|Year : 2013 | Volume
| Issue : 2 | Page : 145-150
Cardiac troponin I as an early predictor of perinatal asphyxia
Ahmed T Mahmoud1, Maha El-Bassuny2, Ayat Shebl3
1 Department of Pediatrics, Menoufia University, Shebin El Kom, Egypt
2 Department of Clinical Pathology, Menoufia University, Shebin El Kom, Egypt
3 Neonatal Intensive Care Unit, El-Ahrar Zagazig General Hospital, Zagazig, Sharqia, Egypt
|Date of Submission||20-Feb-2013|
|Date of Acceptance||15-Jul-2013|
|Date of Web Publication||31-Jan-2014|
Elmahad Eldini St, Building 2, Zagazig, Sharqia
Source of Support: None, Conflict of Interest: None
The objective of this study was to test the hypothesis that cardiac troponin I (cTnI), a known marker of myocardial injury, is also an early predictor of both severity and mortality in cases of perinatal hypoxia.
Delivery is a stressful and risky event that poses a risk to newborns. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply, compromising the survival and development of the central nervous system.
The outcomes of perinatal asphyxia are devastating and permanent, making it a major burden for the patient, the family, and society. Thus, there has been considerable focus on the early identification of newborns exposed to perinatal asphyxia and development of therapeutic strategies to reduce long-term morbidity and mortality.
Troponin is an inhibitory protein complex located on the actin filament in all striated muscles and consists of three subunits: T, C, and I.
cTnI was measured as an indicator of cardiac injury for a long time, but it has been of interest for the prediction of poor neonatal outcome in perinatal asphyxia.
Aim of the study
The aim of this work was to test the hypothesis that cTnI, a known marker of myocardial injury, is also an early predictor of both morbidity and mortality in cases of perinatal hypoxia.
Materials and methods
This study was carried out between October 2011 and June 2012. It included 40 neonates with perinatal asphyxia admitted to the neonatal ICU, El-Ahrar Zagazig General Hospital. Twenty healthy neonates matched for both age and sex were selected randomly as a control group. Blood samples were collected from the two study groups. cTnI was measured in relation to neurological sequelae, and deaths in both the groups were also evaluated.
The mean cTnI of asphyxiated neonates was 4.6 4.4 ng/ml, significantly higher than that of the control neonates, which was 0.55 0.6 ng/ml. This difference was statistically significant.
cTnI was markedly increased in perinatal asphyxia. This was related to the severity of perinatal asphyxia. It can also be used as an early predictor of neonatal morbidity and mortality in perinatal asphyxia.
Keywords: Perinatal asphyxia, predictor, troponin I
|How to cite this article:|
Mahmoud AT, El-Bassuny M, Shebl A. Cardiac troponin I as an early predictor of perinatal asphyxia. Menoufia Med J 2013;26:145-50
| Introduction|| |
Perinatal asphyxia is a well-recognized clinical entity that obstetricians and neonatologists encounter almost daily  .
The outcome of perinatal asphyxia depends on the severity of hypoxia  . Perinatal asphyxia and its complications are one of the main causes of death and permanent disability , .
Although asphyxia is associated with multiple organ injuries, especially adverse neurological outcomes, management still focuses on supportive care. Therefore, if the adverse effects of hypoxia on the newborn are considered, there is a need to identify infants who will be at high risk of hypoxic ischemic encephalopathy and early neonatal death as a consequence of perinatal hypoxia. A variety of markers have been examined to identify perinatal hypoxia, including electronic fetal heart monitoring, low Apgar scores, cord pH, electroencephalograms, computed tomography and MRI scans, and Doppler flow studies. Among these markers, a best predictor has not been determined and this situation has led researchers to investigate other tests  .
Troponin is an inhibitory protein complex located on the actin filament in all striated muscles and consists of three subunits: T, C, and I , .
