1  4202 101 METABOLIC SYNDROME IN CHILDREN BORN SMALL-FOR-GESTATIONAL AGE. BEING BORN SMALL-FOR-GESTATIONAL AGE AND A RAPID INCREASE IN WEIGHT DURING EARLY CHILDHOOD AND INFANCY HAS BEEN STRONGLY LINKED WITH CHRONIC DISEASES, INCLUDING METABOLIC SYNDROME, WHICH HAS BEEN RELATED TO INTRAUTERINE LIFE ENVIRONMENT AND LINKED TO EPIGENETIC FETAL PROGRAMMING. METABOLIC SYNDROME INCLUDES WAIST CIRCUMFERENCE >/= 90(TH) PERCENTILE FOR AGE, SEX AND RACE, HIGHER LEVELS OF BLOOD PRESSURE, TRIGLYCERIDES AND FASTING GLUCOSE, AND LOW LEVELS OF HDL-CHOLESTEROL. INSULIN RESISTANCE MAY BE PRESENT AS EARLY AS 1 YEAR OF AGE, AND OBESITY AND/OR TYPE 2 DIABETES ARE MORE PREVALENT IN THOSE BORN SGA THAN THOSE BORN AGA. THE PROGRAMMING OF ADAPTIVE RESPONSES IN CHILDREN BORN SGA INCLUDES AN ASSOCIATION WITH INCREASED BLOOD PRESSURE, CHANGES IN ENDOTHELIAL FUNCTION, ARTERIAL PROPERTIES AND CORONARY DISEASE. EARLY INTERVENTIONS SHOULD BE DIRECTED TO APPROPRIATE MATERNAL NUTRITION, BEFORE AND DURING PREGNANCY, PROMOTION OF BREAST FEEDING, AND PREVENTION OF RAPID WEIGHT GAIN DURING INFANCY, AND TO PROMOTE A HEALTHY LIFESTYLE.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
2  2757  26 EXPRESSION OF EPIGENETIC MACHINERY GENES IS SENSITIVE TO MATERNAL OBESITY AND WEIGHT LOSS IN RELATION TO FETAL GROWTH IN MICE. BACKGROUND: MATERNAL OBESITY IMPACTS FETAL GROWTH AND PREGNANCY OUTCOMES. TO COUNTERACT THE DELETERIOUS EFFECTS OF OBESITY ON FERTILITY AND PREGNANCY ISSUE, PRECONCEPTIONAL WEIGHT LOSS IS RECOMMENDED TO OBESE WOMEN. WHETHER THIS WEIGHT LOSS IS BENEFICIAL/DETRIMENTAL FOR OFFSPRING REMAINS POORLY EXPLORED. EPIGENETIC MECHANISMS COULD BE AFFECTED BY MATERNAL WEIGHT CHANGES, PERTURBING EXPRESSION OF KEY DEVELOPMENTAL GENES IN THE PLACENTA OR FETUS. OUR AIM WAS TO INVESTIGATE THE EFFECTS OF CHRONIC MATERNAL OBESITY ON FETO-PLACENTAL GROWTH ALONG WITH THE UNDERLYING EPIGENETIC MECHANISMS. WE ALSO TESTED WHETHER PRECONCEPTIONAL WEIGHT LOSS COULD ALLEVIATE THESE EFFECTS. RESULTS: FEMALE MICE WERE FED EITHER A CONTROL DIET (CTRL GROUP), A HIGH-FAT DIET (OBESE (OB) GROUP), OR A HIGH-FAT DIET SWITCHED TO A CONTROL DIET 2 MONTHS BEFORE CONCEPTION (WEIGHT LOSS (WL) GROUP). AT MATING, OB FEMALES PRESENTED AN OBESE PHENOTYPE WHILE WL FEMALES NORMALIZED METABOLIC PARAMETERS. AT EMBRYONIC DAY 18.5 (E18.5), FETUSES FROM OB FEMALES PRESENTED FETAL GROWTH RESTRICTION (FGR; -13 %) AND 28 % OF THE FETUSES WERE SMALL FOR GESTATIONAL AGE (SGA). FETUSES FROM WL FEMALES NORMALIZED THIS PHENOTYPE. THE EXPRESSION OF 60 EPIGENETIC MACHINERY GENES AND 32 METABOLIC GENES WAS MEASURED IN THE FETAL LIVER, PLACENTAL LABYRINTH, AND JUNCTIONAL ZONE. WE REVEALED 23 GENES ALTERED BY MATERNAL WEIGHT TRAJECTORIES IN AT LEAST ONE OF THREE TISSUES. THE FETAL LIVER AND PLACENTAL LABYRINTH WERE MORE RESPONSIVE TO MATERNAL OBESITY THAN JUNCTIONAL ZONE. ONE THIRD (18/60) OF THE EPIGENETIC MACHINERY GENES WERE DIFFERENTIALLY EXPRESSED BETWEEN AT LEAST TWO MATERNAL GROUPS. INTERESTINGLY, GENES INVOLVED IN THE HISTONE ACETYLATION PATHWAY WERE PARTICULARLY ALTERED (13/18). IN OB GROUP, LYSINE ACETYLTRANSFERASES AND BROMODOMAIN-CONTAINING PROTEIN 2 WERE UPREGULATED, WHILE MOST HISTONE DEACETYLASES WERE DOWNREGULATED. IN WL GROUP, THE EXPRESSION OF ONLY A SUBSET OF THESE GENES WAS NORMALIZED. CONCLUSIONS: THIS STUDY HIGHLIGHTS THE HIGH SENSITIVITY OF THE EPIGENETIC MACHINERY GENE EXPRESSION, AND PARTICULARLY THE HISTONE ACETYLATION PATHWAY, TO MATERNAL OBESITY. THESE OBESITY-INDUCED TRANSCRIPTIONAL CHANGES COULD ALTER THE PLACENTAL AND THE HEPATIC EPIGENOME, LEADING TO FGR. PRECONCEPTIONAL WEIGHT LOSS APPEARS BENEFICIAL TO FETAL GROWTH, BUT SOME EFFECTS OF PREVIOUS OBESITY WERE RETAINED IN OFFSPRING PHENOTYPE.	2016	
                                                                                                                                                                                                                            
