In Reply We thank Zhou and Niu for their comments regarding our pragmatic cluster randomized trial. The authors raise 2 specific issues that they believe are legitimate. First, Zhou and Niu question the generalizability of the trial conducted in Chamarajnagar district, South India, to rural children from the rest of India. In support of their concern is cited evidence for genetic diversity among Indian individuals and documentation of rare germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin that can cause iron-refractory iron-deficiency anemia.1 This concern is unfounded for the following reasons. In spite of genetic diversity, anemia prevalence in children younger than 5 years between rural Indian provinces is remarkably similar.2 Moreover, genetic mutations causally associated with iron deficiency anemia in the general population are likely to be randomly distributed. Besides, regardless of heterogeneity in anemia prevalence among genetically diverse individuals, there is no logical reason to think that the relative effect of our intervention would be different because the effect is obtained via education and counselling, mechanisms that are social and cultural rather than genetic.

To the Editor In their pragmatic cluster randomized clinical trial, Shet et al1 reported a perceivable effect of community-based parental education and counseling annexed with usual treatment on children’s anemia cure rate in India. Globally, anemia has escalated to epidemic proportions, with an estimated prevalence of 32.9% in 2010, causing 68.36 million years lived with disability.2 Hence, strategies to prevent anemia and mitigate its adverse effects are of major public importance. To fill this gap in knowledge, Shet et al1 have proposed an effective strategy that might guide policy makers and practitioners to enhance anemia control at a population level. However, we are concerned about result extrapolation and data management.

Relationship abuse and sexual violence are important societal and public health concerns that begin in adolescence, with behaviors and consequences continuing across the life span. They include physical, sexual, and psychological abuse by a current or former partner in same-sex and opposite-sex couples and occurs across all racial/ethnic groups and socioeconomic statuses. All sexes are identified as survivors and perpetrators of relationship abuse and sexual violence.1 However, women and girls are more likely to be survivors and men and boys more likely to be perpetrators.2,3 While not as well studied, gender-nonconforming youths of all identities are more likely than their gender-conforming peers to be targets of physical and sexual violence.4 Overall, female-identified individuals endure the most injury. Intimate partner violence (IPV) is the leading cause of injury in women aged 16 to 24 years. Femicide is the third leading cause of death in that age group, of which IPV accounts for at least half.5 Relationship abuse and sexual violence can result in a range of physical and psychological health needs that increase health care utilization and costs. The combined medical, mental health, and lost productivity costs of IPV against women are estimated to exceed $8.3 billion per year.6

In August 2019, the American Academy of Pediatrics (AAP) published a critically important policy statement2 on the effects of racism on child and adolescent health. This statement (referred to here as the AAP policy statement) powerfully underscores the work undertaken by scholars and scientists regarding racial inequities in health care, and it comes at a critical sociohistorical moment in which public discourse on racism is squarely at the forefront. The AAP policy statement proposes an integrated approach to combating racism by addressing “implicit and explicit biases, institutional structures, and interpersonal relationships,”2(p1) and advocates “untangling the thread of racism sewn through the fabric of society and affecting the health of pediatric populations.”2(p7)

To the Editor In a cross-sectional study, Koopman-Verhoeff et al1 observed that there was an association between subjectively reported and objectively estimated sleep problems and melatonin use in school-aged children. Their observation highlights the importance of close and enhanced monitoring of currently freely available melatonin because an estimated 1 in 17 children are likely to take melatonin at least once a week.1 However, we have 2 major methodological concerns.

