Official reprint from UpToDate® www.uptodate.com
©2012 UpToDate®
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2012 UpToDate, Inc.
Congenital heart disease (CHD) in the newborn: Presentation and screening for critical CHD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Mar 2012. | This topic last updated: Jan 23, 2012.

INTRODUCTION — Congenital heart disease (CHD) is the most common congenital disorder in newborns [1-3]. Critical CHD, defined as those requiring surgery or catheter based intervention in the first year of life, occurs in approximately 25 percent of those with CHD [4]. Although many newborns with critical CHD are symptomatic and identified soon after birth, others are not diagnosed till after discharge from the birth hospitalization [5-7]. In infants with a critical cardiac lesion, the risk of morbidity and mortality increases when there is a delay in diagnosis and timely referral to a tertiary center with expertise in treating these patients [8].

Factors that should lead clinicians to suspect CHD and screen for critical congenital heart lesions will be reviewed here. The evaluation and management of specific cardiac conditions are discussed separately [9]. (See "Cardiac causes of cyanosis in the newborn" and "Diagnosis and initial management of cyanotic heart disease in the newborn".)

EPIDEMIOLOGY — The reported prevalence of congenital heart disease (CHD) at birth ranges from 6 to 21 per 1000 live births [10-14]. Variation is primarily due to the use of different methods to detect CHD, such as referral to a cardiac center or fetal echocardiographic data [14,15].

  • In one English health region, reported prevalence of cardiovascular malformations was 6.5 per 1000 live births [5,13].
  • In a population-based study from Atlanta, the prevalence of CHD was 8.1 per 1000 live births from 1998 to 2005 [12]. The most common diagnosis was muscular and perimembranous ventricular septal defect (VSD), followed by secundum atrial septal defect (ASD) (prevalence of 2.7, 1.1, and 1 per 1000 live births, respectively). Tetralogy of Fallot was the most common cyanotic CHD (0.5 per 1000 births).
  • In a population-based study of all Danish live births from 1977 to 2005, the prevalence of CHD was 10.3 per 1000 live births [16]. Chromosomal defects were detected in 7 percent of those patients, and extracardiac anomalies in 22 percent.
  • The highest prevalence for CHD was observed in a population-based study from Taiwan with a prevalence of 13.1 per 1000 live births between 2000 and 2006 [9]. The most common defect was VSD, followed by secundum ASD and patent ductus arteriosus (prevalence of 4, 3.2, and 2 per 1000 live births, respectively).

In preterm infants (gestational age <37 weeks), CHD is two to three times that found in term infants [11].

CHD is one of the leading causes of perinatal and infant death from congenital malformations [1,13,17]. In a report from the United Kingdom Northern Congenital Abnormality Survey, 10 percent of deaths in this pediatric cohort with at least one congenital anomaly were associated with CHD [1].

CRITICAL CHD — Critical CHD, defined as those requiring surgery or catheter based intervention in the first year of life, occurs in approximately 25 percent of those with CHD [4]. In infants with critical CHD, the risk of morbidity and mortality increases when there is a delay in diagnosis and timely referral to a tertiary center with expertise in treating these patients [8]. Over the past several decades, outcomes have significantly improved for patients with critical CHD with the advancement of corrective or palliative interventions [1,18]. Therefore, timely diagnosis and subsequent intervention, particularly during the newborn hospitalization, are essential to reduce the mortality associated with critical CHD [9].

Timing of presentation — Infants with critical CHD may present during the birth hospitalization, often with serious and life-threatening clinical findings that require immediate intervention. However, in other affected neonates, especially those with ductal dependent lesions, the diagnosis of critical CHD may be missed prior to discharge because the infant appears normal on routine examination. (See 'Early serious or life-threatening presentation' below and 'Few or no symptoms during birth hospitalization' below.)

The timing of presentation varies with the underlying lesion and its dependence upon a patent ductus arteriosus.

Ductal dependent lesions, delayed diagnosis, and death — Many of the critical congenital heart lesions are ductus dependent. As a result, the affected neonate may not be symptomatic during the birth hospitalization because the ductus arteriosus has not closed prior to discharge. The magnitude of the failure to detect critical CHD during the first few days of life was demonstrated in a review of 10 studies that reported 30 percent of patients with critical CHD were diagnosed after birth hospitalization discharge [19]. The lesions that were not diagnosed prior to discharge were primarily ductal dependent and included coarctation of the aorta (COA), interrupted aortic arch, aortic stenosis, hypoplastic left heart syndrome (HLHS), transposition of the great artery, truncus arteriosus, tetralogy of Fallot, and total anomalous pulmonary venous connection.

Closure of a patent ductus arteriosus can precipitate rapid clinical deterioration with potentially life-threatening consequences (ie, severe metabolic acidosis, seizures, cardiogenic shock, cardiac arrest, or end-organ injury) [20]. The risk for death in infants with ductal-dependent critical CHD who are not diagnosed during the birth hospitalization is illustrated by the following studies:

  • In a population-based study from the California statewide death registry, more than half of the 152 neonates with a missed diagnosis of critical CHD died after their initial birth hospitalization [21]. The median age at death was 13.5 days. The most common diagnoses were HLHS and COA.
  • In a retrospective study of 4390 children with CHD, 800 patients died in the first year of life including 76 who died before a diagnosis of heart disease was made (1.7 percent of the entire cohort) [8].

EARLY SERIOUS OR LIFE-THREATENING PRESENTATION — Neonates with critical CHD can precipitously present with serious and life-threatening manifestations of their cardiac disease during the birth hospitalization.

Urgent consultation/referral to a pediatric cardiologist should be made when severe, potentially lethal, CHD is suspected in critically ill neonates who present with shock, cyanosis, or pulmonary edema [22].

Shock — A variety of mechanisms can lead to cardiogenic shock in newborns with ductal-dependent CHD, when the ductus arteriosus closes:

  • In left heart obstructive lesions (eg, hypoplastic left heart syndrome, critical aortic stenosis, coarctation of the aorta, and interrupted aortic arch), systemic perfusion is lost.
  • In right-sided obstructive lesions (eg, total anomalous pulmonary venous connection, tricuspid atresia, and mitral atresia), restricted pulmonary blood flow results in reduced systemic blood flow, which may result in shock.
  • In lesions with parallel pulmonary and systemic circulations (eg, transposition of the great arteries with intact ventricular septum), mixing between the two circulation is decreased leading to hypoxia and metabolic acidosis, which results in failure and shock.

Cardiogenic shock must be differentiated from other causes of shock, such as sepsis. In newborns who present with shock, cardiomegaly is a helpful finding indicating a cardiac etiology [23]. (See "Etiology, clinical manifestations, and evaluation of neonatal shock".)

Cyanosis — Cyanosis, usually detected when the concentration of reduced hemoglobin is 4 to 5 g/dL, is an important sign of CHD and is present in a number of congenital cardiac diseases. Patent ductus arteriosus (PDA) is an essential component of circulation in some, but not all, cyanotic cardiac lesions.

