Correlation of cardiac troponin T levels with inotrope requirements,HIE stages and outcome in asphyxiated neonates

Abstract

Background

Asphyxial event can compromise the function of many vital organs like brain, heart, and kidneys. Cardiac dysfunction results from hypoxic injury to subendocardial tissue, papillary muscle, and myocardium. The aim of this work was to assess correlation between cardiac troponin T levels, myocardial dysfunction, inotrope requirements, hypoxic ischemic encephalopathy (HIE) stages, and outcome in asphyxiated neonates.

Methods

This cohort study was conducted on 48 neonates aged (1–28) days old, both sexes, exposed to perinatal asphyxia, and admitted in NICU unit in Benha University Hospital during the period from September 2022 to August 2023. Neonates had blood drawn for CBC, liver, kidney functions, and serum troponin T levels. Also, assessment by echocardiography and MRI were done to these patients in the first 3 days.

Results

Troponin T levels were significantly higher in neonates with myocardial dysfunction (systolic or diastolic), who required inotropic support, mechanical ventilation, or who were non-survivors. Troponin T levels significantly correlated with HIE severity, as assessed by Apgar scores and Sarnat staging. ROC curve revealed that cardiac troponin T levels have high accuracy at a cutoff value of >0.18 ng/mL, >0.18 ng/mL, and >0.18 ng/mL, respectively, in detecting myocardial dysfunction, morbidity, and mortality in patients with HIE with reliable sensitivity (84.2%–92.3%) and specificity (88.2%–93.1%).

Conclusions

Elevated cardiac troponin T is highly suggestive of myocardial dysfunction in cases of HIE. It is significantly correlated to severity of HIE, morbidity, and mortality in asphyxiated neonate.

Keywords

hypoxic ischemic encephalopathy (HIE)cardiac troponin T neonatal outcome

Introduction

Perinatal asphyxia is a leading cause of neonatal morbidity and mortality especially in low and middle income countries, in high-income countries, perinatal asphyxia affects 16/1000 live births.¹ The reported incidence varies from 2% to 16.2% in community based studies with mortality rates ranging between 38.5% and 74%. In hospital-based studies, approximately 2.8% and 5.6% of all live births have moderate and severe asphyxia, respectively.²

When an asphyxiated event occurs in fetus and newborn, it leads to multiorgan involvement,³ commonly affected abnormalities of birth asphyxia involve kidneys in about 50% of neonates, central nervous system 28%, and pulmonary system in 23%.⁴ Cardiac dysfunction is detected in 24%–31% of patients and is usually secondary to transient myocardial ischemia.⁵

Serum creatinine kinase muscle-brain isoenzyme (CK-MB) lacks cardiac specificity in the neonate and the levels are affected by gestational age, mode of delivery, and birth weight. Unlike CK-MB, cardiac troponin T (cTnT) is not affected by gestational age, mode of delivery, and other related factors,⁶ and cardiac troponin T (cTnT) has been explored as a more specific biomarker for the diagnosis of myocardial injury in asphyxiated neonates.^7,8 Troponin T can be detected at earlier stages than CK-MB and it also remains high for a longer period.⁷ Further, cTnT levels are found to be elevated in 30%–50% of cases having normal CK-MB levels.⁹

Myocardium of neonates is thought to be resistant to hypoxia but cardiac failure is one of the most important manifestations of myocardial dysfunction among cases having perinatal asphyxia.¹⁰

Hemodynamic assessment with echocardiography enables enhanced diagnostic precision with a targeted approach to intervention that may complement a clinical examination and more accurately optimize post insult cerebral blood flow and oxygen delivery. Although echocardiography may offer a blueprint for formulating a diagnostic impression, further investigation is needed to determine the risk/benefit ratio of treatment and the thresholds for initiating treatment.¹¹

The aim of this work was to assess correlation between cardiac troponin T levels and echocardiography, inotrope requirements, HIE stages, and outcome in asphyxiated neonates.

