1   649 136 BIRTHWEIGHT, MATERNAL WEIGHT TRAJECTORIES AND GLOBAL DNA METHYLATION OF LINE-1 REPETITIVE ELEMENTS. LOW BIRTHWEIGHT, PREMATURE BIRTH, INTRAUTERINE GROWTH RETARDATION, AND MATERNAL MALNUTRITION HAVE BEEN RELATED TO AN INCREASED RISK OF CARDIOVASCULAR DISEASE, TYPE 2 DIABETES MELLITUS, OBESITY, AND NEUROPSYCHIATRIC DISORDERS LATER IN LIFE. CONVERSELY, HIGH BIRTHWEIGHT HAS BEEN LINKED TO FUTURE RISK OF CANCER. GLOBAL DNA METHYLATION ESTIMATED BY THE METHYLATION OF REPETITIVE SEQUENCES IN THE GENOME IS AN INDICATOR OF SUSCEPTIBILITY TO CHRONIC DISEASES. WE USED DATA AND BIOSPECIMENS FROM AN EPIGENETIC BIRTH COHORT TO EXPLORE THE ASSOCIATION BETWEEN TRAJECTORIES OF FETAL AND MATERNAL WEIGHT AND LINE-1 METHYLATION IN 319 MOTHER-CHILD DYADS. NEWBORNS WITH LOW OR HIGH BIRTHWEIGHT HAD SIGNIFICANTLY LOWER LINE-1 METHYLATION LEVELS IN THEIR CORD BLOOD COMPARED TO NORMAL WEIGHT INFANTS AFTER ADJUSTING FOR GESTATIONAL AGE, SEX OF THE CHILD, MATERNAL AGE AT DELIVERY, AND MATERNAL SMOKING DURING PREGNANCY (P = 0.007 AND P = 0.036, RESPECTIVELY), BUT THE MAGNITUDE OF THE DIFFERENCE WAS SMALL. INFANTS BORN PREMATURELY ALSO HAD LOWER LINE-1 METHYLATION LEVELS IN CORD BLOOD COMPARED TO TERM INFANTS, AND THIS DIFFERENCE, THOUGH SMALL, WAS STATISTICALLY SIGNIFICANT (P = 0.004). WE DID NOT FIND IMPORTANT ASSOCIATIONS BETWEEN MATERNAL PREPREGNANCY BMI OR GESTATIONAL WEIGHT GAIN AND GLOBAL METHYLATION OF THE CORD BLOOD OR FETAL PLACENTAL TISSUE. IN CONCLUSION, WE FOUND SIGNIFICANT DIFFERENCES IN CORD BLOOD LINE-1 METHYLATION AMONG NEWBORNS WITH LOW AND HIGH BIRTHWEIGHT AS WELL AS AMONG PREMATURELY BORN INFANTS. FUTURE STUDIES MAY ELUCIDATE WHETHER CHROMOSOMAL INSTABILITIES OR OTHER FUNCTIONAL CONSEQUENCES OF THESE CHANGES CONTRIBUTE TO THE INCREASED RISK OF CHRONIC DISEASES AMONG INDIVIDUALS WITH THESE CHARACTERISTICS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
2   518  53 ASSOCIATIONS BETWEEN ANTIBIOTIC EXPOSURE DURING PREGNANCY, BIRTH WEIGHT AND ABERRANT METHYLATION AT IMPRINTED GENES AMONG OFFSPRING. OBJECTIVES: LOW BIRTH WEIGHT (LBW) HAS BEEN ASSOCIATED WITH COMMON ADULT-ONSET CHRONIC DISEASES, INCLUDING OBESITY, CARDIOVASCULAR DISEASE, TYPE II DIABETES AND SOME CANCERS. THE ETIOLOGY OF LBW IS MULTI-FACTORIAL. HOWEVER, RECENT EVIDENCE SUGGESTS EXPOSURE TO ANTIBIOTICS MAY ALSO INCREASE THE RISK OF LBW. THE MECHANISMS UNDERLYING THIS ASSOCIATION ARE UNKNOWN, ALTHOUGH EPIGENETIC MECHANISMS ARE HYPOTHESIZED. IN THIS STUDY, WE EVALUATED THE ASSOCIATION BETWEEN MATERNAL ANTIBIOTIC USE AND LBW AND EXAMINED THE