1   117 138 A STUDY ON NUTRITIONAL STATUS AND TOOTH CROWN SIZE AMONG 6-9-YEAR-OLD CHILDREN: AN OBSERVATIONAL CROSS-SECTIONAL STUDY. BACKGROUND: NUMEROUS FACTORS CONTRIBUTE TO VARIATION IN TOOTH SIZE. THIS IS BROADLY DESCRIBED AS GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. A STRONG GENETIC CONTRIBUTION HAS BEEN SHOWN, BUT ENVIRONMENTAL FACTORS MAY ALSO PLAY A ROLE. AIM: THE AIM OF THIS STUDY WAS TO DETERMINE THE RELATIONSHIP BETWEEN NUTRITIONAL STATUS AND TOOTH CROWN SIZE. DESIGN: AN OBSERVATIONAL CROSS-SECTIONAL SURVEY WAS CONDUCTED AMONG 100 SCHOOL-GOING CHILDREN OF 6-9 YEARS. THE VALUE OBTAINED WAS PLOTTED ON AGE- AND GENDER-SPECIFIC PERCENTILE CURVES CHART GIVEN BY THE CENTERS FOR DISEASE CONTROL AND PREVENTION; INDIVIDUALS WERE CATEGORIZED BASED ON BODY MASS INDEX CRITERIA. THE PARTICIPANTS WERE EXAMINED FOR THE MESIODISTAL WIDTH OF PRIMARY SECOND MOLAR AND PERMANENT FIRST MOLAR BY THREE DIFFERENT OBSERVERS USING A VERNIER CALIPER. DATA OBTAINED WERE STATISTICALLY ANALYZED. RESULTS: TOTAL OF 45, 40, AND 15 BELONGED TO UNDERWEIGHT, NORMAL, AND OVERWEIGHT CATEGORY, RESPECTIVELY. THE TOOTH SIZE OF PRIMARY MOLAR BETWEEN HEALTHY, OVERWEIGHT, AND UNDERWEIGHT CHILDREN WAS 9.87 +/- 0.23, 9.47 +/- 0.48, AND 9.61 +/- 0.7, RESPECTIVELY, AND FOR PERMANENT MOLAR BETWEEN HEALTHY, OVERWEIGHT, AND UNDERWEIGHT CHILDREN WAS 10.63 +/- 0.2, 10.56 +/- 0.5, AND 10.57 +/- 0.6, RESPECTIVELY. CONCLUSION: THE CORRELATION BETWEEN TOOTH CROWN SIZE WITH AN EXOGENOUS CHRONIC STRESSOR, I.E., MALNUTRITION, WAS FOUND TO BE NONSIGNIFICANT WHEN COMPARED WITH THE HEALTHY INDIVIDUALS. THE FINDINGS INDICATE THAT NUTRITIONAL STATUS DOES NOT SIGNIFICANTLY INFLUENCE THE DETERMINATION OF TOOTH SIZE IN HUMANS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
2  5085  33 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
3  4910  21 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
4  4917  24 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
5  4916  26 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6  5958  37 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
7  1956  37 EPIGENETIC AGE IN PERIPHERAL BLOOD AMONG CHILDREN, ADOLESCENT, AND ADULT SURVIVORS OF CHILDHOOD CANCER. IMPORTANCE: CERTAIN CANCER THERAPIES ARE RISK FACTORS FOR EPIGENETIC AGE ACCELERATION (EAA) AMONG SURVIVORS OF CHILDHOOD CANCER, AND EAA IS ASSOCIATED WITH CHRONIC HEALTH CONDITIONS (CHCS). HOWEVER, SMALL NUMBERS OF YOUNGER SURVIVORS (AGED <20 YEARS) PREVIOUSLY EVALUATED HAVE LIMITED THE ABILITY TO CALCULATE EAA AMONG THIS AGE GROUP. OBJECTIVE: TO EVALUATE THE CHANGE RATE OF EPIGENETIC AGE (EA) AND EAA IN YOUNGER COMPARED WITH OLDER SURVIVORS AND THE POSSIBLE ASSOCIATION OF EAA WITH EARLY-ONSET OBESITY (AGED <20 YEARS), SEVERITY/BURDEN OF CHCS, AND LATE MORTALITY (>5 YEARS FROM CANCER DIAGNOSIS). DESIGN, SETTING, AND PARTICIPANTS: STUDY PARTICIPANTS WERE FROM THE ST JUDE LIFETIME COHORT, INITIATED IN 2007 WITH ONGOING FOLLOW-UP. THE PRESENT STUDY WAS CONDUCTED FROM APRIL 17, 2022, TO MARCH 23, 2023. SURVIVORS IN THIS COHORT OF EUROPEAN ANCESTRY WITH DNA METHYLATION DATA WERE INCLUDED. CROSS-SECTIONAL ANNUAL CHANGES IN EA AND EAA WERE COMPARED ACROSS 5 DIFFERENT CHRONOLOGIC AGE GROUPS: AGE 0 TO 9 (CHILDREN), 10 TO 19 (ADOLESCENTS), 20 TO 34 (YOUNGER ADULTS), 35 TO 49 (MIDDLE-AGED ADULTS), AND GREATER THAN OR EQUAL TO 50 (OLDER ADULTS) YEARS. LOGISTIC REGRESSION EVALUATED THE ASSOCIATION BETWEEN EAA AND EARLY-ONSET OBESITY OR SEVERITY/BURDEN OF CHCS. COX PROPORTIONAL HAZARDS REGRESSION ASSESSED THE ASSOCIATION BETWEEN EAA AND LATE MORTALITY. MAIN OUTCOMES AND MEASURES: EARLY-ONSET OBESITY, SEVERITY/BURDEN OF CHCS (GRADED USING THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (GRADE 1, MILD; 2, MODERATE; 3, SEVERE/DISABLING; 4, LIFE-THREATENING) AND WERE COMBINED INTO HIGH VS LOW SEVERITY/BURDEN BASED ON FREQUENCY AND GRADE), AND LATE MORTALITY WERE THE OUTCOMES BASED ON FOLLOW-UP UNTIL APRIL 2020. EXPANDED DNA METHYLATION PROFILING INCREASED THE NUMBER OF SURVIVORS YOUNGER THAN 20 YEARS (N = 690). EPIGENETIC AGE WAS CALCULATED PRIMARILY USING THE LEVINE CLOCK, AND EAA WAS DERIVED FROM LEAST SQUARES REGRESSION OF EA AGAINST CHRONOLOGIC AGE AND WAS STANDARDIZED TO A Z SCORE (LEVINE EEA). RESULTS: AMONG 2846 PARTICIPANTS (MEDIAN AGE, 30.3 [IQR, 9.3-41.5] YEARS; 53% MALES), THE CROSS-SECTIONAL ANNUAL CHANGE IN EA_LEVINE WAS HIGHER IN CHILDREN (1.63 YEARS) AND ADOLESCENTS (1.14 YEARS), AND THE ADJUSTED LEAST-SQUARES MEAN OF LEVINE EEA WAS LOWER IN CHILDREN (-0.22 YEARS) AND OLDER ADULTS (-1.70 YEARS). EACH 1-SD INCREASE IN LEVINE EEA WAS ASSOCIATED WITH INCREASED RISK OF DEVELOPING EARLY-ONSET OBESITY (ODDS RATIO [OR], 1.46; 95% CI, 1.19-1.78), HIGH SEVERITY/BURDEN OF CHCS (OR, 1.13; 95% CI, 1.03-1.24), AND LATE MORTALITY (HAZARD RATIO, 1.75; 95% CI, 1.35-2.26). CONCLUSIONS AND RELEVANCE: THE FINDINGS OF THIS STUDY SUGGEST THAT EAA MEASURED IN CHILDREN AND ADOLESCENT SURVIVORS OF CHILDHOOD CANCER IS ASSOCIATED WITH EARLY-ONSET OBESITY, SEVERITY/BURDEN OF ALL CHCS, AND LATE MORTALITY. EVALUATING EAA MAY HELP IDENTIFY SURVIVORS OF CHILDHOOD CANCER AT INCREASED RISK FOR EARLY-ONSET OBESITY, MORBIDITY IN GENERAL, AND MORTALITY.	2023	
                                                                                                                                                                                                                                       
8  1351  28 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
9  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
