Eating for TwoMetabolic Imprinting:The Role Maternal Health Status and Prenatal, Perinatal, and Postnatal Nutrition Habits Play in the Development of Chronic Diseases into Adulthood for InfantsAbstract Background– There is an increasing collection of research that supports data that suggest that the amount and quality of nutrients that is available and accessible during perinatal periods of development can increase the chances of developing many different adult-onset chronic diseases for affected infants (6). Metabolic imprinting refers to the effects of early life exposures (during pregnancy and infancy) on the development of chronic diseases, including obesity and diabetes. Studies in both humans and animals have shown that the events during gestation and early postnatal stages may have long term consequences for health.  Fetal and maternal undernutrition is linked to an increased risk of cardiovascular disease, obesity, type II diabetes and hypertension, amongst other diseases.Objective– The objective of this research paper is to determine and explore the link between maternal and infant nutrition and long-term health of the infant. Also, the influence pre- and post-natal nutrition has on the development of chronic disease into adulthood.Methods- The articles selected for review to aid in the substance and credibility of this research paper were chosen using inclusion and exclusion criteria listed in a table located in the corresponding section below.Results- The result of the literature review consist of evidence that maternal health status as well as perinatal nutrition aid in the metabolic imprinting and development of chronic disease in adulthood. Majority of chronic diseases can be avoided with educating individual on the consequence over or undernutrition has on the long term health of affected infants.Conclusion- The literature suggests that maternal and pediatric nutrition and genetic makeup play a critical role in the metabolic imprinting and development of chronic diseases in adulting. Also, inclusion of vitamin and mineral supplementation as well as deletion of certain parentally expressed genes can affect the development of chronic diseases and related health problems.IntroductionThe rise in obesity among US adults and children alike and the cost associated with it is astronomical. The increasing number of obese children who remain obese into adulthood is a public health issue that needs to be addressed and intervened upon. The subsequent generations are expected to have a shorter life expectancy partly due to increased incidence of chronic diseases such as obesity and diabetes. (Abbott Nutrition, ILSI Europe Metabolic Imprinting Task Force). Studies show that obesity and related health problems can be identified as early as gestation in many cases. There are maternal conditions and situations that increase the likelihood of infants to develop chronic diseases in adulthood.Established conditions in the mother such as diabetes, obesity, and undernutrition are associated with the development of obesity in their children.  This association is even more prevalent in genetically predisposed individuals. (The Obesity Epidemic: Metabolic Imprinting on Genetically Susceptible Neural Circuits, 2012). Presenting a clear and concise description of how crucial the link between nutrition and an individual’s health is to at risk populations will ultimately reverse the trend we see in metabolic imprinting and its link to health problems such as Obesity, Type II diabetes, Cardiovascular Disease and other metabolic disorders. This research paper provides us with the opportunity to inform colleagues and other healthcare professionals about the causation between maternal and pediatric nutrition status and the metabolic imprinting of chronic diseases.Throughout the research process I reviewed many articles and discovered some knowledge gaps in the research that has already been done on Metabolic Imprinting, In reviewing the 5 original research article I selected, some of the five articles included were developed in other countries or referred to animal studies done were human outcomes were theorized from those results; therefore, this raises questions regarding the generalizability of results to the entire US population and human studies.The purpose of this research paper is to determine and explore the association between maternal and infant nutrition and long-term health of the infant. Also, the influence pre- and post-natal nutrition has on the development of chronic disease into adulthood. Within this study, I aim to determine who, what, when, where, and why of Metabolic Imprinting using the PICO format.Review of literature/BackgroundThere is an increasing collection of research that supports data that suggest that the amount and quality of nutrients that is available and accessible during perinatal periods of development can increase the chances of developing many different adult-onset chronic diseases for affected infants  (6). Metabolic imprinting refers to the effects of early life exposures (during pregnancy and infancy) on the development of chronic diseases, including obesity and diabetes. Studies in both humans and animals have shown that the events during gestation and early postnatal stages may have long term consequences for health.  