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This article challenges the “tyranny of P-value” and promote more valuable and applicable interpretations of the results of research on health care delivery. We provide here solid arguments to retire statistical significance as the unique way to interpret results, after presenting the current state of the debate inside the scientific community. Instead, we promote reporting the much more informative confidence intervals and eventually adding exact P-values. We also provide some clues to integrate statistical and clinical significance by referring to minimal important differences and integrating the effect size of an intervention and the certainty of evidence ideally using the GRADE approach. We have argued against interpreting or reporting results as statistically significant or statistically non-significant. We recommend showing important clinical benefits with their confidence intervals in cases of point estimates compatible with results benefits and even important harms. It seems fair to report the point estimate and the more likely values along with a very clear statement of the implications of extremes of the intervals. We recommend drawing conclusions, considering the multiple factors besides P-values such as certainty of the evidence for each outcome, net benefit, economic considerations and values and preferences. We use several examples and figures to illustrate different scenarios and further suggest a wording to standardize the reporting. Several statistical measures have a role in the scientific communication of studies, but it is time to understand that there is life beyond the statistical significance. There is a great opportunity for improvement towards a more complete interpretation and to a more standardized reporting.

The WHO ACTION-I trial demonstrated that dexamethasone significantly reduced neonatal mortality when administered to women at risk of early preterm birth in low-resource countries. We conducted a secondary analysis to determine how these benefits can be optimised, by evaluating the effect of dexamethasone compared to placebo on newborn mortality and severe respiratory distress outcomes at different administration-to-birth intervals, and identifying the interval with the greatest benefits.The WHO ACTION-I trial was a multi-country, individually-randomised, parallel-group, double-blind, placebo-controlled trial. It was conducted in 29 hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Women with a viable singleton or multiple pregnancy who presented to participating hospitals at a gestational age of 26 weeks 0 days-33 weeks 6 days and who were at risk of imminent preterm birth were eligible. In this secondary analysis, 2638 women and their newborns treated with single course of dexamethasone or placebo were analysed. Multivariate logistic regression was used to assess the effect of dexamethasone versus placebo on neonatal death, stillbirth or neonatal death, and severe respiratory distress at 24 h and at 168 h, by administration-to-birth interval (from 0 through 28 days), adjusting for gestational age at first dose. We used relative risks to identify the administration-to-birth interval with the greatest benefits of dexamethasone compared to placebo on the newborn outcomes.Between 24 December 2017 and 21 November 2019, 2852 women and their 3070 babies were enrolled in the WHO ACTION-I trial; 1332 women (1464 babies) in the dexamethasone group and 1306 women (1440 babies) in the placebo group were included in this secondary analysis. Neonatal mortality risk was lower with increasing time between initiating dexamethasone and birth, achieving peak mortality reduction by days 13 and 14 and then diminishing as the interval approached 28 days, regardless of gestational age at administration. For other outcomes, the overall pattern of risk reduction extending into the second week was consistent with that of neonatal death.In women at risk of preterm birth prior to 34 weeks' gestation, the neonatal benefits of antenatal dexamethasone appear to increase with longer administration-to-birth intervals than previously thought. This knowledge can support clinical assessment and estimation of the risks of adverse preterm newborn outcomes at the time of birth, and the potential benefits of antenatal dexamethasone treatment for a known administration-to-birth interval.Bill and Melinda Gates Foundation; World Health Organization.

BackgroundPost-partum haemorrhage is one of the major causes of maternal mortality in low- and middle-income countries. Oxytocin is the first choice uterotonic for the PPH prevention but it requires cold storage. Heat stable carbetocin appears to be a promising agent for the prevention of PPH. The present study was an ancillary to the WHO CHAMPION Trial conducted to compare the effect of heat-stable carbetocin 100 µg IM versus oxytocin 10 IU IM on post-delivery hemoglobin level in one of the participating facilities in India.MethodsThis was a nested randomized controlled trial designed to compare the effect of heat-stable carbetocin 100 µg IM versus oxytocin 10 IU IM, administered within one minute of vaginal delivery of the baby for prevention of postpartum haemorrhage, on post-delivery 48–72 hours hemoglobin level, adjusted for pre-delivery hemoglobin level. 1,799 women from one hospital in India participated in this study.ResultsPre-delivery hemoglobin and postpartum blood loss were not significantly different between carbetocin and oxytocin. Post-delivery hemoglobin, unadjusted or adjusted for pre-delivery hemoglobin, was slightly lower for carbetocin compared to oxytocin. The drop in hemoglobin was slightly higher for carbetocin, although the difference was very small (1.2 g/dL for carbetocin, 1.1 g/dL for oxytocin). The proportion of participants with a drop in hemoglobin of 2 g/dL or more, adjusted for pre-delivery hemoglobin, was higher for carbetocin (RR = 1.29, 95% CI 1.02 to 1.63). From the regression coefficients it can be derived that post-delivery hemoglobin, adjusted for pre-delivery hemoglobin, decreases on average 0.12g/dL for each dL of blood lost, for the two treatments combined.ConclusionsThe present ancillary study showed that intramuscular administration of 100 µg of heat stable carbetocin can result in a slightly lower post-delivery hemoglobin, slightly higher drop and higher percentage of women having a drop of 2 g/dL or larger, compared to 10 IU of oxytocin, but these differences are not clinically relevant.Study registrationThe trial was registered with Clinical Trial Registry of India CTRI/2016/06/006996.

