National Neonatal Research Database Research Articles

Outcomes following the adoption of standard parenteral nutrition in preterm infants: a whole-population non-concurrent control study

ObjectiveTo evaluate the impact of a quality improvement project of the adoption of standard parenteral nutrition (SPN) in preterm infants.DesignRetrospective, multicentre, whole-population, non-concurrent control study using data from the UK...

The Contribution of Hypertensive Disorders of Pregnancy to Neonatal Unit Admissions and Iatrogenic Preterm Delivery at < 34+0 Weeks' Gestation in the UK: A Population-Based Study Using the National Neonatal Research Database.

The objectives of this study were to (i) quantify the contribution of maternal hypertensive disorders of pregnancy (HDP) to iatrogenic preterm birth (PTB) and neonatal unit (NNU) admissions < 34+0 weeks and (ii) describe short-term population-level outcomes for HDP infants, exploring ethnic disparities and comparing outcomes by HDP exposure. Retrospective population-based study using the National Neonatal Research Database. England and Wales. Infants born < 34+0 weeks and admitted to NNU 2012-2020. Descriptive statistics, linear and logistic regression models to compare outcomes between groups. Survival to discharge with/without comorbidity. 122 228 infants met inclusion criteria. Where collected, 49 839/114 164 (43.7%, 95% CI 43.4%-43.9%) of infants had an iatrogenic PTB. HDP was recorded in 16 510/122 228 (13.5%) of all infants and 13 560/49 839 (27.2%) of iatrogenic PTBs. HDP and/or foetal growth restriction (FGR) were recorded in 24 124/49 839 (48.4%) of iatrogenic PTBs. Singleton HDP infants < 10th BWC had ≥ 90% survival to discharge from 28 weeks' gestation, versus from 26 weeks' gestation for those born ≥ 10th BWC. In extreme preterm HDP infants (< 27 weeks), 27.3% of infants < 10th BWC died compared to 15.2% of those ≥ 10th BWC. Survival without comorbidity was ≥ 90% from 32 weeks' gestation in HDP infants across BWC. These contemporaneous population-level data show that almost one in two PTB < 34+0 weeks' gestation are iatrogenic, with HDP and/or FGR being the major contributors to iatrogenic prematurity. This has substantial implications for strategies to reduce preterm birth in the UK and internationally. The data further inform antenatal and at-birth counselling of HDP-exposed infants.

Preterm birth as a determinant of neurodevelopment and cognition in children (PRENCOG): protocol for an exposure-based cohort study in the UK

IntroductionPreterm birth (PTB) is strongly associated with encephalopathy of prematurity (EoP) and neurocognitive impairment. The biological axes linking PTB with atypical brain development are uncertain. We aim to elucidate the...

PRECIOUS study (PREterm Caesarean/vaginal birth and IVH/OUtcomeS): does mode of birth reduce the risk of death or brain injury in very preterm babies? A cohort and emulated target trial protocol

IntroductionVery preterm babies are at risk of poor neurodevelopmental outcomes and death. Intraventricular haemorrhage (IVH) after birth is the most prevalent cause of this. Birth by caesarean section may protect...

Place of birth and postnatal transfers in infants with congenital diaphragmatic hernia in England and Wales: a descriptive observational cohort study

ObjectiveTo describe clinical pathways for infants with congenital diaphragmatic hernia (CDH) and short-term outcomes.DesignRetrospective observational cohort study using the UK National Neonatal Research Database (NNRD).PatientsBabies with a diagnosis of CDH...

A protocol for neoWONDER: Neonatal whole population data linkage to improve long-term health and wellbeing of preterm and sick babies.

Early-life medical and surgical interventions in babies born preterm and/or with surgical conditions influence later life health and educational outcomes. Obtaining long-term outcomes post-discharge to evaluate the impact of interventions is complex, expensive, and burdensome to families. Linkage of routinely collected data offers a feasible and cost-effective solution. The NeoWONDER research programme aims to describe the short and long-term health and educational outcomes for babies born preterm and/or with surgical conditions and evaluate the impact of neonatal care and interventions on later health and educational outcomes. We will include babies who received care in neonatal units in England and Wales, born between 2007-2020 with a gestational age below 32 weeks (approximately 100,000), and/or born between 2012-2020 (all gestations) with any of six surgical conditions: necrotising enterocolitis, Hirschsprung's disease, gastroschisis, oesophageal atresia, congenital diaphragmatic hernia, and posterior urethral valves (approximately 8,000). A detailed list of surgical condition codes is shown in S3 File. We will obtain long-term health and education outcomes through linkage of the National Neonatal Research Database, which contains routine data for all babies admitted to NHS neonatal units, to other existing health and educational datasets. For England, these are: Hospital Episode Statistics, the Office for National Statistics, Mental Health Services Dataset, Paediatric Intensive Care Audit Network, National Pupil Database; and for Wales, the Secure Anonymised Information Linkage databank. Analysis will be undertaken on de-identified linked datasets. Outcomes of interest for health include mortality, hospital admissions, diagnoses indicative of neurodisability and/or chronic illness, health care utilisation; and for education are attainment (using national curriculum assessments), school absence and special educational needs status.

