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 There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) ( P value 0.878 ) , even ADMA level increased above the cut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 correlate d 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.
Bronchopulmonary dysplasia is the most common chronic lung disease in infants. Pulmonary hypertension is a complication of BPD, with a prevalence estimated between 25% and 37%. PH is associated with an increase in morbidity and mortality [
PH in BPD is likely the result of abnormal vasculature development in the preterm lung. Both the decreased surface area and vasoconstriction of the pulmonary vasculature can contribute to the increased vascular resistance and greater pulmonary arterial pressures in patients with both BPD and PH [
Currently, not only is it difficult to diagnose PH in BPD, but there are no clinical tests for predicting which patients with BPD will develop PH [
Nitric oxide (NO) is produced from L-arginine and it is central in maintaining the normal low pulmonary vasculature resistance seen. In patients with certain forms of PH, endogenous NO production is decreased [
ADMA competes with L-arginine for the active site of NO synthase (NOS), and when ADMA is bound it, NO production by NOS is inhibited. Normally, the balance between production of ADMA and its degradation results in low levels of ADMA and relatively little inhibition of NOS [
Research question: Could the early detection of PH among infants with BPD improve the outcome among these infants?
Hypothesis: ADMA, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone.
To assess Dimethylarginine levels in newborn infants with bronchopulmonary dysplasia. To assess arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with bronchopulmonary dysplasia. To evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia. To correlate between Plasma Asymmetric Dimethylarginine, arginine & arginine-to-ADMA ratio and Echocardiographic parameters in those patients. To compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level.
This study (case-control study) was carried out on nighty (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and ALZhraa University Hospital, Cairo, Egypt from October 2015 to March 2018.
Cases were divided into two groups:
Group I BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates 27 males & 18 females with mean GA = 33.47 ± 3.81 weeks, mean BW = 2.40 ± 0.95 kg.
Group II 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, 24 males and 21 females, the mean GA = 35.40 ± 3.31 weeks, mean BW = 2.64 ± 0.84 kg.
Inclusion criteria: Neonates diagnosed as BPD. BPD was defined as a supplemental oxygen requirement at 28 days of life [
Exclusion criteria: Patients with congenital heart disease (except for patent ductus arteriosus and/or atrial septal defect). Patients with anatomical causes of PH, including diaphragmatic hernia or other causes of lung hypoplasia.
Ethical consideration: An informed consent was obtained from all parents or guardians of the participating neonates to be involved at this study. The study objectives and tools was explained to them. The study was done after approval of ethical committees of pediatric department & faculty of medicine for girls Al-Azhar University on 27/10/2015.
Methods: All patients were subjected to the followings full antenatal, natal and postnatal medical history taking including therapeutic history and through clinical examination.
We used the following criteria in
We screened all neonates in this study with Echocardiography for PH using GE system Vivid-7 Matrix probe M3S multi frequency 2.5 MHz. The diagnosis of PH in patients with BPD was made by one of the following predominant findings on ECHO: right ventricular hypertrophy (RVH), flattening of the intraventricular septum, tricuspid regurgitation in the absence of pulmonary stenosis, or increased right ventricular pressure [
ECHO assessment through: Trans-thoracic echocardiographic (TTE) studies:
Gestational age | ||
---|---|---|
<32 weeks | ≥32 weeks | |
Time point of assessment | 36 weeks PMA or discharge to home, whichever comes first. | >28 days but <56 days postnatal age or discharge to home, whichever comes first. |
Treatment with oxygen > 21% for at least 28 days plus | ||
Mild BPD | Breathing room air at 36 weeks PMA or discharge to home, whichever comes first. | Breathing room air by 56 days postnatal age or discharge to home, whichever comes first. |
Moderate BPD | Need for <30% oxygen at 36 weeks PMA or discharge to home, whichever comes first. | Need for <30% oxygen at 56 days postnatal age or discharge to home, whichever comes first. |
Severe BPD | Need for ≥30% oxygen and/or positive pressure (PPV or NCPAP) at 36 weeks PMA or discharge to home, whichever comes first. | Need for ≥30% oxygen and/or positive pressure (PPV or NCPAP) at 56 days postnatal age or discharge to home, whichever comes first. |
TTE t M-Mode, 2D, Doppler (pulsed and continous wave), color flow mapping in the standard views from all accessible windows were obtained with ECG physio signal displayed with all detected echo-Doppler study.
