Prenatal Iron and Malaria Study (PIMAL)

A Randomised Trial to Assess the Safety and Efficacy or Iron Supplementation in Kenyan Pregnant Women

The purpose of this study is to compare the presence of Plasmodium infection in parturient women who antenatally received a combination of iron-fortified foods with iron supplements versus iron-fortified foods only.

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Dietary supplement: iron

Detailed Description

As per recommendations by the World Health Organization (WHO), iron supplementation in children should be restricted in malaria-endemic areas because of concerns that it can lead to an increased burden of malaria. Universal iron supplementation continues to be recommended, however, for women during pregnancy and 3 months postpartum. Observational studies have shown that iron deficiency in parturient women is associated with a marked reduction in the prevalence and density of malarial parasites in the placenta. Plasmodium infections in pregnant women have devastating effects on the foetus and neonate, causing low birth weight, intrauterine growth retardation, preterm delivery, spontaneous abortion, stillbirth and neonatal mortality. Based on our previous work, the Kenyan government is currently drafting legislation for mandatory iron fortification of industrially milled flour. Implementation of the new fortification policy means that pregnant women will receive iron through a combination of fortified foods and supplementation. The investigators are concerned about the safety of the high iron intake resulting from such a policy.

• Study Type: Interventional
• Enrollment (Actual): 470
• Phase: Phase 4

Contacts and Locations

Study Locations

• Kenya
  • Nairobi, Kenya
    • University of Nairobi

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women aged 15-45 years resident in the predefined study area
• Pregnant, with gestational age <23 weeks

Exclusion Criteria:

• Failure to provide a blood sample
• Initial haemoglobin concentration <90 g/L
• Reported medical history suggestive of sickle cell anaemia, epilepsy, diabetes
• Obstetric history suggestive of eclampsia or pre-eclampsia
• Obvious mental retardation or metabolic disorder;
• No written consent
• Carrying multiples
• Woman planning to leave the homestead or to be absent for prolonged periods in the course of the pregnancy or within a 1-month period thereafter
• Woman planning to deliver outside the research clinic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Dietary supplement: iron; Daily supplementation with iron (60 mg) as ferrous sulphate
Experimental: Supplemental iron	Dietary supplement: iron; Daily supplementation with iron (60 mg) as ferrous sulphate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal Plasmodium infection	Assessed by LDH- and HRP2-based dipstick test and PCR	Parturition

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum non-transferrin bound iron concentration		3 h after ingestion of first supplement with either iron or placebo
Neonatal iron stores	Assessed by plasma ferritin concentration, restricted to infants without inflammation	At 1 month of age
Maternal iron status	To be assessed by haemoglobin concentrations, prevalence of iron deficiency anaemia (plasma ferritin concentration <12 µg/L) and iron stores (ratio of ferritin:transferrin receptor concentrations); indicators based on ferritin and/or transferrin receptor will be restricted to those without inflammation.	At 1 month after delivery
Maternal intestinal pathogens		At 1 month after delivery

Collaborators and Investigators

• Sponsor: London School of Hygiene and Tropical Medicine
• Collaborators: University of Nairobi; Wageningen University
• Investigators: Principal Investigator: Hans Verhoef, PhD, London School of Hygiene and Tropical Medicine

Publications and helpful links

General Publications

• Mwangi MN, Roth JM, Smit MR, Trijsburg L, Mwangi AM, Demir AY, Wielders JP, Mens PF, Verweij JJ, Cox SE, Prentice AM, Brouwer ID, Savelkoul HF, Andang'o PE, Verhoef H. Effect of Daily Antenatal Iron Supplementation on Plasmodium Infection in Kenyan Women: A Randomized Clinical Trial. JAMA. 2015 Sep 8;314(10):1009-20. doi: 10.1001/jama.2015.9496.
• Mwangi MN, Maskey S, Andang o PE, Shinali NK, Roth JM, Trijsburg L, Mwangi AM, Zuilhof H, van Lagen B, Savelkoul HF, Demir AY, Verhoef H. Diagnostic utility of zinc protoporphyrin to detect iron deficiency in Kenyan pregnant women. BMC Med. 2014 Nov 26;12:229. doi: 10.1186/s12916-014-0229-8.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: March 2, 2011
• First Submitted That Met QC Criteria: March 2, 2011
• First Posted (Estimate): March 3, 2011

Study Record Updates

• Last Update Posted (Estimate): May 29, 2013
• Last Update Submitted That Met QC Criteria: May 28, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: Pregnancy; Malaria; Iron; Kenya; Plasmodium
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria
• Other Study ID Numbers: LSHTM-5664