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.

Nasogastric vs Orogastric Feeding in Stable Preterm (≤32 Weeks) Neonates: A Randomized Open-Label Controlled Trial.

BACKGROUND: Optimal route of tube feeding in preterm babies is not known. OBJECTIVES: To compare the frequency of bradycardia and desatu-ration episodes/hours in hemodynamically stable preterm neo-nates (≤32 wk gestational age) fed by nasogastric vs orogastric route. DESIGN: Randomized controlled trial. PARTICIPANTS: Hemodynamically stable preterm neonates (≤32 wk gestational age) requiring tube feeding. INTERVENTION: Nasogastric vs orogastric tube feeding. PRIMARY OUTCOME: Number of episodes of bradycardia and desaturations/hour. METHODS: Eligible preterm neonates fulfilling the inclusion criteria were enrolled. Each episode of insertion of a nasogastric tube or orogastric tube was labelled as a feeding tube insertion episode (FTIE). FTIE lasted from the time of insertion of tube till the time tube needed to be changed. Reinsertion of the tube in same baby was taken as a fresh FTIE. 160 FTIEs were evaluated during the study period, 80 FTIEs each in babies with gestational age <30 weeks and ≥30 weeks. Number of episodes of bradycardia and desaturation per hour were computed using records in the monitor till the time tube was in situ. RESULTS: The mean episodes of bradycardia and desaturations/hour [mean difference (95% CI) 0.144 (0.067-0.220); P<0.001] were higher in FTIE by nasogastric as compared to the oro-gastric route. CONCLUSION: Orogastric route may be preferable to the nasogastric route in hemodynamically stable preterm neonates.

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.

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.

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.

Subcutaneous fat necrosis in an infant with hypoxic ischaemic encephalopathy stage 3: an uncommon association.

Subcutaneous fat necrosis (SCFN) is inflammation and necrosis of adipose tissue associated with hypoxia and hypothermia. It leads to various metabolic abnormalities, of which the most dreaded is hypercalcaemia. We report a case of a 7-week-old boy with history of birth asphyxia (hypoxic ischaemic encephalopathy stage 3) who presented to us with features suggestive of hypercalcaemia with bilateral nephrocalcinosis. On examination, there were multiple subcutaneous nodules on both arms. Evaluation revealed suppressed parathyroid activity along with low levels of 25(OH)vitamin D3 and elevated 1,25-dihydroxyvitamin D3 Skin biopsy confirmed the diagnosis of SCFN. He was managed with intravenous fluids, single dose of intravenous furosemide and oral prednisolone. Hypercalcaemia responded within 14 days of admission, prednisolone was tapered and stopped in a month. SCFN, in our case, can be attributed to the underlying perinatal asphyxia along with use of therapeutic hypothermia. Through this case, we wish to sensitise practicing neonatologists for the need of screening and early identification of these abnormalities, which if missed can be fatal.

Abnormal neurodevelopment outcome in case of neonatal hyperekplexia secondary to missense mutation in GLRB gene.

Hyperekplexia is an exaggerated startle to external stimuli associated with a generalised increase in tone seen in neonates with both sporadic and genetic predisposition. This is an uncommon neurological entity that is misdiagnosed as seizure. A 28-days-old infant was admitted to us with characteristic intermittent generalised tonic spasm being treated as a seizure disorder. The infant had characteristic stiffening episode, exaggerated startle and non-habituation on tapping the nose. Hyperekplexia was suspected and confirmed by genetic testing (mutation in the ß subunit of glycine was found). Initial improvement was seen with the use of clonazepam, which was not sustained. At the age of 4.5 years, the child is still having neurobehavioural issues like hyperactivity and sensory hyper-responsiveness. Usually, hyperekplexia is benign in nature. We report a case of hyperekplexia with non-sense mutation in the ß subunit of GlyR gene having abnormal neurodevelopmental findings at 4.5 years.

Novel homozygous missense mutation in ABCA3 protein leading to severe respiratory distress in term infant.

The term baby presented with respiratory distress with X-ray pictures consistent as hyaline membrane disease (HMD). Baby was ventilated and treated with surfactant. Because of the persistence of high ventilation needs with X-ray pictures consistent with HMD with a transient response to surfactant every time, the possibility of an inherited disorder of surfactant metabolism was kept. Whole-exome sequencing revealed a novel homozygous missense mutation in the gene for ATP binding cassette transporter protein A3. The baby died after 100 days of ventilation.

Pneumocephalus in neonatal meningitis.

Pneumocephalus is collection of gas or air within the cranial cavity. This has been described with trauma, cranial surgery, air embolism, and rarely as a result of central nervous system infections. We report a case of diffuse pneumocephalus secondary to Enterobacter cloacae meningitis. The diagnosis was suspected by cranial ultrasound and confirmed by computer tomography.