Fetal and maternal undernutrition is linked to an increased risk of cardiovascular disease, obesity, type II diabetes and hypertension, amongst other diseases. Depending on the case, the evidence can be incomplete and associative while in others, the causality is between maternal and early nutrition in the infant and health in adolescence and adulthood is very clear.For  clarification, there has been some confusion between Metabolic Imprinting and Metabolic Programing. Metabolic imprinting is not the same as metabolic programing. Both Metabolic programming and metabolic imprinting describe early life events that later have an impact on physiological outcomes. Metabolic Programming can be defined as a vigorous process that depend on critical window to take effect. Metabolic imprinting can be more strictly associated with imprinting at the genomic level. Metabolic Imprinting deals more with epigenetics, which is the study of changes in organisms caused by modification of gene expression rather than alteration of the genetic code itself (Genetics Digest).The result of Metabolic Imprinting  and how it affects epigenetics can lead to the development of chronic diseases and metabolic disorders. A chronic disease is a disease that persists for a long time; 3 months or more, by the definition provided by the U.S. National Center for Health Statistics. Because chronic diseases generally cannot be prevented by vaccines or cured by medication and they don’t go away on their own, it is important to take preventative measures and address the risk factors associated with them. All of the articles reviewed for this research paper explore the connection between Metabolic imprinting and development of obesity and other related chronic diseases such as cardiovascular disease, diabetes, and high blood pressure.MethodsThe method used to select the five original research articles were simple. The goal was to collect articles that built upon each other. I wanted to have articles that provided information on different study subjects and different components of Metabolic Imprinting. The table below contains a break down of the selection process for the original research articles utilized in this paper.Table I. This table is a break down of the criteria used in the search plan of the original research articles and the results of the search.Search Plan and ResultsQuestionDoes Metabolic Imprinting increase the incidence of developing a chronic disease later in life? Is there a strong association between maternal and perinatal nutrition and development of chronic disease in adulthood?Date of Literature Reiew?       November 5, 2018Inclusion Criteria?       Age: Adults 18+?       Setting: Outpatient?       Health Status: any?       Nutrition Related Problem: Healthy adults and adults with chronic diseases or conditions such as obesity, hypertension, CVD, diabetes, elevated cholesterol.?       Study design: RCT, CCT, Cohort, Crossover Study?       Size of study group: 10 or more individuals in each study group?       Year range: 2000-2018?       Authorship: Different authors for each article. If same author, most recent research article on topic will be used?       Language: Limited to articles published in EnglishExclusion Criteria?       Age:<18?       Setting:?       Health Status:  Poor prognosis?       Nutrition Related Problem: Other diseases or critically ill?       Study design:?       Size of study group: < 10 participants in each study group?       Year range: Prior to 200?       Authorship: Studies by same author with similar content?       Language: Articles not published in EnglishSearch Terms: Search VocabularyHealth Conditions?       Diabetes/diabetic?       Obesity/ obese/overweight?       Cardiovascular Disease?       Hypertension/hypertensive?       CholesterolInterventions?       Nutrition Plan?       Education?       Vitamin Supplementation?       Genetic deletionType of Study Design?       RCT, CCT, Cohort, Crossover StudyElectronic Database?       Pub MEDTable II. Five original research articles and subject, methods and type of research used in each studyArticleSubjectMethodType of ResearchHillier et al.9,439 women in a large multiethnic U.S. population universally screened for GDM, whose children had weight measured between ages 5 and 7 years.Universal gestational diabetes mellitus (GDM) screeningMeasured weight in offspring (n = 9,439) was ascertained 5–7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963–1994 standard) and then classified by maternal positive GCT and OGTT resultsRandomized Control Trial using Cohort studyKhulan et al.Non-pregnant women aged between 17 and 45 years from Kiang West, The GambiaNon-pregnant women took either UNIMMAP tablets [containing a balanced combination of 14 vitamins and minerals, specially formulated for use in pregnancy or placebo, and once pregnancy was confirmed (averaging 9.5 week gestation), all women were switched to receive FeFol tabletsUmbilical cord and peripheral blood DNA samples from offspring born to women who took part in the micronutrient supplementation trial were analyzed using the Human Methylation 27 BeadchipsRandomized, Double