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Sexually Transmitted Infection among Adolescents and Young Adults with Autism Spectrum Disorder: A Nationwide Longitudinal Study

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Title: Sexually Transmitted Infection among Adolescents and Young Adults with Autism Spectrum Disorder: A Nationwide Longitudinal Study
Language: English
Authors: Li, Juo-Chi, Tsai, Shih-Jen, Chen, Tzeng-Ji, Chen, Mu-Hong (ORCID 0000-0001-6516-1073)
Source: Journal of Autism and Developmental Disorders. Nov 2023 53(11):4457-4464.
Availability: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
Peer Reviewed: Y
Page Count: 8
Publication Date: 2023
Document Type: Journal Articles
Reports - Research
Descriptors: Sexually Transmitted Diseases, Autism Spectrum Disorders, Adolescents, Young Adults, Drug Therapy, Risk, Outcomes of Treatment, Patients, Sexuality
DOI: 10.1007/s10803-022-05732-7
ISSN: 0162-3257
1573-3432
Abstract: The association between autism spectrum disorder (ASD) and subsequent sexually transmitted infections (STIs) and the potential effects of medications on STI risk remain unknown. In all, 5076 adolescents and young adults with ASD and 57,060 age-/sex-matched individuals without ASD were enrolled between 2001 and 2009 and followed-up to the end of 2011 for identification of subsequent STIs. The results revealed that patients with ASD were prone to acquiring an STI [hazard ratio (HR) 3.36] compared with the comparison group. Long-term use of atypical antipsychotics was associated with a lower risk of acquiring an STI later in life compared with nonuse (HR 0.34). We recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD.
Abstractor: As Provided
Entry Date: 2023
Accession Number: EJ1394316
Database: ERIC
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  Value: <anid>AN0172396195;aut01nov.23;2023Oct03.05:10;v2.2.500</anid> <title id="AN0172396195-1">Sexually Transmitted Infection Among Adolescents and Young Adults with Autism Spectrum Disorder: A Nationwide Longitudinal Study </title> <p>The association between autism spectrum disorder (ASD) and subsequent sexually transmitted infections (STIs) and the potential effects of medications on STI risk remain unknown. In all, 5076 adolescents and young adults with ASD and 57,060 age-/sex-matched individuals without ASD were enrolled between 2001 and 2009 and followed-up to the end of 2011 for identification of subsequent STIs. The results revealed that patients with ASD were prone to acquiring an STI [hazard ratio (HR) 3.36] compared with the comparison group. Long-term use of atypical antipsychotics was associated with a lower risk of acquiring an STI later in life compared with nonuse (HR 0.34). We recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD.</p> <p>Keywords: Autism spectrum disorder; Sexually transmitted infection; Atypical antipsychotics</p> <p>Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s10803-022-05732-7.</p> <hd id="AN0172396195-2">Introduction</hd> <p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairment in social communication, restricted interests, and stereotyped or repetitive behaviors; it ranges in severity, with some patients having profound deficits but others being highly functioning (Lord et al., [<reflink idref="bib19" id="ref1">19</reflink>]). Up to approximately 2% of children and adolescents are estimated to have ASD (Xu et al., [<reflink idref="bib29" id="ref2">29</reflink>]). Patients with ASD often present with a wide range of developmental, psychiatric, physical, and neurologic comorbidities that can influence their functional status, treatment strategies, and childhood development (Gillberg & Billstedt, [<reflink idref="bib14" id="ref3">14</reflink>]).</p> <p>When individuals with ASD reach adolescence and adulthood, they experience sexual attraction and engage in sexual behavior much like their peers without ASD (George & Stokes, [<reflink idref="bib13" id="ref4">13</reflink>]). Adolescents acquire appropriate romantic behaviors and social skills through interactions with family, peers, and the media as well as through observation and sex education. One study demonstrated that adolescents with ASD receive less sexual education than their peers (Stokes & Kaur, [<reflink idref="bib25" id="ref5">25</reflink>]). Parents of children with ASD require additional support and guidance in providing sexual education for their children. Some parents are hesitant to support their child in establishing a sexual identity in case their child's sexual interest and activity consequently increase. However, the literature does not support this assumption (Tissot, [<reflink idref="bib28" id="ref6">28</reflink>]).</p> <p>In sexual education, sexually transmitted infections (STIs) are a crucial topic. According to the World Health Organization, more than 1 million people worldwide contract an STI every day. The incidence is increasing and is especially pronounced in adolescents (15 to 24 years of age) (Organization, [<reflink idref="bib20" id="ref7">20</reflink>]). Individuals with psychiatric disorders including schizophrenia, mood disorders, substance use disorder, and attention-deficit/hyperactivity disorder (ADHD) are at high risk for STIs (Chen et al., [<reflink idref="bib5" id="ref8">5</reflink>], [<reflink idref="bib9" id="ref9">9</reflink>]; Stevens et al., [<reflink idref="bib24" id="ref10">24</reflink>]).