1 3578 100 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 2 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 3 4886 37 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 4 1098 26 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 5 4202 38 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 6 5178 32 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 7 4065 41 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 8 5179 48 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 9 6873 43 [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 10 4066 32 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 11 4504 27 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 12 805 35 CHALLENGES AND PERSPECTIVES OF THE DOUBLE BURDEN OF MALNUTRITION IN LATIN AMERICA. NUTRITION IS A KEY FACTOR IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC DISEASES (NCCDS), ESPECIALLY CARDIOVASCULAR DISEASES (CVD) AND THEIR RISK FACTORS. THE "DOUBLE BURDEN OF MALNUTRITION" (DBM) IS THE COEXISTENCE OF UNDERNUTRITION AND OVERNUTRITION IN THE SAME POPULATION ACROSS THE LIFE-COURSE. IN LATIN AMERICA, THE TRANSITION FROM A PREDOMINANTLY UNDERWEIGHT TO AN OVERWEIGHT AND OBESE POPULATION HAS INCREASED MORE RAPIDLY THAN IN OTHER REGIONS IN THE WORLD. UNDERNUTRITION AND THE MICRONUTRIENT DEFICIENCIES PARTICULARLY IRON, ZINC, AND VITAMINS A AND D, PRESENT HIGH HETEROGENEITY IN LATIN AMERICAN COUNTRIES, AND ARE CURRENTLY CONSIDERED IMPORTANT PUBLIC HEALTH PROBLEMS. IN THIS REGION, NCCDS ACCOUNT FOR 50% OF THE DISABILITY-ADJUSTED LIFE-YEARS, LED BY CVD. THE MOST PREVALENT CARDIOVASCULAR RISK FACTORS ARE OVERWEIGHT, OBESITY, HYPERTENSION, DYSLIPIDEMIA AND TYPE 2 DIABETES MELLITUS. BECAUSE OF THE COST OF TREATMENT AND THE POTENTIAL YEARS OF LIFE LOST DUE TO PREMATURE DEATH, CVD IS KNOWN TO AFFECT THE POOREST SEGMENTS OF THE POPULATION, AFFECTING COMMUNITIES, AND GOVERNMENTS. MORE THAN 80% OF CVD DEATHS OCCUR IN LOW- AND MIDDLE-INCOME COUNTRIES. THE PERSISTENCE OF DAMAGE IN SOME CELLS DUE TO UNDERNUTRITION MAY EXPLAIN CERTAIN FINDINGS REGARDING THE INCREASE IN NCCD. THESE ASPECTS TOGETHER WITH EPIGENETIC CHANGES HAVE HIGHLIGHTED THE IMPORTANCE OF A LIFELONG APPROACH TO NUTRITIONAL POLICY DEVELOPMENT. REDUCING DBM REQUIRES MAJOR SOCIETAL INTERVENTIONS IN PUBLIC HEALTH AND NUTRITION TO ACHIEVE HOLISTIC CHANGE THAT CAN BE SUSTAINED OVER THE LONG TERM AND SPREAD THROUGHOUT THE GLOBAL FOOD SYSTEM. THE IMPLEMENTATION OF EFFECTIVE STATE POLICIES OF DOUBLE IMPACT ACTIONS SHOULD INFLUENCE BOTH SIDES OF THE BURDEN AND BE CONSIDERED AN URGENT PRIORITY, CONSIDERING COUNTRY-SPECIFIC INEQUALITIES AND SOCIO-DEMOGRAPHIC DIFFERENCES IN THE LATIN AMERICAN REGION, USING DIVERSE AND MULTIDISCIPLINARY STRATEGIES. 