Bradley N Manktelow

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.

Neonatal disease severity scoring systems

Illness severity scores have become widely used in neonatal intensive care. Primarily this has been to adjust the mortality observed in a particular hospital or population for the morbidity of their infants, and hence allow standardised comparisons to be performed. However, although risk correction has become relatively commonplace in relation to audit and research involving groups of infants, the use of such scores in giving prognostic information to parents, about their baby, has been much more limited. The strengths and weaknesses of the existing methods of disease severity correction in the newborn are presented in this review.

Factors affecting the incidence of chronic lung disease of prematurity in 1987, 1992, and 1997.

OBJECTIVE To determine changes in the incidence of chronic lung disease of prematurity between 1987, 1992, and 1997. METHODS Observational study based on data derived from a geographically defined population: Trent Health Region, United Kingdom. Three time periods were compared: 1 February 1987 to 31 January 1988 (referred to as 1987); 1 April 1992 to 31 March 1993 (referred to as 1992); 1997. All infants of ⩽ 32 completed weeks gestation born to Trent resident mothers within the study periods and admitted to a neonatal unit were included. Rates of chronic lung disease were determined using two definitions: (a) infants who remained dependent on active respiratory support or increased oxygen at 28 days of age; (b) infants who remained dependent on active respiratory support or increased oxygen at a corrected age of 36 weeks gestation. RESULTS Between 1987 and 1992 there was a fall in the birth rate, but a significant increase was noted in the number of babies of ⩽ 32 weeks gestation admitted to a neonatal unit. There was no significant change in survival when the two groups of infants were directly compared. However, mean gestation and birth weight fell. Adjusting for this change showed a significant improvement in survival (28 day survival: odds ratio (OR) = 1.69; 95% confidence interval (95% CI) = 1.23 to 2.33. Survival to 36 week corrected gestation: OR = 1.45; 95% CI = 1.06 to 1.98). These changes were accompanied by a large increase in the incidence of chronic lung disease even after allowing for the change in population characteristics (28 day definition: OR = 2.20; 95% CI = 1.47 to 3.30. 36 week definition: OR = 3.04; 95% CI = 1.91 to 4.83). Between 1992 and 1997 a different pattern emerged. There was a further increase in the number of babies admitted for neonatal care at ⩽ 32 weeks gestation despite a continuing fall in overall birth rate. Survival, using both raw data and data corrected for changes in gestation and birth weight, improved significantly in 1997 (adjusted data: 28 day survival: OR = 1.72 (95% CI = 1.22 to 2.38); survival to 36 week corrected gestation: OR = 1.90 (95% CI = 1.36 to 2.64)). Rates of chronic lung disease showed no significant change between 1992 and 1997 despite improved survival (adjusted data: 28 day definition: OR = 0.72 (95% CI = 0.50 to 1.03); 36 week definition: OR = 0.88 (95% CI = 0.61 to 1.26). CONCLUSIONS Current high rates of chronic lung disease are the result of policies to offer neonatal intensive care more widely to the most immature infants. Recent improvements in survival have been achieved without further increases in the risk of infants developing chronic lung disease.

Neurodevelopmental outcomes following late and moderate prematurity: a population-based cohort study

Objective There is a paucity of data relating to neurodevelopmental outcomes in infants born late and moderately preterm (LMPT; 32+0–36+6 weeks). This paper present the results of a prospective, population-based study of 2-year outcomes following LMPT birth. Design 1130 LMPT and 1255 term-born children were recruited at birth. At 2 years corrected age, parents completed a questionnaire to assess neurosensory (vision, hearing, motor) impairments and the Parent Report of Childrens Abilities-Revised to identify cognitive impairment. Relative risks for adverse outcomes were adjusted for sex, socio-economic status and small for gestational age, and weighted to account for over-sampling of term-born multiples. Risk factors for cognitive impairment were explored using multivariable analyses. Results Parents of 638 (57%) LMPT infants and 765 (62%) controls completed questionnaires. Among LMPT infants, 1.6% had neurosensory impairment compared with 0.3% of controls (RR 4.89, 95% CI 1.07 to 22.25). Cognitive impairments were the most common adverse outcome: LMPT 6.3%; controls 2.4% (RR 2.09, 95% CI 1.19 to 3.64). LMPT infants were at twice the risk for neurodevelopmental disability (RR 2.19, 95% CI 1.27 to 3.75). Independent risk factors for cognitive impairment in LMPT infants were male sex, socio-economic disadvantage, non-white ethnicity, preeclampsia and not receiving breast milk at discharge. Conclusions Compared with term-born peers, LMPT infants are at double the risk for neurodevelopmental disability at 2 years of age, with the majority of impairments observed in the cognitive domain. Male sex, socio-economic disadvantage and preeclampsia are independent predictors of low cognitive scores following LMPT birth.

