Skip to main content

Advertisement

SpringerLink
Log in

Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Objectives

This study evaluated the question whether length of in utero exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants might affect neonatal outcome and psychomotor development in infancy.

Methods

Birth outcome was determined in the offspring of 55 women with major depressive disorder who used SSRI medication for different durations during their pregnancies. At an average age of 14 months, children underwent a pediatric examination and an evaluation with the Bayley Scales of Infant Development (BSID-II).

Results

Duration of in utero exposure to SSRIs was negatively associated with total Apgar scores, specifically the activity subscale. Odds ratios for a low score (<2) on this scale were 3.8 and 6.0 at 1 and 5 min, respectively. Newborns with longer exposure were more often admitted to the Neonatal Intensive Care Unit (p < .03). Mental Development Index scores of the infants were not associated with the length of gestational exposure to SSRIs. A longer duration of exposure increased the risk for lower Psychomotor Developmental Index and Behavioral Rating Scale scores in infancy (p = 0.012 and p = 0.007, respectively) on the BSID-II.

Conclusions

The findings provide evidence that the length of prenatal SSRI antidepressant use can affect neonatal adjustment and can have an effect on psychomotor test scores in infancy. Importantly, the children’s mental development and motor function by neurological examination were within the normal range. Timing of exposure to SSRIs during susceptible periods of fetal development and variations in the severity of maternal depression may have contributed to the associations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Alwan S, Reefhuis J, Rasmussen SA, Olney RS, Friedman JM (2007) Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 356:2684–2692

    Article  PubMed  CAS  Google Scholar 

  • Ansorge M, Zhou M, Lira A, Hen R, Gingrich J (2004) Early-life blockade of the 5-HT transporter alters emotional behavior in adult mice. Science 306(5697):879–881

    Article  PubMed  CAS  Google Scholar 

  • Bakker MK, Kolling P, van den Berg PB, de Walle HE, de Jong van den Berg LT (2008) Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharmacol 65:600–606

    Article  PubMed  Google Scholar 

  • Bayley N (1993) Bayley scales of infant development, 2nd edn. The Psychological Corporation, San Antonio

    Google Scholar 

  • Beck A (1972) Depression: causes and treatment. University of Pennsylvania Press, Philadelphia

    Google Scholar 

  • Beck A, Ward C, Mendelson M, Mock J, Erbaugh J (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571

    PubMed  CAS  Google Scholar 

  • Berard A, Ramos E, Rey E, Blais L, St-Andre M, Oraichi D (2007) First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage. Birth Defects Res B Dev Reprod Toxicol 80:18–27

    Article  PubMed  CAS  Google Scholar 

  • Casper R, Fleisher B, Lee-Ancajas J, Gilles A, Gaylor E, DeBattista A, Hoyme H (2003) Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 142:402–408

    Article  PubMed  CAS  Google Scholar 

  • Chambers C, Johnson K, Dick L, Felix R, Jones K (1996) Birth outcomes in pregnant women taking fluoxetine. N Engl J Med 335:1010–1015

    Article  PubMed  CAS  Google Scholar 

  • Chambers CD, Hernandez-Diaz S, Van Marter LJ, Werler MM, Louik C, Jones KL, Mitchell AA (2006) Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 354:579–587

    Article  PubMed  CAS  Google Scholar 

  • Diav-Citrin O, Shechtman S, Weinbaum D, Wajnberg R, Avgil M, Di Gianantonio E, Clementi M, Weber-Schoendorfer C, Schaefer C, Ornoy A (2008) Paroxetine and fluoxetine in pregnancy: a prospective, multicentre, controlled, observational study. Br J Clin Pharmacol 66:695–705

    PubMed  CAS  Google Scholar 

  • DiPietro JA, Novak MF, Costigan KA, Atella LD, Reusing SP (2006) Maternal psychological distress during pregnancy in relation to child development at age two. Child Dev 77:573–587

    Article  PubMed  Google Scholar 

  • DSM I (1994) Diagnostic and Statistical Manual of Mental Disorders, 4th edn. American Psychiatric Association, Washington, D.C

    Google Scholar 

  • Ehrenstein V, Pedersen L, Grijota M, Nielsen GL, Rothman KJ, Sorensen HT (2009) Association of Apgar score at five minutes with long-term neurologic disability and cognitive function in a prevalence study of Danish conscripts. BMC Pregnancy Childbirth 9:14

    Article  PubMed  Google Scholar 

  • First M, Spitzer RL, Gibbon M, Williams JBW (1997) Structured clinical interview for DSM IV axis I disorders. APA, Washington, D.C

    Google Scholar 

  • Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  PubMed  CAS  Google Scholar 

