1 5085 152 PILOT STUDY OF ABSOLUTE TELOMERE LENGTHS IN PRETERM INFANTS. BACKGROUND: ANNUALLY, APPROXIMATELY 15 MILLION BABIES ARE BORN PRETERM (<37 WEEKS GESTATIONAL AGE) GLOBALLY. IN THE NEONATAL INTENSIVE CARE UNIT (NICU) ENVIRONMENT, INFANTS ARE EXPOSED TO REPEATED STRESSFUL OR PAINFUL PROCEDURES AS PART OF ROUTINE LIFESAVING CARE. THESE PROCEDURES HAVE BEEN ASSOCIATED WITH EPIGENETIC ALTERATIONS THAT MAY LEAD TO AN INCREASED RISK OF NEURODEVELOPMENTAL DISORDERS. TELOMERE LENGTH HAS BEEN NEGATIVELY ASSOCIATED WITH ADVERSE LIFE EXPERIENCES IN STUDIES OF ADULTS. OBJECTIVES: THIS PILOT STUDY AIMED TO DESCRIBE TELOMERE LENGTH IN A SAMPLE OF PRETERM INFANTS AT NICU DISCHARGE AND EXAMINE ANY ASSOCIATIONS WITH PAIN, FEEDING METHOD, AND NEURODEVELOPMENT. METHODS: THIS DESCRIPTIVE PILOT STUDY SAMPLE INCLUDES BASELINE ABSOLUTE TELOMERE LENGTH (ATL) OF 36 PRETERM INFANTS IMMEDIATELY PRIOR TO DISCHARGE. QUANTITATIVE POLYMERASE CHAIN REACTION WAS USED TO DETERMINE ATL. INFANT DEMOGRAPHICS, PAIN/STRESS, TYPE OF FEEDING, ANTIBIOTIC USE, NEURODEVELOPMENT, AND BUCCAL SWAB DATA WERE COLLECTED. DESCRIPTIVE DATA ANALYSIS WAS USED TO DESCRIBE THE TELOMERE LENGTH USING GRAPHS. RESULTS: AMONG OUR PRETERM INFANT SAMPLES, THE MEAN ATL WAS FAR GREATER THAN THE AVERAGE ADULT TELOMERE LENGTH. ALTHOUGH NO SIGNIFICANT ASSOCIATIONS WERE FOUND BETWEEN ATL AND PAIN, FEEDING METHOD, AND NEURODEVELOPMENT, A TREND BETWEEN SEX WAS NOTED WHERE MALE TELOMERE LENGTHS WERE SHORTER THAN FEMALES AS THEY AGED. DISCUSSION: THIS IS ONE OF FEW STUDIES TO EVALUATE PRETERM INFANT TELOMERE LENGTH. ALTHOUGH OTHER RESEARCHERS HAVE USED RELATIVE TELOMERE LENGTH, WE USED THE MORE ACCURATE ATL. WE FOUND NONSIGNIFICANT SHORTER TELOMERE LENGTHS AMONG MALES. ADDITIONAL LARGE-SCALE, LONGITUDINAL STUDIES ARE NEEDED TO BETTER IDENTIFY THE PREDICTORS OF TELOMERE LENGTH AT THE TIME OF DISCHARGE FROM NICU.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
2 2215  44 EPIGENETIC MODIFICATIONS FOLLOWING NOXIOUS STIMULI IN INFANTS. PURPOSE: TO RECRUIT HEALTHY FULL- AND PRETERM INFANTS INTO GENETIC RESEARCH AND DETERMINE THE EFFECTIVENESS OF A NONINVASIVE DNA SAMPLING TECHNIQUE FOR COMPARING EPIGENETIC MODIFICATIONS. BACKGROUND: NOXIOUS STIMULI DURING A VULNERABLE PERIOD OF INFANT NEURONAL PLASTICITY MAY TRIGGER LONG-TERM EPIGENETIC CHANGES AFFECTING NEURODEVELOPMENT, PAIN MODULATION, AND REACTIVITY. RECOGNIZING EPIGENETIC PAIN FINDINGS IS PROBLEMATIC BECAUSE PARENTS ARE RELUCTANT TO ENROLL NEWBORNS INTO GENETIC RESEARCH. METHODS: DESIGN: WITHIN-SUBJECT CHANGE OVER TIME CANDIDATE-GENE DNA METHYLATION ASSOCIATION STUDY. SETTING/ SAMPLE: URBAN TEACHING HOSPITAL'S NEONATAL INTENSIVE CARE UNIT AND NEWBORN NURSERY. CONVENIENCE SAMPLE OF HEALTHY FULL- (>37 WEEKS, N = 6) AND PRETERM (<37 WEEKS, N = 6) INFANTS. PROCEDURE: PARENTS PARTICIPATED IN A GENETIC PRESENTATION PRIOR TO INFORMED CONSENT. INFANT BUCCAL SALIVA WAS COLLECTED AFTER ADMISSION TO THE UNIT AND PRIOR TO DISCHARGE. ANALYSIS: THE METHYLATION PATTERN AT THE 5' END OF MICRO-OPIOID RECEPTOR GENE ( OPRM1) WAS EXAMINED. DNA WAS TREATED WITH BISULFITE TO CONVERT ALL CYTOSINES TO URACIL RESIDUES, LEAVING METHYLATED CYTOSINES UNCHANGED. SEQUENCING OF UNTREATED AND BISULFITE-CONVERTED DNA WAS CARRIED OUT. THE SEQUENCES OF UNCONVERTED AND BISULFITE-CONVERTED DNA WERE ALIGNED WITH CLUSTALW, FIDELITY OF THE POLYMERASE CHAIN REACTION AND THE SEQUENCING REACTION EVALUATED, AND THE METHYLATION PATTERN IDENTIFIED. RESULTS: RECRUITMENT AND ASSESSMENT OF A NONINVASIVE DNA SAMPLING TECHNIQUE FOR COMPARING EPIGENETIC MODIFICATIONS WERE SUCCESSFUL; HOWEVER, INFANT STRESS DID NOT PRODUCE A CHANGE IN OPRM1 METHYLATION EXPRESSION. RELEVANCE: THIS STUDY ESTABLISHED THE FEASIBILITY OF RECRUITING HEALTHY FULL-TERM INFANTS INTO GENETIC RESEARCH AND THE EFFECTIVENESS OF NONINVASIVE DNA SAMPLING FOR COMPARING EPIGENETIC MODIFICATION IN INFANTS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
