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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 Die

Brief 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.

Detailed Summary:

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
Sponsor: University of Tampere

Current Primary Outcome:

  • 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) ]


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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 ]
    Measured with several different tests
  • Mother - child interaction [ Time Frame: 6 months after delivery ]
    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 ]
    Done with 16s sequencing, from stored stool samples


Original Secondary Outcome:

  • 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 6 mo 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 ]
  • 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 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 ]


Information By: University of Tampere

Dates:
Date Received: November 10, 2010
Date Started: February 2011
Date Completion:
Last Updated: May 11, 2016
Last Verified: May 2016