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Objective: We postulated that calcium supplementation of calcium-deficient pregnant women would lower vascular resistance in uteroplacental and fetoplacental circulations., Study Design: Pulsatility index (PI) and resistance index (RI) (uterine and umbilical arteries) and presence of bilateral uterine artery diastolic notching were assessed by Doppler ultrasound between 20-36 weeks' gestation in 510 healthy, nulliparous Argentinean women with deficient calcium intake in a randomized, placebo-controlled, double-blinded trial., Results: Average umbilical and uterine artery RI and PI tended to be lower in the supplemented group at each study week. Differences became statistically significant for umbilical artery RI and PI from 32 and 36 weeks, respectively. Estimated probabilities of bilateral uterine artery diastolic notching trended toward lower values in calcium-supplemented women., Conclusion: Calcium supplementation of pregnant women with deficient calcium intake may affect uteroplacental and fetoplacental blood flow by preserving the vasodilation of normal gestation., (2010 Mosby, Inc.)

Objective: A dipslide is a plastic paddle coated with agar that is attached to a plastic cap that screws onto a sterile plastic vial. Our objective was to estimate the diagnostic accuracy of the dipslide culture technique to detect asymptomatic bacteriuria during pregnancy and to evaluate the accuracy of nitrate and leucocyte esterase dipslides for screening., Methods: This was an ancillary study within a trial comparing single-day with 7-day therapy in treating asymptomatic bacteriuria. Clean-catch midstream samples were collected from pregnant women seeking routine care. Positive and negative likelihood ratios and sensitivity and specificity for the culture-based dipslide to detect and chemical dipsticks (nitrites, leukocyte esterase, or both) to screen were estimated using traditional urine culture as the "gold standard.", Results: : A total of 3,048 eligible pregnant women were screened. The prevalence of asymptomatic bacteriuria was 15%, with Escherichia coli the most prevalent organism. The likelihood ratio for detecting asymptomatic bacteriuria with a positive dipslide test was 225 (95% confidence interval [CI] 113-449), increasing the probability of asymptomatic bacteriuria to 98%; the likelihood ratio for a negative dipslide test was 0.02 (95% CI 0.01-0.05), reducing the probability of bacteriuria to less than 1%. The positive likelihood ratio of leukocyte esterase and nitrite dipsticks (when both or either one was positive) was 6.95 (95% CI 5.80-8.33), increasing the probability of bacteriuria to only 54%; the negative likelihood ratio was 0.50 (95% CI 0.45-0.57), reducing the probability to 8%., Conclusion: A pregnant woman with a positive dipslide test is very likely to have a definitive diagnosis of asymptomatic bacteriuria, whereas a negative result effectively rules out the presence of bacteriuria. Dipsticks that measure nitrites and leukocyte esterase have low sensitivity for use in screening for asymptomatic bacteriuria during gestation., Clinical Trial Registration: ISRCTN, isrctn.org, 1196608, Level of Evidence: II.

Objective: To evaluate whether a 1-day nitrofurantoin regimen is as effective as a 7-day regimen in eradicating asymptomatic bacteriuria during pregnancy., Methods: A multicenter, double-blind, randomized, placebo controlled noninferiority trial was conducted in antenatal clinics in Thailand, the Philippines, Vietnam, and Argentina. Pregnant women seeking antenatal care between March 2004 and March 2007 who met the inclusion and exclusion criteria were invited to participate in the study. Those who consented were randomly allocated to receive either a 1-day or a 7-day course of 100 mg capsules of nitrofurantoin, which was taken twice daily. The primary outcome was bacteriologic cure on day 14 of treatment., Results: : A total of 1,248 of 24,430 eligible women had asymptomatic bacteriuria, making the overall prevalence of 5.1%. Of these 1,248 women, 778 women were successfully recruited, and 386 and 392 women were randomly allocated to 1-day and 7-day regimens, respectively. Escherichia coli was the most common potentially pathogenic bacteria detected, its prevalence approaching 50%. Bacteriologic cure rates at treatment day 14 were 75.7% and 86.2% for 1-day and 7-day regimens, respectively. The cure rate difference was -10.5% (95% confidence interval -16.1% to -4.9%). Mean birth weight and mean gestational age at delivery were significantly lower in the 1-day regimen group. There were fewer adverse effects in the 1-day regimen group, but the differences were not statistically significant., Conclusion: A 1-day regimen of nitrofurantoin is significantly less effective than a 7-day regimen. Women with asymptomatic bacteriuria in pregnancy should receive the standard 7-day regimen., Clinical Trial Registration: ISRCTN, isrctn.org, ISRCTN11966080, Level of Evidence: I.