3  649  40 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4 2419  28 EPIGENETIC SIGNATURE OF CHRONIC MATERNAL STRESS LOAD DURING PREGNANCY MIGHT BE A POTENTIAL BIOMARKER FOR SPONTANEOUS PRETERM BIRTH. PRETERM BIRTH IS THE LEADING CAUSE OF MORTALITY IN NEWBORN INFANTS AND CAN LEAD TO SIGNIFICANT NEONATAL MORBIDITIES. SPONTANEOUS PRETERM BIRTH ACCOUNTS FOR AT LEAST 50.0% OF ALL PRETERM BIRTHS. WE ARGUE THAT CHRONIC MATERNAL STRESS LOAD, WHICH IS AN IMPORTANT RISK FACTOR FOR SPONTANEOUS PRETERM BIRTH, COULD BE REPRESENTED BY EPIGENETIC SIGNATURE OF SEVERAL SPECIFIC GENETIC LOCI IN THE MOTHER'S BLOOD. A LITERATURE SEARCH WAS DONE IN PUBMED WITH THE FOLLOWING KEYWORDS: "DNA METHYLATION," "EPIGENETICS," "MATERNAL STRESS" AND "PRETERM BIRTH" FROM YEAR 2000 TO 2017. WE SUGGEST THAT THESE GENETIC LOCI MIGHT BE RELATED TO VULNERABILITY AND HYPERSENSIBILITY OF STRESS RESPONSE DURING PREGNANCY IN WOMEN WITH PRETERM BIRTHS. THE MOTHER'S EPI-GENETIC STRESS BIOPROFILE WAS SUPPOSED TO BE A RESULT OF CHRONIC MATERNAL STRESS LOAD SINCE HER BIRTH. THIS EPIGENETIC BIOPROFILE MIGHT ALSO BE A POTENTIAL BIOMARKER FOR SPONTANEOUS PRETERM BIRTH. DNA METHYLATION CHANGES ARE TISSUE-SPECIFIC AND HUMAN STRESS RESPONSE MANIFESTS MOSTLY THROUGH THE CENTRAL NERVOUS SYSTEM (CNS). NEVERTHELESS, WE FOUND EVIDENCE THAT METHYLATION CHANGES OF DNA ISOLATED FROM BLOOD LEUCOCYTES MIGHT BE A RELIABLE MEASURE OF STRESS-RELATED EPIGENETIC CHANGES THAT OCCUR IN THE CNS. EVALUATING BIOLOGICAL MECHANISMS THROUGH THE DEVELOPMENT OF SIMPLE ASSAYS BASED ON EPIGENETIC CHANGES TO MEASURE CHRONIC STRESS LOADS IN EXPECTANT MOTHERS CAN LEAD TO OUR ABILITY TO PREPARE MORE EFFECTIVE MEASURES FOR THE PREVENTION OF PRETERM BIRTHS, AS WELL AS LEADING TO MORE EFFECTIVE TREATMENT STRATEGIES FOR BOTH EXPECTANT MOTHERS AND THEIR NEWBORNS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
5 4612  33 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
6 1235  35 CUMULATIVE PROCEDURAL PAIN AND BRAIN DEVELOPMENT IN VERY PRETERM INFANTS: A SYSTEMATIC REVIEW OF CLINICAL AND PRECLINICAL STUDIES. VERY PRETERM INFANTS MAY MANIFEST NEURODEVELOPMENTAL IMPAIRMENTS, EVEN IN THE ABSENCE OF BRAIN LESIONS. PATHOGENESIS IS COMPLEX AND MULTIFACTORIAL. EVIDENCE SUGGESTS A ROLE OF EARLY ADVERSITIES ON NEURODEVELOPMENTAL OUTCOMES, VIA EPIGENETIC REGULATION AND CHANGES IN BRAIN ARCHITECTURE. IN THIS CONTEXT, WE FOCUSED ON CUMULATIVE PAIN EXPOSURE WHICH PRETERM NEONATES EXPERIENCE IN NEONATAL INTENSIVE CARE UNIT (NICU). WE SYSTEMATICALLY SEARCHED FOR: I) EVIDENCE LINKING PAIN WITH BRAIN DEVELOPMENT AND EXPLORING THE POTENTIAL PATHOGENETIC ROLE OF EPIGENETICS; II) PRECLINICAL RESEARCH SUPPORTING CLINICAL OBSERVATIONAL STUDIES. NINE CLINICAL NEUROIMAGING STUDIES, DURING NEONATAL OR SCHOOL AGE, MOSTLY FROM THE SAME RESEARCH GROUP, REVEALED VOLUME REDUCTION OF WHITE AND GRAY MATTER STRUCTURES IN ASSOCIATION WITH POSTNATAL PAIN EXPOSURE. THREE CONTROLLED ANIMAL STUDIES MIMICKING NICU SETTINGS FOUND INCREASED CELL DEATH OR APOPTOSIS; NEVERTHELESS, ELIGIBLE GROUPS WERE LIMITED IN SIZE. EPIGENETIC MODULATION (SLC6A4 PROMOTER METHYLATION) WAS IDENTIFIED IN ONLY TWO CLINICAL TRIALS. WE CALL FOR ADDITIONAL RESEARCH AND, ALTHOUGH KNOWLEDGE GAPS, WE ALSO POINT OUT THE URGENT NEED OF MINIMIZING PAINFUL PROCEDURES IN NICUS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
7 2677  28 EVALUATING THE CHALLENGES AND REPRODUCIBILITY OF STUDIES INVESTIGATING DNA METHYLATION SIGNATURES OF PSYCHOLOGICAL STRESS. PSYCHOLOGICAL STRESS CAN INCREASE THE RISK OF A WIDE RANGE OF NEGATIVE HEALTH OUTCOMES. STUDIES HAVE BEEN COMPLETED TO DETERMINE IF DNA METHYLATION CHANGES OCCUR IN THE HUMAN BRAIN BECAUSE OF STRESS AND ARE ASSOCIATED WITH LONG-TERM EFFECTS AND DISEASE, BUT RESULTS HAVE BEEN INCONSISTENT. HUMAN CANDIDATE GENE STUDIES (150) AND EPIGENOME-WIDE ASSOCIATION STUDIES (67) WERE SYSTEMATICALLY EVALUATED TO ASSESS HOW DNA METHYLATION IS IMPACTED BY STRESS DURING THE PRENATAL PERIOD, EARLY CHILDHOOD AND ADULTHOOD. THE ASSOCIATION BETWEEN DNA METHYLATION OF NR3C1 EXON 1F AND CHILD MALTREATMENT AND EARLY LIFE ADVERSITY WAS WELL DEMONSTRATED, BUT OTHER GENES DID NOT EXHIBIT A CLEAR ASSOCIATION. THE REPRODUCIBILITY OF INDIVIDUAL CPG SITES IN EPIGENOME-WIDE ASSOCIATION STUDIES WAS ALSO POOR. HOWEVER, BIOLOGICAL PATHWAYS, INCLUDING STRESS RESPONSE, BRAIN DEVELOPMENT AND IMMUNITY, HAVE BEEN CONSISTENTLY IDENTIFIED ACROSS DIFFERENT STRESSORS THROUGHOUT THE LIFE SPAN. FUTURE STUDIES WOULD BENEFIT FROM THE INCREASED SAMPLE SIZE, LONGITUDINAL DESIGN, STANDARDIZED METHODOLOGY, OPTIMAL QUALITY CONTROL, AND IMPROVED STATISTICAL PROCEDURES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
