Impact of obstetric interventions on condition at birth in extremely preterm babies: evidence from a national cohort study.

BACKGROUND: To investigate perinatal decision-making and the use of obstetric interventions, we examined the effects of antenatal steroids, tocolysis, and delivery mode on birth in a good condition (defined as presence of an infant heart rate >100 at five minutes of age) and delivery-room (DR) death in extremely preterm deliveries. METHODS: Prospective cohort of all singleton births in England in 2006 at 22-26 weeks of gestation where the fetus was alive at the start of labour monitoring or decision to perform caesarean section. Odds ratios adjusted for potential confounders (aOR) were calculated using logistic regression. RESULTS: One thousand seven hundred twenty two singleton pregnancies were included. 1231 women received antenatal steroids, 437 tocolysis and 356 delivered by Caesarean section. In babies born vaginally, aOR between a partial course of steroids and improved condition at birth was 1.84, 95% CI: 1.20 to 2.82 and, for a complete course, 1.63, 95% CI: 1.08 to 2.47; for DR death, aORs were 0.34 (0.21 to 0.55) and 0.41 (0.26 to 0.64) for partial and complete courses of steroids. No association was seen for steroid use in babies delivered by Caesarean section. Tocolysis was associated with improved condition at birth (aOR 1.45, 95% CI: 1.05 to 2.0) and lower odds of death (aOR 0.48, 95% CI: 0.32 to 0.73). In women without spontaneous labour, Caesarean delivery at ≤24 and 25 weeks was associated with improved condition at birth ((aORs 12.67 (2.79 to 57.60) and 4.94 (1.44 to 16.90), respectively) and lower odds of DR death (aORs 0.03 (0.01 to 0.21) and 0.13 (0.03 to 0.55)). There were no differences at 26 weeks gestation or in women with spontaneous labour. CONCLUSIONS: Antenatal steroids are strongly associated with improved outcomes in babies born vaginally. Tocolysis was associated with improvements in all analyses. Effects persisted after adjustment for perinatal decision-making. However, associations between delivery mode and birth outcomes may be attributable to case selection.

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.

The EPICure study: association between hemodynamics and lung function at 11 years after extremely preterm birth.

OBJECTIVE: To investigate the relationship between disturbed lung function and large-artery hemodynamics in school-age children born extremely preterm (EP) (at 25 completed weeks of gestation or less). STUDY DESIGN: This was a cross-sectional study of participants from the EPICure study, now aged 11 years (n = 66), and 86 age- and sex-matched term-born classmates. Spirometry parameters (including forced expiratory volume in 1 second), blood pressure, and augmentation index (AIx, a composite of arterial stiffness and global wave reflections) were measured. RESULTS: Compared with their classmates, the EP children had significantly impaired lung function, particularly those with neonatal bronchopulmonary dysplasia. Peripheral blood pressure did not differ significantly between the 2 groups, but AIx values were on average 5% higher (95% CI, 2%-8%) in the preterm infants, remaining significant after adjustment for potential confounders. Neonatal bronchopulmonary dysplasia status was not related to AIx. Lung function and maternal smoking were independently associated with AIx; AIx increased by 2.7% per z-score reduction in baseline forced expiratory volume in 1 second and by 4.9% in those whose mothers smoked during pregnancy. CONCLUSION: The independent association between impaired lung function and cardiovascular physiology in early adolescence implies higher cardiovascular risk for children born EP, and suggests that prevention of chronic neonatal lung disease may be a priority in reducing later cardiovascular risk in preterm infants.

Screening for autism in extremely preterm infants: problems in interpretation.

