PRECODE: Egg Intervention During Pregnancy in Indonesia

• Sponsor: SEAMEO Regional Centre for Food and Nutrition (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04694235
• Collaborator: London School of Hygiene and Tropical Medicine (Other), University of Aberdeen (Other), University of Brighton (Other), University College, London (Other), Royal Veterinary College (Other), Birkbeck, University of London (Other), The International Livestock Research Institute (ILRI) (Other), Cheikh Anta Diop University, Senegal (Other), National Institute of Nutrition, India (Other), International Centre for Research in Agroforestry (Other), Science Made Simple (Other), Liverpool School of Tropical Medicine (Other), International Initiative for Impact Evaluation (Other), Digital Green Foundation (Other), SOAS, University of London (Other), University of Sheffield (Other)
• Enrollment: 653
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 36.6
• Patients Per Site Per Month: 17.9

Study Details

Study Description

Brief Summary

The study consists of two arms: 1) intervention group using eggs as supplementary food given from 2nd trimester of pregnancy to birth, and 2) observational group of pregnant mothers. it aims to assess the effectiveness of improving dietary quality during pregnancy on the epigenetic and stunting related outcomes (growth and development) in infants, who will be followed up until 24 months old

Condition or Disease	Intervention/Treatment	Phase
Weight Gain; Anemia, Iron Deficiency; Birth Weight; Birth Length; Child Development; Zinc Deficiency; Folate Deficiency; B12 Deficiency Vitamin; Amino Acid Deficiency; Mineral Deficiency; Vitamin A Deficiency; Fatty Acid Deficiency; Parasite Infestation; E. Coli Infection; Salmonella Infections; Shigella Infection; Protozoan Infections	Dietary Supplement: Egg intervention	N/A

Detailed Description

The study aims to assess the impact of improving dietary quality during pregnancy on the epigenetic and stunting related outcomes in infants. The open-label intervention study would be conducted alongside the observational study in the same study setting by recruitment of additional number (n=153) of pregnant women. Thus, a total of 653 pregnant women would be enrolled in the study; 153 women would be randomized to intervention arm and 500 to the control arm who would form an observational cohort of women and newborns as described above. The intervention group women will be provided one egg three times per week from recruitment (2nd trimester) until term. The control group women will receive standard intervention in the form of Ante Natal Care from village midwives or Public Health Centre (IFA tablet, calcium tablet, nutrition counselling).

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 653 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: A total of 653 pregnant women will be recruited from 40 villages in three sub-districts. Pregnant women will be randomly allocated into the intervention or control groups. Pregnant women in the intervention group will receive boiled eggs three times per week from 2nd trimester (16-20 weeks) until delivery.A total of 653 pregnant women will be recruited from 40 villages in three sub-districts. Pregnant women will be randomly allocated into the intervention or control groups. Pregnant women in the intervention group will receive boiled eggs three times per week from 2nd trimester (16-20 weeks) until delivery.
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Effect on Pregnancy Outcomes, Infant Growth and Development of an Egg Intervention During Pregnancy in Indonesia
• Actual Study Start Date: Feb 12, 2021
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: Observational cohort (control group) In the observational cohort, pregnant mothers in the 2nd trimester (n=500) will be recruited and they will be followed up until their children are 24 months old. The control group women will receive standard intervention in the form of Ante Natal Care from village midwives (Polindes) or Puskesmas (IFA tablet, calcium tablet, nutrition counselling).
Experimental: Intervention group The intervention group women (n=153) will be provided one egg three times per week from recruitment (2nd trimester) until term along with the standard Ante Natal Care.	Dietary Supplement: Egg intervention; Eggs are boiled until the white and yolk are firm (ca. 8 minutes) to maintain quality and safety and ensure the eggs are safe for consumption.

Outcome Measures

Primary Outcome Measures

1. Prevalence of stunting [birth until 24 months after delivery]

   Z-score of LAZ <-2 SD based on WHO 2006

2. Proportion of children 10-14 months with impaired fine and gross motor skills [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess fine and gross motor skills among children aged 10 to 14 months

3. Proportion of children 10-14 months with impaired expressive and receptive language [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess expressive and receptive language among children aged 10 to 14 months

4. Proportion of children 10-14 months with impaired behavior [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess behavior among children aged 10 to 14 months

5. Proportion of children 10-14 months with impaired executive function [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess executive function among children aged 10 to 14 months

6. Proportion of children 10-14 months with impaired empathy [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess empathy among children aged 10 to 14 months

