Anda di halaman 1dari 6

Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 15, no. 2, 205e210, 2012 Copyright 2012 by The International Society for Clinical Densitometry


Original Article

Bone Quality and Nutritional Status in Children With Congenital Heart Defects

Chico-Barba Laura Gabriela, 1 , 2 Vivanco-Munoz ~ Nalleli, 2 Avil es-Toxqui Dalia Patricia, 3

Tamayo Juan, 3 Rivas-Ru ız Rodolfo, 2 Buend ıa-Hern andez Alfonso, 1 and Clark Patricia * , 2

1 Department of Pediatric Cardiology, National Cardiology Institute ‘‘Ignacio Ch avez’’, Mexico City, Mexico; 2 Clinical

Epidemiology Unit, Children’s Hospital of Mexico Federico G omez, Faculty of Medicine UNAM, Mexico City, Mexico;

and 3 Mexican Committee for the Prevention of Osteoporosis, COMOP, Hip odromo Condesa, Mexico City, Mexico


The aim of this study was to evaluate bone quality and nutritional status in children with congenital heart defects

(CHDs) using quantitative ultrasound. A cross-sectional study was designed. A population-based sample of 75 chil-

dren with CHD (age: 0e6 yr) from the Department of Pediatric Cardiology at the National Cardiology Institute

‘‘Ignacio Ch avez’’ was compared with 106 healthy children during 2009. Weight and height were determined in

both groups; bone status was measured at the radius and tibia as speed of sound (SOS). Nutritional status was

defined according to the Waterloo and G omez index. Chi-square test, Student’s t-test, and analysis of variance

were used to determine the statistical differences. A linear regression analysis adjusted by age, weight, height,

type of CHD, and birth weight was made. Both groups were similar in sex distribution, prematurity, and birth

weight. Acyanotic cardiopathy with increased pulmonary flow was the most frequent (61.3%). Prevalence of mal-

nutrition was higher in CHD group compared with healthy children ( p ! 0.001), and radius SOS was lower in chil-

dren with CHD compared with healthy children (3484 180 vs 3575 159 m/s, respectively; 95% confidence

interval: 39.8e143; p 5 0.001). A positive correlation was found between CHD and reduced SOS in the adjusted

linear regression model, r 2 5 0.455 ( p ! 0.001). Children with CHD have lower SOS radius values compared

with healthy children, suggesting reduced bone quality regardless of the nutritional status.

Key Words: Bone; children; congenital heart defects; nutritional status; quantitative ultrasound.


Osteoporosis is a disease characterized by low bone mass

and structural deterioration of bone tissue, leading to bone

fragility and an increased susceptibility to fractures. It is

well known that the disease occurs primarily as a result of

aging, but there is strong evidence that it can also occur as

a result of impaired development of peak bone mass (1).

Received 05/02/11; Revised 11/04/11; Accepted 11/05/11.

*Address correspondence to: Clark Patricia, PhD, Clinical Epide-

miology Unit, Children’s Hospital of Mexico Federico G omez, Fac-

ulty of Medicine UNAM, Dr M arquez No. 162, Colonia Doctores,

Delegaci on Cuauht emoc, CP 06720, Mexico City, Mexico. E-mail:

Therefore, bone mineral accretion during childhood may be

a critical determinant of osteoporosis risk later in life, making

bone growth a fundamental process (2). Several disorders

may be associated with a reduced bone mineral reserve (ie,

store) in children, particularly in patients with chronic

diseases (3).

Children with congenital heart defects (CHDs) may be ex-

posed to an increased risk of skeletal development with low

bone mineral mass due to hemodynamic and metabolic

changes (4). These factors include hypoxia, increased basal

metabolic rate, fatigue on feeding, low nutrient intake, birth

weight (5), reduced intestinal perfusion, intestinal malabsorp-

tion, type of CHD (6), type of surgical correction (7), and

protein-energy malnutrition (7e18). Malnutrition, a common

cause of morbidity, is prevalent in more than 30% of children



Laura Gabriela et al.

with CHD (19). Patients with increased pulmonary blood

flow, increased metabolic rate, and/or pulmonary hyperten-

sion are more prone to develop malnutrition and show growth

retardation (20). Nevertheless, some studies show that if ade-

quate calories are provided and early corrective surgery is

performed, normal growth potential may be attained in chil-

dren with most cardiac malformations (21).