The normal closure of the PDA in the first days of life can precipitate profound cyanosis in the following scenarios:

In these patients, profound cyanosis is a manifestation of severe hypoxia that is associated with significant metabolic acidosis that may result in cardiac dysfunction (failure) and cardiogenic shock. Initiation of prostaglandin E1 (generic drug name, alprostadil) to re-open or maintain the ductus arteriosus, is life saving in these patients. Timely prostaglandin E1 infusion can prevent the development of shock, severe hypoxemia, acidosis, and resultant end organ damage. The use of prostaglandin E1 is discussed separately in neonates with cyanotic heart disease and in reviews of specific cardiac lesions. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1' and "Management and outcome of D-transposition of the great arteries", section on 'Prostaglandin (alprostadil) infusion' and "Total anomalous pulmonary venous connection", section on 'Initial medical management' and "Hypoplastic left heart syndrome", section on 'Initial medical management'.)

Lesions associated with cyanosis in nonductal dependent congenital heart defects include:

Severe pulmonary edema — Pulmonary edema, resulting in tachypnea and increased work of breathing, can occur when there is a massive, rapid increase in pulmonary blood flow associated with a fall in pulmonary vascular resistance at delivery in conditions such as truncus arteriosus [22] or PDA in premature infants, or pulmonary venous circulation obstruction in total anomalous pulmonary venous connection with obstruction [24]. (See "Pathophysiology, clinical manifestations, and diagnosis of patent ductus arteriosus in premature infants" and "Total anomalous pulmonary venous connection", section on 'Obstructed forms'.)

FEW OR NO SYMPTOMS DURING BIRTH HOSPITALIZATION — As discussed above, identifying all infants with critical CHD during the first few days of life would reduce mortality by allowing either corrective or palliative intervention. However, early detection of neonatal CHD remains challenging because clinical findings may be subtle or absent immediately after birth, and prenatal screening does not reliably detect all cases of CHD. Data have shown that pulse oximetry is an effective screening measure, but there is controversy regarding its overall cost-benefit. (See 'Pulse oximetry screening' below.)

Limitation of history and physical examination — Assessment of the newborn to detect CHD is focused on the history and physical examination, but several studies have shown that the newborn assessment can miss a significant number of patients with critical CHD [21,25,26].

This was illustrated in a retrospective English study of 1067 infants (diagnosed with CHD by 12 months of age) born between 1987 and 1994, in which 82 percent were not recognized to have CHD before hospital discharge [25]. Of these undiagnosed infants, 306 (35 percent) became symptomatic or died without a diagnosis before six weeks of age.

Despite these limitations, the history and physical examination can still contribute to the identification of neonates with critical CHD.

Variability of prenatal ultrasound — The sensitivity of prenatal screening with echocardiography for major heart disease is highly variable, ranging from 0 to 80 percent detection rates. Factors affecting sensitivity include operator training and experience, gestational age, maternal weight, fetal position, and type of defect. The efficacy of prenatal sonographic screening for CHD is discussed separately. (See "Prenatal sonographic diagnosis of fetal cardiac anomalies", section on 'Efficacy'.)

History — Identifying historical factors that are associated with CHD heightens the awareness of the clinician of the possibility of an underlying cardiac defect, thereby focusing their examination to detect any subtle cardiac finding in the well appearing neonate.

Maternal and prenatal history — The following maternal medical conditions or prenatal disorders increase the risk of CHD.

  • Maternal fever or influenza [27]
  • Smoking in the first trimester [28]

Family history — There is an overall threefold increased risk for CHD when a first degree relative has CHD [16,34]. The familial risk of specific malformations is even greater suggesting a stronger genetic effect in these conditions.

This was illustrated in a Danish population-based study that identified about 18,000 individuals with CHD over 28 years with the following findings [16]:

  • The risk of CHD in singletons births with first-, second-, or third-degree relatives with CHD was 3.2 (95% CI 3.0-3.5), 1.8 (95% CI 1.1-2.9), or 1.1 (95% CI 0.8-1.5), respectively.
  • When patients with chromosomal aberrations were excluded, the relative risk of CHD decreased to 2.2 in first degree relatives.
  • The relative risk for CHD for monozygotic twins was 15.2 and for dizygotic twins was 3.3 (similar to that of any first degree relative).
  • Heterotaxy syndrome was the congenital anomaly with the highest relative risk for familial recurrence (79.1) followed by right ventricular outflow tract obstruction (48.6), atrioventricular septal defect (24.3), left ventricular outflow tract obstruction (12.9), conotruncal defect (11.7), isolated atrial septal defect (7.1), and isolated ventricular defect (3.4).

In addition to inquiring about CHD among family members, parents should be questioned about familial occurrence of cardiomyopathies, sudden death, or unexpected death in infancy or childhood that could potentially uncover genetic preponderance of potential congenital cardiac abnormalities within the family. (See "Clinical features of congenital long QT syndrome".)

Physical examination — Although many infants with critical CHD are asymptomatic, subtle clinical findings may be detected that identify underlying cardiac disease. The following discussion reviews the physical findings that may be seen in an infant with CHD; however, as noted above, findings may be absent in those infants with a ductal dependent lesion and a PDA during their birth hospitalization. (See 'Limitation of history and physical examination' above.)

Cardiovascular examination — Cardiovascular findings suggestive of CHD include abnormal heart rate, precordial activity, and heart sounds; pathologic murmurs; and diminished or absent peripheral pulses; all of which merit further evaluation and perhaps referral to clinicians with expertise in caring for neonates with CHD.

Abnormal heart rate — In infants with heart rates that are higher or lower than the normal range of 90 to 160 beats per minute for neonates up to six days of age, electrocardiography is initially performed to determine whether there is an arrhythmia, and to guide further assessment and management [35].

Causes of abnormal neonatal heart rate include:

Precordial activity — Precordial palpation ascertains whether the heart is normally located on the left side of the chest. Dextrocardia is often associated with complex CHD. In addition, palpation may detect the following:

  • Cardiac enlargement which, in a newborn with respiratory symptoms, is more suggestive of cardiac than pulmonary disease [46].
  • Ventricular impulse in the lower left parasternal area suggestive of right ventricular volume or pressure overload.
  • Increased apical activity suggestive of left ventricular volume or pressure overload.
  • Thrill due to outflow tract obstruction or a restrictive ventricular septal defect.

S2 splitting — The second heart sound (S2) normally splits physiologically with inspiration, and becomes single during expiration. Although the presence of S2 splitting reduces the likelihood of severe CHD, the newborn's rapid heart rate often makes it challenging to detect S2 splitting. Splitting is audible in 80 percent of normal newborns by 48 hours of age, usually when the heart rate is less than 150 beats per minute [29,47]. As an infant's heart is positioned more horizontally, splitting may be easier to hear along the mid to lower sternal border than in children or adults. Listening may be facilitated by a gentle breath into the baby's face that may temporarily slow the heart rate. (See "Assessment of the newborn infant" and "Auscultation of heart sounds".)

