Pediatric Pulmonology
Factors Predicting Mortality in Newborn Ventilation Biswanath Basu, MD,1* Sunil K. Sinha,
FRCPCH,
2
T. Basu,
3 PhD,
and T.K.S. Mahapatra,
MD
4
Summary. Objective: Prediction of mortality among newborns on mechanical ventilation is difficult. Our aim was to develop a scoring system for predicting mortality among such neonates. Methods: This multi centre prospective study was performed to develop and validate a scoring system among two equal cohorts of ventilated newborns in India. Mechanical ventilator was used in pressure-limited time-cycled mode. Arterial blood gas, initial pulmonary pressures, septicemia screen along with other basic parameters were recorded in a pre-structured proforma. Blood samples were analyzed for malondialdehyde to determine the possible role and predictive validity of free radical injury. Multiple logistic regression analysis was done to find out independent predictors of mortality for the variables those were significantly associated with outcome after univariate analysis. Results: On univariate analysis, birth-weight, oxygenation-index, septicaemia, malondialdehyde level, and inotropic support were significantly associated with mortality. However, after multiple regression analysis gestational-age, pH and FiO2 lost their significance as predictors. According to cut-off values of ROC-curve, a scoring system ranging from 0 to 20 and four mortality risk groups were developed. Area under ROC-curve was 0.94, compared to 0.90 for both APACHE-III and CRIB-scores; and 0.92 for PRISM-score. Conclusions: Birth-weight, oxygenation-index, malondialdehyde level, inotropic support, and septicemia are independent mortality predictors of neonatal ventilation. Increase in malondialdehyde level is associated with higher mortality rate, indicating possible role of free radical injury. Pediatr Pulmonol. ß 2014 Wiley Periodicals, Inc.
Key words: oxygenation-index; malondialdehyde level.
INTRODUCTION
Neonatal mortality is a major public health problem in both developed & developing countries.1 During last two decades neonatal mortality has diminished considerably due to large scale use of mechanical ventilation in neonatal intensive care units.2 But identification of risk factors is necessary to reduce it further. Unfortunately reports on mortality risk factors are lacking especially from developing world. The present study was therefore designed to evaluate the independent risk factors associated with mortality to establish a scoring system which will quantify mortality risks of neonates on mechanical ventilation in a neonatal intensive care unit. One of the most interesting aspects of this study is incorporation of serum malondialdehyde to assess the extent of free radical injury.3 MATERIALS AND METHODS
After obtaining ethical approval and informed parental consents, 566 newborns, satisfying selection criteria, were enrolled in this prospective study. All enrolled newborns were divided randomly into two equal cohorts to develop and validate a score for mortality risk. ß 2014 Wiley Periodicals, Inc.
1
Department of Pediatrics, NRS Medical College & Hospital, Kolkata, India. 2 Department of Neonatal Paediatrics, James Cook University Hospital, University of Durham, Middlesbrough, UK. 3
Science College, Kolkata, India.
4 Department of Pediatrics, RG Kar Medical College & Hospital, Kolkata, India.
Conflict of interest: None. Authors contributions: B.B. and T.K.S.M. involved in design, conduction, collection of data, its analysis and preparation of manuscript; T.B. involved in biochemical tests and analysis of data; and S.S. is involved in critical review of the manuscript.
Correspondence to: Biswanath Basu, MD, Department of Pediatrics, NRS Medical College & Hospital, Kolkata 700004, West Bengal, India. E-mail: [email protected] Received 11 July 2013; Accepted 26 January 2014. DOI 10.1002/ppul.23019 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Basu et al.
