Drug treatment during pregnancy and isolated orofacial clefts in hungary.
OBJECTIVE
To evaluate the possible association between all kinds of drug treatments during pregnancy and isolated cleft lip with or without cleft palate (CL/P) and posterior cleft palate (PCP) in the offspring.


METHODS
The dataset of the large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996, was evaluated.


METHODS
One thousand three hundred seventy-four cases with isolated CL/P and 601 with PCP, plus 38,151 population controls (without birth defects) and 20,868 malformed controls with other defects.


METHODS
In this observation case-control study the data collection was based on prospective medical records particularly prenatal logbook, retrospective maternal data via a self-reported questionnaire, and home visits of nonresponding mothers.


METHODS
Isolated CL/P and PCP associated with drug treatments during pregnancy.


RESULTS
An increased risk for isolated CL/P was found in cases born to mothers treated with amoxicillin, phenytoin, oxprenolol, and thiethylperazine during the second and third month of pregnancy, i.e., the critical period of isolated CL/P. Risk of isolated PCP was increased in mothers with oxytetracycline and carbamazepine treatment during the third and fourth month of pregnancy, i.e., the critical period of PCP.


CONCLUSIONS
This study confirmed the orofacial cleft (OFC) inducing effect of phenytoin, carbamazepine, oxytetracycline, and thiethylperazine and suggested a possible association between OFCs and oxprenolol and amoxicillin. However, drugs may have only a limited role in the origin of isolated OFCs.
Puhó
Erzsébet H
EH
National Center for Healthcare Audit and Improvement, Department of Human Genetics and Teratology and the Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary.
Szunyogh
Melinda
M
Métneki
Júlia
J
Czeizel
Andrew E
AE
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000658:Amoxicillin / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D000927:Anticonvulsants / Q000009:adverse effects; D002220:Carbamazepine / Q000009:adverse effects; D016022:Case-Control Studies; D002971:Cleft Lip / Q000139:chemically induced / Q000453:epidemiology*; D002972:Cleft Palate / Q000139:chemically induced / Q000453:epidemiology*; D018492:Dopamine Antagonists / Q000009:adverse effects; D004358:Drug Therapy / Q000706:statistics & numerical data; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D006801:Humans; D006814:Hungary; D010096:Oxprenolol / Q000009:adverse effects; D010118:Oxytetracycline / Q000009:adverse effects; D010672:Phenytoin / Q000009:adverse effects; D011159:Population Surveillance; D011247:Pregnancy / Q000187:drug effects*; D011264:Pregnancy Trimesters; D011446:Prospective Studies; D012189:Retrospective Studies; D012307:Risk Factors; D013847:Thiethylperazine / Q000009:adverse effects
D000319:Adrenergic beta-Antagonists; D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D018492:Dopamine Antagonists; D002220:Carbamazepine; D010096:Oxprenolol; D010672:Phenytoin; D000658:Amoxicillin; D013847:Thiethylperazine; D010118:Oxytetracycline