BACKGROUND:Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006.METHODS:We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery. Outcomes to discharge were compared between level 3 (most intensive) and level 2 maternity services, with and without transfers, and by activity level of level 3 neonatal unit; ORs were adjusted for gestation at birth and birthweight for gestation (adjusted ORs (aOR)).FINDINGS:Of this national birth cohort, 56% were born in maternity services with level 3 and 34% with level 2 neonatal units; 10% were born in a setting without ongoing intensive care facilities (level 1). When compared with level 2 settings, risk of death in level 3 services was reduced (aOR 0.73 (95% CI 0.59 to 0.90)), but the proportion surviving without neonatal morbidity was similar (aOR 1.27 (0.93 to 1.74)). Analysis by intended hospital of birth confirmed reduced mortality in level 3 services. Following antenatal transfer into a level 3 setting, there were fewer intrapartum or labour ward deaths, and overall mortality was higher for those remaining in level 2 services (aOR 1.44 (1.09 to 1.90)). Among level 3 services, those with higher activity had fewer deaths overall (aOR 0.68 (0.52 to 0.89)).INTERPRETATION:Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility. Survival was significantly enhanced following birth in level 3 services, particularly those with high activity; this was not at the cost of increased neonatal morbidity.

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Aim: To determine the diversity and stability of cultured vaginal lactobacilli in a multi-ethnic population of pregnant women.Methods and Results: A single-centre, prospective, cohort study was performed in a tertiary perinatal centre in East London, UK. Self-collected vaginal swabs at 13 and 20 weeks gestation were obtained from women attending for routine antenatal care and cultured for lactobacilli. In women who provided both swabs, 37 of 203 (18%) had no lactobacilli cultured at either time. Only 53 (26%) had the same species at both times. Black women were less likely to have lactobacilli cultured at 13 weeks (P = 0.014), and Black and Asian women were less likely to have lactobacilli cultured at 20 weeks (P = 0.002) compared with those in the White and Other groups.Conclusions: Significant differences exist between ethnic groups in the carriage and stability of vaginal lactobacilli.Significance and Impact of the Study: These differences have implications for the design of interventions aimed at normalizing the vaginal microbiota in pregnant women.

Objective To determine outcomes at age 3 years in babies born before 27 completed weeks' gestation in 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation.Design Prospective national cohort studies, EPICure and EPICure 2.Setting Hospital and home based evaluations, England.Participants 1031 surviving babies born in 2006 before 27 completed weeks' gestation. Outcomes for 584 babies born at 22-25 weeks' gestation were compared with those of 260 surviving babies of the same gestational age born in 1995.Main outcome measures Survival to age 3 years, impairment (2008 consensus definitions), and developmental scores. Multiple imputation was used to account for the high proportion of missing data in the 2006 cohort.Results Of the 576 babies evaluated after birth in 2006, 13.4% (n=77) were categorised as having severe impairment and 11.8% (n=68) moderate impairment. The prevalence of neurodevelopmental impairment was significantly associated with length of gestation, with greater impairment as gestational age decreased: 45% at 22-23 weeks, 30% at 24 weeks, 25% at 25 weeks, and 20% at 26 weeks (P<0.001). Cerebral palsy was present in 83 (14%) survivors. Mean developmental quotients were lower than those of the general population (normal values 100 (SD 15)) and showed a direct relation with gestational age: 80 (SD 21) at 22-23 weeks, 87 (19) at 24 weeks, 88 (19) at 25 weeks, and 91 (18) at 26 weeks. These results did not differ significantly after imputation. Comparing imputed outcomes between the 2006 and 1995 cohorts, the proportion of survivors born between 22 and 25 weeks' gestation with severe disability, using 1995 definitions, was 18% (95% confidence interval 14% to 24%) in 1995 and 19% (14% to 23%) in 2006. Fewer survivors had shunted hydrocephalus or seizures. Survival of babies admitted for neonatal care increased from 39% (35% to 43%) in 1995 to 52% (49% to 55%) in 2006, an increase of 13% (8% to 18%), and survival without disability increased from 23% (20% to 26%) in 1995 to 34% (31% to 37%) in 2006, an increase of 11% (6% to 16%).Conclusion Survival and impairment in early childhood are both closely related to gestational age for babies born at less than 27 weeks' gestation. Using multiple imputation to account for the high proportion of missing values, a higher proportion of babies admitted for neonatal care now survive without disability, particularly those born at gestational ages 24 and 25 weeks.