Indications for ventilation were PaO2 60 mmHg or intractable apnoeic spell. Newborns associated with life threatening surgical malformation, complex congenital heart disease, terminally ill with multi-organ dysfunction, apnoea arising out of maternal sedative intake or non-availability of basic data were excluded from the study. Documentation at initiation of ventilation includes: gestational age, sex, inborn/out-born, birth weight, use of antenatal steroids, apgar score at 1 and 5 minute, rectal temperature (admission temperature), septicemia screen, age in hour, capillary refill time, requirement of inotropic support, peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), mean airway pressure (MAP), pulmonary compliance, pulmonary resistance, pulmonary volumes (as displayed on ventilator), PaO2, PaCO2, arterial alveolar oxygen tension ratio(a/A ratio), alveolar arterial oxygen tension difference (AaDO2) and oxygenation index (from the first blood gas sample on ventilator). Pulmonary resistance was calculated from the airway pressure change after an airway occlusion (inspiratory hold) during a constant inspiratory flow. For screening of septicaemia, total leucocyte count (TLC) and absolute neutrophil count (ANC) with ratio of immature- mature neutrophil (I/T) were obtained. Blood culture was sent, whenever any screening parameter was in favour of septicaemia (TLC < 5,000/mm3; ANC < 1,800/mm3; I/T > 0.2) or clinical features were suggestive of sepsis. All deliveries of less than 34 weeks received full course of antenatal steroid. After establishing adequate oxygenation, ventilation, perfusion, and monitoring, we administered early rescue surfactant therapy as soon as the diagnosis of respiratory distress syndrome (RDS) was made and usually within the first hour of age. Prophylactic surfactant therapy was given to very premature infants (27 weeks or less). All neonates were continuously monitored electronically to observe temperature, pulse, respiration, and oxygen saturation (target 88–92%). Mechanical ventilator was used in pressure-limited time-cycled mode (Maquet Servo-i infant) with facility of on line measurements of volumes and pulmonary mechanics. Continuous positive airway pressure (CPAP) was arranged first for most of the babies and shifted to full mechanical ventilation, if no improvement observed with CPAP. Babies requiring high frequency oscillatory ventilation (HFOV) were excluded from the study. An unified ventilation protocol was maintained at all study centres. The study was conducted in accordance with the original protocol and without any amendments. Peripheral venous blood samples of ventilated newborns were collected at initiation of ventilation in sterile heparinised and deionized polyethylene vials. Plasma was separated from blood samples immediately by centrifugation system and was stored in separate deionized vials Pediatric Pulmonology
at 208C. Samples were analyzed for malondialdehyde by thiobarbituric acid assay (NWKMDA01, USA). Continuous variables were analyzed using student ‘t’ test and proportions were tested by Chi square test or Fisher test. P-value 0.05 in all cases.
Score development cohort, n ¼ 283
Score validation cohort, n ¼ 283
2347 (690–213) 36 (25–45) 77 35.6 4.2 7.22 0.43 18.6 7.5 49 35 56 24 74 19 22 7 41 7.9 2.5 0.79 0.14 95 26 5.6 3.6 220 65 0.28 0.17 7.8 5.2 2.6 2.2
2293 (650–4367) 35 (25–44) 77 35.8 3.9 7.24 0.47 16.6 9.1 52 43 58 27 72 23 22 8 41 7.6 2.9 0.76 0.17 98 21 5.4 3.9 211 73 0.31 0.19 8.1 5.4 2.3 2.1
Newborn Ventilation
(associated with HIE 17%, septicaemia 9%) in 14.9%; apnoea (apnoea of prematurity 67%, apnoea out of septicaemia 18%, and apnoea from HIE 23%) in 38.6%, pneumonia (associated with HIE 23%, RDS 32%, apnoea 26%, septicaemia 15%, MAS 21%) in 35.2%, and others 12.5% (percentage values are overlapping among disease subgroups). Out of total 566 enrolled babies, 22 died (extreme prematurity with apnoea 67%, RDS 56%, MAS 5%, septicaemia 13%, refractory shock 87%, HIE 54%, disseminated intravascular coagulation 61%, and necrotising enterocolitis 4%). Numbers and causes of death were almost identical among both cohorts. Initially eight variables were found significant on univariate analysis (gestational age, birth weight, pH, FiO2, oxygenation index, malondialdehyde level, presence of septicaemia and requirement of inotropic support). Apgar score at 1 and 5 min, rectal tempareture, inborn/outborn, sex, age at initiation of ventilation, PaO2, PaCO2, PIP, PEEP, MAP, minute volume and tidal volume failed to reach the point of statistical significance. For logistic regression analysis, statistically significant continuous variables were transformed into three categories each. However, gestational age, pH and FiO2 lost