8 3664  38 INFANT NEUROBEHAVIORAL DEVELOPMENT. THE TREND TOWARD SINGLE-ROOM NEONATAL INTENSIVE CARE UNITS (NICUS) IS INCREASING; HOWEVER SCIENTIFIC EVIDENCE IS, AT THIS POINT, MOSTLY ANECDOTAL. THIS IS A CRITICAL TIME TO ASSESS THE IMPACT OF THE SINGLE-ROOM NICU ON IMPROVING MEDICAL AND NEUROBEHAVIORAL OUTCOMES OF THE PRETERM INFANT. WE HAVE DEVELOPED A THEORETICAL MODEL THAT MAY BE USEFUL IN STUDYING HOW THE CHANGE FROM AN OPEN-BAY NICU TO A SINGLE-ROOM NICU COULD AFFECT INFANT MEDICAL AND NEUROBEHAVIORAL OUTCOME. THE MODEL IDENTIFIES MEDIATING FACTORS THAT ARE LIKELY TO ACCOMPANY THE CHANGE TO A SINGLE-ROOM NICU. THESE MEDIATING FACTORS INCLUDE FAMILY CENTERED CARE, DEVELOPMENTAL CARE, PARENTING AND FAMILY FACTORS, STAFF BEHAVIOR AND ATTITUDES, AND MEDICAL PRACTICES. MEDICAL OUTCOMES THAT PLAN TO BE MEASURED ARE SEPSIS, LENGTH OF STAY, GESTATIONAL AGE AT DISCHARGE, WEIGHT GAIN, ILLNESS SEVERITY, GESTATIONAL AGE AT ENTERAL FEEDING, AND NECROTIZING ENTEROCOLITIS (NEC). NEUROBEHAVIORAL OUTCOMES INCLUDE THE NICU NETWORK NEUROBEHAVIORAL SCALE (NNNS) SCORES, SLEEP STATE ORGANIZATION AND SLEEP PHYSIOLOGY, INFANT MOTHER FEEDING INTERACTION SCORES, AND PAIN SCORES. PRELIMINARY FINDINGS ON THE SAMPLE OF 150 PATIENTS IN THE OPEN-BAY NICU SHOWED A "BASELINE" OF EFFECTS OF FAMILY CENTERED CARE, DEVELOPMENTAL CARE, PARENT SATISFACTION, MATERNAL DEPRESSION, AND PARENTING STRESS ON THE NEUROBEHAVIORAL OUTCOMES OF THE NEWBORN. THE SINGLE-ROOM NICU HAS THE POTENTIAL TO IMPROVE THE NEUROBEHAVIORAL STATUS OF THE INFANT AT DISCHARGE. NEUROBEHAVIORAL ASSESSMENT CAN ASSIST WITH EARLY DETECTION AND THEREFORE PREVENTATIVE INTERVENTION TO MAXIMIZE DEVELOPMENTAL OUTCOME. WE ALSO PRESENT AN EPIGENETIC MODEL OF THE POTENTIAL EFFECTS OF MATERNAL CARE ON IMPROVING INFANT NEUROBEHAVIORAL STATUS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
9 3208  35 HEAD CIRCUMFERENCE AS AN EPIGENETIC RISK FACTOR FOR MATERNAL NUTRITION. NUTRITION INDICATORS FOR MALNUTRITION CAN BE SCREENED BY MANY SIGNS SUCH AS STUNTING, UNDERWEIGHT OR OBESITY, MUSCLE WASTING, AND LOW CALORIC AND NUTRIENTS INTAKE. THOSE DEFICIENCIES ARE ALSO ASSOCIATED WITH LOW SOCIOECONOMIC STATUS. ANTHROPOMETRY CAN ASSESS NUTRITIONAL STATUS BY MATERNAL WEIGHT MEASUREMENTS DURING PREGNANCY. HOWEVER, MOST STUDIES HAVE FOCUSED PRIMARILY ON IDENTIFYING CHANGES IN WEIGHT OR BODY MASS INDEX (BMI), AND THEIR EFFECTS ON NEONATAL MEASURES AT PRESENT TIME. WHEREAS HEAD CIRCUMFERENCE (HC) HAS BEEN ASSOCIATED WITH NUTRITION IN THE PAST. WHEN THE MOTHER WAS EXPOSED TO POOR NUTRITION AND UNFAVORABLE SOCIAL CONDITIONS DURING FETAL LIFE, IT WAS HYPOTHESIZED THAT THE INTERGENERATIONAL CYCLE WAS POTENTIALLY MEDIATED BY EPIGENETIC MECHANISMS. TO INVESTIGATE THIS THEORY, MATERNAL HEAD CIRCUMFERENCE (MHC) WAS ASSOCIATED WITH NEONATAL HEAD CIRCUMFERENCE (NHC) IN PREGNANT WOMEN WITHOUT PREEXISTING CHRONIC CONDITIONS, DIFFERENTIATED BY SOCIODEMOGRAPHIC CHARACTERISTICS. A MULTIPLE LINEAR REGRESSION MODEL SHOWED THAT EACH 1 CM-INCREASE IN MHC CORRELATED WITH A 0.11 CM INCREASE IN NHC (BETA95% CI 0.07 TO 0.15). NOTWITHSTANDING, ASSOCIATIONS BETWEEN MATERNAL AND NEONATAL ANTHROPOMETRICS ACCORDING TO GESTATIONAL AGE AT BIRTH HAVE BEEN EXTENSIVELY EXPLAINED. PATH ANALYSIS SHOWED THE INFLUENCE OF SOCIAL STATUS AND THE LATENT VARIABLE WAS SOCIOECONOMIC STATUS. A MODEL OF MATERNAL HEIGHT AND HEAD CIRCUMFERENCE WAS TESTED WITH EFFECTS ON NEONATAL HC. THE SOCIAL VARIABLE LACKED SIGNIFICANCE TO PREDICT NEONATAL HC IN THE TOTAL SAMPLE (P = 0.212) AND IN THE SOUTH/SOUTHEAST (P = 0.095), IN CONTRAST TO THE NORTHEAST (P = 0.047). THIS STUDY HIGHLIGHTS THE POTENTIAL INTERGENERATIONAL INFLUENCE OF MATERNAL NUTRITION ON HC, SUGGESTING THAT MATERNAL NUTRITION MAY BE MORE RELEVANT IN FAMILIES WITH MAJOR SOCIAL VULNERABILITY.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
10 5957  35 TELOMERE LENGTH AND EPIGENETIC AGE ACCELERATION IN ADOLESCENTS WITH ANXIETY DISORDERS. EVIDENCE ON THE RELATIONSHIP BETWEEN GENETICS AND MENTAL HEALTH ARE FLOURISHING. HOWEVER, FEW STUDIES ARE EVALUATING EARLY BIOMARKERS THAT MIGHT LINK GENES, ENVIRONMENT, AND PSYCHOPATHOLOGY. WE AIMED TO STUDY TELOMERE LENGTH (TL) AND EPIGENETIC AGE ACCELERATION (AA) IN A COHORT OF ADOLESCENTS WITH AND WITHOUT ANXIETY DISORDERS (N = 234). WE EVALUATED A REPRESENTATIVE SUBSAMPLE OF PARTICIPANTS AT BASELINE AND AFTER 5 YEARS (N = 76) AND CATEGORIZED THEM ACCORDING TO THEIR ANXIETY DISORDER DIAGNOSIS AT BOTH TIME POINTS: (1) CONTROL GROUP (NO ANXIETY DISORDER, N = 18), (2) VARIABLE GROUP (ANXIETY DISORDER IN ONE EVALUATION, N = 38), AND (3) PERSISTENT GROUP (ANXIETY DISORDER AT BOTH TIME POINTS, N = 20). WE ASSESSED RELATIVE MEAN TL BY REAL-TIME QUANTITATIVE PCR AND DNA METHYLATION BY INFINIUM HUMANMETHYLATION450 BEADCHIP. WE CALCULATED AA USING THE HORVATH AGE ESTIMATION ALGORITHM AND ANALYZED DIFFERENCES AMONG GROUPS USING GENERALIZED LINEAR MIXED MODELS. THE PERSISTENT GROUP OF ANXIETY DISORDER DID NOT CHANGE TL OVER TIME (P = 0.495). THE VARIABLE GROUP HAD HIGHER BASELINE TL (P = 0.003) BUT NO ACCELERATED TL EROSION IN COMPARISON TO THE NON-ANXIETY CONTROL GROUP (P = 0.053). FURTHERMORE, THERE WERE NO DIFFERENCES IN AA AMONG GROUPS OVER TIME. OUR FINDINGS SUGGEST THAT ADOLESCENTS WITH CHRONIC ANXIETY DID NOT CHANGE TELOMERE LENGTH OVER TIME, WHICH COULD BE RELATED TO A DELAY IN NEURONAL DEVELOPMENT IN THIS PERIOD OF LIFE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