Background Antenatal corticosteroids (ACS) have long been regarded as a cornerstone intervention in mitigating the adverse effects of a preterm birth. However, the safety and efficacy of ACS in hospitals in low-resource countries has not been established in an efficacy trial despite their widespread use. Findings of a large cluster-randomized trial in six low- and middle-income countries showed that efforts to scale up ACS use in low-resource settings can lead to harm. There is equipoise regarding the benefits and harms of ACS use in hospitals in low-resource countries. This randomized controlled trial aims to determine whether ACS are safe and efficacious when given to women at risk of imminent birth in the early preterm period, in hospitals in low-resource countries. Methods/design The trial design is a parallel, two-arm, double-blind, individually randomized, placebo-controlled trial of ACS (dexamethasone) for women at risk of imminent preterm birth. The trial will recruit 6018 women in participating hospitals across five low-resource countries (Bangladesh, India, Kenya, Nigeria and Pakistan). The primary objectives are to compare the efficacy of dexamethasone with placebo on survival of the baby and maternal infectious morbidity. The primary outcomes are: 1) neonatal death (to 28 completed days of life); 2) any baby death (any stillbirth postrandomization or neonatal death); and 3) a composite outcome to assess possible maternal bacterial infections. The trial will recruit eligible, consenting pregnant women from 26 weeks 0 days to 33 weeks 6 days gestation with confirmed live fetuses, in whom birth is planned or expected within 48 h. The intervention comprises a regimen of intramuscular dexamethasone sodium phosphate. The comparison is an identical placebo regimen (normal saline). A total of 6018 women will be recruited to detect a reduction of 15% or more in neonatal deaths in a two-sided 5% significance test with 90% power (including 10% loss to follow-up). Discussion Findings of this trial will guide clinicians, programme managers and policymakers on the safety and efficacy of ACS in hospitals in low-resource countries. The trial findings will inform updating of the World Health Organization’s global recommendations on ACS use. Trial registration ACTRN12617000476336. Registered on 31 March 2017. Electronic supplementary material The online version of this article (10.1186/s13063-019-3488-z) contains supplementary material, which is available to authorized users.

Background Postpartum hemorrhage is the most common cause of maternal death. Oxytocin is the standard therapy for the prevention of postpartum hemorrhage, but it requires cold storage, which is not available in many countries. In a large trial, we compared a novel formulation of heat-stable carbetocin with oxytocin. Methods We enrolled women across 23 sites in 10 countries in a randomized, double-blind, noninferiority trial comparing intramuscular injections of heat-stable carbetocin (at a dose of 100 μg) with oxytocin (at a dose of 10 IU) administered immediately after vaginal birth. Both drugs were kept in cold storage (2 to 8°C) to maintain double-blinding. There were two primary outcomes: the proportion of women with blood loss of at least 500 ml or the use of additional uterotonic agents, and the proportion of women with blood loss of at least 1000 ml. The noninferiority margins for the relative risks of these outcomes were 1.16 and 1.23, respectively. Results A total of 29,645 women underwe...

BACKGROUND: The safety and efficacy of antenatal glucocorticoids in women in low-resource countries who are at risk for preterm birth are uncertain. METHODS: We conducted a multicountry, randomized trial involving pregnant women between 26 weeks 0 days and 33 weeks 6 days of gestation who were at risk for preterm birth. The participants were assigned to intramuscular dexamethasone or identical placebo. The primary outcomes were neonatal death alone, stillbirth or neonatal death, and possible maternal bacterial infection; neonatal death alone and stillbirth or neonatal death were evaluated with superiority analyses, and possible maternal bacterial infection was evaluated with a noninferiority analysis with the use of a prespecified margin of 1.25 on the relative scale. RESULTS: A total of 2852 women (and their 3070 fetuses) from 29 secondary- and tertiary-level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan underwent randomization. The trial was stopped for benefit at the second interim analysis. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI], 0.72 to 0.97; P=0.03). Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) and in 444 of 1519 fetuses and infants (29.2%), respectively (relative risk, 0.88; 95% CI, 0.78 to 0.99; P=0.04); the incidence of possible maternal bacterial infection was 4.8% and 6.3%, respectively (relative risk, 0.76; 95% CI, 0.56 to 1.03). There was no significant between-group difference in the incidence of adverse events. CONCLUSIONS: Among women in low-resource countries who were at risk for early preterm birth, the use of dexamethasone resulted in significantly lower risks of neonatal death alone and stillbirth or neonatal death than the use of placebo, without an increase in the incidence of possible maternal bacterial infection. Fil: Oladapo, Olufemi T.. Organizacion Mundial de la Salud; Argentina Fil: Vogel, Joshua P.. Organizacion Mundial de la Salud; Argentina Fil: Piaggio, Gilda. Organizacion Mundial de la Salud; Argentina Fil: Nguyen, My-Huong. Organizacion Mundial de la Salud; Argentina Fil: Althabe, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina Fil: Metin Gülmezoglu, A.. Organizacion Mundial de la Salud; Argentina Fil: Bahl, Rajiv. Organizacion Mundial de la Salud; Argentina Fil: Rao, Suman P.N.. Organizacion Mundial de la Salud; Argentina Fil: de Costa, Ayesha. Organizacion Mundial de la Salud; Argentina Fil: Gupta, Shuchita. Organizacion Mundial de la Salud; Argentina Fil: Shahidullah, Mohammod. No especifíca; Fil: Chowdhury, Saleha B.. No especifíca; Fil: Ara, Gulshan. No especifíca; Fil: Akter, Shaheen. No especifíca; Fil: Akhter, Nasreen. No especifíca; Fil: Dey, Probhat R.. No especifíca; Fil: Abdus Sabur, M.. No especifíca; Fil: Azad, Mohammad T.. No especifíca; Fil: Choudhury, Shahana F.. No especifíca; Fil: Matin, M.A.. No especifíca; Fil: Goudar, Shivaprasad S.. No especifíca; Fil: Dhaded, Sangappa M.. No especifíca; Fil: Metgud, Mrityunjay C.. No especifíca; Fil: Pujar, Yeshita V.. No especifíca; Fil: Somannavar, Manjunath S.. No especifíca; Fil: Vernekar, Sunil S.. No especifíca; Fil: Herekar, Veena R.. No especifíca; Fil: Bidri, Shailaja R.. No especifíca; Fil: Mathapati, Sangamesh S.. No especifíca; Fil: Patil, Preeti G.. No especifíca; Fil: Patil, Mallanagouda M.. No especifíca; Fil: Gudadinni, Muttappa R.. No especifíca; Fil: Bijapure, Hidaytullah R.. No especifíca; Fil: Mallapur, Ashalata A.. No especifíca; Fil: Katageri, Geetanjali M.. No especifíca; Fil: Chikkamath, Sumangala B.. No especifíca; Fil: Yelamali, Bhuvaneshwari C.. No especifíca; Fil: Pol, Ramesh R.. No especifíca; Fil: Misra, Sujata S.. No especifíca; Fil: Das, Leena. No especifíca