3  4107  33 MECHANISMS AFFECTING NEUROENDOCRINE AND EPIGENETIC REGULATION OF BODY WEIGHT AND ONSET OF PUBERTY: POTENTIAL IMPLICATIONS IN THE CHILD BORN SMALL FOR GESTATIONAL AGE (SGA). SIGNALING PEPTIDES PRODUCED IN PERIPHERAL TISSUES SUCH AS GUT, ADIPOSE TISSUE, AND PANCREAS COMMUNICATE WITH BRAIN CENTERS, SUCH AS HYPOTHALAMUS AND HINDBRAIN TO MANAGE ENERGY HOMEOSTASIS. THESE REGULATORY MECHANISMS OF ENERGY INTAKE AND STORAGE HAVE EVOLVED DURING LONG PERIODS OF HUNGER IN THE EVOLUTION OF MAN TO PROTECT THE SPECIES FROM EXTINCTION. IT IS NOW CLEAR THAT THESE CIRCUITRIES ARE INFLUENCED BY PRENATAL AND POSTNATAL ENVIRONMENTAL FACTORS INCLUDING ENDOCRINE DISRUPTIVE CHEMICALS. HYPOTHALAMIC APPETITE REGULATORY SYSTEMS DEVELOP AND MATURE IN UTERO AND EARLY INFANCY, AND INVOLVE SIGNALING PATHWAYS THAT ARE IMPORTANT ALSO FOR THE REGULATION OF PUBERTY ONSET. RECENT STUDIES IN HUMANS AND ANIMALS HAVE SHOWN THAT METABOLIC PATHWAYS INVOLVED IN REGULATION OF GROWTH, BODY WEIGHT GAIN AND SEXUAL MATURATION ARE LARGELY AFFECTED BY EPIGENETIC PROGRAMMING THAT CAN IMPACT BOTH CURRENT AND FUTURE GENERATIONS. IN PARTICULAR, INTRAUTERINE AND EARLY INFANTILE DEVELOPMENTAL PHASES OF HIGH PLASTICITY ARE SUSCEPTIBLE TO FACTORS THAT AFFECT METABOLIC PROGRAMMING THAT THEREFORE, AFFECT METABOLIC FUNCTION THROUGHOUT LIFE. IN CHILDREN BORN SMALL FOR GESTATIONAL AGE, POOR NUTRITIONAL CONDITIONS DURING GESTATION CAN MODIFY METABOLIC SYSTEMS TO ADAPT TO EXPECTATIONS OF CHRONIC UNDERNUTRITION. THESE CHILDREN ARE POTENTIALLY POORLY EQUIPPED TO COPE WITH ENERGY-DENSE DIETS AND ARE POSSIBLY PROGRAMMED TO STORE AS MUCH ENERGY AS POSSIBLE, LEADING TO LATER OBESITY, METABOLIC SYNDROME, DISTURBED REGULATION OF NORMAL PUBERTY AND EARLY ONSET OF CARDIOVASCULAR DISEASE. MOST CASES OF DISTURBED ENERGY BALANCE ARE LIKELY A RESULT OF A COMBINATION OF GENETICS, EPIGENETICS AND ENVIRONMENT. THIS REVIEW WILL DISCUSS POTENTIAL MECHANISMS LINKING INTRAUTERINE GROWTH RETARDATION WITH CHANGES IN GROWTH, ENERGY HOMEOSTASIS AND SEXUAL MATURATION.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
4  1152  31 CONSEQUENCES OF EARLY LIFE PROGRAMING BY GENETIC AND ENVIRONMENTAL INFLUENCES: A SYNTHESIS REGARDING PUBERTAL TIMING. SEXUAL MATURATION IS CLOSELY TIED TO GROWTH AND BODY WEIGHT GAIN, SUGGESTING THAT REGULATIVE METABOLIC PATHWAYS ARE SHARED BETWEEN SOMATIC AND PUBERTAL DEVELOPMENT. THE PRE- AND POSTNATAL ENVIRONMENT AFFECTS BOTH GROWTH AND PUBERTAL DEVELOPMENT, INDICATING THAT COMMON PATHWAYS ARE AFFECTED BY THE ENVIRONMENT. INTRAUTERINE AND EARLY INFANTILE DEVELOPMENTAL PHASES ARE CHARACTERIZED BY HIGH PLASTICITY AND THEREBY SUSCEPTIBILITY TO FACTORS THAT AFFECT METABOLIC FUNCTION AS WELL AS RELATED REPRODUCTIVE FUNCTION THROUGHOUT LIFE. IN CHILDREN BORN SMALL FOR GESTATIONAL AGE, POOR NUTRITIONAL CONDITIONS DURING GESTATION CAN MODIFY METABOLIC SYSTEMS TO ADAPT TO EXPECTATIONS OF CHRONIC UNDERNUTRITION. THESE CHILDREN ARE POTENTIALLY POORLY EQUIPPED TO COPE WITH ENERGY-DENSE DIETS AND ARE POSSIBLY PROGRAMMED TO STORE AS MUCH ENERGY AS POSSIBLE, CAUSING RAPID WEIGHT GAIN WITH THE RISK FOR ADULT DISEASE AND PREMATURE ONSET OF PUBERTY. ENVIRONMENTAL FACTORS CAN CAUSE MODIFICATIONS TO THE GENOME, SO-CALLED EPIGENETIC CHANGES, TO AFFECT GENE EXPRESSION AND SUBSEQUENTLY MODIFY PHENOTYPIC EXPRESSION OF GENOMIC INFORMATION. EPIGENETIC MODIFICATIONS, WHICH OCCUR IN CHILDREN BORN SMALL FOR GESTATIONAL AGE, ARE THOUGHT TO UNDERLIE PART OF THE METABOLIC PROGRAMMING THAT SUBSEQUENTLY EFFECTS BOTH SOMATIC AND PUBERTAL DEVELOPMENT.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
