Failure to thrive and bone growth retardation in cyanotic and acyanotic congenital heart diseases with and without pulmonary hypertension

Abstract

Background: Growth retardation following malnutrition is prevalent among patients with congenital heart diseases (CHDs). This study was designed to evaluate failure to thrive (FTT) and delay in bone age in children with CHDs who were referred to our hospital and subsequently to determine their relation with cyanosis and the pulmonary artery pressure. Methods: We enrolled 120 consecutive patients who were referred to Rajaie Cardiovascular, Medical, and Research Center for cardiac catheterization or surgical correction. Growth parameters, comprising height (cm), weight (kg), and head circumference (cm), were measured by an experienced nurse. Bone age was evaluated by taking an anteroposterior wrist X-ray and reported by a radiologist, who was not aware of the exact cardiac diagnosis. The pulmonary artery pressure was measured during cardiac catheterization or surgical correction. Results: Bone growth retardation, FTT, short stature, and microcephaly were seen in 46.6%, 43.7%, 29.4%, and 5.1% of the patients, correspondingly. There was a significant relationship between the presence of cyanosis and delayed bone age, particularly when O2 saturation was less than 75% (P < 0.0001). The presence of pulmonary hypertension was significantly related to a higher rate of bone growth retardation (P < 0.0001). FTT and delayed bone age were significantly different between the cyanotic patients and the children with pulmonary hypertension and the acyanotic patients and those without pulmonary hypertension (P < 0.05). Conclusions: According to our results, delayed bone age and growth retardation are common findings in children with CHDs. The presence of cyanosis and/or pulmonary hypertension may further deteriorate these conditions and should be promptly managed.

Full text

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
35
Original Article
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
Failure to Thrive and Bone Growth Retardation in Cyanotic and
Acyanotic Congenital Heart Diseases With and Without Pulmonary
Hypertension
Maryam Moradian1, MD; Hamidreza Pouraliakbar1, MD;
Mohammad Mahdavi1*, MD; Behshid Ghadrdoost1, MS;
Zahra Faritous1, MD; Maryam Shojaei Fard2, MD
ABSTRACT
Background: Growth retardation following malnutrition is prevalent among patients with
congenital heart diseases (CHDs). This study was designed to evaluate failure to thrive
(FTT) and delay in bone age in children with CHDs who were referred to our hospital and
subsequently to determine their relation with cyanosis and the pulmonary artery pressure.
Methods: We enrolled 120 consecutive patients who were referred to Rajaie Cardiovascular,
Medical, and Research Center for cardiac catheterization or surgical correction. Growth
parameters, comprising height (cm), weight (kg), and head circumference (cm), were
measured by an experienced nurse. Bone age was evaluated by taking an anteroposterior
wrist X-ray and reported by a radiologist, who was not aware of the exact cardiac diagnosis.
The pulmonary artery pressure was measured during cardiac catheterization or surgical
correction.
Results: Bone growth retardation, FTT, short stature, and microcephaly were seen in 46.6%, 43.7%,
29.4%, and 5.1% of the patients, correspondingly. There was a significant relationship
between the presence of cyanosis and delayed bone age, particularly when O2 saturation was
less than 75% (P < 0.0001). The presence of pulmonary hypertension was significantly
related to a higher rate of bone growth retardation (P < 0.0001). FTT and delayed bone age
were significantly different between the cyanotic patients and the children with pulmonary
hypertension and the acyanotic patients and those without pulmonary hypertension
(P < 0.05).
Conclusions: According to our results, delayed bone age and growth retardation are common
findings in children with CHDs. The presence of cyanosis and/or pulmonary hypertension
may further deteriorate these conditions and should be promptly managed. (Iranian Heart
Journal 2017; 18(3):35-41)
Keywords: Congenital heart disease, Cyanosis, Failure to thrive, Pulmonary hypertension, Bone age
1 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, I.R. Iran
2 Echocardiography Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, I.R. Iran
*Corresponding Author: Mohammad Mahdavi, MD; Rajaie Cardiovascular, Medical, and Research Center, Mellat Park, Vali-Asr Avenue,
Tehran I.R. Iran.
E-mail: md_niaki@yahoo.com Tel: 02123922015
Received: April 30, 2017 Accepted: August 10, 2017

