ETIOLOGY AND OUTCOME AT DUBAI HEALTH AUTHORITY NEONATAL INTENSIVE CARE UNITS

Document Type:Thesis

Subject Area:Politics

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Declaration: This is to certify that the work entitled “Acute Renal Injury in Neonates; Etiology and Outcome at Dubai Health Authority Neonatal Intensive Care Units from 2005-2016. ” was prepared and submitted to the Arab Board of Health Specialization as required. Student signature:_____________________ Date:____________________ Supervisor signature _____________________ Date:____________________ Hospital Stamp ________________________ Date:____________________ Dedication Acknowledgement Abstract Background: Acute kidney injury (AKI) is a multifaceted pathology characterized by a sudden decrease in kidney function caused by various group of predisposing factors including sepsis, hypovolemia, asphyxia, respiratory distress syndrome, heart failure etc. More recent studies have reported an incidence of AKI of 3–8% of all NICU admissions. Aim: To discuss the epidemiology of AKI, the common risk factors, management and their outcomes on neonates at Dubai Health Authority. Study Design: A retrospective descriptive study on all neonates admitted to the NICU of Dubai Health Authority and were diagnosed with acute kidney injury from January 2005 to December 2016. Setting: One tertiary government center in Dubai under Dubai Health Authority. Subjects: 49 patients with AKI were included in the study. The age limit on admission was 28 days. Results: The total sample had a male to female ratio of 4. and a significant proportion of males from the UAE (95%) had AKI when compared to the female population. The most common cause of AKI was neonatal medications administered (82%). Preterm babies represented the biggest proportion (55%) compared to term babies (45%). The mortality rate stood at 35% and additional 26% were discharged with abnormal kidney function. Conclusion: AKI among neonates admitted at NICUs under Dubai Health Authority has a very high mortality rate (35%) compared to international rates of up to 24%.

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Further, AKI has higher incidence in male with a male to female ratio of 4. and an overall morbidity of 27%. Since there is no clear management method, more research should be carried out in this area to come up with better management techniques to bring these morbidity and mortality rates down. Table of Contents List of Tables and Figures 1 Abbreviations 2 Introduction 3 Materials and Methods 3 Inclusion criteria: 4 Exclusion criteria: 5 Parameters Studied 5 Results 8 Discussions 21 Conclusion 31 Limitation of the Study 31 References 32 Appendix 34 List of Tables and Figures Table 1: GFR Reference Table 4 Table 2: Parameters Studied 5 Figure 1: Gender Distribution of AKI 8 Figure 2: Gender and Ethnic distribution of AKI 9 Figure 3: AKI Outcome 10 Table 3: Parameter and Demographic Factors: 11 Figure 4: Known Risk Factors 17 Figure 5: Mode of Delivery 18 Figure 6: Drugs Administered 18 Figure 7: Management Vs Outcome 20 Abbreviations AKI - Acute Kidney Injury ARDS - Respiratory Distress Syndrome ASD - Autism Spectrum Disorder ASD - Ventricular Septal Defect DIC - Disseminated Intravascular Coagulation ELBW - Extremely Low Birth Weight IVH - Intraventricular Hemorrhage NICU - Neonatal Intensive Care Unit NRDS - Neonatal respiratory distress syndrome NSAIDs - Nonsteroidal Anti-inflammatory Drugs PDA - Patent Ductus Arteriosus PFO - Patent Foramen Ovale PUV - Posterior Urethral Valve UAE – United Arab Emirates UPJ - Ureteropelvic Junction VLBW- Very Low Birth Weight VSD - Ventricular Septal Defect Introduction Acute Kidney Injury (AKI) is a common problem in the neonatal intensive care units (NICUs) and has been shown to occur in 3.

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– 24% of neonates admitted to NICUs. The need for this research in the UAE is to make physicians early aware of these causes that may eventually lead to permanent kidney injury which in turn has high morbidity and mortality. This study will discuss the epidemiology of AKI, the common risk factors, management and their outcomes on neonates since, to the best of our knowledge, there is no current research on it at Dubai health authority. Materials and Methods This is a retrospective descriptive study conducted on all neonates admitted to the NICU of Dubai health authority and were diagnosed with acute kidney injury from January 2005 to December 2016. The study sample included all neonates from 0- 28 days of age admitted to the NICU at Latifa and Dubai hospital during the period of January 2005 to December 2016.