5  3578  38 IMPACT OF PARENTAL OVER- AND UNDERWEIGHT ON THE HEALTH OF OFFSPRING. PARENTAL EXCESS WEIGHT AND ESPECIALLY PREGESTATIONAL MATERNAL OBESITY AND EXCESSIVE WEIGHT GAIN DURING PREGNANCY HAVE BEEN RELATED TO AN INCREASED RISK OF METABOLIC (OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, METABOLIC SYNDROME) AND NONMETABOLIC (CANCER, OSTEOPOROSIS, ASTHMA, NEUROLOGIC ALTERATIONS) DISEASES IN THE OFFSPRING, PROBABLY MEDIATED BY EPIGENETIC MECHANISMS OF FETAL PROGRAMMING. MATERNAL UNDERWEIGHT IS LESS COMMON IN DEVELOPED SOCIETIES, BUT THE DISCREPANCY BETWEEN A POOR NUTRITIONAL ENVIRONMENT IN UTERO AND A NORMAL OR EXCESSIVE POSTNATAL FOOD SUPPLY WITH RAPID GROWTH CATCH-UP APPEARS TO BE THE MAIN CANDIDATE MECHANISM OF THE DEVELOPMENT OF CHRONIC DISEASES DURING THE OFFSPRING'S ADULTHOOD. THE ROLE OF THE POSTNATAL ENVIRONMENT IN BOTH SCENARIOS (PARENTAL OVERWEIGHT OR UNDERWEIGHT) ALSO SEEMS TO INFLUENCE THE OFFSPRING'S HEALTH. LIFESTYLE INTERVENTIONS BEFORE AND DURING PREGNANCY IN BOTH PARENTS, BUT ESPECIALLY IN THE MOTHER, AS WELL AS IN CHILDREN AFTER BIRTH, ARE ADVISABLE TO COUNTERACT THE MANY UNDESIRABLE CHRONIC CONDITIONS DESCRIBED.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
6  4886  35 OVERWEIGHT AND OBESITY BEFORE, DURING AND AFTER PREGNANCY: PART 1: PATHOPHYSIOLOGY, MOLECULAR BIOLOGY AND EPIGENETIC CONSEQUENCES. OVERWEIGHT AND OBESITY BEFORE CONCEPTION AS WELL AS EXCESSIVE WEIGHT GAIN DURING PREGNANCY ARE ASSOCIATED WITH ENDOCRINOLOGICAL CHANGES OF MOTHER AND FETUS. INSULIN RESISTANCE PHYSIOLOGICALLY INCREASES DURING PREGNANCY, ADDITIONAL OBESITY FURTHER INCREASES INSULIN RESISTANCE. IN COMBINATION WITH REDUCED INSULIN SECRETION THIS LEADS TO GESTATIONAL DIABETES WHICH MAY DEVELOP INTO TYPE-2-DIABETES. THE ADIPOSE TISSUE PRODUCES TNF-ALPHA, INTERLEUKINS AND LEPTIN AND UPREGULATES THESE ADIPOKINES. INSULIN RESISTANCE AND OBESITY INDUCE INFLAMMATORY PROCESSES AND VASCULAR DYSFUNCTION, WHICH EXPLAINS THE INCREASED RATE OF PREGNANCY-RELATED HYPERTENSION AND PRE-ECLAMPSIA IN OBESE PREGNANT WOMEN. BETWEEN 14 AND 28 GESTATIONAL WEEKS, THE FETAL ADIPOSE TISSUE IS GENERATED AND THE NUMBER OF FAT LOBULES IS DETERMINED. THEREAFTER, AN INCREASE IN ADIPOSE TISSUE IS ARRANGED BY AN ENLARGEMENT OF THE LOBULES (HYPERTROPHY), OR EVEN AN INCREASE IN THE NUMBER OF FAT CELLS (HYPERPLASIA). HUMAN AND ANIMAL STUDIES HAVE SHOWN THAT MATERNAL OBESITY "PROGRAMMES" THE OFFSPRING FOR FURTHER OBESITY AND CHRONIC DISEASE. PREGNANT WOMEN, MIDWIVES, PHYSICIANS AND HEALTH CARE POLITICIANS SHOULD BE BETTER INFORMED ABOUT PREVENTION, PATHOPHYSIOLOGICAL MECHANISMS, AND THE BURDEN FOR SOCIETY CAUSED BY OBESITY BEFORE, DURING AND AFTER PREGNANCY.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
7  1098  27 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  4086  23 MATERNAL OBESITY DISRUPTS THE METHIONINE CYCLE IN BABOON PREGNANCY. MATERNAL INTAKE OF DIETARY METHYL-MICRONUTRIENTS (E.G. FOLATE, CHOLINE, BETAINE AND VITAMIN B-12) DURING PREGNANCY IS ESSENTIAL FOR NORMAL MATERNAL AND FETAL METHIONINE METABOLISM, AND IS CRITICAL FOR IMPORTANT METABOLIC PROCESSES INCLUDING THOSE INVOLVED IN DEVELOPMENTAL PROGRAMMING. MATERNAL OBESITY AND NUTRIENT EXCESS DURING PREGNANCY INFLUENCE DEVELOPMENTAL PROGRAMMING POTENTIALLY PREDISPOSING ADULT OFFSPRING TO A VARIETY OF CHRONIC HEALTH PROBLEMS. IN THE PRESENT STUDY, WE HYPOTHESIZED THAT MATERNAL OBESITY WOULD DYSREGULATE THE MATERNAL AND FETAL METHIONINE CYCLE. TO TEST