{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:12:48Z","timestamp":1787008368416,"version":"build-2736575974"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 MH120824"],"award-info":[{"award-number":["R21 MH120824"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["2017-00134"],"award-info":[{"award-number":["2017-00134"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>We investigated the relationships between syndromic manifestations of defective placentation and the incidence of intellectual disability (ID) in offspring by conducting a population-based cohort study of 1,581,200 nonmalformed, live singleton infants born in Sweden between 1998 and 2014. Exposures were: 1) placental abruption, 2) preterm preeclampsia (&amp;lt;34 weeks of gestation), 3) preeclampsia combined with infant being small for gestational age (SGA) at birth, and 4) spontaneous preterm birth. The outcome was an ID diagnosis after 3 years of age. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for each syndrome using Cox regression and robust variances. There were 9,451 children with ID (5.5 per 10,000 child-years). ID incidence rates increased with placental abruption (HR\u00a0= 2.8, 95% CI: 2.3, 3.5), preterm preeclampsia (HR\u00a0= 3.7, 95% CI: 2.9, 4.7), preeclampsia combined with SGA (HR\u00a0= 3.3, 95% CI: 2.6, 4.1), and spontaneous preterm birth (for 32\u201336 and 22\u201331 weeks, respectively, HR = 1.6 (95% CI: 1.4, 1.8) and 5.2 (95% CI: 4.3, 6.2)). The same pattern of results was evident in sibling-controlled analyses among 1,043,158 full siblings. The strength of associations increased with ID severity. Preterm birth only partly explained the associations of placental abruption, preeclampsia, or SGA with ID. We conclude that defective placentation is related to increased incidence of ID in the offspring.<\/jats:p>","DOI":"10.1093\/aje\/kwac068","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T09:54:14Z","timestamp":1649152454000},"page":"1557-1567","source":"Crossref","is-referenced-by-count":6,"title":["Defective Placentation Syndromes and Intellectual Disability in the Offspring: Nationwide Cohort and Sibling-Controlled Studies"],"prefix":"10.1093","volume":"191","author":[{"given":"Eduardo","family":"Villamor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ezra S","family":"Susser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Cnattingius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"issue":"1","key":"2022103011175530600_ref1","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2019-2623","article-title":"Global burden of childhood epilepsy, intellectual disability, and sensory impairments","volume":"146","author":"Olusanya","year":"2020","journal-title":"Pediatrics."},{"issue":"4","key":"2022103011175530600_ref2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1073\/pnas.1508093112","article-title":"Discontinuity in the genetic and environmental causes of the intellectual disability spectrum","volume":"113","author":"Reichenberg","year":"2016","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"4","key":"2022103011175530600_ref3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0153655","article-title":"Prenatal, perinatal and neonatal risk factors for intellectual disability: a systemic review and meta-analysis","volume":"11","author":"Huang","year":"2016","journal-title":"PLoS One."},{"issue":"4","key":"2022103011175530600_ref4","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1001\/jamapediatrics.2017.5323","article-title":"Cognitive outcomes of children born extremely or very preterm since the 1990s and associated risk factors: a meta-analysis and meta-regression","volume":"172","author":"Twilhaar","year":"2018","journal-title":"JAMA Pediatr."},{"issue":"7","key":"2022103011175530600_ref5","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s10654-017-0340-1","article-title":"Gestational age at birth and risk of intellectual disability without a common genetic cause","volume":"33","author":"Heuvelman","year":"2018","journal-title":"Eur J Epidemiol."},{"issue":"1","key":"2022103011175530600_ref6","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3109\/10641955.2010.507837","article-title":"The risk of intellectual disability in children born to mothers with preeclampsia or eclampsia with partial mediation by low birth weight","volume":"30","author":"Griffith","year":"2011","journal-title":"Hypertens Pregnancy."},{"issue":"8","key":"2022103011175530600_ref7","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1001\/jamapsychiatry.2020.0306","article-title":"Association of Preeclampsia in term births with neurodevelopmental disorders in offspring","volume":"77","author":"Sun","year":"2020","journal-title":"JAMA Psychiat."},{"issue":"9","key":"2022103011175530600_ref8","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1111\/dmcn.14893","article-title":"Childhood neurodevelopmental disorders and maternal hypertensive disorder of pregnancy","volume":"63","author":"Chen","year":"2021","journal-title":"Dev Med Child Neurol."},{"issue":"3","key":"2022103011175530600_ref9","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/1471-0528.14049","article-title":"Neurodevelopmental outcomes in children in relation to placental abruption","volume":"124","author":"Ananth","year":"2017","journal-title":"BJOG."},{"issue":"7308","key":"2022103011175530600_ref10","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1136\/bmj.323.7308.310","article-title":"Influence of variation in birth weight within normal range and within sibships on IQ at age 7 years: cohort study","volume":"323","author":"Matte","year":"2001","journal-title":"BMJ."