Med. J. Cairo Univ., Vol. 78, No. 1, December 461-467, 2010 www.medicaljournalofcairouniversity.com
Multi-Organ Dysfunction in Neonates with Hypoxic-Ischemic
Encephalopathy
LAILA H. MOHAMMED, M.D.; MAI A .KHAIRY, M.D.; NAGY A. EL-HUSSIENY, M.D.*;
MOHAMMED H. ZAAZOU, M.D.* and RAGHDAA M. ALY, M.D.*
The Departments of Pediatrics, Faculty of Medicine, Cairo University and Ahmed Maher Teaching Hospital*.
Abstract Introduction
Perinatal hypoxic-ischemic cerebral injury remains an NEONATAL hypoxic-ischemic encephalopathy important recognized cause of cerebral palsy. Most cases of (HIE), the most common neurologic complication hypoxic-ischemic encephalopathy (HIE) result from injury in the perinatal period, is a major cause of chronic in the prenatal period secondary to intrauterine asphyxia, with disturbance of gas exchange across the placenta. disability in childhood [1] . HIE is termed as neonatal encephalopathy that results from systemic hypox- The aim of this study was to assess the patients of hypoxic- emia and decreased cerebral perfusion leading to ischemic encephalopathy regarding the patterns of each organ/ [2] system dysfunction in relation to the outcome and also assess- ischemia . ment of occurrence of multi-organ/system dysfunction and its relation to outcome and the severity of acidosis. Etiology of perinatal HIE includes those cir-
cumstances that can affect the cerebral blood flow
Our study included 100 full term neonates diagnosed as in the fetus and neoborn compromising the supply HIE. Data wre collected from patients’ files including full of oxygen to the brain. They may develop antepar- maternal history, detailed neonatal history, general and systemic tum (20%), intrapartum (30%), intrapartum and examination, laboratory studies and the outcome of each one. antepartum (35%), or postpartum (10%). HIE de-
Some risk factors associated with HIE were assessed velops in the setting of perinatal asphyxia, which among our patients. Meconium staining of the amniotic fluid is a multi-organ system disease [3] . was found to be the most common risk factor in our study.
Hypoxia and ischemia can cause damage to Multi-organ dysfunction occurred in 74% of cases, with
the renal dysfunction being the commonest to occur followed almost every tissue and organ of the body and by pulmonary dysfunction. While regarding the outcome, various target organs involved have been reported cardiovascular dysfunction was associated with the highest to the kidneys in 50%, followed by central nervous incidence of mortalities followed by pulmonary dysfuncction. system (CNS) in 28%, cardiovascular system (CVS) We also found that two-organ dysfunction was the com- in 25% and lungs in 23% cases [4] . monest to occur followed by one-organ dysfunction. Highly significant relation was found between the number of organ Multi-organ dysfunction (MOD) is one of four dysfunction and the occurrence of death. consensus based criteria for the diagnosis of intra-
partum asphyxia. The theoretical concept behind Among all our patients (100 patients), death occurred in MOD is the diving reflex (conservation of blood 40% of cases, while 60% of cases were discharged. On the flow to vital organs at the cost of non-vital organs) other hand, death occurred in 39 cases (52.7%) among the the multi-organ dysfunction (MOD) group (74 patients) while (Shah et al., 2004).
35 patients (47.29%) were discharged.
Excessive stimulation of glutamate receptors
Key Words: Organ – Dysfunction – MOD – Neonates – Hypoxic appears to play an important role in the pathogen-
ischemic encephalopathy. esis of neonatal brain injuries caused by lack of
oxygen [5] .
Correspondence to: Dr. Laila H. Mohammed, the Department Improved understanding of the pathophysiolog- of Pediatrics, Faculty of Medicine, Cairo University. ical mechanism involved in perinatal brain lesions
461 462 Multi-Organ Dysfunction in Neonates with Hypoxic-Ischemic Encephalopathy
helps to identify potential targets for neuroprotec- 5- Laboratory studies: CBC, ABG, liver function
tive interventions [6] . tests (ALT, AST, SB), kidney function tests + + (BUN, S.CREAT., Na and K ).
Aim of the work: 6- Cranial ultrasonography (whenever available).