Objective To assess the maternal characteristics and causes associated with refractory postpartum haemorrhage (PPH). Design Secondary analysis of the WHO CHAMPION trial data. Setting Twenty‐three hospitals in ten countries. Population Women from the CHAMPION trial who received uterotonics as first‐line treatment of PPH. Methods We assessed the association between sociodemographic, pregnancy and childbirth factors and refractory PPH, and compared the causes of PPH between women with refractory PPH and women responsive to first‐line PPH treatment. Main outcome measures Maternal characteristics; causes of PPH. Results Women with labour induced or augmented with uterotonics (adjusted odds ratio [aOR] 1.35; 95% CI 1.07–1.72), with episiotomy or tears requiring suturing (aOR 1.82; 95% CI 1.34–2.48) and who had babies with birthweights ≥3500 g (aOR 1.33; 95% CI 1.04–1.69) showed significantly higher odds of refractory PPH compared with the reference categories in the multivariate analysis adjusted by centre and trial arm. While atony was the sole PPH cause in 53.2% (116/218) of the women in the responsive PPH group, it accounted for only 31.5% (45/143) of the causes in the refractory PPH group. Conversely, tears were the sole cause in 12.8% (28/218) and 28% (40/143) of the responsive PPH and refractory PPH groups, respectively. Placental problems were the sole cause in 11 and 5.6% in the responsive and refractory PPH groups, respectively. Conclusion Women with refractory PPH showed a different pattern of maternal characteristics and PPH causes compared with those with first‐line treatment responsive PPH. Tweetable abstract Women with refractory postpartum haemorrhage are different from those with first‐line treatment responsive PPH., Tweetable abstract Women with refractory postpartum haemorrhage are different from those with first‐line treatment responsive PPH.

Background\ud Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage.\ud \ud Methods\ud In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283.\ud \ud Findings\ud Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group.\ud \ud Interpretation\ud Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset.\ud \ud Funding\ud London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation.

Objectives To compare rates of unintended pregnancy, method continuation and reasons for removal among women using the 52-mg levonorgestrel (daily release 20 microg) levonorgestrel IUD (LNG-IUD) or the copper T 380A (TCu380A) intrauterine device. Study design This was an open-label 7-year randomized controlled trial in 20 centres, 11 of which in China. Data on 1884 women with interval insertion of the LNG-IUD and 1871 of the TCu380A were analysed using life tables with 30-day intervals and Cox proportional hazards models. Results The cumulative 7-year pregnancy rate of the LNG-IUD was 0.5 (standard error 0.2) per 100, significantly lower than 2.5 (0.4) per 100 of the TCu380A, cumulative method discontinuation rates at 7 years were 70.6 (1.2) and 40.8 (1.3) per 100, respectively. Dominant reasons for discontinuing the LNG-IUD were amenorrhea (26.1 [1.3] per 100) and reduced bleeding (12.5 [1.1] per 100), particularly in Chinese women and, for the TCu380A, increased bleeding (9.9 [0.9] per 100), especially among non-Chinese women. Removal rates for pain were similar for the two intrauterine devices (IUDs). Cumulative rates of removal for symptoms compatible with hormonal side effects were 5.7 (0.7) and 0.4 (0.2) per 100 for the LNG-IUD and TCu380A, respectively, and cumulative losses to follow-up at 7 years were 26.0 (1.4) and 36.9 (1.3) per 100, respectively. Conclusion The LNG-IUD and the TCu380A have very high contraceptive efficacy, with the LNG-IUD significantly higher than the TCu380A. Overall rates of IUD removals were higher among LNG-IUD users than TCu380A users. Removals for amenorrhea appeared culturally associated. Implications The 52-mg LNG-IUD and the TCu380A have very high contraceptive efficacy through 7 years. As an IUD, the unique side effects of the LNG-IUD are reduced bleeding, amenorrhea and symptoms compatible with hormonal contraceptives.

Background Male and female condom (FC) functional performance failure declines with user experience. With the recent availability of a wider range of FCs, it is important to know if women with experience in using one type of FC are more proficient in using another type, even if the FC design is quite different. Study design A randomized, noninferiority crossover clinical trial assessed the function of four FCs (FC2, Woman's Condom, Cupid and VA w.o.w) among 300 women in Durban, South Africa. FC functional failure (breakage, slippage, invagination and misdirection) by condom type and use period was investigated in women using five FCs of each type (20 FC uses in total). Results Of the 5364 condoms used during intercourse by 272 women, 200 clinical failures occurred in 195 condoms (190 condoms had one failure, and 5 had two failures). Total clinical failure was comparable across FC types. Of the 195 condoms in which failures occurred, the number of failures in the first condom use period was 103 (7.7%), decreasing to 43 events (3.2%) in the second, 33 (2.5%) in the third and 16 (1.2%) in the fourth. Only 2 failures were reported in the 20th use of an FC compared to 29 in the first use, irrespective of condom type. Conclusions FC failure rates decreased markedly after use of the first five condoms regardless of FC type and continued to fall across the next three use periods. Implications FC failure rates decrease over 20 uses, regardless of FC condom type used. The decrease is higher at the beginning of use, indicating that improvement is greatest after the first five uses.

