RESUMO
OBJECTIVE: To determine the rate of occurrence of major malformations in infants whose mothers had taken the drug valproic acid (VPA) as monotherapy during the first trimester of pregnancy and had enrolled in the North American Antiepileptic Drug Pregnancy Registry. METHODS: Data were collected from pregnant women throughout the United States and Canada through telephone-based interviews. Each woman was interviewed at enrollment, at 7 months' gestation, and postpartum. With her written permission, the medical records of each mother and her infant were obtained. The major malformations tabulated were those identified at or before 5 days of age. The prevalence of congenital malformations among offspring of monotherapy VPA-exposed women was compared with that among infants of women exposed to all other antiepileptic drugs (internal comparison group) and with that among newborns in the Active Malformations Surveillance Program at Brigham and Women's Hospital (external comparison group). RESULTS: Sixteen affected cases were identified among 149 VPA-exposed women (proportion: 10.7%; 95% CI: 6.3 to 16.9%). The prevalence in the internal comparison group was 2.9% (95% CI: 2.0 to 4.1%; odds ratio: 4.0, 95% CI: 2.1 to 7.4; p < 0.001). Assuming a 1.62% prevalence in the external comparison group, the relative risk of having an affected offspring for VPA-exposed women was 7.3 (95% CI: 4.4 to 12.2; p < 0.001). CONCLUSION: Maternal exposure to valproic acid during the first trimester of pregnancy significantly increased the risk of major malformations.
Assuntos
Anormalidades Induzidas por Medicamentos/epidemiologia , Anticonvulsivantes/efeitos adversos , Epilepsia/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Ácido Valproico/efeitos adversos , Anormalidades Induzidas por Medicamentos/fisiopatologia , Adulto , Feminino , Humanos , Recém-Nascido , Entrevistas como Assunto , Masculino , América do Norte/epidemiologia , Gravidez , Primeiro Trimestre da Gravidez/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Prevalência , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Fatores de RiscoRESUMO
We report three brothers with Allgrove syndrome. All three had evidence of adrenal insufficiency and deficient tear production, though neither of them had achalasia, the third component of the disorder at the time of this report. Neurological abnormalities were present in the index case. The younger siblings were neurologically normal. The familial association of achalasia, alacrimia and adrenal insufficiency, rather than being fortuitous, is a distinct clinical entity.
