Melinda Csáky-Szunyogh1, Attila Vereczkey2, Balázs Gerencsér3, Andrew E Czeizel4. 1. Hungarian Congenital Abnormality Registry , National Institute for Health Development , Budapest , Hungary. 2. Versys Clinics, Human Reproduction Institute , Budapest , Hungary. 3. Alfréd Rényi Institute of Mathematics, Hungarian Academy of Science , Budapest , Hungary. 4. Foundation for the Community Control of Hereditary Diseases , Budapest , Hungary.
Abstract
OBJECTIVE: To establish possible aetiological factors contributing to congenital heart defects (CHD) overall and separately for different types of CHD, as causes are unknown for the vast majority of patients. DESIGN: To estimate a possible association with maternal diseases and related drug treatments as exposures in the mothers of cases with right-sided obstructive defects of the heart (RSODH). SETTING: A large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities data set. PATIENTS: Newborn infants with four types of RSODH based on autopsy or surgical records. INTERVENTIONS: Comparison of 200 live-born cases with RSODH including 72 (36.0%) with pulmonary valve stenosis, 13 (6.5%) with tricuspid atresia/stenosis, 7 (3.5%) with Ebstein's anomaly and 108 (54.0%) with pulmonary atresia, with 304 matched controls and 38 151 population controls without any defects. MAIN OUTCOME MEASURES: Risk of any RSODH and risk of each type of RSODH. RESULTS: High blood pressure, particularly chronic hypertension with nifedipine treatment, was associated with a risk for RSODH (OR 7.03, 95% CI 3.13 to 13.84). High doses of folic acid reduced the birth prevalence of pulmonary atresia (OR 0.29, 95% CI 0.16 to 0.53). CONCLUSIONS: The multifactorial threshold model provides the best explanation for the origins of RSODH. Genetic predisposition may be triggered by maternal hypertension with nifedipine treatment, while the risk for pulmonary atresia is reduced by high doses of folic acid in early pregnancy.
OBJECTIVE: To establish possible aetiological factors contributing to congenital heart defects (CHD) overall and separately for different types of CHD, as causes are unknown for the vast majority of patients. DESIGN: To estimate a possible association with maternal diseases and related drug treatments as exposures in the mothers of cases with right-sided obstructive defects of the heart (RSODH). SETTING: A large population-based Hungarian Case-Control Surveillance of Congenital Abnormalities data set. PATIENTS: Newborn infants with four types of RSODH based on autopsy or surgical records. INTERVENTIONS: Comparison of 200 live-born cases with RSODH including 72 (36.0%) with pulmonary valve stenosis, 13 (6.5%) with tricuspid atresia/stenosis, 7 (3.5%) with Ebstein's anomaly and 108 (54.0%) with pulmonary atresia, with 304 matched controls and 38 151 population controls without any defects. MAIN OUTCOME MEASURES: Risk of any RSODH and risk of each type of RSODH. RESULTS: High blood pressure, particularly chronic hypertension with nifedipine treatment, was associated with a risk for RSODH (OR 7.03, 95% CI 3.13 to 13.84). High doses of folic acid reduced the birth prevalence of pulmonary atresia (OR 0.29, 95% CI 0.16 to 0.53). CONCLUSIONS: The multifactorial threshold model provides the best explanation for the origins of RSODH. Genetic predisposition may be triggered by maternal hypertension with nifedipine treatment, while the risk for pulmonary atresia is reduced by high doses of folic acid in early pregnancy.
Authors: Lorenzo D Botto; Angela E Lin; Tiffany Riehle-Colarusso; Sadia Malik; Adolfo Correa Journal: Birth Defects Res A Clin Mol Teratol Date: 2007-10