1   646 139 BIRTH MODE AND INFECTIOUS MORBIDITY RISKS IN QOM CHILDREN OF ARGENTINA. OBJECTIVES: CESAREAN DELIVERY MAY INCREASE CHILDHOOD INFECTIOUS MORBIDITY RISKS VIA ALTERED BIRTH EXPOSURES AND SUBSEQUENT IMMUNE, MICROBIAL, AND EPIGENETIC DEVELOPMENT. MANY LATIN AMERICAN INDIGENOUS POPULATIONS EXPERIENCE DUAL BURDENS OF INFECTIOUS AND CHRONIC DISEASES, AND ARE PARTICULARLY VULNERABLE TO RISING RATES OF CESAREAN DELIVERY AND ASSOCIATED ADVERSE OUTCOMES. THE QOM/TOBA ARE AN INDIGENOUS POPULATION IN ARGENTINA EXPERIENCING RAPID LIFESTYLE TRANSITIONS. WE HYPOTHESIZED THAT CESAREAN DELIVERY WOULD BE ASSOCIATED WITH INCREASED RISK OF INFECTIOUS SYMPTOMS IN QOM CHILDREN AFTER ADJUSTING FOR GESTATIONAL AND NUTRITIONAL FACTORS. METHODS: WE CONDUCTED A SECONDARY ANALYSIS OF BIRTH RECORDS AND MONTHLY ANTHROPOMETRIC AND ILLNESS DATA COLLECTED PREVIOUSLY FROM 90 QOM CHILDREN (AGED 1-55 MONTHS). WE TESTED FOR ADDITIVE EFFECTS OF BIRTH MODE ON RISK OF GASTROINTESTINAL (GI) AND RESPIRATORY ILLNESS (RI) IN MIXED-EFFECTS LOGISTIC REGRESSION MODELS ADJUSTING FOR CHILD WEIGHT-FOR-AGE (WAZ), WEANING, AND GESTATIONAL AND MATERNAL AGE. RESULTS: CESAREAN DELIVERIES ACCOUNTED FOR 46% OF BIRTHS AND WERE ASSOCIATED WITH MATERNAL AGE < 20 AND >/= 30 YEARS, GESTATIONAL AGE < 39 WEEKS, AND PRENATAL COMPLICATIONS. GI AND RI RISKS WERE REDUCED IN ASSOCIATION WITH CESAREAN DELIVERY, GREATER WAZ, WEANING, MATERNAL AGE >/= 30 YEARS, AND GESTATIONAL AGE < 39 WEEKS. CONCLUSIONS: THE RELATIONSHIP BETWEEN CESAREAN DELIVERY AND REDUCED INFECTIOUS RISKS MAY REFLECT STATISTICAL CONFOUNDING WITH RELATIVELY RAPID POSTNATAL GROWTH AND GREATER ADIPOSITY. POSTNATAL GROWTH TRAJECTORIES MAY BE IMPORTANT MEDIATORS OF LONG-TERM MORBIDITY RISKS ASSOCIATED WITH CESAREAN DELIVERY. THE FREQUENCY OF CESAREAN DELIVERIES AMONG THE QOM REMAINS CONCERNING GIVEN TRADITIONALLY HIGH RATES OF FERTILITY AND ADOLESCENT PREGNANCY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
2  5001  37 PERINATAL RISK FACTORS IN TOURETTE'S AND CHRONIC TIC DISORDERS: A TOTAL POPULATION SIBLING COMPARISON STUDY. ADVERSE PERINATAL EVENTS MAY INCREASE THE RISK OF TOURETTE'S AND CHRONIC TIC DISORDERS (TD/CTD), BUT PREVIOUS STUDIES HAVE BEEN UNABLE TO CONTROL FOR UNMEASURED ENVIRONMENTAL AND GENETIC CONFOUNDING. WE AIMED TO PROSPECTIVELY INVESTIGATE POTENTIAL PERINATAL RISK FACTORS FOR TD/CTD, TAKING UNMEASURED FACTORS SHARED BETWEEN FULL SIBLINGS INTO ACCOUNT. A POPULATION-BASED BIRTH COHORT, CONSISTING OF ALL SINGLETONS BORN IN SWEDEN IN 1973-2003, WAS FOLLOWED UNTIL DECEMBER 2013. A TOTAL OF 3 026 861 INDIVIDUALS WERE IDENTIFIED, 5597 OF WHICH HAD A REGISTERED TD/CTD DIAGNOSIS. WE THEN STUDIED DIFFERENTIALLY EXPOSED FULL SIBLINGS FROM 947 942 FAMILIES; OF THESE, 3563 FAMILIES INCLUDED SIBLINGS THAT WERE DISCORDANT FOR TD/CTD. PERINATAL DATA WERE COLLECTED FROM THE MEDICAL BIRTH REGISTER AND TD/CTD DIAGNOSES WERE COLLECTED FROM THE NATIONAL PATIENT REGISTER, USING A PREVIOUSLY VALIDATED ALGORITHM. IN THE FULLY ADJUSTED MODELS, IMPAIRED FETAL GROWTH, PRETERM BIRTH, BREECH PRESENTATION AND CESAREAN SECTION WERE ASSOCIATED WITH A HIGHER RISK OF TD/CTD, LARGELY INDEPENDENT FROM SHARED FAMILY CONFOUNDERS AND MEASURED COVARIATES. MATERNAL SMOKING DURING PREGNANCY WAS ASSOCIATED WITH RISK OF TD/CTD IN A DOSE-RESPONSE MANNER BUT THE ASSOCIATION WAS NO LONGER STATISTICALLY SIGNIFICANT IN THE SIBLING COMPARISON MODELS OR AFTER THE EXCLUSION OF COMORBID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER. A DOSE-RESPONSE RELATIONSHIP BETWEEN THE NUMBER OF ADVERSE PERINATAL EVENTS AND INCREASED RISK FOR TD/CTD WAS ALSO OBSERVED, WITH HAZARD RATIOS RANGING FROM 1.41 (95% CONFIDENCE INTERVAL (CI): 1.33-1.50) FOR ONE EVENT TO 2.42 (95% CI: 1.65-3.53) FOR FIVE OR MORE EVENTS. THESE RESULTS PAVE THE WAY FOR FUTURE GENE BY ENVIRONMENT INTERACTION AND EPIGENETIC STUDIES IN TD/CTD.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
