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Background: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most.Objectives: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing.Search Strategy: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239).Selection Criteria: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses.Data Collection and Analysis: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates.Main Results: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake.Conclusions: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate.Tweetable Abstract: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low. [ABSTRACT FROM AUTHOR]

Calcium intake remains inadequate in many low‐ and middle‐income countries, especially in Africa and South Asia, where average intakes can be below 400 mg/day. Given the vital role of calcium in bone health, metabolism, and cell signaling, countries with low calcium intake may want to consider food‐based approaches to improve calcium consumption and bioavailability within their population. This is especially true for those with low calcium intake who would benefit the most, including pregnant women (by reducing the risk of preeclampsia) and children (by reducing calcium‐deficiency rickets). Specifically, some animal‐source foods that are naturally high in bioavailable calcium and plant foods that can contribute to calcium intake could be promoted either through policies or educational materials. Some food processing techniques can improve the calcium content in food or increase calcium bioavailability. Staple‐food fortification with calcium can also be a cost‐effective method to increase intake with minimal behavior change required. Lastly, biofortification is currently being investigated to improve calcium content, either through genetic screening and breeding of high‐calcium varieties or through the application of calcium‐rich fertilizers. These mechanisms can be used alone or in combination based on the local context to improve calcium intake within a population. [ABSTRACT FROM AUTHOR]

Most low‐ and middle‐income countries present suboptimal intakes of calcium during pregnancy and high rates of mortality due to maternal hypertensive disorders. Calcium supplementation during pregnancy is known to reduce the risk of these disorders and associated complications, including preeclampsia, maternal morbidity, and preterm birth, and is, therefore, a recommended intervention for pregnant women in populations with low dietary calcium intake (e.g., where ≥25% of individuals in the population have intakes less than 800 mg calcium/day). However, this intervention is not widely implemented in part due to cost and logistical issues related to the large dose and burdensome dosing schedule (three to four 500‐mg doses/day). WHO recommends 1.5–2 g/day but limited evidence suggests that less than 1 g/day may be sufficient and ongoing trials with low‐dose calcium supplementation (500 mg/day) may point a path toward simplifying supplementation regimens. Calcium carbonate is likely to be the most cost‐effective choice, and it is not necessary to counsel women to take calcium supplements separately from iron‐containing supplements. In populations at highest risk for preeclampsia, a combination of calcium supplementation and food‐based approaches, such as food fortification with calcium, may be required to improve calcium intakes before pregnancy and in early gestation. [ABSTRACT FROM AUTHOR]

Introduction: Antiretrovirals such as dolutegravir (DTG) and tenofovir alafenamide (TAF) have been associated with excessive weight gain. The objective of this study was to understand the potential impact of ART‐associated weight gain on pregnancy outcomes among women living with HIV. Methods: Using data from the Tsepamo birth outcomes surveillance study in Botswana, we evaluated the relationship between maternal weight (and weight gain) and severe birth outcomes (very preterm delivery <32 weeks, very small for gestational age (SGA) <3rd percentile, perinatal death), macrosomia (birthweight > 4000 g) and maternal hypertension. We estimated the relative risk of each outcome by baseline weight (first weight in pregnancy <24 weeks) and second trimester average weekly weight gain (kg/week from 12 ± 2 to 24 ± 2 weeks) using log binomial regression and evaluated effect modification by ART regimen (DTG vs. Efavirenz (EFV)). Results: Of 22,828 women on ART at conception with singleton deliveries between August 2014 and April 2020, 16,300 (71.4%) had a weight measured <24 weeks' gestation (baseline weight) and 4437 (19.2%) had weight measured both at 12 (±2) weeks and 24 (±2) weeks, allowing second trimester weight gain calculation. Compared to women with baseline weight 60 to 70 kg, low baseline weight (<50 kg) was associated with increased risk of very preterm delivery (aRR 1.30, 95% CI 1.03, 1.65) and very SGA (aRR1.96, 95% CI 1.69, 2.28). High baseline weight (>90 kg) was associated with increased risk of macrosomia (aRR 3.24, 95% CI 2.36, 4.44) and maternal hypertension (aRR 1.79, 95% CI 1.62, 1.97). Baseline weight was not associated with stillbirth or early neonatal death. For all outcomes, second trimester weight gain showed weaker associations than did baseline weight. Duration of pre‐pregnancy ART (years) was associated with higher baseline weight for DTG but not for EFV, and the risk of maternal hypertension by baseline weight category was higher for DTG than EFV for all strata. Conclusions: ART regimens associated with weight gain may reduce the number of women at risk for certain severe adverse pregnancy outcomes associated with low weight but increase the number at risk of macrosomia and maternal hypertension. Further research could determine whether weight‐based ART treatment strategies improve maternal and child health. [ABSTRACT FROM AUTHOR]