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
36
ongenital heart diseases (CHDs) like
any other chronic childhood illness
have widely heterogeneous effects on
patients. Among these effects, growth
retardation is one of the most significant.
Children afflicted by growth retardation are
prone to inadequate nutrition, which may lead
to severe malnutrition and even failure to
thrive (FTT). Different types of CHDs,
especially those associated with cyanosis
and/or pulmonary hypertension, may lead to
malnutrition and growth retardation. Even
some lesions such as left-to-right shunts,
vascular rings, and obstructive heart diseases
may give rise to growth retardation without
the accompanying pulmonary hypertension or
cyanosis. Three major causes of growth
failure in these children are decreased energy
intakes, malabsorption, and increased
metabolic demands. In addition, in developing
countries like Iran, poor knowledge of parents
about nutritional requirement of their children
and insufficient financial resources play
important roles in this issue. 1, 2, 3 Meanwhile,
some of these patients may also suffer from
the consequences of different syndromes like
Down, Turner, trisomy 18, trisomy 13, and
other genetic abnormalities. Consequently,
there are different factors contributing to
growth impairment in these children.
In general, congenital cardiac anomalies can
be classified into 2 major groups: cyanotic
and acyanotic. Cyanotic congenital heart
defects are classified based on their
pathophysiology into lesions with decreased
or increased pulmonary blood flows.
Acyanotic lesions encompass 2 large groups:
defects leading to volume overload (eg, left-
to-right shunts, atrioventricular valve
regurgitation, and some types of
cardiomyopathies) and those resulting in
pressure overload often due to ventricular
outflow tract obstruction (eg, aortic or
pulmonary valve stenosis) or stenosis of the
large arteries (eg, coarctation of the aorta). 3
The aims of the current study were to evaluate
FTT and delayed bone age in patients
suffering from CHDs and to compare the
effects of cyanosis and pulmonary
hypertension.
METHODS
Totally, 132 consecutive patients with a
diagnosis of CHDs who underwent cardiac
catheterization or surgical correction in Rajaie
Cardiovascular, Medical, and Research Center
from October 2012 to October 2015 were
studied. The exclusion criteria were
comprised of age less than 6 months, genetic
syndromes, and any kind of endocrinopathy
and neurologic diseases affecting growth.
Eight patients suffering from Down
syndrome, 3 patients with hypothyroidism,
and 1 patient with Williams syndrome were
excluded. CHDs in all the study population
were diagnosed by clinical, paraclinical, and
laboratory examinations such as chest X-ray,
electrocardiography, echocardiography, and
catheterization. Additionally, routine blood
tests (ie, hemoglobin and hematocrit, Na, K,
BUN, and creatinine levels as well as
complete blood count, blood group, and Rh),
urinalysis, and serologic screening for HBS
and HIV were done for all the patients.
Growth parameters, consisting of height (cm),
weight (kg), and head circumference (cm),
were measured accurately using conventional
methods and were plotted on standard growth
curves and compared with standard growth
charts (www.cdc.gov/nchs). The following
definitions were used:
1. Short stature: when the child’s height
is 2 or more standard deviations (SD)
below the mean standard growth curve
of normal children with the same age
and sex 4
2. Low birth weight: birth weight less
than 2500 g. 5 For these children,
specific charts are also available at
(http://static1.1.sqspcdn.com/static/f/2
C

