Bradley N. Manktelow

Aim: To investigate, for preterm babies born between 27⁺⁰ and 31⁺⁶ weeks gestation in England, optimal place of birth and early care. Design: Mixed methods. Setting: National Health Service neonatal care, England. Methods: To investigate whether birth and early care in neonatal intensive care units (tertiary units) compared to local neonatal units (non-tertiary units) influenced gestation-specific survival and other major outcomes, we analysed data from the National Neonatal Research Database, for 29,842 babies born between 27⁺⁰ and 31⁺⁶ weeks gestation and discharged from neonatal care between 1 January 2014 and 31 December 2018. We utilised an instrumental variable (maternal excess travel time between local neonatal units and neonatal intensive care units) to control for unmeasured differences. Sensitivity analyses excluded postnatal transfers within 72 hours of birth and multiple births. Outcome measures were death in neonatal care, infant mortality, necrotising enterocolitis, retinopathy of prematurity, severe brain injury, bronchopulmonary dysplasia, and receipt of breast milk at discharge. We also analysed outcomes by volume of neonatal intensive care activity. We undertook a health economic analysis using a cost-effectiveness evaluation from a National Health Service perspective and using additional lives saved as a measure of benefit, explored differences in quality of care in high compared with low-performing units and performed ethnographic qualitative research. Results: The safe gestational age cut-off for babies to be born between 27⁺⁰ and 31⁺⁶ weeks and early care at either location was 28 weeks. We found no effect on mortality in neonatal care (mean difference −0.001; 99% confidence interval −0.011 to 0.010; p = 0.842) or in infancy (mean difference −0.002; 99% confidence interval −0.014 to 0.009; p = 0.579) (n = 18,847), including after sensitivity analyses. A significantly greater proportion of babies in local neonatal units had severe brain injury (mean difference −0.011; 99% confidence interval −0.022 to −0.001; p = 0.007) with the highest mean difference in babies born at 27 weeks (−0.040). Those transferred in the first 72 hours were more likely to have severe brain injury. For 27 weeks gestation, birth in centres with neonatal intensive care units reduced the risk of severe brain injury by 4.2% from 11.9% to 7.7%. The number needed to treat was 25 (99% confidence interval 10 to 59) indicating that 25 babies at 27 weeks would have to be delivered in a neonatal intensive care unit to prevent one severe brain injury. For babies born at 27 weeks gestation, birth in a high-volume unit (> 1600 intensive care days/year) reduced the risk of severe brain injury from 0.242 to 0.028 [99% confidence interval 0.035 to 0.542; p = 0.003; number needed to treat = 4 (99% confidence interval 2 to 29)]. Estimated annual total costs of neonatal care were £262 million. The mean (standard deviation) cost per baby varied from £75,594 (£34,874) at 27 weeks to £27,401 (£14,947) at 31 weeks. Costs were similar between neonatal intensive care units and local neonatal units for births at 27⁺⁰ to 29⁺⁶ weeks gestation, but higher for local neonatal units for those born at 30⁺⁰ to 31⁺⁶ weeks. No difference in additional lives saved were observed between the settings. These results suggested that neonatal intensive care units are likely to represent value for money for the National Health Service. However, careful interpretation of this results should be exercised due to the ethical and practical concerns around the reorganisation of neonatal care for very preterm babies from local neonatal units to neonatal intensive care units purely on the grounds of cost savings. We identified a mean reduction in length of stay (1 day; 95% confidence interval 1.029 to 1.081; p < 0.001) in higher-performing units, based on adherence to evidence- and consensus-based measures. Staff reported that decision-making to optimise capacity for babies was an important part of their work. Parents reported valuing their baby’s development, homecoming, continuity of care, inclusion in decision-making, and support for their emotional and physical well-being. Conclusions: Birth and early care for babies ≥ 28 weeks is safe in both neonatal intensive care units and local neonatal units in England. For anticipated births at 27 weeks, antenatal transfer of mothers to centres colocated with neonatal intensive care units should be supported. When these inadvertently occur in centres with local neonatal units, clinicians should risk assess decisions for postnatal transfer, taking patient care requirements, staff skills and healthcare resources into consideration and counselling parents regarding the increased risk of severe brain injury associated with transfer. Study registration: This study is registered as Current Controlled Trials NCT02994849 and ISRCTN74230187. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/70/104) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 12. See the NIHR Funding and Awards website for further award information.

Background: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies.Objectives: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm.Methods: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9‐point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds.Results: An initial list of 140 data items was generated. Ninety‐six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio‐economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life.Conclusions: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.