 A single second heart sound occurs in the following conditions:

  • Aortic atresia
  • Pulmonary atresia
  • Truncus arteriosus
  • Conditions with pulmonary hypertension, as increased impedance in the pulmonary circuit causes early closure of the pulmonary valve, resulting in a single S2

In transposition of the great arteries, the pulmonary artery is located posterior and directly behind the aorta; thus, the softer pulmonary component of the second heart sound is often inaudible.

A widely or fixed split S2 occurs with atrial septal defect (ASD) and other lesions associated with right ventricular volume overload or right sided conduction delays. However, the absence of a widely split S2 in an infant does not rule out an ASD. The abnormal splitting may develop later with increasing volume of flow crossing the defect after pulmonary resistance has fallen.

Other heart sounds — The following additional heart sounds may be associated with cardiac abnormalities. Infants with these extra heart sounds should be evaluated by a clinician with expertise in caring for neonates with CHD.

  • Early systolic clicks, which occur with semilunar valve stenosis, bicuspid aortic valve, and truncus arteriosus.
  • Mid-systolic clicks, which are heard with mitral valve prolapse and with Ebstein's anomaly of the tricuspid valve.
  • An S3 gallop, which, in infants, can result from ventricular dysfunction.
  • Pericardial friction rubs occur with small to moderate pericardial effusions and pericarditis. Purulent pericarditis is an unusual complication of neonatal sepsis [48,49]. Pericarditis is also seen in neonatal lupus that may occur in infants of mothers with connective tissue disorders and anti-Ro/SSA and/or anti-La/SSB bodies [50]. (See "Neonatal lupus".)

Murmurs — The presence of a murmur is often associated with CHD. Detection of a murmur depends upon the examiner's skill and experience, and the timing, frequency, and the conditions under which examination takes place. The evaluation of a heart murmur is important because of potentially adverse outcomes when serious CHD remains undetected. In one report, a murmur had been detected in the neonatal period in 38 percent of infants who presented with heart failure due to a left heart obstructive lesion by six weeks of age [51]. In another study, a neonatal murmur was heard in 57 percent of infants who died with CHD after discharge [52].

However, many infants with murmurs do not have structural lesions, and CHD occurs in infants who do not have murmurs. This was illustrated by a study in which echocardiography was performed in all 46 of 7204 newborns (0.6 percent) with murmurs detected during routine examination by obstetric or pediatric house officers [53].

  • Of 46 newborns with a murmur, 13 had normal hearts and 8 had normal hearts with physiologic findings that would account for a murmur (eg, patent ductus arteriosus [PDA] or mild pulmonary artery branch stenosis). Of the 25 infants (54 percent) with cardiac malformations, all of whom were asymptomatic, ventricular septal defect (VSD) occurred in 15, coarctation of the aorta in three, tetralogy of Fallot in three, atrial septal defect in two, and pulmonary stenosis and aortic valve stenosis in one each.
  • CHD was also detected before 12 months of age in 32 infants who had no murmur on the initial examination.

In another report, echocardiography was performed in 170 of 20,323 newborns (0.8 percent) between one and five days of age, who were referred for evaluation of murmur with an otherwise normal examination [54]. Structural heart disease was identified in 146 (86 percent). The most common lesions were VSD (n = 54) and patent ductus arteriosus (n = 34). Seven had complex cardiac disease, and stenosis of the pulmonary or aortic valve occurred in six and three infants.

Innocent murmurs — A substantial proportion of murmurs heard in the newborn period are innocent. In the studies cited above, no structural heart disease was found in 23 and 13 percent of healthy newborns with murmurs [53,54].

The majority of innocent murmurs in term infants are due to benign pulmonary branch stenosis (PBS), also known as peripheral pulmonary stenosis. This condition is usually detected as a grade 1-2/6, mid-systolic, high-pitched or blowing ejection murmur heard best in the pulmonary area with radiation to the axilla and back after the infant is 24 hours of age, when most PDAs have closed [55]. The murmur may be due to the relative hypoplasia at birth of the branch pulmonary arteries compared with the main pulmonary artery (which is large because it feeds the PDA and systemic circulation in utero) and its sharp angle of origin [56-60].

Another innocent finding on auscultation in infants is a Still's murmur thought to arise from the vibrations of the attachments of the pulmonic valve leaflets. These low pitched, vibratory, musical, grade 1-2/6 systolic ejection murmurs are usually best heard between the lower left sternal border and apex. They typically decrease in intensity or resolve with a Valsalva maneuver, which can be induced in infants by gentle pressure on the abdomen. Still's murmurs tend to vary with heart rate, becoming more evident as the heart rate slows; however, they are relatively uncommon in the newborn.

The natural history of neonatal innocent murmurs was investigated with serial two dimensional and pulsed Doppler echocardiograms in 50 healthy term infants with a clinical diagnosis of an innocent murmur and 50 controls without a murmur [55]. Cardiac findings were more frequent in the murmur group than controls, including PBS (50 versus 12 percent) and PDA (30 versus 12 percent). The murmur had disappeared in 64 and 98 percent of babies by six weeks and six months of age. Structural heart disease (pulmonary stenosis) was diagnosed in only one patient by six months of age.

Pathologic murmurs — The intensity and quality of the murmur and associated findings differentiate innocent murmurs from those associated with heart disease [61-63]. The following features of murmurs are associated with structural heart disease [62]:

  • Murmur intensity grade 3 or higher
  • Harsh quality
  • Pansystolic duration
  • Loudest at upper left, upper right sternal border, or apex
  • Abnormal S2

Murmurs that are also accompanied with absent or diminished femoral pulses or noncardiac abnormalities are associated with CHD.

Pathologic murmurs associated with specific cardiac lesions are discussed separately. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Murmur'.)

Absence of a murmur — Many infants with CHD do not have a murmur [53,64] and therefore the absence of a murmur does not rule out congenital heart disease. The following factors may account for the absence of a murmur:

  • The velocity of turbulent blood flow may not be high enough to generate a murmur. This typically occurs in hypoplastic left heart syndrome, simple transposition of the great arteries, total anomalous pulmonary venous connections, pulmonary atresia, and cardiomyopathy.
  • Decreased ventricular function can limit the generation of a murmur. As an example, if the left ventricular myocardium cannot generate enough contraction to create sufficient flow across a critically obstructed aortic valve, a murmur of aortic stenosis will not be heard.
  • Elevated pulmonary resistance may limit flow. The volume or velocity of flow across a ventricular septal defect may not be sufficient to be audible until the resistance has fallen [54].

Peripheral arterial pulses — Assessment of symmetric peripheral arterial pulses is an essential part of the neonatal evaluation. The diagnosis of coarctation of the aorta (COA) or other aortic arch obstruction is strongly suggested in the infant with decreased or absent pulses in the lower extremities with strong upper extremity pulses, or blood pressures that are 10 mmHg or more higher in the arms than legs. (See "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Manifestations according to age'.)

