Guillermo Carroli

Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: A randomised placebo-controlled trial

BACKGROUND Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate. METHODS Eligible women (n=10141) had not given birth or were 24 h or less postpartum; blood pressure of 140/90 mm Hg or more, and proteinuria of 1+ (30 mg/dL) or more; and there was clinical uncertainty about magnesium sulphate. Women were randomised in 33 countries to either magnesium sulphate (n=5071) or placebo (n=5070). Primary outcomes were eclampsia and, for women randomised before delivery, death of the baby. Follow up was until discharge from hospital after delivery. Analyses were by intention to treat. FINDINGS Follow-up data were available for 10,110 (99.7%) women, 9992 (99%) of whom received the allocated treatment. 1201 of 4999 (24%) women given magnesium sulphate reported side-effects versus 228 of 4993 (5%) given placebo. Women allocated magnesium sulphate had a 58% lower risk of eclampsia (95% CI 40-71) than those allocated placebo (40, 0.8%, vs 96, 1.9%; 11 fewer women with eclampsia per 1000 women). Maternal mortality was also lower among women allocated magnesium sulphate (relative risk 0.55, 0.26-1.14). For women randomised before delivery, there was no clear difference in the risk of the baby dying (576, 12.7%, vs 558, 12.4%; relative risk 1.02, 99% CI 0.92-1.14). The only notable difference in maternal or neonatal morbidity was for placental abruption (relative risk 0.67, 99% CI 0.45-0.89). INTERPRETATION Magnesium sulphate halves the risk of eclampsia, and probably reduces the risk of maternal death. There do not appear to be substantive harmful effects to mother or baby in the short term.ARTICLES Summary Background Anticonvulsants are used for pre-eclampsia in the belief they prevent eclamptic convulsions, and so improve outcome. Evidence supported magnesium sulphate as the drug to evaluate.

Caesarean delivery rates and pregnancy outcomes: the 2005 WHO global survey on maternal and perinatal health in Latin America

BACKGROUND Caesarean delivery rates continue to increase worldwide. Our aim was to assess the association between caesarean delivery and pregnancy outcome at the institutional level, adjusting for the pregnant population and institutional characteristics. METHODS For the 2005 WHO global survey on maternal and perinatal health, we assessed a multistage stratified sample, comprising 24 geographic regions in eight countries in Latin America. We obtained individual data for all women admitted for delivery over 3 months to 120 institutions randomly selected from of 410 identified institutions. We also obtained institutional-level data. FINDINGS We obtained data for 97,095 of 106,546 deliveries (91% coverage). The median rate of caesarean delivery was 33% (quartile range 24-43), with the highest rates of caesarean delivery noted in private hospitals (51%, 43-57). Institution-specific rates of caesarean delivery were affected by primiparity, previous caesarean delivery, and institutional complexity. Rate of caesarean delivery was positively associated with postpartum antibiotic treatment and severe maternal morbidity and mortality, even after adjustment for risk factors. Increase in the rate of caesarean delivery was associated with an increase in fetal mortality rates and higher numbers of babies admitted to intensive care for 7 days or longer even after adjustment for preterm delivery. Rates of preterm delivery and neonatal mortality both rose at rates of caesarean delivery of between 10% and 20%. INTERPRETATION High rates of caesarean delivery do not necessarily indicate better perinatal care and can be associated with harm.

Method of delivery and pregnancy outcomes in Asia: the WHO global survey on maternal and perinatal health 2007–08

