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A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate

Jonathan Rampono, Stephen Proud, L. Peter Hackett, Judith H. Kristensen, Kenneth F. Ilett
DOI: http://dx.doi.org/10.1017/S1461145704004286 329-334 First published online: 1 September 2004

Abstract

Antidepressants are often used antenatally, and placental transfer may lead to adverse effects (toxicity) in the neonate. Pregnant women taking fluoxetine (n=4), sertraline (n=4), paroxetine (n=2) or venlafaxine (n=1) in the last trimester were studied. Maternal and cord sera were collected at delivery and infant serum on day 5 after birth for measurement of antidepressant concentrations. Neonatal Abstinence Scores (NAS) were measured in the infants on days 1–3 after birth. In maternal serum, median drug concentrations were: fluoxetine (96 µg/l), norfluoxetine (110 µg/l), sertraline (11 µg/l), desmethylsertraline (38 µg/l), paroxetine (mean 12 µg/l), venlafaxine (220 µg/l), and O-desmethylvenlafaxine (392 µg/l). Corresponding median values in cord serum were: fluoxetine (65 µg/l), norfluoxetine (81 µg/l), sertraline (10 µg/l), desmethylsertraline (27 µg/l), paroxetine (mean 6 µg/l), venlafaxine (232 µg/l), and O-desmethylvenlafaxine (406 µg/l). Corresponding median cord:maternal concentration ratios were 0.67 for fluoxetine and 0.72 for norfluoxetine, 0.67 for sertraline and 0.63 for demethylsertraline, 0.52 (mean) for paroxetine, and 1.1 and 1.0 for venlafaxine and O-desmethylvenlafaxine respectively. The neonates of two patients taking fluoxetine had high NAS. Only fluoxetine and norfluoxetine were detected in infant serum. Our data show substantial placental transfer of antidepressants, but only fluoxetine persisted in the infant's serum. Neonatal toxicity may be associated with serotonin re-uptake blockade, and also be influenced by neonatal clearance.

Key words
  • Antidepressants
  • neonatal intolerance
  • neonatal toxicity
  • neonate
  • pregnancy