3   525  22 ASSOCIATIONS OF BODY COMPOSITION AND PHYSICAL ACTIVITY LEVEL WITH MULTIPLE MEASURES OF EPIGENETIC AGE ACCELERATION. EPIGENETIC CLOCKS USE DNA METHYLATION TO ESTIMATE BIOLOGICAL AGE. WHETHER BODY COMPOSITION AND PHYSICAL ACTIVITY ARE ASSOCIATED WITH THESE CLOCKS IS NOT WELL UNDERSTOOD. USING BLOOD SAMPLES COLLECTED AT ENROLLMENT (2003-2009) FROM 2,758 WOMEN IN THE US NATIONWIDE SISTER STUDY, WE CALCULATED 6 EPIGENETIC AGE ACCELERATION METRICS USING 4 EPIGENETIC CLOCKS (HANNUM, HORVATH, PHENOAGE, GRIMAGE). RECREATIONAL PHYSICAL ACTIVITY WAS SELF-REPORTED, AND ADIPOSITY MEASURES WERE ASSESSED BY TRAINED MEDICAL EXAMINERS (BODY MASS INDEX (BMI), WAIST-TO-HIP RATIO (WTH), WAIST CIRCUMFERENCE). IN CROSS-SECTIONAL ANALYSES, ALL ADIPOSITY MEASURES WERE ASSOCIATED WITH EPIGENETIC AGE ACCELERATION. THE STRONGEST ASSOCIATION WAS FOR BMI AND PHENOAGE, A MEASURE OF BIOLOGICAL AGE THAT CORRELATES WITH CHRONIC DISEASE (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 3.15 YEARS, 95% CONFIDENCE INTERVAL (CI): 2.41, 3.90; P FOR TREND < 0.001). IN A MUTUAL-ADJUSTMENT MODEL, BOTH WERE ASSOCIATED WITH PHENOAGE AGE ACCELERATION (BMI OF >/=35.0 VS. 18.5-24.9, BETA = 2.69 YEARS, 95% CI: 1.90, 3.48; P FOR TREND < 0.001; QUARTILE 4 VS.1 WTH, BETA = 1.00 YEARS, 95% CI: 0.34, 1.65; P FOR TREND < 0.008). AFTER ADJUSTMENT, PHYSICAL ACTIVITY WAS ASSOCIATED ONLY WITH GRIMAGE (QUARTILE 4 VS. 1, BETA = -0.42 YEARS, 95% CI: -0.70, -0.14; P FOR TREND = 0.001). PHYSICAL ACTIVITY ATTENUATED THE WAIST CIRCUMFERENCE ASSOCIATIONS WITH PHENOAGE AND GRIMAGE. EXCESS ADIPOSITY WAS ASSOCIATED WITH EPIGENETIC AGE ACCELERATION; PHYSICAL ACTIVITY MIGHT ATTENUATE ASSOCIATIONS WITH WAIST CIRCUMFERENCE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4   648  28 BIRTH WEIGHT AND MATERNAL ENERGY STATUS DURING PREGNANCY AS PREDICTORS OF EPIGENETIC AGE ACCELERATION IN YOUNG ADULTS FROM METROPOLITAN CEBU, PHILIPPINES. EPIGENETIC CLOCKS QUANTIFY REGULAR CHANGES IN DNA METHYLATION THAT OCCUR WITH AGE, OR IN RELATION TO BIOMARKERS OF AGEING, AND ARE STRONG PREDICTORS OF MORBIDITY AND MORTALITY. HERE, WE ASSESS WHETHER MEASURES OF FETAL NUTRITION AND GROWTH THAT PREDICT ADULT CHRONIC DISEASE ALSO PREDICT ACCELERATED BIOLOGICAL AGEING IN YOUNG ADULTHOOD USING A SUITE OF COMMONLY USED EPIGENETIC CLOCKS. DATA COME FROM THE CEBU LONGITUDINAL HEALTH AND NUTRITION SURVEY (CLHNS), A LONG-RUNNING COHORT FOLLOWED SINCE BIRTH IN METROPOLITAN CEBU, PHILIPPINES. PAST WORK HAS SHOWN THAT BIRTH WEIGHT (BW) AND THE MOTHER'S ARM FAT DURING PREGNANCY (A MEASURE OF PREGNANCY ENERGY STATUS) RELATE INVERSELY TO HEALTH OUTCOMES IN THE CLHNS BUT PRIMARILY IN MALES. GENOME-WIDE DNA METHYLATION WAS ASSESSED IN WHOLE BLOOD USING THE INFINIUM EPIC ARRAY. PARTICIPANTS INCLUDED MALES (N=895) AND FEMALES (N=803) MEASURED IN 2005 (20.8-22.5 YEARS). CLOCKS INCLUDED THE HANNUM AND HORVATH CLOCKS TRAINED ON CHRONOLOGICAL AGE, THE DNAMPHENOAGE AND DNAMGRIMAGE CLOCKS TRAINED ON CLINICAL BIOMARKERS, THE DUNEDIN PACE OF AGEING (DUNEDINPACE) CLOCK TRAINED ON LONGITUDINAL CHANGES IN AGEING BIOMARKERS, AND THE DNAMTL CLOCK TRAINED ON LEUKOCYTE TELOMERE LENGTH. IN MALES, LOWER BW PREDICTED ADVANCED BIOLOGICAL AGEING USING THE HANNUM, DNAMPHENOAGE, DUNEDINPOAM, AND DNAMTL CLOCKS. IN CONTRAST, BW DID NOT PREDICT ANY CLOCK IN FEMALE PARTICIPANTS. PARTICIPANTS' MOTHERS' PREGNANCY ARM FAT ONLY PREDICTED DNAMTL IN MALES. THESE FINDINGS SUGGEST THAT EPIGENETIC CLOCKS ARE A USEFUL TOOL FOR GAUGING LONG-TERM OUTCOMES PREDICTED BY FETAL GROWTH, AND ADD TO EXISTING EVIDENCE IN THE CLHNS FOR SEX DIFFERENCES IN THESE RELATIONSHIPS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
5   518  39 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	
                                                                                                                                                                                                                                                                                                                                                                                 
