{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:26:17Z","timestamp":1790778377501,"version":"4.1.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Is the risk of attention-deficit hyperactivity disorder (ADHD) increased in children born to mothers with infertility, or after receipt of fertility treatment, compared to mothers with unassisted conception?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>Infertility itself may be associated with ADHD in the offspring, which is not amplified by the use of fertility treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>Infertility, and use of fertility treatment, is common. The long-term neurodevelopmental outcome of a child born to a mother with infertility, including the risk of ADHD, remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This population-based cohort study comprised all singleton and multiple hospital births in Ontario, Canada, 2006\u20132014. Outcomes were assessed up to June 2020.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Linked administrative datasets were used to capture all hospital births in Ontario, maternal health and pregnancy measures, fertility treatment and child outcomes. Included were all children born at \u226524\u2009weeks gestation between 2006 and 2014, and who were alive at age 4\u2009years. The main exposure was mode of conception, namely (i) unassisted conception (reference group), (ii) infertility without fertility treatment (history of an infertility consultation with a physician within 2 years prior to conception but no fertility treatment), (iii) ovulation induction (OI) or intrauterine insemination (IUI) and (iv) IVF or intracytoplasmic sperm injection (ICSI). The main outcome was a diagnosis of ADHD after age 4\u2009years and assessed up to June 2020. Hazard ratios (HRs) were adjusted for maternal age, income quintile, rurality, immigration status, smoking, obesity, parity, any drug or alcohol use, maternal history of mental illness including ADHD, pre-pregnancy diabetes mellitus or chronic hypertension and infant sex. In addition, we performed pre-planned stratified analyses by mode of delivery (vaginal or caesarean delivery), infant sex, multiplicity (singleton or multiple), timing of birth (term or preterm &amp;lt;37\u2009weeks) and neonatal adverse morbidity (absent or present).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>The study included 925\u00a0488 children born to 663\u00a0144 mothers, of whom 805\u00a0748 (87%) were from an unassisted conception, 94\u00a0206 (10.2%) followed infertility but no fertility treatment, 11\u00a0777 (1.3%) followed OI\/IUI and 13\u00a0757 (1.5%) followed IVF\/ICSI. Starting at age 4\u2009years, children were followed for a median (interquartile range) of 6 (4\u20138) years. ADHD occurred among 7.0% of offspring in the unassisted conception group, 7.5% in the infertility without fertility treatment group, 6.8% in the OI\/IUI group and 6.3% in the IVF\/ICSI group. The incidence rate (per 1000 person-years) of ADHD was 12.0 among children in the unassisted conception group, 12.8 in the infertility without fertility treatment group, 12.9 in the OI\/IUI group and 12.2 in the IVF\/ICSI group. Relative to the unassisted conception group, the adjusted HR for ADHD was 1.19 (95% CI 1.16\u20131.22) in the infertility without fertility treatment group, 1.09 (95% CI 1.01\u20131.17) in the OI\/IUI group and 1.12 (95% CI 1.04\u20131.20) in the IVF\/ICSI group. In the stratified analyses, these patterns of risk for ADHD were largely preserved. An exception was seen in the sex-stratified analyses, wherein females had lower absolute rates of ADHD but relatively higher HRs compared with that seen among males.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Some mothers in the isolated infertility group may have received undocumented OI oral therapy, thereby leading to possible misclassification of their exposure status. Parenting behaviour, schooling and paternal mental health measures were not known, leading to potential residual confounding.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Infertility, even without treatment, is a modest risk factor for the development of ADHD in childhood. The reason underlying this finding warrants further study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(s)<\/jats:title>\n                    <jats:p>This study was made possible with funding from the Canadian Institutes of Health Research, Grant number PJT 165840. The authors report no conflict of interest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deac129","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T10:18:42Z","timestamp":1654597122000},"page":"2126-2134","source":"Crossref","is-referenced-by-count":27,"title":["Attention-deficit hyperactivity disorder in children born to mothers with infertility: a population-based cohort study"],"prefix":"10.1093","volume":"37","author":[{"given":"Alexa","family":"Fine","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Queen\u2019s University, Kingston Health Sciences Centre , Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Dayan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Obstetrics and Gynaecology and Research Institute, McGill University Health Centre , Montreal, QC, Canada"},{"name":"Department of Epidemiology, Biostatistics and Occupational Health, McGill University , Montreal, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Djerboua","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Pudwell","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Queen\u2019s University, Kingston Health Sciences Centre , Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deshayne B","family":"Fell","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON, Canada"},{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute , Ottawa, ON, Canada"},{"name":"School of Epidemiology and Public Health, University of Ottawa , Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone N","family":"Vigod","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON, Canada"},{"name":"Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto , Toronto, ON, Canada"},{"name":"Women\u2019s College Hospital and Women\u2019s College Research Institute , Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel G","family":"Ray","sequence":"additional","affiliation":[{"name":"ICES , Toronto, ON, Canada"},{"name":"Department of Medicine and Obstetrics and Gynaecology, Temerty Faculty of Medicine, University of Toronto, St Michael\u2019s Hospital , Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4834-8279","authenticated-orcid":false,"given":"Maria P","family":"Velez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Queen\u2019s University, Kingston Health Sciences Centre , Kingston, ON, Canada"},{"name":"ICES , Toronto, ON, Canada"},{"name":"Department of Public Health Sciences, Queen\u2019s University , Kingston, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,7]]},"reference":[{"key":"2022090106013057200_deac129-B1","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1111\/1471-0528.12907","article-title":"Fertility treatment and child intelligence, attention, and executive functions in 5-year-old singletons: a cohort study","volume":"121","author":"Bay","year":"2014","journal-title":"BJOG"},{"key":"2022090106013057200_deac129-B2","doi-asserted-by":"crossref","first-page":"f3978","DOI":"10.1136\/bmj.f3978","article-title":"Fertility treatment and risk of childhood and adolescent mental disorders: register based cohort study","volume":"347","author":"Bay","year":"2013","journal-title":"BMJ"},{"key":"2022090106013057200_deac129-B3","doi-asserted-by":"crossref","first-page":"2116","DOI":"10.1210\/jc.2017-02667","article-title":"Polycystic ovary syndrome is associated with adverse mental health and neurodevelopmental outcomes","volume":"103","author":"Berni","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"key":"2022090106013057200_deac129-B4","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1016\/j.fertnstert.2009.12.023","article-title":"A cross-sectional evaluation of the first cohort of young adults conceived by in vitro fertilization in the United States","volume":"94","author":"Beydoun","year":"2010","journal-title":"Fertil Steril"},{"key":"2022090106013057200_deac129-B5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1055\/s-0031-1284225","article-title":"Role of gender in morbidity and mortality of extremely premature neonates","volume":"29","author":"Binet","year":"2012","journal-title":"Am J Perinatol"},{"key":"2022090106013057200_deac129-B6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.jaac.2015.03.013","article-title":"Parental age and the risk of attention-deficit\/hyperactivity disorder: a nationwide, population-based cohort study","volume":"54","author":"Chudal","year":"2015","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2022090106013057200_deac129-B7","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1111\/jcpp.12351","article-title":"Research review: Birth by caesarean section and development of autism spectrum disorder and attention-deficit\/hyperactivity disorder: a systematic review and meta-analysis","volume":"56","author":"Curran","year":"2015","journal-title":"J Child Psychol Psychiatry"},{"key":"2022090106013057200_deac129-B8","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1001\/jamapsychiatry.2013.4525","article-title":"Paternal age at childbearing and offspring psychiatric and academic morbidity","volume":"71","author":"D'Onofrio","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2022090106013057200_deac129-B9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s10815-012-9715-0","article-title":"Epigenetics and its role in male infertility","volume":"29","author":"Dada","year":"2012","journal-title":"J Assist Reprod Genet"},{"key":"2022090106013057200_deac129-B10","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.fertnstert.2013.10.028","article-title":"Identifying women with indicators of subfertility in a statewide population database: operationalizing the missing link in assisted reproductive technology research","volume":"101","author":"Declercq","year":"2014","journal-title":"Fertil Steril"},{"key":"2022090106013057200_deac129-B11","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s00404-020-05593-4","article-title":"Neonatal outcomes in singleton pregnancies conceived by fresh or frozen embryo transfer compared to spontaneous conceptions: a systematic review and meta-analysis","volume":"302","author":"Elias","year":"2020","journal-title":"Arch Gynecol Obstet"},{"key":"2022090106013057200_deac129-B12","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.fertnstert.2014.01.006","article-title":"Comparing indicators of health and development of singleton young adults conceived with and without assisted reproductive technology","volume":"101","author":"Halliday","year":"2014","journal-title":"Fertil Steril"},{"key":"2022090106013057200_deac129-B13","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.biopsych.2011.11.013","article-title":"Pre-and perinatal risk factors in adults with attention-deficit\/hyperactivity disorder","volume":"71","author":"Halm\u00f8y","year":"2012","journal-title":"Biol Psychiatry"},{"key":"2022090106013057200_deac129-B14","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1093\/humupd\/dmt002","article-title":"The longer-term health outcomes for children born as a result of IVF treatment. Part II\u2013Mental health and development outcomes","volume":"19","author":"Hart","year":"2013","journal-title":"Hum Reprod Update"},{"key":"2022090106013057200_deac129-B15","first-page":"409","article-title":"Parental age and attention-deficit\/hyperactivity disorder (ADHD)","volume":"46","author":"Hvolgaard