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

Infant Malnutrition Clinical Trial

— iLiNS-DYAD-M  

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01239693
• Other study ID #: iLiNS-DYAD-M
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: February 2011
• Est. completion date: March 31, 2025

Study information

• Verified date: November 2023
• Source: Tampere University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

To detect the long-term effect of the LNS supplementation, we now propose to conduct a follow-up study when the children are 9 years old, to see if the intervention had effect on children's growth, cardiometabolic and respiratory status and neurocognitive development.

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 sub-study 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 participants (due to constraints in funding).

A one year post-intervention follow-up for participants in the complete follow-up was added to the study protocol in August 2013. The intervention will be stopped when the participants are 18 months old. Thereafter, there will be an anthropometrirc 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.

In a follow-up study, when the children are 10 years old, we will assess:

1. child growth using standard anthropometric measures,

2. cardiometabolic health by measuring body composition, blood pressure and plasma lipids,

3. neurodevelopment by measuring neural function, cognitive skills and education attainment using EE and EGMA and Raven's questionnaires,

4. lung function with spirometry and allergy symptoms and asthma using ISAAC questionnaire.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1391
• Est. completion date: March 31, 2025
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Infant Malnutrition
• Infant Nutrition Disorders
• Malnutrition
• Malnutrition in Pregnancy

Intervention

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
• 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
• 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)

Locations

Country	Name	City	State
Malawi	University of Malawi, College of Medicine	Mangochi

Sponsors (6)

Lead Sponsor	Collaborator
Tampere University	Bill and Melinda Gates Foundation, Finnish Institute for Health and Welfare, Kamuzu University of Health Sciences, University of California, Davis, University of Oulu, Finland

Country where clinical trial is conducted

Malawi, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Birth weight		approx 20 weeks after enrollment (within 48 hours)
Primary	Newborn length		At 1 week of age
Primary	Length for age Z-score (LAZ) at 18 months of age		12 months after enrollment (age 18 months)
Secondary	Anthropometric status (weight, BMI, mid upper arm circumference and triceps and sub-scapular skin-fold thickness)		at ~ 36 wk gestation and 6 months postpartum
Secondary	Gestational age at delivery, proportion of preterm deliveries		At delivery
Secondary	Proportion of low birth weight babies		At birth
Secondary	Anaemia and iron status (Hb, ZPP, transferrin receptor), other micronutrient status (vitamin A, B-vitamins, zinc), malarial antigen		At ~ 36 wk gestation and 6 mo postpartum
Secondary	Red blood cell essential fatty acid status		At ~ 36 wk gestation
Secondary	Urinary iodine		At ~ 36 wk gestation
Secondary	Total plasma cholesterol concentration		At ~ 36 wk gestation
Secondary	Basal salivary cortisol concentration		At ~ 28 and ~ 36 wk gestation
Secondary	Blood pressure		At 36 wk gestation
Secondary	Breast milk composition (essential fatty acids, vitamin A, B-vitamins)		At 6 mo postpartum
Secondary	Depressive symptoms (which may be related to essential fatty acid status)		At 4 weeks and at 6 months postpartum
Secondary	Incidence of febrile malaria episodes		During pregnancy
Secondary	Peripheral blood malaria parasitaemia		At 32 wk gestation and at delivery
Secondary	Placental malaria histology		At delivery
Secondary	Evidence of defined bacteria in the chorionic membranes at delivery (quantitative DNA amplification method)		At birth
Secondary	Prevalence of Neisseria gonorrhoea, Chlamydia trachomatis, in swab samples taken from maternal uterine cervix(qualitative DNA amplification method)		At one week after delivery
Secondary	Prevalence of bacterial vaginosis, Trichomonas vaginalis, or candidiasis, in swab samples taken from maternal vagina(direct microscopy)		At one week after delivery
Secondary	Malaria immunity		At enrolment, at ~ 36 wk gestation, and 6 months post-partum
Secondary	Anthropometric infant status (weight, length, head circumference and mid upper arm circumference)		At 7 days of age and at 6, 12 and 18 months of age. After the intervention at 24 and 30 months and at 10 y of age.
Secondary	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		At 6 and 18 months of age
Secondary	Incidence of neonatal hospitalizations		At or before age 28 days
Secondary	Clinical morbidity		Between 0 and 18 months of age
Secondary	Child feeding practices and maternal report of child sleep patterns		At 6, 12 and 18 months of age
Secondary	Antibody response to measles vaccination		At 18 months of age
Secondary	Malaria immunity		At 6 and 18 months of age
Secondary	Basal salivary cortisol concentration		At 6, 12 and 18 months of age
Secondary	Cortisol response to acute stress		At 6 and 18 months of age
Secondary	Achievement of five motor milestones and four other developmental milestones		From 0 to 18 mo
Secondary	Neurobehavioral development		At 18 months of age
Secondary	Incidence of serious adverse events		During pregnancy and 18 months of infant follow-up
Secondary	Prevalence of maternal periodontitis		At one week after delivery
Secondary	Maternal cognition	Measured with several different tests	6 months after delivery
Secondary	Mother - child interaction	Measured with a number of observational tests and questionnaires	6 months after delivery
Secondary	The composition of intestinal microbiota	Done with 16s sequencing, from stored stool samples	1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, and 30 months of child age
Secondary	diastolic blood pressure	Mobil-o-Graph blood pressure monitoring system	Child is 10 years
Secondary	central blood pressure	Mobil-o-Graph blood pressure monitoring system	Child is 10 years
Secondary	pulse rate	Mobil-o-Graph blood pressure monitoring system	Child is 10 years
Secondary	vascular resistance	Mobil-o-Graph blood pressure monitoring system	Child is 10 years
Secondary	plasma concentration of glucose	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of cholesterol	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of HDL/LDL cholesterol	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of triglycerides	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of c-reactive protein	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of alkaline phosphatase	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of aspartyl alanine transferase	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of potassium	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of sodium	Cobas c702 machine	Child is 10 years
Secondary	plasma concentration of urate	Cobas c702 machine	Child is 10 years
Secondary	Spirometry measures functional volume of the lungs	Global Lung Function Initiative standards, Medikro pro spirometry	Child is 10 years
Secondary	asthma symptoms	ISAAC questionnaire	Child is 10 years
Secondary	allergy symptoms	ISAAC questionnaire	Child is 10 years
Secondary	neural functioning	EEG	Child is 10 years
Secondary	processing speed	EEG	Child is 10 years
Secondary	oculomotor reaction time	eye-tracking	Child is 10 years
Secondary	academic achievement	Early Grade Mathematics Assessment, EGMA	Child is 10 years
Secondary	height		Child is 10 years
Secondary	sitting height		Child is 10 years
Secondary	weight		Child is 10 years
Secondary	head circumference		Child is 10 years
Secondary	mid-upper arm circumference		Child is 10 years
Secondary	body composition	Tanita MC-780 MAS	Child is 10 years

External Links

•   Publication on the primary birth outcome results
•   Publication on the primary child growth outcome results