Indian Pediatr 2019;56:314-316|
Hypertrophy in Appropriate for Gestational Age Infants Born to
Ma Martha Vela-Huerta1,
Helena Victoria Orozco Villagomez1,
Antonio Heredia Ruiz3
and Juan Manuel Guizar-Mendoza2
From Departments of 1Neonatology and
3Cardiology, Hospital General de Leon; and 2Department
of Research, University De La Salle Bajio; Leon: Mexico.
Correspondence to: Dr Norma Amador Licona, University
De La Salle Bajio. Department of Research, Av Universidad 602, Col Lomas
del Campestre, ZC 37150, Leon, Gto, Mexico.
Received: July 20, 2017;
Initial review: November 15, 2017;
Accepted: January 24, 2019.
Objective: To compare the frequency of asymmetric
septal hypertrophy in appropriate for gestational age infants born to
diabetic mothers with those born to non-diabetic mothers. Methods:
We compared 38 full term infants born to diabetic mothers with 85 full
term infants of non-diabetic mothers. 2-D echocardiography was obtained
in the first 24 hours after birth. Results: Asymmetric septal
hypertrophy was only present in infants born to diabetic mothers (50%
vs. 0%; P<0.001). Intraventricular septum thickness and
intraventricular septum/posterior wall of the left ventricle ratio was
also significantly higher in the first group (P<0.001). We found
no correlation between mother´s glycated hemoglobin levels and
intraventricular septum thickness in newborns. Conclusions:
Asymmetric septal hypertrophy is a common finding in infants born to
diabetic mothers, even if they are appropriate for gestational age.
Keywords: Cardiac abnormality, Echocardiography, Glycated
n spite of advances in perinatal medicine,
infants of diabetic mothers (IDM) continue to show increase
morbidity and mortality .
Asymmetric septal hypertrophy (ASH) is a well-recognized
cardiac functional abnormality in IDM. This term describes the special
feature of the interventricular septum thickness >6 mm and septal/posterior
wall thickness ratio >1.3 [2-4]. Its etiology is not clear, but
endogenous catecholamines, insulin, and other growth factors have been
involved , and its evolution is usually benign [2-4].
However, some cases of ASH and severe hypertrophic
cardiomyopathy have been reported in spite of appropriate prenatal
glucose control [5,6]. In Mexican macrosomic infants born to diabetic or
non-diabetic mothers, ASH has been identified in 38.8% and 7.1%,
respectively, though appropriate for gestational age (AGA) infants were
not evaluated . The aim of this study was to compare the frequency of
ASH in AGA infants born to diabetic with non-diabetic mothers.
An analytical cross-sectional study was carried out
in General Hospital in Leon, Mexico from July 2015 to March 2016.
Thirty-eight AGA babies of diabetic mothers and 85 AGA babies of
non-diabetic mothers were compared. The study included singleton fetuses
without malformations and other diseases that could interfere with the
fetal development. AGA infants were considered according to intrauterine
growth curves as gestational age between 37-41.6 weeks and birthweight
between 10-90 percentiles . Neonates of diabetic mothers (IDM) were
hospitalized and managed according to the recommendations of the STABLE
program . Neonates of mothers without diabetes mellitus (INDM)
correspond to a historical group reported in a previous publication .
Cardiac structures and function parameters were
evaluated by two-dimensional pulsed Doppler M echocardiogram using a
Phillips HD11XE transducer S8-3, within the first 24 hours of
extrauterine life by a single experienced pediatric cardiologist, who
was blinded to the mother´s glycemic control. Intraventricular Septum
(IVS), Intraventricular Septum/Posterior Wall of the Left Ventricle
(IVS/PWLV) index, Ejection Fraction of the Left Ventricle (EFLV),
Diastolic Diameter of the Left Ventricle (DDLV), Transmitral Doppler
(TMD), Transtricuspid Doppler (TTD) and Transaortic Doppler (AoD) were
Diabetes mellitus was classified according to the ADA
criteria , and good
metabolic control was considered in case of glycosylated hemoglobin
(HbA1C) levels <6% .
Signed consent was obtained from mothers to allow clinical chart review
and ongoing echocardiographic evaluation. The study was approved by the
local ethics committee.
Statistical analysis: The fitness to the normal
distribution was determined using the Kolmogorov-Smirnov test.
