Implications of maternal nutrient deficiency in rat offspring: a cognitive and behavioral study

Abstract

Aim: Maternal nutritional insufficiency during pregnancy is a major public health concern associated with adverse neurodevelopmental outcomes in offspring. This study investigated the effects of global maternal nutrient restriction before and/or during gestation on cognitive and behavioral performance in rat offspring and evaluated the potential for recovery following postnatal dietary normalization. Methods: Female Wistar rats were assigned to either a control diet (AIN-93G) or a 50% global nutrient-restricted diet. Nutrient-restricted groups received dietary restriction before pregnancy alone (RD-P) or before and throughout gestation (RD-W), followed by a standard diet after birth or weaning. Offspring were assessed at postnatal days 35–40 using the Y-maze spontaneous alternation test for working memory, the Open Field Test for locomotor activity, and the Elevated Plus Maze (EPM) for anxiety-like behavior. Data were analyzed using one-way ANOVA with Dunnett’s post hoc test (p<0.05). Results: Maternal nutrient restriction did not significantly affect Y-maze spontaneous alternation performance (p > 0.05), indicating preserved working memory. However, offspring from restricted groups exhibited significantly greater time spent in EPM open arms (p<0.001), suggesting reduced anxiety-like behavior, with the strongest effect observed in the RD-W group. Increased locomotor activity was also detected in nutrient-restricted offspring during the Open Field Test (p=0.0118). Gestational maternal food intake showed weak negative correlations with EPM open-arm duration (r=−0.34,p=0.06) and locomotor activity (r=−0.28,p=0.12). Conclusions: Maternal global nutrient restriction induces persistent, domain-specific behavioral alterations in offspring. While postnatal dietary normalization may partially ameliorate deficits in activity-related behaviors, reduced anxiety-like behavior persists into adolescence. These findings emphasize the critical role of adequate maternal nutrition in shaping offspring neurodevelopment and behavioral health, highlighting the importance of nutritional interventions during the preconceptional and gestational periods.

Keywords

maternal nutrition / nutrient restriction / rat offspring / cognitive behavior / anxiety-like behavior / Y-maze / Elevated Plus Maze / Open Field Test

References

[1] Cusick SE, Georgieff MK. The Role of Nutrition in Brain Development: The Golden Opportunity of the “First 1000 Days”. J Pediatr. 2016;175:16-21.

[2] Monk C, Georgieff MK, Osterholm EA. Research Review: Maternal prenatal distress and poor nutrition—mutually influencing risk factors affecting infant neurocognitive development. J Child Psychol Psychiatry. 2012;54:115-30.

[3] Prado EL, Dewey KG. Nutrition and brain development in early life. Nutr Rev. 2014;72:267-84.

[4] Georgieff MK. Iron deficiency in pregnancy. Am J Obstet Gynecol. 2020;223:516—24.

[5] Pivina L, Semenova Y, Doşa MD, Dauletyarova M, Bjørklund G. Iron Deficiency, Cognitive Functions, and Neurobehavioral Disorders in Children. J Mol Neurosci. 2019;68:1-10.

[6] Tia A, Hauser J, Konan AG, Ciclet O, Grzywinski Y, Mainardi F, et al. Unraveling the relationship between nutritional status, cognitive function, and school performance among school—aged children in Taabo, Côte d'Ivoire: a school—based observational study. Front Nutr. 2025;12:1630497.

[7] Kiani AK, Dhuli K, Donato K, Aquilanti B, Velluti V, Matera G, et al. Main nutritional deficiencies. J Prev Med Hyg. 2022;63:E93.

[8] Felt BT, Beard JL, Schallert T, Shao J, Aldridge JW, Connor JR, et al. Persistent neurochemical and behavioral abnormalities in adulthood despite early iron supplementation for perinatal iron deficiency anemia in rats. Behav Brain Res. 2006;171:261—70.

[9] Leikin—Frenkel AI. Perinatal lipid nutrition. Mol Nutr: Mother Infant. 2021:337-59.

[10] Georgieff MK. Nutrition and the developing brain: nutrient priorities and measurement. Am J Clin Nutr. 2007;85:614S-20S.

[11] How micronutrient supplements are nourishing women and babies[Internet]. UNICEF; [cited 2024 Sep 25]. Available from: https://www.unicef.org/rosa/stories/how—micronutrient—supplements—are—nourishing—women—and—babies

[12] Girotra S, Malik M, Roy S, Basu S. Utilization and determinants of adequate quality antenatal care services in India: evidence from the National Family Health Survey (NFHS—5) (2019—21). BMC Pregnancy Childbirth. 2023;23:800.

[13] Ajantha, Singh AK, Malhotra B, Mohan SK, Joshi A. Evaluation of Dietary Choices, Preferences, Knowledge and Related Practices Among Pregnant Women Living in An Indian Setting. J CLIN DIAGN RES. 2015;9:LC04-10.

[14] Xie Y, Liu F, Zhang X, Jin Y, Li Q, Shen H, et al. Benefits and risks of essential trace elements in chronic kidney disease: a narrative review. Ann Transl Med. 2022;10:1400.