THIS HYPOTHESIS, WE DEVELOPED A NULLIPAROUS BABOON OBESITY MODEL FED A HIGH FAT, HIGH ENERGY DIET (HF-HED) PRIOR TO AND DURING GESTATION, AND EXAMINED METHIONINE CYCLE BIOMARKERS (E.G., CIRCULATING CONCENTRATIONS OF HOMOCYSTEINE, METHIONINE, CHOLINE, BETAINE, KEY AMINO ACIDS, FOLATE, AND VITAMIN B-12). ANIMALS WERE GROUP HOUSED ALLOWING FULL PHYSICAL ACTIVITY AND SOCIAL INTERACTION. MATERNAL PREPREGNANCY PERCENT BODY FAT WAS 5% IN CONTROLS AND 19% IN HF-HED MOTHERS, WHILE FETAL WEIGHT WAS 16% LOWER IN OFFSPRING OF HF-HED MOTHERS AT TERM. MATERNAL AND FETAL HOMOCYSTEINE WERE HIGHER, WHILE MATERNAL AND FETAL VITAMIN B-12 AND BETAINE WERE LOWER IN THE HF-HED GROUP. ELEVATIONS IN CIRCULATING MATERNAL FOLATE WERE EVIDENT IN THE HF-HED GROUP INDICATING IMPAIRED FOLATE METABOLISM (METHYL-TRAP) AS A CONSEQUENCE OF MATERNAL VITAMIN B-12 DEPLETION. FINALLY, FETAL METHIONINE, GLYCINE, SERINE, AND TAURINE WERE LOWER IN THE HF-HED FETUSES. THESE DATA SHOW THAT MATERNAL OBESITY DISTURBS THE METHIONINE CYCLE IN PRIMATE PREGNANCY, PROVIDING A MECHANISM FOR THE EPIGENETIC CHANGES OBSERVED AMONG OBESE PREGNANT WOMEN AND SUGGESTING DIAGNOSTIC AND THERAPEUTIC OPPORTUNITIES IN HUMAN PREGNANCIES COMPLICATED BY OBESITY.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
9  2801  39 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
10  3595  28 IMPLICATIONS OF MATERNAL CONDITIONS AND PREGNANCY COURSE ON OFFSPRING'S MEDICAL PROBLEMS IN ADULT LIFE. IN THE LAST DECADE, NUMEROUS EPIDEMIOLOGICAL, CLINICAL AND EXPERIMENTAL DATA SHOW THAT PERICONCEPTIONAL, PERINATAL AND POSTNATAL ENVIRONMENT DETERMINES THE OFFSPRING'S RISK FOR LATER-LIFE CHRONIC DISEASE. FOR THIS PHENOMENON, THE TERM "FETAL" OR "PERINATAL PROGRAMMING" IS USED. IN EXPOSED OFFSPRING ALREADY IN CHILDHOOD AND EARLY ADULTHOOD, METABOLIC AND CARDIOVASCULAR CHANGES CAN BE OBSERVED, LEADING TO OBESITY, DIABETES AND HYPERTENSION. NOWADAYS, THE MODE OF CONCEPTION (E.G., IN VITRO FERTILIZATION), MATERNAL METABOLIC CONDITIONS (E.G., UNDERNUTRITION, OVERNUTRITION, DIABETES) AND COMPLICATIONS DURING PREGNANCY (E.G., PREECLAMPSIA, INTRAUTERINE GROWTH RESTRICTION) ARE SUSPECTED TO BE NEGATIVE PREDICTORS FOR OFFSPRING'S LONG-TERM HEALTH. MECHANISMS RESPONSIBLE FOR THESE EFFECTS STILL REMAIN MAINLY UNCLEAR, BUT INCLUDE EPIGENETIC, TRANSCRIPTIONAL, ENDOPLASMIC RETICULUM STRESS, AND REACTIVE OXYGEN SPECIES. THIS REVIEW PRESENTS A PIECE OF THE PUZZLE WITH REGARDS TO PERICONCEPTIONAL AND EARLY PERINATAL CONDITIONS DETERMINING LATER-LIFE RISK FOR CHRONIC ADULT DISEASE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
11  5178  26 PREGNANCY AS A FUNDAMENTAL DETERMINANT OF CHILD HEALTH: A REVIEW. PURPOSE OF REVIEW: MATERNAL CONDITIONS AND EXPOSURES DURING PREGNANCY INCLUDING OVER- AND UNDERNUTRITION ARE ASSOCIATED WITH POOR CHILDBIRTH OUTCOMES, GROWTH, DEVELOPMENT AND CHRONIC CHILDHOOD DISEASES. WE EXAMINED CONTEMPORARY PREGNANCY-RELATED DETERMINANTS OF CHILD HEALTH. RECENT FINDINGS: WHILE MATERNAL UNDERNUTRITION REMAINS A MAJOR CONTRIBUTOR TO LOW BIRTH WEIGHT, MATERNAL OBESITY AFFECTS FOETAL GROWTH, BIRTH WEIGHT, SURVIVAL AND IS ASSOCIATED WITH CHILDHOOD OBESITY, ASTHMA AND AUTISTIC SPECTRUM DISORDERS. EMERGING EVIDENCE SUGGESTS THAT EPIGENETIC CHANGES, THE PRENATAL MICROBIOME AND MATERNAL IMMUNE ACTIVATION (MIA), A NEUROINFLAMMATORY PROCESS INDUCED BY DIET AND OTHER EXPOSURES CAUSE FOETAL PROGRAMMING RESULTING IN THESE CHRONIC CHILDHOOD DISEASES. MATERNAL DIET IS POTENTIALLY A MODIFIABLE RISK FACTOR FOR CONTROLLING LOW BIRTH WEIGHT, OBESITY AND CHRONIC DISEASE IN CHILDHOOD. FURTHER STUDIES ARE WARRANTED TO REFINE GUIDANCE ON DIETARY RESTRICTION AND PHYSICAL ACTIVITY DURING PREGNANCY AND DETERMINE HOW MIA AND PRENATAL MICROBIOTA CAN BE APPLIED TO CONTROL CHILDHOOD DISEASES ARISING FROM PROGRAMMING.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