Cardiac troponin I (cTnI) was measured as an indicator of cardiac injury for a long time, but it has been of interest for the prediction of poor neonatal outcome in perinatal asphyxia  .
cTnI is the subunit that inhibits actinomyosin ATPase activity, thereby preventing muscle contraction in the absence of Ca 2+  and blocking the formation of actin-myosin bridges. It is also considered a highly specific indicator of myocardial injury in adults. cTnI is released into the bloodstream after myocardial damage and for this reason, cTnI has been used as a marker of myocardial injury. cTnT and cTnI have been proposed to be biochemical indices of myocardial injury in neonates with asphyxia, respiratory distress syndrome (RDS), and septic or cardiogenic shock. Although the half-life of cTnI is relatively short (90 min), its diagnostic time range is unusually wide (ranging from a few hours to 10-14 days after the episode of myocardial injury)  .
| Aim of the study|| |
The aim of this work was to test the hypothesis that cTnI, a known marker of myocardial injury, is also an early predictor of both morbidity and mortality in cases of perinatal hypoxia.
| Materials and methods|| |
This study was carried out on 40 neonates with perinatal asphyxia admitted to the neonatal ICU, El-Ahrar Zagazig General Hospital. Twenty healthy neonates were selected from the outpatient clinic as a control group. This study has been approved by ethical committee, informed consent have been taken from the caregiver of the included patients.
Inclusion criteria that aid the diagnosis of perinatal asphyxia
The inclusion criteria were as follows: profound metabolic or mixed acidemia (pH < 7.00) in an umbilical artery blood sample, if obtained; persistence of an Apgar score of 0-3 for longer than 5 min; neonatal neurologic sequelae (e.g. seizures, coma, and hypotonia); and multiple organ involvement (e.g. the kidney, lung, liver, heart, and intestines).
All neonates in this study were subjected to meticulous assessment of history and a thorough clinical examination. Relevant data were obtained from previous records and a clinical examination was carried out for gestational age, birth weight, sex, mode of delivery, risk factors, Apgar score, and neonatal resuscitation.
Laboratory investigations included complete blood count, C-reactive protein, serum electrolytes, kidney function tests, arterial blood gases, cTnI, and cranial sonar, which were carried out in both the groups studied.
All data were tabulated and processed using the standard statistical program.
| Results|| |
In the present study, there was no significant difference between the studied groups in sex [Figure 1]. The mean gestational age of asphyxiated neonates (38.4 ± 2.5 weeks) was significantly higher than that of the healthy control neonates (35.8 ± 3.2 weeks). The mean body weight of asphyxiated neonates (3.3 ± 0.66 kg) was significantly higher than that of healthy control neonates (2.7 ± 0.5 kg). The mean age of asphyxiated neonates (1.63 ± 0.76 days) was not significantly different from that of healthy control neonates (2.1 ± 1.0 days).
There was no significant difference between both the studied groups in the mode of delivery [Figure 2].
The mean Apgar scores at 1 and 5 min were significantly lower among asphyxiated neonates (4.7 ± 1.76 and 7.0 ± 1.6, respectively) than those among the healthy control neonates (8.0 ± 1.1 and 9.0 ± 0.75, respectively).
There were highly significant differences between the two studied groups in tachycardia, bradycardia, tender liver, tachypnea, lung crepitations, poor reflexes, decreased consciousness, convulsions, and hypotension. There was a significant difference between the two studied groups in cyanosis and bleeding.
Mean nucleated red blood cells (NRBCs)/100 white blood cells (WBCs) and WBCs × 10 3 /mm 3 of asphyxiated neonates (19.79 ± 11.8/100 WBCs, 14.7 ± 9.9 × 10 3 /mm 3 , respectively) were significantly higher than that of the healthy control neonates (4.2 ± 2.0/100 WBCs, 3.4 ± 1.6 × 10 3 /mm 3 , respectively). Mean RBCs of asphyxiated neonates (4.1 ± 1.3 × 10 6 /mm 3 ) were significantly lower than that of the healthy control neonates (5.2 ± 1.9 × 10 6 /mm 3 ). There was no significant difference between the two studied groups in the platelets count (patients 193 ± 91.9 × 10 3 /mm 3 , controls 186.1 ± 60.5 × 10 3 /mm 3 ).
