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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
1,391
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
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
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)
University of Malawi, College of Medicine
Mangochi, Malawi
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)
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 and at 10 y 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
Measured with several different tests
Time frame: 6 months after delivery
Mother - child interaction
Measured with a number of observational tests and questionnaires
Time frame: 6 months after delivery
The composition of intestinal microbiota
Done with 16s sequencing, from stored stool samples
Time frame: 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, and 30 months of child age
diastolic blood pressure
Mobil-o-Graph blood pressure monitoring system
Time frame: Child is 10 years
central blood pressure
Mobil-o-Graph blood pressure monitoring system
Time frame: Child is 10 years
pulse rate
Mobil-o-Graph blood pressure monitoring system
Time frame: Child is 10 years
vascular resistance
Mobil-o-Graph blood pressure monitoring system
Time frame: Child is 10 years
plasma concentration of glucose
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of cholesterol
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of HDL/LDL cholesterol
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of triglycerides
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of c-reactive protein
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of alkaline phosphatase
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of aspartyl alanine transferase
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of potassium
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of sodium
Cobas c702 machine
Time frame: Child is 10 years
plasma concentration of urate
Cobas c702 machine
Time frame: Child is 10 years
Spirometry measures functional volume of the lungs
Global Lung Function Initiative standards, Medikro pro spirometry
Time frame: Child is 10 years
asthma symptoms
ISAAC questionnaire
Time frame: Child is 10 years
allergy symptoms
ISAAC questionnaire
Time frame: Child is 10 years
neural functioning
EEG
Time frame: Child is 10 years
processing speed
EEG
Time frame: Child is 10 years
oculomotor reaction time
eye-tracking
Time frame: Child is 10 years
academic achievement
Early Grade Mathematics Assessment, EGMA
Time frame: Child is 10 years
height
Time frame: Child is 10 years
sitting height
Time frame: Child is 10 years
weight
Time frame: Child is 10 years
head circumference
Time frame: Child is 10 years
mid-upper arm circumference
Time frame: Child is 10 years
body composition
Tanita MC-780 MAS
Time frame: Child is 10 years
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