Receipt of high-frequency ventilation is associated with acute kidney injury in very preterm neonates.

BACKGROUND: High-frequency ventilation (HFV) is frequently used in critically ill preterm neonates. We aimed to determine the incidence of acute kidney injury (AKI) in neonates less than 29 weeks gestation who received HFV in the first week of life and to determine if the rates of AKI differed in those who received other forms of respiratory support. METHODS: This retrospective cohort study of 24 international, level III/IV neonatal intensive care units (NICUs) included neonates less than 29 weeks gestation from the AWAKEN study database. Exclusion criteria included the following: no intravenous fluids ≥ 48 h, admission ≥ 14 days of life, congenital heart disease requiring surgical repair at < 7 days of life, lethal chromosomal anomaly, death within 48 h, severe congenital kidney abnormalities, inability to determine AKI status, insufficient data on ventilation, and when the diagnosis of early AKI was unable to be made. Subjects were grouped into three groups based on ventilation modes (CPAP/no ventilation, conventional ventilation, and HFV). RESULTS: The incidence of AKI was highest in the CPAP/no ventilation group, followed by HFV, followed by conventional ventilation (CPAP/no ventilation 48.5% vs. HFV 42.6% vs. conventional ventilation 28.4% (p = 0.009). An increased risk for AKI was found for those on HFV compared to CPAP/no ventilation (HR = 2.65; 95% CI:1.22-5.73). CONCLUSIONS: HFV is associated with AKI in the first week of life. Neonates on HFV should be screened for AKI. The reasons for this association are not clear. Further studies should evaluate the relationship between ventilator strategies and AKI in premature neonates. A higher resolution version of the Graphical abstract is available as Supplementary information.

Prevalence & Risk Factors for Perinatal Stroke: A Population-Based Study.

Objectives: The study objective was to calculate the birth prevalence of perinatal stroke and examine risk factors in term infants. Some risk factors are present in healthy infants, making it difficult to determine at-risk infants. Study Design: Prospective population-based perinatal stroke data were compared to the Australian general population data using chi-squared and Fisher's exact tests and multivariable logistic regression analysis. Results: Sixty perinatal stroke cases were reported between 2017 and 2019. Estimated stroke prevalence was 9.6/100,000 live births/year including 5.8 for neonatal arterial ischemic stroke and 2.9 for neonatal hemorrhagic stroke. Eighty seven percent had multiple risk factors. Significant risk factors were cesarean section (p = 0.04), 5-min Apgar score <7 (p < 0.01), neonatal resuscitation (p < 0.01) and nulliparity (p < 0.01). Conclusions: Statistically significant independent risk factors do not fully explain the cause of perinatal stroke, because they are not a direct causal pathway to stroke. These data now require validation in a case-control study.

Using Serum Cystatin C to Predict Acute Kidney Injury Following Infant Cardiac Surgery.

Acute kidney injury (AKI) following cardiopulmonary bypass (CPB) is associated with increased morbidity and mortality. Serum Cystatin C (CysC) is a novel biomarker synthesized by all nucleated cells that may act as an early indicator of AKI following infant CPB. Prospective observational study of infants (< 1 year) requiring CPB during cardiac surgery. CysC was measured at baseline and 12, 24, 48, and 72 h following CPB initiation. Each post-op percent difference in CysC (e.g. %CysC12h) from baseline was calculated. Clinical variables along with urine output (UOP) and serum creatinine (SCr) were followed. Subjects were divided into two groups: AKI and non-AKI based upon the Kidney Disease Improving Global Outcomes (KDIGO) classification. AKI occurred in 41.9% (18) of the 43 infants enrolled. Patient demographics and baseline CysC levels were similar between groups. CysC levels were 0.97 ± 0.28 mg/L over the study period, and directly correlated with SCr (R = 0.71, p < 0.0001). Although absolute CysC levels were not significant between groups, the %CysC12h was significantly greater in the AKI group (AKI: - 16% ± 22% vs. Non-AKI - 28% ± 9% mg/L; p = 0.003). However, multivariate analysis demonstrated that a lower UOP (Odds Ratio:0.298; 95% CI 0.073, 0.850; p = 0.02) but not %CysC12h was independently associated with AKI. Despite a significant difference in the %CysC12h, only UOP was independently associated with AKI. Larger studies of a more homogenous population are needed to understand these results and to explore the variability in this biomarker seen across institutions.

