A review of the current policies and guidance regarding Apgar scoring and the detection of jaundice and cyanosis concerning Black, Asian and ethnic minority neonates.

BACKGROUND: Ethnic inequalities in maternal and neonatal health in the UK are well documented. Concerns exist regarding the use of skin colour in neonatal assessments. Healthcare professionals should be trained to recognise symptoms of diverse skin tones, and comprehensive, and inclusive guidance is necessary for the safe assessment of all infants. Disparities in healthcare provision have been emphasised during the COVID-19 pandemic, and additional research is needed to determine whether such policies adequately address ethnic minority neonates. METHODS: A desktop search included searches of guidance produced for the United Kingdom (UK). Further searches of the Cochrane and World Health Organization (WHO) were used to identify any international guidance applicable in the UK context. RESULTS: Several policies and one training resource used descriptors 'pink,' 'pale,' 'pallor,' and 'blue' about neonatal skin and mucous membrane colour. No policies provided specific guidance on how these colour descriptors may appear in neonates with different skin pigmentation. Only the NICE guidance and HEE e-learning resource acknowledged the challenges of assessing jaundice in infants with diverse skin tones, while another guideline noted differences in the accuracy of bilirubin measurements for the assessment of jaundice. Three policies and one training resource advised against relying on visual observation of skin colour when diagnosing neonatal conditions. The training resource included images of ethnic minority neonates, although most images included white infants. CONCLUSIONS: Inadequate consideration of ethnicity in UK policy and training perpetuates disparities, leading to inaccurate assessments. A review is needed for inclusivity in neonatal care, regardless of skin pigmentation.

Impact of daily octenidine skin washing versus nonwashing on antiseptic tolerance of coagulase-negative staphylococci in two neonatal intensive care units with different skin cleansing practices.

Background: There is wide variation in practices regarding routine bathing/washing of babies in neonatal intensive care units (NICUs). Evidence is lacking as to the benefit of routine antiseptic washes for reducing infection. We aimed to compare the antiseptic tolerance of Coagulase Negative Staphylococci (CoNS) within two UK NICUs with very different approaches to skin washing. Methods: We compared antiseptic susceptibility of CoNS isolated from skin swabs of neonates admitted to the Norfolk and Norwich University Hospital (NNUH) NICU in December 2017-March 2018 with those isolated in the Bradford Royal Infirmary (BRI) NICU in January-March 2020. The NNUH does not practise routine whole-body washing whereas BRI practises daily whole-body washing from post-menstrual age 27 weeks using Octenisan wash lotion (0.3% octenidine; 1 minute contact time before washing off with sterile water). A total of 78 CoNS isolates from BRI and 863 from the NNUH were tested for susceptibility against the antiseptics octenidine (OCT) and chlorhexidine (CHX). Results: Isolates from the BRI with practice of routine washing did not show increased antiseptic tolerance to OCT or CHX. Isolates from the NNUH which does not practise routine whole-body washing and rarely uses octenidine, were comparatively less susceptible to both CHX and OCT antiseptics. Conclusions: Daily whole-body skin washing with OCT does not appear to select for CoNS isolates that are antiseptic tolerant towards OCT and CHX. There remains considerable uncertainty about the impact of different antiseptic regimes on neonatal skin microbiota, the benefit of routine washing, and the development of antiseptic tolerance in the NICU.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Frenotomy with breastfeeding support versus breastfeeding support alone for infants with tongue-tie and breastfeeding difficulties: the FROSTTIE RCT.

Background: Tongue-tie can be diagnosed in 3-11% of babies, with some studies reporting almost universal breastfeeding difficulties, and others reporting very few feeding difficulties that relate to the tongue-tie itself, instead noting that incorrect positioning and attachment are the primary reasons behind the observed breastfeeding difficulties and not the tongue-tie itself. The only existing trials of frenotomy are small and underpowered and/or include only very short-term or subjective outcomes. Objective: To investigate whether frenotomy is clinically and cost-effective to promote continuation of breastfeeding at 3 months in infants with breastfeeding difficulties diagnosed with tongue-tie. Design: A multicentre, unblinded, randomised, parallel group controlled trial. Setting: Twelve infant feeding services in the UK. Participants: Infants aged up to 10 weeks referred to an infant feeding service (by a parent, midwife or other breastfeeding support service) with breastfeeding difficulties and judged to have tongue-tie. Interventions: Infants were randomly allocated to frenotomy with standard breastfeeding support or standard breastfeeding support without frenotomy. Main outcome measures: Primary outcome was any breastmilk feeding at 3 months according to maternal self-report. Secondary outcomes included mother's pain, exclusive breastmilk feeding, exclusive direct breastfeeding, frenotomy, adverse events, maternal anxiety and depression, maternal and infant NHS health-care resource use, cost-effectiveness, and any breastmilk feeding at 6 months of age. Results: Between March 2019 and November 2020, 169 infants were randomised, 80 to the frenotomy with breastfeeding support arm and 89 to the breastfeeding support arm from a planned sample size of 870 infants. The trial was stopped in the context of the COVID-19 pandemic due to withdrawal of breastfeeding support services, slow recruitment and crossover between arms. In the frenotomy with breastfeeding support arm 74/80 infants (93%) received their allocated intervention, compared to 23/89 (26%) in the breastfeeding support arm. Primary outcome data were available for 163/169 infants (96%). There was no evidence of a difference between the arms in the rate of breastmilk feeding at 3 months, which was high in both groups (67/76, 88% vs. 75/87, 86%; adjusted risk ratio 1.02, 95% confidence interval 0.90 to 1.16). Adverse events were reported for three infants after surgery [bleeding (n = 1), salivary duct damage (n = 1), accidental cut to the tongue and salivary duct damage (n = 1)]. Cost-effectiveness could not be determined with the information available. Limitations: The statistical power of the analysis was extremely limited due to not achieving the target sample size and the high proportion of infants in the breastfeeding support arm who underwent frenotomy. Conclusions: This trial does not provide sufficient information to assess whether frenotomy in addition to breastfeeding support improves breastfeeding rates in infants diagnosed with tongue-tie. Future work: There is a clear lack of equipoise in the UK concerning the use of frenotomy, however, the effectiveness and cost-effectiveness of the procedure still need to be established. Other study designs will need to be considered to address this objective. Trial registration: This trial is registered as ISRCTN 10268851. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (project number 16/143/01) and will be published in full in Health Technology Assessment; Vol. 27, No. 11. See the NIHR Journals Library website for further project information. The funder had no role in study design or data collection, analysis and interpretation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Many mothers and babies experience difficulties in establishing breastfeeding. In some babies it is thought that their difficulties may be linked to a condition called tongue-tie, in which a piece of skin tightly joins the middle part of the underside of the tongue to the base of the baby's mouth. This can be treated by an operation to divide the tight part/skin in the middle of the underneath of the tongue. We planned to carry out a trial of 870 babies to find out whether an operation together with breastfeeding support helps more mothers and babies with tongue-tie to continue breastfeeding until the baby is 3 months old compared to breastfeeding support on its own and whether the costs were different between the two groups of mothers and babies. We were only able to recruit 169 babies as the trial was stopped because of slow recruitment, changes to services in the COVID-19 pandemic and a high proportion of the babies in the breastfeeding support group going on to have an operation. There were no differences in the rate of breastfeeding at 3 months between the babies in the group who had an operation straightaway and those in the group that had breastfeeding support alone, or had an operation later. More than four in every five babies in both groups were still breastmilk feeding at 3 months. Three babies who had an operation, around 1 in 50 babies, had a complication of the operation (bleeding, scarring or a cut to the tube that makes saliva). Because of the small size of the study, we cannot say whether an operation to divide a tongue-tie along with breastfeeding support helps babies with tongue-tie and breastfeeding difficulties or has different costs. We will need to try different types of research to answer the question.

Health care utilisation and education outcomes of children with rare diseases: a born in Bradford cohort study.

The purpose of this study is to describe the burden of health care utilisation and early education outcomes of children with and without rare diseases. Using the Born in Bradford birth cohort and its linked routine health care and education data, we looked at cumulative primary care episodes, hospital admissions and medication prescriptions. We assessed education outcomes using Early Years Foundation Stage Profile and the National Curriculum Tests-Key Stage 1 results. Among analytical sample of 13,858, 1711 or 12.3% children were identified with a rare disease by an average age of 14 years. Children with rare diseases were twice more likely to be admitted to hospital compared to children without. Average length of stay was around 5 days in those with rare diseases group compared to less than 1 day in those without. The average number of primary care episodes was 45.4 in children with rare diseases and 28.2 visits in those without. These children were over three times more likely to be on multiple medications. Children with rare diseases had 30% higher risk of being below academic expectations at Foundation Year and, depending on subject, between 50 and 60% higher risks at KS1 tests.  Conclusions: Children with rare diseases are significantly more likely to have increased primary care episodes and to have more regular medications. They are likely to have more hospital admissions with a longer stay also. Educationally, they are at higher risk of failing to achieve expected standards in early-year settings. What is Known: • Existing studies of rare diseases have used cross sectional data to describe secondary care data. Previous research has not explored the impact of rare diseases on academic outcomes in children. What is New: • Using Born in Bradford birth cohort and its linked primary and secondary care data, this study provides the most comprehensive estimate of prevalence of rare diseases in any study to date. Children with rare diseases were not only significantly more likely to have contact with primary care and to be admitted to hospitals; they were also more like to be on more regular medications and had higher risk of not achieving expected standards in early-year education outcomes. • Our study is unusual in being able to access linked health and education data and reinforces the importance of adopting a whole system approach to children's health and wellbeing that recognises the close links between health and education.

Regional perspectives on the coordination and delivery of paediatric end-of-life care in the UK: a qualitative study.

BACKGROUND: Provision of and access to paediatric end-of-life care is inequitable, but previous research on this area has focused on perspectives of health professionals in specific settings or children with specific conditions. This qualitative study aimed to explore regional perspectives of the successes, and challenges to the equitable coordination and delivery of end-of-life care for children in the UK. The study provides an overarching perspective on the challenges of delivering and coordinating end-of-life care for children in the UK, and the impact of these on health professionals and organisations. Previous research has not highlighted the successes in the sector, such as the formal and informal coordination of care between different services and sectors. METHODS: Semi-structured interviews with Chairs of the regional Palliative Care Networks across the UK. Chairs or co-Chairs (n = 19) of 15/16 Networks were interviewed between October-December 2021. Data were analysed using thematic analysis. RESULTS: Three main themes were identified: one standalone theme ("Communication during end-of-life care"); and two overarching themes ("Getting end-of-life services and staff in the right place", with two themes: "Access to, and staffing of end-of-life care" and "Inconsistent and insufficient funding for end-of-life care services"; and "Linking up healthcare provision", with three sub-themes: "Coordination successes", "Role of the networks", and "Coordination challenges"). Good end-of-life care was facilitated through collaborative and network approaches to service provision, and effective communication with families. The implementation of 24/7 advice lines and the formalisation of joint-working arrangements were highlighted as a way to address the current challenges in the specialism. CONCLUSIONS: Findings demonstrate how informal and formal relationships between organisations and individuals, enabled early communication with families, and collaborative working with specialist services. Formalising these could increase knowledge and awareness of end of life care, improve staff confidence, and overall improve professionals' experiences of delivering care, and families' experiences of receiving it. There are considerable positives that come from collaborative working between different organisations and sectors, and care could be improved if these approaches are funded and formalised. There needs to be consistent funding for paediatric palliative care and there is a clear need for education and training to improve staff knowledge and confidence.

Consultant-led UK paediatric palliative care services: professional configuration, services, funding.

OBJECTIVES: To systematically gather information on the professional team members, services provided, funding sources and population served for all consultant-led specialised paediatric palliative care (SPPC) teams in the UK. METHODS: Two-part online survey. RESULTS: Survey 1: All 17 medical leads from hospital-based or hospice-based SPPC teams responded to the survey (100% response rate).Only six services met the NICE guidance for minimum SPPC team.All services reported providing symptom management, specialist nursing care, end-of-life planning and care, and supporting discharges and transfers to home or hospice for the child's final days-hours. Most services also provided care coordination (n=14), bereavement support (n=13), clinical psychology (n=10) and social work-welfare support (n=9). Thirteen had one or more posts partially or fully funded by a charity.Survey 2: Nine finance leads provided detailed resource/funding information, finding a range of statutory and charity funding sources. Only one of the National Health Service (NHS)-based services fully funded by the NHS. CONCLUSIONS: One-third of services met the minimum criteria of professional team as defined by NICE. Most services relied on charity funding to fund part or all of one professional post and only one NHS-based service received all its funding directly from the NHS.

Probiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

BACKGROUND: Intestinal dysbiosis may contribute to the pathogenesis of necrotising enterocolitis (NEC) in very preterm or very low birth weight (VLBW) infants. Dietary supplementation with probiotics to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of NEC and associated mortality and morbidity in very preterm or VLBW infants. OBJECTIVES: To determine the effect of supplemental probiotics on the risk of NEC and associated mortality and morbidity in very preterm or very low birth weight infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the Maternity and Infant Care database, and CINAHL from inception to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing probiotics with placebo or no probiotics in very preterm infants (born before 32 weeks' gestation) and VLBW infants (weighing less than 1500 g at birth). DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratios (RRs), risk differences (RDs), and mean differences (MDs), with associated 95% confidence intervals (CIs). The primary outcomes were NEC and all-cause mortality; secondary outcome measures were late-onset invasive infection (more than 48 hours after birth), duration of hospitalisation from birth, and neurodevelopmental impairment. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 60 trials with 11,156 infants. Most trials were small (median sample size 145 infants). The main potential sources of bias were unclear reporting of methods for concealing allocation and masking caregivers or investigators in about half of the trials. The formulation of the probiotics varied across trials. The most common preparations contained Bifidobacterium spp., Lactobacillus spp., Saccharomyces spp., andStreptococcus spp., alone or in combination. Very preterm or very low birth weight infants Probiotics may reduce the risk of NEC (RR 0.54, 95% CI 0.46 to 0.65; I² = 17%; 57 trials, 10,918 infants; low certainty). The number needed to treat for an additional beneficial outcome (NNTB) was 33 (95% CI 25 to 50). Probiotics probably reduce mortality slightly (RR 0.77, 95% CI 0.66 to 0.90; I² = 0%; 54 trials, 10,484 infants; moderate certainty); the NNTB was 50 (95% CI 50 to 100). Probiotics probably have little or no effect on the risk of late-onset invasive infection (RR 0.89, 95% CI 0.82 to 0.97; I² = 22%; 49 trials, 9876 infants; moderate certainty). Probiotics may have little or no effect on neurodevelopmental impairment (RR 1.03, 95% CI 0.84 to 1.26; I² = 0%; 5 trials, 1518 infants; low certainty). Extremely preterm or extremely low birth weight infants Few data were available for extremely preterm or extremely low birth weight (ELBW) infants. In this population, probiotics may have little or no effect on NEC (RR 0.92, 95% CI 0.69 to 1.22, I² = 0%; 10 trials, 1836 infants; low certainty), all-cause mortality (RR 0.92, 95% CI 0.72 to 1.18; I² = 0%; 7 trials, 1723 infants; low certainty), or late-onset invasive infection (RR 0.93, 95% CI 0.78 to 1.09; I² = 0%; 7 trials, 1533 infants; low certainty). No trials provided data for measures of neurodevelopmental impairment in extremely preterm or ELBW infants. AUTHORS' CONCLUSIONS: Given the low to moderate certainty of evidence for the effects of probiotic supplements on the risk of NEC and associated morbidity and mortality for very preterm or VLBW infants, and particularly for extremely preterm or ELBW infants, there is a need for further large, high-quality trials to provide evidence of sufficient validity and applicability to inform policy and practice.

Induction of labour at 39 weeks and adverse outcomes in low-risk pregnancies according to ethnicity, socioeconomic deprivation, and parity: A national cohort study in England.

BACKGROUND: Ethnic and socioeconomic inequalities in obstetric outcomes are well established. However, the role of induction of labour (IOL) to reduce these inequalities is controversial, in part due to insufficient evidence. This national cohort study aimed to identify adverse perinatal outcomes associated with IOL with birth at 39 weeks of gestation ("IOL group") compared to expectant management ("expectant management group") according to maternal characteristics in women with low-risk pregnancies. METHODS AND FINDINGS: All English National Health Service (NHS) hospital births between January 2018 and March 2021 were examined. Using the Hospital Episode Statistics (HES) dataset, maternal and neonatal data (demographic, diagnoses, procedures, labour, and birth details) were linked, with neonatal mortality data from the Office for National Statistics (ONS). Women with a low-risk pregnancy were identified by excluding pregnancies with preexisting comorbidities, previous cesarean section, breech presentation, placenta previa, gestational diabetes, or a baby with congenital abnormalities. Women with premature rupture of membranes, placental abruption, hypertensive disorders of pregnancy, amniotic fluid abnormalities, or antepartum stillbirth were excluded only from the IOL group. Adverse perinatal outcome was defined as stillbirth, neonatal death, or neonatal morbidity, the latter identified using the English composite neonatal outcome indicator (E-NAOI). Binomial regression models estimated risk differences (with 95% confidence intervals (CIs)) between the IOL group and the expectant management group, adjusting for ethnicity, socioeconomic background, maternal age, parity, year of birth, and birthweight centile. Interaction tests examined risk differences according to ethnicity, socioeconomic background, and parity. Of the 1 567 004 women with singleton pregnancies, 501 072 women with low-risk pregnancies and with sufficient data quality were included in the analysis. Approximately 3.3% of births in the IOL group (1 555/47 352) and 3.6% in the expectant management group (16 525/453 720) had an adverse perinatal outcome. After adjustment, a lower risk of adverse perinatal outcomes was found in the IOL group (risk difference -0.28%; 95% CI -0.43%, -0.12%; p = 0.001). This risk difference varied according to socioeconomic background from 0.38% (-0.08%, 0.83%) in the least deprived to -0.48% (-0.76%, -0.20%) in the most deprived national quintile (p-value for interaction = 0.01) and by parity with risk difference of -0.54% (-0.80%, -0.27%) in nulliparous women and -0.15% (-0.35%, 0.04%) in multiparous women (p-value for interaction = 0.02). There was no statistically significant evidence that risk differences varied according to ethnicity (p = 0.19). Key limitations included absence of additional confounding factors such as smoking, BMI, and the indication for induction in the HES datasets, which may mean some higher risk pregnancies were included. CONCLUSIONS: IOL with birth at 39 weeks was associated with a small reduction in the risk of adverse perinatal outcomes, with 360 inductions in low-risk pregnancies needed to avoid 1 adverse outcome. The risk reduction was mainly present in women from more socioeconomically deprived areas and in nulliparous women. There was no significant risk difference found by ethnicity. Increased uptake of IOL at 39 weeks, especially in women from more socioeconomically deprived areas, may help reduce inequalities in adverse perinatal outcomes.

Prebiotics to prevent necrotising enterocolitis in very preterm or very low birth weight infants.

BACKGROUND: Dietary supplementation with prebiotic oligosaccharides to modulate the intestinal microbiome has been proposed as a strategy to reduce the risk of necrotising enterocolitis (NEC) and associated mortality and morbidity in very preterm or very low birth weight (VLBW) infants. OBJECTIVES: To assess the benefits and harms of enteral supplementation with prebiotics (versus placebo or no treatment) for preventing NEC and associated morbidity and mortality in very preterm or VLBW infants. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Maternity and Infant Care database and the Cumulative Index to Nursing and Allied Health Literature (CINAHL), from the earliest records to July 2022. We searched clinical trials databases and conference proceedings, and examined the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing prebiotics with placebo or no prebiotics in very preterm (< 32 weeks' gestation) or VLBW (< 1500 g) infants. The primary outcomes were NEC and all-cause mortality, and the secondary outcomes were late-onset invasive infection, duration of hospitalisation since birth, and neurodevelopmental impairment. DATA COLLECTION AND ANALYSIS: Two review authors separately evaluated risk of bias of the trials, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference (MD), with associated 95% confidence intervals (CIs). The primary outcomes of interest were NEC and all-cause mortality; our secondary outcome measures were late-onset (> 48 hours after birth) invasive infection, duration of hospitalisation, and neurodevelopmental impairment. We used the GRADE approach to assess the level of certainty of the evidence. MAIN RESULTS: We included seven trials in which a total of 705 infants participated. All the trials were small (mean sample size 100). Lack of clarity on methods to conceal allocation and mask caregivers or investigators were potential sources of bias in three of the trials. The studied prebiotics were fructo- and galacto-oligosaccharides, inulin, and lactulose, typically administered daily with enteral feeds during birth hospitalisation. Meta-analyses of data from seven trials (686 infants) suggest that prebiotics may result in little or no difference in NEC (RR 0.97, 95% CI 0.60 to 1.56; RD none fewer per 1000, 95% CI 50 fewer to 40 more; low-certainty evidence), all-cause mortality (RR 0.43, 95% CI 0.20 to 0.92; 40 per 1000 fewer, 95% CI 70 fewer to none fewer; low-certainty evidence), or late-onset invasive infection (RR 0.79, 95% CI 0.60 to 1.06; 50 per 1000 fewer, 95% CI 100 fewer to 10 more; low-certainty evidence) prior to hospital discharge. The certainty of this evidence is low because of concerns about the risk of bias in some trials and the imprecision of the effect size estimates. The data available from one trial provided only very low-certainty evidence about the effect of prebiotics on measures of neurodevelopmental impairment (Bayley Scales of Infant Development (BSID) Mental Development Index score < 85: RR 0.84, 95% CI 0.25 to 2.90; very low-certainty evidence; BSID Psychomotor Development Index score < 85: RR 0.24, 95% 0.03 to 2.00; very low-certainty evidence; cerebral palsy: RR 0.35, 95% CI 0.01 to 8.35; very low-certainty evidence). AUTHORS' CONCLUSIONS: The available trial data provide low-certainty evidence about the effects of prebiotics on the risk of NEC, all-cause mortality before discharge, and invasive infection, and very low-certainty evidence about the effect on neurodevelopmental impairment for very preterm or VLBW infants. Our confidence in the effect estimates is limited; the true effects may be substantially different. Large, high-quality trials are needed to provide evidence of sufficient validity to inform policy and practice decisions.

Bubble devices versus other pressure sources for nasal continuous positive airway pressure in preterm infants.

BACKGROUND: Several types of pressure sources, including underwater bubble devices, mechanical ventilators, and the Infant Flow Driver, are used for providing continuous positive airway pressure (CPAP) to preterm infants with respiratory distress. It is unclear whether the use of bubble CPAP versus other pressure sources is associated with lower rates of CPAP treatment failure, or mortality and other morbidity.  OBJECTIVES: To assess the benefits and harms of bubble CPAP versus other pressure sources (mechanical ventilators or Infant Flow Driver) for reducing treatment failure and associated morbidity and mortality in newborn preterm infants with or at risk of respiratory distress. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2023, Issue 1); MEDLINE (1946 to 6 January 2023), Embase (1974 to 6 January 2023), Maternity & Infant Care Database (1971 to 6 January 2023), and the Cumulative Index to Nursing and Allied Health Literature (1982 to 6 January 2023). We searched clinical trials databases and the reference lists of retrieved articles. SELECTION CRITERIA: We included randomised controlled trials comparing bubble CPAP with other pressure sources (mechanical ventilators or Infant Flow Driver) for the delivery of nasal CPAP to preterm infants. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Two review authors separately evaluated trial quality, extracted data, and synthesised effect estimates using risk ratio (RR), risk difference (RD), and mean difference. We used the GRADE approach to assess the certainty of the evidence for effects on treatment failure, all-cause mortality, neurodevelopmental impairment, pneumothorax, moderate-severe nasal trauma, and bronchopulmonary dysplasia. MAIN RESULTS: We included 15 trials involving a total of 1437 infants. All trials were small (median number of participants 88). The methods used to generate the randomisation sequence and ensure allocation concealment were unclear in about half of the trial reports. Lack of measures to blind caregivers or investigators was a potential source of bias in all of the included trials. The trials took place during the past 25 years in care facilities internationally, predominantly in India (five trials) and Iran (four trials). The studied pressure sources were commercially available bubble CPAP devices versus a variety of mechanical ventilator (11 trials) or Infant Flow Driver (4 trials) devices.  Meta-analyses suggest that the use of bubble CPAP compared with mechanical ventilator or Infant Flow Driver CPAP may reduce the rate of treatment failure (RR 0.76, 95% confidence interval (CI) 0.60 to 0.95; (I² = 31%); RD -0.05, 95% CI -0.10 to -0.01; number needed to treat for an additional beneficial outcome 20, 95% CI 10 to 100; 13 trials, 1230 infants; low certainty evidence). The type of pressure source may not affect mortality prior to hospital discharge (RR 0.93, 95% CI 0.64 to 1.36 (I² = 0%); RD -0.01, 95% CI -0.04 to 0.02; 10 trials, 1189 infants; low certainty evidence). No data were available on neurodevelopmental impairment. Meta-analysis suggests that the pressure source may not affect the risk of pneumothorax (RR 0.73, 95% CI 0.40 to 1.34 (I² = 0%); RD -0.01, 95% CI -0.03 to 0.01; 14 trials, 1340 infants; low certainty evidence). Bubble CPAP likely increases the risk of moderate-severe nasal injury (RR 2.29, 95% CI 1.37 to 3.82 (I² = 17%); RD 0.07, 95% CI 0.03 to 0.11; number needed to treat for an additional harmful outcome 14, 95% CI 9 to 33; 8 trials, 753 infants; moderate certainty evidence). The pressure source may not affect the risk of bronchopulmonary dysplasia (RR 0.76, 95% CI 0.53 to 1.10 (I² = 0%); RD -0.04, 95% CI -0.09 to 0.01; 7 trials, 603 infants; low certainty evidence).  AUTHORS' CONCLUSIONS: Given the low level of certainty about the effects of bubble CPAP versus other pressure sources on the risk of treatment failure and most associated morbidity and mortality for preterm infants, further large, high-quality trials are needed to provide evidence of sufficient validity and applicability to inform context- and setting-relevant policy and practice.

Variation in use of extended pulse oximetry testing to guide decisions around home oxygen provision for ex-preterm infants; A nationwide survey of UK neonatal units.

Differences in the diagnostic approach to bronchopulmonary dysplasia (BPD) may contribute to variation in reported BPD rates. We undertook a nationwide survey of UK neonatal units (NNUs) to describe criteria applied by neonatologists to conduct pulse oximetry studies in ex-preterm infants to assess their need for supplemental oxygen near discharge, as well as criteria applied to interpret saturation studies. Responses from 112 (64.7%) NNUs demonstrated wide variation in both criteria used to select infants for assessment and thresholds for interpretation. Neither demonstrated a clear relationship with reported BPD rates. Variation in clinical practice requires further scrutiny to inform and streamline management of ex-preterm infants at risk of BPD, and potentially improve outcomes.

The effect of maternal BMI, smoking and alcohol on congenital heart diseases: a Mendelian randomisation study.

BACKGROUND: Congenital heart diseases (CHDs) remain a significant cause of infant morbidity and mortality. Epidemiological studies have explored maternal risk factors for offspring CHDs, but few have used genetic epidemiology methods to improve causal inference. METHODS: Three birth cohorts, including 65,510 mother/offspring pairs (N = 562 CHD cases) were included. We used Mendelian randomisation (MR) analyses to explore the effects of genetically predicted maternal body mass index (BMI), smoking and alcohol on offspring CHDs. We generated genetic risk scores (GRS) using summary data from large-scale genome-wide association studies (GWAS) and validated the strength and relevance of the genetic instrument for exposure levels during pregnancy. Logistic regression was used to estimate the odds ratio (OR) of CHD per 1 standard deviation (SD) higher GRS. Results for the three cohorts were combined using random-effects meta-analyses. We performed several sensitivity analyses including multivariable MR to check the robustness of our findings. RESULTS: The GRSs associated with the exposures during pregnancy in all three cohorts. The associations of the GRS for maternal BMI with offspring CHD (pooled OR (95% confidence interval) per 1SD higher GRS: 0.95 (0.88, 1.03)), lifetime smoking (pooled OR: 1.01 (0.93, 1.09)) and alcoholic drinks per week (pooled OR: 1.06 (0.98, 1.15)) were close to the null. Sensitivity analyses yielded similar results. CONCLUSIONS: Our results do not provide robust evidence of an effect of maternal BMI, smoking or alcohol on offspring CHDs. However, results were imprecise. Our findings need to be replicated, and highlight the need for more and larger studies with maternal and offspring genotype and offspring CHD data.

Implementing two-stage consent pathway in neonatal trials.

Perinatal trials sometimes require rapid recruitment processes to facilitate inclusion of participants when interventions are time-critical. A two-stage consent pathway has been used in some trials and is supported by national guidance. This pathway includes seeking oral assent for participation during the time-critical period followed by informed written consent later. This approach is being used in the fluids exclusively enteral from day one (FEED1) trial where participants need to be randomised within 3 hours of birth. There is some apprehension about approaching parents for participation via the oral assent pathway. The main reasons for this are consistent with previous research: lack of a written record, lack of standardised information and unfamiliarity with the process. Here, we describe how the pathway has been implemented in the FEED1 trial and the steps the trial team have taken to support sites. We provide recommendations for future trials to consider if they are considering implementing a similar pathway. Trial registration number: ISRCTN89654042.

Masks versus prongs as interfaces for nasal continuous positive airway pressure in preterm infants.

BACKGROUND: Nasal masks and nasal prongs are used as interfaces for providing continuous positive airway pressure (CPAP) for preterm infants with or at risk of respiratory distress, either as primary support after birth or as ongoing support after endotracheal extubation from mechanical ventilation. It is unclear which type of interface is associated with lower rates of CPAP treatment failure, nasal trauma, or mortality and other morbidity. OBJECTIVES: To assess the benefits and harms of nasal masks versus nasal prongs for reducing CPAP treatment failure, nasal trauma, or mortality and other morbidity in newborn preterm infants with or at risk of respiratory distress. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was October 2021. SELECTION CRITERIA: We included randomised controlled trials comparing masks versus prongs as interfaces for delivery of nasal CPAP in newborn preterm infants (less than 37 weeks' gestation) with or at risk of respiratory distress. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. treatment failure, 2. all-cause mortality, and 3. neurodevelopmental impairment. Our secondary outcomes were 4. pneumothorax, 5. moderate-severe nasal trauma, 6. bronchopulmonary dysplasia, 7. duration of CPAP use, 8. duration of oxygen supplementation, 9. duration of hospitalisation, 10. patent ductus arteriosus receiving medical or surgical treatment, 11. necrotising enterocolitis, 12. severe intraventricular haemorrhage, and 13. severe retinopathy of prematurity. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 12 trials with 1604 infants. All trials were small (median number of participants 118). The trials occurred after 2001 in care facilities internationally, predominantly in India (eight trials). Most participants were preterm infants of 26 to 34 weeks' gestation who received nasal CPAP as the primary form of respiratory support after birth. The studied interfaces included commonly used commercially available masks and prongs. Lack of measures to blind caregivers or investigators was a potential source of performance and detection bias in all the trials. Meta-analyses suggested that use of masks compared with prongs may reduce CPAP treatment failure (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.58 to 0.90; 8 trials, 919 infants; low certainty). The type of interface may not affect mortality prior to hospital discharge (RR 0.83, 95% CI 0.56 to 1.22; 7 trials, 814 infants; low certainty). There are no data on neurodevelopmental impairment. Meta-analyses suggest that the choice of interface may result in little or no difference in the risk of pneumothorax (RR 0.93, 95% CI 0.45 to 1.93; 5 trials, 625 infants; low certainty). Use of masks rather than prongs may reduce the risk of moderate-severe nasal injury (RR 0.55, 95% CI 0.44 to 0.71; 10 trials, 1058 infants; low certainty). The evidence is very uncertain about the effect on bronchopulmonary dysplasia (RR 0.69, 95% CI 0.46 to 1.03; 7 trials, 843 infants; very low certainty). AUTHORS' CONCLUSIONS: The available trial data provide low-certainty evidence that use of masks compared with prongs as the nasal CPAP interface may reduce treatment failure and nasal injury, and may have little or no effect on mortality or the risk of pneumothorax in newborn preterm infants with or at risk of respiratory distress. The effect on bronchopulmonary dysplasia is very uncertain. Large, high-quality trials would be needed to provide evidence of sufficient validity and applicability to inform policy and practice.

Exploring variation in quality of care and clinical outcomes between neonatal units: a novel use for the UK National Neonatal Audit Programme (NNAP).

Neonatology is a relatively new specialty, in which much of the practice remains non-evidence based. Variation in the quality of care delivered is recognised but measuring this is challenging. One possible indicator of this is variation in practice. For more than a decade, the National Neonatal Audit Project (NNAP) has described variation in practice between UK neonatal units in relation to its annually reviewed audit measures. These are based on evidence based national standards or developed by a consensus method and have become de facto measures defining good quality of neonatal healthcare within the UK. In this article we explore the practicality of using the NNAP to look for associations between quality of care and outcomes. This would not be to validate the measures but could help towards a better understanding of the reasons underlying recognised variation in outcomes, even between neonatal units of the same designation.

Benefits and harms adopted by health economic assessments evaluating antenatal and newborn screening programmes in OECD countries: A systematic review of 336 articles and reports.

BACKGROUND: Health economic assessments are used to determine whether the resources needed to generate net benefit from a screening programme, driven by multiple complex benefits and harms, are justifiable. We systematically identified the benefits and harms incorporated within economic assessments evaluating antenatal and newborn screening programmes. METHODS: For this systematic review and thematic analysis, we searched the published and grey literature from January 2000 to January 2021. Studies that included an economic evaluation of an antenatal or newborn screening programme in an OECD country were eligible. We identified benefits and harms using an integrative descriptive analysis, and illustrated a thematic framework. (Systematic review registration PROSPERO, CRD42020165236). FINDINGS: The searches identified 52,244 articles and reports and 336 (242 antenatal and 95 newborn) were included. Eighty-six subthemes grouped into seven themes were identified: 1) diagnosis of screened for condition, 2) life years and health status adjustments, 3) treatment, 4) long-term costs, 5) overdiagnosis, 6) pregnancy loss, and 7) spillover effects on family members. Diagnosis of screened for condition (115 studies, 47.5%), life-years and health status adjustments (90 studies, 37.2%) and treatment (88 studies, 36.4%) accounted for most of the benefits and harms evaluating antenatal screening. The same themes accounted for most of the benefits and harms included in studies assessing newborn screening. Overdiagnosis and spillover effects tended to be ignored. INTERPRETATION: Our proposed framework can be used to guide the development of future health economic assessments evaluating antenatal and newborn screening programmes, to prevent exclusion of important potential benefits and harms.

The Relationship of Maternal Gestational Mass Spectrometry-Derived Metabolites with Offspring Congenital Heart Disease: Results from Multivariable and Mendelian Randomization Analyses.

Background: It is plausible that maternal pregnancy metabolism influences the risk of offspring congenital heart disease (CHD). We sought to explore this through a systematic approach using different methods and data. Methods: We undertook multivariable logistic regression of the odds of CHD for 923 mass spectrometry (MS)-derived metabolites in a sub-sample of a UK birth cohort (Born in Bradford (BiB); N = 2605, 46 CHD cases). We considered metabolites reaching a p-value threshold <0.05 to be suggestively associated with CHD. We sought validation of our findings, by repeating the multivariable regression analysis within the BiB cohort for any suggestively associated metabolite that was measured by nuclear magnetic resonance (NMR) or clinical chemistry (N = 7296, 87 CHD cases), and by using genetic risk scores (GRS: weighted genetic risk scores of single nucleotide polymorphisms (SNPs) that were associated with any suggestive metabolite) in Mendelian randomization (MR) analyses. The MR analyses were performed in BiB and two additional European birth cohorts (N = 38,662, 319 CHD cases). Results: In the main multivariable analyses, we identified 44 metabolites suggestively associated with CHD, including those from the following super pathways: amino acids, lipids, co-factors and vitamins, xenobiotics, nucleotides, energy, and several unknown molecules. Of these 44, isoleucine and leucine were available in the larger BiB cohort (NMR), and for these the results were validated. The MR analyses were possible for 27/44 metabolites and for 11 there was consistency with the multivariable regression results. Conclusions: In summary, we have used complimentary data sources and statistical techniques to construct layers of evidence. We found that pregnancy amino acid metabolism, androgenic steroid lipids, and levels of succinylcarnitine could be important contributing factors for CHD.