A Simplified Regimen Compared with WHO Guidelines Decreases Antenatal Calcium Supplement Intake for Prevention of Preeclampsia in a Cluster-Randomized Noninferiority Trial in Rural Kenya

J Nutr. 2017 Oct;147(10):1986-1991. doi: 10.3945/jn.117.251926. Epub 2017 Sep 6.

Abstract

Background: To prevent preeclampsia, the WHO recommends antenatal calcium supplementation in populations with inadequate habitual intake. The WHO recommends 1500-2000 mg Ca/d with iron-folic acid (IFA) taken separately, a complex pill-taking regimen. Objective: The objective of this study was to test the hypothesis that simpler regimens with lower daily dosages would lead to higher adherence and similar supplement intake.Methods: In the Micronutrient Initiative Calcium Supplementation study, we compared the mean daily supplement intake associated with 2 dosing regimens with the use of a parallel, cluster-randomized noninferiority trial implemented in 16 primary health care facilities in rural Kenya. The standard regimen was 3 × 500 mg Ca/d in 3 pill-taking events, and the low-dose regimen was 2 × 500 mg Ca/d in 2 pill-taking events; both regimens included a 200 IU cholecalciferol and calcium pill and a separate IFA pill. We enrolled 990 pregnant women between 16 and 30 wk of gestation. The primary outcome was supplemental calcium intake measured by pill counts 4 and 8 wk after recruitment. We carried out intention-to-treat analyses with the use of mixed-effect models, with regimen as the fixed effect and health care facilities as a random effect, by using a noninferiority margin of 125 mg Ca/d.Results: Women in facilities assigned to the standard regimen consumed a mean of 1198 mg Ca/d, whereas those assigned to the low-dose regimen consumed 810 mg Ca/d. The difference in intake was 388 mg Ca/d (95% CI = 341, 434 mg Ca/d), exceeding the prespecified margin of 125 mg Ca/d. The overall adherence rate was 80% and did not differ between study arms.Conclusions: Contrary to our expectation, a simpler, lower-dose regimen led to significantly lower supplement intake than the regimen recommended by the WHO. Further studies are needed to precisely characterize the dose-response relation of calcium supplementation and preeclampsia risk and to examine cost effectiveness of lower and simpler regimens in program settings. This trial was registered at clinicaltrials.gov as NCT02238704.

Keywords: adherence; antenatal; calcium supplementation; preeclampsia; pregnancy; prenatal micronutrient supplementation; regimen.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Calcium, Dietary / administration & dosage*
  • Cholecalciferol / administration & dosage
  • Dietary Supplements*
  • Female
  • Folic Acid / administration & dosage
  • Guidelines as Topic
  • Humans
  • Iron / administration & dosage
  • Kenya
  • Micronutrients / administration & dosage
  • Nutrition Therapy* / standards
  • Patient Compliance*
  • Pre-Eclampsia / prevention & control*
  • Pregnancy
  • Prenatal Care / methods*
  • Rural Population
  • World Health Organization
  • Young Adult

Substances

  • Calcium, Dietary
  • Micronutrients
  • Cholecalciferol
  • Folic Acid
  • Iron

Associated data

  • ClinicalTrials.gov/NCT02238704
  • ClinicalTrials.gov/NCT02238704