Patients and methods

This cohort study was conducted on 48 neonates diagnosed with hypoxic ischemic encephalopathy (HIE) aged (1–28) days old, both sexes during the period from September 2022 to August 2023. An informed written consent was obtained from the relatives of the patients. The study was done after approval from the Ethical Committee Benha University Hospitals, matching the Helsinki declaration of interest.¹²

Neonate was considered to have perinatal asphyxia if he/she in need of bag and mask or bag and tube ventilation at birth with Apgar score of ≤6 at 5 min; hypoxic encephalopathy features (lethargy, seizures, hypotonia, coma, or irritability); cord blood pH ≤ 7.0; or arterial pH in neonates ≤7.2.¹³

Exclusion criteria were patients expired during the first 72 hours of birth (before fulfillment of investigations), neonates with other comorbidities such as major congenital malformations, renal failure and liver failure, or other conditions that could elevate troponin levels aside from HIE, such as sepsis, severe infections (e.g., pneumonia and meningitis), significant metabolic disturbances (e.g., metabolic acidosis), myocarditis, or severe respiratory distress syndrome.

All neonates were subjected to detailed history taking.

General examination

Vital signs, general characteristics, and anthropometric measurements were taken. Sarnat staging for degree of HIE was applied to all neonates.¹⁴

Laboratory investigations

Blood gas analysis was performed using a heparinized needle. Additionally, 1 mL of peripheral blood was collected for kidney and liver function tests, with renal dysfunction indicated by high creatinine levels or low urine output, and hepatic dysfunction defined by elevated transaminase levels.⁹

Blood sample was processed for estimation of cTnT levels by human cardiac troponin T (cTnT) ELISA kit (Catalogue No. 201-12-5490). Samples were prepared for analysis by adding standards and test samples to designated wells, with blank wells containing only chromogen solutions and stop solution. The assay involved adding cTnT-antibody and streptavidin-HRP to the test wells, sealing, shaking, and incubating at 37°C for 60 minutes. Following a 30-fold dilution of washing concentrate, the wells were washed, and chromogen solutions A and B were added, with further incubation and reaction stopped by adding stop solution. Optical density (OD) was measured at 450 nm within 15 minutes of stopping the reaction. A standard curve was generated to calculate sample concentrations using OD values, with assay sensitivity determined by subtracting two standard deviations from the mean OD of zero standards. The assay range was 1 ng/L to 300 ng/L, with intra-assay precision tested across 20 replicates and inter-assay precision across 8 replicates on different plates, yielding a coefficient of variation (CV) of less than 12%.

Radiological investigations

Brain MRI was done to detect different patterns of brain injury in these patients. Echocardiography was done by pediatric cardiologist using Philips machine and 6 Hz probe. Myocardial dysfunction was assessed by American Society of Echocardiography (ASE) standards with systolic dysfunction defined by ejection fraction <54% and fractional shortening <28% and diastolic dysfunction via the E/A ratio. Other parameters involved tricuspid and mitral regurgitation, systolic pulmonary artery pressure, and persistence of patent ductus arteriosus (PDA).⁸

Neonates were followed up during their period of NICU stay and outcomes recorded: 1ry outcome in terms of myocardial dysfunction, need for inotropes, and mechanical ventilation. 2ry outcome in terms of mortality.

Statistical analysis

Statistical analysis was done by SPSS version 16 software (Inc, Chicago, ILL Company). Categorical data were presented as number and percentages. Quantitative data were tested for normality using Shapiro–Wilks test assuming normality at p > 0.05. Normally distributed variables were expressed as mean ± standard deviation and analyzed by Student “t” for 2 independent groups, while non parametric data were presented as median and range, and analyzed by Mann–Whitney U-test for 2 independent group and Kruskal–Wallis (KW) test for 3 independent groups. p ≤ 0.05 was considered significant.

Results

The study involved 30 males and 18 females, with a mean gestational age of 37.5 weeks and a mean maternal age of 27.9 years. Most cases had no maternal disease history, though some had hypertension, diabetes, or both. Hypoxia was often due to antepartum hemorrhage, prolonged labor, premature rupture of membranes, or cord around the neck. The most common delivery method was normal vaginal delivery, with only a few responding to initial resuscitation; the rest required aggressive resuscitation steps. The mean Apgar score at 1st min was 2.02 ± 0.9, at 5 min was 3.96 ± 0.8 and at 10 min was 6.56 ± 0.9 (Table 1).

