Enid Hennessy

The EPICure Study: Outcomes to Discharge From Hospital for Infants Born at the Threshold of Viability

Objective. To evaluate the outcome for all infants born before 26 weeks of gestation in the United Kingdom and the Republic of Ireland. This report is of survival and complications up until discharge from hospital. Methodology. A prospective observational study of all births between March 1, 1995 and December 31, 1995 from 20 to 25 weeks of gestation. Results. A total of 4004 births were recorded, and 811 infants were admitted for intensive care. Overall survival was 39% (n = 314). Male sex, no reported chorioamnionitis, no antenatal steroids, persistent bradycardia at 5 minutes, hypothermia, and high Clinical Risk Index for Babies (CRIB) score were all independently associated with death. Of the survivors, 17% had parenchymal cysts and/or hydrocephalus, 14% received treatment for retinopathy of prematurity (ROP), and 51% needed supplementary oxygen at the expected date of delivery. Failure to administer antenatal steroids and postnatal transfer for intensive care within 24 hours of birth were predictive of major scan abnormality; lower gestation was predictive of severe ROP, while being born to a black mother was protective. Being of lower gestation, male sex, tocolysis, low maternal age, neonatal hypothermia, a high CRIB score, and surfactant therapy were all predictive of oxygen dependency. Intensive care was provided in 137 units, only 8 of which had >5 survivors. There was no difference in survival between institutions when divided into quintiles based on their numbers of extremely preterm births or admissions. Conclusions. This study provides outcome data for this geographically defined cohort; survival and neonatal morbidity are consistent with previous data from the United Kingdom and facilitate comparison with other geographically based data.

The EPICure study: associations and antecedents of neurological and developmental disability at 30 months of age following extremely preterm birth

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.

Lung function and respiratory symptoms at 11 years in children born extremely preterm: the EPICure study.

RATIONALE The long-term respiratory sequelae of infants born extremely preterm (EP) and now graduating from neonatal intensive care remains uncertain. OBJECTIVES To assess the degree of respiratory morbidity and functional impairment at 11 years in children born EP (i.e., at or less than 25 completed weeks of gestation) in relation to neonatal determinants and current clinical status. METHODS Pre- and postbronchodilator spirometry were undertaken at school in children born EP and classroom control subjects. Physical examination and respiratory health questionnaires were completed. Multivariable regression was used to estimate the predictive power of potential determinants of lung function. MEASUREMENTS AND MAIN RESULTS Spirometry was obtained in 182 of 219 children born EP (129 with prior bronchopulmonary dysplasia [BPD]) and 161 of 169 classmates, matched for age, sex, and ethnic group. Children born EP had significantly more chest deformities and respiratory symptoms than classmates, with twice as many (25 vs. 13%; P < 0.01) having a current diagnosis of asthma. Baseline spirometry was significantly reduced (P < 0.001) and bronchodilator responsiveness was increased in those born EP, the changes being most marked in those with prior BPD. EP birth, BPD, current symptoms, and treatment with beta-agonists are each associated independently with lung function z-scores (adjusted for age, sex, and height) at 11 years. Fifty-six percent of children born EP had abnormal baseline spirometry and 27% had a positive bronchodilator response, but less than half of those with impaired lung function were receiving any medication. CONCLUSIONS After extremely preterm birth, impaired lung function and increased respiratory morbidity persist into middle childhood, especially among those with BPD. Many of these children may not be receiving appropriate treatment.

Academic attainment and special educational needs in extremely preterm children at 11 years of age: the EPICure Study

Aim: To assess academic attainment and special educational needs (SEN) in extremely preterm children in middle childhood. Methods: Of 307 extremely preterm (⩽25 weeks) survivors born in the UK and Ireland in 1995, 219 (71%) were re-assessed at 11 years of age and compared to 153 classmates born at term, using standardised tests of cognitive ability and academic attainment and teacher reports of school performance and SEN. Multiple imputation was used to correct for selective dropout. Results: Extremely preterm children had significantly lower scores than classmates for cognitive ability (−20 points; 95% CI −23 to −17), reading (−18 points; −22 to −15) and mathematics (−27 points; −31 to −23). Twenty nine (13%) extremely preterm children attended special school. In mainstream schools, 105 (57%) extremely preterm children had SEN (OR 10; 6 to 18) and 103 (55%) required SEN resource provision (OR 10; 6 to 18). Teachers rated 50% of extremely preterm children as having below average attainment compared with 5% of classmates (OR 18; 8 to 41). Extremely preterm children who entered compulsory education an academic year early due to preterm birth had similar academic attainment but required more SEN support (OR 2; 1.0 to 3.6). Conclusions: Extremely preterm survivors remain at high risk for learning impairments and poor academic attainment in middle childhood. A significant proportion require full-time specialist education and over half of those attending mainstream schools require additional health or educational resources to access the national curriculum. The prevalence and impact of SEN are likely to increase as these children approach the transition to secondary school.

