Study on Bone Age in Pediatric Patients with Congenital Heart Disease and its Relation with Cyanosis and Pulmonary Artery Pressure
The aim of this study is to evaluate the growth failure in children with Congenital Heart Diseases (CHD) associated with the Pulmonary Hypertension (PH) and cyanosis. Growth parameters including weight, height and head circumference of 120 cases with congenital heart defects aged 6 months to 14 years were compared with standard growth curves (50th percentile) between November 2007 and November, 2008. Of all, sixty five (54.1%) were male and 55 (45.8%) were female. The patients were classified into four groups based on the presence or absence of PH and cyanosis. The gap between chronological age and bone age (BA) for all subjects was determined. Growth disturbance in weight, height and head circumference was detected in 80 (66.7%), 79 (65.8%) and 41(34.2%) of the patients, respectively. Bone age delay was seen in fifty five percent of the cases. Generally, delay in all parameters was more seen in acyanotic patients with pulmonary hypertension. In subjects with cyanosis whether in addition to PH or not, bone age was significantly retarded. Etiology of growth failure in children with CHD is multifactorial. Further studies are required to assess the role of different factors in this field.
Children with Congenital Heart Disease (CHD) have an increased prevalence of
malnutrition and growth failure. Malnutrition widely ranges from mild undernutrition
to severe failure to thrive (FTT). (Avitzur et al.,
2003; Yilmaz et al., 2007; Varan
et al., 1999). On the basis of multifactorial etiology for growth
retardation in these patients, some causes are presumed. Decreased energy intake,
increased energy requirements and recurrent respiratory infections may all contribute.
Current evidences strongly suggest that pre-operative malnutrition is a major
factor affecting the outcome of cardiac surgery (Nydegger
and Bines, 2006; Vaidyanathan et al., 2008).
Different types of cardiac malformations can affect nutrition and growth to
various degrees. Presence of cyanosis and/or Pulmonary Hypertension (PH), which
are frequently seen in many patients with CHD, appears to influence the growth
pattern of affected children (Nydegger and Bines, 2006;
Vaidyanathan et al., 2008; Avitzur
et al., 2003; Da Silva et al., 2007).
Congenital cardiac lesions are classified into two large groups based on the
presence or absence of cyanosis, which can be revealed by physical examination
applying the pulse oximeter. These two groups are further subdivided considering
the pattern of their chest radiography showing evidence of increased, normal,
or decreased pulmonary vascular markings. Acyanotic defects can be divided into
two major groups on the basis of their dominant load abnormally imposed on the
heart. These two categories are the lesions leading to volume overload and the
defects resulting in pressure overload (Weeks and Friedman,
2004; Chowdhury, 2007; Allen et
al., 2008; Bernstein, 2007).
Likewise, it has been previously proposed that the Bone Age (BA) may be delayed
in children with CHD (White et al., 1972; Danilowicz,
1973; Pelargonio et al., 1975). Chronic hypoxemia
has a direct or indirect effect on serum insulin like growth factor I (IGF-I)
concentrations leading to its reduced level and this may be a cause of increased
growth failure in patients with cyanotic congenital heart disease (Dündar
et al., 2000; Dinleyici et al., 2007).
It is suggested that patients with increased pulmonary blood flow and pulmonary
hypertension are more prone to develop malnutrition and growth retardation and
cyanotic patients with pulmonary hypertension are the ones most severely affected.
In a study growth retardation was related to the size of intra cardiac left
to right shunts. However, available data are conflicting (Varan
et al., 1999; Cameron et al., 1995;
Leite et al., 1995; O'Brien
and Smith, 1994).
The separate influences of hypoxemia and pulmonary hypertension on the growth of these patients have been widely studied but the additive effects of cyanosis and pulmonary hypertension on the prognosis of these children have rarely been assessed. This study was designed to investigate the effect of several types of cardiac malformations on the nutrition and growth status including delayed bone age, weight, height and head circumference and determine their relation with cyanosis and pulmonary artery pressure.