Ultrasound biometry is an important clinical tool for the identification, monitoring, and management of fetal growth restriction and development of macrosomia. This is even truer in populations in which perinatal morbidity and mortality rates are high, which is a reason that much effort is put onto making the technique available everywhere, including low-income societies. Until recently, however, commonly used reference ranges were based on single populations largely from industrialized countries. Thus, the World Health Organization prioritized the establishment of fetal growth charts for international use. New fetal growth charts for common fetal measurements and estimated fetal weight were based on a longitudinal study of 1387 low-risk pregnant women from 10 countries (Argentina, Brazil, Democratic Republic of Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) that provided 8203 sets of ultrasound measurements. The participants were characterized by median age 28 years, 58% nulliparous, normal body mass index, with no socioeconomic or nutritional constraints (median caloric intake, 1840 calories/day), and had the ability to attend the ultrasound sessions, thus essentially representing urban populations. Median gestational age at birth was 39 weeks, and birthweight was 3300 g, both with significant differences among countries. Quantile regression was used to establish the fetal growth charts, which also made it possible to demonstrate a number of features of fetal growth that previously were not well appreciated or unknown: (1) There was an asymmetric distribution of estimated fetal weight in the population. During early second trimester, the distribution was wider among fetuses50th percentile compared with those above. The pattern was reversed in the third trimester, with a notably wider variation50th percentile. (2) Although fetal sex, maternal factors (height, weight, age, and parity), and country had significant influence on fetal weight (1-4.5% each), their effect was graded across the percentiles. For example, the positive effect of maternal height on fetal weight was strongest on the lowest percentiles and smallest on the highest percentiles for estimated fetal weight. (3) When adjustment was made for maternal covariates, there was still a significant effect of country as covariate that indicated that ethnic, cultural, and geographic variation play a role. (4) Variation between populations was not restricted to fetal size because there were also differences in growth trajectories. (5) The wide physiologic ranges, as illustrated by the 5th-95th percentile for estimated fetal weight being 2205-3538 g at 37 weeks gestation, signify that human fetal growth under optimized maternal conditions is not uniform. Rather, it has a remarkable variation that largely is unexplained by commonly known factors. We suggest this variation could be part of our common biologic strategy that makes human evolution extremely successful. The World Health Organization fetal growth charts are intended to be used internationally based on low-risk pregnancies from populations in Africa, Asia, Europe, and South America. We consider it prudent to test and monitor whether the growth charts' performance meets the local needs, because refinements are possible by a change in cut-offs or customization for fetal sex, maternal factors, and populations. In the same line, the study finding of variations emphasizes the need for carefully adjusted growth charts that reflect optimal local growth when public health issues are addressed.

The scientific basis for antenatal corticosteroids (ACS) for women at risk of preterm birth has rapidly changed in recent years. Two landmark trials-the Antenatal Corticosteroid Trial and the Antenatal Late Preterm Steroids Trial-have challenged the long-held assumptions on the comparative health benefits and harms regarding the use of ACS for preterm birth across all levels of care and contexts, including resource-limited settings. Researchers, clinicians, programme managers, policymakers and donors working in low-income and middle-income countries now face challenging questions of whether, where and how ACS can be used to optimise outcomes for both women and preterm newborns. In this article, we briefly present an appraisal of the current evidence around ACS, how these findings informed WHO's current recommendations on ACS use, and the knowledge gaps that have emerged in the light of new trial evidence. Critical considerations in the generalisability of the available evidence demonstrate that a true state of clinical equipoise exists for this treatment option in low-resource settings. An expert group convened by WHO concluded that there is a clear need for more efficacy trials of ACS in these settings to inform clinical practice.

Background In the mid-2000s, neonatal mortality accounted for almost 40% of deaths of children under 5 years worldwide, and constituted 65% of infant deaths in India. The neonatal mortality rate in Andhra Pradesh was 44 per 1,000 live births, and was higher in the rural areas and tribal regions, such as the Nagarkurnool division of Mahabubnagar district (which became Nagarkurnool district in Telangana in 2014). The aim of the CHAMPION trial was to investigate whether a package of interventions comprising community health promotion and provision of health services (including outreach and facility-based care) could lead to a reduction of the order of 25% in neonatal mortality. Methods and findings The design was a trial in which villages (clusters) in Nagarkurnool with a population < 2,500 were randomised to the CHAMPION package of health interventions or to the control arm (in which children aged 6–9 years were provided with educational interventions—the STRIPES trial). A woman was eligible for the CHAMPION package if she was married and, In CHAMPION, a cluster-randomized trial carried out in rural India, Diana Elbourne and colleagues investigate the benefit of a package of interventions for neonatal care., Author summary Why was this study done? At the time this study was planned, the rate of death of children in the first 28 days of life was very high in parts of rural India. Earlier research had suggested that community health promotion, along with buttressing existing maternity and neonatal services, might reduce this rate. What did the researchers do and find? We randomised small villages in the Nagarkurnool district in Telangana either to the package of health interventions or to control. We provided married women in the intervention villages with community health promotion (including health education via village health worker–led participatory discussion groups), outreach (including mobile teams providing antenatal check-ups), and facility-based care (including subsidised access to non-public health centres). We enrolled 14,137 women in 232 control villages and 15,532 in 232 intervention villages. In all, 4,885 control women had 5,474 eligible pregnancies and gave birth to 4,998 eligible children. The corresponding numbers in intervention villages were 5,664 women, 6,351 pregnancies, and 5,798 children. We found that, of the live-born babies, 343 (6.9%) in the control arm and 303 (5.2%) in the intervention arm died in their first 28 days of life, suggesting that there were 92 fewer deaths as a result of the intervention. We also found evidence of improved health knowledge and health practices including health service usage in the intervention arm compared to the control arm. What do these findings mean? The research findings mean that interventions such as those in the CHAMPION trial can be strongly justified in much of rural India. Further research is needed to assess whether the interventions are of use in other rural settings with similar socioeconomic and cultural patterns, similar neonatal mortality rates, and the existence of some private health provision.