Blind Control Trial using Cohort study Bayley et al.81 full-term healthy neonates at 4 months or at 11 and 12 months of ageCentrifuged and fractionated blood samples were used to determine cholesterol biosynthesis measurement, as well as plasma lipid concentrations. A prospective, double-blind, partially randomized, crossover studyMillership et al.MiceClassical imprinting-related phenotypes were studied to further explore the potential role of Nnat in the regulation of body weight and adiposity.Independent cohort studyVan de Pette et al.MiceGlucose Tolerance TestInsulin Tolerance TestIndependent cohort study ResultsHillier et al. aimed to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. The results found suggested that there is an association with maternal glucose levels and obesity in childhood. A positive trend was seen in the results. As maternal glucose levels increased, childhood obesity in ages 5-7 increased (P0.0001; 85th and 95th percentiles) in the children of those mothers. The trend remained the same even after potential maternal co founders were applied to the study. The results across multiple ethnicities within the US population confirm that increasing maternal hyperglycemia in pregnancy increases the risk of childhood obesity. Further research needs to be conducted to determine if treatment of Gestational Diabetes Mellitus may be a risk factor  that can be adapted to reduce the incidence of childhood obesity. Khulan et al. aimed to investigates and assess the effect of maternal supplementation on the offspring of women in rural Gambia. The result of this study found that micronutrient supplementation in early pregnancy is associated with methylation changes, specifically demethylation which they can detect through cord blood and early infancy DNA. Demethylation occurs when glucose levels are low and methylation occurs when glucose levels are high. Also, postnatal changes involve many more genes that highlight differences between the supplemented and placebo cohorts that potentially have a bearing on respective disease outcomes. The data from these pilots suggest that periconceptional nutrition in humans is an important determinant in patterns of addition and subtraction of methyl groups in the DNA of newborns. It also may influence postnatal developmental patterns, linking early nutrition with disease risk. Nutrient supplementation was found to decrease risk of developing health problems and chronic diseases.Bayley et al. aimed to study cholesterol synthesis in the subject group to examine the response of cholesterol homeostasis to long-term dietary cholesterol supplementation to prevent CVD. Results showed that variation is seen between different subject groups, but early supplementation of formula enriched with cholesterol, with levels similar to the cholesterol found in breast milk, does not demonstrate difference in cholesterol central pool synthesis rates. Recent discoveries are in favor of the notion that supplementation of cholesterol in the diet effects a minimal alteration in metabolized cholesterol later in infancy. The data in this study indicate that cholesterol synthesis and circulatory levels are not very sensitive to altered cholesterol supplementation in infants at 1 year of age, with no regard to  cholesterol intakes in early life.Millership et al. aimed to study the role Neuronatin (Nnat), a paternally expressed imprinted gene, deletion plays in causing postnatal growth restriction and adult obesity in 129S2/Sv mice. Results from this study show that mice with Nnat deficiency or deletion experience leptin resistance and hyperphagia. With leptin resistance, your leptin is high, meaning you are overweight, but the brain doesn’t recognize that the body is overweight. Hyperphagia is excessive hunger and an atypical oral consumption of solids. Also, deletion of the Nnat heighten age and diet induced obesity. The gene Nnat plays a key role in postnatal growth, adult energy equilibrium, and the development of obesity, but this role is dependent upon genetic background.Van de Pette et al. aimed to study Cyclin dependent kinase inhibitor 1c (Cdkn1c), a maternally expressed imprinted gene, and its role in promoting brown adipose tissue, good fat, formation in mice. Also, to explore its protective factors against age-related weight gain, diet-induced obesity, and glucose and insulin intolerance. Brown adipose tissue function is to convert nutrients into body heat. Newborns have high levels of brown adipose tissue. The results found that a two-fold increase in the expression of Cdkn1c provides ample protection  against age-related weight gain, glucose, and insulin intolerance. The study also provides evidence that a deficiency in the imprinting Cdkn1c provides protection against diet-induced obesity. The data from this study demonstrates the serious role that this maternally expressed gene plays in regulation of the adult adipose tissue. Also, how a moderate alterations in the expression of this gene can protect against obesity fostered by age and diet. Mice with a single extra copy of Cdkn1c are able to resist both age and diet-driven weight gain and maintain a healthier management of glucose than matched controls.Maternal and Perinatal