</p> <p>Evidence has been found that adolescents and young adults with ASD are more likely to develop health-related risky behaviors, including engaging in unprotected sex, than those without ASD (Sun et al., [<reflink idref="bib26" id="ref11">26</reflink>], [<reflink idref="bib27" id="ref12">27</reflink>]). Sun et al. further revealed that older age, depression, and lower score in the theory-of-mind test were risk factors for health-related risky behaviors in patients with ASD (Sun et al., [<reflink idref="bib26" id="ref13">26</reflink>]). However, Schmidt et al. determined that individuals with ASD are less likely to receive an STI diagnosis compared with those without ASD (Schmidt et al., [<reflink idref="bib22" id="ref14">22</reflink>]). A cross-sectional evaluation also indicated considerably lower rates of STIs among young adults with ASD than those without ASD (Fortuna et al., [<reflink idref="bib12" id="ref15">12</reflink>]). The limitations of these studies included small samples and use of the self-report of STIs rather than physician-assigned diagnoses, and these limitations reduced the diagnostic validity. Furthermore, these studies did not investigate the potential effects of medications on STI risk.</p> <p>In the current study, we used Taiwan's National Health Insurance Research Database (NHIRD), which is a nationally representative database of medical claims data, and adopted a longitudinal follow-up study design to investigate the risk of STIs—human immunodeficiency virus (HIV), syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis—among adolescents and young adults with ASD.</p> <hd id="AN0172396195-3">Methods</hd> <p></p> <hd id="AN0172396195-4">Data Source</hd> <p>Taiwan National Health Insurance Research Database (NHIRD) which consists of healthcare data from > 99% of the entire Taiwan population is audited and released by National Health Research Institute for scientific and study purposes. The database includes comprehensive information on insured individuals such as demographic data, dates of clinical visits, disease diagnoses, and medical interventions. Individual medical records included in the NHIRD are anonymous to protect patient privacy. The NHIRD has been used in numerous epidemiological studies in Taiwan (Chen et al., [<reflink idref="bib7" id="ref16">7</reflink>], [<reflink idref="bib6" id="ref17">6</reflink>]; Cheng et al., [<reflink idref="bib10" id="ref18">10</reflink>]; Huang et al., [<reflink idref="bib16" id="ref19">16</reflink>]). The diagnostic codes used in the present study are based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM). This study was approved by the Institutional Review Board of our Hospital.</p> <hd id="AN0172396195-5">Inclusion Criteria for Adolescents and Young Adults with ASD and for the Control Group</hd> <p>Adolescents aged between 12 and 19 years and young adults aged between 20 and 29 years who were diagnosed with ASD (ICD-9-CM code: 299) by board-certified psychiatrists between January 1, 2001, and December 31, 2009, and who had no history of STIs including HIV, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis, before enrollment were included in the ASD cohort. The time of enrollment was defined as the time of ASD diagnosis. Subjects of the age-, sex-, residence, and time-of-enrollment-matched (1:10) control cohort were randomly selected after eliminating the study cases, individuals who had been given a diagnosis of ASD at any time, and individuals with any type of STI. Diagnoses of STIs—including HIV, syphilis, genital warts, gonorrhea, chlamydial infection, and trichomoniasis—were identified during the follow-up period (from enrollment to December 31, 2011, or until death). Psychiatric comorbidities, including ADHD, alcohol use disorder, substance use disorder, schizophrenia, bipolar disorder, and major depressive disorder, were assessed as confounding factors in our study. The use of psychotropic medications (ADHD drugs, antidepressants, mood stabilizers and atypical antipsychotics) during the follow-up was also examined, and the study cohort was divided into 3 subgroups: nonusers [cumulative defined daily dose (cDDD) during the follow-up < 30), short-term users (cDDD = 30–364), and long-term users (cDDD ≥ 365). ADHD drugs included methylphenidate and atomoxetine. Antidepressants included fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, venlafaxine, duloxetine, milnacipran, buproprion, and mirtazapine. Mood stabilizers included lithium and anticonvulsants (carbamazepine, oxcarbazepine, valproate, lamotrigine, topiramate, and gabapentin), and atypical antipsychotics included aripiprazole, risperidone, paliperidone, olanzapine, amisulpride, ziprasidone, clozapine, and quetiapine. The urbanization levels of patients' residences (level 1 to level 5; level 1: most urbanized; level 5: least urbanized) were also assessed in our study (Liu et al., [<reflink idref="bib18" id="ref20">18</reflink>]).