228 - The impact of enhanced prenatal nutrition and infection management on early childhood neurodevelopment in rural Ethiopia: a pragmatic, factorial, cluster-randomized clinical trial.

Publication Number: 1217.228

Krysten North, Brigham and Women's Hospital, Boston, MA, United States; Kalkidan Yibeltal, University of South Carolina, Cayce, SC, United States; Firehiwot Workneh, Addis Continental Institute of Public Health, Addis Ababa, Adis Abeba, Ethiopia; Yumin Kim, The Warren Alpert Medical School of Brown University, Boston, MA, United States; Sophie Driker, Brigham and Women's Hospital, Somerville, MA, United States; Atsede Teklehaimanot. Legesse, Addis Ababa University, Addis Ababa, Adis Abeba, Ethiopia; Sarah K.G.. Jensen, Women & Infants Hospital of Rhode Island, Newton Centre, MA, United States; Nebiyou Fasil, Addis Continental Institute of Public Health, Addis Ababa, Adis Abeba, Ethiopia; Unmesha Roy Paladhi, The Warren Alpert Medical School of Brown University, Providence, RI, United States; Theresa I. Chin, The Warren Alpert Medical School of Brown University, 200 Chestnut St, RI, United States; Terrie E. Inder, CHOC Children's Hospital of Orange County, Orange, CA, United States; P. Ellen grant, Boston Children's Hospital, Boston, MA, United States; Anne CC Lee, Warren Alpert Medical School of Brown University, Providence, RI, United States; Yemane Berhane, Addis Continental Institute of Public Health, Addis Ababa, Adis Abeba, Ethiopia

Background: Prenatal exposure to undernutrition and inflammation may harm brain development in a growing fetus during a critical window of maturation.

Objective: To examine the effects of packages of enhanced nutrition and infection management interventions delivered during pregnancy on offspring brain growth measured by magnetic resonance imaging (MRI) and neurodevelopment measured using the Hammersmith Infant Neurological Examination (HINE) in rural Ethiopia. We hypothesized that both intervention packages would result in higher global HINE scores and larger total brain volumes.

Design/Methods: This study enrolled the offspring of participants in a 2x2 factorial, cluster-randomized trial of prenatal nutrition and infection treatment interventions in rural Amhara, Ethiopia. The parent study enrolled pregnant women < 24 weeks gestation. Women were cluster-randomized by health center to an enhanced nutrition package (ENP; iron/folic acid, iodized salt, and, for women with mid-upper arm circumference [MUAC] < 23 cm, a balanced-energy protein supplement) or routine care. Participants were individually randomized to an enhanced infection management package (EIMP; screening and treatment of stool parasitic and genitourinary tract infections) or routine care. A subset of children were consecutively enrolled in a follow-up study and evaluated using the HINE and/or ultra low-field MRI. We used MiniMORPH software to estimate total and regional brain volumes. Marginal intervention effects were estimated using cluster-level t-tests for ENP and multivariable regression models for EIMP effects.

Results: Of 462 children, 455 had the HINE (130 ENP + EIMP, 101 ENP only, 110 EIMP only, 114 routine care) at 14 months, and 63 underwent MRI at 16 months (29 ENP + EIMP, 34 routine care). Compared to routine care, we found no effect of either ENP (adjusted mean difference [aMD] -0.2 points; 95% CI -3.6, 3.2) or EIMP (aMD 0.0 points; 95% CI -1.7, 1.8) on HINE scores. We also found no effect of the combined intervention (ENP+EIMP) packages on total brain volumes (aMD 24.6 ml; 95% CI -50.3, 99.6) or regional brain volumes. In subgroup analysis of children born to mothers with a MUAC < 23 cm, there was also no effect of ENP + EIMP on total brain volumes (aMD 33.9 ml; 95% CI -43.9, 111.7) or regional brain volumes.

Conclusion(s): Enhanced prenatal nutrition and infection management did not improve developmental metrics at 1 year of age in this rural Ethiopian cohort. Other factors, such as postnatal environment or illness, may be greater determinants of brain development than these prenatal interventions.

Participant flow diagram showing study randomization and child follow up.


Table 1: HINE global and subdomain scores by nutrition and infection arm allocation.
ENP = enhanced nutrition package. EIMP = enhanced infection management package. *Adjusted for corrected age at MRI, child sex, maternal education, occupation, animal ownership + cluster

Table 2: MRI total and regional tissue volumes comparing ENP + EIMP versus routine care study arms.
ENP = enhanced nutrition package. EIMP = enhanced infection management package. *Adjusted for corrected age at MRI, child sex, maternal education, occupation, animal ownership + cluster