Low calcium intake is common worldwide and can result in nutritional rickets in children and osteomalacia in adults. Calcium‐fortified foods could improve calcium intake. However, there is limited calcium fortification experience, with technical and practical issues that may hamper its adoption. The objective of this landscape review is to summarize these issues to help policymakers guide the planning and design of calcium fortification as a public health strategy. One challenge is the low bioavailability of calcium salts (∼20–40%); thus, large amounts need to be added to food to have a meaningful impact. Solubility is important when fortifying liquids and acidic foods. Calcium salts could change the flavor, color, and appearance of the food and may account for 70–90% of the total fortification cost. Safety is key to avoid exceeding the recommended intake; so the amount of added calcium should be based on the target calcium intake and the gap between inadequate and adequate levels. Monitoring includes the quality of the fortified food and population calcium intake using dietary assessment methods. Calcium fortification should follow regulations, implemented in an intersectorial way, and be informed by the right to health and equity. This information may help guide and plan this public health strategy. [ABSTRACT FROM AUTHOR]

Low dietary calcium is very common in many populations, contributing to nutritional rickets/osteomalacia in children/adults and increasing the risk of several health problems. Calcium is a nutrient of concern as the recommended nutrient requirements are difficult to meet in the absence of dairy products. The provision of culturally acceptable calcium‐fortified foods may improve calcium intake when it is a feasible and cost‐effective strategy in a particular setting. This landscape review was conducted in 2019 and describes current calcium fortification efforts and lessons learned from these experiences. Worldwide, the United Kingdom is the only country where calcium fortification of wheat flour is mandatory. It is estimated that this fortified staple ingredient contributes to 13–14% of calcium intake of the British population. Other items voluntary fortified with calcium include maize flour, rice, and water. Current calcium fortification programs may lack qualified personnel/training, clear guidelines on implementation, regulation, monitoring/evaluation, and functional indicators. Also, the cost of calcium premix is high and the target groups may be hard to reach. There is a lack of rigorous evaluation, particularly in settings with multiple micronutrient programs implemented simultaneously, with low quality of the evidence. Further research is needed to assess the impact of calcium fortification programs. [ABSTRACT FROM AUTHOR]

Synopsis: A novel, re‐usable 'Safe Birth Tray' for blood loss monitoring and early detection of postpartum hemorrhage was found to be easy to use, acceptable, comfortable, and useful by participants and midwives. [ABSTRACT FROM AUTHOR]

Objective: To identify an inexpensive catheter suitable for uterine suction tamponade (UST) for postpartum hemorrhage and assess its functionality.Methods: Randomized, single-center, double-blind feasibility study in East London, South Africa, among 45 women undergoing cesarean delivery between October and November 2018. A search of medical supply websites for catheters with predefined characteristics (inexpensive, flexible, wide-bore, circumferentially-arranged side apertures, rounded tip) identified the FG36 Levin stomach tube. During cesarean, the tube was placed in the uterus and connected transvaginally to a suction unit. Participants were randomized via a computer-generated random sequence to early (after uterine closure; n=24) or delayed (after skin closure; n=21) UST.Results: The tube functioned well with respect to stability in the uterus and aspirating blood from the uterine cavity without blockage. Blood loss was similar between the groups (mean difference, 7.3 mL; 95% confidence interval, -61 to 75; P=0.433), as were secondary outcomes. There were no complications. Absolute effectiveness was not tested because there was no non-suction group.Conclusion: The FG36 Levin tube was found to be a suitable device for "suction-tube uterine tamponade". There was no difference in functionality between early and late UST. Future trials should assess the effectiveness of this approach for postpartum hemorrhage.Clinical Trial Registration: Registered in the Pan African Clinical Trial Registry as PACTR201809584199573. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the effectiveness and safety of the administration of misoprostol, an orally active prostaglandin, in addition to routine uterotonic therapy as part of the active management of the third stage of labor. Methods: The present study was a hospital-based, decentralized, multi-center, randomized, placebo-controlled, double-blind trial. We enrolled 1103 women (out of a target sample size of 1180) at 4 hospitals in South Africa, Uganda, and Nigeria. Participants received a sublingual dose of 400μg of misoprostol or a placebo, in addition to standard active management of the third stage of labor, after vaginal birth. Results: The baseline characteristics of the participants were comparable. The difference in the primary outcome of blood loss of 500mL or more within 1 hour of randomization was not significant between the 2 groups (misoprostol 22/546 [4.0%] versus placebo 35/553 [6.3%]; relative risk, 0.64; 95% confidence interval, 0.38–1.07). Shivering and pyrexia occurred more frequently in the misoprostol group. No maternal deaths occurred. Conclusion: The present study did not confirm a beneficial effect of administering 400μg of misoprostol, in addition to routine uterotonic therapy, during the third stage of labor, but was consistent with other trials showing a cumulative modest benefit. Where routine uterotonics are available for prophylactic use, any potential benefit of misoprostol might not outweigh the likelihood of adverse effects. Trial registered on clinical trials.gov: NCT 00124540. [Copyright &y& Elsevier]

