1 6867 115 [PARENTAL AGEING AND ASSISTED REPRODUCTION TECHNOLOGIES: ANALYSIS OF RISK OF CHRONIC DISEASES IN THE PROGENY]. CONCEPTION OF A CHILD AT ADVANCED PARENTAL AGE (> 35 YEARS) HAS BEEN STEADILY INCREASING IN RECENT DECADES, ESPECIALLY IN DEVELOPED COUNTRIES. SOCIO-ECONOMIC FACTORS, EFFECTIVE CONTRACEPTIVES, AND THE AVAILABILITY OF ASSISTED REPRODUCTION TECHNOLOGIES (ART) HAVE A DIRECT IMPACT ON POSTPONING THE DECISION TO HAVE A BABY. ART ENABLES REPRODUCTIVE SUCCESS FOR PEOPLE DIAGNOSED AS INFERTILE OR WITH REDUCED POSSIBILITIES OF BECOMING PREGNANT DUE TO CONCOMITANT PATHOLOGIES. EPIDEMIOLOGICAL STUDIES INDICATE THAT BOTH ADVANCED PARENTAL AGE AND ART ARE ASSOCIATED WITH PATHOLOGIES OF PREGNANCY, SUCH AS GESTATIONAL DIABETES, RISK OF PRE-ECLAMPSIA, MISCARRIAGE, PLACENTAL ABRUPTION, PRETERM LABOR, STILLBIRTH, NEURODEVELOPMENTAL DISORDERS AND CHRONIC DISEASE OF THE OFFSPRING. IN OUR WORK, WE WILL FOCUS ON THE AVAILABLE INFORMATION ON METABOLIC CHANGES THAT INCREASE THE RISK OF DEVELOPING CARDIOVASCULAR DISEASES IN THE OFFSPRING OF PARENTS AT AN ADVANCED AGE AND CONCEIVED THROUGH ART. FINALLY, WE WILL ADDRESS THE SOURCES OF THE OBSERVED DISTURBANCES AT THE GAMETE AND EMBRYO LEVEL, RELATED TO OXYGEN STRESS, EPIGENETIC MODIFICATIONS AND DNA DAMAGE, CONSIDERING POSSIBLE RESCUE ACTIONS. 2022 2 6173 43 THE HEALTH OUTCOMES OF HUMAN OFFSPRING CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART). CONCERNS HAVE BEEN RAISED ABOUT THE HEALTH AND DEVELOPMENT OF CHILDREN CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) SINCE 1978. CONTROVERSIALLY, ART HAS BEEN LINKED WITH ADVERSE OBSTETRIC AND PERINATAL OUTCOMES, AN INCREASED RISK OF BIRTH DEFECTS, CANCERS, AND GROWTH AND DEVELOPMENT DISORDERS. EMERGING EVIDENCE SUGGESTS THAT ART TREATMENT MAY ALSO PREDISPOSE INDIVIDUALS TO AN INCREASED RISK OF CHRONIC AGEING RELATED DISEASES SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE. THIS REVIEW WILL SUMMARIZE THE AVAILABLE EVIDENCE ON THE SHORT-TERM AND LONG-TERM HEALTH OUTCOMES OF ART SINGLETONS, AS MULTIPLE PREGNANCIES AFTER MULTIPLE EMBRYOS TRANSFER, ARE ASSOCIATED WITH LOW BIRTH WEIGHT AND PRETERM DELIVERY, WHICH CAN SEPARATELY INCREASE RISK OF ADVERSE POSTNATAL OUTCOMES, AND IMPACT LONG-TERM HEALTH. WE WILL ALSO EXAMINE THE POTENTIAL FACTORS THAT MAY CONTRIBUTE TO THESE HEALTH RISKS, AND DISCUSS UNDERLYING MECHANISMS, INCLUDING EPIGENETIC CHANGES THAT MAY OCCUR DURING THE PREIMPLANTATION PERIOD AND REPROGRAM DEVELOPMENT IN UTERO, AND ADULT HEALTH, LATER IN LIFE. LASTLY, THIS REVIEW WILL CONSIDER THE FUTURE DIRECTIONS WITH THE VIEW TO OPTIMIZE THE LONG-TERM HEALTH OF ART CHILDREN. 2017 3 6088 43 THE EFFECTS OF ASSISTED REPRODUCTION TECHNOLOGIES ON METABOLIC HEALTH AND DISEASEDAGGER. THE INCREASING PREVALENCE OF METABOLIC DISEASES PLACES A SUBSTANTIAL BURDEN ON HUMAN HEALTH THROUGHOUT THE WORLD. IT IS BELIEVED THAT PREDISPOSITION TO METABOLIC DISEASE STARTS EARLY IN LIFE, A PERIOD OF GREAT SUSCEPTIBILITY TO EPIGENETIC REPROGRAMMING DUE TO ENVIRONMENTAL INSULTS. ASSISTED REPRODUCTIVE TECHNOLOGIES (ART), I.E., TREATMENTS FOR INFERTILITY, MAY AFFECT EMBRYO DEVELOPMENT, RESULTING IN MULTIPLE ADVERSE HEALTH OUTCOMES IN POSTNATAL LIFE. THE MOST FREQUENTLY OBSERVED ALTERATION IN ART PREGNANCIES IS IMPAIRED PLACENTAL NUTRIENT TRANSFER. MOREOVER, CONSEQUENT INTRAUTERINE GROWTH RESTRICTION AND LOW BIRTH WEIGHT FOLLOWED BY CATCH-UP GROWTH CAN