Jon Dorling

Survival of extremely premature babies in a geographically defined population: prospective cohort study of 1994-9 compared with 2000-5

Objective To assess changes in survival for infants born before 26 completed weeks of gestation. Design Prospective cohort study in a geographically defined population. Setting Former Trent health region of the United Kingdom. Subjects All infants born at 22+0 to 25+6 weeks’ gestation to mothers living in the region. Terminations were excluded but all other births of babies alive at the onset of labour or the delivery process were included. Main outcome measures Outcome for all infants was categorised as stillbirth, death without admission to neonatal intensivecare, death before discharge from neonatal intensivecare, and survival to discharge home in two time periods: 1994-9 and 2000-5 inclusive. Results The proportion of infants dying in delivery rooms was similar in the two periods, but a significant improvement was seen in the number of infants surviving to discharge (P<0.001). Of 497 infants admitted to neonatal intensive care in 2000-5, 236 (47%) survived to discharge compared with 174/490 (36%) in 1994. These changes were attributable to substantial improvements in the survival of infants born at 24 and 25 weeks. During the 12 years of the study none of the 150 infants born at 22 weeks’ gestation survived. Of the infants born at 23 weeks who were admitted to intensive care, there was no significant improvement in survival to discharge in 2000-5 (12/65 (18%) in 2000-5 v 15/81 (19%) in 1994-9). Conclusions Survival of infants born at 24 and 25 weeks of gestation has significantly increased. Although over half the cohort of infants born at 23 weeks wasadmitted to neonatalintensive care, there was no improvement in survival at this gestation. Care for infants born at 22 weeks remained unsuccessful.

Early or Delayed Enteral Feeding for Preterm Growth-Restricted Infants: A Randomized Trial

BACKGROUND: Growth-restricted preterm infants are at increased risk of developing necrotizing enterocolitis (NEC) and initiation of enteral feeding is frequently delayed. There is no evidence that this delay is beneficial and it might further compromise nutrition and growth. METHODS: Infants with gestation below 35 weeks, birth weight below the 10th centile, and abnormal antenatal umbilical artery Doppler waveforms were randomly allocated to commence enteral feeds “early,” on day 2 after birth, or “late,” on day 6. Gradual increase in feeds was guided by a “feeding prescription” with rate of increase the same for both groups. Primary outcomes were time to achieve full enteral feeding sustained for 72 hours and NEC. RESULTS: Four hundred four infants were randomly assigned from 54 hospitals in the United Kingdom and Ireland (202 to each group). Median gestation was 31 weeks. Full, sustained, enteral feeding was achieved at an earlier age in the early group: median age was 18 days compared with 21 days (hazard ratio: 1.36 [95% confidence interval: 1.11–1.67]). There was no evidence of a difference in the incidence of NEC: 18% in the early group and 15% in the late group (relative risk: 1.2 [95% confidence interval: 0.77–1.87]). Early feeding resulted in shorter duration of parenteral nutrition and high-dependency care, lower incidence of cholestatic jaundice, and improved SD score for weight at discharge. CONCLUSIONS: Early introduction of enteral feeds in growth-restricted preterm infants results in earlier achievement of full enteral feeding and does not appear to increase the risk of NEC.

Use of heated humidified high-flow nasal cannula oxygen in neonates: a UK wide survey.

Heated humidified high‐flow nasal cannula (HHHFNC) oxygen is a relatively new form of respiratory support and is increasing in popularity despite lack of supportive evidence and amid safety concerns. We investigated the prevalence of its use in tertiary neonatal units in the UK.

Neonatal outcomes and delivery of care for infants born late preterm or moderately preterm: a prospective population-based study

Objective To describe neonatal outcomes and explore variation in delivery of care for infants born late (34–36  weeks) and moderately (32–33 weeks) preterm (LMPT). Design/setting Prospective population-based study comprising births in four major maternity centres, one midwifery-led unit and at home between September 2009 and December 2010. Data were obtained from maternal and neonatal records. Participants All LMPT infants were eligible. A random sample of term-born infants (≥37 weeks) acted as controls. Outcome measures Neonatal unit (NNU) admission, respiratory and nutritional support, neonatal morbidities, investigations, length of stay and postnatal ward care were measured. Differences between centres were explored. Results 1146 (83%) LMPT and 1258 (79% of eligible) term-born infants were recruited. LMPT infants were significantly more likely to receive resuscitation at birth (17.5% vs 7.4%), respiratory (11.8% vs 0.9%) and nutritional support (3.5% vs 0.3%) and were less likely to be fed breast milk (64.2% vs 72.2%) than term infants. For all interventions and morbidities, a gradient of increasing risk with decreasing gestation was evident. Although 60% of late preterm infants were never admitted to a NNU, 83% required medical input on postnatal wards. Clinical management differed significantly between services. Conclusions LMPT infants place high demands on specialist neonatal services. A substantial amount of previously unreported specialist input is provided in postnatal wards, beyond normal newborn care. Appropriate expertise and planning of early care are essential if such infants are managed away from specialised neonatal settings. Further research is required to clarify optimal and cost-effective postnatal management for LMPT babies.

