A mixed-methods study to investigate feasibility and acceptability of an early warning score for preterm infants in neonatal units in Kenya: results of the NEWS-K study : Neonatal early warning scores in Kenya.

Preterm birth (< 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants' vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (< 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation.

Parents and healthcare professionals' attitudes to Kangaroo Care for preterm infants in the United Kingdom.

AIM: To explore the attitudes of parents and healthcare professionals (HCPs), and facilitators and barrier to implementation of Kangaroo Care (KC) in the United Kingdom. METHODS: Online cross-sectional survey; distributed via the British Association of Perinatal Medicine, Bliss (UK-based charity), social media. RESULTS: Sixty HCPs responded. 37 (62%) were nurses/nurse practitioners. 57 (95%) regularly implement KC. The most important factor that supported KC implementation was the team's belief in benefits of KC. Increased workload, staff shortage and fear about safely of KC in unwell infants were recognised as the challenges preventing implementation. Five hundred eighteen parents responded. 421 (81%) had a preterm baby within 3 years. 338 (80%) were familiar with KC. The main facilitator was the belief that their baby enjoyed it. Excess noise and crowding on the unit were the most frequently reported barriers. Lack of opportunity and limited staff support were the main reasons why they had been unable to practice KC. CONCLUSION: We found that most HCPs and parents believe that KC is beneficial and would like to practice it. Lack of resources to enable effective implementation is the main barrier. Service development and implementation research is required to ensure that KC is delivered in all UK neonatal units.

Anti-reflux medication use in preterm infants.

BACKGROUND: Current recommendations do not support the use of anti-reflux medications to treat gastro-oesophageal reflux disease (GORD) among preterm infants. OBJECTIVE: To describe the prevalence of GORD and the use of anti-reflux medications amongst very preterm infants (<32 weeks' gestational age (GA)) in neonatal units in England and Wales. DESIGN: Retrospective cohort study using the National Neonatal Research Database. RESULTS: Among 58,108 infants [median GA (IQR) 29 (27-30) weeks], 15.8% (n = 9191) had a diagnosis of GORD and 36.9% (n = 12,446) received anti-reflux medications. Those who received anti-reflux medications were more preterm [GA, median (IQR): medications, 28 (26-30) vs. no medications, 30 (28-31); p < 0.001] and had lower birth weight [mean (SD): medications, 1124 g (354) vs. no medications, 1265 g (384); p < 0.001]. Most (57%, n = 12,224) received Gaviscon, or Histamine-2 Receptor Antagonist (H2RA) (56%, n = 11,959). Over time, prokinetic use has declined substantially, the use of H2RAs and Gaviscon has reduced although they continue to be used frequently, whilst the use of PPIs has increased. CONCLUSIONS: Anti-reflux medications are frequently prescribed in very preterm infants, despite evidence to suggest that they are not effective and may be harmful. Clear guidelines for diagnosing GORD and the use of anti-reflux medications are required to rationalise the pharmacological management of GORD in preterm infants. IMPACT: Anti-reflux medications are frequently prescribed, often without a diagnosis of gastro-oesophageal reflux disease, to very preterm infants while in the neonatal unit and at discharge. Half of the infants born at <28 weeks' gestational age receive anti-reflux medications in hospital and a quarter are discharged home on them. Although the use of prokinetics declined following alerts of adverse events, histamine2-receptor antagonists and alginates such as Gaviscon continue to be used and the use of proton-pump inhibitors has increased more than 2-fold.

Drug utilisation in neonatal units in England and Wales: a national cohort study.

