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

NCT01239693 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: iLiNS-DYAD-M
• Study Type: interventional
• Target: 1,391
• Locations: 1 country
• Sites: 1

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. 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.

Conditions

Infant Malnutrition; Malnutrition in Pregnancy

Keywords

Stunting; Growth failure; Malnutrition; Lipid based nutrient supplement; LNS; Prevention; Malawi; Sub-Saharan Africa; Dietary supplementation; Efficacy; Pregnancy; Infancy; Newborn; Child neurocognitive development; Cardiometabolic health; Lung function

Outcome Measures

Primary Outcomes (3)

• Birth weight

  approx 20 weeks after enrollment (within 48 hours)

• Newborn length

  At 1 week of age

• Length for age Z-score (LAZ) at 18 months of age

  12 months after enrollment (age 18 months)

Secondary Outcomes (61)

• Anthropometric status (weight, BMI, mid upper arm circumference and triceps and sub-scapular skin-fold thickness)

  at ~ 36 wk gestation and 6 months postpartum

• Gestational age at delivery, proportion of preterm deliveries

  At delivery

• Proportion of low birth weight babies

  At birth

• Anaemia and iron status (Hb, ZPP, transferrin receptor), other micronutrient status (vitamin A, B-vitamins, zinc), malarial antigen

  At ~ 36 wk gestation and 6 mo postpartum

• Red blood cell essential fatty acid status

  At ~ 36 wk gestation

Study Arms (3)

IFA group

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

Dietary Supplement: IFA

MMN group

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

Dietary Supplement: MMN

LNS group

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)

Dietary Supplement: LNS

Interventions

IFA DIETARY_SUPPLEMENT

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 group

MMN DIETARY_SUPPLEMENT

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 group

LNS DIETARY_SUPPLEMENT

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 group

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tampere University: lead
• Kamuzu University of Health Sciences: collaborator
• University of California, Davis: collaborator
• Bill and Melinda Gates Foundation: collaborator
• Finnish Institute for Health and Welfare: collaborator
• University of Oulu: collaborator

Study Sites (1)

University of Malawi, College of Medicine

Mangochi, Malawi

Location

Related Publications (30)

• Adu-Afarwuah S, Arnold CD, Lartey A, Okronipa H, Maleta K, Ashorn P, Ashorn U, Dewey KG. Prevalence of morbidity symptoms among pregnant and postpartum women receiving different nutrient supplements in Ghana and Malawi: A secondary outcome analysis of two randomised controlled trials. Matern Child Nutr. 2023 Jul;19(3):e13501. doi: 10.1111/mcn.13501. Epub 2023 Apr 6.

  PMID: 37021807 DERIVED

• Liu Z, Fan YM, Ashorn P, Chingwanda C, Maleta K, Hallamaa L, Hyoty H, Chaima D, Ashorn U. Lack of Associations between Environmental Exposures and Environmental Enteric Dysfunction among 18-Month-Old Children in Rural Malawi. Int J Environ Res Public Health. 2022 Sep 1;19(17):10891. doi: 10.3390/ijerph191710891.

  PMID: 36078607 DERIVED

• Salenius M, Pyykko J, Ashorn U, Dewey KG, Gondwe A, Harjunmaa U, Maleta K, Nkhoma M, Vosti SA, Ashorn P, Adubra L. Association between prenatal provision of lipid-based nutrient supplements and caesarean delivery: Findings from a randomised controlled trial in Malawi. Matern Child Nutr. 2022 Oct;18(4):e13414. doi: 10.1111/mcn.13414. Epub 2022 Jul 31.

  PMID: 35909334 DERIVED

• Haskell MJ, Maleta K, Arnold CD, Jorgensen JM, Fan YM, Ashorn U, Matchado A, Monangi NK, Zhang G, Xu H, Belling E, Landero J, Chappell J, Muglia LJ, Hallman M, Ashorn P, Dewey KG. Provision of Small-Quantity Lipid-Based Nutrient Supplements Increases Plasma Selenium Concentration in Pregnant Women in Malawi: A Secondary Outcome of a Randomized Controlled Trial. Curr Dev Nutr. 2022 Mar 7;6(3):nzac013. doi: 10.1093/cdn/nzac013. eCollection 2022 Mar.

  PMID: 35317414 DERIVED

• Smith JW, Matchado AJ, Wu LS, Arnold CD, Burke SM, Maleta KM, Ashorn P, Stewart CP, Shaikh S, Ali H, Labrique AB, West KP Jr, Christian P, Dewey KG, Groopman JD, Schulze KJ. Longitudinal Assessment of Prenatal, Perinatal, and Early-Life Aflatoxin B1 Exposure in 828 Mother-Child Dyads from Bangladesh and Malawi. Curr Dev Nutr. 2022 Jan 7;6(2):nzab153. doi: 10.1093/cdn/nzab153. eCollection 2022 Feb.