6  1521  39 DNA METHYLATION AT IMPRINT REGULATORY REGIONS IN PRETERM BIRTH AND INFECTION. OBJECTIVE: TO AID IN UNDERSTANDING LONG-TERM HEALTH CONSEQUENCES OF INTRAUTERINE INFECTIONS IN PRETERM BIRTH, WE EVALUATED DNA METHYLATION AT 9 DIFFERENTIALLY METHYLATED REGIONS THAT REGULATE IMPRINTED GENES BY TYPE OF PRETERM BIRTH (SPONTANEOUS PRETERM LABOR, PRETERM PREMATURE RUPTURE OF MEMBRANES, OR MEDICALLY INDICATED [FETAL GROWTH RESTRICTION AND PREECLAMPSIA]) AND INFECTION STATUS (CHORIOAMNIONITIS OR FUNISITIS). STUDY DESIGN: DATA ON TYPE OF PRETERM BIRTH AND INFECTION STATUS WERE ABSTRACTED FROM MEDICAL RECORDS AND STANDARDIZED PATHOLOGY REPORTS IN 73 PRETERM INFANTS ENROLLED IN THE NEWBORN EPIGENETICS STUDY, A PROSPECTIVE COHORT STUDY OF MOTHER-INFANT DYADS IN DURHAM, NC. CORD BLOOD WAS COLLECTED AT BIRTH, AND INFANT DNA METHYLATION LEVELS AT THE H19, IGF2, MEG3, MEST, SGCE/PEG10, PEG3, NNAT, AND PLAGL1 DIFFERENTIALLY METHYLATED REGIONS WERE MEASURED USING BISULFITE PYROSEQUENCING. ONE-WAY ANALYSES OF VARIANCE AND LOGISTIC REGRESSION MODELS WERE USED TO COMPARE DNA METHYLATION LEVELS BY TYPE OF PRETERM BIRTH AND INFECTION STATUS. RESULTS: DNA METHYLATION LEVELS DID NOT DIFFER AT ANY OF THE REGIONS (P > .20) BETWEEN INFANTS BORN VIA SPONTANEOUS PRETERM LABOR (AVERAGE N = 29), PRETERM PREMATURE RUPTURE OF MEMBRANES (AVERAGE N = 17), OR MEDICALLY INDICATED PRETERM BIRTH (AVERAGE N = 40). LEVELS WERE SIGNIFICANTLY INCREASED AT PLAGL1 IN INFANTS WITH CHORIOAMNIONITIS (N = 10, 64.4%) COMPARED WITH INFANTS WITHOUT CHORIOAMNIONITIS (N = 63, 57.9%), P < .01. DNA METHYLATION LEVELS WERE ALSO INCREASED AT PLAGL1 FOR INFANTS WITH FUNISITIS (N = 7, 63.3%) COMPARED WITH INFANTS WITHOUT FUNISITIS (N = 66, 58.3%), P < .05. CONCLUSION: DYSREGULATION OF PLAGL1 HAS BEEN ASSOCIATED WITH ABNORMAL DEVELOPMENT AND CANCER. EARLY-LIFE EXPOSURES, INCLUDING INFECTION/INFLAMMATION, MAY AFFECT EPIGENETIC CHANGES THAT INCREASE SUSCEPTIBILITY TO LATER CHRONIC DISEASE.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
7  1351  31 DETERMINATION OF SALIVA EPIGENETIC AGE IN INFANCY, AND ITS ASSOCIATION WITH PARENTAL SOCIO-ECONOMIC CHARACTERISTICS AND PREGNANCY OUTCOMES. EPIGENETIC AGE ACCELERATION (AA) HAS BEEN ASSOCIATED WITH ADVERSE ENVIRONMENTAL EXPOSURES AND MANY CHRONIC CONDITIONS. WE ESTIMATED, IN THE NINFEA BIRTH COHORT, INFANT SALIVA EPIGENETIC AGE, AND INVESTIGATED WHETHER PARENTAL SOCIO-ECONOMIC POSITION (SEP) AND PREGNANCY OUTCOMES ARE ASSOCIATED WITH INFANT EPIGENETIC AA. A TOTAL OF 139 SALIVA SAMPLES COLLECTED AT ON AVERAGE 10.8 (RANGE 7-17) MONTHS WERE USED TO ESTIMATE HORVATH'S DNA METHYLATION AGE. EPIGENETIC AA WAS DEFINED AS THE RESIDUAL FROM A LINEAR REGRESSION OF EPIGENETIC AGE ON CHRONOLOGICAL AGE. LINEAR REGRESSION MODELS WERE USED TO TEST THE ASSOCIATIONS OF PARENTAL SEP AND PREGNANCY OUTCOMES WITH SALIVA EPIGENETIC AA. A MODERATE POSITIVE ASSOCIATION WAS FOUND BETWEEN DNA METHYLATION AGE AND CHRONOLOGICAL AGE, WITH THE MEDIAN ABSOLUTE DIFFERENCE OF 6.8 MONTHS (STANDARD DEVIATION [SD] 3.9). THE EVIDENCE OF THE ASSOCIATION BETWEEN THE INDICATORS OF LOW SEP AND EPIGENETIC AA WAS WEAK; INFANTS BORN TO UNEMPLOYED MOTHERS OR WITH LOW EDUCATION HAD ON AVERAGE 1 MONTH HIGHER EPIGENETIC AGE THAN INFANTS OF MOTHERS WITH HIGH EDUCATION AND EMPLOYMENT (COEFFICIENT 0.78 MONTHS, 95% CONFIDENCE INTERVALS [CIS]: -0.79 TO 2.34 FOR LOW/MEDIUM EDUCATION; 0.96, 95% CI: -1.81 TO 3.73 FOR UNEMPLOYMENT). THERE WAS NO EVIDENCE FOR ASSOCIATION OF GESTATIONAL AGE, BIRTHWEIGHT OR CAESAREAN SECTION WITH INFANT EPIGENETIC AA. USING THE HORVATH'S METHOD, DNA METHYLATION AGE CAN BE FAIRLY ACCURATELY PREDICTED FROM SALIVA SAMPLES ALREADY IN THE FIRST MONTHS OF LIFE. THIS STUDY DID NOT REVEAL CLEAR ASSOCIATIONS BETWEEN EITHER PREGNANCY OUTCOMES OR PARENTAL SOCIO-ECONOMIC CHARACTERISTICS AND INFANT SALIVA EPIGENETIC AA.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  4090  35 MATERNAL PRE-PREGNANCY BMI, OFFSPRING EPIGENOME-WIDE DNA METHYLATION, AND CHILDHOOD OBESITY: FINDINGS FROM THE BOSTON BIRTH COHORT. BACKGROUND: MATERNAL PRE-PREGNANCY OBESITY IS AN ESTABLISHED RISK FACTOR FOR CHILDHOOD OBESITY. INVESTIGATING EPIGENETIC ALTERATIONS INDUCED BY MATERNAL OBESITY DURING FETAL DEVELOPMENT COULD GAIN MECHANISTIC INSIGHT INTO THE DEVELOPMENTAL ORIGINS OF CHILDHOOD OBESITY. WHILE OBESITY DISPROPORTIONATELY AFFECTS UNDERREPRESENTED RACIAL AND ETHNIC MOTHERS AND CHILDREN IN THE USA, FEW STUDIES INVESTIGATED THE ROLE OF PRENATAL EPIGENETIC PROGRAMMING IN INTERGENERATIONAL OBESITY OF THESE HIGH-RISK POPULATIONS. METHODS: THIS STUDY INCLUDED 903 MOTHER-CHILD PAIRS FROM THE BOSTON BIRTH COHORT, A PREDOMINANTLY URBAN, LOW-INCOME MINORITY BIRTH COHORT. MOTHER-INFANT DYADS WERE ENROLLED AT BIRTH AND THE CHILDREN WERE FOLLOWED PROSPECTIVELY TO AGE 