Tachypnea and Lethargy in a One-week-old Boy
After reading this article and answering the review questions, the reader will be able to:
- Recognize the presentation of critical congenital heart disease (CHD) shortly after birth
- Recognize the limitations of current screening methods for critical CHD
- Explain the role of pulse oximetry as a screening tool for critical CHD
Adam is a 7-day-old boy who was brought to his primary care clinic for evaluation of poor feeding, progressive tachypnea and lethargy noted over the last day. His mother is healthy and her pregnancy was uncomplicated. She had a normal prenatal ultrasound and there is no family history of serious childhood illnesses.
Adam was born vaginally and his birth weight was seven pounds. He didn't require any special care after birth. His discharge physical examination was normal; he went home with his mother at 36 hours of age. Although breast-feeding initially went well, he seems less interested and more fatigued over the last day.
Upon arrival, his mother notes that he appears to be worsening. On physical exam, he is noticeably tachypneic and responds only to pain. The automated blood pressure cuff and the pulse oximeter don't seem to be able to get reliable readings. His skin is cool and his capillary refill is poor. His lung fields are clear. His heart rate is 200 beats per minute making it difficult to be sure if there is a murmur. It is also difficult to palpate radial or femoral pulses. His liver is palpable down to his umbilicus. His physician recognizes that he is quite ill and has him transported by ambulance to the nearby Emergency Department for further care.
On arrival to the Emergency Department, an intraosseous line is placed and he receives a fluid bolus. His blood sugar is mildly elevated; however, his blood count and basic metabolic profile are otherwise unremarkable. His blood gas shows a metabolic acidosis. Empiric antibiotics are ordered; an enlarged heart is seen on chest x-ray. The emergency care team is concerned that he could have critical congenital heart disease. They prepare an infusion of prostaglandin and contact the on-call pediatric cardiologist. An echocardiogram demonstrates hypoplastic left heart syndrome (HLHS) (Figure 1).
Unrecognized Critical CHD in the Newborn: The Role of Screening
CHD is the most common serious birth defect and affects approximately 1 in 100 newborns. Life-threatening CHD affects approximately 1 in 1,000 1-5 newborns. Depending on the study, a missed diagnosis of critical CHD occurs in approximately 1:3,500 to 1:25,000 births.1-4, 6
Unfortunately, each year in the United States, between 100 and 200 babies die of unrecognized critical CHD.6, 7 Those newborns who survive a delayed diagnosis have more complications when their heart disease is treated than infants who are diagnosed promptly.8, 9
In the best of circumstances, just over half of babies with HLHS and other critical congenital heart defects will be diagnosed prenatally.10, 11 Furthermore, while the patent ductus arteriosus (PDA) remains open, many of these children will have normal physical examinations. These newborns will typically have abnormal blood levels of oxygen, but the degree of desaturation will not be sufficient to be appreciated as cyanosis by the observer. The use of pulse oximetry in asymptomatic term newborns has been shown to be an effective screening tool to detect the desaturation that is present but not visible to the human eye.
On the physical examination of a newborn, findings that traditionally suggest CHD may include central cyanosis, a heart murmur and abnormal femoral pulses. One of the principal limitations of physical examination is our inability to detect clinically significant decreases in oxygenation with the naked eye. In one study, even trained neonatal intensive care staff did not reliably recognize significantly abnormal oxygen saturations as visible cyanosis.12 In this study, newborns were evaluated during transition immediately after birth. The average saturation at which visible central cyanosis resolved was 69% (Figure 2).12
Central cyanosis is only visible once approximately 3 g/dL of hemoglobin has become desaturated.13 For a baby at 24 hours after birth, the average saturation is 97.2% +/- 1.6%.14 The gap between a normal saturation and what can be seen as central cyanosis is the cyanotic blind spot.15 For a baby with a hemoglobin at the 50th percentile for 24 hours (17.5 g/dL),16 visible cyanosis will not be present until the saturation drops to the low to mid 80s. The lower the hemoglobin falls, the wider this cyanotic blind spot becomes. (Figure 3).15
By the time the hemoglobin falls to the 5th percentile (13.5 g/dL),16 cyanosis will not be seen until the saturation falls below 80%.
