Low hemoglobin levels are independently associated with neonatal acute kidney injury: a report from the AWAKEN Study Group.

BACKGROUND: Studies in adults showed a relationship between low hemoglobin (Hb) and acute kidney injury (AKI). We performed this study to evaluate this association in newborns. METHODS: We evaluated 1891 newborns from the Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN) database. We evaluated the associations for the entire cohort and 3 gestational age (GA) groups: <29, 29-<36, and ≥36 weeks' GA. RESULTS: Minimum Hb in the first postnatal week was significantly lower in neonates with AKI after the first postnatal week (late AKI). After controlling for multiple potential confounders, compared to neonates with a minimum Hb ≥17.0 g/dL, both those with minimum Hb ≤12.6 and 12.7-14.8 g/dL had an adjusted increased odds of late AKI (aOR 3.16, 95% CI 1.44-6.96, p = 0.04) and (aOR 2.03, 95% CI 1.05-3.93; p = 0.04), respectively. This association was no longer evident after controlling for fluid balance. The ability of minimum Hb to predict late AKI was moderate (c-statistic 0.68, 95% CI 0.64-0.72) with a sensitivity of 65.9%, a specificity of 69.7%, and a PPV of 20.8%. CONCLUSIONS: Lower Hb in the first postnatal week was associated with late AKI, though the association no longer remained after fluid balance was included. IMPACT: The current study suggests a possible novel association between low serum hemoglobin (Hb) and neonatal acute kidney injury (AKI). The study shows that low serum Hb levels in the first postnatal week are associated with increased risk of AKI after the first postnatal week. This study is the first to show this relationship in neonates. Because this study is retrospective, our observations cannot be considered proof of a causative role but do raise important questions and deserve further investigation. Whether the correction of low Hb levels might confer short- and/or long-term renal benefits in neonates was beyond the scope of this study.

The impact of fluid balance on outcomes in premature neonates: a report from the AWAKEN study group.

BACKGROUND: We evaluated the epidemiology of fluid balance (FB) over the first postnatal week and its impact on outcomes in a multi-center cohort of premature neonates from the AWAKEN study. METHODS: Retrospective analysis of infants <36 weeks' gestational age from the AWAKEN study (N = 1007). FB was defined by percentage of change from birth weight. OUTCOME: Mechanical ventilation (MV) at postnatal day 7. RESULTS: One hundred and forty-nine (14.8%) were on MV at postnatal day 7. The median peak FB was 0% (IQR: -2.9, 2) and occurred on postnatal day 2 (IQR: 1,5). Multivariable models showed that the peak FB (aOR 1.14, 95% CI 1.10-1.19), lowest FB in first postnatal week (aOR 1.12, 95% CI 1.07-1.16), and FB on postnatal day 7 (aOR 1.10, 95% CI 1.06-1.13) were independently associated with MV on postnatal day 7. In a similar analysis, a negative FB at postnatal day 7 protected against the need for MV at postnatal day 7 (aOR 0.21, 95% CI 0.12-0.35). CONCLUSIONS: Positive peak FB during the first postnatal week and more positive FB on postnatal day 7 were independently associated with MV at postnatal day 7. Those with a negative FB at postnatal day 7 were less likely to require MV.

The impact of fluid balance on outcomes in critically ill near-term/term neonates: a report from the AWAKEN study group.

BACKGROUND: In sick neonates admitted to the NICU, improper fluid balance can lead to fluid overload. We report the impact of fluid balance in the first postnatal week on outcomes in critically ill near-term/term neonates. METHODS: This analysis includes infants ≥36 weeks gestational age from the Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) study (N = 645). Fluid balance: percent weight change from birthweight. PRIMARY OUTCOME: mechanical ventilation (MV) on postnatal day 7. RESULTS: The median peak fluid balance was 1.0% (IQR: -0.5, 4.6) and occurred on postnatal day 3 (IQR: 1, 5). Nine percent required MV at postnatal day 7. Multivariable models showed the peak fluid balance (aOR 1.12, 95%CI 1.08-1.17), lowest fluid balance in 1st postnatal week (aOR 1.14, 95%CI 1.07-1.22), fluid balance on postnatal day 7 (aOR 1.12, 95%CI 1.07-1.17), and negative fluid balance at postnatal day 7 (aOR 0.3, 95%CI 0.16-0.67) were independently associated with MV on postnatal day 7. CONCLUSIONS: We describe the impact of fluid balance in critically ill near-term/term neonates over the first postnatal week. Higher peak fluid balance during the first postnatal week and higher fluid balance on postnatal day 7 were independently associated with MV at postnatal day 7.

