Clinical outcomes of Staphylococcus capitis isolation from neonates, England, 2015-2021: a retrospective case-control study.

OBJECTIVE: Staphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day mortality for the detection of S. capitis versus other CoNS species. METHODS: In this retrospective case-control study, we included hospitalised infants with any CoNS species detected from a normally sterile body site up to 90 days of age. We linked English laboratory reports from the Second Generation Surveillance System database, mortality data from the Personal Demographics Service, and neonatal unit admissions from the National Neonatal Research Database. In primary analysis, multivariable logistic regression was used, with two co-primary outcomes: survival to discharge and death within 30 days of positive specimen date. Sensitivity analyses using multiply imputed datasets followed. RESULTS: We identified 16 636 CoNS episodes relating to 13 745 infants. CoNS episodes were highest among infants born extremely preterm (22-27 weeks) and with extremely low birth weight (400-999 g). In primary analysis, there were no differences in survival to discharge (p=0.71) or 30-day mortality (p=0.77) between CoNS species. In sensitivity analyses, there were no differences in outcomes between infection with four of the most common CoNS species (Staphylococcus epidermidis, S. capitis, Staphylococcus haemolyticus and Staphylococcus warneri) but the remaining CoNS species were at higher risk of adverse outcomes when treated in aggregate. CONCLUSION: Infants with S. capitis detected from sterile site samples did not experience significant differences in either survival to discharge or 30-day mortality compared with infants with detection of other common CoNS species.

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

BACKGROUND: Parenteral nutrition (PN) is used to provide supplemental support to neonates while enteral feeding is being established. PN is a high-cost intervention with beneficial and harmful effects. Internationally, there is substantial variation in how PN is used, and there are limited contemporary data describing use across Great Britain. OBJECTIVE: To describe PN use in the first postnatal week in infants born and admitted to neonatal care in England, Scotland and Wales. METHOD: Data describing neonates admitted to National Health Service neonatal units between 1 January 2012 and 31 December 2017, extracted from routinely recorded data held the National Neonatal Research Database (NNRD); the denominator was live births, from Office for National Statistics. RESULTS: Over the study period 62 145 neonates were given PN in the first postnatal week (1.4% of all live births); use was higher in more preterm neonates (76% of livebirths at <28 weeks, 0.2% of term livebirths) and in neonates with lower birth weight. 15% (9181/62145) of neonates given PN in the first postnatal week were born at term. There was geographic variation in PN administration: the proportion of live births given PN within neonatal regional networks ranged from 1.0% (95% CIs 1.0 to 1.0) to 2.8% (95% CI 2.7 to 2.9). CONCLUSIONS AND RELEVANCE: Significant variation exists in neonatal PN use; it is unlikely this reflects optimal use of an expensive intervention. Research is needed to identify which babies will benefit most and which are at risk of harm from early PN. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03767634; registration date: 6 December 2018.

Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks' gestation: a propensity score matched observational study.

OBJECTIVE: To evaluate whether in preterm neonates parenteral nutrition use in the first 7 postnatal days, compared with no parenteral nutrition use, is associated with differences in survival and other important morbidities. Randomised trials in critically ill older children show that harms, such as nosocomial infection, outweigh benefits of early parenteral nutrition administration; there is a paucity of similar data in neonates. DESIGN: Retrospective cohort study using propensity matching including 35 maternal, infant and organisational factors to minimise bias and confounding. SETTING: National, population-level clinical data obtained for all National Health Service neonatal units in England and Wales. PATIENTS: Preterm neonates born between 30+0 and 32+6 weeks+days. INTERVENTIONS: The exposure was parenteral nutrition administered in the first 7 days of postnatal life; the comparator was no parenteral nutrition. MAIN OUTCOME MEASURES: The primary outcome was survival to discharge from neonatal care. Secondary outcomes comprised the neonatal core outcome set. RESULTS: 16 292 neonates were compared in propensity score matched analyses. Compared with matched neonates not given parenteral nutrition in the first postnatal week, neonates who received parenteral nutrition had higher survival at discharge (absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates of necrotising enterocolitis (absolute rate increase 4.6%), bronchopulmonary dysplasia (absolute rate increase 3.9%), late-onset sepsis (absolute rate increase 1.5%) and need for surgical procedures (absolute rate increase 0.92%). CONCLUSIONS: In neonates born between 30+0 and 32+6 weeks' gestation, those given parenteral nutrition in the first postnatal week had a higher rate of survival but higher rates of important neonatal morbidities. Clinician equipoise in this area should be resolved by prospective randomised trials. TRIAL REGISTRATION NUMBER: NCT03767634.

