The present study examined the occurrence of complex CHD in the largest cohort in the NICU at high altitude. Since newborns with moderate or severe CHD are prone to have other serious illness and admitted to the NICU and subsequently die at young age at high altitude before the screening age in most of the previous studies, our data reveals a truer picture of CHD with the widest spectrum of moderate and severe types to date, in addition to the simple CHD as previously reported[3–7].
It has been well documented that the prevalence CHD is substantially higher at high altitude, consisting predominately of ASD and PDA. This figure is incomplete, largely resulted from the limitations of previous study design. All of them were conducted in children older than 2 years of age[3–5, 7] except for ours[6]. In our previous study, we screened newborns for CHD used echocardiography also in Qinghai province (average altitude 3,000 m) including asymptomatic babies and a small number of 335 sick babies admitted to the NICU before the screening in 3–5 days after birth. Only 2 severe CHD patients (one had the anomalous right superior pulmonary venous return to the right atrium and left inferior pulmonary venous stenosis; another had complete transposition of the great arteries) were found, and both died during the stay in the NICU[6]. This does not represent our clinical observations at high altitude.
The occurrence of moderate and severe CHD at high altitude has been scarcely reported. The only series, to our knowledge, was reported by Zheng et al from a small number of children including critically ill in Tibet [5]. They found 5.2% patients with severe CHD (20 out of 383 CHD patients), including complete atrioventricular septal defect, severe pulmonary stenosis with ASD, coarctation of the aorta with VSD, tetralogy of Fallot, pulmonary atresia with VSD, hypoplastic right heart with partial anomalous pulmonary venous connection or Ebstein’s anomaly, double outlet right ventricle[5]. The incidence of severe CHD was lower as compared to that (13.7%) from low altitude 1,000–2,000 m in Yunnan province, which was attributed to the older age at screening (4–17 years)[5].
In our present study in the NICU population, more types of severe CHD were found including complete transposition of the great arteries, tetralogy of Fallot, double outlet right ventricle, complete atrioventricular septal defect, truncus arteriosus, total anomalous pulmonary venous connection, hypoplastic left heart, hypoplastic right heart with tricuspid atresia, pulmonary atresia with intact ventricular septum and ebstein’s amonaly, interrupted aortic arch, single-ventricle abnormality, severe aortic or pulmonary stenosis. We also found more types of mild and moderate CHD, including large ASD, mild or moderate pulmonic stenosis, aortic stenosis, bicuspid aortic valve, mild pulmonary vein stenosis, partial anomalous pulmonary venous connection and persistent left superior vena cava. As such, this is the widest spectrum to date, consisting almost all types of severe, moderate and mild CHD described by Hoffman and Kaplan[1].
In Zheng et al’s data, right ventricular outflow obstruction, e.g. tetralogy of Fallot, severe pulmonary valvular stenosis and pulmonary artery atresia, was more common than left heart obstructive lesions, e.g. aortic stenosis and coarctation of the aorta. They considered it consistent with the reports demonstrating more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions in Asian or Chinese populations[10, 11]. This difference was not clearly shown in our data, which might be attributable to the particular NICU setting where patients were admitted duo to critical illness other than cardiac malformations.
According to data from low altitude regions, severe CHD occurs in about 15%-25% of all types of CHD[1, 2]. A study from neonatal unit in plain area also using echocardiography screening for CHD found a higher prevalence of CHD of 1.5%, compromising 31% of severe CHD[12]. At high altitude, the substantially high prevalence of ASD and PDA makes the proportion of severe CHD much less, being 4% or 5% even when critically ill patients are included as in our present study and Zheng et al’s[5]. Recent studies report that the prevalence of complex and severe CHD have decreased over time as a result of implementation of fetal echocardiography and pregnancy termination by intervention[2, 13, 14]. Although fetal echocardiography screening has been carried out in large-scales in plateau provincial capitals, such as Xining of Qinghai Province, only a very small portion have received fetal screening in surrounding regions. In our cohort, about 70% patients did not have fetal echocardiography.
The strikingly high incidence of ASD and PDA has been strongly suggested due to a postnatal (i.e., altitude hypoxia) rather than a fetal teratogenic mechanism[3]. The wide spectrum of moderate and severe CHD as seen in the plain regions appears less likely due to the environmental factors related to altitude hypoxia than that of genetics. However, the etiology of CHD is complex involving genetic heterogeneity and environment interactions. The adaptation/maladaptation in CHD development at high altitude remains to be explored.
Death resulting from CHDs still remains the most common cause of infant mortality from birth defects[15]. This is particularly so at high altitude. In our patients, despite early diagnosis in our patients, 90% of severe CHD have died within 2 months after NICU discharge, and 5.3% with mild and moderate CHD died within 2–3 years old. Only 15 patients underwent cardiac surgery with one early death, and other patients survived. Despite fast development, the health concept and medical resources for the interventional and surgical treatment of CHD remain limited at high altitude worldwide.