Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Validation of the STARZ neonatal acute kidney injury risk stratification score in an independent prospective cohort.

OBJECTIVE: A rapid AKI risk assessment score would allow for improving management and outcomes. STARZ (Sethi, Tibrewal, Agrawal, Raina, waZir) score was developed for acute kidney injury (AKI) risk stratification of critically ill neonates. This is the first independent validation for the novel score outside the original enrolled centres. STUDY DESIGN: 750 neonates were included in the study. The STARZ score was calculated after 12 hours of admission. Neonates admitted in NICU and receiving IV fluids for at least 48 hours were included. RESULTS: A total of 8.8% neonates had AKI in the first 7 days post admission. The duration of hospital stay was significantly higher among neonates with AKI [10.5 (7-19) vs. 7 (5-10) days; p < 0.001]. Mortality risk was 6.4 times higher among those with AKI [8 (12.1%) vs. 13 (1.9%); p < 0.001; RR (95% CI): 6.38 (2.74-14.83)]. In this study, the STARZ neonatal scoring model showed a sensitivity of 89.4% in detecting AKI with a 90.9% specificity and a high negative predictive value of 98.9%. The area under ROC was 0.958 (0.934-0981) - a high discriminative power. CONCLUSIONS: The STARZ score allows for AKI risk stratification, providing opportunity for therapeutic interventions which may improve outcomes in critically ill neonates.

Risk factors and outcomes of neonates with acute kidney injury needing peritoneal dialysis: Results from the prospective TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) study.

BACKGROUND: Acute kidney injury (AKI) is common in neonates admitted to neonatal intensive care units (NICUs). There is a need to have prospective data on the risk factors and outcomes of acute peritoneal dialysis (PD) in neonates. The use of kidney replacement therapy in this population compared to older populations has been associated with worse outcomes (mortality rates 17-24%) along with a longer stay in the NICU and/or hospital. METHODS: The following multicentre, prospective study was derived from the TINKER (The Indian PCRRT-ICONIC Neonatal Kidney Educational Registry) database, assessing all admitted neonates ≤28 days who received intravenous fluids for at least 48 h. The following neonates were excluded: death within 48 h, presence of any lethal chromosomal anomaly, requirement of congenital heart surgery within the first 7 days of life and those receiving only routine care in nursery. Demographic data (maternal and neonatal) and daily clinical and laboratory parameters were recorded. AKI was defined according to the Neonatal Kidney Disease: Improving Global Outcomes criteria. RESULTS: Of the included 1600 neonates, a total of 491 (30.7%) had AKI. Of these 491 neonates with AKI, 44 (9%) required PD. Among neonates with AKI, the odds of needing PD was significantly higher among those with significant cardiac disease (odds ratio (95% confidence interval): 4.95 (2.39-10.27); p < 0.001), inotropes usage (4.77 (1.98-11.51); p < 0.001), severe peripartum event (4.37 (1.31-14.57); p = 0.02), requirement of respiratory support in NICU (4.17 (1.00-17.59); p = 0.04), necrotising enterocolitis (3.96 (1.21-13.02); p = 0.03), any grade of intraventricular haemorrhage (3.71 (1.63-8.45); p = 0.001), evidence of fluid overload during the first 12 h in NICU (3.69 (1.27-10.70); p = 0.02) and requirement of resuscitation in the delivery room (2.72 (1.45-5.12); p = 0.001). AKI neonates with PD as compared to those without PD had a significantly lower median (interquartile range) duration of stay in NICU (7 (4-14) vs. 11 (6-21) days; p = 0.004), but significantly higher mortality (31 (70.5%) vs. 50 (3.2%); p < 0.001). This discrepancy is likely attributable to the critical state of the neonates with AKI. CONCLUSIONS: This is the largest prospective, multicentre study specifically looking at neonatal AKI and need for dialysis in neonates. AKI was seen in 30.7% of neonates (with the need for acute PD in 9% of the AKI group). The odds of needing acute PD were significantly higher among those with significant cardiac disease, inotropes usage, severe peripartum event, requirement of respiratory support in NICU, necrotising enterocolitis, any grade of intraventricular haemorrhage, evidence of fluid overload more than 10% during the first 12 h in NICU and requirement of resuscitation in the delivery room. AKI neonates with PD as compared to AKI neonates without PD had a significantly higher mortality. There is a need to keep a vigilant watch in neonates with risk factors for the development of AKI and need for PD.