Objective: To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage.Methods: A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded.Results: The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups.Conclusion: Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280. [ABSTRACT FROM AUTHOR]

To determine the prevalence of uterine rupture worldwide. Systematic review of all available data since 1990. Community-based and facility-based reports from urban and rural studies worldwide. Eighty-three reports of uterine rupture rates are included in the systematic review. Most are facility based using cross-sectional study designs. Following a pre-defined protocol an extensive search was conducted of 10 electronic databases as well as other sources. Articles were evaluated according to specified inclusion criteria. Uterine rupture data were collected along with information on the quality of reporting including definitions and identification of cases. Data were entered into a database and tabulated using SAS software. Prevalence of uterine rupture by country, period, study design, setting, participants, facility type and data source. Prevalence figures for uterine rupture were available for 86 groups of women. For unselected pregnant women, the prevalence of uterine rupture reported was considerably lower for community-based (median 0.053, range 0.016–0.30%) than for facility-based studies (0.31, 0.012–2.9%). The prevalence tended to be lower for countries defined by the United Nations as developed than the less or least developed countries. For women with previous caesarean section, the prevalence of uterine rupture reported was in the region of 1%. Only one report gave a prevalence for women without previous caesarean section, from a developed country, and this was extremely low (0.006%). In less and least developed countries, uterine rupture is more prevalent than in developed countries. In developed countries most uterine ruptures follow caesarean section. Future research on the prevalence of uterine rupture should differentiate between uterine rupture with and without previous caesarean section. [ABSTRACT FROM AUTHOR]

Examines the route of administration and dosage of misoprostol most likely to be effective in the treatment of postpartum hemorrhage (PPH). Review of randomized controlled trials of misoprostol for PPH treatment; Overview of pharmacokinetic studies of pregnant women and non-pregnant women to oral or vaginal administration of misoprostol; Qualitative comparison of various routes of administration of misoprostol.

Reprints the text of the final chapter of the book 'A Guide to Effective Care in Pregnancy and Childbirth.' Alternative forms of care in pregnancy and childcare; Elements of care; Effectiveness of various forms of care.

Abstract: The hypertensive disorders of pregnancy (HDP; pre-existing hypertension, gestational hypertension, and pre-eclampsia) remain important causes of maternal morbidity and mortality, especially in low- and middle-income countries. The paper summarizes the current state of evidence around possible technologies to support community-based improvements in maternal and perinatal outcomes for women with pre-eclampsia. Through the testing and, where proven, introduction of these technologies, we believe that HDP-related progress toward achieving Millennium Development Goal 5 can best be accelerated. The evidence and discussion are presented under the following headings: (1) prediction; (2) prevention; (3) diagnosis; (4) risk stratification; (5) decision aids; (6) treatment; (7) geographic information systems; (8) communication; and (9) community and patient education. [Copyright &y& Elsevier]