MATERIALS AND METHODS
In a cross-sectional study performed from November, 2007 to November, 2008 in Tabriz Shahid Madani Hospital, 120 children with the diagnosis of CHD were investigated. These patients were admitted for surgical correction, medical management or cardiac catheterization. Patients with a history of intrauterine growth retardation, prematurity, known genetic syndromes and dysmorphic features were excluded. The diagnosis of CHD was made through medical history, clinical examinations and laboratory investigations including chest X-ray and electrocardiography confirmed by echocardiography or cardiac catheterization together with echocardiography.
Echocardiographic and angiographic evaluations were done by an expert pediatric
cardiology subspecialist. In order to be able to assess chronic effects of CHD
on growth parameters, patients younger than 6 month old were excluded. Eligible
subjects were allocated to 4 strata based on the presence of cyanosis and/or
||Group A/PH: Acyanotic patients with pulmonary hypertension
(patients with left to right shunt and pulmonary hypertension)
||Group A/No PH: Acyanotic patients without pulmonary hypertension
||Group C/No PH: Cyanotic patients without pulmonary hypertension
||Group C/PH: Cyanotic patients with pulmonary hypertension
Growth parameters including body weight (kg), height (cm) and head circumference
(cm) were measured by a nurse. Anteroposterior wrist X-ray was done as part
of a bone-age study. The graphics were reported by a radiologist blinded to
the type of CHD and patients age, only informed about their sex. The gap
between reported bone age and the chronological age was determined and any delay
was detected. Weight (kg), height (cm) and head circumference (cm) values were
plotted on standard growth curves. The values of 50th percentile were assigned
as standard measures and any differences between the growth parameters and standard
values were determined. Growth retardation and bone-age delay were assessed
regarding the presence of cyanosis and/or PH. The research ethics committee
of Tabriz University of Medical Sciences approved the study and informed consent
was obtained from all parents.
Data were analyzed by SPSS ver15 considering the simultaneous effects of cyanosis
and pulmonary hypertension on growth parameters. The descriptive values were
stated as percent, mean and prevalence. Chi-square, Mann-Whitney U-test and
independent samples t-test were used as required (Neely
et al., 2003; Rosner and Grove, 1999; Conover,
1999). A p-value less than 0.05 was considered statistically significant.
A total of 120 children with CHD aged 6 months to 14 years were investigated over the one year period. The mean age of patients was 39.74 ± 34.78 months. Of these cases, 65 (54.1%) were male and 55 (45.8%) were female. The subjects were categorized into four groups on the basis of presence or absence of cyanosis and pulmonary hypertension. Among these cases, 46 (38.4%) were acyanotic without pulmonary hypertension (A/No PH); 33 (27.5%) were acyanotic with pulmonary hypertension (A/PH); 33 (27.5%) of patients were in cyanotic without pulmonary hypertension group (C/No PH) and 8 (6.6%) were in cyanotic with pulmonary hypertension group (C/PH).
Bone age delay compared with chronological age and weight, height and Head Circumference (HC) disturbance to reach standard percentile of growth curves were evaluated.
Overall, 80 (66.7%), 79 (65.8%) and 41 patients (34.2%) were below 50th percentile
for weight, height and head circumference, respectively. Delay in bone age was
detected in 67 patients (55.8%). Total number and percent of different types
of growth failure in four studied categories are presented in Table
||Total number and percent of different types of growth failure
in four studied groups
|A/No PH: Acyanotic patients without pulmonary hypertension,
A/PH: Acyanotic patients with pulmonary hypertension, C/No PH: Cyanotic
patients without pulmonary hypertension, C/PH: Cyanotic patients with pulmonary
hypertension. Values in brackets are percentages
Assigning acyanotic patients without PH as standard, we compared the parameters in other three categories with this group. There was significant differences in all measured factors (delay in BA, weight, height and head circumference) between A/PH and A/No PH group (p<0.001, p<0.001, p = 0.007, p = 0.014, respectively). The delay in all growth parameters was significantly more frequent in A/PH group. For C/No PH group the only significant finding was delay in bone age (p = 0.006). The differences in weight (p = 0.164), height (p = 0.310) and HC (0.565) were not significant.