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Data was collected through medical records and SAM system (which is computerized recording system) by using ICD codes N17-N19 Renal failure. However, after exclusion, the number went down to 49 patients. Inclusion criteria: • Patient age to be up to first 28 days of life. • Admitted to NICU at Latifa / Dubai hospital. • Males and Females. • Term and preterm. Three functional outcomes studied included, discharged with normal kidney function, discharged with abnormal kidney function, and death. The study neither involves the collection of tissue or fluid samples from the patients nor poses any sort of risk to the participants of the study. The study was undertaken after getting Ethical approval from the Dubai Scientific Research Ethics Committee. The data was collected by the Principal investigator through the use of electronic medical records where the demographic information, medical investigations, medications and discharge summaries of the patients are saved.

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All the data were saved in password encrypted pen drives. with a standard deviation 3. The minimum recorded eGFR was 2. and a maximum of 18. see table 1). For both babies, the eGFR was outside the normal range of the GFR reference table and thus all of them had an abnormal kidney function. The male to female ratio was 4. Further, the condition was experienced more in preterm cases (55%) than in the term babies (45%). Figure 1: Gender Distribution of AKI Majority of the subjects were UAE nationals (55%) followed by residents outside of the Arab region: Canada, India, Iran, Philippines, Afghanistan, and Pakistan (31%), and finally Arabs from Middle Eastern Region: Kuwait, Palestine, Yemen, Iraq, Palestine, and Jordan (14%). While comparing the prevalence of AKI and gender distribution among the different ethnic groups it was found, that males are more frequently affected in the UAE population (93%) than the Arabs (86%) and others (61%) See figure 2 below for details.

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Figure 2: Gender and Ethnic distribution of AKI Most of the neonates involved in this study were preterm infants 27 (55%). days with a standard deviation of 6 days. In fact, most of the babies (80%) were admitted on birth (at age zero). Another observation is that none of the babies were admitted from day 1 to day 7 (within the first week). Therefore, the cohort were either admitted on birth or after a week (see table 3 below). Parameter/Demographic Factors Mean SD Min Max Age on Admission (days) 2. Serum Potassium 5. Serum Phosphate 6. Serum Chloride 107. Serum bicarbonate 16. Albumin 2. Anything below 37 weeks was classified as preterm babies. The mean gestation age (34 weeks) was considerably below the minimum weeks (37) for term pregnancies and therefore it clearly demonstrated that many of the babies in the sample population were preterm. Precisely, 27 babies (55%) were preterm and only 22 (45%) were term babies.

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With regards to birth weight, the normal birth weight was taken as 2,500 grams and above. Low birthweight (below 2500 grams), very low birth weight (VLBW) (below 1,500 grams) and extremely low birthweight (ELBW) (below 1,000 grams). Therefore, cumulatively the total score ranges from 0 to a maximum of 10. A normal score is thus taken to be from 7 to 10. In this study, the focus was on Apgar score at 5 minutes. The results revealed that 40 babies recorded a normal score (7-10), 5 babies recorded a low score, while the test was not recorded for the remaining 4 babies. The mean Apgar score thus stood at 8. Therefore, the reported mean and the standard deviation are calculated based on the 44 subjects whose blood pressure was recorded. The initial mean urea was at 99 with a standard deviation of 98. The minimum recorded urea level was at 10 while the maximum was 574.

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This level was extremely high and therefore on discharge, they had considerably dropped. The mean urea at discharge was 51 with a standard deviation of 48. and a minimum value of 3 and a maximum of 8. The normal range of Serum Potassium for adults is approximately 3. mEq/L. However, the number of infants is age-dependent and may vary around the normal range. Taking 3. However, these values fluctuate with age and it is higher in babies and children than in adults. For the newborn are 4. mg/dL. Taking 4. mg/dL, 24 (73%) recorded a normal serum phosphate level, 3 (9%) recorded a low serum phosphate level (below 4. mEq/L with a standard deviation of 5. mEq/L. The minimum value was 5. mEq/L and a maximum of 28. mEq/L. The minim value recorded was 0. g/dL while the maximum value recorded was 4.

