2012 Chico J Clin Dens

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Original Article

Bone Quality and Nutritional Status in Children With CongenitalHeart Defects

Chico-Barba Laura Gabriela,1,2 Vivanco-Mu~noz Nalleli,2 Aviles-Toxqui Dalia Patricia,3

Tamayo Juan,3 Rivas-Ruz Rodolfo,2 Buenda-Hernandez Alfonso,1 and Clark Patricia*,2

1Department of Pediatric Cardiology, National Cardiology Institute Ignacio Chavez, Mexico City, Mexico;

2Clinical

Epidemiology Unit, Childrens Hospital of Mexico Federico Gomez, Faculty of Medicine UNAM, Mexico City, Mexico;

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

Abstract

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 InstituteIgnacio Chavez was compared with 106 healthy children during 2009. Weight and height were determined inboth groups; bone status was measured at the radius and tibia as speed of sound (SOS). Nutritional status wasdefined according to the Waterloo and Gomez index. Chi-square test, Students t-test, and analysis of variancewere 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 birthweight. 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: 39.8e

143; p5 0.001). A positive correlation was found between CHD and reduced SOS in the adjustedlinear regression model, r25 0.455 (p! 0.001). Children with CHD have lower SOS radius values comparedwith healthy children, suggesting reduced bone quality regardless of the nutritional status.

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

Introduction

Osteoporosis is a disease characterized by low bone massand structural deterioration of bone tissue, leading to bonefragility and an increased susceptibility to fractures. It iswell known that the disease occurs primarily as a result of

aging, but there is strong evidence that it can also occur asa result of impaired development of peak bone mass (1).

Therefore, bone mineral accretion during childhood may bea critical determinant of osteoporosis risk later in life, makingbone growth a fundamental process (2). Several disordersmay be associated with a reduced bone mineral reserve (ie,store) in children, particularly in patients with chronicdiseases (3).

Children with congenital heart defects (CHDs) may be ex-posed to an increased risk of skeletal development with lowbone mineral mass due to hemodynamic and metabolicchanges (4). These factors include hypoxia, increased basalmetabolic rate, fatigue on feeding, low nutrient intake, birthweight(5), reduced intestinal perfusion, intestinal malabsorp-tion, type of CHD (6), type of surgical correction (7), andprotein-energy malnutrition (7e18). Malnutrition, a commoncause of morbidity, is prevalent in more than 30% of children

Received 05/02/11; Revised 11/04/11; Accepted 11/05/11.*Address correspondence to: Clark Patricia, PhD, Clinical Epide-

miology Unit, Childrens Hospital of Mexico Federico Gomez, Fac-ulty of Medicine UNAM, Dr Marquez No. 162, Colonia Doctores,Delegacion Cuauhtemoc, CP 06720, Mexico City, Mexico. E-mail:[email protected]

205

Journal of Clinical Densitometry: Assessment of Skeletal Health, vol. 15, no. 2, 205e210, 2012 Copyright 2012 by The International Society for Clinical Densitometry1094-6950/15:205e210/$36.00DOI:10.1016/j.jocd.2011.11.001
mailto:[email protected]://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001http://dx.doi.org/10.1016/j.jocd.2011.11.001mailto:[email protected]


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with CHD (19). Patients with increased pulmonary bloodflow, increased metabolic rate, and/or pulmonary hyperten-sion are more prone to develop malnutrition and show growthretardation(20). Nevertheless, some studies show that if ade-quate calories are provided and early corrective surgery isperformed, normal growth potential may be attained in chil-dren with most cardiac malformations (21).

Quantitative ultrasound (QUS) has recently been used asa noninvasive method of estimating bone mass accretion atthe peripheral skeleton anatomic sites (mid-radius, tibia,and phalanxes). Broadband ultrasound attenuation (BUA)and speed of sound (SOS) attenuation in bone are measuredusing QUS devices. BUA values depend on the trabecularbone and provide structural information. SOS reflects thecombination of mineral density, maturation phase of the min-eral matrix (primary or secondary mineralization), architec-ture, elasticity, and finally bone strength (22). Some studieshave demonstrated that a reduced value of SOS is associatedwith a reduced bone mass accrual status in children withgrowth disturbances or disorders affecting bone health; soQUS 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 comparedwith healthy children using bone attenuation of ultrasonicwaves (SOS) to determine differences between the groupsas well as differences between the different types of CHDand 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 IgnacioChavez were compared with healthy age- and sex-matchedcontrols from a nearby nursery school. Childrenwith conditionsrelated to growth retardation were excluded (ie, those withDown, Marfan, Noonan, and Turner syndromes; VACTERLassociation, such as vertebral anomalies, anal atresia, tracheoe-sophageal fistula, esophageal atresia, or renal anomalies).None of the children with CHD have undergone any surgicalprocedure 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 normalpulmonary 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 asgestational age of 36 wk and less) and type of cardiac defectwere collected from clinical records; drug prescription infor-mation was obtained interviewing the parents. Nutritionalstatus was defined according to the National Center forHealth Statistics charts for weight/age, height/age, andweight/height indexes using the Waterloo and Gomez cutoff

points (24,25). In children younger than 24 mo, height wasmeasured using an infantometer (1-mm precision); childrenaged older than 25 mo were assessed using a Seca stadiometer(1-mm precision). Weight was measured with a Seca babyscale (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 moand older than 25 mo, respectively.