POTENTIAL ROLE OF ALTERED DNA METHYLATION THAT CONTROLS GROWTH REGULATORY IMPRINTED GENES IN THESE ASSOCIATIONS. METHODS: BETWEEN 2009-2011, 397 PREGNANT WOMEN WERE ENROLLED AND FOLLOWED UNTIL DELIVERY. PRENATAL ANTIBIOTIC USE WAS ASCERTAINED THROUGH MATERNAL SELF-REPORT. IMPRINTED GENES METHYLATION LEVELS WERE MEASURED AT DIFFERENTIALLY METHYLATED REGIONS (DMRS) USING BISULFITE PYROSEQUENCING. GENERALIZED LINEAR MODELS WERE USED TO EXAMINE ASSOCIATIONS AMONG ANTIBIOTIC USE, BIRTH WEIGHT AND DMR METHYLATION FRACTIONS. RESULTS: AFTER ADJUSTING FOR INFANT GENDER, RACE/ETHNICITY, MATERNAL BODY MASS INDEX, DELIVERY ROUTE, GESTATIONAL WEIGHT GAIN, GESTATIONAL AGE AT DELIVERY, FOLIC ACID INTAKE, PHYSICAL ACTIVITY, MATERNAL SMOKING AND PARITY, ANTIBIOTIC USE DURING PREGNANCY WAS ASSOCIATED WITH 138 G LOWER BIRTH WEIGHT COMPARED WITH NON-ANTIBIOTIC USE (BETA-COEFFICIENT=-132.99, S.E.=50.70, P=0.008). THESE ASSOCIATIONS WERE STRONGEST IN NEWBORNS OF WOMEN WHO REPORTED ANTIBIOTIC USE OTHER THAN PENICILLINS (BETA-COEFFICIENT=-135.57, S.E.=57.38, P=0.02). METHYLATION AT FIVE DMRS, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) AND PEG3 (P=0.08), WAS ASSOCIATED WITH MATERNAL ANTIBIOTIC USE; AMONG THESE, ONLY METHYLATION AT THE PLAGL1 DMR WAS ALSO ASSOCIATED WITH BIRTH WEIGHT. CONCLUSION: WE REPORT AN INVERSE ASSOCIATION BETWEEN IN UTERO EXPOSURE TO ANTIBIOTICS AND LOWER INFANT BIRTH WEIGHT AND PROVIDE THE FIRST EMPIRICAL EVIDENCE SUPPORTING IMPRINTED GENE PLASTICITY IN THESE ASSOCIATIONS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
3  4504  42 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
4  3786  49 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	

5  4065  48 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
6  2805  41 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
7  6066  42 THE DEVELOPMENTAL ORIGINS OF HEALTH AND CHRONIC KIDNEY DISEASE: CURRENT STATUS AND PRACTICES IN JAPAN. THE CONCEPT OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) VIEWS UNFAVORABLE PERINATAL CIRCUMSTANCES AS CONTRIBUTING TO THE DEVELOPMENT OF DISEASES IN LATER LIFE. IT IS WELL KNOWN THAT SUCH UNFAVORABLE CIRCUMSTANCES PLAY AN IMPORTANT ROLE AS A RISK FACTOR FOR CHRONIC KIDNEY DISEASE (CKD) IN INFANTS BORN WITH PREMATURITY. LOW BIRTHWEIGHT (LBW) IS BELIEVED TO BE A POTENTIAL CONTRIBUTOR TO CKD IN ADULTHOOD. PRETERM AND/OR LBW INFANTS ARE BORN WITH INCOMPLETE NEPHROGENESIS. AS A RESULT, THE NUMBER OF NEPHRONS IS LOW. THE POOR INTRAUTERINE ENVIRONMENT ALSO CAUSES EPIGENETIC CHANGES THAT ADVERSELY