AIM: The aim of this article was to report the prevalence of, and risk factors for, positive autism screens using the Modified Checklist for Autism in Toddlers (M-CHAT) in children born extremely preterm in England. METHOD: All children born at not more than 26 weeks' gestational age in England during 2006 were recruited to the EPICure-2 study. At 2 years of age, postal questionnaires incorporating the M-CHAT and additional developmental questions were sent to the parents of each survivor (n=1031; 499 male, 532 female), of which 523 (266 male, 257 female; 51%) were returned completed. RESULTS: The prevalence of positive M-CHAT screens in this extremely preterm population was 41% (216/523; 130 male; 86 female). Severe bronchopulmonary dysplasia, administration of postnatal steroids, late-onset bacteraemia, and being male were statistically significantly associated with a positive screen. Coexisting disabilities were present in 320 (62%) children. Of 200 children without disability, 16.5% screened positive. In contrast, 63 (95.5%) of those with severe motor impairment (odds ratio 42; 95% confidence interval [CI] 12.9-135) and 175 (55.9%) of those with cognitive impairment (odds ratio 5.3; CI 3.5-8) screened positive. All children with a significant vision or hearing impairment screened positive. INTERPRETATION: The prevalence of positive M-CHAT screens in extremely preterm children is high, especially in children with neurodevelopmental impairment. Positive screens should be interpreted in the light of other neurodevelopmental sequelae in clinical practice to avoid false-positive referrals.

Cumulative flying time and risk of venous thromboembolism.

The risk of venous thromboembolism (VTE) associated with cumulative flying time remains uncertain. In a case-control study in general practices throughout the UK, participants comprised 550 VTE cases identified from practice records and 1971 age- and gender-matched controls. Participants returned identical questionnaires asking for information including air travel details. Compared to not flying, cumulative flying time >12 h within the previous 4 weeks was associated with a threefold increase in the risk of VTE [odds ratio (OR) 2·75, 95% confidence interval (CI), 1·44-5·28]. Those who had flown >4 h in a single leg in the previous 4 weeks had twice the risk of VTE (OR 2·20, 95% CI, 1·29-3·73). These risks were no longer evident by 12 weeks and were similar to those of day-case or minor surgery (OR 5·35, 95% CI, 2·15-13·33). Equivalent risks for moderate and high-risk surgery were over 30-fold (OR 36·57, 95% CI, 13·05-102·52) and 140-fold (OR 141·71, 95% CI, 19·38-1036·01) respectively. The temporary nature of the association of cumulative and long-haul air travel with VTE suggests a causal relationship. The risks of VTE in those with a higher baseline risk due to surgery, previous VTE or obesity are further increased by air travel.

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.

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.

Colonization and persistence of antibiotic-resistant Enterobacteriaceae strains in infants nursed in two neonatal intensive care units in East London, United Kingdom.

Stool samples were collected from infants nursed in two neonatal intensive care units (NICUs) in East London, United Kingdom. The aim of the study was to determine the incidence of and risk factors for the carriage of multiresistant Enterobacteriaceae strains (MRE; resistant to three or more classes of antibiotic) and the extent of the persistence of resistant strains following discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of postnatal age, and 69 (56%) infants had acquired MRE by discharge. The proportions of infants at 2 weeks carrying strains that were resistant to antibiotics were the following: tetracycline, 79%; amoxicillin, 78%; cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%; chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26 weeks was a risk factor for colonization with MRE at discharge, but not at 2 weeks. Analysis within a NICU showed that exposure of an infant to a specific antibiotic in the NICU was not a risk factor for the carriage of a strain resistant to that antibiotic. Estimates of persistence from discharge to 6 months were the following: for tetracycline, 57% (95% confidence intervals [CI], 0.35 to 0.87); chloramphenicol, 49% (95% CI, 0.20 to 0.83); trimethoprim, 45% (95% CI, 0.22 to 0.74); piperacillin-tazobactam, 42% (95% CI, 0.20 to 0.71); and augmentin, 34% (95% CI, 0.11 to 0.66). Strains resistant to cephalosporins or aminoglycosides showed lower levels of persistence. Nine of 34 infants (26.5%) with Escherichia coli and 4 (7.1%) of 56 infants with Klebsiella spp. at discharge carried strains indistinguishable by randomly amplified polymorphic DNA and antibiotic susceptibility patterns at 6 months. MRE were found at high frequency in the infants during their stay in the NICU and persisted in a proportion of infants.

