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Circulation
Journal
Ocial
Journal
of
the
Japanese
Circulation
Society
http://www.j-circ.or.jp
gain rather than birth size seems to affect both blood pressure
and common carotid intima-media thickness (cIMT) in young
adults.9–11
Editorial p ????
Increased vascular IMT has been demonstrated in SGA aged
3–6 years,12 irrespective of the presence or absence of prenatal
risk factors for intrauterine growth restriction.13
Furthermore, early endothelial dysfunction has been dem-
onstrated in young adults born with low birth weight, particu-
larly in those who did not have other CV risk factors.14
These ndings support the hypothesis that the CV altera-
tions in children born SGA are due to fetal CV reprogramming
rather than to prenatal and postnatal risk factors. Therefore,
mall for gestational age (SGA) is a condition that affects
approximately 3–10% of newborns whose birth weight
and/or length are at least 2 SD below the mean for ges-
tational age.1 Most SGA children have catch-up growth during
the rst 2–4 years of life, but approximately 15% of them
continue to be short throughout childhood, adolescence and
adulthood.2 Children born SGA have an increased risk of devel-
oping permanent metabolic changes as a consequence of intra-
uterine reprogramming, which lead to increased cardiovascular
(CV) risk, excess abdominal fat and type 2 diabetes in adult-
hood.3,4 Additionally, low birth weight combined with rapid
postnatal growth appears to be associated with impaired glu-
cose tolerance,5 obesity5 and non-alcoholic fatty liver disease,6,7
whereas rapid growth after 2 years of age may increase the
risk for CV disease (CVD).8 In particular, childhood weight
S
Received September 29, 2015; revised manuscript received January 10, 2016; accepted January 12, 2016; released online February 10,
2016 Time for primary review: 21 days
Department of Biomedical Sciences and Human Oncology, Section of Pediatrics (M.F.F., M.D., F.D.P., A.N., P.G., L.C.), Department of
Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology (G.B.), Cardiovascular
Diseases Section, Department of Emergency and Organ Transplantation (A.Z., F.C., M.G., G.R., S.C., M.M.C.), University “A. Moro”,
Bari; Department of Pediatric Cardiology, Giovanni XXIII Pediatric Hospital, Bari (E.M.); and Cardiology Unit, Hospital “F. Perinei”,
Bari (P.S.), Italy
Mailing address: Maria Felicia Faienza, MD, Department of Biomedical Science and Human Oncology, Section of Pediatrics, University
“Aldo Moro” Bari, Piazza G. Cesare, 11, 70124 Bari, Italy. E-mail mariafelicia.faienza@uniba.it
ISSN-1346-9843 doi: 10.1253/circj.CJ-15-1038
All rights are reserved to the Japanese Circulation Society. For permissions, please e-mail: cj@j-circ.or.jp
Vascular Function and Myocardial Performance Indices in
Children Born Small for Gestational Age
Maria Felicia Faienza, MD; Giacomina Brunetti, PhD; Maurizio Delvecchio, MD, PhD;
Annapaola Zito, MD; Fabrizia De Palma, MD; Francesca Cortese, MD; Adriana Nitti, MD;
Elena Massari, MD; Michele Gesualdo, MD; Gabriella Ricci, MD; Santa Carbonara, MD;
Paola Giordano, MD; Luciano Cavallo, MD; Pietro Scicchitano, MD; Marco Matteo Ciccone, MD
Background: Small-for-gestational-age (SGA) children have increased cardiovascular risk, but the mediating fac-
tors are poorly understood. We hypothesized that birth size could affect the cardiovascular system since childhood
in the absence of other risk factors. We investigated endothelial and myocardial function in SGA children with regu-
lar catch-up growth.
