Supplementing Maternal and Infant Diet With High-energy, Micronutrient Fortified Lipid-based Nutrient Supplements (LNS) (iLiNS-DYAD-M)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
University of Malawi College of Medicine
University of California, Davis
Bill and Melinda Gates Foundation
Information provided by (Responsible Party):
Per Ashorn, University of Tampere
ClinicalTrials.gov Identifier:
NCT01239693
First received: November 10, 2010
Last updated: February 2, 2014
Last verified: February 2014
  Purpose

The use of lipid-based nutrients (LNS), such as Nutributter or fortified spread (FS), have been associated with improved growth and development outcomes among infants in Ghana and Malawi. Modified versions of such supplements have been developed to improve their nutrient density and quality and to lower their costs. Such modified products have proven acceptable to pregnant women in Malawi and Ghana. In the present trial, the investigators aim to test the effect of LNS on pregnancy and child outcomes, when given during pregnant and lactating women and their infants from 6 to 18 months of age. In control groups, participants will receive either iron+folate tables during pregnancy only or multiple micronutrient tablets during pregnancy and first six months of lactations. The main hypothesis to be tested suggests that the mean length-for-age Z-score (LAZ) of 18-month-old infants who received LNS between 6 and 18 months of age and whose mothers were provided with LNS during pregnancy and the first 6 months of lactation is higher than the mean LAZ score of same age infants who received no dietary supplements and whose mothers received iron-folate supplementation during pregnancy only.


Condition Intervention Phase
Infant Malnutrition
Malnutrition in Pregnancy
Dietary Supplement: IFA
Dietary Supplement: MMN
Dietary Supplement: LNS
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Research Plan for a Randomised, Single-blind, Parallel Group Controlled Trial in Rural Malawi, Testing the Health Effects of Supplementing Maternal Diet During Pregnancy and Lactation and Infant Diet From 6 to 18 Months of Age With High-energy, Micronutrient Fortified Lipid-based Nutrient Supplements (LNS)

Resource links provided by NLM:


Further study details as provided by University of Tampere:

Primary Outcome Measures:
  • Birth weight [ Time Frame: approx 20 weeks after enrollment (within 48 hours) ] [ Designated as safety issue: No ]
  • Newborn length [ Time Frame: At 1 week of age ] [ Designated as safety issue: No ]
  • Length for age Z-score (LAZ) at 18 months of age [ Time Frame: 12 months after enrollment (age 18 months) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Anthropometric status (weight, BMI, mid upper arm circumference and triceps and sub-scapular skin-fold thickness) [ Time Frame: at ~ 36 wk gestation and 6 months postpartum ] [ Designated as safety issue: No ]
  • Gestational age at delivery, proportion of preterm deliveries [ Time Frame: At delivery ] [ Designated as safety issue: No ]
  • Proportion of low birth weight babies [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Anaemia and iron status (Hb, ZPP, transferrin receptor), other micronutrient status (vitamin A, B-vitamins, zinc), malarial antigen [ Time Frame: At ~ 36 wk gestation and 6 mo postpartum ] [ Designated as safety issue: No ]
  • Red blood cell essential fatty acid status [ Time Frame: At ~ 36 wk gestation ] [ Designated as safety issue: No ]
  • Urinary iodine [ Time Frame: At ~ 36 wk gestation ] [ Designated as safety issue: No ]
  • Total plasma cholesterol concentration [ Time Frame: At ~ 36 wk gestation ] [ Designated as safety issue: No ]
  • Basal salivary cortisol concentration [ Time Frame: At ~ 28 and ~ 36 wk gestation ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: At 36 wk gestation ] [ Designated as safety issue: No ]
  • Breast milk composition (essential fatty acids, vitamin A, B-vitamins) [ Time Frame: At 6 mo postpartum ] [ Designated as safety issue: No ]
  • Depressive symptoms (which may be related to essential fatty acid status) [ Time Frame: At 4 weeks and at 6 months postpartum ] [ Designated as safety issue: No ]
  • Incidence of febrile malaria episodes [ Time Frame: During pregnancy ] [ Designated as safety issue: No ]
  • Peripheral blood malaria parasitaemia [ Time Frame: At 32 wk gestation and at delivery ] [ Designated as safety issue: No ]
  • Placental malaria histology [ Time Frame: At delivery ] [ Designated as safety issue: No ]
  • Evidence of defined bacteria in the chorionic membranes at delivery (quantitative DNA amplification method) [ Time Frame: At birth ] [ Designated as safety issue: No ]
  • Prevalence of Neisseria gonorrhoea, Chlamydia trachomatis, in swab samples taken from maternal uterine cervix(qualitative DNA amplification method) [ Time Frame: At one week after delivery ] [ Designated as safety issue: No ]
  • Prevalence of bacterial vaginosis, Trichomonas vaginalis, or candidiasis, in swab samples taken from maternal vagina(direct microscopy) [ Time Frame: At one week after delivery ] [ Designated as safety issue: No ]
  • Malaria immunity [ Time Frame: At enrolment, at ~ 36 wk gestation, and 6 months post-partum ] [ Designated as safety issue: No ]
  • Anthropometric infant status (weight, length, head circumference and mid upper arm circumference) [ Time Frame: At 7 days of age and at 6, 12 and 18 months of age. After the intervention at 24 and 30 months of age. ] [ Designated as safety issue: No ]
  • Infant anaemia and iron status (Hb, ZPP), micronutrient (vitamin A, B-vitamins) and essential fatty acids status, evidence of acute inflammation (CRP, AGP), and malarial antigen and microscopy [ Time Frame: At 6 and 18 months of age ] [ Designated as safety issue: No ]
  • Incidence of neonatal hospitalizations [ Time Frame: At or before age 28 days ] [ Designated as safety issue: No ]
  • Clinical morbidity [ Time Frame: Between 0 and 18 months of age ] [ Designated as safety issue: No ]
  • Child feeding practices and maternal report of child sleep patterns [ Time Frame: At 6, 12 and 18 months of age ] [ Designated as safety issue: No ]
  • Antibody response to measles vaccination [ Time Frame: At 18 months of age ] [ Designated as safety issue: No ]
  • Malaria immunity [ Time Frame: At 6 and 18 months of age ] [ Designated as safety issue: No ]
  • Basal salivary cortisol concentration [ Time Frame: At 6, 12 and 18 months of age ] [ Designated as safety issue: No ]
  • Cortisol response to acute stress [ Time Frame: At 6 and 18 months of age ] [ Designated as safety issue: No ]
  • Achievement of five motor milestones and four other developmental milestones [ Time Frame: From 0 to 18 mo ] [ Designated as safety issue: No ]
  • Neurobehavioral development [ Time Frame: At 18 months of age ] [ Designated as safety issue: No ]
  • Incidence of serious adverse events [ Time Frame: During pregnancy and 18 months of infant follow-up ] [ Designated as safety issue: Yes ]
  • Prevalence of maternal periodontitis [ Time Frame: At one week after delivery ] [ Designated as safety issue: No ]
  • Maternal cognition [ Time Frame: 6 months after delivery ] [ Designated as safety issue: No ]
    Measured with several different tests

  • Mother - child interaction [ Time Frame: 6 months after delivery ] [ Designated as safety issue: No ]
    Measured with a number of observational tests and questionnaires

  • The composition of intestinal microbiota [ Time Frame: 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, and 30 months of child age ] [ Designated as safety issue: No ]
    Done with 16s sequencing, from stored stool samples


Enrollment: 1391
Study Start Date: February 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: IFA group
Women during pregnancy: 1 tablet of iron+ folate daily until delivery (60 mg iron + 400 ug folic acid) Women during lactation (from delivery to 6 months post-partum): 1 daily tablet of calcium (200 mg), akin to placebo Children from 6 to 18 months of age: None
Dietary Supplement: IFA
Women during pregnancy: 1 tablet of iron+ folate daily until delivery (60 mg iron + 400 ug folic acid) Women during lactation (from delivery to 6 months post-partum): 1 daily tablet of calcium (200 mg), akin to placebo Children from 6 to 18 months of age: None
Active Comparator: MMN group
Women during pregnancy: 1 tablet of multiple micronutrients daily until delivery Women during lactation (from delivery to 6 months post-partum): 1 daily tablet of multiple micronutrients' Children from 6 to 18 months of age: None
Dietary Supplement: MMN
Women during pregnancy: 1 tablet of multiple micronutrients daily until delivery Women during lactation (from delivery to 6 months post-partum): 1 daily tablet of multiple micronutrients Children from 6 to 18 months of age: None
Experimental: LNS group
Women during pregnancy: 1 sachet of LNS-P&L (20 g of LNS) daily until delivery Women during lactation (from delivery to 6 months post-partum): 1 daily sachet of LNS-P&L (20 g of LNS) Children from 6 to 18 months of age: 2 daily sachet of LNS-20gM (20 g of LNS)
Dietary Supplement: LNS
Women during pregnancy: 1 sachet of LNS-P&L (20 g of LNS) daily until delivery Women during lactation (from delivery to 6 months post-partum): 1 daily sachet of LNS-P&L (20 g of LNS) Children from 6 to 18 months of age: 2 daily sachet of LNS-20gM (20 g of LNS)