In the United States, more than 7400 pregnancies with laboratory evidence of confirmed or possible Zika virus infection were identified and included in the national surveillance network, the US Zika Pregnancy and Infant Registry, during the Zika virus outbreak in the Region of the Americas from 2015 to 2017.1 These pregnancies included those completed from December 1, 2015, through March 31, 2018, meaning the children from these pregnancies ranged in age from 18 months to nearly 4 years by the fall of 2019. Although between 5% and 10% of these children have received a diagnosis of serious defects of the brain or eye, including microcephaly, many of them have not undergone the recommended postnatal brain imaging and ophthalmological examinations to fully identify these health problems.2-6 Some infants with a standard head circumference measurement at birth may have underlying brain and/or eye defects. In a report from the US territories and freely associated states, 23 children without microcephaly had brain and/or eye defects that would have been missed without the recommended neuroimaging and/or ophthalmological examinations.4

Asthma is one of the most common chronic conditions of childhood and is associated with significant effect on quality of life. An ongoing controversy remains how to best treat asthma in children and adolescents. A provocative evolution in this controversy is the publication of new recommendations by the Global Initiative for Asthma (GINA), which present a significant change in asthma therapy.1 Step 1 recommendations for mild asthma in adolescents 12 years and older and adults changed from as-needed short-acting β-agonist (SABA) to as-needed low-dose inhaled corticosteroid (ICS) formoterol (a long-acting β-agonist [LABA]). In children aged 6 to 11 years, GINA recommends that ICS therapy be used with SABA as needed or regular ICS with as-needed SABA as an alternative approach.

Vision: JAMA Pediatrics will be the most respected source of information for investigators, providers, and policy makers seeking the highest quality evidence to guide decision making. Mission Statement: JAMA Pediatrics seeks to provide state-of-the-art information to individuals and organizations working to advance the health and well-being of infants, children, and adolescents. The journal also provides a forum for discussion of the most important issues and policies affecting child and adolescent health and health care. JAMA Pediatrics will use the most current technology to make timely information available to readers wherever and whenever it is needed.

In the Original Investigation titled “Public Health Insurance Expansion for Immigrant Children and Interstate Migration of Low-Income Immigrants,”1 published online November 18, 2019, the y-axes in the Figure, A and B were incorrect. The measures should have been 0.04, 0.08, and 0.12 instead of 4, 8, and 12. This article has been corrected online.

In Reply The goal of for-profit corporations, such as British American Tobacco (BAT), is undeniably to maximize profits. A novel finding from our study1 is that BAT’s large and sustained price increases suggest that it aimed to maximize short-run profits even if they came at the expense of fewer new young users becoming addicted. Many governments, but surely not all, increased tobacco taxes with the primary goal of increasing tax revenues, with the secondary goal to improve population health. What stands out, and contradicts Braillon’s thesis, is that Chile did not increase tobacco taxes while BAT increased prices and reaped profits. Instead, Chile strengthened existing tobacco control policies such as advertising and smoking restrictions. It banned all tobacco advertising with the exception of point of sale and banned smoking in enclosed workplaces and public spaces. There is strong evidence that such policies can reduce tobacco use,2 and in turn, actually decrease tax revenue.

To the Editor The conclusion that “large cigarette tax increases may be a strategy that can be used to help reduce smoking among youths”1 by Guindon et al deserved comment. First, the goals of tax increases are to increase benefits, the reduction of smoking prevalence being only an ancillary result. In Australia, a most proactive country against tobacco (2016 smoking prevalence: 15%), revenue from taxes increased from A$8.0 million in 2001 to A$10.4 million in 2016 ($5.45 million to $7.09 million US dollars).2 In France, governments shared profits with the industry: since 2005, there have been no relevant increase in taxes (always less than 6%, a level inadequate to decrease sales in high-income countries) and small increases in industrial price until March 2017 (15% increase in price targeting roll-your-own tobacco plus a ban on low-price packs, which represented 40% of sales). This did not preclude the agency Public Health France from overlooking this measure and claiming that “increased reimbursement for nicotine substitutes, plain packaging, month without tobacco caused a decrease in smoking prevalence (from 38.8% in 2016 to 34.0% in 2017 for the lowest income and 49.7% to 43.5% for the unemployed).”3 Coincidentally, experts have been enduringly calling to raise prices to €20 in 2020 ($22.16), but the new government only promised €10 ($11.08). The Chilean case seems between France and Australia.1

