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School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure

  • Erica L. Smearman (a1) (a2), Cassandra L. Hendrix (a1), Dominika A. Winiarski (a3), Katrina C. Johnson (a1), Alicia K. Smith (a4) (a5), Opal Y. Ousley (a4), Zachary N. Stowe (a6), D. Jeffrey Newport (a7) and Patricia A. Brennan (a1)...

Abstract

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother–child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate–caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (β = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only β = 0.28 95% CI [0.02, 0.55], females-only β = −0.21 95% CI [–0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (β = –0.27, 95% CI [–0.53, –0.01], but not ASD (Autism Diagnostic Observation Schedule β = 0.14 95% CI [–0.15, 0.41]; Social Responsiveness Scale β = 0.08 95% CI [–0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Copyright

Corresponding author

Author for correspondence: Erica L. Smearman, Department of Psychology, 36 Eagle Row, Emory University, Atlanta, GA30322. E-mail: esmearm@emory.edu

References

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Achenbach, T. (2001). Child behavior checklist for ages 6-18. Burlington, VT: ASEBA, University of Vermont.
Achenbach, T., & Rescorla, L. (2000). Child behavior checklist for ages 1 1/2-5. Burlington, VT: ASEBA, University of Vermont.
Anderson, G. M. (2002). Genetics of childhood disorders: XLV. Autism, part 4: serotonin in autism. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 15131516.10.1097/00004583-200212000-00025
Andrade, C. (2017). Antidepressant exposure during pregnancy and risk of autism in the offspring, 2: Do the new studies add anything new? The Journal of Clinical Psychiatry, 78, e1052e1056. https://doi.org/10.4088/JCP.17f11916
Austin, M. P. (2006). To treat or not to treat: maternal depression, SSRI use in pregnancy and adverse neonatal effects. Psychological Medicine, 36, 16631670.
Beck, A., Steer, R., & Brown, G. (1996). Beck Depression Inventory-II. San Antonio, TX: Psychological Corporation.
Bérard, A., Boukhris, T., & Sheehy, O. (2016). Selective serotonin reuptake inhibitors and autism: additional data on the Quebec Pregnancy/Birth Cohort. American Journal of Obstetrics and Gynecology, 215, 803805. https://doi.org/10.1016/j.ajog.2016.08.021
Bérard, A., Zhao, J. P., & Sheehy, O. (2017). Antidepressant use during pregnancy and the risk of major congenital malformations in a cohort of depressed pregnant women: an updated analysis of the Quebec Pregnancy Cohort. BMJ Open, 7, e013372.10.1136/bmjopen-2016-013372
Bethea, C. L., Lu, N. Z., Gundlah, C., & Streicher, J. M. (2002). Diverse actions of ovarian steroids in the serotonin neural system. Frontiers in Neuroendocrinology, 23, 41100.10.1006/frne.2001.0225
Bethea, C. L., Pecins-Thompson, M., Schutzer, W. E., Gundlah, C. L. Z. N., & Lu, Z. N. (1998). Ovarian steroids and serotonin neural function. Molecular Neurobiology, 18, 87123.10.1007/BF02914268
Biederman, J., Petty, C. R., Fried, R., Wozniak, J., Micco, J. A., Henin, A., … Faraone, S. V. (2010). Child behavior checklist clinical scales discriminate referred youth with autism spectrum disorder: A preliminary study. Journal of Developmental & Behavioral Pediatrics, 31, 485490. https://doi.org/10.1097/DBP.0b013e3181e56ddd
Bölte, S., Poustka, F., & Constantino, J. N. (2008). Assessing autistic traits: Cross-cultural validation of the social responsiveness scale (SRS). Autism Research, 1, 354363. https://doi.org/10.1002/aur.49