AFFECT POSTNATAL RENAL FUNCTION. AFTER BIRTH, HYPERFILTRATION OF INDIVIDUAL NEPHRONS DUE TO LOW NEPHRON NUMBERS CAUSES PROTEINURIA AND SECONDARY GLOMERULOSCLEROSIS. FURTHERMORE, THE RISK OF CKD INCREASES AS RENAL DAMAGE TAKES A SECOND HIT FROM EXPOSURE TO NEPHROTOXIC SUBSTANCES AND ACQUIRED INSULTS SUCH AS ACUTE KIDNEY INJURY AFTER BIRTH AMONG INFANTS IN NEONATAL INTENSIVE CARE. MEANWHILE, UNFORTUNATELY, RECENT STUDIES HAVE SHOWN THAT THE NUMBER OF NEPHRONS IN HEALTHY JAPANESE INDIVIDUALS IS APPROXIMATELY TWO-THIRDS LOWER THAN THAT IN PREVIOUS REPORTS. THIS MEANS THAT JAPANESE PREMATURE INFANTS ARE CLEARLY AT A HIGH RISK OF DEVELOPING CKD IN LATER LIFE. RECENTLY, SEVERAL DOHAD-RELATED CKD STUDIES FROM JAPANESE RESEARCHERS HAVE BEEN REPORTED. HERE, WE SUMMARIZE THE RELEVANCE OF CKD IN CONJUNCTION WITH DOHAD AND REVIEW RECENT STUDIES THAT HAVE EXAMINED THE IMPACT OF THE UPWARD LBW TREND IN JAPAN ON RENAL HEALTH.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  4066  48 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
9  2605  25 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
10   520  46 ASSOCIATIONS BETWEEN MATERNAL PRENATAL STRESS, METHYLATION CHANGES IN IGF1 AND IGF2, AND BIRTH WEIGHT. MATERNAL STRESS HAS BEEN LINKED TO LOW BIRTH WEIGHT IN NEWBORNS. ONE POTENTIAL PATHWAY INVOLVES EPIGENETIC CHANGES AT CANDIDATE GENES THAT MAY MEDIATE THE EFFECTS OF PRENATAL MATERNAL STRESS ON BIRTH WEIGHT. THIS RELATIONSHIP HAS BEEN DOCUMENTED IN STRESS-RELATED GENES, SUCH AS NR3C1. THERE IS LESS LITERATURE EXPLORING THE EFFECT OF STRESS ON GROWTH-RELATED GENES. IGF1 AND IGF2 HAVE BEEN IMPLICATED IN FETAL GROWTH AND DEVELOPMENT, THOUGH VIA DIFFERENT MECHANISMS AS IGF2 IS UNDER IMPRINTING CONTROL. IN THIS STUDY, WE TESTED FOR ASSOCIATIONS BETWEEN PRENATAL STRESS, METHYLATION OF IGF1 AND IGF2, AND BIRTH WEIGHT. A TOTAL OF 24 MOTHER-NEWBORN DYADS IN THE DEMOCRATIC REPUBLIC OF CONGO WERE ENROLLED. ETHNOGRAPHIC INTERVIEWS WERE CONDUCTED WITH MOTHERS AT DELIVERY TO GATHER CULTURALLY RELEVANT WAR-RELATED AND CHRONIC STRESSORS. DNA METHYLATION DATA WERE GENERATED FROM MATERNAL VENOUS, CORD BLOOD AND PLACENTAL TISSUE SAMPLES. MULTIVARIATE REGRESSIONS WERE USED TO TEST FOR ASSOCIATIONS BETWEEN STRESS MEASURES, DNA METHYLATION AND BIRTH WEIGHT IN EACH OF THE THREE TISSUE TYPES. WE FOUND AN ASSOCIATION BETWEEN IGF2 METHYLATION IN MATERNAL BLOOD AND BIRTH WEIGHT. PREVIOUS LITERATURE ON THE RELATIONSHIP BETWEEN IGF2 METHYLATION AND BIRTH WEIGHT HAS FOCUSED ON METHYLATION AT KNOWN DIFFERENTIALLY METHYLATED REGIONS IN CORD BLOOD OR PLACENTAL SAMPLES. OUR FINDINGS INDICATE THERE MAY BE LINKS BETWEEN THE MATERNAL EPIGENOME AND LOW BIRTH WEIGHT THAT RELY ON MECHANISMS OUTSIDE KNOWN IMPRINTING PATHWAYS. IT THUS MAY BE IMPORTANT TO CONSIDER THE EFFECT OF MATERNAL EXPOSURES AND EPIGENETIC PROFILES ON BIRTH WEIGHT EVEN IN THE SETTING OF MATERNALLY IMPRINTED GENES SUCH AS IGF2.