European Journal of Cardiovascular Medicine

Perinatal asphyxia is the second leading cause of neonatal mortality after infection, accounting for around thirty percent of all deaths globally.1,2 Despite improvements in primary prenatal and obstetric care, the incidence of perinatal hypoxia remains high in developing nations. Newborns with perinatal asphyxia suffer significant neurological dysfunction and sequalae, which are usually avoidable.3,4

The majority of the clinical effects of perinatal asphyxia are potentially deadly, resulting in renal, neurologic, cardiac, and lung failure. The level of multi organ dysfunction defines an asphyxiated newborn's early destiny, with the neonate either succumbing to the effects of the multi organ dysfunction or recovering entirely.5,6 Some intrapartum measures to prevent perinatal asphyxia include regular antenatal care, vigilant labour monitoring, supportive second stage management based on foetal and maternal conditions, and managing pre-eclampsia.7,8 These measures can help improve quality of life by preventing various co morbidities. As a result, managing prenatal asphyxia necessitates a multidimensional strategy including the joint efforts of qualified obstetricians and paediatricians.

Management of perinatal asphyxia is one of those rare occasions when death or life-long damage can be avoided with a few minutes of skilled and prudent action. Effective and rapid postpartum resuscitation and care provided within the first golden minute of life will result in a significant reduction in both immediate and long-term morbidities.9–11 The current study was designed to comprehensively investigate the cardiac dysfunction associated with perinatal hypoxia and its relationship to hypoxic ischemic encephalopathy.

A systematic randomization sampling technique was applied, and every 5th newborn admitted to our NICU who met the eligibility criteria was included and a total of 135 patients were enrolled as they satisfied the criteria for perinatal asphyxia as mentioned in the FBNC 2014 guidelines which is the presence of anyone of the following: Gasping or ineffective breathing or lack of breathing at one minute of life. Need for positive pressure ventilation for >1 minute. APGAR score <3 at 5 minutes or longer. A detailed history was taken, and clinical examination was carried out using a preformed proforma and assessment of gestational age was done based on LMP-EDD date and/or USG report (earliest trimester) whichever was available and then it was confirmed postnatally by Modified Ballard Score. Written and informed consent was obtained from parents/guardians of enrolled neonates before inclusion in the study. All the enrolled neonates were studied in detail for clinical features. Laboratory investigations and imaging was done for primary disease i.e., hypoxic ischemic encephalopathy. Hypoxic ischemic encephalopathy in neonates was graded using the Levene’s classification, which is a simple and practical classification that grades hypoxic ischemic encephalopathy into mild, moderate and severe grades on the basis of consciousness, tone, seizures & sucking/respiration.

Myocardial dysfunction was evaluated using clinical examination, electrocardiogram, echocardiography (2D &M mode) and cardiac enzymes (CPK MB, CPK total &troponin I). Supplemental oxygen if required was given by oxygen by hood (5–6 L/min), nasal continuous positive airway pressure and mechanical ventilation (based on saturation of oxygen (SpO2) and Arterial Blood Gas findings). Intravenous fluids, vitamin K and if required, inotropes and anticonvulsants were also administered. Myocardial involvement was assessed by clinical evaluation (congestive heart failure was diagnosed by careful examination of cardiovascular system including heart rate, character of heart sound, respiratory rate, liver size and gallop rhythm, shock diagnosed by cold extremities, weak femoral pulse, pallor, prolonged capillary refilling time and respiratory distress was diagnosed by intercostal and subcostal retraction, expiratory grunting. Investigations like ECG and cardiac markers (CK Total (25-200IU/L), CK-MB (0-25IU/L) and Troponin I (00.03ug/L)) were used. Myocardial dysfunction was considered if clinical features and altered laboratory parameters and/or ECG changes and/or 2D ECHO changes were there. Neonates were treated using standard guidelines and protocols for HIE and myocardial dysfunction. They were evaluated and followed up to their final outcome, which was recorded as discharge, expiry or left against medical advice.

Statistical Analysis

All the data were collected in proforma and entered in excel sheet. The statistical analysis was performed using the SPSS v23.0 operating on windows 10. The data were summarised as mean, standard deviation, frequency and percent. The summarised data were represented using tables. The mean difference between the continuous data were analysed using t-test and the difference between categorical data was analysed using chi-square test. For all the statistical purpose, a p-value of less than 0.05 was considered statistically significant.  

Total number of newborn admissions in our NICU during the study period was 7990, out of which 863 had perinatal asphyxia. Out of those patients hospitalised for perinatal asphyxia 680 had HIE. A total of 135 neonates were included in this study. Amongst the patients with HIE selected after systemic randomisation using multiples of 5, 72 (53.3%) were found to have myocardial dysfunction in varying degree. 

Out of the 135 babies included in the study, 20 (14.8%) developed mild HIE, 51 (37.7%) developed moderate HIE and 64 (47.4%) developed severe HIE. Out of the 135 babies included in the study, 97 (71.8%) were males and 38 (28.1%) were females, hence the male: female ratio was 2.5:1 showing high male preponderance.

Table 1: Comparison of the Gestational Age with HIE Stage

Table 2: Showing Risk Factor and HIE Stage

 Table 3: Showing the Clinical Features in HIE Patients

Table 4: Comparison of CKMB, CK and Troponin I with HIE Staging

Table 5: Comparison of the HIE Staging with ST Changes on ECG

Table 6: Comparison of outcome with CKMB, CK and Troponin levels

The ECG was suggestive of grade 1 t wave changes in 4 patients and grade 4 t wave change in 1 patient.3 of the patients with grade 1 t wave changes expired and 1 was discharged. The patient with grade 4 t wave changes in the ECG also expired. No significant association was found between ECG changes and outcome of patients with myocardial dysfunction, we also faced difficulty in getting a consistent ECG tracing in our study. Hence with the availability of more feasible and better tools like bedside functional echo and poor yield of ECG changes, we would advocate the usage of functional 2D echo whenever possible.