BACKGROUND: New designs of female condom have been developed to reduce costs and improve acceptability. To secure regulatory approvals, clinical studies are needed to verify performance. We aimed to assess the functional performance and safety of three new condom types-the Woman's Condom, the VA worn-of-women (wow) Condom Feminine, and the Cupid female condom-against the existing second-generation female condom (FC2). METHODS: We did a randomised controlled, non-inferiority, four-period crossover trial at three sites in Shanghai, China, and one site in Durban, South Africa, between May 1, 2011, and Jan 31, 2012. Participants aged 18-45 years who were sexually active, monogamous, not pregnant, and not sex workers, were eligible for inclusion if they were literate, had no known allergies to the study products; used a reliable, non-barrier method of contraception, and had no visible or reported sexually transmitted infections. We used a computer-generated randomisation sequence with a Williams square design of size four to assign patients (1:1:1:1) to the FC2 control device, or the Woman's, VA wow, or Cupid condoms, with 12 potential allocations. Randomisation was stratified by site. Participants were not masked to condom type, but allocation was concealed from study investigators. The primary non-inferiority endpoints were total clinical failure and total female condom failure, with a non-inferiority margin of 3%. Women were asked to use five of each condom type and were interviewed after use of each type. We also assessed safety data for each type. We did both per-protocol and intention-to-treat analyses. We calculated frequencies and percentages for each failure event and estimated differences in performance with a generalised estimating equation model. This study is registered, number DOH-27-0113-4271. FINDINGS: 616 women were assessed for eligibility, of whom 600 were randomly assigned to condom-type order (30, 120, and 150 women in the three sites in China, and 300 women in the site in South Africa). 572 women completed follow-up, with at least one condom of each type. Total female condom failure was 3·43% for FC2, 3·85% for the Woman's Condom (difference 0·42%, 90% CI -1·42 to 2·26), 3·02% for VA wow (-0·42%, -1·86 to 1·32), and 4·52% for Cupid (1·09%, -0·60 to 2·78); total clinical failure was 2·88%, 3·05% (0·17%, -1·48 to 1·81), 2·49% (-0·25%, -1·75 to 1·26), and 3·87% (0·99%, -0·55 to 2·52), respectively. Only two (

Summary Background Evidence suggests that community-based interventions that promote improved home-based practices and care-seeking behaviour can have a large impact on maternal and child mortality in regions where rates are high. We aimed to assess whether an intervention package based on the WHO Integrated Management of Childhood Illness handbook and community mobilisation could reduce under-5 mortality in rural Guinea-Bissau, where the health service infrastructure is weak. Methods We did a non-masked cluster-randomised controlled trial (EPICS) in the districts of Tombali and Quinara in Guinea-Bissau. Clusters of rural villages were stratified by ethnicity and distance from a regional health centre, and randomly assigned (1:1) to intervention or control using a computerised random number generator. Women were eligible if they lived in one of the clusters at baseline survey prior to randomisation and if they were aged 15–49 years or were primary caregivers of children younger than 5 years. Their children were eligible if they were younger than 5 years or were liveborn after intervention services could be implemented on July 1, 2008. In villages receiving the intervention, community health clubs were established, community health workers were trained in case management, and traditional birth attendants were trained to care for pregnant women and newborn babies, and promote facility-based delivery. Registered nurses supervised community health workers and offered mobile clinic services. Health centres were not improved. The control group received usual services. The primary outcome was the proportion of children dying under age 5 years, and was analysed in all eligible children up to final visits to villages between Jan 1 and March 31, 2011. This trial is registered with ISRCTN, number ISRCTN52433336. Findings On Aug 30, 2007, we randomly assigned 146 clusters to intervention (73 clusters, 5669 women, and 4573 children) or control (73 clusters, 5840 women, and 4675 children). From randomisation until the end of the trial (last visit by June 30, 2011), the intervention clusters had 3093 livebirths and the control clusters had 3194. 6729 children in the intervention group and 6894 in the control group aged 0–5 years on July 1, 2008, or liveborn subsequently were analysed for mortality outcomes. 311 (4·6%) of 6729 children younger than 5 years died in the intervention group compared with 273 (4·0%) of 6894 in the control group (relative risk 1·16 [95% CI 0·99–1·37]). Interpretation Our package of community-based interventions did not reduce under-5 mortality in rural Guinea-Bissau. The short timeframe and other trial limitations might have affected our results. Community-based health promotion and basic first-line services in fragile contexts with weak secondary health service infrastructure might be insufficient to reduce child deaths. Funding Effective Intervention.

Background To avoid selection bias in clinical trials, random allocation concealment is crucial to ensure that participants and or researchers remain unaware of assignments. Purpose We aimed to design an allocation concealment method that reduced the possibility of selection bias for a randomized, open-label, crossover trial to evaluate device function of four female condom (FC) types. Methods Using scratch card technology, we devised a simple method of concealment, whereby the treatment sequence was printed on a single card for each participant, and the codes for each treatment in the sequence were concealed beneath foil squares on a stiff A6-sized card. On the first and subsequent follow-up visits, the foil corresponding to that visit was scratched from the square to reveal the condom type allocation for the next condom-use period. Staff in the South African and Chinese trial sites were trained in use and care of the card, and on completion of the study completed a questionnaire on their experience of use. Results Research staff in both countries found the card easy to use and those who had previously used the sequentially numbered, opaque, sealed envelopes (SNOSE) system for random allocation reported the scratch card easier to use. Research staff most commonly used a coin to remove the foil square and some used their fingernails. In both South Africa and China, no errors in allocation sequence were found during study monitoring. Limitations Scratch card system of allocation cannot be printed in-house. Conclusions This novel, effective method of concealment for a crossover random allocation was well liked by study staff. The most important advantage of this method is the ability to conceal consecutive allocations of a crossover design using a single card, thus eliminating the need for multiple envelopes per participant. While we used this method in a clinical trial of FCs, it could be employed in a range of other clinical trials and other randomized studies.