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g/dL. For those outside the normal range, none of the recorded a high albumin level as both of them scored a low level. With regards to Prothrombin Time, the mean for the cohort was 26. Just like PT, PTT is also measured in second and the normal range is 20-34 seconds. The mean PTT was 60 with a standard deviation of 40. It also clear that the mean PTT was far above the normal range. Only 8% (3) of the subjects had a normal PTT scores while 98% (33) had a high PTT scores. The test was not done on 27% (13) of the total sample population. mg/kg/hr with a standard deviation of 1. mg/kg/hr. This indicates, that the mean urine output on discharge within the normal range of 2-3 ml/kg/hr. It is however important to note that the test was not done for more than half (57%) of the sample population.

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Also, a normal urine output on discharge did not automatically mean that the baby was discharged with normal kidney function and vice versa. This was far above the normal range. In fact, 65% of the sample population recorded an above 2mg/dL serum creatinine levels. The ECG (electrocardiogram) test was significantly not performed as the test was only done for 7 subjects. Out of the 7, 5 had normal ECG while only 2 had abnormal ECG. The ECG test is used to measure the electrical activity of the heart to show whether or not it is working normally. There were different varieties of neonatal medications administered. These included Ampi, Genta, Ceftazidine, Flucloxacilin, Captopril, Phenobarbital, Pencilin, Lasix, Metropenem, Cloxacillin, Captorpil, Tyroxine, Spironolactone, Labetalol, Meropenem, Calcium resonium, Sodium bicarbonate, Osteocare syrup, Potasium-free formula, Targocid, Amphotercein, Dopamine, Dobutamine , Adrenaline and vancomycin among others.

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In most of the cases more than one medication was used on the babies and in some cases more than ten medications was used. For the Congenital Heart Disease, there were a variety of conditions that existed. These included Patent Ductus Arteriosus (PDA), Ventricular Septal Defect (VSD), Autism Spectrum Disorder (ASD), Ventricular Septal Defect (VSD), Patent Foramen Ovale (PFO), Aortic Stenosis, and Common Atrium. each). Figure 4: Known Risk Factors Most of the babies studied were delivered through cesarean section (53%) while 47% were delivered through normal virginal delivery (figure below). Note that cesarean section was predominantly used in preterm babies (77%) when compared to term babies (23%) (See figure 5 below) In addition, normal virginal delivery predominantly occurred in term babies (70%) compared to preterm babies (30%). Figure 5: Mode of Delivery From the results, the most common drug administered was aminoglycosides (71%), followed by intravenous contrast (12%), maternal antibiotic administration (8%), ACE inhibitors (8%), Amphotericin (4%) NSAIDs (indomethacin) (4%), and finally acyclovir (2%).

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Morphine was not used in either case Blood loss was found in 16% of the cases while traumatic birth history was found in 12% of the cases (figure 6) Figure 6: Drugs Administered In regards to management and outcome, there were four possible management types and three possible outcomes. A combination of medical, surgical, and dialysis management was used in only one 1 case, and the subject died (see 7 figure below). Figure 7: Management Vs Outcome The erythrocyte sedimentation rate (ESR) was either not required (41%) or not done (59%). In regards to blood culture, 67% (blood culture is used to detect fungi presence of fungi and bacterial so as to identify its type and thus guide its management) of infants did not experience any growth, while 20% experienced growth which included Elibsella ESB, Serratia Marcescens, and Staph Aureus among other growths.

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On the other hand, 8% of the children experienced negative growth while the test was not done for 2% of the kids. With regards to urine routine, 61% of the babies experienced negative growth, 21% experienced positive growth, and 4% experienced no growth, while the test was not done for 14%. Another study by Youssef 23 and others on newborns found a male sex predominance, with a male-female ratio of 1. However, the reason to why male neonates are more susceptible to AKI than the female neonates is still not clear. Therefore the study confirmed that males (82%) are more likely to suffer from AKI than females (18%) and thus more attention needs to be given to male newborns so that proper and immediate attention is given to promote a better outcome. Interestingly the mortality rate for female (44%) neonates was higher than that of males (33%).

