1 3145 150 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 2 3384 24 HOFBAUER CELLS: THEIR ROLE IN HEALTHY AND COMPLICATED PREGNANCY. HOFBAUER CELLS ARE PLACENTAL VILLOUS MACROPHAGES OF FETAL ORIGIN THAT ARE PRESENT THROUGHOUT PREGNANCY. ALTHOUGH HOFBAUER CELL POPULATIONS ARE ANTIGENICALLY AND MORPHOLOGICALLY HETEROGENEOUS, THEIR EPIGENETIC, ANTIGENIC, AND FUNCTIONAL PROFILES MOST CLOSELY RESEMBLE ALTERNATIVELY ACTIVATED MACROPHAGES OR WHAT ARE REFERRED TO AS M2A, M2B, M2C, AND M2D POLARITY SUBTYPES. CONSISTENT WITH AN M2-LIKE PROFILE, THESE CELLS PLAY AN IMPORTANT ROLE IN PLACENTAL DEVELOPMENT INCLUDING VASCULOGENESIS AND ANGIOGENESIS. DURING PLACENTAL INFLAMMATION HOFBAUER CELLS MAY PRODUCE PRO-INFLAMMATORY CYTOKINES OR MEDIATORS THAT DAMAGE THE VILLOUS CELL BARRIER, AND INDUCE FIBROTIC RESPONSES WITHIN THE VILLI AS A CONTINUUM OF CHRONIC INFLAMMATION. HOWEVER, TO DATE, THERE IS NO EVIDENCE THAT HOFBAUER CELLS BECOME CLASSICALLY ACTIVATED OR ADOPT AN M1 POLARITY PHENOTYPE THAT IS ABLE TO KILL MICROBES. TO THE CONTRARY, THEIR PREDOMINANT M2 LIKE QUALITIES MAY BE WHY THESE CELLS ARE INEFFECTIVE IN CONTROLLING MOST TORCH INFECTIONS. MOREOVER, HOFBAUER CELLS MAY CONTRIBUTE TO VERTICAL TRANSMISSION OF VARIOUS PATHOGENS TO THE FETUS SINCE THEY CAN HARBOR LIVE VIRUS AND SERVE AS RESERVOIRS WITHIN THE PLACENTA. THE GOAL OF THIS REVIEW IS TO SUMMARIZE WHAT IS CURRENTLY KNOWN ABOUT THE ROLE OF HOFBAUER CELLS IN NORMAL AND COMPLICATED PREGNANCIES THAT INVOLVE IMMUNOLOGIC DISORDERS, INFLAMMATION, AND/OR INFECTION. 2018 3 648 31 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 4 3166 38 GROCERY DELIVERY TO SUPPORT HEALTHY WEIGHT GAIN AMONG PREGNANT YOUNG WOMEN WITH LOW INCOME: PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL. BACKGROUND: EXCESSIVE WEIGHT GAIN DURING PREGNANCY IS ASSOCIATED WITH COMPLICATIONS FOR BOTH THE MOTHER AND HER INFANT INCLUDING GESTATIONAL DIABETES, HYPERTENSIVE DISORDERS, OPERATIVE DELIVERY, AND LONG-TERM OBESITY. A HEALTHY DIET DURING PREGNANCY PROMOTES HEALTHY GESTATIONAL WEIGHT GAIN AND DETERMINES FETAL EPIGENETIC PROGRAMMING IN INFANTS THAT IMPACTS RISK FOR FUTURE CHRONIC DISEASE. OBJECTIVE: THIS PROJECT WILL EXAMINE THE IMPACT OF GROCERY DELIVERY DURING PREGNANCY ON THE WEIGHT, DIET, AND HEALTH OUTCOMES OF YOUNG PREGNANT WOMEN AND THEIR INFANTS. METHODS: A THREE-ARM RANDOMIZED CONTROLLED TRIAL DESIGN WILL BE PERFORMED. A TOTAL OF 855 YOUNG PREGNANT WOMEN, AGED 14-24 YEARS, FROM ACROSS THE STATE OF MICHIGAN WILL BE ENROLLED AND RANDOMIZED EQUALLY INTO THE THREE STUDY ARMS. PARTICIPANTS IN ARM ONE (CONTROL) WILL RECEIVE USUAL CARE FROM THE SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS, AND CHILDREN (WIC); ARM TWO WILL RECEIVE WIC PLUS BIWEEKLY GROCERY DELIVERY; AND ARM THREE WILL RECEIVE WIC PLUS BIWEEKLY GROCERY AND UNSWEETENED BEVERAGE DELIVERY. WEIGHT WILL BE ASSESSED WEEKLY DURING PREGNANCY, AND TOTAL PREGNANCY WEIGHT GAIN WILL BE CATEGORIZED AS ABOVE, BELOW, OR WITHIN GUIDELINES. ADDITIONALLY, DIETARY INTAKE WILL BE ASSESSED AT THREE TIME POINTS (BASELINE, SECOND TRIMESTER, AND THIRD TRIMESTER), AND PREGNANCY OUTCOMES WILL BE EXTRACTED FROM MEDICAL RECORDS. THE APPROPRIATENESS OF PREGNANCY WEIGHT GAIN, DIET QUALITY, AND OCCURRENCE OF POOR OUTCOMES WILL BE COMPARED BETWEEN GROUPS USING STANDARD PRACTICES FOR MULTINOMIAL REGRESSION AND CONFOUNDER