Table 1.

Characteristics of the studied group.

		N = 48	%
Sex	Male	30	62.5%
Sex	Female	18	37.5%
Gestational age (weeks)	Mean ± SD	37.5 ± 2.1
Gestational age (weeks)	Range	31–40
Maternal age (years)	Mean ± SD	27.9 ± 4.6
Maternal age (years)	Range	20–37
Maternal illness	None	29	60.4%
	HTN	8	16.7%
	DM	6	12.5%
	HTN and DM	5	10.4%
Mode of delivery	CS	18	32.5%
Mode of delivery	NVD	30	62.5%
Cause of hypoxia	Antepartum hemorrhage	14	29.2%
	PROM	11	22.9%
	Cord around neck	10	20.8%
	Prolonged 2nd stage of labor	13	27.1%
Resuscitation measures	Initial steps	3	6.3%
	+Bag and mask	16	33.3%
	+Chest compression and inotropes	19	39.6%
	+ Intubated	10	20.8%
Apgar score
Apgar score 1 min	Mean ± SD	2.02 ± 0.9
Apgar score 1 min	Range	1–5
Apgar score 5 min	Mean ± SD	3.96 ± 0.8
Apgar score 5 min	Range	2–6
Apgar score 10 min	Mean ± SD	6.56 ± 0.9
Apgar score 10 min	Range	5–8

HTN: hypertension, DM: diabetes mellitus, CS: caesarian section, NVD: normal vaginal delivery, PROM: premature rupture of membrane.

There was no significant difference between the studied full-term and preterm groups regarding troponin T level. There were 12 (25%) preterm neonates <37 weeks and 36 (75%) full-term neonates >37 weeks (p value <0.001) (Table 2).

Table 2.

Cardiac troponin T level according to gestational age in the studied group.

Variable (N. = 48)		Troponin T (ng/mL)			Test	p value
Variable (N. = 48)		Mean ± SD	Median	Range	Test	p value
Gestational age	Preterm (N. = 12)	.169 ± .141	.125	.02–.43	U = .095	.924
Gestational age	Full-term (N. = 36)	.154 ± .138	.110	.02–.52	U = .095	.924

U: Mann–Whitney U test, *: significant.

The mean cardiac troponin T level was 0.20 ± 0.14 ng/mL and the median was 0.21 ng/mL. Neonatal reflexes were absent in 68.8% and present in 31.3%. ABG results indicated a lower pH and decreased bicarbonate levels. Hemoglobin, white blood cell count, platelet count, transaminases, urea, and creatinine levels were within normal ranges (Table 3).

Table 3.

Cardiac troponin T level and laboratory investigations in the studied group.

		N = 48
Troponin T (ng/mL)	Mean ± SD	0.20 ± 0.14
	Median	0.21
	Range	0.02–0.52
PH of the cord blood	Mean ± SD	7.2 ± 0.07
PH of the cord blood	Range	7.14–7.29
CO2 (mmHg)	Mean ± SD	45.4 ± 6.8
CO2 (mmHg)	Range	27–66
HCO3 (mmol/L)	Mean ± SD	19.1 ± 1.9
HCO3 (mmol/L)	Range	14–20.1
Hemoglobin (mg/dl)	Mean ± SD	15.3 ± 2.9
Hemoglobin (mg/dl)	Range	8.3–22
Total leucocytes count (x 10³/L)	Mean ± SD	12.9 ± 2.8
Total leucocytes count (x 10³/L)	Range	7.11–9.2
Platelets (x 10³/L)	Mean ± SD	262.4 ± 48.6
Platelets (x 10³/L)	Range	174–385
ALT (IU/L)	Mean ± SD	34.1 ± 11.7
ALT (IU/L)	Range	19.2–72
AST (IU/L)	Mean ± SD	28.4 ± 9.6
AST (IU/L)	Range	16–51
Urea (mg/dl)	Mean ± SD	29.2 ± 8.2
Urea (mg/dl)	Range	13.4–55
Creatinine (mg/dl)	Mean ± SD	0.54 ± 0.16
Creatinine (mg/dl)	Range	0.28–0.94

Echocardiographic evaluation showed that 50% of neonates had patent ductus arteriosus, 50% had pulmonary hypertension, 29.2% had systolic dysfunction, and 41.7% had diastolic dysfunction.

