Prevention of Linear Growth Failure in Infants and Young Children With Lipid-based Nutrient Supplements (iLiNS-DOSE) (iLiNS-DOSE)

Prevention of Linear Growth Failure in Infants and Young Children With Lipid-based Nutrient Supplements (iLiNS-DOSE)

A Two-centre, Randomised, Single-blind, Parallel Group Controlled Trial, Testing the Growth Promoting Effect of Long-term Complementary Feeding of Infants With Different Doses and Formulations of Lipid-based Nutrient Supplements (LNS)

Kamuzu University of Health Sciences, University of California, Davis, Bill and Melinda Gates Foundation

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 infants and their guardians in Malawi and Ghana. In the present trial, the investigator aim to identify the lowest growth-promoting daily dose of modified LNS. Additionally, the investigators will test a hypothesis that LNS that does not contain milk promotes growth as well as milk-containing LNS when given for 12 months at a 10-40 g daily dose to 6-18 month old infants in rural Malawi.

Six-month old healthy infants are identified through community surveys in the study area. 1920 infants meeting set criteria are randomised into receiving the following intervention between 6 and 18 months of age: 1) standard treatment from 6-18 months (i.e.no supplements, with delayed intervention between 18-30 months of age (ST-DI), 2) 10 g / day milk-containing LNS (LNS-10gM), 3) 20 g / day milk-containing LNS (LNS-20gM), 4) 20 g / day milk-free LNS (LNS-20gNoM), 5) 40 g / day milk-containing LNS, (LNS-40gM) 6) 40 g / day milk-free LNS (LNS-40gNoM). The families receive the food supplements at 2-weekly intervals and the participants undergo a morbidity evaluation weekly, a limited development assessment at 4-weekly intervals and anthropometric evaluation at 26-week intervals and laboratory analyses at enrollment and at 18 months. Growth outcome analyses are done at 18 and at 42 months of age.

Stunting, Growth failure, Malnutrition, Lipid based nutrient supplement, LNS, Prevention, Malawi, Sub-Saharan Africa, Dietary supplementation, Efficacy

1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

140 g of milk-containing LNS (LNS-10gM) 2-weekly (10 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

280 g of milk-containing LNS (LNS-20gM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

280 g of milk-free LNS (LNS-20gNoM) 2-weekly (20 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

560 g of milk-containing LNS (LNS-40gM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

560 g of milk-free LNS (LNS-40gNoM) 2-weekly (40 g / day) between 6 and 18 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

No food supplement during the primary trial period (6 to 18 months of age) 1 kg fortified maize / soy flour (Likuni phala, LP) 2-weekly (71 g / day) between 18 and 30 months of age Normal under-five clinic follow-up, including EPI-vaccinations, vitamin A supplementation, and growth monitoring

Change in length-for-age Z-score (LAZ, based on WHO 2005 MGRS) between enrollment and 18 months of age

Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)

Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)

Primarily 12 months after enrollment (age 18 months), secondarily 36 months after enrollment (age 42 months)

Change in hemoglobin and micronutrient status (iron status, measured by zinc protoporphyrin (ZPP); plasma zinc; plasma vitamin A; B-vitamins and related metabolites; urine iodine

Change in erythrocyte essential fatty acid (EFA) concentration (measured from a subsample of 400 participants)

Neuro-behavioral development (timing of acquisition of the certain skills and more comprehensive analysis at the age of 18 months)

Limited assessment every 4 weeks during the 12 months supplementation, more comprehensive at age 18 months

Inclusion Criteria: Signed informed consent from at least one guardian Age 5.50 months to 6.49 months Availability during the period of the study. Permanent resident of Mangochi District Hospital or Namwera Health Centre catchment area Exclusion Criteria: Weight for length Z score (WLZ) < -2.0 Presence of oedema Severe anaemia (Hb<50 g / l) Severe illness warranting hospital referral History of allergy towards peanut History of anaphylaxis or serious allergic reaction to any substance, requiring emergency medical care Concurrent participation in any other clinical trial

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