Correction: Incidence of neonatal hypertension from a large multicentre study [Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates-AWAKEN].

Text for Correction.

Incidence of neonatal hypertension from a large multicenter study [Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates-AWAKEN].

BACKGROUND: Hypertension occurs in up to 3% of neonates admitted to the Neonatal Intensive Care Unit (NICU), and is a potentially under-recognized condition. The aim of this study was to examine the incidence of documented and undiagnosed hypertension from the 24-center Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) database, and to assess risk factors for hypertension according to gestational age. METHODS: Diagnosed hypertension was documented if an infant had a discharge diagnosis of hypertension and/or discharged on antihypertensive medications. Undiagnosed hypertension was defined when infants did not have a diagnosis of hypertension, but >50% of the lowest mean, diastolic and systolic blood pressure recordings were >95th percentile for gestational age. RESULTS: Of the 2162 neonates enrolled in the study, hypertension was documented in 1.8%. An additional 3.7% were defined as having undiagnosed hypertension. There was a significant correlation with neonatal hypertension and acute kidney injury (AKI). Additional risk factors for neonatal hypertension were hyperbilirubinaemia, Caucasian race, outborn, vaginal delivery, and congenital heart disease. Protective factors were small for gestational age, multiple gestations, and steroids for fetal maturation. CONCLUSIONS: Neonatal hypertension may be an under-recognized condition. AKI and other risk factors predispose infants to hypertension.

Comparisons of vaginal flora patterns among sexual behaviour groups of women: implications for the pathogenesis of bacterial vaginosis.

Background Bacterial vaginosis (BV) is the most common cause of vaginal discharge. The objective was to compare the prevalence of BV by Nugent score among African-American women who have sex with women (WSW) and women who have sex with women and men (WSWM) compared with an age-matched group of women who have sex with men (WSM). Secondary objectives were to correlate low versus high Nugent scores with vaginal symptoms among women with BV and to correlate BV diagnosis with sexual practices. METHODS: A secondary analysis of clinical and laboratory data from African-American WSW (n=73) and WSWM (n=68) participating in the Women's Sexual Health Project (August 2011-October 2013) and a 3:1 age-matched group of African-American WSM participating in the Longitudinal Study of Vaginal Flora (August 1999-February 2002) at a sexually transmissible infection clinic (n=423) was performed. RESULTS: Compared with WSM, WSW and WSWM were significantly more likely to have BV based on the Nugent score (OR 2.63; 95% CI 1.55-4.48; P<0.01 and OR 3.67; 95% CI 2.17-6.21; P<0.01 respectively). WSW and WSWM with BV were not significantly more likely to have higher Nugent scores than WSM with BV. Among women with BV reporting symptoms, there was no significant difference in the proportion of women with low-positive versus high-positive Nugent scores. Women who participated in receptive vaginal sex (penile or digital) within the 30 days preceding study enrolment were significantly more likely to have BV (OR 2.50; 95% CI 1.57-3.63; P<0.01). CONCLUSIONS: WSW and WSWM were significantly more likely to have BV than WSM. Further analysis of sexual practices among sexual behaviour groups of women is needed to determine their potential impact on BV rates.

Association Between Early Caffeine Citrate Administration and Risk of Acute Kidney Injury in Preterm Neonates: Results From the AWAKEN Study.