Economic costs associated with moderate and late preterm birth: a prospective population-based study.

We sought to determine the economic costs associated with moderate and late preterm birth.

Feeding infants below 29 weeks’ gestation with abnormal antenatal Doppler: analysis from a randomised trial

Objective To describe feeding and gastrointestinal outcomes in growth-restricted infants <29 weeks’ gestation and to determine the rate of feed advancement which they tolerate. Design Analysis of prospectively collected data from a randomised feeding trial, the Abnormal Doppler Enteral Prescription Trial (ADEPT). Setting 54 neonatal units in the UK and Ireland. Participants 404 preterm, growth-restricted infants with abnormal antenatal Doppler studies from ADEPT. 83 infants <29 weeks and 312 infants ≥29 weeks’ gestation were included in this analysis. Interventions In ADEPT, infants were randomised to start milk ‘early’ on day 2 after birth, or ‘late’ on day 6. Subsequent feed advancement followed a regimen, which should have achieved full feeds by day 16 in the early and day 20 in the late group. Main outcome measures Full feeds were achieved later in infants <29 weeks; median age 28 days {IQR 22–40} compared with 19 days {IQR 17–23} in infants ≥29 weeks (HR 0.35, 95% CI 0.3 to 0.5). The incidence of necrotising enterocolitis was also higher in this group; 32/83 (39%) compared to 32/312 (10%) in those ≥29 weeks (RR 3.7, 95% CI 2.4 to 5.7). Infants <29 weeks tolerated very little milk for the first 10 days of life and reached full feeds 9 days later than predicted from the trial regimen. Conclusions Growth-restricted infants born <29 weeks’ gestation with abnormal antenatal Doppler failed to tolerate even the careful feeding regimen of ADEPT. A slower advancement of feeds may be required for these infants. Trial registration number ISRCTN87351483.

Value and validity of neonatal disease severity scoring systems

For those involved in neonatal care the concept of risk adjustment, in the informal sense, is part of every day 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].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 …

Randomised trial of cord clamping and initial stabilisation at very preterm birth

Objectives For very preterm births, to compare alternative policies for umbilical cord clamping and immediate neonatal care. Design Parallel group randomised (1:1) trial, using sealed opaque numbered envelopes. Setting Eight UK tertiary maternity units. Participants 261 women expected to have a live birth before 32 weeks, and their 276 babies. Interventions Cord 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 measures Intraventricular haemorrhage (IVH), death before discharge. Results 132 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. Conclusions This 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 registration ISRCTN 21456601.

Mechanisms Affecting the Gut of Preterm Infants in Enteral Feeding Trials

Large randomized controlled trials (RCTs) in preterm infants offer unique opportunities for mechanistic evaluation of the risk factors leading to serious diseases, as well as the actions of interventions designed to prevent them. Necrotizing enterocolitis (NEC) a serious inflammatory gut condition and late-onset sepsis (LOS) are common feeding and nutrition-related problems that may cause death or serious long-term morbidity and are key outcomes in two current UK National Institutes for Health Research (NIHR) trials. Speed of increasing milk feeds trial (SIFT) randomized preterm infants to different rates of increases in milk feeds with a primary outcome of survival without disability at 2 years corrected age. Enteral lactoferrin in neonates (ELFIN) randomizes infants to supplemental enteral lactoferrin or placebo with a primary outcome of LOS. This is a protocol for the mechanisms affecting the gut of preterm infants in enteral feeding trials (MAGPIE) study and is funded by the UK NIHR Efficacy and Mechanistic Evaluation programme. MAGPIE will recruit ~480 preterm infants who were enrolled in SIFT or ELFIN. Participation in MAGPIE does not change the main trial protocols and uses non-invasive sampling of stool and urine, along with any residual resected gut tissue if infants required surgery. Trial interventions may involve effects on gut microbes, metabolites (e.g., short-chain fatty acids), and aspects of host immune function. Current hypotheses suggest that NEC and/or LOS are due to a dysregulated immune system in the context of gut dysbiosis, but mechanisms have not been systematically studied within large RCTs. Microbiomic analysis will use next-generation sequencing, and metabolites will be assessed by mass spectrometry to detect volatile organic and other compounds produced by microbes or the host. We will explore differences between disease cases and controls, as well as exploring the actions of trial interventions. Impacts of this research are multiple: translation of knowledge of mechanisms promoting gut health may explain outcomes or suggest alternate strategies to improve health. Results may identify new non-invasive diagnostic or monitoring techniques, preventative or treatment strategies for NEC or LOS, or provide data useful for risk stratification in future studies. Mechanistic evaluation might be especially informative where there are not clear effects on the primary outcome (ISRCTN 12554594).

PB.09 A Feasibility Study of Active Manuka Honey Dressings on Babies Requiring Admission to NICU

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.