Boukhris, T., & Bérard, A. (2015). Selective serotonin reuptake inhibitor use during pregnancy and the risk of autism spectrum disorders: A review. Journal of Pediatric Genetics, 4, 8493.10.1055/s-0035-1556744
Boukhris, T., Sheehy, O., & Mottron, L. (2015). Antidepressant use during pregnancy and the risk of autism spectrum disorder in children. JAMA Pediatrics, 170, 117124.10.1001/jamapediatrics.2015.3356
Brand, S. R., & Brennan, P. A. (2009). Impact of antenatal and postpartum maternal mental illness: How are the children? Clinical Obstetrics and Gynecology, 52, 441455. https://doi.org/10.1097/GRF.0b013e3181b52930
Brennan, P. A., Hammen, C., Andersen, M. J., Bor, W., Najman, J. M., & Williams, G. M. (2000). Chronicity, severity, and timing of maternal depressive symptoms: Relationships with child outcomes at age 5. Developmental Psychology, 36, 759766.
Brown, A. S., Gyllenberg, D., Malm, H., McKeague, I. W., Hinkka-Yli-Salomäki, S., Artama, M., … Sourander, A. (2016). Association of selective serotonin reuptake inhibitor exposure during pregnancy with speech, scholastic, and motor disorders in offspring. JAMA Psychiatry, 73, 11631170. https://doi.org/10.1001/jamapsychiatry.2016.2594
Brown, H. K., Ray, J. G., Wilton, A. S., Lunsky, Y., Gomes, T., & Vigod, S. N. (2017). Association between serotonergic antidepressant use during pregnancy and autism spectrum disorder in children. JAMA, 317, 15441552. https://doi.org/10.1001/jama.2017.3415
Carrow-Woolfolk, E. (1999). CASL: Comprehensive assessment of spoken language. Circle Pines, MN: American Guidance Services.
Castro, V. M., Kong, S. W., Clements, C. C., Brady, R., Kaimal, a J., Doyle, a E., … Perlis, R. H. (2016). Absence of evidence for increase in risk for autism or attention-deficit hyperactivity disorder following antidepressant exposure during pregnancy: A replication study. Translational Psychiatry, 6, e708. https://doi.org/10.1038/tp.2015.190
Clements, C. C., Castro, V. M., Blumenthal, S. R., Rosenfield, H. R., Murphy, S. N., Fava, M., … Perlis, R. H. (2015). Prenatal antidepressant exposure is associated with risk for attention-deficit hyperactivity disorder but not autism spectrum disorder in a large health system. Molecular Psychiatry, 20, 727734. https://doi.org/10.1038/mp.2014.90
Constantino, J., & Gruber, C. (2007). Social responsiveness scale (SRS). Los Angeles, CA: Western Psychological Services.
Cooper, W. O., Willy, M. E., Pont, S. J., & Ray, W. A. (2007). Increasing use of antidepressants in pregnancy. American Journal of Obstetrics and Gynecology, 196, 544.e1-5. https://doi.org/10.1016/j.ajog.2007.01.033
Croen, L. A., Grether, J. K., Yoshida, C. K., Odouli, R., & Hendrick, V. (2011). Antidepressant use during pregnancy and childhood autism spectrum disorders. Archives of General Psychiatry, 68, 11041112. https://doi.org/10.1001/archgenpsychiatry.2011.73
Davalos, D. B., Yadon, C. A., & Tregellas, H. C. (2012). Untreated prenatal maternal depression and the potential risks to offspring: A review. Archives of Women's Mental Health, 15, 114. https://doi.org/10.1007/s00737-011-0251-1
Elliott, C. D. (2007). Differential ability scales (2nd ed.). San Antonio, TX: Harcourt Assessment.
El Marroun, H., White, T. J. H., van der Knaap, N. J. F., Homberg, J. R., Fernández, G., Schoemaker, N. K., … Tiemeier, H. (2014). Prenatal exposure to selective serotonin reuptake inhibitors and social responsiveness symptoms of autism: Population-based study of young children. The British Journal of Psychiatry: The Journal of Mental Science, 205, 95102. https://doi.org/10.1192/bjp.bp.113.127746