Only 7 of neonates had normal MRI brain, 22.9% had cystic encephalomalacia, 10.4% had peri-rolandic involvement, 25% had watershed zone involvement, 10.4% had periventricular leucomalacia, 4.1% had germinal matrix hemorrhage, 6.3% had white matter injury, and 6.3% had mixed pattern. Stage I HIE included 37.5% of studied neonates, 31.3% were stage II, and 31.3% were stage III. Assessment of outcome showed 39.6% of neonates requiring ventilation, 41.7% needed inotropes and 27.1% died (Table 4).

Table 4.

Echocardiography, MRI brain, disease severity, and outcome of the studied group.

		N = 48	%
Patent ductus arteriosus	No	24	50.0
Patent ductus arteriosus	Yes	24	50.0
Tricuspid regurgitation	No	31	64.6
Tricuspid regurgitation	Yes	17	35.4
Mitral regurgitation	No	45	93.8
Mitral regurgitation	Yes	3	6.3
Pulmonary hypertension	No	24	50.0
Pulmonary hypertension	Yes	24	50.0
Systolic dysfunction	No	34	70.8
Systolic dysfunction	Yes	14	29.2
Diastolic dysfunction	No	28	58.3
Diastolic dysfunction	Yes	20	41.7
MRI brain	Normal	7	14.5
	Cystic encephalomalacia	11	22.9
	Peri-rolandic involvement	5	10.4
	Watershed zone involvement	12	25.0
	Periventricular leukomalacia	5	10.4
	Germinal matrix hemorrhage	2	4.1
	White matter injury	3	6.3
	Mixed pattern	3	6.3
HIE stages	Stage I	18	37.5
	Stage II	15	31.3
	Stage III	15	31.3
Mechanical ventilation	No	29	60.4
Mechanical ventilation	Yes	19	39.6
Inotropes	No	28	58.3
Inotropes	Yes	20	41.7
Outcome	Non-survivors	13	27.1
Outcome	Survivors	35	72.9

Troponin T level was significantly higher in neonates with systolic and diastolic dysfunction, while there was no statistical difference in troponin level as regards to other echocardiographic findings (Table 5).

Table 5.

Cardiac troponin T level according to echocardiography in the studied group.

		Troponin T (ng/mL)			Test	p Value
		Mean ± SD	Median	Range	Test	p Value
Patent ductus arteriosus	No	0.15 ± 0.13	0.11	0.02–0.52	U = 0.28	0.78
Patent ductus arteriosus	Yes	0.17 ± 0.14	0.11	0.02–0.51	U = 0.28	0.78
Tricuspid regurgitation	No	0.15 ± 0.12	0.09	0.02–0.51	U = 1.6	0.11
Tricuspid regurgitation	Yes	0.18 ± 0.12	0.12	0.04–0.52	U = 1.6	0.11
Mitral regurgitation	No	0.16 ± 0.13	0.11	0.02–0.52	U = 0.55	0.58
Mitral regurgitation	Yes	0.18 ± 0.15	0.14	0.05–0.35	U = 0.55	0.58
Pulmonary hypertension	No	0.15 ± 0.13	0.11	0.02–0.42	U = 0.31	0.75
Pulmonary hypertension	Yes	0.17 ± 0.14	0.11	0.02–0.51	U = 0.31	0.75
Systolic dysfunction	No	0.09 ± 0.06	0.08	0.02–0.22	U = 4.8	<0.001*
Systolic dysfunction	Yes	0.32 ± 0.13	0.32	0.10–0.52	U = 4.8	<0.001*
Diastolic dysfunction	No	0.07 ± 0.05	0.06	0.02–0.21	U = 5.5	<0.001*
Diastolic dysfunction	Yes	0.28 ± 0.13	0.27	0.11–0.52	U = 5.5	<0.001*

U: Mann–Whitney U test, *: significant.

