#848 Influence of nutrition and other factors on preterm newborns’ kidney development

Abstract

Abstract Background and Aims According to WHO, in 2020, preterm newborns represented around 10% of all newborns in the world. Premature birth is deeply connected with the risk of developing a chronic kidney disease later in life. This is caused by defects in kidney development (primarily the lower number of nephrons) that are often difficult to identify in the complicated clinical picture of premature babies. Our study aims at providing knowledge on the relationship between preterm infant kidney development and morbidities, nutrition, and blood biomarkers. Method Creatinine was measured in 130 extremely preterm newborns (less than 28 weeks of gestation) enrolled in a randomized controlled trial (Mega Donna Mega) in two Swedish neonatal intensive care units. Creatinine was measured in whole blood or serum with the enzymatic method. Individuals with 4 or more serum creatinine measurements (n = 92) were shortlisted for eGFR calculation. eGFR was calculated with the Wilhelm-Bals weight-based equation due to the lack of length measurements. The patients were divided in 3 groups based upon their kidney development status. This was indirectly assessed using the exponential regression curve describing the eGFR trends as model and the doubling time as discriminating parameter. Data about morbidity, treatment, nutrition, blood lipidomics and proteomics were also collected during the MegaDonnaMega trial and has been used to investigate the differences between the three groups. A linear model adjusted for sex and gestational age was used to analyse lipidomics and proteomics data in relation to eGFR. The omics analysis used average data from the first month of age. Data analysis was performed in R, SPSS, SAS and GraphPad statistical programs. Results Subjects were divided in 3 groups from best to worst kidney function development. The parameter used, doubling time, is inversely correlated to eGFR and kidney development. Subjects in group 1 reached the normal at-term birth eGFR (40 ml/min/1.73 m2) at around 50 days of age, whereas the other two groups were delayed (66 days for group 2, 78 for group 3). Subjects in group 2 and 3 were characterized by longer stay at the NICU, lower weight and length in respect to infants in group 1. Subjects in groups 2 and 3 also showed more co-morbidities in respect to group 1. Regarding nutrition, subjects administered with maternal milk had shorter doubling times when compared to those administered with donor or mixed milk. Six serum fatty acids correlated with the eGFR trends: heptadecanoic (FA 17:0) showed a negative correlation, while palmitoleic (16:1n-7), gamma-linolenic (18:3n-6), erucic (22:1n-9) docosapentaenoic (22:5n-6) and tricosanoic (23:0) acid showed positive correlations. 45 serum proteins correlated with the eGFR trends, in particular, inflammatory and proliferative pathways showed an inverse correlation with eGFR. Conclusion We have detected differences in the eGFR trends of preterm newborns that could be traced back to nutrition and other factors. Moreover, we identified several serum fatty acids and proteins that correlated with eGFR and therefore kidney development. The data indicates that postnatal kidney development may be important to consider in the clinical care of preterm newborns.