In C/PH group delay in bone age was significant (p = 0.006). There was no significant disparity in other three parameters (p = 0.253 for weight, p = 0.119 for height and p = 0.092 for head circumference).
Here, we aimed to assess the adverse effects of Congenital Heart Diseases (CHD) on various aspects of growth and evaluate the additive role of cyanosis and pulmonary hypertension. There are not enough studies assessing this concomitance, so, further studies are needed to fulfill these goals.
This study shows that the delay in bone age was significantly more in both cyanotic patients with pulmonary hypertension and cyanotic subjects without PH compared to standard group (the patients without PH and cyanosis). For the patients with PH and without cyanosis there was significant disparity in terms of all growth parameters including weight, height and head circumference as well, bone age compared to those with none of PH and cyanosis.
Patients with CHD and cyanosis, pulmonary hypertension and congestive heart
failure appear to have an increased prevalence of growth failure and malnutrition
compared to normal population (Da Silva et al., 2007).
It is well known that malnutrition accompanies and contributes to morbidity
in CHD. Optimizing nutritional status improves surgical outcome and is associated
with reduced morbidity (Shrivastava, 2008; Ardura
Fernández et al., 2003; Leitch, 2000;
Varan et al., 1999).
In the research done by Jacobs et al. (2000),
40% of patients with CHD had subnormal weight and height values.
Varan et al. (1999) studied 89 children with
proven CHD and showed that 65% of patients were below the 5th percentile for
weight and 41% were below the 5th percentile for both weight and height.
In a large study by Mehrizi and Drash (1962) 890 children
with CHD were enrolled. Of these cases, 55% had short stature, 52% had poor
weight gain and 27% had delayed values of both weight and height for age.
Malnutrition and growth failure were more prevalent in present study. There are several factors that may explain this finding such as the severity of congenital heart defect, difference in definition and interpretation of growth failure and socioeconomic status of the family. The recent one may be the most significant factor in the patients. Delay in medical refers and inappropriately postponed surgical interventions seem to be another reason for increased prevalence of growth retardation in this study.
Any earlier study evaluating the rate of growth failure on the basis of head circumference was not found.
Present data suggest that growth retardation is more relevant to pulmonary
hypertension than cyanosis except for bone age. It may be attributed to the
role of hypoxemia in reducing serum levels of IGF-I and as a result, delay in
appearing bony centers. There are various results about the pathophysiology
and the effect of cyanosis in children with CHD (Da Silva
et al., 2007; Himeno, 2001; Himeno
et al., 2003).
Tambic-Bukovac and Malcic (1993) on 223 children with
CHD showed that growth failure was significantly more prevalent in cyanotic
cases compared to noncyanotic ones. In the earlier studies by Cameron
et al. (1995) and Leite et al. (1995)
cyanotic congenital heart diseases in children cause more pronounced growth
retardation compared to acyanotic ones.
In some studies in children there was no significant correlation between physical
growth parameters and the presence of cyanosis (Vaidyanathan
et al., 2008; Linde et al., 1967).
Even in some reviews acyanotic patients had more prevalence of growth failure
than cyanotic ones (Jacobs et al., 2000; Salzer
et al., 1999).
Considering the role of factors other than cyanosis altering the results is important in explanation of these disparate findings.
The effect of pulmonary hypertension on the status of growth parameters and
skeletal maturation is evaluated in some reviews. Varan
et al. (1999) suggested that pulmonary hypertension was the most
prominent factor associated with failure to thrive (FTT) in patients with CHD.
In the review done by Vaidyanathan et al. (2008)
congestive heart failure and pulmonary hypertension were significant predictors
of growth disturbance consistent with the findings of present study.