  Table 7: Comparison of the HIE Staging with ECHO Findings

The various cardiac markers employed to assess the myocardial dysfunction was compared with presence of valve regurgitation as documented by doing 2D echocardiography. It was found that there was significant correlation between those patients with raised CK MB levels and those who developed valve regurgitation. No such correlation was seen in patients with raised CK Total and Troponin levels. Hence, we can fairly rely on cardiac markers in form of CK MB to diagnose the degree of cardiac dysfunction and its association with abnormal 2D ECHO findings.

The outcome of the neonates enrolled under the 3 HIE categories were analysed. Out of the 20 neonates categorised under HIE stage 1; 2(10%) expired and 15 (75%) were discharged. Out of the 51 neonates categorised under the HIE stage 2; 16 (31.3%) expired and 33(64.7%) were discharged and of the 59 categorised under HIE stage 3; 36 (61%) expired and 23 (38.9%) were discharged. 11.7 % mortality was seen in patients with HIE stage 1, whereas 32.6 % mortality was seen in patients with HIE stage 2 and 61.01 % mortality was seen in HIE stage 3. Maximum mortality was hence seen in patients with HIE stage 3. On calculating the p value by chi square test significant correlation between HIE staging and mortality was seen.

In the present study there was male preponderance amongst the neonates who developed birth asphyxia, whereas in Mohammed AS et.,12 and Nishant et al.,13 there was near equal and equal distribution of both the genders

respectively. The incidence of birth asphyxia in our institution was found to be 10.8%, which   was higher than the incidence seen in the Babu et al., study which had an incidence of 6.6% .Among the 10.8 % neonates 78.9% neonates developed HIE, whereas 45.1 % of the neonates with birth asphyxia developed HIE in the Babu BVA et al study.14 The higher incidence of HIE in our study might be influenced by the number of patients enrolled over double the duration as compared to Babu BVA et al study.14

Out of the 135 patients admitted 19 (14%) were preterm, of which, 6 (31.5%) were HIE stage 1, 8 HIE stage 2(42%),5 HIE stage 3 (26.3%).115 (85.1%) patients out of the total were term, of which 13 (11.3%) were HIE stage 1, 43 (37.3%) were HIE stage 2, 59(51.3%) were HIE stage 3.One patient of the total was post term which was HIE stage1. The p value on applying the chi square test to assess the correlation between the gestational age and severe HIE was found to be 0.10, hence was insignificant. On the other hand, if we compare the gestational age in HIE stage 1, 65% of term neonates and 35% of preterm neonates had HIE 1. Similarly, 84.3% of neonates with HIE stage 2 were full term while only 15.7% were preterm. Also, a significant number of patients with HIE stage 3 belonged to term gestational age, as compared to only 7.8% of patients being preterm, so overall incidence of HIE was more in term (85%) as compared to preterm (14%) in our study

In Mohammed AS et al12 study 38% and in Nishant et al study 23.75% had normal birth weight respectively, which was lesser than that of the present study .Amongst the LBW group 11% in Mohammed AS et al12 study and 7.5% in the Nishant et al13 study were VLBW , the incidence was higher than the present study. The incidence of ELBW was 2.9% in the present study which was comparable with Nishant et al study which had an incidence of 2.5%13 but was lesser than the Mohammed AS et al study which had an incidence of 4%.12

All the babies enrolled in the study were tested for myocardial dysfunction by analysing the levels of cardiac biomarkers in them. The level of CK MB was analysed and it was found to be significantly raised in all stages of HIE staging. The correlation between the levels of ck mb was found to be significant between stage 1 &2, stage 2 &3 and stages 1 & 3. In our present study P value between the stages are significant, P value between 1 & 2, 2 & 3 and 1 &3 were found to be significant. In Kumar PS et al study P value between 1 &2 was not significant whereas the p value between 1&3 was found to be significant.15 In case of Prithviraj D et al study P Value between the stages was found to be 0.001 hence significant.16

This indicates that there is a significant association between altered /abnormal values of CKMB and the severity of HIE, suggestive of severity of myocardial dysfunction. The troponin levels were found to be elevated in all stages of HIE, and significant correlation was seen between the stages of HIE which was similar to the Prithviraj D et al study.16

CONCLUSION

Myocardial dysfunction was found in 53.3% of patients showing the gravity and extent of cardiac involvement in patients with HIE. Significant Positive Correlation was seen between the levels of the cardiac markers (CK-MB, CK total and Troponin I) and the degree of adverse outcome in terms of HIE staging. Detailed history, close monitoring for clinical signs, high index of suspicion, early detection of myocardial dysfunction by various tools will not only help in increasing the chances of survival in an affected neonate, but it would also contribute in decreasing the overall neonatal mortality. Severity in grading of Hypoxic ischemic encephalopathy and myocardial dysfunction strongly correlated with a grave prognosis and a poorer outcome. Functional 2D ECHO done at bedside can be a reliable tool to diagnose and monitor the clinical progress of patients It also can be used to prognosticate the outcome according to HIE staging and help in counselling of the parents.

Funding: Nil

Conflict of interest: Nil

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