The effect of norepinephrine on clinical and hemodynamic parameters in neonates with shock: a retrospective cohort study.

There is limited data on the cardiovascular effects of norepinephrine (NE) in neonates. Our objective was to describe the clinical responses in neonates treated with NE infusion. This retrospective cohort study included neonates with evidence of shock and those who received NE infusion. PRIMARY OUTCOME: changes in mean blood pressure (MBP) at 6, 12, and 24 h post-initiation of NE. SECONDARY OUTCOMES: Changes in (i) diastolic BP, systolic BP, and vasoactive inotrope score (VIS) at 6, 12, and 24 h, (ii) urine output after initiation of NE ii) pH, lactate, fraction of inspired oxygen (FiO2) after initiation of NE, and (iv) adverse outcomes. Fifty infants received NE with mean (SD) gestational age of 34.3 (4.3) weeks and a mean birth weight of 2215 (911) g. Treatment began at a median age of 36 (IQR: 15.2, 67.2) hours of life and lasted 30.5 (IQR: 12.7, 58) hours. MBP improved from 34.4 mm Hg (SD: 6.6) at baseline to 39.4 mm Hg (SD: 10.5, p < 0.001) at 6 h, to 39.6 mm Hg (SD: 12.1, p = 0.002) at 12 h and to 40.4 mm Hg (SD: 15.5, p = 0.004) at 24 h after NE initiation. Vasoactive inotrope score declined from 30 (20, 32) to 10 (4, 30; p < 0.001) at 24 h. Urine output improved within 24 h [1.5 ml/kg/h (0.5, 2.3) at baseline to 3 (1.9, 4.3) at 24 h; p = 0.04]. Oxygen requirement decreased after NE initiation. CONCLUSION: The use of NE appears to be effective and safe for treating systemic hypotension in neonates. TRIAL REGISTRATION: Being a retrospective study, trial registration was not considered. WHAT IS KNOWN: • Dopamine has traditionally been used as the initial agent for treatment of neonatal hypotension. • Norepinephrine has recently been recommended as the first-choice vasopressor agent to correct hypotension in adults and pediatric patients, with insufficient data on the cardiovascular effects of NE in neonates What is new: • Mean blood pressure improved significantly at 6, 12, and 24 h with reduction in vasoactive infusion score at 12 and 24 h after norepinephrine infusion. • No significant change in heart rate or abnormal abdominal adverse effects noted in this study.

Validation of the STARZ neonatal acute kidney injury risk stratification score.

BACKGROUND: Neonatal acute kidney injury (AKI) is common in neonatal intensive care units (NICU) and leads to worse outcomes. Stratifying neonates into an "at risk" category allows health care providers to objectively recognize opportunities for improvements in quality of care. METHODS: The "Neonatal AKI Risk Prediction Scoring" was devised as the "STARZ [Sethi, Tibrewal, Agrawal, Raina, waZir]" Score. The STARZ score was derived from our prior multicentre study analysing risk factors for AKI in neonates admitted to the NICU. This tool includes 10 variables with a total score ranging from 0 to 100 and a cut-off score of 31.5. In the present study, the scoring model has been validated in our multicentre cohort of 744 neonates. RESULTS: In the validation cohort, this scoring model had sensitivity of 82.1%, specificity 91.7%, positive predictive value 81.2%, negative predictive value 92.2% and accuracy 88.8%. Based on the STARZ cut-off score of ≥ 31.5, an area under the receiver operating characteristic (ROC) curve was observed to be 0.932 (95% CI, 0.910-0.954; p < 0.001) signifying that the discriminative power was high. In the validation cohort, the probability of AKI was less than 20% for scores up to 32, 20-40% for scores between 33 and 36, 40-60% for scores between 37 and 43, 60-80% for scores between 44 and 49, and ≥ 80% for scores ≥ 50. CONCLUSIONS: To promote the survival of susceptible neonates, early detection and prompt interventional measures based on highly evidenced research is vital. The risk of AKI in admitted neonates can be quantitatively determined by the rapid STARZ scoring system. A higher resolution version of the Graphical abstract is available as Supplementary information.

Neonatal acute kidney injury risk stratification score: STARZ study.

