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infected mothers, and close monitoring of neonates at risk of US report4 showed decreased incidence of some drugs, such COVID-19. as marijuana and , among people aged 12 to 17 years, while the contrary is true among those aged 18 to 25 years. This Lingkong Zeng, MD suggests an increase in the mean age at initiation of some drugs, Shiwen Xia, MD although we have found no confirmation of this in recent lit- Wenhao Yuan, MD erature. In this study, we examine recent trends in the mean Kai Yan, MD age at initiation for 18 internationally regulated drugs (includ- Feifan Xiao, MS ing and tobacco), focusing on the critical neurodevel- Jianbo Shao, MD opmental period (ages 12-21 years), using data from the Wenhao Zhou, MD National Survey on Drug Use and Health (NSDUH).

Author Affiliations: Department of Neonatology, Institute of Maternal and Methods | Each year from 2004 to 2017, staff from the NSDUH Child Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong drew a random, nationally representative sample of the US University of Science and Technology, Wuhan, China (Zeng, Yuan); Department of Neonatology, Maternal and Child Health Hospital of Hubei Province, Wuhan, population ages 12 years and older through multistage sam- China (Xia); National Children's Medical Center, Children’s Hospital of Fudan pling to assess drug-use and drug-associated behaviors. The University, Shanghai, China (Yan, Xiao, Zhou); Institute of Maternal and Child NSDUH staff used audio computer-assisted self-interviews to Health, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (Shao). collect data on alcohol and drug use, including age at first use, Accepted for Publication: March 10, 2020. after obtaining informed consent/assent. We analyzed - licly available, deidentified NSDUH data that included 338 268 Corresponding Author: Wenhao Zhou, MD, National Children's Medical Center, Children’s Hospital of Fudan University, 399 Wanyuan Rd, Shanghai 201102, individuals aged 12 to 21 years who completed self- China ([email protected]). interviews on their initiation of alcohol, tobacco, and other Published Online: March 26, 2020. doi:10.1001/jamapediatrics.2020.0878 drugs. Because all data came from deidentified, publicly avail- Author Contributions: Dr Zeng had full access to all of the data in the study and able files, the Washington State University institutional re- takes responsibility for the integrity of the data and the accuracy of the data view board ruled that the plan to analyze these data was not analysis. human subjects research. Concept and design: Zeng, Shao, Zhou. Acquisition, analysis, or interpretation of data: All authors. In this study, we identified individuals who initiated drug Drafting of the manuscript: All authors. use within 12 months prior to assessment. We analyzed 18 Critical revision of the manuscript for important intellectual content: Xia, Yuan, drugs, including alcohol and tobacco products (Figure), to es- Xiao, Shao, Zhou. Statistical analysis: Zeng, Yuan, Yan, Xiao. timate the year-by-year drug-specific mean age at initiation Administrative, technical, or material support: Zeng, Xia, Yan, Shao, Zhou. among individuals aged 12 to 21 years. Analysis weights ac- Supervision: Shao, Zhou. count for the complex survey design of the data. We con- Conflict of Interest Disclosures: None reported. ducted joinpoint regression using log-linear model to esti- Additional Contributions: We thank Shoo K. Lee, MD, Department of mate the slope of analysis-weighted, drug-specific mean ages Obstetrics and Gynecology and Department of Public Health, University of between 2004 and 2017. Finally, meta-analysis with a DerSi- Toronto, for editing assistance. He was compensated for his contribution. We thank the patients’ families for granting permission to publish this information. monian and Laird random effects estimator was used to sum- 1. Zhu H, Wang L, Fang C, et al. Clinical analysis of 10 neonates born to mothers marize year-by-year mean age estimates for initiation of each 5 with 2019-nCoV pneumonia. Transl Pediatr. 2020;9(1):51-60. doi:10.21037/tp. drug. All analyses were conducted using Stata SE15 (Stata- 2020.02.06 Corp), with the statistical significance level at .05. Data analy- 2. Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical sis occurred from April 2019 to June 2019. transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809-815. doi:10.1016/S0140-6736(20)30360-3 Results | Between 2004 and 2017, 84 317 adolescents and young 3. National Health Commission of China. New coronavirus pneumonia adults initiated use of any drug. Estimated year-by-year mean prevention and control program (4th edition). Accessed March 9, 2020. ages, slopes, and annual percentage changes for each drug are http://www.gov.cn/zhengce/zhengceku/2020-01/28/5472673/files/ visible in the Figure. Of the 18 drugs analyzed, we observed 0f96c10cc09d4d36a6f9a9f0b42d972b.pdf. an increase in the mean age at initiation for 12 drugs since 2004 4. Wang L, Shi Y, Xiao T, et al; Working Committee on Perinatal and Neonatal (including use, β = 0.003; P < .001; cocaine, β = 0.005; Management for the Prevention and Control of the 2019 Novel Coronavirus Infection. Chinese expert consensus on the perinatal and neonatal management P < .001; ecstasy, β = 0.003; P = .03; hallucinogens, β = 0.004; for the prevention and control of the 2019 novel coronavirus infection (first P = .004; , β = 0.005; P = .02; ; β = 0.004; edition). Ann Transl Med. 2020;8(3):47. doi:10.21037/atm.2020.02.20 P = .02; marijuana, β = 0.002; P < .001; smokeless tobacco, 5. Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in β = 0.001; P = .002; , β = 0.005; P = .007; and to- hospitalized infants under 1 year of age in China. JAMA. 2020. doi:10.1001/jama. bacco , β = 0.006; P < .001). The mean age at initia- 2020.2131 tion increased from 2004 to 2014 for alcohol (β = 0.005; P < .001), but there was no increase in this mean age at initia- Patterns of Mean Age at Drug Use Initiation Among tion after 2014 (β = −0.004; P = .06). The mean age at lyser- Adolescents and Emerging Adults, 2004-2017 gic acid diethylamide (LSD) initiation increased from 2004 to Use of alcohol, marijuana, and other drugs at an early age (eg, 2009 (β = 0.013; P = .03) and declined significantly after 2009 before age 18 years) increases the likelihood of drug use (β = −0.014; P = .04). No statistical difference in the mean ages disorder,1,2 which may disrupt brain development.3 A recent at initiation for crack , , ,