ADJUSTMENT. RESULTS: THIS STUDY WAS FUNDED IN APRIL 2021, DATA COLLECTION STARTED IN DECEMBER 2021, AND DATA COLLECTION IS EXPECTED TO BE CONCLUDED IN 2026. CONCLUSIONS: THIS STUDY WILL TEST WHETHER GROCERY DELIVERY OF HEALTHY FOODS IMPROVES WEIGHT, DIET, AND PREGNANCY OUTCOMES OF YOUNG MOMS WITH LOW INCOME. THE FINDINGS WILL INFORM POLICIES AND PRACTICES THAT PROMOTE A HEALTHY DIET DURING PREGNANCY, WHICH HAS MULTIGENERATIONAL IMPACTS ON HEALTH. TRIAL REGISTRATION: CLINICALTRIALS.GOV NCT05000645; HTTPS://CLINICALTRIALS.GOV/CT2/SHOW/NCT05000645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40568. 2022 5 6625 31 UNDERSTANDING RACIAL DISPARITIES OF PRETERM BIRTH THROUGH THE PLACENTA. THE RACIAL DISPARITY ASSOCIATED WITH PRETERM BIRTH IS A PUBLIC HEALTH CONCERN IN THE UNITED STATES. THE PLACENTA IS THE PRINCIPAL METABOLIC, RESPIRATORY, AND ENDOCRINE ORGAN OF THE FETUS AND A KEY ROUTE BY WHICH ENVIRONMENTAL EXPOSURES ARE TRANSMITTED FROM MOTHER TO OFFSPRING. AVAILABLE AT EVERY DELIVERY, IT MAY SERVE AS A MARKER OF DIFFERENCES IN PRENATAL EXPOSURES THAT MANIFEST DIFFERENTLY BY RACE. RECENTLY, WE DESCRIBED DIFFERENCES IN PLACENTAL PATHOLOGY BETWEEN AFRICAN-AMERICAN AND WHITE PRETERM BIRTHS: THE PREVALENCE OF CHRONIC INFLAMMATION WAS HIGHER AMONG AFRICAN-AMERICAN WOMEN'S PLACENTAS COMPARED WITH THOSE OF WHITE WOMEN. SIMILARLY, RACIAL DIFFERENCES HAVE BEEN SHOWN IN PLACENTAL MALPERFUSION AND PLACENTAL WEIGHT. SOCIAL DETERMINANTS SUCH AS POVERTY AND STRESS FROM DISCRIMINATION HAVE BEEN IMPLICATED IN RACIAL DISPARITIES IN PRETERM BIRTH. TO DATE, HOWEVER, THE UNDERLYING BIOLOGICAL MECHANISMS, WHETHER THROUGH INFLAMMATORY, OXIDATIVE STRESS, OR OTHER PATHWAYS INVOLVING EPIGENETIC PROGRAMMING, REMAIN LARGELY UNKNOWN. THE PLACENTA, COMPLEMENTED BY MATERNAL AND UMBILICAL CORD BLOOD BIOMARKERS, MAY PROVIDE IMPORTANT INFORMATION ON THE PERINATAL ENVIRONMENT THAT EXPLAINS THE ORIGINS OF RACIAL DISPARITIES IN PRETERM BIRTH RATES AND SUBSEQUENT HEALTH OUTCOMES. THIS ARTICLE REVIEWS EXISTING LITERATURE AND CURRENT RESEARCH GAPS. OPPORTUNITIES ARE DISCUSSED FOR FUTURE PLACENTAL RESEARCH THAT MAY REVEAL NOVEL MECHANISMS LEADING TO THE DEVELOPMENT OF NEW APPROACHES IN THE PREVENTION AND MANAGEMENT OF PRETERM BIRTH AND ITS OUTCOMES. 2021 6 167 27 ABNORMAL PLACENTATION ASSOCIATED WITH INFERTILITY AS A MARKER OF OVERALL HEALTH. INFERTILITY AND THE FERTILITY TREATMENTS UTILIZED ARE ASSOCIATED WITH ABNORMAL PLACENTATION LEADING TO ADVERSE PREGNANCY OUTCOMES RELATED TO PLACENTATION, INCLUDING PRETERM BIRTH, LOW BIRTH WEIGHT, PLACENTA ACCRETE AND PLACENTA PREVIA. THIS MAY BE DUE TO THE UNDERLYING GENETICS PREDISPOSING TO INFERTILITY OR THE EPIGENETIC CHANGES ASSOCIATED WITH THE FERTILITY TREATMENTS UTILIZED, AS SPECIFIC DISEASE STATES LEADING TO INFERTILITY ARE AT INCREASED RISK OF ADVERSE OUTCOMES, INCLUDING PLACENTAL ABRUPTION, FETAL LOSS, GDM, AND OUTCOMES RELATED TO PLACENTATION, AS WELL AS THE TREATMENTS UTILIZED INCLUDING IN VITRO FERTILIZATION (IVF) AND NIFT (NON-IVF FERTILITY TREATMENT). PLACENTATION DEFECTS, LEADING TO ADVERSE MATERNAL AND FETAL OUTCOMES, WHICH ARE MORE PRONOUNCED IN THE INFERTILE POPULATION, OCCUR DUE TO CHANGES IN TROPHOBLAST INVASION, VASCULAR DEFECTS, CHANGES IN THE ENVIRONMENTAL MILIEU, CHRONIC INFLAMMATION AND OXIDATIVE STRESS. THESE SIMILAR PROCESSES ARE RECOGNIZED AS MAJOR CONTRIBUTORS TO LIFELONG RISK OF CARDIOVASCULAR AND METABOLIC DISEASE FOR BOTH THE MOTHER AND HER OFFSPRING. THUS, ABNORMAL PLACENTATION, FOUND TO BE MORE PREVALENT IN THE INFERTILE POPULATION, MAY BE THE KEY TO BETTER UNDERSTAND HOW INFERTILITY AFFECTS OVERALL AND LONG TERM HEALTH. 