To assess the patterns of involvement of each major organ/system and combinations of involve- 7- Outcome whether death or discharge. ment in infants with post-asphyxial hypoxi- Outcome was studied in relation to individual cischemic encephalopathy. organ dysfunctions and in relation to number of
organ/system involved. Patients and Methods
All patients were then divided into two groups, This is a retrospective study carried out on 100 the first group included patients with PH<7, and hypoxic-ischemic neonates who were admitted on the second one included patients with PH >_7. Both their first day of life to the Neonatal Intensive Care groups were then compared regarding mode of Unit (NICU) in Kasr El-Aini University and Ahmed delivery, risk factors, distribution of organ affection, Maher Teaching Hospitals, Cairo, Egypt, over a the occurrence of multi-organ affection and the period of 18 months from June 2007 to December relation to the outcome. 2008.
• Criteria for organ/system dysfuncyion: • Inclusion Criteria (Neonates with HIE criteria):
Renal dysfunction: 1- Having one or more of the followings: Anuria or oliguria (0.5
Cardiovascular dysfunction: 2- Neonates who needed mechanical ventilation.
Hypotension treated with ionotropes for more 3- Neonates with evidence of encephalopathy as than 24 hours to maintain blood pressure within altered consciousness and/or seizures. the normal range.
• Exclusion Criteria: Pulmonary dysfunction:
1- Preterm babies (<37 weeks gestation). Need for ventilatory support with oxygen re-
quirement more than 40% during the first 4 2- Babies with congenital anomalies including hours of life. dysmorphism, congenital viral infections, inborn
errors of metabolism,and hemorrhagic shock Hepatic dysfunction: without evidence of intrapartum asphyxia. Aspartate aminotransferase > 10IU/I or alanine
aminotransferase > 100IU/I at any time during Data were collected from patients’files as follows: the first week after birth.
1- Full maternal history including personal (name, Gasteroinetestinal dysfunction: age, gravidity and parity) and medical (anemia,
hypertension, diabetes mellitus and drug intake). GIT bleeding with or without vomiting or ab-
dominal distention. 2- Detailed obstetric history (duration of pregnancy, number of births, mode of delivery and occur- Hematologic dysfunction: rence of complications as APH, PROM, MSAF Signs of DIC with bleeding tendency. and cord around the neck).
3- Neonatal history (estimated gestational age, sex, • Statistical Analysis: Apgar score at 1 and 5 minutes and method of We used computer programs Microsoft Excel resuscitation if needed). 2003 (Microsoft corporation, NY, USA) and SPSS
4- Clinical examination including general (RR, (Statistical Package for the Social Science; SPSS
HR, ABP and TEMP.) and systemic (neurolog- Inc., Chicago, IL, USA) version for Microsoft
ical, chest, heart and abdominal). Windows. Laila H. Mohammed, et al. 463
Results Table (5): Mean and standard deviation of laboratory parameters among the studied cases. Table (1): Sex distribution among cases. Laboratory Std. Minimum Maximum Mean parameters deviation Sex distribution Number Percentage
pH 6.7 7.45 7.175 0.1440
Males 57 57% pO 24 12.122 2 88.9 40.95
Females 43 43% pCo2 11 99 32.50 17.013
HCo3 4 69 13.12 7.878
BE -28 -11 -16.18 3.648
Table (2): Mode of delivery among cases. Hb 4.1 20 13.097 2.9383
TLC 2 48 10.97 7.205 Mode of Vaginal delivery Cesarean section PLT total 10 816 200.81 152.338 delivery N=54 N=46 BUN 3 122 33.995 24.5013
≥ Creatinine 0.1 3.8 1.238 0.7930 pH 7 46 (52.2%) 42 (47.8%) 88 (88%) Na 120 154 137.89 6.914 pH <7 8 (66.7%) 4 (33.3%) 12 (12%) K 2 8 5.50 1.402 p-value: 0.348 Bilirubin 0.4 23.4 5.463 4.1273
ALT 4 597 75.78 99.702
AST 23 1397 156.06 208.336 Table (3): Maternal and obstetric problems among cases.
Obstetric pH >_7 pH <7 Total p-value Table (6): Occurrence of multi-organ dysfunction (MOD) problems n=88 n=12 n=100 among cases.
