Congenital Heart Disease in Low Birth Weight Infants By DANIEL L. LEVIN, M.D., PAUL STANGER, M.D., JOSEPH A. KITTERMAN, M.D., AND
MICHAEL A. HEYMANN, M.D.
SUMMARY In this study of low birth weight infants (. 2500 g), we compared the birth weight distribution of patients with patent ductus arteriosus associated with prematurity with that of patients having congenital heart disease other than patent ductus arteriosus. Among 1436 low birth weight infants 37 infants had congenital heart disease other than patent ductus arteriosus and 198 had isolated ductus arteriosus. Infants with congenital heart disease had a mean birth weight of 2018 grams (standard deviation = 370 g) which was significantly greater than that of infants with patent ductus arteriosus. Four of the 37 infants with congenital heart disease other than ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 3.5/1000 live low birth weight infants. Seventy-eight of the 198 infants with patent ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 70/1000 live low birth weight infants. Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age and 16 were small for gestational age.
CLINICALLY IMPORTANT patent ductus arteriosus is a common occurrence in low birth weight infants (: 2500 g).`- The patency of the ductus arteriosus in these infants is presumably a consequence of immaturity rather than an embryologic abnormality.10 The ductus arteriosus likely would have closed had the infant completed gestation and survived the newborn period. While congenital heart disease is more common in full term infants, it does occur in low birth weight infants. Since the trend in our institution is to treat infants with patent ductus arteriosus associated with prematurity without performing cardiac catheterization or cineangiocardiography, we have undertaken this study to define the relative occurrence of patent ductus arteriosus and congenital heart disease in low birth weight infants and to determine what, if any, differences there were between the two groups.
During the same period the clinical diagnosis of patent ductus arteriosus was made in 198 of the low birth weight infants. The criteria for catheterization were: 1) medically refractory congestive heart failure; 2) worsening of pulmonary status (e.g., carbon dioxide retention) in patients recovering from idiopathic respiratory distress syndrome; 3) idiopathic respiratory distress syndrome requiring unusually prolonged respiratory support in which the role of the patent ductus arteriosus was unclear; and, 4) doubt concerning the diagnosis. Prior to 1970, aortic angiography was performed in all ten infants referred for surgical ligation of the ductus arteriosus. In patients with patent ductus arteriosus, the study was often limited to passing an umbilical arterial catheter" through the ductus arteriosus, obtaining pulmonary arterial and aortic pressures and blood oxygen saturations, and performing a descending thoracic aortogram. During the past four years, we have not routinely catheterized patients with clinical evidence of large left-toright ductus shunts, and during the past 21/2 years have assessed shunt magnitude by echocardiography.'2 The majority, 87% of infants, did not undergo cardiac catheterization and in these the diagnosis and evaluation of patent ductus arteriosus was made on the basis of physical findings and echocardiography with additional evidence from either spontaneous closure or results of surgical ligation. Patients with cardiac abnormalities secondary to metabolic derangements, arrhythmias, or persistent pulmonary hypertension were excluded from the study as were infants with congenital heart disease not severe enough to require
Materials During the 8½/2 year period from July 1, 1966, to December 31, 1974, there were 1436 low birth weight infants (: 2500 g) admitted to the Newborn Intensive Care Unit at the University of California. Thirty-seven of these 1436 had congenital heart disease other than patent ductus arteriosus and underwent cardiac catheterization and angiography because of congestive heart failure or cyanosis.
catheterization during the neonatal period.
Results
From the Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, California. Supported in part by United States Public Health Service Grants HL06285, HD00397, and HL14201 (Pulmonary SCOR). Address for reprints: Paul Stanger, M.D., Department of Pediatrics, University of California, San Francisco, California 94143. Received March 24, 1975; revision accepted for publication April 25, 1975.
