| Congenital heart disease (CHD) is among the most common major congenital anomaly, occurring with an incidence of about8-12/1,000live births. CHD is one of the leading causes of infant death in the developed world, accounting for more deaths than any other type of malformation. Approximately one quarter of these children will have critical congenital heart disease (CCHD), which by definition requires surgery or catheter intervention during the newborn period. Timely diagnosis and treatment of CCHD will result in marked improvements in survival. Conversely, if such defects are not detected sufficiently early then severe hypoxemia, shock, acidosis and death are potential sequelae. However, Children with CCHD (particularly duct dependent CHD) may not initially have symptoms or the symptoms may be vague, and the condition is not detected on routine clinical examination in the majority of cases, they are always readmitted with cardiovascular collapse when the ductus arteriosus closed. About13-48%of newborns with CCHD have been estimated to leave hospital undiagnosed in developed countries.Screening strategies to detect CHD include antenatal ultrasound and physical examination of the newborn baby. Both techniques have a fairly low detection rate for isolated defects. As most CCHD have a degree of hypoxemia that would not necessarily produce visible cyanosis, a number of European studies have recently provided compelling evidence for the addition of POX to routine care as the complementary method for detecting CCHD, and some developed countries have considered it as a universal screening method for newborns. However, widespread use of POX screening still has practical issues including additional benefit from POX screening over the current practice, practicability of conducting such screening in non-medical centers. Furthermore, favorable outcomes of European studies may not predict similar success in developing countries due to different prenatal and postnatal detection rate, different hospital settings and different spectrum of CCHD. Importantly, POX could not completely take place of physical examination such as auscultation; other screening indicators need to be included to enhance the detection rate of CCHD.To date, all screening data were from developed countries. Our study aimed to establish a screening-diagnosis system in China by four-step study (Prevalence of neonatal CHD study, Estimation of proportion of undiagnosed CCHD at discharge, Accuracy study of clinical evaluation plus POX for detecting neonatal CHD, Impact of clinical evaluation plus POX on the detection of neonatal CHD:a multicenter prospective screening study).Part I Accurate Assessment of Prevalence of Congenital Heart Disease at Live BirthAims:Given the wide spectrum of CHD which lead to considerable variability in prevalence and severity, incorporation of neonatal CHD screening into recommended universal screening panel was a challenging question, our study aimed to determine the true prevalence and spectrume of CHD at live birth using echocardiographic screening.Methods:A total of5190consecutive newborns from two secondary hospitals were included. Each neonate had a complete clinical evaluation and POX test with echocardiographic diagnosis at average47h of age. Newborns with persistent CHD underwent at least4months of follow-up, and the temporal trend of prevalence of CHD was assessed.Results:Overall live birth prevalence of CHD was26.6%o (severe3.5%o, moderate5.4%o and mild17.7%o), and prevalence of CHD that could be detected by clinical evaluation was12.1%o. Among undetected CHD cases, mild CHD constituted92%, moderate6.7%and severe1.3%. The most common CHD was ventricular septal defect (VSD,17.3%o), followed by atrial septal defect (ASD,6.2%o), patent ductus arteriosus (PDA,1.3%o), tetralogy of Fallot (TOF,0.4%o), single ventricle (SV,0.4%o), atrioventricular septal defect (AVSD,0.2%o) and double outlet right ventricle (DORV,0.2%o). Female predominance was observed in mild CHD (VSD, ASD), and male predominance was observed in severe CHD. The prevalence of CHD was reduced to19.5%o at the4-month follow-up and14.2%o at the6-month follow-up, which was largely caused by spontaneous closure of mild CHD.Conclusions:Prevalence of CHD determined by echocardiography screening was higher but more accurate than that obtained from birth defect registries.Part II Evaluation of Undiagnosed Critical Congenital Heart Disease Before Discharge Aim:To determine the proportion of newborns with undiagnosed CCHD discharged from the maternity ward.Methods:A retrospective cohort study of neonates who had CCHD and were admitted to a single institution between1January2012and31December2012was conducted. For comparing with the previously reported rate of undiagnosed CCHD at discharge, CCHD was defined as all DDC and any cyanotic CHD that required early surgery.Results:A total of235infants with CCHD were included, the median age at initial diagnosis was10days (1-360days). Of these,71.9%(169/235) underwent antenatal ultrasound examination and7.7%(13/169) were diagnosed. As a whole,57.9%(136/235) of CCHD cases were undiagnosed at discharge, and19.6%(46/235) were still missed after6-week examination. The diagnoses most likely to be unrecognized at discharge included truncus arteriosus (75%), pulmonary atresia (PA)/ventricle septal defect (VSD)(74.4%), critical coarctation of the aorta (CoA)(70%), single ventricle (SV)(68.9%) and total anomalous pulmonary venous