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 Table of Contents  
ORIGINAL ARTICLE
Year : 2017  |  Volume : 30  |  Issue : 3  |  Page : 108-119

Short-term prognostic value of serum cardiac troponin I levels in neonates with perinatal asphyxia


Department of Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt

Date of Submission12-Dec-2017
Date of Acceptance06-Jan-2018
Date of Web Publication20-Apr-2018

Correspondence Address:
Bahaa S Hammad
Director of NICU, Alexandria University, 55 Port Saied Street, El-Shatby, Alexandria 01666
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/AJOP.AJOP_3_18

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  Abstract 


Background Neonatal hypoxic–ischemic encephalopathy (HIE) is a neonatal brain injury caused by perinatal asphyxia and is a major cause of neonatal morbidity and mortality. Cardiac dysfunction forms a part of the clinical spectrum of multiorgan dysfunction in asphyxiated newborns. The more cardiac dysfunction the patients have, the more severe encephalopathy they would suffer. Cardiac troponin I (cTnI) is one of neonatal HIE-related biomarkers that can aid the diagnosis of perinatal asphyxia and anticipate the severity of associated myocardial dysfunction.
Aim The current study was designed to assess the serum cTnI concentration and to evaluate its short-term prognostic value in newborns with HIE.
Patients and methods The present study is a prospective observational study conducted on 100 full-term newborn infants in the period from May 2016 to May 2017. Enrolled newborns were divided into two groups: the case group (50 full-term newborn infants with evidence of perinatal asphyxia) and the control group (50 full-term newborn infants without evidence of perinatal asphyxia). Quantitative estimation of serum cTnI concentrations was done in all enrolled newborns within 12 h of birth using direct chemiluminometric technology performed on ADVIA Centaur Immunoassay System (TnI-Ultra). Serum levels of creatine kinase-MB (CK-MB) were also measured to assess its sensitivity and specificity as a marker of perinatal asphyxia. Additionally, echocardiography was done to exclude structural heart diseases. Left ventricular fractional shortening (LVFS) was also measured to assess cardiac involvement.
Results Serum concentrations of cTnI were statistically significantly higher among the case group when compared with the control group. Additionally, serum levels of cTnI were found to increase with increasing severity of HIE. Serum levels of CK-MB were also statistically higher among the case group. However, pairwise statistical comparison of serum CK-MB concentrations in different stages of HIE revealed no statistical significant difference. No statistical significant difference was found between the two studied groups regarding LVFS. Moreover, LVFS did not differ significantly between the different stages of HIE. Among the different markers of myocardial dysfunction assessed in the current study, cTnI was found to be the most sensitive and specific predictor of poor short-term outcome in newborns with perinatal asphyxia. When comparing serum concentrations of cTnI and CK-MB in both surviving and nonsurviving newborns in the asphyxia group, it was found that serum concentrations of cTnI were statistically significantly lower in the group of survivors. In contrast, there was no statistical significant difference regarding serum concentrations of CK-MB between surviving and nonsurviving asphyxiated newborns.
Conclusion Serum concentrations of cTnI were elevated in asphyxiated newborns with respect to healthy infants and increase with increasing severity of HIE. cTnI can also be used as an excellent early predictor of mortality in newborns with perinatal asphyxia.

Keywords: cardiac troponin I, creatine kinase-MB newborn, hypoxic–ischemic encephalopathy


How to cite this article:
Gouda MH, Hammad BS, Amen MA. Short-term prognostic value of serum cardiac troponin I levels in neonates with perinatal asphyxia. Alex J Pediatr 2017;30:108-19

How to cite this URL:
Gouda MH, Hammad BS, Amen MA. Short-term prognostic value of serum cardiac troponin I levels in neonates with perinatal asphyxia. Alex J Pediatr [serial online] 2017 [cited 2018 May 25];30:108-19. Available from: http://www.ajp.eg.net/text.asp?2017/30/3/108/230765