Infants with significant COA may have cool and/or mottled lower extremities that must be distinguished from cutis marmorata, a purplish, marble-like mottling that appears with exposure to cold [29]. Cutis marmorata is probably caused by constriction of the small cutaneous arterioles, causing the small venules to appear prominent. It is not usually limited to the lower extremities, and disappears once the infant is warm. COA should also be considered in the differential diagnosis of neonatal hypertension [65].

Some cases of COA escape early diagnosis [66]. In the study of the utility of routine exams to detect CHD cited above, 19 of 95 (20 percent) infants diagnosed with COA by 12 months of age were not diagnosed before 12 weeks of age [25]. (See 'Limitation of history and physical examination' above.)

Cyanosis — Cyanosis is an important sign of CHD, but mild desaturation may be difficult to appreciate visually. Cyanosis can usually be detected when the concentration of reduced hemoglobin is >3 g/dL. Therefore, cyanosis may not be apparent in those with mild desaturation (>80 percent saturation) or anemia (hemoglobin of 10, would require to have a saturation <60 percent to appear cyanotic) [67]. Cyanosis can be especially difficult to appreciate in darkly pigmented infants. Pulse oximetry is helpful to detect mild desaturation in patients with ductal-dependent lesions. (See "Overview of cyanosis in the newborn", section on 'Central cyanosis' and 'Pulse oximetry screening' below.)

Noncardiac causes — Noncardiac conditions also can cause cyanosis and are differentiated from CHD by the cardiovascular examination and/or results of the hyperoxia tests. (See 'Hyperoxia test' below.)

  • Pulmonary disorders are the most common cause of cyanosis and include structural abnormalities of the lung, ventilation-perfusion mismatching due to respiratory distress syndrome, congenital or acquired airway obstruction, pneumothorax, and hypoventilation. (See "Overview of neonatal respiratory distress: Disorders of transition".)
  • Abnormal forms of hemoglobin (eg, methemoglobin) can result in cyanosis, and polycythemic infants may appear cyanotic even if they are adequately oxygenated. (See "Genetic disorders of hemoglobin oxygen affinity" and "Neonatal polycythemia".)
  • Poor peripheral perfusion with cyanosis may result from sepsis, hypoglycemia, dehydration, and hypoadrenalism.
  • Right-to-left shunting through the ductus arteriosus, resulting in differences in oxygen saturation measured in the arm (preductal) and leg (postductal), can occur with primary or persistent pulmonary hypertension [68]. (See "Persistent pulmonary hypertension of the newborn".)
  • Acrocyanosis refers to bluish color in the hands and feet and around the mouth (circumoral cyanosis). The mucus membranes generally remain pink. Acrocyanosis usually reflects benign vasomotor changes in the diffuse venous structures in the affected areas. It does not indicate pathology unless cardiac output is extremely low, resulting in cutaneous vasoconstriction [29].

Hyperoxia test — The hyperoxia test is useful in distinguishing cardiac from noncardiac causes of cyanosis, especially pulmonary disease. In this test, arterial oxygen tension (PaO2) is measured in the right radial artery (preductal) and in a lower extremity artery (postductal) during the administration of room air and 100 percent oxygen. The relative changes in PaO2 are used to differentiate the various cardiac and noncardiac causes of neonatal cyanosis (table 1 and table 2). This test and its interpretation are discussed separately. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Hyperoxia test'.)

Respiratory abnormalities — Respiratory abnormalities may be a sign of CHD that must be distinguished from those due to pulmonary disease. Persistently elevated respiratory rate (normal is 45 to 60 breaths per minute), increased respiratory effort at rest, or distress during feeding merit further investigation including chest radiograph, hyperoxia test, and referral to a pediatric cardiologist for echocardiography. (See "Overview of neonatal respiratory distress: Disorders of transition", section on 'Diagnosis'.)

Tachypnea — Cardiac neonatal tachypnea may reflect increased pulmonary venous pressure or volume secondary to a large left-to-right shunt, pulmonary venous obstruction, or increased left ventricular end-diastolic pressure [29]. Tachypnea in heart failure is also thought to have a neurohormonal basis.

Infants with CHD and mild to moderate pulmonary over-circulation frequently have tachypnea without significant increased work of breathing at rest, sometimes referred to as "happy" tachypnea. Infants may become more dyspneic with increasing pulmonary edema or during feeding, and exhibit grunting, nasal flaring, retractions, and head bobbing.

Coughing and wheezing — Cough and wheeze are more likely to be of pulmonary etiology, but they can occur with cardiac malformations. As an example, a tight vascular ring can compress the trachea, leading to wheezing, coughing, or stridor [69,70]. Lesions that cause elevated pulmonary venous pressure result in bronchial edema and bronchial compression by a distended left atrium and tense left pulmonary artery [29,69,71]. These include large left-to-right shunts, mitral stenosis, left ventricular dysfunction (eg, from myocarditis), or pulmonary venous obstruction [29,69,71,72].

Extracardiac abnormalities — Extracardiac abnormalities are frequently detected in children with CHD. Skeletal abnormalities, especially those of the hand and arm, are often associated with cardiac malformations. CHD may be a component of many specific syndromes and chromosomal disorders [73]. In a review of the population-based surveillance data from the Metropolitan Atlanta Congenital Defects Program, 12.3 percent of infants with CHD had a chromosomal abnormality [74]. Infants with conditions listed in the linked table should be evaluated for possible cardiac abnormalities (table 3).

The frequency of extracardiac abnormalities was demonstrated in a retrospective study of 1058 children with CHD evaluated during a ten-year period at a tertiary center in Belgium [75]. About 20 percent of patients (n = 224) had noncardiac abnormalities. Eleven percent (n =118) had an identifiable syndrome or chromosomal disorder. In the previously mentioned Danish population-based study, chromosomal defects were detected in 7 percent of patients with CHD, and extracardiac anomalies in 22 percent [16].

Pulse oximetry screening — Because of the difficulty in visual detection of cyanosis and the potentially severe consequences of missing an early sign of CHD, screening all newborns with pulse oximetry has been investigated as a method to detect asymptomatic infants with ductal dependent CHD. Several large studies have demonstrated the benefits of the use of universal pulse oximetry screening [26,76-78].

A large Swedish study demonstrated the greater effectiveness of universal pulse oximetry screening in detecting infants with mild oxygen desaturation compared with physical examination alone. Six of 16 infants with a SaO2 between 90 and 95 percent were not detected by physical examination by the pediatrician [26]. In addition, there was a lower rate of missed diagnoses of critical CHD for this study cohort compared with infants born in regions of the country where pulse oximetry was not performed (8 versus 28 percent). No infant died from a ductal dependent lesion in the region utilizing routine pulse oximetry versus five deaths from regions without routine oximetry.

However, there are several factors that affect the sensitivity and specificity of pulse oximetry screening for critical CHD [79]. These factors may increase the false-positive rate, which negatively impacts on the cost-benefit of pulse oximetry screening.