Objective To determine survival and neonatal morbidity for babies born between 22 and 26 weeks' gestation in England during 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation.Design Prospective national cohort studies.Setting Maternity and neonatal units in England.Participants 3133 births between 22 and 26 weeks' gestation in 2006; 666 admissions to neonatal units in 1995 and 1115 in 2006 of babies born between 22 and 25 weeks' gestation.Main outcome measures Survival to discharge from hospital, pregnancy and delivery outcomes, infant morbidity until discharge.Results In 2006, survival of live born babies was 2% (n=3) for those born at 22 weeks' gestation, 19% (n=66) at 23 weeks, 40% (n=178) at 24 weeks, 66% (n=346) at 25 weeks, and 77% (n=448) at 26 weeks (P<0.001). At discharge from hospital, 68% (n=705) of survivors had bronchopulmonary dysplasia (receiving supplemental oxygen at 36 weeks postmenstrual age), 13% (n=135) had evidence of serious abnormality on cerebral ultrasonography, and 16% (n=166) had laser treatment for retinopathy of prematurity. For babies born between 22 and 25 weeks' gestation from March to December, the number of admissions for neonatal care increased by 44%, from 666 in 1995 to 959 in 2006. By 2006 adherence to evidence based practice associated with improved outcome had significantly increased. Survival increased from 40% to 53% (P<0.001) overall and at each week of gestation: by 9.5% (confidence interval -0.1% to 19%) at 23 weeks, 12% (4% to 20%) at 24 weeks, and 16% (9% to 23%) at 25 weeks. The proportions of babies surviving in 2006 with bronchopulmonary dysplasia, major cerebral scan abnormality, or weight and/or head circumference <-2 SD were similar to those in 1995, but the proportion treated for retinopathy of prematurity had increased from 13% to 22% (P=0.006). Predictors of mortality and morbidity were similar in both cohorts.Conclusion Survival of babies born between 22 and 25 weeks' gestation has increased since 1995 but the pattern of major neonatal morbidity and the proportion of survivors affected are unchanged. These observations reflect an important increase in the number of preterm survivors at risk of later health problems.

Rationale: Increasing survival at extremely low gestational ages is associated with very high rates of bronchopulmonary dysplasia (BPD) but is rarely quantified. Objectives: To identify respiratory morbidity and risk factors in the EPICure cohort over the first 6 years of life. Methods: 308 babies born at ⩽25 weeks’ gestation in 1995 were followed up at 30 months and 6 years of age. Respiratory outcome was evaluated using clinical assessment, parental questionnaire and peak expiratory flow (PEF) at 6 years. Results: 74% of this population received supplemental oxygen at 36 weeks postmenstrual age and 36% were discharged with supplemental oxygen which continued for a median of 2.5 months (75th percentile: 8.5 months). 236 children were followed to 6 years. Respiratory symptoms and medication use were more prevalent at 30 months and 6 years in children with BPD compared to those without. Children without BPD (n = 56) were not significantly different from their classmates but had consistently higher prevalence of poor respiratory health. Symptoms, need for hospital admission and medication use declined between 30 months and 6 years. 200 index children completed three PEF measures; PEF was lower than in classmates (mean adjusted difference: 39 l/min (95% CI 30 to 47)) and was lowest in children discharged home with oxygen and in those with BPD. Gestational age, BPD and maternal smoking at home and in pregnancy were independent risk factors for symptoms, but BPD was the only independent associate of PEF. Conclusion: Extremely preterm children have a continuum of poor respiratory health over the first 6 years, which is exacerbated by smoking during pregnancy and in the home.