ALL PREDICT FUTURE OBESITY, INSULIN RESISTANCE, AND CHRONIC METABOLIC DISEASES. IN THIS REVIEW, WE HAVE FOCUSED ON EVIDENCE OF ADVERSE METABOLIC ALTERATIONS ASSOCIATED WITH ART, WHICH CAN CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC ADULT-ONSET DISEASES, SUCH AS METABOLIC SYNDROME, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE. DUE TO HIGH PHENOTYPIC PLASTICITY, ART PREGNANCIES CAN PRODUCE BOTH OFFSPRING WITH ADVERSE HEALTH OUTCOMES, AS WELL AS HEALTHY INDIVIDUALS. WE FURTHER DISCUSS THE SEX-SPECIFIC AND AGE-DEPENDENT METABOLIC ALTERATIONS REFLECTED IN ART OFFSPRING, AND HOW THE DEGREE OF INTERFERENCE OF A GIVEN ART PROCEDURE (FROM MILD TO MORE SEVERE MANIPULATION OF THE EGG) AFFECTS THE OCCURRENCE AND DEGREE OF OFFSPRING ALTERATIONS. OVER THE LAST FEW YEARS, STUDIES HAVE REPORTED SIGNS OF CARDIOMETABOLIC ALTERATIONS IN ART OFFSPRING THAT ARE DETECTABLE AT A YOUNG AGE BUT THAT DO NOT APPEAR TO CONSTITUTE A HIGH RISK OF DISEASE AND MORBIDITY PER SE. THESE ABNORMAL PHENOTYPES COULD BE EARLY INDICATORS OF THE DEVELOPMENT OF CHRONIC DISEASES, INCLUDING METABOLIC SYNDROME, IN ADULTHOOD. THE EARLY DETECTION OF METABOLIC ALTERATIONS COULD CONTRIBUTE TO PREVENTING THE ONSET OF DISEASE IN ADULTHOOD. SUCH EARLY INTERVENTIONS MAY COUNTERACT THE RISK FACTORS AND IMPROVE THE LONG-TERM HEALTH OF THE INDIVIDUAL. 2021 4 721 32 CAN ASSISTED REPRODUCTIVE TECHNOLOGIES CAUSE ADULT-ONSET DISEASE? EVIDENCE FROM HUMAN AND MOUSE. MILLIONS OF CHILDREN HAVE BEEN BORN WORLDWIDE THOUGH ASSISTED REPRODUCTIVE TECHNOLOGIES (ART). CONSISTENT WITH THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE HYPOTHESIS, THERE IS CONCERN THAT ART CAN INDUCE ADVERSE EFFECTS, ESPECIALLY BECAUSE PROCEDURES COINCIDE WITH EPIGENETIC REPROGRAMMING EVENTS. ALTHOUGH THE MAJORITY OF STUDIES INVESTIGATING THE EFFECTS OF ART HAVE FOCUSED ON PERINATAL OUTCOMES, MORE RECENT STUDIES DEMONSTRATE THAT ART-CONCEIVED CHILDREN MAY BE AT INCREASED RISK FOR POSTNATAL EFFECTS. HERE, WE PRESENT THE CURRENT EPIDEMIOLOGICAL EVIDENCE THAT ART-CONCEIVED CHILDREN HAVE DETECTABLE DIFFERENCES IN BLOOD PRESSURE, BODY COMPOSITION, AND GLUCOSE HOMEOSTASIS. SIMILAR EFFECTS ARE OBSERVED IN THE ART MOUSE MODEL, WHICH HAVE NO UNDERLYING INFERTILITY, SUGGESTING THAT CARDIOMETABOLIC EFFECTS ARE LIKELY CAUSED BY ART PROCEDURES AND NOT DUE TO REASONS RELATED TO INFERTILITY. WE PROPOSE THAT THE MOUSE SYSTEM CAN, CONSEQUENTLY, BE USED TO ADEQUATELY STUDY, MODIFY, AND IMPROVE OUTCOMES FOR ART CHILDREN. 2017 5 483 37 ART AND HEALTH: CLINICAL OUTCOMES AND INSIGHTS ON MOLECULAR MECHANISMS FROM RODENT STUDIES. SINCE THE BIRTH OF THE FIRST IVF-CONCEIVED CHILD IN 1978, THE USE OF ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) HAS GROWN DRAMATICALLY, CONTRIBUTING TO THE SUCCESSFUL BIRTH OF 5 MILLION INDIVIDUALS WORLDWIDE. HOWEVER, THERE ARE SEVERAL REPORTED ASSOCIATIONS OF ART WITH PREGNANCY COMPLICATIONS, SUCH AS LOW BIRTHWEIGHT (LBW), PRETERM BIRTH, BIRTH DEFECTS, EPIGENETIC DISORDERS, CANCER AND POOR METABOLIC HEALTH. WHETHER THIS IS ATTRIBUTED TO ART PROCEDURES OR TO THE SUBSET OF THE POPULATION SEEKING ART REMAINS A CONTROVERSY, BUT THE MOST RELEVANT QUESTION TODAY CONCERNS THE POTENTIAL LONG-TERM IMPLICATIONS OF ASSISTED CONCEPTION. RECENT EVIDENCE HAS EMERGED SUGGESTING THAT ART-CONCEIVED CHILDREN HAVE DISTINCT METABOLIC PROFILES THAT MAY PREDISPOSE TO CARDIOVASCULAR PATHOLOGIES IN ADULTHOOD. BECAUSE