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Figure. Year-by-Year Mean Age at Drug Initiation Among Adolescents and Emerging Adults Who Started Using Drugs Within 12 Months Prior to Assessment

Alcohol Cigar Cocaine Ecstasy Hallucinogensa 19 19 19 19 19 19

18 18 18 18 18 18 β = 0.003b β2 = –0.004b 17 17 17 17 17 17 β = 0.005b β = 0.002 β = 0.003c β = 0.004c 16 16 16 16 16 16 β1 = 0.005 15 15 15 15 15 15 Mean Age at Initiation, y 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 Year Year Year Year Year Year

Heroin Inhalantsa LSD Marijuana Methamphetaminesa Opioidsa 19 19 19 19 19 19 β1 = 0.013c β = 0.004 18 18 18 18 18 18 β = 0.002 β = 0.001 17 17 17 17 17 17 c β = 0.005c β = 0.004c β2 = –0.014 16 16 16 16 16 16

15 15 15 15 15 15 Mean Age at Initiation, y 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 Year Year Year Year Year Year

PCP Sedativesa Smokeless tobaccoa Stimulantsa Tobacco cigarettes Tranquilizersa 19 19 19 19 19 19 β = 0.005c 18 18 18 18 18 18 β = –0.003 β = 0.003 β = 0.001c β = 0.006 17 17 17 17 17 17 β = 0.001 16 16 16 16 16 16

15 15 15 15 15 15 Mean Age at Initiation, y 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 2004 2008 2012 2016 Year Year Year Year Year Year

