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Updated: Jul 6, 2025
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy
Pratibha Dwarkanath1, Alfa Muhihi1, Christopher R Sudfeld1
1From St. John's Research Institute (P.D., R.F.), St. John's Medical College (T.T., J.M.R., A.V.K.), and Bruhat Bengaluru Mahanagara Palike (N.B., R.S.) - all in Bangalore, India; the Africa Academy for Public Health (A.M., S.M.K., M.M.S.), Muhimbili University of Health and Allied Sciences (M.B., A.B.P.), Dar es Salaam Regional Medical Office of Health (N.O.S.), and Ifakara Health Institute (H.M.M.) - all in Dar es Salaam, Tanzania; the Harvard T.H. Chan School of Public Health (C.R.S., M.W., N.P., C.P.D., W.W.F.), Harvard Medical School (M.W., C.P.D.), and Boston Children's Hospital (C.P.D.) - all in Boston; Columbia University Medical Center, New York (B.J.W.); and the University of South Carolina, Columbia (N.P.).
Background:
The World Health Organization recommends 1500 to 2000 mg of calcium daily as supplementation, divided into three doses, for pregnant persons in populations with low dietary calcium intake in order to reduce the risk of preeclampsia. The complexity of the dosing scheme, however, has led to implementation barriers.
Methods:
We conducted two independent randomized trials of calcium supplementation, in India and Tanzania, to assess the noninferiority of a 500-mg daily dose to a 1500-mg daily dose of calcium supplementation. In each trial, the two primary outcomes were preeclampsia and preterm birth, and the noninferiority margins for the relative risks were 1.54 and 1.16, respectively.
Results:
A total of 11,000 nulliparous pregnant women were included in each trial. The cumulative incidence of preeclampsia was 3.0% in the 500-mg group and 3.6% in the 1500-mg group in the India trial (relative risk, 0.84; 95% confidence interval [CI], 0.68 to 1.03) and 3.0% and 2.7%, respectively, in the Tanzania trial (relative risk, 1.10; 95% CI, 0.88 to 1.36) - findings consistent with the noninferiority of the lower dose in both trials. The percentage of live births that were preterm was 11.4% in the 500-mg group and 12.8% in the 1500-mg group in the India trial (relative risk, 0.89; 95% CI, 0.80 to 0.98), which was within the noninferiority margin of 1.16; in the Tanzania trial, the respective percentages were 10.4% and 9.7% (relative risk, 1.07; 95% CI, 0.95 to 1.21), which exceeded the noninferiority margin.
Conclusions:
In these two trials, low-dose calcium supplementation was noninferior to high-dose calcium supplementation with respect to the risk of preeclampsia. It was noninferior with respect to the risk of preterm live birth in the trial in India but not in the trial in Tanzania. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT03350516; Clinical Trials Registry-India number, CTRI/2018/02/012119; and Tanzania Medicines and Medical Devices Authority Trials Registry number, TFDA0018/CTR/0010/5).