10  2777  39 EXTREMELY LOW BIRTH WEIGHT AND ACCELERATED BIOLOGICAL AGING. BACKGROUND AND OBJECTIVES: EXTREMELY LOW BIRTH WEIGHT (ELBW) (<1000 G) SURVIVORS ARE EXPOSED TO ELEVATED LEVELS OF PHYSIOLOGIC STRESS DURING THEIR LIVES AND MAY BE SUSCEPTIBLE TO ACCELERATED AGING. USING THE OLDEST KNOWN LONGITUDINALLY FOLLOWED COHORT OF ELBW SURVIVORS, WE COMPARED BIOLOGICAL AGING IN THIS GROUP USING AN EPIGENETIC CLOCK TO A SAMPLE OF MATCHED NORMAL BIRTH WEIGHT (NBW) (>2500 G) CONTROL PARTICIPANTS. METHODS: BUCCAL CELLS WERE COLLECTED FROM 45 ELBW SURVIVORS AND 49 NBW CONTROL PARTICIPANTS AT 30 TO 35 YEARS OF AGE. EPIGENETIC AGE WAS CALCULATED FROM THE WEIGHTED AVERAGE OF DNA METHYLATION AT 353 CYTOSINE-PHOSPHATE-GUANINE SEQUENCE WITHIN DNA SITES, BY USING THE ILLUMINA INFINIUM HUMAN METHYLATION EPIC 850K BEADCHIP ARRAY. RESULTS: BEFORE AND AFTER STATISTICALLY ADJUSTING FOR NEUROSENSORY IMPAIRMENT AND THE PRESENCE OF CHRONIC HEALTH CONDITIONS, A SIGNIFICANT SEX BY BIRTH WEIGHT GROUP INTERACTION WAS OBSERVED IN THE 353-SITE EPIGENETIC-CLOCK ASSAY (P = .03), WHEREBY ELBW MEN HAD A SIGNIFICANTLY OLDER EPIGENETIC AGE THAN NBW MEN (4.6 YEARS; P = .01). WOMEN BORN AT ELBW WERE NOT FOUND TO BE EPIGENETICALLY OLDER THAN THEIR NBW PEERS. CONCLUSIONS: THE RESULTS OF THIS STUDY SUGGEST THAT PRENATAL EXPOSURES MAY PLAY AN IMPORTANT ROLE IN AGING, AND THAT MEN BORN PRETERM MAY EXPERIENCE ACCELERATED AGING RELATIVE TO THEIR PEERS. WE FURTHER HIGHLIGHT THE NEED TO MONITOR AND PROMOTE THE HEALTH OF PRETERM SURVIVORS, WITH A PARTICULAR FOCUS ON HEALTHY AGING ACROSS THE LIFE SPAN.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
11   403  39 ANALYSIS OF EPIGENETIC AGE ACCELERATION AND HEALTHY LONGEVITY AMONG OLDER US WOMEN. IMPORTANCE: ACCELERATED BIOLOGICAL AGING IS ASSOCIATED WITH DECREASED PHYSICAL CAPABILITY AND COGNITIVE FUNCTIONING, WHICH ARE ASSOCIATED WITH INCREASED RISK OF MORBIDITY AND MORTALITY. OBJECTIVE: WE INVESTIGATED ASSOCIATIONS BETWEEN EPIGENETIC AGE ACCELERATION (EAA), A BIOMARKER ASSOCIATED WITH AGING, AND HEALTHY LONGEVITY AMONG OLDER WOMEN. DESIGN, SETTING, AND PARTICIPANTS: THIS COHORT STUDY WAS A SECONDARY ANALYSIS OF PARTICIPANTS IN THE WOMEN'S HEALTH INITIATIVE (WHI) WHO WERE ELIGIBLE TO SURVIVE TO AGE 90 YEARS BY SEPTEMBER 30, 2020. PARTICIPANTS WERE LOCATED IN MULTIPLE CENTERS. THIS STUDY WAS RESTRICTED TO WOMEN WITH GENOME-WIDE DNA METHYLATION DATA, GENERATED FROM BASELINE BLOOD SAMPLES WITHIN 3 WHI ANCILLARY STUDIES. MEDIAN (IQR) FOLLOW-UP TIMES FROM BASELINE WERE 21.6 (19.6-22.9) YEARS AND 21.4 (19.8-22.7) YEARS FOR WOMEN WHO SURVIVED TO AGE 90 YEARS WITH AND WITHOUT INTACT MOBILITY, RESPECTIVELY, AND 13.2 (8.8-16.7) FOR WOMEN WHO DID NOT SURVIVE TO AGE 90 YEARS. DATA WERE ANALYZED FROM DECEMBER 2020 TO JULY 2021. EXPOSURES: EAA WAS ESTIMATED USING 4 ESTABLISHED "CLOCKS": HORVATH PANTISSUE, HANNUM, PHENO, AND GRIM. MAIN OUTCOMES AND MEASURES: USING MULTINOMIAL LOGISTIC REGRESSION, ODDS RATIOS (ORS) AND 95% CIS WERE ESTIMATED FOR 3 HEALTHY LONGEVITY OUTCOMES FOR EACH CLOCK: SURVIVAL TO AGE 90 YEARS WITH INTACT MOBILITY, SURVIVAL TO AGE 90 YEARS WITHOUT INTACT MOBILITY, AND NO SURVIVAL TO AGE 90 YEARS. RESULTS: AMONG 1813 WOMEN, THERE WERE 464 WOMEN (MEAN [SD] AGE AT BASELINE, 71.6 [3.5] YEARS) WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTIONING, 420 WOMEN (MEAN [SD] AGE AT BASELINE, 71.3 [3.2] YEARS) WHO SURVIVED TO AGE 90 YEARS WITHOUT INTACT MOBILITY AND COGNITIVE FUNCTIONING, AND 929 WOMEN (MEAN [SD] AGE AT BASELINE, 70.2 [3.4] YEARS) WHO DID NOT SURVIVE TO AGE 90 YEARS. WOMEN WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTION WERE HEALTHIER AT BASELINE COMPARED WITH WOMEN WHO SURVIVED WITHOUT THOSE OUTCOMES OR WHO DID NOT SURVIVE TO AGE 90 YEARS (EG, 143 WOMEN [30.8%] VS 101 WOMEN [24.0%] AND 202 WOMEN [21.7%] WITH 0 CHRONIC CONDITIONS). THE ODDS OF SURVIVING TO AGE 90 YEARS WITH INTACT MOBILITY WERE LOWER FOR EVERY 1 SD INCREASE IN EAA COMPARED WITH THOSE WHO DID NOT SURVIVE TO AGE 90 YEARS AS MEASURED BY AGEACCELHORVATH (OR, 0.82; 95% CI, 0.69-0.96; P = .01), AGEACCELHANNUM (OR, 0.67; 95% CI, 0.56-0.80; P < .001), AGEACCELPHENO (OR, 0.60; 95% CI, 0.51-0.72; P < .001), AND AGEACCELGRIM (OR, 0.68; 95% CI, 0.55-0.84; P < .001). ORS WERE SIMILAR FOR WOMEN WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTION (EG, AGEACCELHORVATH: OR PER 1 SD INCREASE IN EAA, 0.83; 95% CI, 0.71-0.98; P = .03) COMPARED WITH WOMEN WHO DID NOT SURVIVE TO AGE 90 YEARS. CONCLUSIONS AND RELEVANCE: THESE FINDINGS SUGGEST THAT EAA MAY BE A VALID BIOMARKER ASSOCIATED WITH HEALTHY LONGEVITY AMONG OLDER WOMEN AND MAY BE USED FOR RISK STRATIFICATION AND RISK ESTIMATION OF FUTURE FUNCTIONAL AND COGNITIVE AGING. OUTCOMES SUGGEST THAT FUTURE STUDIES MAY FOCUS ON THE POTENTIAL FOR PUBLIC HEALTH INTERVENTIONS TO COUNTERACT EAA AND ITS ASSOCIATION WITH POOR HEALTH OUTCOMES TO LOWER DISEASE BURDEN WHILE INCREASING LONGEVITY.	2022	

12    91  37 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
13  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
14   648  32 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
15  3664  23 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
16  1521  33 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
17  3166  41 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
18   646  31 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
19  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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
20   525  27 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