Troponin T level increased significantly with advanced stages of hypoxic insult. Troponin T level was significantly higher in neonates who required inotropes, mechanical ventilation, and non-survivors (Table 6).

Table 6.

Cardiac troponin T level according to HIE staging, disease severity, and outcome in the studied group.

		Troponin T (ng/mL)			Test	p value
		Mean ± SD	Median	Range	Test	p value
HIE stages	Stage I	0.05 ± 0.04	0.04	0.02–0.17	K = 33.6	<0.001*
	Stage II	0.12 ± 0.06	0.11	0.05–0.22
	Stage III	0.32 ± 0.13	0.31	0.12–0.52
MV	No	0.08 ± 0.05	0.06	0.02–0.21	U = 5.1	<0.001*
MV	Yes	0.27 ± 0.14	0.27	0.07–0.52	U = 5.1	<0.001*
Inotropes	No	0.08 ± 0.05	0.06	0.02–0.21	U = 5.2	<0.001*
Inotropes	Yes	0.28 ± 0.13	0.29	0.09–0.52	U = 5.2	<0.001*
Outcome	Died	0.34 ± 0.12	0.32	0.18–0.52	U = 4.9	<0.001*
Outcome	Survived	0.09 ± 0.07	0.08	0.02–0.31	U = 4.9	<0.001*

K: Kruskal–Wallis test, *: significant.

There was statistically significant negative correlation between cardiac troponin T and (Apgar score at 5th and 10th minutes and PH of the cord blood). However, there was no statistically significant correlation between cardiac troponin T and (gestational age, maternal age, Apgar score at 1st min, CO_2, or HCO₃) (Figure 1).

Figure 1.

Correlation between cardiac troponin T and (a) Apgar score at 10 min (b).

ROC analysis was done to assess the performance of cardiac troponin T to detect myocardial dysfunction by echocardiography, cases of HIE who needed inotropic support and mortality in cases of HIE as AUC was 0.944, 0.955, and 0.973 p < 0.001, respectively. At a cutoff point >0.18 ng/mL, >0.15 ng/mL, and >0.18 ng/mL, respectively, the sensitivity was 85.7%, 84.2%, and 92.3%, respectively, and specificity was 88.2%, 93.1%, and 89.1%, respectively (Table 7; Figure 2).

Table 7.

Performance of cTnT to detect myocardial dysfunction by echocardiography, cases of HIE who needed inotropic support, and mortality in cases of HIE.

	AUC	95% CI		Cutoff value	Sensitivity, %	Specificity, %	p value
Troponin T (ng/mL) to detect myocardial dysfunction by echocardiography	0.944	0.873	1	>0.18	85.7	88.2	<0.001*
Troponin T (ng/mL) to detect cases of HIE who needed inotropic support	0.955	0.903	1	>0.15	84.2	93.1	<0.001*
Troponin T (ng/mL) to detect mortality in cases of HIE	0.973	0.934	1	>0.18	92.3	89.1	<0.001*

AUC: area under the curve, *: statistically significant as p value <0.05.

Figure 2.

ROC curve of performance of cardiac troponin to detect (a) myocardial dysfunction by echocardiography [cutoff >0.18 ng/mL (sensitivity: 85.7% and specificity: 88.2%), AUC = 0.944 (95% CI: 0.873–1.0, p < 0.001], (b) cases of HIE who needed inotropic support [cutoff >0.15 ng/mL (sensitivity: 84.2% and specificity: 93.1%), AUC = 0.955 (95% CI: 0.903–1.0, p < 0.001], and (c) mortality in cases of HIE [cutoff >0.18 ng/mL (sensitivity: 92.3% and specificity: 89.1%), AUC = 0.973 (95% CI: 0.934–1.0, p < 0.001].

Discussion

This cohort study was done on 48 neonates with perinatal asphyxia including 30 males and 18 females; their mean gestational age was 37.5 ± 2.1 weeks. That was in agreement with Yellanthoor and Rajamanickam¹³ who studied correlation of cardiac troponin T levels with inotrope requirements in 57 neonates with perinatal asphyxia. His results revealed that incidence of HIE is more common in males and full-term babies with mean gestational age 38.4 ± 1.6 weeks.