their significance after multiple logistic regression analysis. Table 2 shows the logistic slopes, standard errors, regression coefficients, and “P” values of five independent mortality predictors (birth weight,oxygenation index, malondialdehyde level, requirement of inotropic support and presence of septicemia). In order to keep weightage of variables balanced, oxygenation index less than six was categorized as 1, the birth weight class above 2500 gram as 1 etc. as shown in Table 3. Through simple addition of individual score of each significant variable, a diagnostic total score was computed up to a maximum of 20 points (Table 3). A bivariate analysis was undertaken to look for collinearity. The resultant scores were analyzed thereafter by receiver operating characteristic (ROC) curve to determine the most appropriate cut-off points. Based on optimal cut-off points of the scoring system, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated at each cut-off TABLE 2— Stepwise Forward Multiple Regression Analysis Showing Effect of Five Independent Variables on Mortality in Mechanically Ventilated Newborn
Variable
Logistic b slopes
Standard error
Regression coefficient
Weight (g) Oxygenation index Malondialdehyde level Inotropic supportrequired Septicaemia
0.7869 0.8675 0.7321 0.1342 0.5463
0.1985 0.2435 0.1231 0.1258 0.1153
0.3124 0.3429 0.2176 0.1261 0.1887
P < 0.001 in all cases.
3
TABLE 3— Mortality Risk Score for Mechanically Ventilated Newborn (A Score Up to 8 Point “Mild Risk”; >8 to 12 “Moderate Risk”; >12 to 16 “High risk,” and >16 “Extreme Risk” of Death) Variable
Range/grade
Category
Score
Weight (g)
>2500 2500–2000 8 to 12 as “moderate risk”; from >12 to 16 as “high risk”; and >16 point as “extreme risk” of death). The advantage of this scoring system is it’s unique flexibility, for example a baby of higher risk group may shift to lower risk category following decrease of malondialdehyde level or cure of sepsis. As mentioned in the result section, it was found that, increase in total score can predict outcome more perfectly. The area under ROC curve was 0.94 for our score compared with 0.90 for both APACHE III and CRIB scores; and 0.92 for PRISM score.12–14 Without inclusion Pediatric Pulmonology
of “malondialdehyde level” in our calculation, the prognostic model would be of inferior quality with decrease in area under the ROC curve from 0.9405 to 0.8675. Larger trial is necessary to validate this model and to prove it’s superiority over other scoring systems. Scoring values may defer among different populations and that requires further research. There is also a window for further improvement of this scoring system by making it disease and birth weight specific. This scoring system permits identification and prognosis of newborns on mechanical ventilation with similar disease severity and comparison among neonatal intensive care units. Our score may allow early randomization based on risk of mortality. It also may help to differentiate treatment effects and variations in mortality risk over a period of time. This score was not intended to limit care of the individual infant. Because of the obvious ethical issues involved, we want to emphasize that our scoring system is not sufficiently accurate to identify those newborns who cannot be saved. ACKNOWLEDGMENT
We thank all nursing staff of neonatal intensive care unit and parents of all newborns, enrolled in this study. REFERENCES 1. WHO Report. Levels and trends in child mortality 2013. 2. Henderson-Smart DJ, Wilkinson A, Raynes-Greenow CH. Mechanical ventilation for newborn infants with respiratory failure due to pulmonary disease. Cochrane Database Syst Rev 2002; CD002770. 3. Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 1997;43:1209–1214. 4. Horbar JD, Onstad L, Wright E. Predicting mortality risk for infants weighing 501 to 1500 grams at birth. A National Institutes of Health Neonatal Research Network report. Crit Care Med 1993;21:12–18. 5. Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993;91: 617–623. 6. Ortega M, Ramos AD, Platzker AC, Atkinson JB, Bowman CM. Clinical and laboratory observations. Early prediction of ultimate outcome in newborn infants with severe respiratory failure. J Pediatr 1988;113:744–746. 7. Gillbert R, Keighley JF. The arterial alveolar oxygenation ratio. An index of gas exchange applicable to varying inspired oxygen concentrations. Am Rev Respir Dis 1974;109:142–145. 8. Trachsel D, McCrindle BW, Nakagawa S, Bohn D. Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005;172: 206–211. 9. Schmidt H, Grune T, Mu¨ller R, Siems WG, Wauer RR. Increased levels of lipid peroxidation products malondialdehyde and 4-hydroxynonenal after perinatal hypoxia. Pediatr Res 1996;40: 15–20.
