{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:36:48Z","timestamp":1789591008407,"version":"build-2803163510"},"reference-count":47,"publisher":"American Academy of Pediatrics (AAP)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,5,1]]},"abstract":"<jats:sec>\n                  <jats:title>OBJECTIVE:<\/jats:title>\n                  <jats:p>To examine associations between prenatal use of selective serotonin reuptake inhibitors (SSRIs) and the odds of autism spectrum disorders (ASDs) and other developmental delays (DDs).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS:<\/jats:title>\n                  <jats:p>A total of 966 mother-child pairs were evaluated (492 ASD, 154 DD, 320 typical development [TD]) from the Childhood Autism Risks from Genetics and the Environment (CHARGE) Study, a population-based case-control study. Standardized measures confirmed developmental status. Interviews with biological mothers ascertained prenatal SSRI use, maternal mental health history, and sociodemographic information.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS:<\/jats:title>\n                  <jats:p>Overall, prevalence of prenatal SSRI exposure was lowest in TD children (3.4%) but did not differ significantly from ASD (5.9%) or DD (5.2%) children. Among boys, prenatal SSRI exposure was nearly 3 times as likely in children with ASD relative to TD (adjusted odds ratio [OR]: 2.91; 95% confidence interval [CI]: 1.07\u20137.93); the strongest association occurred with first-trimester exposure (OR: 3.22; 95% CI: 1.17\u20138.84). Exposure was also elevated among boys with DD (OR: 3.39; 95% CI: 0.98\u201311.75) and was strongest in the third trimester (OR: 4.98; 95% CI: 1.20\u201320.62). Findings were similar among mothers with an anxiety or mood disorder history.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS:<\/jats:title>\n                  <jats:p>In boys, prenatal exposure to SSRIs may increase susceptibility to ASD or DD. Findings from published studies on SSRIs and ASD continues to be inconsistent. Potential recall bias and residual confounding by indication are concerns. Larger samples are needed to replicate DD results. Because maternal depression itself carries risks for the fetus, the benefits of prenatal SSRI use should be carefully weighed against potential harms.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1542\/peds.2013-3406","type":"journal-article","created":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:27:19Z","timestamp":1397521639000},"page":"e1241-e1248","source":"Crossref","is-referenced-by-count":140,"title":["Prenatal SSRI Use and Offspring With Autism Spectrum Disorder or Developmental Delay"],"prefix":"10.1542","volume":"133","author":[{"given":"Rebecca A.","family":"Harrington","sequence":"first","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Ching","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa M.","family":"Crum","sequence":"additional","affiliation":[{"name":"Departments of Epidemiology, Psychiatry, and Mental Health, Johns Hopkins Medical Institutions, Baltimore, Maryland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Zimmerman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irva","family":"Hertz-Picciotto","sequence":"additional","affiliation":[{"name":"Department of Public Health Sciences and the MIND Institute, University of California, Davis, Davis, California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2014,5,1]]},"reference":[{"issue":"3","key":"2021120903372483100_B1","first-page":"1","article-title":"Prevalence of autism spectrum disorders\u2014Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008.","volume":"61","author":"Autism and Developmental Disabilities Monitoring Network Surveillance Year 2008 Principal Investigators","year":"2012","journal-title":"MMWR Surveill Summ"},{"issue":"4","key":"2021120903372483100_B2","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1097\/00004583-200404000-00016","article-title":"Platelet serotonin levels in pervasive developmental disorders and mental retardation: diagnostic group differences, within-group distribution, and behavioral correlates.","volume":"43","author":"Mulder","year":"2004","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"issue":"1","key":"2021120903372483100_B3","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ijdevneu.2004.07.022","article-title":"Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism?","volume":"23","author":"Whitaker-Azmitia","year":"2005","journal-title":"Int