Atypical Antipsychotic Administration During Late Pregnancy: Placental Passage and Obstetrical Outcomes

• Published in: The American journal of psychiatry Vol. 164; no. 8; pp. 1214 - 1220
• Main Authors: Newport, D. Jeffrey, Calamaras, Martha R., DeVane, C. Lindsay, Donovan, Jennifer, Beach, Aquila J., Winn, Stephanie, Knight, Bettina T., Gibson, Bryan B., Viguera, Adele C., Owens, Michael J., Nemeroff, Charles B., Stowe, Zachary N.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Psychiatric Association 01-08-2007
• Subjects: Adult; Antipsychotic Agents - blood; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - therapeutic use; Benzodiazepines - blood; Benzodiazepines - pharmacokinetics; Biological and medical sciences; Birth weight; Clinical medicine; Data analysis; Data collection; Dibenzothiazepines - blood; Dibenzothiazepines - pharmacokinetics; Dibenzothiazepines - therapeutic use; Drug therapy; Female; Fetal Blood - chemistry; Fetal Blood - metabolism; Haloperidol - blood; Haloperidol - pharmacokinetics; Haloperidol - therapeutic use; Hazardous materials; Humans; Infant, Low Birth Weight - blood; Infant, Newborn; Intensive Care Units, Neonatal - utilization; Maternal-Fetal Exchange; Medical sciences; Multivariate analysis; Plasma; Pregnancy; Pregnancy Complications - blood; Pregnancy Complications - drug therapy; Pregnancy Complications - metabolism; Pregnancy Outcome - epidemiology; Prospective Studies; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychotic Disorders - blood; Psychotic Disorders - drug therapy; Psychotic Disorders - metabolism; Psychotropic drugs; Quetiapine Fumarate; Risperidone - blood; Risperidone - pharmacokinetics; Risperidone - therapeutic use; Pregnancy; Chemotherapy; Treatment; Atypical antipsychotic; Placenta; Fetal membrane; Psychotropic
• ISSN: 0002-953X; 1535-7228
• DOI: 10.1176/appi.ajp.2007.06111886

Objectives:
There are limited data regarding the use of atypical antipsychotic medications in pregnancy. The objectives of the current study were to quantify placental permeability to antipsychotic medications and to document obstetrical outcomes for women taking these agents proximate to delivery.
Method:
The authors conducted a prospective observational study of women treated with an atypical antipsychotic or haloperidol during pregnancy. Maternal and umbilical cord plasma samples collected at delivery were analyzed for medication concentrations. Placental passage was defined as the ratio of umbilical cord to maternal plasma concentrations (ng ml). Obstetrical outcome was ascertained through maternal reports and reviews of obstetrical records.
Results:
Fifty-four pregnant women with laboratory-confirmed antipsychotic use proximate to delivery were included in the analysis. Complete maternal-infant sample pairs were available for 50 participants. Placental passage ratio was highest for olanzapine (mean=72.1%, SD=42.0%), followed by haloperidol (mean=65.5%, SD=40.3%), risperidone (mean=49.2%, SD=33.9%), and quetiapine (mean=23.8%, SD=11.0%). There were tendencies toward higher rates of low birth weight (30.8%) and neonatal intensive care unit admission (30.8%) among neonates exposed to olanzapine.
Conclusions:
All four antipsychotics demonstrated incomplete placental passage. Quetiapine demonstrated the lowest placental passage of the medications studied. These novel data provide an initial quantification of the placental passage of antipsychotics and fetal exposure in humans, demonstrating significant differences between individual medications.