  • Criteria used for an abnormal test — The choice of the arterial oxygen saturation (SaO2) cutoff threshold directly effects the sensitivity and specificity of oximetry screening in detecting critical CHD [68,80]. As the SaO2 threshold is decreased, the sensitivity of oximetry decreases and the specificity increases. As an example, in one study, (in which postductal SaO2 was measured at 24 hours of age or discharge), the sensitivity and specificity were 0.75 and 0.88 using a SaO2 threshold of <95 percent, but the sensitivity decreased to 0.53 while specificity increased to 1.0 when the SaO2 was lowered to <90 percent [68]. The lower SaO2 threshold resulted in a higher specificity, which decreases the number of false positives and reduces the cost of further evaluation (echocardiography, pediatric cardiology consultation, and possible transfer) for infants with a positive test without critical CHD and a lower sensitivity.

    Of note, false-positive results may be due to other hypoxic diseases, some of which may require clinical intervention. In one of the previously large prospective multicenter studies, there were 169 false-positive cases (0.8 percent of the cohort), of which 40 patients had significant illness that required urgent medical intervention [78].
  • Pulse oximetry fails to identify all patients with left-sided obstructive lesions with a patent ductus arteriosus, and will not detect noncyanotic congenital heart lesions, such as ventricular septal defect. (See 'Ductal dependent lesions, delayed diagnosis, and death' above.)
  • Timing of screening — The optimal time for screening is not known [80-82]. The first hour of life is not suitable as there are a large number of false-positives as the infant makes the transition from fetal circulation [80,83]. First day screening detects CHD earliest but is also not as specific as later screening because other conditions, such as transient tachypnea of the newborn, result in a low SaO2 [80,81].
  • Probe site — Postductal probe placement is the optimal site because defects with right-to-left shunting of desaturated blood through the ductus arteriosus will not be detected with preductal placement. Use of both pre- and postductal sites will enhance detection of infants with coarctation of the aorta but increases the time needed to perform the screening and costs.
  • Signal quality and infant behavior — Measurements should not be performed when the infant is crying or moving because it reduces the quality of the signal and the accuracy of the test [80,84]. Oximetry testing also may miss hypoxia because of interference from ambient light, partial probe detachment, electromagnetic interference, poor perfusion at the site of measurement, and the presence of dyshemoglobinemias [42,85].
  • Health care workers expertise — Training of health care personnel in the proper duration and techniques of measurement improves the reliability and accuracy of measurements [86].

In four large prospective multicenter studies (each study included over 20,000 patients), sensitivity and specificity of pulse oximetry in detecting critical CHD were relatively consistent with values ranging from 62 to 78 percent for sensitivity, and greater than 99 percent for specificity despite some variations in how pulse oximetry was performed [26,76-78]. In all of these studies, the cutoff SaO2 threshold was <95 percent. Although postductal measurement was performed in all four studies, preductal measurements were also obtained in two studies, and a difference of either 2 or 3 percent saturation between the two limbs was an additional criterion for an abnormal test result [26,78]. Screening was performed after 24 hours of life in three studies [26,77,78], and within the first day of life in the fourth study [76].

US Health and Human Services report — In 2011, a report from the United States Health and Human Services Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children recommended routine pulse oximetry newborn screening to detect infants with critical CHD [87]. Newborn screening is specifically directed towards identifying seven specific lesions:

  • Hypoplastic left heart syndrome
  • Pulmonary atresia
  • Tetralogy of Fallot
  • Total anomalous pulmonary venous return
  • Transposition of the great arteries
  • Tricuspid atresia
  • Truncus arteriosus

The following approach was based on a review of the available literature that included the previously discussed prospective studies [26,76-78], and has been endorsed by the American Academy of Pediatrics (AAP), the American Heart Association (AHA), and the American College of Cardiology Foundation (ACCF) [88].

  • Screening should not be performed until after 24 hours of life or as late as possible if early discharge is planned.
  • The screening should be performed using a motion-tolerant pulse oximeter. Either disposable or reusable probes can be used. Reusable probes reduce the cost of screening but must be appropriately cleaned to minimize the risk of infection.
  • Screening is recommended in the right hand and either foot. Screening at both locations can occur simultaneously or in direct sequence.
  • Screening is performed by qualified and trained personnel.
  • A positive screening test includes fulfilling one of the following three criterion:

  • SaO2 measurement <90 percent
  • SaO2 measurement <95 percent in both upper and lower extremities on three measurements, each separated by one hour
  • SaO2 difference >3 percent between the upper and lower extremities

    Of note, these criteria have not been validated for newborns cared for centers at high altitude, and further research is needed to determine the parameters of a positive screening test in high-altitude settings.

  • Each birthing institution should establish a protocol to ensure a timely evaluation for newborns with a positive screening test. Assessment includes the performance of high-quality echocardiography and interpretation by a clinician with expertise in the diagnosis of CHD. Patients should have access to these diagnostic services at the center, via telemedicine, or short-distance transport.
  • At the first outpatient visit, primary care providers should ascertain that screening was performed during the birth hospitalization, and if not, develop strategies for appropriate screening.

Cost-benefit — The cost of universal pulse oximetry screening program includes the direct costs of pulse oximetry (equipment, training of personnel, staff time required for screening), and the follow-up costs of further evaluation and possible transfer of patients who fail the initial screening oximetry test [87]. The cost and quality of follow-up vary depending on the accessibility and cost of pediatric cardiac subspecialty care and the need for transfer.

Because the direct costs are fixed for a given population of newborn infants, the overall cost rises as the false positive rate increases due to the expense of unnecessary additional cardiac evaluation (eg, possible patient transfer, pediatric cardiology consultation, and echocardiography) for patients with a positive screening test who do not have critical CHD. Proponents for routine pulse oximetry screening suggest that currently available data demonstrate a false positive rate of 0.2 percent, which decreases to 0.04 percent when screening is performed after 24 hours of life [19]. Others, however, cite a higher false positive rate of 0.77 percent [89]. This difference in the two false positive rates translates to unnecessary evaluation (possibly transfer) for four additional patients per 1000 births.

In addition, as noted above, pulse oximetry fails to identify all patients with left obstructive lesions and will not detect noncyanotic congenital heart lesions, such as ventricular septal defect. As a result, both care providers and parents must be educated about the limitations of the screening test, and a negative result does not exclude the possibility of CHD.

Implementation and status in the US — Although data demonstrate the effectiveness of oximetry screening for critical CHD, the implementation of a screening program has been challenging because of the costs to train personnel needed to perform testing and establish diagnostic services needed to perform and interpret high-quality echocardiography in a timely manner for infants with positive test results [87]. In particular, the rate of false positive results increases the cost of screening. (See 'Cost-benefit' above.)