18 YEARS. INFINIUM METHYLATION EPIC BEADCHIP WAS USED TO MEASURE EPIGENOME-WIDE METHYLATION LEVEL OF CORD BLOOD. WE PERFORMED AN EPIGENOME-WIDE ASSOCIATION STUDY OF MATERNAL PRE-PREGNANCY BODY MASS INDEX (BMI) AND CORD BLOOD DNA METHYLATION (DNAM). TO QUANTIFY THE DEGREE TO WHICH CORD BLOOD DNAM MEDIATES THE MATERNAL BMI-CHILDHOOD OBESITY, WE FURTHER INVESTIGATED WHETHER MATERNAL BMI-ASSOCIATED DNAM SITES IMPACT BIRTHWEIGHT OR CHILDHOOD OVERWEIGHT OR OBESITY (OWO) FROM AGE 1 TO AGE 18 AND PERFORMED CORRESPONDING MEDIATION ANALYSES. RESULTS: THE STUDY SAMPLE CONTAINED 52.8% MATERNAL PRE-PREGNANCY OWO AND 63.2% OFFSPRING OWO AT AGE 1-18 YEARS. MATERNAL BMI WAS ASSOCIATED WITH CORD BLOOD DNAM AT 8 CPG SITES (GENOME-WIDE FALSE DISCOVERY RATE [FDR] < 0.05). AFTER ACCOUNTING FOR THE POSSIBLE INTERPLAY OF MATERNAL BMI AND SMOKING, 481 CPG SITES WERE DISCOVERED FOR ASSOCIATION WITH MATERNAL BMI. AMONG THEM 123 CPGS WERE ASSOCIATED WITH CHILDHOOD OWO, RANGING FROM 42% DECREASE TO 87% INCREASE IN OWO RISK FOR EACH SD INCREASE IN DNAM. A TOTAL OF 14 IDENTIFIED CPG SITES SHOWED A SIGNIFICANT MEDIATION EFFECT ON THE MATERNAL BMI-CHILD OWO ASSOCIATION (FDR < 0.05), WITH MEDIATING PROPORTION RANGING FROM 3.99% TO 25.21%. SEVERAL OF THESE 14 CPGS WERE MAPPED TO GENES IN ASSOCIATION WITH ENERGY BALANCE AND METABOLISM (AKAP7) AND ADULTHOOD METABOLIC SYNDROME (CAMK2B). CONCLUSIONS: THIS PROSPECTIVE BIRTH COHORT STUDY IN A HIGH-RISK YET UNDERSTUDIED US POPULATION FOUND THAT MATERNAL PRE-PREGNANCY OWO SIGNIFICANTLY ALTERED DNAM IN NEWBORN CORD BLOOD AND PROVIDED SUGGESTIVE EVIDENCE OF EPIGENETIC INVOLVEMENT IN THE INTERGENERATIONAL RISK OF OBESITY.	2023	

9  4916  24 PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE METHYLATION ASSOCIATES WITH EMOTIONAL REGULATION IN 4.5-YEAR-OLD PRETERM-BORN CHILDREN. AIM: THE MAIN GOAL OF THIS STUDY WAS TO ASSESS THE ASSOCIATION BETWEEN PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION AND EMOTIONAL DYSREGULATION IN 4.5-YEAR-OLD PRETERM CHILDREN COMPARED WITH FULL-TERM MATCHED COUNTERPARTS. METHODS: PRETERM (N = 29) AND FULL-TERM (N = 26) CHILDREN RECRUITED FROM TWO ITALIAN HOSPITALS WERE FOLLOWED-UP FROM OCTOBER 2011 TO DECEMBER 2017. SLC6A4 METHYLATION WAS ASSESSED FROM CORD BLOOD AT BIRTH FROM BOTH GROUPS AND PERIPHERAL BLOOD AT DISCHARGE FOR PRETERM ONES. AT 4.5 YEARS, EMOTIONAL REGULATION (IE, ANGER, FEAR AND SADNESS) WAS ASSESSED THROUGH AN OBSERVATIONAL STANDARDISED PROCEDURE. RESULTS: PRETERM CHILDREN (18 FEMALES; MEAN AGE = 4.5, RANGE = 4.3-4.8) SHOWED GREATER ANGER DISPLAY COMPARED WITH FULL-TERM CONTROLS (14 FEMALES; MEAN AGE = 4.5, RANGE = 4.4-4.9) IN RESPONSE TO EMOTIONAL STRESS. CONTROLLING FOR ADVERSE LIFE EVENTS OCCURRENCE FROM DISCHARGE TO 4.5 YEARS AND SLC6A4 METHYLATION AT BIRTH, CPG-SPECIFIC SLC6A4 METHYLATION IN THE NEONATAL PERIOD WAS PREDICTIVE OF GREATER ANGER DISPLAY IN PRETERM CHILDREN BUT NOT IN FULL-TERM ONES. CONCLUSION: THESE FINDINGS CONTRIBUTE TO HIGHLIGHT HOW EPIGENETIC REGULATION OF SEROTONIN TRANSPORTER GENE IN RESPONSE TO NICU PAIN EXPOSURE CONTRIBUTES TO LONG-LASTING PROGRAMMING OF ANGER REGULATION IN PRETERM CHILDREN.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10  3166  38 GROCERY DELIVERY TO SUPPORT HEALTHY WEIGHT GAIN AMONG PREGNANT YOUNG WOMEN WITH LOW INCOME: PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL. BACKGROUND: EXCESSIVE WEIGHT GAIN DURING PREGNANCY IS ASSOCIATED WITH COMPLICATIONS FOR BOTH THE MOTHER AND HER INFANT INCLUDING GESTATIONAL DIABETES, HYPERTENSIVE DISORDERS, OPERATIVE DELIVERY, AND LONG-TERM OBESITY. A HEALTHY DIET DURING PREGNANCY PROMOTES HEALTHY GESTATIONAL WEIGHT GAIN AND DETERMINES FETAL EPIGENETIC PROGRAMMING IN INFANTS THAT IMPACTS RISK FOR FUTURE CHRONIC DISEASE. OBJECTIVE: THIS PROJECT WILL EXAMINE THE IMPACT OF GROCERY DELIVERY DURING PREGNANCY ON THE WEIGHT, DIET, AND HEALTH OUTCOMES OF YOUNG PREGNANT WOMEN AND THEIR INFANTS. METHODS: A THREE-ARM RANDOMIZED CONTROLLED TRIAL DESIGN WILL BE PERFORMED. A TOTAL OF 855 YOUNG PREGNANT WOMEN, AGED 14-24 YEARS, FROM ACROSS THE STATE OF MICHIGAN WILL BE ENROLLED AND RANDOMIZED EQUALLY INTO THE THREE STUDY ARMS. PARTICIPANTS IN ARM ONE (CONTROL) WILL RECEIVE USUAL CARE FROM THE SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS, AND