Selective Serotonin Reuptake Inhibitor Use during Pregnancy and the Risk of Autism Spectrum Disorders: A Review

Abstract

Antidepressants are widely used during pregnancy. Several studies have shown that the use of antidepressants during pregnancy is linked to adverse outcomes, including congenital malformations, prematurity, and low birth weight. However, there is a knowledge gap regarding the potential association between gestational exposure to antidepressants and the risk of autism spectrum disorders (ASD). The etiology of ASD remains unclear, although studies have implicated genetic predispositions and environmental risk factors in the development of ASD in children. In this review, we describe the association between gestational use of antidepressants, specifically selective serotonin reuptake inhibitors, and the risk of ASD.

Keywords

SSRI - pregnancy - autism spectrum disorders - review

• References

• 1 Cooper WO, Willy ME, Pont SJ, Ray WA. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol 2007; 196 (6) 544.e1-544.e5
• 2 Daw JR, Mintzes B, Law MR, Hanley GE, Morgan SG. Prescription drug use in pregnancy: a retrospective, population-based study in British Columbia, Canada (2001-2006). Clin Ther 2012; 34 (1) 239-249.e2
• 3 Kjaersgaard MI, Parner ET, Vestergaard M , et al. Prenatal antidepressant exposure and risk of spontaneous abortion - a population-based study. PLoS ONE 2013; 8 (8) e72095
• 4 Gentile S. Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of birth defects. Acta Psychiatr Scand 2011; 123 (4) 266-275
• 5 Wurst KE, Poole C, Ephross SA, Olshan AF. First trimester paroxetine use and the prevalence of congenital, specifically cardiac, defects: a meta-analysis of epidemiological studies. Birth Defects Res A Clin Mol Teratol 2010; 88 (3) 159-170
• 6 Ross LE, Grigoriadis S, Mamisashvili L , et al. Selected pregnancy and delivery outcomes after exposure to antidepressant medication: a systematic review and meta-analysis. JAMA Psychiatry 2013; 70 (4) 436-443
• 7 Källén B. Neonate characteristics after maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004; 158 (4) 312-316
• 8 Nordeng H, Lindemann R, Perminov KV, Reikvam A. Neonatal withdrawal syndrome after in utero exposure to selective serotonin reuptake inhibitors. Acta Paediatr 2001; 90 (3) 288-291
• 9 De Vera MA, Bérard A. Antidepressant use during pregnancy and the risk of pregnancy-induced hypertension. Br J Clin Pharmacol 2012; 74 (2) 362-369
• 10 Yonkers KA, Gotman N, Smith MV , et al. Does antidepressant use attenuate the risk of a major depressive episode in pregnancy?. Epidemiology 2011; 22 (6) 848-854
• 11 Cohen LS, Nonacs RM, Bailey JW , et al. Relapse of depression during pregnancy following antidepressant discontinuation: a preliminary prospective study. Arch Women Ment Health 2004; 7 (4) 217-221
• 12 Berard A, Karam F, Sheehy O , et al. Antidepressant use during pregnancy and the risk of delay in overall cognitive development at one year old: results from the OTIS Antidepressants Study. Birth Defects Res A Clin Mol Teratol 2012; 94: 253-290
• 13 Christopher M, Alan L , eds. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Diseases, Injuries, and Risk Factors in 1990 and Projected to 2020. Geneva: Harvard School of Public Health; 1996
• 14 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders.4th ed. Washington, DC: American Psychiatric Association; 2000
• 15 Muhle R, Trentacoste SV, Rapin I. The genetics of autism. Pediatrics 2004; 113 (5) e472-e486
• 16 Kogan MD, Blumberg SJ, Schieve LA , et al. Prevalence of parent-reported diagnosis of autism spectrum disorder among children in the US, 2007. Pediatrics 2009; 124 (5) 1395-1403
• 17 Centers for disease Control and Prevention (CDC) MMWR Surveill Summ. Prevalence of Autism Spectrum Disorders—Autism and Developmental Disabilities Monitoring Network, 14 Sites, United States, 2008. 2012;61(3):2–18. Available at: http://www.cdc.gov/mmwr/preview/mmwrhtml/ss6103a1.htm . Accessed March 30, 2012
• 18 Hertz-Picciotto I, Delwiche L. The rise in autism and the role of age at diagnosis. Epidemiology 2009; 20 (1) 84-90
• 19 Hertz-Picciotto I. Commentary: Diagnostic change and the increased prevalence of autism. Int J Epidemiol 2009; 38 (5) 1239-1241 , author reply 1243–1244
• 20 Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism. Environ Health Perspect 2006; 114 (7) 1119-1125
• 21 Ronemus M, Iossifov I, Levy D, Wigler M. The role of de novo mutations in the genetics of autism spectrum disorders. Nat Rev Genet 2014; 15 (2) 133-141
• 22 Sandin S, Hultman CM, Kolevzon A, Gross R, MacCabe JH, Reichenberg A. Advancing maternal age is associated with increasing risk for autism: a review and meta-analysis. J Am Acad Child Adolesc Psychiatry 2012; 51 (5) 477-486
• 23 Lyall K, Pauls DL, Spiegelman D, Ascherio A, Santangelo SL. Pregnancy complications and obstetric suboptimality in association with autism spectrum disorders in children of the Nurses' Health Study II. Autism Res 2012; 5 (1) 21-30
• 24 Moore GS, Kneitel AW, Walker CK, Gilbert WM, Xing G. Autism risk in small- and large-for-gestational-age infants. Am J Obstet Gynecol 2012; 206 (4) 314.e1-314.e9