The birth weight, gestational age, age at catheterization, cardiac diagnosis and associated conditions in each of the 37 patients with congenital heart disease other than patent ductus arteriosus are listed in table 1. The spectrum of lesions was similar to that found in infants with birth weights greater than 2500 500
Circulation, Volume 52, September 1975
CHD IN LOW BIRTH WEIGHT INFANTS
501
Table 1 Low Birth Weight Infants with Congenital Heart Disease Birth Patient wt (g)
Gest age (weeks)
Age at cath (days)
Cardiac diagnosis
1 2 3 4
1500 1600 1700 1715
32 30 34 34
A. Weight Appropriate for Gestational Age Tricuspid atresia 13 40 Mitral insufficiency 4 Hypoplastic right ventricle Truncus arteriosus, tvpe I 15
5 6 7 8 9 10 11 12 13 14 15 16 17
1790 1900 1930 1980 2000 2000 2010 2020 2050 2170 2200 2250 2300
35 32 35 34 36 36 36 35 36 33 34 36 35
14 10 2 12 1 1 12 6 36 16 4 5 1
18 19 20 21
2300 2400 2420 2490
37 36 35 36
22 23 24 25 26 27 28 29 30 31 32 33
1300 1300 1500 1790 1840 1860 2000 2020 2100 2225 2250 2260
32 33 36 36 42 38 40 37 38 38 40 40
VSD Aortic atresia d-TGA; VSD Endocardial cushion defect; PDA Tricuspid atresia Mitral and aortic atresia VSD; ASD d-TGA; PDA d-TGA; VSD; PDA VSD Truncus arteriosus, type II Pulmonary atresia d-TGA; pulmonary atresia; endocardial cushion defect 9 VSD; aortic coarctation; PDA 1 TAPVC; PDA 13 VSD; ASD 3 VSD B. Weight Small for Gestational Age 10 Aortic atresia VSD 35 21 VSD; aortic coarctation; PDA VSD; ASD 33 VSD; ASD 25 18 VSD 2 VSD; PDA; aortic stenosis 22 VSD; ASD; pulmonic stenosis 1 DORV; pulmonic and mitral atresia 7 d-TGA 2 Aortic atresia 1 TAPVC, mixed type
34 35 36
2270 2300 2450 2500
40 41 42 40
2 2 11 1
37
DORV; pulmonary atresia d-TGA; PDA Pulmonary atresia; VSD Mitral and aortic atresia
Associated conditions
Infant of drug addict Mlarfan's syndrome
Infant of drug addict; multiple congenital anomalies Malaria during 1st trimester Twin (sibling 2500 g) Multiple congenital anomalies
Hypoplastic kidney
Infant of drug addict; asplenia Multiple congenital anomalies Multiple congenital anomalies Di George syndrome Twin (sibling 2360 g) Twin (sibling 2400 g)
Russel-Silver syndrome Trisomy 18
Trisomy 21; tracheal atresia; polysplenia Multiple congenital anomalies
Abbreviations: VSD = ventricular septal defect; ASD = atrial septal defect; PDA = patent ductus arteriosus; d-TGA = dextrotransposition of the great arteries; TAPVC = total anomalous pulmonary venous connection; DORV = double outlet right ventricle; wt = weight; gest = gestational; cath = catherization.
presenting with cardiorespiratory distress in the neonatal period. There was a large number of infants with ventricular septal defects (13 of 37), four with associated atrial septal defects and five, isolated. The high incidence of ventricular septal defects is similar to that previously reported.'3'-1 Twenty-two patients had congestive heart failure and 15 had cyanosis. The relation of weight to gestational age of each infant was assessed using the data of Usher'6 and Williams.17 Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age; 16 were small for gestational age, and four of these were also preterm. The presence and grams
Circulation, Volume 52, September 1975
type of cardiac anomalies were similar in both groups.
Multiple extracardiac congenital anomalies occurred equally in both groups. Infants with congenital heart disease had larger birth weights (mean = 2018 g, SD = 318 g) than those with patent ductus arteriosus (mean = 1370 g, SD = 370 g) (P < 0.001 by unpaired t-test) (fig. 1). The distribution curves showed little overlap below 1500 grams and no overlap below 1300 grams. Of the 198 infants with patent ductus arteriosus (fig. 2), 64 required surgical ligation and in 53 the congestive heart failure responded to medical management alone. Although infants requiring medical and/or sur-
LEVIN, STANGER, KITTERMAN, HEYMANN
502 Number of Patients 25-
Pa/tenl duclus orleriosus
20
Congeni/ol *
heart disease
15 _
1o0 5
^1 ri AL.J. 1 1I 11.LA 1 I1 J...L 1I 1 11aI _I (LL.I 1000600-
h I 1 MEW 11 I a] m I
I
-
1500-
1 2400-
2000-
Discussion
Birth Weight (gms)
Figure 1 Birth weights of 198 low birth weight infants (! 2500 g) with patent ductus arteriosus and 37 low birth weight infants with congenital heart disease. Each bar represents a 100 gram birth weight group.