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11  5178  33 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  4202  40 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
13  3578  40 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
14  4007  42 LOW BIRTHWEIGHT AS A RISK FACTOR FOR NON-COMMUNICABLE DISEASES IN ADULTS. ACCORDING TO STUDIES UNDERTAKEN OVER THE PAST 40 YEARS, LOW BIRTHWEIGHT (LBW) IS NOT ONLY A SIGNIFICANT PREDICTOR OF PERINATAL DEATH AND MORBIDITY, BUT ALSO INCREASES THE RISK OF CHRONIC NON-COMMUNICABLE DISEASES (NCDS) IN ADULTHOOD. THE PURPOSE OF THIS PAPER IS TO SUMMARIZE THE RESEARCH ON LBW AS A RISK FACTOR FOR NCDS IN ADULTS. THE BARKER HYPOTHESIS WAS BASED ON THE FINDING THAT ADULTS WITH AN LBW OR AN UNHEALTHY INTRAUTERINE ENVIRONMENT, AS WELL AS A RAPID CATCH-UP, DIE DUE TO NCDS. OVER THE LAST FEW DECADES, TERMINOLOGY SUCH AS THRIFTY GENES, FETAL PROGRAMMING, DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD), AND EPIGENETIC FACTORS HAVE BEEN COINED. THE MOST COMMON NCDS INCLUDE CARDIOVASCULAR DISEASE, DIABETES MELLITUS TYPE 2 (DMT2), HYPERTENSION (HT), DYSLIPIDEMIA, PROTEINURIA, AND CHRONIC KIDNEY DISEASE (CKD). STUDIES IN MOTHERS WHO EXPERIENCED FAMINE AND THOSE THAT SOLELY REPORTED BIRTH WEIGHT AS A RISK FACTOR FOR MORTALITY SUPPORT THE CONCEPT. ALTHOUGH THE ETIOLOGY OF NCD IS UNKNOWN, BARRY BRENNER EXPLAINED THE NOTION OF A LOW GLOMERULAR NUMBER (NGLOM) IN LBW CHILDREN, FOLLOWED BY THE PROGRESSION TO HYPERFILTRATION AS THE PHYSIOPATHOLOGIC ETIOLOGY OF HT AND CKD IN ADULTS BASED ON GUYTON'S RENAL PHYSIOLOGY WORK. AUTOPSIES OF SEVERAL ETHNIC GROUPS HAVE REVEALED ANATOMOPATHOLOGIC EVIDENCE IN FETUSES AND ADULT KIDNEYS. BECAUSE OF THE RENAL RESERVE, DEMONSTRATING RENAL FUNCTION IN PROPORTION TO RENAL VOLUME IN VIVO IS MORE DIFFICULT IN ADULTS. THE GREATEST IMPACT OF THESE THEORIES CAN BE SEEN IN PEDIATRICS AND OBSTETRICS PRACTICE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
