Low-dose on par with high-dose calcium supplementation in preventing pre-eclampsia

Low-dose calcium supplementation during pregnancy was noninferior to standard high-dose supplementation in preventing the risk of pre-eclampsia, according to two randomized clinical trials conducted in India and Tanzania.

“Calcium supplementation [1,500–2,000 mg/day, divided into three doses] in pregnancy has been recommended by the World Health Organization (WHO) since 2011 to reduce the risk of pre-eclampsia in populations with low dietary calcium intake,” said the researchers.

“In more than a decade since the 2011 recommendation, only a few countries have implemented routine high-dose calcium supplementation in pregnancy, mainly owing to adherence concerns and high programmatic costs associated with the complex dosing scheme,” they pointed out.

Hence, to assess the efficacy of a single 500-mg calcium supplement per day, the researchers conducted two inferiority trials involving 11,000 nulliparous pregnant women, mostly aged 18–24 years, in each trial. Participants were randomly assigned to receive either one tablet of calcium 500 mg/day and two tablets of placebo (low-dose group) or three tablets of calcium 500 mg/day (high-dose group). [N Engl J Med 2024;390:143-153]

Calcium supplementation of 500 mg/day showed noninferiority to 1,500 mg/day with respect to the incidence of pre-eclampsia in both trials (India: 3 percent vs 3.6 percent; relative risk [RR], 0.84 and Tanzania: 3.0 percent vs 2.7 percent; RR, 1.10).

In terms of preterm birth rates, low-dose calcium supplementation was also noninferior to high-dose supplementation in the India trial (11.4 percent vs 12.8 percent; RR, 0.89), but not in the Tanzania trial (10.4 percent vs 9.7 percent; RR, 1.07), as it exceeded the noninferiority margin.

Of note, a high adherence rate to calcium supplementation was observed in both the India and Tanzania trials, with a median of 97.7 percent and 92.3 percent, respectively.

Secondary and safety outcomes

The rates of gestational hypertension (RR, 0.85 [India] and 1.02 [Tanzania]) and small-for-gestational-age (RR, 0.96 [India] and 1.02 [Tanzania]) showed no difference between the low- and high-dose groups.

According to the researchers, there was no evidence that the 1,500-mg group outperformed the 500-mg group on any secondary or safety outcomes in either trial.

“Overall, our two trials showed that low-dose supplementation with 500 mg of calcium per day was noninferior to high-dose supplementation for the prevention of pre-eclampsia,” said the researchers.

“The 500-mg dose reduces the pill burden and would be expected to reduce program costs,” they added.