Phuljhele S.1,
Dewangan S.2, Rathi Y.3
1Dr.
Sharja Phuljhele, HOD, Professor, 2Dr. Shashikant Dewangan,
Assistant Professor, 3Dr. Yogita Rathi, Resident, all authors are
affiliated with Department of Paediatrics, Pt J.N.M. Medical College, Raipur,
CG, India
Corresponding
Author: Dr. Shashikant Dewangan, Assistant
Professor, Department of Paediatrics, Pt J.N.M. Medical College, Raipur, CG,
India. E-mail: drshashikantdewangan@gmail.com
Abstract
Introduction:
Perinatal
asphyxia is an important contributor of neonatal morbidity, mortality and
adverse outcome in India. Due to any reason, if blood supplied through placenta
is hampered, it leads to asphyxial injury. Renal involvement is frequent in
perinatal asphyxia. The severity of renal involvement and adverse outcome are
correlated with severity of asphyxia and HIE stage. We performed this study to
determine the incidence of renal failure in birth asphyxia by estimating urine
output, serum creatinine and blood urea. Aim and Objective:
To study
incidence of Acute Kidney Injury (AKI) in Hypoxic Ischemic Encephalopathy (HIE)
and its association with severity of HIE in Newborns. Material Methods: Cross-sectional observational hospital based
study was conducted over a period of six months from March 2018 to August 2018
in Special Newborn Care Unit (SNCU) of Dr. BRAM hospital, Raipur. Sarnat and
Sarnat staging was used to classify HIE. Statistical analyses were performed by
using SPSS21.0 software. Chi square test, P- value and likelihood ratio were
calculated using appropriate tests. Result:
Total 1318 newborns were admitted in SNCU during study period. 415 newborns
were admitted with HIE following perinatal asphyxia. Out of these 52 (12.5%)
were HIE-I cases, 242(58.3%) were HIE-II and 121(29.1%) were HIE-III. Total
70(16.9%) newborns developed AKI. None of newborn in HIE I developed AKI.
20(8.2%) newborns with HIE II developed AKI while in HIE III 50 (41.3%)
newborns had AKI. There was significant correlation between HIE III and AKI (P
value- 0.157).Conclusion: There
is significant correlation of HIE with AKI. As severity of HIE progresses from
stage-I to stage-III, there is increased risk of developing AKI.
Key words: Acute Kidney Injury (AKI), Hypoxic Ischemic Encephalopathy
(HIE), Special Newborn Care Unit (SNCU).
Author Corrected: 6th June 2019 Accepted for Publication: 12th June 2019
Introduction
Hypoxia-ischemia in the perinatal period is an important
cause of cerebral palsy and associated disabilities in children [1]. Perinatal
asphyxia is one of the most common causes of neonatal mortality and morbidity
in developing countries [2].Out of 1000 births
about 1 to 10 newborns develop HIE due to various reasons [3]. Perinatal
asphyxia is a condition characterized by an impairment of exchange of the
respiratory gases (oxygen and carbon dioxide) resulting in hypoxemia and
hypercapnia, accompanied by metabolic acidosis [4]. WHO has defined perinatal
asphyxia as a “failure to initiate and sustain breathing at birth” [5]. The
National Neonatal Perinatal Database (NNPD), 2000 used a similar definition for
perinatal asphyxia [6]. It defined moderate asphyxia as slow gasping breathing
or an Apgar score of 4-6 at 1 minute of age. Severe asphyxia was defined as no
breathing or an Apgar score of 0-3 at 1 minute of age. As per the AAP (American
academy of Pediatrics) and ACOG (American college of Obstetrics and
Gynecology), all the following must be present for designation of asphyxia Viz
(a) Profound metabolic or mixed academia (pH< 7.00) in cord. (b) Persistence
of Apgar scores 0-3 for longer than 5 minutes. (c) Neonatal neurologic sequelae
(eg, seizures, coma, Hypotonia). (d) Multiple organ involvement (eg, of the
kidney, lungs, liver, heart, intestine). Apgar scores are also useful for
predicting long term outcome in infants with perinatal asphyxia
Metabolic
derangements after asphyxia alters hemodynamics of newborn and a redistribution
of cardiac output occur to maintain cerebral, cardiac, and adrenal perfusion
while potentially compromising renal, gastrointestinal, and skin perfusion
resulting in multiple organ dysfunctions [7-9]. In term neonates with asphyxia
Renal, CNS, cardiac and lung dysfunction occur in 50%, 28%, 25% and 25% respectively
[7]. AKI may occur within 24 hours of hypoxic –ischemic events resulting from
decreased renal flow and deprived oxygen. If this is prolonged then it may
result in cortical necrosis and irreversible damage.