gical treatment for patent ductus arteriosus were distributed throughout the weight range, the histogram in figure 2 shows them to be more common in the lower weights. Consequently, if one compares the birth weights of infants with patent ductus arteriosus who required medical and/or surgical management with the birth weights of the congenital heart disease group, there is even less overlap. Multiple congenital anomalies and syndromes were Number of Potients 25 ]Small PDA 20
aI PDA
wi/h
managed
15
medica//jy CHF
a PD2A requiring surgery
10
5
ol 600-
1000-
1500-
2000-
2400-
Birth Weight (gms) Figure 2 Treatment required in. 198 low birth weight infants with patent ductus arteriosus (PDA). Of these, 53 required only medical management for congestive heart failure (CHF) and another 64 required surgical ligation. Each bar represents a 100 gram weight group.
common in the congenital heart disease group (32%) but rare in the patent ductus arteriosus group (0.05%). Three of the infants with congenital heart disease had normal twins and in each case the affected twin was smaller (table 1). The reason for this disparity is not known. During the 81/2 year period there were 1150 infants 5 2500 grams born in this institution, not all of whom required intensive care. Among these, four infants had congenital heart disease requiring cardiac catheterization in the neonatal period, an incidence of 3.5/1000 live, low birth weight infants. The incidence of infants 5 2500 grams born in this institution and having patent ductus arteriosus was 70/1000 live, low birth weight infants (78/1150).
During recent years, we have increasingly relied on clinical evaluation and noninvasive techniques for assessing the role of patent ductus arteriosus in producing cardiorespiratory distress in low birth weight infants. Since the approach to management of infants with other forms of congenital heart disease differs from that of infants with patent ductus arteriosus, we have reviewed our experience with cardiac lesions in low birth weight infants. The number of infants with congenital heart disease is only 1/5 of those with patent ductus arteriosus; however, this ratio may reflect selection in the process of referral as well as comparing patients with congenital heart disease who required cardiac catheterization with all patients 5 2500 grams with patent ductus arteriosus. Nevertheless, there are some differences between the two groups, the most notable being the distribution of birth weights. Although the high incidence of patent ductus arteriosus in the lower weight infants is to be expected,10 the absence of congenital heart disease in infants below 1300 grams was unexpected. It may be the result of considerably fewer births in the very low birth weight range, and/or the large number of small stillbirths with congenital heart disease.'4 The incidence of all forms of congenital heart disease including ductus arteriosus of all severities has been reported as approximately 8-10/1000 live births.'5 18,19 The incidence of congenital heart disease (other than patent ductus arteriosus) requiring catheterization in low birth weight infants born in this institution was 3.5/1000. If one considers that 50% to 60% of patients with congenital heart disease have anomalies with mild hemodynamic disturbances that are not detected until much later,20 the total incidence in low birth weight infants in our series is probably similar to the reported incidence of congenital heart disease in infants with birth weights > 2500 grams. There is an increased incidence of congenital heart disease in infants of diabetic mothers.2' These infants Circulation, Volume 52, September 1975
CHD IN LOW BIRTH WEIGHT INFANTS
may be preterm but large for gestational age and therefore would have been excluded from this study. Of the infants with congenital heart disease in this study, several had ventricular septal defects. Since ventricular septal defects tend to decrease spontaneously in size and close both during late gestation and postnatally,13 it is possible that some of the defects would not have been present had the infants completed gestation. Although the number of low birth weight infants with patent ductus arteriosus has increased during the past three years, the percentages requiring medical (27%) or surgical (32%) intervention are similar to those originally reported from this