PURPOSE: To describe drug utilisation patterns in neonatal units. METHODS: Retrospective observational cohort study using data held in the National Neonatal Research Database (NNRD) for neonatal units in England and Wales including infants born at 23 to 44 weeks' gestational age (GA) from 01 January 2010 to 31 December 2017. RESULTS: The cohort included 17,501 (3%) extremely preterm infants; 40,607 (7%) very preterm infants; 193,536 (31%) moderate-to-late preterm infants; and 371,606 (59%) term infants. The number of unique drugs received by an infant (median (IQR)) increased with decreasing GA: 17 (11-24) in extremely preterm, 7 (5-11) in very preterm, 3 (0-4) in moderate-to-late preterm, and 3 (0-3) in term infants. The two most frequently prescribed drugs were benzylpenicillin and gentamicin in all GA groups, and caffeine in extremely preterm. Other frequently used drugs among preterm infants were electrolytes, diuretics and anti-reflux medications. Among infants <32 weeks' GA, the largest increase in use was for surfactant (given on the neonatal unit), caffeine and probiotics, while domperidone and ranitidine had the largest decline. CONCLUSION: Antibiotics, for all GAs and caffeine, among preterm infants, are the most frequently used drugs in neonatal medicine. Preterm infants are exposed to a high burden of drugs, particularly antibiotics. Changing patterns in use reflect the emergence of evidence in some areas but several non-evidence-based drugs continue to be used widely. Improvements are needed to ensure rational drug use on neonatal units. REGISTRATION: ClinicalTrials.gov (NCT03773289). Date of registration 21 Dec 2018.

Education of family members to support weaning to solids and nutrition in later infancy in term-born infants.

BACKGROUND: Education of family members about infant weaning practices could affect nutrition, growth, and development of children in different settings across the world. OBJECTIVES: To compare effects of family nutrition educational interventions for infant weaning with conventional management on growth and neurodevelopment in childhood. SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 5), MEDLINE via PubMed (1966 to 26 June 2018), Embase (1980 to 26 June 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 26 June 2018). We searched clinical trials databases, conference proceedings, and references of retrieved articles. We ran an updated search from 1 January 2018 to 12 December 2019 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. SELECTION CRITERIA: We included randomised controlled trials that examined effects of nutrition education for weaning practices delivered to families of infants born at term compared to conventional management (standard care in the population) up to one year of age. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible trial reports from the literature search and performed data extraction and quality assessments for each included trial. We synthesised effect estimates using risk ratios (RRs), risk differences (RDs), and mean differences (MDs), with 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included 21 trials, recruiting 14,241 infants. Five of the trials were conducted in high-income countries and the remaining 16 were conducted in middle- and low-income countries. Meta-analysis showed that nutrition education targeted at improving weaning-related feeding practices probably increases both weight-for-age z scores (WAZ) (MD 0.15 standard deviations, 95% CI 0.07 to 0.22; 6 studies; 2551 infants; I² = 32%; moderate-certainty evidence) and height-for-age z scores (0.12 standard deviations, 95% CI 0.05 to 0.19; 7 studies; 3620 infants; I² = 49%; moderate-certainty evidence) by 12 months of age. Meta-analysis of outcomes at 18 months of age was heterogeneous and inconsistent in the magnitude of effects of nutrition education on WAZ and weight-for-height z score across studies. One trial that assessed effects of nutrition education on growth at six years reported an uncertain effect on change in height and body mass index z score. Two studies investigated effects of nutrition education on neurodevelopment at 12 to 24 months of age with conflicting results. No trials assessed effects of nutrition education on long-term neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: Nutrition education for families of infants may reduce the risk of undernutrition in term-born infants (evidence of low to moderate certainty due to limitations in study design and substantial heterogeneity of included studies). Modest effects on growth during infancy may not be of clinical significance. However, it is unclear whether these small improvements in growth parameters in the first two years of life affect long-term childhood growth and development. Further studies are needed to resolve this question.

Investigating ataxia in childhood.

Ataxia is a common presentation to an acute paediatric unit and it can often be difficult to determine the cause. It is important to distinguish between serious causes, for example, brain tumours and encephalitis, and more benign causes in order to guide investigations and treatment. In this review, we describe the different types of ataxia, the causes associated with them, the examination findings and what investigations to perform in order to make a diagnosis.

Sexual Dimorphism of Brown Adipose Tissue Function.