In Reply We thank Wong et al and Riehm and Feder for their comments on our study1 reporting the association of team sports participation in adolescence and long-term mental health outcomes among individuals exposed to adverse childhood experiences (ACEs). To address the comments by Wong et al requesting clarification of the timing of the main variables, we assessed team sports participation prior to the mental health outcomes. Team sports participation was determined in wave I (1994-1995), when respondents were in grades 7 to 12, and the 3 mental health outcomes were assessed in wave IV (2008), when respondents were aged 18 to 26 years. Current depressive symptoms pertained to the preceding 7 days and therefore occurred after adolescent team sports participation. Diagnosis of depression and anxiety were based on the question, “Has a doctor, nurse, or other health care provider ever told you that you have/had: depression/anxiety?” In a small number of cases, the diagnoses of depression or anxiety occurred prior to participation in team sports. In Table 1 of the article, we reported the number of individuals who received a diagnosis of depression (126 [2.4%]) and anxiety (43 [0.9%]) before wave I and the mean (SD) age at diagnosis of depression (20.5 [5.5] years) and anxiety (22.64 [4.9] years). In addition, eTable 1 in the Supplement presented the association between team sports and each mental health outcome after accounting for baseline mental health at wave I. As stated in the article, the association between participation in team sports and mental health remained significant for anxiety and was nearly significant for depression diagnosis and current depressive symptoms.

To the Editor We read with interest the article by Easterlin et al,1 which demonstrated an association between team sports participation in adolescence with long-term mental health outcomes among individuals exposed to adverse childhood experiences. We noted that the main variables of this study, including mental health outcomes (depression, anxiety, and depressive symptoms), adverse childhood experiences, and team sport participation, were recorded without any details surrounding chronology. Mental health outcomes were retrospectively self-reported in wave 4 (phrased as “having ever received a diagnosis of anxiety/depression”), while team sport participation was reported in wave 1 (phrased as current participation or intention to participate).

To the Editor Easterlin et al1 recommend pediatricians encourage team sports participation for patients reporting adverse childhood experiences (ACEs); they argue sports participation could avert negative adult mental health outcomes. Decades of research illustrate the negative health sequelae of ACEs,2 and we applaud the authors’ decision to move beyond simply identifying ACEs’ negative effects and toward identifying interventions that may promote resilience. However, we worry the authors’ conclusions are not fully supported by their analyses.

In Reply Our Research Letter,1 published on July 8, 2019, reported 2 main results. Using national and state Youth Risk Behavior Survey (YRBS) data, we found no evidence of an association between medical marijuana laws (MMLs) and marijuana use among teenagers. In addition, we found a negative and statistically significant association between recreational marijuana laws (RMLs) and marijuana use.

To the Editor The debate on effects of state medical and recreational marijuana laws (MMLs/RMLs) is at the forefront of drug policy. Assessing associations of MMLs/RMLs with youth marijuana use is critical given marijuana’s potential for long-term negative effects on brain development and function.1,2 Anderson et al,3 using Youth Risk Behavior Survey (YRBS) data, report MMLs are not associated with youth marijuana use and RMLs are associated with reduced use. However, their analyses include substantial methodologic flaws that may undermine these findings.

To the Editor We read with great interest the Research Letter by Anderson et al1 investigating associations between marijuana laws and teen marijuana use. With many states considering passage of recreational marijuana laws (RML), it is important to understand the potential effects of these laws for adolescents. To evaluate this, Anderson et al1 analyzed adolescent marijuana use in states where RMLs have been passed and reported an 8% decrease in odds of teen marijuana use following passage of RMLs. However, we are concerned that a potential flaw in their methods may compromise the validity of these results.

