Factors affecting the implementation of calcium supplementation strategies during pregnancy to prevent pre-eclampsia: a mixed-methods systematic review.

OBJECTIVES: Daily calcium supplements are recommended for pregnant women from 20 weeks' gestation to prevent pre-eclampsia in populations with low dietary calcium intake. We aimed to improve understanding of barriers and facilitators for calcium supplement intake during pregnancy to prevent pre-eclampsia. DESIGN: Mixed-method systematic review, with confidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations-Confidence in the Evidence from Reviews of Qualitative research approach. DATA SOURCES: MEDLINE and EMBASE (via Ovid), CINAHL and Global Health (via EBSCO) and grey literature databases were searched up to 17 September 2022. ELIGIBILITY CRITERIA: We included primary qualitative, quantitative and mixed-methods studies reporting implementation or use of calcium supplements during pregnancy, excluding calcium fortification and non-primary studies. No restrictions were imposed on settings, language or publication date. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. We analysed the qualitative data using thematic synthesis, and quantitative findings were thematically mapped to qualitative findings. We then mapped the results to behavioural change frameworks to identify barriers and facilitators. RESULTS: Eighteen reports from nine studies were included in this review. Women reported barriers to consuming calcium supplements included limited knowledge about calcium supplements and pre-eclampsia, fears and experiences of side effects, varying preferences for tablets, dosing, working schedules, being away from home and taking other supplements. Receiving information regarding pre-eclampsia and safety of calcium supplement use from reliable sources, alternative dosing options, supplement reminders, early antenatal care, free supplements and support from families and communities were reported as facilitators. Healthcare providers felt that consistent messaging about benefits and risks of calcium, training, and ensuring adequate staffing and calcium supply is available would be able to help them in promoting calcium. CONCLUSION: Relevant stakeholders should consider the identified barriers and facilitators when formulating interventions and policies on calcium supplement use. These review findings can inform implementation to ensure effective and equitable provision and scale-up of calcium interventions. PROSPERO REGISTRATION NUMBER: CRD42021239143.

Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta-analysis, network meta-analysis and health economic evaluation.

INTRODUCTION: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. METHODS AND ANALYSIS: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. ETHICS AND DISSEMINATION: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021231276.

Morbilidad severa materna y neonatal: vigilancia en servicios y capacidad de respuesta del sistema de salud / Severe Maternal and Neonatal Morbidity: Service Surveillance and Health System Responsiveness

Las complicaciones maternas agudas graves (CMAG), cuadros críticos que evolucionan hacia la sobrevida, comparten características con las muertes maternas y pueden complementarla información necesaria para el análisis. OBJETIVO: Evaluar la incidencia y el manejo de las CMAG maternas asociadas con la mortalidad materna y neonatal en maternidades públicas de las provincias de Corrientes y Santa Fe. MÉTODOS: Se realizó un estudio de corte transversal. Se relevó la incidencia y el manejo de las CMAG asociadas con la mortalidad materna y neonatal en maternidades públicas de Corrientes y Santa Fe durante tres meses. Se evaluó la disponibilidad y el uso de intervenciones preventivas y terapéuticas. RESULTADOS: Se incluyó a 6.121 mujeres de 3 maternidades de Corrientes y 10 de Santa Fe. Hubo condiciones potencialmente fatales en 755 (12,3%) y CMAG en 28 (0,5%). El sulfato de magnesio se utilizó en todas las eclampsias, con elevado uso de uterotónicos para la prevención de la hemorragia posparto. La cobertura con corticoides antenatales fue menor a la esperada. En dos tercios de los casos, las complicaciones se iniciaron antes de la llegada al hospital o durante las primeras 24 horas. CONCLUSIONES: El monitoreo de las CMAG maternas permite conocer las incidencias locales y los patrones de mortalidad y morbilidad severa materna, así como las fortalezas y debilidades en los sistemas de referencia y la correcta utilización de las intervenciones clínicas y los sistemas de salud...

Severe maternal acute complications (SMAC), critical situations evolving to survival, share some characteristics with maternal deaths and can provide complementary information for the analysis. OBJECTIVE: To evaluate the incidence and management of SMAC associated with maternal and neonatal mortality in public health facilities of Corrientes and Santa Fe provinces. METHODS: A cross-sectional study was conducted. It assessed the incidence and management of SMAC associated with maternal and neonatal mortality in public hospitals of Corrientes and Santa Fe provinces during a three-month period. Availability and use of prophylactic and therapeutic interventions were also evaluated. RESULTS: A total of 6121 women from 3 hospitals in Corrientes and 10 in SantaFe were included. Life-threatening conditions were found in 755 cases (12.3%) and SMAC in 28 (0.5%). Magnesium sulfate was given for all eclampsia cases, with a high use of uterotonics for prevention of postpartum hemorrhage. The treatment with antenatal corticosteroids was lower than expected. In two thirds of the cases, complications started before hospital admission or during the first 24 hours. CONCLUSIONS: The monitoring of maternal SAC allows to know not only the local incidences and patterns of severe maternal morbidity and mortality, but also the strengths and weaknesses in the referral systems and the correct use of clinical and health system interventions...