The mean pH and mean PaO2 of asphyxiated neonates (7.2 ± 0.3 and 78.33 ± 28, respectively) were significantly lower than that of the healthy control neonates (7.3 ± 0.1 and 96.3 ± 2.2, respectively). The mean PaCO2 of asphyxiated neonates (47.6 ± 18.0) was significantly higher than that of the healthy control neonates (36.1 ± 2.9). There was no significant difference between the two studied groups in HCO3 (patients 15.1 ± 4.5, controls 17.1 ± 4.9).
The mean sodium level of asphyxiated neonates (129.6 ± 7.2 mEq/l) was significantly lower than that of the healthy control neonates (134.3 ± 6.3 mEq/l); the mean urea and mean creatinine of asphyxiated neonates (26.2 ± 19.2 mmol/l and 0.88 ± 0.36 mg/dl, respectively) were significantly higher than that of the healthy control neonates (12.1 ± 3.9 mmol/l and 0.66 ± 0.2 mg/dl, respectively). There was no significant difference between the two studied groups in potassium level (patients 4.4 ± 0.75 mEq/l, controls 4.5 ± 1.0 mEq/l).
The mean cTnI of asphyxiated neonates (4.6 ± 4.4 ng/ml) was significantly higher than that of the healthy control neonates (0.55 ± 0.6 ng/ml) [Figure 3]. There was no significant correlation between cTnI and gestational age, weight, and age in the asphyxiated group (P > 0.05). There was a highly significant negative correlation between cTnI and the Apgar score in the asphyxiated group (P < 0.001).
There was a highly significant positive correlation between cTnI and NRBCs (r = 0.73, P < 0.001). There was a significant negative correlation between cTnI and both RBCs (r = −0.38, P < 0.001) and platelet count (r = −0.37, P < 0.05). There was no significant correlation between cTnI and WBCs count (r = −0.21, P > 0.05).
There was a highly significant negative correlation between cTnI and pH (r = −0.6, P < 0.001), PaO2 (r = −0.52, P < 0.001), HCO3 (r = −0.6, P < 0.001). There was a highly significant positive correlation between cTnI and PaCO2 (r = 0.7, P < 0.001).
There was a highly significant relation between serum cTnI level and neonatal outcome in the asphyxiated group. Worse outcome was associated with higher serum level of cTnI.
There was a significant relation between cTnI serum level and cranial ultrasound findings in the asphyxiated group. The appearance of severe cerebral lesions on cranial ultrasound was associated with a higher level of cTnI.
| Discussion|| |
There was no significant difference between the asphyxiated group and the control group in sex and age.
In the present study, 77.5% of the asphyxiated neonates were full term. Although 22.5% were preterm, this is in agreement with Szymankiewiez et al.  , who found that the incidence of perinatal asphyxia is more common in full term (38.8 ± 1.3 gestational weeks). In contrast, Nicoletta et al.  found that the incidence of perinatal asphyxia is higher in neonates less than 36 weeks of gestational age and in intrauterine growth-restricted pregnancies. Also, Clark et al.  found that perinatal asphyxia is more common in preterm babies with RDS rather than in full term.
There was a significant difference between group I (asphyxiated neonates) and group II (control) in the weight of the studied neonates; this can be attributed to the higher incidence of macrosomic babies in perinatal asphyxia. This was in agreement with Gomella et al.  , who found that macrosomia of babies with traumatic delivery is one of the major risk factors for development of perinatal asphyxia.
During the neurological examination of our patients, poor reflexes, convulsions, and depressed level of consciousness were found by their order of frequencies, with a highly significant difference between them and the control group.
This is in agreement with Tόrker et al.  , who reported that neurological disorders in a newborn may be primary or secondary in origin, and cerebral hypoxia is a very important factor. Also, a study carried out by Groenendaal et al.  supported our results as they reported that the central nervous system was the most frequently involved (72%) system in asphyxiated neonates.