THE ELDEST IVF INDIVIDUALS ARE STILL TOO YOUNG TO EXHIBIT COMPONENTS OF CHRONIC MIDDLE-AGED SYNDROMES, THE USE OF ANIMAL MODELS HAS BECOME PARTICULARLY USEFUL IN DESCRIBING THE EFFECTS OF UNUSUAL OR STRESSFUL PREIMPLANTATION EXPERIENCES ON ADULT FITNESS. ELUCIDATING THE MOLECULAR MECHANISMS BY WHICH EMBRYOS INTEGRATE ENVIRONMENTAL SIGNALS INTO DEVELOPMENT AND METABOLIC GENE EXPRESSION PROGRAMS WILL BE ESSENTIAL FOR OPTIMIZING ART PROCEDURES SUCH AS IN VITRO CULTURE CONDITIONS, EMBRYO SELECTION AND TRANSFER. IN THE FUTURE, ADDITIONAL ANIMAL STUDIES TO IDENTIFY MECHANISMS UNDERLYING UNFAVORABLE ART OUTCOMES, AS WELL AS MORE EPIDEMIOLOGICAL REVIEWS TO MONITOR THE LONG-TERM HEALTH OF ART CHILDREN ARE REQUIRED, GIVEN THAT ART PROCEDURES HAVE BECOME ROUTINE MEDICAL PRACTICE. 2013 6 4863 34 ORIGINS OF LIFETIME HEALTH AROUND THE TIME OF CONCEPTION: CAUSES AND CONSEQUENCES. PARENTAL ENVIRONMENTAL FACTORS, INCLUDING DIET, BODY COMPOSITION, METABOLISM, AND STRESS, AFFECT THE HEALTH AND CHRONIC DISEASE RISK OF PEOPLE THROUGHOUT THEIR LIVES, AS CAPTURED IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE CONCEPT. RESEARCH ACROSS THE EPIDEMIOLOGICAL, CLINICAL, AND BASIC SCIENCE FIELDS HAS IDENTIFIED THE PERIOD AROUND CONCEPTION AS BEING CRUCIAL FOR THE PROCESSES MEDIATING PARENTAL INFLUENCES ON THE HEALTH OF THE NEXT GENERATION. DURING THIS TIME, FROM THE MATURATION OF GAMETES THROUGH TO EARLY EMBRYONIC DEVELOPMENT, PARENTAL LIFESTYLE CAN ADVERSELY INFLUENCE LONG-TERM RISKS OF OFFSPRING CARDIOVASCULAR, METABOLIC, IMMUNE, AND NEUROLOGICAL MORBIDITIES, OFTEN TERMED DEVELOPMENTAL PROGRAMMING. WE REVIEW PERICONCEPTIONAL INDUCTION OF DISEASE RISK FROM FOUR BROAD EXPOSURES: MATERNAL OVERNUTRITION AND OBESITY; MATERNAL UNDERNUTRITION; RELATED PATERNAL FACTORS; AND THE USE OF ASSISTED REPRODUCTIVE TREATMENT. STUDIES IN BOTH HUMANS AND ANIMAL MODELS HAVE DEMONSTRATED THE UNDERLYING BIOLOGICAL MECHANISMS, INCLUDING EPIGENETIC, CELLULAR, PHYSIOLOGICAL, AND METABOLIC PROCESSES. WE ALSO PRESENT A META-ANALYSIS OF MOUSE PATERNAL AND MATERNAL PROTEIN UNDERNUTRITION THAT SUGGESTS DISTINCT PARENTAL PERICONCEPTIONAL CONTRIBUTIONS TO POSTNATAL OUTCOMES. WE PROPOSE THAT THE EVIDENCE FOR PERICONCEPTIONAL EFFECTS ON LIFETIME HEALTH IS NOW SO COMPELLING THAT IT CALLS FOR NEW GUIDANCE ON PARENTAL PREPARATION FOR PREGNANCY, BEGINNING BEFORE CONCEPTION, TO PROTECT THE HEALTH OF OFFSPRING. 2018 7 3707 33 INFLUENCE OF MATERNAL OVERNUTRITION AND GESTATIONAL DIABETES ON THE PROGRAMMING OF METABOLIC HEALTH OUTCOMES IN THE OFFSPRING: EXPERIMENTAL EVIDENCE. THE INCIDENCE OF OBESITY AND TYPE 2 DIABETES MELLITUS HAVE RISEN ACROSS THE WORLD DURING THE PAST FEW DECADES AND HAS ALSO REACHED AN ALARMING LEVEL AMONG CHILDREN. IN ADDITION, WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. AS A RESULT, THE INCIDENCE OF GESTATIONAL DIABETES MELLITUS IS ALSO ON THE RISE. WHILE DIET AND LIFESTYLE CONTRIBUTE TO THESE TRENDS, POPULATION HEALTH DATA SHOW THAT MATERNAL OBESITY AND DIABETES DURING PREGNANCY DURING CRITICAL STAGES OF DEVELOPMENT ARE MAJOR FACTORS THAT CONTRIBUTE TO THE DEVELOPMENT OF CHRONIC DISEASE IN ADOLESCENT AND ADULT OFFSPRING. FETAL PROGRAMMING OF METABOLIC FUNCTION, THROUGH PHYSIOLOGICAL AND (OR) EPIGENETIC MECHANISMS, MAY ALSO HAVE AN INTERGENERATIONAL EFFECT, AND AS A RESULT MAY PERPETUATE METABOLIC DISORDERS IN THE NEXT GENERATION. IN THIS REVIEW, WE SUMMARIZE THE EXISTING LITERATURE THAT CHARACTERIZES HOW MATERNAL OBESITY AND GESTATIONAL DIABETES MELLITUS CONTRIBUTE TO METABOLIC AND CARDIOVASCULAR DISORDERS IN THE OFFSPRING. IN PARTICULAR, WE FOCUS ON ANIMAL STUDIES THAT INVESTIGATE THE MOLECULAR MECHANISMS THAT ARE PROGRAMMED BY THE GESTATIONAL ENVIRONMENT AND LEAD TO DISEASE PHENOTYPES IN THE OFFSPRING. WE ALSO REVIEW INTERVENTIONAL STUDIES THAT PREVENT DISEASE WITH A DEVELOPMENTAL ORIGIN IN THE OFFSPRING. 