Little information is available about the incidence of complications from vacuum aspiration for first-trimester abortion after cervical preparation with prostaglandin analogues. We compared incidence of complications from vacuum aspiration in women who had had cervical preparation with misoprostol and those who had not.We did a randomised parallel-group trial at 14 centres in nine countries between Oct 22, 2002, and Sept 24, 2005. Healthy women seeking first-trimester abortion were randomly assigned via a computer-generated randomisation sequence stratified by centre, to receive vaginal administration of either two 200 μg tablets of misoprostol or two placebo tablets 3 h before abortion by vacuum aspiration. Participants and health-care personnel other than staff administering the treatment were masked to group assignment. Follow-up was up to 2 weeks. The primary outcome was one or more complications of vacuum aspiration (cervical tear, uterine perforation, incomplete abortion, uterine re-evacuation, pelvic inflammatory disease, or any other serious adverse event). We included women undergoing treatment and vacuum aspiration in the analysis of immediate complications; whereas, in the analysis of delayed complications, we included only those followed-up. In the analysis of any immediate or delayed complication, we excluded women lost to follow-up. This trial is registered, number ISRCTN85366519.We randomly assigned 2485 women to the misoprostol group and 2487 to the placebo group. Two women in the misoprostol group did not have vacuum aspiration. 56 women in each group were lost to follow-up. 50 (2%) of 2427 women in the misoprostol group and 74 (3%) of 2431 in the placebo group had one or more complication of vacuum aspiration (relative risk [RR] 0·68, 95% CI 0·47-0·96). No women in the misoprostol group had cervical tears and three had uterine perforations compared with two women in the placebo group who had cervical tears and one who had perforation. 19 (1%) women given misoprostol and 55 (2%) on placebo had incomplete abortions (0·35, 0·21-0·58), of whom 14 (1%) versus 48 (2%) needed uterine re-evacuation (0·29, 0·16-0·53). We noted no difference between groups in incidence of pelvic inflammatory disease (30 [1%] vs 25 [1%]; RR 1·20, 0·71-2·04) or other serious adverse events. The main side-effects of misoprostol during the 3 h treatment were abdominal pain (1355 [55%] of 2484 women vs 545 [22%] of 2487 women in the placebo group) and vaginal bleeding (909 [37%] vs 167 [7%]).Cervical preparation with 400 μg of vaginal misoprostol can reduce incidence of complications from vacuum aspiration for first trimester abortion.UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research, WHO, and the Packard Foundation.

Please cite this paper as: von Hertzen H, Huong N, Piaggio G, Bayalag M, Cabezas E, Fang A, Gemzell-Danielsson K, Hinh N, Mittal S, Ng E, Chaturachinda K, Pinter B, Puscasiu L, Savardekar L, Shenoy S, Khomassuridge A, Tuyet H, Velasco A, Peregoudov A, for the WHO Research Group on Postovulatory Methods of Fertility Regulation. Misoprostol dose and route after mifepristone for early medical abortion: a randomised controlled noninferiority trial. BJOG 2010;117:1186–1196. Objective To compare 400 and 800 μg sublingual or vaginal misoprostol 24 hours after 200 mg mifepristone for noninferiority regarding efficacy in achieving complete abortion for pregnancy termination up to 63 days of gestation. Design Placebo-controlled, randomised, noninferiority factorial trial, stratified by centre and length of gestation. Misoprostol 400 or 800 μg, administered either sublingually or vaginally, with follow up after 2 and 6 weeks. Setting Fifteen obstetrics/gynaecology departments in ten countries. Population Pregnant women (n = 3005) up to 63 days of gestation requesting medical abortion. Methods Two-sided 95% CI for differences in failure of complete abortion and continuing pregnancy, with a 3% noninferiority margin, were calculated. Proportions of women with adverse effects were recorded. Outcome measures Complete abortion without surgical intervention (main); continuing live pregnancies, induction-to-abortion interval, adverse effects, women’s perceptions (secondary). Results Efficacy outcomes analysed for 2962 women (98.6%): 90.5% had complete abortion after 400 μg misoprostol, 94.2% after 800 μg. Noninferiority of 400 μg misoprostol was not demonstrated for failure of complete abortion (difference: 3.7%; 95% CI 1.8–5.6%). The 400-μg dose showed higher risk of incomplete abortion (P

Objective In the past ten years effective treatments for pre-eclampsia and eclampsia have been evaluated and identified following large trials and systematic reviews. We investigated the extent of those effective interventions’ implementation. Methods Descriptive analysis of data collected as part of a cluster randomized trial. The trial was assigned the International Standardised Randomized Controlled Trial Number ISRCTN 14055385. Hospitals with more than 1000 deliveries per year not directly associated with an academic institution in Mexico City municipal area in Mexico (n = 22) and the north-east region of Thailand (n = 18) were included. All women delivering at the participating hospitals at two time periods in 2000 and 2002 contributed data on practice rates. The use of magnesium sulfate for pre-eclampsia and eclampsia were the outcomes. Findings Eight out of 22 hospitals in Mexico (range 0.8% to 8.5%) and all 18 hospitals in Thailand (range 18.6% to 63.6%) used magnesium sulfate for women with pre-eclampsia. In Mexico, 11 of 22 hospitals used magnesium sulfate for eclampsia (range 9.1% to 60.0%). In Thailand, all 17 hospitals having eclampsia cases used magnesium sulfate (range 25% to 100%). Conclusion Despite compelling evidence, magnesium sulfate use is below desired levels. Clinical practices should be audited and implementation of this effective intervention should be taken up as a priority where universal implementation is not in place.

In 1999, the US Food and Nutrition Board revised the Adequate Intake (AI) for calcium in pregnancy and recommended 1000 mg/day for adult pregnant women and 1300 mg/day for adolescent women (

A study (ISRCTN 77665712) was undertaken to test the effectiveness and the acceptability of vitamin E and low-dose aspirin, alone or in combination, as treatment for prolonged vaginal bleeding induced by Norplant. A total of 486 Norplant users who were requesting treatment for bleeding lasting longer than 7 days were enrolled in five centers: Beijing, China; Jakarta, Indonesia; Santiago, Chile; Santo Domingo, Dominican Republic; and Tunis, Tunisia. They were randomized to one of four different 10-day oral treatments: 200 mg vitamin E daily, 80 mg aspirin daily, both or a placebo. Treatment packs were designed to ensure blinding of both the subjects and the clinical staff. Neither vitamin E nor low-dose aspirin nor their combination was found to have any effect on reducing the length of the bleeding episode for which treatment was taken or on the vaginal bleeding patterns these women experienced during the year of follow-up.

