Calcium for pre-eclampsia prevention: A systematic review and network meta-analysis to guide personalised antenatal care

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.Fil: Woo Kinshella, Mai-Lei. University of British Columbia; CanadáFil: Sarr, Catherine. Kings College London (kcl);Fil: Sandhu, Akshdeep. University of British Columbia; CanadáFil: Bone, Jeffrey N.. University of British Columbia; CanadáFil: Vidler, Marianne. University of British Columbia; CanadáFil: Moore, Sophie E.. Kings College London (kcl);Fil: Elango, Rajavel. University of British Columbia; CanadáFil: Cormick, Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Hofmeyr, G. Justus. University of the Witwatersrand; Sudáfrica. University of Walter Sisulu; Sudáfrica. University of Fort Hare; Sudáfrica. University of Botswana; BotsuanaFil: Magee, Laura A.. University of British Columbia; Canadá. Kings College London (kcl);Fil: von Dadelszen, Peter. University of British Columbia; Canadá. Kings College London (kcl)

Choosing blood pressure thresholds to inform pregnancy care in the community: An analysis of cluster trials

Objective: To inform digital health design by evaluating diagnostic test properties of antenatal blood pressure (BP) outputs and levels to identify women at risk of adverse outcomes.Design: Planned secondary analysis of cluster randomised trials.Setting: India, Pakistan, Mozambique.Population: Women with in-community BP measurements and known pregnancy outcomes.Methods: Blood pressure was defined by its outputs (systolic and/or diastolic, systolic only, diastolic only or mean arterial pressure [calculated]) and level: normotension-1 (\u3c135/85 mmHg), normotension-2 (135-139/85-89 mmHg), non-severe hypertension (140-149/90-99 mmHg; 150-154/100-104 mmHg; 155-159/105-109 mmHg) and severe hypertension (≥160/110 mmHg). Dose-response (adjusted risk ratio [aRR]) and diagnostic test properties (negative [-LR] and positive [+LR] likelihood ratios) were estimated.Main outcome measures: Maternal/perinatal composites of mortality/morbidity.Results: Among 21 069 pregnancies, different BP outputs had similar aRR, -LR, and +LR for adverse outcomes. No BP level (even normotension-1) was associated with low risk (all -LR ≥0.20). Across outcomes, risks rose progressively with higher BP levels above normotension-1. For each of maternal central nervous system events and stillbirth, BP ≥155/105 mmHg showed at least good diagnostic test performance (+LR ≥5.0) and BP ≥135/85 mmHg at least fair performance, similar to BP ≥140/90 mmHg (+LR 2.0-4.99).Conclusions: In the community, normal BP values do not provide reassurance about subsequent adverse outcomes. Given the similar performance of BP cut-offs of 135/85 and 140/90 mmHg for hypertension, and 155/105 and 160/110 mmHg for severe hypertension, digital decision support for women in the community should consider using these lower thresholds