Incidence and Patterns of Non-Benign Arrhythmia in Neonatal Intensive Care Unit at Zagazig University Children Hospitals
Hala Mohammed Amin(1) Laila Rasslan(1)SheriefElgebaly(1)
(1) Pediatrics department, Faculty of medicine, Zagaziguniversity, Egypt Corresponding Author: Hala Mohammed Amin
E-mail: [email protected] Abstract
Background:Neonatal Arrhythmiais defined as abnormal heart rate in the neonatal period. It may occur as a result of cardiovascular, systemic and metabolic problems.
Objectives: The aim was to identify the incidence, common types, and associated risk factors of non-benign Arrhythmia in Neonatal Intensive Care Unit.
Subjects and Methods:In this observational study 950 ICU admitted neonates were studied for clinical, laboratory, Electrocardiography and Echocardiography data beside maternal, obstetrical, and neonatal risk factors for non-benign neonatal Arrhythmia.
Results: During the study period, the incidence of nonbenign arrhythmia among neonates was 1.5%. The mean age at diagnosis was 11.1(2.3) day. The most common type was supraventricular tachycardia with an incidence of 1 %.
Conclusion:We conclude that the incidence ofnon-benign Arrhythmiais 1.5% with supra- ventricular tachycardiais the most frequently observed.
Limitations: This is a single center study
Conflict of interest: The authors declare there are no competing interests.
Keywords:Neonates, Non-benign Arrhythmia,Neonatal ICU, Electrocardiography, supra- ventricular tachycardia
Introduction
The deviation of heart rhythm from its normal pattern is called arrhythmia. Ithas different etiologies as it can occur due to various cardiovascular, systemic and metabolic abnormalities(1).
In the first 10 days of life, 1–5% of newborns have Neonatal Arrhythmia, which usually occur as a continuation of fetal Arrhythmia, as indicated by their similar features. The clinical manifestations of Neonatal Arrhythmiaare variable depending on its rate and duration and it may rarely lead to hemodynamic instability such as congestive heart failure and cardiogenic shock(2,3).
Arrhythmia are classified into two main categories; benign andnon-benign.Thereare different types of non-benign Arrhythmiasuch assupra-ventricular tachycardia, atrioventricular conduction system disorders, ventricular tachycardia,fibrillation, and long QT syndrome. Rapid diagnosis of non-benign Arrhythmialeads to optimal management to avoid sudden clinical compromise(1,4).
Electrocardiographic findings are the basis of diagnosis of Arrhythmia in newborns. The rhythm disturbance can be one of the main three forms: irregular heart rhythm, tachycardia and bradycardia(5).Monitoring rhythm patterns over extended duration makes Holter monitor is a very helpful noninvasive assessment tool in the diagnosis of cardiac Arrhythmia. It provides a cumulative evaluation of heart rhythm and rhythm variability, which is essential in diagnosing silent and episodic Arrhythmia especially in high-risk groups(6).
Over the years, advances in the understanding and diagnosis of neonates with cardiovascular problems have been remarkable. The focus has shifted from the young child to the neonate. The incidence of neonatal Arrhythmia range from 1 to 5% (7), however, the exact incidence and types of arrhythmia in the neonatal intensive care unit is not fully assessed andthere
is need to clarify the different risk factors that could predispose to different types of Arrhythmia tothese ill infants (3).
Therefore, we made a cohort studyon neonates admitted at a large tertiary care university center. The aim of this study was to identify the incidence, common types, and associated risk factors of non-benign Arrhythmia in Neonatal Intensive Care Unit of Zagazig University Hospitals.
Patients and Methods
This is acohort study that was conducted at the neonatal intensive care units at Zagazig University Hospitals. The study population included neonates who were 4 days or older and admitted to the Neonatal ICUs during the period from June 2018 to June 2020. Neonates who were 3 days old or younger were excluded from the study to avoid the possible effects of hemodynamic changes that occur during the transition from the fetal to the infant circulatory pattern, also exclusion criteria included premature neonates who had gestational age lower than 28 weeks of gestation, and neonates with multisystem complex congenital anomalies. Written informed consent was taken from the legal guardians of the neonates included in the study. This study was approved by the local ethical committee of Zagazig University and in accordance with the Helsinki Declaration of 2013.
