Maternal malnutrition and anaemia in India: dysregulations leading to the ‘thin-fat’ phenotype in newborns

Abstract

Maternal and child malnutrition and anaemia remain the leading factors for health loss in India. Low birth weight (LBW) offspring of women suffering from chronic malnutrition and anaemia often exhibit insulin resistance and infantile stunting and wasting, together with increased risk of developing cardiometabolic disorders in adulthood. The resulting self-perpetuating and highly multifactorial disease burden cannot be remedied through uniform dietary recommendations alone. To inform approaches likely to alleviate this disease burden, we implemented a systems-analytical approach that had already proven its efficacy in multiple published studies. We utilised previously published qualitative and quantitative analytical results of rural and urban field studies addressing maternal and infantile metabolic and nutritional parameters to precisely define the range of pathological phenotypes encountered and their individual biological characteristics. These characteristics were then integrated, via extensive literature searches, into metabolic and physiological mechanisms to identify the maternal and foetal metabolic dysregulations most likely to underpin the ‘thin-fat’ phenotype in LBW infants and its associated pathological consequences. Our analyses reveal hitherto poorly understood maternal nutrition-dependent mechanisms most likely to promote and sustain the self-perpetuating high disease burden, especially in the Indian population. This work suggests that it most probably is the metabolic consequence of ‘ill-nutrition’ – the recent and rapid dietary shifts to high salt, high saturated fats and high sugar but low micronutrient diets – over an adaptation to ‘thrifty metabolism’ which must be addressed in interventions aiming to significantly alleviate the leading risk factors for health deterioration in India.

Association between maternal hyperglycemia in pregnancy and offspring anthropometry in early childhood: the pandora wave 1 study

“…Greater mean suprailiac skinfold thickness in children exposed to GDM, despite lower mean weight, BMI and circumferences, may reflect altered fat distribution, and have implications for future metabolic risk [ 28 ]. This is consistent with the “thin-fat” phenotype described in other populations, where there is preferential growth of adipose tissue compared to fat-free lean mass in children exposed to hyperglycemia in-utero [ 40 – 42 ], compounded by maternal malnutrition [ 43 ]. Children exposed to the double burden of malnutrition at different points during pregnancy and their lifecourse, of both nutritional deficiency and dietary excess, are also known to have increased cardiometabolic risk [ 44 ].…”

“…Previous studies have indicated that childhood skinfold thicknesses and circumferences can serve as proxy indicators of lipid and insulin dysregulation, and that differences in fat deposition, as reflected by BMI, circumferences and fat free mass, can be used to assess cardiometabolic risk [ 28 , 41 , 56 ]. This may indicate higher cardiometabolic risk in First Nations children even from early childhood, consistent with studies from other populations describing the ‘thin-fat’ phenotype [ 41 , 43 ].…”

Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomised controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)

“…8,9 Deficiency of these nutrients in the diet of a pregnant mother manifests in adverse effects on the fetus, including developmental defects (e.g., neural tube defects), growth abnormalities (growth restriction), 10 and are also associated with an increased risk of non-communicable diseases in later life. 11,12…”

“…8,9 Deficiency of these nutrients in the diet of a pregnant mother manifests in adverse effects on the fetus, including developmental defects (e.g., neural tube defects), growth abnormalities (growth restriction), 10 and are also associated with an increased risk of non-communicable diseases in later life. 11,12 The Pune Maternal Nutrition Study (PMNS) is a communitybased pre-conceptional birth cohort started in 1993 based on Prof. Barker's theory. 13 It was set up in six villages near Pune to study maternal nutritional determinants of fetal growth and to study life-course evolution of the risk of diabetes and related traits in the offspring.…”

Differential expression of genes influencing mitotic processes in cord blood mononuclear cells after a pre-conceptional micronutrient-based randomized controlled trial: Pune Rural Intervention in Young Adolescents (PRIYA)

“…Deficiency of these nutrients in the diet of a pregnant mother manifests in adverse effects on the fetus, including developmental defects (neural tube defects, midline congenital defects etc. ), growth abnormalities (growth restriction) (Gernand et al, 2016), and are also associated with an increased risk of non-communicable diseases in later life (Deshmukh et al, 2013; Pandit et al, 2021).…”