BACKGROUND There has been concern about rising rates of caesarean section worldwide. This Article reports the third phase of the WHO global survey, which aimed to estimate the rate of different methods of delivery and to examine the relation between method of delivery and maternal and perinatal outcomes in selected facilities in Africa and Latin America in 2004-05, and in Asia in 2007-08. METHODS Nine countries participated in the Asia global survey: Cambodia, China, India, Japan, Nepal, Philippines, Sri Lanka, Thailand, and Vietnam. In each country, the capital city and two other regions or provinces were randomly selected. We studied all women admitted for delivery during 3 months in institutions with 6000 or fewer expected deliveries per year and during 2 months in those with more than 6000 deliveries. We gathered data for institutions to obtain a detailed description of the health facility and its resources for obstetric care. We obtained data from womens medical records to summarise obstetric and perinatal events. FINDINGS We obtained data for 109 101 of 112 152 deliveries reported in 122 recruited facilities (97% coverage), and analysed 107 950 deliveries. The overall rate of caesarean section was 27.3% (n=29 428) and of operative vaginal delivery was 3.2% (n=3465). Risk of maternal mortality and morbidity index (at least one of: maternal mortality, admission to intensive care unit [ICU], blood transfusion, hysterectomy, or internal iliac artery ligation) was increased for operative vaginal delivery (adjusted odds ratio 2.1, 95% CI 1.7-2.6) and all types of caesarean section (antepartum without indication 2.7, 1.4-5.5; antepartum with indication 10.6, 9.3-12.0; intrapartum without indication 14.2, 9.8-20.7; intrapartum with indication 14.5, 13.2-16.0). For breech presentation, caesarean section, either antepartum (0.2, 0.1-0.3) or intrapartum (0.3, 0.2-0.4), was associated with improved perinatal outcomes, but also with increased risk of stay in neonatal ICU (2.0, 1.1-3.6; and 2.1, 1.2-3.7, respectively). INTERPRETATION To improve maternal and perinatal outcomes, caesarean section should be done only when there is a medical indication. FUNDING US Agency for International Development (USAID); UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), WHO, Switzerland; Ministry of Health, Labour and Welfare of Japan; Ministry of Public Health, China; and Indian Council of Medical Research.

WHO antenatal care randomised trial for the evaluation of a new model of routine antenatal care

BACKGROUND We undertook a multicentre randomised controlled trial that compared the standard model of antenatal care with a new model that emphasises actions known to be effective in improving maternal or neonatal outcomes and has fewer clinic visits. METHODS Clinics in Argentina, Cuba, Saudi Arabia, and Thailand were randomly allocated to provide either the new model (27 clinics) or the standard model currently in use (26 clinics). All women presenting for antenatal care at these clinics over an average of 18 months were enrolled. Women enrolled in clinics offering the new model were classified on the basis of history of obstetric and clinical conditions. Those who did not require further specific assessment or treatment were offered the basic component of the new model, and those deemed at higher risk received the usual care for their conditions; however, all were included in the new-model group for the analyses, which were by intention to treat. The primary outcomes were low birthweight (<2500 g), pre-eclampsia/eclampsia, severe postpartum anaemia (<90 g/L haemoglobin), and treated urinary-tract infection. There was an assessment of quality of care and an economic evaluation. FINDINGS Women attending clinics assigned the new model (n=12568) had a median of five visits compared with eight within the standard model (n=11958). More women in the new model than in the standard model were referred to higher levels of care (13.4% vs 7.3%), but rates of hospital admission, diagnosis, and length of stay were similar. The groups had similar rates of low birthweight (new model 7.68% vs standard model 7.14%; stratified rate difference 0.96 [95% CI -0.01 to 1.92]), postpartum anaemia (7.59% vs 8.67%; 0.32), and urinary-tract infection (5.95% vs 7.41%; -0.42 [-1.65 to 0.80]). For pre-eclampsia/eclampsia the rate was slightly higher in the new model (1.69% vs 1.38%; 0.21 [-0.25 to 0.67]). Adjustment by several confounding variables did not modify this pattern. There were negligible differences between groups for several secondary outcomes. Women and providers in both groups were, in general, satisfied with the care received, although some women assigned the new model expressed concern about the timing of visits. There was no cost increase, and in some settings the new model decreased cost. INTERPRETATIONS Provision of routine antenatal care by the new model seems not to affect maternal and perinatal outcomes. It could be implemented without major resistance from women and providers and may reduce cost.

WHO systematic review of randomised controlled trials of routine antenatal care.