Methods
Maternal, obstetrical, and neonatal data were recorded for each subject, including maternal infections, diseases, and medications, resuscitation data, Apgar scores, and gestational age. Neonatal birth weight was also included. Body weight was measured using the seca scale.
Infant was weighed nude or in a clean diaper, centered on the scale and the weight was measured to the nearest 0.01 kg or 10 gm. The measurements were expressed in kilograms. Respiratory rate was measured by counting the number of the newborn breaths in 60 seconds because some newborns breathe at irregular intervals. It was counted by looking tangentially at the side of the neonate to count his or her breaths. Heart Rate was assessed by feeling pulsations at the base of umbilical cord, brachial or femoral pulses or by palpation of the apex of the heart by feeling of the apical pulse at the point of maximal impulse.
Laboratory investigations were done including Complete Blood Count, Electrolytes, creatinine, bilirubin and blood glucose.
Detailed cardiac examination was then performed to assess for the presence of clinical cardiac anomalies, signs of heart failure, poor perfusion, and shock. Laboratory data included complete blood count, electrolytes, and bilirubin levels in blood.
A 12-lead Electrocardiography was performed for all neonates using the portable Eclipse TM 850 Plus electrocardiograph (Spacelabs Burdick, Bothell, WA). The following components from each Electrocardiography were carefully assessed: rhythm, heart rate, P-wave, amplitude, duration, axis, PR interval, QRS axis, duration, amplitudes of V1R, V1S, V6R, and V6S, amplitude of V4R and the highest R- and T-wave polarity, repolarization pattern, QT–QTc intervals, and Arrhythmia. Arrhythmia were classified as benign if nothing serious concurrently existed and no follow-up was necessary. These include Premature Atrial Contractions, Premature Ventricular Contractions, and junctional rhythm. Sinus arrhythmia was counted as a normal pattern in this study. Any other Arrhythmiawere considered non-benign.
Echocardiography was performed in all neonates who were diagnosed with Arrhythmia.
Echocardiography was performed using two-dimensional scans complemented with color flow Doppler mapping using 5- or 7-MHz transducers (Sonos 4500; Hewlett Packard, Palo Alto, CA).
Statistical Analysis:
The data were collected and statistically analyzed using SPSS Statistics for Windows, Version 23.0. Armonk, NY: IBM Corp. Quantitative data were presented as the mean ± Standard Deviation and qualitative data were presented as absolute frequencies (number) & relative frequencies (percentage). Continuous data were checked for normality by using Shapiro Walk test. Independent samples Student's t-test was used to compare between two groups of normally distributed variables. Percent of categorical variables were compared using Chi-square test or Fisher's exact test when appropriate. All tests were two sided.Logistic regression is used to describe data and to explain the relationship between one dependent binary variable and one or more nominal, ordinal, interval or ratio-level independent variables. P-value < 0.05 was considered statistically significant, and p-value ≥ 0.05 was considered statistically insignificant.
Results
Mean ± Standard Deviationgestational age of studied newborn was 37.1(2) weeks and 59% were males. Mean ± Standard Deviationpostnatal age days 11.1(2.3), Apgar 1 min 6(1.1) raised to be 9(0.9)at 5 min, mean ± Standard Deviationof their weight was 2.6(0.3) kg. (Table 1).
Incidence of pathological arrhythmia among newborns was 1.5% and the main underlying causes were Supra-Ventricular Tachycardia, complete Heart Block and Ventricular Tachycardia. (Table 2).
The newborns were divided into two groups according to the pathological arrhythmia.
Significant associations were found with Apgar 1 min, Apgar5min (P = 0.0001), Oxygen saturation by pulse oximetry (P = 0.0001), high Heart Rate (P = 0.006), high potassium level (P
=0.041), creatinine (P = 0.03). However, no statistically significant associations were found with other studied parameters p>0.05. (Table 3).
There was statistically insignificant difference between newborns developed pathological arrhythmia and others regard to mother characters p>0.05. (Table 4).
A logistic regression was performed to ascertain the effects of Oxygen saturation by pulse oximetry, Apgar 5min. likelihood that newborns have pathological arrhythmia. The model explained 79.9% (Nagelkerke R2) of the variance newborn pathological arrhythmia. Decreasing Oxygen saturation by pulse oximetry, Apgar 5min was associated with an increased likelihood of newborns pathological arrhythmia. (Table 5).