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Therefore despite the males having a high likelihood of AKI, mortality was higher in for the females. In fact, preterm births had a mortality rate of 44% while that of term birth was at 23%, almost half of the preterm one. Furthermore, only 22% of the preterm babies were discharged with normal kidney function when on the other hand 55% of term babies were released with normal kidney function. Thus these results indicate that special attention needs to be given to preterm babies with regards to AKI. Birth weight also had a role to play in the incidence and outcome of AKI incidence and outcomes. The normal birth weight was taken as 2,500 grams and above and 55% of the neonates diagnosed with AKI did not meet this weight. Most of the babies studied were delivered through cesarean section (53%).

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However, it is unclear whether AKI had a hand to play in birth complication resulting in an abnormally high number of babies being delivered through the cesarean section as opposed to normal virginal delivery. One thing that is clear that cesarean section was predominantly used in preterm babies (77%) while normal virginal delivery occurred in 70% of term pregnancies. Therefore, it became clear that mothers who experience premature delivery find it hard to deliver through the normal process and have to be helped through cesarean section. The average admission age at the NICU stood at 2. These findings may also explain the high mortality rate (67%) among neonates with very low MAP (below 40). Note that too high MAP is also not desirable because the heart has to work extra-hard so as to push against the elevated blood pressure within the arteries and this may have an adverse impact on the life expectancy of the heart leading to mortality.

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Kidney studies indicate that increased level of blood urea nitrogen and creatinine are a clear indication of kidney failure. Conditions that favor reabsorption of urea into blood suggests the existence of prerenal AKI. This explains why an average, the initial urea levels were extremely high in the neonates since all of them had abnormal kidney function. Thus echocardiogram is an accurate measure of acute kidney function. Imaging techniques are commonly used in the initial evaluation of patients who are of suspected AKI. This because the method is widely available, it is easy to use as it is free of complications. In addition, it is highly portable especially for patients admitted at ICU or NICU. Even though other studies suggest that the rate of abnormal ultrasound findings in the AKI setting is considerably low (about 10%), the findings can have a big impact on the patient management.

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Acute Kidney Injury is also highly associated with high potassium level (hyperkalemia). Hyperkalemia refers to a condition when the potassium levels in the blood are too high. The idea is that AKI results in the reduced function of the kidney and thus its inefficiency to remove excess potassium from the blood. In this study, 37% (18) of the subjects recorded a high Serum Potassium level. This is quite a high level and thus it can be concluded that AKI results in high potassium serum in the blood. Therefore, this provided a strong evidence that there is a strong positive correlation between acute kidney injury and high chloride serum levels in the blood. According to some studies, “lower than normal serum bicarbonate levels are known to be associated with consecutive renal function deterioration. ” In addition, other studies also suggest that “serum bicarbonate on admission may independently be used to make a diagnosis of AKI.

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” In fact, bicarbonate measurements are normally used in the diagnosis and treatment of many potentially serious disorders which are associated with acid-base imbalance metabolic systems. This study revealed a significantly high number of neonates (84%) recorded a lower than normal serum bicarbonate levels. This study, clearly demonstrated this phenomenon because 72% scored a PT above the normal range while 98% had a high PTT scores. There, this teat can adequately be used in the diagnosis of AKI. As earlier notes, PT and PTT are measures of how fast blood clots so as to prevent bleeding. It is the first step in the healing of the wounds. These results, therefore, suggest that AKI has adverse effects on these times and may lead to excessive pleading and thus increase in other condition and mortality. Another significant risk factor was respiratory distress syndrome (73%).

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Evidence suggests that acute respiratory distress syndrome (ARDS) promotes the incidence of AKI. Neonatal respiratory distress syndrome (NRDS) is present majorly in preterm babies especially those born six weeks early. This condition usually develops within the initial 24 hours after birth. The symptoms include sharp, rapid, and shallow breathing, pulling-in of the chest between and below the ribs in each breath. Clinicians sometimes use to cure other complications. However, such a high immunosuppression is frequently attended by bacterial, fungal, and viral infections including certain organism that can specifically result in the infection of the kidney. This study, therefore, provided evidence that phototherapy should be used sparingly because it is a significant risk factor for the neonates developing abnormal kidney function. However, there was no a statistical significant relationship between phototherapy used and cause of death (p=0.