Current approach and attitudes toward neonatal near-miss and perinatal audits: An exploratory international survey.

BACKGROUND: Combined with perinatal mortality review, neonatal near-miss (NNM) audit has the potential to inform strategies to better prevent adverse perinatal outcomes. Nonetheless, there is lack of standardised definitions of NNM and limited evidence of implementation of NNM audits. AIM: To describe definitions of NNM and assess current approaches and attitudes toward perinatal mortality and morbidity audit. MATERIALS AND METHODS: Online survey from December 2021 to February 2022, with a mix of Likert scales, polar, pool, multi-choice, and open-ended questions, disseminated through national and international organisations to perinatal healthcare workers from high-income countries. RESULTS: One hundred and twenty participants came from Australia (n = 86), New Zealand (n = 18), Canada (n = 7), USA (n = 4), Netherlands (n = 2), other countries (n = 3). Neonatologists (35%), midwives (21.7%), obstetricians (12.5%), neonatal nurse practitioners (11.7%) and others (23.3%) responded. Most respondents thought the main characteristics to define NNM were birth asphyxia needing therapeutic hypothermia (68.3%), unexpected resuscitation at birth (67.5%), need for intubation/chest compression/adrenaline (65.0%) and metabolic acidosis at birth (60.0%). There were 97.5% of participants who considered NNM important for identifying cases for perinatal morbidity audits. However, only 10.0% of their institutions used a NNM definition. Overall, 98.4% of participants considered perinatal mortality and morbidity audits important to prevent adverse outcomes. CONCLUSION: Neonatal near-miss audit is viewed as a valuable tool to reduce adverse neonatal outcomes. There was reasonable consensus that NNM encompassed evidence of birth asphyxia and/or advanced neonatal resuscitation. Data from this international survey identifies a starting point for a consensus definition of NNM, which can be used for perinatal audits to identify opportunities for improvement.

Neonatal hypoxic ischemic encephalopathy increases acute kidney injury urinary biomarkers in a rat model.

Hypoxic ischemic encephalopathy (HIE) is associated with acute kidney injury (AKI) in neonates with birth asphyxia. This study aimed to utilize urinary biomarkers to characterize AKI in an established neonatal rat model of HIE. Day 7 Sprague-Dawley rat pups underwent HIE using the Rice-Vannucci model (unilateral carotid ligation followed by 120 mins of 8% oxygen). Controls included no surgery and sham surgery. Weights and urine for biomarkers (NGAL, osteopontin, KIM-1, albumin) were collected the day prior, daily for 3 days post-intervention, and at sacrifice day 14. Kidneys and brains were processed for histology. HIE pups displayed histological evidence of kidney injury including damage to the proximal tubules, consistent with resolving acute tubular necrosis, and had significantly elevated urinary levels of NGAL and albumin compared to sham or controls 1-day post-insult that elevated for 3 days. KIM-1 significantly increased for 2 days post-HIE. HIE did not significantly alter osteopontin levels. Seven days post-start of experiment, controls were 81.2% above starting weight compared to 52.1% in HIE pups. NGAL and albumin levels inversely correlated with body weight following HIE injury. The AKI produced by the Rice-Vannucci HIE model is detectable by urinary biomarkers, which can be used for future studies of treatments to reduce kidney injury.

Humidification Practices of Extremely Preterm Neonates: A Clinical Survey.

Extremely preterm neonates are at risk of morbidity and mortality related to their underdeveloped skin barrier. Humidified incubators are typically used in their care, but there is a paucity of literature to inform the standardization of specific evidence-based humidification practices in the NICU. A brief, voluntary, anonymous survey was distributed to our home institution and numerous national and international external institutions. Survey questions pertained to institutional humidification guidelines and were qualitatively analyzed. We received 89 responses from the home institution and 42 responses from the external institutions. Within the home institution, despite the presence of a guideline, individual practitioners reported varying practices in the starting levels of humidity and length of time spent in humidity. The results also demonstrated significant variability in individual humidification practices between the external institutions. There is no standard humidification guideline for extremely preterm neonates being cared for in the NICU. Further research is required to provide appropriate evidence on which to base clinical guidelines for the management of extremely preterm neonates to prevent morbidity and mortality in this population.