2022 13 751 33 CARDIOMETABOLIC EFFECTS OF POSTNATAL HIGH-FAT DIET CONSUMPTION IN OFFSPRING EXPOSED TO MATERNAL PROTEIN RESTRICTION IN UTERO. IN RECENT DECADES, THE HIGH INCIDENCE OF INFECTIOUS AND PARASITIC DISEASES HAS BEEN REPLACED BY A HIGH PREVALENCE OF CHRONIC AND DEGENERATIVE DISEASES. CONCOMITANTLY, THERE HAVE BEEN PROFOUND CHANGES IN THE BEHAVIOR AND EATING HABITS OF FAMILIES AROUND THE WORLD, CHARACTERIZING A "NUTRITIONAL TRANSITION" PHENOMENON, WHICH REFERS TO A SHIFT IN DIET IN RESPONSE TO MODERNIZATION, URBANIZATION, OR ECONOMIC DEVELOPMENT FROM UNDERNUTRITION TO THE EXCESSIVE CONSUMPTION OF HYPERCALORIC AND ULTRA-PROCESSED FOODS. PROTEIN MALNUTRITION THAT WAS A HEALTH PROBLEM IN THE FIRST HALF OF THE 20TH CENTURY HAS NOW BEEN REPLACED BY HIGH-FAT DIETS, ESPECIALLY DIETS HIGH IN SATURATED FAT, PREDISPOSING CONSUMERS TO OVERWEIGHT AND OBESITY. THIS PANORAMA POINTS US TO THE ALARMING COEXISTENCE OF BOTH MALNUTRITION AND OBESITY IN THE SAME POPULATION. IN THIS WAY, INDIVIDUALS WHOSE MOTHERS WERE UNDERNOURISHED EARLY IN PREGNANCY AND THEN EXPOSED TO POSTNATAL HYPERLIPIDIC NUTRITION HAVE INCREASED RISK FACTORS FOR DEVELOPING METABOLIC DYSFUNCTION AND CARDIOVASCULAR DISEASES IN ADULTHOOD. THUS, OUR MAJOR AIM WAS TO REVIEW THE CARDIOMETABOLIC EFFECTS RESULTING FROM POSTNATAL HYPERLIPIDIC DIETS IN PROTEIN-RESTRICTED SUBJECTS, AS WELL AS TO EXAMINE THE EPIGENETIC REPERCUSSIONS OCCASIONED BY THE NUTRITIONAL TRANSITION. 2022 14 3786 46 INTERGENERATIONAL INFLUENCES ON CHILD GROWTH AND UNDERNUTRITION. INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE WELL DOCUMENTED. SEVERAL GENERATIONS ARE NECESSARY IN ANIMAL MODELS TO 'WASH OUT' EFFECTS OF UNDERNUTRITION, CONSISTENT WITH THE UNFOLDING OF THE SECULAR TREND IN HEIGHT IN EUROPE AND NORTH AMERICA. BIRTHWEIGHT IS CORRELATED ACROSS GENERATIONS AND SHORT MATERNAL STATURE, WHICH REFLECTS INTRAUTERINE AND INFANT GROWTH FAILURE, IS ASSOCIATED WITH LOW BIRTHWEIGHT, CHILD STUNTING, DELIVERY COMPLICATIONS AND INCREASED CHILD MORTALITY, EVEN AFTER ADJUSTING FOR SOCIO-ECONOMIC STATUS. A NUTRITION INTERVENTION IN GUATEMALA REDUCED CHILDHOOD STUNTING; IT ALSO IMPROVED GROWTH OF THE NEXT GENERATION, BUT ONLY IN THE OFFSPRING OF GIRLS. POSSIBLE MECHANISMS EXPLAINING INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE NOT MUTUALLY EXCLUSIVE AND INCLUDE, AMONG OTHERS, SHARED GENETIC CHARACTERISTICS, EPIGENETIC EFFECTS, PROGRAMMING OF METABOLIC CHANGES, AND THE MECHANICS OF A REDUCED SPACE FOR THE FETUS TO GROW. THERE ARE ALSO SOCIO-CULTURAL FACTORS AT PLAY THAT ARE IMPORTANT SUCH AS THE INTERGENERATIONAL TRANSMISSION OF POVERTY AND THE FEAR OF BIRTHING A LARGE BABY, WHICH LEADS TO 'EATING DOWN' DURING PREGNANCY. IT IS NOT CLEAR WHETHER THERE IS AN UPPER LIMIT FOR IMPACT ON INTRAUTERINE AND INFANT LINEAR GROWTH THAT PROGRAMMES IN DEVELOPING COUNTRIES COULD ACHIEVE THAT IS SET BY EARLY CHILDHOOD MALNUTRITION IN THE MOTHER. SUBSTANTIAL IMPROVEMENTS IN LINEAR GROWTH CAN BE ACHIEVED THROUGH ADOPTION AND MIGRATION, AND IN A FEW SELECTED COUNTRIES, FOLLOWING RAPID ECONOMIC AND SOCIAL DEVELOPMENT. IT WOULD SEEM, DESPITE CLEAR DOCUMENTATION OF