Differences between AGA IDMs or INDMs were tested using the unpaired
Student’s t-test or the Mann-Whitney U-test when data showed significant
departure from normality. The correlation between HbA1C and
echocardiographic parameters was evaluated by Pearson´s correlation
No difference in sex, birthweight, gestational age or
mode of delivery was found between IDM and INDM groups (Table
I). ASH was found in 50% of the patients in the group of IDMs, and
in none of the INDMs (P<0.0001).
TABLE I Baseline Charaterstics of Appropriate for Gestational Age Infants Born to Diabetic and Non-diabetic Mothers
Gestational age (wk)
IDM: Infants born to Diabetic Mothers; INDM: Infants born to
Non-diabetic Mothers; All P>0.05.
Gestational diabetes mellitus was the most frequent
type of diabetes 28 (73.7%), followed by type 2 DM, 9 (23.7%). ASH was
found in 15 (54%) and 4 (44.4%) infants born to mothers with gestational
diabetes and type 2 diabetes, respectively without difference (P=0.60)
IVS/PWLV, EFLV, DDLV and AoD were higher in IDMs than
in INDMs, while TMD and TTD were lower (Table II). IVS did
not show any relationship with HbA1C
(r=0.02; P=0.87). ASH was not different in
newborns born to mothers with HbA1C
>6% vs. Ł6%
(60.5% vs. 39.5%; P=0.08), respectively.
TABLE II Echocardiographic Measurements in AGA Babies of Diabetic and Non-Diabetic Mothers
IVS: Intraventricular Septum; bIVS/PWLV: Intraventricular
Septum/Posterior Wall of the Left Ventricle; cEFLV: Ejection
Fraction of the Left Ventricle; DDLV: Diastolic Diameter of the
Left Ventricle; TMD: Transmitral Doppler; TTD: Transtricuspid
Doppler; AoD: Transaortic Doppler; Data are showed as mean (SD);
*P<0.001; #P=0.001; $P>0.05.
Three infants (7.9%) in the IDM group were detected
with patent ductus arteriosus without any hemodynamic repercussions and
hypoglycemia was detected in two patients (5.2%).
This study showed high ASH frequency in AGA IDMs. The
IVS/PWLV index, DDLV and AoD were higher in infants with than in infants
without ASH, while the EFLV was not different between groups. On the
other hand, the TMD and TTD values were lower in IDMs than in INDMs.
ASH frequency in this study could be related to the
poor metabolic control or just the interval of the disease prevalence.
However, a limitation of the study is the
convenience sampling and the historical control group. Furthermore,
insulin levels were not measured either in the
newborn or amniotic fluid, and some grade of hyperinsulinemia could
still maintain glucose and glycosylated hemoglobin in control limits
without general fetal macrosomia induction. It has been reported that
adequate metabolic control especially in the third trimester, decreases
ASH [11,12]. We do not know if the mechanisms of ASH development are
different from the development of large for gestational age infants, but
recently Gordon, et al. , found that only transient
hyperglycemic exposure is required to induce cardiac septal overgrowth
in fetal rats, explaining why markers of chronic hyperglycemia often do
not predict the degree of overgrowth. However, results require
additional trans-lational studies. This could explain the lack of
correlation between IVS size and Hb1Ac levels, also the association may
be non-linear with a threshold effect and our sample size may be
inadequate to show this effect. The IVS/PWLV index and DDLV higher in
infants with than infants without ASH has been previously described
[2,3,5]. However, it seems that IVS thickness was not enough to affect
the left ventricle systolic function, except for obstructed left
ventricle outflow as it has been pointed out
Diastolic dysfunction in both ventricles can be
considered by lower TMD and TTD values in IDMs than in INDMs, and
the difference in AoD between the two groups could be related to the
turbulent flow through the outflow tract of the left ventricle. However,
no child required hemodynamic support or returned to the hospital
because of heart alterations. So we consider there is not enough support
to indicate an echocardiogram in all IDMs.
To conclude, ASH is a common finding in IDMs even if
they are AGA infants, but it does not require hemodynamic support. There
was not a linear correlation between IVS and the metabolic control.
Contributors: MVH, NA: designed the study; HOV,
AHR: collected and analyzed the data; JGM, NA: wrote the manuscript. All
authors read and approved the final manuscript.
Funding: None; Competing interests: None
What This Study Adds?
• Asymmetric septal hypertrophy is frequent
in infants of diabetic mothers even when they are appropriate
for gestational age.
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