Background: There is an inherent tension in neonatal services between the efficiency and specialised care that comes with centralisation and the provision of local services with associated ease of access and community benefits. This study builds on previous work in South West England to address these issues at a national scale.Objectives: (1) To develop an analytical framework to address key issues of neonatal service configuration in England, (2) to investigate visualisation tools to facilitate the communication of findings to stakeholder groups and (3) to assess parental preferences in relation to service configuration alternatives.Main outcome measures: The ability to meet nurse staffing guidelines, volumes of units, costs, mortality, number and distance of transfers, travel distances and travel times for parents.Design: Descriptive statistics, location analysis, mathematical modelling, discrete event simulation and economic analysis were used. Qualitative methods were used to interview policy-makers and parents. A parent advisory group supported the study.Setting: NHS neonatal services across England.Data: Neonatal care data were sourced from the National Neonatal Research Database. Information on neonatal units was drawn from the National Neonatal Audit Programme. Geographic and demographic data were sourced from the Office for National Statistics. Travel time data were retrieved via a geographic information system. Birth data were sourced from Hospital Episode Statistics. Parental cost data were collected via a survey.Results: Location analysis shows that to achieve 100% of births in units with ≥ 6000 births per year, the number of birth centres would need to be reduced from 161 to approximately 72, with more parents travelling > 30 minutes. The maximum number of neonatal intensive care units (NICUs) needed to achieve 100% of very low-birthweight infants attending high-volume units is 36 with existing NICUs, or 48 if NICUs are located wherever there is currently a neonatal unit of any level. Simulation modelling further demonstrated the workforce implications of different configurations. Mortality modelling shows that the birth of very preterm infants in high-volume hospitals reduces mortality (a conservative estimate of a 1.2-percentage-point lower risk) relative to these births in other hospitals. It is currently not possible to estimate the impact of mortality for infants transferred into NICUs. Cost modelling shows that the mean length of stay following a birth in a high-volume hospital is 9 days longer and the mean cost is £5715 more than for a birth in another neonatal unit. In addition, the incremental cost per neonatal life saved is £460,887, which is comparable to other similar life-saving interventions. The analysis of parent costs identified unpaid leave entitlement, food, travel, accommodation, baby care and parking as key factors. The qualitative study suggested that central concerns were the health of the baby and mother, communication by medical teams and support for families.Limitations: The following factors could not be modelled because of a paucity of data – morbidity outcomes, the impact of transfers and the maternity/neonatal service interface.Conclusions: An evidence-based framework was developed to inform the configuration of neonatal services and model system performance from the perspectives of both service providers and parents.Future work: To extend the modelling to encompass the interface between maternity and neonatal services.Funding: The National Institute for Health Research Health Services and Delivery Research programme.

Objective To predict length of stay in neonatal care for all admissions of very preterm singleton babies. Setting All neonatal units in England. Patients Singleton babies born at 24–31 weeks gestational age from 2011 to 2014. Data were extracted from the National Neonatal Research Database. Methods Competing risks methods were used to investigate the competing outcomes of death in neonatal care or discharge from the neonatal unit. The occurrence of one event prevents the other from occurring. This approach can be used to estimate the percentage of babies alive, or who have been discharged, over time. Results A total of 20 571 very preterm babies were included. In the competing risks model, gestational age was adjusted for as a time-varying covariate, allowing the difference between weeks of gestational age to vary over time. The predicted percentage of death or discharge from the neonatal unit were estimated and presented graphically by week of gestational age. From these percentages, estimates of length of stay are provided as the number of days following birth and corrected gestational age at discharge. Conclusions These results can be used in the counselling of parents about length of stay and the risk of mortality.

BACKGROUND AND OBJECTIVE: Stillbirth and in-hospital mortality rates associated with very preterm births (VPT) vary widely across Europe. International comparisons are complicated by a lack of standardized data collection and differences in definitions, registration, and reporting. This study aims to determine what proportion of the variation in stillbirth and in-hospital VPT mortality rates persists after adjusting for population demographics, case-mix, and timing of death. METHODS: Standardized data collection for a geographically defined prospective cohort of VPTs (22⁺⁰–31⁺⁶ weeks gestation) across 16 regions in Europe. Crude and adjusted stillbirth and in-hospital mortality rates for VPT infants were calculated by time of death by using multinomial logistic regression models. RESULTS: The stillbirth and in-hospital mortality rate for VPTs was 27.7% (range, 19.9%–35.9% by region). Adjusting for maternal and pregnancy characteristics had little impact on the variation. The addition of infant characteristics reduced the variation of mortality rates by approximately one-fifth (4.8% to 3.9%). The SD for deaths <12 hours after birth was reduced by one-quarter, but did not change after risk adjustment for deaths ≥12 hours after birth. CONCLUSIONS: In terms of the regional variation in overall VPT mortality, over four-fifths of the variation could not be accounted for by maternal, pregnancy, and infant characteristics. Investigation of the timing of death showed that these characteristics only accounted for a small proportion of the variation in VPT deaths. These findings suggest that there may be an inequity in the quality of care provision and treatment of VPT infants across Europe.

Objective: To explore international variations in the management and survival of extremely low gestational age and birthweight births. Design: Area-based prospective cohort of births Setting: 12 regions across Belgium, France, Italy, Portugal and the UK Participants: 1449 live births and fetal deaths between 22⁺⁰ and 25⁺⁶ weeks gestation born in 2011–2012. Main outcome measures: Percentage of births; recorded live born; provided antenatal steroids or respiratory support; surviving to discharge (with/without severe morbidities). Results: The percentage of births recorded as live born was consistently low at 22 weeks and consistently high at 25 weeks but varied internationally at 23 weeks for those weighing 500 g and over (range 33%–70%) and at 24 weeks for those under 500 g (range 5%–71%). Antenatal steroids and provision of respiratory support at 22–24 weeks gestation varied between countries, but were consistently high for babies born at 25 weeks. Survival to discharge was universally poor at 22 weeks gestation (0%) and at any gestation with birth weight <500 g, irrespective of treatment provision. In contrast, births at 23 and 24 weeks weighing 500 g and over showed significant international variation in survival (23 weeks: range: 0%–25%; 24 weeks range: 21%–50%), reflecting levels of treatment provision. Conclusions: Wide international variation exists in the management and survival of extremely preterm births at 22–24 weeks gestation. Universally poor outcomes for babies at 22 weeks and for those weighing under 500 g suggest little impact of intervention and support the inclusion of birth weight along with gestational age in ethical decision-making guidelines.