2015 8 4803 29 OBESITY AND MALE INFERTILITY. THE WORLDWIDE PREVALENCE OF OBESITY IS INCREASING AMONG BOTH SEXES, WITH ASSOCIATED IMPACTS ON CHRONIC HEALTH AND MEDICAL COMORBIDITIES. SIMILARLY, THE EFFECTS OF OBESITY ON REPRODUCTIVE HEALTH ARE INCREASINGLY BEING RECOGNIZED. ADIPOSITY IS ASSOCIATED WITH REDUCED FERTILITY IN MEN, WITH A COMPLEX AND MULTIFACTORIAL ETIOLOGY. THE REPORTED EFFECTS OF OBESITY ON SEMEN PARAMETERS AND IMPAIRED FERTILITY ARE CONTRASTING, WITH SOME STUDIES SHOWING A CLEAR REDUCTION IN REPRODUCTIVE OUTCOMES ASSOCIATED WITH INCREASED BODY MASS INDEX, WHILE OTHERS DO NOT SHOW SUCH IMPACTS. THESE CONTROVERSIES MAY BE DUE TO THE COMPLEX PATHOPHYSIOLOGY AND INTERPLAY BETWEEN GONADOTROPINS AND END ORGANS, AS WELL AS GENETIC AND EPIGENETIC CHANGES AND OXIDATIVE STRESS ON MALE FERTILITY AND FUNCTION. THESE DIFFERENT ASPECTS HAVE LED TO HETEROGENEOUS PARTICIPANTS IN STUDIES AND VARYING IMPLICATIONS FOR ASSISTED REPRODUCTIVE OUTCOMES AS WELL AS OFFSPRING HEALTH. TREATMENT MODALITIES TO MANAGE OBESITY INCLUDE LIFESTYLE, MEDICAL, AND SURGICAL OPTIONS, WITH EMERGING AND EFFECTIVE MEDICAL TREATMENTS SHOWING PROMISE IN REPRODUCTIVE OUTCOMES. 2023 9 6873 32 [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 1370 36 DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE THEORY IN CARDIOLOGY. NUMEROUS EPIDEMIOLOGICAL AND ANIMAL STUDIES DISCLOSED THAT BIRTH WEIGHT IS INVERSELY ASSOCIATED WITH THE INCIDENCE OF THE LIFESTYLE-RELATED DISORDERS IN ADULT LIFE, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, AND /OR CHRONIC KIDNEY DISEASE. LOWER BIRTH WEIGHT OCCURS IN NUMEROUS UNDESIRED INTRAUTERINE ENVIRONMENTS INCLUDING MALNUTRITION, SMOKING, ALCOHOL CONSUMPTION, OR STRESS. THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE (DOHAD) THEORY IS BASED ON THE CONCEPT THAT THE ORIGINS OF LIFESTYLE-RELATED DISEASE IS FORMED AT THE TIME OF FERTILIZATION, EMBRYONIC, FETAL, AND NEONATAL STAGES BY THE INTERRELATION BETWEEN GENES AND THE ENVIRONMENTS (NUTRITION, STRESS, OR ENVIRONMENTAL CHEMICALS). ADULT DISEASE DEVELOPS AFTER DELIVERY FACING TO ABNORMAL ENVIRONMENTS SUCH AS OVER-NUTRITION, MUCH STRESS, OR LACK OF EXERCISE. DISEASE DEVELOPS THROUGH THESE TWO INSULTS. THIS CONCEPT WAS FIRST PROPOSED AS THE "BARKER HYPOTHESIS." DAVID BARKER HAD DISCOVERED THE RELATION BETWEEN THE LOWER BIRTH WEIGHT AND THE HIGHER PREVALENCE OF ISCHEMIC HEART DISEASE MORTALITY. PREVIOUS EPIDEMIOLOGIC STUDIES HAVE FOUND THE PEOPLE EXPOSED TO FAMINE DURING EARLY LIFE HAD HIGHER RISKS OF CARDIOVASCULAR DISEASES IN ADULTHOOD. YET, THE EXACT MECHANISMS THAT PERMANENTLY CHANGE THE STRUCTURE, PHYSIOLOGY, AND ENDOCRINE STATUS OF AN INDIVIDUAL ACROSS THEIR LIFESPAN FOLLOWING ALTERED GROWTH DURING FETAL LIFE ARE NOT ENTIRELY CLEAR. EPIDEMIOLOGICAL STUDIES INCLUDING PROSPECTIVE COHORT AND OBSERVATIONAL ANALYSIS OF THE PEOPLE EXPOSED TO MALNUTRITION DURING FETAL OR INFANCY HAVE DISCLOSED THE STRONG RELATION BETWEEN THE