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Maternal SSRI exposure increases the risk of autistic offspring: A meta-analysis and systematic review

Published online by Cambridge University Press:  23 March 2020

S. Andalib ,
M.R. Emamhadi ,
S. Yousefzadeh-Chabok ,
S.K. Shakouri ,
P.F. Høilund-Carlsen ,
M.S. Vafaee  and
T.M. Michel
S. Andalib*
Affiliation:
Neuroscience Research Center, Department of Neurosurgery, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
M.R. Emamhadi
Affiliation:
Brachial Plexus and Peripheral Nerve Injury Center, Guilan University of Medical Sciences, Rasht, Iran
S. Yousefzadeh-Chabok
Affiliation:
Neuroscience Research Center, Department of Neurosurgery, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
S.K. Shakouri
Affiliation:
Physical Medicine and Rehabilitation Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
P.F. Høilund-Carlsen
Affiliation:
Department of Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark
M.S. Vafaee
Affiliation:
Department of Nuclear Medicine, Odense University Hospital, University of Southern Denmark, Odense, Denmark Department of Psychiatry, Psychiatry Region of Southern, Odense, Denmark Research Unit of Psychiatry, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Center for Applied Neuroscience, BRIDGE, Odense University Hospital, University of Southern Denmark, Psychiatry in the Region of Southern Denmark, Odense, Denmark Neurosciences Research Center, Department of Neurology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
T.M. Michel
Affiliation:
Department of Psychiatry, Psychiatry Region of Southern, Odense, Denmark Research Unit of Psychiatry, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Center for Applied Neuroscience, BRIDGE, Odense University Hospital, University of Southern Denmark, Psychiatry in the Region of Southern Denmark, Odense, Denmark Neurosciences Research Center, Department of Neurology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
*
*Corresponding author. Fax: +98 133 332 2444. E-mail address:andalib@gums.ac.ir (S. Andalib).
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Abstract

Background:

Selective serotonin reuptake inhibitors (SSRIs) are the most common antidepressants used to preclude maternal pregnancy depression. There is a growing body of literature assessing the association of prenatal exposure to SSRIs with autism spectrum disorder (ASD). The present systematic review and meta-analysis reviewed the medical literature and pooled the results of the association of prenatal exposure to SSRIs with ASD.

Methods:

Published investigations in English by June 2016 with keywords of selective serotonin reuptake inhibitors, SSRI, autism spectrum disorder, ASD, pregnancy, childhood, children, neurodevelopment were identified using databases PubMed and PMC, MEDLINE, EMBASE, SCOPUS, and Google Scholar. Cochran's Q statistic-value (Q), degree of freedom (df), and I2 indices (variation in odds ratio [OR] attributable to heterogeneity) were calculated to analyze the risk of heterogeneity of the within- and between-study variability. Pooled odds ratio (OR) and 95% confidence interval (CI) were reported by a Mantel–Haenszel test.

Results:

There was a non-significant heterogeneity for the included studies ([Q = 3.61, df = 6, P = 0.730], I2 = 0%). The pooled results showed a significant association between prenatal SSRI exposure and ASD (OR = 1.82, 95% CI = 1.59–2.10, Z = 8.49, P = 0.00).

Conclusion:

The evidence from the present study suggests that prenatal exposure to SSRIs is associated with a higher risk of ASD.

Keywords

Selective serotonin reuptake inhibitorsSSRIAutism spectrum disorderASDPregnancyChildhood
Type
Review
Information
European Psychiatry , Volume 45 , September 2017 , pp. 161 - 166
Copyright
Copyright © European Psychiatric Association 2017

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Footnotes

1

Both co-authors have contributed equally.

