Effect of exposure to selective serotonin reuptake inhibitors in utero on fetal growth: potential role for the IGF-I and HPA axes

Pediatr Res. 2009 Feb;65(2):236-41. doi: 10.1203/PDR.0b013e318193594a.

Abstract

To investigate the possible effect of fetal exposure to selective serotonin reuptake inhibitors (SSRIs) on somatic growth and on hormones of the hypothalamic-pituitary-adrenal (HPA) and insulin-like growth factor (IGF)-I axes, we compared the anthropometric parameters and hormonal profile of 21 SSRI-exposed infants and 20 matched controls. The SSRI group was characterized by lower crown-heel length (p < 0.01), smaller head circumference (p = 0.08), and higher percentage of infants with birth weight, birth length, and head circumference below the 10th percentile (p < 0.045, p = 0.08, p < 0.04, respectively), in addition to a significantly lower cord blood level of cortisol (p < 0.03) and higher level of thyroid-stimulating hormone (TSH) (p < 0.004). Infants exposed to citalopram had a lower cord blood IGF-I level than infants exposed to paroxetine (p < 0.001) and controls (p < 0.003). Placental IGF-I receptor (IGF-IR) expression was significantly higher in the SSRI group than in controls (p < 0.01). Urine 5-hydroxyindoleacetic acid (5-HIAA) level was negatively correlated with birth weight (r = -0.71, p < 0.025) and with dehydroepiandrosterone (DHEA) level (r = -0.71, p < 0.025). The Finnegan score was correlated with dehydroepiandrosterone sulfate (DHEAS) (r = 0.8, p < 0.005) and cortisol (r = 0.62, p = 0.05). Fetal exposure to SSRIs causes impaired intrauterine growth accompanied by alterations in the IGF-I and HPA axes. The findings may raise concern regarding maternal use of SSRIs during pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Birth Weight / drug effects
  • Case-Control Studies
  • Citalopram / adverse effects
  • Female
  • Fetal Blood / metabolism
  • Fetal Development / drug effects*
  • Fetal Growth Retardation / chemically induced*
  • Fetal Growth Retardation / metabolism
  • Fetus / drug effects*
  • Fetus / metabolism
  • Fluoxetine / adverse effects
  • Hormones / blood
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Infant, Newborn
  • Insulin-Like Growth Factor I / metabolism*
  • Male
  • Paroxetine / adverse effects
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Placenta / metabolism
  • Pregnancy
  • Selective Serotonin Reuptake Inhibitors / adverse effects*

Substances

  • Hormones
  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • Citalopram
  • Paroxetine
  • Insulin-Like Growth Factor I