Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. This is an update of a review last published in 2014. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (18 September 2017), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), including cluster-randomised trials, comparing high-dose calcium supplementation (at least 1 g daily of calcium) during pregnancy with placebo. For low-dose calcium we included quasi-randomised trials, trials without placebo, trials with cointerventions and dose comparison trials. DATA COLLECTION AND ANALYSIS: Two researchers independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two researchers assessed the evidence using the GRADE approach. MAIN RESULTS: We included 27 studies (18,064 women). We assessed the included studies as being at low risk of bias, although bias was frequently difficult to assess due to poor reporting and inadequate information on methods.High-dose calcium supplementation (≥ 1 g/day) versus placeboFourteen studies examined this comparison, however one study contributed no data. The 13 studies contributed data from 15,730 women to our meta-analyses. The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: average RR 0.45, 95% CI 0.31 to 0.65; I² = 70%; low-quality evidence). This effect was clear for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) but not those with adequate calcium diets. The effect appeared to be greater for women at higher risk of pre-eclampsia, though this may be due to small-study effects (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42). These data should be interpreted with caution because of the possibility of small-study effects or publication bias. In the largest trial, the reduction in pre-eclampsia was modest (8%) and the CI included the possibility of no effect.The composite outcome maternal death or serious morbidity was reduced with calcium supplementation (four trials, 9732 women; RR 0.80, 95% CI 0.66 to 0.98). Maternal deaths were no different (one trial of 8312 women: one death in the calcium group versus six in the placebo group). There was an anomalous increase in the risk of HELLP syndrome in the calcium group (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82, high-quality evidence), however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium supplementation group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%; low-quality evidence); this reduction was greatest amongst women at higher risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%). Again, these data should be interpreted with caution because of the possibility of small-study effects or publication bias. There was no clear effect on admission to neonatal intensive care. There was also no clear effect on the risk of stillbirth or infant death before discharge from hospital (11 trials, 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87).Low-dose calcium supplementation (< 1 g/day) versus placebo or no treatmentTwelve trials (2334 women) evaluated low-dose (usually 500 mg daily) supplementation with calcium alone (four trials) or in association with vitamin D (five trials), linoleic acid (two trials), or antioxidants (one trial). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium reduced the risk of pre-eclampsia (nine trials, 2234 women: RR 0.38, 95% CI 0.28 to 0.52). There was also a reduction in high BP (five trials, 665 women: RR 0.53, 95% CI 0.38 to 0.74), admission to neonatal intensive care unit (one trial, 422 women, RR 0.44, 95% CI 0.20 to 0.99), but not preterm birth (six trials, 1290 women, average RR 0.83, 95% CI 0.34 to 2.03), or stillbirth or death before discharge (five trials, 1025 babies, RR 0.48, 95% CI 0.14 to 1.67).High-dose (=/> 1 g) versus low-dose (< 1 g) calcium supplementationWe included one trial with 262 women, the results of which should be interpreted with caution due to unclear risk of bias. Risk of pre-eclampsia appeared to be reduced in the high-dose group (RR 0.42, 95% CI 0.18 to 0.96). No other differences were found (preterm birth: RR 0.31, 95% CI 0.09 to 1.08; eclampsia: RR 0.32, 95% CI 0.07 to 1.53; stillbirth: RR 0.48, 95% CI 0.13 to 1.83). AUTHORS' CONCLUSIONS: High-dose calcium supplementation (≥ 1 g/day) may reduce the risk of pre-eclampsia and preterm birth, particularly for women with low calcium diets (low-quality evidence). The treatment effect may be overestimated due to small-study effects or publication bias. It reduces the occurrence of the composite outcome 'maternal death or serious morbidity', but not stillbirth or neonatal high care admission. There was an increased risk of HELLP syndrome with calcium supplementation, which was small in absolute numbers.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, hypertension and admission to neonatal high care, but needs to be confirmed by larger, high-quality trials.

Oral antioxidant therapy for prevention and treatment of preeclampsia: Meta-analysis of randomized controlled trials.