nutritional influence on development of chronic disease in offspring into adulthood. Utilizing the five original research articles presented above and supplemental materials, answers were found to the research questions formulated using the PICO format. These answers are tailored to the population that is most at risk due to social and environmental factors. The population at greatest risk are mothers and babies in low SES communities. This is because they lack adequate accessibility to health care facilities and availability of adequate nutrient rich foods. There is also the possibility that they are not educated on healthy eating and how their health and eating habits during pregnancy can affect the health of their child into adulthood. The behaviors that need to be addressed are factors that lead to development of chronic diseases into adulthood for the infant. Interventions need to be made to address maternal over- and undernutrition during pregnancy, as well as in the infant after birth. Both over- and undernutrition during pregnancy have effects on the infant. Both of these extremes can lead to childhood obesity which can lead to obesity, diabetes, and CVD in adulthood. This data elevates the evidence behind the need for a healthy diet during pregnancy. Within this target population, cultural factors also play a role in eating habits and rational behind certain behaviors. With interventions targeting a change in those behavior, educating mothers on the consequences of unhealthy lifestyles and the implications on adult life for their children, and encouragement to take advantage of healthcare services will result in the outcomes we want to see. These outcomes are reduced incidence in development of metabolic disorders such as obesity, diabetes, and CVD in adulthood.Table III. Breakdown of the PICO format and its relation to the topic of Metabolic Imprinting and development of chronic diseases.PopulationInterventionComparison InterventionOutcomesMetabolic ImprintingMothers in low SES communities who have experienced over or undernutrition, diabetes, gestational diabetes, and obesity during pregnancy.Infants in these communities who have experienced over or undernutrition, diabetes, gestational diabetes, and obesity pre-, peri-, and postnatally.Over- and UndernutritionHealthy and adequate nutritional intakeReduce incidence in development of metabolic disorders such as obesity, diabetes, and CVDThough research is being done, there are some gaps in the research for the target population at risk. Some  of the five articles included were developed in other countries or referred to animal studies. From these animal studies human outcomes were theorized. This raises questions regarding the generalizability of results to the entire US population and human studies. Strengths of the articles are that each study analyzed a different perinatal factors that aid in the metabolic imprinting of chronic disease into adulthood. They all have different study subjects and research factors which makes for diverse data and outcomes. On the other hand, these article do present some limitations. Because the articles all have different study subjects and research factors, there is no common thread that links the research other than they all aim to determine the link between perinatal nutrition and other factors and development of metabolic syndromes in adulthood. Considering that some of the studies were done in different countries, it would be ideal to replicate these studies in the united states.  Also, if the research done on the mice in the last two articles was compared to observations in consenting human subjects.ConclusionThis paper focused on reviewing five primary research articles that examined the association between metabolic imprinting and development of chronic diseases in adulthood such as Obesity, CVD, and Diabetes. Out of the five papers included in this review, three papers found evidence linking maternal and perinatal conditions to development of metabolic disorders. They also explore supplementation to reduce the incidence of these chronic diseases. Two papers found linkages between parentally expressed genes and development of obesity and diabetes in mice. Overall, the literature suggests that maternal and pediatric nutrition and genetic makeup play a critical role in the metabolic imprinting and development of chronic diseases in adulting. Also, inclusion of vitamin and mineral supplementation as well as deletion of certain parentally expressed genes can affect the development of chronic diseases and related health problems. A recommendation to consider is to provide programs that educate mothers on how their nutrition during pregnancy and the nutrition of the child in the early ages has an affect on the development of obesity and chronic diseases into adulthood for the child. ReferencesTeresa A. Hillier, Kathryn L. Pedula, Mark M. Schmidt, Judith A. Mullen, Marie-Aline Charles, David J. Pettitt; Childhood Obesity and Metabolic Imprinting Diabetes Care Sep 2007, 30 (9) 2287-2292; DOI: 10.2337/dc06-2361Khulan, B., Cooper, W. N., Skinner, B. M., Bauer, J., Owens, S., Prentice, A. M., . . . Affara, N. A. (2012). 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