  Introduction Top


Hypoxic–ischemic encephalopathy (HIE) following perinatal asphyxia has an incidence of 1–2/1000 live births in the western world and is far more common in developing countries [1],[2]. Despite the significantly better appreciation of higher fetal and neonatal vulnerability in the perinatal period, increased availability of trained personnel, and widespread acceptance of the Neonatal Resuscitation Program offered by the American Academy of Pediatrics, birth asphyxia is still one of the leading causes of perinatal mortality and morbidity [3],[4],[5]. According to estimates, of the ∼130 million births worldwide each year, four million infants will suffer from birth asphyxia, and of these, one million will die and a similar number will develop serious and long-term sequelae including neurodevelopmental disorders [6]. Approximately 15–20% of affected newborns will succumb within the neonatal period, and an additional 25–30% will develop severe and permanent neurological handicaps, including cerebral palsy, seizures, visual defects, mental retardation, cognitive impairment, and epilepsy [7].

Cardiac dysfunction forms a part of the clinical spectrum of multiorgan dysfunction in asphyxiated newborns. Some authors found that the more cardiac dysfunction the patients have, the more severe encephalopathy they would experience. They also suggested that myocardial dysfunction secondary to severe birth asphyxia will lead to loss of cerebral autoregulation with subsequent severe encephalopathy [8]. Therefore, early cardiovascular assessment in asphyxiated newborns will allow more rapid detection of cardiac dysfunction and allow early initiation of inotropic support along with neuroprotective measures. This may preserve cardiac function and decrease morbidity and mortality in these infants [9]. Because any form of intervention would likely be most effective in the first 6 h after onset of hypoxic–ischemic insults, it is important to find rapid, cheap, early, and reliable indicator of perinatal asphyxia that will help to determine when to initiate neuroprotective treatment.

Cardiac troponin complex is a tadpole-shaped structure of three protein subunits that regulate interaction between actin and myosin and interact strongly with each other: the Ca2+-binding troponin C (TnC), the tropomyosin-binding troponin T, and the inhibitory troponin I (TnI) subunits [10]. Muscle contraction is initiated by an increase in the intracellular free Ca2+ which is released from the sarcoplasmic reticulum. The conformational changes associated with the binding of Ca2+ to the regulatory sites of the TnC subunit of troponin provide a signal, which is relayed via other thin-filament proteins. This signal ultimately provides an increase in myosin (thick filament) cross-bridge attachment to actin, an increase in actomyosin ATPase, and an increase in tension development in the muscle fiber [11]. Troponin I (TnI) is part of the troponin complex. It binds to actin in thin myofilaments to hold the actin–tropomyosin complex in place. Myosin cannot bind actin in relaxed muscle because of troponin I’s positioning on actin, and hence, muscle contraction is prevented. The letter I is given because of its inhibitory character [12]. Troponin I exists in three distinct isoforms: cardiac muscle, slow-twitch skeletal muscle, and fast-twitch skeletal muscle [13]. Each isoform is encoded by a distinct gene, each with a unique amino acid sequence, leading to 40% dissimilarity among these isoforms [14]. The cardiac form of troponin I is further unique in having 31 additional amino acid residues on its N-terminal, not present in the skeletal forms, which allows for specific polyclonal and monoclonal antibody development [15]. The cardiac specificity of this isoform improves its diagnostic accuracy in patients with acute or chronic skeletal muscle injury and possible concomitant myocardial injury, and is the basis for its selection as a cardiac marker in the diagnosis of acute myocardial injury [16].

Cardiac troponin I (cTnI) as one of neonatal HIE-related biomarkers can aid the diagnosis of neonatal HIE and can anticipate the severity of associated myocardial dysfunction. Additionally, there is some evidence that cTnI can also be used as a reliable early predictor of poor outcome in newborns with perinatal asphyxia [17]. This would allow earlier initiation of intervention measures to improve neonatal survival and reduce the degree of brain injury.


  Aim Top


This study was designed to assess the serum cTnI concentration and to evaluate its short-term prognostic value in newborns with HIE.