15  2351  54 EPIGENETIC REGULATION OF NEWBORNS' IMPRINTED GENES RELATED TO GESTATIONAL GROWTH: PATTERNING BY PARENTAL RACE/ETHNICITY AND MATERNAL SOCIOECONOMIC STATUS. BACKGROUND: CHILDREN BORN TO PARENTS WITH LOWER INCOME AND EDUCATION ARE AT RISK FOR OBESITY AND LATER-LIFE RISK OF COMMON CHRONIC DISEASES, AND EPIGENETICS HAS BEEN HYPOTHESISED TO LINK THESE ASSOCIATIONS. HOWEVER, EPIGENETIC TARGETS ARE UNKNOWN. WE FOCUS ON A CLUSTER OF WELL-CHARACTERISED GENOMICALLY IMPRINTED GENES BECAUSE THEIR MONOALLELIC EXPRESSION IS REGULATED BY DNA METHYLATION AT DIFFERENTIALLY METHYLATED REGIONS (DMRS), ARE CRITICAL IN FETAL GROWTH, AND DNA METHYLATION PATTERNS AT BIRTH HAVE BEEN ASSOCIATED WITH INCREASED RISK OF BIRTH WEIGHT EXTREMES AND OVERWEIGHT STATUS OR OBESITY IN EARLY CHILDHOOD. METHODS: WE MEASURED DNA METHYLATION AT DMRS REGULATING GENOMICALLY IMPRINTED DOMAINS (IGF2/H19, DLK1/MEG3, NNAT AND PLAGL1) USING UMBILICAL CORD BLOOD LEUCOCYTES FROM 619 INFANTS RECRUITED IN DURHAM, NORTH CAROLINA IN 2010-2011. WE EXAMINED DIFFERENCES IN DNA METHYLATION LEVELS BY RACE/ETHNICITY OF BOTH PARENTS, AND THE ROLE THAT MATERNAL SOCIOECONOMIC STATUS (SES) MAY PLAY IN THE ASSOCIATION BETWEEN RACE/ETHNIC EPIGENETIC DIFFERENCES. RESULTS: UNADJUSTED RACE/ETHNIC DIFFERENCES ONLY WERE EVIDENT FOR DMRS REGULATING MEG3 AND IGF2; RACE/ETHNIC DIFFERENCES PERSISTED IN IGF2/H19 AND NNAT AFTER ACCOUNTING FOR INCOME AND EDUCATION. CONCLUSIONS: RESULTS SUGGEST THAT PARENTAL FACTORS MAY NOT ONLY INFLUENCE DNA METHYLATION, BUT ALSO DO SO IN WAYS THAT VARY BY DMR. FINDINGS SUPPORT THE HYPOTHESIS THAT EPIGENETICS MAY LINK THE OBSERVED LOWER SES DURING THE PRENATAL PERIOD AND POOR OUTCOMES SUCH AS LOW BIRTH WEIGHT; LOWER BIRTH WEIGHT HAS PREVIOUSLY BEEN ASSOCIATED WITH ADULT-ONSET CHRONIC DISEASES AND CONDITIONS THAT INCLUDE CARDIOVASCULAR DISEASES, DIABETES, OBESITY AND SOME CANCERS.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
16  3145  34 GLOBAL POPULATION VARIATION IN PLACENTAL SIZE AND STRUCTURE: EVIDENCE FROM CEBU, PHILIPPINES. INTRODUCTION: PLACENTAL MORPHOLOGY INFLUENCES THE INTRAUTERINE ENVIRONMENT AND FETAL GROWTH, WHICH HELP SET LIFE-COURSE HEALTH TRAJECTORIES ACROSS GENERATIONS. LITTLE IS KNOWN ABOUT PLACENTAL CHARACTERISTICS IN POPULATIONS WITH CHRONIC NUTRITIONAL INSUFFICIENCY WHERE BIRTH WEIGHTS TEND TO BE LOWER, AND HOW THESE RELATIONSHIPS BETWEEN BIRTH AND PLACENTAL WEIGHTS VARY ACROSS POPULATIONS. METHODS: WE COLLECTED WEIGHTS AND STEREOLOGICALLY-DETERMINED VILLOUS MASS AND SURFACE AREA OF 21 PLACENTAS FROM OFFSPRING OF WOMEN ENROLLED IN A BIRTH COHORT STUDY IN METROPOLITAN CEBU, PHILIPPINES, A LOW-INCOME POPULATION. WE IDENTIFIED 15 SAMPLES FROM OTHER GLOBAL POPULATIONS RANGING FROM LOW TO HIGH INCOME THAT HAD SIMILAR DATA TO OURS TO ASSESS PATTERNS