Detailed Description:

Pregnant women will be identified from the antenatal clinics of 4 governmental and 2 other health centres. A total of 1400 women meeting set criteria will be randomised into receiving one of the following interventions: 1) Iron and folic acid supplementation to the mother during pregnancy only (IFA group), 2). Multiple micronutrient supplementation to the mother during pregnancy and six months thereafter (MMN group), 3) Lipid-based nutrient supplements to the mother during pregnancy and six months thereafter and to the child from 6 to 18 months of age (LNS group).

The mothers will receive LNS or the multiple micronutrients at 2-weekly intervals at their homes during pregnancy and weekly during first six months of lactation. Children in the LNS group will receive LNS weekly, starting at 6 months. Mothers will be medically examined and tested for defined laboratory parameters at enrolment, at 36 gestation weeks, at birth or soon thereafter, and at 6 months after delivery. Child size will be assessed at birth or soon thereafter and at 3, 6, 12, and 18 months of age. The mothers will undergo a morbidity evaluation fortnightly and the children weekly.

864 mother-infant pairs will undergo the complete intervention and follow-up, as described above. The remaining 536 participants will undergo a simplified intervention and follow-up, in which there are no interventions after birth and the child follow-up consists only of 4 3 health centre and one home visits; first at 1 week, then at six weeks (at home) and at 6 and 18 months of age.

A stubstudy on the the development of intestinal microbiome was added in August 2011. This entails the collection of stool samples from the mother at 1 month after delivery, breast milk samples from the mothers at 1, 3, and 6 months after delivery and stool and urine samples from the children repeated during the a8 months of intervention. The aim of this subproject is to study the development of the infants' intestinal microbiota, its predictors and its association to child growth and other health outcomes. At the same time point, the sample size was reduced from 2400 to 1400 particpants (due to constraints in funding).

A one year post-intervention follow-up for participants in the complete follow-up was added to the study protocoll in August 2013. The intervention will be stopped when the particpants are 18 months old. Thereafter, there will be an anthropometirc assessment and blood and urine draw at the study clinic at 24 and 30 months of age. Stool samples will be collected from the participants at the age of 21, 24, 27 and 30 months, to study the development of intestinal microbiome.

  Eligibility

Ages Eligible for Study:   15 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Ultrasound confirmed pregnancy of no more than 20 completed gestation weeks
  • Permanent resident of Mangochi District Hospital, Malindi Hospital or Lungwena Health Centre catchment areas
  • Availability during the period of the study
  • Signed informed consent

Exclusion Criteria:

  • Less than 15 years of age
  • Need for frequent medical attention due to a chronic health condition
  • Diagnosed asthma treated with regular medication
  • Severe illness warranting hospital referral
  • History of allergy towards peanuts
  • History of anaphylaxis or serious allergic reaction to any substance, requiring emergency medical care
  • Pregnancy complications evident at enrolment visit (moderate to severe oedema, blood Hb concentration < 5 g / dl, systolic blood pressure (BP) > 160 mmHg or diastolic BP > 100 mmHg)
  • Earlier participation in the iLiNS-DYAD-M trial
  • Concurrent participation in any other clinical trial
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01239693

Locations
Malawi
University of Malawi, College of Medicine
Mangochi, Malawi
Sponsors and Collaborators
University of Tampere
University of Malawi College of Medicine
University of California, Davis
Bill and Melinda Gates Foundation
Investigators
Principal Investigator: Per Ashorn, MD, PhD University of Tampere Medical School
  More Information

Additional Information:
No publications provided

Responsible Party: Per Ashorn, Professor of International Health, University of Tampere
ClinicalTrials.gov Identifier: NCT01239693     History of Changes
Other Study ID Numbers: iLiNS-DYAD-M
Study First Received: November 10, 2010
Last Updated: February 2, 2014
Health Authority: Malawi: College of Medicine Research and Ethics Committee

Keywords provided by University of Tampere:
Newborn
Stunting
Growth failure
Malnutrition
Lipid based nutrient supplement
LNS
Prevention
Malawi
Sub-Saharan Africa
Dietary supplementation
Efficacy
Pregnancy
Infancy

Additional relevant MeSH terms:
Malnutrition
Nutrition Disorders
Micronutrients
Trace Elements
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014