AIMS: To determine whether oral antioxidant therapies, of various types and doses, are able to prevent or treat women with preeclampsia. DATA SYNTHESIS: The following databases were searched: MEDLINE, CENTRAL, LILACS, and Web of Science. Inclusion criteria were: a) randomized clinical trials; b) oral antioxidant supplementation; c) study in pregnant women; d) control group, treated or not with placebo. Papers were excluded if they evaluated antioxidant nutrient supplementation associated with other non-antioxidant therapies. Data were extracted and the risk of bias of each study was assessed. Heterogeneity was analyzed using the Cochran Q test, and I2 statistics and pre-specified sensitivity analyses were performed. Meta-analyses were conducted on prevention and treatment studies, separately. The primary outcome was the incidence of preeclampsia in prevention trials, and of perinatal death in treatment trials. Twenty-nine studies were included in the analysis, 19 for prevention and 10 for treatment. The antioxidants used in these studies were vitamins C and E, selenium, l-arginine, allicin, lycopene and coenzyme Q10, none of which showed beneficial effects on the prevention of preeclampsia (RR: 0.89, CI 95%: [0.79-1.02], P = 0.09; I2 = 39%, P = 0.04) and other outcomes. The antioxidants used in the treatment studies were vitamins C and E, N-acetylcysteine, l-arginine, and resveratrol. A beneficial effect was found in intrauterine growth restriction. CONCLUSIONS: Antioxidant therapy had no effects in the prevention of preeclampsia but did show beneficial effects in intrauterine growth restriction, when used in the treatment of this condition.

Costo efectividad del suplemento de calcio para reducir la mortalidad materna asociada a preeclampsia en Colombia / Cost effectiveness of calcium supplement in reducing preeclampsia-related maternal mortality in Colombia

Objetivo Estimar el costo-efectividad de la administración de calcio (1 200 mg diarios) a partir de la semana 14 de gestación a todas las gestantes, comparada con no administrarlo, para reducir la incidencia de preeclampsia. Métodos Se construyó un árbol de decisión en TreeAge® con desenlace en años de vida ganados (AVG). Los costos se incluyeron desde la perspectiva del sistema de salud colombiano, en pesos (COP) de 2014. La tasa de descuento fue de 0%. Se realizaron análisis de sensibilidad univariados y probabilísticos para costos y efectividad. Resultados El suplemento de calcio es una alternativa dominante frente a la no intervención. Si la incidencia de preeclampsia es menor a 51,7 por 1 000 gestantes o el costo por tableta de calcio de 600 mg es mayor a COP$ 507,85, el suplemento de calcio deja de ser una alternativa costo-efectiva en Colombia para un umbral de 3 veces el PIB per cápita de 2013 (COP$ 45 026 379) por AVG. Conclusiones La administración de calcio a todas las gestantes a partir de la semana 14 de gestación es una alternativa dominante frente a la no intervención, que permite ganar 200 años de vida, al tiempo que disminuye costos del orden de COP$ 5 933 millones por 100 000 gestantes.(AU)

Objectives To estimate the cost-effectiveness of administering calcium (1200 mg per day) starting in week 14 of pregnancy to all pregnant women compared to not supplying it to reduce the incidence of preeclampsia. Methods A decision tree was built in TreeAge® with outcome measured in life years gained (LYG) associated with the reduction in maternal deaths. Costs were included from the perspective of the health system in Colombia and expressed in Colombian pesos in 2014 (COP). The discount rate was 0 %. We performed sensitivity univariate and probabilistic analyses for costs and effectiveness. Results Compared to no intervention, calcium supplement is a dominant alternative. If the incidence of preeclampsia is lower than 51.7 per 1 000 pregnant women or the cost per tablet of calcium of 600 mg is greater than COP $507.85, calcium supplement is no longer a cost-effective alternative in Colombia for a threshold of COP $ 45 026 379 (3 times the Colombian per capita GDP of 2013 per LYG). Conclusions Supplying calcium to all pregnant women from week 14 of gestation is a dominant alternative compared to no intervention, which saves 200 LYG, while it decreases costs to the order of COP$5 933 million per 100.000 pregnant women.(AU)

[Cost effectiveness of calcium supplement in reducing preeclampsia-related maternal mortality in Colombia]. / Costo efectividad del suplemento de calcio para reducir la mortalidad materna asociada a preeclampsia en Colombia.