UK neonatal stoma practice: a population study

ObjectiveThe optimal time for neonatal stoma closure is unclear and there have been calls for a trial to compare early and late surgery. The feasibility of such a trial will...

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

IntroductionPrevention of necrotising enterocolitis (NEC) is vital for improving neonatal outcomes. Feeding own mother’s milk helps prevent NEC. Rates of own mother’s milk feeding in the East Midlands are lower...

Risk factors for infection and outcomes in infants with neonatal encephalopathy: a cohort study

BackgroundTo determine the association between early infection risk factors and short-term outcomes in infants with neonatal encephalopathy following perinatal asphyxia (NE).MethodsA retrospective population-based cohort study utilizing the National Neonatal Research Database that included infants with NE admitted to neonatal units in England and Wales, Jan 2008–Feb 2018. Exposure: one or more of rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics. Primary outcome: death or nasogastric feeds/nil by mouth (NG/NBM) at discharge. Secondary outcomes: organ dysfunction; length of stay; intraventricular hemorrhage; antiseizure medications use.Results998 (13.7%) out of 7265 NE infants had exposure to early infection risk factors. Primary outcome (20.3% vs. 23.1%, OR 0.87 (95% CI 0.71–1.08), p = 0.22), death (12.8% vs. 14.0%, p = 0.32) and NG/NBM (17.4% vs. 19.9%. p = 0.07) did not differ between the exposed and unexposed group. Time to full sucking feeds (OR 0.81 (0.69–0.95)), duration (OR 0.82 (0.71–0.95)) and the number of antiseizure medications (OR 0.84 (0.72–0.98)) were lower in exposed than unexposed infants after adjusting for confounders. Therapeutic hypothermia did not alter the results.ConclusionsInfants with NE exposed to risk factors for early-onset infection did not have worse short-term adverse outcomes.ImpactRisk factors for early-onset neonatal infection, including rupture of membranes >18 h, maternal group B streptococcus colonization, chorioamnionitis, maternal pyrexia or antepartum antibiotics, were not associated with death or short-term morbidity after cooling for NE.Despite exposure to risk factors for early-onset neonatal infection, infants with NE reached oral feeds earlier and needed fewer anti-seizure medications for a shorter duration than infants with NE but without such risk factors.This study supports current provision of therapeutic hypothermia for infants with NE and any risk factors for early-onset neonatal infection.

Paediatric intensive care admissions of preterm children born

ObjectiveSurvival of babies born very preterm (<32 weeks gestational age) has increased, although preterm-born children may have ongoing morbidity. We aimed to investigate the risk of admission to paediatric intensive...

Association between opioid use during mechanical ventilation in preterm infants and evidence of brain injury: a propensity score-matched cohort study

Preterm infants often require mechanical ventilation (MV), which can be a painful experience. Opioids (such as morphine) are used to provide analgesia, despite conflicting evidence about their impact on the developing brain. We aimed to quantify the use of opioids during MV in infants born at <32 weeks' gestational age and to investigate the association between opioid use and evidence of brain injury. In this retrospective propensity score-matched cohort study, we used routinely recorded data from the National Neonatal Research Database to study infants born at 22-31 weeks gestational age who were admitted to neonatal units in England and Wales (between Jan 1, 2012, and Dec 31, 2020) and who were mechanically ventilated on one or more days during their hospital stay. We used propensity score matching to identify pairs of infants (one who received opioids during MV and one who did not) with similar demographic and clinical characteristics. The pre-specified primary outcome was preterm brain injury assessed in all infants who received MV for more than two days and had evidence of preterm brain injury at or before discharge from neonatal care. Adjusted analyses accounted for differences in infants' characteristics, including illness severity and painful/surgical conditions. Of 67,206 infants included, 45,193 (67%) were mechanically ventilated for one or more days and 26,201 (58% of 45,193) received an opioid whilst ventilated. Opioids were given for a median of 67% of ventilated days (IQR 43-92%) and the median exposure was 4 days (2-11). The percentage of mechanically ventilated infants who received opioids while ventilated increased from 52% in 2012 to 60% in 2020 (morphine, 51%-56%; fentanyl, 6%-18%). In the propensity score-matched cohort of 3608 pairs who were ventilated for >2 consecutive days, the odds of any preterm brain injury (adjusted odds ratio 1.22, 95% CI 1.10-1.35) were higher in those who received opioids compared with those who did not (received opioids, 990/3608 (27.4%) vs. did not receive opioids, 855/3608 (23.7%). The adjusted odds of these adverse outcomes increased with increasing number of days of opioid exposure. Use of opioids during mechanical ventilation of preterm infants increased during the study period (2012-2020). Although causation cannot be determined, among those ventilated for >2 consecutive days, these data suggest that opioid use is associated with an increased risk of preterm brain injury and the risk increases with longer durations of exposure. University of Nottingham Impact Fund.