Fluid Homeostasis and Diuretic Therapy in the Neonate.

Understanding physiologic water balance and homeostasis mechanisms in the neonate is critical for clinicians in the NICU as pathologic fluid accumulation increases the risk for morbidity and mortality. In addition, once this process occurs, treatment is limited. In this review, we will cover fluid homeostasis in the neonate, explain the implications of prematurity on this process, discuss the complexity of fluid accumulation and the development of fluid overload, identify mitigation strategies, and review treatment options.

Maternal Hypertension Disorders and Neonatal Acute Kidney Injury: Results from the AWAKEN Study.

OBJECTIVE: This study aimed to examine the association between maternal hypertension (HTN) exposure and neonatal acute kidney injury (AKI). STUDY DESIGN: Retrospective cohort study of 2,162 neonates admitted to 24 neonatal intensive care units (NICUs). Neonates were classified into the following exposure groups: any maternal HTN, chronic maternal HTN, preeclampsia/eclampsia, both, or neither. Demographics, clinical characteristics, and AKI status were compared using Chi-square and analysis of variance. General estimating logistic regression was used to estimate adjusted odds ratios and included a stratified analysis for site of delivery. RESULT: Neonates exposed to any maternal HTN disorder had a tendency toward less overall and early AKI. When stratified by inborn versus outborn, exposure to both maternal HTN disorders was associated with a significantly reduced odds of early AKI only in the inborn neonates. CONCLUSION: Exposure to maternal HTN, especially preeclampsia/eclampsia superimposed on chronic HTN, was associated with less likelihood of early AKI in the inborn group. KEY POINTS: · Maternal HTN is associated with less neonatal AKI.. · Maternal HTN category is variably associated with AKI.. · Inborn status is an important contributor to this association..

Impact of introducing a lactation consultant into a neonatal unit.

AIM: Benefits of mothers' own milk (MOM) for premature and sick neonates are well documented. To increase access, many neonatal units have a lactation consultant (LC) on staff. This study aimed to assess the impact of a permanent LC on (i) maternal access to LC support; (ii) staff confidence in providing Breast Feeding (BF) education and (iii) provision of MOM. METHODS: Study included a staff survey and chart audit. Questions provided feedback on access to lactation support and meeting maternal needs. Audit data included: gestational age, birthweight, intention to breastfeed, documentation of LC appointment, provision of MOM at 12 hours, days 3, 7, 28 and discharge. Student's t-tests were used for numerical data and chi-squared tests for categorical variables. RESULTS: Ninety-one staff surveys were returned, (pre 35/75 (47%), post 56/85 (66%) with staff reporting organising an LC appointment was significantly easier (P < 0.0001). Staff perceived maternal lactation needs and confidence to breastfeed post-discharge had significantly improved post-LC. The chart audit showed a significant increase in maternal access to LC appointments (15% vs. 80%; P < 0.01), breast pump education by day 3 (65% vs. 81%; P < 0.01), and an increase in MOM provision by 12 h (46% vs. 61%; P < 0.01) post-LC but not at days 7, 28 or discharge. CONCLUSION: A dedicated LC increases staff and maternal access to lactation education and support, improving provision of early MOM. Further research is required to assess the effect of LCs in improving breastfeeding rates in neonatal units.

Advances in Neonatal Acute Kidney Injury.

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.

Neonatal Acute Kidney Injury: Understanding of the Impact on the Smallest Patients.

The study of neonatal acute kidney injury (AKI) has transitioned from small, single-center studies to the development of a large, multicenter cohort. The scope of research has expanded from assessment of incidence and mortality to analysis of more specific risk factors, novel urinary biomarkers, interplay between AKI and other organ systems, impact of fluid overload, and quality improvement efforts. The intensification has occurred through collaboration between the neonatology and nephrology communities. This review discusses 2 case scenarios to illustrate the clinical presentation of neonatal AKI, important risk factors, and approaches to minimize AKI events and adverse long-term outcomes.

'Turning the tide' on hyperglycemia in pregnancy: insights from multiscale dynamic simulation modeling.

