ORIGINAL

Niger J Paed 2013; 40 (2): 165 –168

Uzodimma CC

Okoromah CAN

Ekure E

Ezeaka CV

Njokanma FO

Correlation of cardiac troponin T

level, clinical parameters and

myocardial ischaemia in perinatal

asphyxia

DOI:http://dx.doi.org/10.4314/njp.v40i2,11

Accepted: 29th October 2012

Abstract Introduction: Resource pallor, cyanosis, heart murmur and

limitation in developing countries

sensorium.

(

)

Uzodimma CC

may preclude access to cardiac tro- Results: Thirty term, asphyxiated

Okoromah CAN, Ekure E, Ezeaka CV

Department of Paediatrics

Lagos University Teaching Hospital,

Idi-Araba, Lagos, Nigeria.

ponin-T assay thereby necessitating neonates and their matched controls

reliance on clinical judgment for

were studied. Central cyanosis, re-

identification of hypoxic myocar- duced pulse volume, pallor, de-

dial cellular injury.

pressed sensorium; tachycardia and

Tel: +234-8183112818

Objectives: To relate selected clini- tachypnea were all associated with

cal signs with elevated serum car- increased odds ratios for abnormal

diac troponin-T in asphyxiated term cardiac troponin–T levels.

+234-8023186501

E-mail: cuzodimma@yahoo.com

Njokanma FO

neonates.

Methods: Asphyxia was identified resource–limited health facilities

Conclusion: Clinicians working in

Department of Paediatrics

Lagos State University Teaching

Hospital, Ikeja, Lagos, Nigeria.

by low umbilical arterial blood pH should have a high index of suspi-

cion for myocardial cellular injury

≤

7.20 and low five minute Apgar

score ≤ 6 while controls were term, when these signs are elicited.

non–asphyxiated neonates. All ba-

bies were examined for heart rate, Keywords: neonates, asphyxia,

heart rhythm irregularities, periph- troponin-T, myocardial injury

eral pulse volume, respiratory rate,

Introduction

degrees of shock that necessitated the use of the vaso-

pressors in the studied neonates. However studies that

Perinatal asphyxia is one of the leading causes of neona-

tal deaths in Nigeria whe_-₃re up to 100 – 180 per thousand

relate cTnT directly to signs such as pallor, cyanosis,

tachypnoea, tachycardia, low pulse volume and de-

pressed sensorium could not be found by our search.

The authors have previously reported the serum levels of

serum cardiac troponin T in term newborns and demon-

strated that myocardial damage does occur perinatal

1

live births are affected. Severe perinatal asphyxia has

been known to cause ischaemic myocardial injury with

4

-6

potentially fatal outcomes. Serum cardiac troponin T

7

cTnT) is a reliable marker of myocardial injury. In

(

6

spite of the significant burden of perinatal asphyxia in

our practice, many health facilities cannot afford the

necessary equipment for assessment of serum cTnT.

asphyxia. However, we are aware that resource limita-

tion may preclude access to cardiac troponin assay in

many of our practice settings. It is therefore important to

examine the inter-relationship of cardiovascular signs

with serum cardiac troponin levels. Hence we set out to

correlate the occurrence of elevated serum cTnT (and

hence myocardial injury) with selected clinical parame-

ters including the heart rate, respiratory rate, peripheral

pulse volume, heart rhythm irregularities, pallor, cyano-

sis, heart murmur and sensorium. Of particular interest

was to identify high risk clinical pointers for elevated

serum cTnT that could be used to enhance the diagnosis

of asphyxia related myocardial injury in resource limited

health facilities.

Following an asphyxia event, the dive reflex preferen-

tially sustains vital organ perfusion (heart, brain and

adrenals) but as asphyxia progresses, these vital organs

8

including the heart eventually become compromised.

The cardiovascular damage that ensues_-i₆s related to

4

cerebral damage as well as neonatal death Some of the

clinical features of cardiovascular injury include atrio-

ventricular valve regurgitation, hypotension, bradycar-

9

dia, tachycardia and shock. Troponin is an inhibitory

protein complex located on the actin filament of the

cardiac muscle and is elaborated in cardiac damage.

1

0

Troponin-T (cTnT) is specific for myocardial injury and

is unaffected by, mode of delivery, birth weight and

11

gender. Previous studies have noted a significant rela-

tions₁h₂i_-p₁₄_.of troponin T levels with the use of vasopres-

Subjects and methods

sors.

This may not be unconnected to the various

Cases and controls were recruited from the delivery

1

66

rooms and neonatal intensive care units (NICU) of the

Lagos University Teaching Hospital (LUTH) and the

Lagos State University Hospital, Lagos (LASUTH).

