Crescimento Variantes do normal e patológico

Transcription

1 Manuel Fontoura Faculdade de Medicina do Porto Centro Hospitalar de S. João Endocrinologia Pediátrica e Diabetes Crescimento Variantes do normal e patológico Curso Pré-graduado de Pediatria Sociedade Portuguesa de Pediatria Braga, 19 Abril de 2013

2 Porque é que somos o que somos? Porque crescemos como crescemos? larger mammals fewer offspring Walker et als, 2008 Slow growing Late reproducing Long lived Large brained Extreme immaturity after birth Short duration of breast feeding Extended period of dependence of the young beyond breast feeding Multigenerational resource support by older people Menopause and long postmenopausal life Hochberg, 2012

3 Dilema obstétrico Washburn 1960 Brain Growth and Bipedalism head and brain growth along with mental and motor development have been deferred into the post natal period ( Leutenegger 1973). High energy consuming Growth velocity (cm/year) years

4 Plagiocefalia Postural(PP) vs Craniosinostose Diagnóstico diferencial

5 Plagiocefalia Diagnóstico Causas: Torcicolo Torcicolo muscular congénito Torcicolo postural Postura durante o sono Alteração neurológica Alteração cervical Prematuridade Início: Pré-natal Pós-natal

6 Plagiocefalia Postural Tratamento Helmet treatment or DOC (Dynamic Orthotic Cranioplasty) band Início 4 a 6 meses

7 Age (years) The evolution of hominid life history during the first 20 years of life Ze ev Hochberg, Youth Adolescence Juvenility Childhood Infancy Life span (yrs) Aus afarensis H. Habilis H. erectus H. sapiens 3.2 mya 1.9 mya 670 kya 100 kya mya = millions of year ago kya = thousands of year ago

8 Human Growth Racial Familial Genetics (80%) Age Puberty Sex Nutrition Season Diurnal Environmental Socioeconomic Hundreds of variants clustered in genomic loci and biological pathways affect human height Nature 2010; 467: adult height loci 21 skeletal/growth genes Ovum fertilisation Epiphyseal fusion foetal infancy childhood Juvenility (> 6 anos) puberty Physiology of normal growth: Pediatrics and Child Health, , st molar eruption Manuel Fontoura, 2013

9 The Infancy-Childhood-Puberty (ICP) growth model Adaptado de Karlberg J, 1989 Sexual steroids (1) + (2) + (3) Nutrition Good Health GH-IGF1 hgh-igf1 Thyroxine 15% (1) + (2) Juvenility SDHEA 40% 15% Nutrition Placenta Infancy (1) 30% Fetal Childhood (2) Puberty (3) Age in years

10 Concentração plasmática Perinatal Growth Niklasson and Albertsson-Wikland, cm IGF2 14 Kg IGF1 Glucose Insulin hpl 33 cm 0,8 Kg Leptin IGFBP3 GH months Idade gestacional (sem) Idade pós natal (sem)

11 Fetal Weight / Lenght Development plasticity and human disease Origins of health and adult disease LGA +2 SD Poor maternal nutrition Low maternal fat stores Poor placental function IUGR not SGA AGA 0 SD Nutrient demand > placental supply < Fetal Undernutrition SGA -2 SD Hormonal and metabolic adaptations in utero IGF1-GH switched off Amino acid oxidation Insulin Lactate oxidation Cortisol Glucose oxidation SGA and IUGR Gestational Age SGA not IUGR IUGR Survival and brain development - Fetal programming Predictive adaptive response Adjustments in its development and homeostatic systems for later survival and reproductive fitness

12 Development plasticity and human disease Gluckman PD & Hanson MA, J Int Med Integrated responses to the predictive environment Likely response to a secure environment Investment for longevity (predictive response) Commitment to repair Commitment to tissue reserve (neuronal & nephron number) Investment for large adult size (predictive response) Greater bone mass Greater muscle growth Likely response to a threatening environment Expenditure to survive to birth (immediate adaptive response) Smaller birth size Prematurity Fetal sarcopenia Reproductive strategy (predictive response) Altered time of menarche Investment to resist threatening and difficult environment (predictive response) Altered hypothalamic-pituitary-adrenal axis Increased behaviour, altered anxiety Increased propensity to store fat Central components Increased appetite Altered food preference Reduced motor behaviour Peripheral components Altered hepatic development and function Sarcopenia Altered insulin release and action Impaired action of GH and IGF factors Leptin resistance Altered endothelial function