J Dev Neurosci"},{"issue":"2","key":"2021120903372483100_B4","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1177\/0091270010373928","article-title":"Patterns of antidepressant medication use among pregnant women in a United States population.","volume":"51","author":"Alwan","year":"2011","journal-title":"J Clin Pharmacol"},{"issue":"5","key":"2021120903372483100_B5","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1016\/S0361-9230(01)00615-3","article-title":"Serotonin and brain development: role in human developmental diseases.","volume":"56","author":"Whitaker-Azmitia","year":"2001","journal-title":"Brain Res Bull"},{"issue":"7343","key":"2021120903372483100_B6","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/nature09972","article-title":"A transient placental source of serotonin for the fetal forebrain.","volume":"472","author":"Bonnin","year":"2011","journal-title":"Nature"},{"issue":"1","key":"2021120903372483100_B7","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.neulet.2009.12.054","article-title":"Behavior and serotonergic disorders in rats exposed prenatally to valproate: a model for autism.","volume":"470","author":"Dufour-Rainfray","year":"2010","journal-title":"Neurosci Lett"},{"issue":"9","key":"2021120903372483100_B8","doi-asserted-by":"crossref","first-page":"e24003","DOI":"10.1371\/journal.pone.0024003","article-title":"Fluoxetine during development reverses the effects of prenatal stress on depressive-like behavior and hippocampal neurogenesis in adolescence.","volume":"6","author":"Rayen","year":"2011","journal-title":"PLoS ONE"},{"issue":"5","key":"2021120903372483100_B9","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1176\/appi.ajp.160.5.993","article-title":"Placental passage of antidepressant medications.","volume":"160","author":"Hendrick","year":"2003","journal-title":"Am J Psychiatry"},{"issue":"9","key":"2021120903372483100_B10","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1016\/0006-2952(90)90249-K","article-title":"Interaction of fluoxetine with the human placental serotonin transporter.","volume":"40","author":"Cool","year":"1990","journal-title":"Biochem Pharmacol"},{"issue":"3","key":"2021120903372483100_B11","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1203\/01.PDR.0000136278.23672.A0","article-title":"Platelet serotonin in newborns and infants: ontogeny, heritability, and effect of in utero exposure to selective serotonin reuptake inhibitors.","volume":"56","author":"Anderson","year":"2004","journal-title":"Pediatr Res"},{"issue":"1","key":"2021120903372483100_B12","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1203\/PDR.0b013e31821ba11a","article-title":"Third trimester fetal heart rate and Doppler middle cerebral artery blood flow velocity characteristics during prenatal selective serotonin reuptake inhibitor exposure.","volume":"70","author":"Rurak","year":"2011","journal-title":"Pediatr Res"},{"key":"2021120903372483100_B13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2288-11-2","article-title":"Autism spectrum disorders and fetal hypoxia in a population-based cohort: accounting for missing exposures via Estimation-Maximization algorithm.","volume":"11","author":"Burstyn","year":"2011","journal-title":"BMC Med Res Methodol"},{"issue":"11","key":"2021120903372483100_B14","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1001\/archgenpsychiatry.2011.73","article-title":"Antidepressant use during pregnancy and childhood autism spectrum disorders.","volume":"68","author":"Croen","year":"2011","journal-title":"Arch Gen Psychiatry"},{"key":"2021120903372483100_B15","doi-asserted-by":"crossref","first-page":"f2059","DOI":"10.1136\/bmj.f2059","article-title":"Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study.","volume":"346","author":"Rai","year":"2013","journal-title":"BMJ"},{"issue":"25","key":"2021120903372483100_B16","doi-asserted-by":"crossref","first-page":"2406","DOI":"10.1056\/NEJMoa1301449","article-title":"Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism.","volume":"369","author":"Hviid","year":"2013","journal-title":"N Engl J Med"},{"issue":"7","key":"2021120903372483100_B17","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1289\/ehp.8483","article-title":"The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.","volume":"114","author":"Hertz-Picciotto","year":"2006","journal-title":"Environ Health Perspect"},{"key":"2021120903372483100_B18","volume-title":"Autism Diagnostic