INTERGENERATIONAL EFFECTS, THAT NEARLY NORMAL LENGTHS CAN BE ACHIEVED IN CHILDREN BORN TO MOTHERS WHO WERE MALNOURISHED IN CHILDHOOD WHEN PROFOUND IMPROVEMENTS IN HEALTH, NUTRITION AND THE ENVIRONMENT TAKE PLACE BEFORE CONCEPTION. TO ACHIEVE SIMILAR LEVELS OF IMPACT THROUGH PUBLIC HEALTH PROGRAMMES ALONE IN POOR COUNTRIES IS HIGHLY UNLIKELY. THE REALITY IN POOR COUNTRIES LIMITS THE SCOPE, QUALITY AND COVERAGE OF PROGRAMMES THAT CAN BE IMPLEMENTED AND MODEST IMPACT SHOULD BE EXPECTED INSTEAD. THE LANCET SERIES ON MATERNAL AND CHILD UNDERNUTRITION ESTIMATED THAT IMPLEMENTATION TO SCALE OF PROVEN INTERVENTIONS IN HIGH BURDEN COUNTRIES WOULD REDUCE STUNTING BY ONE-THIRD; THIS IS PERHAPS A REALISTIC UPPER BOUND FOR IMPACT FOR HIGH QUALITY PROGRAMMES, UNLESS ACCOMPANIED BY SWEEPING IMPROVEMENTS IN SOCIAL SERVICES AND MARKED REDUCTIONS IN POVERTY. FINALLY, BECAUSE SO MUCH CAN BE ACHIEVED IN A SINGLE GENERATION, INTERGENERATIONAL INFLUENCES ARE UNLIKELY TO BE AN IMPORTANT EXPLANATION FOR LACK OF PROGRAMME IMPACT AIMED AT THE WINDOW OF THE FIRST 1000 DAYS. FAILURE TO PREVENT LINEAR GROWTH FAILURE IN DEVELOPING COUNTRIES HAS SERIOUS CONSEQUENCES FOR SHORT- AND LONG-TERM HEALTH AS WELL AS FOR THE FORMATION OF HUMAN CAPITAL. THE NUTRITION TRANSITION HAS CREATED A DOUBLE BURDEN BY ADDING OBESITY AND RELATED CHRONIC DISEASES TO THE PUBLIC HEALTH AGENDA OF COUNTRIES STILL STRUGGLING WITH THE 'OLD' PROBLEMS OF MATERNAL AND CHILD UNDERNUTRITION. THE CHALLENGE AHEAD IS TO INCREASE EFFORTS TO PREVENT LINEAR GROWTH FAILURE WHILE KEEPING CHILD OVERWEIGHT AT BAY. 2012 15 4080 25 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 16 3595 34 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 17 4046 44 MADE IN THE WOMB: MATERNAL PROGRAMMING OF OFFSPRING CARDIOVASCULAR FUNCTION BY AN OBESOGENIC WOMB. OBESITY INCIDENCE HAS BEEN INCREASING AT AN ALARMING RATE, ESPECIALLY IN WOMEN OF REPRODUCTIVE AGE. IT IS ESTIMATED THAT 50% OF PREGNANCIES OCCUR IN OVERWEIGHT OR OBESE WOMEN. IT HAS BEEN DESCRIBED THAT MATERNAL OBESITY (MO) PREDISPOSES THE OFFSPRING TO AN INCREASED RISK OF DEVELOPING MANY CHRONIC DISEASES IN AN EARLY STAGE OF LIFE, INCLUDING OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE (CVD). CVD IS THE MAIN CAUSE OF DEATH WORLDWIDE AMONG MEN AND WOMEN, AND IT IS MANIFESTED IN A SEX-DIVERGENT WAY. MATERNAL NUTRITION AND MO DURING GESTATION COULD PROMPT CVD DEVELOPMENT IN THE OFFSPRING THROUGH ADAPTATIONS OF THE OFFSPRING'S CARDIOVASCULAR SYSTEM IN THE WOMB, INCLUDING CARDIAC EPIGENETIC AND PERSISTENT METABOLIC PROGRAMMING OF SIGNALING PATHWAYS AND MODULATION OF MITOCHONDRIAL METABOLIC FUNCTION. CURRENTLY, DESPITE DIET SUPPLEMENTATION, EFFECTIVE THERAPEUTICAL SOLUTIONS TO PREVENT THE DELETERIOUS CARDIAC OFFSPRING FUNCTION PROGRAMMING BY AN OBESOGENIC WOMB ARE LACKING. IN THIS REVIEW, WE DISCUSS THE MECHANISMS BY WHICH AN OBESOGENIC INTRAUTERINE ENVIRONMENT COULD PROGRAM THE OFFSPRING'S CARDIOVASCULAR