Efficacy of Sprinkles® and Iron Folic Acid Tablets to Control Anemia During Pregnancy

Iron deficiency and anemia during pregnancy have been identified by the World Health Organization (WHO) as a priority issue. The current intervention recommended for developing countries, iron and folic acid tablets, has been shown to have low effectiveness. Alternate approaches are thus called for. It is proposed to test a new micronutrient intervention including iron and folic acid in the form of Sprinkles® to help decrease the high prevalence of iron deficiency and anemia during pregnancy. The proposed study is a cluster randomized trial to be carried out in 40 community-based antenatal care centres (ANCCs) operated by BRAC (formerly known as the Bangladesh Rural Advancement Committee), the largest non-governmental organization (NGO) in Bangladesh.

Two interventions are planned: (i) iron-folic acid (IFA) tablets; and (ii) Sprinkles®. As per guidelines set by the WHO for countries where the prevalence of anemia is > 40% (e.g. Bangladesh), 60 mg of elemental iron (as Sprinkles® or IFA tablets) will be provided to pregnant women for daily use starting at the first ANCC visit and lasting throughout the pregnancy and continued until 3 months post-partum. In addition, as per previous WHO guidelines, each tablet or Sprinkles® sachets will also contain 400μg of folic acid. For women in the IFA tablet group, one IFA tablet will be taken daily. For women in the Sprinkles® group, one sachet will be taken daily by sprinkling the entire contents of the sachet over a semi-solid food prior to consumption. Sprinkles® will contain 60 mg of elemental iron as encapsulated ferrous fumarate and 400 μg of folic acid. During the study, participants will be monitored for hematological status as well as for adherence and side effects using structured, pre-tested questionnaires.

Women will be recruited from ANCCs in the rural sub-district of Kaligonj, Bangladesh. Kaligonj has a relatively homogenous population in terms of socio-economic status, language and culture, and importantly, is located in a flood-free zone less than 50 km from Dhaka. As of December 2004, there were 100 community-based ANCCs in the Kaligonj sub-district, each operated by a trained BRAC health worker and assisted by an indigenous female community health worker (CHW). Each ANCC serves a village or a population of around 300 households. An ANCC is set up in a village for one day every month to reach all pregnant women residing in that village; thus women routinely attend the ANCC in their own village.

The inclusion criteria for the study are pregnant women, ages between 15-45 years, who have a gestational age between 14-20 weeks. For logistical reasons it is not possible to start all women at the same point. This difference in post conceptual age will be accounted for statistically. Recall of Last Menstrual Period (LMP) will approximate the gestational age in weeks; gestational age is estimated from the first day of the LMP. Therefore, any woman with gestational age > 20 weeks will be excluded. A calendar of local events will be developed to assist each of the women to recall their LMP with a greater precision. Women with Hb < 70 g/L (severely anemic according to WHO) at the start of the study will be excluded and referred to the Medical Officer at the nearest government or BRAC health centre for appropriate investigation and therapy. Women already on iron supplementation prior to the study start will not be included. Trained health workers at the ANCC will assess each potential subject for uncontrolled hypertension. Those with a known history of liver, heart or kidney disease, cancer or severe infections will be excluded. It is not possible to define all illnesses that would lead to exclusion, but generally those women requiring significant medical care, above that normally received during pregnancy will be excluded. All women must freely consent to participation.

The primary outcome is the hemoglobin (Hb) concentration. Trained nurses will collect finger-prick blood using standard techniques at 24, 28 and 32 weeks of gestation. Repeated measures are planned at specific gestational ages because a U-shaped curve of mean Hb concentrations by stage of pregnancy has been described . Hb will be measured from a drop of blood using a portable HEMOCUE B-hemoglobin photometer (HemoCue®, Angelholm, Sweden). Trained field workers will also use structured questionnaires to collect information on side effects during visits 2-7. The structured questionnaires are developed from PUQE for information on nausea and vomiting, and from previous studies which collected information on GI symptoms and stool colour, consistency and frequency. Other side effects including hospitalization, adverse events and deaths will also be collected. All forms will be pre-tested and finalized.