CHILDREN (WIC); ARM TWO WILL RECEIVE WIC PLUS BIWEEKLY GROCERY DELIVERY; AND ARM THREE WILL RECEIVE WIC PLUS BIWEEKLY GROCERY AND UNSWEETENED BEVERAGE DELIVERY. WEIGHT WILL BE ASSESSED WEEKLY DURING PREGNANCY, AND TOTAL PREGNANCY WEIGHT GAIN WILL BE CATEGORIZED AS ABOVE, BELOW, OR WITHIN GUIDELINES. ADDITIONALLY, DIETARY INTAKE WILL BE ASSESSED AT THREE TIME POINTS (BASELINE, SECOND TRIMESTER, AND THIRD TRIMESTER), AND PREGNANCY OUTCOMES WILL BE EXTRACTED FROM MEDICAL RECORDS. THE APPROPRIATENESS OF PREGNANCY WEIGHT GAIN, DIET QUALITY, AND OCCURRENCE OF POOR OUTCOMES WILL BE COMPARED BETWEEN GROUPS USING STANDARD PRACTICES FOR MULTINOMIAL REGRESSION AND CONFOUNDER ADJUSTMENT. RESULTS: THIS STUDY WAS FUNDED IN APRIL 2021, DATA COLLECTION STARTED IN DECEMBER 2021, AND DATA COLLECTION IS EXPECTED TO BE CONCLUDED IN 2026. CONCLUSIONS: THIS STUDY WILL TEST WHETHER GROCERY DELIVERY OF HEALTHY FOODS IMPROVES WEIGHT, DIET, AND PREGNANCY OUTCOMES OF YOUNG MOMS WITH LOW INCOME. THE FINDINGS WILL INFORM POLICIES AND PRACTICES THAT PROMOTE A HEALTHY DIET DURING PREGNANCY, WHICH HAS MULTIGENERATIONAL IMPACTS ON HEALTH. TRIAL REGISTRATION: CLINICALTRIALS.GOV NCT05000645; HTTPS://CLINICALTRIALS.GOV/CT2/SHOW/NCT05000645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40568.	2022	
                                                                                                                                                                              
11   464  35 ARE HEIGHT AND LEG LENGTH UNIVERSAL MARKERS OF CHILDHOOD CONDITIONS? THE GUANGZHOU BIOBANK COHORT STUDY. OBJECTIVE: IN DEVELOPED WESTERN POPULATIONS LONGER LEGS HAVE BEEN SHOWN TO BE A MARKER OF BETTER EARLY CHILDHOOD CONDITIONS. IN THE FIRST GENERATIONS TO EXPERIENCE THE EPIDEMIOLOGIC TRANSITION AND ASSOCIATED ECONOMIC DEVELOPMENT, EPIGENETIC CONSTRAINTS ON GROWTH MIGHT PRECLUDE IMPROVED CHILDHOOD CONDITIONS FROM INCREASING LEG GROWTH OR HEIGHT. DESIGN, SETTING AND PARTICIPANTS: MULTIVARIABLE LINEAR REGRESSION WAS USED TO ASSESS THE ASSOCIATION OF PARENTAL GROWTH ENVIRONMENT, PROXIED BY PARENTAL LITERACY, AND CHILDHOOD CONDITIONS, PROXIED BY PARENTAL POSSESSIONS, WITH LEG LENGTH, SITTING HEIGHT AND HEIGHT IN A CROSS-SECTIONAL SAMPLE FROM 2005-6 OF 9998 CHINESE PEOPLE AGED AT LEAST 50 YEARS FROM PHASE 2 OF THE GUANGZHOU BIOBANK COHORT STUDY. MAIN RESULTS: ADJUSTED FOR AGE AND SEX, THE ASSOCIATION OF CHILDHOOD CONDITIONS WITH LEG LENGTH AND HEIGHT VARIED WITH PARENTAL LITERACY (INTERACTION P VALUES <0.01 AND 0.03), BUT NOT FOR SITTING HEIGHT (P VALUE 0.43), WITH STATISTICALLY SIGNIFICANT TRENDS (P VALUES <0.01) FOR PARENTAL POSSESSIONS TO BE ASSOCIATED WITH LONGER LEGS AND GREATER HEIGHT ONLY IN THE OFFSPRING OF TWO LITERATE PARENTS WHERE LEGS WERE LONGER BY 0.56 CM (95% CI 0.27 TO 0.86) AND HEIGHT GREATER BY 1.16 CM (95% CI 0.74 TO 1.58) FOR PARTICIPANTS WITH MOST, COMPARED WITH LEAST, PARENTAL POSSESSIONS IN CHILDHOOD. CONCLUSIONS: EPIGENETIC INFLUENCES ORIGINATING IN EARLIER GENERATIONS MAY CONSTRAIN GROWTH DURING THE INFANCY AND/OR CHILDHOOD PHASES IN VERY RECENTLY DEVELOPED POPULATIONS. NEITHER HEIGHT NOR LEG LENGTH SHOULD BE ASSUMED TO BE CONSISTENT PROXIES OF EARLY LIFE ENVIRONMENT WITH CORRESPONDING IMPLICATIONS FOR ECONOMIC HISTORY, THE AETIOLOGY OF SOME CHRONIC DISEASES AND THE MONITORING OF POPULATION HEALTH.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
12  4504  28 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
13  4910  27 PAIN EXPOSURE ASSOCIATES WITH TELOMERE LENGTH EROSION IN VERY PRETERM INFANTS. VERY PRETERM (VPT) INFANTS (GESTATIONAL AGE < 32 WEEKS) REQUIRE LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU), EVEN IN ABSENCE OF SEVERE MORBIDITIES. DURING NICU STAY, LIFE-SAVING INTERVENTIONS OCCUR AND INCLUDE INVASIVE AND PAINFUL SKIN-BREAKING PROCEDURES (NICU-RELATED STRESS), WHICH CONSTITUTE A MAJOR EARLY ADVERSE EXPERIENCE FOR VPT INFANTS. TELOMERES ARE REPEAT-SEQUENCE AT THE END OF CHROMOSOMES, WHICH SHORTEN WITH AGE AND ARE HIGHLY SUSCEPTIBLE TO LIFE ADVERSITIES: THE EXPOSURE TO EARLY ADVERSE EXPERIENCES IS ASSOCIATED WITH SHORTER TELOMERE LENGTH (TL). NONETHELESS, PREVIOUS RESEARCH DID NOT ASSESS LONGITUDINALLY THE ASSOCIATION BETWEEN NICU-RELATED STRESS AND TL IN VPT INFANTS. IN THE