Objectives To compare the side effect profiles of regimens of oral and vaginal administration of misoprostol after a single oral dose of 200 mg of mifepristone and to investigate patients' perceptions of medical abortion. Design Double-blind, randomised controlled trial. Setting Fifteen gynaecological clinics in 11 countries. Population A total of 2219 healthy pregnant women requesting medical abortion with

We conducted a clinical single-arm trial to evaluate the effectiveness of 10 mg mifepristone for emergency contraception (EC) in a large population in China. The participating centers were 31 family-planning clinics and hospitals in the following 19 provinces or municipalities in China: Beijing, Shanghai, Tianjin, Harbin, Changchun, Shengyang, Shijiazhuang, Zhengzhou, Taiyuan, Nanjing, Jinan, Hangzhou, Guangzhou, Wuhan, Changsha, Chongqing, Guiyang, Chengdu, Kunming. A total of 4945 women requesting EC within 120 h after a single act of unprotected intercourse were recruited and treated with 10 mg mifepristone. A total of 28 women were lost to follow-up, and 4917 women were included in the analysis, of whom, 69 became pregnant. The combined pregnancy rate was 1.4 [95% confidence interval (CI): 1.0–1.9] and the percentage of pregnancies prevented was 82.2% (95% CI: 77.5–86.2%). There was a significant inverse trend in pregnancy rate with body mass index that disappeared when adjusted for other variables. The pregnancy risk was double among nulliparous women compared to parous women (2.3% compared to 1.0%), and it increased by a factor of 1.5 when the treatment was administered at 25–48 h and at 49–72 h compared to administration within 24 h, although this association was not significant. The risk of pregnancy was higher if intercourse took place during the follicular or preovulatory phase of the cycle. Women having repeated intercourse after treatment without any contraceptive methods had a dramatic increase in the risk of pregnancy, while those who used contraceptives had similar risk to those without acts. Side effects were mild and present in only small proportions of women: nausea and vomiting in 9% and other side effects in 2–3%. Delay of menstruation of 7 days or more occurred in 6.5% of women. The expanded study confirmed the high efficacy and safety of 10 mg mifepristone for EC.

Increasingly researchers are recognizing that in many situations, using a cluster-randomized trial (in which groups of individuals are randomized rather than individuals directly) may be more appropriate than an individually randomized trial. Cluster-randomized trials are more complex to design, however, primarily because observations on individuals within the same cluster tend to be correlated. The statistical measure of this correlation within clusters is known as the intraclass or intracluster correlation coefficient (ICC). In this article, we discuss the measurement and impact of the ICC on the design and analysis of cluster-randomized trials. In particular we outline how an ICC can be calculated, the likely magnitude of ICCs in specific settings, the factors that influence the ICC estimate, how an ICC should be reported, and the impact of the ICC on sample-size requirements and analysis. Keywords: cluster randomization; intraclass (intracluster) correlation; design effect; inflation factor

Cluster randomization trials have become a very attractive research strategy, particularly for the evaluation of health service interventions. The need to conduct meta-analyses of such trials is also becoming more common. However, as with cluster randomization trials in general, such analyses raise special methodologic challenges. In this paper, we discuss and illustrate several statistical approaches that might be applied to a meta-analysis of cluster randomization trials, each of which has a binary endpoint. Statistical methods for constructing inferences for a summary intervention odds ratio include those based on Mantel-Haenszel procedures, the ratio estimator approach, Woolf procedures and generalized estimating equations using robust variance estimation. The advantages and disadvantages of each method are discussed in the context of an example.

The World Health Organization and collaborating institutions in four developing countries have conducted a multi-centre randomized controlled trial, in which clinics were allocated at random to two antenatal care (ANC) models. These were the standard Western' ANC model and a new' ANC model consisting of tests, clinical procedures and follow-up actions scientifically demonstrated to be effective in improving maternal and newborn outcomes. The two models were compared using the equivalence approach. This paper discusses the implications of the equivalence approach in the sample size calculation, analysis and interpretation of results of this cluster randomized trial. It reviews the ethical aspects regarding informed consent, concluding that the Zelen design has a place in cluster randomization trials. It describes the estimation of the intracluster correlation coefficient (ICC) in a stratified cluster randomized trial using two methods and reports estimates of the ICC obtained for many maternal, newborn and perinatal outcomes. Finally, it discusses analytical problems that arose: issues encountered using a composite index, heterogeneity of the intervention effect across sites, the choice of the method of analysis and the importance of efficacy analyses. The choice of the clustered Woolf estimator and the generalized estimating equations (GEE) as the methods of analysis applied is discussed.

Erratum to “The frameless copper IUD (GyneFix) and the TCu380A IUD: results of an 8-year multicenter randomized comparative trial” [Contraception 2009;80:133–41] Olav Meirik⁎, Patrick J. Rowe, Alexandre Peregoudov, Gilda Piaggio, Max Petzold for the IUD Research Group at the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, 1211 Geneva 27, Switzerland Instituto Chileno de Medicina Reproductiva (ICMER), 8320162 Santiago, Chile Vesancy, 01170 Gex, France Nordic School of Public Health, 402 42 Gothenburg, Sweden

