Prepregnancy and early pregnancy calcium supplementation among women at high risk of pre-eclampsia : a multicentre, double-blind, randomised, placebo-controlled trial
Date
2019
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
Background: 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.
Description
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.com
The original publication is available at https://www.thelancet.com
Keywords
Prepregnancy -- Calcium, Nutrition in pregnancy, Preeclampsia -- Risk factors, Placebos (Medicine), Nutritional supplements
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