Quantitative ultrasound (QUS) has recently been used as

a noninvasive method of estimating bone mass accretion at

the peripheral skeleton anatomic sites (mid-radius, tibia,

and phalanxes). Broadband ultrasound attenuation (BUA)

and speed of sound (SOS) attenuation in bone are measured

using QUS devices. BUA values depend on the trabecular

bone and provide structural information. SOS reflects the

combination of mineral density, maturation phase of the min-

eral matrix (primary or secondary mineralization), architec-

ture, elasticity, and finally bone strength (22). Some studies

have demonstrated that a reduced value of SOS is associated

with a reduced bone mass accrual status in children with

growth disturbances or disorders affecting bone health; so

QUS can identify a population of children with an increased

risk of bone fragility (3).

Because growth retardation is linked with bone accretion,

this study was designed to evaluate the bone quality and nu-

tritional status in a group of children with CHD compared

with healthy children using bone attenuation of ultrasonic

waves (SOS) to determine differences between the groups

as well as differences between the different types of CHD

and its association with nutritional risk factors.

Materials and Methods

Seventy-five children diagnosed with CHD (age: 0e6 yr) at-

tending a scheduled visit at the Department of Pediatric

Cardiology at the National Cardiology Institute ‘‘Ignacio

Ch avez’’ were compared with healthy age- and sex-matched

controls from a nearby nursery school. Children with conditions

related to growth retardation were excluded (ie, those with

Down, Marfan, Noonan, and Turner syndromes; VACTERL

association, such as vertebral anomalies, anal atresia, tracheoe-

sophageal fistula, esophageal atresia, or renal anomalies).

None of the children with CHD have undergone any surgical

procedure to evaluate if CHD per se affects the bone status.

Children with CHD were categorized into 1 of 4 groups ac-

cording to the cardiac malformations: (1) acyanotic with in-

creased pulmonary flow (AIPF), (2) acyanotic with normal

pulmonary flow, (3) cyanotic with increased pulmonary flow

(CIPF), and (4) cyanotic with decreased pulmonary flow

(CDPF) (23).

The following demographic and anthropometric parame-

ters were evaluated in both groups: Prematurity (defined as

gestational age of 36 wk and less) and type of cardiac defect

were collected from clinical records; drug prescription infor-

mation was obtained interviewing the parents. Nutritional

status was defined according to the National Center for

Health Statistics charts for weight/age, height/age, and

weight/height indexes using the Waterloo and G omez cutoff

points (24,25). In children younger than 24 mo, height was

measured using an infantometer (1-mm precision); children

aged older than 25 mo were assessed using a Seca stadiometer

(1-mm precision). Weight was measured with a Seca baby

scale (0.5-g precision, Seca GmbH & Co., Hamburg,

Germany) and Tanita digital scale (0.1-kg precision, Tanita,

Arlington Heights, Illinois) for children younger than 24 mo

and older than 25 mo, respectively.

A QUS device (Sunlight Omnisense 7000P, Sunlight Med-

ical, Tel Aviv, Israel) was used for bone assessment (in vivo

variation coefficient of 0.3-0.4% reported on the manufac-

turer’s manual). Measurements were performed at the distal

third of the radius and midshaft tibia using a single type of

ultrasonic probe. Measurements were done by 2 previously

standardized operators (r 5 0.94).

The participation of the children was obtained according to

institutional standards and approved protocols for research in-

volving human subjects. Written informed consent was ob-

tained for each participant from his or her legal guardian.

The study protocol was approved by the Ethics and Investiga-

tion Committee of the National Cardiology Institute.

To study the possible SOS changes in bone tissue accrual

associated with CHD, each patient was matched with

a healthy control subject based on age and gender. SOS differ-

ences were then calculated, and the resulting mean value

between the 2 groups was assessed by conducting a t-test.

Chi-square test and Student’s t-test were done to determine

the statistical differences in every variable. A linear regres-

sion analysis adjusted for age, prematurity, and nutritional

status was made to find a relation between lower bone mass

levels and CHD. All statistical analyses were made using

SPSS version 16.0 for Windows (SPSS Inc., Chicago, IL).