Maternal 16 2 18 0.898 pH >_7 pH <7 Total MOD
diseases (88.9)% (11.1%) (18%) n=88 n=12 n=100
Placental 4 2 6 0.097 yes 63 11 74
abnormalities (66.7%) (33.3%) (6%) (85.13%) (14.86%) (74%)
PROM 1 2 13 0.687 No 25 1 26
(84.6%) (15.4%) (13%) (96.15%) (3.84%) (26%)
Meconium 29 5 34 0.550
staining (85.3%) (14.7%) (34%)
Cord around 4 0 4 0.470
neck (100%) (4%) 74% MOD
Obstructed 16 3 19 0.572
labor (84.2%) (15.8%) (19%)
Fig. (1): Occurrence of multi-organ dys- Table (4): Clinical presentation of the studied neonates. function (MOD) among cases.
Clinicalpresentation Number percentage
Table (7): Distribution of organ dysfunction among MOD
1-Neurological: group. a-Convulsions 92 92%
b-Lethargy 48 48% pH >_7 pH <7 Total Organ/system p-value c-Irritability 4 4% N=63 N=11 N=74
2-Respiratory: Renal 42 5 47 0.178 a-Delayed initiation of respiration 25 25% (89.3%) (10.7%) (63.5%) b-Respiratory distress 24 24%
c-Meconium aspiration 34 34% Pulmonary 30 5 35 0.578
(85.7%) (14.3%) (47.3%) 3-Renal:
a-Anuria 6 6% Hepatic 22 4 26 0.589
b-Oliguria 4 4% (84.7%) (15.3%) (35.1%)
4-Gastrointestinal: Cardiac 19 2 21 0.339
a-Abdominal distention 10 10% (90.4%) (9.6%) (28.4%)
b-Vomiting 5 5%
c-GIT bleeding 4 4% Gastrointestinal 2 2 4 0.103
(50%) (50%) (5.4%) 5-Cardiac:
a-Hypotension 21 21% Hematological 0 1 1 0.016
b-Tachycardia 15 15% (100%) (1.35%) 464 Multi-Organ Dysfunction in Neonates with Hypoxic-Ischemic Encephalopathy
Table (8): Distribution of organ dysfunction in relation to One organ outcome.
Two organs Discharge Death Total Organ/system p-value
N=35 N=39 N=74 Three organs
Renal 22 25 47 0.011 Four organs
(46.8%) (53.19%) (63.5%) Five organs
Pulmonary 13 22 35 0.001
(37.14%) (62.85%) (47.3%) Fig. (3): Number of organ dysfunction
among the MOD group.
Hepatic 12 14 26 0.094
(46.15%) (53.84% (35.1 %) Table (10): Relation between number of organ dysfunction
and outcome. Cardiac 5 16 21 0.001
(23.8%) (76.19%) (28.4%) Number of Dischage Death Total
organ affection N=35 N=39 n=74 Gastrointestinal 2 2 4 0.677
(50%) (50%) (5.4%) One organ 20 8
(71.4%) (28.6%)
Hematological 0 1 1 0.218
(100%) (1.35%) Two organs 13 23
(36.1%) (63.9%)
Three organs 1 6 50 Total (14.3%) (85.7%)
45 Death Four organs 0 2
40 (100%)
35 Five organs 1 0
30 (100%)
25 p-value: <0.001
20
15 40 Total
10 35 Death
5
30 0
25 Renal
Cardiac Hepatic 20 pulmonary 15 Hematological Gastrointestinal 10 Fig. (2): Relation between organ dysfunc-
tion and outcome. 5
0 Table (9): Number of organ dysfunctions among MOD group.
One Two Five organ Number of pH >_7 pH <7 Total Four Three organs organs organs organs organ dysfunction n=63 n=11 n=74
Fig. (4): Relation between number of organ
One organ 23 5 dysfunction and outcome.
(31.08%) (6.75%)
Table (11): Relation between pH and outcome among the Two organs 31 5 whole group. (41.89%) (6.75%)
Death Discharge Total Outcome
Three organs 7 0 N=40 N=60 N=100 (9.45%) pH >_7 30 58 88
Four organs 1 1 n=88 (34%) (66%) (88%) (1.35%) (1.35%) pH <7 10 2 12
Five organs 1 0 n=12 (83%) (17%) (12%)
(1.35%) p-value: 0.001 Laila H. Mohammed, et al. 465
Table (12): Relation between pH and outcome among the The recorded risk factors in our study were MOD group. maternal diseases, placental abnormalities, PROM,
Death Discharge Total meconium staining, cord around the neck and Outcome N=39 N=35 N=74 obstructed labour. Our results revealed that meco- pH >_7 29 34 63 nium staining was the commonest risk factor (34%).
