Estimated neonatal survival of very preterm births across the care pathway: a UK cohort 2016-2020.

OBJECTIVE: Currently used estimates of survival are nearly 10 years old and relate to only those babies admitted for neonatal care. Due to ongoing improvements in neonatal care, here we update estimates of survival for singleton and multiple births at 22+0 to 31+6 weeks gestational age across the perinatal care pathway by gestational age and birth weight. DESIGN: Retrospective analysis of routinely collected data. SETTING: A national cohort from the UK and British Crown Dependencies. PATIENTS: Babies born at 22+0 to 31+6 weeks gestational age from 1 January 2016 to 31 December 2020. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Survival to 28 days. RESULTS: Estimates of neonatal survival are provided for babies: (1) alive at the onset of care during the birthing process (n=43 763); (2) babies where survival-focused care was initiated (n=42 004); and (3) babies admitted for neonatal care (n=41 158). We have produced easy-to-use survival charts for singleton and multiple births. Generally, survival increased with increasing gestational age at birth and with increasing birth weight. For all births with a birthweight over 1000 g, survival was 90% or higher at all three stages of care. CONCLUSIONS: Survival estimates are a vital tool to support and supplement clinical judgement within perinatal care. These up-to-date, national estimates of survival to 28 days are provided based on three stages of the perinatal care pathway to support ongoing clinical care. These novel results are a key resource for policy and practice including counselling parents and informing care provision.

Methods for Constructing Normalised Reference Scores: An Application for Assessing Child Development at 24 Months of Age.

The use of the lambda-mu-sigma (LMS) method for estimating centiles and producing reference ranges has received much interest in clinical practice, especially for assessing growth in childhood. However, this method may not be directly applicable where measures are based on a score calculated from question response categories that is bounded within finite intervals, for example, in psychometrics. In such cases, the main assumption of normality of the conditional distribution of the transformed response measurement is violated due to the presence of ceiling (and floor) effects, leading to biased fitted centiles when derived using the common LMS method. This paper describes the methodology for constructing reference intervals when the response variable is bounded and explores different distribution families for the centile estimation, using a score derived from a parent-completed assessment of cognitive and language development in 24 month-old children. Results indicated that the z-scores, and thus the extracted centiles, improved when kurtosis was also modeled and that the ceiling effect was addressed with the use of the inflated binomial distribution. Therefore, the selection of the appropriate distribution when constructing centile curves is crucial.

Understanding ethnic inequalities in stillbirth rates: a UK population-based cohort study.

OBJECTIVES: To investigate inequalities in stillbirth rates by ethnicity to facilitate development of initiatives to target those at highest risk. DESIGN: Population-based perinatal mortality surveillance linked to national birth and death registration (Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK). SETTING: UK. PARTICIPANTS: 4 391 569 singleton births at ≥24+0 weeks gestation between 2014 and 2019. MAIN OUTCOME MEASURES: Stillbirth rate difference per 1000 total births by ethnicity. RESULTS: Adjusted absolute differences in stillbirth rates were higher for babies of black African (3.83, 95% CI 3.35 to 4.32), black Caribbean (3.60, 95% CI 2.65 to 4.55) and Pakistani (2.99, 95% CI 2.58 to 3.40) ethnicities compared with white ethnicities. Higher proportions of babies of Bangladeshi (42%), black African (39%), other black (39%) and black Caribbean (37%) ethnicities were from most deprived areas, which were associated with an additional risk of 1.50 stillbirths per 1000 births (95% CI 1.32 to 1.67). Exploring primary cause of death, higher stillbirth rates due to congenital anomalies were observed in babies of Pakistani, Bangladeshi and black African ethnicities (range 0.63-1.05 per 1000 births) and more placental causes in black ethnicities (range 1.97 to 2.24 per 1000 births). For the whole population, over 40% of stillbirths were of unknown cause; however, this was particularly high for babies of other Asian (60%), Bangladeshi (58%) and Indian (52%) ethnicities. CONCLUSIONS: Stillbirth rates declined in the UK, but substantial excess risk of stillbirth persists among babies of black and Asian ethnicities. The combined disadvantage for black, Pakistani and Bangladeshi ethnicities who are more likely to live in most deprived areas is associated with considerably higher rates. Key causes of death were congenital anomalies and placental causes. Improved strategies for investigation of stillbirth causes are needed to reduce unexplained deaths so that interventions can be targeted to reduce stillbirths.

