Association of prenatal phenobarbital and phenytoin exposure with genital anomalies and menstrual disorders.
BACKGROUND
Animal studies demonstrated that early exposure to phenobarbital decreases reproductive function. This study investigates whether prenatal exposure to these anticonvulsants affects human genital tract development.


METHODS
Genital anomalies at birth were studied retrospectively in 90 phenobarbital-exposed, 108 phenobarbital plus phenytoin-exposed, and 198 matched control infants. Of this group, 72 drug-exposed males, 75 drug-exposed females, and 147 matched control subjects participated in a follow-up and were interviewed at age 19-35. Differences between groups were tested by chi-square and t-tests.


RESULTS
A total of 15% of the phenobarbital-exposed boys versus 2.8% control boys had undescended testes at birth. More anticonvulsant-exposed (24%) than control males (11%) had received medical treatment for genital anomalies. Anticonvulsant-exposed females more often had irregularities in menstrual cycles (31% vs. 17%) and bleeding (15% vs. 3%) and reported more problems during pregnancy.


CONCLUSIONS
Prenatal exposure to anticonvulsants seems to induce minor genital anomalies and may affect reproductive function.
Dessens
A B
AB
Department of Obstetrics, Gynecology and Neonatology, Academic Medical Center, Graduate School Neurosciences Amsterdam, University of Amsterdam, P.O. Box 22700, 1100 DE Amsterdam, The Netherlands. arides@delta-pz.nl
Cohen-Kettenis
P T
PT
Mellenbergh
G J
GJ
Koppe
J G
JG
Poll
N E
NE
Boer
K
K
D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D016022:Case-Control Studies; D003456:Cryptorchidism / Q000209:etiology; D005260:Female; D005500:Follow-Up Studies; D005835:Genitalia / Q000002:abnormalities* / Q000196:embryology; D006801:Humans; D008297:Male; D008423:Maternal Age; D018811:Maternal Exposure; D008599:Menstruation Disturbances / Q000209:etiology*; D010634:Phenobarbital / Q000009:adverse effects*; D010672:Phenytoin / Q000009:adverse effects*; D011247:Pregnancy; D012189:Retrospective Studies
D000927:Anticonvulsants; D010672:Phenytoin; D010634:Phenobarbital