Objectives To estimate the cost-effectiveness of administering calcium (1200 mg per day) starting in week 14 of pregnancy to all pregnant women compared to not supplying it to reduce the incidence of preeclampsia. Methods A decision tree was built in TreeAge® with outcome measured in life years gained (LYG) associated with the reduction in maternal deaths. Costs were included from the perspective of the health system in Colombia and expressed in Colombian pesos in 2014 (COP). The discount rate was 0 %. We performed sensitivity univariate and probabilistic analyses for costs and effectiveness. Results Compared to no intervention, calcium supplement is a dominant alternative. If the incidence of preeclampsia is lower than 51.7 per 1 000 pregnant women or the cost per tablet of calcium of 600 mg is greater than COP $507.85, calcium supplement is no longer a cost-effective alternative in Colombia for a threshold of COP $ 45 026 379 (3 times the Colombian per capita GDP of 2013 per LYG). Conclusions Supplying calcium to all pregnant women from week 14 of gestation is a dominant alternative compared to no intervention, which saves 200 LYG, while it decreases costs to the order of COP$5 933 million per 100.000 pregnant women.

Health workers' knowledge on future vascular disease risk in women with pre-eclampsia in south western Nigeria.

BACKGROUND: Pre-eclampsia progressing to eclampsia is one of the major causes of maternal death in Nigeria. Since there is long term association of pre-eclampsia with cardiovascular disease, cerebrovascular disease, renal disease, short life expectancy and mortality, it is essential to obtain obstetric history for better counseling and long term monitoring. The study assessed the knowledge of health workers about the association of pre-eclampsia with future cardiovascular disease and offering any risk-reduction counseling to women with pre-eclampsia. METHODS: During a training workshop, a validated questionnaire on the association between pre-eclampsia and cardiovascular risk was distributed among health care workers working at the infant welfare and family planning clinics in Osun State. Data were analysed using descriptive and inferential statistics. RESULTS: One hundred and forty-six out of 150 health workers approached participated in the study (response rate 97.3%). Mean age of respondents was 35.6 ± 9.1 years. Median age of practice was 7 years, ranging from 1-40 years. They were medical doctors (60.3%), community health workers (26.7%) and nurses/midwives (13.0%). Most participants had good knowledge on future cardiovascular risk of pre-eclampsia. The medical doctors had better knowledge compared to nurses/midwives and community health workers (78.4 vs. 57.9 vs. 53.8%; p < 0.05). Below half (45.9%) offered risk-reduction counseling. CONCLUSION: Knowledge of the cardiovascular risk factors was lower among the nurses/midwives and community health workers. Risk reduction counseling was quite low across all the health workers. There is need for continuous medical education and possible review of the training curriculum of the lower cadres of health workers.

Pregnancy outcome and placental findings in pregnancies complicated by fetal growth restriction with and without preeclampsia.