PRESENT STUDY, LEUKOCYTE TL WAS ASSESSED FROM CORD BLOOD AT BIRTH IN 46 VPT INFANTS AND IN A GROUP OF 31 FULL-TERM (FT) INFANTS, AS WELL AS AT NICU DISCHARGE IN VPTS ONLY. NICU-RELATED STRESS WAS MEASURED AS THE NUMBER OF SKIN-BREAKING PROCEDURES OCCURRING THROUGHOUT THE NICU STAY. A SIGNIFICANT DIFFERENCE EMERGED FOR TL BETWEEN VPT INFANTS AND FT COUNTERPARTS AT BIRTH. TL DECREASED FROM BIRTH TO DISCHARGE IN VPT INFANTS, ALTHOUGH THE CHANGE WAS NOT SIGNIFICANT IN THE GROUP AS A WHOLE. THE AMOUNT OF NICU-RELATED STRESS EMERGED AS THE PRIMARY PREDICTOR OF TL EROSION IN VPT INFANTS, EVEN CONTROLLING FOR NEONATAL AND CLINICAL CONFOUNDERS. FURTHERMORE, VPT INFANTS EXPOSED TO HIGH NICU-RELATED STRESS EXHIBITED A MARKED AND SIGNIFICANT DECREASE IN TL, WHEREAS VPT EXPOSED TO LOW NICU-RELATED STRESS EXHIBITED A NON-SIGNIFICANT INCREASE. THE PRESENT STUDY CONFIRMS PREVIOUS EVIDENCE OF LONGER TELOMERES IN VPT INFANTS AT BIRTH COMPARED TO FT CONTROLS. MOREOVER, NICU-RELATED STRESS EMERGED AS A KEY REGULATOR OF TL EROSION FROM BIRTH TO DISCHARGE IN VPT INFANTS. FUTURE RESEARCH IS WARRANTED TO FURTHER EXPLORE TL EROSION IN VPT INFANTS AND THE FACTORS ASSOCIATED WITH INDIVIDUAL DIFFERENCES IN NICU-RELATED STRESS SUSCEPTIBILITY AT THE EPIGENETIC LEVEL.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
14  4917  23 PAIN-RELATED STRESS DURING THE NEONATAL INTENSIVE CARE UNIT STAY AND SLC6A4 METHYLATION IN VERY PRETERM INFANTS. VERY PRETERM (VPT) INFANTS NEED LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU) DURING WHICH THEY ARE DAILY EXPOSED TO PAIN-RELATED STRESS. ALTERATIONS OF DNA METHYLATION AT THE PROMOTER REGION OF THE SLC6A4 HAVE BEEN ASSOCIATED WITH EARLY ADVERSE EXPERIENCES IN INFANTS. THE MAIN AIM OF THE PRESENT WORK WAS TO INVESTIGATE THE ASSOCIATION BETWEEN LEVEL OF EXPOSURE TO PAIN-RELATED STRESS DURING HOSPITALIZATION AND CHANGES IN SLC6A4 DNA METHYLATION AT NICU DISCHARGE IN VPT INFANTS. IN ORDER TO EXCLUDE THE POTENTIAL EFFECT OF BIRTH STATUS (I.E., PRETERM VS. FULL-TERM BIRTH) ON SLC6A4 METHYLATION, WE PRELIMINARILY ASSESSED SLC6A4 EPIGENETIC DIFFERENCES BETWEEN VPT AND FULL-TERM (FT) INFANTS AT BIRTH. FIFTY-SIX VPT AND THIRTY-TWO FT INFANTS PARTICIPATED IN THE STUDY. THE LEVEL OF EXPOSURE TO PAIN-RELATED STRESS WAS QUANTIFIED ON THE BASIS OF THE AMOUNT OF SKIN-BREAKING PROCEDURES TO WHICH THEY WERE EXPOSED. VPT INFANTS WERE DIVIDED IN TWO SUB-GROUPS: LOW-PAIN EXPOSURE (LPE, N = 25) AND HIGH-PAIN EXPOSURE (HPE, N = 31). DNA METHYLATION WAS EVALUATED AT BIRTH FOR BOTH VPT AND FT INFANTS, ASSESSING 20 CPG SITES WITHIN THE SLC6A4 PROMOTER REGION. THE SAME CPG SITES WERE RE-EVALUATED FOR VARIATIONS IN DNA METHYLATION AT NICU DISCHARGE IN LPE AND HPE VPT INFANTS. NO DIFFERENCES IN SLC6A4 CPG SITES' METHYLATION EMERGED BETWEEN FT AND VPT INFANTS AT BIRTH. METHYLATION AT CPG SITES 5 AND 6 SIGNIFICANTLY INCREASED FROM BIRTH TO NICU DISCHARGE ONLY FOR HPE VPT INFANTS. FINDINGS SHOW THAT PRETERM BIRTH PER SE IS NOT ASSOCIATED WITH EPIGENETIC ALTERATIONS OF THE SLC6A4, WHEREAS HIGHER LEVELS OF PAIN-RELATED STRESS EXPOSURE DURING NICU STAY MIGHT ALTER THE TRANSCRIPTIONAL FUNCTIONALITY OF THE SEROTONIN TRANSPORTER GENE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
15  5958  31 TELOMERE LENGTH AND SALIVARY CORTISOL STRESS REACTIVITY IN VERY PRETERM INFANTS. DURING THE NEONATAL INTENSIVE CARE UNIT (NICU) STAY, VERY PRETERM (VPT) INFANTS ARE EXPOSED TO LIFE-SAVING YET PAIN-INDUCING SKIN-BREAKING PROCEDURES (I.E., NICU PAIN-RELATED STRESS) WHICH CONTRIBUTE TO THE PROGRAMMING OF HYPO-RESPONSIVE HPA AXIS DEVELOPMENT DURING THE FIRST MONTHS OF LIFE. UNFORTUNATELY, TO DATE THE MECHANISMS LINKING NICU PAIN-RELATED STRESS AND ALTERED HPA AXIS REGULATION ARE ONLY LIMITEDLY KNOWN. TELOMERE LENGTH (TL) REGULATION IS AN EPIGENETIC MECHANISM PREVIOUSLY SHOWN TO BE AFFECTED BY EARLY STRESS EXPOSURES AND CAPABLE OF ASSOCIATING WITH HPA AXIS REACTIVITY IN CHILDREN. IN VPT INFANTS, NICU PAIN-RELATED STRESS WAS FOUND TO ASSOCIATE WITH DECREASED TL FROM BIRTH TO DISCHARGE, BUT THERE IS NO EVIDENCE FOR THE ASSOCIATION BETWEEN TL AND HPA AXIS IN THESE INFANTS. IN THIS STUDY, WE PROSPECTIVELY EXAMINED THE RELATIONSHIP BETWEEN NICU PAIN-RELATED STRESS AND HPA AXIS REACTIVITY TO AN AGE-APPROPRIATE SOCIO-EMOTIONAL