Maturation of GFR in Term-Born Neonates: An Individual Participant Data Meta-Analysis
Nori J.L. Smeets, Joanna IntHout, Maurice J.P. van der Burgh, George J. Schwartz, Michiel F. Schreuder, Saskia N. de Wildt
Abstract
Background The evidence from individual studies to support the maturational pattern of GFR in healthy, term-born neonates is inconclusive. We performed an individual participant data (IPD) meta-analysis of reported measured GFR (mGFR) data, aiming to establish neonatal GFR reference values. Furthermore, we aimed to optimize neonatal creatinine-based GFR estimations. Methods We identified studies reporting mGFR measured by exogenous markers or creatinine clearance (CrCL) in healthy, term-born neonates. The relationship between postnatal age and clearance was investigated using cubic splines with generalized additive linear mixed models. From our reference values, we estimated an updated coefficient for the Schwartz equation (eGFR [ml/min per 1.73 m 2 ]=(k×height [cm])/serum creatinine [mg/dl]). Results Forty-eight out of 1521 screened articles reported mGFR in healthy, term-born neonates, and 978 mGFR values from 881 neonates were analyzed. IPD were available for 367 neonates, and the other 514 neonates were represented by 41 aggregated data points as means/medians per group. GFR doubled in the first 5 days after birth, from 19.6 (95% CI, 14.7 to 24.6) to 40.6 (95% CI, 36.7 to 44.5) ml/min per 1.73 m 2 , and then increased more gradually to 59.4 (95% CI, 45.9 to 72.9) ml/min per 1.73 m 2 by 4 weeks of age. A coefficient of 0.31 to estimate GFR best fitted the data. Conclusions These reference values for healthy, term-born neonates show a biphasic increase in GFR, with the largest increase between days 1 and 5. Together with the re-examined Schwartz equation, this can help identify altered GFR in term-born neonates. To enable widespread implementation of our proposed eGFR equation, validation in a large cohort of neonates is required.