INTRODUCTION: Hyperglycemia in pregnancy (HIP, including gestational diabetes and pre-existing type 1 and type 2 diabetes) is increasing, with associated risks to the health of women and their babies. Strategies to manage and prevent this condition are contested. Dynamic simulation models (DSM) can test policy and program scenarios before implementation in the real world. This paper reports the development and use of an advanced DSM exploring the impact of maternal weight status interventions on incidence of HIP. METHODS: A consortium of experts collaboratively developed a hybrid DSM of HIP, comprising system dynamics, agent-based and discrete event model components. The structure and parameterization drew on a range of evidence and data sources. Scenarios comparing population-level and targeted prevention interventions were simulated from 2018 to identify the intervention combination that would deliver the greatest impact. RESULTS: Population interventions promoting weight loss in early adulthood were found to be effective, reducing the population incidence of HIP by 17.3% by 2030 (baseline ('business as usual' scenario)=16.1%, 95% CI 15.8 to 16.4; population intervention=13.3%, 95% CI 13.0 to 13.6), more than targeted prepregnancy (5.2% reduction; incidence=15.3%, 95% CI 15.0 to 15.6) and interpregnancy (4.2% reduction; incidence=15.5%, 95% CI 15.2 to 15.8) interventions. Combining targeted interventions for high-risk groups with population interventions promoting healthy weight was most effective in reducing HIP incidence (28.8% reduction by 2030; incidence=11.5, 95% CI 11.2 to 11.8). Scenarios exploring the effect of childhood weight status on entry to adulthood demonstrated significant impact in the selected outcome measure for glycemic regulation, insulin sensitivity in the short term and HIP in the long term. DISCUSSION: Population-level weight reduction interventions will be necessary to 'turn the tide' on HIP. Weight reduction interventions targeting high-risk individuals, while beneficial for those individuals, did not significantly impact forecasted HIP incidence rates. The importance of maintaining interventions promoting healthy weight in childhood was demonstrated.

Uncertainty over implications of placental histopathological findings: A survey of Australian and New Zealand neonatologists.

AIM: Placental examination is known to provide useful information following an adverse pregnancy outcome. Despite existing literature and guidelines for placental examination; current workplace practices, attitudes towards the value of placental examination and the knowledge of perinatal clinicians regarding placental lesions of significance are unknown. The aim of the study is to explore the current knowledge of neonatologists and maternal fetal medicine specialists on placental histopathological findings and clinical management based on placental pathology. METHODS: A total of 280 specialists working in perinatal centres across Australia and New Zealand were invited to complete a 20-question online multiple-choice-based survey addressing work-place placental examination practices, and participant beliefs regarding the utility of histopathological findings and follow-up practices. RESULTS: A total of 74 neonatologists participated in the survey (28.2% response rate). Maternal fetal medicine specialists were excluded due to low response rate (2%). A total of 100% of respondents believed placental examination provided useful information regarding recent pregnancy and neonatal outcomes. They reported being aware of the presence of protocols for macroscopic examination of, and indications for histopathological examination of the placenta (55.4 and 54.1%, respectively). Nine neonatologists reported a system for actioning abnormal placental reports. There was no consensus amongst neonatologists as to which specific placental lesions held implications for future pregnancy or neonatal outcomes, and how these findings should be followed. CONCLUSIONS: Our findings show placental examination is valued amongst neonatologists in Australia and New Zealand, but highlights the need for better education regarding the significance and utility of the results and what would be best practice for following up reports.

A pilot randomised clinical trial of 670 nm red light for reducing retinopathy of prematurity.

BACKGROUND: Photobiomodulation by 670 nm red light in animal models reduced severity of ROP and improved survival. This pilot randomised controlled trial aimed to provide data on 670 nm red light exposure for prevention of ROP and survival for a larger randomised trial. METHODS: Neonates <30 weeks gestation or <1150 g at birth were randomised to receive 670 nm for 15 min (9 J/cm2) daily until 34 weeks corrected age. DATA COLLECTED: placental pathology, growth, days of respiratory support and oxygen, bronchopulmonary dysplasia, patent ductus arteriosus, necrotising enterocolitis, sepsis, worst stage of ROP, need for laser treatment, and survival. RESULTS: Eighty-six neonates enrolled-45 no red light; 41 red light. There was no difference in severity of ROP (<27 weeks-p = 0.463; ≥27 weeks-p = 0.558) or requirement for laser treatment (<27 weeks-p = 1.00; ≥27 weeks-no laser treatment in either group). Survival in 670 nm red light treatment group was 100% (41/41) vs 89% (40/45) in untreated infants (p = 0.057). CONCLUSION: Randomisation to receive 670 nm red light within 24-48 h after birth is feasible. Although no improvement in ROP or survivability was observed, further testing into the dosage and delivery for this potential therapy are required.