In the present study, the mean maternal age was 27.9 ± 4.6 years. Most cases (60.4%) had no history of maternal diseases, while 16.7%, 12.5%, and 10.4% had diabetes, hypertension, or both, respectively. Most cases (62.5%) were born by NVD. Regarding cause of hypoxia, the most common cause was antepartum hemorrhage (29.2%), followed by prolonged 2nd stage of labor (27.1%), PROM (22.9%), and cord around neck (20.8%).

In the same way, Namusoke et al.,¹⁵ who enrolled 751 newborns with 399 (53%) male and 352 (47%) female, reported that the factors that were significantly associated with HIE at bivariate analysis included prolonged labor, prolonged rupture of membranes, antepartum hemorrhage, and prolonged pregnancy. The incidence of HIE was 30.6 per 1000 live births and the mortality in HIE was 26% (6/23), predominantly in severe HIE.

Most of the asphyxiated neonates in this study required aggressive resuscitative maneuvers in the form of mask and bag, chest compression, and inotropes or intubation at birth room with only 6.3% of cases responding to initial resuscitation steps.

In agreement with Yellanthoor and Rajamanickam¹³ who reported that mode of resuscitation at birth included intubation in 26 (45.6%) and bag and mask ventilation is 15 (26.3%). However, the study by Joseph et al.¹⁶ who included 120 term neonates found that incidence of myocardial dysfunction was 55% (66/120) in asphyxiated neonates with mean cTnT levels 0.277 ± 0.231 ng/mL where all neonates required positive pressure ventilation and 85% of them required endotracheal intubation in the delivery room .

The mean Apgar score at 1st min was 2.02 ± 0.9, at 5 min was 3.96 ± 0.8 and at 10 min was 6.56 ± 0.9. Similarly, Lally et al.,¹⁷ who included 223 infants, reported that the mean (SD) Apgar score at 10 min was 5.6 (2.2). This correlates with accepted criteria for diagnosing neonates with perinatal asphyxia.

In the present study, the mean weight was 3.3 ± 0.5 kg, the mean height was 47.8 ± 0.8 cm, and the mean head circumference was 34.8 ± 0.9 cm. Similarly, Mahmoud et al.,¹⁸ who included 50 full-term neonates [32 males (64%) and 18 females (36 %)], reported that the mean weight of neonates with HIE was 3.7 kg, with a range of 3–4 kg suggesting that macrosomia of babies with traumatic deliveries may be one of risk factors for perinatal asphyxia. While in the study by Joseph et al.,¹⁶ mean (SD) birth weight was 2.816 kg.

Neonates in the study commonly displayed cyanosis, bradycardia, hypotension, hypothermia, and hypoglycemia. Most of these respiratory complications may be attributed to persistent pulmonary hypertension in these asphyxiated neonates. Many also exhibited hypotonia and flaccidity, with a range of neurological symptoms including hyperactivity, lethargy, stupor, and convulsions. Neonatal reflexes were absent in a majority of cases. In agreement with Mahmoud et al.¹⁹ whose study was carried out on 40 neonates with perinatal asphyxia, he reported that cardiac injury was common with cardiac troponin I serving as an early biomarker for myocardial damage. The asphyxiated group had statistically higher frequencies of tachycardia, bradycardia, tender liver, tachypnea, lung crepitations, poor reflexes, decreased consciousness, convulsions, and hypotension.

The study revealed that the mean cord blood pH was lower than normal, with elevated CO₂ and reduced bicarbonate levels. This reflects the effect of perinatal hypoxia in the development of CO₂ retention and acidosis, therefore increasing the risk of myocardial injury. Routine laboratory investigations showed that hemoglobin, total leucocytes count, platelets, and liver enzymes (ALT and AST) were within normal ranges. Urea and creatinine levels were also found to be normal.

Mahmoud et al.¹⁹ reported that WBCs × 10³/mm³ of asphyxiated neonates were significantly higher than that of the healthy control neonates, while mean value of RBCs of asphyxiated neonates were significantly lower. There was no significant difference between the two studied groups in the platelets count. The mean values of pH and PaO₂ of asphyxiated neonates were significantly lower, while mean PaCO₂ was significantly higher than that of the healthy control neonates. There was no significant difference between the two studied groups in HCO₃.