Full term asphyxiated neonates with gestational age ≥ 37

weeks were consecutively recruited. Asphyxia was de-

fined based on double criteria of five minute Apgar

score ≤ 6 and umbilical arterial blood pH < 7.2. The

controls were normal non-asphyxiated term neonates

matched for age, birth weight and sex. Echocardiogram

was done to exclude congenital heart disease in all cases

and controls. All babies were examined between 1–6

hours of life for heart rate, heart rhythm irregularities,

peripheral pulse volume, respiratory rate, pallor, cyano-

sis, heart murmur and sensorium. Written and verbal

consent was obtained from at least one parent. Approval

was gotten from the Research and Ethics Committees of

both institutions.

General description of study population

Subjects and controls were similar in distribution of gen-

der, mode of delivery, and birth weight (table 1). Chi-

square analysis of mode of delivery has been limited to

caesarean section and spontaneous vertex delivery be-

cause of the small number of patients in the other two

groups. Also chi-square analysis for birth weight was

limited to the first two groups (1500-2499g and 2500-

3499g) because of the small number of patients in the

third group. The mean gestational age of primary sub-

jects was similar to that of controls (39.0 ± 1.5 weeks Vs

38.4 ±1.2 weeks, t = 1.65, p = 0.1). The mean birth

weight was 3168 ± 628.5g and 3143 ± 574.1g, respec-

tively for subjects and controls (p = 0.87).

Table 1: Selected general characteristics of subjects and

Controls

Variable

Laboratory procedures

Subjects

n = 30

Controls

n = 30

Total

n = 60

pH: was measured using Ion Selective Electrode (ISE)

electrolyte analyser 6000 manufactured by SFRI France.

Gender*

Male

Female

Mode of delivery**

Spontaneous vertex

Caesarean section

Breech

Vacuum extraction

Birth weight (gm) ***

17 (56.7)

13 (43.3)

17 (56.7)

13 (43.3)

34 (56.7)

26 (43.3)

Cardiac Troponin-T test

16 (53.3)

12 (40.0)

1 (3.3)

10 (33.3)

20 (66.7)

0 (0.0)

26 (43.3)

32 (53.3)

1 (1.7)

The bedside kit, Cobas h232 ® system manufactured by

ROCHE, England was used. The result of cTnT analysis

is stratified by the Cobas h232 system manufacturer as

low risk (< 0.03ng/ml), medium risk (0.03 to 0.1ng/ml)

and high risk (> 0.1ng/ml). For high risk results (>

1 (3.3)

0 (0.0)

1 (1.7)

1

2

500- 2499

500-3999

6 (20.0)

22 (73.3)

2 (6.7)

6 (20.0)

22 (73.3)

2 (6.7)

12 (20.0)

44 (73.7)

4 (13.3)

0

.1ng/ml), absolute values were displayed on the equip-

≥

4000

ment while for low and medium risk values, results were

displayed as ‘< 0.03ng/ml’ or ‘0.03 to 0.1ng/ml” respec-

tively. A high risk result is synonymous with a positive

test indicative of myocardial cell damage.

2

*

χ = 0.00, p = 1.00 (degrees of freedom=1)

* χ = 3.32, p = 0.07 (degrees of freedom=1)

** χ = 0.00, p = 1.00 (degrees of freedom=1)

2

*

2

*

Figures in brackets are percentages of n.

Echocardiography

pH:

ALOKA Prosound 4000 ® ultrasound diagnostic equip-

ment was used with the multi frequency paediatric

phased array transducer. (Frequency range of 3.0 – 7.5

MHz)

The mean level of pH for the subjects and controls were

7.11 ± 0.08 and 7.26 ± 0.04 respectively.

Serum cTnT:

Asphyxiated subjects were significantly more likely to

have high risk test results than controls (p = 0.00, table

Data collection

2

). The association between the Apgar score and the

A pre-designed proforma was used to record both clini-

cal and laboratory data for all eligible newborns. Data

was analyzed using EP1 info 2008 version 3.5.1. Chi

square test (Pearson) and odds ratios with 95% confi-

dence intervals were used to test for statistical signifi-

cance with respect to discrete data while Student t- test

was used for continuous data. Probability value less than

serum cTnT level is depicted in figures 1 and 2. All

thirty subjects had Apgar scores in the range of 4 – 6 at

five minutes.

Table 2: Distribution of Serum cTnT test results

Serum cTnT (ng/ml)

Subjects

Controls

0

.05 was considered statistically significant.

<

0

>

0.03

.03 – 0.10

0.10

Total

4 (13.3)

6 (20.0)

20 (66.7)

30 (100.0)

26 (86.7)

4 (13.3)

0 (0.0)

30(100.0)

Results

2

∗χ = 30.0, p = 0.00 (degrees of freedom = 2)

Figures in brackets are percentages of column total

A total of thirty asphyxiated and thirty non asphyxiated

babies who met the study criteria were recruited from

December 2009 to May 2010.

1

67

Fig 1: Association between serum cTnT risk level and

Fig 2: Association between serum cTnT risk level and

Apgar score at one minute for subjects

Apgar score at five minutes for subjects

Clinical findings and serum level of cTnT

For ease of analysis, two groups of study population were recognised; those with abnormal cTnT test result (cTnT >

.1ng/ml) and those with cTnT ≤ 0.1ng/ml.

