Planned Cesarean or planned vaginal delivery for twins: secondary analysis of randomized controlled trial.

OBJECTIVE: To evaluate whether there is a differential benefit of planned Cesarean delivery (CD) over planned vaginal delivery (VD) in women with a twin pregnancy and the first twin in cephalic presentation, depending on prespecified baseline maternal and pregnancy characteristics, and/or gestational age (GA) at delivery. METHODS: This was a secondary analysis of the Twin Birth Study, which included 2804 women with a twin pregnancy and the first twin (Twin A) in cephalic presentation between 32 + 0 and 38 + 6 weeks' gestation at 106 centers in 25 countries. Women were assigned randomly to either planned CD or planned VD. The main outcome measure was composite adverse perinatal outcome, defined as the occurrence of perinatal mortality or serious neonatal morbidity in at least one twin. The baseline maternal and pregnancy characteristics (markers) considered were maternal age, parity, history of CD, use of antenatal corticosteroids, estimated fetal weight (EFW) of Twin A, EFW of Twin B, > 25% difference in EFW between the twins, presentation of Twin B, chorionicity on ultrasound, method of conception, complications of pregnancy, ruptured membranes at randomization and GA at randomization. Separate logistic regression models were developed for each marker in order to model composite adverse perinatal outcome as a function of the specific marker, planned delivery mode and the interaction between these two terms. In addition, multivariable logistic regression analysis with backward variable elimination was performed separately in each arm of the trial. The association between planned mode of delivery and composite adverse perinatal outcome, according to GA at delivery, was assessed using logistic regression analysis. RESULTS: Of the 2804 women initially randomized, 1391 were included in each study arm. None of the studied baseline markers was associated with a differential benefit of planned CD over planned VD in the rate of composite adverse perinatal outcome. GA at delivery was associated differentially with composite adverse perinatal outcome in the treatment arms (P for interaction < 0.001). Among pregnancies delivered at 32 + 0 to 36 + 6 weeks, there was a trend towards a lower rate of composite adverse perinatal outcome in those in the planned-VD group compared with those in planned-CD group (29 (2.2%) vs 48 (3.6%) cases; odds ratio (OR) 0.62 (95% CI, 0.37-1.03)). In pregnancies delivered at or after 37 + 0 weeks, planned VD was associated with a significantly higher rate of composite adverse perinatal outcome, as compared with planned CD (23 (1.5%) vs 10 (0.7%) cases; OR, 2.25 (95% CI, 1.06-4.77)). CONCLUSION: The perinatal outcome of twin pregnancies with the first twin in cephalic presentation may differ depending on GA at delivery and planned mode of delivery. At 32-37 weeks, planned VD seems to be favorable, while, from around 37 weeks onwards, planned CD might be safer. The absolute risks of adverse perinatal outcomes at term are low and must be weighed against the increased maternal risks associated with planned CD. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cesarean delivery or induction of labor in pre-labor twin gestations: a secondary analysis of the twin birth study.