METABOLISM IN A SEX-DIVERGENT WAY, WITH A SPECIAL FOCUS ON CARDIAC MITOCHONDRIAL FUNCTION, AND DEBATE POSSIBLE STRATEGIES TO IMPLEMENT DURING MO PREGNANCY THAT COULD AMELIORATE, REVERT, OR EVEN PREVENT DELETERIOUS EFFECTS OF MO ON THE OFFSPRING'S CARDIOVASCULAR SYSTEM. THE IMPACT OF MATERNAL PHYSICAL EXERCISE DURING AN OBESOGENIC PREGNANCY, NUTRITIONAL INTERVENTIONS, AND SUPPLEMENTATION ON OFFSPRING'S CARDIAC METABOLISM ARE DISCUSSED, HIGHLIGHTING CHANGES THAT MAY BE FAVORABLE TO MO OFFSPRING'S CARDIOVASCULAR HEALTH, WHICH MIGHT RESULT IN THE ATTENUATION OR EVEN PREVENTION OF THE DEVELOPMENT OF CVD IN MO OFFSPRING. THE OBJECTIVES OF THIS MANUSCRIPT ARE TO COMPREHENSIVELY EXAMINE THE VARIOUS ASPECTS OF MO DURING PREGNANCY AND EXPLORE THE UNDERLYING MECHANISMS THAT CONTRIBUTE TO AN INCREASED CVD RISK IN THE OFFSPRING. WE REVIEW THE CURRENT LITERATURE ON MO AND ITS IMPACT ON THE OFFSPRING'S CARDIOMETABOLIC HEALTH. FURTHERMORE, WE DISCUSS THE POTENTIAL LONG-TERM CONSEQUENCES FOR THE OFFSPRING. UNDERSTANDING THE MULTIFACETED EFFECTS OF MO ON THE OFFSPRING'S HEALTH IS CRUCIAL FOR HEALTHCARE PROVIDERS, RESEARCHERS, AND POLICYMAKERS TO DEVELOP EFFECTIVE STRATEGIES FOR PREVENTION AND INTERVENTION TO IMPROVE CARE. 2023 18 2805 39 FETAL MALNUTRITION AND LONG-TERM OUTCOMES. EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT LOWER BIRTHWEIGHT IS ASSOCIATED WITH A WIDE RANGE OF ADVERSE OUTCOMES IN LATER LIFE, INCLUDING POORER 'HUMAN CAPITAL' (SHORTER STATURE, LOWER COGNITIVE PERFORMANCE), INCREASED RISK FACTORS FOR LATER DISEASE (HIGHER BLOOD PRESSURE AND REDUCED GLUCOSE TOLERANCE, AND LUNG, KIDNEY AND IMMUNE FUNCTION), CLINICAL DISEASE (DIABETES, CORONARY HEART DISEASE, CHRONIC LUNG AND KIDNEY DISEASE), AND INCREASED ALL-CAUSE AND CARDIOVASCULAR MORTALITY. HIGHER BIRTHWEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CANCER AND (IF CAUSED BY GESTATIONAL DIABETES) OBESITY AND DIABETES. THE 'DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE' HYPOTHESIS PROPOSES THAT FETAL NUTRITION HAS PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM ('PROGRAMMING'). THIS IS SUPPORTED BY STUDIES IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVERNUTRITION DURING PREGNANCY CAN PRODUCE SIMILAR ABNORMALITIES IN THE ADULT OFFSPRING. COMMON CHRONIC DISEASES COULD POTENTIALLY BE PREVENTED BY ACHIEVING OPTIMAL FETAL NUTRITION, AND THIS COULD HAVE ADDITIONAL BENEFITS FOR SURVIVAL AND HUMAN CAPITAL. RECENT FOLLOW-UP OF CHILDREN BORN AFTER RANDOMIZED NUTRITIONAL INTERVENTIONS IN PREGNANCY PROVIDES WEAK EVIDENCE OF BENEFICIAL EFFECTS ON GROWTH, VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. ANIMAL STUDIES INDICATE THAT EPIGENETIC PHENOMENA MAY BE AN IMPORTANT MECHANISM UNDERLYING PROGRAMMING, AND THAT NUTRITIONAL INTERVENTIONS MAY NEED TO START PRECONCEPTIONALLY. 