• 25 Daniels JL, Forssen U, Hultman CM , et al. Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics 2008; 121 (5) e1357-e1362
• 26 Jokiranta E, Brown AS, Heinimaa M, Cheslack-Postava K, Suominen A, Sourander A. Parental psychiatric disorders and autism spectrum disorders. Psychiatry Res 2013; 207 (3) 203-211
• 27 Folstein S, Rutter M. Infantile autism: a genetic study of 21 twin pairs. J Child Psychol Psychiatry 1977; 18 (4) 297-321
• 28 Steffenburg S, Gillberg C, Hellgren L , et al. A twin study of autism in Denmark, Finland, Iceland, Norway and Sweden. J Child Psychol Psychiatry 1989; 30 (3) 405-416
• 29 Bailey A, Le Couteur A, Gottesman I , et al. Autism as a strongly genetic disorder: evidence from a British twin study. Psychol Med 1995; 25 (1) 63-77
• 30 Piven J, Vieland VJ, Parlier M , et al. A molecular genetic study of autism and related phenotypes in extended pedigrees. J Neurodev Disord 2013; 5 (1) 30
• 31 Sumi S, Taniai H, Miyachi T, Tanemura M. Sibling risk of pervasive developmental disorder estimated by means of an epidemiologic survey in Nagoya, Japan. J Hum Genet 2006; 51 (6) 518-522
• 32 Ritvo ER, Jorde LB, Mason-Brothers A , et al. The UCLA-University of Utah epidemiologic survey of autism: recurrence risk estimates and genetic counseling. Am J Psychiatry 1989; 146 (8) 1032-1036
• 33 Ozonoff S, Young GS, Carter A , et al. Recurrence risk for autism spectrum disorders: a Baby Siblings Research Consortium study. Pediatrics 2011; 128 (3) e488-e495
• 34 Whitaker-Azmitia PM. Serotonin and brain development: role in human developmental diseases. Brain Res Bull 2001; 56 (5) 479-485
• 35 Sodhi MS, Sanders-Bush E. Serotonin and brain development. Int Rev Neurobiol 2004; 59: 111-174
• 36 Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 2003; 4 (12) 1002-1012
• 37 Il'ková G, Rehák P, Veselá J , et al. Serotonin localization and its functional significance during mouse preimplantation embryo development. Zygote 2004; 12 (3) 205-213
• 38 Ansorge MS, Zhou M, Lira A, Hen R, Gingrich JA. Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306 (5697) 879-881
• 39 Oberlander TF, Gingrich JA, Ansorge MS. Sustained neurobehavioral effects of exposure to SSRI antidepressants during development: molecular to clinical evidence. Clin Pharmacol Ther 2009; 86 (6) 672-677
• 40 Chugani DC, Muzik O, Behen M , et al. Developmental changes in brain serotonin synthesis capacity in autistic and nonautistic children. Ann Neurol 1999; 45 (3) 287-295
• 41 Chandana SR, Behen ME, Juhász C , et al. Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism. Int J Dev Neurosci 2005; 23 (2-3) 171-182
• 42 Murphy DG, Daly E, Schmitz N , et al. Cortical serotonin 5-HT2A receptor binding and social communication in adults with Asperger's syndrome: an in vivo SPECT study. Am J Psychiatry 2006; 163 (5) 934-936
• 43 Hanley HG, Stahl SM, Freedman DX. Hyperserotonemia and amine metabolites in autistic and retarded children. Arch Gen Psychiatry 1977; 34 (5) 521-531
• 44 Tordjman S, Anderson GM, Cohen D , et al. Presence of autism, hyperserotonemia, and severe expressive language impairment in Williams-Beuren syndrome. Mol Autism 2013; 4 (1) 29
• 45 Kahne D, Tudorica A, Borella A , et al. Behavioral and magnetic resonance spectroscopic studies in the rat hyperserotonemic model of autism. Physiol Behav 2002; 75 (3) 403-410
• 46 Schain RJ, Freedman DX. Studies on 5-hydroxyindole metabolism in autistic and other mentally retarded children. J Pediatr 1961; 58: 315-320
• 47 Marazziti D, Muratori F, Cesari A , et al. Increased density of the platelet serotonin transporter in autism. Pharmacopsychiatry 2000; 33 (5) 165-168
• 48 Cook EH, Leventhal BL. The serotonin system in autism. Curr Opin Pediatr 1996; 8 (4) 348-354
• 49 Anderson GM. Monoamines in autism: an update of neurochemical research on a pervasive developmental disorder. Med Biol 1987; 65 (2-3) 67-74
• 50 Ansorge MS, Hen R, Gingrich JA. Neurodevelopmental origins of depressive disorders. Curr Opin Pharmacol 2007; 7 (1) 8-17
• 51 Croen LA, Grether JK, Yoshida CK, Odouli R, Hendrick V. Antidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68 (11) 1104-1112
• 52 Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C. Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 2013; 346: f2059
• 53 Sørensen MJ, Grønborg TK, Christensen J , et al. Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clin Epidemiol 2013; 5: 449-459
• 54 Hviid A, Melbye M, Pasternak B. Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. N Engl J Med 2013; 369 (25) 2406-2415
• 55 Harrington RA, Lee LC, Crum RM, Zimmerman AW, Hertz-Picciotto I. Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics 2014; 133 (5) e1241-e1248
• 56 Clements CC, Castro VM, Blumenthal SR , et al. Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Mol Psychiatry 2014;
• 57 Boukhris T, Sheehy O, Bérard A. Antidepressant use during pregnancy is increasing the risk of autism spectrum disorder even after taking genetic predisposition into account. J Popul Ther Clin Pharmacol 2014; 21 (2) e308-e337