Effects of Protein Deficiency on Perinatal and Postnatal Health Outcomes

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads to metabolic disease, and it identifies the mechanisms that have been elucidated, to date. These include alterations in transcriptional and epigenetic mechanisms, as well as indirect means such as endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, nutritional and pharmaceutical interventions are highlighted to illustrate that the plasticity of the underdeveloped organs during perinatal life can be exploited to prevent onset of long-term metabolic disease

Polymorphisms in genes involved in folate metabolism as risk factors for oedematous severe childhood malnutrition: a hypothesis-generating study.

BACKGROUND: Severe childhood malnutrition (SCM) occurs as both oedematous and non-oedematous syndromes. The reasons why some children develop oedematous SCM (OSCM) have remained elusive but differences in clinical presentation among malnourished children from similar backgrounds suggests that there might be inter-individual variation in susceptibility to OSCM. AIM: To estimate the strength of the association between variants of three genes involved in folate/methyl group metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine beta-synthase (CBS)] and risk of OSCM. METHODS: Patients previously admitted to the Tropical Metabolism Research Unit (TMRU) for treatment of either OSCM (cases, n = 74) or non-oedematous SCM (NOSCM, controls, n = 50) were recruited. Genotypes at four sites within the three genes (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) were determined using PCR-based assays. RESULTS: The MTHFR 677T [odds ratio (OR) 0.63, 95% CI 0.2-1.7] and MTR 2756G (OR 0.74, 95% CI 0.4-1.4) alleles were associated with moderate reduction in risk of OSCM whereas the CBS 844ins68 allele (OR 1.4, 0.7-2.4) was associated with an increased risk. None of these risks was significant at the 5% level. CONCLUSIONS: Genetic variation within folate/methyl group metabolic pathways might have a small but potentially important influence on risk of OSCM. Additional, larger data-sets will be required to test the specific hypotheses (about the putative effect size and direction of association) generated in this preliminary study. Such observations have the potential to improve our understanding of the pathogenesis of clinical heterogeneity in severe malnutrition

Predictors of physical activity energy expenditure in Afro-Caribbean children

Background/Objectives: We hypothesized that maternal size during pregnancy and birth size are determinants of childhood physical activity energy expenditure (PAEE). Also, childhood PAEE is inversely related to adiposity and levels of cardiovascular risk factors.Subjects/Methods: The Vulnerable Windows Cohort Study is a longitudinal observational study of 569 Afro-Jamaican mothers recruited from the first trimester and their offspring. Anthropometry, bioelectrical impedance, PAEE (using the Actical monitor) and cardiovascular risk factors (blood pressure, fasting glucose, insulin and lipids) were measured in 124 boys and 160 girls at a mean age of 13.2 years.Results: Boys had more fat-free mass (FFM) and expended more energy than girls (12.3±3.3 vs 9.6±2.8?kcal/kg/day; P&lt;0.001). Maternal weight was associated with child's PAEE (r=0.29; P&lt;0.001). PAEE was not significantly associated with birth weight. Maternal weight, after adjusting for child's age and sex, was positively associated with the child's FFM, fat mass and %fat (P-values 0.01). Age- and sex-adjusted PAEE was positively associated with FFM, fat mass and % fat (P-values &lt;0.001), but not after adjusting for current weight. Age- and sex-adjusted PAEE was positively associated with triglycerides, insulin and systolic blood pressure (P-values &lt;0.05), but not after adjusting for weight and height. PAEE was associated with fasting glucose after controlling for age, sex, weight and height (r=?0.12; P=0.02).Conclusions: Maternal size, but not birth weight, is a determinant of childhood PAEE. PAEE is not strongly associated with childhood body composition, but is inversely related to fasting glucose concentration.<br/