  PMID: 35155983 DERIVED

• Kortekangas E, Fan YM, Chaima D, Lehto KM, Malamba-Banda C, Matchado A, Chingwanda C, Liu Z, Ashorn U, Cheung YB, Dewey KG, Maleta K, Ashorn P. Associations between Gut Microbiota and Intestinal Inflammation, Permeability and Damage in Young Malawian Children. J Trop Pediatr. 2022 Feb 3;68(2):fmac012. doi: 10.1093/tropej/fmac012.

  PMID: 35149871 DERIVED

• Adu-Afarwuah S, Arnold CD, Lartey A, Okronipa H, Maleta K, Ashorn P, Ashorn U, Fan YM, Matchado A, Kortekangas E, Oaks BM, Jackson KH, Dewey KG. Small-Quantity Lipid-Based Nutrient Supplements Increase Infants' Plasma Essential Fatty Acid Levels in Ghana and Malawi: A Secondary Outcome Analysis of the iLiNS-DYAD Randomized Trials. J Nutr. 2022 Jan 11;152(1):286-301. doi: 10.1093/jn/nxab329.

  PMID: 34543432 DERIVED

• Jorgensen JM, Young R, Ashorn P, Ashorn U, Chaima D, Davis JCC, Goonatilleke E, Kumwenda C, Lebrilla CB, Maleta K, Sadalaki J, Totten SM, Wu LD, Zivkovic AM, Dewey KG. Associations of Human Milk Oligosaccharides and Bioactive Proteins with Infant Morbidity and Inflammation in Malawian Mother-Infant Dyads. Curr Dev Nutr. 2021 Apr 29;5(5):nzab072. doi: 10.1093/cdn/nzab072. eCollection 2021 May.

  PMID: 34084993 DERIVED

• Jorgensen JM, Young R, Ashorn P, Ashorn U, Chaima D, Davis JCC, Goonatilleke E, Kumwenda C, Lebrilla CB, Maleta K, Prado EL, Sadalaki J, Totten SM, Wu LD, Zivkovic AM, Dewey KG. Associations of human milk oligosaccharides and bioactive proteins with infant growth and development among Malawian mother-infant dyads. Am J Clin Nutr. 2021 Jan 4;113(1):209-220. doi: 10.1093/ajcn/nqaa272.

  PMID: 33096556 DERIVED

• Adu-Afarwuah S, Arnold CD, Maleta K, Ashorn P, Ashorn U, Jorgensen JM, Fan YM, Nkhoma M, Bendabenda J, Matchado A, Dewey KG. Consumption of multiple micronutrients or small-quantity lipid-based nutrient supplements containing iodine at the recommended dose during pregnancy, compared with iron and folic acid, does not affect women's urinary iodine concentration in rural Malawi: a secondary outcome analysis of the iLiNS DYAD trial. Public Health Nutr. 2021 Jul;24(10):3049-3057. doi: 10.1017/S1368980020003250. Epub 2020 Oct 15.

  PMID: 33054890 DERIVED

• Kamng'ona AW, Young R, Arnold CD, Patson N, Jorgensen JM, Kortekangas E, Chaima D, Malamba C, Ashorn U, Cheung YB, Ashorn P, Maleta K, Dewey KG. Provision of Lipid-Based Nutrient Supplements to Mothers During Pregnancy and 6 Months Postpartum and to Their Infants from 6 to 18 Months Promotes Infant Gut Microbiota Diversity at 18 Months of Age but Not Microbiota Maturation in a Rural Malawian Setting: Secondary Outcomes of a Randomized Trial. J Nutr. 2020 Apr 1;150(4):918-928. doi: 10.1093/jn/nxz298.

  PMID: 31909811 DERIVED

• Kortekangas E, Young R, Cheung YB, Fan YM, Jorgensen JM, Kamng'ona AW, Chaima D, Ashorn U, Dewey KG, Maleta K, Ashorn P. A Prospective Study on Child Morbidity and Gut Microbiota in Rural Malawi. J Pediatr Gastroenterol Nutr. 2019 Oct;69(4):431-437. doi: 10.1097/MPG.0000000000002435.

  PMID: 31436705 DERIVED

• Bendabenda J, Patson N, Hallamaa L, Ashorn U, Dewey KG, Ashorn P, Maleta K. Does anthropometric status at 6 months predict the over-dispersion of malaria infections in children aged 6-18 months? A prospective cohort study. Malar J. 2019 Apr 22;18(1):143. doi: 10.1186/s12936-019-2778-y.