The Effect of Preterm Birth on Renal Development and Renal Health Outcome.

Preterm birth is associated with adverse renal health outcomes including hypertension, chronic kidney disease, and an increased rate of progression to end-stage renal failure. This review explores the antenatal, perinatal, and postnatal factors that affect the functional nephron mass of an individual and contribute to long-term kidney outcome. Health-care professionals have opportunities to increase their awareness of the risks to kidney health in this population. Optimizing maternal health around the time of conception and during pregnancy, providing kidney-focused supportive care in the NICU during postnatal nephrogenesis, and avoiding accelerating nephron loss throughout life may all contribute to improved long-term outcomes. There is a need for ongoing research into the long-term kidney outcomes of preterm survivors in mid-to-late adulthood as well as a need for further research into interventions that may improve ex utero nephrogenesis.

Incidence and Risk Factors of Early Onset Neonatal AKI.

BACKGROUND AND OBJECTIVES: Neonatal AKI is associated with poor short- and long-term outcomes. The objective of this study was to describe the risk factors and outcomes of neonatal AKI in the first postnatal week. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The international retrospective observational cohort study, Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), included neonates admitted to a neonatal intensive care unit who received at least 48 hours of intravenous fluids. Early AKI was defined by an increase in serum creatinine >0.3 mg/dl or urine output <1 ml/kg per hour on postnatal days 2-7, the neonatal modification of Kidney Disease: Improving Global Outcomes criteria. We assessed risk factors for AKI and associations of AKI with death and duration of hospitalization. RESULTS: Twenty-one percent (449 of 2110) experienced early AKI. Early AKI was associated with higher risk of death (adjusted odds ratio, 2.8; 95% confidence interval, 1.7 to 4.7) and longer duration of hospitalization (parameter estimate: 7.3 days 95% confidence interval, 4.7 to 10.0), adjusting for neonatal and maternal factors along with medication exposures. Factors associated with a higher risk of AKI included: outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children's hospital. Those factors that were associated with a lower risk included multiple gestations, cesarean section, and exposures to antimicrobials, methylxanthines, diuretics, and vasopressors. Risk factors varied by gestational age strata. CONCLUSIONS: AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as "red flags" for clinicians at the initiation of the neonatal intensive care unit course.

Renal dysfunction is already evident within the first month of life in Australian Indigenous infants born preterm.

Antecedents of the high rates of chronic kidney disease in Australian Indigenous peoples may originate early in life. Fourteen percent of Australian Indigenous infants are born preterm (under 37 weeks gestation) and, therefore, at risk. Here, our observational cohort study sought to determine the impact of preterm birth on renal function in Australian Indigenous and non-Indigenous infants. Renal function was assessed between 4-29 days postnatally in 60 Indigenous and 42 non-Indigenous infants born at 24-36 weeks gestation. Indigenous ethnicity was associated with impaired renal function, with significantly higher serum creatinine (geometric mean ratio (GMR) 1.15 [1.06, 1.25]), fractional excretion of sodium (GMR 1.21 [1.04, 1.39]), and urine albumin (GMR 1.57 [1.05, 2.34]), ß-2 microglobulin (GMR 1.82 [1.11, 2.98]) and cystatin C (GMR 3.27 [1.54, 6.95]) when controlling for gestational/postnatal age, sex and birth weight Z-score. Renal injury, as indicated by high urine neutrophil gelatinase-associated lipocalin levels, was associated with maternal smoking and postnatal antibiotic exposure. Indigenous infants appeared to be most susceptible to the adverse impact of antibiotics. These findings show that preterm Australian Indigenous infants are highly vulnerable to renal dysfunction. Preterm birth may contribute to their increased risk of chronic kidney disease. Thus, we recommended that renal function should be closely monitored life-long in Indigenous children born preterm.