</p> <hd id="AN0172396195-6">Statistical Analysis</hd> <p>In intergroup comparisons, the F test was used for continuous variables and Pearson's X2 test for nominal variables, where appropriate. Cox regression analyses with adjustment of demographic data (age, sex, level of urbanization), psychiatric comorbidities, and medications were performed to calculate the hazard ratio (HR) with a 95% confidence interval (CI) for STIs among patients with ASD and the controls. The risks of specific STIs for patients with ASD were further analyzed. Subanalyses stratified by age group (adolescents and young adults) were also conducted to further assess the relationship between ASD and STI risk. Sensitivity analyses were performed to investigate the association between ASD and STI contraction after excluding the first year or first 3 years of observation. The specific effects of antidepressants, mood stabilizers and atypical antipsychotics on STI risk were investigated separately. A 2-tailed P-value of less than 0.05 was considered statistically significant. All data processing and statistical analyses were performed using SPSS version 17 software (SPSS Inc.) and SAS version 9.1 (SAS Institute, Cary, NC, USA).</p> <hd id="AN0172396195-7">Results</hd> <p>Our study enrolled 5076 adolescents and young adults aged 17.20 ± 4.58 years with ASD and 57,060 age/sex-matched controls, with a male predominance (78.2%). The ASD cohort exhibited an increased incidence of acquiring an STI (7.5 vs. 2.1 ‰, <emph>P</emph> < 0.001) and younger age at STI diagnosis (22.02 ± 5.65 vs. 28.50 ± 6.38 years, <emph>P</emph> < 0.001) compared with the control group (Table 1). The psychiatric comorbidities, including ADHD (25.5% vs. 1.7%, <emph>P</emph> < 0.001), schizophrenia (17.6% vs. 0.7%, P < 0.001), bipolar disorder (17.6% vs. 0.7%, <emph>P</emph> < 0.001), and major depressive disorder (3.0% vs. 0.8%, <emph>P</emph> < 0.001), were more common in the ASD cohort than in the control group (Table 1).</p> <p>Table 1 Demographic data and incidence of any STI among adolescents and young adults with ASD and controls</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left"><p>Adolescents and young adults with ASD (n = 5706)</p></th><th align="left"><p>Controls (n = 57,060)</p></th><th align="left"><p><italic>p</italic>-value</p></th></tr></thead><tbody><tr><td align="left"><p>Age at enrollment (years, SD, n, %)</p></td><td align="left"><p>17.20 (4.58)</p></td><td align="left"><p>17.20 (4.75)</p></td><td char="." align="char"><p>0.998</p></td></tr><tr><td align="left"><p>Sex (%)</p></td><td align="left" /><td align="left" /><td char="." align="char"><p>1.000</p></td></tr><tr><td align="left"><p> Male</p></td><td align="left"><p>4460 (78.2)</p></td><td align="left"><p>44,600 (78.2)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> Female</p></td><td align="left"><p>1246 (21.8)</p></td><td align="left"><p>12,460 (21.8)</p></td><td char="." align="char" /></tr><tr><td align="left"><p>ADHD drugs (n, %)</p></td><td align="left" /><td align="left" /><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>4639 (81.3)</p></td><td align="left"><p>56,600 (99.2)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 30–364 cDDD</p></td><td align="left"><p>653 (11.4)</p></td><td align="left"><p>335 (0.6)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> ≧365 cDDD</p></td><td align="left"><p>414 (7.3)</p></td><td align="left"><p>125 (0.2)</p></td><td char="." align="char" /></tr><tr><td align="left"><p>Antidepressants (n, %)</p></td><td align="left" /><td align="left" /><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>3524 (61.8)</p></td><td align="left"><p>55,588 (97.4)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 30–364 cDDD</p></td><td align="left"><p>1158 (20.3)</p></td><td align="left"><p>1073 (1.9)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> ≧365 cDDD</p></td><td align="left"><p>1024 (17.9)</p></td><td align="left"><p>399 (0.7)</p></td><td char="." align="char" /></tr><tr><td align="left"><p>Mood stabilizers (n, %)</p></td><td align="left" /><td align="left" /><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>3819 (66.9)</p></td><td align="left"><p>56,318 (98.7)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 30–364 cDDD</p></td><td align="left"><p>698 (12.2)</p></td><td align="left"><p>412 (0.7)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> ≧365 cDDD</p></td><td align="left"><p>1189 (20.8)</p></td><td align="left"><p>330 (0.6)</p></td><td char="." align="char" /></tr><tr><td align="left"><p>Atypical antipsychotics (n, %)</p></td><td align="left" /><td align="left" /><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>3413 (59.8)</p></td><td align="left"><p>56,542 (99.1)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 30–364 cDDD</p></td><td align="left"><p>1001 (17.5)</p></td><td align="left"><p>277 (0.5)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> ≧365 cDDD</p></td><td align="left"><p>1292 (22.6)</p></td><td align="left"><p>241 (0.4)</p></td><td char="." align="char" /></tr><tr><td align="left"><p>Incidence of any STI (n, ‰)</p></td><td align="left"><p>43 (7.5)</p></td><td align="left"><p>120 (2.1)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> HIV (n, ‰)</p></td><td align="left"><p>2 (0.4)</p></td><td align="left"><p>9 (0.2)</p></td><td char="." align="char"><p>0.264</p></td></tr><tr><td align="left"><p> Syphilis (n, ‰)</p></td><td align="left"><p>8 (0.1)</p></td><td align="left"><p>8 (0.0)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Genital warts (n, ‰)</p></td><td align="left"><p>11 (1.9)</p></td><td align="left"><p>26 (0.5)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Gonorrhea (n, ‰)</p></td><td align="left"><p>4 (0.7)</p></td><td align="left"><p>6 (0.2)</p></td><td char="." align="char"><p>0.009</p></td></tr><tr><td align="left"><p> Chlamydial infection (n, ‰)</p></td><td align="left"><p>9 (1.6)</p></td><td align="left"><p>16 (0.3)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Trichomoniasis (n, ‰)</p></td><td align="left"><p>11 (1.9)</p></td><td align="left"><p>60 (1.1)</p></td><td char="." align="char"><p>0.093</p></td></tr><tr><td align="left"><p>Age at any STI (years, SD)</p></td><td align="left"><p>22.02 (5.65)</p></td><td align="left"><p>28.50 (6.38)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p>Duration between enrollment and any STI (years, SD)</p></td><td align="left"><p>6.76 (2.83)</p></td><td align="left"><p>6.78 (2.83)</p></td><td char="." align="char"><p>0.635</p></td></tr><tr><td align="left"><p>Psychiatric comorbidities (n, %)</p></td><td align="left" /><td align="left" /><td char="." align="char" /></tr><tr><td align="left"><p> ADHD</p></td><td align="left"><p>1456 (25.5)</p></td><td align="left"><p>988 (1.7)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Schizophrenia</p></td><td align="left"><p>1007 (17.6)</p></td><td align="left"><p>406 (0.7)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Bipolar disorder</p></td><td align="left"><p>312 (5.5)</p></td><td align="left"><p>173 (0.3)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Major depressive disorder</p></td><td align="left"><p>171 (3.0)</p></td><td align="left"><p>484 (0.8)</p></td><td char="." align="char"><p> < 0.001</p></td></tr><tr><td align="left"><p> Alcohol use disorder</p></td><td align="left"><p>71 (1.2)</p></td><td align="left"><p>656 (1.1)</p></td><td char="." align="char"><p>0.520</p></td></tr><tr><td align="left"><p> Substance use disorder</p></td><td align="left"><p>101 (1.8)</p></td><td align="left"><p>915 (1.6)</p></td><td char="." align="char"><p>0.350</p></td></tr><tr><td align="left"><p>Level of urbanization</p></td><td align="left" /><td align="left" /><td char="." align="char"><p>1.000</p></td></tr><tr><td align="left"><p> 1 (most urbanized)</p></td><td align="left"><p>1066 (18.7)</p></td><td align="left"><p>10,660 (18.7)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 2</p></td><td align="left"><p>1736 (30.4)</p></td><td align="left"><p>17,360 (30.4)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 3</p></td><td align="left"><p>543 (9.5)</p></td><td align="left"><p>5430 (9.5)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 4</p></td><td align="left"><p>490 (8.6)</p></td><td align="left"><p>4900 (8.6)</p></td><td char="." align="char" /></tr><tr><td align="left"><p> 5 (most rural)</p></td><td align="left"><p>1871 (32.8)</p></td><td align="left"><p>18,710 (32.8)</p></td><td char="." align="char" /></tr></tbody></table> </ephtml> </p> <p> <emph>ASD</emph> autism spectrum disorder, <emph>STI</emph> sexually transmitted infection, <emph>ADHD</emph> Attention-deficit hyperactivity disorder, <emph>NTD</emph> new Taiwan dollar, <emph>SD</emph> standard deviation, <emph>cDDD</emph> cumulative defined daily dose</p> <p>The Kaplan–Meier survival curve indicated that patients with ASD had a significantly higher risk of developing any STI than the control group (P < 0.001) (Fig. 1). The Cox regression model showed that ASD increased the risk of subsequent STIs [HR 3.36 (95% CI 2.04–5.51)], including syphilis [HR 10.26 (95% CI 2.92–36.08)], genital warts [HR 3.13 (95% CI 1.15–8.52)], chlamydial infection [HR 5.25 (95% CI 1.65–16.74)], and trichomoniasis [HR 2.61 (95% CI 1.07–6.35)], after adjusting for demographic data, psychiatric comorbidities, and medications (Tables 2, 3). Sub-analyses stratified by age revealed that only adolescents [HR 7.59 (95% CI 3.81–15.12)] with ASD, but not young adults with ASD [HR 1.60 (95% CI 0.73–3.60)], were prone to acquiring an STI during the follow-up compared with the controls (Table 2). Sub-analyses stratified by sex found that males [HR 4.59 (95% CI 2.05–10.24)] and females [HR 2.91 (95% CI 1.52–5.59)] with ASD had an elevated risk of subsequent STIs compared with those without ASD (Table 2).</p> <p>Graph: Fig. 1Survival curve of developing any STI among adolescents and young adults with ASD and controls. ASD autism spectrum disorder, STI sexually transmitted infection</p> <p>Table 2 Cox regression analyses of the risk of any STI among adolescents and young adults with ASD and controls</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" /><th align="left"><p>Adolescents (< 20 years)</p></th><th align="left"><p>Young adults (20–29 years)</p></th><th align="left"><p>Male</p></th><th align="left"><p>Female</p></th><th align="left"><p>Total</p></th></tr><tr><th align="left"><p>HR (95% CI)</p></th><th align="left"><p>HR (95% CI)</p></th><th align="left"><p>HR (95% CI)</p></th><th align="left"><p>HR (95% CI)</p></th><th align="left"><p>HR (95% CI)</p></th></tr></thead><tbody><tr><td align="left"><p>ASD</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Absence</p></td><td align="left"><p>1 (ref)</p></td><td align="left"><p>1 (ref)</p></td><td align="left"><p>1 (ref)</p></td><td align="left"><p>1 (ref)</p></td><td align="left"><p>1 (ref)</p></td></tr><tr><td align="left"><p> Presence</p></td><td align="left"><p><bold>7.59 (3.81–15.12)</bold></p></td><td align="left"><p>1.60 (0.71–3.60)</p></td><td align="left"><p><bold>4.59 (2.05–10.24)</bold></p></td><td align="left"><p><bold>2.91 (1.52–5.56)</bold></p></td><td align="left"><p><bold>3.36 (2.04–5.51)</bold></p></td></tr></tbody></table> </ephtml> </p> <p>Bold type means the statistical significance (p < 0.05) <emph>ASD</emph> autism spectrum disorder, <emph>STI</emph> sexually transmitted infection, <emph>HR</emph> hazard ratio, <emph>CI</emph> confidence interval *Adjusted for demographic data, psychiatric comorbidities, and