson, PhD3; Janet Jackson-Coty, DPT, PCS4; Monica Rivera, PT, DPTSc5; Laura Flynn, PT, PCS6; Pamela K. Burrows, MS3; N. Scott Adzick, MD7; Jack Fletcher, PhD8; Nalin Gupta, MD, PhD9; Lori J. Howell, DNP10; John W. Brock III, MD11; Hanmin Lee, MD12; William O. Walker, MD13; Elizabeth A. Thom, PhD3
doi : 10.1001/jamapediatrics.2020.5674
JAMA Pediatr. 2021;175(4):e205674
Importance The Management of Myelomeningocele Study (MOMS), a randomized clinical trial of prenatal vs standard postnatal repair for myelomeningocele, found that prenatal repair reduced hydrocephalus and hindbrain herniation and improved motor function in children aged 12 to 30 months. The Management of Myelomeningocele Study Follow-up (MOMS2) was conducted in children at ages 5 to 10 years. The primary (neurocognitive) outcome has already been reported.
Association of Umbilical Cord Management Strategies With Outcomes of Preterm Infants
Bonny Jasani, MD, DM1,2; Ranjit Torgalkar, DNB1,2; Xiang Y. Ye, MSc3; Sulaiman Syed4; Prakesh S. Shah, MD2,3
doi : 10.1001/jamapediatrics.2021.0102
JAMA Pediatr. 2021;175(4):e210102
Importance It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants.
Experimental Designs to Optimize Treatments for Individuals
Karina W. Davidson, PhD, MASc1,2; Michael Silverstein, MD, MPH3; Ken Cheung, PhD4; Rocco A. Paluch, MA5; Leonard H. Epstein, PhD5
doi : 10.1001/jamapediatrics.2020.5801
JAMA Pediatr. 2021;175(4):404-409
Conventional randomized clinical trials (RCTs) compare treatment effectiveness to provide support for evidence-based treatments that can be generalized to the average patient. However, the information obtained from RCTs may not always be useful for selecting the best treatment for individual patients. This article presents a complementary approach to identifying optimized treatments using experimental designs that focus on individuals. Personalized, or N-of-1, designs provide both a comparative analysis of treatments and a functional analysis demonstrating that changes in patient symptoms are likely because of the treatment implemented. This approach contributes to the zeitgeist of personalized medicine and provides clinicians with a paradigm for investigating optimal treatments for rare diseases for which RCTs are not always feasible, identifying personally effective treatments for patients with comorbidities who have historically been excluded from most RCTs, handling clinical situations in which patients respond idiosyncratically (either positively or negatively) to treatment, and shortening the time lag between identification and implementation of an evidence-based treatment. These designs merge experimental analysis of behavior methods used for decades in psychology with new methodological and statistical advances to assess significance levels of changes in individual patients, and they can be generalized to larger populations for meta-analytic purposes. This article presents a case for why these models are needed, an overview of how to apply personalized designs for different types of clinical scenarios, and a brief discussion of challenges associated with interpretation and implementation of personalized designs. The goal is to empower pediatricians to take personalized trial designs into clinical practice to identify optimal treatments for their patients.
What Parents Need to Know About Teen Vaping and What They Can Do About It
Ramzi G. Salloum, PhD1; Andy S. L. Tan, PhD, MBBS2; Lindsay Thompson, MD, MS1,3
doi : 10.1001/jamapediatrics.2020.6689
JAMA Pediatr. 2021;175(4):440
Body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) has become the standard metric for assessing excess weight in clinical, public health, and research contexts because of its high levels of accessibility, measurement reliability and validity, clinical validity, and sensitivity to change over time.1,2 In children and adolescents, overweight and obesity are defined as BMI at or above the 85th and 95th percentiles, respectively, for age and sex on the US Centers for Disease Control and Prevention (CDC) BMI growth charts.1,3 However, BMI units and their corresponding percentiles and z scores may not be easy to understand for many patients, families, and clinicians themselves, potentially making these measures of excess weight difficult to interpret, communicate, compare over time, and act on. Therefore, this analysis investigates new age-adjusted and sex-adjusted metrics, kilograms (or pounds) overweight and kilograms (or pounds) obese, arithmetically transformed from BMI data and the CDC growth references.