The diagnosis of HLHS (Figure 4) in the immediate neonatal period is particularly challenging because the physical examination may be normal. With little or no blood flow across the mitral and aortic valves, there will be no heart murmur. As the ductus arteriosus is large and unrestrictive, there will be no PDA murmur and the femoral pulses will be easily palpable. To complicate matters further, the arterial oxygenation will usually be in a range which falls easily into the cyanotic blind spot. These same events may conspire to make other forms of critical congenital heart disease very difficult to detect during the routine physical examination of the newborn. Other heart defects which could fall into the cyanotic blind spot include both cyanotic lesions and left sided obstructive lesions other than hypoplastic left heart syndrome.
Examples of cyanotic heart defects include but are not limited to Transposition of the Great Arteries (Figure 5), Tetralogy of Fallot (Figure 6), Tetralogy of Fallot with Pulmonary Atresia (Figure 7), Tricuspid Atresia (Figure 8), Pulmonary Atresia with intact Ventricular Septum (Figure 9), Truncus Arteriosus (Figure 10), and Total Anomalous Pulmonary Venous Return (Figure 11). Other left-sided obstructive lesions include but aren't limited to Critical Aortic Stenosis (Figure 12), Interruption of the Aortic Arch (Figure 13), and Critical Coarctation (Figure 14).
Non-invasive Pulse Oximetry Screening for Critical CHD
In recent years, a body of literature has grown which demonstrates that non-invasive pulse oximetry in the evaluation of newborns is a useful addition to our screening tools to detect critical CHD. Pulse oximetry has its greatest utility in those heart defects in which an additional screening tool is most desperately needed, namely the cyanotic and ductal-dependent cardiac lesions. Pulse oximetry screening will not reliably detect isolated valve lesions such as aortic or pulmonic stenosis. However these infants will typically have a characteristic murmur that alerts the clinician to the presence of heart disease (Figure 15).
Pulse oximetry also will not reliably detect cardiac defects with left to right shunts such as a ventricular septal defect (Figure 16), PDA or atrioventricular canal. Fortunately, infants with these types of defects will not usually become acutely ill in the immediate newborn period and will also typically have physical exam findings that will alert the clinician to the presence of heart disease before symptoms develop.
The interpretation of literature on pulse oximetry has been complicated by the use of several different screening protocols, wide variability regarding the time of screening, variable definitions of what type of CHD should be detected, and whether the detection of significant pulmonary disease or sepsis should be considered a false positive test. Although most screening protocols are performed after 24 hours, there have been attempts to perform the screening earlier.5, 17 Most studies have been performed using post-ductal measurements performed in the feet with screening failure defined as any measurement less than 95%. The addition of a pre-ductal (right hand) to the post-ductal measurement may increase the sensitivity of the screening protocol.4
A study of 15,233 babies from Dallas in 200817 used an initial post-ductal measurement at four hours of age, followed by a repeat measurement before discharge if the initial measurement was <96%. Seven hundred sixty-eight (5.6%) of the measurements at four hours were less than 96% and needed to be repeated. Only one baby failed both screenings. This baby had a normal echocardiogram resulting in an eventual false positive rate of 1 in 15,233 (0.007%). Because a missed diagnosis of CHD occurs in somewhere between 1 in 3,500 to 1 in 25,000 births, this study may have been slightly smaller than ideal to evaluate the ability to detect unrecognized critical CHD.
A Norwegian study5 of more than 50,000 babies evaluated with an single post-ductal pulse oximetry measurement done earlier than in most studies (average 5 hours after birth) demonstrated a decrease in the missed diagnosis of critical CHD compared to the control population. As these measurements were done very shortly after birth, pulse oximetry was the method of detection in 54% of the babies with critical CHD, but the false positive rate was high (0.26%).
In a large study from Sweden published in 2009,4 the rate of missed diagnoses of critical CHD and the number of deaths due to a missed diagnosis of critical CHD were decreased using pulse oximetry screening. Both pre- and post-ductal saturation measurements were performed at an average age of 38 hours. In this study, the false positive rate for oximetry screening was 69 in 39,821 (0.17%), but 31 of these 69 babies had other clinically relevant disease processes present. Only 38 in 39,821 neonates failed the screening and were found to be entirely healthy (0.095%).
Another study from Germany in 201018 showed that despite an impressive prenatal detection rate of 60% of babies with critical congenital heart disease, 16% were detected by post-ductal pulse oximetry alone. Only post-ductal pulse oximetry measurements were performed and were recorded more than 24 hours after birth. In this study the false positive rate was 40 in 41,445 (0.097%). However, 28 of these 40 babies had persistent pulmonary hypertension or neonatal sepsis. Only 12 in 41,445 neonates failing the screening were found to be healthy (0.029%).