medications</p> <p>Table 3 Risk of each STI among adolescents and young adults with ASD and controls</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" /><th align="left"><p>HIV</p></th><th align="left"><p>Syphilis</p></th><th align="left"><p>Genital warts</p></th><th align="left"><p>Gonorrhea</p></th><th align="left"><p>Chlamydial infection</p></th><th align="left"><p>Trichomoniasis</p></th><th align="left"><p>Any STI</p></th></tr><tr><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th><th align="left"><p>(HR 95% CI)</p></th></tr></thead><tbody><tr><td align="left"><p>ASD</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p>Absence</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td><td align="left"><p>1</p></td></tr><tr><td align="left"><p>Presence</p></td><td align="left"><p>2.72 (0.33–22.25)</p></td><td align="left"><p><bold>10.26 (2.92–36.08)</bold></p></td><td align="left"><p><bold>3.13 (1.15–8.52)</bold></p></td><td align="left"><p>2.24 (0.36–14.04)</p></td><td align="left"><p><bold>5.25 (1.65–16.74)</bold></p></td><td align="left"><p><bold>2.61 (1.07–6.35)</bold></p></td><td align="left"><p><bold>3.36 (2.04–5.51)</bold></p></td></tr></tbody></table> </ephtml> </p> <p>Adjusted for demographic data, psychiatric comorbidities, and medications Bold type means the statistical significance (p < 0.05) <emph>ASD</emph> autism spectrum disorder, <emph>STI</emph> sexually transmitted infection, <emph>HR</emph> hazard ratio, <emph>CI</emph> confidence interval</p> <p>Long-term users [HR 0.34 (95% CI 0.14–0.84)] of atypical antipsychotics were associated with a decreased risk of acquiring an STI later in life compared with nonusers (Table 4). Sensitivity analyses after excluding the first year [HR 4.78 (95% CI 2.44–9.36)] or first 3 years [HR 2.65 (95% CI 1.09–6.41)] of observation had consistent findings that ASD was associated with an elevated risk of subsequent STIs (Table 5).</p> <p>Table 4 Medications and the risk of any STI among adolescents and young adults with ASD and controls</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" /><th align="left"><p>Total</p></th></tr><tr><th align="left"><p>HR (95% CI)</p></th></tr></thead><tbody><tr><td align="left"><p>ADHD drugs</p></td><td align="left" /></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>1 (ref.)</p></td></tr><tr><td align="left"><p>30 ~ 364 cDDD</p></td><td align="left"><p>0.79 (0.26–2.61)</p></td></tr><tr><td align="left"><p>≧365 cDDD</p></td><td align="left"><p>0.38 (0.05–3.09)</p></td></tr><tr><td align="left"><p>Antidepressants</p></td><td align="left" /></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>1 (ref.)</p></td></tr><tr><td align="left"><p>30 ~ 364 cDDD</p></td><td align="left"><p>1.23 (0.64–2.36)</p></td></tr><tr><td align="left"><p>≧365 cDDD</p></td><td align="left"><p>1.77 (0.89–3.52)</p></td></tr><tr><td align="left"><p>Mood stabilizers</p></td><td align="left" /></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>1 (ref.)</p></td></tr><tr><td align="left"><p>30 ~ 364 cDDD</p></td><td align="left"><p>1.17 (0.54–2.55)</p></td></tr><tr><td align="left"><p>≧365 cDDD</p></td><td align="left"><p>0.96 (0.46–1.97)</p></td></tr><tr><td align="left"><p>Atypical antipsychotics</p></td><td align="left" /></tr><tr><td align="left"><p> < 30 cDDD</p></td><td align="left"><p>1 (ref.)</p></td></tr><tr><td align="left"><p>30 ~ 364 cDDD</p></td><td align="left"><p>0.64 (0.29–1.41)</p></td></tr><tr><td align="left"><p>≧365 cDDD</p></td><td align="left"><p><bold>0.34 (0.14–0.84)</bold></p></td></tr></tbody></table> </ephtml> </p> <p>Adjusted for demographic data and psychiatric comorbidities Bold type means the statistical significance (p < 0.05) <emph>ASD</emph> autism spectrum disorder, <emph>STI</emph> sexually transmitted infection, <emph>HR</emph> hazard ratio, <emph>CI</emph> confidence interval, <emph>cDDD</emph> cumulative defined daily dose</p> <p>Table 5 Sensitivity analysis of the risk of any STI among adolescents and young adults with ASD and controls</p> <p> <ephtml> <table frame="hsides" rules="groups"><thead><tr><th align="left" /><th align="left" colspan="2"><p>Total</p></th><th align="left" colspan="2"><p>≧1 year<sup>a</sup></p></th><th align="left" colspan="2"><p>≧3 year<sup>b</sup></p></th></tr><tr><th align="left" /><th align="left"><p>HR</p></th><th align="left"><p>95% CI</p></th><th align="left"><p>HR</p></th><th align="left"><p>95% CI</p></th><th align="left"><p>HR</p></th><th align="left"><p>95% CI</p></th></tr></thead><tbody><tr><td align="left"><p>ASD</p></td><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /><td align="left" /></tr><tr><td align="left"><p> Absence</p></td><td align="left"><p>1</p></td><td align="left"><p>–</p></td><td align="left"><p>1</p></td><td align="left"><p>–</p></td><td align="left"><p>1</p></td><td align="left"><p>–</p></td></tr><tr><td align="left"><p> Presence</p></td><td align="left"><p><bold>3.36</bold></p></td><td align="left"><p><bold>2.04–5.51</bold></p></td><td align="left"><p><bold>4.78</bold></p></td><td align="left"><p><bold>2.44–9.36</bold></p></td><td align="left"><p><bold>2.65</bold></p></td><td align="left"><p><bold>1.09–6.41</bold></p></td></tr></tbody></table> </ephtml> </p> <p>Bold type means the statistical significance <emph>ASD</emph> autism spectrum disorder, <emph>STI</emph> sexually transmitted infection, <emph>HR</emph> hazard ratio, <emph>CI</emph> confidence interval *Adjusted for demographic data, psychiatric comorbidities, and medications <sups>a</sups>Excluding the first year of observation <sups>b</sups>Excluding the first 3-years of observation</p> <hd id="AN0172396195-8">Discussion</hd> <p>The association between ASD and STIs has received little attention. In our study, patients with ASD, especially adolescents, were at higher risk of contracting an STI—such as syphilis, genital warts, chlamydial infection, and trichomoniasis—compared with those without ASD. In addition, long-term treatment with atypical antipsychotics was related to a reduced STI risk.