2017 7 5091 30 PLACENTAL DISEASES ASSOCIATED WITH ASSISTED REPRODUCTIVE TECHNOLOGY. THE PLACENTA DEVELOPS FROM THE OUTER TROPHOBLASTIC LAYER FOLLOWING THE DIFFERENTIATION OF THE FERTILIZED OVUM AND IS THEREFORE MORE SUSCEPTIBLE TO EPIGENETIC REGULATORY CHANGES CAUSED BY ENVIRONMENTAL INTERVENTIONS AND INFLUENCES DURING ASSISTED REPRODUCTIVE TECHNOLOGY. FURTHERMORE, THE PLACENTA REGULATES THE DEVELOPMENT OF THE FETAL HEART, BRAIN, KIDNEYS, BONES, AND OTHER TISSUES AND ORGANS [1]. PLACENTAL DYSPLASIA LEADS TO POOR PERINATAL OUTCOMES AS WELL AS LONG-TERM HEALTH RISKS LATER IN LIFE, INCLUDING NEURODEVELOPMENTAL DISORDERS, TUMORS, AND ADULT METABOLIC SYNDROME [2,3]. IN VIEW OF THE DECISIVE ROLE OF THE PLACENTA DURING INTRAUTERINE FETAL DEVELOPMENT, GRAHAM J. BURTON, AN EXPERT IN PLACENTOLOGY FROM THE UNIVERSITY OF CAMBRIDGE, FORMALLY PROPOSED THE THEORY OF "PLACENTA-DERIVED CHRONIC DISEASES" IN 2018 BASED ON EMBRYONIC-DERIVED DISEASES [4]. IN THIS REVIEW, WE SUMMARIZED THE CHANGES IN PLACENTAL MORPHOLOGY AND STRUCTURE, GROWTH DYNAMICS, IMPRINTED AND NON-IMPRINTED GENES, AND OTHER ASPECTS ATTRIBUTABLE TO ASSISTED REPRODUCTION TECHNOLOGY. OUR REVIEW PROVIDES A THEORETICAL BASIS FOR FURTHER RESEARCH ON PLACENTAL CHANGES CAUSED BY ASSISTED REPRODUCTIVE TECHNOLOGY THAT ARE MOST STRONGLY ASSOCIATED WITH AN INCREASED RISK OF NEONATAL LONG-TERM DISEASES. 2021 8 5178 25 PREGNANCY AS A FUNDAMENTAL DETERMINANT OF CHILD HEALTH: A REVIEW. PURPOSE OF REVIEW: MATERNAL CONDITIONS AND EXPOSURES DURING PREGNANCY INCLUDING OVER- AND UNDERNUTRITION ARE ASSOCIATED WITH POOR CHILDBIRTH OUTCOMES, GROWTH, DEVELOPMENT AND CHRONIC CHILDHOOD DISEASES. WE EXAMINED CONTEMPORARY PREGNANCY-RELATED DETERMINANTS OF CHILD HEALTH. RECENT FINDINGS: WHILE MATERNAL UNDERNUTRITION REMAINS A MAJOR CONTRIBUTOR TO LOW BIRTH WEIGHT, MATERNAL OBESITY AFFECTS FOETAL GROWTH, BIRTH WEIGHT, SURVIVAL AND IS ASSOCIATED WITH CHILDHOOD OBESITY, ASTHMA AND AUTISTIC SPECTRUM DISORDERS. EMERGING EVIDENCE SUGGESTS THAT EPIGENETIC CHANGES, THE PRENATAL MICROBIOME AND MATERNAL IMMUNE ACTIVATION (MIA), A NEUROINFLAMMATORY PROCESS INDUCED BY DIET AND OTHER EXPOSURES CAUSE FOETAL PROGRAMMING RESULTING IN THESE CHRONIC CHILDHOOD DISEASES. MATERNAL DIET IS POTENTIALLY A MODIFIABLE RISK FACTOR FOR CONTROLLING LOW BIRTH WEIGHT, OBESITY AND CHRONIC DISEASE IN CHILDHOOD. FURTHER STUDIES ARE WARRANTED TO REFINE GUIDANCE ON DIETARY RESTRICTION AND PHYSICAL ACTIVITY DURING PREGNANCY AND DETERMINE HOW MIA AND PRENATAL MICROBIOTA CAN BE APPLIED TO CONTROL CHILDHOOD DISEASES ARISING FROM PROGRAMMING. 2022 9 6724 34 VITAMIN D: EFFECTS ON PREGNANCY, MATERNAL, FETAL AND POSTNATAL OUTCOMES. A HIGH PREVALENCE OF VITAMIN D DEFICIENCY AND ITS NEGATIVE CONSEQUENCES FOR HEALTH IS IDENTIFIED AS AREA OF PRIMARY CONCERN FOR SCIENTISTS AND CLINICIANS WORLDWIDE. VITAMIN D DEFICIENCY AFFECTS NOT ONLY BONE HEALTH BUT MANY SOCIALLY SIGNIFICANT ACUTE AND CHRONIC DISEASES. OBSERVATIONAL STUDIES SUPPORT THAT PREGNANT AND LACTATING WOMEN, CHILDREN AND TEENAGERS REPRESENT THE HIGH RISK GROUPS FOR DEVELOPING VITAMIN