Mikkelsen","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2022090106013057200_deac129-B16","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.ejpn.2010.12.004","article-title":"Is there an increased risk for drug treated attention deficit\/hyperactivity disorder in children born after in vitro fertilization?","volume":"15","author":"K\u00e4ll\u00e9n","year":"2011","journal-title":"Eur J Paediatr Neurol"},{"key":"2022090106013057200_deac129-B17","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2018-0776","article-title":"The risk of offspring psychiatric disorders in the setting of maternal obesity and diabetes","volume":"142","author":"Kong","year":"2018","journal-title":"Pediatrics"},{"key":"2022090106013057200_deac129-B18","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1186\/s12884-021-03711-x","article-title":"Caesarean section in pregnancies conceived by assisted reproductive technology: a systematic review and meta-analysis","volume":"21","author":"Lodge-Tulloch","year":"2021","journal-title":"BMC Pregnancy Childbirth"},{"key":"2022090106013057200_deac129-B19","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1093\/humrep\/deq218","article-title":"Achievement test performance in children conceived by IVF","volume":"25","author":"Mains","year":"2010","journal-title":"Hum Reprod"},{"key":"2022090106013057200_deac129-B20","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1001\/jamapsychiatry.2013.4081","article-title":"A comprehensive assessment of parental age and psychiatric disorders","volume":"71","author":"McGrath","year":"2014","journal-title":"JAMA Psychiatry"},{"key":"2022090106013057200_deac129-B21","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1093\/humrep\/des347","article-title":"Infertility and the risk of adverse pregnancy outcomes: a systematic review and meta-analysis","volume":"28","author":"Messerlian","year":"2013","journal-title":"Hum Reprod"},{"key":"2022090106013057200_deac129-B22","author":"Ontario","year":"2019"},{"key":"2022090106013057200_deac129-B23","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/1742-4755-1-6","article-title":"Genomic imprinting and assisted reproduction","volume":"1","author":"Paoloni-Giacobino","year":"2004","journal-title":"Reprod Health"},{"key":"2022090106013057200_deac129-B24","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1111\/1471-0528.17019","article-title":"Caesarean birth in women with infertility: population-based cohort study","volume":"129","author":"Richmond","year":"2022","journal-title":"BJOG"},{"key":"2022090106013057200_deac129-B25","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1007\/s00787-019-01433-2","article-title":"The risk of psychiatric disorders among Finnish ART and spontaneously conceived children: Finnish population-based register study","volume":"29","author":"Rissanen","year":"2020","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"2022090106013057200_deac129-B26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11920-017-0753-2","article-title":"Prenatal risk factors and the etiology of ADHD\u2014review of existing evidence","volume":"19","author":"Sciberras","year":"2017","journal-title":"Curr Psychiatry Rep"},{"key":"2022090106013057200_deac129-B27","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/humrep\/dev172","article-title":"Mental disorders in childhood and young adulthood among children born to women with fertility problems","volume":"30","author":"Svahn","year":"2015","journal-title":"Hum Reprod"},{"key":"2022090106013057200_deac129-B28","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1093\/humupd\/dmv044","article-title":"Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome","volume":"22","author":"Vannuccini","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2022090106013057200_deac129-B29","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1177\/0706743717714468","article-title":"Temporal trends in the prevalence and incidence of diagnosed ADHD in children and young adults between 1999 and 2012 in Canada: a data linkage study","volume":"62","author":"Vasiliadis","year":"2017","journal-title":"Can J Psychiatry"},{"key":"2022090106013057200_deac129-B30","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1093\/humrep\/deu067","article-title":"Universal coverage of IVF pays off","volume":"29","author":"Velez","year":"2014","journal-title":"Hum Reprod"},{"key":"2022090106013057200_deac129-B31","first-page":"1","article-title":"Diagnostic experiences of children with attention-deficit\/hyperactivity disorder","volume":"81","author":"Visser","year":"2015","journal-title":"Natl Health Stat Report"},{"key":"2022090106013057200_deac129-B32","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1093\/humrep\/den455","article-title":"Information processing, attention and visual-motor function of adolescents born after in vitro fertilization compared with spontaneous conception","volume":"24","author":"Wagenaar","year":"2009","journal-title":"Hum Reprod"},{"key":"2022090106013057200_deac129-B33","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1007\/s10995-016-2047-4","article-title":"Severe neonatal morbidity among births to refugee women","volume":"20","author":"Wanigaratne","year":"2016","journal-title":"Matern Child Health J"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/37\/9\/2126\/45537109\/deac129.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/humrep\/article-pdf\/37\/9\/2126\/45537109\/deac129.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T02:12:41Z","timestamp":1661998361000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/37\/9\/2126\/6603694"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,7]]},"references-count":33,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,6,7]]},"published-print":{"date-parts":[[2022,8,25]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deac129","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9,1]]},"published":{"date-parts":[[2022,6,7]]}}}