Optimal brain development during fetal life and early childhood depends on adequate and balanced nutrition. The developing brain requires an adequate and constant supply of essential nutrients to support vital processes such as neurogenesis, synapse formation, and myelination.1 Malnutrition, whether caused by insufficient or excessive intake, disrupts these processes and can lead to long-term neurodevelopmental impairments.

Research has emphasized the neurodevelopmental consequences of undernutrition, including deficiencies in protein, iron, iodine, folate, vitamin B12, and essential fatty acids. These deficiencies are particularly harmful during critical periods such as the third trimester of pregnancy and the first two years of life, when the brain is undergoing rapid growth.2, 3, 4 Studies have demonstrated structural brain changes, reduced gray matter volume, impaired cognitive performance, and increased vulnerability to infections among children who experience early-life undernutrition 2,3,5

However, overnutrition is also an emerging global concern. Diets high in ultra-processed foods, added sugars, and unhealthy fats, which are often observed in high-income settings but are also now increasingly available in urban low- and middle-income countries, can also impair brain development. Excess calorie intake in early life has been linked to a state of systemic inflammation,6,7 altered gut-brain signaling,8 disrupted dopamine pathways,9 which can lead to cognitive impairments and increased risks of neuropsychiatric disorders.10,11

Maternal nutritional status is also paramount, as it impacts fetal nervous system development.12 Inadequate nutrient intake during pregnancy is associated with diminished cerebral volume, alterations in hypothalamic and hippocampal pathways, and increased risks of neural tube defects, which can lead to long-term cognitive impairments and behavioral abnormalities.13,14 In contrast, maternal overnutrition, particularly obesity and high-fat diets, induces chronic low-grade inflammation that can spread to the fetal brain, disrupting neuronal connectivity and impairing cognitive functions 10,15

This review examines the spectrum of malnutrition and its effects on the developing brain. We discuss the biological mechanisms linking nutrition to neurodevelopment, the specific roles of key nutrients, and the long-term impact of nutritional imbalance. We also explore population-based strategies and targeted interventions aimed at preventing and mitigating the cognitive and behavioral consequences of both undernutrition and overnutrition.

Undernutrition during critical windows of brain development, particularly from the third trimester of pregnancy to the first two years of life, can result in irreversible structural and functional damage.16,17 Early studies demonstrated significantly lower levels of brain weight, protein, RNA, and DNA in infants who died from severe undernutrition, including those with kwashiorkor or marasmus, compared to those who died of unrelated causes.4 The reduction in brain mass and biochemical constituents demonstrated in neuropathological studies reflects impaired neurogenesis and synaptogenesis when exposed to undernutrition.18 Undernutrition particularly affects the cerebral cortex, hippocampus, and cerebellum, regions that are essential for memory consolidation, learning, and coordination.2,3 The most vulnerable period is from late fetal life to five months of age, during which brain cellular proliferation is at its peak.4,19,20

While nutritional supplementation or rehabilitation can recover some of the deleterious effects of undernutrition, some of its effects can be irreversible, mainly if they occur prenatally.21, 22, 23 Prenatal undernutrition has long-lasting and often irreversible effects on brain development and cell proliferation, as exposure to undernutrition during critical periods of fetal development can induce lasting alterations in neurodevelopment through mechanisms such as epigenetic programming and organ structural changes.24 Studies have shown that maternal undernutrition during gestation can lead to intrauterine growth restriction (IUGR) and reduced cell proliferation in regions of the brain that are critical for neurodevelopment, such as the hippocampus.12,25 These effects are partly due to impaired placental nutrient transfer of key elements such as iron, and impaired epigenetic modifications that permanently alter gene expression and brain structure 26,27 Postnatal undernutrition, though potentially reversible structurally, often causes long-lasting behavioral and cognitive effects.28,29 Nutritional interventions during early childhood can lead to catch-up growth and partial recovery of neurodevelopmental deficits, and some studies have demonstrated that improved nutritional status can lead to some recovery in neurocognitive development.24