Methods and Results: Biochemical markers, blood pressure, flow-mediated vasodilation (FMD), common carotid
intima-media thickness (cIMT), anteroposterior diameter of the infrarenal abdominal aorta (APAO) and echocardio-
graphic parameters of left and right ventricular (LV and RV) function were studied in 27 SGA and 25 appropriate-for-
gestational-age (AGA) subjects. SGA subjects had a higher homeostasis model assessment index than controls
(2.61±1.27 vs. 1.56±0.40, P=0.01), higher cIMT (0.51±0.04 mm vs. 0.45±0.07 mm, P=0.007) and APAO (1.31±1.35 cm
vs. 1.30±0.16 cm, P=0.005), and lower FMD (10.11±4.17% vs. 12.34±4.28, P=0.04) than controls. On echocardiog-
raphy SGA had higher Tei index both at LV and RV than controls (P=0.001). Reduced RV systolic function was also
observed in SGA subjects.
Conclusions: SGA subjects had vascular morphological and function abnormalities compared with AGA, which
increase their cardiovascular risk profile. Furthermore, a subtle cardiac alteration in both RV and LV functions was
seen in SGA patients compared with AGA.
Key Words: Anteroposterior diameter; Carotid intima-media thickness; Flow-mediated vasodilation; Infrarenal
abdominal aorta; Small for gestational age
Advance Publication by-J-STAGE
FAIENZA MF et al.
lipoprotein cholesterol (HDL-C) and low-density lipoprotein
cholesterol (LDL-C), and triglycerides (TG) were measured
after overnight fasting in all subjects.
TC, LDL-C, HDL-C and TG within the 5th and the 95th
percentiles were dened as normal.24 Insulin resistance (IR)
was measured using the homeostasis model assessment
(HOMA) index, calculated as insulin (μU/ml)×blood glucose
(mmol/L)/22.5.25 IR was dened as HOMA-IR >2.5.25
Ultrasonography
SGA children and controls underwent high-denition vascular
and cardiac ultrasound assessment according to the following
protocols in order to identify arteries with early atherosclerotic
lesions and/or early signs of cardiac function impairment.
cIMT Ultrasonographic echo-color Doppler study of left
and right common carotid arteries was performed bilaterally
by the same physician with a Philips Sonos 5500 using a 7.5-
MHz high-resolution probe. The patients were placed in the
supine position, with the neck extended and rotated contralat-
erally by 45°, and the common carotid arteries were examined
on the sagittal axis in lateral view. cIMT was dened as a
low-level echo gray band not projecting into the arterial lumen,
and was measured during end-diastole according to the method
described by Pignoli et al.26 The measurements were performed
bilaterally 1 cm proximally to the carotid bulb, 3 times, and
then mean cIMT was calculated.27,28 Intra-observer variability
was good (intraclass correlation coefcient [ICC]=0.99; good
if >0.80).29
FMD of the Brachial Artery All the patients were fasted
(including avoidance of stimulants such as coffee/tea, choco-
late) and physical exercise free for at least 8–12 h before the
examination in order to avoid negative inuences on test results.
The tests were carried out in a quiet air conditioned room
(22–24°C), early in the morning. We performed a preliminary
scan in order to explore the anatomy and identify landmarks.
The scan was done at the right brachial artery on long-axis
projection between 5 and 10 cm above the elbow using a ≥7.0-
MHz linear probe. The study was performed using a high-
resolution ultrasonograph (Philips Sonos 5500) connected to
an image analysis system, certied by the National Research
Council of Pisa (MVE II), for computing the brachial artery
diameter in real-time by analyzing B-mode ultrasound images.30
All the ultrasound examinations were performed by the same
physician in order to reduce observer bias. With the subject in
a supine position for at least 10 min, the arm was positioned
comfortably in order to identify the humeral artery. A sphyg-
momanometer cuff was placed distally to the artery. After 1 min
of ow image baseline acquisition, the artery was occluded by
inating the cuff to a pressure of 200–220 mmHg for exactly
5 min. After deation, the following increased shear stress
provides the stimulus for the dilatation of the humeral artery.
