Programación fetal Evidencias actuales y papel de la nutrición fetal
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1 Programación fetal Evidencias actuales y papel de la nutrición fetal Eduard Gratacos BCNatal Centre de Medicina Maternofetal i Neonatologia de Barcelona Hospital Sant Joan de Déu i Hospital Clínic, Universitat de Barcelona
2 Neonatal and Fetal GA-adjusted normal weight in the same population
3 Prognostic criteria for true placental insufficiency CS for distress and/or neonatal acidosis UtA >p95 CPR <p5 EFW CENTILE <3 N=447 SGA controls % Figueras 2012
4 Restricción crecimiento fetal Adaptación = Epigenetica = Programación permanente Reorganización cerebral Remodelado Cardiovascular Programación Metabolica
5
6 Gemelos bicoriales. Parto 34 semanas Twin 1: 1950 g (p45) Twin 2: 1200 g (p1) * * * Bayley Score cognitive languag motor socio-emot adap beha Lagercrantz H. Better born too soon than too small. Lancet 1997 Satchev, 2012 Figueras Baschat 2009, 2011 Vohr 2004 Geva Marsal Visser 01-11
7 exposure Fetal programming Brain reorganiza0on (+/- injury)
8
9 Neuroimage 2012 PLoS One 2012
10 IUGR = reduced connectivity normal IUGR
11 IUGR IS ASSOCIATED WITH REDUCED DEEPER FISSURES Case%(N=31) Control%(N=19) p* BPD 95,33+2,95 100,64+3,23 <0,01 Left_Insular_Depth 0,30+0,06 0,27+0,02 0,021 Right_Insular_Depth 0,3+0,07 0,27+0,03 0,16 Left_Sylvian_Fiss 0,16+0,05 0,14+0,03 0,37 Right_Sylvian_Fiss 0,15+0,04 0,15+0,03 0,57 Left_PO_Fiss 0,13+0,03 0,11+0,04 0,09 Right_PO_Fiss 0,14+0,04 0,11+0,04 0,02 Left_Cing_Fiss 0,09+0,02 0,09+0,02 0,79 Right_Cing_Fiss 0,09+0,02 0,09+0,02 0,98 Left_Calc_Fiss 0,18+0,03 0,16+0,04 0,06 Right_Calc_Fiss 0,18+0,04 0,16+0,05 0,11 L/R%Insular%ratio 1,03+0,29 0,95+0,1 0,05
12 NEURO-METABOLOME PROJECT NEURO&METABOLOME,PROJECT, MRS:MAGNETIC,RESONANCE, SPECTROSCOPY, Cell culture and experimental tissue markers NAA Myo Ino Cho MRS validation of best candidates Metabolites and neural function-maturation: -N-acetyl-aspartate (NAA): Neuronal marker. -Choline (Cho): Myelination and cell membrane turnover -Creatine (Cre): Cellular energy -Myo-Inositol (Myo-Ino): Glial marker. Osmoregulation Sanz 2010 Experimental and Clinical MR-Spectroscopy Van Vliet, PLoS 2012
13 Restricción crecimiento fetal Adaptación = Epigenetica = Programación permanente Reorganización cerebral Remodelado Cardiovascular Programación Metabolica
14 1986 Barker (MRC Unit, Southampton, UK): Coronary heart disease mortality rates
15 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
16 IMPACT OF FETAL GROWTH ON CARDIOVASCULAR REMODELLING Normal growth IUGR BP 90/65 BP 115/80 cimt = mm cimt = mm Crispi Circula8on 2010
17 postnatal cardiovascular remodelling Cardiovascular remodeling IMPACT OF LATE IUGR/SGA globular heart longitudinal mo0on stroke volume heart rate = cardiac output hypertension pre- arteriosclerosis near term SGA fetuses without signs of poor prognosis also presented CV remodeling Skilton Lancet 2007, Crispi Circula8on 2010, Crispi AJOG 2012
18 Fetal growth and molecular/ultrastructural remodelling Shorter sarcomere length Torre 2011, Iruretagoyena 2013 Protein expression and isoforms Torre 2011, Tintu 2010 B x Titin isoforms: N2BA compliant N2B stiffer CONTROL FGR Gene set analysis (FatiScan) Up#regula*on- Down#regula*on-
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20 BIOLOGIC PROGRAMMING AND AGE IMPACT OF ENVIRONMENT OPPORTUNITY FOR CORRECTION Fetus Child Young Mature Old
21 IDENTIFICATION OF THE PROBLEM: UNDERNUTRITION, NOT WEIGHT INDIVIDUAL BIOMARKERS INTERVENTION BIRTH WINDOW OF OPPORTUNITY Fetus Child Programming / Organ remodelling Problem evident
22 fetal composite CV score for the prediction of postnatal hypertension sensitivity 90%, specificity 77% IDENTIFICATION OF RISK INDIVIDUAL BIOMARKERS INTERVENTION BIRTH WINDOW OF OPPORTUNITY Fetus Child Func0onal / structural organ remodeling Cruz- Lemini FMF 2013, Skilton Pediatric 2012, Rodriguez 2013 Problem evident
23 Restricción crecimiento fetal Adaptación = Epigenetica = Programación permanente Reorganización cerebral Remodelado Cardiovascular Programación Metabolica
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