Discussion
The incidence of arrhythmia in the neonatal period has beenreported to be about 1%.Most of these Arrhythmia areasymptomatic and rarely life-threatening (8).
In the present study, 59% of patients were males. This came in agreement with Badrawi et al.(3)who found that, regardless of the severity, occurrence of arrhythmia in Neonatal ICU was significantly greater in males.
In general, the ‘‘Y chromosome effect’’ is blamed for an array of increased morbidity and mortality in male fetuses and newborns (9). Animal studies linked the male morbidity to altered estradiol levels (10)and dysregulation of dopamine, norepinephrine, and serotonin concentrations in males (11).
In the present study, the incidence of non-benign arrhythmia in the Neonatal ICU was 1.5%. This came in agreement with Badrawi and colleagues (3) who reported the incidence of arrhythmia in the Neonatal ICU as 1.5% for non-benign arrhythmia.
In the present study, the incidence of Supra-Ventricular Tachycardia, Ventricular Tachycardia, and complete Heart Block were 1, 0.2, 0.2 respectively. This came relatively in agreement with Badrawi and colleagues (3) who found that Supra-ventricular Tachycardia and
complete heart block, occurred in 0.7 and 0.2% in their random population while Dubin, (7) reported the incidences of 0.004 and 0.006%, respectively.
Silva et al. (12) reported that Supra-Ventricular Tachycardiawas the most commonly diagnosed type of tachycardia in their study. and Atrioventricular Re-entry Tachycardia was the most frequent type of Supra-Ventricular TachycardiaandWolff-Parkinson-White Syndrome pattern was verified in 8.6% of neonates with Supra-Ventricular Tachycardia.
Supra-ventricular tachycardia in newborns is a relatively rare disease with only a few cases per year at each perinatal center. The presentation during the first days of life is often more dramatic than Supra-ventricular tachycardialater in infancy and childhood with a high proportion of cases being in cardiac failure or even hydropic (13,14).
About tachycardia, the most frequent origin is supra-ventricular and it is the most commonly associated with significant clinical impact in the neonatal period. The major mechanism of supra-ventricular tachycardia in neonates is a re-entry circuit through an Atrioventricular accessory pathway. Ventricular tachycardia is rare and is often consequence of an underlying heart abnormality (15,16).
Supra-ventricular tachycardiacan be generally defined as a rapid heart rate resulting from an abnormal mechanism requiring tissues proximal to the bifurcation of the bundle of His for its perpetuation. It describes a group of Arrhythmia with similar electrocardiographic manifestations but with different mechanisms (3).
Ventricular tachycardia is extremely rare in the neonatal period, in half of cases is seen in apparently healthy babies and is related with a positive outcome (17). This is consistent with our results.
Congenital complete Atrioventricularblock had an observed rate of 1/15000–20000 for live births (18). Generally, it is secondary to structural cardiac defects or maternal systemic lupus erythematosus (19). Complete Atrioventricular block with severe bradycardia leading to low cardiac output may result in heart failure. Symptomatic complete Atrioventricularblock and asymptomatic block with heart rate below 55 beats/min, accompanied by wide QRS escape rhythm or accompanying cardiomegaly, are indications for emergency pacemaker implantation (18).
Although in our study group the most frequent accompanying pathology was Ventricular Septal Defect, Satar et al. (20)found that patent ductus arteriosus was the most frequent pathology while Binnetoğlu et al. (21) found that Atrial Septal Defect was the most frequent pathology.
Infants with a non-benign arrhythmia had significantly higher heart rates. The mean heart rate was 193 beats/min. This came in agreement with Badrawi et al. (3)who found that the mean heart rate was higher in non-benign group(270 beats/min).
In the current study, the non-benign arrhythmia group had significantly lower oxygen saturations, with a mean of 91.6% compared to the no arrhythmia group. This came in agreement with Badrawi et al.(3) who found that the mean Oxygen saturation by pulse oximetry was 92%.
However, oxygen saturation was mostly within the limit (89%) accepted by the American Academy of Pediatrics (22).
In the current study, there was no difference between the two groups in their overall laboratory values except potassium and creatinine. This came in agreement with Badrawi and colleagues (3)who found that there was no difference between the two groups in their overall laboratory values.
