Background: International guidelines suggest that growth of preterm infants should match intrauterine rates. However, the trajectory for extrauterine growth may deviate from the birth percentile due to an irreversible, physiological loss of extracellular fluid during postnatal adaptation to extrauterine conditions. To which "new" physiological growth trajectory preterm infants should adjust to after completed postnatal adaptation is unknown. This study analyzes the postnatal growth trajectories of healthy preterm infants using prospective criteria defining minimal support, as a model for physiological adaptation. Methods: International, multi-center, longitudinal, observational study at five neonatal intensive care units (NICUs). Daily weights until day of life (DoL) 21 of infants with undisturbed postnatal adaptation were analyzed (gestational ages: (i) 25-29 wk, (ii) 30-34 wk). results: 981 out of 3,703 admitted infants included. Maximum weight loss was 11% (i) and 7% (ii) by DoL 5, birth weight regained by DoL 15 (i) and 13 (ii). Infants transitioned to growth trajectories parallel to Fenton chart percentiles, 0.8 z-scores below their birth percentiles. The new trajectory after completed postnatal adaptation could be predicted for DoL 21 with R 2 = 0.96. conclusion: This study provides a robust estimate for physiological growth trajectories of infants after undisturbed postnatal adaptation. In the future, the concept of a target postnatal trajectory during NICU care may be useful. i mproved survival rates of very-low-birth-weight (<1,500 g birth weight) infants have shifted the focus of neonatal care onto improving postnatal growth and nutrition, aiming to achieve growth rates that optimize later health outcomes (1). Pediatric societies in North America and Europe have recommended that postnatal growth of preterm infants match the in utero growth rates of fetuses that remain in utero until full-term (2-4). These recommendations gain importance in light of the Developmental Origins of Health and Disease (DOHaD) hypothesis (5). The DOHaD concept suggests that suboptimal growth of a fetus or a newborn infant can impact the early onset of adult metabolic and cardiovascular diseases. In utero, the growth rate of an individual fetus is determined by its genetic potential and modified by "environmental" factors such as maternal nutrition, body composition, pathologies, or altitude above sea level. After birth, growth patterns of preterm infants are under external control by neonatal staff who modify the infants' nutrient intake. Figure 1 shows three hypothetical postnatal trajectories for a given preterm infant (27 wk of gestation, birth weight 1,000 g). It is of interest to note that these trajectories have similar slopes and hence not dramatically different growth rates. However, postnatal adjustment to different percentiles during the phase of stable growth will lead to different body compositions-potentially affecting later health outcomes.The current evidence for optimal postnatal growth trajectories is scarce....

Recent research focuses on the variability of breast milk composition, its impact on postnatal growth patterns and the usefulness of target fortification. As well, diets exclusively composed of human milk are a promising approach to improve feeding tolerance. For safe fortification, osmolality cutoff levels are needed.

GVA provides an evidence-based approach for individualized growth trajectories. GVA is based on physiologic data and that healthy preterm infants adjust their postnatal trajectory below their birth percentile. GVA may reflect a biologic principle because it matches consistently with WHOGS at 42+0/7 weeks for all preterm infants from 24 to 34 weeks. This concept could become a bedside tool to aid clinicians in monitoring growth, guiding nutrition, and minimizing chronic adult disease risks as a consequence of unguided, inappropriate growth.

Objective To test whether the assessment of growth in very low birth weight infants during the hospital stay using z-score differences (Z diff ) is confounded by gestational age (GA), birth weight percentiles (BW%ile), and length of the observation period (LOP). We hypothesize that Z diff calculated from growth charts based on birth weight data introduces a systematic statistical error leading to falsely classified growth as restricted in infants growing similarly to the 50 th percentile. Methods This observational study included 6,926 VLBW infants from the German Neonatal Network (2009 to 2015). Inclusion criterion was discharge between 37 and 41 weeks postmenstrual age. For each infant, Z diff , weight gain velocity, and reference growth rate (50 th percentile Fenton) from birth to discharge were calculated. To account for gestational age dependent growth rates, assessment of growth was standardized calculating the weight gain ratio (WGR) = weight gain velocity/reference growth rate. The primary outcome is the variation of the Z diff -to-WGR relationship. Results Z diff and WGR showed a weak agreement with a Z diff of -0.74 (-1.03, -0.37) at the reference growth rate of the 50 th percentile (WGR = 1). A significant proportion (n = 1,585; 23%) of infants with negative Z diff had weight gain velocity above the 50 th percentile’s growth rate. Z diff to WGR relation was significantly affected by the interaction of GA x BW%ile x LOP. Conclusion This study supports the hypothesis that Z diff , which are calculated using birth weights, are confounded by skewed reference data and can lead to misinterpretation of growth rates. New concepts like individualized growth trajectories may have the potential to overcome this limitation.