13 Mean growth velocity Mini-puberty HPG in male < 9 months and in female HPG < 24 months FSH LH Boys Girls Inhibin EE2/Testosterone Age (months) Age (months)

14 IGF growth factors and infancy-childhood transition Kalberg and Albertsson-Wikland (1988) Weaning < plasma fatty acids and ketones < fatty acid oxidation < ketogenesis < gluconeogenesis Rise in fatty acid synthesis Transition from high-fat to high carbohydrate diet < GHrelin < IGF1 > Leptin IGF1 IGFBP3 DICT Delay Infancy-Childhood Transition IGF1 DICT - delay in the rise of IGF1 C-onset < 10 m C-onset > 10 m Age (months)

15 Deficiência em hgh Manutenção da desaceleração do crescimento lactente Hipófise Fígado Plasma Tec. Alvo GH IGF1 IGFBP3 IGF1 IGFBP3 ALS Bone N0 infant-childhood growth transition

16 Eixo GH IGF1 20% Manuel Fontoura, 2012

17 Transition from infancy to childhood Adaptado de Hochberg, energy balance - disease - undernutrition - gastrointestinal infection - socioeconomics < 8.8 months months Catch-up growth Down syndrome Noonan syndrome Silver-Russell syndrome months 15.2 months

18 Growth Acceleration Mean Growth Velocity Infancy Childhood Juvenility Adolescence Life-history phases Hochberg, 2009 Transição infantil - escolar Boys Adrenarca < velocidade crescimento 1º molar > adiposidade Girls Boys Girls

19 JUVENILITY coincides with age children go to school and compete with adults for food and space Age of adiposity rebound is inversely related to the BMI percentiles Younger age of rebound In the obese T Testosterone EE2 Estradiol SDHEA Adrenarche SDHEA SDHEA EE2 T EE2 T Age (years) Energy stored as abdominal fat preparing accelerating growth during adolescence Cole et als, 1995

20 Growth of the juvenile Brain growth is complete, social adult competition (big may be a threat) More efficient energy economy, longer lower limbs relative to BMI reduce energetic cost of walking SDHEA inibe crescimento condrócitos Neurological effects preparing the CNS for Puberty 1) Social interactions + 2) Memory +, social e cognitive capacity + 3) + cortical maturation Leg length velocity ( ) Leg length velocity( )

21 The juvenility-adolescence transition Hochberg, 2012 Delayed Puberty Mean SDS 8 anos 9 anos 13 anos 14 anos Precocious Puberty early and late transitions do not change final height.

22 Final height Tall and short children Veldhuis, Roemmich, 2005 Prepubertal Growth Normal prepubertal growth Normal pubertal growth Tall Short Short prepubertal growth Normal/longer pubertal growth Precocious puberty

23 Growth failure mechanisms Height Growth Velocity -5 Adrenarche , ,5 S. Noonan - < 19 cm S. Silver-Russell - < 26 cm S. Down - < 17 cm

24 Turner Syndrome Even L at al. J Pediatrics, 2000 Growth velocity Length EE SDs - 3SDs

25 Periods of adaptive plasticity in the transition between life-history stages Predictive adaptive responses Prenatal environment Postnatal environment Endocrine control Prematurity Size at birth Transition to Childhood Transition to juvenility Childhood growth Transition to puberty Juvenile growth Pubertal growth Prenatal Growth Infantile growth Body composition & metabolic adjustment? Fertility & lifespan Adult height Adult phenotype Adapted from Hochberg Z, Feil et al, 2011

26 Obrigado! Live fast, remain small, reproduce early and die young Nuno Milheiro Live slow, grow much, reproduce late and die old Charnov EL. 1991