Cardiovascular fetal programming and remodelling Long term effects of adverse fetal environment on the heart
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1 Cardiovascular fetal programming and remodelling Long term effects of adverse fetal environment on the heart Eduard Gratacos Maternal-Fetal Medicine Department and Research Center Hospital Clinic - University of Barcelona
2 Fetal growth restriction (and other conditions leading to adverse fetal environment) Adaptation = Epigenetics = Permanent programming Brain reorganization Cardiovascular remodelling Metabolic programming
3 1986 Barker (MRC Unit, Southampton, UK): Coronary heart disease mortality rates
4 GROWTH RESTRICTION AND THE FETAL HEART IUGR target organ in hypoxic centralization Adaptive response Progressive failure Permanent Epigenetic changes CLINICAL MONITORING CARDIAC PROGRAMMING
5 CLASSIC HYPOTHESIS Fetal growth restriction Epigenetic changes in metabolic regulation Normalization of diet (or overnutrition) Insulin resistance Obesity/Diabetes/ Hypertension Cardiovascular disease ALTERNATIVE/COMPLEMENTARY HYPOTHESIS Fetal growth restriction Epigenetic changes in cardiac regulation Persistence of abnormal cardiac function Lack of ability to further adaptation Cardiovascular disease
6 FETAL CARDIOVASCULAR PROGRAMMING INTRAUTERINE GROWTH RESTRICTION hypertension coronary disease stroke obesity diabetes fetal cardiac dysfunction postnatal persistance of cardiovascular remodeling cardiovascular disease in adulthood Barker BMJ 1986, Barker BMJ 1995, Hecher Circula6on 1995, Crispi AJOG 2008, Crispi Circula6on 2010, Cruz FDT 2011, Crispi AJOG 2012
7 postnatal cardiovascular remodelling Cardiovascular remodeling control IUGR globular heart longitudinal mo;on stroke volume heart rate = cardiac output IMPACT OF LATE IUGR/SGA TA 90/65 TA 115/80 hypertension pre- arteriosclerosis cimt = mm cimt = mm near term SGA fetuses without signs of poor prognosis also presented CV remodeling Skilton Lancet 2007, Crispi Circula6on 2010, Crispi AJOG 2012
8 control ART decreased systolic mo;on impaired relaxa;on right S TAPSE E dec IRT CONTROL ART Right longitudinal systolic motion Annular peak velocity (S, cm/s) Displacement (TAPSE, mm) * * Diastolic function Left isolumetric relaxation time (IRT, ms) Right E deleceleration time (Edec, ms) * * Data are median+sem. *P<0.05 adjusted by GA, birthweight cen;le and preeclampsia Valenzuela- Alcaraz Circula6on 2013
9 cardiovascular remodelling in IUGR NORMAL Crispi 2010, Cruz-Lemini 2013, Stergiotou 2014
10 cardiovascular remodelling in IUGR NORMAL IUGR more globular heart systolic & diastolic dysfunction Pr STARVATION HYPOXIA VOLUME OVERLOAD Pr Pr PLACENTAL INSUFFICIENCY PRESSURE OVERLOAD increased aimt Crispi 2010, Cruz-Lemini 2013, Stergiotou 2014
11 NORMAL ART Thicker ventricular walls Dilated atria Systolic & diastolic dysfunction pressure overload Pr aimt ART systemic & pulmonary hypertension in infancy & childhood aimt
12 hyperglycemia embryo manipulation toxics undernutrition infection hypoxia Fetal cardiovascular remodeling & programming of adult disease Intrauterine growth restriction Twin-to-twin transfusion syndrome Maternal diabetes prediction of postnatal hypertension limited utility in staging or predicting prognosis potential utility in predicting outcome? Assisted reproductive technologies? Crispi Circula+on 2010, Karatza Heart 2002, Gardiner Circula+on 2003, Rychik AJOG 2007,S+rneman UOG 2010, Gardiner Heart 2006, Valenzuela Circula+on 2013
13 BIOLOGIC PROGRAMMING AND AGE IMPACT OF ENVIRONMENT OPPORTUNITY FOR CORRECTION Fetus Child Young Mature Old
14 IDENTIFICATION OF RISK 4P medicine Predictive Preventive Personalized Participatory INDIVIDUAL BIOMARKERS INTERVENTION BIRTH WINDOW OF OPPORTUNITY Fetus Child Brain organiza;on Problem evident
15 fetal composite CV score for the prediction of postnatal hypertension sensitivity 90%, specificity 77% IDENTIFICATION OF RISK cimt IUGR 4P medicine Predictive Preventive Personalized Participatory INDIVIDUAL BIOMARKERS AGA % polyunsaturated fats INTERVENTION BIRTH WINDOW OF OPPORTUNITY Fetus Child Func;onal / structural organ remodeling Problem evident Cruz- Lemini FMF 2013, Skilton Pediatric 2012, Rodriguez 2013
16 hyperglycemia embryo manipulation toxics undernutrition infection hypoxia Fetal cardiovascular remodeling & programming of adult disease Intrauterine growth restriction Twin-to-twin transfusion syndrome Maternal diabetes prediction of postnatal hypertension limited utility in staging or predicting prognosis potential utility in predicting outcome? Assisted reproductive technologies?
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