Kundak et al. (4) reported that the most common electrolyte disorders associated to Neonatal Arrhythmia was potassium disturbance.
Potassium level deviation to both extremes (hypo- and hyperkalemia) is related to cardiac Arrhythmia. Potassium level <3 mEq/L causes significant Q-T interval prolongation with
subsequent risk of torsades de pointes, ventricular fibrillation and sudden cardiac death, also severe hyperkalemia >7 mEq/L assosciated with cardiac Arrhythmia, it causes tall peaked T wave, prolonged QRS complex, atrioventricular block, bundle branch block and cardiac arrest due to asystole or ventricular fibrillation (23).
In the present study, maternal age, smoking, maternal disease and method of delivery did not differ between the two groups. This came in agreement withBadrawi and colleagues (3)who found that the mode of delivery and maternal diseases did not differ between the two groups.
However, maternal age and smoking were significantly associated with non-benign Arrhythmia in their study.
Further research on the outcome of cardiacArrhythmia in neonates is needed, mainly withprospective studies and with longer follow-up toevaluate the long-term prognosis of these patients.
Conclusion
Although the frequency of non-benign Arrhythmia in the newborn period is not high, Supra-ventricular tachycardiais the most frequently observed non-benign Arrhythmia in this period. Diagnosis of Arrhythmia in the prenatal period is essential for appropriate and optimal treatment in the postnatal period.
Limitation
1. The current study is limited by its single-center nature, and the results must therefore be interpreted in the context of the local unit-specific policies and patient population.
2. It is possible that identifiers were entered into monitors more reliably for infants with certain characteristics such as longer length of stay.
Funding:The authors received no funding for this work.
Conflict of interest: The authors declare there are no competing interests.
Table (1): Demographic, clinical and laboratory data of our group.
Items Total
(n.950) Demographic characters
Gender n. (%) Females Males
Gestational age Postnatal age days Apgar 1 min Apgar 5min Weight Kg
390 (41.05) 560(58.95)
37.1± 2 11.03±2.3
5.95±1.1 8.99±0.9 2.6±0.3 Clinical picture
HR SBP DBP RR SpO2
Temperature
151.3±15.7 74.2±6.3 43.6±5.4 47.9±4.4 95.7±1.3 37.6±0.7
Laboratory finding HB
WBCs Glucose Sodium Potassium Calcium Magnesium Creatinine
Total serum bilirubin Direct serum bilirubin
13.8±1.8 9.9±2.1 110.2±7.8 138.6±2.7 4.2±0.4 9.5±0.5 2.1±0.2 .7±0.1 12.96±1.4
0.5±0.1
Continuous data: expressed as mean ±SD ...categorical data expressed as: number (percent) Abbreviations: HR: Heart Rate SBP: Systolic Blood Pressure DBP: Diastolic Blood Pressure
RR: Respiratory Rate HB: Hemoglobin WBCs: White Blood Cells
Table (2): Incidence of pathological arrhythmia among newborns.
n. %
Underlying causes of pathological arrhythmia
2nd degree HB Complete HB SVT
VT
1 2 9 2
0.1 0.21 0.95 0.21 Incidence of pathological arrhythmia
among newborns 14 1.47
Echo finding (n.14) ASD
ASD+ VSD
Dilated cardiomyopathy Normal
VSD
3 1 2 3 5
21.43 7.14 14.29 21.43 35.71 HB: Heart Block SVT: Supraventricular Tachycardia VT: Ventricular Tachycardia ASD: Atrial Septal Defect VSD: Ventricular Septal Defect
Table (3): Relation between demographic, clinical and laboratory data with the presence of pathological arrhythmias.
variables Total
(n.950)
Pathological Arrhythmia
(n.14)
No arrhythmia
(n. 936)
t p
Gender n. (%) Females Males
390 (41.05) 560(58.95)
5(1.3) 9(1.6)
385(98.7)
551(98.4) χ 2=17 0.86
Gestational age 37.1± 2 37.4±2.24 37.05±1.9 0.6 0.56
Postnatal age days 11.03±2.3 10.4±2.7 11.04±2.3 1.1 0.26
Apgar 1 min 5.95±1.1 4.4±0.5 5.97±1.1 11.7 0.0001
Apgar 5min 8.99±0.9 8.14±0.4 8.99±0.9 8.4 0.0001
Weight (Kg) 2.6±0.3 2.7±0.3 2.6±0.3 1.4 0.17
HR 151.3±15.7 193.7±49.3 150.7±13.