Longitudinal trends in quality of life after starting home parenteral nutrition: a randomised controlled study of telemedicine.

BACKGROUND AND AIMS: This study defines and quantifies longitudinal changes in quality of life (QoL) at the time of first discharge home on home parenteral nutrition (HPN) and over the first year. METHODS: Results were compared in patients in standard contact with a nutrition nurse specialist by telephone, with results of those in contact via telemedicine in a randomised controlled trial. Participants were recruited from nine UK HPN centres. Patients were randomised to receive telemedicine upon initial discharge or after 1 year. The SF36 was the principal instrument chosen to determine QoL throughout the year on three predetermined occasions. EQ5D and hospital anxiety and depression scores were also recorded. RESULTS: Thirty participants were recruited to the study from March 2001 to June 2003. In all domains, QoL scores were significantly lower than normative data at discharge. QoL scores significantly improved over the first 6 months in physical functioning, physical role (RP), vitality (VT), social functioning (SF), emotional-role (RE) domains, and mental component summary (MCS). At 6 months RE, mental health (MH) and MCS were no longer significantly lower than normative data. There was no significant change in bodily pain (BP), general health (GH), MH, and physical component summary (PCS). Opiate use significantly reduced SF36 domains RP, BP, VT, SF, MH, and MCS at 6 months and was associated with more subsequent inpatient episodes and central line reinsertions. Patients with an acute onset of intestinal failure had less pain and better GH scores at 6 months, and had less inpatient episodes after discharge than patients with a more chronic onset. Telemedicine had no impact on QoL or subsequent clinical outcome. CONCLUSIONS: Aspects of QoL improve over the first 6 months of HPN. Opiate use and chronic diagnosis have a negative impact on some elements of QoL and clinical outcome variables.

Measurements of gastric emptying during continuous nasogastric infusion of liquid feed: electric impedance tomography versus gamma scintigraphy.

BACKGROUND & AIMS: Continuous nasogastric infusion is commonly used to deliver enteral feed but current methods used to assess tolerance based on aspiration and measurement of gastric residual volume have been criticised. Electric impedance tomography (EIT) measures gastric emptying by monitoring changes in epigastric impedance when a meal progressively empties from the stomach. AIMS: (1) to establish whether EIT was a valid method for measuring gastric emptying during continuous nasogastric infusion by comparing it with gamma scintigraphy (GS) and (2) to provide data on gastric emptying patterns during continuous nasogastric infusion. METHODS: Gastric emptying of 400 ml of enteral feed given over 200 min was measured simultaneously using EIT and GS in 10 healthy volunteers (five male and five female). RESULTS: Gastric emptying curves were obtained in 10 subjects by EIT but only eight by GS. Visual examination of the curves showed reasonable agreement. Patterns of emptying and filling during continuous nasogastric infusion were variable between individuals; the prevailing pattern was a trend towards a steady-state volume of approximately 50-125 ml. CONCLUSIONS: While EIT does not provide an accurate estimate of gastric volume during continuous infusion, it does show patterns of gastric emptying over time. With further development this could make it a useful tool for monitoring gastric emptying in patients at risk of gastroparesis.

Antecedents of Attention-Deficit/Hyperactivity Disorder Symptoms in Children Born Extremely Preterm.