Freire, C., de Oliveira, C.C.M., & Pereira Pondé, M. (2016). Antidepressants in pregnancy and autism spectrum disorder: A systematic review. Journal of Psychiatry, 19, 392. https://doi.org/10.4172/2378-5756.1000392
Gentile, S. (2015). Prenatal antidepressant exposure and the risk of autism spectrum disorders in children. Are we looking at the fall of Gods? Journal of Affective Disorders, 182, 132137. https://doi.org/10.1016/j.jad.2015.04.048
Gidaya, N. B., Lee, B. K., Burstyn, I., Yudell, M., Mortensen, E. L., & Newschaffer, C. J. (2014). In utero exposure to selective serotonin reuptake inhibitors and risk for autism spectrum disorder. Journal of Autism and Developmental Disorders, 44, 25582567. https://doi.org/10.1007/s10803-014-2128-4
Grigoriadis, S., VonderPorten, E. H., Mamisashvili, L., Tomlinson, G., Dennis, C. L., Koren, G., … & Martinovic, J. (2013). The impact of maternal depression during pregnancy on perinatal outcomes: a systematic review and meta-analysis. The Journal of clinical Psychiatry, 74, e321e341. https://doi.org/10.4088/JCP.12r07968
Hall, C., & Hamel, J. (2012). The role of comprehensive evaluation in the differential diagnosis of autism in a clinic setting. In International Meeting for Autism Research. Toronto, Ontario.
Handal, M., Skurtveit, S., Roth, C., Hernandez-Diaz, S., & Selmer, R. (2016). Prenatal exposure to folic acid and antidepressants and language development: A population-based cohort study. Journal of Clinical Psychopharmacology, 36, 333339. https://doi.org/10.1097/JCP.0000000000000519
Hanley, G. E., Brain, U., & Oberlander, T. F. (2015) Prenatal exposure to serotonin reuptake inhibitor antidepressants and childhood behavior. Pediatric Research, 78:174180. doi: 10.1038/pr.2015.77
Harrington, R. A., Lee, L.-C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2013). Serotonin hypothesis of autism: Implications for selective serotonin reuptake inhibitor use during pregnancy. Autism Research, 6, 149168. https://doi.org/10.1002/aur.1288
Harrington, R. A., Lee, L.-C., Crum, R. M., Zimmerman, A. W., & Hertz-Picciotto, I. (2014). Prenatal SSRI use and offspring with autism spectrum disorder or developmental delay. Pediatrics, 133, e1241e1248. https://doi.org/10.1542/peds.2013-3406
Healy, D., Le Noury, J., & Mangin, D. (2016). Links between serotonin reuptake inhibition during pregnancy and neurodevelopmental delay/spectrum disorders: A systematic review of epidemiological and physiological evidence. International Journal of Risk & Safety in Medicine, 28, 125141. https://doi.org/10.3233/JRS-160726
Hresko, W. P., Reid, D. K., & Hammill, D. D. (1999). Test of early language development. Austin, TX: Pro-ed.
Huybrechts, K. F., Palmsten, K., Avorn, J., Cohen, L. S., Holmes, L. B., Franklin, J. M., … & Hernández-Díaz, S. (2014). Antidepressant use in pregnancy and the risk of cardiac defects. New England Journal of Medicine, 370, 23972407.
Huybrechts, K. F., Palmsten, K., Mogun, H., Kowal, M., Avorn, J., Setoguchi-Iwata, S., & Hernández-Díaz, S. (2013). National trends in antidepressant medication treatment among publicly insured pregnant women. General Hospital Psychiatry, 35, 265271.
Hviid, A., Melbye, M., & Pasternak, B. (2013). Use of selective serotonin reuptake inhibitors during pregnancy and risk of autism. New England Journal of Medicine, 369, 24062415. https://doi.org/10.1056/NEJMoa1301449
Johnson, K. C., Smith, A. K., Stowe, Z. N., Newport, D. J., & Brennan, P. A. (2016). Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: Differences in language and behavior, but not cognitive function. The Journal of Clinical Psychiatry, 77, e176e182. https://doi.org/10.4088/JCP.14m09348