Undernourished children consistently perform worse on standardized tests of IQ, language development, and school achievement.3,29,30 Studies have shown that children with a history of severe acute malnutrition exhibit persistent cognitive deficits even after nutritional rehabilitation. A longitudinal study from India revealed that children successfully treated for kwashiorkor in early childhood performed significantly worse on tests of perception, sensory integration, and abstract reasoning compared to well-nourished peers.30 A more recent study assessing Malawian children seven years after surviving acute malnutrition found that these children had significantly poorer scores in cognitive tests and were more likely to be in lower school grades compared to their peers.31 A systematic review and meta-analysis also demonstrated that malnourished children had worse scores on various cognitive domains. This study included 12 studies with 7,607 participants aged 1 to 12 years and found that malnourished children had significantly worse scores on cognitive tests such as the Wechsler Intelligence Scale, visual processing, short memory tests, Raven's Coloured Progressive Matrices compared to well-nourished controls.32

Undernutrition also has a significant impact on emotional regulation and social behavior. Children who experience undernutrition during brain development, including prenatal exposure, are at higher risk for adult-onset mental health conditions, including schizophrenia, depression, anxiety, and cognitive decline.33 Studies, such as those examining the Dutch Hunger Winter and the Chinese Famine, have shown that early gestational exposure to severe malnutrition significantly increases the risk of schizophrenia later in life.34,35 This is thought to be mediated by disruptions in myelination and epigenetic changes in genes with essential roles in neuronal, neuroendocrine, and immune processes.36 Depression is another mental health condition associated with early-life undernutrition. A systematic review showed that early-life undernutrition is linked to an increased risk of depression in adulthood, therefore further suggesting that nutritional deficiencies during critical periods of brain development can have long-lasting effects on mental health.37

Moreover, undernutrition compromises immune function, increasing vulnerability to infections like meningitis and encephalitis.38,39 Recurrent illness further suppresses appetite and nutrient absorption, worsening malnutrition and impairing both physical and cognitive growth.40 Malnourished children have higher rates of hospitalization for infections, which further disrupts schooling and cognitive development.23,40

While undernutrition has long been a focus in global child health, overnutrition, that is, excess calorie intake, particularly from processed foods high in sugar, saturated fats, and refined carbohydrates, is a growing public health concern. Overnutrition can impair neurodevelopment through mechanisms distinct from those associated with undernutrition, yet it is also detrimental. Overnutrition has usually been referred to as an increasingly prevalent issue mainly in high- and middle-income countries, however it is now also recognized as an increasingly prevalent issue in low- and middle-income countries, in which the phenomenon of the double burden of malnutrition, which includes both undernutrition and overnutrition, is now more identified. This dual burden is driven by rapid changes in the food system, including the availability of cheaper, ultra-processed food.41

Excess energy intake in early life promotes chronic low-grade inflammation, insulin resistance, and alterations in gut microbiota, all of which influence brain development and function.6 High-sugar and high-fat diets have been linked to reduced hippocampal volume, impaired learning, and deficits in executive function in children and adolescents.42,43 In rodent models, high-fat, high-sugar, and combined high-fat-high-sugar diets adversely affected performance on hippocampal-dependent tasks, indicating impaired spatial learning and memory.44 There are also studies in rodent models showing the impact of high-sugar and high-fat diets on the dopaminergic system, dopaminergic reward pathways, increasing susceptibility to hyperactivity and emotional dysregulation.45 These studies collectively indicate that overnutrition not only impacts hippocampal volume, learning, and executive function but also significantly alters the dopaminergic system, contributing to cognitive and behavioral deficits.

Overnutrition also impacts mental health in childhood and has potential long-lasting effects later in adulthood. Children with obesity have higher rates of depression, anxiety, and ADHD, which may be mediated by altered neuroendocrine and inflammatory signaling, such as a subclinical inflammatory and oxidative state.46 Emerging evidence also suggests that overnutrition in early life may contribute to structural brain changes, including decreased white matter integrity.47,48 These changes can mirror some of the cognitive impairments traditionally associated with undernutrition, highlighting the need for balanced, nutrient-rich diets across all socioeconomic settings.