  PMID: 31010435 DERIVED

• Barua P, Beeson JG, Maleta K, Ashorn P, Rogerson SJ. The impact of early life exposure to Plasmodium falciparum on the development of naturally acquired immunity to malaria in young Malawian children. Malar J. 2019 Jan 18;18(1):11. doi: 10.1186/s12936-019-2647-8.

  PMID: 30658632 DERIVED

• Oaks BM, Jorgensen JM, Baldiviez LM, Adu-Afarwuah S, Maleta K, Okronipa H, Sadalaki J, Lartey A, Ashorn P, Ashorn U, Vosti S, Allen LH, Dewey KG. Prenatal Iron Deficiency and Replete Iron Status Are Associated with Adverse Birth Outcomes, but Associations Differ in Ghana and Malawi. J Nutr. 2019 Mar 1;149(3):513-521. doi: 10.1093/jn/nxy278.

  PMID: 30629202 DERIVED

• Bendabenda J, Patson N, Hallamaa L, Mbotwa J, Mangani C, Phuka J, Prado EL, Cheung YB, Ashorn U, Dewey KG, Ashorn P, Maleta K. The association of malaria morbidity with linear growth, hemoglobin, iron status, and development in young Malawian children: a prospective cohort study. BMC Pediatr. 2018 Dec 28;18(1):396. doi: 10.1186/s12887-018-1378-2.

  PMID: 30593271 DERIVED

• Barua P, Chandrasiri UP, Beeson JG, Dewey KG, Maleta K, Ashorn P, Rogerson SJ. Effect of nutrient supplementation on the acquisition of humoral immunity to Plasmodium falciparum in young Malawian children. Malar J. 2018 Feb 7;17(1):74. doi: 10.1186/s12936-018-2224-6.

  PMID: 29415730 DERIVED

• Doyle R, Gondwe A, Fan YM, Maleta K, Ashorn P, Klein N, Harris K. A Lactobacillus-Deficient Vaginal Microbiota Dominates Postpartum Women in Rural Malawi. Appl Environ Microbiol. 2018 Mar 1;84(6):e02150-17. doi: 10.1128/AEM.02150-17. Print 2018 Mar 15.

  PMID: 29305501 DERIVED

• Adams KP, Ayifah E, Phiri TE, Mridha MK, Adu-Afarwuah S, Arimond M, Arnold CD, Cummins J, Hussain S, Kumwenda C, Matias SL, Ashorn U, Lartey A, Maleta KM, Vosti SA, Dewey KG. Maternal and Child Supplementation with Lipid-Based Nutrient Supplements, but Not Child Supplementation Alone, Decreases Self-Reported Household Food Insecurity in Some Settings. J Nutr. 2017 Dec;147(12):2309-2318. doi: 10.3945/jn.117.257386. Epub 2017 Oct 4.

  PMID: 28978680 DERIVED

• Jorgensen JM, Arnold C, Ashorn P, Ashorn U, Chaima D, Cheung YB, Davis JC, Fan YM, Goonatilleke E, Kortekangas E, Kumwenda C, Lebrilla CB, Maleta K, Totten SM, Wu LD, Dewey KG. Lipid-Based Nutrient Supplements During Pregnancy and Lactation Did Not Affect Human Milk Oligosaccharides and Bioactive Proteins in a Randomized Trial. J Nutr. 2017 Oct 1;147(10):1867-1874. doi: 10.3945/jn.117.252981.

  PMID: 28794206 DERIVED

• Oaks BM, Young RR, Adu-Afarwuah S, Ashorn U, Jackson KH, Lartey A, Maleta K, Okronipa H, Sadalaki J, Baldiviez LM, Shahab-Ferdows S, Ashorn P, Dewey KG. Effects of a lipid-based nutrient supplement during pregnancy and lactation on maternal plasma fatty acid status and lipid profile: Results of two randomized controlled trials. Prostaglandins Leukot Essent Fatty Acids. 2017 Feb;117:28-35. doi: 10.1016/j.plefa.2017.01.007. Epub 2017 Jan 25.

  PMID: 28237085 DERIVED

• Nkhoma M, Ashorn P, Ashorn U, Dewey KG, Gondwe A, Mbotwa J, Rogerson S, Taylor SM, Maleta K. Providing lipid-based nutrient supplement during pregnancy does not reduce the risk of maternal P falciparum parasitaemia and reproductive tract infections: a randomised controlled trial. BMC Pregnancy Childbirth. 2017 Jan 17;17(1):35. doi: 10.1186/s12884-016-1215-2.

