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Journal of Tropical Pediatrics Advance Access originally published online on March 1, 2009
Journal of Tropical Pediatrics 2009 55(5):302-306; doi:10.1093/tropej/fmp010
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© The Author [2009]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Linear Growth in Relation to the Circulating Concentration of Insulin-like Growth Factor-I and Free Thyroxine in Infants and Children with Congenital Cyanotic Heart Disease Before vs. After Surgical Intervention

Amal El-Sisia, Aiman Khellaa, Mohamed Numana, Mohamed Dilwara, Akhlaque Bhata and Ashraf Solimanb

aDepartment of Pediatric Cardiology, Hamad General Hospital, P O Box 3050, Doha, Qatar
bDepartment of Endocrinology, Hamad General Hospital, P O Box 3050, Doha, Qatar

Correspondence: Ashraf T Soliman, Consultant Pediatric Endocrinologist, Department of Pediatrics, Hamad General Hospital, P O Box 3050, Doha, Qatar. Tel.: 009745983874. E-mail <atsoliman{at}yahoo.com>.


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
This prospective controlled study recorded the anthropometric data and measured the circulating insulin-like growth factor-I (IGF-I) in 16 children with congenital cyanotic heart disease before and a year after surgical intervention. At presentation patients were significantly shorter [length SD scores (LSDS) = –2.44 ± 1.31], vs. controls (LSDS = –0.25 ± 0.18). After surgical treatment the LSDS and growth velocity SD scores (GVSDS) increased significantly to (–) 0.25 ± 0.95 and 3.7 ± 2.1, respectively. IGF-I increased from 45.7 ± 26.3 ng ml–1 to 67.7 ± 16.4 ng ml–1. The GVSDS after treatment was correlated with the body mass index (BMI) (r = 0.339, p < 0.05) and negatively with the LSDS before surgery (r = –0.461, p < 0.05). The percentage increase of IGF-I after operation was correlated significantly with the BMI after surgical intervention (r = 0.82, p < 0.001). It appears that the postoperative growth spurt in infants with cyanotic congenital heart disease (CHD) is mediated through activation of the GH/IGF-I system and improved nutrition.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Children with congenital heart disease (CHD) have been reported to show significant growth retardation both prenatally and postnatally [1–8]. Although catch-up growth after successful surgical repair has been reported [8–10], medical therapy has been associated with little improvement of their slow growth. Retardation in height as well as weight seems most pronounced in children with cyanotic heart disease, who show more severe weight than height retardation [4]. Advances and recent developments in surgical approach and enteral nutrition have improved the care of these patients [1,11–13]. Although catch-up growth usually occurs in children with CHD after surgical intervention, the degree of growth retardation at presentation and the magnitude of catch-up growth and their relation to the change, if any, with important hormones controlling growth [insulin-like growth factor-I (IGF-I), free T4 (FT4) and thyrotropin (TSH)] needs further clarification.

The aim of the present prospective study was to evaluate long-term growth of infants with cyanotic CHD and to look for a possible relationship between echocardiographic parameters at the moment of surgical correction and IGF-I concentration on the one hand and the degree of postsurgical catch-up growth on the other hand.

Patients and methods
Growth parameters for 16 infants with some specific cyanotic CHD were recorded prospectively. These data represent all patients followed up in the department of Pediatric Cardiology, HMC, between 1- 2006 and 1- 2008. Patients with multiple CHDs, those with associated chromosomal malformations or peculiar syndromes or prematurity were not included in the present study. Our patients were eight females and eight males. They were subdivided in two different groups according to the surgical approach applied. The first group (n = 8) had palliative repair and the second group had full surgical repair of their CHD. Mean operation ages of our patients are given in Table 1. Mean birth-weight and -length were normal for all patient groups and did not differ among the two patient groups.


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  		TABLE 1 Growth and hormonal data before vs. after intervention in patients and controls

 
Ethical approval
Research Ethics Board, Hamad Medical Centre, Doha Qatar approved the protocol of the study and informed consents were obtained from all the parents of the children included in this study.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
All patients were examined thoroughly with special emphasis on:

  1. Detailed history taking including nutritional intake.
  2. Anthropometric measurements including weight, length.
  3. Length SD scores (LSDS), length growth velocity SD scores (GVSDS) and body mass index (BMI) were calculated prospectively before and at least 6 months or more after treatment. Annual length/height velocity (GV) was calculated from length measurements taken 12 months apart. Length was measured with an infant/child length measuring board: This board has 130 cm capacity (collapses to 75 cm) and has 0.1 cm increments, with the sliding head-foot piece (Shorr Productions, Olney, MD, USA). The standard deviation of the difference between blind triplicate height measurements of 20 children was 0.15 cm. Weight (child lightly clothed) was measured using an electronic Baby scale with Digital Display. SD scores (SDS) were calculated for length and length velocity (using Tanner et al. standards [14]) and BMI (using Cole, et al. standards [15]).
  4. Investigations included: measurement of circulating IGF-I, FT4 and TSH.
  5. During each clinic visit (every 3–4 months for at least 12 months), the anthropometric parameters were reassessed and recorded and the laboratory tests repeated.
  6. All children were vitamin D sufficient and were on maintenance dose of 400 IU per day during the study.

IGF-I, TSH and FT4 were measured by radioimmunometric assay using reagents purchased from Mediagnost, Reutlingen, Germany. Intraassay coefficient of variations (CVs) were 6.6%, 5.9% and 5.8%, respectively, and interassay CVs were 7.9%, 6.9 and 7.2%, respectively. Results are expressed as the mean ± SD and analyzed by paired student t-test to compare growth parameters and analyte concentrations before vs. after surgical treatment. A non-paired student t-test was used to compare growth parameters and analyte concentrations between patients with CHD and control group. Correlation and linear regression analysis were used to investigate the relation between growth parameters and the other variables. For ethical reasons hormonal and analyte concentrations for normal controls were not measured.

None of the included patients were subsequently excluded. For age periods, three measurements were used in the first year of life. For postoperative periods, three measurements were taken for every patient. Preoperative measurements were taken in the preoperative 2 weeks closest to operation. The relationship between catch-up growth and the severity of preoperative growth failure was evaluated by correlating GVSDS after operation with the growth parameters before surgery. The relationship between catch-up growth and age at time of surgical intervention was also evaluated. Measurement of circulating IGF-I, free thyroxine (FT4) and TSH was done before and 6–12 months after surgery. Hormonal data are correlated with anthropometric and echocardiographic data.

Statistical analysis
Usual parametric statistics were used for calculation of the mean values and confidence intervals. A significant difference was considered to exist between the reference population and our patient data if the mean value of the data set differed from 0 at the 0.05 confidence level. The Pearson correlation coefficient was used for studying the relationships between catch-up growth and the severity of initial growth retardation. The Excel statistical package was used for data management.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
Anthropometric and hormonal data (Table 1) showed that at preoperatively patients’ mean age = 11.6 ± 6 months, LSDS = (–) 2.44 ± 1.31 and BMI = 15.3 ± 2.7. They were significantly shorter and had markedly lower GVSDS compared with normal controls (LSDS = 0.25 ± 0.18 and 0.31 ± 0.22, respectively). One year after the surgical treatment, the LSDS increased significantly in patients to –0.25 ± 0.95 with a significantly increased GVSDS = 3.7 ± 2.1 and BMI = 16.66 ± 1.5. They had significantly higher GVSDS compared with normal controls. Circulating concentrations of IGF-I increased significantly from 45.7 ± 26.3 ng ml–1 before the surgical treatment to 66.75 ± 37.2 ng ml–1 after the surgical treatment. No significant change was detected in circulating FT4 or TSH concentration after vs. before surgery.

Tables 2 and 3 compare the anthropometric data for two groups of patients with cyanotic CHD: Group-1 (n = 8) who had palliative surgery and Group-2 who had complete surgical repair of the defect (n = 8). Group-1 patients were operated on significantly earlier in their life and their LSDS were significantly lower than Group-2 patients before surgery. Group-1 patients had significantly higher GVSDS after surgical intervention. Both groups had significantly increased IGF-I concentrations after vs. before surgery.


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  		TABLE 2 Growth and hormonal data before vs. after intervention

 

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  		TABLE 3 Growth and hormonal data of patients with cyanotic CHD before vs. intervention

 
The GVSDS after treatment was correlated with the BMI before surgery (r = 0.339, p < 0.05) and negatively with the height SDS (HtSDS) before surgery (r = –0.461, p < 0.05). The percentage increase of IGF-I after operation was correlated significantly with the BMI after surgical intervention (r = 0.82, p < 0.001). GV after surgery was correlated negatively with the age at operation (r = –0.639, p < 0.001). None of the echocardiographic parameters were correlated significantly with the anthropometric parameters.