</p> <p>Several explanations are offered for the mechanisms underlying the relationship between ASD and the risk of acquiring an STI. First, deficits of inhibitory control are common in individuals with ASD. Schmitt et al. revealed that age-related improvements in inhibitory control during adolescence are reduced in those with ASD, which may increase the frequency of health-related risky behaviors (Schmitt et al., [<reflink idref="bib23" id="ref21">23</reflink>]). Impulsive decision-making is associated with risky sexual behaviors, elevating STI risk (Charnigo et al., [<reflink idref="bib4" id="ref22">4</reflink>]; Rodriguez-Nieto et al., [<reflink idref="bib21" id="ref23">21</reflink>]). Comorbidities of ADHD, schizophrenia, bipolar disorder, and major depressive disorder with ASD may also be associated with inhibitory control deficits, which indirectly increase the risk of STIs in patients with ASD (Chen et al., [<reflink idref="bib5" id="ref24">5</reflink>]; Stevens et al., [<reflink idref="bib24" id="ref25">24</reflink>]). However, because we fully adjusted for psychiatric comorbidities in the current study, we determined ASD to be an independent risk factor for contracting an STI later in life.</p> <p>Second, individuals with ASD have lower levels of sexual knowledge but more deficits in social communication and social interaction than their peers, which may cause individuals with ASD to be more likely to misunderstand intentions (Boria et al., [<reflink idref="bib1" id="ref26">1</reflink>]), miss social subtleties (Zürcher et al., [<reflink idref="bib30" id="ref27">30</reflink>]), and have limited peer interactions (Gonzalez-Lopez & Kamps, [<reflink idref="bib15" id="ref28">15</reflink>]). Brown-Lavoie et al. demonstrated that individuals with ASD were 2.53 to 3.35 times less likely to report that they had been given information related to STIs by their parents and teachers (Brown-Lavoie et al., [<reflink idref="bib3" id="ref29">3</reflink>]). Individuals with ASD may choose to acquire the majority of their sexual knowledge from nonsocial sources, including television, pornography, and the internet. These nonsocial sources are mostly unmonitored, potentially inaccurate, and not personalized to individuals with ASD. The barriers to acquiring crucial sexual knowledge and the lack of individualized sex education may result in low levels of sexual knowledge and low awareness of STI risks, further increasing the STI risk among individuals with ASD (Stokes & Kaur, [<reflink idref="bib25" id="ref30">25</reflink>]). Despite STIs share the similar transmission route, we found the difference in STI profiles between those with and without ASD. ASD group had higher proportion of syphilis (18%), genital warts (24%), and chlamydial infection (20%), and non-ASD group had higher proportion of trichomoniasis (48%) and HIV (7%), respectively (Supplementary Fig. 1). Further studies may be necessary to clarify this difference.</p> <p>Furthermore, the deficits in social communication and cognition, which are core symptoms of ASD, may cause individuals with ASD to misunderstand various sex-related social situations, further resulting in them engaging in inappropriate sexual behaviors (Brown et al., [<reflink idref="bib2" id="ref31">2</reflink>]). Brown et al. stated that college students with ASD reported a higher rate (8.2%) of unwanted sexual contact than did those without ASD (4.6%) (Brown et al., [<reflink idref="bib2" id="ref32">2</reflink>]). Sun et al. demonstrated that low scores in the theory-of-mind test were associated with risky sexual behaviors in patients with ASD (Sun et al., [<reflink idref="bib26" id="ref33">26</reflink>]).</p> <p>Finally, we noted that long-term treatment with atypical antipsychotics was related to a reduced risk of contracting an STI among patients with ASD. Fazel et al. determined that the anti-impulsivity effect of atypical antipsychotics reduced the prevalence of impulsivity-related risky behaviors, such as violence (Fazel et al., [<reflink idref="bib11" id="ref34">11</reflink>]). Our other studies also indicated that optimal and regular treatment with atypical antipsychotics reduced the STI risk among patients with schizophrenia and bipolar disorder (Chen et al., [<reflink idref="bib8" id="ref35">8</reflink>]; Liang et al., [<reflink idref="bib17" id="ref36">17</reflink>]), which are commonly comorbid with ASD. Further studies are necessary to clarify the direct effect (through treating ASD) or indirect effect (through treating psychiatric comorbidities) of atypical antipsychotics in the prevention of STIs among patients with ASD.