EPICE cohort: two-year neurodevelopmental outcomes after very preterm birth.

OBJECTIVE: To determine whether the variation in neurodevelopmental disability rates between populations persists after adjustment for demographic, maternal and infant characteristics for an international very preterm (VPT) birth cohort using a standardised approach to neurodevelopmental assessment at 2 years of age. DESIGN: Prospective standardised cohort study. SETTING: 15 regions in 10 European countries. PATIENTS: VPT births: 22+0-31+6 weeks of gestation. DATA COLLECTION: Standardised data collection tools relating to pregnancy, birth and neonatal care and developmental outcomes at 2 years corrected age using a validated parent completed questionnaire. MAIN OUTCOME MEASURES: Crude and standardised prevalence ratios calculated to compare rates of moderate to severe neurodevelopmental impairment between regions grouped by country using fixed effects models. RESULTS: Parent reported rates of moderate or severe neurodevelopmental impairment for the cohort were: 17.3% (ranging 10.2%-26.1% between regions grouped by country) with crude standardised prevalence ratios ranging from 0.60 to 1.53. Adjustment for population, maternal and infant factors resulted in a small reduction in the overall variation (ranging from 0.65 to 1.30). CONCLUSION: There is wide variation in the rates of moderate to severe neurodevelopmental impairment for VPT cohorts across Europe, much of which persists following adjustment for known population, maternal and infant factors. Further work is needed to investigate whether other factors including quality of care and evidence-based practice have an effect on neurodevelopmental outcomes for these children.

Standardisation of the Parent Report of Children's Abilities-Revised (PARCA-R): a norm-referenced assessment of cognitive and language development at age 2 years.

BACKGROUND: The Parent Report of Children's Abilities-Revised (PARCA-R) can be used to identify preterm born children at risk for developmental delay at age 24 months. However, standardised scores for assessing all children in the general population and quantifying development relative to the norm are unavailable, thus limiting the use of the questionnaire. We aimed to develop scores that are standardised by age and sex for the PARCA-R to assess children's cognitive and language development at age 24-27 months. METHODS: Anonymised data from PARCA-R questionnaires that were completed by parents of 2-year-old children in three previous studies were obtained to form a standardisation sample that was representative of the UK general population. Anonymised data were obtained from three further studies to assess the external validity and clinical validity of the standardised scores. We used the lambda-mu-sigma (lambda for skewness, mu for median, sigma for the coefficient of variation) method to develop scores that are standardised by age and sex for three scales (non-verbal cognitive development, language development, and total parent report composite [PRC]) for children in four 1-month age bands, spanning age 23·5-27·5 months. FINDINGS: We included 6402 children (mean age 25 months and 1 day [range 23 months and 16 days to 27 months and 15 days]) in the standardisation sample and 709 (mean age 24 months and 19 days [23 months and 16 days to 27 months and 15 days]) to test the external validity and 1456 (mean age 24 months and 8·5 days [23 months and 16 days to 27 months and 15 days]) to test the clinical validity of the standardised scores. For all PARCA-R scales, mean standardised scores approximated 100 (SD 15) in both sexes and all age groups. These scores were independent of socioeconomic status. Standardised scores were close to 100 (15) in the external validation sample, showing the validity of the scores. Standardised scores for the total PRC scale for children born very preterm (<32 weeks' gestation) were 0·47 SD lower on average than the normative mean, and for children with neonatal sepsis were 0·73 SD lower on average than the normative mean. These scores were equivalent to a standardised score of 93 (95% CI 91-94) for children born very preterm and 89 (88-91) for children with neonatal sepsis, thus showing clinical validity. INTERPRETATION: The PARCA-R provides a norm-referenced, standardised assessment of cognitive and language development at 24-27 months of age. The questionnaire is available non-commercially in English with translations available in 14 other languages, thus providing clinicians and researchers with a cost-effective tool for assessing development and identifying children with delay. FUNDING: Action Medical Research (Ref: GN2580).