OF VARIATION BETWEEN BIRTH AND PLACENTAL WEIGHTS AND MICROSCOPIC CHARACTERISTICS. WE RANKED THE POPULATION SAMPLES IN ORDER FOR EACH CHARACTERISTIC. RESULTS: MEAN BIRTH WEIGHT IN CEBU WAS 3162 +/- 80 G (RANKED 9/16) AND PLACENTAL WEIGHT WAS 454 +/- 32 G (RANKED 12/16). BIRTH:PLACENTAL WEIGHT RATIO WAS 7.0 (RANKED 3/16). AVERAGE VILLOUS SURFACE AREA FOR CEBU PLACENTAS WAS 6.5 M(2) (RANKED 9/12); BIRTH WEIGHT:VILLOUS SURFACE AREA WAS 0.048 G/M(2) (RANKED 4/12). DISCUSSION: PLACENTAS FROM CEBU PRODUCED HEAVIER NEONATES PER UNITS OF PLACENTAL WEIGHT AND VILLOUS SURFACE AREA THAN MOST OTHER POPULATIONS, DESPITE LOWER VILLOUS SURFACE AREAS AND LESS COMPLEX SURFACE-TO-VOLUME TOPOGRAPHY. THIS RANGE OF PLACENTAL EFFICIENCY SPURS QUESTIONS ABOUT THE MECHANISMS BY WHICH PLACENTAL MORPHOLOGY OPTIMIZES EFFICIENCY IN DIFFERENT ENVIRONMENTAL CONTEXTS DURING GESTATION. PLACENTAL VARIATION BOTH WITHIN AND ACROSS POPULATIONS IS LIKELY DUE TO MANY INTERSECTING ENVIRONMENTAL, METABOLIC, AND (EPI)GENETIC FACTORS THAT WILL REQUIRE ADDITIONAL RESEARCH TO CLARIFY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
17  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
18  3595  30 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
19  6625  37 UNDERSTANDING RACIAL DISPARITIES OF PRETERM BIRTH THROUGH THE PLACENTA. THE RACIAL DISPARITY ASSOCIATED WITH PRETERM BIRTH IS A PUBLIC HEALTH CONCERN IN THE UNITED STATES. THE PLACENTA IS THE PRINCIPAL METABOLIC, RESPIRATORY, AND ENDOCRINE ORGAN OF THE FETUS AND A KEY ROUTE BY WHICH ENVIRONMENTAL EXPOSURES ARE TRANSMITTED FROM MOTHER TO OFFSPRING. AVAILABLE AT EVERY DELIVERY, IT MAY SERVE AS A MARKER OF DIFFERENCES IN PRENATAL EXPOSURES THAT MANIFEST DIFFERENTLY BY RACE. RECENTLY, WE DESCRIBED DIFFERENCES IN PLACENTAL PATHOLOGY BETWEEN AFRICAN-AMERICAN AND WHITE PRETERM BIRTHS: THE PREVALENCE OF CHRONIC INFLAMMATION WAS HIGHER AMONG AFRICAN-AMERICAN WOMEN'S PLACENTAS COMPARED WITH THOSE OF WHITE WOMEN. SIMILARLY, RACIAL DIFFERENCES HAVE BEEN SHOWN IN PLACENTAL MALPERFUSION AND PLACENTAL WEIGHT. SOCIAL DETERMINANTS SUCH AS POVERTY AND STRESS FROM DISCRIMINATION HAVE BEEN IMPLICATED IN RACIAL DISPARITIES IN PRETERM BIRTH. TO DATE, HOWEVER, THE UNDERLYING BIOLOGICAL MECHANISMS, WHETHER THROUGH INFLAMMATORY, OXIDATIVE STRESS, OR OTHER PATHWAYS INVOLVING EPIGENETIC PROGRAMMING, REMAIN LARGELY UNKNOWN. THE PLACENTA, COMPLEMENTED BY MATERNAL AND UMBILICAL CORD BLOOD BIOMARKERS, MAY PROVIDE IMPORTANT INFORMATION ON THE PERINATAL ENVIRONMENT THAT EXPLAINS THE ORIGINS OF RACIAL DISPARITIES IN PRETERM BIRTH RATES AND SUBSEQUENT HEALTH OUTCOMES. THIS ARTICLE REVIEWS EXISTING LITERATURE AND CURRENT RESEARCH GAPS. OPPORTUNITIES ARE DISCUSSED FOR FUTURE PLACENTAL RESEARCH THAT MAY REVEAL NOVEL MECHANISMS LEADING TO THE DEVELOPMENT OF NEW APPROACHES IN THE PREVENTION AND MANAGEMENT OF PRETERM BIRTH AND ITS OUTCOMES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
