Perinatal risk factors associated with acute kidney injury severity and duration among infants born extremely preterm.

BACKGROUND: We evaluated time-varying perinatal risk factors associated with early (≤7 post-natal days) and late (>7 post-natal days) severe acute kidney injury (AKI) occurrence and duration. METHODS: A secondary analysis of Preterm Erythropoietin Neuroprotection Trial data. We defined severe AKI (stage 2 or 3) per neonatal modified Kidney Disease: Improving Global Outcomes criteria. Adjusted Cox proportional hazards models were conducted with exposures occurring at least 72 h before severe AKI. Adjusted negative binomial regression models were completed to evaluate risk factors for severe AKI duration. RESULTS: Of 923 participants, 2% had early severe AKI. In the adjusted model, gestational diabetes (adjusted HR (aHR) 5.4, 95% CI 1.1-25.8), non-steroidal anti-inflammatory drugs (NSAIDs) (aHR 3.2, 95% CI 1.0-9.8), and vancomycin (aHR 13.9, 95% CI 2.3-45.1) were associated with early severe AKI. Late severe AKI occurred in 22% of participants. Early severe AKI (aHR 2.5, 95% CI 1.1-5.4), sepsis (aHR 2.5, 95% CI 1.4-4.4), vasopressors (aHR 2.9, 95% CI 1.8-4.6), and diuretics (aHR 2.6, 95% CI 1.9-3.6) were associated with late severe AKI. Participants who had necrotizing enterocolitis or received NSAIDs had longer severe AKI duration. CONCLUSION: We identified major risk factors for severe AKI that can be the focus of future research. IMPACT STATEMENT: Time-dependent risk factors for severe acute kidney injury (AKI) and its duration are not well defined among infants born <28 weeks' gestation. Over 1 in 5 infants born <28 weeks' gestation experienced severe AKI, and this study identified several major time-dependent perinatal risk factors occurring within 72 h prior to severe AKI. This study can support efforts to develop risk stratification and clinical decision support to help mitigate modifiable risk factors to reduce severe AKI occurrence and duration.

Neonatal Extracorporeal Membrane Oxygenation: Associations between Continuous Renal Replacement Therapy, Thrombocytopenia, and Outcomes.

INTRODUCTION: The incidence of thrombocytopenia in neonates receiving extracorporeal membrane oxygenation (ECMO) with and without concurrent continuous renal replacement therapy (CRRT) and associated complications have not been well described. The primary aims of the current study were to (1) characterize thrombocytopenia in neonates receiving ECMO (including those treated concurrently with CRRT) and (2) evaluate risk factors (including CRRT utilization) associated with severe thrombocytopenia. In a planned exploratory secondary aim, we explored the association of severe thrombocytopenia with outcomes in neonates receiving ECMO. METHODS: We conducted a retrospective single-center chart review of neonates who received ECMO 07/01/14-03/01/20 and evaluated associations between CRRT, severe thrombocytopenia (platelet count <50,000/mm3), and outcomes (ECMO duration, length of stay, and survival). RESULTS: Fifty-two neonates received ECMO; 35 (67%) received concurrent CRRT. Severe thrombocytopenia occurred in 27 (52%) neonates overall and in 21 (60%) neonates who received concurrent CRRT. Underlying diagnosis, ECMO mode, care unit, and moderate/severe hemolysis differed between those who did and did not receive CRRT. CRRT receivers experienced shorter hospital stays than CRRT non-receivers, but ECMO duration, length of intensive care unit (ICU) stay, and survival did not differ between groups. CRRT receipt was associated with severe thrombocytopenia. Exploratory classification and regression tree (CART) analysis suggests CRRT use, birthweight, and ICU location are all predictors of interest for severe thrombocytopenia. CONCLUSIONS: In our cohort, CRRT use during ECMO was associated with severe thrombocytopenia, and patients who received ECMO with CRRT experienced shorter hospital stays than those who did not receive CRRT. Exploratory CART analysis suggests CRRT use, birthweight, and ICU location are all predictors for severe thrombocytopenia and warrant further investigations in larger studies.

Post-natal steroid exposure in very low birthweight neonates and associations with acute kidney injury.

OBJECTIVE: The relationship between adrenal insufficiency (AI), post-natal steroids (PNS) and neonatal acute kidney injury (AKI) remains understudied. We investigated associations between PNS and AKI in very low birthweight (VLBW) neonates, hypothesizing PNS is associated with reduced AKI. STUDY DESIGN: We conducted a single-center retrospective review of VLBW infants comparing those with and without PNS exposure. Associations between PNS exposure and AKI were evaluated using generalized linear mixed-modeling adjusted for confounders. RESULT: Of 567 neonates, 97 (17.1%) were exposed to PNS and 130 (22.9%) experienced AKI. Infants with PNS had lower gestational age, birthweight, Apgar scores, and experienced more AI versus those without PNS (all p < 0.05). PNS was associated with AKI (aRR 1.72, 95% CI 1.09-2.72) though hydrocortisone alone was not. CONCLUSION: PNS exposure, but not hydrocortisone alone, is associated with increased AKI in VLBW neonates. Further analysis is needed to investigate the role of AI and AKI.

Optimizing Nutrition in Neonates with Kidney Dysfunction.

