Prenatal antipsychotic exposure and neuromotor performance during infancy

Arch Gen Psychiatry. 2012 Aug;69(8):787-94. doi: 10.1001/archgenpsychiatry.2012.160.

Abstract

Context: Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce.

Objective: To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants.

Design, setting, and participants: A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n=202), or no psychotropic agents (n=85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face.

Main outcome measures: The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials.

Results: Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F(2,281)=4.51; P=.01; partial η(2)=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P's.05) and maternal depression during pregnancy was associated with less efficient habituation (r(245)=0.16; P.02). There were no significant differences regarding habituation between medication exposure groups.

Conclusions: Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / pharmacokinetics
  • Antipsychotic Agents* / administration & dosage
  • Antipsychotic Agents* / adverse effects
  • Antipsychotic Agents* / pharmacokinetics
  • Child Development / drug effects*
  • Depressive Disorder / diagnosis
  • Depressive Disorder / drug therapy
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Habituation, Psychophysiologic / drug effects*
  • Humans
  • Infant
  • Longitudinal Studies
  • Maternal Exposure
  • Neuropsychological Tests
  • Pregnancy
  • Pregnancy Complications / diagnosis
  • Pregnancy Complications / drug therapy*
  • Prenatal Exposure Delayed Effects* / diagnosis
  • Prenatal Exposure Delayed Effects* / physiopathology
  • Prenatal Exposure Delayed Effects* / psychology
  • Psychomotor Performance / drug effects*
  • Psychotic Disorders / diagnosis
  • Psychotic Disorders / drug therapy*
  • Psychotropic Drugs / administration & dosage
  • Psychotropic Drugs / adverse effects
  • Psychotropic Drugs / pharmacokinetics
  • Risk Assessment

Substances

  • Antidepressive Agents
  • Antipsychotic Agents
  • Psychotropic Drugs