In group I, 95% presented with tachypnea, 35% with lung crepitations, and 25% with bleeding tendency. This incidence of respiratory complications was higher than that reported by Distefano et al.  , who reported pulmonary involvement in 30% of the asphyxiated newborns studied in the form of RDS and persistent pulmonary hypertension. They also found that bleeding tendency occurred in 29% of the neonates studied because of a shortened lifespan of platelets and development of necrotizing enterocolitis.
In this study, the incidence of tachycardia was higher in asphyxiated neonates (70%) compared with the incidence of bradycardia (20%), and this was in agreement with Gomella et al.  , who found that birth asphyxia may be associated with tachycardia with hypotension because of cardiogenic shock.
Routine laboratory studies showed that there was a highly significant difference between asphyxiated infants and the control group in NRBCs and WBCs. This was in agreement with Boskabadi et al.  , who found that the NRBC/100 WBC and absolute NRBC levels in the blood of newborns in the control group were 3.87 ± 5.06 and 58.21 ± 87.57/mm 3 , respectively, whereas the corresponding values in the asphyxiated neonates were 18.63 ± 16.63 and 634.04 ± 1002/mm 3 , respectively (P < 0.001). They found a statistically significant negative correlation between NRBC level and indicators of the severity of perinatal asphyxia, first minute Apgar score, and blood pH (P < 0.001), respectively. A positive correlation was found between these parameters and the severity of asphyxia, acidosis, and poor outcome (P < 0.05).
In the present study, in terms of cTnI serum levels, a very low level of cTnI was found in healthy neonates (mean = 0.55 ng/ml), which was elevated significantly in asphyxiated neonates (mean = 4.6 ng/ml).
This is in agreement with David and Collinson  , who reported that healthy neonates had undetectable levels of cTnI. Trevisanuto et al.  also found a low level of cTnI in healthy neonates compared with sick infants with perinatal asphyxia. This is also in agreement with Tόrker et al.  , who found that cTnI was significantly higher in asphyxiated neonates than in healthy neonates.
There were no significant correlations between the serum level of cTnI and gestational age, postnatal age, and birth weight, but there was a highly significant correlation with Apgar score at 1 and 5 min. This is in agreement with Tόrker et al.  , who found no correlation between cTnI and gestational age and birth weight, and a negative significant correlation with Apgar score. However, in contrast to our study, Trevisanuto et al.  found no statistically significant correlations in asphyxiated neonates, between concentrations of cTnI and 1-min Apgar score (r = 0.23, P = 0.45), 5-min Apgar score (r = 0.33, P = 0.28), and between cTnI concentrations and birth weight or gestational age.
The results of the present study indicate that there was a significant positive correlation between PaCO2 and cTnI level in asphyxiated neonates; this reflects the effect of perinatal insult in the development of CO2 retention and acidosis, therefore increasing the risk of myocardial injury and subsequently resulting in a higher cTnI serum level. This differs from the results of Trevisanuto et al.  , who found no correlation between cTnI and pH and HCO3.
In our study, there was a highly significant correlation between cTnI and neonatal outcome in the asphyxiated group; this is in agreement with Caliskan et al. , who found a significant relation between the levels of cTnI and neonatal outcomes.
There was a highly significant relation between the concentration of cTnI and cranial ultrasound findings in asphyxiated neonates.
| Conclusion|| |
This study found that a cTnI level of 1.3 ng/ml can be used to predict neonatal morbidity and mortality in perinatal asphyxia [Figure 4] [Table 1],[Table 2],[Table 3],[Table 4] and [Table 5].
|Table 4: Correlation between cardiac troponin I and arterial blood gases in asphyxiated groups|
Click here to view
|Table 5: Cardiac troponin I level in relation to neonatal outcome in the asphyxiated group|
Click here to view
[Figure 4] Receiver operating characteristic (ROC) graph to discriminate the sensitivity and specificity of cardiac troponin I with a cut-off point of 1.3 ng/ml in the diagnosis of perinatal asphyxiated infants. Area under the curve: 0.951 (0.897−1.004).