When performed at least 24 hours after delivery, the false positive rate for the detection of critical congenital heart disease by pulse oximetry is surprisingly low. Although several different protocols are available, a two-site screening protocol which uses both pre- and post-ductal saturations may strike the best balance between sensitivity and specificity. A newborn is considered to have failed this screening protocol if one of the saturation measurements is less than 95% or if there is a 3% or more difference between the right arm and the leg measurements.
The figure showing critical coarctation demonstrates the situation in which only some of the blood supply to the lower body is provided by the ductus arteriosus. When this occurs, the post-ductal saturation may be normal, but will be lower than the pre-ductal saturation. (Figure 14)
If an asymptomatic baby fails the screening test, the measurements are usually repeated within 2 hours before any further testing is performed. If the child fails the second attempt, additional evaluation, usually including an echocardiogram, is performed to exclude critical CHD.
The use of pulse oximetry as a screening tool increases the detection of critical CHD that is missed by both prenatal ultrasound and neonatal physical examination. As the literature on this topic has grown, pulse oximetry has evolved from an attractive use for existing technology towards a new standard of care.
For more information on this topic, please consider the following references or our research website: http://www.pediatrics.wisc.edu/hokanson
- 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(1):F33-5.
- Mellander M, Sunnegardh J. Failure to diagnose critical heart malformations in newborns before discharge - an increasing problem? Acta Paediatr 2006;95(4):407-13.
- Aamir T, Kruse L, Ezeakudo O. Delayed diagnosis of critical congenital cardiovascular malformations (CCVM) and pulse oximetry screening of newborns. Acta Paediatr 2007;96(8):1146-9.
- de-Wahl Granelli A, Wennergren M, Sandberg K, Mellander M, Bejlum C, Inganas L, 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.
- Meberg A, Andreassen A, Brunvand L, Markestad T, Moster D, Nietsch L, et al. Pulse oximetry screening as a complementary strategy to detect critical congenital heart defects. Acta Paediatr 2009;98(4):682-6.
- Ng B, Hokanson J. Missed congenital heart disease in neonates. Congenit Heart Dis 2010;5(3):292-6.
- Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of critical congenital heart disease. Arch Pediatr Adolesc Med 2008;162(10):969-74.
- Schultz AH, Localio AR, Clark BJ, Ravishankar C, Videon N, Kimmel SE. Epidemiologic features of the presentation of critical congenital heart disease: implications for screening. Pediatrics 2008;121(4):751-7.
- Brown KL, Ridout DA, Hoskote A, Verhulst L, Ricci M, Bull C. Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates. Heart 2006;92(9):1298-302.
- Friedberg MK, Silverman NH, Moon-Grady AJ, Tong E, Nourse J, Sorenson B, et al. Prenatal detection of congenital heart disease. J Pediatr 2009;155(1):26-31, 31 e1.
- Sharland G. Fetal cardiac screening; why bother? Arch Dis Child 2009.
- O'Donnell CP, Kamlin CO, Davis PG, Carlin JB, Morley CJ. Clinical assessment of infant colour at delivery. Arch Dis Child Fetal Neonatal Ed 2007;92(6):F465-7.
- Lees MH. Cyanosis of the newborn infant. Recognition and clinical evaluation. J Pediatr 1970;77(3):484-98.
- Levesque BM, Pollack P, Griffin BE, Nielsen HC. Pulse oximetry: what's normal in the newborn nursery? Pediatr Pulmonol 2000;30(5):406-12.
- Hokanson J. Pulse Oximetry Screening for Unrecognized Congenital Heart Disease in Neonates. Neonatology Today 2010;5(12):1-6.
- Jopling J, Henry E, Wiedmeier SE, Christensen RD. Reference ranges for hematocrit and blood hemoglobin concentration during the neonatal period: data from a multihospital health care system. Pediatrics 2009;123(2):e333-7.
- Sendelbach DM, Jackson GL, Lai SS, Fixler DE, Stehel EK, Engle WD. Pulse oximetry screening at 4 hours of age to detect critical congenital heart defects. Pediatrics 2008;122(4):e815-20.
- Riede FT, Worner C, Dahnert I, Mockel A, Kostelka M, Schneider P. 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(8):975-81.