Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study
Introduction Maternal undernutrition and infections during pregnancy may influence birth and long-term child development outcomes. Characterising the micronutrient, metabolomic and microbiome profiles of pregnant women and infants may elucidate the underlying biology of adverse birth outcomes and ea...
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BMJ Publishing Group
2025-04-01
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| author | Alemayehu Worku Yemane Berhane Parul Christian Estifanos Baye Krysten North Mulatu Melese Derebe Nebiyou Fasil Kalkidan Yibeltal Fred Van Dyk Firehiwot Workneh Sarah K G Jensen Unmesha Roy Paladhi Sophie Driker Theresa I Chin Anne C Lee |
| author_facet | Alemayehu Worku Yemane Berhane Parul Christian Estifanos Baye Krysten North Mulatu Melese Derebe Nebiyou Fasil Kalkidan Yibeltal Fred Van Dyk Firehiwot Workneh Sarah K G Jensen Unmesha Roy Paladhi Sophie Driker Theresa I Chin Anne C Lee |
| author_sort | Alemayehu Worku |
| collection | DOAJ |
| description | Introduction Maternal undernutrition and infections during pregnancy may influence birth and long-term child development outcomes. Characterising the micronutrient, metabolomic and microbiome profiles of pregnant women and infants may elucidate the underlying biology of adverse birth outcomes and early child development in the first 1000 days.Methods and analysis The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study was a 2×2 factorial, randomised clinical effectiveness study conducted in Amhara, Ethiopia from August 2020 to June 2022. We cluster-randomised pregnant women (n=2399) to receive either a nutrition intervention (iron-folic acid (IFA), iodised salt and balanced energy-protein supplementation for women with mid-upper arm circumference <23 cm) or routine care (IFA only), and individually randomised women to an infection control intervention (genitourinary tract infection screening-treatment and screening-treatment of stool parasites) or routine care (syndromic approach). Participants were followed until 1 month postpartum. A subset of 532 women-infant dyads were consecutively enrolled in the biospecimen substudy from July 2021 to August 2022. Specimens were collected at enrolment (<24 weeks) and antenatal care follow-up (third trimester), and 1–6 months postdelivery. A subset of ENAT mother–infant dyads (n=462) was enrolled in the Longitudinal Infant Development and Growth study that followed infants until 24 months postpartum, from February 2023 to June 2024. We will determine the impact of ENAT interventions on micronutrient status, inflammation biomarkers and metabolomic and microbiome profiles. We will also determine the association of these profiles with birth outcomes and infant neurodevelopment.Ethics and dissemination These studies were approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to international stakeholders via peer-reviewed journals and locally via strategic dissemination sessions.Trial registration numbers ISRCTN15116516 and NCT06296238. |
| format | Article |
| id | doaj-art-9c3ad130346944d798fa0ccdbf31b6a3 |
| institution | DOAJ |
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| language | English |
| publishDate | 2025-04-01 |
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| spelling | doaj-art-9c3ad130346944d798fa0ccdbf31b6a32025-08-20T02:57:52ZengBMJ Publishing GroupBMJ Open2044-60552025-04-0115410.1136/bmjopen-2024-098686Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness studyAlemayehu Worku0Yemane Berhane1Parul Christian2Estifanos Baye3Krysten North4Mulatu Melese Derebe5Nebiyou Fasil6Kalkidan Yibeltal7Fred Van Dyk8Firehiwot Workneh9Sarah K G Jensen10Unmesha Roy Paladhi11Sophie Driker12Theresa I Chin13Anne C Lee14Department of Epidemiology and Biostatistics, Addis Continental Institute of Public Health, Addis Ababa, EthiopiaDepartment of Epidemiology and Biostatistics, Addis Continental Institute of Public Health, Addis Ababa, EthiopiaCenter for Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Pediatric Newborn Medicine, Global Advancement of Infants and Mothers, Brigham and Women`s Hospital, Boston, Massachusetts, USAHarvard Medical School, Boston, Massachusetts, USAAmhara Public Health Institute, Bahir Dar, EthiopiaDepartment of Global Health and Health Policy, Addis Continental Institute of Public Health, Addis Ababa, EthiopiaReproductive Health, Addis Continental Institute of Public Health, Addis Ababa, EthiopiaDepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USADepartment of Epidemiology and Biostatistics, Addis Continental Institute of Public Health, Addis Ababa, EthiopiaDevelopmental Medicine, Boston Children’s Hospital, Boston, Massachusetts, USADepartment of Pediatrics, Brigham and Women`s Hospital, Boston, Massachusetts, USADepartment of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USABrown University Division of Biology and Medicine, Providence, Rhode Island, USABrown University Division of Biology and Medicine, Providence, Rhode Island, USAIntroduction Maternal undernutrition and infections during pregnancy may influence birth and long-term child development outcomes. Characterising the micronutrient, metabolomic and microbiome profiles of pregnant women and infants may elucidate the underlying biology of adverse birth outcomes and early child development in the first 1000 days.Methods and analysis The Enhancing Nutrition and Antenatal Infection Treatment (ENAT) study was a 2×2 factorial, randomised clinical effectiveness study conducted in Amhara, Ethiopia from August 2020 to June 2022. We cluster-randomised pregnant women (n=2399) to receive either a nutrition intervention (iron-folic acid (IFA), iodised salt and balanced energy-protein supplementation for women with mid-upper arm circumference <23 cm) or routine care (IFA only), and individually randomised women to an infection control intervention (genitourinary tract infection screening-treatment and screening-treatment of stool parasites) or routine care (syndromic approach). Participants were followed until 1 month postpartum. A subset of 532 women-infant dyads were consecutively enrolled in the biospecimen substudy from July 2021 to August 2022. Specimens were collected at enrolment (<24 weeks) and antenatal care follow-up (third trimester), and 1–6 months postdelivery. A subset of ENAT mother–infant dyads (n=462) was enrolled in the Longitudinal Infant Development and Growth study that followed infants until 24 months postpartum, from February 2023 to June 2024. We will determine the impact of ENAT interventions on micronutrient status, inflammation biomarkers and metabolomic and microbiome profiles. We will also determine the association of these profiles with birth outcomes and infant neurodevelopment.Ethics and dissemination These studies were approved by the Institutional Review Boards of Addis Continental Institute of Public Health (ACIPH/IRB/002/2022) and Mass General Brigham (2023P000461). Results will be disseminated to international stakeholders via peer-reviewed journals and locally via strategic dissemination sessions.Trial registration numbers ISRCTN15116516 and NCT06296238.https://bmjopen.bmj.com/content/15/4/e098686.full |
| spellingShingle | Alemayehu Worku Yemane Berhane Parul Christian Estifanos Baye Krysten North Mulatu Melese Derebe Nebiyou Fasil Kalkidan Yibeltal Fred Van Dyk Firehiwot Workneh Sarah K G Jensen Unmesha Roy Paladhi Sophie Driker Theresa I Chin Anne C Lee Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study BMJ Open |
| title | Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study |
| title_full | Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study |
| title_fullStr | Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study |
| title_full_unstemmed | Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study |
| title_short | Investigating biological mechanisms of adverse birth outcomes and early child development in Amhara, Ethiopia: protocol of biospecimen collection and analysis of the Enhancing Nutrition and Antenatal Infection Treatment (ENAT) randomised effectiveness study |
| title_sort | investigating biological mechanisms of adverse birth outcomes and early child development in amhara ethiopia protocol of biospecimen collection and analysis of the enhancing nutrition and antenatal infection treatment enat randomised effectiveness study |
| url | https://bmjopen.bmj.com/content/15/4/e098686.full |
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