BACKGROUND: In the Twin Birth Study, women at 320/7-386/7 weeks of gestation, in whom the first twin was in cephalic presentation, were randomized to planned vaginal delivery or cesarean section. The study found no significant differences in neonatal or maternal outcomes in the two planned mode of delivery groups. We aimed to compare neonatal and maternal outcomes of twin gestations without spontaneous onset of labor, who underwent induction of labor or pre-labor cesarean section as the intervention of induction may affect outcomes. METHODS: In this secondary analysis of the Twin Birth Study we compared those who had an induction of labor with those who had a pre-labor cesarean section. The primary outcome was a composite of fetal or neonatal death or serious neonatal morbidity. Secondary outcome was a composite of maternal morbidity and mortality. TRIAL REGISTRATION: NCT00187369. RESULTS: Of the 2804 women included in the Twin Birth Study, a total of 1347 (48%) women required a delivery before a spontaneous onset of labor occurred: 568 (42%) in the planned vaginal delivery arm and 779 (58%) in the planned cesarean arm. Induction of labor was attempted in 409 (30%), and 938 (70%) had a pre-labor cesarean section. The rate of intrapartum cesarean section in the induction of labor group was 41.3%. The rate of the primary outcome was comparable between the pre-labor cesarean section group and induction of labor group (1.65% vs. 1.97%; p = 0.61; OR 0.83; 95% CI 0.43-1.62). The maternal composite outcome was found to be lower with pre-labor cesarean section compared to induction of labor (7.25% vs. 11.25%; p = 0.01; OR 0.61; 95% CI 0.41-0.91). CONCLUSION: In women with twin gestation between 320/7-386/7 weeks of gestation, induction of labor and pre-labor cesarean section have similar neonatal outcomes. Pre-labor cesarean section is associated with favorable maternal outcomes which differs from the overall Twin Birth Study results. These data may be used to better counsel women with twin gestation who are faced with the decision of interventional delivery.

Urinary stress incontinence and other maternal outcomes 2 years after caesarean or vaginal birth for twin pregnancy: a multicentre randomised trial.

OBJECTIVE: Does planned caesarean compared with planned vaginal birth lower the risk of problematic urinary stress, faecal, or flatal incontinence? DESIGN: Women between 320/7 and 386/7 weeks of gestation with a twin pregnancy were randomised to planned caesarean or planned vaginal birth. SETTING: The trial took place at 106 centres in 25 countries. POPULATION: A total of 2305 of the 2804 women enrolled in the study completed questionnaires at 2 years (82.2% follow-up): 1155 in the planned caesarean group and 1150 in the planned vaginal birth group. METHODS: A structured self-administered questionnaire completed at 2 years postpartum. MAIN OUTCOME MEASURES: The primary maternal outcome of the Twin Birth Study was problematic urinary stress, or fecal, or flatal incontinence at 2 years RESULTS: Women in the planned caesarean group had lower problematic urinary stress incontinence rates compared with women in the planned vaginal birth group [93/1147 (8.11%) versus 140/1143 (12.25%); odds ratio, 0.63; 95% confidence interval, 0.47-0.83; P = 0.001]. Among those with problematic urinary stress incontinence, quality of life (measured using the Incontinence Impact Questionnaire, IIQ-7) was not different for planned caesarean versus planned vaginal birth groups [mean (SD): 18.4 (21.0) versus 19.1 (21.5); P = 0.82]. There were no differences in problematic faecal or flatal incontinence, or in other maternal outcomes. CONCLUSIONS: Among women with a twin pregnancy and no prior history of urinary stress incontinence, a management strategy of planned caesarean compared with planned vaginal birth reduces the risk of problematic urinary stress incontinence at 2 years postpartum. Our findings show that the prevalence but not the severity of urinary stress incontinence was associated with mode of birth. FUNDING: Canadian Institutes of Health Research (CIHR) (grant no. MCT-63164). TWEETABLE ABSTRACT: For women with twins, planned caesarean compared with planned vaginal birth is associated with decreased prevalence but not severity of urinary stress incontinence at 2 years.

Maternal outcomes at 3 months after planned caesarean section versus planned vaginal birth for twin pregnancies in the Twin Birth Study: a randomised controlled trial.

