Experiences with maternal and perinatal death reviews in the UK--the MBRRACE-UK programme.

Established in 1952, the programme of surveillance and Confidential Enquiries into Maternal Deaths in the UK is the longest running such programme worldwide. Although more recently instituted, surveillance and confidential enquiries into perinatal deaths are also now well established nationally. Recent changes to funding and commissioning of the Enquiries have enabled both a reinvigoration of the processes and improvements to the methodology with an increased frequency of future reporting. Close engagement with stakeholders and a regulator requirement for doctors to participate have both supported the impetus for involvement of all professionals leading to greater potential for improved quality of care for women and babies.

Assessment of liquid captopril formulations used in children.

OBJECTIVE: Unlicensed liquid captopril formulations are commonly used to treat children with heart disease. This study assessed the bioequivalence of two liquid preparations against a licensed tablet form. DESIGN: An open label, single dose, three-treatment, three-period, crossover trial. SETTING: Outpatient. PATIENTS: Healthy adult volunteers (n=18). INTERVENTIONS: Each subject was randomly assigned to one of six dosing sequences, and dosed with 25 mg captopril on each of three dosing visits separated by a washout of at least 14 days. Blood samples for pharmacokinetic analysis were taken at regular intervals (0 min to 10 h) post-dose. MAIN OUTCOME MEASURES: Bioequivalence of the formulations would be concluded if the 90% CI for the estimated ratio of the means of C(max) (maximum plasma concentrations) and area under curve(AUC) (extent of absorption) lay entirely within the range 0.8 to 1.25 RESULTS: Both liquid formulations failed the bioequivalence assessment with respect to C(max) and AUC. The 90% CI of the mean ratios of liquid/licensed tablet for both C(max) and AUC, fell outside the 0.8 to 1.25 limits. There was also considerable within-subject variability in C(max) (97.5%) and AUC (78.5%). CONCLUSIONS: Unlicensed captopril formulations are not bioequivalent to the licensed tablet form, or to each other, and so cannot be assumed to behave similarly in therapeutic use. Thus formulation substitution must be done with care and may require a period of increased monitoring of the patient. There is also significant within-subject variability in performance which has clinical implications with respect to titrating to an optimum therapeutic dose.

Neonatal intensive care outcomes and resource utilisation of infants born <26 weeks in the former Trent region: 2001-2003 compared with 1991-1993.

OBJECTIVES: To provide survival data and rates of severe disability at 2 years of corrected age in infants born prior to 26 weeks' gestation in 2001-2003 and to compare these outcomes with an earlier cohort from 1991 to 1993. DESIGN: Population-based prospective cohort study. SETTING: Former Trent region of UK covering a population of approximately five million and around 55 000 births per annum. PARTICIPANTS: The authors identified a 3-year cohort of infants born before 26 weeks' gestation between 1 January 2001 and 31 December 2003 from The Neonatal Survey (TNS). Questionnaires based on the Oxford minimum dataset were completed. MAIN OUTCOME MEASURES: Survival, service use and disability levels were compared between the 2001- 2003 cohort and the cohort from 1991 to 1993. RESULTS: In 2001-2003, 0%, 18% and 35% of live born babies were alive at 2 years without any evidence of severe disability at 23, 24 and 25 weeks' gestation, respectively. Overall, of those children admitted to neonatal care, the proportion with no evidence of severe disability at 2 years corrected age improved from 14.5% in 1991-1993 to 26.5% in 2001-2003. There was an increase in the proportion of children with at least one severe disability, out of total admissions to neonatal unit (8% vs 17%) and of those assessed at 2 years (35% vs 39%). CONCLUSIONS: This study has shown an improvement in survival to discharge in babies admitted for neonatal care. However, this improved survival has been associated with an increase in the proportion of children with at least one severe disability at a corrected age of 2 years.

Predicting neonatal mortality among very preterm infants: a comparison of three versions of the CRIB score.

OBJECTIVE: To validate Clinical Risk Index for Babies (CRIB) and CRIB II mortality prediction scores in a UK population of infants born at

Nursing workload in UK tertiary neonatal units.