In present study, both cyanosis and pulmonary hypertension were associated
with significantly more prevalence of bone age retardation. We did not find
any recent review relating the bone age with CHD. Plargonio et al. (1975)
showed the adverse effects of congenital heart diseases on the appearance and
development of ossification centers in roentgenograms. In another study by Danilowicz
(1973) cyanosis was put forward to be a risk factor for delay in bone age.
The findings of these two studies are consistent with the results of present
survey. Considering the lack of recent studies assessing the role of CHD and
the separate effects of cyanosis and pulmonary hypertension on the appearance
and growth of bony centers, further reviews should be designed.
According to the results of this study, bone-age delay and growth retardation are common findings in children with CHD. Presence of cyanosis and/or PH may further deteriorate these conditions and should be promptly managed. Considering the significance of growth failure in patients with PH. The results of present study underline the importance of referring patients with CHD and PH for early corrective surgery. This is important to emphasize that in children with congenital heart disease and increased pulmonary blood flow, timely corrective intervention remains the most important factor in improving the growth and nutritional status. In the present era most of the congenital heart defects can be corrected if diagnosed early. This study reports a significantly high prevalence of delayed bone age in hypoxemic patients, suggesting that correction of the cardiac anomaly in cyanotic patients may favorably influence the skeletal maturation.
Considering the positive correlation between chronic hypoxemia and reduced level of serum IGF-I and the role of this factor in growth retardation, further studies are needed to assess the relationship between IGF-I levels and growth status.
Allen, H.D., D.J. Driscoll, R.E. Shaddy and T.F. Feltes, 2008. Moss and Adam`s Heart Diseases in Infants, Children and Adolescents. Lippincott Williams and Wilkins, Philadelphia.
Ardura Fernandez, J., C. Gonzalez Herrera and M.P. Aragón García, 2003. Hemodynamics and delayed growth in children after surgery for atrial septal defect. An Pediatr. (Barc), 58: 302-308.
Avitzur, Y., P. Singer, O. Dagan, E. Kozer and D. Abramovitch et al., 2003. Resting energy expenditure in children with cyanotic and noncyanotic congenital heart disease before and after open-heart surgery. JPEN J. Parenter. Enteral. Nutr., 27: 47-51.
Bernstein, D., 2007. Congenital Heart Diseases. In: Nelson Textbook of Pediatrics, Behrman, R.E., R.M. Kliegman, J.B. Jenson and B.F. Stanton (Eds.). B Saunders Elsevier, JOHN F. Kennedy Blvd., Philadelphia, PA., pp: 1881-1929.
Cameron, J.W., A. Rosenthal and A.D. Olson, 1995. Malnutrition in hospitalized children with congenital heart disease. Arch. Pediatr. Adolesc. Med., 149: 1098-1102.
Chowdhury, D., 2007. Pathophysiology of congenital heart diseases. Ann. Cardiovasc. Anaesth., 10: 19-26.
Conover, W.J., 1999. Practical Nonparametric Statistics. 3rd Edn., John Wiley and Sons, New York, ISBN: 978-0-471-16068-7, pp: 269-427.
Da Silva, V.M., M.V. de Oliveira Lopes and T.L. de Araujo, 2007. Growth and nutritional status of children with congenital heart disease. J. Cardiovasc. Nurs., 22: 390-396.
Danilowicz, D.A., 1973. Delay in bone age in children with congenital heart disease. Radiology, 108: 655-658.
Dinleyici, E.C., Z. Kilic, B. Buyukkaragoz, B. Ucar and O. Alatas et al., 2007. Serum IGF-1, IGFBP-3 and growth hormone levels in children with congenital heart disease: Relationship with nutritional status, cyanosis and left ventricular functions. Neurol. Endocrinol. Lett., 28: 279-283.
Dundar, B., A. Akçoral, G. Saylam, N. Unal and T. Meşe et al., 2000. Chronic hypoxemia leads to reduced serum IGF-I levels in cyanotic congenital heart disease. J. Pediatr. Endocrinol. Metab., 13: 431-436.