Outcomes in very preterm infants receiving an exclusive human milk diet, or their own mother's milk supplemented with preterm formula

BackgroundAn infant's Own Mother's Milk (OMM) is the mainstay of very preterm nutrition. When a supplement is required, preterm formula and pasteurised human donor milk (pHDM), are options. Which is optimal is unknown. Aims and outcome measuresComparison of “survival to 34 weeks postmenstrual age (PMA) without surgery for necrotising enterocolitis (NEC)” and other outcomes, in infants receiving OMM supplemented with pHDM without bovine macronutrient fortification (exclusive human milk diet), and infants receiving OMM supplemented with preterm formula. DesignCohort analysis of observational data from the National Neonatal Research Database; data-adaptive Super Learner approach with Targeted Maximum Likelihood Estimation to calculate Adjusted Risk Differences (ARD) between the groups. ParticipantsInfants born below 32 weeks gestation admitted to neonatal units in England and Wales between 01 and 06-2017 and 31-05-2022. ResultsCompared to the formula supplemented group (n = 7133), infants receiving an exclusive human milk diet (n = 1007), had lower survival to 34 weeks PMA without NEC surgery (ARD -9.8 %, 95%CI -11.4 to −8.2), higher all-cause (10.7 %, 9.1 to 12.2) and NEC-related mortality (1.0 %, 0.4 to 1.5), and lower rates of treated retinopathy of prematurity (−2.8 %, −3.4 to −2.3) and bronchopulmonary dysplasia (−12.1 %, −14.0 to −10.1). ConclusionsThe lower survival to 34 weeks PMA without NEC surgery in infants receiving an exclusive human milk diet is unexpected. We adjusted for factors that influence outcomes but cannot exclude the possibility of confounding, hence our data justify a randomised controlled trial to identify optimal supplementary feeds for very preterm infants.

Two-year neurodevelopmental data for preterm infants born over an 11-year period in England and Wales, 2008–2018: a retrospective study using the National Neonatal Research Database

ObjectiveUnited Kingdom guidelines recommend all infants born <30 weeks’ gestation receive neurodevelopmental follow-up at 2 years corrected age. In this study, we describe completeness and results of 2-year neurodevelopmental records...

Clinical outcomes of Staphylococcus capitis isolation from neonates, England, 2015–2021: a retrospective case–control study

ObjectiveStaphylococcus capitis, a coagulase-negative staphylococci (CoNS) species, has been increasingly detected from UK sterile site samples and has caused neonatal unit outbreaks worldwide. We compared survival to discharge and 30-day...

Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard

IntroductionBronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population.PurposeEvaluate the...

Impact of postnatal dexamethasone timing on preterm mortality and bronchopulmonary dysplasia: a propensity score analysis.

Postnatal dexamethasone (PND) is used in high-risk preterm infants after the first week of life to facilitate extubation and prevent bronchopulmonary dysplasia (BPD) but the optimal treatment timing remains unclear. Our objective was to explore the association between the timing of PND commencement and mortality and respiratory outcomes. This was a retrospective National Neonatal Research Database study of 84 440 premature infants born <32 weeks gestational age from 2010 to 2020 in England and Wales. Propensity score weighting analysis was used to explore the impact of PND commenced at three time-points (2-3 weeks (PND2/3), 4-5 weeks (PND4/5) and after 5 weeks (PND6+) chronological age) on the primary composite outcome of death before neonatal discharge and/or severe BPD (defined as respiratory pressure support at 36 weeks) alongside other secondary respiratory outcomes. 3469 infants received PND. Compared with PND2/3, infants receiving PND6+ were more likely to die and/or develop severe BPD (OR 1.68, 95% CI 1.28-2.21), extubate at later postmenstrual age (mean difference 3.1 weeks, 95% CI 2.9-3.4 weeks), potentially require respiratory support at discharge (OR 1.34, 95% CI 1.06-1.70) but had lower mortality before discharge (OR 0.38, 95% CI 0.29-0.51). PND4/5 was not associated with severe BPD or discharge respiratory support. PND treatment after 5 weeks of age was associated with worse respiratory outcomes although residual bias cannot be excluded. A definitive clinical trial to determine the optimal PND treatment window, based on early objective measures to identify high-risk infants, is needed.