11 5748  34 SOCIAL AND PHYSICAL ENVIRONMENTS EARLY IN DEVELOPMENT PREDICT DNA METHYLATION OF INFLAMMATORY GENES IN YOUNG ADULTHOOD. CHRONIC INFLAMMATION CONTRIBUTES TO A WIDE RANGE OF HUMAN DISEASES, AND ENVIRONMENTS IN INFANCY AND CHILDHOOD ARE IMPORTANT DETERMINANTS OF INFLAMMATORY PHENOTYPES. THE UNDERLYING BIOLOGICAL MECHANISMS CONNECTING EARLY ENVIRONMENTS WITH THE REGULATION OF INFLAMMATION IN ADULTHOOD ARE NOT KNOWN, BUT EPIGENETIC PROCESSES ARE PLAUSIBLE CANDIDATES. WE TESTED THE HYPOTHESIS THAT PATTERNS OF DNA METHYLATION (DNAM) IN INFLAMMATORY GENES IN YOUNG ADULTHOOD WOULD BE PREDICTED BY EARLY LIFE NUTRITIONAL, MICROBIAL, AND PSYCHOSOCIAL EXPOSURES PREVIOUSLY ASSOCIATED WITH LEVELS OF INFLAMMATION. DATA COME FROM A POPULATION-BASED LONGITUDINAL BIRTH COHORT STUDY IN METROPOLITAN CEBU, THE PHILIPPINES, AND DNAM WAS CHARACTERIZED IN WHOLE BLOOD SAMPLES FROM 494 PARTICIPANTS (AGE 20-22 Y). ANALYSES FOCUSED ON PROBES IN 114 TARGET GENES INVOLVED IN THE REGULATION OF INFLAMMATION, AND WE IDENTIFIED 10 SITES ACROSS NINE GENES WHERE THE LEVEL OF DNAM WAS SIGNIFICANTLY PREDICTED BY THE FOLLOWING VARIABLES: HOUSEHOLD SOCIOECONOMIC STATUS IN CHILDHOOD, EXTENDED ABSENCE OF A PARENT IN CHILDHOOD, EXPOSURE TO ANIMAL FECES IN INFANCY, BIRTH IN THE DRY SEASON, OR DURATION OF EXCLUSIVE BREASTFEEDING. TO EVALUATE THE BIOLOGICAL SIGNIFICANCE OF THESE SITES, WE TESTED FOR ASSOCIATIONS WITH A PANEL OF INFLAMMATORY BIOMARKERS MEASURED IN PLASMA OBTAINED AT THE SAME AGE AS DNAM ASSESSMENT. THREE SITES PREDICTED ELEVATED INFLAMMATION, AND ONE SITE PREDICTED LOWER INFLAMMATION, CONSISTENT WITH THE INTERPRETATION THAT LEVELS OF DNAM AT THESE SITES ARE FUNCTIONALLY RELEVANT. THIS PATTERN OF RESULTS POINTS TOWARD DNAM AS A POTENTIALLY IMPORTANT BIOLOGICAL MECHANISM THROUGH WHICH DEVELOPMENTAL ENVIRONMENTS SHAPE INFLAMMATORY PHENOTYPES ACROSS THE LIFE COURSE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
12 2485  33 EPIGENETIC-BASED AGE ACCELERATION IN A REPRESENTATIVE SAMPLE OF OLDER AMERICANS: ASSOCIATIONS WITH AGING-RELATED MORBIDITY AND MORTALITY. BIOMARKERS DEVELOPED FROM DNA METHYLATION (DNAM) DATA ARE OF GROWING INTEREST AS PREDICTORS OF HEALTH OUTCOMES AND MORTALITY IN OLDER POPULATIONS. HOWEVER, IT IS UNKNOWN HOW EPIGENETIC AGING FITS WITHIN THE CONTEXT OF KNOWN SOCIOECONOMIC AND BEHAVIORAL ASSOCIATIONS WITH AGING-RELATED HEALTH OUTCOMES IN A LARGE, POPULATION-BASED, AND DIVERSE SAMPLE. THIS STUDY USES DATA FROM A REPRESENTATIVE, PANEL STUDY OF US OLDER ADULTS TO EXAMINE THE RELATIONSHIP BETWEEN DNAM-BASED AGE ACCELERATION MEASURES IN THE PREDICTION OF CROSS-SECTIONAL AND LONGITUDINAL HEALTH OUTCOMES AND MORTALITY. WE EXAMINE WHETHER RECENT IMPROVEMENTS TO THESE SCORES, USING PRINCIPAL COMPONENT (PC)-BASED MEASURES DESIGNED TO REMOVE SOME OF THE TECHNICAL NOISE AND UNRELIABILITY IN MEASUREMENT, IMPROVE THE PREDICTIVE CAPABILITY OF THESE MEASURES. WE ALSO EXAMINE HOW WELL DNAM-BASED MEASURES PERFORM AGAINST WELL-KNOWN PREDICTORS OF HEALTH OUTCOMES SUCH AS DEMOGRAPHICS, SES, AND HEALTH BEHAVIORS. IN OUR SAMPLE, AGE ACCELERATION CALCULATED USING "SECOND AND THIRD GENERATION CLOCKS," PHENOAGE, GRIMAGE, AND DUNEDINPACE, IS CONSISTENTLY A SIGNIFICANT PREDICTOR OF HEALTH OUTCOMES INCLUDING CROSS-SECTIONAL COGNITIVE DYSFUNCTION, FUNCTIONAL LIMITATIONS AND CHRONIC CONDITIONS ASSESSED 2 Y AFTER DNAM MEASUREMENT, AND 4-Y MORTALITY. PC-BASED EPIGENETIC AGE ACCELERATION MEASURES DO NOT SIGNIFICANTLY CHANGE THE RELATIONSHIP OF DNAM-BASED AGE ACCELERATION MEASURES TO HEALTH OUTCOMES OR MORTALITY COMPARED TO EARLIER VERSIONS OF THESE MEASURES. WHILE THE USEFULNESS OF DNAM-BASED AGE ACCELERATION AS A PREDICTOR OF LATER LIFE HEALTH OUTCOMES IS QUITE CLEAR, OTHER FACTORS SUCH AS DEMOGRAPHICS, SES, MENTAL HEALTH, AND HEALTH BEHAVIORS REMAIN EQUALLY, IF NOT MORE ROBUST, PREDICTORS OF LATER LIFE OUTCOMES.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