Brain development relies on an array of macro- and micronutrients that support neurogenesis, myelination, neurotransmitter synthesis, and synaptic plasticity. Deficiencies in these nutrients, especially during critical periods, can have long-term consequences on cognitive, emotional, and behavioral outcomes. Below, we highlight several key nutrients implicated in neurodevelopment. For more comprehensive discussions, readers are referred to several detailed reviews on the topic 13,18,49, 50, 51

Iron is essential for myelination, energy metabolism, and the synthesis of neurotransmitters. Deficiencies can lead to impaired myelination, altered monoamine neurotransmitter synthesis, and disrupted hippocampal energy metabolism, which are critical for cognitive functions and processing speed.52, 53, 54 The importance of iron deficiency is that, as would be expected, the most prominent clinical presentation is anaemia, yet the cognitive and behavioural impact of its deficiency far outlasts the treatment period.55,56 Iron also presents dosing considerations given that both iron deficiency and iron overload are detrimental to the brain and other organs.57

Zinc deficiency affects the autonomic nervous system regulation and the development of the hippocampus and cerebellum.58 Zinc is crucial for synaptic plasticity and neurotransmission, and its deficiency can lead to impaired neurogenesis and synaptic function, contributing to cognitive deficits and slower processing speeds 18

Folate (vitamin B9) is critical for DNA synthesis and neural tube closure during early gestation.59,60 Folic acid supplementation has consistently been shown to reduce neural tube defects and anaemia-related complications, 61 with less consistent evidence but suggesting a modest protective effect for congenital heart disease,62,63 all especially when supplementation is started before conception.

Vitamin B12 is also essential for myelination and DNA methylation.64 Deficiencies in either mother or child can cause cerebral atrophy, delayed myelination, and language regression 65,66 . Early supplementation can prevent these outcomes, but evidence on the benefits of B12 supplementation in non-deficient populations is conflicting.67,68

Some case studies highlight dramatic improvement following B12 replacement in children of vegan mothers, emphasizing the importance of targeted interventions for at-risk groups.69

Docosahexaenoic acid (DHA), a key omega-3 fatty acid, is vital for cell membrane integrity, synaptic transmission, and neurogenesis.70, 71, 72 Adequate levels of DHA are necessary for the maturation of cortical astrocytes, neurovascular coupling, and glucose metabolism in the brain.73,74 Although there is some evidence to suggest that children with low baseline DHA status, those with underperforming cognitive or behavioral profiles, may be more likely to benefit from DHA supplementation,75, 76, 77 reviews highlight the heterogeneity of study designs, populations, and outcome measures, and highlight that any observed benefits are not robust or consistent enough to recommend routine DHA supplementation 76,78,79

Inadequate maternal intake of omega-3 fatty acids during pregnancy and lactation has been linked to poorer neurodevelopmental outcomes in children, including deficits in learning, working memory, and executive function, though the magnitude and consistency of these effects are modest and not uniform across all cognitive domains 80 .

Iodine is a critical component of thyroid hormones, which are indispensable for neurodevelopment, especially during the first half of gestation when the fetal brain depends entirely on maternal T4.81 Iodine deficiency in pregnancy can lead to intellectual disability and cretinism, even in the presence of normal brain structure.82,83

Although evidence on individual iodine supplementation during pregnancy remains mixed,84 population-level interventions such as universal salt iodization have dramatically reduced the incidence of iodine-related intellectual disability.85

Choline plays a key role in neurodevelopment, particularly during pregnancy and early childhood.86 It is essential for the biosynthesis of cell membranes, neurotransmission, and DNA and histone methylation.87 Choline supports the formation of the nervous system, cognitive development, and reduces the risk of neural tube defects.88,89 Due to its role in brain development and function, low choline intake during pregnancy is linked to a higher risk of neurodevelopmental disorders such as ADHD and autism spectrum disorder.90 Ensuring adequate choline intake through a combination of dietary sources and supplements is crucial for optimal brain development during pregnancy and the first 1000 days of life.87

Malnutrition does not occur in isolation. Socioeconomic status, food insecurity, education, and access to healthcare all play significant roles in a child's nutritional environment and, consequently, in their neurodevelopment. These social determinants create persistent disparities in neurodevelopmental outcomes.