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Studies suggest that acute kidney injury is highly associated with significant mortality as well as morbidity in patients with congenital heart disease who undergo cardiac surgery or in the paediatric patients with congestive heart failure. This is because the study revealed that there was statistical significant relationship between hypotension and cause of death (p=0. Seizure was also a significant risk fact among the cohort, present in 35% of all the cases. Seizure refers to a sudden surge of electrical activities within the brain and it affects how individuals appear and act. Studies suggest that acute renal failure is the most common complication of rhabdomyolysis. Note that rhabdomyolysis is common in patients presenting increased muscular activity such as seizures. The resultant reflux of urine into the renal pelvis may result in damage to the kidney.

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Urological anomalies were present in 31% of the subject population. Also, there was a statistically significant relationship between urological anomalies and death (p=0. The other risk factors studies were not predominantly present (below 30%) of the cases. In summary, the most dominant risk factor in this study was neonatal medications administered (82%) followed by respiratory distress syndrome (73%), and intubation (67%), phototherapy. In fact, the mortality rate was in 43% of the cases where aminoglycosides were administered. Only 40% of the subjects were discharged with normal kidney function an additional 17% were discharged with abnormal kidney function. Other drugs were sparingly administered since the second most used drug was intravenous contrast and was only used in 12% of the subjects. Morphine was not used on any of the subjects. Perhaps the reason to why other drugs were not used is because they end up increasing the prevalence of AKI rather than treating it.

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One interesting finding was that AKI is significantly prevalent in male neonates than the female neonates although mortality was higher in female neonates than make neonates. This finding calls for studies on the relationship of gender and AKI so as to determine the best measure to be taken for either gender. The study also revealed that AKI has a very high morbidity and mortality among neonates. There are many risk factors that promote the incidence of AKI and neonatal medication administered was the common risk factor. The morbidity rate stood at 27% while the mortality rate stood at 35%. Acute kidney injury in critically ill newborns: what do we know? What do we need to learn? Pediatr Nephrol 2009; 24: 265-74. Ottonello G, Dessì A, Neroni P, Trudu ME, Manus D, Fanos V. Acute kidney injury in neonatal age.

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J Pediatr Neonat Individual Med. e030246. Indian J Pediatr. PubMed: 16816511] 7. Kleinman LI, Stewart CL, Kaskel FJ. Renal disease in the newborn. In: Edelman CM Jr, editor. Iran J Kidney Dis. PubMed: 19617661] 10. Gharehbaghi MM, Peirovifor A. Evaluating causes of acute renal failure in newborn intants. Pak J Med Sci. Arch Dis Child Fetal Neonatal Ed. ;73:F187–92. PMCID: PMC2528481] [PubMed: 8535880] 14. Kanarek KS, Root E, Sidebottom RA, Williams PR. Successful peritoneal dialysis in an infant weighing less than 800 grams. Stapleton FB, Jones DP, Green RS. Acute renal failure in neonates: Incidence, etiology and outcome. Pediatr Nephrol. PubMed: 3153295] 18. Chevalier RL, Campbell F, Brenbridge AN. th ed. Philadelphia: Elsevier Saunders; 2005. p. Cuzzolin L, Fanos V, Pinna B, et al. Postnatal renal function in preterm newborns: A role of diseases, drugs and therapeutic interventions. Shehab, M. M.

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Abd-Elrheem, M. Incidence of acute kidney injury in the neonatal intensive care unit.  Saudi journal of kidney diseases and transplantation, 26(1), 67. Fisher's Exact Test. Linear-by-Linear Association 8. N of Valid Cases 49 a. cells (25. have expected count less than 5. Not assuming the null hypothesis. b. Using the asymptotic standard error assuming the null hypothesis. c. Based on normal approximation. a 1. Continuity Correctionb. Likelihood Ratio. Fisher's Exact Test. Linear-by-Linear Association. Interval by Interval Pearson's R -. c Ordinal by Ordinal Spearman Correlation -. c N of Valid Cases 49 a. Not assuming the null hypothesis. b. BOTH * DISCHARGED_WITH_ABNORMAL_KIDNEYFUNCTION Crosstab Count DISCHARGED_WITH_ABNORMAL_KIDNEYFUNCTION Total Y N BOTH Y 7 5 12 N 6 31 37 Total 13 36 49 Chi-Square Tests Value df Asymp. Sig. sided) Exact Sig. sided) Exact Sig. sided) Pearson Chi-Square 8. Computed only for a 2x2 table Symmetric Measures Value Asymp.

