4. Discussion
critically ill, ROP, Malnutrition, metabolic complications, hyperglycemia, BPD, sepsis
CRITICALLY ILL, MALNUTRITION, HYPERGLYCEMIA, REGRESSION, SEPSIS, COMPLICATIONS
Delayed target achievement of recommended nutritional intake reduces the risk of HG in preterm newborns. The occurrence of HG in the first week of life is an independent risk factor for mortality during hospitalization. Additionally, early target achievement reduces the risk of sepsis but is associated with an increased risk of ROP. Contrasting effects on brief- and long-term growth were observed comparing the two nutritional strategies adopted in the trial. If PN strategy characterized by early introduction of macronutrients was associated with an improvement in short-term growth, the analysis of long-term growth parameters revealed that delayed target achievement was advantageous for body weight and length as showed in multivariate model analysis.The drawbacks of an early target achievement seem to overcome the related advantages. We observed that the amino acid intake within the first week of life was similar between the two groups, whereas the amount of dextrose and lipids during the first week of life were significantly different between Group 1 and Group 2. Thus, it is plausible that the related effects of a nutritional strategy characterized by delayed target achievement may depend on the amount of nonprotein calories. Previous studies comparing PN strategies focused mainly on the effects of maximum macronutrient target intake but not on the modalities of advancement of macronutrient intake by PN. So far, in critically ill newborns, there is a dearth of adequately powered, randomized, controlled trials that address the effects of PN on clinical outcomes. Previous recommendations for the optimal amount and composition of PN were based on very few observational studies on infants in critical conditions, in which PN support was advised without focusing on the facts that critically ill infants face different clinical phases during NICU hospitalization [The PEPaNIC trial showed that starting PN after 1 week in critically ill children is clinically superior to providing early PN as soon as possible after hospitalization [Our results are in keeping with those of Stensvold et al. whereby, in a prospective cohort study comparing enhanced PN with standard PN, HG is an independent risk factor of mortality in preterm newborns [Our finding of greater morbidity in neonates receiving the early PN target is in keeping with previous evidence in critically ill adults, children and newborns, which has led to calls for the deimplementation of early PN in these groups [Despite our data disconfirm the relation between early PN intake and BPD occurrence, this aspect is still an ongoing debate. Several retrospective studies reported the association between low caloric intake and BPD development. Malnutrition seems to worsen BPD probably by compromising lung development and function; a recent study found that preterm infants who developed BPD received low caloric intake [The finding of increased sepsis in the delayed target group is out of keeping with the outcomes in children comparing early versus late PN [An early target achievement PN resulted in a reduction of EUGR occurrence. Previous studies have shown the association between early PN and improved short-term growth in preterm newborns [Despite interesting results, our study had some limitations. Parents of neonates included in the study and neonatologists were aware of the group assignment. Individualized PN solution adjusting is the milestone of our policy on PN in order to avoid deleterious consequences of PN-related complications. Despite being a potential information bias, we have preferred that neonatologists in charge knew the composition of PN in order to easily adjust the PN prescription in case of metabolic complications related to PN administration. To limit selection bias, physicians evaluating eligibility were blinded to the study aims and used objective inclusion criteria (such as GA and BW). To limit observer bias, outcome assessors were unaware of group assignment. We discussed and defined a protocol for the collection, measurement and interpretation of data before starting the study. Finally, a blinded statistician performed the data analysis.The overall morbidity and mortality were higher in Group 2, and it is very close to statistical significance. Further, Group 2 had a significantly higher risk for sepsis. However, we performed a multivariate analysis that identified hyperglycemia as independent risk factor for mortality in a model including sepsis. Additionally, we speculate that overcoming EUGR at 12 months of life could be explained by the increased morbidities, which in turn limit neonates’ growth. To verify this hypothesis, we performed a linear regression analysis showing that energy intake independently influences growth at 12 months of life.The trial was not designed for evaluating the difference in long-term growth; thus, the sample power of the study is insufficient to evaluate differences between study groups in body weight at 12 months of life.