CONDITION (I.E., THE STILL-FACE PROCEDURE, SFP) IN HEALTHY VPT INFANTS AT 3-MONTH CORRECTED AGE. NICU PAIN-RELATED STRESS WAS COMPUTED AS THE RATIO BETWEEN THE NUMBER OF SKIN-BREAKING PROCEDURES AND LENGTH OF NICU STAY. A DIFFERENTIAL SCORE (I.E., ?TL) WAS OBTAINED SUBTRACTING TL AT BIRTH FROM TL AT DISCHARGE. A NORMALIZED (LOG10) CORTISOL REACTIVITY INDEX (CRI) WAS OBTAINED BY AVERAGING POST-STRESS (20 MIN AFTER SFP) SALIVARY CORTISOL SAMPLE ON BASELINE VALUE. A REGRESSION MODEL CONTROLLING FOR NEONATAL AND SOCIO-DEMOGRAPHIC CONFOUNDERS SHOWED THAT ?TL WAS THE ONLY SIGNIFICANT PREDICTOR OF CRI. ALTHOUGH PRELIMINARY, THESE FINDINGS CONTRIBUTE TO OUR KNOWLEDGE OF THE MECHANISMS LINKING EARLY EXPOSURES TO ADVERSITY AND LATER IN LIFE REGULATION OF THE HPA AXIS IN VPT INFANTS.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
16  3145  29 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  4612  27 NEONATAL PAIN AND COMT VAL158MET GENOTYPE IN RELATION TO SEROTONIN TRANSPORTER (SLC6A4) PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT SCHOOL AGE. CHILDREN BORN VERY PRETERM ARE EXPOSED TO REPEATED NEONATAL PROCEDURES THAT INDUCE PAIN AND STRESS DURING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU). THE COMT VAL158MET GENOTYPE IS INVOLVED WITH PAIN SENSITIVITY, AND EARLY LIFE STRESS IS IMPLICATED IN ALTERED EXPRESSION OF METHYLATION OF THE SEROTONIN TRANSPORTER. WE EXAMINED: (1) WHETHER METHYLATION OF THE SEROTONIN TRANSPORTER GENE (SLC6A4) PROMOTER DIFFERS BETWEEN VERY PRETERM CHILDREN AND FULL-TERM CONTROLS AT SCHOOL AGE, (2) RELATIONSHIPS WITH CHILD BEHAVIOR PROBLEMS, AND (3) WHETHER THE EXTENT OF NEONATAL PAIN EXPOSURE INTERACTS WITH THE COMT VAL158MET GENOTYPE TO PREDICT SLC6A4 METHYLATION AT 7 YEARS IN THE VERY PRETERM CHILDREN. WE EXAMINED THE ASSOCIATIONS BETWEEN THE COMT GENOTYPES, NEONATAL PAIN EXPOSURE (ADJUSTED FOR NEONATAL CLINICAL CONFOUNDERS), SLC6A4 METHYLATION AND BEHAVIOR PROBLEMS. VERY PRETERM CHILDREN HAD SIGNIFICANTLY HIGHER METHYLATION AT 7/10 CPG SITES IN THE SLC6A4 PROMOTER COMPARED TO FULL-TERM CONTROLS AT 7 YEARS. NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) WAS SIGNIFICANTLY ASSOCIATED WITH TOTAL CHILD BEHAVIOR PROBLEMS ON THE CHILD BEHAVIOR CHECKLIST (CBCL) QUESTIONNAIRE (ADJUSTED FOR CONCURRENT STRESSORS AND 5HTTLPR GENOTYPE) (P = 0.035). CBCL TOTAL PROBLEMS WAS SIGNIFICANTLY ASSOCIATED WITH GREATER SLC6A4 METHYLATION IN VERY PRETERM CHILDREN (P = 0.01). NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) AND COMT MET/MET GENOTYPE WERE ASSOCIATED WITH SLC6A4 PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT 7 YEARS (P = 0.001). THESE FINDINGS PROVIDE EVIDENCE THAT BOTH GENETIC PREDISPOSITION AND EARLY ENVIRONMENT NEED TO BE CONSIDERED IN UNDERSTANDING SUSCEPTIBILITY FOR DEVELOPING BEHAVIORAL PROBLEMS IN THIS VULNERABLE POPULATION.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
18  1095  41 COHORT PROFILE: THE EWHA BIRTH AND GROWTH STUDY. WITH THE INTRODUCTION OF LIFE-COURSE EPIDEMIOLOGY, RESEARCHERS REALIZED THE IMPORTANCE OF IDENTIFYING RISK FACTORS IN EARLY LIFE TO PREVENT CHRONIC DISEASES. THIS LED TO THE ESTABLISHMENT OF THE EWHA BIRTH AND GROWTH STUDY IN 2001; THE STUDY IS A PROSPECTIVE BIRTH COHORT DESIGNED TO PROVIDE EVIDENCE OF EARLY LIFE RISK FACTORS FOR A CHILD'S GROWTH AND HEALTH. PARTICIPANTS WERE RECRUITED FROM THOSE WHO VISITED EWHA WOMANS UNIVERSITY MOKDONG HOSPITAL (A TERTIARY HOSPITAL IN SOUTHWEST SEOUL, KOREA) FOR PRENATAL CARE AT 24-28 WEEKS OF GESTATION. IN TOTAL, 891 MOTHERS ENROLLED IN THIS STUDY BETWEEN 2001 AND 2006 AND THEIR OFFSPRING (N=940) WERE FOLLOWED-UP. REGULAR CHECK-UP EXAMINATIONS OF OFFSPRING WERE CONDUCTED AT 3 YEARS, 5 YEARS, AND 7 YEARS OF AGE AND EVERY YEAR THEREAFTER. TO CONSIDER AGE-RELATED HEALTH ISSUES, EXTENSIVE DATA WERE COLLECTED USING QUESTIONNAIRES AND MEASUREMENTS. IN 2021, THE STUDY SUBJECTS WILL REACH 19 YEARS OF AGE, AND WE ARE PLANNING A CHECK-UP EXAMINATION FOR EARLY ADULTHOOD. ABOUT 20 YEARS HAVE PASSED SINCE THE COHORT DATA WERE COLLECTED, AND WE HAVE PUBLISHED RESULTS ON CHILDHOOD HEALTH OUTCOMES ASSOCIATED WITH PRENATAL AND BIRTH CHARACTERISTICS, GENETIC AND EPIGENETIC CHARACTERISTICS RELATED TO CHILDHOOD METABOLISM, THE EFFECTS OF EXPOSURE TO ENDOCRINE DISRUPTORS, AND DIETARY PATTERNS IN CHILDHOOD. RECENTLY, WE STARTED REPORTING ON TOPICS RELATED TO ADOLESCENT HEALTH. THE FINDINGS WILL FACILITATE IDENTIFICATION OF EARLY LIFE RISK FACTORS FOR CHRONIC DISEASES AND THE DEVELOPMENT OF INTERVENTIONS FOR DISEASES LATER IN LIFE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