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.

Nature of socioeconomic inequalities in neonatal mortality: population based study

Objective To investigate time trends in socioeconomic inequalities in cause specific neonatal mortality in order to assess changing patterns in mortality due to different causes, particularly prematurity, and identify key areas of focus for future intervention strategies. Design Retrospective cohort study. Setting England. Participants All neonatal deaths in singleton infants born between 1 January 1997 and 31 December 2007. Main outcome measure Cause specific neonatal mortality per 10 000 births by deprivation tenth (deprivation measured with UK index of multiple deprivation 2004 at super output area level). Results 18 524 neonatal deaths occurred in singleton infants born in the 11 year study period. Neonatal mortality fell between 1997-9 and 2006-7 (from 31.4 to 25.1 per 10 000 live births). The relative deprivation gap (ratio of mortality in the most deprived tenth compared with the least deprived tenth) increased from 2.08 in 1997-9 to 2.68 in 2003-5, before a fall to 2.35 in 2006-7. The most common causes of death were immaturity and congenital anomalies. Mortality due to immaturity before 24 weeks’ gestation did not decrease over time and showed the widest relative deprivation gap (2.98 in 1997-9; 4.14 in 2003-5; 3.16 in 2006-7). Mortality rates for all other causes fell over time. For congenital anomalies, immaturity, and accidents and other specific causes, the relative deprivation gap widened between 1997-9 and 2003-5, before a slight fall in 2006-7. For intrapartum events and sudden infant deaths (only 13.5% of deaths) the relative deprivation gap narrowed slightly. Conclusions Almost 80% of the relative deprivation gap in all cause mortality was explained by premature birth and congenital anomalies. To reduce socioeconomic inequalities in mortality, a change in focus is needed to concentrate on these two influential causes of death. Understanding the link between deprivation and preterm birth should be a major research priority to identify interventions to reduce preterm birth.

Population-Based Estimates of In-Unit Survival for Very Preterm Infants

BACKGROUND: Estimates of the probability of survival of very preterm infants admitted to NICU care are vital for counseling parents, informing care, and planning services. In 1999, easy-to-use charts of survival according to gestation, birth weight, and gender were published in the United Kingdom. These charts are widely used in clinical care and for benchmarking survival, and they form the core of the Clinical Risk Index for Babies II score. Since their publication, the survival of preterm infants has improved, and the charts therefore need updating. METHODS: A logistic model was fitted with gestational age, birth weight, and gender. Nonlinear functions were estimated by using fractional polynomials. Bootstrap methods were used to assess the internal validity of the final model. The final model was assessed both overall and for subgroups of infants by using Farrington’s statistic, the c-statistic, Cox regression coefficients, and the Brier score. RESULTS: A total of 2995 white singleton infants born at 23+0 to 32+6 weeks’ gestation in 2008 through 2010 were identified; 2751 (91.9%) infants survived to discharge. A prediction model was estimated and good model fit confirmed (area under receiver-operating characteristics curve = 0.86). Survival ranged from 27.7% (23 weeks) to 99.1% (32 weeks) for boys and from 34.5% (23 weeks) to 99.3% (32 weeks) for girls. Updated charts were produced showing estimated survival according to gestation, birth weight and gender, together with contour plots displaying points of equal survival. CONCLUSIONS: These survival charts have been updated and will be of use to clinicians, parents, and managers.