Two-dimensional echocardiography: Routine examination was done from the parasternal, apical and subcostal views focusing on: Exclusion of congenital heart disease & Guidance for M-Mode and color Doppler.
M-Mode echocardiography: Parameters were obtained by the guidance of two dimensional (2-D) echocardiography from the parasternal long axis view, at the level of the papillary muscle and at the level of aorta and left atrium using the leading edge technique [
Assessment of pulmonary artery pressure: The tricuspid regurgitant (TR) jet is used to estimate pulmonary artery pressure, and represents the most common and reliable method to evaluate for the presence and severity of PH [
Radiological investigation including Cranium Ultrasonography & x-ray chest and heart.
Laboratory investigations include routine investigations as CBC, Electrolytes, liver and kidney function tests, CRP, Blood gases analysis.
Specific laboratory investigation: Plasma ADMA and arginine were done by using competitive enzyme linked immune-assay (ELISA) method, using both ADMA and arginine ELIZA kits. SinoGeneClon Biotech company, Hangzhou, China. Arginine-to-ADMA ratio
Laboratory techniques: Peripheral venous blood samples were taken and serum was examined by Enzyme-linked immunosorbent assay (ELISA) for quantitative evaluation of Plasma Asymmetric Dimethyl arginine and arginine in all participants. This was done in Al Zahra University Hospital laboratories.
Statistical analysis of data: Data was analyzed using Statistical Package for the Social Sciences (SPSS) version 20, Data are reported as mean and SD, or as number and percent. Demographics and clinical characteristics of cases (BPD and PH) and controls (BPD alone) were compared using c2 test for categorical data and Student t test for continuous data. ADMA, Arginine & ADMA/Arginine ratio levels were compared between study populations by Student t test. p value < 0.05 was considered statistically significant. Mann-Whitney test was used for comparison between two groups with quantitative data and non-parametric distribution [
Among 90 patients with BPD enrolled in the study, 45 had both BPD and PH (cases), 45 had BPD alone (controls). The diagnosis of PH in patients with BPD was made by one of the following predominant findings on echocardiography: right ventricular hypertrophy (51%), flattening of the intraventricular septum (2%), TR (31%), or increased right ventricular pressure (16%) with 17.7% had mild PH, 46.8% had moderate PH & 35.5% had sever PH. There was many of the risk factors for PH overlap with those for BPD, such as gender, oligohydramnios and APGAR, but infants with PH had lower gestational age, lower BW, lack of administration of surfactant when indicated, severe grades of BPD and longer period of hospital stay, than those without PH as shown in (
BPD + PH group | BPD alone | Test value | P-value | Sig. | ||
---|---|---|---|---|---|---|
No. = 45 | No. = 45 | |||||
Gestational age (wks) | Mean ± SD | 33.47 ± 3.81 | 35.40 ± 3.31 | −2.571• | 0.012 | S |
Range | 26 - 41 | 30 - 40 | ||||