OBJECTIVE: To compare pregnancy outcome and placental pathology in pregnancies complicated by fetal growth restriction (FGR) with and without preeclampsia. METHODS: Labor, fetal/neonatal outcome, and placental pathology parameters from neonates with a birth weight below the 10 th percentile (FGR), born between 24 and 42 weeks of gestation, were reviewed. Results were compared between pregnancies complicated with preeclampsia (hypertensive FGR [H-FGR]) to those without preeclampsia (normotensive FGR [N-FGR]). Composite neonatal outcome, defined as 1 or more of early complication (respiratory distress, necrotizing enterocolitis, sepsis, transfusion, ventilation, seizure, hypoxic-ischemic encephalopathy, phototherapy, or death), Apgar score ≤ 7 at 5 minutes, and days of hospitalization, were compared between the groups. Placental lesions, classified as lesions related to maternal vascular supply, lesions consistent with fetal thrombo-occlusive disease and inflammatory lesions, maternal inflammatory response, and fetal inflammatory response, were also compared. RESULTS: Women in the H-FGR group (n = 72) were older, with higher body mass index (BMI) and higher rate of preterm labor (<34 weeks) than in the N-FGR group (n = 270), P < .001 for all. Composite neonatal outcome was worse in the H-FGR than in the N-FGR group, 50% versus 15.5%, P < .001. Higher rate of maternal placental vascular lesions was detected in H-FGR compared with N-FGR, 82% versus 57.7%, P < .001. Using a stepwise logistic regression model, maternal BMI (1.13 odds ratio [OR], confidence interval [CI] 1.035-1.227, P = .006) and neonatal birth weight (0.996 OR, CI 0.995-0.998, P < .001) were independently associated with worse neonatal outcome. CONCLUSION: Worse neonatal outcome and more maternal placental vascular lesions in pregnancy complicated by FGR with preeclampsia versus FGR without preeclampsia suggest different pathophysiology in these entities.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia, and may help to prevent preterm birth. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (28 March 2013) and contacted study authors for more data where possible. We updated the search in May 2014 and added the results to the 'Awaiting Classification' section of the review. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing high-dose (at least 1 g daily of calcium) or low-dose calcium supplementation during pregnancy with placebo or no calcium. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: High-dose calcium supplementation (≥1 g/day)We included 14 studies in the review, however one study contributed no data. We included 13 high-quality studies in our meta-analyses (15,730 women). The average risk of high blood pressure (BP) was reduced with calcium supplementation compared with placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81; I² = 74%). There was also a significant reduction in the risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65; I² = 70%). The effect was greatest for women with low calcium diets (eight trials, 10,678 women: average RR 0.36, 95% CI 0.20 to 0.65; I² = 76%) and women at high risk of pre-eclampsia (five trials, 587 women: average RR 0.22, 95% CI 0.12 to 0.42; I² = 0%). These data should be interpreted with caution because of the possibility of small-study effect or publication bias.The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97; I² = 0%). Maternal deaths were not significantly different (one trial of 8312 women: calcium group one death versus placebo group six deaths). There was an anomalous increase in the risk of HELLP (haemolysis, elevated liver enzymes and low platelets) syndrome (two trials, 12,901 women: RR 2.67, 95% CI 1.05 to 6.82; I² = 0%) in the calcium group, however, the absolute number of events was low (16 versus six).The average risk of preterm birth was reduced in the calcium group (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97; I² = 60%) and amongst women at high risk of developing pre-eclampsia (four trials, 568 women: average RR 0.45, 95% CI 0.24 to 0.83; I² = 60%), but no significant reduction in neonatal high care admission. There was no overall effect on the risk of stillbirth or infant death before discharge from hospital (11 trials 15,665 babies: RR 0.90, 95% CI 0.74 to 1.09; I² = 0%).One study showed a reduction in childhood systolic BP greater than 95th percentile among children exposed to calcium supplementation in utero (514 children: RR 0.59, 95% CI 0.39 to 0.91). In a subset of these children, dental caries at 12 years old was also reduced (195 children, RR 0.73, 95% CI 0.62 to 0.87). Low-dose calcium supplementation (< 1 g/day)We included 10 trials (2234 women) that evaluated low-dose supplementation with calcium alone (4) or in association with vitamin D (3), linoleic acid (2), or antioxidants (1). Most studies recruited women at high risk for pre-eclampsia, and were at high risk of bias, thus the results should be interpreted with caution. Supplementation with low doses of calcium significantly reduced the risk of pre-eclampsia (RR 0.38, 95% CI 0.28 to 0.52; I² = 0%). There was also a reduction in hypertension, low birthweight and neonatal intensive care unit admission. AUTHORS' CONCLUSIONS: Calcium supplementation (≥ 1 g/day) is associated with a significant reduction in the risk of pre-eclampsia, particularly for women with low calcium diets. The treatment effect may be overestimated due to small-study effects or publication bias. It also reduces preterm birth and the occurrence of the composite outcome 'maternal death or serious morbidity'. We considered these benefits to outweigh the increased risk of HELLP syndrome, which was small in absolute numbers. The World Health Organization recommends calcium 1.5 g to 2 g daily for pregnant women with low dietary calcium intake.The limited evidence on low-dose calcium supplementation suggests a reduction in pre-eclampsia, but needs to be confirmed by larger, high-quality trials. Pending such results, in settings of low dietary calcium where high-dose supplementation is not feasible, the option of lower-dose supplements (500 to 600 mg/day) might be considered in preference to no supplementation.

