Overview

This trial is active, not recruiting.

Conditions infant malnutrition, malnutrition in pregnancy
Treatments ifa, mmn, lns
Phase phase 3
Sponsor University of Tampere
Collaborator University of Malawi College of Medicine
Start date February 2011
End date April 2015
Trial size 1391 participants
Trial identifier NCT01239693, iLiNS-DYAD-M

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking single blind (outcomes assessor)
Primary purpose prevention
Arm
(Active Comparator)
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
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)
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
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)
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)
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)

Primary Outcomes

Measure
Birth weight
time frame: approx 20 weeks after enrollment (within 48 hours)
Newborn length
time frame: At 1 week of age
Length for age Z-score (LAZ) at 18 months of age
time frame: 12 months after enrollment (age 18 months)

Secondary Outcomes

Measure
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
Gestational age at delivery, proportion of preterm deliveries
time frame: At delivery
Proportion of low birth weight babies
time frame: At birth
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
Red blood cell essential fatty acid status
time frame: At ~ 36 wk gestation
Urinary iodine
time frame: At ~ 36 wk gestation
Total plasma cholesterol concentration
time frame: At ~ 36 wk gestation
Basal salivary cortisol concentration
time frame: At ~ 28 and ~ 36 wk gestation
Blood pressure
time frame: At 36 wk gestation
Breast milk composition (essential fatty acids, vitamin A, B-vitamins)
time frame: At 6 mo postpartum
Depressive symptoms (which may be related to essential fatty acid status)
time frame: At 4 weeks and at 6 months postpartum
Incidence of febrile malaria episodes
time frame: During pregnancy
Peripheral blood malaria parasitaemia
time frame: At 32 wk gestation and at delivery
Placental malaria histology
time frame: At delivery
Evidence of defined bacteria in the chorionic membranes at delivery (quantitative DNA amplification method)
time frame: At birth
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
Prevalence of bacterial vaginosis, Trichomonas vaginalis, or candidiasis, in swab samples taken from maternal vagina(direct microscopy)
time frame: At one week after delivery
Malaria immunity
time frame: At enrolment, at ~ 36 wk gestation, and 6 months post-partum
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.
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
Incidence of neonatal hospitalizations
time frame: At or before age 28 days
Clinical morbidity
time frame: Between 0 and 18 months of age
Child feeding practices and maternal report of child sleep patterns
time frame: At 6, 12 and 18 months of age
Antibody response to measles vaccination
time frame: At 18 months of age
Malaria immunity
time frame: At 6 and 18 months of age
Basal salivary cortisol concentration
time frame: At 6, 12 and 18 months of age
Cortisol response to acute stress
time frame: At 6 and 18 months of age
Achievement of five motor milestones and four other developmental milestones
time frame: From 0 to 18 mo
Neurobehavioral development
time frame: At 18 months of age
Incidence of serious adverse events
time frame: During pregnancy and 18 months of infant follow-up
Prevalence of maternal periodontitis
time frame: At one week after delivery
Maternal cognition
time frame: 6 months after delivery
Mother - child interaction
time frame: 6 months after delivery
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

Eligibility Criteria

Male or female participants at least 15 years old.

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

Additional Information

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)
Principal investigator Per Ashorn, MD, PhD
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2015.
Information provided to ClinicalTrials.gov by University of Tampere.