A QUS device (Sunlight Omnisense 7000P, Sunlight Med-ical, Tel Aviv, Israel) was used for bone assessment (in vivovariation coefficient of 0.3-0.4% reported on the manufac-turers manual). Measurements were performed at the distalthird of the radius and midshaft tibia using a single type ofultrasonic probe. Measurements were done by 2 previouslystandardized operators (r5 0.94).

The participation of the children was obtained according toinstitutional 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 accrualassociated with CHD, each patient was matched witha healthy control subject based on age and gender. SOS differ-ences were then calculated, and the resulting mean valuebetween the 2 groups was assessed by conducting a t-test.Chi-square test and Students t-test were done to determinethe statistical differences in every variable. A linear regres-sion analysis adjusted for age, prematurity, and nutritionalstatus was made to find a relation between lower bone masslevels and CHD. All statistical analyses were made usingSPSS version 16.0 for Windows (SPSS Inc., Chicago, IL).

Results

Among the 181 eligible healthy patients and 145 childrenwith CHD, 106 (97.2%) and 75 (51.7%), respectively, agreedto participate in the study (May to September 2009). QUS wasperformed in 173 (99.4%) patients and 179 (96.1%) healthy sub-

jects at radius and tibia. Missing values in radius measurementwere due to positioning difficulties of the age group.

The CHD group comprised 44 females (58.7%), median agewas37.4 19 mo (median standard deviation [SD]),and av-erage birth weight was 2.920 0.520 kg (median SD); 6 ofthese children (9.4%) were premature (Table 1). There wasno 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(n5 46, 61.3%), followed by the CDPF group (n5 15, 20%).The most common CHDs were ventricular septal defect(n5 40, 53.3%), patent ductus arteriosus (n5 22, 29.3%), aor-tic stenosis (n5 13, 29.3%), and pulmonary stenosis (n5 10,13.3%).

Prevalence of malnutrition was higher in children withCHD compared with the healthy group (42.7% vs 2.8%,p! 0.001). A normal nutritional status was found in most

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of the children in both groups (CHD: n5 41, 54.7% andhealthy: n5 86, 81.1%).

SOS in radius was lower in the CHD group (3484 180m/s) than in healthy children (3575 159 m/s; 95% confidenceinterval: 39.8e143;p5 0.001). SOS in tibia was also lower inchildren with CHD, but the difference was not significant(p5 0.12), as shown in Fig. 1. SOS increased with age inboth groups of children.

Regardless of CHD, SOS differences were significant for ageand nutritional status. Malnourished children had lower SOSthan 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 mostaffected group is CIPF (p5 0.003). Differences in SOS valueswere not significant among females and males either for radiusor for tibia (p5 0.27 and 0.33, respectively) (Table 2).

A linear regression model adjusted for age, weight andheight at baseline assessment, type of CHD, and birth weightwas performed. According to this model, the correlation-adjusted association between CHD and reduced SOS at radius

was r25 0.455 (p! 0.001). No differences in SOS valueswere found in weight, height, and birth weight ( p5 0.814,0.861, and 0.090, respectively). Age and type of CHD showedstatistical significance for SOS values in radius ( p5 0.003and 0.010, respectively) (Table 3). SOS values were increas-ing according to age in all children.

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

mass determination using SOS attenuation values in bonesof young children with CHD compared with healthy matchedcontrols. This is a preliminary study.

We assessed bone mass using QUS, a device for bone tis-sue/structure assessment. QUS is very convenient for thiskind of population because it is portable and radiation free,making it safe for use in young children; earlier studieshave 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 SOSvalues.

