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

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:

• child growth using standard anthropometric measures,
• cardiometabolic health by measuring body composition, blood pressure and plasma lipids,
• neurodevelopment by measuring neural function, cognitive skills and education attainment using EE and EGMA and Raven's questionnaires,
• lung function with spirometry and allergy symptoms and asthma using ISAAC questionnaire.

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