Within 15 s from the end of ischemia, the ow rate was mea-
sured and then the degree of hyperemia. The image of the
artery was then recorded continuously for 2–3 min after isch-
emia. Reactive hyperemia was calculated as the ratio of the
change in diameter (maximum dilatation after deation-base-
line) divided by the baseline, which corresponds to maximum
FMD recovery. FMD was analyzed as the percentage increase
in brachial artery diameter after the application of a pressure
stimulus.28,31 Intra-observer variability was good (ICC=0.93).
APAO To improve the image acquisition, subjects were
asked to keep fasting for at least 8–12 h and to follow a ber
diet for the 2 days prior to the examination to reduce intestinal
bloating (diet preparation). Ultrasonography of the infra-renal
abdominal aorta was performed by a single operator using a
subjects born SGA could develop early impairment in vascu-
lar morphology and function. One more interesting question
is whether SGA children are at increased risk for myocardial
function alterations, a subtle cardiomyopathy whose future
evolution is still unknown. The literature contains contrasting
results: some authors reported altered cardiac performance in
SGA individuals as compared with subjects born appropriate
for gestational age (AGA),15–17 while others found no inu-
ence of low birth length and/or weight on future development
of early cardiac dysfunction.18,19
We hypothesized that birth size could affect the CV system
since childhood in the absence of other risk factors. We there-
fore investigated endothelial and myocardial function by
evaluating cIMT, ow-mediated dilatation (FMD) of brachial
artery, anteroposterior diameter of infra-renal abdominal aorta
(APAO) and echocardiographic tissue Doppler imaging (TDI)
markers in a group of children born SGA with regular catch-
up growth within the rst year of life.
Methods
Patients
Twenty-seven children (15 male; mean age, 10.03±3.0 years)
out of 30 meeting the inclusion criteria agreed to participate to
this study. All children were born at term at the Neonatology
Unit at University “Aldo Moro” Bari, Italy, and were classi-
ed as SGA (birth weight and/or length <3rd percentile for
gestational age).20 In particular, 11 subjects were SGA for
weight, 13 for weight and length and the remaining 3 only for
length. They were followed up for the rst 4 years of life at the
Pediatric Endocrinology Unit according to established follow-
up in SGA subjects. Between January and September 2014,
they were invited by telephone to participate in the study. All
subjects had weight gain equally distributed in the rst 6
months of life and continued to have regular growth during the
rst year of life. Catch-up growth was dened as attainment
of height centile within the midparental height range.21
Medical and family history was obtained from all subjects.
Exclusion criteria were renal, liver and/or CVD, hypertension,
metabolic and/or endocrine disorders, genetic syndromes, his-
tory of chronic allergy, and acute infectious or inammatory
disease during the 3 months preceding the study. Physical
examination, including anthropometric parameters (height,
weight, body mass index-standard deviation score; BMI-SDS)
using Italian growth charts,22 and assessment of pubertal stage
according to Tanner criteria were performed.23 Both systolic
blood pressure (SBP) and diastolic blood pressure (DBP) were
measured in all patients from the right brachial artery using a
mercury gauge in the supine position prior to examination
after resting for a minimum of 5 min.
The control group consisted of 25 healthy children born at
term and AGA (birth weight >−2 SDS and <+2 SDS), matched
for age, gender and BMI-SDS. The control group was recruited
on a voluntary basis in the outpatient clinic and consisted of
children referred to hospital for minor surgery or electrocardi-
ography for minor trauma to head, limbs, or chest pain All
subjects were in good general health and were not taking drugs
in the last 3 months.
Written informed consent was obtained from the children’s
parents. All procedures were in accordance with the guidelines
of the Helsinki Declaration on Human Experimentation and
were approved by the local ethics committee.
Biochemistry
Blood glucose, insulin, total cholesterol (TC), high-density
Advance Publication by-J-STAGE
CV Function in Children Born SGA
ity: ICC=0.87.