Using Metrics of Kilograms (or Pounds) Overweight or Kilograms (or Pounds) Obese to Help Interpret and Communicate Magnitudes of Excess Body Mass Index
Thomas N. Robinson, MD, MPH1,2,3,4
doi : 10.1001/jamapediatrics.2020.5196
JAMA Pediatr. 2021;175(4):410-412
Obesity and Eating Disorder Disparities Among Sexual and Gender Minority Youth
Natasha A. Schvey, PhD1; Arielle T. Pearlman, BA1; David A. Klein, MD, MPH2,3; Mikela A. Murphy, BA1; Joshua C. Gray, PhD1
doi : 10.1001/jamapediatrics.2020.5152
JAMA Pediatr. 2021;175(4):412-415
Obesity and eating disorders in youth are prevalent,1,2 are associated with medical and psychosocial consequences, and may persist into adulthood. Therefore, identifying subgroups of youth vulnerable to 1 or both conditions is critical. One group that may be at risk for obesity3 and disordered eating4 is sexual and gender minorities (SGM; those who identify as lesbian, gay, bisexual, and/or transgender or whose sexual orientation and/or gender identity/expression do not conform to societal conventions).
Trends in Pediatric Hospitalizations for Coronavirus Disease 2019
Zachary Levin, BA1; Kimberly Choyke, MS2; Archelle Georgiou, MD3; Soumya Sen, PhD4; Pinar Karaca-Mandic, PhD2
doi : 10.1001/jamapediatrics.2020.5535
JAMA Pediatr. 2021;175(4):415-417.
Translation of a Host Blood RNA Signature Distinguishing Bacterial From Viral Infection Into a Platform Suitable for Development as a Point-of-Care Test
Ivana Pennisi, MSc1; Jesus Rodriguez-Manzano, PhD1; Ahmad Moniri, MEng2; Myrsini Kaforou, PhD1; Jethro A. Herberg, PhD1; Michael Levin, PhD1; Pantelis Georgiou, PhD2
doi : 10.1001/jamapediatrics.2020.5227
JAMA Pediatr. 2021;175(4):417-419
Solitary Use of Alcohol and Marijuana by US 12th Grade Students, 1976-2019
Yvonne M. Terry-McElrath, MSA1; Patrick M. O’Malley, PhD1; Megan E. Patrick, PhD2
doi : 10.1001/jamapediatrics.2020.5211
JAMA Pediatr. 2021;175(4):419-421
Recent reviews have highlighted adolescent solitary alcohol and marijuana use as risk indicators associated with negative consequences, coping motives, and negative affect1,2; solitary use may reflect self-medication.1,2 Adolescent solitary alcohol use is associated with health and academic problems,3 deviant behavior,3 and alcohol use disorder.4 Data on sex differences in solitary alcohol and marijuana use have been mixed.1,2 Nationally representative estimates of prevalence and change in adolescent solitary alcohol and marijuana use are needed.1 This study provides 2018-2019 prevalence estimates of and 1976-2019 trends in solitary alcohol and marijuana use among all 12th grade students and those who used alcohol and marijuana in the past 12 months, separated by sex.
A Survey of Camp Leadership to Assess Immunization Requirements, Policies, and Practices in a National Cohort of Summer Camps
Carissa Bunke, MD1; Natalie Schellpfeffer, MD1; Barry Garst, PhD2; Stuart Bradin, DO3; Tracey Gaslin, PhD4; Michael Ambrose, MD5; Andrew N. Hashikawa, MD, MS1
doi : 10.1001/jamapediatrics.2020.5342
JAMA Pediatr. 2021;175(4):421-423
More than 14 million children attend summer camps yearly.1 While all states require immunizations for children attending public schools,2 most do not mandate immunizations for campers. Multiple vaccine-preventable outbreaks have been reported at camps.3,4 A 2019 American Academy of Pediatrics (AAP) camp health policy strongly recommended age-appropriate vaccinations for all campers and staff with elimination of nonmedical exemptions.5 We assessed the state of camps’ immunization requirements, policies, and practices by surveying a national cohort of camp leadership.
Children With Disabilities Must Be More Than an Afterthought in School Reopening
Maurice G. Sholas, MD, PhD1; Susan D. Apkon, MD2,3; Amy J. Houtrow, MD, MPH, PhD4
doi : 10.1001/jamapediatrics.2020.5308
JAMA Pediatr. 2021;175(4):423-424
Ways to Support Low-Income, At-Risk Young Children During and After Coronavirus Disease 2019
Venus Wong, PhD1
doi : 10.1001/jamapediatrics.2020.5284
JAMA Pediatr. 2021;175(4):424-425
Ways to Support Low-Income, At-Risk Young Children During and After Coronavirus Disease 2019—Reply
Danielle G. Dooley, MD, MPhil1; Asad Bandealy, MD, MPH1; Megan M. Tschudy, MD, MPH2
doi : 10.1001/jamapediatrics.2020.5287
JAMA Pediatr. 2021;175(4):425
Maternal Elimination Diet and Symptoms of Cow’s Milk Allergy in Breastfed Infants
Mika Hilvo, PhD1
doi : 10.1001/jamapediatrics.2020.5311
JAMA Pediatr. 2021;175(4):425-426.
