Safety of haloperidol and penfluridol in pregnancy: a multicenter, prospective, controlled study.
OBJECTIVE
To assess the safety of the butyrophenone neuroleptics haloperidol and penfluridol in pregnancy.


METHODS
The rate of major anomalies was compared between a cohort of pregnant women counseled for gestational exposure to haloperidol or penfluridol and a control group counseled for nonteratogen exposure. This multicenter, prospective, controlled study was conducted within the European Network of Teratology Information Services (ENTIS) and included women who contacted 1 of 4 teratology information services for counseling between January 1989 and December 2001.


RESULTS
We followed up on the outcomes of 215 pregnancies exposed to haloperidol (N = 188) or penfluridol (N = 27)-78.2% (of 206) were in the first trimester-and compared to outcomes of 631 ENTIS controls. The rate of congenital anomalies did not differ between the haloperidol/penfluridol-exposed group and the control group (6/179 = 3.4% vs. 22/581 = 3.8%, p = .787). No difference was found by limiting the analysis to those exposed to butyrophenones during the first trimester. There were 2 cases of limb defects in the butyrophenone-exposed group (1 after haloperidol and 1 after penfluridol exposure) and none in the controls. A higher rate of elective terminations of pregnancy (8.8% vs. 3.8%, p = .004), a higher rate of preterm birth (13.9% vs. 6.9%, p = .006), a lower median birth weight (3155 g vs. 3370 g, p < .001), and a lower median birth weight of full-term infants (3250 g vs. 3415 g, p = .004) were found in the butyrophenone-exposed group compared to the controls.


CONCLUSIONS
This study suggests that haloperidol and penfluridol do not represent a major teratogenic risk. Since a possible association between butyrophenone exposure and limb defects cannot be ruled out with this sample size, a level II ultrasound with emphasis on the limbs should be considered in pregnancies with first trimester exposure.
Diav-Citrin
Orna
O
Israeli Teratogen Information Service, Jerusalem 91120, Israel.
Shechtman
Svetlana
S
Ornoy
Shani
S
Arnon
Judy
J
Schaefer
Christof
C
Garbis
Hanneke
H
Clementi
Maurizio
M
Ornoy
Asher
A
D000014:Abnormalities, Drug-Induced / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001724:Birth Weight; D002090:Butyrophenones / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D018811:Maternal Exposure / Q000706:statistics & numerical data*; D008431:Maternal-Fetal Exchange; D010298:Parity; D010395:Penfluridol / Q000009:adverse effects* / Q000627:therapeutic use; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D011256:Pregnancy Outcome / Q000453:epidemiology; D011261:Pregnancy Trimester, First; D047928:Premature Birth / Q000139:chemically induced / Q000453:epidemiology; D011446:Prospective Studies
D014150:Antipsychotic Agents; D002090:Butyrophenones; D010395:Penfluridol; D006220:Haloperidol