References

Lord, CRisi, SDiLavore, PSShulman, CThurm, APickles, AAutism from 2 to 9 years of age. Arch Gen Psychiatry 2006; 63: 694–701.CrossRefGoogle ScholarPubMed
Carper, RAMoses, PTigue, ZDCourchesne, ECerebral lobes in autism: early hyperplasia and abnormal age effects. Neuroimage 2002; 16: 1038–1051.CrossRefGoogle ScholarPubMed
Palmen, SJPol, H.E.H.Kemner, CSchnack, HGDurston, SLahuis, BE, et al.Increased gray-matter volume in medication-naive high-functioning children with autism spectrum disorder. Psychol Med 2005; 35: 561–570.CrossRefGoogle Scholar
Stigler, KAMcDonald, BCAnand, ASaykin, AJMcDougle, CJStructural and functional magnetic resonance imaging of autism spectrum disorders. Brain Res 2011; 1380: 146–161.CrossRefGoogle ScholarPubMed
Uddin, LQMenon, VYoung, CBRyali, SChen, TKhouzam, A, et al.Multivariate searchlight classification of structural magnetic resonance imaging in children and adolescents with autism. Biol Psychiatry 2011; 70: 833–841.CrossRefGoogle ScholarPubMed
Brun, CCNicolson, RLeporé, NChou, YYVidal, CNDeVito, TJ, et al.Mapping brain abnormalities in boys with autism. Hum Brain Mapp 2009; 30: 3887–3900.CrossRefGoogle ScholarPubMed
Nickl-Jockschat, THabel, UMaria Michel, TManning, JLaird, ARFox, PT, et al.Brain structure anomalies in autism spectrum disorder – a meta-analysis of VBM studies using anatomic likelihood estimation. Hum Brain Mapp 2012; 33: 1470–1489.CrossRefGoogle ScholarPubMed
Boddaert, NChabane, NBarthelemy, CBourgeois, MPoline, JBrunelle, F, et al.Bitemporal lobe dysfonction in infantile autism: positron emission tomography study. J Radiol 2002; 83: 1829–1833.Google ScholarPubMed
Nickl-Jockschat, TMichel, TThe role of neurotrophic factors in autism. Mol Psychiatry 2011; 16: 478–490.CrossRefGoogle ScholarPubMed
Nickl-Jockschat, TMichel, TGenetic and brain structure anomalies in autism spectrum disorders. Towards an understanding of the aetiopathogenesis?. Der Nervenarzt 2011; 82: 618–627.CrossRefGoogle ScholarPubMed
Abdallah, MWMichel, TMMatrix metalloproteinases in autism spectrum disorders. J Mol Psychiatry 2013;1:1.CrossRefGoogle ScholarPubMed
Woods, AGWetie, A.G.N.Sokolowska, IRussell, SRyan, JPMichel, TM, et al.Mass spectrometry as a tool for studying autism spectrum disorder. J Mol Psychiatry 2013;1:1.CrossRefGoogle ScholarPubMed
Michel, TSheldrick, AFrentzel, THerpertz-Dahlmann, BHerpertz, SHabel, U, et al.Evaluation of diagnostic and therapeutic services in German university hospitals for adults with autism spectrum disorder (ASD). Fortschr Neurol Psychiatr 2010; 78: 402–413.CrossRefGoogle Scholar
Andrade, SERaebel, MABrown, JLane, KLivingston, JBoudreau, D, et al.Use of antidepressant medications during pregnancy: a multisite study. Am J Obstet Gynecol 2008;198:194e1–194e5.CrossRefGoogle ScholarPubMed
Alwan, SReefhuis, JRasmussen, SAFriedman, JMPatterns of antidepressant medication use among pregnant women in a United States population. J Clin Pharmacol 2011; 51: 264–270.CrossRefGoogle Scholar
El Marroun, HJaddoe, VWHudziak, JJRoza, SJSteegers, EAHofman, A, et al.Maternal use of selective serotonin reuptake inhibitors, fetal growth, and risk of adverse birth outcomes. Arch Gen Psychiatry 2012; 69: 706–714.CrossRefGoogle ScholarPubMed
Munk-Olsen, TGasse, CLaursen, TPrevalence of antidepressant use and contacts with psychiatrists and psychologists in pregnant and postpartum women. Acta Psychiatr Scand 2012; 125: 318–324.CrossRefGoogle ScholarPubMed
Kieler, HArtama, MEngeland, AEricsson, Ö.Furu, KGissler, M, et al.Selective serotonin reuptake inhibitors during pregnancy and risk of persistent pulmonary hypertension in the newborn: population based cohort study from the five Nordic countries. BMJ 2012;344:d8012.CrossRefGoogle ScholarPubMed
Wu, JDavis-Ajami, MLKeiser, SSykes, LAntidepressant prescription medication use patterns among insured, low income pregnant women. Am J Public Health Res 2013; 1: 72–77.CrossRefGoogle Scholar
Lattimore, KADonn, SMKaciroti, NKemper, ARNeal, CRVazquez, DMSelective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis. J Perinatol 2005; 25: 595–604.CrossRefGoogle ScholarPubMed
Ansorge, MSZhou, MLira, AHen, RGingrich, JAEarly-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 2004; 306: 879–881.CrossRefGoogle ScholarPubMed
Smit-Rigter, LANoorlander, CWvon Oerthel, LChameau, PSmidt, MPvan Hooft, JAPrenatal fluoxetine exposure induces life-long serotonin 5-HT 3 receptor-dependent cortical abnormalities and anxiety-like behaviour. Neuropharmacology 2012; 62: 865–870.CrossRefGoogle ScholarPubMed
Boukhris, TSheehy, OMottron, LBérard, AAntidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatr 2016; 170: 117–124.CrossRefGoogle ScholarPubMed
Croen, LAGrether, JKYoshida, CKOdouli, RHendrick, VAntidepressant use during pregnancy and childhood autism spectrum disorders. Arch Gen Psychiatry 2011; 68: 1104–1112.CrossRefGoogle ScholarPubMed
El Marroun, HWhite, TJvan der Knaap, NJHomberg, JRFernández, GSchoemaker, NK, et al.Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: population-based study of young children. Br J Psychiatry 2014; 205: 95–102.CrossRefGoogle ScholarPubMed
Hviid, AMelbye, MPasternak, BUse of selective serotonin reuptake inhibitors during pregnancy and risk of autism. New Engl J Med 2013; 369: 2406–2415.CrossRefGoogle ScholarPubMed
Huedo-Medina, TBSánchez-Meca, JMarín-Martínez, FBotella, JAssessing heterogeneity in meta-analysis: Q statistic or I 2 index?. Psychol Methods 2006;11:193.CrossRefGoogle ScholarPubMed
Gidaya, NBLee, BKBurstyn, IYudell, MMortensen, ELNewschaffer, CJIn utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. J Autism Dev Disord 2014; 44: 2558–2567.CrossRefGoogle ScholarPubMed
Sorensen, MJGronborg, TKChristensen, JParner, ETVestergaard, MSchendel, D, et al.Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clin Epidemiol 2013; 5: 449–459.CrossRefGoogle ScholarPubMed
Cryan, JFMarkou, ALucki, IAssessing antidepressant activity in rodents: recent developments and future needs. Trends Pharmacol Sci 2002; 23: 238–245.CrossRefGoogle ScholarPubMed
Whitaker-Azmitia, PMBehavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism?. Int J Dev Neurosci 2005; 23: 75–83.CrossRefGoogle ScholarPubMed
Gardier, AMalagie, ITrillat, AJacquot, CArtigas, FRole of 5-HT1A autoreceptors in the mechanism of action of serotoninergic antidepressant drugs: recent findings from in vivo microdialysis studies. Fundam Clin Pharmacol 1996; 10: 16–27.CrossRefGoogle ScholarPubMed
Anderson, GMCzarkowski, KRavski, NEpperson, CNPlatelet serotonin in newborns and infants: ontogeny, heritability, and effect of in utero exposure to selective serotonin reuptake inhibitors. Pediatr Res 2004; 56: 418–422.CrossRefGoogle ScholarPubMed
Cook, EHLeventhal, BLFreedman, DXFree serotonin in plasma: autistic children and their first-degree relatives. Biol Psychiatry 1988; 24: 488–491.CrossRefGoogle ScholarPubMed
Lam, KSAman, MGArnold, LENeurochemical correlates of autistic disorder: a review of the literature. Res Dev Disabil 2006; 27: 254–289.CrossRefGoogle ScholarPubMed
Borue, XChen, JCondron, BGDevelopmental effects of SSRIs: lessons learned from animal studies. Int J Dev Neurosci 2007; 25: 341–347.CrossRefGoogle ScholarPubMed
Harrington, RALee, LCCrum, RMZimmerman, AWHertz-Picciotto, ISerotonin hypothesis of autism: implications for selective serotonin reuptake inhibitor use during pregnancy. Autism Res 2013; 6: 149–168.CrossRefGoogle Scholar
Vorhees, CVAcuff-Smith, KDSchilling, MAFisher, JEMoran, MSBuelke-Sam, JA developmental neurotoxicity evaluation of the effects of prenatal exposure to fluoxetine in rats. Toxicol Sci 1994; 23: 194–205.CrossRefGoogle ScholarPubMed
Maciag, DSimpson, KLCoppinger, DLu, YWang, YLin, RC, et al.Neonatal antidepressant exposure has lasting effects on behavior and serotonin circuitry. Neuropsychopharmacology 2006; 31: 47–57.CrossRefGoogle ScholarPubMed
Jones, WKlin, AHeterogeneity and homogeneity across the autism spectrum: the role of development. J Am Acad Child Adolesc Psychiatry 2009; 48: 471–473.CrossRefGoogle Scholar
Rai, DLee, BKDalman, CGolding, JLewis, GMagnusson, C Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study; 2013.CrossRefGoogle Scholar
Harrington, RALee, L.-C.Crum, RMZimmerman, AWHertz-Picciotto, IPrenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics 2014;133:e1241–e1248.CrossRefGoogle ScholarPubMed
Brown, HKRay, JGWilton, ASLunsky, YGomes, TVigod, SNAssociation between serotonergic antidepressant use during pregnancy and autism spectrum disorder in children. JAMA 2017; 317: 1544–1552.CrossRefGoogle ScholarPubMed
Daniels, JLForssen, UHultman, CMCnattingius, SSavitz, DAFeychting, M, et al.Parental psychiatric disorders associated with autism spectrum disorders in the offspring. Pediatrics 2008;121:e1357–e1362.CrossRefGoogle ScholarPubMed
Jose, AGupta, SGulati, SSapra, SPrevalence of depression in mothers of children having ASD. Curr Med Res Pract 2017; 7: 11–15.CrossRefGoogle Scholar
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