  Patients and methods Top


This is a prospective case–control study conducted in the NICU of El Shatby Children Hospital, Alexandria, Egypt, from May 2016 till May 2017. Fifty full-term newborn infants with perinatal asphyxia were assigned to the asphyxia group and 50 nonasphyxiated healthy gestational age and postnatal age-matched neonates were enrolled in the study comprising the control group. Asphyxiated newborns were further classified as mild (grade I), moderate (grade II), or severe (grade III) HIE based on the criteria described by Sarnat and Sarnat [18]. Short-term outcome of these infants in terms of mortality or survival to discharge was also evaluated.

Ethical approval for the study was obtained from the Ethical Review Committee, Alexandria University, Egypt. Moreover, an informed written consent was obtained from the parents.

Detailed maternal, obstetric, and perinatal history was reviewed thoroughly for all participants.

Thorough clinical examination was done for all participants with special emphasis on the neurological status and neonatal encephalopathy grade according to the criteria described by Sarnat and Sarnat.

Quantitative estimation of cTnI levels was done for all participants using direct chemiluminometric technology performed on ADVIA Centaur Immunoassay System (TnI-Ultra; Siemens Medical Solutions Diagnostics, USA). In addition, serum concentrations of creatine kinase-MB (CK-MB) were also measured.

Echocardiographic examination was performed within 24 h of life with a 3–8 MHz probe (HD 11 XE machine; Philips, Yorba Linda, USA) to exclude major structural heart diseases. Left ventricular fractional shortening (LVFS) was obtained using M mode in long-axis parasternal view at mitral valve level. The presence of mitral or tricuspid regurgitation was also evaluated. Additionally, the diameter of inferior vena cava (IVC) was also assessed.

Statistical analysis

Data were fed to the computer and analysed using SPSS software package version 21.0, IBM Corp., Armonk, NY. Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum) mean, SD, and median. Significance of the obtained results was judged at the 5% level. The used tests were χ2-test, Monte Carlo correction, post-hoc test, Mann–Whitney U-test, and Kruskal–Wallis test.


  Results Top


[Table 1] presents the analysis of the demographic data of the two studied groups and shows no statistical significant differences between the studied groups regarding sex and gestational age. However, birth weight was found to be significantly higher among the control group.
Table 1 Demographic data of the two studied groups

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[Table 2] shows the differences between the two studied groups regarding delivery room data. No statistical significant difference was encountered between both groups regarding mode of delivery. Within the asphyxiated group, 30% were born through meconium-stained liquor, whereas in the remaining 70% the liquor was clear. Regarding resuscitation data, it was found that 86% of newborns within the asphyxiated group needed positive pressure ventilation, whereas the remaining 14% needed initial steps of resuscitation. Statistically significant differences were detected between asphyxiated and healthy newborns regarding Apgar score at 1 and 5 min and cord blood pH and bicarbonate (HCO3) values.
Table 2 Comparison between the two studied groups according to delivery room data

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[Table 3] shows that shock was present in 21.05% of asphyxiated newborns with stage II HIE and in 100% of those with stage III. Additionally, clinical seizures were present in 47.37% of newborns with stage II HIE, whereas in 85.71% of those with stage III. It was also found that 31.58% of newborns with stage II HIE and 100% of those with stage III needed inotropic support and mechanical ventilation within the first 24 h.
Table 3 Clinical data in different stages of hypoxic–ischemic encephalopathy among the asphyxiated group

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[Table 4] shows that serum concentrations of cTnI and CK-MB were statistically higher among the asphyxiated group.
Table 4 Comparison between the two studied groups according to serum concentrations of cardiac troponin I and creatine kinase-MB

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[Table 5] shows that serum cTnI concentrations were statistically different among the three stages of HIE and control group (χ2=80.063, P=0.000). Pairwise statistical comparison revealed that patients with stages II and III HIE had higher levels of cTnI when compared with stage I and control group. Moreover, patients with stage I HIE had higher levels of cTnI when compared with the control group. On the contrary, pairwise statistical comparison of serum CK-MB concentrations in different stages of HIE revealed no statistical significant difference ([Figure 1] and [Figure 2]).
Table 5 Serum cardiac troponin I and creatine kinase-MB concentrations in different stages of hypoxic–ischemic encephalopathy and control group