Efficacy of prone ventilation in adult patients with acute respiratory failure: A meta-analysis

PURPOSE The use of prone ventilation in acute respiratory failure has been investigated by several randomized controlled trials in the recent past. To date, there has been no systematic review or meta-analysis of these trials. MATERIAL AND METHODS Systematic literature search was performed between 1966 and July 2006 to identify randomized trials evaluating prone ventilation. Outcome measures included mortality, changes in oxygenation, incidence of pneumonia, duration of mechanical ventilation, intensive care unit (ICU) and hospital stay, cost-effectiveness, and adverse effects including pressure sores, endotracheal tube, or intravascular catheter complications. RESULTS Prone ventilation was not associated with reduction in mortality, but improvement in oxygenation was statistically significant (mean difference, 21.2 mm Hg; P < .001). There was no significant difference in incidence of pneumonia, ICU stay, and endotracheal tube complications. There was a trend toward an increased incidence of pressure sores in prone ventilated patients (odds ratio = 1.95; 95% confidence interval, 0.09-4.15; P = .08). The data on other outcomes were not suitable for meta-analysis. CONCLUSIONS The use of prone ventilation is associated with improved oxygenation. It is not associated with a reduction in mortality, pneumonia, or ICU stay and may be associated with an increased incidence of pressure sores.

Infants born late/moderately preterm are at increased risk for a positive autism screen at 2 years of age.

OBJECTIVES To assess the prevalence of positive screens using the Modified Checklist for Autism in Toddlers (M-CHAT) questionnaire and follow-up interview in late and moderately preterm (LMPT; 32-36 weeks) infants and term-born controls. STUDY DESIGN Population-based prospective cohort study of 1130 LMPT and 1255 term-born infants. Parents completed the M-CHAT questionnaire at 2-years corrected age. Parents of infants with positive questionnaire screens were followed up with a telephone interview to clarify failed items. The M-CHAT questionnaire was re-scored, and infants were classified as true or false positives. Neurosensory, cognitive, and behavioral outcomes were assessed using parent report. RESULTS Parents of 634 (57%) LMPT and 761 (62%) term-born infants completed the M-CHAT questionnaire. LMPT infants had significantly higher risk of a positive questionnaire screen compared with controls (14.5% vs 9.2%; relative risk [RR] 1.58; 95% CI 1.18, 2.11). After follow-up, significantly more LMPT infants than controls had a true positive screen (2.4% vs 0.5%; RR 4.52; 1.51, 13.56). This remained significant after excluding infants with neurosensory impairments (2.0% vs 0.5%; RR 3.67; 1.19, 11.3). CONCLUSIONS LMPT infants are at significantly increased risk for positive autistic screen. An M-CHAT follow-up interview is essential as screening for autism spectrum disorders is especially confounded in preterm populations. Infants with false positive screens are at risk for cognitive and behavioral problems.

Socioeconomic inequalities in survival and provision of neonatal care: population based study of very preterm infants

Objectives To assess socioeconomic inequalities in survival and provision of neonatal care among very preterm infants. Design Prospective cohort study in a geographically defined population. Setting Former Trent health region of the United Kingdom (covering about a twelfth of UK births). Participants All infants born between 22+0 and 32+6 weeks’ gestation from 1 January 1998 to 31 December 2007 who were alive at the onset of labour and followed until discharge from neonatal care. Main outcome measures Survival to discharge from neonatal care per 1000 total births and per 1000 very preterm births. Neonatal care provision for very preterm infants surviving to discharge measured with length of stay, provision of ventilation, and respiratory support. Deprivation measured with the UK index of multiple deprivation 2004 score at super output area level. Results 7449 very preterm singleton infants were born in the 10 year period. The incidence of very preterm birth was nearly twice as high in the most deprived areas compared with the least deprived areas. Consequently rates of mortality due to very preterm birth per 1000 total births were almost twice as high in the most deprived areas compared with the least deprived (incidence rate ratio 1.94, 95% confidence interval 1.62 to 2.32). Mortality rates per 1000 very preterm births, however, showed little variation across all deprivation fifths (incidence rate ratio for most deprived fifth versus least deprived 1.02, 0.86 to 1.20). For infants surviving to discharge from neonatal care, measures of length of stay and provision of ventilation and respiratory support were similar across all deprivation fifths. Conclusions The burden of mortality and morbidity is greater among babies born to women from deprived areas because of increased rates of very preterm birth. After very preterm birth, however, survival rates and neonatal care provision is similar for infants from all areas.