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.

Objective: To assess the risks and benefits associated with caesarean delivery compared with vaginal delivery., Design: Prospective cohort study within the 2005 WHO global survey on maternal and perinatal health., Setting: 410 health facilities in 24 areas in eight randomly selected Latin American countries; 123 were randomly selected and 120 participated and provided data, Participants: 106,546 deliveries reported during the three month study period, with data available for 97,095 (91% coverage)., Main Outcome Measures: Maternal, fetal, and neonatal morbidity and mortality associated with intrapartum or elective caesarean delivery, adjusted for clinical, demographic, pregnancy, and institutional characteristics., Results: Women undergoing caesarean delivery had an increased risk of severe maternal morbidity compared with women undergoing vaginal delivery (odds ratio 2.0 (95% confidence interval 1.6 to 2.5) for intrapartum caesarean and 2.3 (1.7 to 3.1) for elective caesarean). The risk of antibiotic treatment after delivery for women having either type of caesarean was five times that of women having vaginal deliveries. With cephalic presentation, there was a trend towards a reduced odds ratio for fetal death with elective caesarean, after adjustment for possible confounding variables and gestational age (0.7, 0.4 to 1.0). With breech presentation, caesarean delivery had a large protective effect for fetal death. With cephalic presentation, however, independent of possible confounding variables and gestational age, intrapartum and elective caesarean increased the risk for a stay of seven or more days in neonatal intensive care (2.1 (1.8 to 2.6) and 1.9 (1.6 to 2.3), respectively) and the risk of neonatal mortality up to hospital discharge (1.7 (1.3 to 2.2) and 1.9 (1.5 to 2.6), respectively), which remained higher even after exclusion of all caesarean deliveries for fetal distress. Such increased risk was not seen for breech presentation. Lack of labour was a risk factor for a stay of seven or more days in neonatal intensive care and neonatal mortality up to hospital discharge for babies delivered by elective caesarean delivery, but rupturing of membranes may be protective., Conclusions: Caesarean delivery independently reduces overall risk in breech presentations and risk of intrapartum fetal death in cephalic presentations but increases the risk of severe maternal and neonatal morbidity and mortality in cephalic presentations.

Objective: The objective of the study was to examine whether blood pressure in early pregnancy and its rise in the second half of gestation are associated with spontaneous preterm birth in healthy, normotensive, nulliparous women., Study Design: We included 5167 women with singleton gestation who participated in the World Health Organization Calcium Supplementation for the Prevention of Preeclampsia Trial. Systolic, diastolic, and mean arterial blood pressure and pulse pressure at baseline (12-19 weeks of gestation) and at the midthird trimester (30-34 weeks) were calculated. Rise in blood pressure was the difference between the midthird trimester and baseline. Preterm birth was defined as early preterm (less than 34 completed weeks) and late preterm birth (34-36 weeks)., Results: Women experiencing early or late preterm birth had over 10 mm Hg and 3 mm Hg higher rise, respectively, in systolic, diastolic, and mean arterial blood pressure than women delivering at term. A rise in systolic pressure over 30 mm Hg or diastolic pressure over 15 mm Hg was associated with a statistically significant 2- to 3-fold increase in risk of spontaneous preterm birth., Conclusion: An excessive rise in either systolic or diastolic blood pressures from early pregnancy to the midthird trimester is associated with spontaneous preterm birth in a dose-response pattern.

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.