13 6112  38 THE EPIGENETIC CLOCK AS A PREDICTOR OF DISEASE AND MORTALITY RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS. BACKGROUND: AGEING IS ONE OF THE PRINCIPAL RISK FACTORS FOR MANY CHRONIC DISEASES. HOWEVER, THERE IS CONSIDERABLE BETWEEN-PERSON VARIATION IN THE RATE OF AGEING AND INDIVIDUAL DIFFERENCES IN THEIR SUSCEPTIBILITY TO DISEASE AND DEATH. EPIGENETIC MECHANISMS MAY PLAY A ROLE IN HUMAN AGEING, AND DNA METHYLATION AGE BIOMARKERS MAY BE GOOD PREDICTORS OF AGE-RELATED DISEASES AND MORTALITY RISK. THE AIMS OF THIS SYSTEMATIC REVIEW WERE TO IDENTIFY AND SYNTHESISE THE EVIDENCE FOR AN ASSOCIATION BETWEEN PERIPHERALLY MEASURED DNA METHYLATION AGE AND LONGEVITY, AGE-RELATED DISEASE, AND MORTALITY RISK. METHODS: A SYSTEMATIC SEARCH WAS CONDUCTED IN LINE WITH THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES (PRISMA) GUIDELINES. USING RELEVANT SEARCH TERMS, MEDLINE, EMBASE, COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, AND PSYCHINFO DATABASES WERE SEARCHED TO IDENTIFY ARTICLES MEETING THE INCLUSION CRITERIA. STUDIES WERE ASSESSED FOR BIAS USING JOANNA BRIGGS INSTITUTE CRITICAL APPRAISAL CHECKLISTS. DATA WAS EXTRACTED FROM STUDIES MEASURING AGE ACCELERATION AS A PREDICTOR OF AGE-RELATED DISEASES, MORTALITY OR LONGEVITY, AND THE FINDINGS FOR SIMILAR OUTCOMES COMPARED. USING REVIEW MANAGER 5.3 SOFTWARE, TWO META-ANALYSES (ONE PER EPIGENETIC CLOCK) WERE CONDUCTED ON STUDIES MEASURING ALL-CAUSE MORTALITY. RESULTS: TWENTY-THREE RELEVANT ARTICLES WERE IDENTIFIED, INCLUDING A TOTAL OF 41,607 PARTICIPANTS. FOUR STUDIES FOCUSED ON AGEING AND LONGEVITY, 11 ON AGE-RELATED DISEASE (CANCER, CARDIOVASCULAR DISEASE, AND DEMENTIA), AND 11 ON MORTALITY. THERE WAS SOME, ALTHOUGH INCONSISTENT, EVIDENCE FOR AN ASSOCIATION BETWEEN INCREASED DNA METHYLATION AGE AND RISK OF DISEASE. META-ANALYSES INDICATED THAT EACH 5-YEAR INCREASE IN DNA METHYLATION AGE WAS ASSOCIATED AN 8 TO 15% INCREASED RISK OF MORTALITY. CONCLUSION: DUE TO THE SMALL NUMBER OF STUDIES AND HETEROGENEITY IN STUDY DESIGN AND OUTCOMES, THE ASSOCIATION BETWEEN DNA METHYLATION AGE AND AGE-RELATED DISEASE AND LONGEVITY IS INCONCLUSIVE. INCREASED EPIGENETIC AGE WAS ASSOCIATED WITH MORTALITY RISK, BUT POSITIVE PUBLICATION BIAS NEEDS TO BE CONSIDERED. FURTHER RESEARCH IS NEEDED TO DETERMINE THE EXTENT TO WHICH DNA METHYLATION AGE CAN BE USED AS A CLINICAL BIOMARKER.	2019	
                                                                                                                                                                                                                                                                                                                                                                           
14 5961  40 TELOMERE LENGTH IN PRETERM INFANTS: A PROMISING BIOMARKER OF EARLY ADVERSITY AND CARE IN THE NEONATAL INTENSIVE CARE UNIT? PRETERM INFANTS PRESENT AN IMMATURE NEUROBEHAVIORAL PROFILE AT BIRTH, EVEN IN ABSENCE OF SEVERE BRAIN INJURIES AND PERINATAL COMPLICATIONS. AS SUCH, THEY REQUIRE A LONG-LASTING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU), WHICH IS THOUGHT TO GRANT AT-RISK NEWBORNS' SURVIVAL, BUT STILL ENTAILS A NUMBER OF PHYSICAL, PAINFUL, AND SOCIO-EMOTIONAL STRESSORS. HENCE, PRETERM BIRTH AND NICU STAY REPRESENT AN EARLY ADVERSE EXPERIENCE, WHICH HAS BEEN LINKED TO DETRIMENTAL CONSEQUENCES FOR NEUROLOGICAL, NEURO-ENDOCRINAL, BEHAVIORAL, AND SOCIO-EMOTIONAL DEVELOPMENT, AS WELL AS TO DISEASE LATER IN LIFE. RECENT ADVANCES IN THE BEHAVIORAL EPIGENETIC FIELD ARE HELPING US TO UNVEIL THE POTENTIAL MECHANISMS THROUGH WHICH EARLY NICU-RELATED STRESS MAY LEAD TO NEGATIVE DEVELOPMENTAL OUTCOMES. FROM THIS PERSPECTIVE, TELOMERE REGULATION MIGHT BE A KEY PROGRAMMING MECHANISM. TELOMERES ARE THE TERMINAL PORTION OF CHROMOSOMES AND ARE KNOWN TO GET SHORTER WITH AGE. MOREOVER, TELOMERE LENGTH (TL) IS AFFECTED BY THE EXPOSURE TO STRESS DURING EARLY DEVELOPMENT. AS SUCH, TL MIGHT BE AN INNOVATIVE BIOMARKER OF EARLY ADVERSE EXPOSURES IN YOUNG INFANTS AND CHILDREN. UNFORTUNATELY, THERE IS PAUCITY OF STUDIES INVESTIGATING TL IN POPULATIONS OF PRETERM INFANTS AND ITS ASSOCIATION WITH KNOWN NICU-RELATED STRESSORS REMAINS UNEXPLORED. IN THE PRESENT PAPER, THE POTENTIAL RELEVANCE OF TL FOR RESEARCH AND CLINICAL WORK WITH PRETERM INFANTS WILL BE UNDERLINED IN THE LIGHT OF RECENT CONTRIBUTIONS LINKING PROGRESSIVE TELOMERE SHORTENING AND EARLY EXPOSURE TO ADVERSE EXPERIENCES AND STRESSFUL ENVIRONMENTS IN HUMANS. FINALLY, INSIGHTS WILL BE PROVIDED TO GUIDE CLINICALLY RELEVANT TRANSLATIONAL RESEARCH ON TL IN THE FIELD OF VPT BIRTH AND NICU STAY.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