OBJECTIVE: To compare outcomes at 3 months post partum for women randomised to give birth by planned caesarean section (CS) or by planned vaginal birth (VB) in the Twin Birth Study (TBS). DESIGN: We invited women in the TBS to complete a 3-month follow-up questionnaire. SETTING: Two thousand and eight hundred and four women from 25 countries. POPULATION: Two thousand and five hundred and seventy women (92% response rate). METHODS: Women randomised between 13 December 2003 and 4 April 2011 in the TBS completed a questionnaire and outcomes were compared using an intention-to-treat approach. MAIN OUTCOME AND MEASURES: Breastfeeding, quality of life, depression, fatigue and urinary incontinence. RESULTS: We found no clinically important differences between groups in any outcome. In the planned CS versus planned VB groups, breastfeeding at any time after birth was reported by 84.4% versus 86.4% (P = 0.13); the mean physical and mental Short Form (36) Health Survey (SF-36) quality of life scores were 51.8 versus 51.6 (P = 0.65) and 46.7 versus 46.0 (P = 0.09), respectively; the mean Multidimensional Assessment of Fatigue score was 20.3 versus 20.8 (P = 0.14); the frequency of probable depression on the Edinburgh Postnatal Depression Scale was 14.0% versus 14.8% (P = 0.57); the rate of problematic urinary incontinence was 5.5% versus 6.4% (P = 0.31); and the mean Incontinence Impact Questionnaire-7 score was 20.5 versus 20.4 (P = 0.99). Partner relationships, including painful intercourse, were similar between the groups. CONCLUSION: For women with twin pregnancies randomised to planned CS compared with planned VB, outcomes at 3 months post partum did not differ. The mode of birth was not associated with problematic urinary incontinence or urinary incontinence that affected the quality of life. Contrary to previous studies, breastfeeding at 3 months was not increased with planned VB. TWEETABLE ABSTRACT: Planned mode of birth for twins doesn't affect maternal depression, wellbeing, incontinence or breastfeeding.

Maternal and infant predictors of attendance at Neonatal Follow-Up programmes.

BACKGROUND: Neonatal Follow-Up (NFU) programmes provide health services for families of infants at high risk of developmental problems following difficult or extremely premature birth: yet, up to 30% of families do not attend these programmes with their infants. METHODS: The study objective was to determine maternal and infant factors that predicted attendance at NFU programmes. Utilizing Andersen's Behavioural Model of Health Services Use, a prospective two-phase multi-site descriptive cohort study was conducted in three Canadian Neonatal Intensive Care Units (NICU) that refer to two affiliated NFU programmes. In Phase 1, 357 mothers completed standardized questionnaires that addressed maternal and infant factors, prior to their infants' NICU discharge. In Phase 2, attendance at NFU was followed at three time points over a 12-month period. Factors of interest included predisposing factors (e.g. demographic characteristics and social context); enabling factors (e.g. social support, travel distance, and income); and infant illness severity (i.e. needs factors). Multivariate logistic regression was used to estimate the odds ratio for each independent factor. RESULTS: Mothers parenting alone, experiencing higher levels of worry about maternal alcohol or drug use, or at greater distances from NFU were less likely to attend. Mothers experiencing higher maternal stress at the time of the infant's NICU hospitalization were more likely to attend NFU. No infant factors were predictive of NFU attendance. CONCLUSIONS: Mothers at risk of not attending NFU programmes with their infants require better identification, triage, referral and additional support to promote engagement with NFU programmes and improved quality of life for their high-risk infants.

Haemophilia prophylaxis: how can we justify the costs?

Severe haemophilia results in increased mortality and poorer quality of life. Factor prophylaxis leads to a more normal life, but is very costly; most of the cost is due to the high cost of replacement factor. Despite its high cost, factor prophylaxis has been adopted throughout the developed world--even in different health care systems. We argue that there are at least five possible reasons why societies may value factor prophylaxis despite its cost: (i) it is directed towards an inherited disease, (ii) the treatment is largely directed towards children, (iii) the disease is rare and the overall cost to society is small, (iv) the treatment is preventative, and v) the high cost is largely the result of providing safe products. In an era of rising health care costs, there is a strong research agenda to establish the factors that determine the value of expensive therapies for rare diseases like haemophilia.

The Early External Cephalic Version (ECV) 2 Trial: an international multicentre randomised controlled trial of timing of ECV for breech pregnancies.