(46%) (54%) (85.13%) This is in agreement with Ross and Gala [14] who considered the presence of meconium-stained am- pH <7 10 1 11
(90.9%) (9.1%) (14.87%) niotic fluid a strong evidence of fetal distress. Also,
Shrestha et al. [15] studied the risk factors of HIE p-value: 0.006 and showed that meconium staining of the amniotic
fluid was the commonest risk factor reaching up Discussion to 65% of cases. On the contrary, Majeed et al. [16] Hypoxic ischemic brain injury during the peri- found that absence of antenatal care was the com- natal period remains the single major cause of monest risk factor among their study which includ- acute mortality and chronic disability in newborn ed 125 neonates with HIE. It occurred in 64% of infants, leading to permanent neurodevelopmental cases, while meconium stained amniotic fluid sequelae [7] . occurred only in 9.6% of cases. Absence of ante-
natal care was also the commonest risk factor of In spite of major advances in technology and HIE according to West et al. [17] . Since our study knowledge of fetal and neonatal pathology and is a retrospective one, this makes it difficult to pathophysiology, HIE remains a serious condition discuss antenatal care as a risk factor for HIE due leaving significant handicaps in 100% of survivors to lack of data about the antenatal period. of severe HIE and in 30% of survivors of moderate
HIE [8] . In our study the clinical presentations of the
patients showed evidence of encephalopathy with This retrospective study included 100 hypoxic or without manifestations of other organ dysfunc- ischemic neonates who were admitted on their first tion where convulsions were the commonest pre- day of life to the NICU at Kasr El Aini university sentation recorded in 92% of cases, followed by and Ahmed Maher Teaching Hospitals over a period lethargy in 4% of cases. Our results disagree with of 18 months from june 2007 to december 2008.
Afzal et al. who carried out a study analyzing the
In our study, 57% of our patients were males, risk factors of HIE, they found that lethargy was
while 43% were females. These results concur with the commonest neurological presentation (52%)
Futrakul et al. [9] , who studied the risk factors of followed by irritability (36%) while convulsions
HIE in 84 neonates and found out that there was were the least to occur (28%).
a statistically significant relationship between HIE
and male gender. Parkash and Das [10] , also found Concerning the occurrence of multi-organ dys-
a significant relationship between HIE and male function in our study, 74% of our patients had at
gender and their study under the risk factors of least one-organ dysfunction in addition to the CNS
HIE. affection. This result agrees with Shankaran et al.
[18]who studied the occurrence of multi-organ Concerning the mode of delivery in our study, dysfunction in 106 hypoxic ischemic neonates and 54% of our patients were delivered by vaginal they found that 73% of their patients had evidence delivery, while 46% of them were delivered by of multi-organ dysfunction while Wheeler et al. cesarean section. This agrees with Butt et al. [11] [19]recorded higher incidence of multi-organ dys- who carried out the study on the risk factors of function in their study. They found that multi-organ HIE on 153 neonates diagnosed as hypoxic dysfunction occurred in 95% of their patients. ischemic encephalopathy, and they found that
vaginal delivery occurred in 76.5% of cases while The distribution of organ dysfunction among
cesarean section occurred in 23.5% of cases. On the MOD group was studied. Our results revealed
the other hand, our results disagree with Kaye [12] that renal dysfunction was the commonest to occur
who stated that cesarean section was highly asso- (64%) followed by pulmonary dysfunction (47%).
ciated with HIE. According to Milsom et al. [13] , This agrees with Zlatnik et al., who found that
emergency cesarean section was more frequent in renal dysfunction was the commonest to occur
HIE. The variation in different studies concerning (42%) followed by pulmonary dysfunction (26%).
the mode of delivery may be explained by the fact According to Tekin [19] , renal dysfunction was also
that neonatal encephalopathy may originate early the commonest to occur followed by pulmonary
in the antepartum period in some cases of HIE. dysfunction. On the other hand, our results disagree 466 Multi-Organ Dysfunction in Neonates with Hypoxic-Ischemic Encephalopathy
with Higgins et al. [20] who carried out a retrospec- Finally, the outcomes (whether death or dis-
tive study on 130 term neonates with perinatal charge) were studied in relation to the pH of the
asphyxia, they found that pulmonary dysfunction whole group and the MOD group. Regarding the
was the commonest to occur (86%, followed by whole group, the relation between death and pH
hepatic dysfunction in (85%) of cases, the renal was statistically highly significant with p-value
dysfunction in (70%) of cases and the least or- less than 0.001 and it was significant in the MOD
gan/system dysfunction was cardiovascular dys- group with p-value 0.006.