LOWER BIRTH WEIGHT AND THE HIGHER CARDIOVASCULAR RISKS IN ADULTS. RECENT PROGRESS OF EPIGENETIC STUDIES UNVEILED STRONG GENETIC ASSOCIATION. HORMONAL REGULATION AND EPIGENETIC MODIFICATIONS HAVE AN IMPORTANT ROLE FOR PROPER ORGAN DEVELOPMENT AND PHYSIOLOGICAL FUNCTIONS. THE MOLECULAR MECHANISM OF PREDISPOSITION IS SUPPOSED TO BE THE EPIGENETICS MODIFICATIONS. THEIR DYSREGULATION IS RELATED TO THE ACQUISITION OF THE DISEASE-SUSCEPTIBLE TRAIT. IN THIS REVIEW, WE OVERVIEW THE CONCEPT OF DOHAD AND INTRODUCE RELATED CLINICAL AND BASIC RESEARCH. 2020 11 5089 36 PLACENTAL ADAPTATIONS TO MICRONUTRIENT DYSREGULATION IN THE PROGRAMMING OF CHRONIC DISEASE. POOR NUTRITION DURING PREGNANCY IS KNOWN TO IMPAIR FOETAL DEVELOPMENT AND INCREASE THE RISK OF CHRONIC DISEASE IN OFFSPRING. BOTH MACRONUTRIENTS AND MICRONUTRIENTS ARE REQUIRED FOR A HEALTHY PREGNANCY ALTHOUGH SIGNIFICANTLY LESS IS UNDERSTOOD ABOUT THE ROLE OF MICRONUTRIENTS IN THE PROGRAMMING OF CHRONIC DISEASE. THIS IS DESPITE THE FACT THAT MODERN CALORIE RICH DIETS ARE OFTEN ALSO DEFICIENT IN KEY MICRONUTRIENTS. THE IMPORTANCE OF MICRONUTRIENTS IN GESTATIONAL DISORDERS IS CLEARLY UNDERSTOOD BUT HOW THEY IMPACT LONG TERM DISEASE IN HUMANS REQUIRES FURTHER INVESTIGATION. IN CONTRAST, ANIMAL STUDIES HAVE DEMONSTRATED HOW DIETS HIGH OR LOW IN SPECIFIC MICRONUTRIENTS INFLUENCE OFFSPRING PHYSIOLOGY. MANY OF THESE STUDIES HIGHLIGHT THE IMPORTANCE OF THE PLACENTA IN DETERMINING DISEASE RISK. THIS REVIEW WILL EXPLORE THE EFFECTS OF INDIVIDUAL VITAMINS, MINERALS AND TRACE ELEMENTS ON OFFSPRING DISEASE OUTCOMES AND DISCUSS SEVERAL KEY PLACENTAL ADAPTATIONS THAT ARE AFFECTED BY MULTIPLE MICRONUTRIENTS. THESE PLACENTAL ADAPTATIONS INCLUDE MICRONUTRIENT INDUCED DYSREGULATION OF OXIDATIVE STRESS, ALTERED METHYL DONOR AVAILABILITY AND ITS IMPACT ON EPIGENETIC MECHANISMS AS WELL AS ENDOCRINE DYSFUNCTION. CRITICAL GAPS IN OUR CURRENT KNOWLEDGE AND THE RELATIVE IMPORTANCE OF DIFFERENT MICRONUTRIENTS AT DIFFERENT GESTATIONAL AGES WILL ALSO BE HIGHLIGHTED. FINALLY, THIS REVIEW WILL DISCUSS THE NEED FOR FURTHER STUDIES TO CHARACTERISE THE MICRONUTRIENT STATUS OF AUSTRALIAN WOMEN OF REPRODUCTIVE AGE AND CORRELATE MICRONUTRIENT STATUS TO PLACENTAL ADAPTATIONS, PREGNANCY COMPLICATIONS AND OFFSPRING DISEASE. 2018 12 4078 30 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 13 6234 32 THE LONG-TERM EFFECTS OF PRENATAL DEVELOPMENT ON GROWTH AND METABOLISM. PEOPLE WHO WERE SMALL AT BIRTH AND HAD POOR INFANT GROWTH HAVE AN INCREASED RISK OF ADULT CARDIOVASCULAR DISEASE, OSTEOPOROSIS, AND TYPE 2 DIABETES, PARTICULARLY IF THEIR RESTRICTED EARLY GROWTH WAS FOLLOWED BY INCREASED CHILDHOOD WEIGHT GAIN. THESE RELATIONS EXTEND ACROSS THE NORMAL RANGE OF BIRTH SIZE IN A GRADED MANNER, SO REDUCED SIZE IS NOT A PREREQUISITE. IN ADDITION, LARGER BIRTH SIZE IS ASSOCIATED WITH RISKS OF OBESITY AND TYPE 2 DIABETES. THE ASSOCIATIONS APPEAR TO REFLECT DEVELOPMENTAL PLASTIC RESPONSES MADE BY THE FETUS AND INFANT BASED ON CUES ABOUT THE ENVIRONMENT, INFLUENCED BY MATERNAL CHARACTERISTICS INCLUDING DIET, BODY COMPOSITION, STRESS, AND EXERCISE LEVELS. THESE RESPONSES INVOLVE EPIGENETIC PROCESSES THAT MODIFY THE OFFSPRING'S PHENOTYPE. VULNERABILITY TO ILL HEALTH RESULTS IF THE ENVIRONMENT IN INFANCY, CHILDHOOD, AND LATER LIFE IS MISMATCHED TO THE PHENOTYPE INDUCED IN DEVELOPMENT, INFORMED BY THE DEVELOPMENTAL CUES. THIS MISMATCH MAY ARISE THROUGH UNBALANCED DIET OR BODY COMPOSITION OF THE MOTHER OR A CHANGE IN LIFESTYLE FACTORS BETWEEN GENERATIONS. THESE INSIGHTS OFFER NEW POSSIBILITIES FOR THE EARLY DIAGNOSIS AND PREVENTION OF CHRONIC DISEASE. 