The practicalities of adapting UK maternity clinical information systems for observational research: Experiences of the POOL study.

Using routinely collected clinical data for observational research is an increasingly important method for data collection, especially when rare outcomes are being explored. The POOL study was commissioned to evaluate the safety of waterbirth in the UK using routine maternity and neonatal clinical data. This paper describes the design, rationale, set-up and pilot for this data linkage study using bespoke methods. Clinical maternity information systems hold many data items of value for research purposes, but often lack specific data items required for individual studies. This study used the novel method of amending an existing clinical maternity database for the purpose of collecting additional research data fields. In combination with the extraction of existing data fields, this maximised the potential use of existing routinely collected clinical data for research purposes, whilst reducing NHS staff data collection burden.Wellbeing Software®, provider of the Euroking® Maternity Information System, added new study specific data fields to their information system, extracted data from participating NHS sites and transferred data for matching with the National Neonatal Research Database to ascertain outcomes for babies admitted to neonatal units. Study set-up processes were put in place for all sites. The data extraction, linkage and cleaning processes were piloted with one pre-selected NHS site. Twenty-six NHS sites were set-up over 27 months (January 2019 - April 2021). Twenty-four thousand maternity records were extracted from the one NHS site, pertaining to the period January 2015 to March 2019. Data field completeness for maternal and neonatal primary outcomes were mostly acceptable. Neonatal identifiers flowed to the National Neonatal Research Database for successful matching and linkage between maternity and neonatal unit records. Piloting the data extraction and linkage highlighted the need for additional governance arrangements, training at NHS sites and new processes for the study team to ensure data quality and confidentiality are upheld during the study. Amending existing NHS electronic information systems and accessing clinical data at scale, is possible, but continues to be a time consuming and a technically challenging exercise.

The contribution of hypertensive disorders of pregnancy to late preterm and term admissions to neonatal units in the UK 2012-2020 and opportunities to avoid admission: A population-based study using the National Neonatal Research Database.

To quantify maternal hypertensive disorder of pregnancy (HDP) prevalence in late preterm and term infants admitted to neonatal units (NNU) and assess opportunities to avoid admissions. A retrospective population-based study using the National Neonatal Research Database. England and Wales. Infants born ≥34 weeks' gestation admitted to NNU between 2012 and 2020. Outcomes in HDP infants are compared with non-HDP infants using regression models. Hypertensive disorder of pregnancy, primary reason for admission, clinical diagnoses and resource use. 16 059/136 220 (11.8%) of late preterm (34+0 to 36+6 weeks' gestation) and 14 885/284 646 (5.2%) of term (≥37 weeks' gestation) admitted infants were exposed to maternal HDP. The most common primary reasons for HDP infant admission were respiratory disease (28.3%), prematurity (22.7%) and hypoglycaemia (16.4%). HDP infants were more likely to be admitted with primary hypoglycaemia than were non-HDP infants (odds ratio [OR] 2.1, 95% confidence interval [CI] 2.0-2.2, P < 0.0001). 64.5% of HDP infants received i.v. dextrose. 35.7% received mechanical or non-invasive ventilation. 8260/30 944 (26.7%) of HDP infants received intervention for hypoglycaemia alone (i.v. dextrose) with no other major intervention (respiratory support, parenteral nutrition, central line, arterial line or blood transfusion). The burden of maternal HDP on late preterm and term admissions to NNU is high, with hypoglycaemia and respiratory disease being the main drivers for admission. Over one in four were admitted solely for management of hypoglycaemia. Further research should determine whether maternal antihypertensive agent choice or postnatal pathways may reduce NNU admission.

Pilot feasibility study of a digital technology approach to the systematic electronic capture of parent-reported data on cognitive and language development in children aged 2 years

BackgroundThe assessment of language and cognition in children at risk of impaired neurodevelopment following neonatal care is a UK standard of care but there is no national, systematic approach for...

Data-driven approach to understanding neonatal palliative care needs in England and Wales: a population-based study 2015–2020

ObjectiveTo quantify admissions to neonatal units in England and Wales with potential need for palliative care.Design, setting and patientsDiagnoses and clinical attributes indicating a high likelihood of requiring palliative care...