Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial

CITATION: Hofmeyr, G. J., et al. 2019. Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial. The Lancet, 393(10169):P330-339, doi:10.1016/S0140-6736(18)31818-X.The original publication is available at https://www.thelancet.comBackground: Reducing deaths from hypertensive disorders of pregnancy is a global priority. Low dietary calcium might account for the high prevalence of pre-eclampsia and eclampsia in low-income countries. Calcium supplementation in the second half of pregnancy is known to reduce the serious consequences of pre-eclampsia; however, the effect of calcium supplementation during placentation is not known. We aimed to test the hypothesis that calcium supplementation before and in early pregnancy (up to 20 weeks’ gestation) prevents the development of pre-eclampsia Methods: We did a multicountry, parallel arm, double-blind, randomised, placebo-controlled trial in South Africa, Zimbabwe, and Argentina. Participants with previous pre-eclampsia and eclampsia received 500 mg calcium or placebo daily from enrolment prepregnancy until 20 weeks’ gestation. Participants were parous women whose most recent pregnancy had been complicated by pre-eclampsia or eclampsia and who were intending to become pregnant. All participants received unblinded calcium 1·5 g daily after 20 weeks’ gestation. The allocation sequence (1:1 ratio) used computer-generated random numbers in balanced blocks of variable size. The primary outcome was pre-eclampsia, defined as gestational hypertension and proteinuria. The trial is registered with the Pan-African Clinical Trials Registry, number PACTR201105000267371. The trial closed on Oct 31, 2017. Findings: Between July 12, 2011, and Sept 8, 2016, we randomly allocated 1355 women to receive calcium or placebo; 331 of 678 participants in the calcium group versus 320 of 677 in the placebo group became pregnant, and 298 of 678 versus 283 of 677 had pregnancies beyond 20 weeks’ gestation. Pre-eclampsia occurred in 69 (23%) of 296 participants in the calcium group versus 82 (29%) of 283 participants in the placebo group with pregnancies beyond 20 weeks’ gestation (risk ratio [RR] 0·80, 95% CI 0·61–1·06; p=0·121). For participants with compliance of more than 80% from the last visit before pregnancy to 20 weeks’ gestation, the pre-eclampsia risk was 30 (21%) of 144 versus 47 (32%) of 149 (RR 0·66, CI 0·44–0·98; p=0·037). There were no serious adverse effects of calcium reported. Interpretation: Calcium supplementation that commenced before pregnancy until 20 weeks’ gestation, compared with placebo, did not show a significant reduction in recurrent pre-eclampsia. As the trial was powered to detect a large effect size, we cannot rule out a small to moderate effect of this intervention. ernal and Child Health.https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31818-X/fulltextPublisher's versio

The effect of calcium supplementation on blood pressure in non-pregnant women with previous pre-eclampsia: An exploratory, randomized placebo controlled study

Background Epidemiological findings suggest that the link between poverty and pre-eclampsia might be dietary calcium deficiency. Calcium supplementation has been associated with a modest reduction in pre-eclampsia, and also in blood pressure (BP). Methods This exploratory sub-study of the WHO Calcium and Pre-eclampsia (CAP) trial aims to determine the effect of 500 mg/day elemental calcium on the blood pressure of non-pregnant women with previous pre-eclampsia. Non-pregnant women with at least one subsequent follow-up trial visit at approximately 12 or 24 weeks after randomization were included. Results Of 836 women randomized by 9 September 2014, 1st visit data were available in 367 women of whom 217 had previously had severe pre-eclampsia, 2nd visit data were available in 201 women. There was an overall trend to reduced BP in the calcium supplementation group (1-2.5 mmHg) although differences were small and not statistically significant. In the subgroup with previous severe pre-eclampsia, the mean diastolic BP change in the calcium group (-2.6 mmHg) was statistically larger than in the placebo group (+0.8 mmHg), (mean difference -3.4, 95% CI -0.4 to -6.4; p = 0.025). The effect of calcium on diastolic BP at 12 weeks was greater than in those with non-severe pre-eclampsia (p = 0.020, ANOVA analysis). Conclusions There is an overall trend to reduced BP but only statistically significant in the diastolic BP of women with previous severe pre-eclampsia. This is consistent with our hypothesis that this group is more sensitive to calcium supplementation, however results need to be interpreted with caution.Fil: Hofmeyr, G. J.. University of the Witwatersrand; SudáfricaFil: Seuc, A. H.. World Health Organization; SuizaFil: Betrán, A. P.. World Health Organization; SuizaFil: Purnat, T. D.. World Health Organization; DinamarcaFil: Ciganda, Álvaro. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Munjanja, S. P.. University of Zimbabwe; ZimbabueFil: Manyame, S.. University of Zimbabwe; ZimbabueFil: Singata, M.. Fort Hare University; SudáfricaFil: Fawcus, S.. University of Cape Town; Sudáfrica. Mowbray Maternity Hospital; SudáfricaFil: Frank, K.. University of the Witwatersrand; SudáfricaFil: Hall, D. R.. Stellenbosch University; Sudáfrica. Tygerberg Hospital; SudáfricaFil: 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: Roberts, J. M.. University of Pittsburgh; Estados UnidosFil: Bergel, Eduardo F.. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Drebit, S.K.. University of British Columbia; CanadáFil: von Dadelszen, P.. University of British Columbia; CanadáFil: 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: Calcium and Pre-eclampsia Study Group. No especifica