To the Editor The Special Communication by Munblit et al, “Assessment of Evidence About Common Infant Symptoms and Cow’s Milk Allergy,”1 concluded that recommendations to manage common infant symptoms as cow’s milk allergy (CMA) are not evidence based, especially in breastfed infants who are not directly consuming cow’s milk. Analysis of the authors suggested that for more than 99% of the infants with proven CMA, breast milk from a cow’s milk–consuming mother contains insufficient ?-lactoglobulin levels to trigger an allergic reaction. Although the authors admitted limitations in their analysis, it should be furthermore noted that the analysis was based on indirect evidence; it compares thresholds of proteins needed to induce allergic reaction in older children than breast-fed infants with the concentration of a single cow’s milk component in breast milk. In fact, this is not evidence based, and one should look at more direct evidence.
Maternal Elimination Diet and Symptoms of Cow’s Milk Allergy in Breastfed Infants—Reply
Daniel Munblit, MD, PhD1; Debra J. Palmer, BSc, BND, PhD2; Robert J. Boyle, MB, ChB, PhD3
doi : 10.1001/jamapediatrics.2020.5320
JAMA Pediatr. 2021;175(4):426-427
In Reply We thank Hilvo for commenting on our article1 and highlighting studies from the 1980s that reported infant responses to maternal dietary exclusions. In fact, there is a longer history of this concept that a breastfeeding woman’s dietary intake may cause allergic reactions in her infant, with the first report of infant “allergic” response to maternal intake of chocolate published in 1918.2 However, as Hilvo rightly points out, and Cochrane reviews have also identified, randomized clinical trial evidence in this field is inconsistent. Case reports, observational studies, and personal and clinical experience support the existence of infants whose symptoms respond to maternal dietary intake. But this phenomenon occurs in both allergic and nonallergic infants.
Pros and Cons in Using Population-Based Registers for Assessing the Fetal Safety of Drugs
Stefania Triunfo, MD, PhD1; Alessandro Ceschi, MD, MSc2
doi : 10.1001/jamapediatrics.2020.5314
JAMA Pediatr. 2021;175(4):427
To the Editor Andersson et al1 investigate the risk of adverse fetal outcomes associated with the use of a second-generation antihistamine (fexofenadine) among 2962 pregnancies with fexofenadine use matched in a 1:1 ratio with those with the use of the currently recommended second-generation antihistamines (cetirizine). No association has been noted between fexofenadine use during pregnancy and increased risk of major birth defects, spontaneous, preterm birth, and stillbirth.
Pros and Cons in Using Population-Based Registers for Assessing the Fetal Safety of Drugs—Reply
Niklas Worm Andersson, MD1; Jon Tr?rup Andersen, MD, PhD2
doi : 10.1001/jamapediatrics.2020.5323
JAMA Pediatr. 2021;175(4):427-428
In Reply We thank Triunfo et al for their interest in our article.1 They relevantly note that caution is warranted when drawing conclusions from registry-based studies owing to the limitations of observational designs, including the lack of randomization. With the view that randomized clinical trials are in general unlikely to be conducted within the field of drug safety in pregnancy, observational data provide means to help inform patients, clinicians, and drug regulatory agencies on this issue. In addition, while the relative rarity of both exposure and outcomes brings difficulties in performing studies of drug safety in pregnancy, the use of nationwide registry data allows the identification of a sufficient number of exposed pregnancies to reach adequate power.