  PMID: 28095801 DERIVED

• Chandrasiri UP, Fowkes FJ, Beeson JG, Richards JS, Kamiza S, Maleta K, Ashorn P, Rogerson SJ. Association between malaria immunity and pregnancy outcomes among Malawian pregnant women receiving nutrient supplementation. Malar J. 2016 Nov 9;15(1):547. doi: 10.1186/s12936-016-1597-7.

  PMID: 27829430 DERIVED

• Klevor MK, Adu-Afarwuah S, Ashorn P, Arimond M, Dewey KG, Lartey A, Maleta K, Phiri N, Pyykko J, Zeilani M, Ashorn U. A mixed method study exploring adherence to and acceptability of small quantity lipid-based nutrient supplements (SQ-LNS) among pregnant and lactating women in Ghana and Malawi. BMC Pregnancy Childbirth. 2016 Aug 30;16(1):253. doi: 10.1186/s12884-016-1039-0.

  PMID: 27577112 DERIVED

• Prado EL, Abbeddou S, Adu-Afarwuah S, Arimond M, Ashorn P, Ashorn U, Brown KH, Hess SY, Lartey A, Maleta K, Ocansey E, Ouedraogo JB, Phuka J, Some JW, Vosti SA, Yakes Jimenez E, Dewey KG. Linear Growth and Child Development in Burkina Faso, Ghana, and Malawi. Pediatrics. 2016 Aug;138(2):e20154698. doi: 10.1542/peds.2015-4698.

  PMID: 27474016 DERIVED

• Prado EL, Maleta K, Ashorn P, Ashorn U, Vosti SA, Sadalaki J, Dewey KG. Effects of maternal and child lipid-based nutrient supplements on infant development: a randomized trial in Malawi. Am J Clin Nutr. 2016 Mar;103(3):784-93. doi: 10.3945/ajcn.115.114579. Epub 2016 Feb 3.

  PMID: 26843155 DERIVED

• Stewart CP, Oaks BM, Laugero KD, Ashorn U, Harjunmaa U, Kumwenda C, Chaima D, Maleta K, Ashorn P, Dewey KG. Maternal cortisol and stress are associated with birth outcomes, but are not affected by lipid-based nutrient supplements during pregnancy: an analysis of data from a randomized controlled trial in rural Malawi. BMC Pregnancy Childbirth. 2015 Dec 22;15:346. doi: 10.1186/s12884-015-0793-8.

  PMID: 26694646 DERIVED

• Chandrasiri UP, Fowkes FJ, Richards JS, Langer C, Fan YM, Taylor SM, Beeson JG, Dewey KG, Maleta K, Ashorn P, Rogerson SJ. The impact of lipid-based nutrient supplementation on anti-malarial antibodies in pregnant women in a randomized controlled trial. Malar J. 2015 May 10;14:193. doi: 10.1186/s12936-015-0707-2.

  PMID: 25957793 DERIVED

• Ashorn P, Alho L, Ashorn U, Cheung YB, Dewey KG, Gondwe A, Harjunmaa U, Lartey A, Phiri N, Phiri TE, Vosti SA, Zeilani M, Maleta K. Supplementation of Maternal Diets during Pregnancy and for 6 Months Postpartum and Infant Diets Thereafter with Small-Quantity Lipid-Based Nutrient Supplements Does Not Promote Child Growth by 18 Months of Age in Rural Malawi: A Randomized Controlled Trial. J Nutr. 2015 Jun;145(6):1345-53. doi: 10.3945/jn.114.207225. Epub 2015 Apr 29.

  PMID: 25926413 DERIVED

• Ashorn P, Alho L, Ashorn U, Cheung YB, Dewey KG, Harjunmaa U, Lartey A, Nkhoma M, Phiri N, Phuka J, Vosti SA, Zeilani M, Maleta K. The impact of lipid-based nutrient supplement provision to pregnant women on newborn size in rural Malawi: a randomized controlled trial. Am J Clin Nutr. 2015 Feb;101(2):387-97. doi: 10.3945/ajcn.114.088617. Epub 2014 Dec 10.

  PMID: 25646337 DERIVED

Related Links

• College of Medicine homepage
• Publication on the primary birth outcome results
• Publication on the primary child growth outcome results

MeSH Terms

Conditions

Infant Nutrition Disorders; Growth Disorders; Failure to Thrive; Malnutrition

Condition Hierarchy (Ancestors)

Nutrition Disorders; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Per Ashorn, MD, PhD

  University of Tampere Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Paediatrics

Study Record Dates

• First Submitted: November 10, 2010
• First Posted: November 11, 2010
• Study Start: February 1, 2011
• Primary Completion: April 1, 2015
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 28, 2025

Record last verified: 2025-03

Locations

MA (1)