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
37
4500/186746/1129059500317/LBW+
Premature+Boys.pdf?token).
3. Microcephaly: when the head
circumference is 2 or more SDs below
the mean standard curve of normal
children with the same age and sex 6
4. FTT: weight for age less than the fifth
percentile on standard growth charts
(Among the different definitions for
FTT, we used this definition because it
is more practical.) 7
5. Delayed bone age: skeletal age more
than 10% below chronological age
Anteroposterior wrist X-ray was evaluated to
determine bone age by an expert radiologist,
who was blinded to the patients’ age and
types of CHDs. In normal subjects, bone age
should be roughly within 10% of
chronological age (Fig. 1). A greater
difference is considered abnormal. 8
Figure 1. An example of the anteroposterior wrist
X-ray of a young baby.
The pulmonary artery pressure, systemic
blood pressure, and arterial oxygen saturation
were measured. The pulmonary artery
pressure was measured during cardiac
catheterization or surgical correction. If the
mean pulmonary artery pressure was above
25 mm Hg, it was regarded as pulmonary
hypertension 9 and if the pulmonary artery
pressure (mean and or systolic) was more than
67% of the systemic blood pressure (mean
and or systolic), it was considered as severe
pulmonary hypertension. 10
The present study was approved by our local
ethics committee and was conducted in
accordance with the Helsinki Declaration of
the World Medical Association (2000). The
parents or guardians of the children enrolled
gave written informed consent.
RESULTS
The baseline and angiographic data of the
study population are illustrated in Table 1.
The minimum age of the patients was 6
months and the maximum age was 180
months. From the 120 patients, 44 (37%) had
cyanotic CHDs and 35 (29.4%) pulmonary
hypertension. Thirty-five (29.4%) patients
had short stature, 21 (18.6%) low weight at
birth, and 18 (15.1%) microcephaly. Bone
growth retardation and FTT were observed in
56 (47.1%) and 52 (43.7%) patients,
correspondingly. During our study, 8 (6.7%)
patients underwent pulmonary artery banding,
9 (7.6%) underwent shunt surgery, and 14
(11.8%) had total correction surgery. All the
hemodynamic data were gathered during
catheterization or surgeries.
O2 saturation in the cyanotic patients varied
between 44% and 88% (mean = 76 ± 6). The
mean of the pulmonary artery pressure in the
patients with pulmonary hypertension was
47.5 ± 15 mm Hg (range = 30–100 mm Hg).
The relationship between growth status
factors and bone growth retardation is
demonstrated in Table 2. There were
significant differences in all the measured
factors, including FTT (P <0.0001), short
stature (P = 0.002), head circumference (P =
0. 01), and birth weight (P = 0.04) between
the patients with delayed bone age and those
with normal bone age; nonetheless, there was
no significant difference between them in
terms of sex (P = 0.23). The delay in bone age
was significantly more frequent in the patients
with cyanotic CHDs (P < 0.0001) and those
with pulmonary hypertension (P < 0.0001).

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
38
Comparisons regarding FTT, short stature,
and microcephaly between the patients with
cyanotic and acyanotic CHDs can be seen in
Table 3. FTT (P = 0.002) and short stature (P
= 0.006) were significantly more common
among the cyanotic patients, but there was no
significant difference between the 2 groups in
terms of head circumference (P = 0.31).
Comparisons between the patients with
pulmonary hypertension and those without it
vis-à-vis FTT, short stature, and microcephaly
are presented in Table 4. There were
significant differences between the 2 groups
in terms of FTT (P = 0.001), short stature (P
= 0.004), and microcephaly (P = 0.001).
Table1. Baseline and angiographic data in all the patients
Variables
Mean ± SD / N (%)
Age (mon)
61.54 ±52.01
Sex (male)
56(46.6%)
Height (cm)
102.02±29.49
Weight (kg)
17.7±12.71
Bone age (mon)
51.97±50.12
Birth weight (kg)
3.03±0.56
MPAP (mm Hg)
47.51±15.07
Short stature
35 (29.4%)
FTT
52(43.7%)
Bone growth retardation
56(47.1%)
Microcephaly
18 (15.1%)
Cyanosis
44(37%)
PH
35(29.4%)
Cyanosis with PH
8(18.6%)
MPAP, Mean pulmonary artery pressure; FTT, Failure to thrive; PH, Pulmonary hypertension
Table 2. Relationship between growth status factors and bone age retardation
Bone Growth
Retardation (n=56)
P
Sex male
66(55%)
0.23
female
54(45%)
Short stature +
26(74.3%)
0.002
-
30(43.4%)
FTT +
38(73%)
<0.0001
-
18(37.3%)
Microcephaly
14(77.7%)
0.01
Normocephaly
42(47.4%)
Low birth weight
Appropriate birth weight
15(71.4%)
41(47.8%)
0.04
Cyanosis with PH
22(58.3%)
0.007
without PH
14(29.2%)
Cyanosis O2 sat<75%
9(67%)
<0.0001
O2 sat>75%
15(50%)
Acyanosis with PH
12(81.5%)
<0.0001
without PH
17(29.2%)
FTT, Failure to thrive; PH, Pulmonary hypertension
Table 3. FTT, short stature, and microcephaly in the patients with cyanotic CHDs compared
with the patients with acyanotic CHDs
Cyanotic CHDs
(n=44)
Acyanotic CHDs
(n=76)
P
FTT
27(51.9%)
11(21.1%)
0.002
Short stature
14(40%)
5(14.2%)
0.006
Microcephaly
3(16.6%)
1(5.5%)
0.31
FTT, Failure to thrive; CHDs, Congenital heart diseases