High
serum creatinine and high blood urea had 100 per cent sensitivity and negative
predictive value to predict adverse outcome while serum creatinine >1.5
mg/dl alone had the best specificity and positive predictive value [10]. According
to the Acute Kidney Injury Network (AKIN), AKI is an absolute increase in serum
creatinine of ≥ 26.4µmol/l (or a percentage increase in serum creatinine of at
least 50%) over two consecutive days [11].
AKI can be of two types based on urine output Oligoanuric
and Non oliguric [12].It can be of 3 types based on the site of origin: Pre
renal (75- 80%), Intrinsic renal (10-15%) and Post renal (5%) [13].
Early identification and
intervention in AKI can prevent dangerous complications. Intrinsic AKI can
result in disturbed fluid, electrolyte and acid-base balance [14]. Hence prompt
management is important in AKI in ill newborns.
Since HIE is considered as one of
the common and dreadful complication of birth asphyxia we performed this study
to determine the incidence of AKI in birth asphyxia and to correlate the AKI
with severity of HIE grading of asphyxiated neonates.
Material
and Methods
Study
design: Cross-sectional observational study
Setting:
Hospital based
study at Special Newborn Care Unit (SNCU) of Dr.
BRAM hospital, Raipur (Chhattisgarh)
Inclusion criteria: Newborns admitted in SNCU with
perinatal asphyxia.
Exclusion criteria: Neonates
with perinatal history of maternal azotemia or kidney disorders, congenital
anomalies of kidney or urinary tract (as detected by antenatal or postnatal
ultrasonography) and neonates with other factor which may change kidney
function tests such as septicemia, respiratory distress syndrome(RDS),
necrotizing enterocolitis (NEC), major congenital anomalies.
Participants:
Newborns
admitted with perinatal asphyxia.
Variables: Gestational age, birth weight, sex, HIE, AKI
Data
Source: A predesigned
and pretested proforma was used to collect data
Bias:
Reporting bias, observation bias
Study
size: 415 newborns with HIE out of 1318
newborns admitted in SNCU
Statistical methods: Statistical
analyses were performed by using SPSS21.0 software. Chi square test, P- value
and likelihood ratio were calculated using appropriate tests.
Ethical
approval: The study was conducted after taking
ethical approval from the Institute’s Ethical Committee.
Result
A total of 1318 neonates were
admitted in SNCU for various problems, out of which 415 newborns had perinatal
asphyxia. They were 241(58.1%) males and 174(41.9%) females. Out of these 52
(12.5%) were HIE-I cases, 242(58.3%) were HIE-II and 121(29.1%) were HIE-III.
Table-1: Staging
of HIE in neonates with perinatal asphyxia
Staging
of HIE |
Number
of newborns |
Percentage |
HIE I |
52 |
12.5 |
HIE II |
242 |
58.3 |
HIE III |
121 |
29.2 |
Total |
415 |
100 |
Total
cases admitted with HIE 415. Majority 242(58.3%) had HIE II.
