Egg Intervention During Pregnancy in Indonesia

Child Development Clinical Trial

— PRECODE  

Official title:

Effect on Pregnancy Outcomes, Infant Growth and Development of an Egg Intervention During Pregnancy in Indonesia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04694235
• Other study ID #: AASH Egg intervention
• Status: Recruiting
• Phase: N/A
• Start date: February 12, 2021
• Est. completion date: March 2024

Study information

• Verified date: March 2021
• Source: SEAMEO Regional Centre for Food and Nutrition
• Contact: Arienta RP Sudibya, M.Sc
• Phone: +628118113811
• Email: arientasudibya[@]seameo-recfon.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 653
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amino Acid Deficiency
• Anemia, Iron Deficiency
• Anemia, Iron-Deficiency
• B12 Deficiency Vitamin
• Birth Length
• Birth Weight
• Body Weight
• Child Development
• Communicable Diseases
• Dysentery, Bacillary
• E. Coli Infection
• Escherichia coli Infections
• Fatty Acid Deficiency
• Folate Deficiency
• Folic Acid Deficiency
• Infection
• Mineral Deficiency
• Night Blindness
• Parasite Infestation
• Protozoan Infections
• Salmonella Infections
• Shigella Infection
• Vitamin A Deficiency
• Vitamin B 12 Deficiency
• Weight Gain
• Zinc Deficiency

Intervention

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.

Locations

Country	Name	City	State
Indonesia	Aikmel, Sakra, and Sikur Subdistrict	Mataram	West Nusa Tenggara

Sponsors (17)

Lead Sponsor

Collaborator

SEAMEO Regional Centre for Food and Nutrition

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

Country where clinical trial is conducted

Indonesia, 

References & Publications (19)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Prevalence of stunting	Z-score of LAZ <-2 SD based on WHO 2006	birth until 24 months after delivery
Primary	Proportion of children 10-14 months with impaired fine and gross motor skills	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess fine and gross motor skills among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired expressive and receptive language	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess expressive and receptive language among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired behavior	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess behavior among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired executive function	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess executive function among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired empathy	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess empathy among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired problem solving	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess problem solving among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired attention	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess attention among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 10-14 months with impaired social-emotional reactivity	Oxford Neurodevelopment Assessment (OX-NDA) is used to assess social-emotional reactivity among children aged 10 to 14 months	10-14 months of age
Primary	Proportion of children 20-24 months with impaired motor development	INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess motor development among children aged 20 to 24 months	20-24 months of age
Primary	Proportion of children 20-24 months with impaired cognition	INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess cognition among children aged 20 to 24 months	20-24 months of age
Primary	Proportion of children 20-24 months with impaired language	INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess language among children aged 20 to 24 months	20-24 months of age
Primary	Proportion of children 20-24 months with impaired social-emotional development	INTERGROWTH Neurodevelopment Assessment (INTER-NDA) is used to assess social-emotional development among children aged 20 to 24 months	20-24 months of age
Primary	Scores of CDI vocabulary comprehension scale in children 10-12 months	MacArthur-Bates Communicative Development Inventories (CDI) is used to assess vocabulary comprehension scale among children aged 10 to 12 months	10-12 months of age
Primary	Scores of CDI vocabulary production scale in children 10-12 months	MacArthur-Bates Communicative Development Inventories (CDI) is used to assess vocabulary production among children aged 10 to 12 months	10-12 months of age
Primary	Epigenetic state of genes associated with stunting	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.	parents: 72 h after delivery; baby: 72 h after delivery, 24 month
Primary	Epigenetic markers of birth anthropometry, adult stature, metabolic state, and cognitive ability	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.	parents: 72 h after delivery; baby: 72 h after delivery, 24 month
Secondary	Weight gain during pregnancy	All measurements will be taken to the nearest 0.1 kg using standard procedures with SECA weighing machine.	2nd trimester (16-20 weeks gestation) and 3rd trimester (28-32 weeks gestation) of pregnancy
Secondary	Birth weight	All measurements will be taken to the nearest 0.1 kg using standard procedures with SECA weighing machine.	24 hours after birth
Secondary	Birth length	All measurements will be taken to the nearest milimeter using standard procedures with SECA stadiometer/infantometer.	24 hours after birth
Secondary	Hemoglobin concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their hemoglobin.	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum ferritin concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum ferritin	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum transferrin receptor concentration	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	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum zinc concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum zinc	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum retinol concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum retinol	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	RBC folate concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their RBC folate	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum vitamin B12 concentration	Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B12	Mothers: second and third trimester of pregnancy
Secondary	RBC fatty acids concentration	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	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum essential amino acids concentration	Nutritional status measured by biochemical assessment to the mothers for their serum essential amino acids	Mothers: second and third trimester of pregnancy
Secondary	Serum methylmalonic acid concentration	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	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum choline concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum choline	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum betaine concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum betaine	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum vitamin B2 concentration	Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B2	Mothers: second and third trimester of pregnancy
Secondary	Serum vitamin B6 concentration	Nutritional status measured by biochemical assessment to the mothers for their serum vitamin B6	Mothers: second and third trimester of pregnancy
Secondary	Serum vitamin D concentration	Nutritional status measured by biochemical assessment to the mothers for their serum vitamin D	Mothers: second and third trimester of pregnancy
Secondary	Serum CRP concentration	Subclinical inflammation will be measured by serum CRP in pregnant mothers and children	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum AGP concentration	Subclinical inflammation will be measured by serum AGP in pregnant mothers and children	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum RBP concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum RBP	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum hepcidine concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum hepcidine	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum homocysteine concentration	Nutritional status measured by biochemical assessment to the mothers and children. Both the pregnant mothers and children will be measured for their serum homocysteine	Mothers: second and third trimester of pregnancy; children: 6 months (+/- 2 weeks) after delivery; breastmilk: 3 and 6 months (+/- 2 weeks) after delivery
Secondary	Serum HbA1C concentration	Gestational diabetes status will be assesed to the mothers for their serum HbA1C	Mothers: second and third trimester of pregnancy
Secondary	Fecal myeloperoxidase (MPO)	Gut inflammation from fecal will be measured by faecal myeloperoxidase (MPO) using ELISA	baby: 1, 6, 24 months of age
Secondary	Fecal a1-antitrypsin (AAT)	Gut inflammation from fecal will be measured by fecal a1-antitrypsin (AAT) using ELISA	baby: 1, 6, 24 months of age
Secondary	Soil-transmitted helminths infection	Fecal parasites from fecal will be assesed by Kato Katz and confirmed by qPCR	mothers: 3rd trimester (28-32 gestational weeks) of pregnancy; baby: 1, 6, 24 months of age
Secondary	Bacteria infection	Type of bacteria (Salmonella, Shigella) from fecal will be assesed by culture method	baby: 1, 6, 24 months of age
Secondary	Gut microbiota	Gut microbiota species (EPEC, ETEC, EHEC, EIEC) from fecal will be assesed using qPCR	baby: 1, 6, 24 months of age
Secondary	Gut microbiome	Faecal microbiome would be analyzed using 16S RNA sequencing of the V4 region on the Illumina MiSeq and BSAS.	baby: 1, 6, 24 months of age
Secondary	Intestinal fatty acid binding protein	Intestinal fatty acid binding protein from serum will be measured using ELISA	baby: 6 months of age