institution.5 Our current approach to diagnosis and management of low birth weight infants with cardiac problems is as follows. If an infant has unequivocal physical findings of patent ductus arteriosus, and the chest roentgenographic, electrocardiographic, and echocardiographic features are compatible with a large left-to-right ductus shunt, then we do not obtain verification by cardiac catheterization and/or angiocardiography. Catheterization is performed if any of the features are unusual for patent ductus arteriosus, if there is doubt concerning the diagnosis, if the contribution of the ductus to the cardiorespiratory failure is uncertain, or if the infant has some other form of congenital heart disease requiring catheterization.22 Based on the experience presented in this study, we now feel more confident when making the clinical diagnosis of patent ductus arteriosus in infants less than 1300 grams and managing them without cardiac catheterization. All the low birth weight infants referred for surgical ligation of a patent ductus arteriosus have had that diagnosis confirmed at surgery. References 1. DANILOWICZ D, RUDOLPH AM, HOFFMAN JIE: Delayed closure of the ductus arteriosus in premature infants. Pediatrics 37: 74, 1966 2. AULD PAM: Delayed closure of the ductus arteriosus. J Pediatr 69: 61, 1966 3. SIAssI B, EMMANOUILIDES GC, CLEVELAND RJ, HIROS F: Patent ductus arteriosus complicating prolonged assisted ventilation in respiratory distress syndrome. J Pediatr 74: 11, 1969 4. GIRLING DJ, HALLIDIE-SMITH KA: Persistent patent ductus arteriosus in ill premature babies. Arch Dis Child 46: 117, 1971
Circulation, Volume 52, September 1975
503 5. KITTERMAN JA, EDMUNDS LH, GREGORY GA, HEYMANN MA, TOOLEY WH, RUDOLPH AM: Patent ductus arteriosus in premature infants. Incidence, relation to pulmonary disease and management. N Engl J Med 287: 473, 1972 6. EDMUNDS LH, GREGORY GA, HEYMANN MA, KITTERMAN JA, RUDOLPH AM, TOOLEY WH: Surgical closure of the ductus arteriosus in premature infants. Circulation 48: 856, 1973 7. THIBEAULT DW, EMMANOUILIDES GC, NELSON PJ, LACHMAN RS, ROSENGART RM, OH W: Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants. J Pediatr 86: 120, 1975 8. NEAL WA, BESSINGER FB, HUNT CE, LUCAS RV: Patent ductus arteriosus complicating respiratory distress syndrome. J Pediatr 86: 127, 1975 9. LEES MH: Commentary: Patent ductus arteriosus in premature infants - a diagnostic and therapeutic dilemma. J Pediatr 86: 132, 1975 10. MCMURPHY DM, HEYMANN MA, RUDOLPH AM, MELMON KL: Developmental changes in constriction of the ductus arteriosus; responses to oxygen and vasoactive agents in the isolated ductus arteriosus of the fetal lamb. Pediatr Res 6: 231, 1972 11. HEYMANN MA: A simple method for changing an umbilical artery catheter. Pediatrics 53: 109, 1974 12. SILVERMAN NH, LEWIS AB, HEYMANN MA, RUDOLPH AM: Echocardiographic diagnosis of ductus arteriosus shunt in premature infants. Circulation 50: 821, 1974 13. HOFFMAN JIE: Natural history of congenital heart disease: Problems in its assessment with special reference to ven-
tricular septal defects. Circulation 37: 97, 1968 14. RICHARDS MR, MERRIrr KK, SAMUELS MH, LANGMANN AG: Congenital malformations of the cardiovascular system in a series of 6,053 infants. Pediatrics 15: 12, 1955 15. MITCHELL SC, KORONES SB, BERENDES HW: Congenital heart disease in 56,109 births: Incidence and history. Circulation 43: 323, 1971 16. USHER R, McLEAN F: Intrauterine growth of live-born caucasian infants at sea level: Standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr 74: 901, 1969 17. WILLIAMS RL: Outcome-based measurements of medical care output: The case of maternal and infant health. Doctoral thesis, University of California, Santa Barbara, 1974 18. KERREBIJN KF: Incidence of infants and mortality from congenital malformations of the circulatory system. Acta Paed Scand 55: 316, 1966 19. CALGREN L-E: Incidence of congenital heart disease in children born in Gothenburg, 1941-1950. Br Heart J 21: 40, 1959 20. NEEL JV: Study of major congenital defects in Japanese infants. Am J Hum Genet 10: 398, 1958 21. PILDES RS: Infants of diabetic mothers. N Engl J Med 289: 902, 1973 22. RUDOLPH AM: Congenital Diseases of the Heart - Clinical Physiologic Considerations in Diagnosis and Management. Chicago, Year Book Medical Publishers, Inc., 1975, p 181
MICHAEL A. HEYMANN, M.D.