The nutritional management of neonates with kidney disease is complex. There may be significant differences in nutritional needs based on the duration and cause of kidney dysfunction, including acute kidney injury (AKI) and chronic kidney disease (CKD). Furthermore, the treatment modality, including acute (continuous renal replacement therapy and peritoneal dialysis [PD]) and chronic (intermittent hemodialysis and PD) approaches may differentially affect nutritional losses and dietary needs. In this review, we discuss the pathophysiology of compromised nutrition in neonates with AKI and CKD. We also summarize the existing data and consensus recommendations on the provision of nutrition to neonates with AKI and CKD. We highlight the paucity of data on micronutrient losses and the need for future prospective studies to enhance nutritional supplementation to hopefully improve outcomes in these patients.

Prenatal and Postnatal Disparities in Very-Preterm Infants in a Study of Infections between 2018-2023 in Southeastern US.

BACKGROUND: The birthrate of Black preterm (BPT) infants is 65% higher than White preterm (WPT) infants with a BPT mortality that is 2.3 times higher. The incidence of culture-positive late-onset sepsis is as high as 41% in very-preterm infants. The main purpose of this study was to examine thermal gradients and the heart rate in relation to the onset of infection. This report presents disparities in very-preterm infection incidence, bacteria, and mortality data amongst BPT and WPT infants. METHODS: 367 preterms born at <32 weeks gestational age (GA) between 2019-2023 in five neonatal intensive care units (NICUs) were enrolled to study the onset of infections and dispositions; REDCap data were analyzed for descriptive statistics. RESULTS: The 362 infants for analyses included 227 BPTs (63.7%) and 107 WPTs (29.6%), with 28 infants of other races/ethnicities (Hispanic, Asian, and other), 50.6% female, mean GA of 27.66 weeks, and 985.24 g birthweight. BPT infants averaged 968.56 g at birth (SD 257.50), and 27.68 (SD 2.07) weeks GA, compared to WPT infants with a mean birthweight of 1006.25 g (SD 257.77, p = 0.2313) and 27.67 (SD 2.00, p = 0.982) weeks GA. Of the 426 episodes of suspected infections evaluated across all the enrolled infants, the incidence of early-onset sepsis (EOS) was 1.9%, with BPT infants having 2.50 times higher odds of EOS than WPT infants (p = 0.4130, OR (odds ratio) = 2.50, p_or = 0.408). The overall incidence of late-onset sepsis (LOS) was 10.8%, with LOS in 11.9% of BPT infants versus 9.3% (p = 0.489, OR = 1.21, p_or = 0.637) of WPT infants. BPT infants made up 69.2% of the 39 infants with Gram-positive infections vs. 25.6% for WPT infants; 16 infants had Gram-negative culture-positive infections, with 81.2% being BPT infants versus 18.8% being WPT infants. Of the 27 urinary tract infections, 78% were in BPTs. The necrotizing enterocolitis incidence was 6.9%; the incidence in BPT infants was 7.5% vs. 6.5% in WPT infants. The overall mortality was 8.3%, with BPTs at 8.4% vs. WPT infants at 9.3%, (p = 0.6715). CONCLUSIONS: BPTs had a higher rate of positive cultures, double the Gram-negative infections, a much higher rate of urinary tract infections, and a higher rate of mortality than their WPT counterparts. This study emphasizes the higher risk of morbidity and mortality for BPTs.

Incidence, Risk Factors, and Outcomes Associated With Recurrent Neonatal Acute Kidney Injury in the AWAKEN Study.

Importance: The incidence and associated outcomes of recurrent acute kidney injury (rAKI) in neonates remain largely unknown. Objective: To determine the incidence, risk factors, and clinical outcomes associated with rAKI in critically ill neonates. Design, Setting, and Participants: This cohort study was a secondary analysis of the multicenter, international Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates retrospective study. Comparisons were made among neonates with no AKI, a single AKI episode (sAKI), and rAKI. All neonates younger than 14 days who were admitted between January 1 and March 31, 2014, to 24 participating level II to IV neonatal intensive care units and received intravenous fluids for at least 48 hours were considered for inclusion. Neonates with congenital heart disease requiring surgery within the first week of life, lethal chromosomal anomalies, death within 48 hours of admission, or severe congenital kidney abnormalities were excluded. Data were analyzed from May 23, 2022, to December 8, 2023. Exposure: Recurrent AKI using the neonatal Kidney Disease: Improving Global Outcomes criteria. Determination of each rAKI required a complete return to the baseline serum creatinine level that defined the prior AKI episode. Main Outcomes and Measures: Incidence and risk factors of rAKI and associations of rAKI with length of stay (LOS; ie, birth to hospital discharge) and mortality. Results: The study cohort (n = 2162) included 1233 male neonates (57.0%). Gestational age distribution was less than 29 weeks for 276 neonates (12.8%), 29 to less than 36 weeks for 958 (44.3%), and 36 weeks or older for 928 (42.9%). Of 605 neonates with AKI, 133 (22.0%) developed rAKI with risk factors including younger gestational age, lower birthweight, and higher stage of initial AKI. Infants with rAKI experienced longer median LOS (no AKI, 17 [IQR, 8-34] days; sAKI, 18 [IQR, 9-45] days; rAKI, 60 [IQR, 25-109] days; P < .001). Time-varying Cox proportional hazards regression models suggest rAKI is independently associated with a lower hazard of discharge (adjusted hazard ratio, 0.7 [95% CI, 0.6-0.9]; P = .01) when compared with sAKI, but mortality did not differ between groups (adjusted hazard ratio, 1.4 [95% CI, 0.6-3.0]; P = .44). Conclusions and Relevance: In this cohort study, neonatal rAKI was independently associated with longer LOS when compared with sAKI, suggesting that rAKI in neonates may be an important clinical distinction warranting further study and careful monitoring after an initial AKI episode.