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
39
Table 4. FTT, short stature, and microcephaly in the patients with PH compared with the
patients without PH
With PH (n=35)
Without PH (n=85)
P
FTT
31(59.6%)
11(21.1%)
0.001
Short stature
16(45.7%)
4(11.4%)
0.004
Microcephaly
6(33.3%)
1(5.5%)
0.001
FTT, Failure to thrive; PH, Pulmonary hypertension
DISCUSSION
Well-being of children is judged by their
growth. Any chronic disease, like CHDs, can
impair a child’s growth. We evaluated the
different parameters of growth such as
weight, height, head circumference, and bone
age in 120 Iranian children suffering from
CHDs and found that 43%, 29.4%, and 15.1%
of them suffered from FTT, short stature, and
microcephaly, respectively. The prevalence of
poor weight and height gain seems to be
slightly dissimilar in different studies. 11, 12, 13
It has been proven that the etiology of growth
failure in patients with CHDs is multifactorial
and genetic factors also have an important
role in this regard. Thus, the difference can be
attributed not only to inadequate energy
intake and more energy expenditure but also
to different genotypes of heterogeneous
groups of children from different parts of the
world, which calls for further in-depth
investigation. 14 Dalili et al 15 showed that
growth retardation was more prevalent among
the girls than the boys in their study. In our
study, FTT and short stature were more
prevalent in the cyanotic patients than in the
non-cyanotic ones (P = 0.002 and P = 0.006,
respectively). Previous studies have reported
the occurrence of acute or chronic
malnutrition in about 70% of pediatric
patients with cyanotic CHDs and/or
congestive heart failure. 16 Studies have
shown that retardation in weight and height is
more severe in cyanotic CHDs and growth
retardation is more significant in cyanotic
patients than in acyanotic ones. 17, 18
The prevalence rate of bone growth
retardation among our patients was 47.1%. In
our study, delayed bone age was more
common in the cyanotic patients whether or
not they had pulmonary hypertension. Also,
bone age retardation was significantly higher
in the patients with cyanotic CHDs without
pulmonary hypertension than in the patients
with acyanotic CHDs without pulmonary
hypertension (P = 0.007). In addition, if O2
saturation in the cyanotic patients was lower
than 75%, the prevalence of bone age
retardation was even higher (P = 0.000).
These findings also chime in with those
reported by other similar studies. 17-19
Among our acyanotic patients, the prevalence
of bone age retardation was significantly
higher in those suffering from pulmonary
hypertension (P = 0.000). El Batrawy et al 20
also reported the same results. We showed
that the prevalence of bone age retardation
was higher if the mean pulmonary artery
pressure was more than 40 mm Hg (P =
0.000).
Our results also demonstrated a meaningful
relation between bone age retardation and the
occurrence of FTT, short stature,
microcephaly, and low birth weight. Patients
with CHDs and cyanosis, pulmonary
hypertension, and congestive heart failure
appear to have an increased prevalence of
growth failure and malnutrition compared to
the normal population. 1-3-20 According to the
results of the present study, bone-age delay
and growth retardation are common findings
in children with CHDs. The presence of
cyanosis and/or pulmonary hypertension may
further deteriorate these conditions and should

 Iranian Heart Journal; 2017; 18 (3)
Failure to Thrive and Bone Growth Retardation in Congenital Heart Disease
Moradian M, et al
40
be promptly managed. 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 among cyanotic patients
with O2 saturation lower than 75%,
pulmonary hypertension patients with a mean
pulmonary artery pressure greater than 40 mm
Hg, and/or systolic pulmonary artery
pressure/systolic aortic pressure greater than
67%. Furthermore, our findings underline the
importance of the referral of patients with
CHDs and pulmonary hypertension for early
corrective surgery. It is vitally important that
children with CHDs and increased pulmonary
blood flows be placed under precise
surveillance in order to minimize the adverse
effects of malnutrition and the harmful results
of hypoxia and pulmonary hypertension on
their growth and bone maturation.
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