Cluster-randomized non-inferiority trial to compare supplement consumption and adherence to different dosing regimens for antenatal calcium and iron-folic acid supplementation to prevent preeclampsia and anaemia: rationale and design of the Micronutrient Initiative study

  • Moshood O. Omotayo
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
  • Katherine L. Dickin
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
  • Gina M. Chapleau
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
  • Stephanie L. Martin
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
  • Christopher Chang
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.
  • Erick O. Mwanga
    Malava Sub-county Health Management Team, Ministry of Health, Kakamega County, Kenya.
  • Jacqueline K. Kung’u
    Micronutrient Initiative, Africa Regional Office, Dakar, Senegal.
  • Rebecca J. Stoltzfus
    Program in International Nutrition, Division of Nutritional Sciences, Cornell University, Ithaca, NY, United States.

ABSTRACT

Background: To prevent pre-eclampsia in populations with insufficient dietary calcium (Ca) intake, the World Health Organisation (WHO) recommends routine Ca supplementation during antenatal care (ANC). WHO guidelines suggest a complex dosing regimen, requiring as many as 5 pill-taking events per day when combined with iron and folic acid (IFA) supplements. Poor adherence may undermine public health effectiveness, so simpler regimens may be preferable. This trial will compare the effect of the WHO-recommended (higher-dose) regimen vs. a simpler, lower-dose regimen on supplement consumption and pill-taking behaviours in Kenyan ANC clients.

Design and methods:
 This is a parallel, non-inferiority, cluster-randomized trial; we examined 16 primary care health facilities in Kenya, 1047 pregnant women between 16-30 weeks gestational age. Higher-dose regimen: 1.5 g elemental calcium in 3 separate doses (500 mg Ca/pill) and IFA (60 mg Fe + 400 μg folic acid) taken with evening dose. Lower-dose regimen: 1.0 g calcium in 2 separate doses (500 mg Ca/pill) with IFA taken as above.

Measurements: Primary outcome is Ca pills consumed per day, measured by pill counts. Secondary outcomes include IFA pills consumed per day, client knowledge, motivation, social support, and satisfaction, measured at 4 to 10 weeks post-enrolment. Statistical analyses: Unit of randomization is the health-care facility; unit of analysis is individual client. Intent-to-treat analysis will be implemented with multi-level models to account for clustering.

Expected public health impact:
 If pregnant women prescribed lower doses of Ca ingest as many pills as women prescribed the WHO-recommended regimen, developing a lower-dose recommendation for antenatal Ca and IFA supplementation programs could save resources.