Newborn Ventilation 10. Shouman BO, Mesbah A, Aly H. Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy. J Perinatol 2008;28:487–491. 11. Sudarsanam TD, Jeyaseelan L, Thomas K, John G. Predictors of mortality in mechanically ventilated patients. Postgrad Med J 2005;81:780–783. 12. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio CA, Murphy DJ, Lotring T, Damiano A, et al. The APACHE III prognostic system. Risk prediction of hospital
5
mortality for critically ill hospitalized adults. Chest 1991;100:1619–1636. 13. Pollack MM, Ruttimann UR, Getson PR. Pediatric risk of mortality (PRISM) score. Crit Care Med 1988;16:1110– 1116. 14. The International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993;342:193–198.
Pediatric Pulmonology
Factors Predicting Mortality in Newborn Ventilation Biswanath Basu, MD,1* Sunil K. Sinha,
FRCPCH,
2
T. Basu,
3 PhD,
and T.K.S. Mahapatra,
MD
4
Summary. Objective: Prediction of mortality among newborns on mechanical ventilation is difficult. Our aim was to develop a scoring system for predicting mortality among such neonates. Methods: This multi centre prospective study was performed to develop and validate a scoring system among two equal cohorts of ventilated newborns in India. Mechanical ventilator was used in pressure-limited time-cycled mode. Arterial blood gas, initial pulmonary pressures, septicemia screen along with other basic parameters were recorded in a pre-structured proforma. Blood samples were analyzed for malondialdehyde to determine the possible role and predictive validity of free radical injury. Multiple logistic regression analysis was done to find out independent predictors of mortality for the variables those were significantly associated with outcome after univariate analysis. Results: On univariate analysis, birth-weight, oxygenation-index, septicaemia, malondialdehyde level, and inotropic support were significantly associated with mortality. However, after multiple regression analysis gestational-age, pH and FiO2 lost their significance as predictors. According to cut-off values of ROC-curve, a scoring system ranging from 0 to 20 and four mortality risk groups were developed. Area under ROC-curve was 0.94, compared to 0.90 for both APACHE-III and CRIB-scores; and 0.92 for PRISM-score. Conclusions: Birth-weight, oxygenation-index, malondialdehyde level, inotropic support, and septicemia are independent mortality predictors of neonatal ventilation. Increase in malondialdehyde level is associated with higher mortality rate, indicating possible role of free radical injury. Pediatr Pulmonol. ß 2014 Wiley Periodicals, Inc.
Key words: oxygenation-index; malondialdehyde level.
INTRODUCTION
Neonatal mortality is a major public health problem in both developed & developing countries.1 During last two decades neonatal mortality has diminished considerably due to large scale use of mechanical ventilation in neonatal intensive care units.2 But identification of risk factors is necessary to reduce it further. Unfortunately reports on mortality risk factors are lacking especially from developing world. The present study was therefore designed to evaluate the independent risk factors associated with mortality to establish a scoring system which will quantify mortality risks of neonates on mechanical ventilation in a neonatal intensive care unit. One of the most interesting aspects of this study is incorporation of serum malondialdehyde to assess the extent of free radical injury.3 MATERIALS AND METHODS
After obtaining ethical approval and informed parental consents, 566 newborns, satisfying selection criteria, were enrolled in this prospective study. All enrolled newborns were divided randomly into two equal cohorts to develop and validate a score for mortality risk. ß 2014 Wiley Periodicals, Inc.
