Newborn screening for congenital heart disease using echocardiography and follow-up at high altitude in China
Introduction
According to data from low altitudes, the incidence of congenital heart disease (CHD) is about 6–9‰, with critical CHD in 15%–25% [1,2]. Pulse oximetry has been recommended as a newborn screening tool for critical CHD with the cutoff SpO2 < 95%. However, this screening method is inapplicable to high altitude for a number of reasons. First, newborns at high altitude have a lower corresponding SpO2 and wider standard deviations across different levels of altitude [3]. A recent study from moderate altitude in Aurora, Colorado, USA (1694 m) showed significantly higher failure rates of pulse oximetry screening than those at sea level, even with a cut-off value of 90% [4]. The United States workgroup has expressed concern about adapting such protocol in high altitude communities and recommended further research [5]. Second, previous studies from high altitudes have reported extremely rare incidence of critical CHD [[6], [7], [8], [9]]. Almost all the CHDs are the simple forms with left to right shunt including secundum atrial septal defect (ASD), patent ductus arteriosus (PDA), and ventricular septal defect (VSD) [[6], [7], [8], [9]]. Third, altitude hypoxia induces pulmonary arterial hypertension (PAH) in healthy people [[10], [11], [12]]. PAH may be compounded in high altitude children with left to right shunt types of CHD [[13], [14], [15]]. Noticeably, all the previous high altitude screening studies were conducted in older children aged from 2 to 18 years [[6], [7], [8], [9]]. Many of them developed PAH, and some with severe CHD may have died before the age of screening. As such, early detection of CHD is crucial. Until now, the true picture of CHD occurrence and natural history at high altitude worldwide remains lacking.
The study aimed to examine the incidence and spectrum of CHD at high altitude using the intensive methodology with echocardiography screening newborns and follow up their outcomes, and consisted of two parts. Study 1 was to screen asymptomatic newborns for CHD in postnatal day 3–5 and follow-up their outcomes; Study 2 retrospectively examined the occurrence of CHD in newborns who were admitted to NICU within 2 postnatal days in order to depict a truer spectrum of CHD and follow-up their outcomes.
Section snippets
Study 1
This study was prospectively conducted at the Qinghai Women and Children's Hospital in Xining (2261 m), Qinghai province from Mar, 2015 to Aug, 2017. As part of a quality initiative to implement newborn echocardiography screening and follow-up program, the study did not require approval from the Institutional Ethics Board. Consent was obtained by verbal explanations from parents. All asymptomatic newborns in postnatal day 3–5 were eligible for this study, irrespective of gestational age. The
Study 1. In asymptomatic newborns
There were 1396 live births during the study period. Among them, 1002 asymptomatic newborns (71.8%) underwent the screening, 101 (10.0%) babies' parents rejected the study, and 41 (4.1%) were missed due to the unavailability of personnel or devices. The remaining 394 (28.2%) babies were transferred to NICU and echocardiography was performed in 335 (see Study 2 section). Fig. 1 shows that the distribution of altitudes in 1337 babies was uneven, concentrating in Xining (2261 m) (398 babies,
Discussion
The incidence of CHD varies and is usually expressed as per thousand live births [1,2]. Hoffman and Kaplan in 2002 examined the incidences reported in 62 studies published after 1955 and determined the reasons for the variability. The incidence of CHD depended primarily on the number of small VSDs and this number in turn depended upon how early the diagnosis was made [2]. They suggested that any assessment of the incidence of CHD must take into account of the ages of the patients with special
Limitations
First, our hospital is located in area where the main habitats are Hui and Han, with considerably less Tibetans. The proportion of ethnics in our study population was 28.4% Han, 64.3% Hui, Salar and others and 7.3% Tibetan. This figure does not represent the overall population composition in Qinghai which includes 53.0% of Han, 22.5% Hui, Salar and others and 24.4% Tibetan. This might, to some degree, limited us to detect the relation between the incidence and spontaneous closure rate of CHD
Conclusion
The incidence of CHD in newborns at high altitude is about 20 times higher than the reported values from low altitude regions, consisting mostly of simple forms of ASD and PDA, and rare complex CHD. The spontaneous closure of the simple defects occurs much later as compared to the low altitude figures. By 12–18 months of age, about 30% CHD remain open, leaving the incidence of 10%, which is still about 10 times higher than that at low altitude. Longer history of migration is associated with
Acknowledgements
The authors gratefully acknowledge the cooperation and support from the clinicians in the Departments of Obstetrics and Gynecology and Echocardiography of the Women and Children's Hospital of Qinghai Province.
Funding
Start-up fund for Jia Li from the Capital Institute of Pediatrics.
Disclosures
None.
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The two authors made equal contributions.