Table-2:
Gender wise distribution of study population
Sex |
Staging
of HIE |
|
Total |
% |
||||
I |
% |
II |
% |
III |
% |
|||
Female |
24 |
46.2 |
111 |
45.9 |
39 |
32.2 |
174 |
41.9 |
Male |
28 |
53.8 |
131 |
54.1 |
82 |
67.8 |
241 |
58.1 |
Total |
52 |
100 |
242 |
100 |
121 |
100 |
415 |
100 |
Out
of 415 neonates 241(58.1%) were males and 174(41.9%) were females. In HIE III
category 67.8% neonates were males.
Table-3: Distribution of neonates as per birth
weight
Birth
Weight |
Staging
of HIE |
Total |
% |
|||||
I |
% |
II |
% |
III |
% |
|||
Extremely low birth
weight |
0 |
0 |
1 |
0.4 |
0 |
0 |
1 |
0.2 |
Very low birth weight |
1 |
1.9 |
5 |
2.1 |
5 |
4.1 |
11 |
2.7 |
Low birth weight |
21 |
40.4 |
110 |
45.5 |
45 |
37.2 |
176 |
42.4 |
Normal birth weight |
30 |
57.7 |
126 |
52.1 |
71 |
58.7 |
227 |
54.7 |
Total |
52 |
100 |
242 |
100 |
121 |
100 |
415 |
100 |
As
per birth weight, Most of the HIE around 54.7% were of normal birth weight followed
by low birth weight 42.4
Table-4: Incidence of AKI
AKI |
HIE |
Total |
% |
|||||
I |
% |
II |
% |
III |
% |
|||
NO |
52 |
100 |
222 |
91.7 |
71 |
58.7 |
345 |
83.1 |
YES |
0 |
0 |
20 |
8.3 |
50 |
41.3 |
70 |
16.9 |
Total |
52 |
100 |
242 |
100 |
121 |
100 |
415 |
100 |
None
of newborn in HIE I developed AKI. 20(8.2%) newborns with HIE II developed AKI
while in HIE III 50 (41.3%) newborns had AKI.
Table-5:
Distribution of Types of AKI
HIE |
Type
of AKI |
Total |
% |
|||
Perinatal |
% |
Intrinsic |
% |
|||
I |
0 |
0 |
0 |
0 |
0 |
0 |
II |
18 |
90 |
2 |
10 |
20 |
100 |
III |
47 |
94 |
3 |
6 |
50 |
100 |
Total |
65 |
92.85 |
5 |
7.15 |
70 |
100 |
Out
of 84 neonatal cases of AKI, 65(92.85%) neonates had pre-renal Azotemia and
only 5(7.15%) neonates had intrinsic renal failure.
Table-6: Incidence of Oliguric AKI:
HIE |
Urine
output |
Total |
% |
|||
Nonoliguric |
% |
Oliganuric |
% |
|||
I |
0 |
0 |
0 |
0 |
0 |
0 |
II |
20 |
100 |
0 |
0 |
20 |
100 |
III |
39 |
78 |
11 |
22 |
50 |
100 |
Total |
59 |
84.3 |
11 |
15.7 |
70 |
100 |
Of
all AKI cases, 11(15.7%) babies developed Oliganuric renal failure (urine
output <0.5ml/kg/hr) and 59(84.3%) had Non oliguric renal failure (urine
output >0.5/kg/hr).
Discussion
In this study we determined the
incidence of AKI and its correlation with place of delivery, birth weight and
severity of HIE. AKI were classified according to site of origin and urine
output.
A total of 1318 neonates were
admitted in SNCU for various problems, among them a total of 415 neonates were
admitted for management of perinatal asphyxia. Percentage of male babies was
higher (58.1% males versus 41.9% females) which was statistically significant
(p- value 0.03). Majority (66%) of neonates were out born (p- value 0.001). In our
study majority of neonates had presented with HIE II 242 (58.3%) followed by121
(29.1%) had HIE-III and only52 (12.5%) hadHIE-I. In 38.6% cases fetal distress
resulting in passage of meconium in utero was cause of asphyxia in neonates. Other
causes of birth asphyxia were eclampsia, preeclampsia, obstructed labor, cord
around neck etc.
