Am J Perinatol 2013; 30(04): 297-302
DOI: 10.1055/s-0032-1324697
Original Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

In Utero Antidepressant Exposure and Neurodevelopment in Preterm Infants

Beau Batton
1   Department of Pediatrics, Southern Illinois University School of Medicine, St. John's Children's Hospital, Springfield, Illinois
,
Emily Batton
1   Department of Pediatrics, Southern Illinois University School of Medicine, St. John's Children's Hospital, Springfield, Illinois
,
Kara Weigler
1   Department of Pediatrics, Southern Illinois University School of Medicine, St. John's Children's Hospital, Springfield, Illinois
,
Glen Aylward
1   Department of Pediatrics, Southern Illinois University School of Medicine, St. John's Children's Hospital, Springfield, Illinois
,
Daniel Batton
1   Department of Pediatrics, Southern Illinois University School of Medicine, St. John's Children's Hospital, Springfield, Illinois
› Author Affiliations
Further Information

Publication History

12 January 2012

15 May 2012

Publication Date:
14 August 2012 (online)

Abstract

Objective To investigate the impact of in utero selective serotonin reuptake inhibitor (SSRI) exposure on neurodevelopment in a cohort of preterm infants.

Study Design Retrospective case control study of preterm infants ≤366/7 weeks gestation with in utero SSRI exposure. Subjects were matched to controls by gestational age, year of birth, birth weight, gender, and age at neurodevelopmental assessment. Neurodevelopment was assessed with the Bayley Infant Neurodevelopmental Screener and the Bayley Scales of Infant Development.

Results The 19 infants with in utero SSRI exposure were similar to controls in demographic data, birth weight, and in-hospital morbidity. The mean ± standard deviation (SD) Mental Developmental Index score for study infants at 36 months was 94 ± 15 versus 91 ± 10 for controls (p = 0.46). The mean ± SD Psychomotor Developmental Index score was also similar between groups: 79 ± 21 for study infants versus 75 ± 20 for control infants (p = 0.72). Other neurodevelopmental outcomes were comparable.

Conclusion In this cohort of preterm infants, in utero SSRI exposure was not associated with adverse neurodevelopment above the baseline risk for this degree of prematurity. Larger studies are needed to obviate the risk of a type II error.

 
  • References

  • 1 Gavin NI, Gaynes BN, Lohr KN, Meltzer-Brody S, Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol 2005; 106 (5 Pt 1) 1071-1083
  • 2 Stewart DE. Clinical practice. Depression during pregnancy. N Engl J Med 2011; 365: 1605-1611
  • 3 Stowe ZN, Nemeroff CB. Women at risk for postpartum-onset major depression. Am J Obstet Gynecol 1995; 173: 639-645
  • 4 Grote NK, Bridge JA, Gavin AR, Melville JL, Iyengar S, Katon WJ. A meta-analysis of depression during pregnancy and the risk of preterm birth, low birth weight, and intrauterine growth restriction. Arch Gen Psychiatry 2010; 67: 1012-1024
  • 5 Pincus HA, Tanielian TL, Marcus SC , et al. Prescribing trends in psychotropic medications: primary care, psychiatry, and other medical specialties. JAMA 1998; 279: 526-531
  • 6 Owens MJ, Morgan WN, Plott SJ, Nemeroff CB. Neurotransmitter receptor and transporter binding profile of antidepressants and their metabolites. J Pharmacol Exp Ther 1997; 283: 1305-1322
  • 7 Rice D, Barone Jr S. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal models. Environ Health Perspect 2000; 108 (Suppl. 03) 511-533
  • 8 Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997; 340: 249-258
  • 9 Gaspar P, Cases O, Maroteaux L. The developmental role of serotonin: news from mouse molecular genetics. Nat Rev Neurosci 2003; 4: 1002-1012
  • 10 Durig J, Hornung JP. Neonatal serotonin depletion affects developing and mature mouse cortical neurons. Neuroreport 2000; 11: 833-837
  • 11 Casper RC, Fleisher BE, Lee-Ancajas JC , et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003; 142: 402-408
  • 12 Casper RC, Gilles AA, Fleisher BE, Baran J, Enns G, Lazzeroni LC. Length of prenatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants: effects on neonatal adaptation and psychomotor development. Psychopharmacology (Berl) 2011; 217: 211-219
  • 13 Pedersen LH, Henriksen TB, Olsen J. Fetal exposure to antidepressants and normal milestone development at 6 and 19 months of age. Pediatrics 2010; 125: e600-e608
  • 14 Nulman I, Rovet J, Stewart DE , et al. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997; 336: 258-262
  • 15 Nulman I, Rovet J, Stewart DE , et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002; 159: 1889-1895
  • 16 Oberlander TF, Grunau RE, Fitzgerald C, Papsdorf M, Rurak D, Riggs W. Pain reactivity in 2-month-old infants after prenatal and postnatal serotonin reuptake inhibitor medication exposure. Pediatrics 2005; 115: 411-425
  • 17 Oberlander TF, Papsdorf M, Brain UM, Misri S, Ross C, Grunau RE. Prenatal effects of selective serotonin reuptake inhibitor antidepressants, serotonin transporter promoter genotype (SLC6A4), and maternal mood on child behavior at 3 years of age. Arch Pediatr Adolesc Med 2010; 164: 444-451
  • 18 Volpe J. Intracranial hemorrhage: germinal matrix-intraventricular hemorrhage of the premature infant. In: Volpe J, eds. Neurology of the Newborn. 5th ed. Philadelphia, PA: W.B. Saunders; 2008: 517-588
  • 19 Bell MJ, Ternberg JL, Feigin RD , et al. Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging. Ann Surg 1978; 187: 1-7
  • 20 International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited. Arch Ophthalmol 2005; 123: 991-999
  • 21 Walsh MC, Wilson-Costello D, Zadell A, Newman N, Fanaroff A. Safety, reliability, and validity of a physiologic definition of bronchopulmonary dysplasia. J Perinatol 2003; 23: 451-456
  • 22 Aylward GP. Bayley Infant Neurodevelopmental Screener. San Antonio, TX: The Psychological Corporation; 1995
  • 23 Bayley N. Bayley Scales of Infant Development. 2nd ed. San Antonio, TX: The Psychological Corporation; 1993
  • 24 Bayley N. Bayley Scales of Infant and Toddler Development. 3rd ed. San Antonio, TX: Pearson; 2006
  • 25 Aylward GP, Verhulst SJ. Predictive utility of the Bayley Infant Neurodevelopmental Screener (BINS) risk status classifications: clinical interpretation and application. Dev Med Child Neurol 2000; 42: 25-31
  • 26 Broekman BF, Chan YH, Goh L , et al. Influence of birth weight on internalizing traits modulated by serotonergic genes. Pediatrics 2011; 128: e1250-e1258
  • 27 Homberg JR, Schubert D, Gaspar P. New perspectives on the neurodevelopmental effects of SSRIs. Trends Pharmacol Sci 2010; 31: 60-65
  • 28 Borue X, Chen J, Condron BG. Developmental effects of SSRIs: lessons learned from animal studies. Int J Dev Neurosci 2007; 25: 341-347
  • 29 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: 672-677