OBJECTIVE: To investigate whether initiating external cephalic version (ECV) earlier in pregnancy might increase the rate of successful ECV procedures, and be more effective in decreasing the rate of non-cephalic presentation at birth and of caesarean section. DESIGN: An unblinded multicentred randomised controlled trial. SETTING: A total of 1543 women were randomised from 68 centres in 21 countries. POPULATION: Women with a singleton breech fetus at a gestational age of 33(0/7) weeks (231 days) to 35(6/7) weeks (251 days) of gestation were included. METHODS: Participants were randomly assigned to having a first ECV procedure between the gestational ages of 34(0/7) (238 days) and 35(6/7) weeks of gestation (early ECV group) or at or after 37(0/7) (259 days) weeks of gestation (delayed ECV group). MAIN OUTCOME MEASURES: The primary outcome was the rate of caesarean section; the secondary outcome was the rate of preterm birth. RESULTS: Fewer fetuses were in a non-cephalic presentation at birth in the early ECV group (314/765 [41.1%] versus 377/768 [49.1%] in the delayed ECV group; relative risk [RR] 0.84, 95% CI 0.75, 0.94, P=0.002). There were no differences in rates of caesarean section (398/765 [52.0%] versus 430/768 [56.0%]; RR 0.93, 95% CI 0.85, 1.02, P=0.12) or in risk of preterm birth (50/765 [6.5%] versus 34/768 [4.4%]; RR 1.48, 95% CI 0.97, 2.26, P=0.07) between groups. CONCLUSION: External cephalic version at 34-35 weeks versus 37 or more weeks of gestation increases the likelihood of cephalic presentation at birth but does not reduce the rate of caesarean section and may increase the rate of preterm birth.

Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

BACKGROUND: The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. OBJECTIVES: To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. METHODS: Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? RESULTS: The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. CONCLUSIONS: The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

Women's views of their experiences in the CHIPS (Control of Hypertension in Pregnancy Study) Pilot Trial.

BACKGROUND: Satisfaction with maternity care is strongly related to the patient-caregiver relationship and involvement in the decision-making process. We sought to compare women's views about their care in a randomized trial of 'less tight' vs. 'tight' control of non-proteinuric pre-existing or gestational hypertension in pregnancy. METHODS: In the CHIPS Pilot Trial, women completed a postpartum questionnaire to assess their likes and dislikes about their blood pressure (BP) management and trial participation. Comparisons were descriptive. RESULTS: Baseline information was similar for the 'less tight' and 'tight' control groups. Of 132 women, 126 (95.5%) from 17 centers completed a postpartum questionnaire, usually within days of delivery. At least 90% of women in both groups were satisfied with their care, and would be willing to participate again or recommend participation to a friend. Women in both the 'less tight' and 'tight' groups were satisfied with BP management (98.4% vs. 95.1%), and the frequency of tests of maternal and fetal well being. Half of women in both groups perceived that their BP was too high and that caregivers thought that their BP was too high. More women in the 'less tight' (vs. the 'tight') control group took less medication than expected (71.7% vs. 38.2%). More women in the 'tight' (vs. the 'less tight') group took more medication than they expected (60.0% vs. 22.2%). At least 60% of all women used home BP monitoring. CONCLUSION: In the CHIPS Pilot Trial, while women stated that they were satisfied with their BP management and care, a surprising 50% in both groups thought that their BP was too high. The majority of women used home BP monitoring, the role of which must be further defined in hypertensive pregnancies.

The Control of Hypertension In Pregnancy Study pilot trial.

