{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T11:09:22Z","timestamp":1792580962919,"version":"4.5.0"},"reference-count":30,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit\/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n A co-twin design was applied to this case-control study conducted in Sweden. Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n Birth weight.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Categorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n The study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized \u03b2 [B],\u2009\u22125.51 [95% CI, \u221210.09 to \u22120.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, \u221217.35 [95% CI, \u221228.66 to \u22126.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, \u22120.25 [95% CI, \u22120.39 to \u22120.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n The findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.21165","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T11:31:35Z","timestamp":1688124695000},"page":"e2321165","source":"Crossref","is-referenced-by-count":26,"title":["Evaluation of Birth Weight and Neurodevelopmental Conditions Among Monozygotic and Dizygotic Twins"],"prefix":"10.1001","volume":"6","author":[{"given":"Johan","family":"Isaksson","sequence":"first","affiliation":[{"name":"Child and Adolescent Psychiatry Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"},{"name":"Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladislav","family":"Ruchkin","sequence":"additional","affiliation":[{"name":"Child and Adolescent Psychiatry Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"},{"name":"Child Study Center, Yale University School of Medicine, New Haven, Connecticut"},{"name":"Sala Forensic Psychiatric Clinic, Sala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"Ljungstr\u00f6m","sequence":"additional","affiliation":[{"name":"Child and Adolescent Psychiatry Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"B\u00f6lte","sequence":"additional","affiliation":[{"name":"Center of Neurodevelopmental Disorders, Centre for Psychiatry Research, Department of Women\u2019s and Children\u2019s Health, Karolinska Institutet and Stockholm Health Care Services, Stockholm, Sweden"},{"name":"Curtin Autism Research Group, School of Occupational Therapy, Social Work and Speech Pathology, Curtin University, Perth, Australia"},{"name":"Child and Adolescent Psychiatry, Stockholm Health Care Services, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"issue":"4","key":"zoi230625r1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2019-0811","article-title":"Prevalence and trends of developmental disabilities among children in the United States: 2009-2017.","volume":"144","author":"Zablotsky","year":"2019","journal-title":"Pediatrics"},{"issue":"2","key":"zoi230625r2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/mp.2017.17","article-title":"The familial co-aggregation of ASD and ADHD: a register-based cohort study.","volume":"23","author":"Ghirardi","year":"2018","journal-title":"Mol Psychiatry"},{"key":"zoi230625r3","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/j.neubiorev.2021.01.022","article-title":"The World Federation of ADHD international consensus statement: 208 evidence-based conclusions about the disorder.","volume":"128","author":"Faraone","year":"2021","journal-title":"Neurosci Biobehav Rev"},{"issue":"4","key":"zoi230625r4","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1017\/S0954579420000620","article-title":"Early environmental risk factors for neurodevelopmental disorders\u2014a systematic review of twin and sibling studies.","volume":"33","author":"Carlsson","year":"2021","journal-title":"Dev Psychopathol"},{"issue":"5","key":"zoi230625r5","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1016\/j.jpeds.2012.04.058","article-title":"Risk of autism spectrum disorders in low birth weight and small for gestational age infants.","volume":"161","author":"Lampi","year":"2012","journal-title":"J Pediatr"},{"issue":"1","key":"zoi230625r6","doi-asserted-by":"publisher","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"},{"issue":"1","key":"zoi230625r7","doi-asserted-by":"publisher","first-page":"18035","DOI":"10.1038\/s41598-017-18234-9","article-title":"A gradient relationship between low birth weight and IQ: a meta-analysis.","volume":"7","author":"Gu","year":"2017","journal-title":"Sci Rep"},{"issue":"4","key":"zoi230625r8","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1176\/appi.ajp.2016.16020138","article-title":"Fetal origins of mental health: the developmental origins of health and disease hypothesis.","volume":"174","author":"O\u2019Donnell","year":"2017","journal-title":"Am J Psychiatry"},{"issue":"1","key":"zoi230625r9","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2016.269","article-title":"Medical history of discordant twins and environmental etiologies of autism.","volume":"7","author":"Willfors","year":"2017","journal-title":"Transl Psychiatry"},{"issue":"5","key":"zoi230625r10","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1017\/S0033291711002339","article-title":"Lower birth weight indicates higher risk of autistic traits in discordant twin pairs.","volume":"42","author":"Losh","year":"2012","journal-title":"Psychol Med"},{"issue":"1","key":"zoi230625r11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1097\/01.chi.0000242244.00174.d9","article-title":"Attention problems and attention-deficit\/hyperactivity disorder in discordant and concordant monozygotic twins: evidence of environmental mediators.","volume":"46","author":"Lehn","year":"2007","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"12","key":"zoi230625r12","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1016\/j.jaac.2011.09.007","article-title":"Evidence for a causal association of low birth weight and attention