Background The EPICure 2 study shows increased survival (40–52%, p Objective To explore reasons for increased survival by studying survival curves and changes in the population and clinical practice between 1995 and 2006. Results Analysis of survival curves of admissions (1995: n = 811; 2006: n = 952) shows that the difference in survival is apparent shortly after birth; survival curves for babies still alive at 7 days are not significantly different at any gestation. Comparing demographic and clinical items known within 24 h of birth shows increased use of steroids (67–82%) and tocolysis (24–34%), fewer white (78–66%) and more Afro-Caribbean mothers (13–20%), more babies with heart rate greater than 100 bpm at 5 minutes (86–91%), less neonatal hypothermia (40–16%) and more surfactant use (85–97%), all p⩽0.001. There was a non-significant trend towards a lower CRIB 1 score at all gestations. Logistic regression analysis using these and other factors with the outcomes: death, severely abnormal head scan, treated retinopathy of prematurity and oxygen supplementation at expected delivery date shows similar patterns of association in the two cohorts. Conclusions The increase in survival for babies less than 26 weeks seen in EPICure 2 is confined to the first week. This is associated with evidence of babies being in better condition around the time of birth.

Acinetobacter spp. are increasingly reported as important causes of human infection. Many isolates exhibit multi-drug resistance, raising concerns over our ability to treat serious infections with these organisms. The impact of infection on clinical outcome as well as the importance of multi-drug resistance is poorly defined. A descriptive retrospective observational study was undertaken of all episodes of Acinetobacter bacteremia occurring in a UK tertiary care centre from 1998-2006. Demographics of infected patients, characteristics and antimicrobial susceptibility of infecting strains were recorded and the impact of antimicrobial therapy on all causes of 30-day mortality assessed. Three hundred ninety-nine episodes of Acinetobacter bacteremia were identified, with A. baumannii being the most frequently isolated species. Most episodes occurred in critical care and were associated with multidrug resistance, with carbapenem resistance rising from 0% in 1998 to 55% in 2006. Although bacteremia due to carbapenem-resistant Acinetobacter and a requirement for critical care were associated with a higher mortality, mortality was not reduced by the administration of appropriate empirical antimicrobial therapy. A prospective study is required to identify both the most effective intervention and those most likely to benefit from treatment.

Live birth rate (LBR), age and basal serum FSH values were analysed in 1589 women undergoing their first cycle of IVF. Four age groups (<30, 30-34, 35-38, 39-45 years) and three FSH groups (<5, 5-9.9, > or =10 IU/l) were established. Logistic regression analysis was used to determine the effect of age and FSH on live birth. A model to predict the probability of a live birth suggests that an additional 10 years of age reduces the odds for live birth (OR = 0.66, 95% CI 0.48-0.91); an increase of FSH by 5 IU/l reduces the probability of live birth (OR = 0.75, 95% CI 0.61-0.92); women > or =39 years have an additional reduction in probability of live birth (OR = 0.58, 95% CI 0.61-0.92). Analysis by age and FSH categories showed that pregnancy rate (PR) did not change significantly with rising FSH for women <35 years old. In cycles started with serum FSH <5 IU/l, increasing age did not effect PR and LBR. Cycles started with serum FSH > or =10 IU/l had a PR and LBR of 23.6 and 16.9% respectively. The clinical relevance of elevated FSH varies according to age; younger women with elevated FSH and older women with low FSH still have an acceptable LBR.

Background: Preterm children are at risk for reduced growth in early childhood, which may predispose them to later changes in blood pressure (BP). Objective: To study growth and BP in extremely preterm (EP) children at age 6 years. Methods: Children who were born at 25 completed weeks of gestation or less in the United Kingdom and Ireland in 1995 were evaluated when they reached early school age. Children underwent standardised assessments, including auxology and sitting BP. Results: Of 308 surviving children, 241 (78%) were assessed at a median age of 6 years 4 months; 160 full-term classmates acted as a comparison group. Compared with classmates, EP children were 1.2 standard deviations (SDs) lighter, 0.97 SD shorter, body mass index (BMI) was 0.95 SD lower and head circumference 1.3 SD lower. Compared with 2.5 years of age, EP children had shown “catch-up” in their weight by 0.37 SD, height by 0.42 SD and head circumference by 0.13 SD. Systolic and diastolic BP were lower by 2.3 mm Hg and 2.4 mm Hg, respectively, in EP children, but these differences were accounted for by differences in height and BMI. Maternal smoking in pregnancy was associated with lower BP. Children born before 24 weeks had higher systolic pressures and children given postnatal steroids higher diastolic pressures. Conclusions: Poor postnatal growth seen after birth and in the third year persists into school age. Catch-up growth reduces some of the early deficit but is least for head growth. Despite serious postnatal growth restriction BP appears similar in both EP and term classmates.