OBJECTIVE: To determine whether 'less tight' (versus 'tight') control of nonsevere hypertension results in a difference in diastolic blood pressure (dBP) between groups. DESIGN: Randomised controlled trial (ISRCTN#57277508). SETTING: Seventeen obstetric centres in Canada, Australia, New Zealand, and UK. POPULATION: Inclusion: pregnant women, dBP 90-109 mmHg, pre-existing/gestational hypertension; live fetus(es); and 20-33(+6) weeks. Exclusion: systolic blood pressure > or = 170 mmHg and proteinuria, contraindication, or major fetal anomaly. METHODS: Randomisation to less tight (target dBP, 100 mmHg) or tight (target dBP, 85 mmHg) blood pressure control. MAIN OUTCOME MEASURES: Primary: mean dBP at 28, 32 and 36 weeks. Secondary: clinician compliance and women's satisfaction. Other: serious perinatal and maternal complications. RESULTS: A total of 132 women were randomised to less tight (n = 66; seven had no study visit) or tight control (n= 66; one was lost to follow up; seven had no study visit). Mean dBP was significantly lower with tight control: -3.5 mmHg, 95% credible interval (-6.4, -0.6). Clinician compliance was 79% in both groups. Women were satisfied with their care. With less tight (versus tight) control, the rates of other treatments and outcomes were the following: post-randomisation antenatal antihypertensive medication use: 46 (69.7%) versus 58 (89.2%), severe hypertension: 38 (57.6%) versus 26 (40.0%), proteinuria: 16 (24.2%) versus 20 (30.8%), serious maternal complications: 3 (4.6%) versus 2 (3.1%), preterm birth: 24 (36.4%) versus 26 (40.0%), birthweight: 2675 +/- 858 versus 2501 +/- 855 g, neonatal intensive care unit (NICU) admission: 15 (22.7%) versus 22 (34.4%), and serious perinatal complications: 9 (13.6%) versus 14 (21.5%). CONCLUSION: The CHIPS pilot trial confirms the feasibility and importance of a large definitive trial to determine the effects of less tight control on serious perinatal and maternal complications.

Using inverse-weighting in cost-effectiveness analysis with censored data.

Due to induced dependent censoring, estimating mean costs and quality-adjusted survival in a cost-effectiveness analysis using standard life-table methods leads to biased results. In this paper we propose methods for estimating the difference in mean costs and the difference in effectiveness, together with their respective variances and covariance in the presence of dependent censoring. We consider the situation in which the measure of effectiveness is either the probability of patients surviving a duration of interest, mean survival time over a duration of interest or mean quality-adjusted survival time over a duration of interest. The method of inverse-weighting is used for censored cost and quality of life data. The methods are illustrated in an example using an incremental net benefit analysis.

Cost-effectiveness analysis when the WTA is greater than the WTP.

The incremental cost effectiveness ratio has long been the standard parameter of interest in the assessment of the cost-effectiveness of a new treatment. However, due to concerns with interpretability and statistical inference, authors have suggested using the willingness-to-pay for a unit of health benefit to define the incremental net benefit as an alternative. The incremental net benefit has a more consistent interpretation and is amenable to routine statistical procedures. These procedures rely on the fact that the willingness-to-accept compensation for a loss of a unit of health benefit (at some cost saving) is the same as the willingness-to-pay for it. Theoretical and empirical evidence suggest, however, that in health care the willingness-to-accept is about twice as much as the willingness-to-pay. We use Bayesian methods to provide a statistical procedure for the cost-effectiveness comparison of two arms of a randomized clinical trial that allows the willingness-to-pay and the willingness-to-accept to have different values. An example is provided.

On the probability of cost-effectiveness using data from randomized clinical trials.

BACKGROUND: Acceptability curves have been proposed for quantifying the probability that a treatment under investigation in a clinical trial is cost-effective. Various definitions and estimation methods have been proposed. Loosely speaking, all the definitions, Bayesian or otherwise, relate to the probability that the treatment under consideration is cost-effective as a function of the value placed on a unit of effectiveness. These definitions are, in fact, expressions of the certainty with which the current evidence would lead us to believe that the treatment under consideration is cost-effective, and are dependent on the amount of evidence (i.e. sample size). METHODS: An alternative for quantifying the probability that the treatment under consideration is cost-effective, which is independent of sample size, is proposed. RESULTS: Non-parametric methods are given for point and interval estimation. In addition, these methods provide a non-parametric estimator and confidence interval for the incremental cost-effectiveness ratio. An example is provided. CONCLUSIONS: The proposed parameter for quantifying the probability that a new therapy is cost-effective is superior to the acceptability curve because it is not sample size dependent and because it can be interpreted as the proportion of patients who would benefit if given the new therapy. Non-parametric methods are used to estimate the parameter and its variance, providing the appropriate confidence intervals and test of hypothesis.