BACKGROUND: Neonates admitted in the neonatal intensive care unit are vulnerable to acute kidney injury leading to worse outcomes. It is important to identify "at-risk" neonates for early preventive measures. METHODS: The study was a multicenter, national, prospective cohort study done in 11 centers in India. A multivariable logistic regression technique with step-wise backward elimination method was used, and a "Risk Prediction Scoring" was devised [the STARZ score]. RESULTS: The neonates with admission in the NICU within <25.5 h of birth, requirement of positive pressure ventilation in the delivery room, <28 weeks gestational age, sepsis, significant cardiac disease, urine output <1.32 ml/kg/h or serum creatinine ≥0.98 mg/dl during the first 12 h post admission, use of nephrotoxic drugs, use of furosemide, or use of inotrope had a significantly higher risk of AKI at 7 days post admission in the multivariate logistic regression model. This scoring model had a sensitivity of 92.8%, specificity of 87.4% positive predictive value of 80.5%, negative predictive value of 95.6%, and accuracy of 89.4%. CONCLUSIONS: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. IMPACT: The STARZ neonatal score serves to rapidly and quantitatively determine the risk of AKI in neonates admitted to the neonatal intensive care unit. These neonates with a higher risk stratification score need intense monitoring and daily kidney function assessment. With this intensification of research in the field of AKI risk stratification prediction, there is hope that we will be able to decrease morbidity and mortality associated with AKI in this population.

Multisystem inflammatory syndrome in a neonate masquerading as surgical abdomen.

Worldwide, thousands of cases of multisystem inflammatory syndrome in children (MIS-C) have already been reported in children. Evidence regarding neonatal MIS-C is limited. We present the first case report of a neonate presenting within 48 hours of life with predominant abdominal signs mimicking surgical abdomen. Clinical picture comprised fever, multiorgan dysfunction (gastrointestinal, cardiorespiratory, hepatic and dermatological), positive inflammatory markers, high ferritin and high D-dimer levels. Cardiac enzyme N-terminal-pro-B-type natriuretic peptide as well as D-dimer levels were elevated. Blood, urine, stool and cerebrospinal fluid cultures were sterile. Positive anti-SARS-CoV-2 IgG in both the mother and the infant, along with an epidemiological evidence of maternal contact with COVID-19, clinched the diagnosis of MIS-C. Immunomodulatory drugs (intravenous immunoglobulin and systemic steroids) were administered and showed good clinical response. A high index of suspicion of MIS-C in critically ill neonates can improve outcomes.

Incidence, Risk Factors, and Outcomes of Neonatal Acute Kidney Injury: Protocol of a Multicentric Prospective Cohort Study [The Indian Iconic Neonatal Kidney Educational Registry].

Background: Acute kidney injury (AKI) is a significant problem in neonates, but the evidence is sparse. Neonatal AKI is an independent risk factor for increased mortality and prolonged hospital stay. There are stark differences in the epidemiology of AKI in neonates amongst the developing and the developed world. Increased prevalence of neonatal sepsis, lack of awareness about neonatal AKI and poor access to pediatric nephrologists add to the improper management of neonatal AKI in the developing countries. Methods: This study is a multicentric, national, prospective cohort study [The Indian iconic Neonatal Kidney Educational Registry (TINKER)] conducted in level 2-3 NICUs in 11 centers across India. We have enrolled nearly 2,000 neonates over the study period. Neonates (≤ 28 days) who were admitted in NICU and those who received intravenous (IV) fluids for at least 48 h for hydration and/or nutrition have been included. Data collection included: (1) baseline demographics (2) daily physiologic and laboratory parameters (3) discharge data. KDIGO workgroup AKI definition modified for neonates was used for defining AKI. Data entry was carried out by individual participating centers using a web-based database (akiregistry.org). De-identified data has been maintained and handled by the principal investigator (PI). This collaboration plans to disseminate data through peer-reviewed publications and through presentations at educational conferences. Conclusions: The purpose of this study is to create the first prospective neonatal all-cause AKI data repository and describe the incidence of neonatal AKI in NICUs in the country and determine the risk factors as well as the outcomes of such neonates-both short-term and long-term outcomes. This will eventually spur therapeutic advancements, facilitate decipherment of epidemiological trends, risk factors as well as outcomes and identify disparities in management across the nation.

