Association of high-dose bifonazole administration during early pregnancy and severe limb reduction defects in the newborn.
BACKGROUND
Neonatal limb reduction defects may be caused by exposure to an external agent. The azole derivatives are used in the treatment of systemic and dermal mycoses. Their relative teratogenic risk is still controversial.


METHODS
We describe two newborns with severe limb defects who were exposed to high doses of oral (an unacceptable route) and/or intravaginal bifonazole during the entire first trimester of pregnancy.


CONCLUSIONS
Although only two cases are insufficient to establish a relationship, our data suggest that maternal intake of bifonazole in early pregnancy poses a risk of morphogenic malformations. The literature suggests several possible mechanisms.
Linder
Nehama
N
Department of Neonatology, Rabin Medical Center, Petach Tikva, Israel. linderm@ netvision.net.il
Amarilla
Mandola
M
Hernandez
Adriana
A
Tamiri
Tsippy
T
Sirota
Lea
L
Klinger
Gil
G
Levy
Itzhak
I
Merlob
Paul
P
D000014:Abnormalities, Drug-Induced; D000015:Abnormalities, Multiple / Q000209:etiology* / Q000473:pathology; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects*; D007231:Infant, Newborn; D017880:Limb Deformities, Congenital / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D012307:Risk Factors
D000935:Antifungal Agents; D007093:Imidazoles; C036596:bifonazole