},{"issue":"2","key":"2022103011175530600_ref11","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1352\/1944-7558-118.2.156","article-title":"Prenatal and perinatal factors associated with intellectual disability","volume":"118","author":"Bilder","year":"2013","journal-title":"Am J Intellect Dev Disabil."},{"issue":"3","key":"2022103011175530600_ref12","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.bpobgyn.2010.10.012","article-title":"Defective deep placentation","volume":"25","author":"Khong","year":"2011","journal-title":"Best Pract Res Clin Obstet Gynaecol."},{"issue":"2","key":"2022103011175530600_ref13","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41390-019-0405-9","article-title":"Placental programming of neuropsychiatric disease","volume":"86","author":"Kratimenos","year":"2019","journal-title":"Pediatr Res."},{"issue":"3","key":"2022103011175530600_ref14","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1111\/ppe.12184","article-title":"Placental abruption and subsequent risk of pre-eclampsia: a population-based case-control study","volume":"29","author":"Parker","year":"2015","journal-title":"Paediatr Perinat Epidemiol."},{"key":"2022103011175530600_ref15","article-title":"Term complications and subsequent risk of preterm birth: registry based study","volume":"369","author":"Kvalvik","year":"2020","journal-title":"BMJ."},{"issue":"1","key":"2022103011175530600_ref16","doi-asserted-by":"crossref","first-page":"66.e1","DOI":"10.1016\/j.ajog.2013.09.010","article-title":"Placental pathology suggesting that preeclampsia is more than one disease","volume":"210","author":"Nelson","year":"2014","journal-title":"Am J Obstet Gynecol."},{"key":"2022103011175530600_ref17","first-page":"177","article-title":"The role of the spiral arteries in the pathogenesis of preeclampsia","volume":"1","author":"Brosens","year":"1972","journal-title":"Obstet Gynecol Annu."},{"issue":"6","key":"2022103011175530600_ref18","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/ppe.12317","article-title":"The impact of small for gestational age births in early and late Preeclamptic pregnancies for preeclampsia recurrence: a cohort study of successive pregnancies in Sweden","volume":"30","author":"Cnattingius","year":"2016","journal-title":"Paediatr Perinat Epidemiol."},{"issue":"2","key":"2022103011175530600_ref19","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1016\/0002-9378(93)90499-9","article-title":"Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes","volume":"168","author":"Arias","year":"1993","journal-title":"Am J Obstet Gynecol."},{"key":"2022103011175530600_ref20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.placenta.2019.06.374","article-title":"Preterm birth subtypes, placental pathology findings, and risk of neurodevelopmental disabilities during childhood","volume":"83","author":"Raghavan","year":"2019","journal-title":"Placenta."},{"issue":"12","key":"2022103011175530600_ref21","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.1111\/1471-0528.12752","article-title":"Retained placenta is associated with pre-eclampsia, stillbirth, giving birth to a small-for-gestational-age infant, and spontaneous preterm birth: a national register-based study","volume":"121","author":"Endler","year":"2014","journal-title":"BJOG."},{"issue":"7","key":"2022103011175530600_ref22","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.placenta.2009.04.007","article-title":"Placental blood flow and the risk of preterm delivery","volume":"30","author":"Misra","year":"2009","journal-title":"Placenta."},{"key":"2022103011175530600_ref23","volume-title":"The Swedish Medical Birth Register: a summary of content and quality","author":"Swedish National Board of Health and Welfare","year":"2003"},{"key":"2022103011175530600_ref24","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish National Inpatient Register","volume":"11","author":"Ludvigsson","year":"2011","journal-title":"BMC Public Health."},{"issue":"7","key":"2022103011175530600_ref25","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1002\/pds.3457","article-title":"The Nordic prescription databases as a resource for pharmacoepidemiological research\u2013a literature review","volume":"22","author":"Wettermark","year":"2013","journal-title":"Pharmacoepidemiol Drug Saf."},{"issue":"2","key":"2022103011175530600_ref26","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10654-016-0117-y","article-title":"Registers of the Swedish total population and their use in medical research","volume":"31","author":"Ludvigsson","year":"2016","journal-title":"Eur J Epidemiol."},{"key":"2022103011175530600_ref27","volume-title":"Evaluation of the Swedish Register of Education","author":"Statistics Sweden","year":"2006"},{"key":"2022103011175530600_ref28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/978-1-59745-423-0_10","article-title":"The Swedish Multi-generation Register","volume":"675","author":"Ekbom","year":"2011","journal-title":"Methods Mol Biol."},{"issue":"11","key":"2022103011175530600_ref29","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research","volume":"24","author":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol."},{"issue":"7","key":"2022103011175530600_ref30","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1111\/j.1651-2227.1996.tb14164.x","article-title":"Intrauterine growth curves based on ultrasonically estimated foetal weights","volume":"85","author":"Mars\u00e1l","year":"1996","journal-title":"Acta Paediatr."