15 4085  45 MATERNAL OBESITY AND GESTATIONAL DIABETES REPROGRAM THE METHYLOME OF OFFSPRING BEYOND BIRTH BY INDUCING EPIGENETIC SIGNATURES IN METABOLIC AND DEVELOPMENTAL PATHWAYS. BACKGROUND: OBESITY IS A NEGATIVE CHRONIC METABOLIC HEALTH CONDITION THAT REPRESENTS AN ADDITIONAL RISK FOR THE DEVELOPMENT OF MULTIPLE PATHOLOGIES. EPIDEMIOLOGICAL STUDIES HAVE SHOWN HOW MATERNAL OBESITY OR GESTATIONAL DIABETES MELLITUS DURING PREGNANCY CONSTITUTE SERIOUS RISK FACTORS IN RELATION TO THE APPEARANCE OF CARDIOMETABOLIC DISEASES IN THE OFFSPRING. FURTHERMORE, EPIGENETIC REMODELLING MAY HELP EXPLAIN THE MOLECULAR MECHANISMS THAT UNDERLIE THESE EPIDEMIOLOGICAL FINDINGS. THUS, IN THIS STUDY WE EXPLORED THE DNA METHYLATION LANDSCAPE OF CHILDREN BORN TO MOTHERS WITH OBESITY AND GESTATIONAL DIABETES DURING THEIR FIRST YEAR OF LIFE. METHODS: WE USED ILLUMINA INFINIUM METHYLATIONEPIC BEADCHIP ARRAYS TO PROFILE MORE THAN 770,000 GENOME-WIDE CPG SITES IN BLOOD SAMPLES FROM A PAEDIATRIC LONGITUDINAL COHORT CONSISTING OF 26 CHILDREN BORN TO MOTHERS WHO SUFFERED FROM OBESITY OR OBESITY WITH GESTATIONAL DIABETES MELLITUS DURING PREGNANCY AND 13 HEALTHY CONTROLS (MEASUREMENTS TAKEN AT 0, 6 AND 12 MONTH; TOTAL N = 90). WE CARRIED OUT CROSS-SECTIONAL AND LONGITUDINAL ANALYSES TO DERIVE DNA METHYLATION ALTERATIONS ASSOCIATED WITH DEVELOPMENTAL AND PATHOLOGY-RELATED EPIGENOMICS. RESULTS: WE IDENTIFIED ABUNDANT DNA METHYLATION CHANGES DURING CHILD DEVELOPMENT FROM BIRTH TO 6 MONTHS AND, TO A LESSER EXTENT, UP TO 12 MONTHS OF AGE. USING CROSS-SECTIONAL ANALYSES, WE DISCOVERED DNA METHYLATION BIOMARKERS MAINTAINED ACROSS THE FIRST YEAR OF LIFE THAT COULD DISCRIMINATE CHILDREN BORN TO MOTHERS WHO SUFFERED FROM OBESITY OR OBESITY WITH GESTATIONAL DIABETES. IMPORTANTLY, ENRICHMENT ANALYSES SUGGESTED THAT THESE ALTERATIONS CONSTITUTE EPIGENETIC SIGNATURES THAT AFFECT GENES AND PATHWAYS INVOLVED IN THE METABOLISM OF FATTY ACIDS, POSTNATAL DEVELOPMENTAL PROCESSES AND MITOCHONDRIAL BIOENERGETICS, SUCH AS CPT1B, SLC38A4, SLC35F3 AND FN3K. FINALLY, WE OBSERVED EVIDENCE OF AN INTERACTION BETWEEN DEVELOPMENTAL DNA METHYLATION CHANGES AND MATERNAL METABOLIC CONDITION ALTERATIONS. CONCLUSIONS: OUR OBSERVATIONS HIGHLIGHT THE FIRST SIX MONTHS OF DEVELOPMENT AS BEING THE MOST CRUCIAL FOR EPIGENETIC REMODELLING. FURTHERMORE, OUR RESULTS SUPPORT THE EXISTENCE OF SYSTEMIC INTRAUTERINE FOETAL PROGRAMMING LINKED TO OBESITY AND GESTATIONAL DIABETES THAT AFFECTS THE CHILDHOOD METHYLOME BEYOND BIRTH, WHICH INVOLVES ALTERATIONS RELATED TO METABOLIC PATHWAYS, AND WHICH MAY INTERACT WITH ORDINARY POSTNATAL DEVELOPMENT PROGRAMMES.	2023	
                                                                                                                 
16 5875  30 SYMPTOMS OF ALLERGIC RHINITIS IN WOMEN DURING EARLY PREGNANCY ARE ASSOCIATED WITH HIGHER PREVALENCE OF ALLERGIC RHINITIS IN THEIR OFFSPRING. BACKGROUND: EPIGENETIC CONTROL OF GENE EXPRESSION PROFILES IS A UBIQUITOUS MECHANISM DURING CELL DIFFERENTIATION, ORGANOGENESIS AND CHRONIC INFLAMMATORY REACTIONS. RECENT STUDIES HAVE SHOWN THAT ALLERGEN EXPOSURE DURING VERY EARLY PREGNANCY INCREASES BRONCHIAL HYPERSENSITIVITY IN OFFSPRING IN A MURINE MODEL OF BRONCHIAL ASTHMA. HOWEVER, NO SUCH PHENOMENA WERE REPORTED IN HUMANS. IN THE PRESENT STUDY, THE ROLE OF EPIGENETIC CONTROL IN THE ONSET OF ALLERGIC DISEASES WAS INVESTIGATED. METHODS: A TOTAL OF 400 PAIRS OF MOTHERS WITH PHYSICIAN-DIAGNOSED ALLERGIC RHINITIS (AR) AND THEIR OFFSPRING (AGE 7-18 MONTHS) WHO PARTICIPATED IN A LARGE-SCALE MEDICAL CHECK-UP WERE ENROLLED IN THIS RETROSPECTIVE COHORT STUDY. FAMILY HISTORY OF ALLERGIC DISEASES AND THE PRESENCE OR ABSENCE OF AR SYMPTOMS DURING PREGNANCY WERE INQUIRED ABOUT USING A SELF-ANSWERED QUESTIONNAIRE. A LOGISTIC REGRESSION MODEL ADJUSTED FOR AGE, GENDER, BIRTH MONTH AND FATHER'S HISTORY OF ALLERGIC DISEASES WAS STATISTICALLY ANALYZED. RESULTS: OFFSPRING WHOSE MOTHERS HAD ANY AR SYMPTOMS DURING EARLY PREGNANCY SHOWED A SIGNIFICANTLY HIGHER ADJUSTED ODDS RATIO FOR THE ONSET OF AR IN OFFSPRING THAN THOSE WHOSE MOTHERS HAD NO SYMPTOMS DURING PREGNANCY (ADJUSTED ODDS RATIO: 6.26, P = 0.036). HOWEVER, THE SYMPTOMS OF AR DURING LATE PREGNANCY SHOWED NO EFFECTS ON THE ODDS RATIO. IN CONTRAST, THE PRESENCE OR ABSENCE OF AR SYMPTOMS DURING EARLY OR LATE PREGNANCY SHOWED NO ASSOCIATION WITH THE PREVALENCE OF FOOD ALLERGY, ATOPIC DERMATITIS OR ASTHMA IN OFFSPRING. CONCLUSIONS: OUR RESULTS SUGGEST THE PRESENCE OF POSSIBLE EPIGENETIC MECHANISMS REGULATING THE ONSET OF AR IN HUMANS PRESUMABLY THROUGH INCREASED ORGAN-SPECIFIC HYPERSENSITIVITY.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