Importance: Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality. Objectives: To examine the association between caffeine citrate administration and AKI in preterm neonates in the first 7 days after birth and to test the hypothesis that caffeine administration would be associated with reduced incidence and severity of AKI. Design, Setting, and Participants: This study was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study, a retrospective observational cohort that enrolled neonates born from January 1 to March 31, 2014. The dates of analysis were October 2016 to December 2017. The setting was an international, multicenter cohort study of neonates admitted to 24 participating level III or IV neonatal intensive care units. Participants met the original inclusion and exclusion criteria of the AWAKEN study. Additional exclusion criteria for this study included participants greater than or equal to 33 weeks' gestation at birth, admission after age 7 days, use of theophylline in the neonatal intensive care unit, or lack of data to define AKI. There were 675 preterm neonates available for analysis. Exposure: Administration of caffeine in the first 7 days after birth. Main Outcomes and Measures: The primary outcome was the incidence of AKI (based on the modified neonatal Kidney Disease: Improving Global Outcomes [KDIGO] definition) in the first 7 days after birth. The hypothesis that caffeine administration would be associated with reduced AKI incidence was formulated before data analysis. Results: The study cohort (n = 675) was 55.4% (n = 374) male, with a mean (SD) gestational age of 28.9 (2.8) weeks and a mean (SD) birth weight of 1285 (477) g. Acute kidney injury occurred in 122 neonates (18.1%) in the first 7 days after birth. Acute kidney injury occurred less frequently among neonates who received caffeine than among those who did not (50 of 447 [11.2%] vs 72 of 228 [31.6%], P < .01). After multivariable adjustment, administration of caffeine remained associated with reduced odds of developing AKI (adjusted odds ratio, 0.20; 95% CI, 0.11-0.34), indicating that for every 4.3 neonates exposed to caffeine one case of AKI was prevented. Among neonates with early AKI, those receiving caffeine were less likely to develop stage 2 or 3 AKI (adjusted odds ratio, 0.20; 95% CI, 0.12-0.34). Conclusions and Relevance: Caffeine administration in preterm neonates is associated with reduced incidence and severity of AKI. Further studies should focus on the timing and dosage of caffeine to optimize the prevention of AKI.

Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study.

Background: Single-center studies suggest that neonatal acute kidney injury (AKI) is associated with poor outcomes. However, inferences regarding the association between AKI, mortality, and hospital length of stay are limited due to the small sample size of those studies. In order to determine whether neonatal AKI is independently associated with increased mortality and longer hospital stay, we analyzed the Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) database. Methods: All neonates admitted to 24 participating neonatal intensive care units from four countries (Australia, Canada, India, United States) between January 1 and March 31, 2014, were screened. Of 4273 neonates screened, 2022 (47·3%) met study criteria. Exclusion criteria included: no intravenous fluids ≥48 hours, admission ≥14 days of life, congenital heart disease requiring surgical repair at <7 days of life, lethal chromosomal anomaly, death within 48 hours, inability to determine AKI status or severe congenital kidney abnormalities. AKI was defined using a standardized definition -i.e., serum creatinine rise of ≥0.3 mg/dL (26.5 mcmol/L) or ≥50% from previous lowest value, and/or if urine output was <1 mL/kg/h on postnatal days 2 to 7. Findings: Incidence of AKI was 605/2022 (29·9%). Rates varied by gestational age groups (i.e., ≥22 to <29 weeks =47·9%; ≥29 to <36 weeks =18·3%; and ≥36 weeks =36·7%). Even after adjusting for multiple potential confounding factors, infants with AKI had higher mortality compared to those without AKI [(59/605 (9·7%) vs. 20/1417 (1·4%); p< 0.001; adjusted OR=4·6 (95% CI=2·5-8·3); p=<0·0001], and longer hospital stay [adjusted parameter estimate 8·8 days (95% CI=6·1-11·5); p<0·0001]. Interpretation: Neonatal AKI is a common and independent risk factor for mortality and longer hospital stay. These data suggest that neonates may be impacted by AKI in a manner similar to pediatric and adult patients. Funding: US National Institutes of Health, University of Alabama at Birmingham, Cincinnati Children's, University of New Mexico.