Assessing the deprivation gap in stillbirths and neonatal deaths by cause of death: a national population-based study.

OBJECTIVE: To investigate socioeconomic inequalities in cause-specific stillbirth and neonatal mortality to identify key areas of focus for future intervention strategies to achieve government ambitions to reduce mortality rates. DESIGN: Retrospective cohort study. SETTING: England, Wales, Scotland and the UK Crown Dependencies. PARTICIPANTS: All singleton births between 1 January 2014 and 31 December 2015 at ≥24 weeks' gestation. MAIN OUTCOME MEASURE: Cause-specific stillbirth or neonatal death (0-27 days after birth) per 10 000 births by deprivation quintile. RESULTS: Data on 5694 stillbirths (38.1 per 10 000 total births) and 2368 neonatal deaths (15.9 per 10 000 live births) were obtained from Mothers and Babies: Reducing Risk through Audits and Confidential Enquiries across the UK (MBRRACE-UK). Women from the most deprived areas were 1.68 (95% CI 1.56 to 1.81) times more likely to experience a stillbirth and 1.67 (95% CI 1.48 to 1.87) times more likely to experience a neonatal death than those from the least deprived areas, equating to an excess of 690 stillbirths and 231 neonatal deaths per year associated with deprivation. Small for gestational age (SGA) unexplained antepartum stillbirth was the greatest contributor to excess stillbirths accounting for 33% of the deprivation gap in stillbirths. Congenital anomalies accounted for the majority (59%) of the deprivation gap in neonatal deaths, followed by preterm birth not SGA (24-27 weeks, 27%). CONCLUSIONS: Cause-specific mortality rates at a national level allow identification of key areas of focus for future intervention strategies to reduce mortality. Despite a reduction in the deprivation gap for stillbirths and neonatal deaths, public health interventions should primarily focus on socioeconomic determinants of SGA stillbirth and congenital anomalies.

Wide variation in severe neonatal morbidity among very preterm infants in European regions.

OBJECTIVE: To investigate the variation in severe neonatal morbidity among very preterm (VPT) infants across European regions and whether morbidity rates are higher in regions with low compared with high mortality rates. DESIGN: Area-based cohort study of all births before 32 weeks of gestational age. SETTING: 16 regions in 11 European countries in 2011/2012. PATIENTS: Survivors to discharge from neonatal care (n=6422). MAIN OUTCOME MEASURES: Severe neonatal morbidity was defined as intraventricular haemorrhage grades III and IV, cystic periventricular leukomalacia, surgical necrotizing enterocolitis and retinopathy of prematurity grades ≥3. A secondary outcome included severe bronchopulmonary dysplasia (BPD), data available in 14 regions. Common definitions for neonatal morbidities were established before data abstraction from medical records. Regional severe neonatal morbidity rates were correlated with regional in-hospital mortality rates for live births after adjustment on maternal and neonatal characteristics. RESULTS: 10.6% of survivors had a severe neonatal morbidity without severe BPD (regional range 6.4%-23.5%) and 13.8% including severe BPD (regional range 10.0%-23.5%). Adjusted inhospital mortality was 13.7% (regional range 8.4%-18.8%). Differences between regions remained significant after consideration of maternal and neonatal characteristics (P<0.001) and severe neonatal morbidity rates were not correlated with mortality rates (P=0.50). CONCLUSION: Severe neonatal morbidity rates for VPT survivors varied widely across European regions and were independent of mortality rates.

Estimating neonatal length of stay for babies born very preterm.

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.

Differentiating the Preterm Phenotype: Distinct Profiles of Cognitive and Behavioral Development Following Late and Moderately Preterm Birth.

