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.

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.

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.

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.

Motor and executive function at 6 years of age after extremely preterm birth.

BACKGROUND: Studies of very preterm infants have demonstrated impairments in multiple neurocognitive domains. We hypothesized that neuromotor and executive-function deficits may independently contribute to school failure. METHODS: We studied children who were born at < or = 25 completed weeks' gestation in the United Kingdom and Ireland in 1995 at early school age. Children underwent standardized cognitive and neuromotor assessments, including the Kaufman Assessment Battery for Children and NEPSY, and a teacher-based assessment of academic achievement. RESULTS: Of 308 surviving children, 241 (78%) were assessed at a median age of 6 years 4 months. Compared with 160 term classmates, 180 extremely preterm children without cerebral palsy and attending mainstream school performed less well on 3 simple motor tasks: posting coins, heel walking, and 1-leg standing. They more frequently had non-right-hand preferences (28% vs 10%) and more associated/overflow movements during motor tasks. Standardized scores for visuospatial and sensorimotor function performance differed from classmates by 1.6 and 1.1 SDs of the classmates' scores, respectively. These differences attenuated but remained significant after controlling for overall cognitive scores. Cognitive, visuospatial scores, and motor scores explained 54% of the variance in teachers' ratings of performance in the whole set; in the extremely preterm group, additional variance was explained by attention-executive tasks and gender. CONCLUSIONS: Impairment of motor, visuospatial, and sensorimotor function, including planning, self-regulation, inhibition, and motor persistence, contributes excess morbidity over cognitive impairment in extremely preterm children and contributes independently to poor classroom performance at 6 years of age.