7. Proportion of children 10-14 months with impaired problem solving [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess problem solving among children aged 10 to 14 months

8. Proportion of children 10-14 months with impaired attention [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess attention among children aged 10 to 14 months

9. Proportion of children 10-14 months with impaired social-emotional reactivity [10-14 months of age]

   Oxford Neurodevelopment Assessment (OX-NDA) is used to assess social-emotional reactivity among children aged 10 to 14 months

10. Proportion of children 20-24 months with impaired motor development [20-24 months of age]

    INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess motor development among children aged 20 to 24 months

11. Proportion of children 20-24 months with impaired cognition [20-24 months of age]

    INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess cognition among children aged 20 to 24 months

12. Proportion of children 20-24 months with impaired language [20-24 months of age]

    INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess language among children aged 20 to 24 months

13. Proportion of children 20-24 months with impaired social-emotional development [20-24 months of age]

    INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess social-emotional development among children aged 20 to 24 months

14. Scores of CDI vocabulary comprehension scale in children 10-12 months [10-12 months of age]

    MacArthur-Bates Communicative Development Inventories (CDI) is used to assess vocabulary comprehension scale among children aged 10 to 12 months

15. Scores of CDI vocabulary production scale in children 10-12 months [10-12 months of age]

    MacArthur-Bates Communicative Development Inventories (CDI) is used to assess vocabulary production among children aged 10 to 12 months

16. Epigenetic state of genes associated with stunting [parents: 72 h after delivery; baby: 72 h after delivery, 24 month]

    Genome-wide analysis of epigenetic states using the Illumina Infinium Methylation EPIC 850k Bead Chip (EPIC array) will be performed for selected samples from the core cohort. The outcomes will be the epigenetic state of a large number of genes which are associated with child stunting.

17. Epigenetic markers of birth anthropometry, adult stature, metabolic state, and cognitive ability [parents: 72 h after delivery; baby: 72 h after delivery, 24 month]

    All samples (newborn, children 24 mo, parents) will be analyzed using Next Generation Bisulphite Amplicon Sequencing (BSAS) from Illumina MiSeq platform in targeted regions of the genome. The outcomes will be profiles of specific epigenetic markers of birth anthropometry, adult stature, metabolic state, and cognitive ability.

Secondary Outcome Measures

1. Weight gain during pregnancy [2nd trimester (16-20 weeks gestation) and 3rd trimester (28-32 weeks gestation) of pregnancy]

   All measurements will be taken to the nearest 0.1 kg using standard procedures with SECA weighing machine.

2. Birth weight [24 hours after birth]

   All measurements will be taken to the nearest 0.1 kg using standard procedures with SECA weighing machine.

3. Birth length [24 hours after birth]

   All measurements will be taken to the nearest milimeter using standard procedures with SECA stadiometer/infantometer.

4. Hemoglobin concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their hemoglobin.

5. Serum ferritin concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum ferritin

6. Serum transferrin receptor concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum transferrin receptor

7. Serum zinc concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum zinc

8. Serum retinol concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum retinol

9. RBC folate concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

   Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their RBC folate

10. Serum vitamin B12 concentration [Mothers: second and third trimester of pregnancy]

    Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B12

11. RBC fatty acids concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their RBC fatty acids

12. Serum essential amino acids concentration [Mothers: second and third trimester of pregnancy]

    Nutritional status measured by biochemical assessment to the mothers for their serum essential amino acids

13. Serum methylmalonic acid concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum methylmalonic acid

14. Serum choline concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum choline

15. Serum betaine concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum betaine

16. Serum vitamin B2 concentration [Mothers: second and third trimester of pregnancy]

    Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B2

17. Serum vitamin B6 concentration [Mothers: second and third trimester of pregnancy]

    Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B6

18. Serum vitamin D concentration [Mothers: second and third trimester of pregnancy]

    Nutritional status measured by biochemical assessment to the mothers for their serum vitamin D

19. Serum CRP concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Subclinical inflammation will be measured by serum CRP in pregnant mothers and children

20. Serum AGP concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Subclinical inflammation will be measured by serum AGP in pregnant mothers and children

21. Serum RBP concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum RBP

22. Serum hepcidine concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum hepcidine

23. Serum homocysteine concentration [Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery]

    Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum homocysteine

24. Serum HbA1C concentration [Mothers: second and third trimester of pregnancy]

    Gestational diabetes status will be assesed to the mothers for their serum HbA1C

25. Fecal myeloperoxidase (MPO) [baby: 1, 6, 24 months of age]

    Gut inflammation from fecal will be measured by faecal myeloperoxidase (MPO) using ELISA

