Early versus later initiation of parenteral nutrition for very preterm infants: a propensity score-matched observational study

Abstract

ObjectiveTo evaluate the impact of timing of initiation of parenteral nutrition (PN) after birth in very preterm infants.DesignPropensity-matched analysis of data from the UK National Neonatal Research Database.Patients65 033 babies <31 weeks gestation admitted to neonatal units in England and Wales between 2008 and 2019.InterventionsPN initiated in the first 2 days (early) versus after the second postnatal day (late). Babies who died in the first 2 days without receiving PN were analysed as ‘late’.Main outcome measuresThe main outcome measure was morbidity-free survival to discharge. The secondary outcomes were survival to discharge, growth and other core neonatal outcomes.FindingsNo difference was found in the primary outcome (absolute rate difference (ARD) between early and late 0.50%, 95% CI −0.45 to 1.45, p=0.29). The early group had higher rates of survival to discharge (ARD 3.3%, 95% CI 2.7 to 3.8, p<0.001), late-onset sepsis (ARD 0.84%, 95% CI 0.48 to 1.2, p<0.001), bronchopulmonary dysplasia (ARD 1.24%, 95% CI 0.30 to 2.17, p=0.01), treated retinopathy of prematurity (ARD 0.50%, 95% CI 0.17 to 0.84, p<0.001), surgical procedures (ARD 0.80%, 95% CI 0.20 to 1.40, p=0.01) and greater drop in weight z-score between birth and discharge (absolute difference 0.019, 95% CI 0.003 to 0.035, p=0.02). Of 4.9% of babies who died in the first 2 days, 3.4% were in the late group and not exposed to PN.ConclusionsResidual confounding and survival bias cannot be excluded and justify the need for a randomised controlled trial powered to detect differences in important functional outcomes.

Use of parenteral nutrition in the first postnatal week in England and Wales: an observational study using real-world data

“…As has been found in previous studies, due to the lack of additional information about PN in the data extracted, we are unable to describe changes in how PN was used (eg, when PN was commenced or types of PN used). [37][38][39] Our findings show that PN use in the first postnatal week is common in England and Wales, with regional variation. In light of the potential harm found with early PN in critically unwell children, 7 and the lack of evidence of benefit for clinically important endpoints in infants 3 40 research is needed to ensure that PN use in neonates is underpinned by a robust evidence base.…”

“…As MBRRACE-UK did not produce a report in 2012, this limited the number of years for which we could undertake network-level comparisons. As has been found in previous studies, due to the lack of additional information about PN in the data extracted, we are unable to describe changes in how PN was used (eg, when PN was commenced or types of PN used) 37–39…”

Nutrition for the micro preemie: Beyond milk

“…However, the current Cochrane review finds no evidence to suggest benefit from these newer emulsions [38]. Two large trials of SMOF Lipid in preterm infants found no benefit from use in comparison to Intralipid (based on soybean oil) in preventing liver disease [37,39].…”

“…In the light of these studies and the possibility of harm in very preterm populations, we carried out a propensity score matched study of over 65,000 babies born <31 weeks gestation. We compared outcomes in babies who commenced PN before or after the age of two days [37]. We found no difference in survival to discharge without major morbidity.…”

Early parenteral nutrition is associated with improved growth in very low birth weight infants: a retrospective study

“…However, there are concerns that aggressive supply of parenteral amino acids may cause metabolic acidosis,10 elevated blood urea and refeeding-hypophosphataemia syndrome. Furthermore, increased risk of morbidities, such as necrotising enterocolitis (NEC) and late-onset sepsis, has been associated with early initiation of PN 11–14. In critically ill term infants, early PN has been associated with increased mortality 15.…”