Kobayashi, T., Matsuyama, T., Takeuchi, M., & Ito, S. (2016). Autism spectrum disorder and prenatal exposure to selective serotonin reuptake inhibitors: A systematic review and meta-analysis. Reproductive Toxicology, 65, 170178. https://doi.org/10.1016/j.reprotox.2016.07.016
Lattimore, K. A., Donn, S. M., Kaciroti, N., Kemper, A. R., Neal, C. R., & Vazquez, D. M. (2005). Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: A meta-analysis. Journal of Perinatology, 25, 595604. https://doi.org/10.1038/sj.jp.7211352
Liu, X., Agerbo, E., Ingstrup, K. G., Musliner, K., Meltzer-Brody, S., Bergink, V., & Munk-Olsen, T. (2017). Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study. BMJ, 358, j3668. https://doi.org/10.1136/BMJ.J3668
Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., … Rutter, M. (2000). The autism diagnostic observation schedule-generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorders, 30, 205223.
Lundström, S., Reichenberg, A., Anckarsäter, H., Lichtenstein, P., & Gillberg, C. (2015). Autism phenotype versus registered diagnosis in Swedish children: Prevalence trends over 10 years in general population samples. BMJ, 350, h1961. https://doi.org/10.1136/BMJ.H1961
Lupattelli, A., Wood, M., Ystrom, E., Skurtveit, S., Handal, M., & Nordeng, H. (2018). Effect of time-dependent selective serotonin reuptake inhibitor antidepressants during pregnancy on behavioral, emotional, and social development in preschool-aged children. Journal of the American Academy of Child & Adolescent Psychiatry, 57, 200208. doi: 10.1016/j.jaac.2017.12.010
Malm, H., Brown, A. S., Gissler, M., Gyllenberg, D., Hinkka-Yli-Salomäki, S., McKeague, I. W., … & Sourander, A. (2016). Gestational exposure to selective serotonin reuptake inhibitors and offspring psychiatric disorders: A national register-based study. Journal of the American Academy of Child & Adolescent Psychiatry, 55, 359366.
Maloney, S. E., Rahn, R., Akula, S., Rieger, M. A., McCullough, K. B., Jakes, C., … Dougherty, J. D. (2017). Maternal SSRI treatment during offspring development results in long-term behavioral, cellular, and neuroimaging disruptions. bioRxiv, 205708. https://doi.org/10.1101/205708
Man, K. K. C., Tong, H. H. Y., Wong, L. Y. L., Chan, E. W., Simonoff, E., & Wong, I. C. K. (2015). Exposure to selective serotonin reuptake inhibitors during pregnancy and risk of autism spectrum disorder in children: A systematic review and meta-analysis of observational studies. Neuroscience and Biobehavioral Reviews, 49, 8289. https://doi.org/10.1016/j.neubiorev.2014.11.020
Mezzacappa, A., Lasica, P.-A., Gianfagna, F., Cazas, O., Hardy, P., Falissard, B., … Gressier, F. (2017). Risk for autism spectrum disorders according to period of prenatal antidepressant exposure: A systematic review and meta-analysis. JAMA Pediatrics, 171, 555563. https://doi.org/10.1001/jamapediatrics.2017.0124
Newport, D., Brennan, P., Green, P., Ilardi, D., Whitfield, T., Morris, N., … Stowe, Z. (2008). Maternal depression and medication exposure during pregnancy: Comparison of maternal retrospective recall to prospective documentation. BJOG: An International Journal of Obstetrics and Gynaecology, 115, 681688. https://doi.org/10.1111/j.1471-0528.2008.01701.x
Nulman, I., Koren, G., Rovet, J., Barrera, M., Streiner, D. L., & Feldman, B. M. (2015). Neurodevelopment of children prenatally exposed to selective reuptake inhibitor antidepressants: Toronto sibling study. The Journal of clinical psychiatry, 76, e842e847.