To the Editor Anderson et al1 claimed that data from 7 states with recreational marijuana laws (RML) supported the hypothesis that teen marijuana use decreased because “it is more difficult for teenagers to obtain marijuana as drug dealers are replaced by licensed dispensaries that require proof of age.”1 However, their conclusion is erroneous because they do not have data from 7 states following the initiation of legal commercial sales of recreational marijuana by these age-verifying stores. In fact, they only have data from 2 states following legal sales,2 and neither state saw teen use drop more than the national average.

To the Editor The Research Letter by Anderson et al1 has been widely reported in the media as indicating that legalization of cannabis for recreational use actually reduces teen marijuana use. This counterintuitive and startling finding deserves close scrutiny. As the authors themselves state in the introduction, “repeated marijuana use during adolescence may lead to long-lasting changes in brain function that adversely affect educational, professional, and social outcomes.”1,2 Therefore, it behooves us as phsyicians and scientists (and editors) to carefully assess any evidence that may lead (advertently or inadvertently) to increased cannabis use in young people. The authors state that they examined data from the Youth Risk Behavior Surveys 1993 to 2017. They state that they examined data from 7 states that contributed data to the YRBS before and after legalization of marijuana for recreational use. However, they do not list these states in the article, and it is not clear where they got this number. Two states listed in YRBS (Colorado and Alaska) legalized marijuana for recreational use in 2012 and 2014. However, another 4 states only legalized in 2016 and had not begun commercial sales as of January 1, 2017, which would not have allowed sufficient time to see a meaningful effect. The authors do not report the overall trends for teen marijuana use in the period in question.

To the Editor A publication in JAMA Pediatrics1 has a technical issue that has unfortunately become too common in biomedical journals: the failure to present both adjusted and unadjusted results. In the case of this particular data set, being able to view the unadjusted results assumes even greater importance because most of the numerous adjustment factors are not specified in the current publication nor in a prior publication of the authors cited by them. Adjusting for “indicators for 50 states”1 (Table 1 footnotes) is an unacceptably vague descriptor for a scientific publication. In an ideal world, the reader would be given enough information to ascertain the specific adjustment factors that had the most impact in modifying the outcome.

In Reply Our Viewpoint1 summarized animal studies with respect to the association of cyclooxygenase (COX) 2 and prostaglandin-E2 (PGE2) disruption with neurodevelopment, including the use of COX inhibitors such as aspirin or indomethacin.1 Relevant research needs to be introduced in pediatric clinical discussions and warrants future neurobehavioral studies, especially because clinical data will probably lead to (1) treatment of considerably more pregnant women (almost 11% of total) at high risk for preeclampsia with low-dose aspirin (LDA) and (2) increased and prolonged fetal exposure to aspirin.2

To the Editor Preterm birth increases risk of neurodevelopmental delays.1 High-risk pregnancies for preeclampsia development are at increased risk of preterm birth, the rate of which is dependent on the definitions and screening criteria.2 Voutetakis et al3 raise concern of a potential long-term effect of aspirin given to prevent preterm preeclampsia in high-risk pregnancies owing to disruption of cyclooxygenase (COX) 2 and prostaglandin-E2 (PGE2) signaling, potentially affecting prenatal and postnatal brain development with subsequent neurodevelopmental impairments. There are some considerations for this argument. Several prior studies have shown that prophylactic use of low-dose aspirin (LDA) during pregnancy has no negative association with perinatal morbidity and mortality.2 Aspirin, particularly at low dose, is less effective at inhibiting COX2, an inducible enzyme, as opposed to COX1, a constitutive enzyme.2 The few studies in murine models that investigated the COX2/PGE2 pathway in brain and neurodevelopment only considered COX2-deficient knock-in rodents, ie, selective inhibition of COX2 as opposed to a dose-response effect of aspirin, an effect that might also be tissue dependent. In assessment of 5-year neurodevelopmental outcomes of children born preterm (22-32 weeks of gestation) using the Etude Epidemiologique des Petites Ages Gestationnels cohort study, prenatal LDA was not associated with adverse neonatal or long-term outcomes.4 The data also suggest LDA may even reduce neurobehavioral difficulties. This observation was based on findings by Harding et al,4 who reported preterm infants (<32 weeks of gestation) carrying the COX2–765 C allele had a slightly worse cognitive outcome at 2 to 5 years, presumably owing to production of lower levels of COX2. The negative adverse neurodevelopmental outcomes of prenatal LDA treatment in offspring are consistent with findings from several investigations demonstrating a marked increase in autism and attention-deficit/hyperactivity disorder in the early 1980s, with the substitution of acetaminophen for aspirin from birth to early childhood.5 Maternal use of acetaminophen during pregnancy has also been associated with hyperactivity and emotional symptoms at age 7 years,5 which has not been reported with LDA treatment during pregnancy.4