D DEFICIENCY. CURRENT EVIDENCE HIGHLIGHTS A CRUCIAL ROLE OF VITAMIN D IN PROVIDING THE FETAL LIFE-SUPPORT SYSTEM AND FETUS DEVELOPMENT, INCLUDING IMPLANTATION, PLACENTAL FORMATION, INTRA- AND POSTPARTUM PERIODS. HYPOVITAMINOSIS D DURING PREGNANCY IS ASSOCIATED WITH A HIGHER INCIDENCE OF PLACENTAL INSUFFICIENCY, SPONTANEOUS ABORTIONS AND PRETERM BIRTH, PREECLAMPSIA, GESTATIONAL DIABETES, IMPAIRED FETAL AND CHILDHOOD GROWTH, INCREASED RISK OF AUTOIMMUNE DISEASES FOR OFFSPRINGS. POTENTIAL MECHANISMS FOR THE OBSERVED ASSOCIATIONS CONTAIN METABOLIC, IMMUNOMODULATORY AND ANTIINFLAMMATORY EFFECTS OF VITAMIN D. EPIGENETIC MODIFICATIONS IN VITAMIN D-ASSOCIATED GENES AND FETAL PROGRAMMING ARE OF PARTICULAR INTEREST. THE CONCEPT OF PREVENTING VITAMIN D DEFICIENCY IS ACTIVELY DISCUSSED, INCLUDING SUPPLEMENTATION IN DIFFERENT ETHNIC GROUPS, REQUIRED DOSES, TIME OF INITIATION AND THERAPY DURATION, INFLUENCE ON GESTATION AND CHILDBIRTH. AN ADEQUATE SUPPLY OF VITAMIN D DURING PREGNANCY IMPROVES THE MATERNAL AND FETAL OUTCOMES, SHORT AND LONG TERM HEALTH OF THE OFFSPRING. STILL CURRENT DATA ON RELATIONSHIP BETWEEN MATERNAL VITAMIN D STATUS AND PREGNANCY OUTCOMES REMAINS CONTROVERSIAL. THE LARGE OBSERVATIONAL AND INTERVENTIONAL RANDOMIZED CONTROL TRIALS ARE REQUIRED TO CREATE EVIDENCE-BASED GUIDELINES FOR THE SUPPLEMENTATION OF VITAMIN D IN PREGNANT AND LACTATING WOMEN. 2018 10 1098 23 COLLATERAL DAMAGE: MATERNAL OBESITY DURING PREGNANCY CONTINUES TO RISE. IMPORTANCE: THE PANDEMIC OF OBESITY DURING PREGNANCY NOW AFFLICTS 1 OUT OF EVERY 2 PREGNANT WOMEN IN THE UNITED STATES. EVEN THOUGH UNINTENDED PREGNANCY HAS DECREASED TO 45% OF ALL PREGNANCIES, 50% OF THOSE UNINTENDED PREGNANCIES OCCUR IN OBESE WOMEN. OBJECTIVE: THIS STUDY AIMS TO IDENTIFY WHY CURRENT LIFESTYLE INTERVENTIONS FOR OBESE PREGNANCY ARE NOT EFFECTIVE AND WHAT THE NEWER COMPLICATIONS ARE FOR OBESITY DURING PREGNANCY. EVIDENCE ACQUISITION: AVAILABLE LITERATURES ON CURRENT TREATMENTS FOR MATERNAL OBESITY WERE REVIEWED FOR EFFECTIVENESS. EMERGING MATERNAL AND INFANT COMPLICATIONS FROM OBESITY DURING PREGNANCY WERE EXAMINED FOR SIGNIFICANCE. RESULTS: LIMITATIONS IN SUCCESSFUL INTERVENTIONS FELL INTO 3 BASIC CATEGORIES TO INCLUDE THE FOLLOWING: (1) PRECONCEPTION WEIGHT LOSS; (2) BARIATRIC SURGERY BEFORE PREGNANCY; AND (3) PREVENTION OF EXCESSIVE GESTATIONAL WEIGHT GAIN DURING PREGNANCY. EMERGING SIGNIFICANT PHYSIOLOGICAL CHANGES FROM MATERNAL OBESITY IS COMPOSED OF INFLAMMATION (PLACENTA AND HUMAN MILK), METABOLISM (HORMONES, MICROBIOME, FATTY ACIDS), AND OFFSPRING OUTCOMES (BODY COMPOSITION, CONGENITAL MALFORMATIONS, CHRONIC KIDNEY DISEASE, ASTHMA, NEURODEVELOPMENT, AND BEHAVIOR). CONCLUSIONS AND RELEVANCE: ARE CURRENT PREPREGNANCY LIFESTYLE AND BEHAVIORAL INTERVENTIONS FEASIBLE TO PREVENT MATERNAL OBESITY COMPLICATIONS? EPIGENETIC AND METABOLOMIC RESEARCH WILL BE CRITICAL TO DETERMINE WHAT IS NEEDED TO BLUNT THE EFFECTS OF MATERNAL OBESITY AND TO DISCOVER SUCCESSFUL TREATMENT. 