BACKGROUND: Neonatal intensive care requires adequate numbers of trained neonatal nurses to provide safe, effective care, but existing research into the relationship between nurse numbers and the care needs of babies is over 10 years old. Since then, the preterm population and treatment practices have changed considerably. AIMS: To validate the dependency categories of the British Association of Perinatal Medicine (BAPM, 2001) and to revalidate the Northern Region categories (NR, 1993) in relation to contemporary nursing workload. SETTING: Three tertiary neonatal intensive care services in England. METHODS: Nursing activity around each baby was captured every 10 min by direct observations by trained observers. Time spent on each nursing activity was related to the baby's dependency category and the nurse's grade. RESULTS: Both scales detected differences between categories. Discrimination between individual categories was improved when nasal continuous positive airway pressure (nCPAP) was distinguished from ventilation and combined with BAPM2/NRA. On this revised four-point scale, babies in BAPM1/NRA occupied nursing time for a median of 56 min per hour (IQR 48-70), those on nCPAP or in BAPM2/NRB for 36 min, (27-42), those in BAPM3/NRC for 20-22 min (15-33) and those in BAPM4/NRD for 31-32 min (24-36). The NR scale was easier to apply and had greater interobserver agreement (98.5%) than the BAPM scale (93%). All categories attracted more time compared to 1993. CONCLUSIONS: Both scales predict average nursing workload. A revised categorisation which separates nCPAP from ventilation is more robust and practical. Nursing time attracted in all categories has increased since 1993.

Geographically based investigation of the influence of very-preterm births on routine mortality statistics from the UK and Australia.

BACKGROUND: Comparisons of national perinatal and neonatal mortality often neglect the underlying causes. OBJECTIVE: To assess effects of very-preterm births in the UK and Australia. SETTING: Two geographically defined populations: the former Trent Health Region of the UK and New South Wales (NSW)/the Australian Capital Territory (ACT), Australia. METHOD: All births 22(+0) to 31(+6) weeks in 2000, 2001 and 2002 were identified by established surveys of perinatal care. Rates of birth and death were compared. RESULTS: The population of NSW/ACT was 35% higher and there were 66% more births than in Trent (273 495 vs 164 824). The proportion of liveborn infants between 22 and 31 weeks gestation was about 25% higher in Trent (NSW/ACT 2945, rate per 1000 live births 10.82 (95% CI 10.43 to 11.22); Trent 2208, rate per 1000 live births 13.47 (95% CI 12.92 to 14.05)). The proportion of these infants admitted to a neonatal unit was also higher in Trent (91.2% vs 94.4%; OR 1.63 (95% CI 1.30 to 2.05)). Unadjusted mortality in infants admitted to a neonatal unit was similar: NSW/ACT 332/2686 (12.4%); Trent 284/2085 (13.6%); unadjusted OR 1.12 (95% CI 0.94 to 1.33; p = 0.21). CONCLUSIONS: The higher rates of very premature birth and more ready admission to neonatal intensive care for infants in the UK may help to explain why perinatal and neonatal mortality are higher there than in Australia. Efforts to understand why the rate of premature birth in the UK is so high should be a national priority.

Respiratory outcome in late childhood after neonatal continuous negative pressure ventilation.

BACKGROUND: The outcome in late childhood for children entered into a randomised trial of continuous negative extrathoracic pressure (CNEP) versus standard respiratory management for the treatment of neonatal respiratory distress was studied. In the original trial, there were advantages in the duration of oxygen and the prevalence of chronic lung disease for those assigned to receive CNEP. AIM: To determine whether the above differences had persisted into childhood. METHODS: Outpatient evaluation of children by a paediatrician using Spirometry (Vitalograph Spirometer 2120, Ennis, Ireland) and MicroRint (Micro Medical, Rochester, Kent, UK) techniques independently of the original trial. Parents completed questionnaires about their child's respiratory history and social-demographic information. RESULTS: 133 (65%) survivors were evaluated at 9.6-14.9 years of age. The group examined were representative of the original cohort and no significant baseline differences were observed between children evaluated who had been allocated to CNEP or standard treatments. We compared Rint (before and after bronchodilator) and forced expiratory flow, volume and vital capacity between the two study groups; none were significant. Children in the standard group had received paediatric intensive care more often (p = 0.19) and were more likely to be receiving inhaled drugs for asthma (p = 0.19; all not significant). CONCLUSIONS: No important differences were found at follow-up in late childhood in respiratory outcomes for children treated with neonatal CNEP or standard treatment. Caution should be exercised, as the original trial was not powered to show these differences, but there seems to be no long-term detriment in respiratory outcomes for children treated with CNEP in the neonatal period.

Socioeconomic inequalities in very preterm birth rates.