8 3.2 0.006
SBP 74.2±6.3 73.6±5.6 74.2±6.3 0.34 0.74
DBP 43.6±5.4 44.9±5.1 43.6±5.4 0.94 0.35
RR 47.9±4.4 48.2±4.04 47.9±4.4 0.28 0.78
SpO2 95.7±1.3 91.6±1.9 95.8±1.2 8.2 0.0001
Temperature 37.6±0.7 37.5±0.6 37.6±0.7 0.72 0.47
HB 13.8±1.8 13.8±1.6 13.8±1.8 0.087 0.93
WBCs 9.9±2.1 9.6±2.3 9.95±2.1 0.66 0.51
Glucose 110.2±7.8 111.6±9.7 110.2±7.7 0.64 0.52
Sodium 138.6±2.7 138.6±2.3 138.6±2.7 0.086 0.93
Potassium 4.2±0.4 4.5±0.6 4.24±0.4 2.04 0.041
Calcium 9.5±0.5 9.6±0.4 9.5±0.5 0.5 0.6
Magnesium 2.1±0.2 2.05±0.14 2.09±0.15 1.2 0.24
Creatinine 0.7±0.1 0.68±0.08 0.73±0.12 2.4 0.03
Total serum. bilirubin 12.96±1.4 13.3±1.6 12.95±1.4 0.99 0.32 Direct serum. bilirubin 0.5±0.1 0.48±0.16 0.5±0.11 1.14 0.25 Continuous data: expressed as mean ±SD .... categorical data expressed as: number(percent) χ 2 =Chisquare test t= student t test p<0.05=significant
HR: Heart Rate SBP: Systolic Blood Pressure DBP: Diastolic Blood Pressure RR:
Respiratory Rate SpO2: Oxygen saturation measured by pulse oximeter HB: Hemoglobin WBCs: White Blood Cells
Table (4): Relation between maternal risk factorsand presence of pathological arrhythmias.
Total (n.950) pathological arrhythmia
(n.14)
No arrhythmia
(n.936)
Test p
Maternal age 26.8±2.95 27.6±3.5 26.8±2.95 t=1.1 0.27
Smoking No Yes
898 (94.5) 52(5.5)
12(1.3) 2(3.8)
886(98.7)
50(96.2) f 0.175
Chronic disease No
Yes
780 (82.1) 170(17.9)
12(1.5) 2(1.2)
768 (98.5)
168(98.8) f 0.99
Method of delivery CS NVD
640 (67.4) 310(32.6)
9(1.4) 5(1.6)
631 (98.6)
305(98.4) f 0.78
Mother fever No
Yes
920 (96.8) 30(3.2)
12(1.3) 2(6.7)
908(98.7)
28(93.3) F 0.07
Continuous data: expressed as mean ±SD ...categorical data expressed as :number(percent) t= student t test f=Fisher Exact test p>0.05=insignificant
CS: Cesarean Section NVD: Normal Vaginal Delivery
Table (5): Logistic regression for predicting pathological arrhythmia of newborns.
β S. E Sig. Exp (β) 95% C.I. for EXP (B) Lower Upper
SpO2 -4.545 1.215 .000 .011 .001 .115
Apgar 5min -2.764 .940 .003 .063 .010 .398
β regression coefficient S.E -Standard error Exp(β) –the odds ratios for the predictors CI=Confidence interval
SpO2: Oxygen saturation measured by pulse oximeter References
1. Ban JE. Neonatal Arrhythmia: Diagnosis, treatment, and clinical outcome. Korean J Pediatr. 2017;60(11):344–52.
2. Tanel RE, Rhodes LA. Fetal and neonatal Arrhythmia. Clin Perinatol [Internet]. 2001 Mar 1 [cited 2020 Dec 14];28(1):187–207. Available from:
http://www.perinatology.theclinics.com/article/S0095510805700749/fulltext
3. Badrawi N, Hegazy RA, Tokovic E, Lotfy W, Mahmoud F, Aly H. Arrhythmia in the neonatal intensive care unit. Pediatr Cardiol. 2009;30(3):325–30.