2011 14 3573 33 IMPACT OF MATERNAL UNDERNUTRITION ON DIABETES AND CARDIOVASCULAR DISEASE RISK IN ADULT OFFSPRING. EPIDEMIOLOGICAL, CLINICAL, AND EXPERIMENTAL OBSERVATIONS HAVE LED TO THE HYPOTHESIS THAT THE RISK OF DEVELOPING CHRONIC DISEASES IN ADULTHOOD IS INFLUENCED NOT ONLY BY GENETIC AND ADULT LIFESTYLE FACTORS, BUT ALSO BY ENVIRONMENTAL FACTORS DURING EARLY LIFE. LOW BIRTH WEIGHT, A MARKER OF INTRAUTERINE STRESS, HAS BEEN LINKED TO PREDISPOSITION TO CARDIOVASCULAR DISEASE (CVD) AND DIABETES. THE COMPELLING ANIMAL EVIDENCE AND SIGNIFICANT HUMAN DATA TO SUPPORT THIS CONCLUSION ARE REVIEWED. SPECIFICALLY, THE REVIEW DISCUSSES THE ROLE OF MATERNAL NUTRITION BEFORE AND DURING PREGNANCY, PLACENTAL INSUFFICIENCIES AND EPIGENETIC CHANGES IN THE INCREASED PREDISPOSITION TO DIABETES AND CVD IN ADULT LIFE. THE IMPACT OF LOW BIRTH WEIGHT AND CATCH-UP GROWTH AS THEY PERTAIN TO RISK OF DISEASE IN ADULT LIFE IS ALSO DISCUSSED. IN ADDITION, ADULT DISEASE RISK IN THE OVERNOURISHED FETUS IS ALSO MENTIONED. REFERENCE IS MADE TO SOME OF THE MECHANISMS OF THE INDUCTION OF DIABETES AND CVD PHENOTYPE. IT IS PROPOSED THAT FETAL NUTRITION, GROWTH AND DEVELOPMENT THROUGH EFFICIENT MATERNAL NUTRITION BEFORE AND DURING PREGNANCY COULD CONSTITUTE THE BASIS FOR NUTRITIONAL STRATEGIES FOR THE PRIMARY PREVENTION OF DIABETES AND CVD. 2009 15 4782 27 NUTRIGENETICS, EPIGENETICS AND GESTATIONAL DIABETES: CONSEQUENCES IN MOTHER AND CHILD. GESTATIONAL DIABETES MELLITUS (GDM) IS THE MOST COMMON METABOLIC CONDITION DURING PREGNANCY AND MAY RESULT IN SHORT- AND LONG-TERM COMPLICATIONS FOR BOTH MOTHER AND OFFSPRING. THE COMPLEXITY OF PHENOTYPIC OUTCOMES SEEMS INFLUENCED BY GENETIC SUSCEPTIBILITY, NUTRIENT-GENE INTERACTIONS AND LIFESTYLE INTERACTING WITH CLINICAL FACTORS. THERE IS STRONG EVIDENCE THAT NOT ONLY THE ADVERSE GENETIC BACKGROUND BUT ALSO THE EPIGENETIC MODIFICATIONS IN RESPONSE TO NUTRITIONAL AND ENVIRONMENTAL FACTORS COULD INFLUENCE THE MATERNAL HYPERGLYCEMIA IN PREGNANCY AND THE FOETAL METABOLIC PROGRAMMING. IN THIS VIEW, THE CORRELATION BETWEEN EPIGENETIC MODIFICATIONS AND THEIR TRANSGENERATIONAL EFFECTS REPRESENTS A VERY INTERESTING FIELD OF STUDY. THE PRESENT REVIEW GIVES INSIGHT INTO THE ROLE OF GENE VARIANTS AND THEIR INTERACTIONS WITH NUTRIENTS IN GDM. IN ADDITION, WE PROVIDE AN OVERVIEW OF THE EPIGENETIC CHANGES AND THEIR ROLE IN THE MATERNAL-FOETAL TRANSMISSION OF CHRONIC DISEASES. OVERALL, THE KNOWLEDGE OF EPIGENETIC MODIFICATIONS INDUCED BY AN ADVERSE INTRAUTERINE AND PERINATAL ENVIRONMENT COULD SHED LIGHT ON THE POTENTIAL PATHOPHYSIOLOGICAL MECHANISMS OF LONG-TERM DISEASE DEVELOPMENT IN THE OFFSPRING AND PROVIDE USEFUL TOOLS FOR THEIR PREVENTION. 2019 16 6554 24 TRANSGENERATIONAL EFFECTS OF EARLY ENVIRONMENTAL INSULTS ON AGING AND DISEASE INCIDENCE. ADVERSE EARLY LIFE EXPERIENCES ARE MAJOR INFLUENCES ON DEVELOPMENTAL TRAJECTORIES WITH POTENTIALLY LIFE-LONG CONSEQUENCES. PRENATAL OR EARLY POSTNATAL EXPOSURE TO STRESS, UNDERNUTRITION OR ENVIRONMENTAL TOXICANTS MAY REPROGRAM BRAIN DEVELOPMENT AND INCREASE RISK OF BEHAVIOURAL AND NEUROLOGICAL DISORDERS LATER IN LIFE. NOT ONLY EXPERIENCE WITHIN A SINGLE LIFETIME, BUT ALSO ANCESTRAL EXPERIENCE AFFECTS