1
Department of Pediatrics, NRS Medical College & Hospital, Kolkata, India. 2 Department of Neonatal Paediatrics, James Cook University Hospital, University of Durham, Middlesbrough, UK. 3
Science College, Kolkata, India.
4 Department of Pediatrics, RG Kar Medical College & Hospital, Kolkata, India.
Conflict of interest: None. Authors contributions: B.B. and T.K.S.M. involved in design, conduction, collection of data, its analysis and preparation of manuscript; T.B. involved in biochemical tests and analysis of data; and S.S. is involved in critical review of the manuscript.
Correspondence to: Biswanath Basu, MD, Department of Pediatrics, NRS Medical College & Hospital, Kolkata 700004, West Bengal, India. E-mail: [email protected] Received 11 July 2013; Accepted 26 January 2014. DOI 10.1002/ppul.23019 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Basu et al.
Indications for ventilation were PaO2 60 mmHg or intractable apnoeic spell. Newborns associated with life threatening surgical malformation, complex congenital heart disease, terminally ill with multi-organ dysfunction, apnoea arising out of maternal sedative intake or non-availability of basic data were excluded from the study. Documentation at initiation of ventilation includes: gestational age, sex, inborn/out-born, birth weight, use of antenatal steroids, apgar score at 1 and 5 minute, rectal temperature (admission temperature), septicemia screen, age in hour, capillary refill time, requirement of inotropic support, peak inspiratory pressure (PIP), positive end expiratory pressure (PEEP), mean airway pressure (MAP), pulmonary compliance, pulmonary resistance, pulmonary volumes (as displayed on ventilator), PaO2, PaCO2, arterial alveolar oxygen tension ratio(a/A ratio), alveolar arterial oxygen tension difference (AaDO2) and oxygenation index (from the first blood gas sample on ventilator). Pulmonary resistance was calculated from the airway pressure change after an airway occlusion (inspiratory hold) during a constant inspiratory flow. For screening of septicaemia, total leucocyte count (TLC) and absolute neutrophil count (ANC) with ratio of immature- mature neutrophil (I/T) were obtained. Blood culture was sent, whenever any screening parameter was in favour of septicaemia (TLC < 5,000/mm3; ANC < 1,800/mm3; I/T > 0.2) or clinical features were suggestive of sepsis. All deliveries of less than 34 weeks received full course of antenatal steroid. After establishing adequate oxygenation, ventilation, perfusion, and monitoring, we administered early rescue surfactant therapy as soon as the diagnosis of respiratory distress syndrome (RDS) was made and usually within the first hour of age. Prophylactic surfactant therapy was given to very premature infants (27 weeks or less). All neonates were continuously monitored electronically to observe temperature, pulse, respiration, and oxygen saturation (target 88–92%). Mechanical ventilator was used in pressure-limited time-cycled mode (Maquet Servo-i infant) with facility of on line measurements of volumes and pulmonary mechanics. Continuous positive airway pressure (CPAP) was arranged first for most of the babies and shifted to full mechanical ventilation, if no improvement observed with CPAP. Babies requiring high frequency oscillatory ventilation (HFOV) were excluded from the study. An unified ventilation protocol was maintained at all study centres. The study was conducted in accordance with the original protocol and without any amendments. Peripheral venous blood samples of ventilated newborns were collected at initiation of ventilation in sterile heparinised and deionized polyethylene vials. Plasma was separated from blood samples immediately by centrifugation system and was stored in separate deionized vials Pediatric Pulmonology
at 208C. Samples were analyzed for malondialdehyde by thiobarbituric acid assay (NWKMDA01, USA). Continuous variables were analyzed using student ‘t’ test and proportions were tested by Chi square test or Fisher test. P-value 0.05 in all cases.