Objective: Preeclampsia, gestational hypertension, and unexplained intrauterine growth restriction may have similar determinants and consequences. In this study, we compared determinants and perinatal outcomes associated with these obstetric conditions., Study Design: We analyzed 39,615 pregnancies (data from the WHO Antenatal Care Trial), of which 2.2% were complicated by preeclampsia, 7.0% by gestational hypertension, and 8.1% by unexplained intrauterine growth restriction (ie, not associated with maternal smoking, maternal undernutrition, preeclampsia, gestational hypertension, or congenital malformations). We compared the risk factors associated with these groups. Fetal death, preterm delivery, and severe neonatal morbidity and mortality were the primary outcomes. Logistic regression analyses were adjusted for study site, socioeconomic status, and (if appropriate) birth weight and gestational age., Results: Diabetes, renal or cardiac disease, previous preeclampsia, urinary tract infection, high maternal age, twin pregnancy, and obesity increased the risk of both hypertensive conditions. Previous large-for-age birth, reproductive tract surgery, antepartum hemorrhage and reproductive tract infection increased the risk for gestational hypertension only. Independent of maternal age, primiparity was a risk factor only for preeclampsia. Both preeclampsia and gestational hypertension were associated with increased risk for fetal death and severe neonatal morbidity and mortality. Mothers with preeclampsia compared with those with unexplained intrauterine growth restriction were more likely to have a history of diabetes, renal or cardiac disease, chronic hypertension, previous preeclampsia, body mass index more than 30 kg/cm2, urinary tract infection and extremes of maternal age. Conversely, unexplained intrauterine growth restriction was associated with higher risk of low birth weight in previous pregnancies, but not with previous preeclampsia. Both conditions increased the risk for perinatal outcomes independently but preeclampsia was associated with considerable higher risk., Conclusion: Preeclampsia and gestational hypertension shared many risk factors, although there are differences that need further evaluation. Both conditions significantly increased morbidity and mortality. Conversely, preeclampsia and unexplained intrauterine growth restriction, often assumed to be related to placental insufficiency, seem to be independent biologic entities.

Objective: The purpose of this trial was to determine whether calcium supplementation of pregnant women with low calcium intake reduces preeclampsia and preterm delivery., Study Design: Randomized placebo-controlled, double-blinded trial in nulliparous normotensive women from populations with dietary calcium < 600 mg/d. Women who were recruited before gestational week 20 received supplements (1.5 g calcium/d or placebo) throughout pregnancy. Primary outcomes were preeclampsia and preterm delivery; secondary outcomes focused on severe morbidity and maternal and neonatal mortality rates., Results: The groups comprised 8325 women who were assigned randomly. Both groups had similar gestational ages, demographic characteristics, and blood pressure levels at entry. Compliance were both 85% and follow-up losses (calcium, 3.4%; placebo, 3.7%). Calcium supplementation was associated with a non-statistically significant small reduction in preeclampsia (4.1% vs 4.5%) that was evident by 35 weeks of gestation (1.2% vs 2.8%; P = .04). Eclampsia (risk ratio, 0.68: 95% CI, 0.48-0.97) and severe gestational hypertension (risk ratio, 0.71; 95% CI, 0.61-0.82) were significantly lower in the calcium group. Overall, there was a reduction in the severe preeclamptic complications index (risk ratio, 0.76; 95% CI, 0.66-0.89; life-table analysis, log rank test; P = .04). The severe maternal morbidity and mortality index was also reduced in the supplementation group (risk ratio, 0.80; 95% CI, 0.70-0.91). Preterm delivery (the neonatal primary outcome) and early preterm delivery tended to be reduced among women who were < or = 20 years of age (risk ratio, 0.82; 95% CI, 0.67-1.01; risk ratio, 0.64; 95% CI, 0.42-0.98, respectively). The neonatal mortality rate was lower (risk ratio, 0.70; 95% CI, 0.56-0.88) in the calcium group., Conclusion: A 1.5-g calcium/day supplement did not prevent preeclampsia but did reduce its severity, maternal morbidity, and neonatal mortality, albeit these were secondary outcomes.

Unlabelled: Episiotomy, the unkindest cut of all, persists despite clinical practice guidelines recommending its restrictive use. The purpose of this paper was to compile international statistics on the use of this practice and examine whether current guidance on the restrictive use of episiotomy was being followed., Methods: We searched government websites and the Internet, contacted colleagues for references, and checked the references of retrieved citations., Results: Statistics from around the world revealed overall high rates of episiotomy with a decreasing trend in some countries. Considerable variation occurs in the use of the operation by country, within countries, and even within the same professional provider group., Conclusions: Greater efforts are needed than currently in place to reduce the episiotomy rate, particularly in the developing world.