SUMMARY In this study of low birth weight infants (. 2500 g), we compared the birth weight distribution of patients with patent ductus arteriosus associated with prematurity with that of patients having congenital heart disease other than patent ductus arteriosus. Among 1436 low birth weight infants 37 infants had congenital heart disease other than patent ductus arteriosus and 198 had isolated ductus arteriosus. Infants with congenital heart disease had a mean birth weight of 2018 grams (standard deviation = 370 g) which was significantly greater than that of infants with patent ductus arteriosus. Four of the 37 infants with congenital heart disease other than ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 3.5/1000 live low birth weight infants. Seventy-eight of the 198 infants with patent ductus arteriosus were among 1150 low birth weight infants born in this institution, an incidence of 70/1000 live low birth weight infants. Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age and 16 were small for gestational age.
CLINICALLY IMPORTANT patent ductus arteriosus is a common occurrence in low birth weight infants (: 2500 g).`- The patency of the ductus arteriosus in these infants is presumably a consequence of immaturity rather than an embryologic abnormality.10 The ductus arteriosus likely would have closed had the infant completed gestation and survived the newborn period. While congenital heart disease is more common in full term infants, it does occur in low birth weight infants. Since the trend in our institution is to treat infants with patent ductus arteriosus associated with prematurity without performing cardiac catheterization or cineangiocardiography, we have undertaken this study to define the relative occurrence of patent ductus arteriosus and congenital heart disease in low birth weight infants and to determine what, if any, differences there were between the two groups.
During the same period the clinical diagnosis of patent ductus arteriosus was made in 198 of the low birth weight infants. The criteria for catheterization were: 1) medically refractory congestive heart failure; 2) worsening of pulmonary status (e.g., carbon dioxide retention) in patients recovering from idiopathic respiratory distress syndrome; 3) idiopathic respiratory distress syndrome requiring unusually prolonged respiratory support in which the role of the patent ductus arteriosus was unclear; and, 4) doubt concerning the diagnosis. Prior to 1970, aortic angiography was performed in all ten infants referred for surgical ligation of the ductus arteriosus. In patients with patent ductus arteriosus, the study was often limited to passing an umbilical arterial catheter" through the ductus arteriosus, obtaining pulmonary arterial and aortic pressures and blood oxygen saturations, and performing a descending thoracic aortogram. During the past four years, we have not routinely catheterized patients with clinical evidence of large left-toright ductus shunts, and during the past 21/2 years have assessed shunt magnitude by echocardiography.'2 The majority, 87% of infants, did not undergo cardiac catheterization and in these the diagnosis and evaluation of patent ductus arteriosus was made on the basis of physical findings and echocardiography with additional evidence from either spontaneous closure or results of surgical ligation. Patients with cardiac abnormalities secondary to metabolic derangements, arrhythmias, or persistent pulmonary hypertension were excluded from the study as were infants with congenital heart disease not severe enough to require
Materials During the 8½/2 year period from July 1, 1966, to December 31, 1974, there were 1436 low birth weight infants (: 2500 g) admitted to the Newborn Intensive Care Unit at the University of California. Thirty-seven of these 1436 had congenital heart disease other than patent ductus arteriosus and underwent cardiac catheterization and angiography because of congestive heart failure or cyanosis.
catheterization during the neonatal period.
Results
From the Department of Pediatrics and the Cardiovascular Research Institute, University of California, San Francisco, California. Supported in part by United States Public Health Service Grants HL06285, HD00397, and HL14201 (Pulmonary SCOR). Address for reprints: Paul Stanger, M.D., Department of Pediatrics, University of California, San Francisco, California 94143. Received March 24, 1975; revision accepted for publication April 25, 1975.