OBJECTIVES: To explore patterns of comorbidity in cognitive and behavioral outcomes at 2 years' corrected age among children born late or moderately preterm (LMPT) and to identify predictors of different patterns of comorbidity. STUDY DESIGN: Geographical, prospective population-based cohort study of 1139 infants born LMPT (320/7 to 366/7 weeks' gestation) and 1255 infants born at term (370/7 to 426/7 weeks' gestation). Parent questionnaires were obtained to identify impaired cognitive and language development, behavioral problems, delayed social-emotional competence, autistic features, and clinically significant eating difficulties at 24 months corrected age for 638 (57%) children born LMPT and 765 (62%) children born at term. RESULTS: Latent class analysis revealed 2 profiles of development among the term group: optimal (84%) and a profile of social, emotional, and behavioral impairments termed "nonoptimal" (16%). These 2 profiles were also identified among the LMPT group (optimal: 67%; nonoptimal: 26%). In the LMPT group, a third profile was identified (7%) that was similar to the phenotype previously identified in infants born very preterm. Nonwhite ethnicity, socioeconomic risk, and not receiving breast milk at hospital discharge were risk factors for nonoptimal outcomes in both groups. Male sex, greater gestational age, and pre-eclampsia were only associated with the preterm phenotype. CONCLUSIONS: Among children born LMPT with parent-reported cognitive or behavioral impairments, most had problems similar to the profile of difficulties observed in children born at term. A smaller proportion of children born LMPT had impairments consistent with the "very preterm phenotype" which are likely to have arisen through a preterm pathway. These results suggest that prematurity may affect development through several etiologic pathways in the late and moderately preterm population.

Variability in Very Preterm Stillbirth and In-Hospital Mortality Across Europe.

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.

Causes and temporal changes in nationally collected stillbirth audit data in high-resource settings.

Few high-income countries have an active national programme of stillbirth audit. From the three national programmes identified (UK, New Zealand, and the Netherlands) steady declines in annual stillbirth rates have been observed over the audit period between 1993 and 2014. Unexplained stillbirth remains the largest group in the classification of stillbirths, with a decline in intrapartum-related stillbirths, which could represent improvements in intrapartum care. All three national audits of stillbirths suggest that up to half of all reviewed stillbirths have elements of care that failed to follow standards and guidance. Variation in the classification of stillbirth, cause of death and frequency of risk factor groups limit our ability to draw meaningful conclusions as to the true scale of the burden and the changing epidemiology of stillbirths in high-income countries. International standardization of these would facilitate direct comparisons between countries. The observed declines in stillbirth rates over the period of perinatal audit, a possible consequence of recommendations for improved antenatal care, should serve to incentivise other countries to implement similar audit programmes.

Variability in the management and outcomes of extremely preterm births across five European countries: a population-based cohort study.

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.

What factors predict length of stay in a neonatal unit: a systematic review.

OBJECTIVE: In the UK, 1 in 10 babies require specialist neonatal care. This care can last from hours to months depending on the need of the baby. The increasing survival of very preterm babies has increased neonatal care resource use. Evidence from multiple studies is crucial to identify factors which may be important for predicting length of stay (LOS). The ability to predict LOS is vital for resource planning, decision-making and parent counselling. The objective of this review was to identify which factors are important to consider when predicting LOS in the neonatal unit. DESIGN: A systematic review was undertaken which searched MEDLINE, EMBASE and Scopus for papers from 1994 to 2016 (May) for research investigating prediction of neonatal LOS. Strict inclusion and exclusion criteria were applied. Quality of each study was discussed, but not used as a reason for exclusion from the review. MAIN OUTCOME MEASURE: Prediction of LOS in the neonatal unit. RESULTS: 9 studies were identified which investigated the prediction of neonatal LOS indicating a lack of evidence in the area. Inherent factors, particularly birth weight, sex and gestational age allow for a simple and objective prediction of LOS, which can be calculated on the first day of life. However, other early occurring factors may well also be important and estimates may need revising throughout the baby's stay in hospital. CONCLUSIONS: Predicting LOS is vital to aid the commissioning of services and to help clinicians in their counselling of parents. The lack of evidence in this area indicates a need for larger studies to investigate methods of accurately predicting LOS.