Importance Given the importance of sports-related concussions among youth athletes, the rapid progress of research on this topic over the last decade, and the need to provide further guidance to youth athletes, their families, medical professionals, and athletic personnel and organizations, a panel of experts undertook a modified Delphi consensus process to summarize the current literature and provide recommendations regarding the prevention, assessment, and management of sports-related concussions for young athletes. Methods A consensus panel of 11 experts was created to represent a broad spectrum of expertise in youth sports and concussions. The specific questions to be addressed were developed through an iterative process consisting of 3 rounds, and a review of the literature was conducted to identify research studies related to each question. The consensus panel used a modified Delphi process to reach consensus on the conclusions and recommendations for each question. Results and Conclusions In 3 Delphi consensus rounds, 7 questions were addressed by the consensus panel of 11 experts, and 26 recommendations for the prevention, assessment, and management of sports-related concussions among young athletes were developed. For many of the questions addressed in this consensus statement, limitations existed in the quantity and quality of the evidence available to develop specific recommendations for youth sports stakeholders.

Evidence of an association between early-life adversity and heightened risk of chronic disease in adulthood has been found, but the optimal biomarkers for identifying vulnerable or resilient individuals remain unclear.1 Global trends, including widening socioeconomic disparities, the refugee crises, and climate change, increasingly sculpt trauma exposure and call for scalable early-risk identification and treatment strategies. Pediatricians often serve on the frontline of early identification and treatment of at-risk children, intervening during crucial windows of opportunity to prevent longer-term bioembedding that confers risk of disease across the life course. However, problems of scale need solutions that scale, which is one reason why the discoveries by Rasmussen et al,2 reported in this issue, represent a promising step forward. Using high-quality assessments of multidomain, multireporter adversity exposure, these investigators present prospective, longitudinal evidence from a large, socioeconomically diverse sample that soluble urokinase plasminogen activator receptor (suPAR) may be a useful immune biomarker of early-life adversity, having a stronger and more exposure-specific association than current clinical markers, such as C-reactive protein. This type of rigorous epidemiologic “big data” work, complemented with “deep data,” will accelerate biomarker discovery for clinical diagnosis and treatment of early risk and resilience profiles and provide the foundation for precision medicine strategies in pediatrics.

Atopic dermatitis is a chronic inflammatory skin disease that affects 15% to 20% of children and 1% to 3% of adults worldwide.1 Omalizumab, a medication administered by subcutaneous injection every 2 to 4 weeks, was approved for moderate-to-severe persistent asthma in patients aged 6 years or older by the US Food and Drug Administration in 2003.2 Atopic dermatitis in children is often IgE mediated, and omalizumab is an anti-IgE medication that binds to human IgE and thus limits mast cell degranulation and inhibits the release of inflammatory mediators. Therefore, it makes logical sense that omalizumab could be efficacious in atopic dermatitis treatment.3 In this issue of JAMA Pediatrics, Chan et al4 conducted a 24-week double-blind, placebo-controlled randomized clinical trial to determine if omalizumab is effective in severe childhood atopic dermatitis. Their results suggested improved atopic dermatitis severity, as measured by the SCORAD (Scoring Atopic Dermatitis) index, and improved quality-of-life scores in the omalizumab group compared with the placebo group.4 Although the study by Chan et al4 suggested that omalizumab is efficacious for atopic dermatitis in children, more questions need to be answered before the drug can be used to treat atopic dermatitis in clinical practice. Specifically, this study questions whether omalizumab is cost-effective for atopic dermatitis. Cost-effectiveness analyses can help health care decision-makers choose between new and existing interventions as well as compare costs, benefits, and harms associated with each intervention.5 Although no cost-effectiveness analyses on omalizumab as a treatment for atopic dermatitis have been published to date, thinking through the associated costs, benefits, and harms can add perspective to the Chan et al study.4