   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
In this study, infants and children with cyanotic CHD (n = 16, below 2 years of age) presented with short stature [LSDS = (–) 2.44 ± 1.31]. Marked improvement in their LSDS was achieved 1 year after the treatment with vitamin D [LSDS = (–) 0.25 ± 0.95] with a period of significant catch-up growth evidenced by GVSDS = 3.7 ± 2.1 during the year after surgery. This growth spurt appeared to compensate adequately for the period of the previous growth retardation in most of the patients.

Many factors can contribute to impaired linear growth in these infants including: (i) hypoxia and defective perfusion to the growing tissues including the epiphyseal growth plate, (ii) increased metabolic rate inducing a hyper-metabolic state, (iii) decreased appetite and (iv) possible effect on GH/IGF-I axis [5,16,17].

In our patients with cyanotic CHD, circulating IGF-I concentrations increased significantly after vs. before surgical intervention. After surgery, the percentage change in IGF-I was correlated significantly with GV (r = 0.589, p < 0.01) and BMI (r = 0.82, p < 0.001). These findings supported the view that the attained growth spurt after treatment is mediated through increased IGF-I synthesis (stimulation of GH-IGF-I axis). The GVSDS after treatment was correlated with the BMI before surgery (r = 0.339, p < 0.05) and negatively with the HtSDS before surgery (r = –0.461, p < 0.05). GV after surgery was correlated negatively with the age at operation (r = –0.639, p < 0.001) denoting that early surgical interference and higher BMI preoperatively are associated with a better growth spurt.

Comparing growth and hormonal data for the two groups of patients with palliative surgery (Group-1) and total correction (Group-2) showed that both groups had significantly accelerated linear growth associated with increased IGF-I after surgery. The GVSDS was significantly higher in the palliative group which may be explained by better growth potential due to their younger age at operation.

In summary, significantly accelerated linear growth after surgical treatment of cyanotic CHD appears to be mediated through activation of the IGF-I synthesis. The correlation between GV after surgery with the BMI before surgery and the significant correlation between percentage increase of IGF-I and the BMI after surgery support the idea that intensive nutritional support to increase BMI before and after surgery appears to be an essential factor determining growth spurt after the operation.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Varan B, Tokel K, Yilmaz G. Malnutrition and growth failure in cyanotic and acyanotic congenital heart disease with and without pulmonary hypertension. Arch Dis Child (1999) 81:49–52.[Abstract/Free Full Text]
  2. Mehrizi A, Drash A. Growth disturbance in congenital heart disease. J Pediatr (1962) 61:418–29.[CrossRef][Web of Science][Medline]
  3. Weintraub RG, Menahem S. Growth and congenital heart disease. J Paediatr Child Health (1993) 29:95–8.[Web of Science][Medline]
  4. Norris MKG, Hill CS. Nutritional issues in infants and children with congenital heart disease. Crit Care Nurs Clin North Am (1994) 46:457.
  5. Abad-Sinden A, Sutphen J. Growth and nutrition. In: In: Allen HD, Gutgesell P, Clark EB, Driscoll D (eds.). Moss and Adams Heart Disease in Infants, Children and Adolescents, Chapter 17 (2000) Philadelphia: Lippincott Williams & Wilkins. 326.
  6. Silove ED. Assessment and management of congenital heart disease in the newborn by the district paediatrician. Arch Dis Child Fetal Neonatal Ed (1994) 70:F71–4.[Free Full Text]
  7. Strangeway A, Fowler R, Cunningham K, et al. Diet and growth in congenital heart disease. J Pediatr (1976) 57:57–86.
  8. Vogt KN, Manlhiot C, Van Arsdell G, et al. Somatic growth in children with single ventricle physiology. Impact of physiologic state. J Am Coll Cardiol (2007) 50:1876–83.[Abstract/Free Full Text]
  9. Leitch CA, Karn CA, Peppard RJ, et al. Increased energy expenditure in infants with cyanotic congenital heart disease. J Pediatr (1998) 133:755–60.[CrossRef][Web of Science][Medline]
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  12. Page RE, Deverall PB, Watson DA, et al. Height and weight gain after total correction of Fallot's tetralogy. Br Heart J (1978) 40:416–20.[Abstract/Free Full Text]
  13. Forchielli ML, McColl R, Walker WA, et al. Children with congenital heart disease: a nutrition challenge. Nutr Rev (1994) 52:348–53.[Web of Science][Medline]
  14. Unger R, DeKleermaeker M, Gidding SS, et al. Improved weight gain with dietary intervention in congenital heart disease. Am J Dis Child (1992) 146:1078–84.[Abstract/Free Full Text]
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This Article
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