BACKGROUND There is a lack of strong evidence on the effectiveness of the content, frequency, and timing of visits in standard antenatal-care programmes. We undertook a systematic review of randomised trials assessing the effectiveness of different models of antenatal care. The main hypothesis was that a model with a lower number of antenatal visits, with or without goal-oriented components, would be as effective as the standard antenatal-care model in terms of clinical outcomes, perceived satisfaction, and costs. METHODS The interventions compared were the provision of a lower number of antenatal visits (new model) and a standard antenatal-visits programme. The selected outcomes were pre-eclampsia, urinary-tract infection, postpartum anaemia, maternal mortality, low birthweight, and perinatal mortality. We also selected measures of womens satisfaction with care and cost-effectiveness. This review drew on the search strategy developed for the Cochrane Pregnancy and Childbirth Group of the Cochrane Collaboration. FINDINGS Seven eligible randomised controlled trials were identified. 57418 women participated in these studies: 30799 in the new-model groups (29870 with outcome data) and 26619 in the standard-model groups (25821 with outcome data). There was no clinically differential effect of the reduced number of antenatal visits when the results were pooled for pre-eclampsia (typical odds ratio 0.91 [95% CI 0.66-1.26]), urinary-tract infection (0.93 [0.79-1.10]). postpartum anaemia (1.01), maternal mortality (0.91 [0.55-1.51]), or low birthweight (1.04 [0.93-1.17]). The rates of perinatal mortality were similar, although the rarity of the outcome did not allow formal statistical equivalence to be attained. Some dissatisfaction with care, particularly among women in more developed countries, was observed with the new model. The cost of the new model was equal to or less than that of the standard model. INTERPRETATION A model with a reduced number of antenatal visits, with or without goal-oriented components, could be introduced into clinical practice without risk to mother or baby, but some degree of dissatisfaction by the mother could be expected. Lower costs can be achieved.

Moving beyond essential interventions for reduction of maternal mortality (the WHO Multicountry Survey on Maternal and Newborn Health): a cross-sectional study

BACKGROUND We report the main findings of the WHO Multicountry Survey on Maternal and Newborn Health (WHOMCS), which aimed to assess the burden of complications related to pregnancy, the coverage of key maternal health interventions, and use of the maternal severity index (MSI) in a global network of health facilities. METHODS In our cross-sectional study, we included women attending health facilities in Africa, Asia, Latin America, and the Middle East that dealt with at least 1000 childbirths per year and had the capacity to provide caesarean section. We obtained data from analysis of hospital records for all women giving birth and all women who had a severe maternal outcome (SMO; ie, maternal death or maternal near miss). We regarded coverage of key maternal health interventions as the proportion of the target population who received an indicated intervention (eg, the proportion of women with eclampsia who received magnesium sulphate). We used areas under the receiver operator characteristic curves (AUROC) with 95% CI to externally validate a previously reported MSI as an indicator of severity. We assessed the overall performance of care (ie, the ability to produce a positive effect on health outcomes) through standardised mortality ratios. RESULTS From May 1, 2010, to Dec 31, 2011, we included 314,623 women attending 357 health facilities in 29 countries (2538 had a maternal near miss and 486 maternal deaths occurred). The mean period of data collection in each health facility was 89 days (SD 21). 23,015 (7.3%) women had potentially life-threatening disorders and 3024 (1.0%) developed an SMO. 808 (26.7%) women with an SMO had post-partum haemorrhage and 784 (25.9%) had pre-eclampsia or eclampsia. Cardiovascular, respiratory, and coagulation dysfunctions were the most frequent organ dysfunctions in women who had an SMO. Reported mortality in countries with a high or very high maternal mortality ratio was two-to-three-times higher than that expected for the assessed severity despite a high coverage of essential interventions. The MSI had good accuracy for maternal death prediction in women with markers of organ dysfunction (AUROC 0.826 [95% CI 0.802-0.851]). INTERPRETATION High coverage of essential interventions did not imply reduced maternal mortality in the health-care facilities we studied. If substantial reductions in maternal mortality are to be achieved, universal coverage of life-saving interventions need to be matched with comprehensive emergency care and overall improvements in the quality of maternal health care. The MSI could be used to assess the performance of health facilities providing care to women with complications related to pregnancy. FUNDING UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP); WHO; USAID; Ministry of Health, Labour and Welfare of Japan; Gynuity Health Projects.