Cost effectiveness in Canada of a multidrug prepackaged regimen (Hp-PAC)+ for Helicobacter pylori eradication.

OBJECTIVE: To assess the cost effectiveness of a multidrug prepackaged regimen for Helicobacter pylori, the Hp-PAC (lansoprazole 30mg, clarithromycin 500 mg, amoxicillin 1 g, all twice daily), relative to alternative pharmacological strategies in the management of confirmed duodenal ulcer over a 1-year period from 2 perspectives: (i) a strict healthcare payer perspective (Ontario Ministry of Health) excluding the patient copayment; and (ii) a healthcare payer perspective including the patient copayment. DESIGN: A decision-analytical model was developed to estimate expected per patient costs [1998 Canadian dollars ($ Can)], weeks without ulcer and symptomatic ulcer recurrences for the Hp-PAC compared with: proton pump inhibitor (PPI)-clarithromycin-amoxicillin (PPI-CA), PPI-clarithromycin-metronidazole (PPI-CM), PPI-amoxicillin-metronidazole (PPI-AM) and ranitidine-bismuthmetronidazole-tetracycline (RAN-BMT). MAIN OUTCOME MEASURES AND RESULTS: All PPI-based regimens had higher expected costs but better outcomes relative to RAN-BMT. From a strict healthcare payer perspective, PPI-CM ($Can 209) yielded lower expected costs than PPI-CA ($Can 221) and slightly lower costs than Hp-PAC ($Can 211). However, these 3 regimens all shared identical outcomes (51.2 weeks without ulcer). When the current Ontario, Canada, $Can 2 patient copayment was added to the dispensing fee, Hp-PAC yielded lower costs ($Can 214) than PPI-CM ($Can 216). CONCLUSION: From a strict healthcare payer perspective, Hp-PAC is weakly dominated by PPI-CM with an incremental cost effectiveness (relative to RAN-BMT) of $Can 5.77 per ulcer week averted. When the patient copayment is added to this perspective, Hp-PAC weakly dominates PPI-CM ($Can 5 per ulcer week averted). Regardless of perspective, Hp-PAC and PPI-CM differed by only $Can 2 per patient over 1 year and the expected time without ulcer was 51.2 weeks for both. More data on the clinical and statistical differences in H. pylori eradication with Hp-PAC and PPI-CM would be useful. This analysis does not in clude the possible advantage of Hp-PAC in terms of compliance and antibacterial resistance.

Analysis, sample size, and power for estimating incremental net health benefit from clinical trial data.

Stinnett and Mullahy recently introduced the concept of net health benefit as an alternative to cost-effectiveness ratios for the statistical analysis of patient-level data on the costs and health effects of competing interventions. Net health benefit addresses a number of problems associated with cost-effectiveness ratios by assuming a value for the willingness-to-pay for a unit of effectiveness. We extend the concept of net health benefit to demonstrate that standard statistical procedures can be used for the analysis, power, and sample size determinations of cost-effectiveness data. We also show that by varying the value of the willingness-to-pay, the point estimate and confidence interval for the incremental cost-effectiveness ratio can be determined. An example is provided.

Incremental net benefit in randomized clinical trials.

There are three approaches to health economic evaluation for comparing two therapies. These are (i) cost minimization, in which one assumes or observes no difference in effectiveness, (ii) incremental cost-effectiveness, and (iii) incremental net benefit. The latter can be expressed either in units of effectiveness or costs. When analysing data from a clinical trial, expressing incremental net benefit in units of cost allows the investigator to examine all three approaches in a single graph, complete with the corresponding statistical inferences. Furthermore, if costs and effectiveness are not censored, this can be achieved using common two-sample statistical procedures. The above will be illustrated using two examples, one with censoring and one without.