2020 11 646 29 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 12 2801 27 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL. 2013 13 3428 24 HUMANS AT HIGH ALTITUDE: HYPOXIA AND FETAL GROWTH. HIGH-ALTITUDE STUDIES OFFER INSIGHT INTO THE EVOLUTIONARY PROCESSES AND PHYSIOLOGICAL MECHANISMS AFFECTING THE EARLY PHASES OF THE HUMAN LIFESPAN. CHRONIC HYPOXIA SLOWS FETAL GROWTH AND REDUCES THE PREGNANCY-ASSOCIATED RISE IN UTERINE ARTERY (UA) BLOOD FLOW. MULTIGENERATIONAL VS. SHORTER-TERM HIGH-ALTITUDE RESIDENTS ARE PROTECTED FROM THE ALTITUDE-ASSOCIATED REDUCTIONS IN UA FLOW AND FETAL GROWTH. PRESENTLY UNKNOWN IS WHETHER THIS FETAL-GROWTH PROTECTION IS DUE TO THE GREATER DELIVERY OR METABOLISM OF OXYGEN, GLUCOSE OR OTHER SUBSTRATES OR TO OTHER CONSIDERATIONS SUCH AS MECHANICAL FACTORS PROTECTING FRAGILE FETAL VILLI, THE CREATION OF A RESERVE PROTECTING AGAINST ISCHEMIA/REPERFUSION INJURY, OR IMPROVED PLACENTAL O(2) TRANSFER AS THE RESULT OF NARROWING THE A-V O(2) DIFFERENCE AND RAISING UTERINE P(V)O(2). PLACENTAL GROWTH AND DEVELOPMENT APPEAR TO BE NORMAL OR MODIFIED AT HIGH ALTITUDE IN WAYS LIKELY TO BENEFIT DIFFUSION. MUCH REMAINS TO BE LEARNED CONCERNING THE EFFECTS OF CHRONIC HYPOXIA ON EMBRYONIC DEVELOPMENT. FURTHER RESEARCH IS REQUIRED FOR IDENTIFYING THE FETOPLACENTAL AND MATERNAL MECHANISMS RESPONSIBLE FOR TRANSFORMING THE MATERNAL VASCULATURE AND REGULATING UA BLOOD FLOW AND FETAL GROWTH. GENOMIC AS WELL AS EPIGENETIC STUDIES ARE OPENING NEW AVENUES OF INVESTIGATION THAT CAN YIELD INSIGHTS INTO THE BASIC PATHWAYS AND EVOLUTIONARY PROCESSES INVOLVED. 2011 14 6914 26 [VITAMIN D DEFICIENCY IN PREGNANCY AND ITS IMPACT ON THE FETUS, THE NEWBORN AND IN CHILDHOOD]. OBJECTIVE: VITAMIN D DEFICIENCY (VDD) IN PREGNANT WOMEN AND THEIR CHILDREN IS AN IMPORTANT HEALTH PROBLEM WITH SEVERE CONSEQUENCES FOR THE HEALTH OF BOTH. THUS, THE OBJECTIVES OF THIS REVIEW WERE TO REASSESS THE MAGNITUDE AND CONSEQUENCES OF VDD DURING PREGNANCY, LACTATION AND INFANCY, ASSOCIATED RISK FACTORS, PREVENTION METHODS, AND TO EXPLORE EPIGENETIC MECHANISMS IN EARLY FETAL LIFE CAPABLE OF EXPLAINING MANY OF THE NON-SKELETAL BENEFITS OF VITAMIN D (VID). DATA SOURCE: ORIGINAL AND REVIEW ARTICLES, AND CONSENSUS DOCUMENTS WITH ELEVATED LEVEL OF EVIDENCE FOR VDD-RELATED CLINICAL DECISIONS ON THE HEALTH OF PREGNANT WOMEN AND THEIR CHILDREN, AS WELL AS ARTICLES ON THE INFLUENCE OF VID ON EPIGENETIC MECHANISMS OF FETAL PROGRAMMING OF CHRONIC DISEASES IN ADULTHOOD WERE SELECTED AMONG ARTICLES PUBLISHED ON PUBMED OVER THE LAST 20 YEARS, USING THE SEARCH TERM VITD STATUS, IN COMBINATION WITH PREGNANCY, OFFSPRING HEALTH, CHILD OUTCOMES, AND PROGRAMMING. DATA SYNTHESIS: THE FOLLOWING ITEMS WERE ANALYZED: VID PHYSIOLOGY AND METABOLISM, RISK FACTORS FOR VDD AND IMPLICATIONS IN PREGNANCY, LACTATION AND INFANCY, CONCENTRATION CUTOFF TO DEFINE VDD, THE VARIABILITY OF METHODS FOR VDD DETECTION, RECOMMENDATIONS ON VID REPLACEMENT IN PREGNANT WOMEN, THE NEWBORN AND THE CHILD, AND THE EPIGENETIC INFLUENCE OF VID. CONCLUSIONS: VDD IS A COMMON CONDITION AMONG HIGH-RISK PREGNANT WOMEN AND THEIR CHILDREN. THE ROUTINE MONITORING OF SERUM 25(OH)D3 LEVELS IN ANTENATAL PERIOD IS MANDATORY. EARLY PREVENTIVE MEASURES SHOULD BE TAKEN AT THE SLIGHTEST SUSPICION OF VDD IN PREGNANT WOMEN, TO REDUCE MORBIDITY DURING PREGNANCY AND LACTATION, AS WELL AS ITS SUBSEQUENT IMPACT ON THE FETUS, THE NEWBORN AND THE CHILD. 