HEALTH TRAJECTORIES AND CHANCES OF SUCCESSFUL AGING. THE CENTRAL MECHANISM IN TRANSGENERATIONAL PROGRAMMING OF A DISEASE MAY BE THE FORMATION OF EPIGENETIC MEMORY. THIS REVIEW EXPLORES TRANSGENERATIONAL EFFECTS OF EARLY ADVERSE EXPERIENCE ON HEALTH AND DISEASE INCIDENCE IN OLDER AGE. FIRST, WE ADDRESS MECHANISMS OF DEVELOPMENTAL AND TRANSGENERATIONAL PROGRAMMING OF DISEASE AND INHERITANCE. SECOND, WE DISCUSS EXPERIMENTAL AND CLINICAL FINDINGS LINKING EARLY ENVIRONMENTAL DETERMINANTS TO ADVERSE AGING TRAJECTORIES IN ASSOCIATION WITH POSSIBLE PARENTAL CONTRIBUTIONS AND SEX-SPECIFIC EFFECTS. THIRD, WE OUTLINE THE MAIN MECHANISMS OF AGE-RELATED FUNCTIONAL DECLINE AND SUGGEST POTENTIAL INTERVENTIONS TO REVERSE NEGATIVE EFFECTS OF TRANSGENERATIONAL PROGRAMMING. THUS, STRATEGIES THAT SUPPORT HEALTHY DEVELOPMENT AND SUCCESSFUL AGING SHOULD TAKE INTO ACCOUNT THE POTENTIAL INFLUENCES OF TRANSGENERATIONAL INHERITANCE. 2020 17 2802 26 FETAL AND INFANT ORIGINS OF ASTHMA. PREVIOUS STUDIES HAVE SUGGESTED THAT ASTHMA, LIKE OTHER COMMON DISEASES, HAS AT LEAST PART OF ITS ORIGIN EARLY IN LIFE. LOW BIRTH WEIGHT HAS BEEN SHOWN TO BE ASSOCIATED WITH INCREASED RISKS OF ASTHMA, CHRONIC OBSTRUCTIVE AIRWAY DISEASE, AND IMPAIRED LUNG FUNCTION IN ADULTS, AND INCREASED RISKS OF RESPIRATORY SYMPTOMS IN EARLY CHILDHOOD. THE DEVELOPMENTAL PLASTICITY HYPOTHESIS SUGGESTS THAT THE ASSOCIATIONS BETWEEN LOW BIRTH WEIGHT AND DISEASES IN LATER LIFE ARE EXPLAINED BY ADAPTATION MECHANISMS IN FETAL LIFE AND INFANCY IN RESPONSE TO VARIOUS ADVERSE EXPOSURES. VARIOUS PATHWAYS LEADING FROM ADVERSE FETAL AND INFANT EXPOSURES TO GROWTH ADAPTATIONS AND RESPIRATORY HEALTH OUTCOMES HAVE BEEN STUDIED, INCLUDING FETAL AND EARLY INFANT GROWTH PATTERNS, MATERNAL SMOKING AND DIET, CHILDREN'S DIET, RESPIRATORY TRACT INFECTIONS AND ACETAMINOPHEN USE, AND GENETIC SUSCEPTIBILITY. STILL, THE SPECIFIC ADVERSE EXPOSURES IN FETAL AND EARLY POSTNATAL LIFE LEADING TO RESPIRATORY DISEASE IN ADULT LIFE ARE NOT YET FULLY UNDERSTOOD. CURRENT STUDIES SUGGEST THAT BOTH ENVIRONMENTAL AND GENETIC FACTORS IN VARIOUS PERIODS OF LIFE, AND THEIR EPIGENETIC MECHANISMS MAY UNDERLIE THE COMPLEX ASSOCIATIONS OF LOW BIRTH WEIGHT WITH RESPIRATORY DISEASE IN LATER LIFE. NEW WELL-DESIGNED EPIDEMIOLOGICAL STUDIES ARE NEEDED TO IDENTIFY THE SPECIFIC UNDERLYING MECHANISMS. THIS REVIEW IS FOCUSED ON SPECIFIC ADVERSE FETAL AND INFANT GROWTH PATTERNS AND EXPOSURES, GENETIC SUSCEPTIBILITY, POSSIBLE RESPIRATORY ADAPTATIONS AND PERSPECTIVES FOR NEW STUDIES. 2012 18 4790 29 NUTRITIONAL ADVERSITY, SEX AND REPRODUCTION: 30 YEARS OF DOHAD AND WHAT HAVE WE LEARNED? IT IS WELL ESTABLISHED THAT EARLY LIFE ENVIRONMENTAL SIGNALS, INCLUDING NUTRITION, SET THE STAGE FOR LONG-TERM HEALTH AND DISEASE RISK - EFFECTS THAT SPAN MULTIPLE GENERATIONS. THIS RELATIONSHIP BEGINS EARLY, IN THE PERICONCEPTIONAL PERIOD AND EXTENDS INTO EMBRYONIC, FETAL AND EARLY INFANT PHASES OF LIFE. NOW KNOWN AS THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD), THIS CONCEPT DESCRIBES THE ADAPTATIONS THAT A DEVELOPING ORGANISM MAKES IN RESPONSE TO EARLY LIFE CUES, RESULTING IN ADJUSTMENTS IN HOMEOSTATIC SYSTEMS THAT MAY PROVE MALADAPTIVE IN POSTNATAL LIFE, LEADING TO AN INCREASED RISK OF CHRONIC DISEASE AND/OR THE INHERITANCE OF RISK FACTORS ACROSS GENERATIONS. REPRODUCTIVE MATURATION AND FUNCTION IS SIMILARLY INFLUENCED BY EARLY LIFE EVENTS. THIS SHOULD NOT BE