Cost prediction models for the comparison of two groups.

For trial-based economic evaluation where patient-specific cost data are not routinely available, cost prediction models are commonly used to estimate total cost for each patient. Typically, multiple regression techniques are used on data from diagnosis-matched, non-trial patients (where patient-level cost data are available) to model cost as a function of covariates that are observed on the trial subjects (e.g. length of hospital stay, procedures, etc.). The estimated beta coefficients provide a means of estimating the total cost for each patient in the trial. However, the variability of the beta coefficients due the measurement and sampling error is seldom included in the overall variance expression for mean costs by treatment group. In this paper we provide a method for estimating this variance and provide an example application

Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Term Breech Trial Collaborative Group.

BACKGROUND: For 3-4% of pregnancies, the fetus will be in the breech presentation at term. For most of these women, the approach to delivery is controversial. We did a randomised trial to compare a policy of planned caesarean section with a policy of planned vaginal birth for selected breech-presentation pregnancies. METHODS: At 121 centres in 26 countries, 2088 women with a singleton fetus in a frank or complete breech presentation were randomly assigned planned caesarean section or planned vaginal birth. Women having a vaginal breech delivery had an experienced clinician at the birth. Mothers and infants were followed-up to 6 weeks post partum. The primary outcomes were perinatal mortality, neonatal mortality, or serious neonatal morbidity; and maternal mortality or serious maternal morbidity. Analysis was by intention to treat. FINDINGS: Data were received for 2083 women. Of the 1041 women assigned planned caesarean section, 941 (90.4%) were delivered by caesarean section. Of the 1042 women assigned planned vaginal birth, 591 (56.7%) delivered vaginally. Perinatal mortality, neonatal mortality, or serious neonatal morbidity was significantly lower for the planned caesarean section group than for the planned vaginal birth group (17 of 1039 [1.6%] vs 52 of 1039 [5.0%]; relative risk 0.33 [95% CI 0.19-0.56]; p<0.0001). There were no differences between groups in terms of maternal mortality or serious maternal morbidity (41 of 1041 [3.9%] vs 33 of 1042 [3.2%]; 1.24 [0.79-1.95]; p=0.35). INTERPRETATION: Planned caesarean section is better than planned vaginal birth for the term fetus in the breech presentation; serious maternal complications are similar between the groups.

Quality of life in spina bifida: importance of parental hope.

BACKGROUND AND AIMS: Prognosis in spina bifida (SB) is often based only on neurological deficits present at birth. We hypothesised that both parental hope and the neurophysical examination predict quality of life in children and adolescents with SB. METHODS: A previously validated disease and age specific health related quality of life (HRQL) instrument was posted to families of children (aged 5-12 years) and adolescents (aged 13-20 years) with SB. We measured parental hope, determined the child's current physical function, and obtained retrospective data on the neonatal neurophysical examination (NPE). Regression analysis modelled HRQL firstly as a dependent variable on parental hope and NPE ("birth status"); and secondly on parental hope and current physical function ("current function"). RESULTS: Response rates were 71% (137 of 194) for families of children, and 54% (74 of 138) for families of adolescents. NPE data were available for 121 children and 60 adolescents. In children, the birth status model predicted 26% of the variability (R(2) hope 21%) compared with 23% of the variability (R(2) hope 23%)in the adolescents. The current function model explained 47% of the variability (R(2) hope 19%) in children compared with 31% of the variability (R(2) hope 24%) in the adolescents. CONCLUSIONS: In both age groups, parental hope was more strongly associated with the HRQL than neonatal or current physical deficits. A prospective study is required to determine whether a causal relation exists between parental hope and HRQL of children and adolescents with SB.