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Concentration of novel urinary tract infection biomarkers in neonates – Scientific Reports


To our knowledge this is the first study that identified the presence of RNase 7 and BD-1 in neonatal urine and characterized the effect of GA and birthweight on AMP concentration. We detected RNase 7 and BD-1 in the neonatal urine even in those neonates who were born at the limits of viability at 22 weeks of gestation. The neonatal urinary concentrations of RNase 7 and BD-1 decreased with increasing GA and birthweight and were higher than the reported levels in older pediatric patients and adults. The urinary concentration of RNase 7 was higher in female compared to male neonates.

The urinary concentration of NGAL, another AMP, has been shown to be higher in neonates compared to older pediatric patients and adults and has an inverse relationship with GA and birthweight9,10. Similarly, we found that BD-1 and RNase 7 levels decreased as birthweight increased. A correlation or lack thereof between BD-1 and RNase 7 concentrations has not been investigated previously and the patterns of AMPs concentration in neonates with small, appropriate, or large weight for GA remain to be evaluated.

The diagnosis of UTI in the pediatric and neonatal population has several limitations including lack of specificity for the urinalysis and the invasive nature of obtaining sterile urinary samples for culture. Measuring the concentration of urinary AMPs could be utilized to improve the speed and accuracy of UTI diagnosis in children as recently shown17. One of the strengths of this study is the ability to identify the presence and baseline concentration values of neonatal urinary AMPs and characterize the variation by GA and birthweight. This could be the first step in utilizing AMPs as novel biomarkers to improve neonatal UTI diagnostics.

One limitation of our study is the method of neonatal urine collection which involved placement of cotton balls in the diaper. AMPs, as discussed previously, are made throughout the body, including the skin6,8,11,12,13. Therefore, our measured urinary AMPs may possibly be reflective of dermal RNase 7 and BD-1. At this time there is no means of separating out those AMPs made by the skin from those made within the GU tract without obtaining urinary samples directly via catheterization. Since previous literature demonstrated that the GU tract is the major source of both RNase 7 and BD-1 in children and adults8,11, we assumed for this study that the AMPs we measured were of GU tract origin rather than dermal origin. Future studies should address whether AMP concentrations could vary based on the urine collection methods. Another limitation is that neonatal eGFR, urine osmolality and urine creatinine are physiologically lower compared to older children18. We elected to normalize AMP concentrations to urine creatinine only and speculated that similar patterns will be noticed if AMP concentrations were normalized with eGFR and/or urine osmolality.

This study confirmed the presence of RNase 7 and BD-1 in neonatal urine, defined the overall median concentrations and outlined their variation with GA and birthweight. These findings represent initial necessary steps toward the eventual implementation of novel biomarkers such as AMPs in improving neonatal UTI diagnostics.



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