},{"issue":"12","key":"2022103011175530600_ref31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1002717","article-title":"Small for gestational age and risk of childhood mortality: a Swedish population study","volume":"15","author":"Ludvigsson","year":"2018","journal-title":"PLoS Med."},{"issue":"5","key":"2022103011175530600_ref32","doi-asserted-by":"crossref","first-page":"507","DOI":"10.3109\/03014460.2014.969488","article-title":"Optimal treatment of replicate measurements in anthropometric studies","volume":"42","author":"Villamor","year":"2015","journal-title":"Ann Hum Biol."},{"issue":"22","key":"2022103011175530600_ref33","doi-asserted-by":"crossref","first-page":"2362","DOI":"10.1001\/jama.2013.6295","article-title":"Maternal obesity and risk of preterm delivery","volume":"309","author":"Cnattingius","year":"2013","journal-title":"JAMA."},{"key":"2022103011175530600_ref34","author":"World Health Organization","year":"2022"},{"issue":"11","key":"2022103011175530600_ref35","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1080\/00016340600935433","article-title":"Self-reported nicotine exposure and plasma levels of cotinine in early and late pregnancy","volume":"85","author":"George","year":"2006","journal-title":"Acta Obstet Gynecol Scand."},{"issue":"2","key":"2022103011175530600_ref36","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1037\/a0031034","article-title":"Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros","volume":"18","author":"Valeri","year":"2013","journal-title":"Psychol Methods."},{"issue":"2","key":"2022103011175530600_ref37","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1097\/EDE.0000000000000253","article-title":"SAS macro for causal mediation analysis with survival data","volume":"26","author":"Valeri","year":"2015","journal-title":"Epidemiology."},{"key":"2022103011175530600_ref38","volume-title":"Causal Inference: What If.","author":"Hernan","year":"2020"},{"issue":"6","key":"2022103011175530600_ref39","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1001\/archgenpsychiatry.2011.1374","article-title":"Preterm birth and psychiatric disorders in young adult life","volume":"69","author":"Nosarti","year":"2012","journal-title":"Arch Gen Psychiatry."},{"issue":"4","key":"2022103011175530600_ref40","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1097\/EDE.0000000000001350","article-title":"Term birth weight and neurodevelopmental outcomes","volume":"32","author":"Cortese","year":"2021","journal-title":"Epidemiology."},{"issue":"9606","key":"2022103011175530600_ref41","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0140-6736(08)60074-4","article-title":"Epidemiology and causes of preterm birth","volume":"371","author":"Goldenberg","year":"2008","journal-title":"Lancet."},{"issue":"4","key":"2022103011175530600_ref42","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1093\/aje\/kwm319","article-title":"Familial patterns of preterm delivery: maternal and fetal contributions","volume":"167","author":"Wilcox","year":"2008","journal-title":"Am J Epidemiol."},{"issue":"5","key":"2022103011175530600_ref43","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1097\/EDE.0b013e31825fa230","article-title":"Sibling comparison designs: bias from non-shared confounders and measurement error","volume":"23","author":"Frisell","year":"2012","journal-title":"Epidemiology."},{"issue":"5","key":"2022103011175530600_ref44","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1017\/thg.2019.67","article-title":"Sibling comparison designs: addressing confounding bias with inclusion of measured confounders","volume":"22","author":"Saunders","year":"2019","journal-title":"Twin Res Hum Genet."},{"issue":"4","key":"2022103011175530600_ref45","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1097\/EDE.0000000000000649","article-title":"Confounders, mediators, or colliders: what types of shared covariates does a sibling comparison design control for?","volume":"28","author":"Sj\u00f6lander","year":"2017","journal-title":"Epidemiology."},{"issue":"6","key":"2022103011175530600_ref46","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1097\/EDE.0000000000000541","article-title":"Carryover effects in sibling comparison designs","volume":"27","author":"Sj\u00f6lander","year":"2016","journal-title":"Epidemiology."}],"container-title":["American Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/aje\/advance-article-pdf\/doi\/10.1093\/aje\/kwac068\/43845164\/kwac068.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/aje\/article-pdf\/191\/9\/1557\/46686372\/kwac068.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/aje\/article-pdf\/191\/9\/1557\/46686372\/kwac068.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,30]],"date-time":"2022-10-30T07:18:31Z","timestamp":1667114311000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/aje\/article\/191\/9\/1557\/6563610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,5]]},"references-count":46,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,4,5]]},"published-print":{"date-parts":[[2022,8,22]]}},"URL":"https:\/\/doi.org\/10.1093\/aje\/kwac068","relation":{},"ISSN":["0002-9262","1476-6256"],"issn-type":[{"value":"0002-9262","type":"print"},{"value":"1476-6256","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,9]]},"published":{"date-parts":[[2022,4,5]]}}}