Children living in low-middle income countries (LMICs), or in marginalized communities within high-income countries, are more likely to experience undernutrition due to poverty, limited food diversity, and poor education. In contrast, overnutrition disproportionately affects urban populations with limited access to healthy foods.41 Both forms of malnutrition, that is, undernutrition and overnutrition, are linked to lifelong cognitive and developmental challenges, reduced academic achievement, lower economic productivity, and increased risk of mental health disorders such as depression, schizophrenia, and anxiety. These neurodevelopmental impairments perpetuate intergenerational cycles of disadvantage.

Addressing the neurodevelopmental effects of malnutrition requires early, sustained, and context-specific interventions. Effective, context-specific interventions to prevent nutritional deficiencies that may negatively impact neurodevelopment in children and adolescents should focus on ensuring adequate intake of essential nutrients through a combination of micronutrient supplementation and food fortification. Public health initiatives, such as supplementation initiatives, school feeding programs, and policies promoting nutrient-rich foods, play a crucial role in reducing deficiencies. Additionally, addressing socioeconomic disparities, improving maternal nutrition, and raising awareness about the importance of early-life nutrition are key strategies to support optimal brain development and overall well-being.

Given the impact of maternal undernutrition on the developing brain, strategies aiming at addressing undernutrition during the preconception and prenatal period are key. Nutrient supplementation for women of reproductive age, particularly folate, iron, iodine, and B12, may improve fetal outcomes; however, indiscriminate use of high-dose multinutrient supplements is not recommended due to uncertain benefit and potential for harm of excess doses.91 Breastfeeding support is another crucial area to aim at. Exclusive breastfeeding for the first six months provides optimal nutrition, including DHA and antibodies, which are essential for the development of the brain and nervous system. Fortification of breast milk in preterm infants enhances neurodevelopmental outcomes.92,93 Programs that help provide nutrient-rich food during the first months of life support brain development during the complementary feeding window. Introducing nutrient-rich foods such as iron-fortified cereals, fish, eggs, fruits, and vegetables supports brain development during the complementary feeding window.

One of the programs that has been implemented in many countries to address undernutrition in children is the provision of free meals in schools. Free or subsidized school meals rich in protein, iron, and healthy fats help address undernutrition during the school-age years. Micronutrient supplementation is another strategy, such as programs providing vitamin A, iron, and zinc, which can improve nutritional status and support cognitive growth 93 . Deworming programs enable children to maximize the benefits of nutrients eaten as opposed to losing nutrients on account of parasitic infestation.94 Nutrition education in schools also empowers children to make better nutritional decisions 95

Growth monitoring and promotion (GMP) and early detection of undernutrition at health centres and the community level present the opportunity to detect growth faltering and intervene promptly. Current evidence from low- and middle-income countries offers limited evidence for the effectiveness of GMP programs in improving nutritional status, feeding behaviors, or access to health services in young children. While GMP is widely implemented, the available studies highlight significant gaps in evidence, suggesting that the benefits of these programs remain unclear and that further high-quality research is needed to evaluate their role in addressing undernutrition and promoting healthy development,96 which may help reshape programs, policies, and strategies to address the needs better.

Ready-to-Use Therapeutic Foods (RUTFs) such as Plumpy’Nut for the management of children with severe acute undernutrition have proven effective in restoring normal nutritional status in the majority.97 Parental or caregiver education on proper feeding practices improves children’s nutritional intake.98 Cash transfer programs to support food security in low-income families put power in the hands of caregivers to diversify dietary intake, leading to improved nutritional status.99 Social and economic empowerment to improve access to better nutrition presents a wholesome solution to address neurodevelopment. Focusing on nutrition as an independent factor downplays the impact it has on the social environment and vice versa.

Large-scale fortification of food products further widens the reach of nutritional benefits without increasing the financial and decision-making burden to individual members of society.100 Such law-bound interventions (e.g., iron to flour, vitamin A to cooking oil and zinc to prevent deficiencies) have a broad reach[100]. Universal Salt Iodization has also significantly reduced the prevalence of iodine deficiency and associated cretinism.101 Nutrition-sensitive agriculture leads to dietary diversification for children with a potential long-term impact on anthropometric markers of nutritional status, such as stunting 102].