The US population is grappling with basic questions about values. The mass shooting in El Paso, Texas, on August 3, 2019, confirmed what many people have felt for some time; immigrant communities appear to be under siege. As we reflect on how the nation can recover from this tragedy and other assaults, we must ask a fundamental question, Are we committed to recognizing the basic humanity of each person in the United States? We unquestionably believe the answer should be yes. If so, then every person in the United States deserves access to health care regardless of their immigration status.

A baby is born prematurely at 23 weeks’ gestational age with many typical complications of extreme prematurity. At 47 weeks’ adjusted gestational age, she continues to receive ventilation, is fed through a nasal-duodenal tube, and has grade IV bilateral intraventricular hemorrhages resulting in global encephalomalacia. Her parents are counselled that she has a “poor prognosis” and a decision needs to be made about whether life-sustaining treatments should be continued or stopped.

Somatic symptom disorder (SSD) is one of the most common complaints in adolescents1,2 and its prevalence is increasing in recent years. The Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) defines SSDs as the presence of 1 or more somatic symptoms (commonly pain), that it is associated with excessive worries, and that thoughts and energies are spent dealing with them, causing a loss of opportunities in personal and social lives (eg, school absenteeism, abandonment of leisure and sports activities, and isolation from social settings).

Home nursing care is often warranted—but, too often, not reliably available1—for children with medical complexity (CMCs) who live with serious and sometimes life-threatening conditions and who usually depend on medical technology for their well-being and safety. When these children reside at home, parents or guardians are expected to provide medical care during many, or even all, hours of the day and night. Parental duties might include administering medication, providing enteral tube feedings or parenteral nutrition, performing chest physiotherapy, and perpetually monitoring the child for signs of critical decompensation, among other tasks. Many of these caregiving activities involve sustained attention and physical labor and must be performed multiple times each day.

Experiences of childhood adversity are common, with more than 50% of adults reporting having experienced at least 1 adversity as children and more than 6% exposed to 4 or more adverse childhood experiences (ACEs).1 There is currently a controversial debate in the medical field as to whether the ACEs questionnaire, which asks about abuse, neglect, and household dysfunction before age 18 years, should be administered as routine practice by pediatricians. While some argue that identifying and addressing ACEs can lead to support that may promote resilience and help decrease the well-established health burden of ACEs,2 others caution against its limited evidence and effectiveness as a universal “screening tool” as well as its potential harms in terms of revictimization and increased patient stigma.3,4 Although research on the potential benefits and consequences of universal screening for ACEs is in its infancy, the ACEs questionnaire has been rapidly adopted into pediatric care settings across North America. For example, $45 million has recently been allocated to state funding in California to increase ACEs screening and trauma-related training in pediatric care settings. Moreover, there are now 27 states that have statutes and resolutions associated with ACEs and trauma-informed approaches to care.