Interview\u2013Revised","author":"Rutter","year":"2005"},{"key":"2021120903372483100_B19","volume-title":"Autism Diagnostic Observation Schedule","author":"Lord","year":"2007"},{"issue":"9","key":"2021120903372483100_B20","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1097\/01.chi.0000227880.42780.0e","article-title":"Combining information from multiple sources in the diagnosis of autism spectrum disorders.","volume":"45","author":"Risi","year":"2006","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"2021120903372483100_B21","volume-title":"Social Communication Questionnaire","author":"Rutter","year":"2003"},{"key":"2021120903372483100_B22","volume-title":"Vineland Adaptive Behavior Scales Interview Edition Expanded Form","author":"Sparrow","year":"1984"},{"key":"2021120903372483100_B23","volume-title":"Mullen Scales of Early Learning","author":"Mullen","year":"1995"},{"key":"2021120903372483100_B24","first-page":"128","article-title":"Validity in epidemiologic studies","volume-title":"Modern Epidemiology","author":"Rothman","year":"2008","edition":"3rd ed."},{"issue":"1","key":"2021120903372483100_B25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.2307\/2529310","article-title":"The measurement of observer agreement for categorical data.","volume":"33","author":"Landis","year":"1977","journal-title":"Biometrics"},{"issue":"2","key":"2021120903372483100_B26","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/BF02914268","article-title":"Ovarian steroids and serotonin neural function.","volume":"18","author":"Bethea","year":"1998","journal-title":"Mol Neurobiol"},{"issue":"1","key":"2021120903372483100_B27","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.euroneuro.2008.08.003","article-title":"Dopaminergic and serotonergic activity in neostriatum and nucleus accumbens enhanced by intranasal administration of testosterone.","volume":"19","author":"de Souza Silva","year":"2009","journal-title":"Eur Neuropsychopharmacol"},{"issue":"1","key":"2021120903372483100_B28","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1086\/426697","article-title":"Sex-specific genetic architecture of whole blood serotonin levels.","volume":"76","author":"Weiss","year":"2005","journal-title":"Am J Hum Genet"},{"key":"2021120903372483100_B29","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.brainres.2006.12.095","article-title":"Neonatal serotonin depletion alters behavioral responses to spatial change and novelty.","volume":"1139","author":"Hohmann","year":"2007","journal-title":"Brain Res"},{"issue":"1","key":"2021120903372483100_B30","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1159\/000103097","article-title":"Behavioral evaluation of male and female mice pups exposed to fluoxetine during pregnancy and lactation.","volume":"80","author":"Lisboa","year":"2007","journal-title":"Pharmacology"},{"issue":"3","key":"2021120903372483100_B31","doi-asserted-by":"crossref","DOI":"10.1542\/peds.2008-3655","article-title":"Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age.","volume":"125","author":"Pedersen","year":"2010","journal-title":"Pediatrics"},{"issue":"3","key":"2021120903372483100_B32","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.psychres.2013.01.005","article-title":"Parental psychiatric disorders and autism spectrum disorders.","volume":"207","author":"Jokiranta","year":"2013","journal-title":"Psychiatry Res"},{"issue":"2","key":"2021120903372483100_B33","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1007\/s10488-006-0088-5","article-title":"Treatment with antidepressant medications in private health plans.","volume":"34","author":"Larson","year":"2007","journal-title":"Adm Policy Ment Health"},{"issue":"6","key":"2021120903372483100_B34","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/j.1471-0528.2008.01701.x","article-title":"Maternal depression and medication exposure during pregnancy: comparison of maternal retrospective recall to prospective documentation.","volume":"115","author":"Newport","year":"2008","journal-title":"BJOG"},{"issue":"1-2","key":"2021120903372483100_B35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2010.02.125","article-title":"Prenatal exposure to antidepressant medications and neurodevelopmental outcomes: a systematic review.","volume":"128","author":"Gentile","year":"2011","journal-title":"J Affect Disord"},{"issue":"4","key":"2021120903372483100_B36","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1067\/mpd.2003.139","article-title":"Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy.","volume":"142","author":"Casper","year":"2003","journal-title":"J