In the current study, the mean cardiac troponin T level was 0.20 ± 0.14 ng/mL and the median was 0.21 ng/mL. Yellanthoor and Rajamanickam¹³ reported that elevated cTnT levels were observed in 41 (71.9%) neonates studied, with median (IQR) of 0.285 (0.211–0.422) ng/mL. The maximum value observed was 1.99 ng/mL. Also Mahmoud et al.¹⁸ reported that asphyxiated neonates had significantly higher cTnT levels (4.6 ± 4.4 ng/mL) compared to controls (0.55 ± 0.6 ng/mL). Higher cTnT correlated with lower Apgar scores, acidosis (lower pH and higher PaCO2), and worse outcomes (neurological abnormalities or death).

Echocardiography was used as the gold standard for detection of myocardial dysfunction. 50% of neonates had patent ductus arteriosus, 6.3% had mitral regurgitation, 50% had pulmonary hypertension, 29.2% had systolic dysfunction, and 41.7% had diastolic dysfunction.

In agreement with Shahidi et al.,²⁰ who examined cardiovascular complications following birth asphyxia in 29 asphyxiated term neonates , found that patent arterial duct was a common finding in asphyxiated neonates (62%) while mitral valve regurgitation was relatively rare. About one-third of asphyxiated neonates had different levels of systolic dysfunction. Diastolic dysfunction and pulmonary hypertension were detected in about half and near two-thirds of asphyxiated neonates, respectively. Left ventricular dysfunction is attributed to ischemic insult and reactive oxygen species from reperfusion injury, while hypoxic induced vasoconstriction of pulmonary vascular bed leads to pulmonary hypertension.

The most common MRI findings in our study with decreasing order of frequency included 25% with watershed zone involvement, 22.9% with cystic encephalomalacia, 10.4% peri-rolandic involvement, 10.4% periventricular leucomalacia, 6.3% white matter injury, and 6.3% had a mixed pattern.

In the same way, Li et al.²¹ who studied pattern of MRI brain injury in 149 infants with HIE, reported that prevalence of brain injury was 61% of infants with mild injury predominant in 44% of neonates and fewer cases of moderate (11%) or severe (4%) injury. The most common brain injury patterns were watershed (22%), deep gray nuclei (20%), punctate white matter (18%), and atypical lesions (18%).

While in the study by Jose et al.,²² who identified 31 babies with perinatal asphyxia and hypoxic ischemic encephalopathy, the MRI was normal in 16 (61.5%). There were abnormal signals in basal ganglia in two (7.7%) in the cerebral cortex and scattered signal abnormalities in both cortex and basal ganglia in six (23.1%).

In the present study, according to Sarnat staging, most neonates (37.5%) were stage I, 31.3% were stage II, and 31.3% were stage III.¹⁴

In the same way, Mahmoud et al.¹⁸ reported that 46% of the cases had Sarnat stage I, 40% had Sarnat stage II while only 14% had stage III. While in the study by Michniewicz et al.,²³ patients were divided into groups according to Sarnat staging: 27 out of 57 (47.4%) met the criteria of a group HIE - A moderate; the rest of them 30 out of 57 (52.6%) were classified as cases of severe HIE.

In the current study, 39.6% of neonates required ventilation, 41.7% needed inotropes, and 27.1% of cases expired out.

In agreement with Yellanthoor and Rajamanickam,¹³ mechanical ventilation was needed in 20 (35.1%) neonates, inotropic support in 19 (33.3%) neonates, and 6 cases (10.5%) were non-survivors. In contrast to Bruckmann et al.²⁴ who reported the incidence of asphyxia was between 8.7 and 15.2 per 1000 live births, and moderate to severe HIE was seen in 60% of cases. The overall mortality rate was 7.8%, with mortality rates of 7.1% in moderate and 62.5% in severe HIE cases.

Cardiac troponin TnT level in our study was significantly higher in neonates with myocardial dysfunction, and other echo findings showed no statistical difference in troponin level.