OBJECTIVE: To determine whether brown adipose tissue (BAT) activity in school-age children differs between the sexes and to explore the impact of dietary intake, sedentary behavior, and picky/fussy eating. STUDY DESIGN: Children aged 8.5-11.8 years of age (n = 36) underwent infrared thermography to determine the temperature of the skin overlying the main superficial BAT depot in the supraclavicular region before and after 5 minutes of mild cold exposure (single-hand immersion in cool tap water at about 20°C). The relationships between the supraclavicular region temperature and parental reports of food consumption, eating behavior, and inactivity were explored. RESULTS: The supraclavicular region temperature was higher in boys (n = 16) at baseline, and after cold exposure. Boys displayed a greater thermogenic response to cold. Strong negative correlations were observed between the supraclavicular region temperature and body mass index percentile, and differences in supraclavicular region temperature between girls and boys persisted after adjustment for body mass index percentile. A negative linear relationship was observed between protein and vegetable intake and supraclavicular region temperature in girls only, but did not persist after adjustment for multiple comparisons. There was no difference in the adjusted supraclavicular region temperature between active or inactive children, or picky and nonpicky eaters. CONCLUSIONS: These findings indicate sexual dimorphism in BAT thermogenic activity and a sex-specific impact of diet. Future studies should aim to quantify the contribution of BAT to childhood energy expenditure, energy imbalance, and any role in the origins of childhood obesity.

Education of family members to support weaning to solids and nutrition in infants born preterm.

BACKGROUND: Weaning refers to the period of introduction of solid food to complement breast milk or formula milk. Preterm infants are known to acquire extrauterine growth restriction by the time of discharge from neonatal units. Hence, the postdischarge and weaning period are crucial for optimal growth. Optimisation of nutrition during weaning may have long-term impacts on outcomes in preterm infants. Family members of preterm infants may require nutrition education to promote ideal nutrition practices surrounding weaning in preterm infants who are at high risk of nutritional deficit. OBJECTIVES: To investigate the role of nutrition education of family members in supporting weaning in preterm infants with respect to their growth and neurodevelopment compared with conventional management. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE via PubMed (1966 to 26 June 2018), Embase (1980 to 26 June 2018), and CINAHL (1982 to 26 June 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: RCTs and quasi-RCTs were eligible for inclusion if they examined the effects of nutrition education of family members as compared to conventional management for weaning of preterm infants up to one year of corrected gestational age. We defined prematurity as less than 37 completed weeks of gestation. DATA COLLECTION AND ANALYSIS: At least two review authors independently screened potential studies for inclusion and planned to identify, extract data, and assess the quality of eligible studies. We resolved any differences in opinion through discussion with a third review author and consensus among all three review authors. MAIN RESULTS: No eligible trials looking at the impact of nutrition education of family members in weaning of preterm infants fulfilled the inclusion criteria of this systematic review. Two studies investigating the ideal timing for weaning in premature infants reported conflicting results, AUTHORS' CONCLUSIONS: We were unable to assess the impact of nutrition education of family members in weaning of preterm infants as there were no eligible studies. This may be due to the lack of evidence to determine the ideal weaning strategies for preterm infants with regards to the time of initiating weaning and type of solids to introduce. Trials are needed to assess the many aspects of infant weaning in preterm infants. Long-term neurodevelopment and metabolic outcomes should also be assessed in addition to growth parameters.

Oropharyngeal colostrum in preventing mortality and morbidity in preterm infants.