12  4065  37 MATERNAL AND GESTATIONAL INFLUENCES ON CHILDHOOD BLOOD PRESSURE. EXPOSURES THAT CONTRIBUTE TO A SUB-OPTIMAL INTRAUTERINE ENVIRONMENT CAN HAVE AN EFFECT ON THE DEVELOPING FETUS. IMPAIRED FETAL GROWTH THAT RESULTS IN LOW BIRTH WEIGHT IS AN ESTABLISHED RISK FACTOR FOR CARDIO-METABOLIC DISORDERS LATER IN LIFE. RECENT EPIDEMIOLOGIC AND PROSPECTIVE COHORT STUDIES THAT INCLUDE THE MATERNAL AND GESTATIONAL PERIOD HAVE IDENTIFIED MATERNAL AND GESTATIONAL CONDITIONS THAT CONFER INCREASED RISK FOR SUBSEQUENT CARDIO-METABOLIC DISORDERS IN THE ABSENCE OF LOW BIRTH WEIGHT. MATERNAL PRE-CONCEPTION HEALTH STATUS, INCLUDING CHRONIC OBESITY AND TYPE 2 DIABETES, INCREASE RISK FOR CHILDHOOD OBESITY AND OBESITY-RELATED HIGHER BLOOD PRESSURE (BP) IN CHILD OFFSPRING. MATERNAL GESTATIONAL EXPOSURES, INCLUDING GESTATIONAL DIABETES, GESTATIONAL HYPERTENSION, AND PREECLAMPSIA, ARE ASSOCIATED WITH HIGHER BP IN OFFSPRING. OTHER MATERNAL EXPOSURES SUCH AS CIGARETTE SMOKE AND AIR POLLUTION ALSO INCREASE RISK FOR HIGHER BP IN CHILD OFFSPRING. RECENT, BUT LIMITED, DATA INDICATE THAT ASSISTED REPRODUCTIVE TECHNOLOGIES CAN BE ASSOCIATED WITH HYPERTENSION IN CHILDHOOD, DESPITE OTHERWISE NORMAL GESTATION AND HEALTHY NEWBORN. GESTATIONAL EXPOSURES ASSOCIATED WITH HIGHER BP IN CHILDHOOD CAN BE RELATED TO FAMILIAL LIFESTYLE FACTORS, GENETICS, OR EPIGENETIC MODIFICATION OF FETAL DEOXYRIBONUCLEIC ACID (DNA). THESE FACTORS, OR COMBINATION OF FACTORS, AS WELL AS OTHER ADVERSE INTRAUTERINE CONDITIONS, COULD INDUCE FETAL PROGRAMING LEADING TO HEALTH CONSEQUENCES IN LATER LIFE. CURRENT AND DEVELOPING RESEARCH WILL PROVIDE ADDITIONAL INSIGHTS ON GESTATIONAL EXPOSURES AND FETAL ADJUSTMENTS THAT INCREASE RISK FOR HIGHER BP LEVELS IN CHILDHOOD.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
13  4504  26 MOTHER'S PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNAS: FINDINGS FROM THE ENVIRONAGE BIRTH COHORT. THERE IS INCREASING EVIDENCE THAT THE PREDISPOSITION FOR DEVELOPMENT OF CHRONIC DISEASES ARISES AT THE EARLIEST TIMES OF LIFE. IN THIS CONTEXT, MATERNAL PRE-PREGNANCY WEIGHT MIGHT MODIFY FETAL METABOLISM AND THE CHILD'S PREDISPOSITION TO DEVELOP DISEASE LATER IN LIFE. THE AIM OF THIS STUDY IS TO INVESTIGATE THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) AND MIRNA ALTERATIONS IN PLACENTAL TISSUE AT BIRTH. IN 211 MOTHER-NEWBORN PAIRS FROM THE ENVIRONAGE BIRTH COHORT, WE ASSESSED PLACENTAL EXPRESSION OF SEVEN MIRNAS IMPORTANT IN CRUCIAL CELLULAR PROCESSES IMPLICATED IN ADIPOGENESIS AND/OR OBESITY. MULTIPLE LINEAR REGRESSION MODELS WERE USED TO ADDRESS THE ASSOCIATIONS BETWEEN PRE-PREGNANCY BMI AND PLACENTAL CANDIDATE MIRNA EXPRESSION. MATERNAL PRE-PREGNANCY BMI AVERAGED (+/-SD) 23.9 (+/-4.1) KG/M(2). IN NEWBORN GIRLS (NOT IN BOYS) PLACENTAL MIR-20A, MIR-34A AND MIR-222 EXPRESSION WAS LOWER WITH HIGHER MATERNAL PRE-PREGNANCY BMI. IN ADDITION, THE ASSOCIATION BETWEEN MATERNAL PRE-PREGNANCY BMI AND PLACENTAL EXPRESSION OF THESE MIRNAS IN GIRLS WAS MODIFIED BY GESTATIONAL WEIGHT GAIN. THE LOWER EXPRESSION OF THESE MIRNAS IN PLACENTA IN ASSOCIATION WITH PRE-PREGNANCY BMI, WAS ONLY EVIDENT IN MOTHERS WITH LOW WEIGHT GAIN (<14 KG). THE PLACENTAL EXPRESSION OF MIR-20A, MIR-34A, MIR-146A, MIR-210 AND MIR-222 MAY PROVIDE A SEX-SPECIFIC BASIS FOR EPIGENETIC EFFECTS OF PRE-PREGNANCY BMI.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
14  5179  40 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES.	2017	

15  4066  35 MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION AS AN INDICATOR OF OFFSPRING METABOLIC SYNDROME RISK IN LATER LIFE THROUGH EPIGENETIC IMPRINTING: A SYSTEMATIC REVIEW. AIMS: THIS REVIEW EXAMINED WHETHER MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION EFFECTS AN OFFSPRING'S LIKELIHOOD OF DEVELOPING CHRONIC METABOLIC RELATED CONDITIONS DUE TO EPIGENETIC IMPRINTING. METHODS: A LITERATURE SEARCH WAS CONDUCTED IN MULTIPLE SCIENCE DATABASES AND LIMITED TO STUDIES PUBLISHED AFTER 2012, IN ENGLISH LANGUAGE AND PEER REVIEWED. THE DATA FROM SELECTED ARTICLES WERE EXTRACTED AND A QUALITATIVE APPROACH WAS EMPLOYED DUE TO HETEROGENEITY OF RESULTS. RESULTS: NEWBORNS FROM OBESE FATHERS SHOWED ALTERED METHYLATION OVERALL AND SIGNIFICANT HYPOMETHYLATION AT THE INSULIN-LIKE GROWTH FACTOR 2 (IGF2) GENE. HIGH MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) WAS ASSOCIATED WITH ALTERED OFFSPRING DNA METHYLATION LEVELS AND GESTATIONAL DIABETES MELLITUS INDUCED SIGNIFICANTLY INCREASED METHYLATION LEVELS IN OFFSPRING. GESTATIONAL WEIGHT GAIN WAS NOT ASSOCIATED WITH DIFFERENTIALLY METHYLATED CORD BLOOD. BIRTH WEIGHT WAS HIGHER IN OFFSPRING EXPOSED TO FAMINE IN EARLY GESTATION. OFFSPRING BORN POST MATERNAL BARIATRIC SURGERY SHOWED A LOWER PERCENTAGE OF BODY FAT AND IMPROVED FASTING INSULIN LEVELS COMPARED TO SIBLINGS BORN PRE-MATERNAL BARIATRIC SURGERY. CONCLUSIONS: THE AVAILABLE EVIDENCE SUGGESTS THAT POOR MATERNAL AND PATERNAL PERICONCEPTIONAL NUTRITION CAN INCREASE THE RISK OF METABOLIC SYNDROME IN OFFSPRING, THROUGH EPIGENETIC IMPRINTING. POTENTIAL PARENTS SHOULD BE ADVISED THAT MAINTAINING A HEALTHY DIET AND BMI IS LIKELY TO REDUCE THE RISK OF METABOLIC SYNDROME IN OFFSPRING.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
16  6724  30 VITAMIN D: EFFECTS ON PREGNANCY, MATERNAL, FETAL AND POSTNATAL OUTCOMES. A HIGH PREVALENCE OF VITAMIN D DEFICIENCY AND ITS NEGATIVE CONSEQUENCES FOR HEALTH IS IDENTIFIED AS AREA OF PRIMARY CONCERN FOR SCIENTISTS AND CLINICIANS WORLDWIDE. VITAMIN D DEFICIENCY AFFECTS NOT ONLY BONE HEALTH BUT MANY SOCIALLY SIGNIFICANT ACUTE AND CHRONIC DISEASES. OBSERVATIONAL STUDIES SUPPORT THAT PREGNANT AND LACTATING WOMEN, CHILDREN AND TEENAGERS REPRESENT THE HIGH RISK GROUPS FOR DEVELOPING VITAMIN D DEFICIENCY. CURRENT EVIDENCE HIGHLIGHTS A CRUCIAL ROLE OF VITAMIN D IN PROVIDING THE FETAL LIFE-SUPPORT SYSTEM AND FETUS DEVELOPMENT, INCLUDING IMPLANTATION, PLACENTAL FORMATION, INTRA- AND POSTPARTUM PERIODS. HYPOVITAMINOSIS D DURING PREGNANCY IS ASSOCIATED WITH A HIGHER INCIDENCE OF PLACENTAL INSUFFICIENCY, SPONTANEOUS ABORTIONS AND PRETERM BIRTH, PREECLAMPSIA, GESTATIONAL DIABETES, IMPAIRED FETAL AND CHILDHOOD GROWTH, INCREASED RISK OF AUTOIMMUNE DISEASES FOR OFFSPRINGS. POTENTIAL MECHANISMS FOR THE OBSERVED ASSOCIATIONS CONTAIN METABOLIC, IMMUNOMODULATORY AND ANTIINFLAMMATORY EFFECTS OF VITAMIN D. EPIGENETIC MODIFICATIONS IN VITAMIN D-ASSOCIATED GENES AND FETAL PROGRAMMING ARE OF PARTICULAR INTEREST. THE CONCEPT OF PREVENTING VITAMIN D DEFICIENCY IS ACTIVELY DISCUSSED, INCLUDING SUPPLEMENTATION IN DIFFERENT ETHNIC GROUPS, REQUIRED DOSES, TIME OF INITIATION AND THERAPY DURATION, INFLUENCE ON GESTATION AND CHILDBIRTH. AN ADEQUATE SUPPLY OF VITAMIN D DURING PREGNANCY IMPROVES THE MATERNAL AND FETAL OUTCOMES, SHORT AND LONG TERM HEALTH OF THE OFFSPRING. STILL CURRENT DATA ON RELATIONSHIP BETWEEN MATERNAL VITAMIN D STATUS AND PREGNANCY OUTCOMES REMAINS CONTROVERSIAL. THE LARGE OBSERVATIONAL AND INTERVENTIONAL RANDOMIZED CONTROL TRIALS ARE REQUIRED TO CREATE EVIDENCE-BASED GUIDELINES FOR THE SUPPLEMENTATION OF VITAMIN D IN PREGNANT AND LACTATING WOMEN.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