In the same way, Joseph et al.¹⁶ reported that the mean cTnT value in birth asphyxia was 0.207 ± 0.289 ng/mL with significant difference in the mean cTnT values between asphyxiated neonates with and without myocardial dysfunction. However, Yellanthoor and Rajamanickam¹³ reported that the median cTnT level showed an increasing trend with the increase in changes in echocardiography (p = 0.002).

In the current study, increasing severity of HIE showed increasing troponin T level significantly from stage I to stage II to stage III, which is in the same line with Yellanthoor and Rajamanickam,¹³ who reported that neonates who had HIE stage III had significantly higher levels of cTnT levels when compared to neonates with HIE stage I and II (p = 0.013).

Similarly, Yellanthoor and Rajamanickam¹³ reported that cTnT levels were significantly higher in neonates requiring inotropic support. Moreover, median cTnT levels were comparatively higher in the six neonates who succumbed.

Our results showed a significant negative correlation between cardiac troponin T and (Apgar score at 5^th &10^th minutes and PH of the cord blood). However, there was no statistically significant correlation between cardiac troponin T and (gestational age, maternal age, Apgar score at 1st min, CO₂, or HCO₃).

This goes in agreement with Mahmoud et al,¹⁹ who reported that there was a highly significant negative correlation between cTnT and the Apgar score in the asphyxiated group (p < 0.001). There was a highly significant negative correlation between cTnT and pH (r = −0.6, p < 0.001), HCO3 (r = −0.6, p < 0.001), and a highly significant positive correlation between cTnT and PaCO2 (r = 0.7, p < 0.001).

Using ROC analysis to evaluate the effectiveness of cardiac troponin T in identifying myocardial dysfunction, yielding AUC values of 0.966 and 0.944 (p<0.001). At a cutoff of >0.18 ng/mL, sensitivity was 86.7% and 85.7%, with specificity at 91.1% and 88.2%, respectively. The analysis also assessed cardiac troponin T’s ability to identify HIE cases requiring inotropic support and mortality, showing AUC values of 0.955 and 0.973 (p<0.001). For cutoffs of >0.15 ng/mL and >0.18 ng/mL, sensitivity was 84.2% and 92.3%, respectively, and specificity was 93.1% and 89.1%.

This was in agreement with Joseph et al.¹⁶ reported that the sensitivity of cTnT in diagnosing myocardial dysfunction (gold standard as echocardiography and cutoff cTnT as 0.1 ng/mL) was 92.4%; specificity 74.5%. Using ROC curve analysis, cutoff cTnT of 0.11 ng/mL, increased the specificity to 94.1% with sensitivity remaining at 92.4%. Using ROC curve analysis, a cutoff cTnT of 0.13 ng/mL had 83.6% sensitivity and 94.3% specificity for diagnosing clinical shock. For mortality, a cutoff cTnT of 0.25 ng/mL had a sensitivity of 83.9% and specificity of 96.6 %. For severe HIE (HIE 3), a sensitivity of 81.6% and specificity of 91.5% with a cutoff cTnT of 0.188 ng/mL was found.

While in the study by Sweetman et al.,⁹ they reported that troponin T levels on days 1, 2, and 3 were highly significant predictors of mortality (AUC = 0.99, 0.99, and 0.99; p = 0.005, 0.005, and 0.02, respectively). The cutoff values of troponin T for best prediction of mortality were 0.84 ng/mL, 0.63 ng/mL, and 0.58 ng/mL on days 1, 2, and 3, respectively.

Limitation

Limited number of cases, lack of healthy controls and serial monitoring of cardiac troponin T values was not done.

Conclusions

Cardiac troponin T increased significantly with severity of HIE and correlated negatively with Apgar score. In addition, cardiac troponin T demonstrates good sensitivity to predict myocardial dysfunction and mortality in asphyxiated neonates. So, it may be a candidate for a biomarker panel to aid outcome prediction, but requires validation in larger multicenter studies.

Footnotes

ORCID iDs

Eman Rateb Abd Almonaem

Dina Saad Abdelmotaleb

Author contributions

EGA, ERA, and DSA conceived and supervised the study; MAA was responsible for data collection and analyzed and interpreted the data. All authors provided comments on the manuscript at various stages of development. All authors read and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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