AIMS: To investigate the extent of socioeconomic inequalities in the incidence of very preterm birth over the past decade. METHODS: Ecological study of all 549 618 births in the former Trent health region, UK, from 1 January 1994 to 31 December 2003. All singleton births of 22(+0) to 32(+6) weeks gestation (7 185 births) were identified from population surveys of neonatal services and stillbirths. Poisson regression was used to calculate incidence of very preterm birth (22-32 weeks) and extremely preterm birth (22-28 weeks) by year of birth and decile of deprivation (child poverty section of the Index of Multiple Deprivation). RESULTS: Incidence of very preterm singleton birth rose from 11.9 per 1000 births in 1994 to 13.7 per 1000 births in 2003. Those from the most deprived decile were at nearly twice the risk of very preterm birth compared with those from the least deprived decile, with 16.4 per 1000 births in the most deprived decile compared with 8.5 per 1000 births in the least deprived decile (incidence rate ratio 1.94; 95% CI (1.73 to 2.17)). This deprivation gap remained unchanged throughout the 10-year period. The magnitude of socio-economic inequalities was the same for extremely preterm births (22-28 weeks incidence rate ratio 1.94; 95% CI (1.62 to 2.32)). CONCLUSIONS: This large, unique dataset of very preterm births shows wide socio-economic inequalities that persist over time. These findings are likely to have consequences on the burden of long-term morbidity. Our research can assist future healthcare planning, the monitoring of socio-economic inequalities and the targeting of interventions in order to reduce this persistent deprivation gap.

The potential impact on costs and staffing of introducing clinical networks and British Association of Perinatal Medicine standards to the delivery of neonatal care.

OBJECTIVE: To produce models to estimate the impact of introducing clinical networks and the 2001 BAPM standards to the delivery of neonatal care. DESIGN: Prospective observational study using a geographically defined population and data collected by questionnaire on staffing levels and cot availability. SETTING: Trent Health Region UK. SUBJECTS: All infants born to Trent resident mothers at or before 32 weeks gestation between 1 January 1998 and 31 December 1999. Staffing numbers and cot availability for neonatal care in 2001. METHODS: A modelling exercise was carried out using information for all neonatal admissions for Trent resident infants. Three models were investigated: (a). the current care provision; (b). a network where three lead centres provided the intensive care for the region and the remaining units provided either high dependency or special care alone; (c). a network where six lead centres provided the intensive care for the region and the remaining units provided either high dependency or special care alone. Overall costings, staffing levels, and cot requirements were calculated for each model. Data on staffing levels and cot availability were used to calculate current care provision costings. RESULTS: The current cost of running the service is approximately pound 33.35 million, although a proportion of nursing posts are currently unfilled. Estimates for the introduction of a three centre model meeting BAPM 2001 standards range from pound 37.31 to pound 43.40 million. Equivalent figures for the six centre model were: pound 36.32 to pound 42.62 million. Approximately 370 and 230 babies a year would be involved in transfer in the three and six centre models respectively. This is in contrast with 374 and 368 urgent transfers that actually took place in 1998 and 1999 respectively. CONCLUSION: The costs associated with the introduction of managed clinical networks and meeting BAPM standards of care are not excessive, especially when considered against the likely implementation timetable of perhaps 7-10 years. Attracting and retaining sufficient staff will pose the major challenge.

Cerebral autoregulatory responses to head-up tilt in normal subjects and patients with recurrent vasovagal syncope.

BACKGROUND: The effect of orthostatic stress on dynamic cerebral autoregulation (CA) in normal subjects and patients with recurrent vasovagal syncope (VVS) is unclear. This study assessed the dynamic CA responses of both groups to head-up tilt. METHODS AND RESULTS: Seventeen patients with recurrent VVS and 17 pair-matched control subjects underwent 70 degrees head-up tilt for up to 30 minutes. Bilateral middle cerebral artery blood flow velocities (CBFV) were measured with transcranial Doppler ultrasound along with noninvasive beat-to-beat blood pressure (BP), heart rate, and transcutaneous and end-tidal CO(2) concentrations. Indices of dynamic CA were derived for periods before, during, and after tilt. Eight normal subjects who developed VVS in an identical protocol but who had no previous clinical history of syncope were also studied. CBFV and transcutaneous and end-tidal CO(2) levels declined significantly during head-up tilt in all groups (P<0.0001). Dynamic CA indices were unchanged throughout tilt in nonsyncopal control subjects and were initially unchanged in patients but deteriorated significantly in patients and syncopal control subjects in the minutes before (P=0.027 and P=0.012, respectively) and after (P=0.002 and P=0.007, respectively) syncope. CONCLUSIONS: Dynamic CA is preserved in patients and control subjects initially after head-up tilt. Autoregulatory function remains intact in nonsyncopal control subjects during prolonged orthostasis but deteriorates in patients and syncopal control subjects immediately before and after VVS.

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 < or = 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 < or = 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

Changes in baroreceptor sensitivity for heart rate during normotensive pregnancy and the puerperium.

