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Proefschrift binnenwerk Manon Ernst_DEF.indd

C H A P T E R   1   posure   to   infection   after   birth,   determine   its   susceptibility   to   chronic   disease   in   later  life”.  Adequate  and  balanced  protein,  energy  and  micronutrient  intake  during   pregnancy  might  be  a  protective  factor  for  adult  obesity.  Thus,  improving  women’s   nutritional  status  prior  to  and  during  pregnancy  can  substantially  reduce  the  risk  of   low   birth   weight.   Children   born   with   low   birth   weight   appeared   to   have   less   lean   body  mass,  lower  BMI  and  greater  fat  mass  in  adults19.     In  SGA  children,  poor  nutritional  conditions  during  gestation  can  modify  metabolic   systems   to   adapt   to   expectations   of   chronic   under   nutrition.   These   children   are   potentially  poorly  equipped  to  cope  with  energy-­‐dense  diets  and  are  possibly  pro-­‐ grammed   to   store   as   much   energy   as   possible,   leading   to   later   obesity,   metabolic   syndrome,  disturbed  regulation  of  normal  puberty  and  early  onset  of  cardiovascu-­‐ lar  disease35.  A  follow  up  of  5654  men  born  from  1911  to  1930  in  England  demon-­‐ strated  that  men  with  the  lowest  weights  at  birth  had  highest  death  rates  from  is-­‐ chemic  heart  disease36.     Fetal  growth  restraint  is  associated  with  maternal-­‐uterine  factors  such  as  primipar-­‐ ity,  smoking,  restrictions  in  the  maternal  diet,  maternal  insulin  resistance,  and  ges-­‐ tational  diabetes.  Alternatively,  if  an  insulin  resistant  state  was  manifested  in  utero,   then   diminished   fetal   growth   with   SGA   might   be   anticipated,   because   insulin   is   a   powerful  prenatal  growth  hormone14.     Insulin  plays  a  central  role  in  fetal  growth.  During  the  first  two  years  of  life,  espe-­‐ cially  during  the  first  12  months  of  life,  SGA  newborns  are  usually  able  to  catch-­‐up   growth  velocity  above  the  50th  percentile37.  Not  only  does  this  trend  improve  the   final  height,  but  it  has  also  been  associated  with  changes  in  insulin  sensitivity38,39.  If   a   SGA   child   shows   a   growth   pattern   that   transcends   the   normal   trend,   the   risk   to   develop  obesity  is  evident.     Also  children  with  growth  hormone  deficiency  (GHD)  are  at  risk  to  develop  obesity.   GDH  children  appear  to  have  a  higher  fat  mass.  In  children  who  do  not  suffer  from   growth   hormone   deficiency,   the   growth   in   length   compensates   the   increase   in   weight.  In  GDH  children  this  compensation  mechanism  does  not  work.  In  GHD  chil-­‐ dren  it  is  shown  that  besides  its  positive  effect  on  growth,  rhGH  influences  metabo-­‐ lism  too40,41.  The  basal  metabolic  rate  increases  visible  as  a  change  in  body  compo-­‐ sition  by  an  increase  in  fat-­‐free  mass  (FFM)42,43.       Adults  with  GHD  are  characterized  by  disturbances  in  body  composition,  lipid  me-­‐ tabolism,  cardiovascular  risk  profile  and  bone  mineral  density.  It  is  well-­‐known  that   adult  GHD  usually  is  accompanied  by  an  increase  in  fat  accumulation.  Growth  hor-­‐ mone  replacement  in  adult  patients  with  GHD  results  in  reduction  of  fat  mass  and   abdominal  fat  mass  in  particular44.   16    


Proefschrift binnenwerk Manon Ernst_DEF.indd
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