Among the 181 eligible healthy patients and 145 children

with CHD, 106 (97.2%) and 75 (51.7%), respectively, agreed

to participate in the study (May to September 2009). QUS was

performed in 173 (99.4%) patients and 179 (96.1%) healthy sub-

jects at radius and tibia. Missing values in radius measurement

were due to positioning difficulties of the age group.

The CHD group comprised 44 females (58.7%), median age

was 37.4 19 mo (median standard deviation [SD]), and av-

erage birth weight was 2.920 0.520 kg (median SD); 6 of

these children (9.4%) were premature (Table 1). There was

no statistical significance in birth weight and prematurity.

There were 54 females in the healthy group (50.9%); their me-

dian age was 43.8 16.6 mo (mean SD).

The AIPF group was the most prevalent in this sample

(n 5 46, 61.3%), followed by the CDPF group (n 5 15, 20%).

The most common CHDs were ventricular septal defect

(n 5 40, 53.3%), patent ductus arteriosus (n 5 22, 29.3%), aor-

tic stenosis (n 5 13, 29.3%), and pulmonary stenosis (n 5 10,


Prevalence of malnutrition was higher in children with

CHD compared with the healthy group (42.7% vs 2.8%,

p ! 0.001). A normal nutritional status was found in most

Journal of Clinical Densitometry: Assessment of Skeletal Health

Volume 15, 2012

Bone Quality and Nutritional Status in Children With CHD



Table 1

Baseline Characteristics


Children with

CHD, n 5 75

Healthy children,



n 5 106 (58.4%)




31 (41.3)

52 (49.1)


44 (58.7)

54 (50.9)




6 (9.4)

13 (12.4)


58 (90.6)

92 (87.6)


Nutritional status


41 (54.7)

86 (81.1)


32 (42.7)

3 (2.8)


2 (2.7)

17 (16)


Cardiac defect


105 (100)


46 (61.3)


5 (6.7)


9 (12)


15 (20.0)


Mean ( SD)

Mean ( SD)

Birth weight (kg) 2.920 ( 0.520) 3.099 ( 0.429)


Age (mo)

37.4 ( 19)

43.8 ( 16.6)


SOS (m/s)


3484 ( 180)

3575 ( 159)



3468 ( 138.8)

3497 ( 117.7)


Abbr: CHD, congenital heart defect; AIPF, acyanotic with in-

creased pulmonary flow; ANPF, acyanotic with normal pulmonary

flow; CIPF, cyanotic with increased pulmonary flow; CDPF, cyanotic

with decreased pulmonary flow; SD, standard deviation; SOS, speed

of sound.

of the children in both groups (CHD: n 5 41, 54.7% and

healthy: n 5 86, 81.1%).

SOS in radius was lower in the CHD group (3484 180

m/s) than in healthy children (3575 159 m/s; 95% confidence

interval: 39.8e143; p 5 0.001). SOS in tibia was also lower in

children with CHD, but the difference was not significant

( p 5 0.12), as shown in Fig. 1. SOS increased with age in

both groups of children.

Regardless of CHD, SOS differences were significant for age

and nutritional status. Malnourished children had lower SOS

than children with a normal nutritional status for both measure-

ment sites ( p ! 0.001). When comparing SOS in healthy chil-

dren and type of cardiac defects, we found that the most

affected group is CIPF ( p 5 0.003). Differences in SOS values

were not significant among females and males either for radius

or for tibia ( p 5 0.27 and 0.33, respectively) (Table 2).

A linear regression model adjusted for age, weight and

height at baseline assessment, type of CHD, and birth weight

was performed. According to this model, the correlation-

adjusted association between CHD and reduced SOS at radius

was r 2 5 0.455 ( p ! 0.001). No differences in SOS values

were found in weight, height, and birth weight ( p 5 0.814,

0.861, and 0.090, respectively). Age and type of CHD showed

statistical significance for SOS values in radius ( p 5 0.003

and 0.010, respectively) (Table 3). SOS values were increas-

ing according to age in all children.


To our knowledge, this is the first study that reports bone

mass determination using SOS attenuation values in bones

of young children with CHD compared with healthy matched

controls. This is a preliminary study.