Normal pregnancy is associated with marked changes in cardiovascular haemodynamics, which in part may be due to changes in autonomic control mechanisms. Baroreflex sensitivity for heart rate (BRS) was calculated in the supine and standing positions using power spectral analysis of pulse interval (PI) and systolic blood pressure (SBP) in 16 normotensive pregnant women and 10 normotensive non-pregnant controls. The pregnant women were studied on three occasions during their pregnancy (early, mid- and late gestation) and once during the puerperium. Supine total SBP variability increased between early and late pregnancy by 79% [95% confidence intervals (CI) 30%, 145%; P<0. 001], and supine high-frequency PI variability decreased by 75% (CI 51%, 88%; P<0.001). Supine BRS fell by 50% (P<0.001), with values returning to early-pregnancy levels in the puerperium, which were similar to those recorded in the control group. Standing SBP variability and BRS values were unchanged during pregnancy and post partum. The low/high frequency ratio of PI variability, taken as a surrogate measure of sympathovagal balance, increased by 137% (CI 42%, 296%; P<0.01) in the supine but not the standing position from early to late pregnancy. This was due to a decrease in high-frequency variability rather than to an increase in low-frequency variability, suggesting that these changes may have been due to vagal withdrawal rather than increased sympathetic activity. Normotensive pregnancy is associated with a marked decrease in supine BRS, although the exact mechanisms for these changes remain unclear. Further studies are required to define whether changes in BRS and sympathovagal tone in early pregnancy can be used to predict the onset of pregnancy-induced hypertension.

Which parameters of beat-to-beat blood pressure and variability best predict early outcome after acute ischemic stroke?

BACKGROUND AND PURPOSE: In hypertensive populations, increasing blood pressure (BP) levels and BP variability (BPV) are associated with a greater incidence of target organ damage. After stroke, elevated 24-hour BP levels predict a poor outcome, although it is uncertain whether shorter-length BP recordings assessing mean BP levels and BPV have a similar predictive role. The objectives of this study were to compare the different measures of beat-to-beat BP and BPV on outcome after acute ischemic stroke and assess whether these parameters were affected by stroke subtype. METHODS: Ninety-two consecutive admissions with a CT-confirmed diagnosis of acute ischemic stroke were recruited, of whom 54 had cortical infarction, 29 subcortical, and 9 posterior circulation infarction. Casual and two 5-minute recordings of beat-to-beat BP (Finapres, Ohmeda) were made under standardized conditions within 72 hours of ictus, with mean BP levels taken as the average of this 10-minute recording and BPV as the standard deviation. Outcome was assessed at 30 days as dead/dependent or independent (Rankin

Diurnal blood pressure change varies with stroke subtype in the acute phase.

BACKGROUND AND PURPOSE: It is unclear whether acute stroke is associated with a loss of the normal diurnal blood pressure (BP) change and whether stroke type influences this. Some of this confusion results from the use of fixed time definitions of day and night, which can be overcome by the use of cumulative sums analysis (cusums). METHODS: Ninety-eight stroke patients had 24-hour BP monitoring (Spacelabs 90207) performed within 48 hours of ictus. Three subgroups were identified: cortical infarct, n=50; subcortical infarct, n=29; and primary intracerebral hemorrhage [PICH], n= 19. An age-matched control group of 74 subjects was also studied. Diurnal change was assessed by both day-night differences (absolute and percentage) and cusums (cusums plot height [CPH] and circadian alteration magnitude [CDCAM]); ANCOVA was used to compare groups. RESULTS: Compared with control subjects, cortical infarct and PICH subgroups had significantly reduced mean diurnal systolic changes using day-night differences (absolute, -12 and -17 mm Hg; percentage, -10 and -12, respectively; P < 0.0001) and cusums (CDCAM, -6.96 and -8.6 mm Hg; CPH, -32.05 and -46.04 mm Hg, respectively; P < 0.005), only the subcortical infarct subgroup demonstrated reduced percentage differences (-4.4%, P < 0.02). Mean diastolic differences were significantly reduced in all stroke subgroups(CPH, -24.84, -17.31, and -36.92 mm Hg; absolute, -8.26, -4.04, and -11.44 mm Hg; percentage, -10.65, -5.81, and -15.23%, for cortical infarct, subcortical infarct, and PICH subgroups, respectively; P < 0.05), except for CDCAM, which was not reduced in subcortical infarcts (-4.78 and -7.70 mm Hg for cortical infarct and PICH subgroups, respectively; P < 0.001). CONCLUSIONS: Diurnal BP change was reduced in the 3 stroke subgroups studied, especially in patients with cortical infarcts and PICH. This may reflect damage to the central modulation of autonomic BP control. The implications in terms of prognosis and therapy in the acute period require further study.