Effects of calcium supplementation on fetal growth in mothers with deficient calcium intake: a randomised controlled trial.

Calcium supplementation in mothers with low calcium intake has been of interest recently because of its association with optimal fetal growth and improved pre-eclampsia-related outcomes. While the effects of calcium supplementation have demonstrated benefits in prolonging gestation and subsequently improving birthweight, no specific studies have identified the longitudinal effects of supplementation on fetal growth in utero. Data were analysed in the context of the World Health Organization trial of calcium supplementation in calcium-deficient women. Five hundred and ten healthy, primiparous pregnant Argentinean women were randomised (at <20 weeks gestation) to either placebo (n = 230) or calcium supplements (1500 mg calcium/day in 3 divided doses; n = 231). Growth parameters in utero were assessed with serial ultrasound scans. Birthweight, length, head, abdominal and thigh circumferences were recorded at delivery. No differences were found in fetal biometric measurements recorded at 20, 24, 28, 32 and 36 weeks gestation between fetuses of women who were supplemented with calcium and those who were not. Similarly, neonatal characteristics and anthropometric measurements recorded at delivery were comparable in both groups. We conclude that calcium supplementation of 1500 mg calcium/day in pregnant women with low calcium intake does not appear to impact on fetal somatic or skeletal growth.

Effects of calcium supplementation on uteroplacental and fetoplacental blood flow in low-calcium-intake mothers: a randomized controlled trial.

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.

Strategies to prevent and treat preeclampsia: evidence from randomized controlled trials.

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.

Nutritional interventions during pregnancy for the prevention or treatment of maternal morbidity and preterm delivery: an overview of randomized controlled trials.

This overview assesses the effectiveness of nutritional interventions to prevent or treat maternal morbidity, mortality and preterm delivery. Cochrane systematic reviews and other up-to-date systematic reviews and individual randomized controlled trials were sought. Searches were carried out up to July 2002. Iron and folate supplements reduce anemia and should be included in antenatal care programs. Calcium supplementation to women at high risk of hypertension during pregnancy or low calcium intake reduced the incidence of both preeclampsia and hypertension. Fish oil and vitamins E and C are promising for preventing preeclampsia and preterm delivery and need further testing. Vitamin A and beta-carotene reduced maternal mortality in a large trial; ongoing trials should provide further evaluation. No specific nutrient supplementation was identified for reducing preterm delivery. Nutritional advice, magnesium, fish oil and zinc supplementation appear promising and should be tested alone or together in methodologically sound randomized controlled trials. Anema in pregnancy can be prevented and treated effectively. Considering the multifactorial etiology of the other conditions evaluated, it is unlikely that any specific nutrient on its own, blanket interventions or magic bullets will prevent or treat preeclampsia, hemorrhage, obstructed labor, infections, preterm delivery or death during pregnancy. The few promising interventions for specific outcomes should be tested or reconsidered when results of ongoing trials become available. Until then, women and their families should receive support to improve their diets as a general health rule, which is a basic human right.

Nutritional interventions during pregnancy for the prevention or treatment of impaired fetal growth: an overview of randomized controlled trials.

This paper reviews the efficacy of nutrition interventions to prevent or treat impaired fetal growth. Searches were made for Cochrane systematic reviews and randomized controlled trials published before October 2002. Balanced protein energy supplementation reduced the risk of small for gestational age (SGA) by 30% (95%CI: 20% to 43%) while one trial conducted in New York, U.S., reported a negative effect of high protein supplementation on SGA (RR 1.58; 95%CI: 1.03-2.41). Calcium supplementation protected against low birth weight (RR 0.83; 95%CI: 0.71-0.98). Micronutrient supplements did not affect birth weight, except for magnesium supplementation, which reduced the risk of SGA by 30%. This finding, however, needs or be interpreted with caution because of methodological issues in the data analysis. Programmatic recommendations can be made only for intervening with balanced protein energy supplements, especially in population with a high prevalence of undernutrition. Research is needed to determine the efficacy of multiple micronutrient supplementation and the effect of single micronutrients supplementation on specific growth outcomes such as fetal organ and bone growth. In addition, the public health relevance of these outcomes and their relation to morbidity need to be evaluated.