Abstract: Background: Each year, approximately 2million babies die because of complications of childbirth, primarily in settings where effective care at birth, particularly prompt cesarean delivery, is unavailable. Objective: We reviewed the content, impact, risk-benefit, and feasibility of interventions for obstetric complications with high population attributable risk of intrapartum-related hypoxic injury, as well as human resource, skill development, and technological innovations to improve obstetric care quality and availability. Results: Despite ecological associations of obstetric care with improved perinatal outcomes, there is limited evidence that intrapartum interventions reduce intrapartum-related neonatal mortality or morbidity. No interventions had high-quality evidence of impact on intrapartum-related outcomes in low-resource settings. While data from high-resource settings support planned cesarean for breech presentation and post-term induction, these interventions may be unavailable or less safe in low-resource settings and require risk-benefit assessment. Promising interventions include use of the partograph, symphysiotomy, amnioinfusion, therapeutic maneuvers for shoulder dystocia, improved management of intra-amniotic infections, and continuous labor support. Obstetric drills, checklists, and innovative low-cost devices could improve care quality. Task-shifting to alternative cadres may increase coverage of care. Conclusions: While intrapartum care aims to avert intrapartum-related hypoxic injury, rigorous evidence is lacking, especially in the settings where most deaths occur. Effective care at birth could save hundreds of thousands of lives a year, with investment in health infrastructure, personnel, and research—both for innovation and to improve implementation. [Copyright &y& Elsevier]

The use of tranexamic acid for postpartum hemorrhage has entered obstetrical practice globally with the evidence-based expectation of saving lives. This improvement in the care of women with postpartum hemorrhage has come at a price. For the anesthetist, having tranexamic acid ampoules close at hand would seem an obvious strategy to facilitate its use during cesarean delivery, an important setting for severe hemorrhage. Tragically, we have identified a number of recent instances of inadvertent intrathecal administration of tranexamic acid instead of local anesthetic for spinal anesthesia. Reported cases of this catastrophic error seem to be increasing. The profound neurotoxicity of tranexamic acid causes rapid-onset convulsions, with mortality of 50%. How can these tragic errors be averted? Drug safety alerts have been issued by the US Food and Drug Administration and the World Health Organization, but that is not enough. We recommend extensive dissemination of information to raise awareness of this potential hazard, and local hospital protocols to ensure that tranexamic acid is stored separately from anesthetic drugs, preferably outside the operating room and with an auxiliary warning label. Implementation of safety strategies on a very large scale will be needed to ensure that the life-saving potential of tranexamic acid is not eclipsed by drug-error mortality., (© 2022 The Authors. Published by Elsevier Inc /Elsevier B.V./ Wiley on behalf of The International Federation of Gynecology and Obstetrics (FIGO) / John Wiley & Son Ltd.)

Background: Calcium supplementation reduces the risk of pre-eclampsia, but questions remain about the dosage to prescribe and who would benefit most., Objectives: To evaluate the effectiveness of high (≥1 g/day) and low (<1 g/day) calcium dosing for pre-eclampsia prevention, according to baseline dietary calcium, pre-eclampsia risk and co-interventions, and intervention timing., Search Strategy: CENTRAL, PubMed, Global Index Medicus and CINAHL, from inception to 2 February 2021, clinical trial registries, reference lists and expert input (CRD42018111239)., Selection Criteria: Randomised controlled trials of calcium supplementation for pre-eclampsia prevention, for women before or during pregnancy. Network meta-analysis (NMA) also included trials of different calcium doses., Data Collection and Analysis: Two independent reviewers extracted published data. The meta-analysis employed random-effects models and the NMA, a Bayesian random-effects model, to obtain direct and indirect effect estimates., Main Results: The meta-analysis included 30 trials (N = 20 445 women), and the NMA to evaluate calcium dosage included 25 trials (N = 15 038). Calcium supplementation prevented pre-eclampsia similarly with a high dose (RR 0.49, 95% CI 0.36-0.66) or a low dose (RR 0.49, 95% CI 0.36-0.65). By NMA, high-dose (vs low-dose) calcium did not differ in effect (RR 0.79, 95% CI 0.43-1.40). Calcium was similarly effective regardless of baseline pre-eclampsia risk, vitamin D co-administration or timing of calcium initiation, but calcium was ineffective among women with adequate average baseline calcium intake., Conclusions: Low- and high-dose calcium supplementation are effective for pre-eclampsia prevention in women with low calcium intake. This has implications for population-level implementation where dietary calcium is low, and targeted implementation where average intake is adequate., Tweetable Abstract: A network meta-analysis of 25 trials found that low-dose calcium supplementation (<1 g/day) is as effective as high-dose calcium supplementation (≥1 g/day) in halving the risk of pre-eclampsia when baseline calcium intake is low., (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)