19    91  28 A PILOT STUDY EXAMINING THE RELATIONSHIP BETWEEN CHRONIC HEROIN USE AND TELOMERE LENGTH AMONG INDIVIDUALS OF AFRICAN ANCESTRY. BACKGROUND: PRIOR RESEARCH HAS SUGGESTED A POSSIBLE LINK BETWEEN HEROIN USE AND SHORTENED TELOMERE LENGTH (TL), A MARKER OF CELLULAR AGING AND GENOMIC STABILITY. WE SOUGHT TO REPLICATE THESE FINDINGS BY EXAMINING THE RELATIONSHIP BETWEEN TL AND HEROIN USE AMONG INDIVIDUALS OF AFRICAN ANCESTRY. METHODS: THIS CROSS-SECTIONAL STUDY EXAMINED TL AMONG 57 PARTICIPANTS [17.5 % FEMALE; MEAN AGE 48.0 (+/-6.80) YEARS] OF AFRICAN ANCESTRY WITH OPIOID USE DISORDER (OUD) AND A MEAN HEROIN USE DURATION OF 18.2 (+/-10.7) YEARS. QUANTITATIVE POLYMERASE CHAIN REACTION (QPCR) WAS USED TO CALCULATE TL AS THE RATIO BETWEEN TELOMERE REPEAT COPY NUMBER (T) AND A SINGLE-COPY GENE, COPY NUMBER (S). THE PRIMARY DEPENDENT VARIABLE WAS TL (T/S RATIO) MEASURED IN KILOBASE PAIRS. COVARIATES INCLUDED HEROIN USE YEARS AND PERSONALITY TRAITS. USING A HYBRID APPROACH, MULTIPLE LINEAR REGRESSION AND BAYESIAN LINEAR REGRESSION EXAMINED THE ASSOCIATION OF CHRONOLOGICAL AGE, HEROIN USE YEARS AND PERSONALITY TRAITS WITH TL. RESULTS: THE MULTIPLE LINEAR REGRESSION MODEL FIT THE DATA WELL, R(2) = 0.265, F(7,49) = 2.53, P < .026. CHRONOLOGICAL AGE (BETA = -0.36, P = .017), NEUROTICISM (BETA = 0.46, P = .044), AND CONSCIENTIOUSNESS (BETA = 0.52, P = .040) WERE SIGNIFICANT PREDICTORS OF TL. BAYESIAN LINEAR REGRESSION PROVIDED MODERATE SUPPORT FOR THE ALTERNATE HYPOTHESIS THAT CHRONOLOGICAL AGE AND TL ARE ASSOCIATED, BF(10) = 5.77, R(2) = 0.120. THE POSTERIOR SUMMARY OF THE COEFFICIENT WAS M = 0.719 (SD = 0.278, 95 % CREDIBLE INTERVAL [-1.28, -0.163]). CONCLUSIONS: CONTRARY TO PRIOR STUDIES, THESE FINDINGS SUGGEST THAT HEROIN USE DURATION MAY NOT BE SIGNIFICANTLY ASSOCIATED WITH TL AMONG INDIVIDUALS OF AFRICAN ANCESTRY, HIGHLIGHTING THE NEED FOR MORE RIGOROUS RESEARCH TO ELUCIDATE THE COMPLEXITY OF THIS RELATIONSHIP.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
20  6018  36 THE ASSOCIATION OF EPIGENETIC AGE ACCELERATION AND MULTIMORBIDITY AT AGE 90 IN THE WOMEN'S HEALTH INITIATIVE. BACKGROUND: EPIGENETIC AGE ACCELERATION (EAA), A MEASURE OF ACCELERATED BIOLOGICAL AGING, HAS BEEN ASSOCIATED WITH INCREASED RISK OF SEVERAL AGE-RELATED CHRONIC CONDITIONS. THIS IS THE FIRST STUDY TO PROSPECTIVELY EXAMINE THE RELATIONSHIP BETWEEN EAA AND BOTH MULTIMORBIDITY COUNT AND A WEIGHTED MULTIMORBIDITY SCORE AMONG LONG-LIVED POSTMENOPAUSAL WOMEN. METHODS: WE INCLUDED 1,951 WOMEN FROM THE WOMEN'S HEALTH INITIATIVE WHO COULD HAVE SURVIVED TO AGE 90. EAA WAS ESTIMATED USING THE HORVATH PAN-TISSUE, HANNUM, PHENOAGE AND GRIMAGE "CLOCKS." TWELVE CHRONIC CONDITIONS WERE INCLUDED IN THE MULTIMORBIDITY COUNT. THE MULTIMORBIDITY SCORE WAS WEIGHTED FOR EACH MORBIDITY'S RELATIONSHIP WITH MORTALITY IN THE STUDY POPULATION. USING MIXED-EFFECTS POISSON AND LINEAR REGRESSION MODELS THAT INCLUDED BASELINE COVARIATES ASSOCIATED WITH BOTH EAA AND MULTIMORBIDITY, WE ESTIMATED RELATIVE RISKS (RRS) AND 95% CONFIDENCE INTERVALS (CIS) FOR THE RELATIONSHIPS BETWEEN EACH EAA MEASURE AT STUDY BASELINE WITH BOTH MULTIMORBIDITY COUNT AND WEIGHTED MULTIMORBIDITY SCORE AT AGE 90, RESPECTIVELY. RESULTS: FOR EVERY ONE-STANDARD DEVIATION INCREASE IN AGEACCELPHENO, THE RATE OF MULTIMORBIDITY ACCUMULATION INCREASED 6% (RR=1.06; 95% CI=1.01-1.12; P=0.025) AND THE MULTIMORBIDITY SCORE BY 7% (RR=1.07; 95% CI=1.01-1.13; P=0.014) FOR WOMEN WHO SURVIVED TO AGE 90. THE RESULTS FOR A ONE-STANDARD DEVIATION INCREASE IN AGEACCELHORVATH, AGEACCELHANNUM AND AGEACCELGRIM WITH MULTIMORBIDITY ACCUMULATION AND SCORE WERE WEAKER COMPARED TO AGEACCELPHENO, AND THE LATTER TWO DID NOT REACH STATISTICAL SIGNIFICANCE. CONCLUSION: AGEACCELPHENO AND AGEACCELHANNUM MAY PREDICT MULTIMORBIDITY COUNT AND SCORE AT AGE 90 IN OLDER WOMEN AND, THUS, MAY BE USEFUL AS A BIOMARKER PREDICTOR OF MULTIMORBIDITY BURDEN IN THE LAST DECADES OF LIFE.	2022