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Figure 1 Box and whisker graph of serum cardiac troponin I (cTnI) concentration (ng/ml) in control group and different stages of hypoxic–ischemic encephalopathy (HIE): the thick line in the middle of the box represents the median, the box represents the interquartile range (from 25th to 75th percentiles), and the whiskers represent the minimum and maximum after excluding outliers (black-filled circles) and extremes (black asterisks).

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Figure 2 Box and whisker graph of serum creatine kinase-MB (CK-MB) concentration (ng/ml) in control group and different stages of hypoxic–ischemic encephalopathy (HIE): the thick line in the middle of the box represents the median, the box represents the interquartile range (from 25th to 75th percentiles), and the whiskers represent the minimum and maximum after excluding outliers (black-filled circles) and extremes (black asterisks).

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[Table 6] shows that incidences of tricuspid and mitral regurgitation were statistically higher among the case group. No statistically significant difference was encountered between the studied groups regarding fractional shortening (FS). IVC diameter was statistically higher among the case group ([Figure 3]).
Table 6 Comparison between the two studied groups according to echocardiographic findings

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Figure 3 Scatter plot graph with regression line shows significant negative correlation between serum cTnI and fractional shortening (FS) among asphyxiated newborns.

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[Table 7] shows that cTnI and CK-MB are statistically significant discriminators of occurrence of HIE. In contrast, FS is not a statistically significant discriminator of occurrence of perinatal asphyxia ([Figure 4]).
Table 7 Diagnostic test accuracy comparison between cardiac troponin I, creatine kinase-MB and fractional shortening as discriminators of occurrence of hypoxic–ischemic encephalopathy

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Figure 4 Pairwise comparison of receiver operating characteristic curves of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) as discriminators of occurrence of hypoxic–ischemic encephalopathy.

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[Table 8] shows that cTnI was a statistically significant discriminator of occurrence of death among asphyxiated neonates. In contrast, CK-MB and FS were not statistically significant discriminators of death occurrence in asphyxiated newborns.
Table 8 Diagnostic test accuracy comparison between cardiac troponin I and other markers of myocardial dysfunction in discrimination of death occurrence among asphyxiated neonates

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[Table 9] shows statistically higher cTnI concentrations in the nonsurviving asphyxiated newborns when compared with the survivors. In contrast, there was no statistically significant difference regarding serum concentrations of CK-MB between the two groups ([Figure 5]).
Table 9 Differences between survivors and nonsurvivors in the asphyxiated group regarding serum concentrations of cardiac troponin I and creatine kinase-MB

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Figure 5 Scatter plot graph with regression line shows significant positive correlation between serum cardiac troponin I concentrations (cTnI) and duration of hospital stay among asphyxiated newborns (deaths were excluded).

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  Discussion Top


In the present study, no statistically significant differences were encountered between the two studied groups regarding gestational age and sex. However, birth weight was found to be higher among the control group (P=0.000). This may be attributed to higher prevalence of uteroplacental insufficiency among asphyxiated newborns. On the contrary, Jain et al. [19] found significantly higher birth weight in perinatal asphyxia group (P<0.05). They attributed this difference in birth weight between both groups to higher possibility of obstetric complications among larger sized newborns.

Delivery room data of both studied groups are demonstrated in [Table 2]. It was found that 30% of newborns within the case group were born through meconium-stained liquor, whereas in the remaining 70% the liquor was clear. Higher incidence of meconium-stained liquor was reported in the study of Jain et al. [19] and Martin-Ancel et al. [20], where the authors documented an incidence of 42%. Different sample sizes may explain the different incidences of meconium-stained liquor among our study and the others.

Regarding resuscitation data, it was found that 14% of newborns within the asphyxiated group needed initial steps of resuscitation, whereas 86% of the cases required positive pressure ventilation either through self-inflating bag or endotracheal tube. In the present study, no one needed chest compression during resuscitation.