2015 15 1095 36 COHORT PROFILE: THE EWHA BIRTH AND GROWTH STUDY. WITH THE INTRODUCTION OF LIFE-COURSE EPIDEMIOLOGY, RESEARCHERS REALIZED THE IMPORTANCE OF IDENTIFYING RISK FACTORS IN EARLY LIFE TO PREVENT CHRONIC DISEASES. THIS LED TO THE ESTABLISHMENT OF THE EWHA BIRTH AND GROWTH STUDY IN 2001; THE STUDY IS A PROSPECTIVE BIRTH COHORT DESIGNED TO PROVIDE EVIDENCE OF EARLY LIFE RISK FACTORS FOR A CHILD'S GROWTH AND HEALTH. PARTICIPANTS WERE RECRUITED FROM THOSE WHO VISITED EWHA WOMANS UNIVERSITY MOKDONG HOSPITAL (A TERTIARY HOSPITAL IN SOUTHWEST SEOUL, KOREA) FOR PRENATAL CARE AT 24-28 WEEKS OF GESTATION. IN TOTAL, 891 MOTHERS ENROLLED IN THIS STUDY BETWEEN 2001 AND 2006 AND THEIR OFFSPRING (N=940) WERE FOLLOWED-UP. REGULAR CHECK-UP EXAMINATIONS OF OFFSPRING WERE CONDUCTED AT 3 YEARS, 5 YEARS, AND 7 YEARS OF AGE AND EVERY YEAR THEREAFTER. TO CONSIDER AGE-RELATED HEALTH ISSUES, EXTENSIVE DATA WERE COLLECTED USING QUESTIONNAIRES AND MEASUREMENTS. IN 2021, THE STUDY SUBJECTS WILL REACH 19 YEARS OF AGE, AND WE ARE PLANNING A CHECK-UP EXAMINATION FOR EARLY ADULTHOOD. ABOUT 20 YEARS HAVE PASSED SINCE THE COHORT DATA WERE COLLECTED, AND WE HAVE PUBLISHED RESULTS ON CHILDHOOD HEALTH OUTCOMES ASSOCIATED WITH PRENATAL AND BIRTH CHARACTERISTICS, GENETIC AND EPIGENETIC CHARACTERISTICS RELATED TO CHILDHOOD METABOLISM, THE EFFECTS OF EXPOSURE TO ENDOCRINE DISRUPTORS, AND DIETARY PATTERNS IN CHILDHOOD. RECENTLY, WE STARTED REPORTING ON TOPICS RELATED TO ADOLESCENT HEALTH. THE FINDINGS WILL FACILITATE IDENTIFICATION OF EARLY LIFE RISK FACTORS FOR CHRONIC DISEASES AND THE DEVELOPMENT OF INTERVENTIONS FOR DISEASES LATER IN LIFE. 2021 16 2511 22 EPIGENETICS AND PREECLAMPSIA: PROGRAMMING OF FUTURE OUTCOMES. PREGNANCY IS KNOWN TO INDUCE RAPID, PROGRESSIVE, AND SUBSTANTIAL CHANGES TO THE CARDIOVASCULAR SYSTEM, ULTIMATELY FACILITATING SUCCESSFUL PREGNANCY OUTCOMES. WOMEN WHO DEVELOP HYPERTENSIVE DISORDERS DURING PREGNANCY ARE CONSIDERED TO HAVE "FAILED" THE CARDIOVASCULAR STRESS TEST OF PREGNANCY AND LIKELY REPRESENT A SUBPOPULATION WITH INADEQUATE CARDIOVASCULAR ACCOMMODATION. PREECLAMPSIA IS A SERIOUS COMPLICATION WITH A MYRIAD OF MANIFESTATIONS IN BOTH MOTHER AND OFFSPRING. THIS PREGNANCY SYNDROME IS A POLYGENIC DISEASE AND HAS NOW BEEN LINKED TO A GREATER INCIDENCE OF CARDIOVASCULAR DISEASE. MOREOVER, OFFSPRINGS BORN TO PREECLAMPTIC MOTHERS EXHIBIT AN ELEVATED RISK OF CARDIOVASCULAR DISEASE, STROKE, AND MENTAL DISORDERS DURING ADULTHOOD. THIS SUGGESTS THAT PREECLAMPSIA NOT ONLY EXPOSES THE MOTHER AND THE FETUS TO COMPLICATIONS DURING PREGNANCY BUT ALSO PROGRAMS CHRONIC DISEASES DURING ADULTHOOD IN THE OFFSPRING. THE ETIOLOGY OF PREECLAMPSIA REMAINS UNKNOWN, WITH VARIOUS THEORIES BEING SUGGESTED TO EXPLAIN ITS ORIGIN. IT IS PRIMARILY THOUGHT TO BE ASSOCIATED WITH POOR PLACENTATION AND ENTAILS EXCESSIVE MATERNAL INFLAMMATION AND ENDOTHELIAL DYSFUNCTION. IT IS WELL ESTABLISHED NOW THAT THE MATERNAL IMMUNE SYSTEM AND THE PLACENTA ARE INVOLVED IN A HIGHLY CHOREOGRAPHED CROSS TALK THAT UNDERLIES ADEQUATE SPIRAL ARTERY REMODELING REQUIRED FOR UTEROPLACENTAL PERFUSION AND FREE FLOW OF NUTRIENTS TO THE FETUS. ALTHOUGH IT IS NOT CLEAR WHETHER IMMUNOLOGICAL ALTERATIONS OCCUR EARLY DURING PREGNANCY, STUDIES HAVE PROPOSED THAT DYSREGULATED SYSTEMIC AND PLACENTAL IMMUNITY CONTRIBUTE TO IMPAIRED ANGIOGENESIS AND THE ONSET OF PREECLAMPSIA. RECENTLY EMERGED STRONG EVIDENCE SUGGESTS A POTENTIAL LINK AMONG EPIGENETICS, MICRORNAS (MIRNAS), AND PREGNANCY COMPLICATIONS. THIS CHAPTER WILL FOCUS ON IMPORTANT ASPECTS OF EPIGENETICS, IMMUNOLOGICAL ASPECTS, AND CARDIOVASCULAR AND VASCULAR REMODELING OF PREECLAMPSIA. 