Statistical Analysis
For statistical analysis, SPSS for Windows, version 22.0 (SPSS,
Chicago, IL, USA) were used. Results are given as mean ± SD.
The Kolmogorov-Smirnov test was applied to test normality
of distribution. In parameters with normal distribution, means
were compared using unpaired Student t-test, whereas linear
correlations were calculated using Pearson’s correlation coef-
cient; in parameters with skewed distribution, signicance
was assessed with the Mann-Whitney test and Spearman’s
correlation coefcient, respectively. Finally, multiple regres-
sion analysis was used to determine the relative strength of
each biochemical and clinical variable in predicting CV param-
eters. The limit of statistical signicance was set at 0.05.
Results
Baseline clinical characteristics, biochemical markers of glu-
cidic and lipid metabolism, and HOMA-IR index are listed in
Table 1. No signicant differences were found between SGA
children and controls according to age, sex, pubertal stage,
weight, height, BMI-SDS, SPB and DBP. Blood glucose level
was normal in all examined subjects, but HOMA-IR was sig-
nicantly higher in SGA children compared with controls
(2.61±1.27 vs. 1.56±0.40, P=0.01). No statistically signicant
differences for TC, HDL-C and LDL-C, and TG were seen
between SGA children and controls. We did not observe any
differences between SGA groups according to metabolic and
cardiovascular risk parameters.
Vascular Assessment
c-IMT, FMD and APAO are listed in Table 2. Mean cIMT
was signicantly higher in SGA children than controls (0.51±
0.04 mm vs. 0.45±0.07 mm, P=0.007). Furthermore, SGA sub-
jects had statistically signicantly worsened endothelial func-
tion as compared with healthy controls (10.11±4.17% vs.
single high-resolution vascular ultrasound Philips 5500 equipped
with a 3-MHz electronic probe. With the patient in a supine
position, the electronic probe was placed 1 cm left of the umbi-
licus. The best image in long-axis projection of the abdominal
aorta was then obtained. APAO was dened as the maximum
external cross-sectional measurement.30 It was calculated as
the distance between the near and the far walls of the abdom-
inal aorta. Measurements were performed 2 cm above and
distal to the umbilicus and expressed in centimeters.30 Intra-
observer variability was good (ICC=0.97).
M-Mode, B-Mode Echocardiography and TDI
All patients underwent echocardiography of both the left and
right chambers, in agreement with international guidelines.32
Pulsed-wave TDI was used in order to evaluate the velocity of
the ventricle walls and the related parameters of systolic and
diastolic function of both the left and right ventricles (LV and
RV).33 TDI information is less load dependent than standard
Doppler.34 On apical 4-chamber projection, the cardiac struc-
tures examined were the mitral valve annulus, both lateral and
medial, the basal and mid part of the LV lateral wall and
interventricular septum, the basal part of the RV lateral wall
and the lateral tricuspid annulus.35 We considered as main
parameters: systolic velocity (S’); early diastolic velocity (E’);
and late diastolic velocity (A’). We calculated E’/Avfor all the
anatomic territories considered and E/E’ at the lateral and
medial parts of the mitral annulus. Systolic and diastolic time
parameters related to both the RV and LV were measured
throughout the entire cardiac cycle:33–36 for the LV, isovolu-
metric contraction time (l-IVCT), ejection time (l-ET), iso-
volumetric relaxation time (l-IVRT) were used to obtain the
LV Tei index [(l-IVRT+l-IVCT)/l-ET]; and for the RV, iso-
volumetric contraction time (r-IVCT), ejection time (r-ET),
and isovolumetric relaxation time (r-IVRT) were used to obtain
the RV Tei index [(r-IVRT+r-IVCT)/r-ET].