Autism spectrum disorders in extremely preterm children.

OBJECTIVES To investigate the prevalence, correlates, and antecedents of autism spectrum disorders (ASD) in extremely preterm children. STUDY DESIGN We conducted a prospective study of all births <26 weeks gestation in the United Kingdom and Ireland in 1995. Of 307 survivors at 11 years, 219 (71%) were assessed and compared with 153 term-born classmates. Parents completed the Social Communication Questionnaire (SCQ) to assess autism spectrum symptoms, and ASD were diagnosed by using a psychiatric evaluation. An IQ test and clinical evaluation were also administered. Longitudinal outcome data were available for extremely preterm children. RESULTS Extremely preterm children had significantly higher SCQ scores than classmates (mean difference, 4.6 points; 95% CI, 3.4-5.8). Sixteen extremely preterm children (8%) were assigned an ASD diagnosis, compared with none of the classmates. By hospital discharge, male sex, lower gestation, vaginal breech delivery, abnormal cerebral ultrasound scanning results, and not having had breast milk were independently associated with autism spectrum symptoms. By 6 years, independent associates were cognitive impairment, inattention and peer problems, withdrawn behavior at 2.5 years, and not having had breast milk. CONCLUSIONS Extremely preterm children are at increased risk for autism spectrum symptoms and ASD in middle childhood. These symptoms and disorders were associated with neurocognitive outcomes, suggesting that ASD may result from abnormal brain development in this population.

The EPICure study: growth and associated problems in children born at 25 weeks of gestational age or less

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 ⩽ 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.

Educational Outcomes in Extremely Preterm Children: Neuropsychological Correlates and Predictors of Attainment

This study assessed the impact of extremely preterm birth on academic attainment at 11 years of age, investigated neuropsychological antecedents of attainment in reading and mathematics, and examined early predictors of educational outcomes. Children born extremely preterm had significantly poorer academic attainment and a higher prevalence of learning difficulties than their term peers. General cognitive ability and specific deficits in visuospatial skills or phoneme deletion at 6 years were predictive of mathematics and reading attainment at 11 years in both extremely preterm and term children. Phonological processing, attention, and executive functions at 6 years were also associated with academic attainment in children born extremely preterm. Furthermore, social factors, neonatal factors (necrotizing enterocolitis, breech delivery, abnormal cerebral ultrasound, early breast milk provision), and developmental factors at 30 months (head circumference, cognitive development), were independent predictors of educational outcomes at 11 years. Neonatal complications combined with assessments of early cognitive function provide moderate prediction for educational outcomes in children born extremely preterm.

Relationship between test scores using the second and third editions of the Bayley Scales in extremely preterm children.

OBJECTIVE To define the relationship between current Bayley Scales of Infant and Toddler Development, Third edition (Bayley-III) scores and the Bayley Scales of Infant Development, second edition Mental Development Index (MDI) to aid the comparison of population outcomes. STUDY DESIGN MDI and Bayley-III cognitive/language scales were administered concurrently in 185 extremely preterm children (≤26 weeks) at 29-41 months of age. Cognitive and language scores were combined (combined Bayley-III score [CB-III scores]) for comparison with MDI scores. RESULTS Bayley-III cognitive and language scores were 10 and 3 points higher than MDI scores, respectively; CB-III scores were 7 points higher. The relationship between CB-III and MDI scores was not a simple offset: CB-III values were increasingly higher than MDI at lower scores. Bayley-III scores underidentified MDI scores <70 (sensitivity 58%; specificity 100%). An algorithm for converting Bayley-III scores into MDI scores improved predictive value (sensitivity 95%; specificity 97%). Bayley-III scores <80 were similarly predictive (sensitivity 89%; specificity 99%). CONCLUSIONS We recommend caution in the interpretation of Bayley-III scores in population studies as the correlation with the previous edition appears worse at lower test score values and the predictive value for IQ is as yet unclear.

Respiratory health in pre-school and school age children following extremely preterm birth

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.

Bloodstream infection due to Acinetobacter spp: epidemiology, risk factors and impact of multi-drug resistance

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.