Umbilical cord blood pH and bicarbonate were significantly lower in the case group in comparison with the control group (P=0.000) for both. Similar findings were also documented by Trevisanuto et al. [21], who found that arterial umbilical pH and bicarbonate were significantly lower among asphyxiated newborns (P<0.01). Moreover, a statistically significant difference was detected between the two studied groups regarding the 1 and 5 min Apgar score, which were lower in the case group in comparison with the control group (P=0.000) for both.

Clinical characteristics of asphyxiated newborns are demonstrated in [Table 3]. Newborns enrolled in the case group were classified to have stage I, II, or III HIE based on the criteria described by Sarnat and Sarnat [18]. Of the overall 50 HIE cases, 24 (48%) infants were in stage I, 19 (38%) in stage II, and 7 (14%) in stage III.

Of the overall 50 HIE cases, shock was present in 22%. It was detected in 21.05% of asphyxiated newborns with stage II HIE and in 100% of those with stage III. This is somewhat different from what was reported by Jain et al. [19] and Rajakumar et al. [22], who documented the presence of shock in 16.7 and 41.93% of the cases, respectively. Additionally, clinical seizures were present in 47.37% of newborns with stage II HIE, whereas in 85.71% of those with stage III.

It was also found that asphyxiated newborns with stage I HIE required no inotropic support or mechanical ventilation. However, 31.58% of newborns with stage II HIE and 100% of those with stage III needed inotropic support and mechanical ventilation within the first 24 h. On the contrary, Shastri et al. [23] found that 17, 76, and 95% of asphyxiated newborns with stages I, II, and III, respectively, required inotropic support. They also found that ventilation for more than 12 h was needed in 33, 79, and 95% of asphyxiated newborns with stages I, II, and III, respectively.

Serum cTnI and CK-MB concentrations were statistically higher among the asphyxiated group when compared with the control group. Similar to our results were those of Jain et al. [19], who also reported significantly higher levels of cTnI and CK-MB in asphyxiated neonates compared with controls.

In the current study we have also compared serum cTnI and CK-MB concentrations in different stages of HIE ([Table 5]). It was found that serum cTnI concentrations were statistically significantly different among the three stages of HIE and the control group (χ2=80.063, P=0.000). Additionally, pairwise statistical comparison revealed that patients with stages II and III HIE had significantly higher levels of serum cTnI when compared with stage I and control group. Moreover, patients with stage I HIE had significantly higher levels of cTnI when compared with the control group. Similar findings were also reported by Jain et al. [19].

In the current study, newborns with stage III HIE were found to have higher levels of serum cTnI when compared with those with stage II HIE. However, this difference could not reach a statistical significance. Jain et al. [19], on the contrary, reported a statistically significant difference in serum cTnI concentrations between newborns with stage II and those with stage III HIE (P<0.001). These different findings may be owing to different numbers of infants enrolled in each stage of HIE in both studies.

Serum cTnI concentrations were found to increase with increasing severity of HIE. Median [interquartile range (IQR)] cTnI concentrations were 0.070 ng/ml (0.037–0.070 ng/ml) in stage I HIE, 0.300 ng/ml (0.200–0.300 ng/ml) in stage II HIE, and 0.900 ng/ml (0.500–1.300 ng/ml) in stage III HIE. Similar to our results were those of Shastri et al. [23], Simovic et al. [24], and Jain et al. [19]. They showed that significantly higher levels of cTnI were observed with increasing severity of HIE. Therefore, serum levels of cTnI can be used to predict severity of HIE.

On the contrary, pairwise statistical comparison of serum CK-MB concentrations in different stages of HIE revealed no statistically significant difference. Similar results were reported by Montaldo et al. [25], who stated that no statistically significant difference was found in the levels of CK-MB among different stages of HIE (P>0.05). Additionally, no statistical significance was encountered when newborns with stage III HIE were compared with the control group regarding serum CK-MB concentrations. Therefore, unlike cTnI, CK-MB may not be a reliable indicator of the severity of HIE.