17 3391  27 HORMETIC ASSOCIATION BETWEEN PERCEIVED STRESS AND HUMAN EPIGENETIC AGING BASED ON RESILIENCE CAPACITY. CHRONIC STRESS IS ASSOCIATED WITH DELETERIOUS HEALTH OUTCOMES AND MORTALITY RISK. A POTENTIAL MECHANISM BY WHICH STRESS AFFECTS HEALTHSPAN AND LIFESPAN IS ACCELERATION OF CELLULAR AGING. BIOLOGIC AGE PREDICTION MODELS, TERMED EPIGENETIC CLOCKS, HAVE BEEN DEVELOPED TO ESTIMATE BIOLOGIC AGE DIFFERENCES AMONG PEOPLE WITH THE SAME CHRONOLOGIC AGE. THIS STUDY EVALUATES THE SIMULTANEOUS IMPACT OF PERCEIVED CHRONIC STRESS AND RESILIENCE ON GRIM AGE ACCELERATION. THE PERCEIVED STRESS SCORE (PSS) AND CONNOR-DAVIDSON RESILIENCE SCALE (CD-RISC) WERE USED TO MEASURE CHRONIC STRESS AND RESILIENCE, RESPECTIVELY. DNA WAS EXTRACTED FROM WHOLE BLOOD AND ANALYZED USING THE METHYLATIONEPIC BEADCHIP. GRIMAGE ESTIMATES WERE CALCULATED USING THE METHYLATION AGE CALCULATOR. FORTY-SEVEN BUSINESS EXECUTIVES WERE CATEGORIZED BY LEVELS OF HIGH OR LOW STRESS AND RESILIENCE SCORES. COMPARED TO PARTICIPANTS WITH LOW STRESS AND HIGH RESILIENCE, THOSE WITH LOW STRESS AND LOW RESILIENCE DEMONSTRATED THE STRONGEST ASSOCIATION WITH GRIM AGE ACCELERATION (P = 0.044), AFTER CONTROLLING FOR AGE AND ESTIMATED CELLULAR PROPORTIONS. INTERESTINGLY, AMONG PARTICIPANTS WITH LOW RESILIENCE, THOSE WITH HIGH PERCEIVED STRESS HAD A WEAKER ASSOCIATION WITH GRIM AGE ACCELERATION THAN PARTICIPANTS WITH LOW PERCEIVED STRESS. HOWEVER, AMONG PARTICIPANTS WITH HIGH RESILIENCE, LOW PERCEIVED STRESS HAD A WEAKER ASSOCIATION WITH GRIM AGE ACCELERATION THAN HIGH PERCEIVED STRESS. OUR FINDINGS SUGGEST THAT THE IMPACT OF PERCEIVED STRESS ON EPIGENETIC AGE ACCELERATION MAY DIFFER BASED ON RESILIENCE CAPACITY, WITH A POTENTIAL PARADOXICAL BENEFICIAL EFFECT AMONG THOSE WITH LOW RESILIENCE.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
18 1439  36 DIFFERENTIAL PLACENTAL CPG METHYLATION IS ASSOCIATED WITH CHRONIC LUNG DISEASE OF PREMATURITY. BACKGROUND: CHRONIC LUNG DISEASE (CLD) IS THE MOST COMMON PULMONARY MORBIDITY IN EXTREMELY PRETERM INFANTS. IT IS UNCLEAR TO WHAT EXTENT PRENATAL EXPOSURES INFLUENCE THE RISK OF CLD. EPIGENETIC VARIATION IN PLACENTA DNA METHYLATION MAY BE ASSOCIATED WITH DIFFERENTIAL RISK OF CLD, AND THESE ASSOCIATIONS MAY BE DEPENDENT UPON SEX. METHODS: DATA WERE OBTAINED FROM A MULTI-CENTER COHORT OF INFANTS BORN EXTREMELY PRETERM (<28 WEEKS' GESTATION) AND AN EPIGENOME-WIDE APPROACH WAS USED TO IDENTIFY ASSOCIATIONS BETWEEN PLACENTAL DNA METHYLATION AND CLD (N = 423). ASSOCIATIONS WERE EVALUATED USING ROBUST LINEAR REGRESSION ADJUSTING FOR COVARIATES, WITH A FALSE DISCOVERY RATE OF 0.05. ANALYSES STRATIFIED BY SEX WERE USED TO ASSESS DIFFERENCES IN METHYLATION-CLD ASSOCIATIONS. RESULTS: CLD WAS ASSOCIATED WITH DIFFERENTIAL METHYLATION AT 49 CPG SITES REPRESENTING 46 GENES IN THE PLACENTA. CLD WAS ASSOCIATED WITH DIFFERENTIAL METHYLATION OF PROBES WITHIN GENES RELATED TO PATHWAYS INVOLVED IN FETAL LUNG DEVELOPMENT, SUCH AS P53 SIGNALING AND MYO-INOSITOL BIOSYNTHESIS. ASSOCIATIONS BETWEEN CPG METHYLATION AND CLD DIFFERED BY SEX. CONCLUSIONS: DIFFERENTIAL PLACENTAL METHYLATION WITHIN GENES WITH KEY ROLES IN FETAL LUNG DEVELOPMENT MAY REFLECT COMPLEX CELL SIGNALING BETWEEN THE PLACENTA AND FETUS WHICH MEDIATE CLD RISK. THESE PATHWAYS APPEAR TO BE DISTINCT BASED ON FETAL SEX. IMPACT: IN EXTREMELY PRETERM INFANTS, DIFFERENTIAL METHYLATION OF CPG SITES WITHIN PLACENTAL GENES INVOLVED IN PATHWAYS RELATED TO CELL SIGNALING, OXIDATIVE STRESS, AND TROPHOBLAST INVASION IS ASSOCIATED WITH CHRONIC LUNG DISEASE OF PREMATURITY. DNA METHYLATION PATTERNS ASSOCIATED WITH CHRONIC LUNG DISEASE WERE DISTINCTLY BASED ON FETAL SEX, SUGGESTING A POTENTIAL MECHANISM UNDERLYING DIMORPHIC PHENOTYPES. MECHANISMS RELATED TO FETAL HYPOXIA AND PLACENTAL MYO-INOSITOL SIGNALING MAY PLAY A ROLE IN FETAL LUNG PROGRAMMING AND THE DEVELOPMENTAL ORIGINS OF CHRONIC LUNG DISEASE. CONTINUED RESEARCH OF THE RELATIONSHIP BETWEEN THE PLACENTAL EPIGENOME AND CHRONIC LUNG DISEASE COULD INFORM EFFORTS TO AMELIORATE OR PREVENT THIS CONDITION.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