WHO multicentre randomised trial of misoprostol in the management of the third stage of labour

BACKGROUND Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including use of a uterotonic agent, has been shown to reduce blood loss. Misoprostol (a prostaglandin E1 analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind, randomised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour. METHODS In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Africa, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly, according to routine practice, plus corresponding identical placebos. The medications were administered immediately after delivery as part of the active management of the third stage of labour. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence, which was assessed by the confidence interval of the relative risk. Analysis was by intention to treat. FINDINGS 9264 women were assigned misoprostol and 9266 oxytocin. 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded. 366 (4%) of women on misoprostol had a measured blood loss of 1000 mL or more, compared with 263 (3%) of those on oxytocin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additional uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also associated with a significantly higher incidence of shivering (3.48 [3.15-3.84]) and raised body temperature (7.17 [5.67-9.07]) in the first hour after delivery. INTERPRETATION 10 IU oxytocin (intravenous or intramuscular) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm.

Caesarean section without medical indications is associated with an increased risk of adverse short-term maternal outcomes: the 2004-2008 WHO Global Survey on Maternal and Perinatal Health

BackgroundThere is worldwide debate about the appropriateness of caesarean sections performed without medical indications. In this analysis, we aim to further investigate the relationship between caesarean section without medical indication and severe maternal outcomes.MethodsThis is a multicountry, facility-based survey that used a stratified multistage cluster sampling design to obtain a sample of countries and health institutions worldwide. A total of 24 countries and 373 health facilities participated in this study. Data collection took place during 2004 and 2005 in Africa and the Americas and during 2007 and 2008 in Asia. All women giving birth at the facility during the study period were included and had their medical records reviewed before discharge from the hospital. Univariate and multilevel analysis were performed to study the association between each groups mode of delivery and the severe maternal and perinatal outcome.ResultsA total of 286,565 deliveries were analysed. The overall caesarean section rate was 25.7% and a total of 1.0 percent of all deliveries were caesarean sections without medical indications, either due to maternal request or in the absence of other recorded indications. Compared to spontaneous vaginal delivery, all other modes of delivery presented an association with the increased risk of death, admission to ICU, blood transfusion and hysterectomy, including antepartum caesarean section without medical indications (Adjusted Odds Ratio (Adj OR), 5.93, 95% Confidence Interval (95% CI), 3.88 to 9.05) and intrapartum caesarean section without medical indications (Adj OR, 14.29, 95% CI, 10.91 to 18.72). In addition, this association is stronger in Africa, compared to Asia and Latin America.ConclusionsCaesarean sections were associated with an intrinsic risk of increased severe maternal outcomes. We conclude that caesarean sections should be performed when a clear benefit is anticipated, a benefit that might compensate for the higher costs and additional risks associated with this operation.

Epidemiology of postpartum haemorrhage: a systematic review

Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We conducted a systematic review of the prevalence of PPH with the objective of evaluating its magnitude both globally and in different regions and settings: global figures, as well as regional, country and provincial variations, are likely to exist but are currently unknown. We used prespecified criteria to select databases, recorded the database characteristics and assessed their methodological quality. After establishing PPH (>or=500 mL blood loss) and severe PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379 women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH is approximately 6% and 1.86% of all deliveries, respectively, with a wide variation across regions of the world. The figures we obtained give a rough estimate of the prevalence of PPH and suggest the existence of some variations. For a reliable picture of PPH worldwide - its magnitude, distribution and consequences - a global survey tackling this condition is necessary.

Causes of stillbirths and early neonatal deaths: data from 7993 pregnancies in six developing countries

OBJECTIVE To report stillbirth and early neonatal mortality and to quantify the relative importance of different primary obstetric causes of perinatal mortality in 171 perinatal deaths from 7993 pregnancies that ended after 28 weeks in nulliparous women. METHODS A review of all stillbirths and early newborn deaths reported in the WHO calcium supplementation trial for the prevention of pre-eclampsia conducted at seven WHO collaborating centres in Argentina, Egypt, India, Peru, South Africa and Viet Nam. We used the Baird-Pattinson system to assign primary obstetric causes of death and classified causes of early neonatal death using the International classification of diseases and related health problems, Tenth revision (ICD-10). FINDINGS Stillbirth rate was 12.5 per 1000 births and early neonatal mortality rate was 9.0 per 1000 live births. Spontaneous preterm delivery and hypertensive disorders were the most common obstetric events leading to perinatal deaths (28.7% and 23.6%, respectively). Prematurity was the main cause of early neonatal deaths (62%). CONCLUSIONS Advancements in the care of premature infants and prevention of spontaneous preterm labour and hypertensive disorders of pregnancy could lead to a substantial decrease in perinatal mortality in hospital settings in developing countries.