Universal Screening for SARS-CoV-2 in Asymptomatic Pregnant Women: A Multi-center Experience.

BACKGROUND: Novel coronavirus (SARS-CoV-2) is responsible for the current global pandemic and understandably, Obstetrics is not spared. Private maternity hospitals have a unique challenge of reassuring unaffected patients of uneventful delivery with the lowest possible rate of coronavirus infection while consequently offering compassionate and state of art services to women who turn out to be positive for SARS-CoV-2. This has led to a routine SARS-CoV-2 testing of all patients before admission in many of the private hospitals in India. The current study was undertaken to determine the incidence of SARS-COV-2 among asymptomatic pregnant women and to ascertain the utility of universal screening in these women. METHODOLOGY: A retrospective observational multi-center study was conducted over a period of approximately 5 months (1-May-2020 to 10-September-2020) in a chain of privately run maternity hospitals with presence in multiple cities across India. All asymptomatic pregnant women were tested for SARS-CoV-2 prior to elective/emergency hospital admission. RESULTS: Among 4158 women tested, 54 (1.3%) were positive for SARS-CoV-2 and intra partum and postnatal period was uneventful for all of them. CONCLUSION: Universal screening should be continued as preferred approach to ensure low anxiety levels of delivering women and safety of frontline workers. Further, universal screening helps avoid emergence of maternity centers as virus clusters by effective isolation of identified positive cases and minimizing points of contact.

Surfactant dysfunction disorder masquerading as meconium aspiration syndrome and persistent pulmonary hypertension of the newborn.

About 10% of term neonates present with respiratory distress at birth. The most common aetiologies include transient tachypnoea of the newborn, pneumonia and meconium aspiration syndrome (MAS). Hyaline membrane disease (HMD) in a term infant occurs either as primary HMD, secondary surfactant deficiency or congenital surfactant dysfunction. A detailed history supported with appropriate radiological and laboratory investigations can help a clinician reach a diagnosis. We report a case of surfactant dysfunction disorder which presented as severe MAS and persistent pulmonary hypertension of the newborn. In the infant described, the significant history of a sibling death with severe neonatal respiratory disease led us to think of diffuse developmental lung diseases especially surfactant dysfunction syndromes. Exome sequencing detected a heterozygous missense variation in exon 21 of the ATP binding cassette protein member 3 (ABCA3) gene. Based on the clinical picture supported with the exome sequencing, a diagnosis of surfactant dysfunction disorder (ABCA3 deficiency) was confirmed.

A comparative evaluation of portable Doppler ultrasound versus electrocardiogram in heart-rate accuracy and acquisition time immediately after delivery: a multicenter observational study.

BACKGROUND: The assessment of newborns' heart rate (HR) in the delivery room is one of the important steps to ascertain the need for initiation and continuation of resuscitation. At present, ECG is the "gold standard" to monitor neonatal HR in the delivery room. However, various limitations with the use of ECG exist. Furthermore, in developing countries, ECG may not be universally available in delivery rooms. OBJECTIVE: To compare the accuracy and HR acquisition time of portable Doppler ultrasound (PDU) versus electrocardiogram (ECG) in newborns. METHODS: This multicenter, prospective, observational study across five centers in India between January and September 2017 included neonates more than 34 weeks of gestation (n = 131) delivered by cesarean section. The accuracy of HR recorded by PDU (HRPDU) versus that by ECG (HRECG) was the primary outcome. Secondary outcomes included time to acquisition of an audible and/or visible signal and device application. RESULTS: Mean (±SD) gestational age and birthweight were 37.7 (±1.2) weeks and 2954 (±457) g, respectively. The mean (±SD) visible HRPDU was 158 (±21) bpm versus HRECG of 161.3 (±20) bpm (p = .07) which were comparable. The median (1st, third quartile) time to acquisition of audible HRPDU (76 [51, 91] s), was significantly shorter than that of HRECG (96.5 [74.2, 118] s; p < .001). CONCLUSION: Portable Doppler has similar accuracy to ECG and is faster in acquiring the signal.

Neonatal lupus erythematosus presenting with rash, thrombocytopenia compounded by cytomegalovirus colonisation: a diagnostic dilemma.

