Atypical antipsychotic administration during late pregnancy: placental passage and obstetrical outcomes.
OBJECTIVE
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.


METHODS
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.
Newport
D Jeffrey
DJ
Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA. jeff.newport@emory.edu
Calamaras
Martha R
MR
DeVane
C Lindsay
CL
Donovan
Jennifer
J
Beach
Aquila J
AJ
Winn
Stephanie
S
Knight
Bettina T
BT
Gibson
Bryan B
BB
Viguera
Adele C
AC
Owens
Michael J
MJ
Nemeroff
Charles B
CB
Stowe
Zachary N
ZN
D000328:Adult; D014150:Antipsychotic Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000097:blood / Q000493:pharmacokinetics; D003987:Dibenzothiazepines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000378:metabolism; D006220:Haloperidol / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D007230:Infant, Low Birth Weight / Q000097:blood; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal / Q000706:statistics & numerical data; D008431:Maternal-Fetal Exchange; D000077152:Olanzapine; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D000069348:Quetiapine Fumarate; D018967:Risperidone / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine