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BackgroundParenteral nutrition is commonly administered during therapeutic hypothermia. Randomised trials in critically ill children indicate that parenteral nutrition may be harmful.ObjectiveTo examine the association between parenteral nutrition during therapeutic hypothermia and clinically important outcomes.DesignRetrospective, population-based cohort study using the National Neonatal Research Database; propensity scores were used to create matched groups for comparison.SettingNational Health Service neonatal units in England, Scotland and Wales.Participants6030 term and near-term babies, born 1/1/2010 and 31/12/2017, who received therapeutic hypothermia; 2480 babies in the matched analysis.ExposureWe compared babies that received any parenteral nutrition during therapeutic hypothermia with babies that did not.Main outcome measuresPrimary 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.Results1475/6030 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; pConclusionsReceipt 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.

BackgroundThe provision of neonatal care is variable and commonly lacks adequate evidence base; strategic development of methodologically robust clinical trials is needed to improve outcomes and maximise research resources. Historically, neonatal research topics have been selected by researchers; prioritisation processes involving wider stakeholder groups have generally identified research themes rather than specific questions amenable to interventional trials.ObjectiveTo involve stakeholders including parents, healthcare professionals and researchers to identify and prioritise research questions suitable for answering in neonatal interventional trials in the UK.DesignResearch questions were submitted by stakeholders in population, intervention, comparison, outcome format through an online platform. Questions were reviewed by a representative steering group; duplicates and previously answered questions were removed. Eligible questions were entered into a three-round online Delphi survey for prioritisation by all stakeholder groups.ParticipantsOne hundred and eight respondents submitted research questions for consideration; 144 participants completed round one of the Delphi survey, 106 completed all three rounds.ResultsTwo hundred and sixty-five research questions were submitted and after steering group review, 186 entered into the Delphi survey. The top five ranked research questions related to breast milk fortification, intact cord resuscitation, timing of surgical intervention in necrotising enterocolitis, therapeutic hypothermia for mild hypoxic ischaemic encephalopathy and non-invasive respiratory support.ConclusionsWe have identified and prioritised research questions suitable for practice-changing interventional trials in neonatal medicine in the UK at the present time. Trials targeting these uncertainties have potential to reduce research waste and improve neonatal care.

Background Routine measurement of gastric residual volume to guide feeding is widespread in neonatal units but not supported by high-quality evidence. Outcome selection is critical to trial design. Objective To determine optimal outcome measures for a trial of not routinely measuring gastric residual volume in neonatal care. Design A focused literature review, parent interviews, modified two-round Delphi survey and stakeholder consensus meeting. Participants Sixty-one neonatal healthcare professionals participated in an eDelphi survey; 17 parents were interviewed. 19 parents and neonatal healthcare professionals took part in the consensus meeting. Results Literature review generated 14 outcomes, and parent interviews contributed eight additional outcomes; these 22 outcomes were then ranked by 74 healthcare professionals in the first Delphi round where four further outcomes were proposed; 26 outcomes were ranked in the second round by 61 healthcare professionals. Five outcomes were categorised as ‘consensus in’, and no outcomes were voted ‘consensus out’. ‘No consensus’ outcomes were discussed and voted on in a face-to-face meeting by 19 participants, where four were voted ‘consensus in’. The final nine consensus outcomes were: mortality, necrotising enterocolitis, time to full enteral feeds, duration of parenteral nutrition, time feeds stopped per 24 hours, healthcare-associated infection; catheter-associated bloodstream infection, change in weight between birth and neonatal discharge and pneumonia due to milk aspiration. Conclusions and relevance We have identified outcomes for a trial of no routine measurement of gastric residual volume to guide feeding in neonatal care. This outcome set will ensure outcomes are important to healthcare professionals and parents.

ObjectiveTo report outcomes at 2 years corrected age for children of women recruited to a trial comparing alternative policies for timing of cord clamping and immediate neonatal care at very preterm birth.DesignParallel group randomised (1:1) trial.SettingEight UK tertiary maternity units.ParticipantsTwo hundred and seventy-six babies born to 261 women expected to have a live birth before 32+0 weeks’ gestation.InterventionsDeferred cord clamping (≥2 min) and immediate neonatal care with cord intact or immediate (≤20 s) clamping and immediate neonatal care after clamping.Main outcome measureComposite of death or adverse neurodevelopmental outcome at 2 years corrected age.ResultsSix babies born after 35+6 weeks were excluded. At 2 years corrected age, outcome data were not available for a further 52 children, leaving 218 for analysis (115 deferred clamping, 103 immediate clamping). Overall, 24/115 (21%) children allocated deferred clamping died or had an adverse neurodevelopmental outcome compared with 35/103 (34%) allocated immediate clamping; risk ratio (RR) 0.61 (95% CI 0.39 to 0.96); risk difference (RD) −13% (95% CI −25% to −1%). Multiple imputation for missing data gave an RR 0.69 (95% CI 0.44 to 1.09) and RD −9% (95% CI −21% to 2%).ConclusionsDeferred clamping and immediate neonatal care with cord intact may reduce the risk of death or adverse neurodevelopmental outcome at 2 years of age for children born very premature. Confirmation in larger studies is needed to determine the real benefits and harms.Trial registration numberISRCTN21456601.

ObjectivesFor very preterm births, to compare alternative policies for umbilical cord clamping and immediate neonatal care.DesignParallel group randomised (1:1) trial, using sealed opaque numbered envelopes.SettingEight UK tertiary maternity units.Participants261 women expected to have a live birth before 32 weeks, and their 276 babies.InterventionsCord clamping after at least 2 min and immediate neonatal care with cord intact, or clamping within 20 s and immediate neonatal care after clamping.Main outcome measuresIntraventricular haemorrhage (IVH), death before discharge.Results132 women (137 babies) were allocated clamping ≥2 min and neonatal care cord intact, and 129 (139) clamping ≤20 s and neonatal care after clamping; six mother-infant dyads were excluded (2, 4) as birth was after 35+6 weeks, one withdrew (death data only available) (0, 1). Median gestation was 28.9 weeks for those allocated clamping ≥2 min, and 29.2 for those allocated clamping ≤20 s. Median time to clamping was 120 and 11 s, respectively. 7 of 135 infants (5.2%) allocated clamping ≥2 min died and 15 of 135 (11.1%) allocated clamping ≤20 s; risk difference (RD) −5.9% (95% CI −12.4% to 0.6%). Of live births, 43 of 134 (32%) had IVH vs 47 of 132 (36%), respectively; RD −3.5% (−14.9% to 7.8%). There were no clear differences in other outcomes for infants or mothers.ConclusionsThis is promising evidence that clamping after at least 2 min and immediate neonatal care with cord intact at very preterm birth may improve outcome; a large trial is urgently needed.Trial registrationISRCTN 21456601.

Objectives To provide survival data and rates of severe disability at 2 years of corrected age in infants born prior to 26 weeks9 gestation in 2001–2003 and to compare these outcomes with an earlier cohort from 1991 to 1993. Design Population-based prospective cohort study. Setting Former Trent region of UK covering a population of approximately five million and around 55 000 births per annum. Participants The authors identified a 3-year cohort of infants born before 26 weeks9 gestation between 1 January 2001 and 31 December 2003 from The Neonatal Survey (TNS). Questionnaires based on the Oxford minimum dataset were completed. Main outcome measures Survival, service use and disability levels were compared between the 2001– 2003 cohort and the cohort from 1991 to 1993. Results In 2001–2003, 0%, 18% and 35% of live born babies were alive at 2 years without any evidence of severe disability at 23, 24 and 25 weeks9 gestation, respectively. Overall, of those children admitted to neonatal care, the proportion with no evidence of severe disability at 2 years corrected age improved from 14.5% in 1991–1993 to 26.5% in 2001–2003. There was an increase in the proportion of children with at least one severe disability, out of total admissions to neonatal unit (8% vs 17%) and of those assessed at 2 years (35% vs 39%). Conclusions This study has shown an improvement in survival to discharge in babies admitted for neonatal care. However, this improved survival has been associated with an increase in the proportion of children with at least one severe disability at a corrected age of 2 years.

Background Comparisons of national perinatal and neonatal mortality rates often neglect the underlying causes. This study assessed effects of very preterm births in the UK and Australia. Setting Two geographically defined populations: the former Trent Health Region of the UK and New South Wales (NSW) / the Australian Capital Territory (ACT), Australia. Method All births 22+0 to 31+6 weeks born in 2000, 2001 and 2002 were identified by established surveys of perinatal care. Rates of birth and death were compared. Results The population of NSW/ACT was 35% higher and there were 66% more births than in Trent (273,495 vs 164,824). The proportion of liveborn infants between 22 and 31 weeks gestation was about 25% higher in Trent (NSW/ACT 2945, rate per 1000 livebirths 10.82 [95% C.I. 10.43-11.22]; Trent 2208, rate per 1000 livebirths 13.47 [95% C.I. 12.92-14.05]). The proportion of these infants admitted to a neonatal unit was also higher in Trent (91.2% vs 94.4%; OR 1.63; 95%CI 1.30-2.05). Unadjusted mortality in infants admitted to a neonatal unit was similar : NSW/ACT 332 / 2686 (12.4%), Trent 284 / 2085 (13.6%); unadjusted odds ratio = 1.12 (95% CI: 0.94-1.33) p = 0.21. Conclusion The higher rates of very premature birth and more ready admission to neonatal intensive care for those infants in the UK could help explain why its perinatal and neonatal mortality rates are higher than Australia9s. Efforts to understand why the rate of premature birth in the UK is so high should be a national priority.

Absence or reversal of end diastolic flow (AREDF) in the umbilical artery is associated with poor outcome, and elective premature delivery is common. Feeding these infants is a challenge. They often have poor tolerance of enteral feeding, and necrotising enterocolitis may develop. This review explores current practice to see if there is evidence on which to base guidelines. The incidence of necrotising enterocolitis is increased in infants with fetal AREDF, especially when complicated by fetal growth restriction. Abnormalities of splanchnic blood flow persist postnatally, with some recovery during the first week of life, providing justification for a delayed and careful introduction of enteral feeding. Such a policy exposes babies to the risks of parenteral nutrition, with no trials to date showing any benefit of delayed enteral nutrition. Trials are required to determine the optimum timing for introduction of enteral feeds in growth restricted infants with fetal AREDF.

A 7-year-old boy is referred to you with h concerns about developmental delay. On assessment, he is found to have moderate mental retardation (1Q of 50) but no remarkable physical findings. His parents are considering having another child, and they wonder what caused the retardation in their first child and whether it is likely to recur in future offspring.

For those involved in neonatal care the concept of risk adjustment, in the informal sense, is part of everyday life. We regularly talk to parents about the risk of death in their baby if he or she is born at a particular gestation. Similarly we are aware that the risk of death as we perceive it can be weighted by other events such as being born with particularly low Apgar scores. The disease severity scoring systems that exist in neonatal care have developed through a process that formalises the assessment of the risks attached to a particular baby. Archives of Disease in Childhood has published previously a review of how such scores are derived with a commentary on some of the most widely used systems.1 The use of disease severity scores arose first in other specialties primarily as a means of allowing comparison between heterogeneous groups of patients. For example how can you compare the efficiency of two adult orthopaedic units if the length of stay in hospital A is significantly longer than hospital B but the average age of the patients is significantly greater in hospital A? The development of a disease severity score would allow such variation in patient mix to be taken into account and the two units compared fairly with variation in their mix of patients, at baseline, removed. In neonatal care, survival rate was chosen as the most important outcome for comparison and hence most scores were designed to adjust for risk of death particularly in preterm babies. Those who have developed the scores have made different decisions about the importance of accuracy of prediction versus complexity of the score. For example is it better to have a score based on just five factors which can account for 90% of the patient variation or …

Background and aims A report suggested the UK neonatal mortality rate (NMR) in 2010 was the second highest of 22 Western European Countries having been the ninth lowest in 1990.1 There are a number of known differences in data categorisation that could explain some of these differences.2 Excluding babies below a certain gestational age or birthweight is frequently done in other countries but not in the UK. CMACE information on all UK neonatal deaths was therefore analysed to determine the effect of different cut-offs. Methods Data on all neonatal deaths across the UK were collected by CMACE with Office of National Statistics data utilised to obtain missing and denominator data. Deaths of babies born before different gestational ages were sequentially removed from the cohort and the NMR recalculated. In a separate analysis birthweight cut-offs were applied in the same way. Results In 2008, there were 734 342 livebirths, 2394 neonatal deaths and a NMR of 3.3 deaths per 1000 livebirths. Applying gestational and birthweight cut offs substantially reduced the calculated NMR bringing it into line with other countries. 22, 24 and 25+5 week cut offs removed 256, 694 and 985 deaths respectively lowering the calculated NMR to 2.9, 2.3 and 1.9. Similarly 500 g and 1000 g birthweight cut-offs removed 412, and 1220 deaths respectively lowering the calculated NMR to 2.7 and 1.6. Conclusions Cut-offs applied to neonatal deaths significantly alter calculated NMRs. A standardised approach to gestational age and birthweight is required to enable accurate comparisons between different countries.

Honey dressings have important anti-infective and wound healing properties in adults but have not been adequately studied in newborns. Osmotic and antinflammatory effects are believed to be important mechanisms of action. We carried out a pre-trial feasibility study and assessed safety and acceptability to staff and parents. Methods Following informed parental consent, babies were recruited to an observational study of Active Manuka Honey Dressings (Advancis Activon Tulle). Parents completed a questionnaire examining the acceptability and performance of the dressings and staff members who used the dressings filled out a similar questionnaire. The study was fully approved by the Nottingham 2 Research Ethics Committee and funded by Bliss. Results 28 wounds (8 different types) were dressed using the Active Manuka Honey dressings. Median gestational age at birth was 25 weeks (range 166–284 days), median age at entry into the study was 6 days (2–64 days). Median birth weight, 770 g, (500- 5305 g). Other parents declined to take part due to not wishing to disturb the dressing applied whilst considering taking part. Surgeons expressed strong preferences for other dressings. Analysis of predictive variables for time to wound healing did not identify any associations Conclusions Honey Dressings were easy to apply, well tolerated, with little pain on application or removal but there were fewer wounds than expected. No infant required escalation of pain relief or developed hyperglycaemia felt to be due to the dressings. These results suggest that Honey dressings are safe but that a trial may be challenging.

Background Deferring cord clamping allows blood flow between the placenta and baby to continue for a few minutes after birth; net flow is known as ‘placental transfusion’. The Cochrane Review suggests deferring cord clamping for preterm births may be beneficial. We have developed strategies for providing initial neonatal care at the mother’s bedside with the cord intact. The Cord Pilot Trial aims to assess whether it is feasible to conduct a large randomised trial of timing of cord clamping in the UK. Methods Women expected to have a live birth before 32 weeks are eligible. Allocation is to cord clamping either within 20 seconds or after at least 2 min (with neonatal care at the bedside). Consent is by two pathways; written consent during pregnancy, or oral assent at time of birth with written consent after birth. Follow up is until the children are age two years (corrected). The target for feasibility is to recruit 100–110 women at 8 sites over one year. Results Overall 125 women were recruited between March 2013 and February 2014; data are available for 124. Of these, 35 (28%) were recruited via the oral assent pathway; 20 (16%) were Conclusions A large multicentre trial would be feasible, implications for design and conduct will be discussed.

Background Despite advances in neonatal care some preterm infants still require home oxygen. In our tertiary neonatal service there was a transition with the management of infants with chronic lung disease requiring oxygen at discharge moving to Paediatric Respiratory led care. Our hypothesis was a formalised home oxygen service with a structured monitoring and weaning programme would reduce the length of time spent in oxygen and the number of hospital readmissions. Method We retrospectively identified two cohorts of preterm neonates requiring home oxygen. The first cohort received care led by the neonatal team and the second the respiratory team. The first cohort were discharged between January 2004–December 2006 and the second between January 2008–December 2010. Demographic, hospital readmission and home oxygen data were collected from hospital based computer systems and clinical notes. Results Conclusions Provision of the service has led to a greater number infants being discharged in oxygen but a shorter duration of oxygen therapy. In our experience the increase in neonates requiring home oxygen is likely to be secondary to shorter neonatal stays, increased awareness and provision of oxygen saturation sleep studies prior to discharge However, the structured monitoring and weaning programme led to a shorter duration of home oxygen therapy and fewer children requiring readmission.

Objective Honey Dressings have been demonstrated to have important anti-infective and wound healing properties in adults and children. Mechanisms of action include an osmotic effect on bacteria and anti-inflammatory properties. They have yet to be adequately studied in newborn infants and this study aimed to determine if honey dressings are safe and acceptable to staff and parents. In this abstract we present the themes obtained from asking parents and staff what they thought of the dressings. Methods Questionnaires were distributed to parents of babies who had Active Manuka Honey Dressings applied to their wounds in a feasibility study. Similar questionnaires were given to staff that had used the dressings. Responses were grouped into themes reflecting similar comments. Results 12 parents responded, giving responses grouped into the themes of ‘natural product’ and the ‘effect on healing’. 46 staff commented and their responses were grouped into three themes: ‘ease of application’, ‘smell’ and ‘effect on healing’. Some negative comments were also received covering 5 areas: ‘properties of the dressings’, ‘wastage’, ‘inappropriate use’, ‘appearance’ and ‘lack of adhesion’ under certain conditions. Conclusion Honey Dressings appear to be acceptable to parents and staff with both groups saying that they felt the dressings helped the wounds heal more quickly. More research is required to fully assess the effectiveness and role of honey dressings in newborn infants.

Objective Maternal diabetes substantially increases the risk of late IUD. A greater understanding of the underlying mechanism might allow identification of pregnancies at increased risk. We have studied post-mortem reports to investigate differences between IUD of fetuses from women with and without diabetes. Methods From the Centre for Maternal and Child Enquiries (CMACE), we obtained post mortem reports of cases of perinatal death in women with and without diabetes. Case pairs were matched for gestational age, birth weight, maternal BMI, deprivation index and ethnicity. We excluded cases/controls with multiple birth, lethal congenital abnormality, and neonatal death. Results Data are presented on 24 pairs; gestational ages ranged from 173 to 280 days and birth weights from 150 to 4650g. In women with diabetes, the mean placental weight was significantly less than in controls (328g vs 399g; p=0.034; 95% confidence interval -135 to -6g) and the gestational age corrected placental weight was 0.81 (SEM 0.41) standard deviations below population reference values (P=0.05). Brain and spleen weights were significantly lower in the infants of diabetic mothers (brain: mean 235 (SEM 25)g vs 274 (27)g; p=0.032; spleen: 3.5 (0.7)g vs 5.5 (1.1)g; p=0.04). There was a trend for the thymus and liver to be lighter and the heart heavier in the fetuses of diabetic mothers. Conclusion In pregnancies in women with diabetes which end in late IUD, the placenta, brain and spleen are lighter than in controls and we postulate placental and organ growth may identify diabetic women at risk of IU.

Background and aims There has been much interest in increasing staff cover across the week both in labour wards and in neonatal units with the hope that this will improve pregnancy outcomes. CMACE collects information on all stillbirth and neonatal deaths across the UK and analysed the pattern of deaths across the 24 h time period and between different days of the week to see if there are times that staff might be targeted towards. Methods 8 years (2000–2007) Data on all UK stillbirths and neonatal deaths including the date and time of birth were collected by CMACE. Missing and denominator data was obtained from the Office of national statistics. Results A clear diurnal pattern of stillbirths was demonstrated with a nadir of 3% of stillbirths occurring per hour between 07:00 and 10:00. This rises in the late afternoon and evening to a peak of approximately 5% of stillbirths per hour between 14:00 and 20:00. No such association with time of birth was seen for neonatal deaths and intrapartum related deaths. Intrapartum death was however more common on Thursdays and Fridays. Conclusions Stillbirths were more common in number during the later afternoon and evening. The underlying causes of these findings are likely to be multifactorial and complex but warrant further examination. In particular, further research to explore the relationship of staffing availability to the timing of stillbirths may be especially beneficial either to reduce stillbirths or save staffing costs.

The Royal College of Obstetricians and Gynaecologists’ Scientific Advisory Committee did not advise that there is “no evidence that the timing of cord clamping affected postpartum bleeding.”1 Rather, it said there is “no statistically significant difference” for postpartum haemorrhage or severe postpartum haemorrhage, and therefore the optimal timing for cord clamping is “unclear.”2 Lack of evidence of an effect is not the same as evidence of …

An 18 month old boy was referred to the local child development centre because he was not walking independently. He walked around by holding on to furniture; he had first crawled at age 11 months. We wanted to use an evidence based approach to guide our assessment and management, so before seeing him, we considered three issues. Firstly, we wanted to know whether, in an 18 month old child referred to a community paediatrician because he cannot walk independently, the most likely outcome is cerebral palsy, a primary muscle disorder, another neurological abnormality, or simply delayed motor development. Secondly, we wanted to know how many children with Duchenne muscular dystrophy present with delayed walking at 18 months. Thirdly, we wanted to know whether a creatine kinase level is a worthwhile screening test if there are no abnormal signs. To determine the most likely outcome, we used a Medline database to obtain evidence (at http://biomed.niss.ac.uk/). We used a filter to select articles dealing with prognosis (from wwwlib.jr2.ox.ac.uk/caspfew/filters/). We found additional papers by using the exploded form of “prognosis” (“exp prognosis”) instead of the text word. We combined …

Background Abnormal antenatal Dopplers with intrauterine growth restriction (IUGR) are associated with increased adverse outcomes in premature infants. Anxiety about necrotising enterocolitis (NEC) often results in delay in enteral feeding. Babies of less than 35-week gestation with IUGR and abnormal antenatal Dopplers were randomised to early (24–48 h) or late (120–144 h) initiation of milk feeds, with protocol for increasing feed volume the same in both groups. Data collected included daily milk intake, evidence of gut pathology, sepsis and need for parenteral nutrition. Primary end points were days to full feeds (150 ml/kg/day) sustained for 3 days and NEC. Secondary end points included death, sepsis, growth and duration of parenteral nutrition and hospital stay.1 Results 404 babies were randomised – 202 in each group. Data are presented on 372 completed outcome sets to date. Conclusion Preterm infants with absent or reversed end-diastolic flow velocity on umbilical Doppler who were fed on Day 2 of life achieved full feeds earlier than those commenced on Day 6, with no difference in the incidence of NEC or sepsis.

Aim Pregnancies complicated by abnormal antenatal Doppler blood flow often result in the preterm delivery of a growth restricted baby. These babies have a high risk of milk intolerance and necrotising enterocolitis (NEC), and introduction of milk feeds is frequently delayed. The authors9 aim was to determine the effect of early or late introduction on the time to successful establishment of full enteral feeding and on adverse outcomes including NEC. Methods Babies with birth weight below 10th centile and gestation below 34+6 weeks, born after abnormal antenatal Dopplers, were randomised between 20 and 48 h to either early (24–48 h) or late (120–144 h) introduction of milk feeds. Written, informed parental consent was obtained. Babies with major congenital anomaly, in utero transfusion, multiorgan failure or need for inotropes were excluded. Feed volumes and rate of increase were standardised and were the same for both groups. Daily feed logs were kept. Results 404 babies were randomised from 54 hospitals in the UK and Ireland (202 in each group) between 1 April 2006 and 31 May 2009. There were no important differences between groups at randomisation. Outcome data have been received on 372 babies to date and are presented below. Conclusion Growth-restricted preterm infants born after absent or reversed end-diastolic flow in the umbilical artery who are fed from the second day after birth achieve full feeds earlier than those commencing feeds on day 6. No difference has been seen to date in the incidence of NEC or sepsis.