BACKGROUND: Placing a small volume of colostrum directly onto the buccal mucosa of preterm infants during the early neonatal period may provide immunological and growth factors that stimulate the immune system and enhance intestinal growth. These benefits could potentially reduce the risk of infection and necrotising enterocolitis (NEC) and improve survival and long-term outcome. OBJECTIVES: To determine if early (within the first 48 hours of life) oropharyngeal administration of mother's own fresh or frozen/thawed colostrum can reduce rates of NEC, late-onset invasive infection, and/or mortality in preterm infants compared with controls. To assess trials for evidence of safety and harm (e.g. aspiration pneumonia). To compare effects of early oropharyngeal colostrum (OPC) versus no OPC, placebo, late OPC, and nasogastric colostrum. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 8), MEDLINE via PubMed (1966 to August 2017), Embase (1980 to August 2017), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to August 2017). We also searched clinical trials registries for ongoing and recently completed trials (clinicaltrials.gov; the World Health Organization International Trials Registry (www.whoint/ictrp/search/en/), and the ISRCTN Registry), conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We performed the last search in August 2017. We contacted trial investigators regarding unpublished studies and data. SELECTION CRITERIA: We searched for published and unpublished randomised controlled trials comparing early administration of oropharyngeal colostrum (OPC) versus sham administration of water, oral formula, or donor breast milk, or versus no intervention. We also searched for studies comparing early OPC versus early nasogastric or nasojejunal administration of colostrum. We considered only trials that included preterm infants at < 37 weeks' gestation. We did not limit the review to any particular region or language. DATA COLLECTION AND ANALYSIS: Two review authors independently screened retrieved articles for inclusion and independently conducted data extraction, data analysis, and assessments of 'Risk of bias' and quality of evidence. We graded evidence quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We contacted study authors for additional information or clarification when necessary. MAIN RESULTS: We included six studies that compared early oropharyngeal colostrum versus water, saline, placebo, or donor, or versus no intervention, enrolling 335 preterm infants with gestational ages ranging from 25 to 32 weeks' gestation and birth weights of 410 to 2500 grams. Researchers found no significant differences between OPC and control for primary outcomes - incidence of NEC (typical risk ratio (RR) 1.42, 95% confidence interval (CI) 0.50 to 4.02; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence), incidence of late-onset infection (typical RR 0.86, 95% CI 0.56 to 1.33; six studies, 335 infants; P = 0.50; I² = 0%; very low-quality evidence), and death before hospital discharge (typical RR 0.76, 95% CI 0.34 to 1.71; six studies, 335 infants; P = 0.51; I² = 0%; very low-quality evidence). Similarly, meta-analysis showed no difference in length of hospital stay between OPC and control groups (mean difference (MD) 0.81, 95% CI -5.87 to 7.5; four studies, 293 infants; P = 0.65; I² = 49%). Days to full enteral feeds were reduced in the OPC group with MD of -2.58 days (95% CI -4.01 to -1.14; six studies, 335 infants; P = 0.0004; I² = 28%; very low-quality evidence).The effect of OPC was uncertain because of small sample sizes and imprecision in study results (very low-quality evidence).No adverse effects were associated with OPC; however, data on adverse effects were insufficient, and no numerical data were available from the included studies.Overall the quality of included studies was low to very low across all outcomes. We downgraded GRADE outcomes because of concerns about allocation concealment and blinding, reporting bias, small sample sizes with few events, and wide confidence intervals. AUTHORS' CONCLUSIONS: Large, well-designed trials would be required to evaluate more precisely and reliably the effects of oropharyngeal colostrum on important outcomes for preterm infants.