26. Fecal α1-antitrypsin (AAT) [baby: 1, 6, 24 months of age]

    Gut inflammation from fecal will be measured by fecal α1-antitrypsin (AAT) using ELISA

27. Soil-transmitted helminths infection [mothers: 3rd trimester (28-32 gestational weeks) of pregnancy; baby: 1, 6, 24 months of age]

    Fecal parasites from fecal will be assesed by Kato Katz and confirmed by qPCR

28. Bacteria infection [baby: 1, 6, 24 months of age]

    Type of bacteria (Salmonella, Shigella) from fecal will be assesed by culture method

29. Gut microbiota [baby: 1, 6, 24 months of age]

    Gut microbiota species (EPEC, ETEC, EHEC, EIEC) from fecal will be assesed using qPCR

30. Gut microbiome [baby: 1, 6, 24 months of age]

    Faecal microbiome would be analyzed using 16S RNA sequencing of the V4 region on the Illumina MiSeq and BSAS.

31. Intestinal fatty acid binding protein [baby: 6 months of age]

    Intestinal fatty acid binding protein from serum will be measured using ELISA

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Woman is between 16 and 20 weeks of pregnancy based on the date of the first day of her last menstrual period.

• She is 18-40 years of age.

• She is planning to remain in the study area over the next 30 months.

• She is of Sasak ethnicity

Exclusion Criteria:

• She is expecting multiple births.

• She has a known egg allergy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aikmel, Sakra, and Sikur Subdistrict	Mataram	West Nusa Tenggara	Indonesia

Sponsors and Collaborators

• SEAMEO Regional Centre for Food and Nutrition
• London School of Hygiene and Tropical Medicine
• University of Aberdeen
• University of Brighton
• University College, London
• Royal Veterinary College
• Birkbeck, University of London
• The International Livestock Research Institute (ILRI)
• Cheikh Anta Diop University, Senegal
• National Institute of Nutrition, India
• International Centre for Research in Agroforestry
• Science Made Simple
• Liverpool School of Tropical Medicine
• International Initiative for Impact Evaluation
• Digital Green Foundation
• SOAS, University of London
• University of Sheffield

Investigators

• Principal Investigator: Umi Fahmida, Dr., SEAMEO RECFON

Study Documents (Full-Text)

None provided.