Data are from the National Survey on Drug Use and Health, 2004-2017 b P < .001. (N = 84 317 adolescents and young adults). Individuals who initiated drug use c Differences are significant (ecstasy, β = 0.003; P = .03; , are individuals aged 12 to 21 years with first-time drug use within 12 months β = 0.004; P = .004; heroin, β = 0.005; P = .02; inhalants; β = 0.004; prior to the survey. PCP indicates phenylcyclohexyl piperidine. P = .02; smokeless tobacco, β = 0.001; P = .002; stimulants, β = 0.005; a Because of survey methodological changes, mean ages from 2015 to 2017 are P = .007; lysergic acid diethylamide [LSD], β = −0.014; P = .04). not included.

phenylcyclohexyl piperidine (PCP), sedatives, and tranquil- at initiation may have already ended. Study limitations in- izers was noted. clude self-reported data and recall bias. The NSDUH survey The overall summary mean age at initiation and the does not yet include vaping and e- use. mean percentage change over the years of data for each drug Drug use, including marijuana, appears to be especially are presented in the Table. Adolescents and emerging adults harmful to developing brains. This study provides evidence began to use inhalants during early adolescence to midado- that, since 2004, a decreasing proportion of adolescents ini- lescence (mean age, 15.4 [95% CI, 15.2-15.6] years), the earli- tiate drugs at 15 years and younger, the age group typically clas- est mean age compared with those of other drugs. The mean sified as early onset.6 ages at initiation for cocaine and crack cocaine were 18.0 (95% CI, 17.7-18.2) years and 18.0 (95% CI, 17.8-18.2) years, Karl C. Alcover, PhD respectively, indicative of initiation in late adolescence or Christopher L. Thompson, MD, MHI the beginning of young adulthood. There were no significant changes in the trends in the mean ages at initiation of crack Author Affiliations: Elson S. Floyd College of Medicine, Department of Medical cocaine, methamphetamines, opioids, PCP, sedatives, and Education and Clinical Sciences, Washington State University, Spokane (Alcover); Peds AI, East Lansing, Michigan (Thompson). tranquilizers. Accepted for Publication: August 18, 2019.

Discussion | Our findings show that the mean age at initiation Corresponding Author: Karl C. Alcover, PhD, Elson Floyd College of Human Medicine, Department of Medical Education and Clinical Sciences, Washington is increasing for most drugs under study. For example, the State University, 665 N Riverpoint Blvd, Spokane, WA 99202 mean age at alcohol initiation was approximately 16 years in ([email protected]). 2004. By 2017, the mean age had risen to about 17 years—a full Published Online: March 2, 2020. doi:10.1001/jamapediatrics.2019.6235 year after the minimum age for an unrestricted driver’s li- Correction: This article was corrected on April 6, 2020, to replace an “Elson cense in the United States. For alcohol and LSD, the stable es- Floyd College of Human Medicine” with “Elson S. Floyd College of Medicine”; timates in recent years suggest that trends toward later ages add a degree, MHI, after the name of author Christopher L. Thompson, MD,

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Table. Meta-analytic Summary Estimates of Mean Age at Drug Initiation Among Individuals With Past-Year Initiation at Ages 12 to 21 Yearsa Meta-analytic Summary, Annual Percentage Psychoactive Drug Age, Mean (95% CI), y Change, % P Value Alcohol 2004-2014 0.4 <.001 16.5 (16.4-16.7) 2015-2017 0.1 .06 Cigar 17.0 (16.9-17.1) 0.3 <.001 Cocaine 18.0 (17.7-18.2) 0.5 <.001 Crack cocaine 18.0 (17.8-18.2) 0.3 .10 Ecstasy 17.6 (17.4-17.7) 0.3 .03 Hallucinogens 17.2 (17.0-17.3) 0.4 .004 Heroin 17.7 (17.4-18.0) 0.5 .02 Inhalants 15.4 (15.2-15.6) 0.4 .02 Lysergic acid diethylamide 2004-2009 1.3 .03 17.5 (17.3-17.7) 2010-2019 −0.1 .70 Marijuana 16.4 (16.3-16.5) 0.2 <.001 Methamphetamines 17.0 (16.7-17.3) 0.4 .16 Opioids 16.6 (16.6-16.7) 0.1 .13 Phenylcyclohexyl piperidine 16.2 (15.8-16.5) −0.2 .22 Sedatives 16.3 (16.0-16.6) 0.3 .37 Smokeless tobacco 16.7 (16.7-16.8) 0.1 .002 Stimulants 17.1 (17.0-17.3) 0.4 .008 Tobacco cigarettes 16.6 (16.4-16.8) 0.6 <.001 a Data from the National Survey on Drug Use and Health (N = 84 317 Tranquilizers 17.3 (17.2-17.4) 0.1 .19 adolescents and young adults).