  • Hansen H, Mikkelsen J (1998) Long term effects on serotonin transporter mRNA expression of chronic neonatal exposure to a serotonin reuptake inhibitor. Eur J Pharmacol 352:307–315

    Article  PubMed  CAS  Google Scholar 

  • Hendrick V, Stowe Z, Altshuler L, Hwang S, Lee E, Haynes D (2003) Placental passage of antidepressant medications. Am J Psychiatry 160:993–996

    Article  PubMed  Google Scholar 

  • Homberg JR, Schubert D, Gaspar P (2009) New perspectives on the neurodevelopmental effects of SSRIs. Trends Pharmacol Sci 31:60–65

    Article  PubMed  Google Scholar 

  • Jacobs B, Azmitia E (1992) Structure and function of the brain serotonin system. Physiol Rev 72:165–215

    PubMed  CAS  Google Scholar 

  • Jacobs B, Fornal C (1995) Serotonin and behavior, a general hypothesis. In: Bloom F, Kupfer D (eds) Psychopharmacology, the fourth generation of progress. Raven, New York, pp 461–469

    Google Scholar 

  • Laine K, Heikkinen T, Ekblad U, Kero P (2003) Effects of exposure to selective serotonin reuptake inhibitors during pregnancy on serotonergic symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 60:720–726

    Article  PubMed  CAS  Google Scholar 

  • Loubinoux I, Pariente J, Boulanouar K, Carel C, Manelfe C, Rascol O, Celsis P, Chollet F (2002) A single dose of the serotonin neurotransmission agonist paroxetine enhances motor output: double-blind, placebo-controlled, fMRI study in healthy subjects. Neuroimage 15:26–36

    Article  PubMed  Google Scholar 

  • Loughhead AM, Fisher AD, Newport DJ, Ritchie JC, Owens MJ, DeVane CL, Stowe ZN (2006) Antidepressants in amniotic fluid: another route of fetal exposure. Am J Psychiatry 163:145–147

    Article  PubMed  Google Scholar 

  • Louik C, Lin AE, Werler MM, Hernandez-Diaz S, Mitchell AA (2007) First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 356:2675–2683

    Article  PubMed  CAS  Google Scholar 

  • Lund N, Pedersen LH, Henriksen TB (2009) Selective serotonin reuptake inhibitor exposure in utero and pregnancy outcomes. Arch Pediatr Adolesc Med 163:949–954

    Article  PubMed  Google Scholar 

  • Mattson SN, Calarco K, Kao KK, Jones KL, Chambers CD (2004) Neurodevelopmental outcome of infants and toddlers exposed prenatally to selective serotonin reuptake inhibitors. Clinical and Molecular Teratology 70:261

    Google Scholar 

  • Merlob P, Birk E, Sirota L, Linder N, Berant M, Stahl B, Klinger G (2009) Are selective serotonin reuptake inhibitors cardiac teratogens? Echocardiographic screening of newborns with persistent heart murmur. Birth Defects Res A Clin Mol Teratol 85:837–841

    Article  PubMed  CAS  Google Scholar 

  • Misri S, Reebye P, Kendrick K, Carter D, Ryan D, Grunau RE, Oberlander TF (2006) Internalizing behaviors in 4-year-old children exposed in utero to psychotropic medications. Am J Psychiatry 163:1026–1032

    Article  PubMed  Google Scholar 

  • Mortensen JT, Olsen J, Larsen H, Bendsen J, Obel C, Sorensen HT (2003) Psychomotor development in children exposed in utero to benzodiazepines, antidepressants, neuroleptics, and anti-epileptics. Eur J Epidemiol 18:769–771

    Article  PubMed  CAS  Google Scholar 

  • Moses-Kolko EL, Bogen D, Perel J, Bregar A, Uhl K, Levin B, Wisner KL (2005) Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications. JAMA 293:2372–2383

    Article  PubMed  CAS  Google Scholar 

  • Nulman I, Rovet J, Stewart D, Wolpin J, Gardner H, Theis J, Kulin N, Koren G (1997) Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 336:258–262

    Article  PubMed  CAS  Google Scholar 

  • Nulman I, Rovet J, Stewart DE, Wolpin J, Pace-Asciak P, Shuhaiber S, Koren G (2002) Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 159:1889–1895

    Article  PubMed  Google Scholar 

  • Oberlander T, Eckstein Grunau R, Fitzgerald C, Ellwood A, Misri S, Rurak D, Riggs K (2002) Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response. Pediatr Res 51:443–453

    Article  PubMed  CAS  Google Scholar 

  • Oberlander T, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, Riggs W (2005) Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 115:411–425