Birth Weight (BW)(kg) | Mean ± SD | 2.40 ± 0.95 | 2.80 ± 0.85 | −2.059• | 0.042 | S |
Range | 0.87 - 4.6 | 1.5 - 4.5 | ||||
Gender | Male | 24 (53.3%) | 24 (53.3%) | 0.000* | 1.000 | NS |
Female | 21 (46.7%) | 21 (46.7%) | ||||
Mode of Delivery | Vaginal delivery | 15 (33.3%) | 20 (44.4%) | 1.169* | 0.280 | NS |
Cesarean delivery | 30 (66.7%) | 25 (55.6%) | ||||
Period of hospital stay | Mean ± SD | 51.09 ± 16.30 | 40.82 ± 12.82 | 3.321• | 0.001 | HS |
Range | 28 - 97 | 29 - 84 | ||||
APGAR Score At 1 min | Median (IQR) | 6 (5 - 8) | 8 (6 - 8) | −1.320#: | 0.187 | NS |
Range | 3 - 9 | 3 - 9 | ||||
APGAR Score At 5 min | Median (IQR) | 9 (8 - 9) | 9 (8 - 9) | −1.434#: | 0.151 | NS |
Range | 6 - 10 | 7 - 10 | ||||
Need For Active Resuscitation | Initial steps | 18 (40.0%) | 17 (37.8%) | 5.171* | 0.270 | NS |
PPV | 3 (6.7%) | 9 (20.0%) | ||||
ET | 14 (31.1%) | 14 (31.1%) | ||||
Compression | 4 (8.9%) | 3 (6.7%) | ||||
Medication | 6 (13.3%) | 2 (4.4%) | ||||
Administration of surfactant | No | 26 (57.8%) | 15 (33.3%) | 11.951* | 0.002 | HS |
One dose | 15 (33.3%) | 30 (66.7%) | ||||
Two doses | 4 (8.9%) | 0 (0.0%) | ||||
Patent ducts arteriosus | Yes | 18 (40.0%) | 14 (31.1%) | 0.776* | 0.378 | NS |
No | 27 (60.0%) | 31 (68.9%) | ||||
Age in days at Sampling | Mean ± SD | 28.70 ± 3.62 | 27.52 ± 1.66 | 1.531• | 0.131 | NS |
Range | 23 - 40 | 23 - 30 | ||||
Grades of BPD | Mild | 2 (0.04%) | 23 (51.1%) | 8.349* | 0.015 | S |
Moderate | 15 (33.3%) | 14 (31.1%) | ||||
Severe | 28 (62.2%) | 8 (17.7%) |
*: Chi-square test; •: Independent t-test; #: Mann-Whitney test.
As shown in
Complications | BPD + PH group | BPD alone | Test value | P-value | Sig. | |||
---|---|---|---|---|---|---|---|---|
No. | % | No. | % | |||||
Neonatal sepsis | Yes | 37 | 82.2% | 24 | 53.3% | 8.598* | 0.053 | S |
No | 8 | 17.8% | 21 | 46.7% | ||||
Necrotizing Enterocolitis | Yes | 23 | 51.1% | 14 | 31.1% | 3.717* | 0.054 | NS |
No | 22 | 48.9% | 31 | 68.9% | ||||
Pneumothorax | Yes | 12 | 26.7% | 17 | 37.8% | 1.272* | 0.259 | NS |
No | 33 | 73.3% | 28 | 62.2% | ||||
Intracranial Hemorrhage | Yes | 19 | 42.2% | 15 | 33.3% | 0.756* | 0.384 | NS |
No | 26 | 57.8% | 30 | 66.7% | ||||
Outcome | Death | 29 | 64.4% | 12 | 26.7% | 3.876* | 0.049 | S |
Discharge home | 16 | 35.5% | 33 | 73.3% | ||||
The use of prenatal corticosteroid | Complete course | 6 | 13.3% | 22 | 48.9% | 6.017* | 0.049 | S |
Partial course | 13 | 28.8% | 0 | 0.0% | ||||
No prenatal steroid | 26 | 57.7% | 23 | 51.1% | ||||
Maternal Age (Years) | Mean ± SD | 29.04 ± 4.63 | 29.91 ± 8.64 | −0.593• | 0.555 | NS | ||
Range | 18 - 38 | 18 - 66 | ||||||
Choriamnionitis | Yes | 16 | 35.6% | 17 | 37.8% | 0.048* | 0.827 | NS |
No | 29 | 64.4% | 28 | 62.2% | ||||
Maternal Risk factor | Diabetes mellitus | 10 | 22.2% | 12 | 26.6% | 3.965* | 0.432 | NS |
PIH | 19 | 42.2% | 14 | 31.1% | ||||
Others (APH, Severe olighydrmnios, PROM, …) | 13 | 28.8% | 19 | 42.2% |
NS: Non significant; S: Significant. p value ≤ 0.05 is considered significant and ≤0.01 is highly significant. *: Chi-square test; •: Independent t-test.