connection (TAPVC)(61.5%). Among newborns diagnosed prior to discharge,50.5%(50/99) due to symptom or prenatal diagnosis,49.5%(49/99) due to abnormal findings in routine examination. Among asymptomatic CCHD cases without prenatal diagnosis,73.5%(136/185) were undiagnosed, the most common delayed diagnosis were transposition of the great arteries(TGA) with intact ventricular septum(IVS)(90.9%), SV (86.1%), PA/VSD (85.3%)、interruption of the aortic arch (IAA)(83.3%) and critical CoA (77.8%). Newborns with DDC were more likely to develop symptoms within the first few days after birth, in comparison with non-DDC cases (25.4%vs.6.7%), leading to a higher detection rate at discharge (63/130vs.36/105, P=0.029). However, if all symptomatic CCHD cases were excluded, their undiagnosed rates were close to each other (23/90vs.26/95, P>0.05)。Conclusions:The overall proportion of newborns with CCHD undiagnosed at discharge was very high (57.9%), particularly for asymptomatic CCHD cases (72%). China has a greater need to conduct postnatal screening than do developed countries.Part Ⅲ Diagnostic accuracy of Pulse Oximetry Combined With Clinical Evaluation for Detecting Neonatal Congenital Heart DiseaseAims:Although POX has been recognized as promising screening tool for CCHD, CE still play an important role. We aimed to validate the accuracy of7specific clinical indicators (CE plus POX) for detecting CHD with different severity.Methods:A total of5190consecutive newborns from2participating hospitals were included. All newborns were screened by7indicators (family history of CHD, tachypnea, cyanosis, particular facial features, heart murmur, abnormal POX reading, extracardiac malformations) and underwent echocardiography, any newborn with at least one of these conditions was considered positive-screened. Six months follow-up was performed for newborns with CHDs.Results:Of401positive-screened newborns,63had CHD. An additional75negative-screened newborns were diagnosed with CHD. Sensitivity of7indicators for detecting major CHD and CCHD was94.6%and100%, the corresponding specificity was92.9%and92.4%. The sensitivity of POX alone for detecting major CHDs was low (16.2%), but it was increased up to83.3%for CCHD. POX plus heart murmur had the same efficacy as that of all7indicators for detecting CHDs with different severity, but lower false positive rate (FPR)(6.5%vs.7.1%for major CHDs,7%vs.7.4%for CCHDs).≥30h was found to be the optimal timing for ascertainment of heart murmur on the premise of reducing FPR.Conclusions:Screening with7indicators had high sensitivity and specificity for detecting CHDs (except for non-significant CHDs), while POX plus heart murmur was likely to be an effective and quiker mean that could take place of7indicators which should be validated in a larger population.Part IV Using Pulse Oximetry Combined With Clinical Evaluation to Detect Neonatal Congenital Heart Disease:A Prospective Multicenter StudyAims:The incremental value of POX varied among studies, and it was not clear that the benefits of CHD screening demonstrated in studies from developed countries would translate with similar success to developing countries. We aimed to evaluate the effectiveness of POX with CE for detecting CHD in China.Methods:A large, prospective multicenter screening study was conducted in18hospitals throughout China. All newborns without a prenatal diagnosis of CHD were eligible for screening. Newborns with either an abnormal POX or abnormal CE were considered to have a positive screening result. All positive-screened newborns in asymptomatic group and all symptomatic newborns underwent echocardiography. False negative results were identified by clinical follow-up and through regional congenital anomalies registries. The accuracy of POX plus CE for detecting CCHD or major CHD was calculated separately.Results:A total122,738newborns were screened (120,707asymptomatic,2031symptomatic), and1071were detected to have CHD (157critical,329major). For asymptomatic newborns, the sensitivity of POX plus CE was93%for CCHD and90%for major CHD. The addition of POX to the routine CE improved sensitivity for detecting CCHD by16%(from77%to93%). Ten CCHD cases were missed (6left heart obstructive defects and4cyanotic heart defects). FPR for detecting CCHD was2.7%for CE alone and0.3%for POX alone. A significant decrease in the FPR for both POX and CE with a later screening time was observed, while no significant difference in FPR existed for POX after18h, and the sensitivity for both POX and CE did not change over time. POX plus murmur alone and POX plus CE (which included4aspects of clinical screening) had the same sensitivity for detecting asymptomatic major CHD (90%) and CCHD (93%). FPR was significantly lower for POX plus murmur versus POX plus CE (2.39%vs.2.74%, respectively, for major CHD;2.51%vs.2.86%, respectively, for CCHD). For symptomatic newborns,10overtly cyanotic newborns and one newborn with tachypnea had CCHD, resulting in7%(11/157) of CCHD cases in total who developed symptoms prior to screemng.Conclusions:The addition of POX screening to routine CE in newborns resulted in a significant improvement in the detection rate of CCHD in China. POX plus abnormal murmur proved to be an effective and quick method for detecting major CHD in asymptomatic newborns. The results of this study provide a strong argument for implementing routine CHD screening in Chinese nurseries. |
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