2013 19 3572 40 IMPACT OF MATERNAL DIABETES ON EPIGENETIC MODIFICATIONS LEADING TO DISEASES IN THE OFFSPRING. GESTATIONAL DIABETES, OCCURRING DURING THE HYPERGLYCEMIC PERIOD OF PREGNANCY IN MATERNAL LIFE, IS A PATHOLOGIC STATE THAT INCREASES THE INCIDENCE OF COMPLICATIONS IN BOTH MOTHER AND FETUS. OFFSPRING THUS EXPOSED TO AN ADVERSE FETAL AND EARLY POSTNATAL ENVIRONMENT MAY MANIFEST INCREASED SUSCEPTIBILITY TO A NUMBER OF CHRONIC DISEASES LATER IN LIFE. COMPELLING EVIDENCE FOR THE ROLE OF EPIGENETIC TRANSMISSION IN THESE COMPLICATIONS HAS COME FROM COMPARISON OF SIBLINGS BORN BEFORE AND AFTER THE DEVELOPMENT OF MATERNAL DIABETES, EXPOSURE TO THIS INTRAUTERINE DIABETIC ENVIRONMENT BEING SHOWN TO CAUSE ALTERATIONS IN FETAL GROWTH PATTERNS WHICH PREDISPOSE THESE INFANTS TO DEVELOPING OVERWEIGHT AND OBESITY LATER IN LIFE. DIABETES OF THE OFFSPRING IS ALSO MAINLY THE CONSEQUENCE OF EXPOSURE TO THE DIABETIC INTRAUTERINE ENVIRONMENT, IN ADDITION TO GENETIC SUSCEPTIBILITY. SINCE OBESITY AND DIABETES ARE KNOWN TO INCREASE THE RISK OF CARDIOVASCULAR DISEASE, CARDIOVASCULAR SEQUELAE IN THE OFFSPRING OF DIABETIC MOTHERS ARE VIRTUALLY INEVITABLE. RESEARCH DATA ALSO SUGGEST THAT EXPOSURE TO A DIABETIC INTRAUTERINE ENVIRONMENT DURING PREGNANCY IS ASSOCIATED WITH AN INCREASE IN DYSLIPIDEMIA, SUBCLINICAL VASCULAR INFLAMMATION, AND ENDOTHELIAL DYSFUNCTION PROCESSES IN THE OFFSPRING, ALL OF WHICH ARE LINKED WITH DEVELOPMENT OF CARDIOVASCULAR DISEASE LATER IN LIFE. THE MAIN UNDERLYING MECHANISMS INVOLVE PERSISTENT HYPERGLYCEMIA HYPERINSULINEMIA AND LEPTIN RESISTANCE. 2012 20 1373 32 DEVELOPMENTAL ORIGINS OF NONALCOHOLIC FATTY LIVER DISEASE. OBESE PREGNANT WOMEN MAY TRANSMIT THEIR METABOLIC PHENOTYPE TO OFFSPRING, LEADING TO A CYCLE OF OBESITY AND DIABETES OVER GENERATIONS. EARLY CHILDHOOD OBESITY PREDICTS NONALCOHOLIC FATTY LIVER DISEASE (NAFLD), THE MOST COMMON CHRONIC HUMAN LIVER DISEASE. THE FETUS MAY BE VULNERABLE TO STEATOSIS BECAUSE IMMATURE FETAL ADIPOSE DEPOTS ARE NOT AVAILABLE TO BUFFER THE EXCESS TRANSPLACENTAL LIPID DELIVERY IN MATERNAL OBESITY. IN ANIMAL MODELS, IN UTERO HIGH-FAT DIET EXPOSURE RESULTS IN AN INCREASE IN THE ACCUMULATION OF LIVER TRIGLYCERIDES IN OFFSPRING AND INCREASED HEPATIC OXIDATIVE STRESS AND APOPTOSIS, PERHAPS PRIMING THE LIVER FOR LATER DEVELOPMENT OF NAFLD. INNATE IMMUNE DYSFUNCTION AND NECROINFLAMMATORY CHANGES HAVE BEEN OBSERVED IN POSTNATAL OFFSPRING LIVER OF ANIMALS BORN TO HIGH-FAT-FED DAMS. POSTWEANING, LIVERS OF OFFSPRING EXPOSED TO MATERNAL HIGH-FAT FEEDING IN UTERO SHARE PATHOPHYSIOLOGIC FEATURES WITH HUMAN NAFLD, INCLUDING INCREASED DE NOVO LIPOGENESIS AND DECREASED FREE FATTY ACID OXIDATION. HUMAN STUDIES USING MAGNETIC RESONANCE IMAGING HAVE SHOWN THAT MATERNAL BMI PREDICTS INFANT INTRAHEPATOCELLULAR LIPID STORAGE, AS SEEN IN ANIMAL MODELS. THE GENERATIONAL TRANSFER OF NAFLD MAY OCCUR VIA EPIGENETIC CHANGES IN OFFSPRING LIVER. TRANSMISSION OF MICROBIOTA FROM MOTHER TO INFANT MAY IMPACT ENERGY RETENTION AND IMMUNE FUNCTION THAT CONTRIBUTE TO A PREDISPOSITION TO NAFLD. 2014