In the current study, echocardiography was performed within the first 24 h of life to provide some comparative cardiac function data. Results of echocardiographic analysis in both studied groups are shown in [Table 6]. It was found that incidences of tricuspid and mitral regurgitation were statistically higher in the case group (P=0.000). Tricuspid regurgitation was present in 66% of asphyxiated newborns. This is more than that reported in the previous studies by Rajakumar et al. [26] and Jain et al. [19], who documented incidences of tricuspid regurgitation in 23.3 and 35.48%, respectively. On the contrary, mitral regurgitation was present in 20% of the cases. This incidence is less than that was documented by Simovic et al. [24] and Jain et al. [19], who observed mitral regurgitation in 27 and 22.6% of the cases, respectively.

FS was not significantly different between the two studied groups (P=0.281). Similar findings were reported by Matter et al. [27], who also found no statistically significant difference between cases and controls regarding FS (P=0.290). On the contrary, Barberi et al. [28] demonstrated lower FS in infants with severe perinatal asphyxia compared with the controls. Additionally, IVC diameter was statistically significantly higher among the case group when compared with the control group (P=0.024).

We also showed a significant negative correlation between cTnI and FS (τ=−0.242; P=0.020). This is in agreement with Simovic et al. [24] and Montaldo et al. [25], who stated that cTnI was negatively correlated with FS (τ=−0.445; P=0.004 and r=−0.64; P<0.05, respectively).

The cutoff values, sensitivity, specificity, and area under receiver operating characteristic (ROC) curves for different markers of myocardial dysfunction as discriminators of occurrence of HIE are demonstrated in [Table 7]. It was found that cTnI and CK-MB were statistically significant discriminators of occurrence of perinatal asphyxia with area under the ROC curve=0.971 [95% confidence interval (CI): 0.917–0.994] (Z=34.727, P<0.0001) and 0.810 (95% CI: 0.720–0.882) (Z=7.405, P<0.0001), respectively.

However, pairwise comparison of receiver operator curves of cTnI and CK-MB revealed that cTnI was the marker with highest sensitivity (88%), specificity (98%), positive predictive value (97.8%), and negative predictive value (89.1%) for prediction of perinatal hypoxia. Using the Youden index (J), we identified serum cTnI concentration of more than 0.03 ng/ml as the optimal cutoff concentration for prediction of myocardial damage among asphyxiated newborns. This in turn can be used as an evidence of occurrence of perinatal asphyxia.

Similarly, Türker et al. [29] reported that cTnI was the most sensitive factor for prediction of perinatal hypoxia compared with CK-MB. They identified cord cTnI concentration of 0.35 ng/ml as the optimal cutoff value for predicting perinatal hypoxia. This was clearly different from the identified cutoff value of cTnI concentration (>0.03 ng/ml) in our study. Such difference may be attributed to the different natures of samples (cord vs. venous blood) and variety of assays used. Türker et al. [29] measured cTnI using AxSYM System (Abbott Lab, Abbott Park, Illinois, USA) with limit of detection of 0.3 ng/ml. On the contrary, we used the ADVIA Centaur TnI-Ultra assay with a minimum detectable concentration of 0.006 ng/ml.

We also revealed that FS was not a statistically significant discriminator of occurrence of HIE with area under the ROC curve=0.563 (95% CI: 0.459–0.662) (Z=1.025, P=0.3053). This was similar to Matter et al. [27], who found that FS had the lowest sensitivity and specificity when compared with other markers of myocardial dysfunction in prediction of occurrence of perinatal asphyxia, with area under the ROC curve=0.170.

Therefore, among different markers of myocardial dysfunction, cTnI was the most sensitive and specific biochemical marker in the detection of ischemic cardiac injury, which in turn can be used as a quite powerful retrospective indicator of birth asphyxia.

Apart from the high sensitivity and specificity of cTnI as a HIE-related biomarker in predicting perinatal asphyxia, the current study also assessed the value of cTnI as a predictor of poor outcome in asphyxiated newborns.