</p> <p>This study has several limitations. First, the incidence of STIs may have been underestimated because only those who sought medical treatment and consultation were identified in the NHIRD. However, STI diagnoses in the NHIRD were assigned by board-certified physicians, thus ensuring diagnostic validity. Second, the NHIRD does not provide information on the severity of ASD symptoms; therefore, we could not investigate the association between ASD severity and the risk of contracting an STI. Additional clinical studies are required to elucidate this association. Third, the NHIRD does not provide information on factors such as psychosocial stress, personal lifestyle, and environmental factors; therefore, we were unable to investigate their potential influence.</p> <p>In conclusion, adolescents with ASD were more likely to contract an STI later in life compared with those without ASD. Following adjustment for demographic factors, psychiatric comorbidities, and medications, we discovered that ASD was an independent risk factor for STIs. Furthermore, long-term treatment with atypical antipsychotics for a cumulative exposure of ≥ 365 cDDD was related to a reduced risk of subsequent STIs. On the basis of these results, we recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD.</p> <hd id="AN0172396195-9">Acknowledgments</hd> <p>We thank Mr I-Fan Hu for his support and friendship.</p> <hd id="AN0172396195-10">Author Contributions</hd> <p>Dr MHC designed the study and wrote the protocol. Drs MHC and JCL draft manuscript. Dr MHC performed the statistical analyses. Drs MHC, TJC and SJT reviewed the draft and revision, assisted with the preparation and proof-reading of the manuscript.</p> <hd id="AN0172396195-11">Funding</hd> <p>Funding Source: The study was supported by grant from Taipei Veterans General Hospital (V111C-010, V111C-040, V111C-029), Yen Tjing Ling Medical Foundation (CI-109-21, CI-109-22, CI-110-30) and Ministry of Science and Technology, Taiwan (MOST110-2314-B-075-026, MOST110-2314-B-075-024 -MY3, MOST 109-2314-B-010-050-MY3, MOST111-2314-B-075 -014 -MY2, MOST 111-2314-B-075 -013). The funding source had no role in any process of our study. <emph>Financial Disclosure</emph> All authors have no financial relationships relevant to this article to disclose.</p> <hd id="AN0172396195-12">Data Availability</hd> <p>The NHIRD was released and audited by the Department of Health and Bureau of the NHI Program for the purpose of scientific research (https://nhird.nhri.org.tw/). NHIRD can be obtained through the formal application that is regulated by Department of Health and Bureau of the NHI Program.</p> <hd id="AN0172396195-13">Declarations</hd> <p></p> <hd id="AN0172396195-14">Conflict of interest</hd> <p>No conflict of interest.</p> <hd id="AN0172396195-15">Supplementary Information</hd> <p>Below is the link to the electronic supplementary material.</p> <p>Graph: Supplementary file1 (DOCX 145 kb)</p> <hd id="AN0172396195-16">Publisher's Note</hd> <p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p> <ref id="AN0172396195-17"> <title> References </title> <blist> <bibl id="bib1" idref="ref26" type="bt">1</bibl> <bibtext> Boria S, Fabbri-Destro M, Cattaneo L, Sparaci L, Sinigaglia C, Santelli E, Cossu G, Rizzolatti G. Intention understanding in autism. 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PLoS ONE. 2013; 8. 10.1371/journal.pone.0081206. 24324679. 3852523</bibtext> </blist> </ref> <aug> <p>By Juo-Chi Li; Shih-Jen Tsai; Tzeng-Ji Chen and Mu-Hong Chen</p> <p>Reported by Author; Author; Author; Author</p> </aug> <nolink nlid="nl1" bibid="bib19" firstref="ref1"></nolink> <nolink nlid="nl2" bibid="bib29" firstref="ref2"></nolink> <nolink nlid="nl3" bibid="bib14" firstref="ref3"></nolink> <nolink nlid="nl4" bibid="bib13" firstref="ref4"></nolink> <nolink nlid="nl5" bibid="bib25" firstref="ref5"></nolink> <nolink nlid="nl6" bibid="bib28" firstref="ref6"></nolink> <nolink nlid="nl7" bibid="bib20" firstref="ref7"></nolink> <nolink nlid="nl8" bibid="bib24" firstref="ref10"></nolink> <nolink nlid="nl9" bibid="bib26" firstref="ref11"></nolink> <nolink nlid="nl10" bibid="bib27" firstref="ref12"></nolink> <nolink nlid="nl11" bibid="bib22" firstref="ref14"></nolink> <nolink nlid="nl12" bibid="bib12" firstref="ref15"></nolink> <nolink nlid="nl13" bibid="bib10" firstref="ref18"></nolink> <nolink nlid="nl14" bibid="bib16" firstref="ref19"></nolink> <nolink nlid="nl15" bibid="bib18" firstref="ref20"></nolink> <nolink nlid="nl16" bibid="bib23" firstref="ref21"></nolink> <nolink nlid="nl17" bibid="bib21" firstref="ref23"></nolink> <nolink nlid="nl18" bibid="bib30" firstref="ref27"></nolink> <nolink nlid="nl19" bibid="bib15" firstref="ref28"></nolink> <nolink nlid="nl20" bibid="bib11" firstref="ref34"></nolink> <nolink nlid="nl21" bibid="bib17" firstref="ref36"></nolink>
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Items – Name: Title
  Label: Title
  Group: Ti
  Data: Sexually Transmitted Infection among Adolescents and Young Adults with Autism Spectrum Disorder: A Nationwide Longitudinal Study
– Name: Language
  Label: Language
  Group: Lang
  Data: English
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Li%2C+Juo-Chi%22">Li, Juo-Chi</searchLink><br /><searchLink fieldCode="AR" term="%22Tsai%2C+Shih-Jen%22">Tsai, Shih-Jen</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Tzeng-Ji%22">Chen, Tzeng-Ji</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Mu-Hong%22">Chen, Mu-Hong</searchLink> (ORCID <externalLink term="http://orcid.org/0000-0001-6516-1073">0000-0001-6516-1073</externalLink>)
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="SO" term="%22Journal+of+Autism+and+Developmental+Disorders%22"><i>Journal of Autism and Developmental Disorders</i></searchLink>. Nov 2023 53(11):4457-4464.