Hypertensive emergencies of pregnancy.

Hypertension is commonly encountered in pregnancy and has both maternal and fetal effects. Acute hypertensive crisis most commonly occurs in severe preeclampsia and is associated with maternal stroke, cardiopulmonary decompensation, fetal decompensation due to decreased uterine perfusion, abruption, and stillbirth. Immediate stabilization of the mother including the use of intervenous antihypertensives is required and often delivery is indicated. With appropriate management, maternal and fetal outcomes can be excellent.

Effect of a facility-based multifaceted intervention on the quality of obstetrical care: a cluster randomized controlled trial in Mali and Senegal.

BACKGROUND: Maternal mortality in referral hospitals in Mali and Senegal surpasses 1% of obstetrical admissions. Poor quality obstetrical care contributes to high maternal mortality; however, poor care is often linked to insufficient hospital resources. One promising method to improve obstetrical care is maternal death review. With a cluster randomized trial, we assessed whether an intervention, based on maternal death review, could improve obstetrical quality of care. METHODS: The trial began with a pre-intervention year (2007), followed by two years of intervention activities and a post-intervention year. We measured obstetrical quality of care in the post-intervention year using a criterion-based clinical audit (CBCA). We collected data from 32 of the 46 trial hospitals (16 in each trial arm) and included 658 patients admitted to the maternity unit with a trial of labour. The CBCA questionnaire measured 5 dimensions of care- patient history, clinical examination, laboratory examination, delivery care and postpartum monitoring. We used adjusted mixed models to evaluate differences in CBCA scores by trial arms and examined how levels of hospital human and material resources affect quality of care differences associated with the intervention. RESULTS: For all women, the mean percentage of care criteria met was 66.3 (SD 13.5). There were significantly greater mean CBCA scores in women treated at intervention hospitals (68.2) compared to control hospitals (64.5). After adjustment, women treated at intervention sites had 5 points' greater scores than those at control sites. This difference was mostly attributable to greater clinical examination and post-partum monitoring scores. The association between the intervention and quality of care was the same, irrespective of the level of resources available to a hospital; however, as resources increased, so did quality of care scores in both arms of the trial.

La preeclampsia un problema de salud pública mundial / Preeclampsia as a global public health problem

La preeclampsia es un problema de salud pública y una de las principales causas de muerte materna. La prevalencia oscila entre 1,8-16,7 por ciento. La causa sigue desconocida y se asocia a problemas de salud importantes, existiendo muchos retos para la predicción, prevención y tratamiento. Las medidas profilácticas como dosis baja de aspirina y suplementos de calcio, requieren mayor evidencia para uso rutinario. El control prenatal, diagnóstico oportuno, manejo adecuado, y parto son las medidas más eficaces para disminuir la tasa de mortalidad por esta causa. Los factores sociales y de atención médica oportuna deben prevalecer en la población, sin embargo, estos son limitados en poblaciones marginadas sin acceso a servicios médicos. Podemos concluir que los sistemas de salud de todas las poblaciones deben identificar y asistir medicamente a las mujeres que están en mayor riesgo de desarrollar preeclampsia por la importante carga económica mundial que demanda esta enfermedad.