function in 62% of cases. The range of organ involvement varies among different studies, de- In conclusion, we found evidence in support
of the MOD criterion in the definition of asphyxia, pending in part upon definitions used for perinatal
asphyxia and upon criteria of organ dysfunction. with renal dysfunction being the most commonly occuring dysfunction. Increased number of organ
Despite the fact that the cause of death in MODS dysfunctions was strongly associated with increased is multi-factorial, our study revealed that the oc- incidence of mortalities. No correlation was found currence of death was the highest among patients between the severity of acidosis and increased with cardiovascular dysfunction (76%) followed number of organ dysfunctions. by pulmonary dysfunction (63%) and then renal
dysfunction (53%). The p-value was statistically Recommendations: significant in the cases of renal dysfunction and • Prevention of hypoxic ischemic encephalopathy was highly significant in cases of cardiovascular in utero by proper antepartum and intrapartum and pulmonary dysfunctions. On the contrary, surveillance of all deliveries specially high risk Chauhan et al., found that renal dysfunction was groups. associated with the highest adverse outcome (67%)
followed by cardiovscular dysfunction (63%). • Optimizing obstetric care is important to limit These differences may be explained by the fact many neurological damages by using new tech-
that “adverse outcomes” according to them referred niques to detect fetal distress.
to death or CP while in our study “adverse • Special care should be directed for early recog- outcome” refers to death only. Also, Devarajan nition of symptoms and signs of target organ and Woroniecki [21] found that mortality rate in expected to be affected by hypoxia. the presence of renal dysfunction was 80% when
associated with multi-organ failure, although death • Special care should be directed towards neonates
was almost never caused by renal failure. with multi-organ dysfunction.
The number of organ/system dysfunction was • Applying new approaches in treatment specially
also studied and we found that two organ dysfunc- the neuroprotective techniques as hypothermia
tion was the commonest to occur (49%) followed and other new modalities of treatment. by one organ dysfunction (38%). In a similar study carried out by Shah et al. [22] , one-organ dysfunc- References tion occurred in 5% of cases, two-organ dysfunction
occurred in 25% of cases, three-organ dysfunction 1- YONEDA S., IBARA S., KOBAYASHI K., KATO E., occurred in 33% of cases and four-organ dysfunc- MARUYAMA Y., MARUYAMA H., SUMIDA Y., SU- NAMI R., SAKAI M., IKENOUE T. and SAITO S.: Low tion occurred in 37% of cases. Another similar adjusted serum ionized calcium shortly after birth predicts [23] study was carried out by Bennet et al. , they poor outcome in neonatal hypoxic-ischemic encephalop- found one-organ dysfunction occurred in 47% of athy: J. Obstet. Gynecol. Res., 31 (1): pp 57-64, 2005. cases, two-organ dysfunctioon occurred in 17% of 2- FAHEY J.O. and KING T.L.: Intrauterine asphyxia; cases, three-organ dysfunction occurred in 13%of neonatal encephalopathy, hypoxic-ischemic encephalop- cases and four-organ dysfunction occurred in 12% athy and cerebral palsy. J. Midwife Women’s health, 50 of cases. (6): pp 498-506, 2005. The relation between additional organs dysfunc- 3- LEGIDO A., KATSETOS C., MISHRA O. and DELIVOR-
tion and adverse outcome "death" was also studied. IA-PAPADOPOULOS M.: Perenatal hypoxic ischemic encephalopathy; current and future treatments. Interna- It was found that the highest incidence of death occurred in cases of four-organ dysfunction repre- tional pediatrics, 15 (3): pp 143-151, 2000.
senting 100% of cases followed by three-organ 4- GUPTA B.D., SHARMA P., BALGA J., PARAKH M.
dysfunction representing 86% of cases showing a and SONI J.P.: Renal Failure In Asphyxiated Neonates.
Indian pediatrics, 42: pp 928-34, 2005. high statistical significance. Despite the difference
in defining the term "adverse outcomes", Chauhan 5- JOHNSTON M.V.: Excitotoxicity in neonatal hypoxia.
et al. [24] recorded nearly the same results. Ment. Retard. Dev. Disabil. Res., 7: pp 229-34, 2001. Laila H. Mohammed, et al. 467
6- PERRONE S., TURRISI G. and BUONOCORE G.: Anti- 16- MAJEED R., MEMON Y., MAJEED F., et al.: Risk factors
oxidant therapy and neuroprotection in the new born. of birth asphyxia. Journal of Ayub Med. Coll. Abbottabad,
Pediatric health, 2 (6): pp 715-732, 2008. 19 (3): pp 67-71, 2007.