Feed thickener for infants up to six months of age with gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux (GOR) is common in infants, and feed thickeners are often used to manage it in infants as they are simple to use and perceived to be harmless. However, conflicting evidence exists to support the use of feed thickeners. OBJECTIVES: To evaluate the use of feed thickeners in infants up to six months of age with GOR in terms of reduction in a) signs and symptoms of GOR, b) reflux episodes on pH probe monitoring or intraluminal impedance or a combination of both, or c) histological evidence of oesophagitis. SEARCH METHODS: We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 2), MEDLINE via PubMed (1966 to 22 November 2016), Embase (1980 to 22 November 2016), and CINAHL (1982 to 22 November 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials. SELECTION CRITERIA: We included randomised controlled trials if they examined the effects of feed thickeners as compared to unthickened feeds (no treatment or placebo) in treating GOR in term infants up to six months of age or six months of corrected gestational age for those born preterm. DATA COLLECTION AND ANALYSIS: Two review authors independently identified eligible studies from the literature search. Two review authors independently performed data extraction and quality assessments of the eligible studies. Differences in opinion were resolved by discussion with a third review author, and consensus was reached among all three review authors. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: Eight trials recruiting a total of 637 infants met the inclusion criteria for the systematic review. The infants included in the review were mainly formula-fed term infants. The trials were of variable methodological quality. Formula-fed term infants with GOR on feed thickeners had nearly two fewer episodes of regurgitation per day (mean difference -1.97 episodes per day, 95% confidence interval (CI) -2.32 to -1.61; 6 studies, 442 infants, moderate-certainty evidence) and were 2.5 times more likely to be asymptomatic from regurgitation at the end of the intervention period (risk ratio 2.50, 95% CI 1.38 to 4.51; number needed to treat for an additional beneficial outcome 5, 95% CI 4 to 13; 2 studies, 186 infants, low-certainty evidence) when compared to infants with GOR on unthickened feeds. No studies reported failure to thrive as an outcome. We found low-certainty evidence based on 2 studies recruiting 116 infants that use of feed thickeners improved the oesophageal pH probe parameters of reflux index (i.e. percentage of time pH < 4), number of reflux episodes lasting longer than 5 minutes, and duration of longest reflux episode. No major side effects were reported with the use of feed thickeners. Information was insufficient to conclude which type of feed thickener is superior. AUTHORS' CONCLUSIONS: Gastro-oesophageal reflux is a physiological self resolving phenomenon in infants that does not necessarily require any treatment. However, we found moderate-certainty evidence that feed thickeners should be considered if regurgitation symptoms persist in term bottle-fed infants. The reduction of two episodes of regurgitation per day is likely to be of clinical significance to caregivers. Due to the limited information available, we were unable to assess the use of feed thickeners in infants who are breastfeeding or preterm nor could we conclude which type of feed thickener is superior.

The Placenta, Maternal Diet and Adipose Tissue Development in the Newborn.

BACKGROUND: A majority of adipose tissue present in the newborn possess the unique mitochondrial protein, uncoupling protein (UCP1). It is thus highly metabolically active and capable of producing 300 times more heat per unit mass than any other organ in the body. The extent to which maternal obesity and/or an obesogenic diet impacts on placental function thereby resetting the relative distribution of different types of fat in the fetus is unknown. SUMMARY: Developmentally the majority (if not all) fat in the fetus can be considered as classical brown fat, in which UCP1 is highly abundant. In contrast, beige (or recruitable) fat which possess 90% less UCP1 may only appear after birth, as a majority of fat depots undergo a pronounced transformation that is usually accompanied by the loss of UCP1. The extent to which this process can be modulated in a depot-specific manner and/or changes in the maternal metabolic environment remain unknown. Key Messages: An increased understanding of the mechanism by which offspring born to mothers possess excessive adipose tissue could enable sustainable interventions designed to promote the abundance of UCP1 possessing adipocytes. Ultimately, this would increase their energy expenditure and improve glucose homeostasis in these individuals.

Suboptimal maternal nutrition during early-to-mid gestation in the sheep enhances pericardial adiposity in the near-term fetus.

Manipulation of the maternal diet at defined stages of gestation influences long-term health by inducing changes in fetal adipose tissue development, characterised as possessing brown and white adipocytes. We determined whether suboptimal maternal nutrition in early-to-mid gestation, followed by ad libitum feeding until term, increases adiposity in the pericardial depot of the sheep fetus. Pericardial adipose tissue was sampled from near-term (140 days) fetuses delivered to mothers fed either 100% (C) or 60% (i.e. nutrient restricted (NR)) of their total metabolisable requirements from 28 to 80 days gestation and then fed ad libitum. Adipose tissue mass, uncoupling protein (UCP) 1 and gene expression of brown and white adipogenic genes was measured. Total visceral and pericardial adiposity was increased in offspring born to NR mothers. The abundance of UCP1 was increased, together with those genes involved in brown (e.g. BMP7 and C/EBPß) and white (e.g. BMP4 and C/EBPα) adipogenesis, whereas insulin receptor gene expression was downregulated. In conclusion, suboptimal maternal nutrition between early-to-mid gestation followed by ad libitum feeding enhances pericardial adiposity near to term. A combination of raised UCP1 and adipose tissue mass could improve survival following cold exposure at birth. In the longer term, this enhanced adipogenic potential could predispose to greater pericardial adiposity.

