Trial of the Impact of Vitamin A on Maternal Mortality
Condition: Vitamin A Deficiency; Maternal Mortality; Maternal Morbidity
MeSH terms: Night Blindness; Maternal Death; Vitamin A Deficiency
Study type: Interventional
Phase: Phase 3

Summary: 
      Main objectives: To evaluate the impact of weekly vitamin A supplementation (VAS) to women of
      reproductive age (15-45 years) on maternal mortality in rural Ghana, and to compare this with
      the impact on overall mortality.

      Hypotheses:

        1. Weekly supplementation with vitamin A (7000 µg retinol equivalent [RE]) to reproductive
           age women will reduce maternal deaths by 33%.

        2. This impact will be achieved by reductions in both pregnancy-related and
           non-pregnancy-related deaths.

        3. There will be a reduction in non-maternal deaths, similar in size to that in maternal
           non-pregnancy related deaths.

      Outcome measures: Maternal mortality rate, and overall mortality rate. Deaths will be
      identified through monthly demographic surveillance, and classified as maternal
      (pregnancy-related, non-pregnancy-related) or non-maternal using verbal autopsies.
    

Detailed description: 
      Pregnancy accounts for nearly 600,000 deaths of women each year; maternal health problems are
      the largest contributors to the disease burden of adult women. Conventional primary health
      care approaches, which included Traditional Birth Attendant training and antenatal screening,
      had little impact on the maternal mortality ratio. Instead, the Safe Motherhood paradigm now
      aims to ensure emergency obstetric care (EMOC) at the district hospital level for the 10-15%
      of women who develop potentially life threatening complications, and is moving towards
      recommending that professionals attend all deliveries.

      While the latter configurations of care have been shown to reduce maternal mortality, they
      require considerable political will, attention to health systems, and expansion of access to
      supervised delivery and EMOC. For the poorest countries, such capacity is some years down the
      line. Low-tech interventions which effectively reduce maternal mortality, and which can be
      delivered at the community level would be a welcome addition to the armamentarium of public
      health measures for preventing maternal mortality. Should vitamin A supplementation prove to
      be effective in reducing maternal mortality, or indeed all-cause female mortality, it would
      provide such a tool. Moreover, as there is considerable policy and programmatic interest in
      VAS for children, it is likely that such interest can be broadened to encompass
      supplementation for women. Furthermore, it is increasingly recognised that poverty not only
      increases the risk of ill health, but that ill health in turn plays a major role in creating
      and perpetuating poverty. A community-based intervention such as Vitamin A is likely to
      address the needs of the very poorest women, as these are the individuals least likely to
      have access to emergency obstetric care and professional birth attendants.

      This will be a cluster-randomised double-blind placebo-controlled trial. All women between
      the ages of 15 and 45 years will be randomised, according to their cluster of residence to
      receive weekly capsules of either 7000 RE of vitamin A in peanut oil or identical looking
      placebo capsules containing peanut oil only. Thus, supplements will be delivered to women
      both in antenatal and inter-pregnancy periods.

      The trial will be conducted by the Kintampo Health Research Centre (KHRC) in four contiguous
      districts - Kintanpo, Techiman, Wenchi and Nkoranza -- in the Brong Ahafo region of Ghana.
      The districts fall within the forest-savannah transitional ecological zone, and vitamin A
      rich food sources are less available than in the forest regions to the south. Data from
      previous studies by KHRC and from a national prevalence survey, both indicate a VAD problem
      of public health significance in the area -- 26% of breastmilk samples have retinol
      concentrations lower than 30µg/dl, exceeding the WHO cut-off of 25% for defining areas with a
      severe problem (WHO, 1996). VAS has been found to substantially reduce childhood morbidity
      and mortality in similar areas, thus it is suitable for testing the potential benefits of VAS
      to women.

      All women aged 15-45 years who are permanent residents in the study areas will be eligible
      for recruitment into the trial. They will be identified from existing databases. Permanent
      residence is defined as having been resident in the area for the three months preceding the
      start of recruitment, with intention to remain in the study area for the following 12 months.
      There will be no exclusions to participation, except for women who have nightblindness or
      other signs of VAD. These, and any women who develop VAD in the course of the study will be
      treated according to current IVACG recommendations (IVACG, 1997). They will continue to be
      followed, but will be given vitamin A and considered separately in the analysis. Continuous
      recruitment will be done for women who migrate into the study area, or those who become
      eligible by age as the study progresses. Allocation to treatment will be determined by the
      cluster of residence.
    

Intervention name(s): Vitamin A
Intervention type(s): Dietary Supplement
Intervention description(s): Weekly single oral dose 7000 micrograms
Intervention MeSH terms: Vitamin A
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Pregnancy; Mortality; Maternal; Vitamin A