Himeno, W., 2001. Angiogenic growth factors in patients with cyanotic congenital heart disease and in normal children. Kurume Med. J., 48: 111-116.
Himeno, W., T. Akagi, J. Furui, Y. Maeno and M. Ishii et al., 2003. Increased angiogenic growth factor in cyanotic congenital heart disease. Pediatr. Cardiol., 24: 127-132.
Jacobs, E.G., M.P. Leung and J.P. Karlberg, 2000. Postnatal growth in southern Chinese children with symptomatic congenital heart disease. J. Pediatr. Endocrinol. Metab., 13: 387-401.
Leitch, C.A., 2000. Growth, nutrition and energy expenditure in pediatric heart failure. Prog. Pediatr. Cardiol., 11: 195-202.
Leite, H.P., A.C. de Camargo Carvalho and M. Fisberg, 1995. Nutritional status of children with congenital heart disease and left-toright shunt: The importance of the presence of pulmonary hypertension. Arq. Bras. Cardiol., 65: 403-407.
Linde, L.M., O.J. Dunn, R. Schireson and B. Rasof, 1967. Growth in children with congenital heart disease. J. Pediatr., 70: 413-419.
Mehrizi, A. and A. Drash, 1962. Growth disturbance in congenital heart disease. J. Pediatr., 61: 418-429.
Neely, J.G., J.M. Hartman, J.W. Forsen Jr. and M.S. Wallace, 2003. Tutorials in clinical research: VII. Understanding comparative statistics (contrast)-part B: Application of T-test, Mann-Whitney U and chi-square. Laryngoscope, 113: 1719-1725.
Nydegger, A. and J.E. Bines, 2006. Energy metabolism in infants with congenital heart disease. Nutrition, 22: 697-704.
O'Brien, P. and P.A. Smith, 1994. Chronic hypoxemia in children with cyanotic heart disease. Critc. Care Nurs. Clin. North Am., 6: 215-226.
Pelargonio, S., M. Lorizio and F. Paone, 1975. Influence of congenital heart diseases on the appearance and maturation of ossification nuclei. Boll Soc. Ital. Cardiol., 20: 1085-1090.
Rosner, B. and D. Grove, 1999. Use of the Mann-Whitney U-test for clustered data. Stat. Med., 18: 1387-1400.
Salzer, H.R., F. Haschke, M. Wimmer, M. Heil and R. Schilling, 1999. Growth and nutritional intake of infants with congenital heart disease. Pediatr. Cardiol., 10: 17-23.
Shrivastava, S., 2008. Malnutrition in congenital heart disease. Indian Pediatr., 45: 535-536.
Tambić-Bukovac, L. and I. Malcić, 1993. Growth and development in children with congenital heart defects. Lijec Vjesn, 115: 79-84.
Vaidyanathan, B., S.B. Nair, K.R. Sundaram, U.K. Babu and K. Shivaprakasha et al., 2008. Malnutrition in children with congenital heart disease (CHD) determinants and short-term impact of corrective intervention. Indian Pediatr., 45: 541-546.
Varan, B., K. Tokel and G. Yilmaz 1999. Malnutrition and growth failure in cyanotic and acyanotic congenital heart disease with and without pulmonary hypertension. Arch. Dis. Child., 81: 49-52.
Weeks, B. and A.H. Friedman, 2004. Training pediatric residents to evaluate congenital heart disease in the current era. Pediatr. Ciin. North Am., 51: 1641-1651.
White, R.I., C.E. Jordan, K.C. Fischer, L. Lampton, C.A. Neil and J.P. Dorst, 1972. Skeletal changes associated with adolescent congenital heart disease. Am. J. Roentgenol. Radium Ther. Nucl. Med., 116: 531-538.
Yilmaz, E., B. Ustundag, Y. Sen, S. Akarsu, A.N. Kurt and Y. Dogan, 2007. The levels of Ghrelin, TNF-alpha and IL-6 in children with cyanotic and acyanotic congenital heart disease. Mediators Inflamm., 2007: 32403-32403.
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