Nutrition and Inflammation in Pregnancy: Impacts on Early Human Brain Development in Ethiopia

NCT06296238 | Completed

• 1 other identifier: 2023P000461
• Study Type: observational
• Target: 463
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational child follow-up study is to examine the effects of prenatal nutrition and infection management interventions on long-term child neurodevelopment. Participants are the offspring of mothers in the main study entitled "Enhancing Nutrition and Antenatal Infection Treatment (ENAT)" that was conducted in the rural Amhara region of Ethiopia. In the ENAT pragmatic clinical effectiveness study, 2399 pregnant women were randomized to receive routine prenatal care, a package of enhanced nutrition interventions (balanced energy protein supplement, iodized salt, iron-folic acid and counseling), a package of enhanced infection management interventions (genitourinary tract infection screening-treatment, deworming), or a combination of both packages. The impact of these antenatal nutrition and infection interventions on birth outcomes (infant birth size and gestational length) was examined in the main study. In this longitudinal cohort study, we will follow the offspring from the ENAT pregnancy cohort up to 24 months postnatal age and assess their growth, health and neurodevelopment. The main questions it aims to answer are:

1. 1.What are the effects of pregnancy interventions from the parent study (ENAT) on offspring neurodevelopmental outcomes?
2. 2.What are the associations between maternal-newborn iron status and inflammation on infant neurodevelopment?
3. 3.What are the associations between maternal iodine status and thyroid function on infant neurodevelopment?

Conditions

Prenatal Exposure Delayed Effects

Outcome Measures

Primary Outcomes (1)

• Child resting brain function

  Measured by absolute power of alpha frequency band on mobile electroencephalography

  24 months

Secondary Outcomes (8)

• Child resting brain function, secondary measures

  24 months

• Brain functional connectivity

  24 months

• Neural processing speed

  24 months

• Visual Attention

  12 months

• Nonverbal Visual Attention

  12 months

Study Arms (4)

Enhanced Nutrition Package (ENP) health center + Enhanced Infection Management Package (EIMP)

ENP: Health centers were strengthened to provide WHO/FMOH-recommended nutrition interventions in pregnancy. Pregnant women received a supply of adequately iodized salt for household use and iron-folate tablets from enrollment to birth. Women with undernutrition (MUAC \<23 cm), also received a daily balanced energy protein supplement. EIMP: Pregnant women were screened at enrollment for bacteriuria with urine culture and antimicrobial susceptibility testing and presumptive deworming with mebendazole 500mg. Some women also received screening for chlamydia and gonorrhea and symptomatic women were tested for bacterial vaginosis and trichomonas. For women with chlamydia or gonorrhea, the participant was treated per FMOH guidelines with recommended antibiotics. STI/RTI screening was eventually discontinued due to supply shortage and the low prevalence of STI. At ANC follow-up visits, infected women were treated with antibiotics and persistent infection was retreated.

ENP health center, routine care infection management participant

ENP: The health centers were strengthened to provide WHO/FMOH-recommended nutrition interventions in pregnancy. Pregnant women received a supply of adequately iodized salt for household use and iron-folate tablets from enrollment to birth. Women with undernutrition (MUAC \<23 cm), also received a daily balanced energy protein supplement. Standard infection care: Maternal genitourinary tract infections is managed as per standard FMOH health center guidelines that utilize a syndromic management approach.

Routine nutrition care health center, EIMP participant

Routine nutrition care: Maternal nutrition was managed as per standard FMOH health center guidelines. EIMP: Pregnant women were screened at enrollment for bacteriuria with urine culture and antimicrobial susceptibility testing and presumptive deworming with mebendazole 500mg. Some women also received screening for chlamydia and gonorrhea and symptomatic women were tested for bacterial vaginosis and trichomonas. For women with chlamydia or gonorrhea, the participant (and partner) was treated per FMOH guidelines with recommended antibiotics. STI/RTI screening was eventually discontinued due to supply shortage and the low prevalence of STI. At ANC follow-up visits, infected women were treated with antibiotics and persistent infection was retreated.

Routine of care nutrition and infection management

Pregnant women received routine strengthened antenatal care services at the health center per FMOH guidelines. Maternal genitourinary tract infections were managed as per standard FMOH health center guidelines that utilize a syndromic management approach.

Eligibility Criteria

• Age: 9 Months - 27 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

The participants of this study will be recruited from 6 rural health centers (serving a \~25,000 population) involved in ENAT study in West Gojjam and South Gondar zones, Amhara, Ethiopia (Lee et al., 2022). In this infant follow-up study, up to 500 selected infants from the parent ENAT study will be followed for 24 months for general health, growth, and development. A subset of these infants (up to 480) whose mothers provided biospecimens or whose mothers had mid-upper arm circumference (MUAC) of \<23 cm in the parent study will be recruited for an advanced neurodevelopmental assessment study.

You may qualify if:

• Mothers who have participated in ENAT study who consent to participate in the infant follow up study
• Intention to stay in the study catchment area
• Healthy infants without severe clinical signs or symptoms including headache, vomiting, or dizziness

You may not qualify if:

• Major congenital anomalies
• Infants with severe morbidity or developmental disorder
• Neonatal encephalopathy
• Plan to move out of study catchment area

Sponsors & Collaborators

• Brown University: lead
• Addis Continental Institute of Public Health: collaborator
• Boston Children's Hospital: collaborator
• New York University: collaborator
• Johns Hopkins University: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (1)

Health Centers in West Gojjam and South Gondar zones

Bahir Dar, Amhara, Ethiopia

Location

Related Publications (2)

• Roy Paladhi U, Workneh F, Baye E, Derebe MM, Yibeltal K, Fasil N, Driker S, Van Dyk F, I Chin T, North K, Jensen SKG, Christian P, Worku A, Berhane Y, Lee AC. 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. 2025 Apr 28;15(4):e098686. doi: 10.1136/bmjopen-2024-098686.

  PMID: 40295129 DERIVED

• Workneh F, Chin TI, Yibeltal K, Fasil N, North K, Jensen SKG, Kidane WT, Melese M, Tsegaye S, Berhane YY, Roy Paladhi U, Abate BH, Teklehaimanot A, Melka TL, Pihl S, An WW, Van Dyk F, Mullany LC, Folger LV, Cherkerzian S, Troller-Renfree SV, Thomason ME, Andersson M, Inder T, Nelson CA, Grant PE, Christian P, Worku A, Berhane Y, Lee AC. Impact of maternal antenatal nutrition and infection treatment interventions on Longitudinal Infant Development and Growth in rural Ethiopia: protocol of the LIDG child follow-up study. BMJ Paediatr Open. 2024 Dec 24;8(1):e002840. doi: 10.1136/bmjpo-2024-002840.

  PMID: 39725450 DERIVED

MeSH Terms

Conditions

Prenatal Exposure Delayed Effects

Condition Hierarchy (Ancestors)

Prenatal Injuries; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Yemane Berhane

  Addis Continental Institute of Public Health

  PRINCIPAL INVESTIGATOR

• Anne CC Lee

  Warren Alpert Medical School of Brown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Levinger Family Professor of Pediatrics

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 6, 2024
• Study Start: February 15, 2023
• Primary Completion: July 1, 2024
• Study Completion: July 1, 2024
• Last Updated: March 26, 2025

Record last verified: 2025-03

Locations

ET (1)