BPD + PH group | BPD alone group | Test value | P-value | Sig. | ||
---|---|---|---|---|---|---|
No. = 45 | No. = 45 | |||||
Period of invasive ventilation (Days) | Median (IQR) | 20 (13 - 48) | 12 (8 - 19) | −3.501# | 0.000 | HS |
Range | 5 - 92 | 4 - 67 | ||||
Period on CPAP (Days) | Median (IQR) | 10 (5 - 12) | 9 (8 - 11) | −0.355# | 0.723 | NS |
Range | 2 - 28 | 3 - 20 | ||||
Period on Head Box in days | Mean ± SD | 7.48 ± 2.16 | 8.44 ± 3.69 | −1.241• | 0.219 | NS |
Range | 3 - 12 | 3 - 21 | ||||
Period On Incubator Oxygen In Days | Mean ± SD | 6.29 ± 2.83 | 5.40 ± 2.00 | 1.454• | 0.151 | NS |
Range | 2 - 14 | 2 - 12 |
P-value > 0.05: Non significant; P-value < 0.05: Significant; P-value < 0.01: Highly significant, •: Independent t-test; #: Mann-Whitney test.
BPD + PH group | BPD alone | Test value• | P-value | Sig. | ||
---|---|---|---|---|---|---|
No. = 45 | No. = 45 | |||||
Asymmetric Dimethylarginine (ADMA) ng/ml | Median (IQR) | 604 (501 - 798) | 87 (43.9 - 142) | −8.171 | 0.000 | HS |
Range | 360 - 906 | 17.4 - 186 | ||||
Arginine level | Median (IQR) | 7.9 (5.2 - 12) | 10.1 (6 - 14) | −1.328 | 0.184 | NS |
Range | 3.7 - 23 | 3.9 - 39 | ||||
Arginine to ADMA ratio | Median (IQR) | 0.01 (0.01 - 0.02) | 0.104 (0.071 - 0.185) | −7.785 | 0.000 | HS |
Range | 0.010 - 0.050 | 0 - 0.984 |
•: Mann Whitney test.
Parameter | Cut off point | AUC | Sensitivity | Specificity | +PV | −PV |
---|---|---|---|---|---|---|
ADMA | >186 ng/dl | 1.000 | 100.00 | 100.00 | 100.0 | 100.0 |
Arginine to ADMA ratio | ≤0.04 ng/dL | 0.987 | 95.56 | 91.11 | 91.5 | 95.3 |
<28 days | ≥28 days | Test value• | P-value | Sig. | ||
---|---|---|---|---|---|---|
Asymmetric Dimethylarginine (ADMA) ng/ml | Mean ± SD | 643.35 ± 180.23 | 650.75 ± 140.98 | 0.154 | 0.878 | NS |
Range | 36 0 - 906 | 435 - 879 | ||||
Arginine level | Mean ± SD | 10.30 ± 6.19 | 8.87 ± 4.95 | 0.855 | 0.397 | NS |
Range | 4.1 - 23 | 3.7 - 22.9 | ||||
Arginine to ADMA ratio | Mean ± SD | 0.018 ± 0.011 | 0.015 ± 0.012 | 0.922 | 0.362 | NS |
Range | 0.006 - 0.04 | 0.005 - 0.055 |
•: Independent t-test.