Neonatal lupus erythematosus (NLE) should be considered when a newborn develops atrioventricular heart block along with the presence of autoantibodies to Sjogren's syndrome autoantigens in the maternal serum. NLE can also present with features such as cutaneous lesions, hepatic dysfunction or haematological abnormalities. Differential diagnosis usually includes congenital infections as there is a significant overlap of symptoms with NLE. We report a case of NLE who had multiorgan involvement with macular erythematous skin lesions present at birth, and on investigation was found to have cytomegalovirus (CMV) infection. The diagnostic dilemma was whether to consider this infection as symptomatic or just colonisation. In the infant described, the absence of end organ damage specific to CMV infection (hearing loss, intracranial calcifications, retinitis, brain involvement) made a diagnosis of symptomatic CMV unlikely.

Primary dengue infection triggered haemophagocytic lymphohistiocytosis in a neonate.

Haemophagocytic lymphohistiocytosis (HLH) is an aggressive syndrome which has characteristic symptoms and laboratory findings. Infection is a common trigger of HLH. We report a 2700 g male infant with persistent fever, massive hepatosplenomegaly and severe thrombocytopaenia. Laboratory evidence of primary dengue infection was detected. Investigations revealed hypertriglyceridaemia, hypofibrinogenaemia, hyperferritinaemia and elevated soluble CD25. Bone marrow examination revealed haemophagocytes. The diagnostic criteria for HLH were fulfilled. A diagnosis of secondary HLH triggered by primary dengue infection was considered. Dexamethasone was initiated and continued for 8 weeks. He responded clinically with regression of hepatosplenomegaly, was afebrile and platelet counts normalised. Dengue-associated HLH is often missed clinically as treating physicians focus more on the underlying infection and its treatment. In neonates, HLH should be considered as differential diagnosis of sepsis and other viral infections, particularly in situations of inappropriate response to standard management.

Experience of Perinatal and Neonatal Chikungunya Virus (CHIKV) Infection in a Tertiary Care Neonatal Centre during Outbreak in North India in 2016: A Case Series.

BACKGROUND: In 2016, there was a massive outbreak of chikungunya in North India. During the epidemic, we observed many neonatal and early infantile cases of chikungunya, with a probable perinatal transmission. METHODS: This retrospective study was carried out in a tertiary care neonatal centre between August 2016 and November 2016. Chikungunya virus (CHIKV) infection was detected and confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and/or serology (anti-CHIKV IgM) in mothers and infants. Clinical features and laboratory parameters were recorded. RESULTS: There were 16 cases of confirmed CHIKV infections during the study period. For babies presenting during the neonatal period (n = 13), the median age of presentation was 9.5 (range: 3-15) days, whereas for babies (three) presenting after the neonatal period, the median age was between 1 and 3 months. The most common presentation was fever (69%), followed by lethargy (56%) and seizures (50%). Skin manifestations were observed in 25% of the cases, which included maculopapular rashes, bullous lesions and hyperpigmentation over the axilla, perioral and genital areas. None of the cases had any feature of arthritis. Of all the cases included in the study (n = 16), RT-PCR for CHIKV was positive in 14 (87.5%), whereas the serum anti-CHIKV IgM antibody test was positive in two (12.5%) cases. Six (37.5%) cases were documented as perinatal CHIKV, as RT-PCR for CHIKV was positive in both mothers and babies. Fifteen babies survived and were discharged in a stable condition with no oxygen requirement and on full feeds. One baby died because of multi-organ failure and catecholamine refractory hypotension. CONCLUSION: In endemic areas, paediatricians should have a low threshold of suspicion for perinatal or neonatal chikungunya in any infant presenting with signs and symptoms mimicking sepsis, especially with skin manifestations, seizure and/or encephalopathy.

Neonatal Acute Kidney Injury: A Survey of Perceptions and Management Strategies Amongst Pediatricians and Neonatologists.