20  1094  39 COHORT PROFILE: THE DUTCH FAMINE BIRTH COHORT (DFBC)- A PROSPECTIVE BIRTH COHORT STUDY IN THE NETHERLANDS. PURPOSE: THE DUTCH FAMINE BIRTH COHORT STUDY WAS SET UP TO INVESTIGATE THE EFFECTS OF ACUTE MATERNAL UNDERNUTRITION OF THE 1944-1945 DUTCH FAMINE DURING THE SPECIFIC STAGES OF GESTATION ON LATER HEALTH, WITH A PARTICULAR FOCUS ON CHRONIC CARDIOVASCULAR AND METABOLIC DISEASES, AGEING AND MENTAL HEALTH. PARTICIPANTS: THE DUTCH FAMINE BIRTH COHORT CONSISTS OF 2414 SINGLETONS BORN ALIVE AND AT TERM IN THE WILHELMINA GASTHUIS IN AMSTERDAM AROUND THE TIME OF THE DUTCH FAMINE (1943-1947) WHOSE BIRTH RECORDS HAVE BEEN KEPT. THE COHORT HAS BEEN TRACED AND STUDIED SINCE 1994, WHEN THE FIRST DATA COLLECTION STARTED. THE COHORT HAS BEEN INTERVIEWED AND PHYSICALLY EXAMINED IN SEVERAL WAVES OF DATA COLLECTION SINCE THAT TIME, ALLOWING REPEATED MEASURES OF A WIDE RANGE OF PHENOTYPIC INFORMATION AS WELL AS THE COLLECTION OF BIOLOGICAL SAMPLES (BLOOD, URINE, BUCCAL SWABS), FUNCTIONAL TESTING (OF HEART, LUNGS, KIDNEY, HPA AXIS) AND IMAGING OF THE BRAIN (MRI) AND VASCULATURE (ULTRASOUND). ADDITIONALLY, GENETIC AND EPIGENETIC INFORMATION WAS COLLECTED. THROUGH LINKAGE WITH REGISTRIES, MORTALITY AND MORBIDITY INFORMATION OF THE ENTIRE COHORT HAS BEEN OBTAINED. FINDINGS TO DATE: PRENATAL FAMINE EXPOSURE HAD LASTING CONSEQUENCES FOR HEALTH IN LATER LIFE. THE EFFECTS OF FAMINE DEPENDED ON ITS TIMING DURING THE GESTATION AND THE ORGANS AND TISSUES DEVELOPING AT THAT TIME, WITH MOST EFFECTS AFTER EXPOSURE TO FAMINE IN EARLY GESTATION. THE EFFECTS OF FAMINE WERE WIDESPREAD AND AFFECTED THE STRUCTURE AND FUNCTION OF MANY ORGANS AND TISSUES, RESULTED IN ALTERED BEHAVIOUR AND INCREASED RISKS OF CHRONIC DEGENERATIVE DISEASES AND INCREASED MORTALITY. THE EFFECTS OF FAMINE WERE INDEPENDENT OF SIZE AT BIRTH, WHICH SUGGESTS THAT PROGRAMMING MAY OCCUR WITHOUT ALTERING SIZE AT BIRTH. FUTURE PLANS: AS THE COHORT AGES, WE WILL BE ASSESSING THE EFFECTS OF PRENATAL UNDERNUTRITION ON (BRAIN) AGEING, COGNITIVE DECLINE AND DEMENTIA, AS WELL AS OVERALL MORBIDITY AND MORTALITY. REGISTRATION: THE DUTCH FAMINE BIRTH COHORT IS NOT LINKED TO A CLINICAL TRIAL.	2021