MHI; specify that Dr Thompson’s affiliation is called “Peds AI” and not “Peds AI performance and brain activation. Dev Cogn Neurosci. 2015;16:84-92. Clinic”; and add 2 missing notations denoting significance to the graphs for cigar doi:10.1016/j.dcn.2015.03.003 and cocaine in the Figure. Author Contributions: Dr Alcover had full access to all of the data in the study Prevalence of Special Health Care Needs Among and takes responsibility for the integrity of the data and the accuracy of the data analysis. Foster Youth in a Nationally Representative Survey Concept and design: Alcover. Children in foster care have the highest rates of chronic con- Acquisition, analysis, or interpretation of data: Both authors. ditions of any child population.1 While the National Survey Drafting of the manuscript: Both authors. of Child and Adolescent Well-Being remains the gold stan- Critical revision of the manuscript for important intellectual content: Both authors. dard for data on special health care needs (SCHNs) of chil- Statistical analysis: Alcover. dren in foster care, the data do not permit comparisons Administrative, technical, or material support: Alcover. between children in foster care and other types of care.2 We Supervision: Both authors. address this gap by describing current rates of SHCNs and Conflict of Interest Disclosures: None reported. specific mental health and developmental conditions for 1. King KM, Chassin L. A prospective study of the effects of age of initiation of children across a range of caregiving circumstances. alcohol and drug use on young adult . J Stud Alcohol Drugs. 2007;68(2):256-265. doi:10.15288/jsad.2007.68.256 2. Chen C-Y, Storr CL, Anthony JC. Early-onset drug use and risk for drug Methods | We combined 2 years of parent-proxy survey data dependence problems. Addict Behav. 2009;34(3):319-322. doi:10.1016/j. from the 2016-2017 National Survey of Children’s Health addbeh.2008.10.021 (N = 71 811 households).3 Weighted estimates are representa- 3. Jordan CJ, Andersen SL. Sensitive periods of : Early risk for tive of children who are noninstitutionalized and aged 0 to 17 the transition to dependence. Dev Cogn Neurosci. 2017;25:29-44. doi:10.1016/j. years old in the United States. The mean overall response rate dcn.2016.10.004 was 39.1%. Because the study data are publicly available from 4. Bose J, Hedden SL, Lipari RN, Park-Lee E; Substance Abuse and Mental Health Services Administration. Key substance use and mental health indicators the US Census Bureau and deidentified, the study is not con- in the United States: results from the 2017 National Survey on Drug Use and sidered human subjects research and does not require insti- Health. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/ tutional review board approval. NSDUHFFR2017/NSDUHFFR2017.htm. Published 2018. Accessed January 21, 2020. For the first time in 2016, the National Survey of Chil- dren’s Health provided a public-use variable that identifies 5. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-188. doi:10.1016/0197-2456(86)90046-2 responses from foster parents as a category of caregivers. We 6. Sagar KA, Dahlgren MK, Gönenç A, Racine MT, Dreman MW, Gruber SA. The examined 4 mutually exclusive caregiver types: foster par- impact of initiation: early onset marijuana smokers demonstrate altered Stroop ents; biological or adoptive parents; other, related caregivers

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