Background: Parenteral nutrition is central to the care of very immature infants. Current international recommendations favor higher amino acid intake

Current practice in relation to the prescribing, compounding and administration of parenteral nutrition for extremely preterm infants is inconsistent and based on largely historical evidence. Increasingly there are calls for more 'aggressive' nutritional interventions to prevent 'postnatal growth failure'. However the evidence base for these recommendations is weak, and there are no long-term studies examining the impact of such practices. Here we summarise the evidence for preterm parenteral nutrition interventions. We suggest principles to guide practice based on evidence from a systematic search and review of evidence to date, and recommend actions necessary to advance the understanding of this important aspect of preterm care.

Objectives The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes. Design Observational cohort study using the UK National Neonatal Research Database. Setting England and Wales. Participants Admissions to National Health Service neonatal units from 2012 to 2020. Main outcome measures Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes. Methods We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019–February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring–winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion. Results Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: −1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; −64, +35; p<0.001) whereas Asian (−137; −14, +101; p<0.001) and white (−319; −235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; −4, +88; p<0.001) and decreased (−47; −25, +12; p<0.001), respectively. Total preterm admissions decreased (−350; −26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles. Conclusions Our findings indicate substantial changes occurred in care pathways and clinical thresholds, with disproportionate effects on black ethnic groups, during the immediate COVID-19 period, and raise the intriguing possibility that non-healthcare interventions may reduce extremely preterm births.

Preterm infants receiving a diet of exclusive human milk compared to predominantly preterm formula have lower weight and non-adipose tissue mass by term. Human milk fortification is recommended. However, it is not known if the protein source affects body composition. To compare the effect of an exclusive human milk based diet (intervention) with a diet containing cow milk products (control) on body composition. Infants born below 30 weeks gestation. Randomised multicentre, open label, controlled trial. Infants preferentially received their own mother's milk. Infants were randomised to either an exclusive human milk diet (human milk formula to make up a shortfall in own mother's milk and human milk derived fortifier) or cow milk-based supplementation (preterm formula to make up a shortfall in own mother's milk and cow milk-based fortifier). Fortification began at an enteral intake of 150 ml/kg/day. Infants underwent whole-body magnetic resonance imaging at term. Body composition (adipose tissue (ATM) and non-adipose tissue mass (N-ATM)) at term. We randomly assigned 38 infants to intervention (n = 19) and control arms (n = 19). Primary outcomes were analysed in 15 infants in the intervention arm and 12 in the control arm. The estimates of the effect of the intervention following adjustment for length and sex, were non-significant (ATM (kg): 0.137, 95 % confidence interval (CI) -0.01, 0.29; N-ATM: -0.137; -0.01, 0.29). We identified no clinically relevant differences in body composition in preterm babies <30 weeks gestation receiving a macronutrient-equivalent exclusive human milk diet compared with a diet containing cow milk products.

Objective Describe the population of babies who do and do not receive postnatal corticosteroids for prevention or treatment of bronchopulmonary dysplasia (BPD). Design Retrospective cohort study using data held in the National Neonatal Research Database. Setting National Health Service neonatal units in England and Wales. Patients Babies born less than 32 weeks gestation and admitted to neonatal units from 1 January 2012 to 31 December 2019. Main outcomes Proportion of babies given postnatal corticosteroid; type of corticosteroid; age at initiation and duration, trends over time. Secondary outcomes Survival to discharge, treatment for retinopathy of prematurity, BPD, brain injury, severe necrotising enterocolitis, gastrointestinal perforation. Results 8% (4713/62019) of babies born <32 weeks and 26% (3525/13527) born <27 weeks received postnatal corticosteroids for BPD. Dexamethasone was predominantly used 5.3% (3309/62019), followed by late hydrocortisone 1.5%, inhaled budesonide 1.5%. prednisolone 0.8%, early hydrocortisone 0.3% and methylprednisolone 0.05%. Dexamethasone use increased over time (2012: 4.5 vs 2019: 5.8%, p=0.04). Median postnatal age of initiation of corticosteroid course was around 3 weeks for late hydrocortisone, 4 weeks for dexamethasone, 6 weeks for inhaled budesonide, 12 weeks for prednisolone and 16 weeks for methylprednisolone. Babies who received postnatal corticosteroids were born more prematurely, had a higher incidence of comorbidities and a longer length of stay. Conclusions In England and Wales, around 1 in 12 babies born less than 32 weeks and 1 in 4 born less than 27 weeks receive postnatal corticosteroids to prevent or treat BPD. Given the lack of convincing evidence of efficacy, challenges of recruiting to and length of time taken to conduct randomised controlled trial, our data highlight the need to monitor long-term outcomes in children who received neonatal postnatal corticosteroids.

Objective To evaluate the impact of timing of initiation of parenteral nutrition (PN) after birth in very preterm infants. Design Propensity-matched analysis of data from the UK National Neonatal Research Database. Patients 65 033 babies <31 weeks gestation admitted to neonatal units in England and Wales between 2008 and 2019. Interventions PN 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 measures The main outcome measure was morbidity-free survival to discharge. The secondary outcomes were survival to discharge, growth and other core neonatal outcomes. Findings No 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. Conclusions Residual confounding and survival bias cannot be excluded and justify the need for a randomised controlled trial powered to detect differences in important functional outcomes.