Pediatr"},{"issue":"2","key":"2021120903372483100_B37","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s00213-011-2270-z","article-title":"Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development.","volume":"217","author":"Casper","year":"2011","journal-title":"Psychopharmacology (Berl)"},{"issue":"8","key":"2021120903372483100_B38","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.earlhumdev.2006.09.015","article-title":"Agreement between maternal report and antenatal records for a range of pre and peri-natal factors: the influence of maternal and child characteristics.","volume":"83","author":"Rice","year":"2007","journal-title":"Early Hum Dev"},{"issue":"3","key":"2021120903372483100_B39","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.1177\/0269881198012003021","article-title":"Selective serotonin reuptake inhibitors in affective disorders\u2014I. Basic pharmacology.","volume":"12","author":"Goodnick","year":"1998","journal-title":"J Psychopharmacol"},{"issue":"1","key":"2021120903372483100_B40","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/01.pra.0000410986.61593.46","article-title":"The use of biomarkers in psychiatric research: how serotonin transporter occupancy explains the dose-response curves of SSRIs.","volume":"18","author":"Preskorn","year":"2012","journal-title":"J Psychiatr Pract"},{"issue":"3","key":"2021120903372483100_B41","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0028-1103296","article-title":"Placental transfer of SSRI and SNRI antidepressants and effects on the neonate.","volume":"42","author":"Rampono","year":"2009","journal-title":"Pharmacopsychiatry"},{"issue":"3","key":"2021120903372483100_B42","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/aur.1288","article-title":"Serotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy.","volume":"6","author":"Harrington","year":"2013","journal-title":"Autism Res"},{"key":"2021120903372483100_B43","doi-asserted-by":"crossref","first-page":"47","DOI":"10.3389\/fncel.2013.00047","article-title":"Placental serotonin: implications for the developmental effects of SSRIs and maternal depression.","volume":"7","author":"Velasquez","year":"2013","journal-title":"Front Cell Neurosci"},{"issue":"12","key":"2021120903372483100_B44","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1016\/j.annepidem.2011.08.009","article-title":"Have secular changes in perinatal risk factors contributed to the recent autism prevalence increase? Development and application of a mathematical assessment model.","volume":"21","author":"Schieve","year":"2011","journal-title":"Ann Epidemiol"},{"issue":"11","key":"2021120903372483100_B45","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1177\/070674370404901103","article-title":"Perinatal risks of untreated depression during pregnancy.","volume":"49","author":"Bonari","year":"2004","journal-title":"Can J Psychiatry"},{"issue":"3","key":"2021120903372483100_B46","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1097\/AOG.0b013e3181ba0632","article-title":"The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists.","volume":"114","author":"Yonkers","year":"2009","journal-title":"Obstet Gynecol"},{"issue":"8","key":"2021120903372483100_B47","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1111\/j.1471-0528.2008.01752.x","article-title":"The impact of maternal depression in pregnancy on early child development.","volume":"115","author":"Deave","year":"2008","journal-title":"BJOG"}],"container-title":["Pediatrics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/133\/5\/e1241\/1059832\/peds_2013-3406.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/publications.aap.org\/pediatrics\/article-pdf\/133\/5\/e1241\/1059832\/peds_2013-3406.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T19:08:39Z","timestamp":1639076919000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.aap.org\/pediatrics\/article\/133\/5\/e1241\/32800\/Prenatal-SSRI-Use-and-Offspring-With-Autism"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,5,1]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,1]]},"published-print":{"date-parts":[[2014,5,1]]}},"URL":"https:\/\/doi.org\/10.1542\/peds.2013-3406","relation":{},"ISSN":["0031-4005","1098-4275"],"issn-type":[{"value":"0031-4005","type":"print"},{"value":"1098-4275","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,1]]}}}