Effects of Formula Milk on Weight Changes in Healthy Term and Preterm Neonates
Mélanie Wilbaux (1), Sven Wellmann (2), Severin Kasser (2), Isabella Mancino (2), Julia Gromann (2), Tania Coscia (2), Marc Pfister (1,3)
(1) Pediatric Pharmacology and Pharmacometrics, University of Basel Children’s Hospital (UKBB), Basel, Switzerland, (2) Division of Neonatology, University of Basel Children’s Hospital (UKBB), Basel, Switzerland, (3) Quantitative Solutions LP, Menlo Park, CA, USA
Objectives: A model has been developed to describe the physiological weight changes during the first week of life in neonates and has been implemented in an online tool to forecast individual weight change as soon as possible after birth [1]. But the current version is limited to healthy, exclusively breastfed term neonates. Objectives of the current work were to expand the existing model by (i) characterizing effects of formula milk on weight changes during the first week of life in term and preterm neonates; (ii) identifying and quantifying maternal and neonatal factors influencing weight changes in newborns; (iii) enhancing the decision support tool to allow neonatologists to optimize and individualize monitoring and management of neonates.
Methods: Longitudinal weight data from a total of 3638 healthy term and preterm neonates were available up to 7 days of life. Two thirds of neonates (n=2425) were randomly selected to update the semi-mechanistic model characterizing weight changes as a function of the balance between time-dependent rates of weight gain and weight loss. Two additional weight gain rates were described as linear dose-effects of formula and pumped breast milk. Population analysis was implemented using NONMEM7.3. Model selection and evaluation were based on statistical criteria, goodness-of-fit plots and simulations. Advanced evaluation was performed on the remaining third of neonates (n=1213).
Results: Key individual characteristics (median, full range) were as follows: gestational age 39.8 weeks (34.7-42.4), birth weight 3394 g (1980–5230), girls 51%, mother age 32 years (15-47). According to goodness-of-fit plots, weight changes were properly fitted by the model. Advanced evaluation demonstrated a good predictive performance of the expanded model (bias=-0.01%, precision=0.5%). The model was able to accurately forecast individual weight with 3 initial weight measurements during the first 48 hours of life and predict effects of formula milk feeding on weight changes up to 1 week (bias=0.4%, precision=1.6%).
Conclusion: We present the first pharmacometric model that describes physiological weight changes and effects of formula milk feeding on weight changes during the first week of life in term and preterm neonates. A user-friendly online tool will allow caregivers to forecast individual weight changes and formula milk effects, optimize and personalize care, monitoring and feeding of neonates.
References:
[1] Wilbaux M, Kasser S, Wellmann S, Lapaire O, van den Anker JN, Pfister M. Characterizing and forecasting individual weight changes in term neonates. Journal of Pediatrics 173: 101-107. 2016.