Preeclampsia is a public health problem and a major cause of maternal death. The prevalence ranges from 1.8-16.7 percent, but the cause remains unknown and is associated with significant health problems, many challenges exist for the prediction, prevention and treatment, prophylactic measures such as low-dose aspirin and calcium supplements still require more evidence for routine use, prenatal care, timely diagnosis, proper management, and childbirth are the most effective measures to reduce mortality from this cause. Social factors and prompt medical attention should prevail in the population, but these are limited in underserved populations without access to medical services. We can conclude that the health systems of all populations to identify and medically assist women who are at greater risk of developing preeclampsia by the global economic toll this disease demand.

An estimate of the global reduction in mortality rates through doubling vitamin D levels.

BACKGROUND/OBJECTIVES: The goal of this work is to estimate the reduction in mortality rates for six geopolitical regions of the world under the assumption that serum 25-hydroxyvitamin D (25(OH)D) levels increase from 54 to 110 nmol/l. SUBJECTS/METHODS: This study is based on interpretation of the journal literature relating to the effects of solar ultraviolet-B (UVB) and vitamin D in reducing the risk of disease and estimates of the serum 25(OH)D level-disease risk relations for cancer, cardiovascular disease (CVD) and respiratory infections. The vitamin D-sensitive diseases that account for more than half of global mortality rates are CVD, cancer, respiratory infections, respiratory diseases, tuberculosis and diabetes mellitus. Additional vitamin D-sensitive diseases and conditions that account for 2 to 3% of global mortality rates are Alzheimer's disease, falls, meningitis, Parkinson's disease, maternal sepsis, maternal hypertension (pre-eclampsia) and multiple sclerosis. Increasing serum 25(OH)D levels from 54 to 110 nmol/l would reduce the vitamin D-sensitive disease mortality rate by an estimated 20%. RESULTS: The reduction in all-cause mortality rates range from 7.6% for African females to 17.3% for European females. Reductions for males average 0.6% lower than for females. The estimated increase in life expectancy is 2 years for all six regions. CONCLUSIONS: Increasing serum 25(OH)D levels is the most cost-effective way to reduce global mortality rates, as the cost of vitamin D is very low and there are few adverse effects from oral intake and/or frequent moderate UVB irradiance with sufficient body surface area exposed.

Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems.

BACKGROUND: Pre-eclampsia and eclampsia are common causes of serious morbidity and death. Calcium supplementation may reduce the risk of pre-eclampsia through a number of mechanisms, and may help to prevent preterm birth. OBJECTIVES: To assess the effects of calcium supplementation during pregnancy on hypertensive disorders of pregnancy and related maternal and child outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (May 2010) and contacted study authors. SELECTION CRITERIA: Randomised trials comparing at least 1 g daily of calcium during pregnancy with placebo. DATA COLLECTION AND ANALYSIS: We assessed eligibility and trial quality, extracted and double-entered data. MAIN RESULTS: We included 13 studies of good quality (involving 15,730 women). The average risk of high blood pressure was reduced with calcium supplementation rather than placebo (12 trials, 15,470 women: risk ratio (RR) 0.65, 95% confidence interval (CI) 0.53 to 0.81). There was also a reduction in the average risk of pre-eclampsia associated with calcium supplementation (13 trials, 15,730 women: RR 0.45, 95% CI 0.31 to 0.65). The effect was greatest for high-risk women (five trials, 587 women: RR 0.22, 95% CI 0.12 to 0.42), and those with low baseline calcium intake (eight trials, 10,678 women: RR 0.36, 95% CI 0.20 to 0.65).The average risk of preterm birth was reduced in the calcium group overall (11 trials, 15,275 women: RR 0.76, 95% CI 0.60 to 0.97) and amongst women at high risk of developing pre-eclampsia recruited to four small trials (568 women: RR 0.45, 95% CI 0.24 to 0.83).There was no overall effect on the risk of stillbirth or death before discharge from hospital (11 trials 15,665 babies; RR 0.90, 95% CI 0.74 to 1.09). The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women; RR 0.80, 95% CI 0.65 to 0.97). Most of the women in these trials were low risk and had a low calcium diet. Maternal deaths were reported in only one trial. One death occurred in the calcium group and six in the placebo group, a difference which was not statistically significant (RR 0.17, 95% CI 0.02 to 1.39).Blood pressure in childhood has been assessed in two studies, only one of which is currently included: childhood systolic blood pressure greater than 95th percentile was reduced (514 children: RR 0.59, 95% CI 0.39 to 0.91). AUTHORS' CONCLUSIONS: Calcium supplementation appears to approximately halve the risk of pre-eclampsia, to reduce the risk of preterm birth and to reduce the rare occurrence of the composite outcome 'death or serious morbidity'. There were no other clear benefits, or harms.