Pre term | Full term | Test value• | P-value | Sig. | ||
---|---|---|---|---|---|---|
No. = 35 | No. = 10 | |||||
ADMA ng/ml | Mean ± SD | 707.68 ± 199.47 | 564 ± 178.93 | 152.658 | 0.002 | S |
Arginine level | Mean ± SD | 9.20 ± 3.83 | 10.10 ± 4.40 | −0.483 | 0.632 | NS |
Arginine to ADMA ratio | Mean ± SD | 0.02 ± 0.01 | 0.03 ± 0.01 | 2.966 | 0.005 | HS |
•: Independent t-test.
Group A (preterm) | Group B (full term) | Test value• | P-value | Sig. | |
---|---|---|---|---|---|
n = 22 | n = 23 | ||||
Asymmetric Dimethylarginine (ADMA) ng/ml | 142.68 ± 27.47 | 47.36 ± 22.93 | 12.658 | 0.000 | HS |
Arginine level | 10.72 ± 4.43 | 9.54 ± 4.93 | 0.846 | 0.402 | NS |
Arginine to ADMA ratio | 0.08 ± 0.03 | 0.27 ± 0.23 | 3.785 | 0.000 | HS |
•: Independent t-test.
As shown in
As presented in
Bronchopulmonary dysplasia remains a common complication of premature birth with short- and long-term morbidity. Although the disorder is most often associated with premature birth, it can also occur in infants born at term who
Asymmetric Dimethylarginine (ADMA) ng/ml | Death in neonates with BPD & PH | Test value• | P-value | Sig. | |
---|---|---|---|---|---|
No | Yes | ||||
Mean ± SD | 525.45 ± 100.46 | 769.03 ± 99.63 | 8.146 | 0.000 | HS |
Range | 360 - 800 | 500 - 906 |
•: Independent t-test.
Cut off point | AUC | Sensitivity | Specificity | +PV | −PV |
---|---|---|---|---|---|
>634 | 0.940 | 90.48 | 91.67 | 90.5 | 91.7 |
need aggressive ventilator therapy for severe, acute lung disease [
Pulmonary hypertension can be considered the gravest complication of BPD as it worsens the prognosis of affected infants, it is associated with an increase in morbidity and mortality [
Asymmetric dimethylarginine inhibits NO production. In patients with PH, endogenous NO production is decreased, so increased ADMA levels are indicative of endothelial dysfunction. Arginine to ADMA ratio, a better indicator of NO availability than either arginine or ADMA separately [
Up till now, there are serval studies linking ADMA to endothelial dysfunction in adults but little is known about relating ADMA activity in BPD [
Screening methods for the development of BPD-associated PH may allow for novel interventions to improve morbidity and mortality. Diagnostic biomarkers that can enable early diagnosis, predict the risk of individual patients to develop BPD-PH represent an important unmet medical need [
Our study was a case control study conducted on ninety (90) newborns. Infants were defined as suffering from BPD if they were on oxygen support ≥ 28 days. Demographic data in this study showed that infants with BPD and PH had a statistically significant lower gestational age, lower BW than those without PH.