Yasenov and colleagues conducted a difference-in-differences analysis to examine whether expanding public health insurance in some states to non–US-born children and pregnant women who are lawful permanent residents during their first 5 years of residency in the United States is associated with increased interstate migration among these groups. Their findings suggest that states expanding health care benefits for immigrant children and pregnant women may be unlikely to experience changes in in-migration among eligible non–US-born adults from other states. Editorial Chan and colleagues conducted a randomized clinical trial of 62 children with severe atopic dermatitis. They found treatment led to a significant reduction in eczema severity that was observed in the omalizumab group compared with placebo after adjustment for the baseline objectives of Scoring Atopic Dermatitis index, age, and IgE level. This improvement occurred in the context of markedly potent topical corticosteroid sparing in the omalizumab group.

In the Research Letter titled “National Prevalence of Pain Among Children and Adolescents With Autism Spectrum Disorders,”1 published October 28, 2019, there was an error in the Results section. The first sentence of the Results section should have said 1093 of 51 156 children instead of 50 063 children so it reads, “Data were missing on ASD, comorbidities, or pain for 1093 of 51 156 children (2.1%) and were excluded from analysis.” This article was corrected online.

To the Editor This letter is in response to the Editorial, “Is Fluoride Potentially Neurotoxic?”,1 published online on August 19, 2019. While stating the position of the US Centers for Disease Control and Prevention in support of water fluoridation (WF), the Editorial mentions some of the opposition arguments that merit addressing. Water fluoridation is the adjustment of natural fluoride levels in water to safely maximize caries prevention on a population level. Water fluoridation is not considered as medication to treat existing disease but provides disease prevention. Water is safe to drink if it meets regulatory standards, and WF at 0.7 mg/L (ppm) is well within those standards. The courts have ruled that WF is not compulsory because consumers have choices with bottled water and filtration systems.2 Each community provides consent through its voters or elected representatives. Water fluoridation is not administered indiscriminately but is well controlled within a narrow range around the target 0.7 ppm level.3

In Reply We appreciate the widespread interest in our study and the opportunity to respond to the critiques and clarify some facts. We agree that our study reported an association, not causation. Still, observational studies are optimal for testing many important questions in public health, and they are often used to infer causality. Indeed, if we dismissed observational studies, we would have no evidence that water fluoridation prevents tooth decay in children.

To the Editor Many media accounts and critic comments on the Green et al study1 state “this is just one study” and “more research is needed.” We disagree. A search of PubMed and other sources found more than 60 human epidemiologic studies on fluoride neurotoxicity, with the overwhelming majority reporting significant associations with adverse effects including lowered IQ. Many of those studies were done at exposure levels that some people will experience in artificially fluoridated areas. More than 200 animal studies have also been published, most finding adverse neuroanatomical, neurochemical, and/or neurobehavioral effects.

To the Editor This letter is in response to the Green et al article,1 published online on August 19, 2019. While the results of the study by Green et al1 may support hypothesis testing, they should not be used to make public health recommendations. This is especially true given the number of limitations noted by the researchers themselves. In addition, we would like to raise awareness of several important methodologic omissions from the article.

To the Editor Green et al1 question the safety of public water fluoridation and fluoride supplementation, based on finding (1) an increase of 1 mg/L in maternal urinary fluoride (MUFSG) was associated with a 4.49 lower FSIQ score in boys (P = .02), and (2) an increase of 1 mg in fluoride intake was associated with a 3.66-lower FSIQ score among boys and girls (P = .04).1 We ask: what is the likelihood that these statistically significant findings are true?

To the Editor We have 4 concerns about the article and editorial on the association between maternal fluoride exposure during pregnancy and offspring IQ.1,2 First, there was no significant IQ difference between children from fluoridated and nonfluoridated communities and no overall association with maternal urinary fluoride (MUFSG). The authors did not mention this and instead emphasized the significant sex interaction, where the association appeared for boys but not girls. No theoretical rationale for this test was provided; in the absence of a study preregistration, we cannot know whether it was planned a priori. If not, the false-positive probability increases because there are many potential subgroups that might show the result by chance. Importantly, the result was contradicted by the self-report analysis, which showed an overall effect but no sex interaction, casting doubt on the latter’s validity.