In order to evaluate the reproducibility of the echocardio-
graphic evaluations, we calculated the intra-observer variabil-
Table 1. Clinical and Biochemistry Characteristics
SGA Controls P-value
Subjects (n) 27 25 –
Age (years) 10.03±3.0
10.41±3.9
0.17
Gender (M/F) 15/12 13/12 0.25
Tanner (I/II) 15/12 12/13 0.33
Birth weight (kg) 2.268±0.4
3.25±0.37 0.0001
Birth length (cm) 45.9±3.6
49.71±3.81
0.01
Weight-SDS 0.23±1.05 0.22±0.67 0.40
Height-SDS 0.34±0.91 0.31±0.74 0.21
BMI-SDS 0.09±1.23 0.1±0.64 0.32
SBP (mmHg) 103.65±2.28
107±2.54 0.51
DBP (mmHg) 63.26±6.29
64.04±3.39
0.33
Glucose (mg/dl) 85±12 81.16±8.14
0.20
Insulin (μU/ml) 12.15±5.25
9.74±4.59 0.27
HOMA-IR 2.61±1.27 (1.01–5.27) 1.56±0.40 (0.96–2.00) 0.01
Triglycerides (mg/dl) 73±44 57.24±19.16 0.46
TC (mg/dl) 165±31
144.8±28.32 0.20
HDL-C (mg/dl) 55±9
58.67±9.30
0.252
LDL-C (mg/dl) 83.4±23.5 78.10±21.03 0.39
Data given as mean ± SD (range). BMI, body mass index; DBP, diastolic blood pressure; HDL-C, high-density lipoprotein
cholesterol; HOMA, homeostasis model assessment; IR, insulin resistance; LDL-C, low-density lipoprotein cholesterol;
SBP, systolic blood pressure; SDS, standard deviation score; SGA, small for gestational age; TC, total cholesterol.
Advance Publication by-J-STAGE
FAIENZA MF et al.
TAPSE.
It is well established that the atherosclerotic process starts
in childhood and proceeds silently over a long period of time
before clinical manifestations.37 SGA is associated with the
risk of atherosclerosis,38,39 probably due to the increase of risk
factors for the development of metabolic syndrome, particu-
larly in SGA subjects with spontaneous catch-up growth.40
The present SGA subjects had statistically signicantly higher
HOMA-IR compared with the AGA subjects, indicating an
insulin-resistant condition that is well known to induce accel-
eration of the systemic atherosclerotic process.30 The present
SGA subjects had reduced FMD. In our previous study such
endothelial dysfunction in SGA patients was found to be
related to a dysfunction in endothelial progenitor cells result-
ing in reduced proliferation and migration of such cells.41 Such
a condition might be triggered by an anti-angiogenic state
enhanced by the low birth weight via alteration of the vascular
endothelial growth factor pathway.41 Unfortunately, this expla-
nation of endothelial dysfunction in the present subjects is an
hypothesis only, because we did not evaluate endothelial pro-
genitor cells.
The role of birth weight on endothelial vasodilatation was
also supported by Touwslager et al,42 who demonstrated that
the vessels’ dilatation after acetylcholine use was related to
anthropometric parameters of the newborns such as birth weight,
length and head circumference. Therefore, SGA patients could
effectively be characterized by early signs of systemic athero-
sclerosis represented by altered endothelial function.
Furthermore, the morphology of the vessels could also be
impaired in SGA subjects as compared with healthy controls.
We observed marked alterations in cIMT and APAO in the
present SGA subjects. These results are in line with those of
Stergiotou et al, who noted increased carotid and aortic IMT
in SGA subjects, even after adjusting for neonatal weight and
vessel diameter.13 Furthermore, low birth weight has been
associated with increased cIMT in young adults who had
severe fetal growth restriction and in those who had exagger-
ated postnatal growth.43 Martyn et al calculated a 5.3-fold
increased risk of carotid stenosis and a 2.3-fold increased
incidence of atherosclerotic disease in the lower limbs in
patients with the lowest birth weight.44 The present data seem
to conrm such a trend in SGA subjects. Such a condition is
very dangerous because these data are strongly associated with
cardiac disease. As outlined by Vågerö and Leon, low birth
weight could increase the risk for ischemic heart disease, and
such a condition may be triggered by early onset of atheroscle-
12.34±4.28%, P=0.04). There was also a statistically signi-
cant increase in APAO in SGA patients compared with con-
trols (1.31±1.35 cm vs. 1.30±0.16 cm, P=0.005).
