Moderate maternal nutrient restriction during pregnancy occurs in both developing and developed countries. In addition to poverty, maternal dieting, teenage pregnancy, and uterine vascular problems in older mothers are causes of decreased fetal nutrition. We evaluated the impact of global 30% maternal nutrient reduction (MNR) on early fetal baboon brain maturation. MNR induced major cerebral developmental disturbances without fetal growth restriction or marked maternal weight reduction. Mechanisms evaluated included neurotrophic factor suppression, cell proliferation and cell death imbalance, impaired glial maturation and neuronal process formation, down-regulation of gene ontological pathways and related gene products, and up-regulated transcription of cerebral catabolism. Contrary to the known benefits from this degree of dietary reduction on life span, MNR in pregnancy compromises structural fetal cerebral development, potentially having an impact on brain function throughout life.oderate malnutrition during pregnancy is widespread in both developing and industrialized countries. Worldwide, 852 million people experienced food insecurity in 2004 (1) and 35-40% of children experience moderate malnutrition (2). In industrialized countries, maternal lifestyle, in which dieting (including global food reduction) is used for cosmetic reasons, is a common cause of moderate malnutrition. Recently, one study has shown that most women do not improve their dietary and lifestyle patterns in pregnancy (3). Decreased nutrient delivery to the fetus also occurs in teenage pregnancy (4) and during pregnancy in women over 35 y of age (5). Severe global reduction in nutrition during pregnancy has long been known to result in fetal growth restriction and to cause permanent brain dysfunction, especially cognitive and behavior deficits (6-10). In rodents, these deficits are accompanied by alterations of neuronal excitability as well as structural changes in the developing and adult brain (11,12). In contrast, effects of moderate maternal global reduction in nutrition on the fetus have been poorly examined. It is often assumed that moderate degrees of maternal nutrient reduction (MNR) are without unwanted consequences because it has generally been considered that the mother prioritizes fetal nutrient supply at the expense of her own needs, and brain growth is assumed to be spared from the other fetal effects of moderate decreases in fetal nutrient availability. This concept no longer appears to be tenable. Several rodent studies have demonstrated significant changes in fetal body and brain composition, often in the absence of major reduction of birth weight following poor maternal nutrition during pregnancy (11,12). In relation to the changes in brain development that we report here in a nonhuman primate species, evidence is accumulating that birth weight at the lower end of the normal range is associated with impaired higher mental function in later life (5,13,14).We addressed effects of 30% global moderate MNR on early fetal cereb...