OBJECTIVE: To investigate antecedents of attention-deficit/hyperactivity disorder (ADHD) symptoms in children born extremely preterm (EP; <26-wk gestation). METHOD: The EPICure study recruited all babies born EP in the United Kingdom and Ireland in March-December 1995. Neurodevelopmental outcomes were assessed at 2.5 (n = 283; 90%), 6 (n = 160; 78%), and 11 (n = 219; 71%) years of age. Parents and teachers completed the DuPaul Rating Scale IV to assess inattention and hyperactivity/impulsivity symptoms at 11 years. Regression analyses were used to explore the association of neonatal, neurodevelopmental, and behavioral outcomes to 6 years with ADHD symptoms at 11 years. RESULTS: Extremely preterm (EP) children had significantly more inattention (mean difference, 1.2 SD; 95% CI, 0.9-1.5) and hyperactivity/impulsivity (mean difference, 0.5 SD; 95% CI, 0.2-0.7) than controls, with a significantly greater effect size for inattention than hyperactivity/impulsivity. Significant independent predictors of inattention at 11 years included smaller head circumference, lower intelligence quotient (IQ), and pervasive peer relationship problems at 6 years, and motor development at 2.5 years. In contrast, significant independent predictors of hyperactivity/impulsivity included lower IQ, pervasive conduct problems and ADHD symptoms at 6 years, externalizing problems at 2.5 years, and non-white maternal ethnicity. CONCLUSIONS: Extremely preterm children are at increased risk for ADHD symptoms, predominantly inattention, for which the antecedents differ by symptom domain. Attention deficits after EP birth were associated with poor brain growth and neurological function. Cognitive and behavioral assessments in early and middle childhood to identify neurodevelopmental and peer relationship problems may be beneficial for identifying EP children at risk for inattention.

TOIB Study. Are topical or oral ibuprofen equally effective for the treatment of chronic knee pain presenting in primary care: a randomised controlled trial with patient preference study. [ISRCTN79353052].

BACKGROUND: Many older people have chronic knee pain. Both topical and oral non- steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat this. Oral NSAIDS are effective, at least in the short term, but can have severe adverse effects. Topical NSAIDs also appear to be effective, at least in the short term. One might expect topical NSAIDs both to be less effective and to have fewer adverse effects than oral NSAIDs. If topical NSAIDs have fewer adverse effects this may outweigh both the reduction in effectiveness and the higher cost of topical compared to oral treatment. Patient preferences may influence the comparative effectiveness of drugs delivered via different routes. METHODS: TOIB is a randomised trial comparing topical and oral ibuprofen, with a parallel patient preference study. We are recruiting people aged 50 or over with chronic knee pain, from 27 MRC General Practice Research Framework practices across the UK. We are seeking to recruit 283 participants to the RCT and 379 to the PPS. Participants will be followed up for up to two years (with the majority reaching one year). Outcomes will be assessed by postal questionnaire, nurse examination, laboratory tests and medical record searches at one and two years or the end of the study. DISCUSSION: This study will provide new evidence on the overall costs and benefits of treating chronic knee pain with either oral or topical ibuprofen. The use of a patient preference design is unusual, but will allow us to explore how preference influences response to a medication. In addition, it will provide more information on adverse events. This study will provide evidence to inform primary care practitioners, and possibly influence practice.

A comparison of mid upper arm circumference, body mass index and weight loss as indices of undernutrition in acutely hospitalized patients.

A nutritional supplementation trial (Vlaming et al., Clin Nutr 2001; 20: 517) enabled us to assess the nutrition of 1561 patients on emergency admission to hospital. Patients acutely admitted to the 15 relevant medical, surgical and orthopaedic wards were identified. Mid upper arm circumference (MUAC) measurements were obtained in 95% (848 m, 635f) patients. For clinical reasons, Body mass index (BMI) was assessable in only 44% patients (408 m, 285f). Data on three month weight loss were obtainable in 509 patients. These measurements combined to demonstrate that 18.3% of patients were undernourished (At least one of : BMI<20 kg/m(2) or MUAC<25 cm or loss of weight > or =10%). There was a close relationship between BMI and MUAC. Regression equations (excluding age)were for men : BMI=1.01 x MUAC-4.7, (R(2)=0.76), and for women BMI=1.10 x MUAC-6.7, (R(2)=0.76). After adjustment for age, weight loss > or =10% was the most significant of the three as a predictor of mortality. Among patients in whom weight loss was not recorded MUAC was a significant predictor of mortality either alone (P=0.002) or after adjustment for BMI (P=0.007), but BMI was not significant. All three measures, even when adjusted for age and sex, were poor predictors of hospital stay although MUAC was significant in the larger group with a MUAC measure (R(2)=0.7% P<0.001). MUAC correlates closely with BMI, is easier to measure and predicts poor outcome better.