Score development cohort, n ¼ 283
Score validation cohort, n ¼ 283
2347 (690–213) 36 (25–45) 77 35.6 4.2 7.22 0.43 18.6 7.5 49 35 56 24 74 19 22 7 41 7.9 2.5 0.79 0.14 95 26 5.6 3.6 220 65 0.28 0.17 7.8 5.2 2.6 2.2
2293 (650–4367) 35 (25–44) 77 35.8 3.9 7.24 0.47 16.6 9.1 52 43 58 27 72 23 22 8 41 7.6 2.9 0.76 0.17 98 21 5.4 3.9 211 73 0.31 0.19 8.1 5.4 2.3 2.1
Newborn Ventilation
(associated with HIE 17%, septicaemia 9%) in 14.9%; apnoea (apnoea of prematurity 67%, apnoea out of septicaemia 18%, and apnoea from HIE 23%) in 38.6%, pneumonia (associated with HIE 23%, RDS 32%, apnoea 26%, septicaemia 15%, MAS 21%) in 35.2%, and others 12.5% (percentage values are overlapping among disease subgroups). Out of total 566 enrolled babies, 22 died (extreme prematurity with apnoea 67%, RDS 56%, MAS 5%, septicaemia 13%, refractory shock 87%, HIE 54%, disseminated intravascular coagulation 61%, and necrotising enterocolitis 4%). Numbers and causes of death were almost identical among both cohorts. Initially eight variables were found significant on univariate analysis (gestational age, birth weight, pH, FiO2, oxygenation index, malondialdehyde level, presence of septicaemia and requirement of inotropic support). Apgar score at 1 and 5 min, rectal tempareture, inborn/outborn, sex, age at initiation of ventilation, PaO2, PaCO2, PIP, PEEP, MAP, minute volume and tidal volume failed to reach the point of statistical significance. For logistic regression analysis, statistically significant continuous variables were transformed into three categories each. However, gestational age, pH and FiO2 lost their significance after multiple logistic regression analysis. Table 2 shows the logistic slopes, standard errors, regression coefficients, and “P” values of five independent mortality predictors (birth weight,oxygenation index, malondialdehyde level, requirement of inotropic support and presence of septicemia). In order to keep weightage of variables balanced, oxygenation index less than six was categorized as 1, the birth weight class above 2500 gram as 1 etc. as shown in Table 3. Through simple addition of individual score of each significant variable, a diagnostic total score was computed up to a maximum of 20 points (Table 3). A bivariate analysis was undertaken to look for collinearity. The resultant scores were analyzed thereafter by receiver operating characteristic (ROC) curve to determine the most appropriate cut-off points. Based on optimal cut-off points of the scoring system, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated at each cut-off TABLE 2— Stepwise Forward Multiple Regression Analysis Showing Effect of Five Independent Variables on Mortality in Mechanically Ventilated Newborn
Variable
Logistic b slopes
Standard error
Regression coefficient
Weight (g) Oxygenation index Malondialdehyde level Inotropic supportrequired Septicaemia
0.7869 0.8675 0.7321 0.1342 0.5463
0.1985 0.2435 0.1231 0.1258 0.1153
0.3124 0.3429 0.2176 0.1261 0.1887
P < 0.001 in all cases.