Khemani et al. [
Bhat et al. [
We found that gender and mode of delivery had no effect on development of PH in BPD as male to female ratio were in group I BPD with PH (27 males & 18 females) While Group II BPD only (24 males and 21 females) with a p value 1.000. Also mode of delivery in cases group (vaginal delivery 33.3% cesarean delivery 66.7% while in control group (vaginal delivery 44.4% cesarean delivery 55.6% with a p value 0.280. This result confirmed the results reached by An et al. [
Patients in BPD and PH group had a longer period of hospital stay than those without PH with a p value 0.001. Also Bhat et al. [
We found that prenatal maternal steroid intake showed statistical significance between the studied groups as BPD + PH group mother’s had almost no prenatal steroid intake or had received partial course of steroid with a p value 0.049. This is similar to Rob et al. [
On studying the clinical data, we found most of patients who developed PH had severe grades of BPD (sever 62.2%, moderate 33.3% and mild 4.3%), while in group II BPD only (severe 17.7%, moderate 31.1% and mild 51.1%) with a p value 0.015 between both groups. It is in agreement with result of Al-Ghanem et al. [
We observed a statically significant difference between BPD with PH group and BPD group, as regard administration of surfactant. Lack of administration of surfactant when indicated was mainly found in BPD and PH group with a p value 0.002. In contrast to this result, Slaughter et al. [
There was significant difference in sepsis and mortality between newborn infants with BPD and BPD with PH. These data agreed with others as Ali et al. [
Our study showed a statically significant difference concerning the period of invasive ventilation. BPD with PH group had stayed longer period on invasive ventilation. This result confirmed the results reached by other studies Ali et al. [
Khemani et al. [
W assessed severity of PH in BPD with PH group, we found 17.7% had mild PH, 46.8% had moderate PH and 35.5% had sever PH, then we found significant correlation between grades of BPD and severity of PH.PH was found mainly in sever and moderate cases of BPD. In accordance to this result, del Cerro et al. [
Our study showed that higher levels of ADMA and lower level of arginine to ADMA ratio were found in BPD with PHgroup. Shao et al. [
In our work we observed that there is no statically significance difference between level of ADMA, Arginine and Arginine to ADMA ratio whether it was drawn before or after 28 days of age In contrast to our work, Jennifer et al. [
We found the most predominant signs of PH in ECHO were RVH 51%, TR 31%, increased RT. ventricular pressure 16%, Flat intraventricular septum 2%. Paul H and Milenka [
In our study we found significant correlation between level of ADMA and grades of PH in our cases. Higher level of ADMA was found in sever grades of PH. This result is similar to, Shao et al. [
In this work we observed a statically significant difference between preterm neonates and full-term neonates as regard level of ADMA and Arginine/ADMA ratio. Higher level of ADMA is seen in preterm group and also this group had lower level of Arginine/ADMA ratio. Moreover we found significant negative correlation between ADMA level and BW, higher level of ADMA was seen in smaller birth weight. In accordance to these results, Tsukahara et al. [
Dzik et al. [
We can explain this difference in ADMA between preterm and full term as it might be a consequence of increased ADMA synthesis, decreased metabolism by DDAH, decreased clearance by immature kidneys, or some combination of those factors in preterms.
In the current work we observed, no significant correlation between ADMA and gender with a P value 0.088. We met the result reached by Richir et al. [
In our study there was significant positive correlation of ADMA level with period of invasive ventilation in BPD + PH group, higher level of ADMA level was seen in patient had longer period of invasive mechanical ventilation. Our result met the result reached by Richir et al. [
In our study we found significant positive correlation between ADMA level and development of necrotizing enterocolitis. In agreement with result Richir et al. [
In the current study, we observed that ADMA can predict death in neonates with BPD &PH at cut off point > 643 with sensitivity 90.48% &specificity 91.67%. In agreement with result, Judy L and Candice D [
Avoid late and wrong diagnosis and treatment by using safe tools; updated guidelines and clinical path may decrease errors from prolonged/excessive oxygen use and invasive ventilation that lead to development of BPD and subsequent complications as PH ELMeneza et al. [
Pulmonary hypertension development in BPD was found mainly in sever and moderate cases of BPD so screening for PH in those patients is a must. Neonates with BPD who developed PH by echocardiographic criteria had greater plasma levels of ADMA and lower plasma arginine to ADMA ratios than those patients with BPD that did not develop PH. ADMA level can predict severity of pulmonary hypertension in patient with BPD, also can be used as prognostic marker. Preterm neonates with BPD had greater level of ADMA than full term neonates. Studies are needed also to determine whether increased ADMA levels in BPD associated PH are caused by an increase in ADMA synthesis or a decrease in ADMA catabolism.
The authors declare no conflicts of interest regarding the publication of this paper.
EL Meneza, S.A.E., Bahgat, S.M. and Nasr, A.E.S. (2018) Plasma Asymmetric Dimethylarginine Levels in Neonates with Bronchopulmonary Dysplasia Associated with Pulmonary Hypertension. Open Journal of Pediatrics, 8, 221-237. https://doi.org/10.4236/ojped.2018.83024