Prenatal Opioid Exposure and Motor Cortex Volume
Gideon Koren, MD1,2
doi : 10.1001/jamapediatrics.2020.5317
JAMA Pediatr. 2021;175(4):428-429
To the Editor Hartwell et al1 published evidence, based on a very large cohort, that prenatal opioid exposure is negatively associated with the volume of motor cortex, which may explain neurodevelopmental deficits. By their nature, observational studies can document association but not causation. Any attempt to move toward causation must deal with identifying and adjusting for confounders that may affect the measured differences in motor cortex. Hartwell et al1 have attempted to adjust for differences between prenatal opioid users and controls by considering race/ethnicity, alcohol and tobacco exposure, measures of financial risks, and single-adult household,1 all of which are important confounders that may help separate the 2 comparison groups. However, mothers who use opioids in late pregnancy are very different in many other aspects that may affect offspring outcome, which were not adjusted for in the analysis. Here is a partial list of variables proven to cluster among mothers using opioid prenatally, which were not included in the Hartwell et al1 analysis and may affect neurologic outcome:
Prenatal Opioid Exposure and Motor Cortex Volume—Reply
Micah L. Hartwell, PhD1; Julie M. Croff, PhD2
doi : 10.1001/jamapediatrics.2020.5332
JAMA Pediatr. 2021;175(4):429-430
In Reply Our study, titled “Association of Prenatal Opioid Exposure With Precentral Gyrus Volume in Children,”1 is among the first to identify an association between prenatal prescription opioids exposure (RxPOE), which was understated in the original article, and the precentral gyrus, a part of the brain used to control motor function. Our hypothesis arose from earlier research noting delayed motor skills among children with RxPOE2 and studies of children with prenatal exposure to other opiates and drugs.3-5 Our retrospective, cross-sectional analysis, using data from more than 10?000 participants from the Adolescent Brain Cognitive Development study, shows that structural differences in this region of the motor cortex are discernable among children with RxPOE. Koren notes several studies involving methadone, buprenorphine, or illicit opioid use; however, none of the studies involved measures from magnetic resonance imaging or brain development. One study from the Appalachian region of Tennessee focused on neonatal abstinence syndrome and noted the differences in use patterns between the Appalachian region of Tennessee and the state as a whole. This study identified a use rate of 28.7% illicit opioids at the state level and a 36.2% use rate in the Appalachian region. Moreover, 58.0% of prescription opioid use in this region was for prescriptions not prescribed to the mother. These points differ from our study in that we compared structural components of the brain among children with and without RxPOE, not dependent on neonatal abstinence syndrome diagnosis or treatment. While our modeling holds to statistical parsimony, it is well informed and extends further in consideration of additional variables than what has been explored in previous, relevant studies involving magnetic resonance imaging data, and prenatal exposure to opiates.3,4 Our adjusted models controlled for prenatal exposures to alcohol and tobacco, arguably the most important known factors in fetal development, age, sex, race/ethnicity, and socioeconomic factors (financial risk and single-adult households) to account for the child’s social environment. While we did not explicitly state it as a limitation of the study, we did acknowledge that “analysis of other variables within the Adolescent Brain Cognitive Development study data set may elucidate the functional, cognitive, and behavioral results of these neuroanatomical differences,”1 and acknowledge there is potential for a future study to examine the stability of effects6 among the included variables and other covariates within this area of research, as well as the exploration of the collinearity between them. Further, because the nature of the study is associative, we made no mention of causality; however, given our findings, we recommend clinical screening for RxPOE during pregnancy, which should be included among other associated risk factors, such as a mother’s medical diagnoses, because our intention was and is to create the best possible outcomes for all children.
Nonintervention Is Not Noninferior to Oral Ibuprofen for Treatment of Patent Ductus Arteriosus
Abdul Razak, MD1
doi : 10.1001/jamapediatrics.2020.5326
JAMA Pediatr. 2021;175(4):430
To the Editor This Letter highlights the flaws of a recent randomized clinical trial by Sung et al1 that concluded that nonintervention is noninferior to oral ibuprofen for patent ductus arteriosus (PDA) treatment in reducing death or bronchopulmonary dysplasia (BPD) in preterm infants.
Nonintervention Is Not Noninferior to Oral Ibuprofen for Treatment of Patent Ductus Arteriosus—Reply
Se In Sung, MD, PhD1; Myung Hee Lee, PhD2; Won Soon Park, MD, PhD1
doi : 10.1001/jamapediatrics.2020.5329
JAMA Pediatr. 2021;175(4):430-431
In Reply We thank Razak for the comments on our randomized clinical trial comparing nonintervention and oral ibuprofen treatment for patent ductus arteriosus (PDA).1First, because the PDA might close spontaneously,2 we could avoid unnecessary treatment exposure in 37% (143 of 383) of patients by delaying their enrollment for approximately 1 week.1 In contrast with other trials showing 21% pulmonary hemorrhage, 12.5% of intraventricular hemorrhage, and 40% of backup treatments,3 6% of intraventricular hemorrhage and no pulmonary hemorrhage nor backup treatment were observed in the nonintervention arm of our trial.1 Therefore, nonintervention alone is not enough, but meticulous neonatal intensive care including judicious fluid restriction starting at 67 mL/kg per day is essential for the success of this approach.1,2,4,5 Considering no significantly higher odds of PDA closure (1.63; 95% CI, 0.83-3.25) with high vs standard dose of oral ibuprofen and lowest incidence of bronchopulmonary dysplasia (BPD)/death with standard dose observed in a meta-analysis,6 our data showing significant PDA closure only in infants at the gestational age of 27 to 30 weeks but not at the gestational age of 23 to 26 weeks might thus reflect that it is gestational age rather than dose-dependent variation for PDA closure.1,2 Because only patients with symptomatic PDA requiring respiratory support, with the average PDA size of 2.5 mm and left atrium/aorta ratio of 1.69 and 1.61 in the ibuprofen and nonintervention arm, respectively, were enrolled, our study population was homogenous with moderate to severe clinical and echocardiographic severity in both arms.