We assessed bone mass using QUS, a device for bone tis-

sue/structure assessment. QUS is very convenient for this

kind of population because it is portable and radiation free,

making it safe for use in young children; earlier studies

have shown it to be useful in identifying bone abnormalities.

A previous study by Witzel et al (26), with a smaller sam-

ple than ours, showed no association between bone develop-

ment and CHD in adolescents and young adults using

peripheral quantitative computed tomography. In our study,

sample size showed sufficient statistical power (80%) to dem-

onstrate differences between both groups of study in SOS


Results show that radius SOS is lower in CHD group than

in healthy children. There are two ways by which bone mass

can be affected in children with CHD. The first is through nu-

tritional status. Studies have shown that malnutrition affects

bone development; nevertheless, it has been shown that if

adequate calories are provided, normal growth potential

may be fulfilled (21). The second way is represented by he-

modynamic and metabolic changes, which include hypoxia

and increased basal metabolic rate. Hypoxia leads to reduced

intestinal perfusion, resulting in intestinal malabsorption of

nutrients, including calcium and vitamin D, which are funda-

mental in bone development (5,6). In contrast to healthy chil-

dren, most children with CHD are affected by malnutrition

Bone Quality and Nutritional Status in Children With CHD 207 Table 1 Baseline Characteristics Children with

Fig. 1. SOS in radius and tibia per group. SOS, speed of

sound; CHD, congenital heart defect.

Journal of Clinical Densitometry: Assessment of Skeletal Health

Volume 15, 2012


Table 2

Laura Gabriela et al.

Difference in SOS per Variable


SOS radius (m/s)

SOS tibia (m/s)



Mean ( SD)



Mean ( SD)





3523 (177)


3495 (148)



3552 (169)



3476 (105)





3466 (212)


3458 (138)



3551 (164)



3488 (126)


Nutritional status





3556 (164)


3501 (117)



3423 (184)



3416 (144)




3617 (124)



3503 (124)



Healthy children


3575 (159)


3497 (117.7)

Children with CHD


3484 (180)



3468 (138.8)


Cardiac defect





3501 (172)



3461 (135)




3459 (131)



3542 (156)




3365 (216)



3419 (157)




3520 (178)



3494 (131)


Abbr: SOS, speed of sound; SD, standard deviation; CHD, congenital heart defect; AIPF, acyanotic with increased pulmonary flow; ANPF,

acyanotic with normal pulmonary flow; CIPF, cyanotic with increased pulmonary flow; CDPF, cyanotic with decreased pulmonary flow; NS,

not significant.

and hypoxia, particularly the CIPF group; consequently, they

could have disturbances in bone mineralization. This is dem-

onstrated in our study showing lower SOS values in the CHD

group and malnourished children.

However, a linear regression model was done, adjusted for

age, weight, height, type of CHD, and birth weight. We con-

sider that difference in age (3 mo) has no clinical impact;

nonetheless, it was included in the model.

Weight and height at baseline assessment were included in

the regression model as they influence bone density. It is well

documented that prematurity has an effect on bone status; in

Table 3

Linear Regression Model

Unstandardized coefficients



Standard error


Age (mo)




Weight at baseline (kg)




Height at baseline (cm)




Birth weight




Type of CHD




Abbr: CHD, congenital heart defect.

Radius is the dependent variable.

our study, prematurity was directly recorded from the mother,

leading information to recall bias, and so we decided to in-

clude birth weight as an indicator of prematurity. Regarding

the presence of CHD, type of CHD was included in the anal-

ysis as an indicator of severity of the disease. As the children

with CHD were all considered surgically untreated, age at

baseline assessment could be considered as duration of the

disease; this was one of the most important predictors for

bone status in the regression model analysis.

The model accounts for 45% of the variance of low SOS

values. Specifically, age and type of CHD have more influ-

ence on low SOS values ( p 5 0.003 and 0.010, respectively).

The impact of age on SOS scores is explained by bone accre-

tion during childhood; bone mass rises as age increases until

peak bone mass is reached during adolescence. SOS is nega-

tively affected by the presence of CHD as shown in the linear

regression model and when compared with healthy children

using Student’s t-test. In the analysis model, weight, height,

and birth weight have no influence on SOS values. Sex was

not included in the model because there are no sex differences

on bone accretion during childhood until puberty.