Body mass index as a determinant of brown adipose tissue function in healthy children.

OBJECTIVE: To determine whether body mass index (BMI) percentile and ethnicity influence skin temperature overlying brown adipose tissue (BAT) depots in the supraclavicular region in healthy children. STUDY DESIGN: Infrared thermography measured supraclavicular region temperature (T(SCR)) at baseline and after exposure to a mild cool stimulus (single hand immersion in water at 20.1 °C) for 5 minutes in children aged 6-11 years (n = 55). The studies were undertaken in a normal school environment. RESULTS: BMI percentile and ethnicity were significant predictors of baseline T(SCR), with an inverse relationship between BMI percentile persisting after adjustment for ethnicity. Twenty-four children demonstrated a significant rise in T(SCR) after exposure to the cool stimulus. BMI percentile was a significant predictor of T(SCR) response, although there was no effect of ethnicity on T(SCR) change after exposure to the cool stimulus. CONCLUSION: We have demonstrated a negative relationship between BMI percentile and both baseline T(SCR), colocating with the primary region of BAT, and the change in T(SCR) in response to the cool stimulus. Future studies aimed at determining the primary factors regulating BAT function in healthy children should be targeted at the goal of maintaining a healthy BMI trajectory during childhood.

Impact of NICE clinical guidelines for prevention and treatment of neonatal infections on antibiotic use in very preterm infants in England and Wales: an interrupted time series analysis.

OBJECTIVE: To assess the impact of publication of UK National Institute for Health and Care Excellence (NICE) guidelines on the prevention and treatment of early-onset infections (EOIs) in neonates (clinical guideline 149 (CG149), published in 2012, and its 2021 update (NG195) on antibiotic use in very preterm infants. DESIGN: Interrupted time series analysis using data from the National Neonatal Research Database. SETTING: Neonatal units in England and Wales. PARTICIPANTS: Infants born at 22-31 weeks' gestation from 1 January 2010 to 31 December 2022 and survived to discharge. INTERVENTIONS: Publication of CG149 (August 2012) and NG195 (April 2021). MAIN OUTCOME MEASURES: Measures of antibiotic use, aggregated by month of birth: antibiotic use rate (AUR), the proportion of care days in receipt of at least one antibiotic; percentage of infants who received ≥1 day of antibiotics on days 1-3 for EOI and after day 3 for late-onset infection (LOI); percentage who received ≥1 prolonged antibiotic course ≥5 days for EOI and LOI. RESULTS: 96% of infants received an antibiotic during inpatient stay. AUR declined at publication of CG149, without further impact at NG195 publication. There was no impact of CG149 on the underlying trend in infants receiving ≥1 day antibiotics for EOI or LOI, but post-NG195 the monthly trend began to decline for EOI (-0.20%, -0.26 to -0.14) and LOI (-0.23%, -0.33 to -0.12). Use of prolonged antibiotic courses for EOI and LOI declined at publication of CG149 and for LOI this trend accelerated post-NG195. CONCLUSIONS: Publications of NICE guidance were associated with reductions in antibiotic use; however neonatal antibiotic exposure remains extremely high.

Identifying neonatal transport research priorities: a modified Delphi consensus.