problems.","volume":"50","author":"Groen-Blokhuis","year":"2011","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"3","key":"zoi230625r13","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1097\/01.chi.0000246059.62706.22","article-title":"Birth weight and attention-deficit\/hyperactivity symptoms in childhood and early adolescence: a prospective Swedish twin study.","volume":"46","author":"Hultman","year":"2007","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"4","key":"zoi230625r14","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1111\/jcpp.12299","article-title":"Birth weight as an independent predictor of ADHD symptoms: a within-twin pair analysis.","volume":"56","author":"Pettersson","year":"2015","journal-title":"J Child Psychol Psychiatry"},{"issue":"2","key":"zoi230625r15","doi-asserted-by":"publisher","first-page":"F22","DOI":"10.1111\/desc.2006.9.issue-2","article-title":"Birthweight-discordance and differences in early parenting relate to monozygotic twin differences in behaviour problems and academic achievement at age 7.","volume":"9","author":"Asbury","year":"2006","journal-title":"Dev Sci"},{"issue":"3","key":"zoi230625r16","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1017\/thg.2018.13","article-title":"The association of intrapair birth-weight differences with internalizing and externalizing behavior problems.","volume":"21","author":"Tore","year":"2018","journal-title":"Twin Res Hum Genet"},{"issue":"4","key":"zoi230625r17","doi-asserted-by":"publisher","first-page":"F310","DOI":"10.1136\/adc.2002.021626","article-title":"Long term outcome of small versus appropriate size for gestational age co-twins\/triplets.","volume":"89","author":"Monset-Couchard","year":"2004","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"zoi230625r18","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1212\/WNL.15.4.341","article-title":"The relationship between intelligence and birth weight in twins.","volume":"15","author":"Churchill","year":"1965","journal-title":"Neurology"},{"issue":"2","key":"zoi230625r19","doi-asserted-by":"publisher","first-page":"25161","DOI":"10.1080\/02646830701292324","article-title":"Cognitive and verbal development of discordant twins without neurological morbidity.","volume":"25","author":"Bellido-Gonz\u00e1lez","year":"2007","journal-title":"J Reprod Infant Psychol"},{"issue":"1","key":"zoi230625r20","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s13229-022-00487-5","article-title":"Nonshared environmental factors in the aetiology of autism and other neurodevelopmental conditions: a monozygotic co-twin control study.","volume":"13","author":"Isaksson","year":"2022","journal-title":"Mol Autism"},{"issue":"1","key":"zoi230625r21","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ajog.2012.10.880","article-title":"Twin-twin transfusion syndrome.","volume":"208","author":"Simpson","year":"2013","journal-title":"Am J Obstet Gynecol"},{"issue":"3","key":"zoi230625r22","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1017\/thg.2014.12","article-title":"The Roots of Autism and ADHD Twin Study in Sweden (RATSS).","volume":"17","author":"B\u00f6lte","year":"2014","journal-title":"Twin Res Hum Genet"},{"issue":"4","key":"zoi230625r23","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1375\/twin.10.4.604","article-title":"Large-scale zygosity testing using single nucleotide polymorphisms.","volume":"10","author":"Hannelius","year":"2007","journal-title":"Twin Res Hum Genet"},{"issue":"3","key":"zoi230625r24","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1111\/biom.2008.64.issue-3","article-title":"Conditional generalized estimating equations for the analysis of clustered and longitudinal data.","volume":"64","author":"Goetgeluk","year":"2008","journal-title":"Biometrics"},{"issue":"1","key":"zoi230625r25","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1515\/em-2014-0021","article-title":"Doubly robust estimation with the R package drgee.","volume":"4","author":"Zetterqvist","year":"2015","journal-title":"Epidemiol Methods"},{"key":"zoi230625r26","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1186\/1471-2431-10-91","article-title":"Behavioural symptoms of attention deficit\/hyperactivity disorder in preterm and term children born small and appropriate for gestational age: a longitudinal study.","volume":"10","author":"Heinonen","year":"2010","journal-title":"BMC Pediatr"},{"issue":"4","key":"zoi230625r27","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1177\/0165025409340805","article-title":"The discordant MZ-twin method: one step closer to the holy grail of causality.","volume":"33","author":"Vitaro","year":"2009","journal-title":"Int J Behav Dev"},{"issue":"1","key":"zoi230625r28","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1017\/S0001566000001859","article-title":"Zygosity as a risk factor for complications and outcomes of twin pregnancy.","volume":"44","author":"Hoskins","year":"1995","journal-title":"Acta Genet Med Gemellol (Roma)"},{"issue":"6","key":"zoi230625r29","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1017\/S0033291700035856","article-title":"The treated incidence of psychotic and affective illness in twins compared with population expectation: a study in the Swedish Twin and Psychiatric Registries.","volume":"26","author":"Kendler","year":"1996","journal-title":"Psychol Med"},{"issue":"17","key":"zoi230625r30","doi-asserted-by":"publisher","first-page":"1770","DOI":"10.1001\/jama.2014.4144","article-title":"The familial risk of autism.","volume":"311","author":"Sandin","year":"2014","journal-title":"JAMA"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2806714\/isaksson_2023_oi_230625_1687536386.07343.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T11:31:39Z","timestamp":1688124699000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2806714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,30]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.21165","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,30]]}}}