Background: Neonatal Acute Kidney Injury (AKI) occurs in 40-70% of critically ill newborn infants and is independently associated with increased morbidity and mortality. Understanding the practice patterns of physicians (neonatologists and pediatricians), caring for neonates in India is important to optimize care and outcomes in neonatal AKI. Aim: The aim of this study was to identify differences in physician's perception and practice variations of diagnosis, management, and follow-up of newborn infants with AKI in India. Methods: An online survey of neonatologists and pediatricians in India caring for newborn infants with AKI. Results: Out of 800 correspondents, 257 (135 neonatologists and 122 pediatricians) completed the survey, response rate being 32.1%. Resources available to the respondents included level III NICU (59%), neonatal surgery (60%), dialysis (11%), and extracorporeal membrane oxygenation (ECMO, 3%). Most respondents underestimated the risk of AKI due to various risk factors such as prematurity, asphyxia, sepsis, cardiac surgery, and medications. Less than half the respondents were aware of the AKIN or KDIGO criteria, which are the current standard criteria for defining neonatal AKI. Only half of the respondents were aware of the risk of CKD in preterm neonates and nearly half were unaware of the need to follow up with a pediatric nephrologist. Conclusions: Similar to other regions worldwide, there exists a knowledge gap in early recognition, optimal management and follow up of newborn infants with AKI amongst Indian physicians.

Routine versus Selective Fortification of Human Milk with Powdered Human Milk Fortifiers in Very Low Birth Weight (VLBW) Preterm Infants: A Retrospective Pre-Post Cohort Study.

OBJECTIVES: The objective of this study was to show the effects of routine vs. selective fortification of human milk (HM) on short-term growth and metabolic parameters. METHODS: Single-centre retrospective pre-post cohort study in India. Preterm infants ≤32 weeks' gestation and weighing ≤1500 g were included. Routine fortification: pre-fixed feed volume (100 ml/kg/day in our unit) at which fortification was done. Selective fortification: feed volume was gradually optimized till 180-200 ml/kg/day. If weight gain was below the expected threshold (<10 g/kg/day), then fortification was considered. Primary outcome measure was rate of growth till discharge. RESULTS: The median rate of weight gain (g/kg/day) in the routine fortification group [10.8 (3.3, 17.1)] was comparable with that in the selective fortification group [8.4 (0, 14.2), p = 0.6]. Serum phosphorus showed a significantly higher value (5.9 vs. 4.8, p = 0.03), while rest of the metabolic parameters showed a trend towards a favourable outcome in the selective fortification group. Adverse outcomes showed a trend towards decreased feed intolerance, necrotizing enterocolitis, and sepsis in the selective fortification group. CONCLUSIONS: Selective fortification had a comparable growth rate and showed a trend towards better metabolic parameters and lesser adverse outcomes compared with routine fortification of HM.

Phase Changing Material for Therapeutic Hypothermia in Neonates with Hypoxic Ischemic Encephalopathy - A Multi-centric Study.

OBJECTIVE: To assess the feasibility and safety of cooling asphyxiated neonates using phase changing material based device across different neonatal intensive care units in India. DESIGN: Multi-centric uncontrolled clinical trial. SETTING: 11 level 3 neonatal units in India from November 2014 to December 2015. PARTICIPANTS: 103 newborn infants with perinatal asphyxia, satisfying pre-defined criteria for therapeutic hypothermia. INTERVENTION: Therapeutic hypothermia was provided using phase changing material based device to a target temperature of 33.5±0.5oC, with a standard protocol. Core body temperature was monitored continuously using a rectal probe during the cooling and rewarming phase and for 12 hours after the rewarming was complete. OUTCOME MEASURES: Feasibility measure - Time taken to reach target temperature, fluctuation of the core body temperature during the cooling phase and proportion of temperature recordings outside the target range. Safety measure - adverse events during cooling. RESULTS: The median (IQR) of time taken to reach target temperature was 90 (45, 120) minutes. The mean (SD) deviation of temperature during cooling phase was 33.5 (0.39) ºC. Temperature readings were outside the target range in 10.8% (5.1% of the readings were <33oC and 5.7% were >34oC). Mean (SD) of rate of rewarming was 0.28 (0.13)oC per hour. The common adverse events were shock/ hypotension (18%), coagulopathy (21.4%), sepsis/probable sepsis (20.4%) and thrombocytopenia (10.7%). Cooling was discontinued before 72 hours in 18 (17.5%) babies due to reasons such as hemodynamic instability/refractory shock, persistent pulmonary hypertension or bleeding. 7 (6.8%) babies died during hospitalization. CONCLUSIONS: Using phase changing material based cooling device and a standard protocol, it was feasible and safe to provide therapeutic hypothermia to asphyxiated neonates across different neonatal units in India. Maintenance of target temperature was comparable to standard servo-controlled equipment.