The birth weight, gestational age, age at catheterization, cardiac diagnosis and associated conditions in each of the 37 patients with congenital heart disease other than patent ductus arteriosus are listed in table 1. The spectrum of lesions was similar to that found in infants with birth weights greater than 2500 500
Circulation, Volume 52, September 1975
CHD IN LOW BIRTH WEIGHT INFANTS
501
Table 1 Low Birth Weight Infants with Congenital Heart Disease Birth Patient wt (g)
Gest age (weeks)
Age at cath (days)
Cardiac diagnosis
1 2 3 4
1500 1600 1700 1715
32 30 34 34
A. Weight Appropriate for Gestational Age Tricuspid atresia 13 40 Mitral insufficiency 4 Hypoplastic right ventricle Truncus arteriosus, tvpe I 15
5 6 7 8 9 10 11 12 13 14 15 16 17
1790 1900 1930 1980 2000 2000 2010 2020 2050 2170 2200 2250 2300
35 32 35 34 36 36 36 35 36 33 34 36 35
14 10 2 12 1 1 12 6 36 16 4 5 1
18 19 20 21
2300 2400 2420 2490
37 36 35 36
22 23 24 25 26 27 28 29 30 31 32 33
1300 1300 1500 1790 1840 1860 2000 2020 2100 2225 2250 2260
32 33 36 36 42 38 40 37 38 38 40 40
VSD Aortic atresia d-TGA; VSD Endocardial cushion defect; PDA Tricuspid atresia Mitral and aortic atresia VSD; ASD d-TGA; PDA d-TGA; VSD; PDA VSD Truncus arteriosus, type II Pulmonary atresia d-TGA; pulmonary atresia; endocardial cushion defect 9 VSD; aortic coarctation; PDA 1 TAPVC; PDA 13 VSD; ASD 3 VSD B. Weight Small for Gestational Age 10 Aortic atresia VSD 35 21 VSD; aortic coarctation; PDA VSD; ASD 33 VSD; ASD 25 18 VSD 2 VSD; PDA; aortic stenosis 22 VSD; ASD; pulmonic stenosis 1 DORV; pulmonic and mitral atresia 7 d-TGA 2 Aortic atresia 1 TAPVC, mixed type
34 35 36
2270 2300 2450 2500
40 41 42 40
2 2 11 1
37
DORV; pulmonary atresia d-TGA; PDA Pulmonary atresia; VSD Mitral and aortic atresia
Associated conditions
Infant of drug addict Mlarfan's syndrome
Infant of drug addict; multiple congenital anomalies Malaria during 1st trimester Twin (sibling 2500 g) Multiple congenital anomalies
Hypoplastic kidney
Infant of drug addict; asplenia Multiple congenital anomalies Multiple congenital anomalies Di George syndrome Twin (sibling 2360 g) Twin (sibling 2400 g)
Russel-Silver syndrome Trisomy 18
Trisomy 21; tracheal atresia; polysplenia Multiple congenital anomalies
Abbreviations: VSD = ventricular septal defect; ASD = atrial septal defect; PDA = patent ductus arteriosus; d-TGA = dextrotransposition of the great arteries; TAPVC = total anomalous pulmonary venous connection; DORV = double outlet right ventricle; wt = weight; gest = gestational; cath = catherization.
presenting with cardiorespiratory distress in the neonatal period. There was a large number of infants with ventricular septal defects (13 of 37), four with associated atrial septal defects and five, isolated. The high incidence of ventricular septal defects is similar to that previously reported.'3'-1 Twenty-two patients had congestive heart failure and 15 had cyanosis. The relation of weight to gestational age of each infant was assessed using the data of Usher'6 and Williams.17 Twenty-one of the 37 infants with congenital heart disease were of appropriate weight for gestational age; 16 were small for gestational age, and four of these were also preterm. The presence and grams
Circulation, Volume 52, September 1975
type of cardiac anomalies were similar in both groups.
Multiple extracardiac congenital anomalies occurred equally in both groups. Infants with congenital heart disease had larger birth weights (mean = 2018 g, SD = 318 g) than those with patent ductus arteriosus (mean = 1370 g, SD = 370 g) (P < 0.001 by unpaired t-test) (fig. 1). The distribution curves showed little overlap below 1500 grams and no overlap below 1300 grams. Of the 198 infants with patent ductus arteriosus (fig. 2), 64 required surgical ligation and in 53 the congestive heart failure responded to medical management alone. Although infants requiring medical and/or sur-
LEVIN, STANGER, KITTERMAN, HEYMANN
502 Number of Patients 25-
Pa/tenl duclus orleriosus
20
Congeni/ol *
heart disease
15 _
1o0 5
^1 ri AL.J. 1 1I 11.LA 1 I1 J...L 1I 1 11aI _I (LL.I 1000600-
h I 1 MEW 11 I a] m I
I
-
1500-
1 2400-
2000-
Discussion
Birth Weight (gms)
Figure 1 Birth weights of 198 low birth weight infants (! 2500 g) with patent ductus arteriosus and 37 low birth weight infants with congenital heart disease. Each bar represents a 100 gram birth weight group.
