Stopping Postpartum Vitamin A Supplementation: Missing Concealed Benefit

Stopping Postpartum Vitamin A Supplementation: Are we Missing Concealed Benefit?

The purpose of this study is to evaluate the effect of post-partum maternal vitamin A supplementation on breast milk bioactive compounds and immune status, growth and morbidity of children in the first four months of life.

Study Overview

• Status: Completed
• Conditions: Vitamin A Deficiency
• Intervention / Treatment: Dietary supplement: Vitamin A (<3-day postpartum); Dietary supplement: Vitamin A (6 wk postpartum); Dietary supplement: Vitamin A (<3-day and 6 wk postpartum); Dietary supplement: Placebo

Detailed Description

The effect will be assessed by the milk and blood.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh, 1212
    • International Centre for Diarrhoeal Disease Research, Bangladesh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 32 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Pregnant women >-18 years of age with low-risk obstetric

Exclusion Criteria:

• Pregnant women expecting a multiple birth
• Take vitamin A supplements during postpartum apart from study intervention
• Premature birth
• Newborn babies with birth defects and / or other serious diseases

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early postpartum vitamin A suppl.; Single dose 200,000 IU vitamin A supplementation at <3-day and placebo supplementation at 6-wk postpartum.	Dietary supplement: Vitamin A (<3-day postpartum); Single dose 200,000 IU vitamin A supplementation at <3-day and placebo supplementation at 6-wk postpartum.
Experimental: Late postpartum vitamin A suppl.; Placebo supplementation at <3-day and single dose 200,000 IU vitamin A supplementation at 6-wk postpartum.	Dietary supplement: Vitamin A (6 wk postpartum); Placebo supplementation at <3-day and single dose 200,000 IU vitamin A supplementation at 6-wk postpartum.
Experimental: Early & late postpartum vitamin A suppl; 200,000 IU vitamin A supplementation, both at <3-day and 6-wk postpartum	Dietary supplement: Vitamin A (<3-day and 6 wk postpartum); 200,000 IU vitamin A supplementation, both at <3-day and 6-wk postpartum
Experimental: No postpartum vitamin A suppl.; Placebo supplementation, both at <3-day and 6-wk postpartum.	Dietary supplement: Placebo; Placebo supplementation, both at <3-day and 6-wk postpartum.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breast milk immune regulators	immune regulators in breast milk e.g. B-cell activating factor (BAFF); IL-7; Lactoferrin; sCD14, sIgA and TGF-beta levels at three time points-; < 3-day postpartum (before 1st dose of supplementation); 7 wk postpartum (1wk after 2nd dose of supplementation); 15 wk postpartum	Four months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant T helper cell immune responses	Mitogen stimulated whole blood IL-10, IL-13, IFN-gamma, IL-21 and IL-17 responses at two time points-; 7 wk of age (1wk after 2nd dose of maternal supplementation , as well as, 1wk after first doses of pentavalent vaccination); 15 wk of age (1wk after three doses of pentavalent vaccination)	Four months
Infant innate immune responses	Tall like receptor (TLR)-4 and TLR9 agonist stimulated whole blood TNF-alpha and IL-10 and IFN-alpha responses at two time points-; 7 wk of age (1wk after 2nd dose of maternal supplementation , as well as, 1wk after first doses of pentavalent vaccination); 15 wk of age (1wk after three doses of pentavalent vaccination)	Four months
Infant vaccines (Hepatitis B, Tetanus and Oral polio) specific antibody responses	Hepatitis B and Tetanus Toxoid specific plasma cell IgG responses at 15 wk of age (1wk after three doses of pentavalent vaccination) And Hepatitis B and Tetanus Toxoid specific IgG in plasma and Polio (3 serotypes) specific secretory IgA (sIgA) in stool at two time points-; 7 wk of age (1wk after 2nd dose of maternal supplementation , as well as, 1wk after first doses of pentavalent vaccination); 15 wk of age (1wk after three doses of pentavalent vaccination)	Four months
Relative abundance of infant gut microbial community and gut inflammatory markers	Next generation sequencing (NGS) of bacterial 16s rDNA (+qPCR) in extracted stool samples and assessment of infant gut inflammatory markers e.g. human β-defensin-2 (HBD2); Neopterin; α-1-antitrypsin (AAT); neutrophil gelatinase-associated lipocalin (NGAL)-2 and S100A at two time points-; 7 wk of age (1wk after 2nd dose of maternal supplementation , as well as, 1wk after first doses of pentavalent vaccination); 15 wk of age (1wk after three doses of pentavalent vaccination)	Four months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infant vitamin A status	Infant plasma vitamin A status at 7 wk and 15 wk of age	Four months
Infant growth	Infant Weight-for-Age z-score (WAZ) at 7 wk and 15 wk of age	Four months
Infant morbidity	Infant morbidity status up to four months of age	Four months
Mother vitamin A status	Plasma Retinol Binding Protein (RBP) and breast milk vitamin A level at two time points-; < 3-day postpartum (before 1st dose of supplementation); 15 wk postpartum	Four months

Collaborators and Investigators

• Sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
• Collaborators: Karolinska University Hospital; Peter Bergman, MD, PhD
• Investigators: Principal Investigator: Shaikh M Ahmad, Ph.D, International Centre for Diarrhoeal Disease Research, Bangladesh

Publications and helpful links

General Publications

• Ahmad SM, Hossain MI, Bergman P, Kabir Y, Raqib R. The effect of postpartum vitamin A supplementation on breast milk immune regulators and infant immune functions: study protocol of a randomized, controlled trial. Trials. 2015 Mar 31;16:129. doi: 10.1186/s13063-015-0654-9.

Study record dates

Study Major Dates

• Study Start: October 1, 2013
• Primary Completion (Actual): July 1, 2016

Study Registration Dates

• First Submitted: December 5, 2013
• First Submitted That Met QC Criteria: January 19, 2014
• First Posted (Estimate): January 23, 2014

Study Record Updates

• Last Update Posted (Estimate): September 21, 2016
• Last Update Submitted That Met QC Criteria: September 20, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Vitamin A; Breast milk; Postpartum vitamin A supplementation; Infant vaccine response
• Additional Relevant MeSH Terms: Eye Diseases; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Vision Disorders; Night Blindness; Vitamin A Deficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Antioxidants; Anticarcinogenic Agents; Vitamins; Vitamin A; Retinol palmitate
• Other Study ID Numbers: PR-13060