17  4078  31 MATERNAL INFLAMMATION, GROWTH RETARDATION, AND PRETERM BIRTH: INSIGHTS INTO ADULT CARDIOVASCULAR DISEASE. THE "FETAL ORIGIN OF ADULT DISEASE HYPOTHESIS" ORIGINALLY DESCRIBED BY BARKER ET AL. IDENTIFIED THE RELATIONSHIP BETWEEN IMPAIRED IN UTERO GROWTH AND ADULT CARDIOVASCULAR DISEASE RISK AND DEATH. SINCE THEN, NUMEROUS CLINICAL AND EXPERIMENTAL STUDIES HAVE CONFIRMED THAT EARLY DEVELOPMENTAL INFLUENCES CAN LEAD TO CARDIOVASCULAR, PULMONARY, METABOLIC, AND PSYCHOLOGICAL DISEASES DURING ADULTHOOD WITH AND WITHOUT ALTERATIONS IN BIRTH WEIGHT. THIS SO CALLED "FETAL PROGRAMMING" INCLUDES DEVELOPMENTAL DISRUPTION, IMMEDIATE ADAPTATION, OR PREDICTIVE ADAPTATION AND CAN LEAD TO EPIGENETIC CHANGES AFFECTING A SPECIFIC ORGAN OR OVERALL HEALTH. THE INTRAUTERINE ENVIRONMENT IS DRAMATICALLY IMPACTED BY THE OVERALL MATERNAL HEALTH. BOTH PREMATURE BIRTH OR LOW BIRTH WEIGHT CAN RESULT FROM A VARIETY OF MATERNAL CONDITIONS INCLUDING UNDERNUTRITION OR DYSNUTRITION, METABOLIC DISEASES, CHRONIC MATERNAL STRESSES INDUCED BY INFECTIONS AND INFLAMMATION, AS WELL AS HYPERCHOLESTEROLEMIA AND SMOKING. NUMEROUS ANIMAL STUDIES HAVE SUPPORTED THE IMPORTANCE OF BOTH MATERNAL HEALTH AND MATERNAL ENVIRONMENT ON THE LONG TERM OUTCOMES OF THE OFFSPRING. WITH INCREASING RATES OF OBESITY AND DIABETES AND SURVIVAL OF PRETERM INFANTS BORN AT EARLY GESTATIONAL AGES, THE NEED TO ELUCIDATE MECHANISMS RESPONSIBLE FOR PROGRAMMING OF ADULT CARDIOVASCULAR DISEASE IS ESSENTIAL FOR THE TREATMENT OF UPCOMING GENERATIONS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
18  2806  38 FETAL PROGRAMMING AND THE RISK OF NONCOMMUNICABLE DISEASE. THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) HYPOTHESIS PROPOSES THAT ENVIRONMENTAL CONDITIONS DURING FETAL AND EARLY POST-NATAL DEVELOPMENT INFLUENCE LIFELONG HEALTH AND CAPACITY THROUGH PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM. THIS HAS BEEN CALLED 'PROGRAMMING'. THE HYPOTHESIS IS SUPPORTED BY EPIDEMIOLOGICAL EVIDENCE IN HUMANS LINKING NEWBORN SIZE, AND INFANT GROWTH AND NUTRITION, TO ADULT HEALTH OUTCOMES, AND BY EXPERIMENTS IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVER-NUTRITION AND OTHER INTERVENTIONS (E.G., GLUCOCORTICOID EXPOSURE) DURING PREGNANCY LEAD TO ABNORMAL METABOLISM AND BODY COMPOSITION IN THE ADULT OFFSPRING. EARLY LIFE PROGRAMMING IS NOW THOUGHT TO BE IMPORTANT IN THE ETIOLOGY OF OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE, OPENING UP THE POSSIBILITY THAT THESE COMMON DISEASES COULD BE PREVENTED BY ACHIEVING OPTIMAL FETAL AND INFANT DEVELOPMENT. THIS IS LIKELY TO HAVE ADDITIONAL BENEFITS FOR INFANT SURVIVAL AND HUMAN CAPITAL (E.G., IMPROVED COGNITIVE PERFORMANCE AND PHYSICAL WORK CAPACITY). FETAL NUTRITION IS INFLUENCED BY THE MOTHER'S DIET AND BODY SIZE AND COMPOSITION, BUT HARD EVIDENCE THAT THE NUTRITION OF THE HUMAN MOTHER PROGRAMMES CHRONIC DISEASE RISK IN HER OFFSPRING IS CURRENTLY LIMITED. RECENT FINDINGS FROM FOLLOW-UP OF CHILDREN BORN AFTER RANDOMISED NUTRITIONAL INTERVENTIONS IN PREGNANCY ARE MIXED, BUT SHOW SOME EVIDENCE OF BENEFICIAL EFFECTS ON VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. WORK IN EXPERIMENTAL ANIMALS SUGGESTS THAT EPIGENETIC PHENOMENA, WHEREBY GENE EXPRESSION IS MODIFIED BY DNA METHYLATION, AND WHICH ARE SENSITIVE TO THE NUTRITIONAL ENVIRONMENT IN EARLY LIFE, MAY BE ONE MECHANISM UNDERLYING PROGRAMMING.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