Evidence-based medicine is the conscientious, explicit and judicious use of the current best evidence in making decisions about the care of individual patients. Along with individual clinical expertise, it is a required core skill for clinical problem solving and it is considered to be a comprehensive component of the medical curricula. This chapter is a general overview of the steps to be followed by clinicians to search, identify and appraise the best-available evidence that could help them to resolve a particular clinical problem. It includes the principles for the identification of a clinical problem and its translation into a question, and the main sources for searching and locating the best-available evidence. References for guidelines designed for appraisal of the methods used in the original papers and for the interpretation of its results are also provided.

Preeclampsia-eclampsia is a major cause of morbidity and mortality in mothers, fetuses, and neonates worldwide, most devastating in developing nations. Its cause is still uncertain, and many controversies exist concerning its management. The World Health Organization is aware of this and is coordinating a series of systematic reviews that focus on the etiology and the best strategies for the screening, prevention, and treatment of preeclampsia. This article summarizes results from systematic reviews of randomized trials to prevent and manage preeclampsia. There is a prophylactic role of modest magnitude for low-dose aspirin but the number to treat (90 women) to avoid one case of preeclampsia still is considered high. Antioxidant and calcium supplement trials remain to be completed before firm conclusions can be rendered on their efficacy for prevention. Magnesium sulfate is effective in preventing and treating eclampsia, while severe hypertension (with or without proteinuria) requires drug therapy, but there appears to be no benefits to treating mild to moderate hypertension without proteinuria in pregnancy. Finally, our review focuses on the quality of data reviewed, suggesting the need for better evidence, and discusses the use of systematic reviews as a strategy to focus future research on this important area of reproductive medicine.

Objective: This study estimates the costs of maternal health services in Rosario, Argentina., Material and Methods: The provider costs (US$ 1999) of antenatal care, a normal vaginal delivery and a caesarean section, were evaluated retrospectively in two municipal hospitals. The cost of an antenatal visit was evaluated in two health centres and the patient costs associated with the visit were evaluated in a hospital and a health centre., Results: The average cost per hospital day is $114.62. The average cost of a caesarean section ($525.57) is five times greater than that of a normal vaginal delivery ($105.61). A normal delivery costs less at the general hospital and a c-section less at the maternity hospital. The average cost of an antenatal visit is $31.10. The provider cost is lower at the health centre than at the hospital. Personnel accounted for 72-94% of the total cost and drugs and medical supplies between 4-26%. On average, an antenatal visit costs women $4.70. Direct costs are minimal compared to indirect costs of travel and waiting time., Conclusions: These results suggest the potential for increasing the efficiency of resource use by promoting antenatal care visits at the primary level. Women could also benefit from reduced travel and waiting time. Similar benefits could accrue to the provider by encouraging normal delivery at general hospitals, and complicated deliveries at specialised maternity hospitals.

Objective: To evaluate the side effects of 600 microg misoprostol orally during the first 24 hours after administration in the third stage of labour., Design: Double blind randomised controlled trial., Setting: Tertiary care hospitals in Nigeria and Thailand., Sample: All women participating in the WHO Misoprostol trial in these two hospitals between January 1, 1999 and June 17, 1999., Methods: All women were followed up during the first 24 hours postpartum to evaluate the occurrence of shivering, nausea, vomiting, diarrhoea and other misoprostol-related side effects., Main Outcome Measures: Rates of shivering, nausea, vomiting, diarrhoea and pyrexia within 1 hour and in the intervals 2-6, 7-12, 13-18 and 19-24 hours after delivery., Results: A total of 1686 women were enrolled. Women who received misoprostol had higher incidence than the oxytocin group of 'any' shivering in the first hour (RR 6.4, 95% CI 3.9 to 10.4) and the period covering 2-6 hours following delivery (RR 4.7, 95% CI 1.9 to 11.2). Pyrexia was also more common in the misoprostol group in both the same time intervals (RR 2.8, 95% CI 1.4 to 5.3 and RR 6.3, 95% CI 3.7 to 10.8, respectively). Diarrhoea was not present in the first hour in either group but appeared in the second time period (2-6 hours) and third time period (7-12 hours) more frequently in the misoprostol group than with oxytocin., Conclusion: The increased incidence of shivering and pyrexia that occurs with postpartum use of misoprostol persists up to 6 hours following delivery. Approximately 5% of women experience diarrhoea that starts after 1 hour and subsides within 12 hours.

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.