2018 17 5179 34 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES. 2017 18 4995 30 PERINATAL ENVIRONMENT AND ITS INFLUENCES ON METABOLIC PROGRAMMING OF OFFSPRING. THE INTRAUTERINE ENVIRONMENT SUPPORTS THE DEVELOPMENT AND HEALTH OF OFFSPRING. PERTURBATIONS TO THIS ENVIRONMENT CAN HAVE DETRIMENTAL EFFECTS ON THE FETUS THAT HAVE PERSISTENT PATHOLOGICAL CONSEQUENCES THROUGH ADOLESCENCE AND ADULTHOOD. THE DEVELOPMENTAL ORIGINS OF THE HEALTH AND DISEASE CONCEPT, ALSO KNOWN AS THE "BARKER HYPOTHESIS", HAS BEEN PUT FORTH TO DESCRIBE THE INCREASED INCIDENCE OF CHRONIC DISEASE SUCH AS CARDIOVASCULAR DISEASE AND DIABETES IN HUMANS AND ANIMALS EXPOSED TO A LESS THAN IDEAL INTRAUTERINE ENVIRONMENT. MATERNAL INFECTION, POOR OR EXCESS NUTRITION, AND STRESSFUL EVENTS CAN NEGATIVELY INFLUENCE THE DEVELOPMENT OF DIFFERENT CELL TYPES, TISSUES AND ORGAN SYSTEMS ULTIMATELY PREDISPOSING THE ORGANISM TO PATHOLOGICAL CONDITIONS. ALTHOUGH THERE ARE A VARIETY OF CONDITIONS ASSOCIATED TO EXPOSURE TO ALTERED INTRAUTERINE ENVIRONMENTS, THE FOCUS OF THIS REVIEW WILL BE ON THE CONSEQUENCES OF STRESS AND HIGH FAT DIET DURING THE PRE- AND PERINATAL PERIODS AND ASSOCIATED OUTCOMES RELATED TO OBESITY AND OTHER METABOLIC CONDITIONS. WE FURTHER DISCUSS POSSIBLE NEUROENDOCRINE AND EPIGENETIC MECHANISMS RESPONSIBLE FOR THE METABOLIC PROGRAMMING OF OFFSPRING. THE PAPER REPRESENTS AN INVITED REVIEW BY A SYMPOSIUM, AWARD WINNER OR KEYNOTE SPEAKER AT THE SOCIETY FOR THE STUDY OF INGESTIVE BEHAVIOR [SSIB] ANNUAL MEETING IN PORTLAND, JULY 2009. 2010 19 5169 26 PRECONCEPTIONAL STRESS AND RACIAL DISPARITIES IN PRETERM BIRTH: AN OVERVIEW. OBJECTIVE: WE REVIEWED THE EVIDENCE FOR THREE THEORIES OF HOW PRECONCEPTIONAL PSYCHOSOCIAL STRESS COULD ACT AS A CONTRIBUTING DETERMINANT OF EXCESS PRETERM BIRTH RISK AMONG AFRICAN AMERICAN WOMEN: EARLY LIFE DEVELOPMENTAL PLASTICITY AND EPIGENETIC PROGRAMMING OF ADULT NEUROENDOCRINE SYSTEMS; BLUNTING, WEATHERING, OR DYSFUNCTION OF NEUROENDOCRINE AND IMMUNE FUNCTION IN RESPONSE TO CHRONIC STRESS ACTIVATION THROUGH THE LIFE COURSE; INDIVIDUALS' ADOPTION OF RISKY BEHAVIORS SUCH AS SMOKING AS A RESPONSE TO STRESSFUL STIMULI. METHODS: BASIC SCIENCE, CLINICAL, AND EPIDEMIOLOGIC STUDIES INDEXED IN MEDLINE AND WEB OF SCIENCE DATABASES ON PRECONCEPTIONAL PSYCHOSOCIAL STRESS, PRETERM BIRTH AND RACE WERE REVIEWED. RESULTS: MIXED EVIDENCE LEANS TOWARDS MODEST ASSOCIATIONS BETWEEN PRECONCEPTIONAL CHRONIC STRESS AND PRETERM BIRTH (FOR EXAMPLE COMMON ODDS RATIOS OF 1.2-1.4), PARTICULARLY IN AFRICAN AMERICAN WOMEN, BUT IT IS UNCLEAR WHETHER THIS ASSOCIATION IS CAUSAL OR EXPLAINS A SUBSTANTIAL PORTION OF THE BLACK-WHITE RACIAL DISPARITY IN PRETERM BIRTH. THE STRESS-PRETERM BIRTH ASSOCIATION MAY BE MEDIATED BY HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DYSFUNCTION AND SUSCEPTIBILITY TO BACTERIAL VAGINOSIS, ALTHOUGH THESE MECHANISMS ARE INCOMPLETELY UNDERSTOOD. EVIDENCE FOR THE ROLE OF EPIGENETIC OR EARLY LIFE PROGRAMMING AS A DETERMINANT OF RACIAL DISPARITIES IN PRETERM BIRTH RISK IS MORE CIRCUMSTANTIAL. CONCLUSIONS: PRECONCEPTIONAL STRESS, DIRECTLY OR IN INTERACTION WITH HOST GENETIC SUSCEPTIBILITY OR INFECTION, REMAINS AN IMPORTANT HYPOTHESIZED RISK FACTOR FOR UNDERSTANDING AND REDUCING RACIAL DISPARITIES IN PRETERM BIRTH. FUTURE STUDIES THAT INTEGRATE ADEQUATELY SIZED EPIDEMIOLOGIC SAMPLES WITH MEASURES OF STRESS, INFECTION, AND GENE EXPRESSION, WILL ADVANCE OUR KNOWLEDGE AND ALLOW DEVELOPMENT OF TARGETED INTERVENTIONS. 