SURPRISING, SINCE PRIMORDIAL GERM CELLS ARE ESTABLISHED EARLY IN LIFE AND THUS VULNERABLE TO EARLY LIFE ADVERSITY. A MULTITUDE OF 'MODIFYING' CUES INDUCING DEVELOPMENTAL ADAPTATIONS HAVE BEEN IDENTIFIED THAT RESULT IN CHANGES IN REPRODUCTIVE DEVELOPMENT AND IMPAIRMENTS IN REPRODUCTIVE FUNCTION. MANY TYPES OF NUTRITIONAL CHALLENGES INCLUDING CALORIC RESTRICTION, MACRONUTRIENT EXCESS AND MICRONUTRIENT INSUFFICIENCIES HAVE BEEN SHOWN TO INDUCE EARLY LIFE ADAPTATIONS THAT PRODUCE LONG-TERM REPRODUCTIVE DYSFUNCTION. MANY PATHWAYS HAVE BEEN SUGGESTED TO UNDERPIN THESE ASSOCIATIONS, INCLUDING EPIGENETIC REPROGRAMMING OF GERM CELLS. WHILE THE MECHANISMS STILL REMAIN TO BE FULLY INVESTIGATED, IT IS CLEAR THAT A LIFECOURSE APPROACH TO UNDERSTANDING LIFETIME REPRODUCTIVE FUNCTION IS NECESSARY. FURTHERMORE, INVESTIGATIONS OF THE IMPACTS OF EARLY LIFE ADVERSITY MUST BE EXTENDED TO INCLUDE THE PATERNAL ENVIRONMENT, ESPECIALLY IN EPIDEMIOLOGICAL AND CLINICAL STUDIES OF OFFSPRING REPRODUCTIVE FUNCTION. 2019 19 3582 25 IMPACT OF PRENATAL AND EARLY LIFE ENVIRONMENTAL EXPOSURES ON NORMAL HUMAN DEVELOPMENT. THE GLOBAL BURDEN AND PATTERN OF DISEASE HAS CHANGED IN RECENT DECADES, WITH FEWER EARLY CHILDHOOD DEATHS AND LONGER LIVES COMPLICATED BY CHRONIC DISEASE. DISRUPTION OF NORMAL HUMAN GROWTH AND DEVELOPMENT BY ADVERSE ENVIRONMENTAL EXPOSURES, ESPECIALLY DURING FOETAL DEVELOPMENT AND EARLY POSTNATAL LIFE INCREASE LIFE-LONG RISK OF CHRONIC DISEASE. THE DEVELOPMENTAL TIMING AND METHOD OF ADVERSE EXPOSURE DETERMINES THE LIKELY IMPACT ON HEALTH AND DEVELOPMENT. WHILE MANY ORGAN SYSTEMS ARE STRUCTURALLY AND FUNCTIONALLY MATURE AT BIRTH, THE CNS, RESPIRATORY AND IMMUNE SYSTEMS ARE NOT AND UNDERGO PROLONGED PERIODS OF POSTNATAL GROWTH AND DEVELOPMENT. AS SUCH, THESE ORGAN SYSTEMS ARE VULNERABLE TO ADVERSE EFFECTS OF BOTH PRENATAL AND POSTNATAL ENVIRONMENTAL EXPOSURES. WHILE THE PRECISE MECHANISMS UNDERLYING CHRONIC DISEASE ARE UNKNOWN, EPIGENETIC MECHANISMS AND THE INDUCTION OF OXIDATIVE STRESS ARE LIKELY TO BE INVOLVED. AN UNDERSTANDING OF THESE PROCESSES IS NECESSARY TO DEVELOP MITIGATION STRATEGIES AIMED AT REDUCING CHRONIC DISEASE PREVALENCE. 2021 20 6064 31 THE DEVELOPMENTAL ORIGINS OF ADULT DISEASE. EPIDEMIOLOGICAL AND CLINICAL OBSERVATIONS HAVE LED TO THE HYPOTHESIS THAT THE RISK OF DEVELOPING SOME CHRONIC DISEASES IN ADULTHOOD IS INFLUENCED NOT ONLY BY GENETIC AND ADULT LIFESTYLE FACTORS, BUT ALSO BY ENVIRONMENTAL FACTORS ACTING IN EARLY LIFE. THESE FACTORS ACT THROUGH THE PROCESSES OF DEVELOPMENTAL PLASTICITY AND POSSIBLY EPIGENETIC MODIFICATION, AND CAN BE DISTINGUISHED FROM DEVELOPMENTAL DISRUPTION. THE CONCEPT OF PREDICTIVE ADAPTATION HAS BEEN DEVELOPED TO EXPLAIN THE RELATIONSHIP BETWEEN EARLY LIFE EVENTS AND THE RISK OF LATER DISEASE. AT ITS BASE, THE MODEL SUGGESTS THAT A MISMATCH BETWEEN FETAL EXPECTATION OF ITS POSTNATAL ENVIRONMENT AND ACTUAL POSTNATAL ENVIRONMENT CONTRIBUTE TO LATER ADULT DISEASE RISK. THIS MISMATCH IS EXACERBATED, IN PART, BY THE PHENOMENON OF "MATERNAL CONSTRAINT" ON FETAL GROWTH, WHICH IMPLICITLY PROVIDES AN UPPER LIMIT OF POSTNATAL NUTRITIONAL ENVIRONMENT THAT HUMANS HAVE ADAPTED FOR AND IS NOW FREQUENTLY EXCEEDED. THESE EXPERIMENTAL, CLINICAL AND CONCEPTUAL CONSIDERATIONS HAVE IMPORTANT IMPLICATIONS FOR PREVENTION AND INTERVENTION IN THE CURRENT EPIDEMIC OF CHILDHOOD OBESITY AND ADULT METABOLIC AND CARDIOVASCULAR DISORDERS. 2005