gical treatment for patent ductus arteriosus were distributed throughout the weight range, the histogram in figure 2 shows them to be more common in the lower weights. Consequently, if one compares the birth weights of infants with patent ductus arteriosus who required medical and/or surgical management with the birth weights of the congenital heart disease group, there is even less overlap. Multiple congenital anomalies and syndromes were Number of Potients 25 ]Small PDA 20
aI PDA
wi/h
managed
15
medica//jy CHF
a PD2A requiring surgery
10
5
ol 600-
1000-
1500-
2000-
2400-
Birth Weight (gms) Figure 2 Treatment required in. 198 low birth weight infants with patent ductus arteriosus (PDA). Of these, 53 required only medical management for congestive heart failure (CHF) and another 64 required surgical ligation. Each bar represents a 100 gram weight group.
common in the congenital heart disease group (32%) but rare in the patent ductus arteriosus group (0.05%). Three of the infants with congenital heart disease had normal twins and in each case the affected twin was smaller (table 1). The reason for this disparity is not known. During the 81/2 year period there were 1150 infants 5 2500 grams born in this institution, not all of whom required intensive care. Among these, four infants had congenital heart disease requiring cardiac catheterization in the neonatal period, an incidence of 3.5/1000 live, low birth weight infants. The incidence of infants 5 2500 grams born in this institution and having patent ductus arteriosus was 70/1000 live, low birth weight infants (78/1150).
During recent years, we have increasingly relied on clinical evaluation and noninvasive techniques for assessing the role of patent ductus arteriosus in producing cardiorespiratory distress in low birth weight infants. Since the approach to management of infants with other forms of congenital heart disease differs from that of infants with patent ductus arteriosus, we have reviewed our experience with cardiac lesions in low birth weight infants. The number of infants with congenital heart disease is only 1/5 of those with patent ductus arteriosus; however, this ratio may reflect selection in the process of referral as well as comparing patients with congenital heart disease who required cardiac catheterization with all patients 5 2500 grams with patent ductus arteriosus. Nevertheless, there are some differences between the two groups, the most notable being the distribution of birth weights. Although the high incidence of patent ductus arteriosus in the lower weight infants is to be expected,10 the absence of congenital heart disease in infants below 1300 grams was unexpected. It may be the result of considerably fewer births in the very low birth weight range, and/or the large number of small stillbirths with congenital heart disease.'4 The incidence of all forms of congenital heart disease including ductus arteriosus of all severities has been reported as approximately 8-10/1000 live births.'5 18,19 The incidence of congenital heart disease (other than patent ductus arteriosus) requiring catheterization in low birth weight infants born in this institution was 3.5/1000. If one considers that 50% to 60% of patients with congenital heart disease have anomalies with mild hemodynamic disturbances that are not detected until much later,20 the total incidence in low birth weight infants in our series is probably similar to the reported incidence of congenital heart disease in infants with birth weights > 2500 grams. There is an increased incidence of congenital heart disease in infants of diabetic mothers.2' These infants Circulation, Volume 52, September 1975
CHD IN LOW BIRTH WEIGHT INFANTS
may be preterm but large for gestational age and therefore would have been excluded from this study. Of the infants with congenital heart disease in this study, several had ventricular septal defects. Since ventricular septal defects tend to decrease spontaneously in size and close both during late gestation and postnatally,13 it is possible that some of the defects would not have been present had the infants completed gestation. Although the number of low birth weight infants with patent ductus arteriosus has increased during the past three years, the percentages requiring medical (27%) or surgical (32%) intervention are similar to those originally reported from this institution.5 Our current approach