2011 20 3786 34 INTERGENERATIONAL INFLUENCES ON CHILD GROWTH AND UNDERNUTRITION. INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE WELL DOCUMENTED. SEVERAL GENERATIONS ARE NECESSARY IN ANIMAL MODELS TO 'WASH OUT' EFFECTS OF UNDERNUTRITION, CONSISTENT WITH THE UNFOLDING OF THE SECULAR TREND IN HEIGHT IN EUROPE AND NORTH AMERICA. BIRTHWEIGHT IS CORRELATED ACROSS GENERATIONS AND SHORT MATERNAL STATURE, WHICH REFLECTS INTRAUTERINE AND INFANT GROWTH FAILURE, IS ASSOCIATED WITH LOW BIRTHWEIGHT, CHILD STUNTING, DELIVERY COMPLICATIONS AND INCREASED CHILD MORTALITY, EVEN AFTER ADJUSTING FOR SOCIO-ECONOMIC STATUS. A NUTRITION INTERVENTION IN GUATEMALA REDUCED CHILDHOOD STUNTING; IT ALSO IMPROVED GROWTH OF THE NEXT GENERATION, BUT ONLY IN THE OFFSPRING OF GIRLS. POSSIBLE MECHANISMS EXPLAINING INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE NOT MUTUALLY EXCLUSIVE AND INCLUDE, AMONG OTHERS, SHARED GENETIC CHARACTERISTICS, EPIGENETIC EFFECTS, PROGRAMMING OF METABOLIC CHANGES, AND THE MECHANICS OF A REDUCED SPACE FOR THE FETUS TO GROW. THERE ARE ALSO SOCIO-CULTURAL FACTORS AT PLAY THAT ARE IMPORTANT SUCH AS THE INTERGENERATIONAL TRANSMISSION OF POVERTY AND THE FEAR OF BIRTHING A LARGE BABY, WHICH LEADS TO 'EATING DOWN' DURING PREGNANCY. IT IS NOT CLEAR WHETHER THERE IS AN UPPER LIMIT FOR IMPACT ON INTRAUTERINE AND INFANT LINEAR GROWTH THAT PROGRAMMES IN DEVELOPING COUNTRIES COULD ACHIEVE THAT IS SET BY EARLY CHILDHOOD MALNUTRITION IN THE MOTHER. SUBSTANTIAL IMPROVEMENTS IN LINEAR GROWTH CAN BE ACHIEVED THROUGH ADOPTION AND MIGRATION, AND IN A FEW SELECTED COUNTRIES, FOLLOWING RAPID ECONOMIC AND SOCIAL DEVELOPMENT. IT WOULD SEEM, DESPITE CLEAR DOCUMENTATION OF INTERGENERATIONAL EFFECTS, THAT NEARLY NORMAL LENGTHS CAN BE ACHIEVED IN CHILDREN BORN TO MOTHERS WHO WERE MALNOURISHED IN CHILDHOOD WHEN PROFOUND IMPROVEMENTS IN HEALTH, NUTRITION AND THE ENVIRONMENT TAKE PLACE BEFORE CONCEPTION. TO ACHIEVE SIMILAR LEVELS OF IMPACT THROUGH PUBLIC HEALTH PROGRAMMES ALONE IN POOR COUNTRIES IS HIGHLY UNLIKELY. THE REALITY IN POOR COUNTRIES LIMITS THE SCOPE, QUALITY AND COVERAGE OF PROGRAMMES THAT CAN BE IMPLEMENTED AND MODEST IMPACT SHOULD BE EXPECTED INSTEAD. THE LANCET SERIES ON MATERNAL AND CHILD UNDERNUTRITION ESTIMATED THAT IMPLEMENTATION TO SCALE OF PROVEN INTERVENTIONS IN HIGH BURDEN COUNTRIES WOULD REDUCE STUNTING BY ONE-THIRD; THIS IS PERHAPS A REALISTIC UPPER BOUND FOR IMPACT FOR HIGH QUALITY PROGRAMMES, UNLESS ACCOMPANIED BY SWEEPING IMPROVEMENTS IN SOCIAL SERVICES AND MARKED REDUCTIONS IN POVERTY. FINALLY, BECAUSE SO MUCH CAN BE ACHIEVED IN A SINGLE GENERATION, INTERGENERATIONAL INFLUENCES ARE UNLIKELY TO BE AN IMPORTANT EXPLANATION FOR LACK OF PROGRAMME IMPACT AIMED AT THE WINDOW OF THE FIRST 1000 DAYS. FAILURE TO PREVENT LINEAR GROWTH FAILURE IN DEVELOPING COUNTRIES HAS SERIOUS CONSEQUENCES FOR SHORT- AND LONG-TERM HEALTH AS WELL AS FOR THE FORMATION OF HUMAN CAPITAL. THE NUTRITION TRANSITION HAS CREATED A DOUBLE BURDEN BY ADDING OBESITY AND RELATED CHRONIC DISEASES TO THE PUBLIC HEALTH AGENDA OF COUNTRIES STILL STRUGGLING WITH THE 'OLD' PROBLEMS OF MATERNAL AND CHILD UNDERNUTRITION. THE CHALLENGE AHEAD IS TO INCREASE EFFORTS TO PREVENT LINEAR GROWTH FAILURE WHILE KEEPING CHILD OVERWEIGHT AT BAY. 2012