TITLE:
Plasma Asymmetric Dimethylarginine Levels in Neonates with Bronchopulmonary Dysplasia Associated with Pulmonary Hypertension
AUTHORS:
Safaa Abd Elhamid EL Meneza, Seham Mohamed Bahgat, Asmaa EL Saudi Nasr
KEYWORDS:
Asymmetric Dimethylarginine, Bronchopulmonary Dysplasia, Pulmonary Hypertension
JOURNAL NAME:
Open Journal of Pediatrics,
Vol.8 No.3,
September
5,
2018
ABSTRACT: Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in
neonates especially premature infants despite improved facilities of care,
monitoring and treatment. Pulmonary hypertension (PH) is a major complicating
factor and key cause of mortality in this population. Altered vascular and
alveolar growth particularly in canalicular and early saccular stages of lung
development following mechanical ventilation and oxygen therapy result in
arrest of the lung development leading to BPD with PH. Early recognition of PH
in infants with these risk factors is important for optimal management. We
tested the hypothesis that asymmetric dimethylarginine, would be greater in
infants with bronchopulmonary dysplasia associated pulmonary hypertension than
in infants with BPD alone. The Aim: The aim of the current study was to
measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels &
the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary
dysplasia, to evaluate echocardiographic parameters among neonates with
bronchopulmonary dysplasia, to correlate between plasma ADMA &
arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare
full term & preterm neonates with bronchopulmonary dysplasia as regard to
plasma ADMA level. Methods: A case-control study was carried out of
ninety (90) newborns selected from those admitted to Neonatal Intensive Care
Unit at Maternity & Children Hospital and Alzhraa University hospital
during the period from October 2015 to March 2018. Neonates were divided into 2
groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD
& PH, 35
preterm neonates and 10 full term neonates. Patient with BPD only (Control
group): It included 45 neonates with BPD without PH. These 45 neonates were
divided as 22 preterm neonates and 23 full term neonates. Laboratory work was
done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels
& arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results:
Patients with both BPD and PH had greater plasma levels of ADMA than patients
with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict
development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm
neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference
between level of ADMA if withdrawn before or after 28 days of age (range of age
at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased
above the cut point early in the disease before we screened some cases by ECHO.
There was no statically significance difference between level of arginine in
cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases
than in controls suggesting a greater likelihood of inhibition of nitric oxide
production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict
severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of
pulmonary hypertension (P value 0.006). ADMA
level is higher in neonates with BPD and PH who died than those who survived; it can predict death in
neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may
have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with
severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those
who survived. There was no statically significance difference between levels of ADMA, whether it
was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic
screening and ADMA measurement could help in prevention of PH, diagnosis and early
treatment of newborn infants suffering from BPD.