4. Kundak AA, Dilli D, Karagöl B, Karadağ N, Zenciroğlu A, Okumuş N, et al. Non benign neonatal Arrhythmia observed in a tertiary neonatal intensive care unit. Indian J Pediatr.
2013;80(7):555–9.
5. Skinner JR, Sharland G. Detection and management of life threatening Arrhythmia in the perinatal period. Vol. 84, Early Human Development. Elsevier; 2008. p. 161–72.
6. Baghel A, Kumar M, Soni JP, Agarwal M, Kumar R. Experience with Holter monitoring for evaluation of infant arrhythmia. Int J Contemp Pediatr. 2019;6(3):1362.
7. Dubin AM. Arrhythmia in the Newborn. Neoreviews [Internet]. 2000 Aug 1 [cited 2020
Dec 14];1(8):146e – 151. Available from:
https://neoreviews.aappublications.org/content/1/8/e146
8. Long WA, Frantz EG, Henry GW, Freed MD and Brook M. Evaluationof newborns with possible cardiac problems. In Taeusch HW, BallardRA, eds. Avery’s Diseases of the Newborn. 7th edn. Noida; HarcourtAsia, 2000, 711–763.
9. Tioseco JA, Aly H, Essers J, Patel K, El-Mohandes AA.Male sex and intraventricular hemorrhage. Pediatr Crit Care Med. 2006;7:40–44
10. Nunez JL, McCarthy MM. Estradiol exacerbates hippocampal damage in a model of preterm infant brain injury. Endocrinology. 2003; 144:2350–2359.
11. El-Khodor BF, Boksa P. Differential vulnerability of maleversus female rats to long-term effects of birth insult on braincatecholamine levels. Exp Neurol. 2003; 182:208–219.
12. Silva A., Soares P., Flor-de-Lima F., et al. Neonatal Arrhythmia–morbidity and mortality at discharge. JPNIM.2016; 5(2), e050212.
13. Deal B. Supra-ventricular tachycardia mechanisms and naturalhistory. In: Deal B, Wolff G, Gelbrand H, editors. Currentconcepts in diagnosis of Arrhythmia in infants and children,Futura Armonk, NY, 1998; 117–43.
14. Lemler MS, Schaffer MS. Neonatal supra-ventricular tachycardia: predictors of successful treatment withdrawal.Am Heart J 1997; 133: 130–1.
15. Sekarski N, Meijboom EJ, Bernardo SD, Ksontini TB, Mivelaz Y.Perinatal Arrhythmia. Eur J Pediatr. 2014;173:983-96.
16. Stacy AS, Killen M, Frank A, Fish M. Fetal and NeonatalArrhythmia. Neoreviews.
2008;9:e242-52.
17. Levin MD, Stephens P, Tanel RE, Vetter VL, Rhodes LA.Ventricular tachycardia in infants with structurally normal heart:a benign disorder. Cardiol Young. 2010;20(6):641-7.
18. Pinsky WW, Gillette PC, Garson AT, Mc Namara DG. Diagnosis,management and long- term results of patients with complete atrioventricular block. Pediatrics 1982; 69: 728–733.
19. Litsey SE, Noonan JA, O’Connor WN, Cottrill CM, Mitchell B.Maternal connective tissue disease and congenital heart block: demonstration of immunoglobulin in cardiac tissue. N Engl J Med 1985; 312:98–100.
20. Satar M, Narlı N, Özbarlas N ve ark. Yenidoğan döneminde aritmigelişen 21 vakanın değerlendirilmesi. Çocuk Sağlığı ve HastalıklarıDergisi 2006; 49: 107–111.
21. Binnetoğlu, F. K., Babaoğlu, K., Altun, G., &Türker, G. Diagnosis, treatment and follow up of neonatal Arrhythmia. Cardiovascular journal of Africa. 2014; 25(2), 58.
22. Committee on Fetus and Newborn. Guidelines for perinatalcare, 3rd edn. American Academy of Pediatrics, Washington,DC. 1992; pp 197–203.
23. Hoppe, L. K., Muhlack, D. C., Koenig, W., Carr, P. R., Brenner, H., & Schöttker, B.
Association of abnormal serum potassium levels with Arrhythmia and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Cardiovascular drugs and therapy. 2018; 32(2), 197-212.