Boosting uptake of influenza immunisation: a randomised controlled trial of telephone appointing in general practice.

BACKGROUND: Immunisation against influenza is an effective intervention that reduces serologically confirmed cases by between 60% and 70%. Almost all influenza immunisation in the UK is done within general practice. Current evidence on the effectiveness of patient reminders for all types of immunisation programmes is largely based on North American studies. AIM: To determine whether telephone appointments offered bygeneral practice receptionists increase the uptake of irfluenza immunisation among the registered population aged over 65 years in east London practices. DESIGN OF STUDY: Randomised controlled trial. SETTING: Three research general practices within the East London and Essex network of researchers (ELENoR). METHOD: Participants were 1,820 low-risk patients aged 65 to 74 years who had not previously been in a recall system for influenza immunisation at their general practice. The intervention, during October 2000, was a telephone call from the practice receptionist to intervention group households, offering an appointment for influenza immunisation at a nurse-run. clinic Main outcome measures were the numbers of individuals in each group receiving immunisation, and practice costs of a telephone-appointing programme. RESULTS: intention to treat analysis showed an immunisation rate in the control group of 44%, compared with 50% in the intervention group (odds ratio = 1.29, 95% confidence interval = 1.03 to 1.63). Of the patients making a telephone appointment, 88% recieved immunisation, while 22% of those not wanting an appointment went on to be immunised. In the controlgroup, income generated was 11.35 pounds per immunisation, for each additional immunisation in the intervention group the income was 5.20 pounds. The 'number needed to telephone' was 17. CONCLUSION: Uptake of influenza immunisation among the low-risk older population in inner-city areas can be boosted by around 6% using a simple intervention by receptionists. Immunisation rates in this low-risk group fell well short of the 60% government target. Improving immunisation rates will require a sustained public health campaign. Retaining the item-of-service payments to practices should support costs of practice-based interventions.

Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies.

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.

Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies).

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.

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.

Screening for autism in preterm children: diagnostic utility of the Social Communication Questionnaire.

OBJECTIVE: Preterm survivors are at high risk for autism spectrum disorders (ASD). The diagnostic utility of the Social Communication Questionnaire (SCQ) in screening for ASD was assessed in extremely preterm children at 11 years of age. DESIGN: All babies born at <26 weeks gestation in UK and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors, 219 (71%) were assessed at 11 years. Parents of 173 children completed the SCQ to screen for autistic features and the Development and Well Being Assessment (DAWBA) psychiatric interview. A consensus diagnosis of ASD was assigned by two child psychiatrists following review of the DAWBA parental interview and corresponding DAWBA teacher questionnaire. SETTING: Community-based follow-up. RESULTS: Using the established SCQ cut-off (scores ≥15), 28 (16%) extremely preterm children screened positive for ASD. Eleven (6%) were assigned a diagnosis of ASD. Using this cut-off, the SCQ had 82% sensitivity and 88% specificity for identifying ASD in this population. Using a receiver operating characteristic curve, SCQ scores ≥14 had optimal diagnostic utility (area under curve: 0.94; sensitivity: 91%; specificity: 86%). Positive predictive value was relatively low (31%) resulting in numerous over-referrals. However, children with false positive screens had significantly worse neuro-developmental, cognitive and behavioural outcomes than those with true negative screens. CONCLUSION: The SCQ has good diagnostic utility for identifying ASD in extremely preterm children and is a useful screening tool in this population. Children with false positive screens represent a high-risk group in whom further diagnostic assessment would be beneficial.