| Acknowledgements|| |
Conflicts of interest
| References|| |
|1.||Chnayna J, Truttmann A. Perinatal asphyxia and neonatal hydronephrosis. Rev Med Suisse 2010; 6 :63-66. |
|2.||Nagdyman N, Komen W, Ko HK, Muller C, Obladen M. Early biochemical indicators of hypoxic-ischemic encephalopathy after birth asphyxia. Pediatr Res 2001; 49 :502-506. |
|3.||Aggarwal A, Kumar P, Chowdhary G, et al. Evaluation of renal functions in asphyxiated newborns. J Trop Pediatr 2005; 51 :295-299. |
|4.||Abbot R, Shankaran S, Namasivayam A, et al. Prediction of early childhood outcome of term infants using Apgar scores at 10 minutes following hypoxic-ischemic encephalopathy. Pediatrics 2009; 124 :1619. |
|5.||Trevisanuto D, Picco G, Golin R, et al. Cardiac troponin I in asphyxiated neonates. Biol Neonate 2006; 89 :190-193. |
|6.||Parmacek MS, Solaro RJ. Biology of the troponin complex in cardiac myocytes. Prog Cardiovasc Dis 2004; 47 :159-176. |
|7.||Douglas-Escobar M, Yang C, Bennett J, et al. A pilot study of novel biomarkers in neonates with hypoxic-ischemic encephalopathy. Pediatr Res 2010; 68 :531-536. |
|8.||Sharma S, Jackson PG, Makan J. Cardiac troponins. J Clin Pathol 2004; 57 :1025-1026. |
|9.||Adamcova M, Pelouch V. Isoforms of troponin in normal and diseased myocardium. Physiol Res 1999; 48 :235. |
|10.||Szymankiewiez M, Matuszezak-Wleklak M, Hodgman J, et al. Usefulness of cardiac troponin T and echocardiography in the diagnosis of hypoxic myocardial full-term neonates. Biol Neonate 2005; 88 :19-23. |
|11.||Nicoletta I, Maria B, Demetrios G, et al. Perinatal changes of cardiac troponin I in normal and intrauterine growth-restricted pregnancies. Mediators Inflamm 2007; 53921 :1-5. |
|12.||Clark SJ, Newland P, Yoxall CW, et al. Concentrations of cardiac troponin T in neonates with and without respiratory distress. Arch Dis Child Fetal Neonatal Ed 2004; 89 :F348-F352. |
|13.||Gomella T, Cunningham M, Eyal F, et al. Perinatal asphyxia. In: Gomella T, editor. Neonatology management, on call problems, disease and drugs. California: Appleton and Lang; 2002. |
|14.||Türker G, Sarper N, Babaoðlu K, Gökalp AS, et al . Early prognostic significance of umbilical cord troponin I in critically ill newborns. Prospective study with a control group. J Perinat Med 2004; 33 :54-59. |
|15.||Groenendaal F, De Vooght KM, Van Bel F, et al. Blood gas values during hypothermia in asphyxiated term neonates. Pediatrics 2009; 123 :170-172. |
|16.||Distefano G, Sciacca BR, Mattia C, et al. Troponin I as a biomarker of cardiac injury in neonates with idiopathic respiratory distress. Am J Perinatol 2006; 23 :229-232. |
|17.||Boskabadi H, Maamouri G, Sadeghian MH, et al. Early diagnosis of perinatal asphyxia by nucleated red blood cell count: a case-control study. Arch Iran Med 2010; 13 :275-281. |
|18.||David GC, Collinson PO. Interpretation of cardiac troponin measurements in neonates: the devil is in the details. Biol Neonate 2006; 89 :194-196. |
|19.||Caliskan E, Doger E, Cakiroglu Y, et al. Cord blood cardiac troponin I and creatine kinase MB levels in poor neonatal outcomes. J Turkish German Gynecol Assoc 2006; 7 :98-102.Departments of a Pediatrics, b Clinical Pathology, Menoufia University, Shebin El Kom, and c Neonatal Intensive Care Unit, El-Ahrar Zagazig General Hospital, Zagazig, Sharqia, Egypt |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]