OBJECTIVES: With increasing advances in neonatal transport, a focused research strategy is required to increase the evidence base towards providing optimal care. We aimed to identify the most important neonatal transport research questions as prioritised by parents and healthcare professionals (HCPs). DESIGN: Key stakeholders participated in a modified three-stage Delphi consensus process. Research questions were identified and submitted through two survey stages before the final priority setting workshop. PARTICIPANTS: Parents of babies who received neonatal care, neonatal HCPs and stakeholders. OUTCOME: Identify the top 10 research priorities for neonatal transport. RESULTS: Overall, 269 survey responses from HCPs/stakeholders (n=161) and parents (n=108) were analysed from two survey rounds. Consensus was reached on 22 of 43 research priorities for the final priority setting workshop. The agreed top research priorities covered the domains of: (1) Pain assessment and management, (2) Long-term neurological outcomes, (3) Impact of transfer on birth-related brain injury, (4) Investigating risk of transport, (5) Safety restraints for infants, (6) Optimal temperature management, (7) Respiratory management and outcomes, (8) Benchmarking of important of transport measures, (9) Understanding transport environmental exposures, (10) Mental health and burden of transfer on families. CONCLUSION: We have identified the top research questions for neonatal transport through an extensive process actively engaging parents, HCPs and key stakeholders. Targeted funding and research resources, directed towards addressing these prioritised research areas, will inform evidence-based practices and international frameworks specific to neonatal transport, helping minimise research waste and ultimately improve outcomes for these high-risk infants and their families.

Effects of implementation of a care bundle on rates of necrotising enterocolitis and own mother's milk feeding in the East Midlands: protocol for a mixed methods impact and process evaluation study.

INTRODUCTION: Prevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother's milk helps prevent NEC. Rates of own mother's milk feeding in the East Midlands are lower than the national average and the incidence of NEC is higher. The East Midlands Neonatal Operational Delivery Network (EMNODN) has created a care bundle to improve these in babies born at <32 weeks' gestation, the group at the highest risk of NEC. The bundle was introduced in September 2022 and embedded by December 2022. We will evaluate its effectiveness and conduct a process evaluation to understand barriers and facilitators to implementation. METHODS AND ANALYSIS: We will conduct a retrospective cohort study (workstream 1) using data from the National Neonatal Research Database (NNRD). We will identify infants receiving any own mother's milk on day 14 and at discharge, and cases of severe NEC. We will aggregate outcomes by birth month and use interrupted time series analysis to estimate an incidence rate ratio for changes after the care bundle was embedded, relative to pre-implementation. We will model data from all other NNRD units and assess whether there are any concurrent changes to exclude confounding due to other events.We will apply the RE-AIM framework (workstream 2), supplemented by the Consolidated Framework for Implementation Research and Framework for Implementation Fidelity, to conduct a mixed methods evaluation in EMNODN units. We will triangulate data from several sources, including questionnaires and semistructured interviews with parents and healthcare professionals, and data from patient records. ETHICS AND DISSEMINATION: The study has approval from the South East Scotland Research Ethics Committee 01 and the Health Research Authority and Health and Care Research Wales (IRAS 323099). Results will be disseminated via scientific journals and conferences, to neonatal service commissioners and through public-facing infographics. TRIAL REGISTRATION NUMBER: NCT05934123.

Nutrition and the gut-brain axis in neonatal brain injury and development.

Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.

Brown adipose tissue genes in pericardial adipose tissue of newborn sheep are downregulated by maternal nutrient restriction in late gestation.

BACKGROUND: Brown adipose tissue (BAT) thermogenesis is essential for newborn survival. Pericardial adipose tissue is a visceral depot that promotes metabolic and cardiovascular adaptations. We determined whether BAT is present in pericardial adipose tissue in newborns and whether maternal nutrition during late gestation compromises BAT in the postnatal period. METHODS: We measured uncoupling protein 1 (UCP1) and other BAT-specific genes (e.g., ß3-adrenergic receptor (ß3ADR) and deiodinase type 2 (DIO2)), together with markers of white adipose tissue (WAT) in sheep on either the first or 30th day after birth. These were twin offspring born to mothers fed with either 100% or nutrient restricted (NR) to 60% of their total metabolizable requirements from 110 d gestation to term. RESULTS: Gene expression of UCP1 and other BAT-related genes decreased significantly with age. In newborns, maternal nutrient restriction downregulated gene expression of DIO2 and the ß3-adrenergic receptor with reduced UCP1 but had no effect on genes predominantly expressed in WAT. CONCLUSION: BAT is present around the heart in newborns. Exposure to a suboptimal maternal diet in late gestation specifically compromises BAT development and has the potential to place these offspring at increased risk of hypothermia after birth without effects on the subsequent appearance of WAT.