0

Central cyanosis, reduced pulse volume, pallor, depressed sensorium; tachycardia and tachypnea were all associated

with increased odds ratios for abnormal cardiac troponin T levels. (OR=0.0, 0.0, 107, 0.0, 0.11 and 0.24 respectively:

table 3)

Table 3: Associations between clinical findings and troponin level

Elevated serum cTnT level

Present

No (%)

Absent

No (%)

Odds ratio

95% confidence limit

Heart rate (beats/min)

120

20 – 160

160

Regularity of heart rate

Regular

<

1

>

2(50.0)

9 (20.0)

9 (69.2)

0 (0.0)

36 (80.0)

4 (30.8)

undefined

reference group

0.11*

0.02 – 0.53

0.00 - 8.81

19 (32.2)

1 (100.0)

40 (67.8)

0 (0.00)

Irregular

0.00

Pulse volume

Full

Moderate

Small

2 (5.6)

15 (71.4)

3 (100.0)

34 (94.4)

6 (28.6)

0 (100.0)

reference group

0.02*

0.00*

0.00 – 0.15

0.00 – 0.24

Murmur

Present

1 (50.0)

Absent

19 (32.8)

39 (67.2)

0.49

0.01 – 19.05

Respiratory rate (cycles/min)

<

3

>

30

0 – 60

60

1 (100.0)

10 (23.3)

9 (56.3)

0 (100.0)

33 (76.7)

7 (43.7)

undefined

reference group

0.24*

0.06 – 0.92

Pallor

Present

Absent

Central Cyanosis

Present

Absent

Sensorium

Alert

Depressed

19 (76.0)

2 (2.9)

6 (24.0)

34 (97.1)

107.67*

0.00*

11.0 – 2611.25

20 (74.1)

0 (0)

7 (25.9)

33 (100.0)

0.00 – 0.07

0.00 – 0.13

(0)

20 (62.5)

28 (100)

12 (37.5)

0.00*

Figures in brackets are percentages of row total

* Significant

1

68

Discussion

focused physical examination which is very cost effec-

tive. The predominant profile associated with an

Myocardial ischaemia does occur in perinatal asphyxia.

Serum₆_,c₁T₀_an_n_dT₁₁i_.s a biochemical marker of myocardial cell

increased cTnT in our study is that of a term baby with

perinatal asphyxia who develops pallor, cyanosis,

tachypnoea, tachycardia, low volume peripheral pulses

and depressed sensorium within the first few hours of

delivery. This profile is not uncommon in most practice

settings in developing countries and without doubt, it is

beneficial that physicians begin to include myocardial

ischaemia in the assessment of asphyxiated newborns.

Future studies may derive scoring or grading systems

that will form a guideline for assessment of perinatal

asphyxia related myocardial infarction. There is no

doubt that adequate cardiovascular monitoring as well as

adequate fluid and shock management could reduce

morbidity and improve asphyxia related mortality in

affected babies. Overall, tackling neonatal mortality

related to asphyxia could go a long way in meeting the

nation’s Millennium Development Goal (M₁₅DG- 4)

which focuses on reducing childhood mortality.

death.

The current study focused on correlating

selected physical findings with presence of elevated

cTnT as a means of enhancing the diagnosis of asphyxia

related myocardial ischaemia in resource poor health

facilities where equipment for estimation of serum cTnT

may not be available routinely.

The physical findings which were of high clinical inter-

est include tachypnoea, tachycardia, cyanosis, low pulse

volume, pallor and depressed sensorium. All these fea-

tures had significant odds of elevated cTnT. This may be

explained by varying severities of circulatory failure

(

shock) in affected neonates. Th₂is finds support in the

1

report of Clarke and colleagues that hypotensive sick

infants had significantly higher troponin T concentra-

tions than the normotensive sick counterparts. Myocar-

dial ischaemia causes shock which manifests with low

pulse volume, tachycardia, tachypnoea, cyanosis, pal-

9

lor. Depressed sensorium is an indication₈that hypoxic

ischaemic encephalopathy has occurred. Therefore,

even though the initial dive reflex preferentially sustains

perfusion of the brain, the heart and adrenals, as as-

phyxia progresses, these vital organs eventually become

compromised with consequent organ damage.

Conflict of interest: None

Funding: None

Acknowledgments

It is striking to also note that while there are guidelines

for the evaluation of hypoxic ischaemic encephalopathy

in perinatal asphyxia, there is no similar guideline for

myocardial ischaemia in perinatal asphyxia. Meanwhile,

such guidelines could be derived from simple but

The authors acknowledge the painstaking proof reading

by Dr Charles Uzodimma, parents of the babies who

gave their consent, the staff of the neonatal intensive

care, delivery and laboratory units of both hospitals.

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