科研之友
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摘要
Congenital heart defects (CHDs) are the most common anomaly in infants and are a major cause of infant morbidity and mortality despite advances in medical care. The origins of CHDs therefore need to be better studied for prevention and earlier detection. Recent studies have studied biomarkers associated with heart defects and preeclampsia, a disorder characterized by excess soluble endoglin and Fms-like tyrosine kinase 1 relative to placental growth factor and vascular endothelial growth factor. Biomarkers related to heart defects include imbalances in proangiogenic signaling proteins, such as vascular endothelial growth factor and placental growth factor, and antiangiogenic proteins, such as soluble endoglin and Fms-like tyrosine kinase 1. These same biomarkers are abnormally altered in preeclampsia. Angiogenic mechanisms may be part of a shared pathway in preeclampsia and CHDs. Studies show that the pathology of preeclampsia begins early (perhaps at the start of pregnancy), around the time of fetal heart morphogenesis. This study tries to determine the relationship between preeclampsia and prevalence of CHDs in offspring. A population-based study was conducted using hospital discharge abstracts compiled in the Maintenance and Use of Data for the Study of Hospital Clientele database (for the entire Province of Quebec, Canada). Discharge abstracts were extracted for women paired with infants delivered at 20 weeks of gestation or greater between 1989 and 2012. All women who delivered an infant with or without heart defects in any Quebec hospital were included (N = 1,942,072 neonates). Congenital heart defects were defined as structural abnormalities of the heart or intrathoracic great vessels formed before birth. Critical defects considered in the study were tetralogy of Fallot; transposition of the great vessels, including double outlet right and left ventricle; truncus arteriosus; hypoplastic left heart; common ventricle; coarctation of the aorta, including interrupted aortic arch; and other critical defects (total anomalous pulmonary venous return, Ebstein anomaly, and tricuspid and pulmonary atresia). Noncritical defects of the endocardial cushion, ventricular septum, atrial septum, valves, aorta, and pulmonary artery; heterotaxy; and all remaining noncritical defects were also considered. The possibility that CHDs could be more strongly associated with some variants of preeclampsia (mild, severe, superimposed, early onset, late onset) was also considered. The study included 1,942,072 infants delivered at 20 weeks of gestation or more, this included 17,296 with heart defects and 50,840 multiple births but excluded 7609 stillbirths and 2797 infants with chromosomal anomalies. The absolute prevalence of CHD was higher for infants of women with preeclampsia than without preeclampsia (16.7 vs 8.6 per 1000). Site-specific defects (septum, valve, and aorta/pulmonary artery) were more common in infants of women with preeclampsia than without preeclampsia. Gestational age at onset of preeclampsia appeared to be the most important risk factor for heart defects. Early-onset preeclampsia was associated with critical (prevalence ratio [PR], 2.78; 95% confidence interval [CI], 1.71-4.50), noncritical (PR, 5.55; 95% CI, 4.98-6.19), septal (PR, 6.21; 95% CI, 5.47-7.05), valve (PR, 3.69; 95% CI, 2.34-5.80), aorta/pulmonary artery (PR, 6.33; 95% CI, 4.87-8.23), and multiple defects (PR, 5.31; 95% CI, 4.11-6.86) relative to no preeclampsia. No variant of preeclampsia yielded associations with heart defects that were as strong as early onset. In this population-based study, although the absolute risk of CHDs was low, preeclampsia was significantly associated with noncritical heart defects in offspring, and preeclampsia before 34 weeks was associated with critical heart defects.
- 出版日期2016-2