Blood samples were collected for quantitative 16S rDNA analysis from the vascular access device (VAD) of patients presenting with fever at participating centres of the UK Children's Cancer and Leukaemia Group. In total, 260 of 301 episodes of fever were evaluable and were classified as probable, possible, unlikely or unclassifiable VAD-associated infection. The sensitivity of the 16S rDNA assay declined concomitantly with delays from time of presentation to sampling. The sensitivity with >0.125 pg of bacterial DNA/microL of whole blood was 80% for the 20 probable VAD-associated infections diagnosed with samples collected on the day of or day following presentation. The specificity rose with increasing amounts of bacterial DNA, from 93% with >0.125 pg, to 98% with 0.25-0.5 pg, and to 100% with >0.5 pg/microL blood. The positive predictive value (for probable or possible) was 88% (95% CI 70-98%) with 0.25 pg/microL, and 100% (95% CI 83-100%) with >0.5 pg/microL. All 18 (6.8%) episodes with >0.5 pg of bacterial DNA/microL blood were associated with positive blood cultures. Identifications derived from the DNA sequence were consistent with the blood culture identifications for 15 of the 17 episodes with a DNA sequence identification. The VAD was removed because of suspected infection in six (2.8%) of 216 episodes with <0.125 pg of bacterial DNA/microL, in one (5%) of 20 episodes with 0.125-0.25 pg/microL, in one (16.7%) of six episodes with 0.25-0.5 pg/microL, and in nine (50%) of 18 episodes with >0.5 pg/microL. A bacterial DNA concentration of >0.5 pg/microL in blood drawn through a central venous catheter at the time of fever presentation had a high positive predictive value for VAD-associated infection and predicted an increased risk of VAD removal because of suspected infection.

Aims: To describe perinatal factors associated with later morbidity among extremely preterm children at 30 months of age corrected for prematurity. Population: Of 308 surviving children born at ⩽25 weeks gestation in the United Kingdom and Ireland from March to December 1995, 283 (92%) were evaluated at 30 months of age corrected for prematurity. Methods: Cerebral palsy, severe motor disability, and Bayley scores were used as dependent variables in sequential multiple regression analyses to identify factors associated with adverse outcomes. Results: Adverse outcomes were consistently more common in boys. Factors related to perinatal illness, ultrasound evidence of brain injury, and treatment (particularly postnatal steroids) were associated with adverse motor outcomes (cerebral palsy, disability or Bayley psychomotor development index). Increasing duration of postnatal steroid treatment was associated with poor motor outcomes. A score was developed for severe motor disability with good negative predictive value. In contrast, mental development was associated with a broader range of factors: ethnic group, maternal educational level, the use of antenatal steroids, and prolonged rupture of membranes in addition to chronic lung disease. Conclusion: Male sex is a pervasive risk factor for poor outcome at extremely low gestations. Avoidable or effective treatment factors are identified, which may indicate the potential for improving outcome.

AIM:To define growth outcomes of a geographically defined population of extremely preterm babies. POPULATION:The EPICure study identified all surviving children in the United Kingdom and Ireland born at < or = 25 weeks 6 days gestation between March and December 1995. Of 308 survivors, 283 (92%) were evaluated at 30 months of age corrected for prematurity. METHODS:Growth was measured as part of a medical and full neurodevelopmental assessment. Growth parameters were evaluated in relation to other 30 month outcomes and perinatal variables. RESULTS:The children were smaller in each of the five growth measures compared with published population norms: mean (SD) standard deviation scores were -1.19 (1.32) for weight, -1.40 (1.37) for head circumference, -0.70 (1.19) for height, -1.00 (1.38) for body mass index, and -0.75 (0.95) for mid-upper arm circumference. Despite being of average size at birth, children were significantly lighter with smaller head circumferences at the expected date of delivery, compared with population norms, and only weight showed later catch up, by 0.5 SD. Poorer growth was found in children whose parents reported feeding problems and with longer duration of oxygen dependency, as a marker for neonatal respiratory illness. Although severe motor disability was associated with smaller head circumference, overall there was no relation between Bayley scores and head growth. CONCLUSIONS:Poor growth in early childhood is common in extremely preterm children, particularly when prolonged courses of systemic steroids have been given for chronic lung disease. Improving early growth must be a priority for clinical care.