As of 2011, there are a small number of states that require mandatory newborn pulse oximetry screening to detect critical CHD. However, most academic centers in the United States including our own do not currently perform oximetry screening primarily because of limited healthcare resources. The implementation of pulse oximetry screening will require regional and institutional planning and funding to establish standardized and validated screening programs at each birthing center, and the necessary diagnostic services infrastructure to ensure timely and high-quality cardiac evaluation for all newborns with a positive screening test [87].

LATER PRESENTATION — As noted above, some newborns who have critical CHD but are asymptomatic at the time of hospital discharge will develop signs and symptoms of cardiac disease, often by two weeks of age [21,25,53]. Thus, clinicians should be alert to clinical manifestations of CHD that may be detected in the course of initial routine visits.

In the previously discussed California population study, the diagnoses of critical CHD most commonly missed after discharge that resulted in death were hypoplastic left heart syndrome, coarctation of the aorta, and tetralogy of Fallot [21]. The median age of death in these infants occurred before two weeks of age. It is unclear whether these infants might have been identified with a careful cardiovascular evaluation for left heart obstructive CHD during the first postdischarge visit at the pediatrician's office at three to five days of age, which would have allowed for life-saving palliative or corrective intervention. (See 'Routine examination' below.)

Clinical manifestations — In affected newborn infants, parents most commonly notice difficulty with feeding. This may be manifested by intake of a limited volume of milk, or feedings that are taking too long or are frequently interrupted by sleeping or resting, choking, gagging, and/or vomiting. Infants may have respiratory distress that is reported by parents as fast or hard breathing, worse with feedings, or a persistent cough or wheeze.

Other manifestations include:

  • Color changes, such as central cyanosis or persistent pallor
  • Excessive, unexplained irritability
  • Excessive sweating that is increased with feeding and may occur during sleep
  • Poor weight gain
  • Decreased activity or excessive sleeping
  • Delay in motor milestones [90]

Routine examination — The routine examination should include careful cardiac auscultation and assessment of peripheral pulses.

Murmurs detected for the first time in a routine examination at six weeks of age can lead to the detection of CHD. In one report, 47 of 5395 babies (0.9 percent) had heart murmurs at six weeks [6]. Of these, 11 of the 25 referred for echocardiographic evaluation had CHD. Ventricular septal defect was the most common lesion. CHD was later diagnosed in six other infants before 12 months of age from the initial cohort who did not have a documented murmur at the six week check-up. (See "Pathophysiology and clinical features of isolated ventricular septal defects in infants and children", section on 'Cardiac examination'.)

Diminished and absent peripheral pulses are findings consistent with the diagnosis of coarctation of the aorta (COA), which is frequently delayed. In the regional study from the United Kingdom of all infants with CHD diagnosed before 12 months of age, 27 and 20 percent of infants with coarctation remained undiagnosed by six weeks and three months [25]. In a retrospective review of patients older than one year who had repair of COA, pulses were decreased but not absent in the majority of patients [66]. (See "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Manifestations according to age'.)

SUMMARY AND RECOMMENDATIONS — Congenital heart disease (CHD) is the most common congenital disorder in newborns.

  • A positive history of maternal or prenatal factors, or a positive family history of CHD increases the risk of CHD. If present, these factors increase the awareness of the clinician of the possibility of CHD. (See 'History' above.)
  • Physical findings associated with CHD include abnormal cardiovascular examination (ie, abnormal heart rate, precordial activity, and heart sounds, pathologic murmurs, and diminished/absent peripheral pulses), presence of cyanosis, respiratory symptoms, and noncardiac anomalies. (See 'Physical examination' above.)
  • In a cyanotic neonate, hyperoxia test is used to differentiate between cardiac and respiratory etiologies. (See 'Hyperoxia test' above.)

  • Cyanosis is an important sign of CHD, but it may be difficult to appreciate mild desaturation visually, especially in darkly pigmented infants or those with anemia. Routine pulse oximetry is an effective screening test to detect critical CHD; however, there are challenges in implementing a new screening program such as training personnel to ensure reliable and accurate universal screening, and establishing services that can accurately diagnosis critical CHD in a timely manner in patients with a positive screening test. (See 'Pulse oximetry screening' above.)
  • Because the diagnosis of critical CHD may be missed during the birth hospitalization, clinicians should be aware and look for clinical manifestations of CHD during the first discharge visit at three to five days of age. Symptoms are nonspecific and include difficulty in feeding, poor weight gain, cyanosis, respiratory findings, decreased activity, irritability, and excessive sweating. The routine examination should include careful auscultation to detect a cardiac murmur and assessment of lower extremity pulses. (See 'Later presentation' above.)

Use of UpToDate is subject to the Subscription and License Agreement.