In our study 41.3% babies in HIE
III developed AKI while in HIE II 8.3% babies and HIE I none developed AKI. As
HIE stage progressed, more renal dysfunction was seen in asphyxiated babies.
This difference in incidence was found statistically significant (p value <0.05
done by Chi-square test). In a prospective cohort study in Kenya there was 15
fold increased risk of developing AKI in HIE III as compared to HIE I [18]. In
a prospective hospital based study in Sudan most of the babies with AKI had HIE
II [15]. In an Indian study conducted at a teaching hospital out of 70
asphyxiated babies 33(47.1%) had renal failure majority of which Nonoliguric
type (78%) [16]. A similar observation was noted as Non oliguric AKI was much
more common (84.3%). In a Tunisian study out of 15 neonates with renal failure
10 had HIE stage II according to sarnat staging [17].
In our study around 93% newborn had
Prerenal type of AKI. Even in HIE III category 94% had Prerenal AKI while only
6% had intrinsic AKI. In this study overall
84% newborn had Nonoliguric renal failure out of all AKI. Even in HIE III
category 78% newborn had Nonoliguric renal failure while in HIE II category all
newborn had Nonoliguric renal failure. Karlowicz et all found acute renal
failure in 61 % neonates with severe asphyxia predominantly of which
Nonoliguric type (60%)[19].In contrasts a study by Jayashree et al 1 found
oliguric renal failure was more common in birth asphyxia [20]. Majority of
research finding were suggestive of predominantly Nonoliguric renal failure in
birth asphyxia [21-23].
In this study overall mortality
rate is 27.5% while most of neonates belong to HIE III (p- value 0.000). In our
study Total 32 newborns had shock out of which all newborn had renal failure.
This is highly significant (p- value 0.000). 90% newborns in HIE III ultimately
developed shock. This means low organ perfusion is also responsible for renal
dysfunction irrespective of HIE. As HIE worsen, there is multiorgan dysfunction
which also involve renal system. Thus intensive hemodynamic monitoring is
necessary for early recognition of shock and appropriate management to prevent
renal dysfunction. This finding is similar to previous studies [24-25].
Conclusion
The current study demonstrates
frequency of perinatal asphyxia-31%%. Out born neonates were found to have
higher measurably huge frequency of perinatal asphyxia. The most common
perinatal danger component was MSAF (40%). In our study the commonest type of
ARF in every one of the three phases of HIE was non-oliguric sort. The
frequency of characteristic renal disappointment in our study was 9.4%. Monitoring
of blood urea, serum creatinine and urine yield helps in the early conclusion
and administration of renal disappointment. In birth asphyxia, even
non-oliguric neonates had ARF. Hence, checking just urine yield does not help
in the conclusion of ARF, renal biochemical parameters ought to be observed.ARF
in suffocated neonates is dominatingly pre-renal and reacts to liquid revival
with 100% recuperation. Shock was observed to be a critical inclining variable
and a clinical marker connected with ARF in birth asphyxia. ARF in birth
asphyxia demonstrates a solid positive relationship with HIE arranging.
What this study adds to existing knowledge/practice: This study help in early
detection of renal dysfunction in asphyxiated babies can help to prepare
guidelines for management of these patients. An early intervention can prevent
intrinsic renal failure and thus improve survival of these babies and early
establishment the best approach to reduce mortality due to renal failure in
asphyxiated neonate is to identify high risk cases for perinatal asphyxia in
antepartum and intrapartum stage itself, and prevent this unfortunate event.
Contributions by authors: Phuljhele
S conceived and supervised the study and helped in finalizing manuscript
writing. Dewangan S helped in protocol writing and conceptualization, analyzed
data, prepared and finalized the manuscript; will be the principal
corresponding author. Rathi Y wrote the protocol, recruited patients and helped
in data analysis and manuscript writing. The final manuscript was approved by
all authors.
Conflict of Interest:
None
Funding:
None
Acknowledgements:
We acknowledge the supporting staff of department of paediatrics and our
pediatrics resident doctors who helped and support during study period.
References