Results show that radius SOS is lower in CHD group thanin healthy children. There are two ways by which bone masscan be affected in children with CHD. The first is through nu-tritional status. Studies have shown that malnutrition affectsbone development; nevertheless, it has been shown that ifadequate calories are provided, normal growth potentialmay be fulfilled (21). The second way is represented by he-modynamic and metabolic changes, which include hypoxiaand increased basal metabolic rate. Hypoxia leads to reduced

intestinal perfusion, resulting in intestinal malabsorption ofnutrients, 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

Table 1

Baseline Characteristics

Characteristics

Children withCHD, n5 75

(41.6%)Healthy children,n5 106 (58.4%) p

Sex

Male 31 (41.3) 52 (49.1)Female 44 (58.7) 54 (50.9) 0.304

PregnancyPreterm 6 (9.4) 13 (12.4)Term 58 (90.6) 92 (87.6) 0.374

Nutritional statusNormal 41 (54.7) 86 (81.1)Malnutrition 32 (42.7) 3 (2.8)Obese 2 (2.7) 17 (16) 0

Cardiac defectNone 105 (100)AIPF 46 (61.3)

ANPF 5 (6.7)CIPF 9 (12)CDPF 15 (20.0) 0

Mean (SD) Mean (SD)Birth weight (kg) 2.920 (0.520) 3.099 (0.429) 0.014Age (mo) 37.4 (19) 43.8 (16.6) 0.018

SOS (m/s)Radius 3484 (180) 3575 (159) 0.001Tibia 3468 (138.8) 3497 (117.7) 0.131

Abbr: CHD, congenital heart defect; AIPF, acyanotic with in-creased pulmonary flow; ANPF, acyanotic with normal pulmonaryflow; CIPF, cyanotic with increased pulmonary flow; CDPF, cyanotic

with decreased pulmonary flow; SD, standard deviation; SOS, speedof sound.

Fig. 1. SOS in radius and tibia per group. SOS, speed ofsound; CHD, congenital heart defect.

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and hypoxia, particularly the CIPF group; consequently, theycould 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 forage, 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 inthe regression model as they influence bone density. It is welldocumented that prematurity has an effect on bone status; in

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 childrenwith CHD were all considered surgically untreated, age atbaseline assessment could be considered as duration of thedisease; this was one of the most important predictors forbone status in the regression model analysis.

The model accounts for 45% of the variance of low SOSvalues. Specifically, age and type of CHD have more influ-ence on low SOS values (p5 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 untilpeak bone mass is reached during adolescence. SOS is nega-tively affected by the presence of CHD as shown in the linearregression model and when compared with healthy childrenusing Students t-test. In the analysis model, weight, height,and birth weight have no influence on SOS values. Sex wasnot included in the model because there are no sex differenceson 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 andadequate nutritional therapy (with a correct amount of nutri-ents important for bone development, such as calcium and

Table 2

Difference in SOS per Variable

Variable

SOS radius (m/s) SOS tibia (m/s)

n Mean (SD) p n Mean (SD) p

Sex

Male 78 3523 (177) 83 3495 (148)Female 95 3552 (169) 0.27 96 3476 (105) 0.333

PregnancyPreterm 18 3466 (212) 18 3458 (138)Term 143 3551 (164) 0.048 149 3488 (126) 0.363

Nutritional status 0.000 0.002Normal 124 3556 (164) 126 3501 (117)Malnutrition 31 3423 (184) 0.000 34 3416 (144) 0.001Obese 18 3617 (124) 0.311 19 3503 (124) 0.998

GroupHealthy children 105 3575 (159) 105 3497 (117.7)Children with CHD 68 3484 (180) 0.001 74 3468 (138.8) 0.131

Cardiac defect 0.002 0.194AIPF 42 3501 (172) 0.115 45 3461 (135) 0.493ANPF 5 3459 (131) 0.552 5 3542 (156) 0.939CIPF 9 3365 (216) 0.003 9 3419 (157) 0.389CDPF 12 3520 (178) 0.814 15 3494 (131) NS

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.

Table 3

Linear Regression Model

Variable

Unstandardized coefficients

pb Standard error

Age (mo) 6.201 2.062 0.003Weight at baseline (kg) 1.756 7.441 0.814Height at baseline (cm) 0.648 3.7 0.861Birth weight 37.874 22.218 0.090Type of CHD 25.124 9.662 0.010

Abbr: CHD, congenital heart defect.Radius is the dependent variable.




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vitamin D) as well as a timely palliative/corrective surgerymay 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, birthweight or gestational age data were not available on the med-ical records and/or family recalls. Although dual-energyX-ray absorptiometry measurement is the gold standard foradults, 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 analysisbecause 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 factorswe included in the study are reported to have an impact onbone accretion (age and prematurity), and their impact wasshown in the analysis. Further studies with a wider analysis

of clinical factors are needed to determine the mechanismsby which bone accretion may be altered.

Regarding tibia results, the sample size might have beentoo small to achieve statistical power. We selected QUS be-cause it is a noninvasive, portable, and radiation-free methodthat is safe for use in children.

In conclusion, in this preliminary study, we demonstratethat children with CHD have lower SOS values comparedwith healthy children, suggesting reduced bone quality re-gardless of nutritional status although malnutrition is presentin 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 previousstudies describing bone status using QUS in this group ofchildren were found. Further longitudinal studies are neededto assess bone health after a surgical procedure. Specialmedical 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 andadulthood.

Acknowledgments

Funding was received from the Science and TechnologyNational Council (CONACYT).

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