3
TABLE 3— Mortality Risk Score for Mechanically Ventilated Newborn (A Score Up to 8 Point “Mild Risk”; >8 to 12 “Moderate Risk”; >12 to 16 “High risk,” and >16 “Extreme Risk” of Death) Variable
Range/grade
Category
Score
Weight (g)
>2500 2500–2000 8 to 12 as “moderate risk”; from >12 to 16 as “high risk”; and >16 point as “extreme risk” of death). The advantage of this scoring system is it’s unique flexibility, for example a baby of higher risk group may shift to lower risk category following decrease of malondialdehyde level or cure of sepsis. As mentioned in the result section, it was found that, increase in total score can predict outcome more perfectly. The area under ROC curve was 0.94 for our score compared with 0.90 for both APACHE III and CRIB scores; and 0.92 for PRISM score.12–14 Without inclusion Pediatric Pulmonology
of “malondialdehyde level” in our calculation, the prognostic model would be of inferior quality with decrease in area under the ROC curve from 0.9405 to 0.8675. Larger trial is necessary to validate this model and to prove it’s superiority over other scoring systems. Scoring values may defer among different populations and that requires further research. There is also a window for further improvement of this scoring system by making it disease and birth weight specific. This scoring system permits identification and prognosis of newborns on mechanical ventilation with similar disease severity and comparison among neonatal intensive care units. Our score may allow early randomization based on risk of mortality. It also may help to differentiate treatment effects and variations in mortality risk over a period of time. This score was not intended to limit care of the individual infant. Because of the obvious ethical issues involved, we want to emphasize that our scoring system is not sufficiently accurate to identify those newborns who cannot be saved. ACKNOWLEDGMENT
We thank all nursing staff of neonatal intensive care unit and parents of all newborns, enrolled in this study. REFERENCES 1. WHO Report. Levels and trends in child mortality 2013. 2. Henderson-Smart DJ, Wilkinson A, Raynes-Greenow CH. Mechanical ventilation for newborn infants with respiratory failure due to pulmonary disease. Cochrane Database Syst Rev 2002; CD002770. 3. Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P. Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 1997;43:1209–1214. 4. Horbar JD, Onstad L, Wright E. Predicting mortality risk for infants weighing 501 to 1500 grams at birth. A National Institutes of Health Neonatal Research Network report. Crit Care Med 1993;21:12–18. 5. Richardson DK, Gray JE, McCormick MC, Workman K, Goldmann DA. Score for neonatal acute physiology: a physiologic severity index for neonatal intensive care. Pediatrics 1993;91: 617–623. 6. Ortega M, Ramos AD, Platzker AC, Atkinson JB, Bowman CM. Clinical and laboratory observations. Early prediction of ultimate outcome in newborn infants with severe respiratory failure. J Pediatr 1988;113:744–746. 7. Gillbert R, Keighley JF. The arterial alveolar oxygenation ratio. An index of gas exchange applicable to varying inspired oxygen concentrations. Am Rev Respir Dis 1974;109:142–145. 8. Trachsel D, McCrindle BW, Nakagawa S, Bohn D. Oxygenation index predicts outcome in children with acute hypoxemic respiratory failure. Am J Respir Crit Care Med 2005;172: 206–211. 9. Schmidt H, Grune T, Mu¨ller R, Siems WG, Wauer RR. Increased levels of lipid peroxidation products malondialdehyde and 4-hydroxynonenal after perinatal hypoxia. Pediatr Res 1996;40: 15–20.
Newborn Ventilation 10. Shouman BO, Mesbah A, Aly H. Iron metabolism and lipid peroxidation products in infants with hypoxic ischemic encephalopathy. J Perinatol 2008;28:487–491. 11. Sudarsanam TD, Jeyaseelan L, Thomas K, John G. Predictors of mortality in mechanically ventilated patients. Postgrad Med J 2005;81:780–783. 12. Knaus WA, Wagner DP, Draper EA, Zimmerman JE, Bergner M, Bastos PG, Sirio CA, Murphy DJ, Lotring T, Damiano A, et al. The APACHE III prognostic system. Risk prediction of hospital
5
mortality for critically ill hospitalized adults. Chest 1991;100:1619–1636. 13. Pollack MM, Ruttimann UR, Getson PR. Pediatric risk of mortality (PRISM) score. Crit Care Med 1988;16:1110– 1116. 14. The International Neonatal Network. The CRIB (clinical risk index for babies) score: a tool for assessing initial neonatal risk and comparing performance of neonatal intensive care units. Lancet 1993;342:193–198.
Pediatric Pulmonology