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  Label: Availability
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  Data: Springer. Available from: Springer Nature. One New York Plaza, Suite 4600, New York, NY 10004. Tel: 800-777-4643; Tel: 212-460-1500; Fax: 212-460-1700; e-mail: customerservice@springernature.com; Web site: https://link.springer.com/
– Name: PeerReviewed
  Label: Peer Reviewed
  Group: SrcInfo
  Data: Y
– Name: Pages
  Label: Page Count
  Group: Src
  Data: 8
– Name: DatePubCY
  Label: Publication Date
  Group: Date
  Data: 2023
– Name: TypeDocument
  Label: Document Type
  Group: TypDoc
  Data: Journal Articles<br />Reports - Research
– Name: Subject
  Label: Descriptors
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22Sexually+Transmitted+Diseases%22">Sexually Transmitted Diseases</searchLink><br /><searchLink fieldCode="DE" term="%22Autism+Spectrum+Disorders%22">Autism Spectrum Disorders</searchLink><br /><searchLink fieldCode="DE" term="%22Adolescents%22">Adolescents</searchLink><br /><searchLink fieldCode="DE" term="%22Young+Adults%22">Young Adults</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Therapy%22">Drug Therapy</searchLink><br /><searchLink fieldCode="DE" term="%22Risk%22">Risk</searchLink><br /><searchLink fieldCode="DE" term="%22Outcomes+of+Treatment%22">Outcomes of Treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Patients%22">Patients</searchLink><br /><searchLink fieldCode="DE" term="%22Sexuality%22">Sexuality</searchLink>
– Name: DOI
  Label: DOI
  Group: ID
  Data: 10.1007/s10803-022-05732-7
– Name: ISSN
  Label: ISSN
  Group: ISSN
  Data: 0162-3257<br />1573-3432
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: The association between autism spectrum disorder (ASD) and subsequent sexually transmitted infections (STIs) and the potential effects of medications on STI risk remain unknown. In all, 5076 adolescents and young adults with ASD and 57,060 age-/sex-matched individuals without ASD were enrolled between 2001 and 2009 and followed-up to the end of 2011 for identification of subsequent STIs. The results revealed that patients with ASD were prone to acquiring an STI [hazard ratio (HR) 3.36] compared with the comparison group. Long-term use of atypical antipsychotics was associated with a lower risk of acquiring an STI later in life compared with nonuse (HR 0.34). We recommend that clinicians closely monitor risky sexual behaviors and STI risk in patients with ASD.
– Name: AbstractInfo
  Label: Abstractor
  Group: Ab
  Data: As Provided
– Name: DateEntry
  Label: Entry Date
  Group: Date
  Data: 2023
– Name: AN
  Label: Accession Number
  Group: ID
  Data: EJ1394316
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=eric&AN=EJ1394316
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      – Type: doi
        Value: 10.1007/s10803-022-05732-7
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      – Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 8
        StartPage: 4457
    Subjects:
      – SubjectFull: Sexually Transmitted Diseases
        Type: general
      – SubjectFull: Autism Spectrum Disorders
        Type: general
      – SubjectFull: Adolescents
        Type: general
      – SubjectFull: Young Adults
        Type: general
      – SubjectFull: Drug Therapy
        Type: general
      – SubjectFull: Risk
        Type: general
      – SubjectFull: Outcomes of Treatment
        Type: general
      – SubjectFull: Patients
        Type: general
      – SubjectFull: Sexuality
        Type: general
    Titles:
      – TitleFull: Sexually Transmitted Infection among Adolescents and Young Adults with Autism Spectrum Disorder: A Nationwide Longitudinal Study
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            NameFull: Chen, Tzeng-Ji
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            – TitleFull: Journal of Autism and Developmental Disorders
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