Perceptions of Australian and New Zealand clinicians caring for neonates born at the borderline of viability have changed since the 2005 consensus guideline.

AIM: To determine whether clinician and consumer considerations have changed regarding the resuscitation and support of neonates born at the borderlines of viability since the 2005 New South Wales (NSW) and Australian Capital Territory (ACT) consensus guidelines were developed. METHODS: A prospective survey based on the hypotheses and scenarios developed in the original NSW and ACT consensus workshop on perinatal care at the borderlines of viability was sent to neonatologists, fetal medicine specialists, clinical midwife and clinical neonatal consultants and consumer representatives in Australia and New Zealand. Four scenarios and 16 questions were used to explore the respondent's views towards different aspects of the management of neonates born at the borderlines of viability. Australian and New Zealand Neonatal Network data from 2013 or NSW/ACT Neonatal Intensive Care Units (NICUS) data from 1998 to 2004 were used to provide outcome data for each scenario. RESULTS: A total of 87% or more of respondents advocated for resuscitation of neonates at 24 and 25 weeks' gestation in 2015. Only 29% (49/169) would agree to parental request not to resuscitate at 25 weeks and only 10% (17/170) at 260-6 weeks. The number of perinatal clinical care providers considering resuscitation at 235 weeks' gestation increased from 23% in 2005 to more than 50% in 2015. CONCLUSION: These findings support the development of updated guidelines for the management of neonates in Australia and New Zealand born at the borderlines of viability to reflect the changes in clinical perceptions and management.

Neonatal hypertension: an educational review.

Hypertension is encountered in up to 3% of neonates and occurs more frequently in neonates requiring hospitalization in the neonatal intensive care unit (NICU) than in neonates in newborn nurseries or outpatient clinics. Former NICU neonates are at higher risk of hypertension secondary to invasive procedures and disease-related comorbidities. Accurate measurement of blood pressure (BP) remains challenging, but new standardized methods result in less measurement error. Multiple factors contribute to the rapidly changing BP of a neonate: gestational age, postmenstrual age (PMA), birth weight, and maternal factors are the most significant contributors. Given the natural evolution of BP as neonates mature, a percentile cutoff of 95% for PMA has been the most common definition used; however, this is not based on outcome data. Common causes of neonatal hypertension are congenital and acquired renal disease, history of umbilical arterial catheter placement, and bronchopulmonary dysplasia. The treatment of neonatal hypertension has mostly been off-label, but as evidence accumulates, the safety of medical management has increased. The prognosis of neonatal hypertension remains largely unknown and thankfully most often resolves unless secondary to renovascular disease, but further research is needed. This review discusses important factors related to neonatal hypertension including BP measurement, determinants of BP, and management of neonatal hypertension.

Late onset neonatal acute kidney injury: results from the AWAKEN Study.

BACKGROUND: Most studies of neonatal acute kidney injury (AKI) have focused on the first week following birth. Here, we determined the outcomes and risk factors for late AKI (>7d). METHODS: The international AWAKEN study examined AKI in neonates admitted to an intensive care unit. Late AKI was defined as occurring >7 days after birth according to the KDIGO criteria. Models were constructed to assess the association between late AKI and death or length of stay. Unadjusted and adjusted odds for late AKI were calculated for each perinatal factor. RESULTS: Late AKI occurred in 202/2152 (9%) of enrolled neonates. After adjustment, infants with late AKI had higher odds of death (aOR:2.1, p = 0.02) and longer length of stay (parameter estimate: 21.9, p < 0.001). Risk factors included intubation, oligo- and polyhydramnios, mild-moderate renal anomalies, admission diagnoses of congenital heart disease, necrotizing enterocolitis, surgical need, exposure to diuretics, vasopressors, and NSAIDs, discharge diagnoses of patent ductus arteriosus, necrotizing enterocolitis, sepsis, and urinary tract infection. CONCLUSIONS: Late AKI is common, independently associated with poor short-term outcomes and associated with unique risk factors. These should guide the development of protocols to screen for AKI and research to improve prevention strategies to mitigate the consequences of late AKI.