More Information

Publications

• Boeke CE, Gillman MW, Hughes MD, Rifas-Shiman SL, Villamor E, Oken E. Choline intake during pregnancy and child cognition at age 7 years. Am J Epidemiol. 2013 Jun 15;177(12):1338-47. doi: 10.1093/aje/kws395. Epub 2013 Feb 20.
• Caudill MA, Strupp BJ, Muscalu L, Nevins JEH, Canfield RL. Maternal choline supplementation during the third trimester of pregnancy improves infant information processing speed: a randomized, double-blind, controlled feeding study. FASEB J. 2018 Apr;32(4):2172-2180. doi: 10.1096/fj.201700692RR. Epub 2018 Jan 5.
• Cho E, Zeisel SH, Jacques P, Selhub J, Dougherty L, Colditz GA, Willett WC. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr. 2006 Apr;83(4):905-11.
• Clare CE, Brassington AH, Kwong WY, Sinclair KD. One-Carbon Metabolism: Linking Nutritional Biochemistry to Epigenetic Programming of Long-Term Development. Annu Rev Anim Biosci. 2019 Feb 15;7:263-287. doi: 10.1146/annurev-animal-020518-115206. Epub 2018 Nov 9. Review.
• Dighe MK, Frederick IO, Andersen HF, Gravett MG, Abbott SE, Carter AA, Algren H, Rocco DA, Waller SA, Sorensen TK, Enquobahrie D, Blakey I, Knight HE, Cheikh Ismail L; International Fetal and Newborn Growth Consortium for the 21st Century. Implementation of the INTERGROWTH-21st Project in the United States. BJOG. 2013 Sep;120 Suppl 2:123-8, v. doi: 10.1111/1471-0528.12126. Epub 2013 Jul 11.
• Fenson L, Pethick S, Renda C, Cox JL, Dale PS, Reznick JS. Short-form versions of the MacArthur communicative development inventories. Applied Psycholinguistics. 2000;21(1):95-116.
• Haggarty P, Hoad G, Campbell DM, Horgan GW, Piyathilake C, McNeill G. Folate in pregnancy and imprinted gene and repeat element methylation in the offspring. Am J Clin Nutr. 2013 Jan;97(1):94-9. doi: 10.3945/ajcn.112.042572. Epub 2012 Nov 14.
• Haggarty P. Epigenetic consequences of a changing human diet. Proc Nutr Soc. 2013 Nov;72(4):363-71. doi: 10.1017/S0029665113003376. Epub 2013 Sep 13.
• Jacobson SW, Carter RC, Molteno CD, Stanton ME, Herbert JS, Lindinger NM, Lewis CE, Dodge NC, Hoyme HE, Zeisel SH, Meintjes EM, Duggan CP, Jacobson JL. Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Alcohol Clin Exp Res. 2018 Jul;42(7):1327-1341. doi: 10.1111/acer.13769. Epub 2018 Jun 15.
• Lorgen-Ritchie M, Murray AD, Ferguson-Smith AC, Richards M, Horgan GW, Phillips LH, Hoad G, Gall I, Harrison K, McNeill G, Ito M, Haggarty P. Imprinting methylation in SNRPN and MEST1 in adult blood predicts cognitive ability. PLoS One. 2019 Feb 1;14(2):e0211799. doi: 10.1371/journal.pone.0211799. eCollection 2019. Erratum in: PLoS One. 2019 Apr 10;14(4):e0215422.
• Lutter CK, Iannotti LL, Stewart CP. Cracking the egg potential during pregnancy and lactation. Sight Life. 2016;30:75-81.
• Masser DR, Stanford DR, Freeman WM. Targeted DNA methylation analysis by next-generation sequencing. J Vis Exp. 2015 Feb 24;(96). doi: 10.3791/52488.
• Mhila G, DeRenzi B, Mushi C, Wakabi T, Steele M, Dhaldialla P, et al. Using mobile applications for community-based social support for chronic patients. Health Informatics in Africa. 2009.
• Patterson KY, Bhagwat SA, Williams JR, Howe JC, Holden J, Zeisel S, et al. USDA database for the choline content of common foods, release two. Nutrient Data Laboratory, Beltsville Human Nutrition Research Center, ARS, USDA. 2008.
• Sethi V, Tiwari K, Sareen N, Singh S, Mishra C, Jagadeeshwar M, Sunitha K, Kumar SV, de Wagt A, Sachdev HPS. Delivering an Integrated Package of Maternal Nutrition Services in Andhra Pradesh and Telangana (India). Food Nutr Bull. 2019 Sep;40(3):393-408. doi: 10.1177/0379572119844142. Epub 2019 Jun 16.
• Weisenberger D, Van Den Berg D, Pan F, Berman B, Laird P. Comprehensive DNA methylation analysis on the Illumina Infinium assay platform. Illumina, San Diego. 2008.
• Whitelaw N, Bhattacharya S, Hoad G, Horgan GW, Hamilton M, Haggarty P. Epigenetic status in the offspring of spontaneous and assisted conception. Hum Reprod. 2014 Jul;29(7):1452-8. Epub 2014 May 8.
• Yan J, Jiang X, West AA, Perry CA, Malysheva OV, Devapatla S, Pressman E, Vermeylen F, Stabler SP, Allen RH, Caudill MA. Maternal choline intake modulates maternal and fetal biomarkers of choline metabolism in humans. Am J Clin Nutr. 2012 May;95(5):1060-71. doi: 10.3945/ajcn.111.022772. Epub 2012 Mar 14.
• Zeisel SH, Mar MH, Howe JC, Holden JM. Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003 May;133(5):1302-7. Erratum in: J Nutr. 2003 Sep;133(9):2918.

• Responsible Party: Dr.Umi Fahmida, Senior Researcher, SEAMEO Regional Centre for Food and Nutrition
• ClinicalTrials.gov Identifier: NCT04694235
• Other Study ID Numbers: AASH Egg intervention
• First Posted: Jan 5, 2021
• Last Update Posted: Mar 19, 2021
• Last Verified: Mar 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Dr.Umi Fahmida, Senior Researcher, SEAMEO Regional Centre for Food and Nutrition: Egg; Pregnancy; Indonesia; Epigenetic; Growth; Child development
• Additional relevant MeSH terms: Infections; Communicable Diseases; Dysentery, Bacillary; Protozoan Infections; Salmonella Infections; Escherichia coli Infections; Night Blindness; Anemia, Iron-Deficiency; Vitamin A Deficiency; Folic Acid Deficiency; Vitamin B 12 Deficiency; Body Weight; Birth Weight; Weight Gain

Study Results

No Results Posted as of Mar 19, 2021