    Article  PubMed  Google Scholar 

  • Oberlander TF, Reebye P, Misri S, Papsdorf M, Kim J, Grunau RE (2007) Externalizing and attentional behaviors in children of depressed mothers treated with a selective serotonin reuptake inhibitor antidepressant during pregnancy. Arch Pediatr Adolesc Med 161:22–29

    Article  PubMed  Google Scholar 

  • Oberlander TF, Warburton W, Misri S, Aghajanian J, Hertzman C (2008) Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study. Br J Psychiatry 192:338–343

    Article  PubMed  Google Scholar 

  • Pastuszak A, Schick-Boschetto B, Zuber C (1993) Pregnancy outcome following first-trimester exposure to fluoxetine (Prozac). J Am Med Assoc 269:2246–2248

    Article  CAS  Google Scholar 

  • Pedersen LH, Henriksen TB, Vestergaard M, Olsen J, Bech BH (2009) Selective serotonin reuptake inhibitors in pregnancy and congenital malformations: population based cohort study. Bmj 339:b3569

    Article  PubMed  Google Scholar 

  • Pedersen LH, Henriksen TB, Olsen J (2010) Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age. Pediatrics 125:e600–e608

    Article  PubMed  Google Scholar 

  • Radloff L (1977) The CES-D scale: a self report depression scale for research in the general population. Appl Psychol Meas 1:385–401

    Article  Google Scholar 

  • Simon G, Cunningham M, Davis R (2002) Outcomes following prenatal antidepressant exposure. Am J Psychiatry 159:2055–2061

    Article  PubMed  Google Scholar 

  • Stowe Z, Hostetter A, Owens M, Ritchie J, Sternberg K, Cohen L, Nemeroff C (2003) The pharmacokinetics of sertraline excretion into human breast milk: determinants of infant serum concentrations. J Clin Psychiatry 64:73–80

    Article  PubMed  CAS  Google Scholar 

  • Suri R, Altshuler L, Hellemann G, Burt VK, Aquino A, Mintz J (2007) Effects of antenatal depression and antidepressant treatment on gestational age at birth and risk of preterm birth. Am J Psychiatry 164:1206–1213

    Article  PubMed  Google Scholar 

  • Thompson B, Wasserman J, Matula K (1996) The factor structure of the behavior rating scale of the Bayley scales of infant development—II: cross-sample, cross-sectional, and cross-method investigations of construct validity. Educ Psychol Meas 56:460–474

    Article  Google Scholar 

  • Toh S, Mitchell AA, Louik C, Werler MM, Chambers CD, Hernandez-Diaz S (2009) Antidepressant use during pregnancy and the risk of preterm delivery and fetal growth restriction. J Clin Psychopharmacol 29:555–560

    Article  PubMed  CAS  Google Scholar 

  • Wisner KL, Sit DK, Hanusa BH, Moses-Kolko EL, Bogen DL, Hunker DF, Perel JM, Jones-Ivy S, Bodnar LM, Singer LT (2009) Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes. Am J Psychiatry 166:557–566

    Article  PubMed  Google Scholar 

  • Wogelius P, Norgaard M, Gislum M, Pedersen L, Munk E, Mortensen PB, Lipworth L, Sorensen HT (2006) Maternal use of selective serotonin reuptake inhibitors and risk of congenital malformations. Epidemiology 17:701–704

    Article  PubMed  Google Scholar 

  • Zeskind PS, Stephens LE (2004) Maternal selective serotonin reuptake inhibitors use during pregnancy and newborn neurobehavior. Pediatrics 113:368–375

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to thank the women and the children who participated in this study, and we appreciate the support of the Edwards and Matcovich Family Trust Fund.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Road, Room 2365, Stanford, CA, 94305-5723, USA

    Regina C. Casper, Allyson A. Gilles & Laura C. Lazzeroni

  2. Division of Neonatology and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Barry E. Fleisher & Joan Baran

  3. Division of Medical Genetics, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Gregory Enns

  4. Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA

    Laura C. Lazzeroni

Authors
  1. Regina C. Casper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Allyson A. Gilles
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Barry E. Fleisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Joan Baran
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Gregory Enns
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Laura C. Lazzeroni
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Regina C. Casper.

Additional information

The study received support from the Edwards and Matcovich Family Trust Fund. The authors have no financial relationship with the Edwards and Matcovich Family Trust Fund. The Edwards and Matcovich Family Trust Fund had no input in any aspect or part of the study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Casper, R.C., Gilles, A.A., Fleisher, B.E. et al. Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development. Psychopharmacology 217, 211–219 (2011). https://doi.org/10.1007/s00213-011-2270-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-011-2270-z

Keywords

Search

Navigation