O'Donnell, K. J., Glover, V., Jenkins, J., Browne, D., Ben-Shlomo, Y., Golding, J., & O'Connor, T. G. (2013). Prenatal maternal mood is associated with altered diurnal cortisol in adolescence. Psychoneuroendocrinology, 38, 16301638. https://doi.org/10.1016/j.psyneuen.2013.01.008
Pedersen, L. H., Henriksen, T. B., & Olsen, J. (2010). Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age. Pediatrics, 125, e600e608. doi:10.1542/peds.2008-3655
Pratt, L. A., Brody, D. J., & Gu, Q. (2011). Antidepressant use in persons aged 12 and over: United States, 2005-2008. NCHS Data Brief, (76), 18.
Rai, D., Lee, B. K., Dalman, C., Golding, J., Lewis, G., & Magnusson, C. (2013). Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: Population based case-control study. BMJ (Clinical Research Ed.), 346, f2059. https://doi.org/10.1136/BMJ.F2059
Rai, D., Lee, B. K., Dalman, C., Newschaffer, C., Lewis, G., & Magnusson, C. (2017). Antidepressants during pregnancy and autism in offspring: population based cohort study. BMJ, 358, j2811.
Rampono, J., Simmer, K., Ilett, K. F., Hackett, L. P., Doherty, D. A., Elliot, R., … Forman, T. (2009). Placental transfer of SSRI and SNRI antidepressants and effects on the neonate. Pharmacopsychiatry, 42, 95100. https://doi.org/10.1055/s-0028-1103296
Reichow, B., Salamack, S., Paul, R., Volkmar, F. R., & Klin, A. (2008). Pragmatic assessment in autism spectrum disorders: A comparison of a standard measure with parent report. Communication Disorders Quarterly, 29, 169176. https://doi.org/10.1177/1525740108318697
Skurtveit, S., Selmer, R., Roth, C., Hernandez-Diaz, S., & Handal, M. (2014). Prenatal exposure to antidepressants and language competence at age three: Results from a large population-based pregnancy cohort in Norway. BJOG: An International Journal of Obstetrics & Gynaecology, 121, 16211631. https://doi.org/10.1111/1471-0528.12821
Sørensen, M. J., Grønborg, T. K., Christensen, J., Parner, E. T., Vestergaard, M., Schendel, D., & Pedersen, L. H. (2013). Antidepressant exposure in pregnancy and risk of autism spectrum disorders. Clinical Epidemiology, 5, 449459. https://doi.org/10.2147/CLEP.S53009
Sujan, A. C., Rickert, M. E., Öberg, A. S., Quinn, P. D., Hernández-Díaz, S., Almqvist, C., … D'Onofrio, B. M. (2017). Associations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. JAMA, 317, 15531562. https://doi.org/10.1001/jama.2017.3413
Swales, D. A., Winiarski, D. A., Smith, A. K., Stowe, Z. N., Newport, D. J., Brennan, P. A. (2018). Maternal depression and cortisol in pregnancy predict offspring emotional reactivity in the preschool period. Developmental Psychobiology, 60, 557566. https://doi.org/10.1002/dev.21631
Viktorin, A., Uher, R., Reichenberg, A., Levine, S. Z., & Sandin, S. (2017). Autism risk following antidepressant medication during pregnancy. Psychological Medicine, 47, 27872796. https://doi.org/10.1017/S0033291717001301
Whitaker-Azmitia, P. M. (2001). Serotonin and brain development: Role in human developmental diseases. Brain Research Bulletin, 56, 479485.
Yirmiya, N., & Shaked, M. (2005). Psychiatric disorders in parents of children with autism: A meta-analysis. Journal of Child Psychology and Psychiatry, 46, 6983.

Keywords

School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure

  • Erica L. Smearman (a1) (a2), Cassandra L. Hendrix (a1), Dominika A. Winiarski (a3), Katrina C. Johnson (a1), Alicia K. Smith (a4) (a5), Opal Y. Ousley (a4), Zachary N. Stowe (a6), D. Jeffrey Newport (a7) and Patricia A. Brennan (a1)...

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