to diagnosis and management of low birth weight infants with cardiac problems is as follows. If an infant has unequivocal physical findings of patent ductus arteriosus, and the chest roentgenographic, electrocardiographic, and echocardiographic features are compatible with a large left-to-right ductus shunt, then we do not obtain verification by cardiac catheterization and/or angiocardiography. Catheterization is performed if any of the features are unusual for patent ductus arteriosus, if there is doubt concerning the diagnosis, if the contribution of the ductus to the cardiorespiratory failure is uncertain, or if the infant has some other form of congenital heart disease requiring catheterization.22 Based on the experience presented in this study, we now feel more confident when making the clinical diagnosis of patent ductus arteriosus in infants less than 1300 grams and managing them without cardiac catheterization. All the low birth weight infants referred for surgical ligation of a patent ductus arteriosus have had that diagnosis confirmed at surgery. References 1. DANILOWICZ D, RUDOLPH AM, HOFFMAN JIE: Delayed closure of the ductus arteriosus in premature infants. Pediatrics 37: 74, 1966 2. AULD PAM: Delayed closure of the ductus arteriosus. J Pediatr 69: 61, 1966 3. SIAssI B, EMMANOUILIDES GC, CLEVELAND RJ, HIROS F: Patent ductus arteriosus complicating prolonged assisted ventilation in respiratory distress syndrome. J Pediatr 74: 11, 1969 4. GIRLING DJ, HALLIDIE-SMITH KA: Persistent patent ductus arteriosus in ill premature babies. Arch Dis Child 46: 117, 1971
Circulation, Volume 52, September 1975
503 5. KITTERMAN JA, EDMUNDS LH, GREGORY GA, HEYMANN MA, TOOLEY WH, RUDOLPH AM: Patent ductus arteriosus in premature infants. Incidence, relation to pulmonary disease and management. N Engl J Med 287: 473, 1972 6. EDMUNDS LH, GREGORY GA, HEYMANN MA, KITTERMAN JA, RUDOLPH AM, TOOLEY WH: Surgical closure of the ductus arteriosus in premature infants. Circulation 48: 856, 1973 7. THIBEAULT DW, EMMANOUILIDES GC, NELSON PJ, LACHMAN RS, ROSENGART RM, OH W: Patent ductus arteriosus complicating the respiratory distress syndrome in preterm infants. J Pediatr 86: 120, 1975 8. NEAL WA, BESSINGER FB, HUNT CE, LUCAS RV: Patent ductus arteriosus complicating respiratory distress syndrome. J Pediatr 86: 127, 1975 9. LEES MH: Commentary: Patent ductus arteriosus in premature infants - a diagnostic and therapeutic dilemma. J Pediatr 86: 132, 1975 10. MCMURPHY DM, HEYMANN MA, RUDOLPH AM, MELMON KL: Developmental changes in constriction of the ductus arteriosus; responses to oxygen and vasoactive agents in the isolated ductus arteriosus of the fetal lamb. Pediatr Res 6: 231, 1972 11. HEYMANN MA: A simple method for changing an umbilical artery catheter. Pediatrics 53: 109, 1974 12. SILVERMAN NH, LEWIS AB, HEYMANN MA, RUDOLPH AM: Echocardiographic diagnosis of ductus arteriosus shunt in premature infants. Circulation 50: 821, 1974 13. HOFFMAN JIE: Natural history of congenital heart disease: Problems in its assessment with special reference to ven-
tricular septal defects. Circulation 37: 97, 1968 14. RICHARDS MR, MERRIrr KK, SAMUELS MH, LANGMANN AG: Congenital malformations of the cardiovascular system in a series of 6,053 infants. Pediatrics 15: 12, 1955 15. MITCHELL SC, KORONES SB, BERENDES HW: Congenital heart disease in 56,109 births: Incidence and history. Circulation 43: 323, 1971 16. USHER R, McLEAN F: Intrauterine growth of live-born caucasian infants at sea level: Standards obtained from measurements in 7 dimensions of infants born between 25 and 44 weeks of gestation. J Pediatr 74: 901, 1969 17. WILLIAMS RL: Outcome-based measurements of medical care output: The case of maternal and infant health. Doctoral thesis, University of California, Santa Barbara, 1974 18. KERREBIJN KF: Incidence of infants and mortality from congenital malformations of the circulatory system. Acta Paed Scand 55: 316, 1966 19. CALGREN L-E: Incidence of congenital heart disease in children born in Gothenburg, 1941-1950. Br Heart J 21: 40, 1959 20. NEEL JV: Study of major congenital defects in Japanese infants. Am J Hum Genet 10: 398, 1958 21. PILDES RS: Infants of diabetic mothers. N Engl J Med 289: 902, 1973 22. RUDOLPH AM: Congenital Diseases of the Heart - Clinical Physiologic Considerations in Diagnosis and Management. Chicago, Year Book Medical Publishers, Inc., 1975, p 181