REFERENCES

  1. Tennant PW, Pearce MS, Bythell M, Rankin J. 20-year survival of children born with congenital anomalies: a population-based study. Lancet 2010; 375:649.
  2. Bird TM, Hobbs CA, Cleves MA, et al. National rates of birth defects among hospitalized newborns. Birth Defects Res A Clin Mol Teratol 2006; 76:762.
  3. Canfield MA, Honein MA, Yuskiv N, et al. National estimates and race/ethnic-specific variation of selected birth defects in the United States, 1999-2001. Birth Defects Res A Clin Mol Teratol 2006; 76:747.
  4. Talner CN. Report of the New England Regional Infant Cardiac Program, by Donald C. Fyler, MD, Pediatrics, 1980;65(suppl):375-461. Pediatrics 1998; 102:258.
  5. Wren C, Reinhardt Z, Khawaja K. Twenty-year trends in diagnosis of life-threatening neonatal cardiovascular malformations. Arch Dis Child Fetal Neonatal Ed 2008; 93:F33.
  6. Gregory J, Emslie A, Wyllie J, Wren C. Examination for cardiac malformations at six weeks of age. Arch Dis Child Fetal Neonatal Ed 1999; 80:F46.
  7. Samánek M, Slavík Z, Zborilová B, et al. Prevalence, treatment, and outcome of heart disease in live-born children: a prospective analysis of 91,823 live-born children. Pediatr Cardiol 1989; 10:205.
  8. Kuehl KS, Loffredo CA, Ferencz C. Failure to diagnose congenital heart disease in infancy. Pediatrics 1999; 103:743.
  9. Wu MH, Chen HC, Lu CW, et al. Prevalence of congenital heart disease at live birth in Taiwan. J Pediatr 2010; 156:782.
  10. Ferencz C, Rubin JD, McCarter RJ, et al. Congenital heart disease: prevalence at livebirth. The Baltimore-Washington Infant Study. Am J Epidemiol 1985; 121:31.
  11. Tanner K, Sabrine N, Wren C. Cardiovascular malformations among preterm infants. Pediatrics 2005; 116:e833.
  12. Reller MD, Strickland MJ, Riehle-Colarusso T, et al. Prevalence of congenital heart defects in metropolitan Atlanta, 1998-2005. J Pediatr 2008; 153:807.
  13. Wren C, Irving CA, Griffiths JA, et al. Mortality in infants with cardiovascular malformations. Eur J Pediatr 2012; 171:281.
  14. Ishikawa T, Iwashima S, Ohishi A, et al. Prevalence of congenital heart disease assessed by echocardiography in 2067 consecutive newborns. Acta Paediatr 2011; 100:e55.
  15. Hoffman JI, Kaplan S. The incidence of congenital heart disease. J Am Coll Cardiol 2002; 39:1890.
  16. Øyen N, Poulsen G, Boyd HA, et al. Recurrence of congenital heart defects in families. Circulation 2009; 120:295.
  17. Rosano A, Botto LD, Botting B, Mastroiacovo P. Infant mortality and congenital anomalies from 1950 to 1994: an international perspective. J Epidemiol Community Health 2000; 54:660.
  18. Boneva RS, Botto LD, Moore CA, et al. Mortality associated with congenital heart defects in the United States: trends and racial disparities, 1979-1997. Circulation 2001; 103:2376.
  19. Hoffman JI. It is time for routine neonatal screening by pulse oximetry. Neonatology 2011; 99:1.
  20. Schultz AH, Localio AR, Clark BJ, et al. Epidemiologic features of the presentation of critical congenital heart disease: implications for screening. Pediatrics 2008; 121:751.
  21. Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of critical congenital heart disease. Arch Pediatr Adolesc Med 2008; 162:969.
  22. Danford DA, McNamara DG. Infants with congenital heart disease in the first year of life. In: The Science and Practice of Pediatric Cardiology, Garson A, Bricker JT, Fisher DJ, Neish SR (Eds), Williams & Wilkins, Baltimore 1998. p.2228.
  23. Pickert CB, Moss MM, Fiser DH. Differentiation of systemic infection and congenital obstructive left heart disease in the very young infant. Pediatr Emerg Care 1998; 14:263.
  24. Ward KE, Mullins CE. Anomalous pulmonary venous connections, pulmonary vein stenosis, and atresia of the common pulmonary vein. In: The Science and Practice of Pediatric Cardiology, Garson A, Bricker JT, Fisher DJ, Neish SR (Eds), Williams and Wilkins, Baltimore 1998. p.1445.
  25. Wren C, Richmond S, Donaldson L. Presentation of congenital heart disease in infancy: implications for routine examination. Arch Dis Child Fetal Neonatal Ed 1999; 80:F49.
  26. de-Wahl Granelli A, Wennergren M, Sandberg K, et al. Impact of pulse oximetry screening on the detection of duct dependent congenital heart disease: a Swedish prospective screening study in 39,821 newborns. BMJ 2009; 338:a3037.
  27. Oster ME, Riehle-Colarusso T, Alverson CJ, Correa A. Associations between maternal fever and influenza and congenital heart defects. J Pediatr 2011; 158:990.
  28. Alverson CJ, Strickland MJ, Gilboa SM, Correa A. Maternal smoking and congenital heart defects in the Baltimore-Washington Infant Study. Pediatrics 2011; 127:e647.
  29. Duff, FD, McNamara, DG. History and physical examination of the cardiovascular system. In: The Science and Practice of Pediatric Cardiology, Garson A, Bricker JT, Fisher DJ, Neish SR (Eds), Williams and Wilkins, Baltimore 1998. p.693.
  30. Cohen LS, Friedman JM, Jefferson JW, et al. A reevaluation of risk of in utero exposure to lithium. JAMA 1994; 271:146.
  31. Pinelli JM, Symington AJ, Cunningham KA, Paes BA. Case report and review of the perinatal implications of maternal lithium use. Am J Obstet Gynecol 2002; 187:245.
  32. Löser H, Majewski F. Type and frequency of cardiac defects in embryofetal alcohol syndrome. Report of 16 cases. Br Heart J 1977; 39:1374.
  33. Tararbit K, Houyel L, Bonnet D, et al. Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J 2011; 32:500.
  34. Romano-Zelekha O, Hirsh R, Blieden L, et al. The risk for congenital heart defects in offspring of individuals with congenital heart defects. Clin Genet 2001; 59:325.
  35. Garson A. The electrocardiogram in infants and children: a systematic approach, Lea & Febiger, Philadelphia 1983.
  36. Press S, Lipkind RS. Acute myocarditis in infants. Initial presentation. Clin Pediatr (Phila) 1990; 29:73.
  37. Kimball TR, Daniels SR, Meyer RA, et al. Relation of symptoms to contractility and defect size in infants with ventricular septal defect. Am J Cardiol 1991; 67:1097.
  38. Clark BJ 3rd. Treatment of heart failure in infants and children. Heart Dis 2000; 2:354.
  39. Tanel RE, Rhodes LA. Fetal and neonatal arrhythmias. Clin Perinatol 2001; 28:187.
  40. Perry JC. Supraventricular tachycardia. In: The Science and Practice of Pediatric Cardiology, Garson A, Bricker JT, Fisher DJ, Neish SR (Eds), Williams and Wilkins, Baltimore 1998. p.2059.
  41. Mehta AV. Rhabdomyoma and ventricular preexcitation syndrome. A report of two cases and review of literature. Am J Dis Child 1993; 147:669.
  42. Trippel DL, Parsons MK, Gillette PC. Infants with long-QT syndrome and 2:1 atrioventricular block. Am Heart J 1995; 130:1130.
  43. Schwartz PJ, Stramba-Badiale M, Segantini A, et al. Prolongation of the QT interval and the sudden infant death syndrome. N Engl J Med 1998; 338:1709.
  44. Towbin, JA, Greenberg, F. Genetic syndromes and clinical molecular genetics. In: The Science and Practice of Pediatric Cardiology, Garson A, Bricker JT, Fisher DJ, Neish SR (Eds), Williams and Wilkins, Baltimore 1998. p.2627.