In the preparation of a randomised controlled trial to evaluate a new programme of antenatal care (ANC) in different parts of the world, we conducted a baseline survey of the ANC procedures in all 53 clinics participating in the trial. There were two components of this survey: (1) description of clinic characteristics and services offered: the staff of each clinic was interviewed and direct observation was made by field supervisors, and (2) the actual use of services by pregnant women attending these clinics: we reviewed a random sample of 2913 clinical histories. The clinical units surveyed were offering most of the activities, screening, laboratory tests and interventions recommended as effective according to the Cochrane Pregnancy and Childbirth Database (PCD), although some of these were not available in some sites. On the other hand, some tests and interventions that are considered not effective according to these criteria are reportedly offered. There was a difference across sites in the availability and offer to low-risk women of vaginal examination, evaluation of pelvic size, dental examination, external version for breech presentation and formal risk score classification, and a notable difference in the type of principal provider of ANC. There was a large variation in the actual use of screening and laboratory tests and interventions that should be offered to all women according to Cochrane PCD criteria: some of these are simply not available in a site; others are available, but only a fraction of women attending the clinics are receiving them. The participating sites all purport to follow the traditional 'Western' schedule for ANC, but in three sites we found that a high percentage of women initiate their ANC after the first trimester, and therefore do not have either the recommended minimum number of visits during pregnancy or the minimum first trimester evaluation. It is concluded that the variability and heterogeneity of ANC services provided in the four study sites are disturbing to the profession and cast doubts on the rationale of routine ANC.This paper reports the results of an antenatal care (ANC) baseline survey in four study sites in different parts of the world participating in the WHO ANC randomized controlled trial. The health care units surveyed are providing most of the activities, screening, laboratory tests and interventions recommended as effective based on the Cochrane Pregnancy and Childbirth Database (PCD), although some of these are not available in some clinics. Some tests and interventions that are considered ineffective according to the PCD criteria are reportedly offered. A variation is observed across sites in the availability and offer to low-risk women of vaginal exam, pelvic size assessment, dental exam, external version for breech presentation, and formal risk score classification. Moreover, there is a significant difference in the type of principal ANC provider and a great variation in the actual performance of screening and laboratory tests and interventions that should be provided to all women according to these criteria. This is partly due to the unavailability of these services in the site, or only a fraction of women attending the clinics are receiving them. The participating clinics all declared to follow the traditional Western schedule for ANC; however, three clinics are found to have a high percentage of women who begin their ANC after the first trimester of pregnancy. It is generalized that the variability and heterogeneity of ANC services offered in the four sites are annoying to the profession and cast doubts on the rationale behind routine ANC.

Summary Background Active management of the third stage of labour reduces the risk of post-partum haemorrhage. We aimed to assess whether controlled cord traction can be omitted from active management of this stage without increasing the risk of severe haemorrhage. Methods We did a multicentre, non-inferiority, randomised controlled trial in 16 hospitals and two primary health-care centres in Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally generated allocation sequence, stratified by country, to placental delivery with gravity and maternal effort (simplified package) or controlled cord traction applied immediately after uterine contraction and cord clamping (full package). After randomisation, allocation could not be concealed from investigators, participants, or assessors. Oxytocin 10 IU was administered immediately after birth with cord clamping after 1–3 min. Uterine massage was done after placental delivery according to local policy. The primary (non-inferiority) outcome was blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin for the risk ratio was 1·3. Analysis was by modified intention-to-treat, excluding women who had emergency caesarean sections. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN 12608000434392. Findings Between June 1, 2009, and Oct 30, 2010, 12 227 women were randomly assigned to the simplified package group and 12 163 to the full package group. After exclusion of women who had emergency caesarean sections, 11 861 were in the simplified package group and 11 820 were in the full package group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of 1·09 (95% CI 0·91–1·31) and the upper 95% CI limit crossed the pre-stated non-inferiority margin. One case of uterine inversion occurred in the full package group. Other adverse events were haemorrhage-related. Interpretation Although the hypothesis of non-inferiority was not met, omission of controlled cord traction has very little effect on the risk of severe haemorrhage. Scaling up of haemorrhage prevention programmes for non-hospital settings can safely focus on use of oxytocin. Funding United States Agency for International Development and UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research.

Contraceptive-induced vaginal bleeding changes may be an undesired side effect, or a welcome opportunity to alter menstrual patterns. In Europe and the US, such changes are increasingly accepted; this study explores the perceptions of women around the globe.Norplant users from five countries (Chile, China, the Dominican Republic, Indonesia and Tunisia; N = 486) were surveyed at entry into a contraceptive clinical trial regarding preferred frequency of menstruation, menses-associated symptoms, and activities during menses.Most women preferred once-monthly menstruation (81%); women in Chile, younger women, women neither married nor cohabitating, Christian women, and women experienced with hormonal contraception were more likely to accept alternative bleeding patterns. Women in Tunisia and Chile reported more symptoms associated with menses, while women in Beijing reported very few; decreased energy (32%), headaches (26%), abdominal pain (23%) and depression (22%) were most common. Avoidance of activities during menses such as physical work, sports, praying and entering religious sites, was closely tied to study centre. Across all sites, women (90%) avoided sexual intercourse during menses.Despite growing acceptance of altering bleeding patterns, women in this study preferred monthly vaginal bleeding. Understanding sociocultural contexts and individual preferences is important when addressing this issue with women from diverse backgrounds.

Background Levonorgestrel is an effective method for emergency contraception (EC) and is used worldwide. Consistent with its mechanism of action in delaying ovulation, the earlier it is administered within 72 h of an unprotected act of intercourse, the more effective it is. There is uncertainty, however, about its effectiveness after 72 h. This analysis explores the effect of 24-h intervals of delay in levonorgestrel administration on pregnancy rates when used until 120 h of an unprotected act of intercourse. Study Design Data were analyzed from 6794 women participating in four World Health Organization randomized trials and receiving 1.5 mg of levonorgestrel for EC in a single dose or split into two doses 12 h apart, within 48, 72 or 120 h of an act of unprotected intercourse. The pregnancy rates among women in successive days after an unprotected act of intercourse and odds ratios of pregnancy were calculated using logistic regression with the first day as the reference. Results For the four trials combined, odds ratios for pregnancy in the second, third and fourth day with respect to the first day were not significantly different from 1 at the 5% level of significance. On the fifth day, the odds ratio of pregnancy compared to the first day was almost 6. Conclusions Levonorgestrel for EC should be administered as soon as possible after unprotected intercourse. Delaying levonorgestrel administration until the fifth day after unprotected intercourse increases the risk of pregnancy over five times compared with administration within 24 h. It is uncertain whether levonorgestrel administration on the fifth day still offers some protection against unwanted pregnancy.