title: Prolonged prenatal psychotropic medication exposure alters neonatal acute pain response.
abstract: Selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines are frequently used to treat maternal depression during pregnancy, however the effect of increased serotonin (5HT) and gamma-amino-butyric acid (GABA) agonists in the fetal human brain remains unknown. 5HT and GABA are active during fetal neurologic growth and play early roles in pain modulation, therefore, if prolonged prenatal exposure alters neurodevelopment this may become evident in altered neonatal pain responses. To examine biologic and behavioral effects of prenatal exposure, neonatal responses to acute pain (phenylketonuria heel lance) in infants with prolonged prenatal exposure were examined. Facial action (Neonatal Facial Coding System) and cardiac autonomic reactivity derived from the relationship between respiratory activity and short term variations of heart rate (HRV) were compared between 22 infants with SSRI exposure (SE) [fluoxetine (n = 7), paroxetine (n = 11), sertraline (n = 4)]; 16 infants exposed to SSRIs and clonazepam (SE+) [paroxetine (n = 14), fluoxetine (n = 2)]; and 23 nonexposed infants during baseline, lance, and recovery periods of a heel lance. Length of maternal SSRI use did not vary significantly between exposure groups-[mean (range)] SE:SE+ 183 (31-281):141 (54-282) d (p > 0.05). Infants exposed to SE and SE+ displayed significantly less facial activity to heel lance than control infants. Mean HR increased with lance, but was significantly lower in SE infants during recovery. Using measures of HRV and the transfer relationship between heart rate and respiration, SSRI infants had a greater return of parasympathetic cardiac modulation in the recovery period, whereas a sustained sympathetic response continued in the control group. Prolonged prenatal SSRI exposure appears to be associated with reduced behavioral pain responses and increased parasympathetic cardiac modulation in recovery following an acute neonatal noxious event. Possible 5HT-mediated pain inhibition, pharmacologic factors and the developmental course remain to be studied.
authors.affiliation: Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada. toberlander@cw.bc.ca
authors.forename: Tim F
authors.initials: TF
authors.lastname: Oberlander
authors.forename: Ruth
authors.initials: R
authors.lastname: Eckstein Grunau
authors.forename: Colleen
authors.initials: C
authors.lastname: Fitzgerald
authors.forename: Ann-Louise
authors.initials: AL
authors.lastname: Ellwood
authors.forename: Shaila
authors.initials: S
authors.lastname: Misri
authors.forename: Dan
authors.initials: D
authors.lastname: Rurak
authors.forename: Kenneth Wayne
authors.initials: KW
authors.lastname: Riggs
mesh_terms: D000818:Animals; D002998:Clonazepam / Q000494:pharmacology*; D005149:Facial Expression; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D010146:Pain; D010147:Pain Measurement; D010661:Phenylketonurias / Q000175:diagnosis; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012119:Respiration / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
chemical_list: D002998:Clonazepam; D018757:GABA Modulators; D017367:Selective Serotonin Reuptake Inhibitors