Cardiovascular consequences of extreme prematurity: the EPICure study.

OBJECTIVES: The long-term consequences of extreme prematurity are becoming increasingly important, given recent improvements in neonatal intensive care. The aim of the current study was to examine the cardiovascular consequences of extreme prematurity in 11-year-olds born at or before 25 completed weeks of gestation. METHODS: Age and sex-matched classmates were recruited as controls. Information concerning perinatal and maternal history was collected, and current anthropometric characteristics were measured in 219 children born extremely preterm and 153 classmates. A subset of the extremely preterm children (n = 68) and classmates (n = 90) then underwent detailed haemodynamic investigations, including measurement of supine blood pressure (BP), aortic pulse wave velocity (aPWV, a measure of aortic stiffness) and augmentation index (AIx, a measure of arterial pressure wave reflections). RESULTS: Seated brachial systolic and diastolic BP were not different between extremely preterm children and classmates (P = 0.3 for both), although there was a small, significant elevation in supine mean and diastolic BP in the extremely preterm children (P < 0.05 for both). Arterial pressure wave reflections were significantly elevated in the extremely preterm children (P < 0.001) and this persisted after adjusting for confounding variables. However, aortic stiffness was not different between the groups (P = 0.1). CONCLUSIONS: These data suggest that extreme prematurity is associated with altered arterial haemodynamics in children, not evident from the examination of brachial BP alone. Moreover, the smaller, preresistance and resistance vessels rather than large elastic arteries appear to be most affected. Children born extremely preterm may be at increased future cardiovascular risk.

Psychiatric disorders in extremely preterm children: longitudinal finding at age 11 years in the EPICure study.

OBJECTIVE: To investigate the prevalence and risk factors for psychiatric disorders in extremely preterm children. METHOD: All babies born <26 weeks gestation in the United Kingdom and Ireland from March through December 1995 were recruited to the EPICure Study. Of 307 survivors at 11 years of age, 219 (71%) were assessed alongside 153 term-born classmates. Parents completed a structured psychiatric interview about their child, and teachers completed a corresponding questionnaire from which DSM-IV diagnoses were assigned for 219 (100%) extremely preterm children and 152 (99%) classmates. An IQ test and a physical evaluation were also administered. Longitudinal data were available for extremely preterm children. RESULTS: Extremely preterm children were more than three times more likely to have a psychiatric disorder than classmates (23% vs. 9%; odds ratio [OR] = 3.2; 95% confidence interval [CI] = 1.7, 6.2). Risk was significantly increased for: attention-deficit/hyperactivity disorder (ADHD; 11.5% vs. 2.9%; OR = 4.3; CI = 1.5 to 13.0), with increased risk for ADHD inattentive subtype (OR = 10.5; CI = 1.4 to 81.1) but not ADHD combined subtype (OR = 2.1; CI = 0.5 to 7.9); emotional disorders (9.0% vs. 2.1%; OR = 4.6; CI = 1.3 to 15.9), with increased risk for anxiety disorders (OR = 3.5; CI = 1.0 to 12.4); and autism spectrum disorders (8.0% vs. 0%; p = .000). Psychiatric disorders were significantly associated with cognitive impairment (OR = 3.5; CI = 1.8 to 6.4). Parent-reported behavioral problems at 2.5 and 6 years were independent predictors of psychiatric disorders at 11 years. CONCLUSIONS: Extremely preterm children are at increased risk for ADHD, emotional disorders, and autism spectrum disorders at 11 years of age. The mechanism of association with psychiatric disorder may include both cognitive impairment and early traumatic experiences that have an impact on both child and parent. Early screening for cognitive and behavioral problems may identify those at greatest risk.