Diagnostic test accuracy comparison between cTnI and other markers of myocardial dysfunction in discrimination of death occurrence among asphyxiated neonates is shown in [Table 8]. It was found that cTnI was the most sensitive discriminator of death occurrence among asphyxiated neonates. Calculated area under the ROC curve was 0.983 (95% CI: 0.899–1.000) (Z=34.420, P<0.0001), and cutoff value for lethal outcome was 0.3 ng/ml with sensitivity of 100%, specificity of 90.70%, positive predictive value of 63.6%, and negative predictive value of 100%. Similar to our results are those of Türker et al. [17], Simovic et al. [24], and Montaldo et al. [25], who all confirmed that cTnI was a very sensitive single parameter in predicting mortality in newborns with perinatal asphyxia. In the current study, we also found a significant positive correlation between serum cTnI levels and duration of hospital stay among asphyxiated newborns after exclusion of those who died (τ=0.650; P=0.0008). This may reflect the more severe clinical course in asphyxiated newborns with high serum levels of cTnI, a finding that also supports the importance of cTnI as a marker with reliable short-term prognostic value in newborns with perinatal asphyxia.Unlike cTnI, levels of CK-MB were not statistically significant discriminators of death occurrence among asphyxiated neonates with area under the ROC curve=0.623 (95% CI: 0.475–0.756) (Z=1.049, P=0.2942). This is in agreement with recently published reports, which showed that CK-MB is both less specific and less sensitive in detecting cardiac involvement and in the prediction of poor outcome in asphyxiated neonates [24],[26],[30].

The current study also revealed that FS was not a statistically significant predictor of mortality in newborns with perinatal asphyxia with area under the ROC curve of 0.631 (95% CI: 0.528–0.726) (Z=1.028, P=0.3040). Kanik et al. [31] and Matter et al. [27] also reported similar results.

On the contrary, Simovic et al. [24] demonstrated that standard echocardiographic parameters of myocardial damage, such as FS, do have a statistically significant predictive value for mortality outcome in neonates with perinatal asphyxia.

In the present study, comparison between surviving and nonsurviving asphyxiated newborns regarding serum concentrations of cTnI and CK-MB is demonstrated in [Table 9]. It was found that serum concentrations of cTnI were statistically significantly lower in the group of asphyxiated neonates who survived compared with the group with lethal outcome. The median value of serum cTnI in the surviving group was 0.08 ng/ml (IQR: 0.06–0.30 ng/ml) compared with 0.90 ng/ml (IQR: 0.50–1.30 ng/ml) in the group of asphyxiated neonates who died (P=0.000). In contrast, there was no statistically significant difference regarding serum concentrations of CK-MB between the two groups (P=0.308). Similar findings were also reported by Shastri et al. [23] and Simovic et al. [24].

Our study has several limitations. Being a prospective study; it could not assess the effect of whole-body therapeutic hypothermia on serum concentrations of cTnI because of ethical issues. Therefore, our limited data are insufficient to either show or exclude the possibility of beneficial effects of cooling on cardiac protection. However, data to support the cardioprotective effects of therapeutic hypothermia in neonates may come indirectly from further studies in adults and animal models, and possibly directly from retrospective reviews of cTnI concentrations in the historical large randomized controlled studies of therapeutic hypothermia for neuroprotection. Another limitation is that the left ventricular function has been studied by LVFS. Although LVFS is easily measured, it does not assess the entire left ventricular function. More sophisticated examinations, such as Doppler tissue imaging, are more relevant and should be mandatory.


  Conclusion Top


It could be concluded that cTnI is the most sensitive and specific biochemical marker in the detection of ischemic cardiac injury in asphyxiated newborns, which in turn can be used as a quite powerful retrospective indicator of birth asphyxia.

Acknowledgements

This study was approved by Medical Research Ethics Committee at Alexandria Faculty of Medicine, and an informed consent was obtained from children’s guardians.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9]



 

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