These results encourage clinicians to include bone assess-

ment in children with CHD to achieve an adequate bone de-

velopment and normal growth. Providing an early and

adequate nutritional therapy (with a correct amount of nutri-

ents important for bone development, such as calcium and

Journal of Clinical Densitometry: Assessment of Skeletal Health

Volume 15, 2012

Bone Quality and Nutritional Status in Children With CHD


vitamin D) as well as a timely palliative/corrective surgery

may help to prevent bone disturbances.

Although reference SOS values are available in healthy Is-

raeli children (27), the normal reference values for SOS atten-

uation in the normal Mexican population are not available;

therefore, a control group was required to have a good com-

parative group.

This study has certain limitations. In some cases, birth

weight or gestational age data were not available on the med-

ical records and/or family recalls. Although dual-energy

X-ray absorptiometry measurement is the gold standard for

adults, there is much controversy in its use in children;

some clinical factors described in the Introduction section

(such as hypoxia, basal metabolic rate, nutrient intake, and in-

testinal perfusion) were not included in the present analysis

because they were not described in detail in the clinical re-

cords. Although they may have an influence on bone develop-

ment, we could not explore their impact. However, the factors

we included in the study are reported to have an impact on

bone accretion (age and prematurity), and their impact was

shown in the analysis. Further studies with a wider analysis

of clinical factors are needed to determine the mechanisms

by which bone accretion may be altered.

Regarding tibia results, the sample size might have been

too small to achieve statistical power. We selected QUS be-

cause it is a noninvasive, portable, and radiation-free method

that is safe for use in children.

In conclusion, in this preliminary study, we demonstrate

that children with CHD have lower SOS values compared

with healthy children, suggesting reduced bone quality re-

gardless of nutritional status although malnutrition is present

in most of the children in the CHD group.

In our review of literature regarding bone status and chil-

dren with CHD, only 1 cross-sectional study was found, and

there is no evidence of longitudinal studies. No previous

studies describing bone status using QUS in this group of

children were found. Further longitudinal studies are needed

to assess bone health after a surgical procedure. Special

medical attention in this vulnerable group of children is re-

quired so as to assure optimal bone development and there-

fore prevent bone accretion disturbances in adolescence and



Funding was received from the Science and Technology

National Council (CONACYT).


  • 1. World Health Organization. 2003 Prevention and management of osteoporosis: report of scientific group. WHO Technical Support Series. World Health Organ Tech Rep Ser 921: 1e164.

  • 2. Tau C. 2006 Densitometr osea en pediatr ıa [Bone densitometry


in pediatrics. Updates on osteology]. Actualizaciones en

Osteolog ıa 2(1):26e28.

  • 3. Baroncelli GI. 2008 Quantitative ultrasound methods to assess bone mineral status in children: technical characteristics, perfor- mance, and clinical application. Pediatr Res 63:220e228.

  • 4. Wheat J. 2002 Nutritional management of children with congen- ital heart disease. Nutr Bytes 8(2):1e5.

  • 5. Vaidyanathan B, Reshma R, Sarala DA, et al. 2009 What de- termines nutritional recovery in malnourished children after correction of congenital heart defects? Pediatrics 124(2): 294e299.

  • 6. Da Silva VM, de Oliveira Lopes M, de Araujo TL. 2007 Growth and nutritional status of children with congenital heart disease. J Cardiovasc Nurs 22:390e396.

  • 7. Buend ıa A, Calder on-Colmenero J, Pati~no E, et al. 2004 Secuen-

cia de estudio en el ni~no con cardiopat ıa cong enita [Sequence of

assessment in children with congenital heart disease]. In: PAC

Pediatr ıa I. Academia Mexicana de Pediatr ıa. Intersistemas

Editorial, M exico, 507e605.

  • 8. Velasco C. 2007 Nutrici on en el ni~no cardi opata [Nutrition in

children with congenital heart defects]. Colombia m edica

38(Suppl 1):50e55.