Substandard care in maternal mortality due to hypertensive disease in pregnancy in the Netherlands.

OBJECTIVES: To review the standard of care in cases of maternal mortality due to hypertensive diseases in pregnancy and to make recommendations for its improvement. DESIGN: Care given to women with hypertensive disease in pregnancy was audited and substandard care factors identified. SETTING: Confidential enquiry by the Dutch Maternal Mortality Committee (MMC) from the Netherlands Society of Obstetrics and Gynaecology. POPULATION: All maternal deaths reported to the MMC due to hypertensive disease in pregnancy in the Netherlands during the years 2000-04. METHODS: Assessment for substandard care factors using a checklist based on the Dutch guideline of 'Hypertensive Disorders in Pregnancy'. MAIN OUTCOME MEASURES: Substandard care in cases of maternal mortality due to hypertensive diseases in pregnancy. RESULTS: A total of 27 cases of maternal death due to hypertensive disease in pregnancy were reported to the committee in the study period. In 26 cases (96%), substandard care factors were present, of which in 17 cases (63%), these were for more than five different items. In community midwifery care, the most frequent substandard care factor was no testing for proteinuria when clearly indicated (41%). In hospital care, the most frequent substandard care was related to insufficient diagnostic testing when indicated (41%), insufficient management of hypertension by obstetricians (85%), no use or inadequate use of magnesium sulphate (67%), inadequate stabilisation before transport to tertiary care centres and/or delivery (52%) and failure to consider timely delivery (44%). CONCLUSIONS: Education of pregnant women concerning danger signs of hypertensive disease should be improved. Training of midwives and obstetricians should be improved in the following areas: performing basic diagnostic tests, adequate management of hypertension and eclampsia, with more attention to treatment of systolic blood pressure. This training should be guided by clear local protocols. Delivery should not be delayed in serious cases of hypertensive disease in pregnancy, not only after 32-34 weeks but also in early-onset pre-eclampsia as maternal risks often outweigh possible fetal benefits of temporising management.

Dietary calcium supplementation for prevention of pre-eclampsia and related problems: a systematic review and commentary.

BACKGROUND: Calcium supplementation during pregnancy may reduce the risk of hypertensive disorders of pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Central Register of Controlled Trials (March 2006). SELECTION CRITERIA: Randomised trials comparing at least 1 g of calcium daily during pregnancy with placebo. Eligibility and trial quality were assessed. DATA COLLECTION AND ANALYSIS: Data were extracted and analysed using Review Manager software. MAIN RESULTS: Twelve studies (15,528 women) were included, all of good quality. Most women were at low risk and had low dietary calcium. High blood pressure was reduced with calcium supplementation rather than placebo (11 trials, 14,946 women: relative risk [RR] random effects model 0.70; 95% CI 0.57-0.86), as was pre-eclampsia (12 trials, 15,206 women: RR 0.48; 95% CI 0.33-0.69). The effect was greatest for women at high risk (five trials, 587 women: RR 0.22; 95% CI 0.12-0.42) and for those with low baseline calcium intake (seven trials, 10,154 women: RR 0.36; 95% CI 0.18-0.70). There was heterogeneity, with less effect in the larger trials. The composite outcome maternal death or serious morbidity was reduced (four trials, 9732 women: RR 0.80; 95% CI 0.65-0.97). The syndrome of haemolysis, elevated liver enzymes and low platelets was increased (two trials, 12,901 women: RR 2.67; 95% CI 1.05-6.82). There was no overall effect on the risk of preterm birth or stillbirth or death before discharge from hospital. CONCLUSIONS: Calcium supplementation appears to reduce the risk of pre-eclampsia and to reduce the rare occurrence of the composite outcome 'maternal death or serious morbidity'. There were no other clear benefits or harms. COMMENTARY: We present the hypothesis that adequate dietary calcium before and in early pregnancy may be needed to prevent the underlying pathology responsible for pre-eclampsia. We suggest that the research agenda be redirected towards calcium supplementation at a community level.