Modelling Neonatal Care Pathways for Babies Born Preterm: An Application of Multistate Modelling.

Modelling length of stay in neonatal care is vital to inform service planning and the counselling of parents. Preterm babies, at the highest risk of mortality, can have long stays in neonatal care and require high resource use. Previous work has incorporated babies that die into length of stay estimates, but this still overlooks the levels of care required during their stay. This work incorporates all babies, and the levels of care they require, into length of stay estimates. Data were obtained from the National Neonatal Research Database for singleton babies born at 24-31 weeks gestational age discharged from a neonatal unit in England from 2011 to 2014. A Cox multistate model, adjusted for gestational age, was used to consider a baby's two competing outcomes: death or discharge from neonatal care, whilst also considering the different levels of care required: intensive care; high dependency care and special care. The probabilities of receiving each of the levels of care, or having died or been discharged from neonatal care are presented graphically overall and adjusted for gestational age. Stacked predicted probabilities produced for each week of gestational age provide a useful tool for clinicians when counselling parents about length of stay and for commissioners when considering allocation of resources. Multistate modelling provides a useful method for describing the entire neonatal care pathway, where rates of in-unit mortality can be high. For a healthcare service focussed on costs, it is important to consider all babies that contribute towards workload, and the levels of care they require.

Use of evidence based practices to improve survival without severe morbidity for very preterm infants: results from the EPICE population based cohort.

OBJECTIVES:  To evaluate the implementation of four high evidence practices for the care of very preterm infants to assess their use and impact in routine clinical practice and whether they constitute a driver for reducing mortality and neonatal morbidity. DESIGN:  Prospective multinational population based observational study. SETTING:  19 regions from 11 European countries covering 850 000 annual births participating in the EPICE (Effective Perinatal Intensive Care in Europe for very preterm births) project. PARTICIPANTS:  7336 infants born between 24+0 and 31+6 weeks' gestation in 2011/12 without serious congenital anomalies and surviving to neonatal admission. MAIN OUTCOME MEASURES:  Combined use of four evidence based practices for infants born before 28 weeks' gestation using an "all or none" approach: delivery in a maternity unit with appropriate level of neonatal care; administration of antenatal corticosteroids; prevention of hypothermia (temperature on admission to neonatal unit ≥36°C); surfactant used within two hours of birth or early nasal continuous positive airway pressure. Infant outcomes were in-hospital mortality, severe neonatal morbidity at discharge, and a composite measure of death or severe morbidity, or both. We modelled associations using risk ratios, with propensity score weighting to account for potential confounding bias. Analyses were adjusted for clustering within delivery hospital. RESULTS:  Only 58.3% (n=4275) of infants received all evidence based practices for which they were eligible. Infants with low gestational age, growth restriction, low Apgar scores, and who were born on the day of maternal admission to hospital were less likely to receive evidence based care. After adjustment, evidence based care was associated with lower in-hospital mortality (risk ratio 0.72, 95% confidence interval 0.60 to 0.87) and in-hospital mortality or severe morbidity, or both (0.82, 0.73 to 0.92), corresponding to an estimated 18% decrease in all deaths without an increase in severe morbidity if these interventions had been provided to all infants. CONCLUSIONS:  More comprehensive use of evidence based practices in perinatal medicine could result in considerable gains for very preterm infants, in terms of increased survival without severe morbidity.

Correcting for prematurity affects developmental test scores in infants born late and moderately preterm.