19 1537  34 DNA METHYLATION IN ADOLESCENTS WITH ANXIETY DISORDER: A LONGITUDINAL STUDY. ANXIETY DISORDERS (AD) TYPICALLY MANIFEST IN CHILDREN AND ADOLESCENTS AND MIGHT PERSIST INTO ADULTHOOD. HOWEVER, THERE ARE STILL FEW DATA CONCERNING EPIGENETIC MECHANISMS ASSOCIATED WITH ONSET, PERSISTENCE OR REMISSION OF AD OVER TIME. WE INVESTIGATED A COHORT OF ADOLESCENTS AND YOUNG ADULTS AT BASELINE (AGE; 13.19 +/- 2.38) AND AFTER 5 YEARS AND CLASSIFIED THEM ACCORDING TO THE AD DIAGNOSIS AND THEIR LONGITUDINAL TRAJECTORIES INTO 4 GROUPS: (1) TYPICALLY DEVELOPING COMPARISONS (TDC; CONTROL GROUP, N = 14); (2) INCIDENT (AD IN THE SECOND EVALUATION ONLY, N = 11); (3) PERSISTENT (AD IN BOTH EVALUATIONS, N = 14) AND (4) REMITTENT (AD IN THE FIRST EVALUATION ONLY, N = 8). DNA METHYLATION WAS EVALUATED WITH THE INFINIUM HUMANMETHYLATION450 BEADCHIP FROM SALIVA SAMPLES COLLECTED AT BOTH EVALUATIONS. GENE SET ENRICHMENT ANALYSIS WAS APPLIED TO CONSIDER BIOLOGICAL PATHWAYS. WE FOUND DECREASED DNA METHYLATION IN TDC GROUP WHILE THE CHRONIC CASES OF AD PRESENTED HYPERMETHYLATION IN CENTRAL NERVOUS SYSTEM DEVELOPMENT PATHWAYS. MOREOVER, WE SHOWED THAT THIS PERSISTENT GROUP ALSO PRESENTED HYPERMETHYLATION WHILE THE OTHER THREE GROUPS WERE ASSOCIATED WITH HYPOMETHYLATION IN NERVOUS SYSTEM DEVELOPMENT PATHWAY. INCIDENCE AND REMISSION GROUPS WERE ASSOCIATED WITH INCREASED AND DECREASED METHYLATION IN NEURON DEVELOPMENT PATHWAYS, RESPECTIVELY. LARGER STUDIES ARE LIKELY TO DETECT SPECIFIC GENES RELEVANT TO AD.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
20 6315  42 THE RELATIONSHIP OF MATERNAL AND CHILD METHYLATION OF THE GLUCOCORTICOID RECEPTOR NR3C1 DURING EARLY CHILDHOOD AND SUBSEQUENT CHILD PSYCHOPATHOLOGY AT SCHOOL-AGE IN THE CONTEXT OF MATERNAL INTERPERSONAL VIOLENCE-RELATED POST-TRAUMATIC STRESS DISORDER. INTRODUCTION: INTERPERSONAL VIOLENT (IPV) EXPERIENCES WHEN THEY BEGIN IN CHILDHOOD AND CONTINUE IN VARIOUS FORMS DURING ADULTHOOD OFTEN LEAD TO CHRONIC POST-TRAUMATIC STRESS DISORDER (PTSD) THAT IS ASSOCIATED IN MULTIPLE STUDIES WITH HYPOCORTISOLISM AND LOWER PERCENTAGE OF METHYLATION OF THE PROMOTER REGION OF THE GENE CODING FOR THE GLUCOCORTICOID RECEPTOR (NR3C1). THIS PROSPECTIVE, LONGITUDINAL STUDY EXAMINED THE RELATIONSHIP OF NR3C1 METHYLATION AMONG MOTHERS WITH IPV-RELATED PTSD AND THEIR TODDLERS AND THEN LOOKED AT THE RELATIONSHIP OF MATERNAL NR3C1 METHYLATION AND CHILD PSYCHOPATHOLOGY AT SCHOOL AGE. METHODS: FORTY-EIGHT MOTHERS WERE EVALUATED FOR LIFE-EVENTS HISTORY AND POST-TRAUMATIC STRESS DISORDER VIA STRUCTURED CLINICAL INTERVIEW WHEN THEIR CHILDREN WERE AGES 12-42 MONTHS (MEAN AGE 26.7 MONTHS, SD 8.8). THEIR CHILDREN'S PSYCHOPATHOLOGY IN TERMS OF INTERNALIZING SYMPTOMS AND EXTERNALIZING BEHAVIORS WAS EVALUATED USING THE CHILD BEHAVIOR CHECKLIST AT AGES 5-9 YEARS (MEAN AGE 7 YEARS, SD 1.1). PERCENTAGE OF METHYLATION FOR THE NR3C1 GENE PROMOTER REGION WAS ASSESSED FROM DNA EXTRACTED FROM MATERNAL AND CHILD SALIVA USING BISULFITE PYROSEQUENCING. DATA ANALYSIS INVOLVED PARAMETRIC AND NON-PARAMETRIC CORRELATIONS AND MULTIPLE LINEAR AND LOGISTIC REGRESSION MODELING. RESULTS: LOGISTIC REGRESSION MODELS USING CHILD NR3C1 METHYLATION AS THE DEPENDENT VARIABLE AND MATERNAL NR3C1 METHYLATION AND PTSD GROUP STATUS AS PREDICTORS, AS WELL AS THE INTERACTION INDICATED THAT ALL THREE OF THESE SIGNIFICANTLY PREDICTED CHILD NR3C1 METHYLATION. THESE FINDINGS REMAINED SIGNIFICANT WHEN CONTROLLING FOR CHILD AGE, SEX AND MATERNAL CHILD ABUSE HISTORY. OVERALL, MATERNAL NR3C1 METHYLATION WHEN CHILDREN WERE TODDLERS WAS NEGATIVELY AND SIGNIFICANTLY ASSOCIATED WITH CHILD EXTERNALIZING BEHAVIOR SEVERITY AT SCHOOL AGE. DISCUSSION: WE FOUND THAT CORRELATIONS BETWEEN MOTHERS AND THEIR CHILDREN OF NR3C1 METHYLATION LEVELS OVERALL AND AT ALL INDIVIDUAL CPG SITES OF INTEREST WERE SIGNIFICANT ONLY IN THE IPV-PTSD GROUP. THE LATTER FINDINGS SUPPORT THAT NR3C1 METHYLATION IN MOTHERS POSITIVELY AND STATISTICALLY SIGNIFICANTLY CORRELATES WITH NR3C1 METHYLATION IN THEIR CHILDREN ONLY IN PRESENCE OF IPV-PTSD IN THE MOTHERS. THIS MATERNAL EPIGENETIC SIGNATURE WITH RESPECT TO THIS GLUCOCORTICOID RECEPTOR IS SIGNIFICANTLY ASSOCIATED WITH CHILD BEHAVIOR THAT MAY WELL POSE A RISK FOR INTERGENERATIONAL TRANSMISSION OF VIOLENCE AND RELATED PSYCHOPATHOLOGY.	2022