  • 9. Olivares JL. 2003 Nutrici on en el ni~no con cardiopat ıa con-

g enita [Nutrition in children with congenital heart diseas]. In:

Nutrici on en pediatr ıa [Nutrition in pediatrics]. Bueno M,

Sarr ıa A and P erez-Gonz alez JM, eds. Madrid, Spain: Ergon,


  • 10. Toussaint G, Garc ıa-Aranda JA. 2001 Desnutrici on energ etico-

prote ınica [Protein-energy malnutrition]. In: Nutriolog ıa M edica

[Medical nutriology]. Casanueva E, Kauffer-Horwitz M,

P erez-Lizaur AB and Arroyo P, eds. M exico: Editorial M edica

Panamericana, 212e242.

  • 11. G omez F. 2003 Desnutrici on [Malnutrition]. Salud P ublica de

M exico 45(Suppl 4):s576es582.

  • 12. 2001 Hormona paratiroidea, calcitonina, metabolismo de calcio y fosfato, vitamina D, huesos y dientes [Parathyroid hormone, calcitonin, calcium and phosphate metabolism, vitamin D, bones and teeth]. In: Tratado de Fisiolog ıa M edica [Textbook of med- ical physiology]. Guyton AC and Hall JE, eds. M exico: McGraw-Hill Interamericana, 1081e1100.

  • 13. 2002 Control hormonal del metabolismo del calcio y la fisiolog ıa del hueso [Hormonal control of calcium metabolism and bone physiology]. In: Fisiolog ıa m edica [Medical physiol- ogy]. Ganong W, ed. M exico: Manual Moderno, 417e432.

  • 14. 2008 Bone mineral acquisition in utero and during infancy and childhood. In: Osteoporosis. Marcus R, Feldman D and Nelson D, eds. San Diego, CA: Elsevier Academic Press, 705e723.

  • 15. Thompson-Chagoy an OC, Reyes-Tsubaki N, Rabiela-Barrios OL, et al. 1998 Estado nutricio del ni~no con cardiopat ıa cong enita [The nutritional status of the child with congenital cardiopa- thy]. Archivos del Instituto de Cardiolog ıa de M exico 68: 119e123.

  • 16. Lyon GR. 2007 Nelson textbook of pediatrics. In: Kliegman R, Behrman R, Jenson H and Stanton B, eds. New York, NY: Saunders.

  • 17. Malagon I, Onkenhout W, Klok G, et al. 2005 Gut permeability in paediatric cardiac surgery. Br J Anaesth 94(2):181e185.

  • 18. Park M. 2008 Pediatric cardiology for practitioners. Philadelphia, PA: Mosby Elsevier.

  • 19. Villas ıs-Keever MA, Pineda-Cruz RA, Halley-Castillo E, Alva-Espinosa C. 2001 Frecuencia y factores de riesgo asocia-

dos a desnutrici on de ni~nos con cardiopat ıa cong enita [Fre-

quency and risk factors associated with malnutrition in

children with congenital cardiopathy]. Salud P ublica de M exico


  • 20. Shrivastava S. 2008 Malnutrition in congenital heart disease. Indian Pediatr 45:535e536.

Journal of Clinical Densitometry: Assessment of Skeletal Health Volume 15, 2012


Laura Gabriela et al.

  • 21. Tokel K, Azak E, Ayabakan C, et al. 2010 Somatic growth after corrective surgery for congenital heart disease. Turk J Pediatr 52(1):58e67.

  • 22. Knapp K. 2009 Quantitative ultrasound and bone health. Salud p ublica M ex 51(Suppl 1):S18eS24.

  • 23. Fausse A, Buend ıa A, Zabal C. 1993 Cardiolog ıa Pedi atrica, di-

agn ostico y tratamiento [Pediatric cardiology. Diagnosis and

treatment]. M exico: Editorial M edica Panamericana.

  • 24. Waterlow J. 1996. Malnutrici on Proteico-Energ etica, 555.

Washington, DC: PAHO-WHO.

  • 25. World Health Organization. Child Growth Standards, 2007. Avail- able at: Accessed December 9, 2011.

  • 26. Witzel C, Sreeram N, Coburger S, et al. 2006 Outcome of mus- cle and bone development in congenital heart disease. Eur J Pe- diatr 165(3):168e174.

  • 27. Zadik Z, Price D, Diamond G. 2003 Pediatric reference curves for multi-site quantitative ultrasound and its modulators. Osteo- poros Int 14(10):857e862.

Journal of Clinical Densitometry: Assessment of Skeletal Health

Volume 15, 2012