  45. Bonnet D, Martin D, Villain E, et al. Arrhythmias and conduction defects as presenting symptoms of fatty acid oxidation disorders in children. Circulation 1999; 100:2248.
  46. Yabek SM. Neonatal cyanosis. Reappraisal of response to 100% oxygen breathing. Am J Dis Child 1984; 138:880.
  47. Rowe RD, et al. Abnormalities of the cardiovascular transition of the newborn: current views on vascular and myocardial responses. In: Pediatric Cardiology, Godman MJ (Ed), Churchill Livingstone, New York 1981.
  48. Kanarek KS, de Brigard T, Coleman J, Silbiger ML. Purulent pericarditis in a neonate. Pediatr Infect Dis J 1991; 10:549.
  49. El Hassan N, Dbaibo G, Diab K, et al. Pseudomonas pericarditis in an immunocompetent newborn: unusual presentation with review of the literature. J Infect 2002; 44:49.
  50. White PH. Pediatric systemic lupus erythematosus and neonatal lupus. Rheum Dis Clin North Am 1994; 20:119.
  51. Abu-Harb M, Wyllie J, Hey E, et al. Presentation of obstructive left heart malformations in infancy. Arch Dis Child Fetal Neonatal Ed 1994; 71:F179.
  52. Beebe SA, Britton JR, Britton HL, et al. Neonatal mortality and length of newborn hospital stay. Pediatrics 1996; 98:231.
  53. Ainsworth S, Wyllie JP, Wren C. Prevalence and clinical significance of cardiac murmurs in neonates. Arch Dis Child Fetal Neonatal Ed 1999; 80:F43.
  54. Rein AJ, Omokhodion SI, Nir A. Significance of a cardiac murmur as the sole clinical sign in the newborn. Clin Pediatr (Phila) 2000; 39:511.
  55. Arlettaz R, Archer N, Wilkinson AR. Natural history of innocent heart murmurs in newborn babies: controlled echocardiographic study. Arch Dis Child Fetal Neonatal Ed 1998; 78:F166.
  56. Dunkle LM, Rowe RD. Transient murmur simulating pulmonary artery stenosis in premature infants. Am J Dis Child 1972; 124:666.
  57. Danilowicz DA, Rudolph AM, Hoffman JI, Heymann M. Physiologic pressure differences between main and branch pulmonary arteries in infants. Circulation 1972; 45:410.
  58. Rodriguez RJ, Riggs TW. Physiologic peripheral pulmonic stenosis in infancy. Am J Cardiol 1990; 66:1478.
  59. Chatelain P, Oberhänsli I, Friedli B. Physiological pulmonary branch stenosis in newborns: 2D-echocardiographic and Doppler characteristics and follow up. Eur J Pediatr 1993; 152:559.
  60. Snider AR, Enderlein MA, Teitel DF, Juster RP. Two-dimensional echocardiographic determination of aortic and pulmonary artery sizes from infancy to adulthood in normal subjects. Am J Cardiol 1984; 53:218.
  61. Hansen LK, Birkebaek NH, Oxhøj H. Initial evaluation of children with heart murmurs by the non-specialized paediatrician. Eur J Pediatr 1995; 154:15.
  62. McCrindle BW, Shaffer KM, Kan JS, et al. Cardinal clinical signs in the differentiation of heart murmurs in children. Arch Pediatr Adolesc Med 1996; 150:169.
  63. Smythe JF, Teixeira OH, Vlad P, et al. Initial evaluation of heart murmurs: are laboratory tests necessary? Pediatrics 1990; 86:497.
  64. MCNAMARA DG. Prevention of infant deaths from congenital heart disease. Pediatr Clin North Am 1963; 10:127.
  65. Guignard JP, Gouyon JB, Adelman RD. Arterial hypertension in the newborn infant. Biol Neonate 1989; 55:77.
  66. Ing FF, Starc TJ, Griffiths SP, Gersony WM. Early diagnosis of coarctation of the aorta in children: a continuing dilemma. Pediatrics 1996; 98:378.
  67. Lees MH. Cyanosis of the newborn infant. Recognition and clinical evaluation. J Pediatr 1970; 77:484.
  68. Hoke TR, Donohue PK, Bawa PK, et al. Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study. Pediatr Cardiol 2002; 23:403.
  69. Moss AJ, McDonald LV. Cardiac disease in the wheezing child. Chest 1977; 71:187.
  70. Ledwith MV, Duff DF. A review of vascular rings 1980-1992. Ir Med J 1994; 87:178.
  71. Go RO, Martin TR, Lester MR. A wheezy infant unresponsive to bronchodilators. Ann Allergy Asthma Immunol 1997; 78:449.
  72. Singer JI, Isaacman DJ, Bell LM. The wheezer that wasn't. Pediatr Emerg Care 1992; 8:107.
  73. Pierpont ME, Basson CT, Benson DW Jr, et al. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007; 115:3015.
  74. Hartman RJ, Rasmussen SA, Botto LD, et al. The contribution of chromosomal abnormalities to congenital heart defects: a population-based study. Pediatr Cardiol 2011; 32:1147.
  75. Massin MM, Astadicko I, Dessy H. Noncardiac comorbidities of congenital heart disease in children. Acta Paediatr 2007; 96:753.
  76. Meberg A, Brügmann-Pieper S, Due R Jr, et al. First day of life pulse oximetry screening to detect congenital heart defects. J Pediatr 2008; 152:761.
  77. Riede FT, Wörner C, Dähnert I, et al. Effectiveness of neonatal pulse oximetry screening for detection of critical congenital heart disease in daily clinical routine--results from a prospective multicenter study. Eur J Pediatr 2010; 169:975.
  78. Ewer AK, Middleton LJ, Furmston AT, et al. Pulse oximetry screening for congenital heart defects in newborn infants (PulseOx): a test accuracy study. Lancet 2011; 378:785.
  79. Mahle WT, Newburger JW, Matherne GP, et al. Role of pulse oximetry in examining newborns for congenital heart disease: a scientific statement from the AHA and AAP. Pediatrics 2009; 124:823.
  80. Valmari P. Should pulse oximetry be used to screen for congenital heart disease? Arch Dis Child Fetal Neonatal Ed 2007; 92:F219.
  81. Thangaratinam S, Daniels J, Ewer AK, et al. Accuracy of pulse oximetry in screening for congenital heart disease in asymptomatic newborns: a systematic review. Arch Dis Child Fetal Neonatal Ed 2007; 92:F176.
  82. Richmond S, Reay G, Abu Harb M. Routine pulse oximetry in the asymptomatic newborn. Arch Dis Child Fetal Neonatal Ed 2002; 87:F83.
  83. Koppel RI, Druschel CM, Carter T, et al. Effectiveness of pulse oximetry screening for congenital heart disease in asymptomatic newborns. Pediatrics 2003; 111:451.
  84. Poets CF, Stebbens VA. Detection of movement artifact in recorded pulse oximeter saturation. Eur J Pediatr 1997; 156:808.
  85. Fouzas S, Priftis KN, Anthracopoulos MB. Pulse oximetry in pediatric practice. Pediatrics 2011; 128:740.
  86. Reich JD, Connolly B, Bradley G, et al. Reliability of a single pulse oximetry reading as a screening test for congenital heart disease in otherwise asymptomatic newborn infants: the importance of human factors. Pediatr Cardiol 2008; 29:371.
  87. Kemper AR, Mahle WT, Martin GR, et al. Strategies for implementing screening for critical congenital heart disease. Pediatrics 2011; 128:e1259.
  88. Mahle WT, Martin GR, Beekman RH 3rd, et al. Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease. Pediatrics 2012; 129:190.
  89. Walsh W. Evaluation of pulse oximetry screening in Middle Tennessee: cases for consideration before universal screening. J Perinatol 2011; 31:125.
  90. Aisenberg RB, Rosenthal A, Nadas AS, Wolff PH. Developmental delay in infants with congenital heart disease. Correlation with hypoxemia and congestive heart failure. Pediatr Cardiol 1982; 3:133.
Topic 5774 Version 13.0

TOPIC OUTLINE

GRAPHICS

RELATED TOPICS

All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.