19  4752  27 NOVEL ROLE OF GESTATIONAL HYDRALAZINE IN LIMITING MATERNAL AND DIETARY OBESITY-RELATED CHRONIC KIDNEY DISEASE. BACKGROUND: MATERNAL OBESITY IS A RISK FACTOR FOR CHRONIC KIDNEY DISEASE (CKD) IN OFFSPRING, UNDERPINNING THE THEORY OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. DNA METHYLATION HAS BEEN IMPLICATED IN THE PROGRAMMING OF ADULT CHRONIC DISEASE BY MATERNAL OBESITY, THEREFORE, DNA DEMETHYLATING AGENTS MAY MITIGATE OFFSPRING RISK OF DISEASE. IN RODENT MODELS, LOW-DOSE HYDRALAZINE HAS PREVIOUSLY BEEN SHOWN TO REDUCE RENAL FIBROSIS VIA DNA DEMETHYLATION. WE USED MOUSE MODELS OF MATERNAL OBESITY AND OFFSPRING OBESITY TO DETERMINE WHETHER ADMINISTRATION OF LOW-DOSE HYDRALAZINE DURING GESTATION CAN PREVENT FETAL PROGRAMMING OF CKD IN OFFSPRING. METHODS: FEMALE C57BL/6 MICE RECEIVED HIGH FAT DIET (HFD) OR CHOW PRIOR TO MATING, DURING GESTATION AND LACTATION. DURING GESTATION, DAMS RECEIVED SUBCUTANEOUS HYDRALAZINE (5 MG/KG) OR SALINE THRICE-WEEKLY. MALE OFFSPRING WEANED TO HFD OR CHOW, WHICH CONTINUED UNTIL ENDPOINT AT 32 WEEKS. BIOMETRIC AND METABOLIC PARAMETERS, RENAL GLOBAL DNA METHYLATION, RENAL FUNCTIONAL AND STRUCTURAL CHANGES, AND RENAL MARKERS OF FIBROSIS, INFLAMMATION AND OXIDATIVE STRESS WERE ASSESSED AT ENDPOINT. RESULTS: OFFSPRING EXPOSED TO MATERNAL OBESITY OR DIET-INDUCED OBESITY HAD SIGNIFICANTLY INCREASED RENAL GLOBAL DNA METHYLATION, TOGETHER WITH OTHER ADVERSE RENAL EFFECTS INCLUDING ALBUMINURIA, GLOMERULOSCLEROSIS, RENAL FIBROSIS, AND OXIDATIVE STRESS. OFFSPRING EXPOSED TO GESTATIONAL HYDRALAZINE HAD SIGNIFICANTLY REDUCED RENAL GLOBAL DNA METHYLATION. IN OBESE OFFSPRING OF OBESE MOTHERS, GESTATIONAL HYDRALAZINE SIGNIFICANTLY DECREASED ALBUMINURIA, GLOMERULOSCLEROSIS, AND SERUM CREATININE. OBESE OFFSPRING OF HYDRALAZINE-TREATED LEAN MOTHERS DISPLAYED REDUCED MARKERS OF RENAL FIBROSIS AND OXIDATIVE STRESS. CONCLUSION: GESTATIONAL HYDRALAZINE DECREASED RENAL GLOBAL DNA METHYLATION AND EXERTED RENOPROTECTIVE EFFECTS IN OFFSPRING. THIS SUPPORTS A POTENTIAL THERAPEUTIC EFFECT OF HYDRALAZINE IN PREVENTING MATERNAL OBESITY OR DIETARY OBESITY-RELATED CKD, THROUGH AN EPIGENETIC MECHANISM.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20  6873  37 [PREVENTION OF OBESITY FROM PERINATAL STAGE]. OBESITY IS ONE OF THE MAJOR HEALTH PROBLEMS AND A DETERMINING FACTOR IN THE PREVALENCE OF DISEASES SUCH AS METABOLIC SYNDROME, ASTHMA, SLEEP APNEA, INFERTILITY AND VARIOUS TYPES OF CANCER. ITS ORIGIN IS MULTIFACTORIAL, INVOLVING GENETIC, SOCIOECONOMIC AND ENVIRONMENTAL FACTORS. THESE LAST ONES CONTRIBUTE MOSTLY TO EXPLAIN THE CURRENT EPIDEMIC GROWTH OF THIS DISEASE. THE SEDENTARY LIFESTYLE, INADEQUATE DIET, LACK OF SLEEP, ALTERATIONS IN INTESTINAL MICROBIOTA AND STRESS ARE FACTORS RELATED TO ITS DEVELOPMENT. SINCE BARKER PRESENTED HIS HYPOTHESIS ABOUT THE "FETAL ORIGIN OF ADULT DISEASES", THERE ARE INCREASING NUMBER OF STUDIES THAT SHOW THE INFLUENCE OF AN INADEQUATE NUTRITIONAL STATUS AND MATERNAL WEIGHT IN THE DEVELOPMENT OF CHRONIC DISEASES, AS OBESITY IN OFFSPRING. THE NUTRITIONAL DEFICIENCIES OF THE PREGNANT MOTHER CAUSE EPIGENETIC MODIFICATIONS AND ABNORMAL PROGRAMMING OF THE DEVELOPMENT OFORGANS AND DEVICES, ADAPTING THE FETUS TO THIS SITUATION OF DEFICIENCY AND BEING ABLE TO ADAPT TO AN OBESOGENIC ENVIRONMENT AFTER BIRTH, INCREASING ITS PROPENSITY TO OBESITY. ALSO, POOR MATERNAL NUTRITIONAL STATUS IS RELATED TO INTRAUTERINE GROWTH RETARDATION AND LOW BIRTH WEIGHT INFANTS, WITH A HIGHER RISK OF CHILDHOOD AND ADULT CENTRAL OBESITY. CURRENTLY, DEFICIENT INTAKE OF MICRONUTRIENTS AND OVERWEIGHT OR MATERNAL OBESITY TEND TO OVERLAP, AND THIS COMBINATION MAY EXACERBATE THE INCREASE IN OBESITY IN THE OFFSPRING. IT IS IMPORTANT TO IDENTIFY PREGNANT MOTHERS AT RISK OF SUFFERING NUTRITIONAL ALTERATIONS AND ESTABLISH THEIR IMPROVEMENT AS A PRIMARY PREVENTION STRATEGY FOR OVERWEIGHT AND OBESITY.	2017