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Std. Errora Approx. Tb Approx. Sig. at 5% level of significance hence we reject the null hypothesis. We conclude that there is enough evidence to indicate that there is an association between s both (surgical and medical procedures) used and patients discharged with abnormal kidney function. The relationship is positive hence an increase in the use of both (surgical and medical procedures) will lead to an increase in patients discharged with abnormal kidney function (correlation=0. BOTH * DISCHARGED_WITH_NORMAL_KIDNEY_FUNCTION Crosstab Count DISCHARGED_WITH_NORMAL_KIDNEY_FUNCTION Total Y N BOTH Y 4 8 12 N 15 22 37 Total 19 30 49 Chi-Square Tests Value df Asymp. Sig. have expected count less than 5. The minimum expected count is 4. b. Computed only for a 2x2 table Symmetric Measures Value Asymp. Std. Based on normal approximation. The null hypothesis states that there is no statistically significant association between use of both (surgical and medical procedures) used and patients discharged with normal kidney function, while the alternative hypothesis states that there is a statistically significant association between both (surgical and medical procedures) used and patients discharged with normal kidney function.

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The p-value is greater than 0. at 5% level of significance hence we do not reject the null hypothesis. We conclude that there is enough evidence to indicate that there is no association between both (surgical and medical procedures) used and patients discharged with normal kidney function. Total 49 100. DISCHARGED_WITH_NORMAL_KIDNEY_FUNCTION Frequency Percent Valid Percent Cumulative Percent Valid Y 19 38. N 30 61. Total 49 100. DISCHARGED_WITH_ABNORMAL_KIDNEYFUNCTION Frequency Percent Valid Percent Cumulative Percent Valid Y 13 26. at 5% level of significance. There is a statistical significant relationship between hypotension and cause of death p=0. at 5% level of significance. There is a statistically significant relationship between IVH and cause of death p=0. at 5% level of significance. Urological anomalies (Y/N) * DEATH (Y/N) 49 100. Dehydration (Y/N) * DEATH (Y/N) Crosstab Count DEATH (Y/N) Total Y N Dehydration (Y/N) Y 0 5 5 N 17 27 44 Total 17 32 49 Chi-Square Tests Value df Asymp.

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Sig. sided) Exact Sig. sided) Exact Sig. b. Computed only for a 2x2 table Symmetric Measures Value Asymp. Std. Errora Approx. Tb Approx. Sig. sided) Exact Sig. sided) Exact Sig. sided) Pearson Chi-Square. a 1. Std. Errora Approx. Tb Approx. Sig. Interval by Interval Pearson's R. sided) Exact Sig. sided) Pearson Chi-Square 2. a 1. Continuity Correctionb 1. Likelihood Ratio 1. Tb Approx. Sig. Interval by Interval Pearson's R. c Ordinal by Ordinal Spearman Correlation. c N of Valid Cases 49 a. a 1. Continuity Correctionb. Likelihood Ratio 1. Fisher's Exact Test. Linear-by-Linear Association 1. Interval by Interval Pearson's R -. c Ordinal by Ordinal Spearman Correlation -. c N of Valid Cases 49 a. Not assuming the null hypothesis. b. Likelihood Ratio 18. Fisher's Exact Test. Linear-by-Linear Association 17. N of Valid Cases 49 a. cells (0. c N of Valid Cases 49 a. Not assuming the null hypothesis.

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b. Using the asymptotic standard error assuming the null hypothesis. c. Linear-by-Linear Association 3. N of Valid Cases 49 a. cells (25. have expected count less than 5. The minimum expected count is 4. b. Using the asymptotic standard error assuming the null hypothesis. c. Based on normal approximation. Urological anomalies (Y/N) * DEATH (Y/N) Crosstab Count DEATH (Y/N) Total Y N Urological anomalies (Y/N) Y 0 11 11 N 17 21 38 Total 17 32 49 Chi-Square Tests Value df Asymp. cells (25. have expected count less than 5. The minimum expected count is 3. b. Computed only for a 2x2 table Symmetric Measures Value Asymp. c. Based on normal approximation.

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