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.

Hypertension in pregnancy: current concepts of preeclampsia.

Hypertensive disorders (gestational hypertension, preeclampsia, chronic hypertension, superimposed preeclampsia) are the most common medical complications of pregnancy and constitute a major cause of maternal and perinatal morbidity and mortality. Prediction of those women destined to develop preeclampsia remains elusive. The benefits of calcium supplementation for prevention of preeclampsia are encouraging; however, the definitive study is not yet complete. Aspirin therapy for high-risk has not been helpful; results of therapy for high-risk women are pending. More experience is being gained with antihypertensive therapy and expectant management in severe preeclampsia. Conservative management of severe preeclampsia, when performed in a tertiary care center, may benefit a select group of women and their fetuses.

Guinea-Bissau: maternal mortality assessment.

With more than 40% of all female deaths attributable to pregnancy, delivery, and the puerperium period, the study established a maternal mortality ratio of 914 deaths per 100,000 live births. The principal risk factors for dying from pregnancy-related causes are: no attendance at antenatal care, too great a distance between the home and the nearest hospital facility, home delivery, belonging to specific ethnic/religious groups, and delivery assistance from family members and TBAs. The health policy implications to improve this situation are: increased coverage with appropriate services, increased numbers of rural midwives, in-service training of existing staff in maternity issues and problems, culture-specific educational approaches using the existing value system, educational campaigns to discourage harmful practices and behaviour, continued educational efforts to upgrade the knowledge of TBAs, and a culturally sensitive integration of TBAs into the government programmes.

PIP: This article reports on an examination of maternal mortality in Guinea-Bissau during 1989-90. Verbal autopsies were conducted and matched to hospital and health center records. The 145 maternal deaths identified in this study were matched to controls. The estimated maternal mortality ratio (MMR) was 914/100,000 live births. The MMR for hospitals was 779/100,000. Few women with infections or hemorrhage received proper medical attention. Cases of obstructed labor usually involved malpresentation of the fetus and cephalopelvic disproportion. The main indirect causes of maternal mortality were anemia and malaria. Almost 70% of deaths were to women younger than 30. 32% of deaths to women younger than 20, 9% of deaths to women 20-29 years old, and 22% of deaths to women 30-39 years old were due to eclampsia. 27% of deaths among 30-39 year old women and 33% of deaths among women 40-49 years old were due to postpartum hemorrhage. The comparison of prepregnancy symptoms among women who died and women who did not showed that death was related to female genital mutilation, specifically excision or infibulation. This practice is common among certain tribes, which also have a young marriage age and slight stature. The highest mortality was among women with no prenatal care (45 deaths). 41 women who died made a few prenatal visits. 33 deaths were to women who made over 3 visits. 71% of the 145 women who died had experienced some complications (anemia, malaria, generalized edema with or without hypertension). Only 20.4% of women who died and 30.2% of living women were temporarily admitted to the hospital for these symptoms during pregnancy. 43% of survivors of a similar condition to those women who died made prenatal visits during the first trimester. Twice as many controls delivered at home compared to the hospital; the reverse held for women who died. 40% of women who died and only 26% of the control group had deliveries attended by family or traditional birth attendants. 14% versus 40% in the control had midwives delivering births. 28% versus 19% of control reached the health facility in over 24 hours. 53.7% versus 86.9% of controls had live births.