Applying Neural ODEs to Derive a Mechanism-Based Model for Characterizing Maturation-Related Serum Creatinine Dynamics in Preterm Newborns.

Serum creatinine in neonates follows complex dynamics due to maturation processes, most pronounced in the first few weeks of life. The development of a mechanism-based model describing complex dynamics requires high expertise in pharmacometric (PMX) modeling and substantial model development time. A recently published machine learning (ML) approach of low-dimensional neural ordinary differential equations (NODEs) is capable of modeling such data from newborns automatically.

Dose-Related Adverse Drug Events in Neonates: Recognition and Assessment.

The efficacy and safety of a drug is dose or exposure related, and both are used to assess the benefit-risk balance of a given drug and ultimately to decide on the specific drug license, including its dose and indication(s). Unfortunately, both efficacy and safety are much more difficult to establish in neonates, resulting in very few drugs licensed for use in this vulnerable population. This review will focus on dose-related adverse events in neonates.

Pharmacometric Evaluation of Umbilical Cord Blood Concentration-Based Early Initiation of Treatment in Methadone-Exposed Preterm Neonates.

In methadone-exposed preterm neonates, early identification of those at risk of severe neonatal abstinence syndrome (NAS) and use of a methadone dosing regimen that can provide effective and safe drug exposure are two important aspects of optimal care. To this end, we reviewed 17 methadone dosing recommendations in the international guidelines and literature and explored their variability in key dosing strategies. We selected three of the reviewed dosing regimens for their pharmacokinetics (PK) characteristics and their exposure-response relationship in three gestational age groups of preterm neonates (28, 32 and 36 gestational age weeks) at risk for development of severe NAS (defined as an umbilical cord methadone concentration of ≤60 ng/mL, following fetal exposure).

Creatinine Trends to Detect Ibuprofen-Related Maturational Adverse Drug Events in Neonatal Life: A Simulation Study for the ELBW Newborn.

Recognizing a change in serum creatinine concentrations is useful to detect a renal adverse drug reaction signal. Assessing and characterizing the nephrotoxic side-effects of drugs in extremely low birth weight (ELBW, ≤1000 g) neonates remain challenging due to the high variability in creatinine in this population. This study aims to investigate and quantify the impact of ibuprofen treatment on kidney function, reflected by serum creatinine.

Amikacin or Vancomycin Exposure Alters the Postnatal Serum Creatinine Dynamics in Extreme Low Birth Weight Neonates.

Background: Disentangling renal adverse drug reactions from confounders remains a major challenge to assess causality and severity in neonates, with additional limitations related to the available tools (modified Kidney Disease Improving Global Outcome, or Division of Microbiology and Infectious Diseases pediatric toxicity table). Vancomycin and amikacin are nephrotoxic while still often prescribed in neonates. We selected these compounds to assess their impact on creatinine dynamics as a sensitive tool to detect a renal impairment signal.

Creatinine at Birth Correlates with Gestational Age and Birth Weight: Another Factor of the Imbroglio in Early Neonatal Life.

Background: Serum creatinine (Scr) in early neonatal life (first week of life) displays extensive variability; hence, a better understanding is needed to use Scr as a diagnostic biomarker for acute kidney injury (AKI).

Objective: The objective of this study was to explore Scr trends and its covariates in early neonatal life.

Methods: Analysis of a rich, pooled Scr dataset (enzymatic assay) of 4,509 Scr observations in 1,181 neonates in the first week of life with birth weight, gestational age (GA), and postnatal age as covariates was conducted.

Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first 6 weeks of life.

Background: Characterizing the dynamics of serum creatinine concentrations (Scr) and associated creatinine clearance (CLcr) as a measure of kidney function in extremely low birth weight (≤ 1000 g; ELBW) neonates remains challenging.

Methods: We performed a retrospective study that included longitudinal Scr (enzymatic assay) data from 148 ELBW neonates up to 6 weeks after birth. Change of Scr and inter-individual variability was characterized with nonlinear mixed-effect modeling.

Age appropriate reference intervals for eight kidney function and injury markers in infants, children and adolescents.

Objectives: The use of kidney function and injury markers for early detection of drug-related glomerular or tubular kidney injury in infants, children and adolescents requires age-specific data on reference intervals in a pediatric healthy population. This study characterizes serum values for eight kidney function and injury markers in healthy infants, children and adolescents.

Methods: A single center prospective observational study was conducted between December 2018 and June 2019.