BACKGROUND: Corrected age is typically applied when assessing the development of children born <32 weeks of gestation. There is no consensus as to whether corrected age should be applied when assessing children born late/moderately preterm (LMPT; 32-36 weeks of gestation). AIMS: This study explored the impact of corrected age on developmental test scores in infants born LMPT. STUDY DESIGN: 221 LMPT infants were assessed at two years corrected age using the Bayley-III cognitive and language scales, from which cognitive and language composite scores were derived (Normative Mean 100; SD 15). Assessments were then re-scored using chronological age. Bayley-III composite scores <80 were used to define developmental delay. Paired sample t-tests were used to assess the difference in mean test scores derived using corrected versus chronological age, and McNemar's tests to assess the difference in the proportion of infants with developmental delay using corrected versus chronological age. RESULTS: Mean corrected age scores were significantly higher than chronological age scores (cognitive: 2.1 points; 95% CI 1.6, 2.5; language 2.5; 95% CI 2.1, 2.8). Overall, significantly more LMPT infants were classified with developmental delay when chronological (18.3%) versus corrected (15.0%) age was used (p=0.016). CONCLUSIONS: Correcting for prematurity results in significantly higher developmental test scores and a significantly lower prevalence of developmental delay in LMPT infants and may affect eligibility for intervention services. Researchers and clinicians should be aware that the use of corrected age may impact on developmental test scores at both an individual and population level among infants born LMPT.

Eating difficulties in children born late and moderately preterm at 2 y of age: a prospective population-based cohort study.

BACKGROUND: Very preterm (<32 wk of gestation) infants are at increased risk of eating difficulties compared with their term-born peers. Little is known about the impact of late and moderately preterm (LMPT; 32-36 wk of gestation) birth on eating difficulties in early childhood. OBJECTIVES: The aims were to assess the prevalence of eating difficulties in infants born LMPT at 2 y corrected age and to explore the impact of neonatal and neurodevelopmental factors. DESIGN: A geographic population-based cohort of 1130 LMPT and 1255 term-born controls was recruited at birth. The parents of 651 (59%) LMPT and 771 (62%) term-born infants completed questionnaires at 2 y corrected age to assess neurodevelopmental outcomes. Parents also completed a validated questionnaire to assess eating behaviors in 4 domains: refusal/picky eating, oral motor problems, oral hypersensitivity, and eating behavior problems. Infants with scores >90th percentile were classified with eating difficulties in each domain. Neonatal data were collected at discharge, and sociodemographic information was collected via maternal interview. Poisson regression was used to assess between-group differences in eating difficulties and to explore associations with neonatal factors and neurodevelopmental outcomes at 2 y of age. RESULTS: In unadjusted analyses, LMPT infants were at increased risk of refusal/picky eating (RR: 1.53; 95% CI: 1.03, 2.25) and oral motor problems (RR: 1.62; 95% CI: 1.06, 2.47). Prolonged nasogastric feeding >2 wk (RR: 1.87; 95% CI: 1.07, 3.25), behavior problems (RR: 2.95; 95% CI: 1.93, 4.52), and delayed social competence (RR: 2.28; 95% CI: 1.49, 3.48) were independently associated with eating difficulties in multivariable analyses. After adjustment for these factors, there was no excess of eating difficulties in LMPT infants. CONCLUSIONS: Infants born LMPT are at increased risk of oral motor and picky eating problems at 2 y corrected age. However, these are mediated by other neurobehavioral sequelae in this population. This trial was registered on the UK Clinical Research Network Portfolio at http://public.ukcrn.org.uk/search/ as UKCRN Study ID 7441.

Funnel plot control limits to identify poorly performing healthcare providers when there is uncertainty in the value of the benchmark.

There is an increasing use of statistical methods, such as funnel plots, to identify poorly performing healthcare providers. Funnel plots comprise the construction of control limits around a benchmark and providers with outcomes falling outside the limits are investigated as potential outliers. The benchmark is usually estimated from observed data but uncertainty in this estimate is usually ignored when constructing control limits. In this paper, the use of funnel plots in the presence of uncertainty in the value of the benchmark is reviewed for outcomes from a Binomial distribution. Two methods to derive the control limits are shown: (i) prediction intervals; (ii) tolerance intervals Tolerance intervals formally include the uncertainty in the value of the benchmark while prediction intervals do not. The probability properties of 95% control limits derived using each method were investigated through hypothesised scenarios. Neither prediction intervals nor tolerance intervals produce funnel plot control limits that satisfy the nominal probability characteristics when there is uncertainty in the value of the benchmark. This is not necessarily to say that funnel plots have no role to play in healthcare, but that without the development of intervals satisfying the nominal probability characteristics they must be interpreted with care.