Why Is Antibiotic Treatment Rarely Performed in COVID-19–Positive Children Admitted in Pediatric Intensive Care Units?
Vassilios Fanos, MD1; Flaminia Bardanzellu, MD1; Maria Antonietta Marcialis, MD1
doi : 10.1001/jamapediatrics.2020.5348
JAMA Pediatr. 2021;175(4):431-432
Why Is Antibiotic Treatment Rarely Performed in COVID-19–Positive Children Admitted in Pediatric Intensive Care Units?—Reply
Lara S. Shekerdemian, MD, ChB, MD, MHA1; Jeffrey P. Burns, MD, MPH2
doi : 10.1001/jamapediatrics.2020.5360
JAMA Pediatr. 2021;175(4):432
Rapid Implementation of Model-Based Dosing Recommendations During the Coronavirus Disease 2019 Pandemic
Saskia N. de Wildt, MD, PhD1,2; Laurens F. M. Verscheijden, MSc2; Tjitske M. van der Zanden, BSc3
doi : 10.1001/jamapediatrics.2020.5395
JAMA Pediatr. 2021;175(4):432-433
Rapid Implementation of Model-Based Dosing Recommendations During the Coronavirus Disease 2019 Pandemic—Reply
Anil R. Maharaj, PhD1; Christoph P. Hornik, MD, PhD, MPH2,3; Michael Cohen-Wolkowiez, MD, PhD2,3
doi : 10.1001/jamapediatrics.2020.5398
JAMA Pediatr. 2021;175(4):433
Efficacy of 3 Major Ketogenic Diet Therapies in Children With Drug-Resistant Epilepsy
Jiong Yue, MD1; Shi-Yong Liu, MD, PhD1; Hui Yang, MD, PhD1
doi : 10.1001/jamapediatrics.2020.5448
JAMA Pediatr. 2021;175(4):434
To the Editor We read with interest the Original Investigation “Efficacy of Ketogenic Diet, Modified Atkins Diet, and Low Glycemic Index Therapy Diet Among Children With Drug-Resistant Epilepsy: A Randomized Clinical Trial” by Sondhi et al,1 published in JAMA Pediatrics. The authors indicate that the modified Atkins diet and low glycemic index therapy diet are not noninferior to the classic ketogenic diet (KD) with respect to seizure reduction at 24 weeks after diet initiation among children with drug-resistant epilepsy. There are several concerns about this study.
Efficacy of 3 Major Ketogenic Diet Therapies in Children With Drug-Resistant Epilepsy—Reply
Vishal Sondhi, MD, DM1; Sheffali Gulati, MD2
doi : 10.1001/jamapediatrics.2020.5451
JAMA Pediatr. 2021;175(4):434-435
In Reply We thank Yue et al for their interest in our article and value the opportunity to clarify some aspects of our study.1 First, they raise concerns about the exclusion of surgically remediable epilepsy. We agree with Yue et al that using the ketogenic diet reduces seizure burden among children with surgically remediable epilepsy and can be used as a bridge to epilepsy surgery. However, the ketogenic diet in this scenario is palliative, and removing the epileptogenic focus is often curative. Hence, we excluded 4 children with surgically remediable epilepsy from our study, and they were offered curative surgery. These included focal heterotopia (n?=?2) and mesial temporal sclerosis (n?=?2). The same has also been highlighted in Figure 1 of our article.1 Thus, to reiterate, although the ketogenic diet can reduce seizure burden in surgically remediable epilepsy, surgery is the modality of choice for these children’s treatment.2
Misspelled Author Name in the Byline
doi : 10.1001/jamapediatrics.2021.0031
JAMA Pediatr. 2021;175(4):435