7- JU M., LEE H.J., LEE S.J., et al.: Neuroprotective effect 17- WEST C.R., CURR L., BATTIN M.R., et al.: Antenatal
of geneticin (G418) via apoptosis in perinatal hypoxic antecedents of moderate or severe neonatal encephalopathy
ischemic brain injury. Korean journal of pediatrics, 51 in term infants; a regional review. Aust. N. Z. J. Obstet.
(2): pp-170-180, 2008. Gynecol., pp 207-10, 2005.
SHANKARAN S., PAPPAS A., LAPTOOK A., et al.: 8- KHREISAT W. HABAHBEH Z.: Risk factors of birth 18-
asphyxia; A study at prince Ali Ben Al Hussein hospital, Outcomes of safety and effectiveness in a multicenter
Jordan. Pakistan Journal Of Medical science, 21 (1): pp randomized, controlled trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy. Pediatrics, 30-32, 2005. 122 (4): pp 791-798, 2008. 9- FUTRAKUL S., PRAISUWANNA P. and THAITUMY- ANON P.: Risk Factors For Hypoxic-Ischemic Encepha- 19- TEKIN N.: Postresuscitative management of asphyxiated term/preterm infant. Turkish Journal of Perinatology, 11 lopathy In Asphyxiated Newborn Infants. Journal of Med. (3-4): pp 78-84, 2003. Assoc. Thai., 89 (3): pp 322-8, 2006.
19- WHEELER D.S., WONG H.R. and SHANLEY T.P.: 10- PARKASH J. and DAS N.: Pattern of admissions to neonatal unit. J. Coll. Physicians Surg. Pak., 15: pp 341- Multible organ dysfunction syndromes. “Pediatric critical care medicine; basic science and clinical evidence”, 4, 2005. Springer-Verlag London Limited, Ch. (118): pp 1445-
11-BUTT T.K., FAROOQUI R. and KHAN M.A.: Risk factors 1456, 2007.
of hypoxic ischemic encephalopathy in children. Journal 20- HIGGINS R.D., RAJU T.N.K.,PERLMAN J., et al.: of the college of physicians and surgeons Pakistan, 18 Hypothermia and perinatal asphyxia; executive summary (7): pp 428-432, 2008. of the national institute of child health and human devel-
opment workshop. J. Pediatr., 148: pp 170-175, 2006. 12- KAY D.: Antenatal and intrapartum risk factors for birth
asphyxia among emergency obstetric referrals in mulago 21- DEVARAJAN P. and WORONEIKI R.: Acute tubular hospital Kampala, Uganda. East Afr. Med. J., 80: pp 140- necrosis. URL: http://www.eMedicine.com , 2008. 3, 2003.
22- SHAH P., REPHAGEN S., BEYENE J. and PERLMAN MILSOM I., LADFORS L., THIRINGER K., et al.: 13- M.: Multiorgan dysfunction in infants with post-asphyxial Influence of maternal, obstetric and fetal risk factors on hypoxic ischemic encephalopathy. Arch. Dis. Child Fetal the prevalence of birth asphyxia at term in a Swedish Neonatal Ed, 89: F 125-F 159, 2004. urban population. Acta. Obstet. Gynecol. Scand., 81: pp
909-917, 2002. 23- BENNET L., DEAN J.M., WASSINK G. and GUNN A.J.: Differential effects of hypothermia on early and late
14- ROSS M.G. and GALA R.: Use of umbilical artery base epileptiform events after severe hypoxia in preterm fetal
excess: Algorithm for the timing of hypoxic injury. A.M. sheep. J. Neurophysiol., 97 (1): pp 572-578, 2007.
J. Obstet. Gynecol., 187 (1): pp 1-9, 2002. 24- CHAUHAN S.P., MAGANN E.F. and MORRISON J.C.:
15- SHRESTHA M., et al.: Profile of asphyxiated babies at Neonatal organ system injury in acute birth asphyxia
Tribhuvan University Teaching Hospital. J. Nepal. pediatr. sufficient to result in neonatal encephalopathy. Obstet.
Soc., 29 (1): pp 3-5, 2009. Gynecol., 101: pp 203-4, 2003.