Mean cIMT was positively related to age (r=0.367, P=0.05),
while FMD was inversely correlated with age (r=−0.660,
P=0.0003), and TC (r=−0.231, P=0.001).
Echocardiography
Interesting insights came from the echocardiographic evalua-
tion of both RV and LV function. SGA subjects had increased
left Tei index (0.41±0.07 vs. 0.24±0.20, P=0.001) and right
Tei index (0.41±0.09 vs. 0.16±0.10, P=0.001) compared with
healthy controls (Table 2). Furthermore, even indirect mark-
ers of systolic RV function (ie, tricuspid annular plane systolic
excursion [TAPSE]) were reduced in SGA subjects as
compared with controls (21.54±4.75 mm vs. 27.03±1.89 mm,
P=0.002). We also observed an increase in both left (2.14±0.47
vs. 1.50±0.89, P=0.001) and right (1.94±1.83 vs. 1.33±0.10,
P=0.001) E/A for the 2 groups (Table 2). SGA subjects had
higher LV ejection fraction (LVEF) as compared with AGA
subjects (62.55±6.29% vs. 59.62±0.10% P=0.001). As regards
the inuence of birth weight, we found a negative correlation
with LVEF (r=−0.320, P<0.0001) and RV Tei index (r=−0.230,
P<0.0001).
Multiple Regression Analysis
In SGA subjects, cIMT was signicantly inuenced by HOMA-
IR (β=0.159) and LDL-C (β=0.294; r=0.359, P=0.0001), while
left E/A was negatively inuenced by HOMA-IR (β=−0.333)
and positively by HDL-C (β=0.360; r=0.480, P=0.0001), on
multiple regression analysis. Multiple regression analysis also
showed that metabolic parameters did not inuence APAO
and TAPSE.
Discussion
The present study has shown that SGA subjects have an early,
subtle impairment of the CV system, the implications of which
for overall growth and outcomes are still unknown.
Vascular and echocardiographic comparisons of SGA and
AGA controls identied the following: (1) morphological
alterations in the systemic arterial vessels in SGA subjects, as
reected by increased cIMT and APAO; (2) reduced endothe-
lial function in SGA subjects; and (3) right and left cardiac
chamber alterations in both systolic and diastolic function in
SGA subjects, as reected by left and right Tei index and/or
Table 2. Vascular and Echocardiographic Parameters
Ultrasound parameters SGA Controls P-value
Mean cIMT (mm) 0.51±0.04 0.45±0.07 0.007
FMD (%) 10.11±4.17
12.34±4.28
0.04
APAO (cm) 1.31±1.35 1.30±0.16 0.005
TAPSE (mm) 21.54±4.75
27.03±1.89
0.002
LVEF (%) 62.55±6.29
59.62±0.10
0.001
LV Tei index 0.41±0.07 0.24±0.20 0.001
RV Tei index 0.41±0.09 0.16±0.10 0.001
Left E/A ratio 2.14±0.47 1.50±0.89 0.001
Right E/A ratio 1.94±1.83 1.33±0.10 0.001
E/e’ ratio 8.10±1.59 11.91±0.89
0.001
Data given as mean ± SD. APAO, anteroposterior diameter of the infrarenal abdominal aorta diameter; cIMT, carotid
intima-media thickness; FMD, flow-mediated dilatation; LV, left ventricular; LVEF, LV ejection fraction; RV, right
ventricular; SGA, small for gestational age; TAPSE, tricuspid annular plane systolic excursion.
