Randomized prenatal and postnatal nutrient supplementation shows no long-term impact on cortical gray matter in Ghanaian children

Fatimah Bintu Ayete Labi^1,2Ludmila Midrigan-Ciochina³Elizabeth L Prado^4,5Seth Adu-Afarwuah⁶Kathryn G Dewey^7,8Charles D Arnold⁹Adom Manu¹⁰Seth Angmorterh²John Arko-Mensah¹Mavis Osipi Mensah⁶Helena Nti^11,6Lois M Donkor Aryee⁶Yaw Mensah¹²Becky Amponsaa Appiah¹³David Atawone¹⁴Norbert Azantilow¹³Brietta Oaks¹⁵Benjamin Amponsah¹⁶Paul D Hastings^17,3Amanda E Guyer^18,3*

• ¹Department of Biological, Environmental and Occupational Health, School of Public Health, University of Ghana College of Health Sciences, Accra, Ghana
• ²Department of Medical Imaging, University of Health and Allied Sciences, Ho, Ghana
• ³Center for Mind and Brain, University of California, Davis, Davis, United States
• ⁴Department of Nutrition, University of California, Davis, Davis, United States
• ⁵Institute of Global Nutrition, University of California Davis, Davis, United States
• ⁶Department of Nutrition and Food Science, University of Ghana, Accra, Ghana
• ⁷Department of Nutrition, University of California Davis, Davis, United States
• ⁸Institute for Global Nutrition, University of California, Davis, Davis, United States
• ⁹Institute for Global Nutrition, University of California Davis, Davis, United States
• ¹⁰Department of Population, Family and Reproductive Health, School of Public Health, University of Ghana, Accra, Ghana
• ¹¹Department of Nutrition and Dietetics, University of Health and Allied Sciences, Ho, Ghana
• ¹²Department of Radiology, Korle Bu Teaching Hospital, Accra, Ghana
• ¹³Department of Radiology, International Maritime Hospital, Tema, Ghana
• ¹⁴International Maritime Hospital, Tema, Ghana
• ¹⁵Department of Nutrition, University of Rhode Island, Kingston, United States
• ¹⁶Department of Psychology, University of Ghana, Accra, Ghana
• ¹⁷Department of Psychology, University of California Davis, Davis, United States
• ¹⁸Department of Human Ecology, University of California Davis, Davis, United States

Maternal and child undernutrition are linked to atypical brain development in children. Provision of pre-and post-natal small-quantity lipid-based nutrient supplements (SQ-LNS) has been shown to positively impact children's growth and development. It is unknown, however, whether SQ-LNS affects child brain morphology. The present study used data from the International Lipid-based Nutrient Supplements randomized controlled trial in Ghana. Participants were 231 children (Mage=10.6 years; 49.4% female) exposed to iron and folic acid only supplements prenatally and until 6 months (n=113, control group) or SQ-LNS prenatally and from age 6-18 months (n=118, SQ-LNS group). Children underwent magnetic resonance imaging of brain anatomy. Primary outcomes were total gray matter volume, cortical gray matter thickness, and cortical gray matter volume assessed with whole-brain analyses. Secondary outcomes were thickness and volume of a priori specified cortical and subcortical regions assessed with region-of-interest (ROI) analyses. Basic and full covariate models were tested and corrected for multiple comparisons. Whole-brain analyses revealed no significant differences between groups in total gray matter volume or cortical gray matter thickness or volume. Cortical ROI analyses showed the SQ-LNS versus control group had greater right caudal anterior cingulate cortex (ACC) thickness (mean [95%CI]: 2.78 [2.73, 2.84] vs. 2.72 [2.67, 2.77]; effect size=0.21) and reduced left rostral ACC volume (2575.1 [2477.3, 2672.8] vs. 2678.74 [2568.7, 2788.8]; effect size=0.18). Subcortical ROI analyses showed the SQ-LNS versus control group had greater volume of the left pallidus (1794.45 [1759.10, 1829.80] vs. 1726.13 [1685.05, 1767.21]; effect size=0.33) and right nucleus accumbens (751.54 [729.83, 773.24] vs 705.73 [684.21, 727.24]; effect size=0.39). Significant group differences did not hold after correction for multiple comparisons. In this cohort, pre-and post-natal SQ-LNS supplementation did not significantly alter total or cortical gray matter thickness and volume at 10 years, though secondary ROI analyses indicated subtle, non-robust differences in select regions.