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

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.

Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database.

BACKGROUND: Parenteral nutrition is commonly administered during therapeutic hypothermia. Randomised trials in critically ill children indicate that parenteral nutrition may be harmful. OBJECTIVE: To examine the association between parenteral nutrition during therapeutic hypothermia and clinically important outcomes. DESIGN: Retrospective, population-based cohort study using the National Neonatal Research Database; propensity scores were used to create matched groups for comparison. SETTING: National Health Service neonatal units in England, Scotland and Wales. PARTICIPANTS: 6030 term and near-term babies, born 1/1/2010 and 31/12/2017, who received therapeutic hypothermia; 2480 babies in the matched analysis. EXPOSURE: We compared babies that received any parenteral nutrition during therapeutic hypothermia with babies that did not. MAIN OUTCOME MEASURES: Primary outcome: blood culture confirmed late-onset infection; secondary outcomes: treatment for late onset infection, necrotising enterocolitis, survival, length of stay, measures of breast feeding, hypoglycaemia, central line days, time to full enteral feeds, discharge weight. RESULTS: 1475/6030 babies (25%) received parenteral nutrition. In comparative matched analyses, the rate of culture positive late onset infection was higher in babies that received parenteral nutrition (0.3% vs 0.9%; difference 0.6; 95% CI 0.1, 1.2; p=0.03), but treatment for presumed infection was not (difference 0.8%, 95% CI -2.1 to 3.6, p=0.61). Survival was higher in babies that received parenteral nutrition (93.1% vs 90.0%; rate difference 3.1, 95% CI 1.5, 4.7; p<0.001). CONCLUSIONS: Receipt of parenteral nutrition during therapeutic hypothermia is associated with higher late-onset infection but lower mortality. This finding may be explained by residual confounding. Research should address the risks and benefits of parenteral nutrition in this population.

Increase in the use of inhaled nitric oxide in neonatal intensive care units in England: a retrospective population study.

Objective: To describe temporal changes in inhaled nitric oxide (iNO) use in English neonatal units between 2010 and 2015. Design: Retrospective analysis using data extracted from the National Neonatal Research Database. Setting: All National Health Service neonatal units in England. Patients: Infants of all gestational ages born 2010-2015 admitted to a neonatal unit and received intensive care. Main outcome measures: Proportion of infants who received iNO; age at initiation and duration of iNO use. Results: 4.9% (6346/129 883) of infants received iNO; 31% (1959/6346) were born <29 weeks, 18% (1152/6346) 29-33 weeks and 51% (3235/6346)>34 weeks of gestation. Between epoch 1 (2010-2011) and epoch 3 (2014-2015), there was (1) an increase in the proportion of infants receiving iNO: <29 weeks (4.9% vs 15.9%); 29-33 weeks (1.1% vs 4.8%); >34 weeks (4.5% vs 5.0%), (2) increase in postnatal age at iNO initiation: <29 weeks 10 days vs 18 days; 29-33 weeks 2 days vs 10 days, (iii) reduction in iNO duration: <29 weeks (3 days vs 2 days); 29-33 weeks (2 days vs 1 day). Conclusions: Between 2010 and 2015, there was an increase in the use of iNO among infants admitted to English neonatal units. This was most notable among the most premature infants with an almost fourfold increase. Given the cost of iNO therapy, limited evidence of efficacy in preterm infants and potential for harm, we suggest that exposure to iNO should be limited, ideally to infants included in research studies (either observational or randomised placebo-controlled trial) or within a protocolised pathway. Development of consensus guidelines may also help standardise practice.