Advance Publication by-J-STAGE
CV Function in Children Born SGA
patients had an LV function (62.55±6.29%) higher than their
counterpart (59.62±0.10%, P<0.001). Although LVEF was
within the normal range (ie, higher than 55%) in both groups,
the meaning of this statistically signicant difference is still a
matter of debate. Further studies are needed in order to clarify
the underlying mechanisms of subtle cardiac performance
imbalance in SGA patients, although linked to improved LVEF.
Conclusions
SGA subjects have subtle cardiac and vascular impairment
compared with healthy AGA controls. The implications of
such alterations for the immediate CV future of such individu-
als are still unknown. Long-term follow-up is necessary in
order to evaluate the effects of these alterations on morbidity
and mortality.
Conict of Interest
The authors declare no conicts of interest.
Funding Source
None.
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The association between morphological and function alter-
ations of systemic arterial vessels and the function alterations
of both cardiac chambers is well-established. Bekkers et al
observed that increased abdominal aorta diameter is directly
related to increased ascending aorta diameter, larger LV dimen-
sions, higher LV mass index, and lower LVEF.46 The same
relationships were noted between endothelial function and
myocardial performance indices. Akgul et al found that TDI
determines LV performance changes in acromegaly, as well
as endothelial dysfunction assessed using FMD.47 Other stud-
ies noted the relationship between alteration in vascular endo-
thelial function and myocardial performance indices.48,49 Such
correlations have also been observed in pediatric patients,50
although the present study is the rst to investigate all these
vascular and cardiac function indices in SGA patients.
One of the most interesting research elds emerging with
regard to the clinical background of SGA is related to the pos-
sible alterations of cardiac performance. The literature is
undecided with regard to such matters, although the majority
of studies support the present data. Most of the data relate to
the neonatal period but they do not include follow-up.18,51,52
Signicant variations were observed in myocardial perfor-
mance indices of both RV and LV within the rst month after
delivery in very low-birth-weight infants.52
It is possible that the reduced anthropometric characteristics
of SGA subjects may impair the development of cardiomyo-
cytes and the intracellular molecular signaling useful for the
regulation of cardiac cell proliferation, apoptosis and nal
differentiation.53 Moreover, subjects with very low birth weight
for gestational age have a 2.0-fold risk increase in myocardial
infarction occurrence, especially if combined with increase in
body weight in adulthood (increasing the risk to 10.8-fold).54
The present data indicate that there is reduced performance
of myocardial bers in SGA patients as compared with AGA.
We found that both right and left Tei indices were higher in
SGA as compared with AGA; that is, it seems that the SGA
patients had reduced performance of both RV and LV in term
of systolic and diastolic function. The nding that SGA patients
express higher troponin I in umbilical cord blood as compared
with AGA55 supports the hypothesis of original damage to
cardiomyocytes, the impact of which on future cardiac perfor-
mance is still unknown. Nevertheless, in the present study the
subtle alteration in cardiomyocytes was reected by TAPSE:
this indirect marker of RV systolic function was reduced in
SGA patients compared with controls. Although the values
were all in the normal range for age and sex, the statistically
signicant difference could be considered a marker of future
negative evolution of cardiac performance.
The most important echocardiography nding is that SGA
patients had a more favorable diastolic lling pattern (elevated
E/A, reduced E/e’) compared with controls, but they also had
impaired overall myocardial function as assessed on Tei index.
The great increase in SGA E/A ratio could be considered a
predisposing factor for reduced ventricle compliance rather
than an amelioration of it. We considered it as a pseudonor-
malization pattern of the ventricle diastolic pattern. Neverthe-
less, E/e ratio appears to contradict such a hypothesis, although
the diastolic alteration is corroborated by the increased Tei
index. There may be a subtle ber impairment in SGA patients
that could alter TDI measurements, and speckle tracking may
be more useful in such cases. Nevertheless, the nding of bet-
ter LVEF in SGA patients compared with healthy controls is
in contrast to the supposed impairment in cardiac performance
in the former compared with controls. The present SGA
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