[15] Bale TL, Baram TZ, Brown AS, Goldstein JM, Insel TR, McCarthy MM, et al. Early Life Programming and Neurodevelopmental Disorders. Biol Psychiatry. 2010;68:314—9.

[16] Entringer S, Buss C, Kumsta R, Hellhammer DH, Wadhwa PD, Wüst S. Prenatal psychosocial stress exposure is associated with subsequent working memory performance in young women. Behav Neurosci. 2009;123:886-93.

[17] Lucassen PJ, Naninck EF, van Goudoever JB, Fitzsimons C, Joels M, Korosi A. Perinatal programming of adult hippocampal structure and function; emerging roles of stress, nutrition and epigenetics. Trends Neurosci. 2013;36:621—31.

[18] Radlowski EC, Johnson RW. Perinatal iron deficiency and neurocognitive development. Front Hum Neurosci. 2013;7:585.

[19] Perry RE, Finegood ED, Braren SH, Dejoseph ML, Putrino DF, Wilson DA, et al. Developing a neurobehavioral animal model of poverty: Drawing cross—species connections between environments of scarcity—adversity, parenting quality, and infant outcome. Dev Psychopathol. 2018;31:399-418.

[20] Reeves PG, Nielsen FH, Fahey GC Jr. AIN—93 Purified Diets for Laboratory Rodents: Final Report of the American Institute of Nutrition Ad Hoc Writing Committee on the Reformulation of the AIN—76A Rodent Diet. J Nutr. 1993;123:1939-51.

[21] Lam LF, Lawlis TR. Feeding the brain—The effects of micronutrient interventions on cognitive performance among school—aged children: A systematic review of randomized controlled trials. Clin Nutr. 2017;36:1007-14.

[22] Van den Bergh BRH, van den Heuvel MI, Lahti M, Braeken M, de Rooij SR, Entringer S, et al. Prenatal developmental origins of behavior and mental health: The influence of maternal stress in pregnancy. Neurosci Biobehav Rev. 2020;117:26-64.

[23] Meer MS, Sandhya R. Geospatial analysis of maternal healthcare utilization and socioenvironmental determinants in Tamil Nadu, India. Discov Public Health. 2026;23:392.

[24] Balsevich G, Häusl AS, Meyer CW, Karamihalev S, Feng X, Pöhlmann ML, et al. Stress—responsive FKBP51 regulates AKT2—AS160 signaling and metabolic function. Nat Commun. 2017;8:1725.

[25] Pellow S, Chopin P, File SE, Briley M. Validation of open : closed arm entries in an elevated plus—maze as a measure of anxiety in the rat. J Neurosci Methods. 1985;14:149-67.

[26] Carobrez AP, Bertoglio LJ. Ethological and temporal analyses of anxiety—like behavior: The elevated plus—maze model 20 years on. Neurosci Biobehav Rev. 2005;29:1193-205.

[27] Reddan JM, Macpherson H, White DJ, Scholey A, Pipingas A. Examining the relationship between nutrition and cerebral structural integrity in older adults without dementia. Nutr Res Rev. 2018;32:79-98.

[28] Jain S, Maheshwari A, Jain SK. Maternal Nutrition and Fetal/Infant Development. Clin Perinatol. 2022;49:313—30.

[29] de Matos Reis ÁE, Teixeira IS, Maia JM, Luciano LAA, Brandião LM, Silva MLS, et al. Maternal nutrition and its effects on fetal neurodevelopment. Nutrition. 2024;125:112483.

[30] Soni R, Verma D, Chopra R, Singh V, Goswami D. Demystifying intricate factors of nutritional anemia beyond iron deficiency—A narrative review. Clin Nutr ESPEN. 2025;69:745-64.

[31] Francis HM, Stevenson RJ. Potential for diet to prevent and remediate cognitive deficits in neurological disorders. Nutr Rev. 2018;76:204-17.

[32] Alsharshani DA. Risk factors for autism spectrum disorders in the state of Qatar[dissertation]. Doha: Hamad Bin Khalifa University; 2019.

[33] Begum S, Latunde—Dada GO. Anemia of Inflammation with An Emphasis on Chronic Kidney Disease. Nutrients. 2019;11:2424.

[34] Hassan MA, Wadan AHS, Elhelw JS, Atia NE, Sarhan MM. The impact of micronutrients on cognitive functions. In: Mohamed W, Özge A, editors. Feeding the mind: the connection between diet, drugs, and mental health Volume 1. Nutritional neurosciences. Singapore: Springer; 2025. pp. 243-64.

[35] Kumar DSTG. Role of Antenatal Maternal Psychological Factors in the Genesis of Childhood Neurodevelopmental Disorders. Genet Mol Res. 2026.

[36] Bhutta ZA, Berkley JA, Bandsma RHJ, Kerac M, Trehan I, Briend A. Severe childhood malnutrition. Nat Rev Dis Primers. 2017;3:17067.

[37] Agaram S, Chandrababu P, Bhavani S, Saravanan B, Chinnakannu M, Sundaram T, et al. Impact of maternal endocrine health on foetal development and pregnancy outcomes. Scr Med. 2025;56:985-1005.