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Ultrasound  &  Fetal   Growth  Restric9on  

Faculty  Disclosure  

Alfred  Abuhamad,  MD.   Eastern  Virginia  Medical  School  

•  I  have  no  financial  rela>onship  with  any   manufacturer  of  any  commercial  product  and/or   provider  of  commercial  services  discussed  in  the   CME  ac>vity.   •  I  do  not  intend  to  discuss  an  unapproved/ inves>ga>ve  use  of  a  commercial  product  or  device   in  my  presenta>on.   •  I  affirm  that  my  presenta>on  complies  with  the  U.S.   Government  Health  Insurance  Portability  and   Accountability  Act  of  1996  (HIPAA)  privacy  and   security  standards.  

Lecture  Outline  

Fetal  Growth  Restric>on  

• Fetal  Growth  Restric>on   • Role  of  Ultrasound  in  Diagnosis   and  Management   • Future  Direc>ons  

Treatment:  

FGR  

• Bed  rest   • Aspirin   • Nutrient  supplements  with  Calcium/Zinc   • Maternal  oxygena>on   • Heparin   • Plasma  volume  expansion   • Calcium  channel  blockers   • Hormonal  therapy   • Smoking  cessa>on    

No Benefit

ACOG  IUGR  bulle>n  2000.  Reaffirmed  2010  

Complex  Problem:   • Various  published  defini>ons   • Poor  detec>on  rates   • Limited  preven>ve  or  treatment  op>ons   • Mul>ple  associated  morbidi>es   • Increased  likelihood  of  perinatal  mortality  

Defini>on   •  Fetal  Growth  Restric>on  (FGR)  is   sonographically  es>mated  fetal  weight   (SEFW)  onal  age  (SGA)  is  actual  birth   weight  (BW)  <  10%  for  GA          (POSTNATAL  STATUS)   ACOG  PB  2013;  RCOG  GG  2013;  SOGC  2013;  RCPI  2014  

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Defini>on  

Risk  Factors  for  FGR  

Other  diagnos>c  criteria:   • SEFW  <  5%   • SEFW  <  3%   • AC  <  10%   • AC  <  5%   • Ac  <  3%   ACOG  PB  134,  2013  

Predic>on  of  FGR  

•  Severity  of  FGR  in  previous  pregnancy  correlates   with  recurrence  risk     •  Abnormal  first  trimester  serum  analytes:   –  Low  PAPPA  (  24  weeks   Ø 

If  fundus  cannot  be  palpated,  e.g.  obesity,  mul>ple   gesta>on,  sonography  is  preferred  

•  Sonographic  screening  may  be  used  in  the  presence   of  risk  factors   •  No  evidence  that  rou>ne  sonography,  serum   analytes,  or  uterine  artery  Doppler  improve   outcomes   ACOG  PB  134,  2013  

Predic>on  of  FGR   • Isolated  2VC  (  OR  2.23)   • Velamentous  cord  inser>on   (increased  risk  of  SGA,  PTD,  low  Apgar   scores)   • Marginal  cord  inser>on  not  associated   with  FGR   Murphy-­‐Kaulbeck  L,  Obstet  Gynecol,  2010   Heinonen  S,  Obstet  Gynecol,  1996  

Fundal  Height  Screening   •  Reliable  screening  tool  in  low-­‐risk,  normal   weight  pa>ents  (24-­‐38  weeks)   •  At  32-­‐34  weeks,  sensi>vity  65-­‐85%  and   specificity  96%    

ACOG  PB  134,  2013  

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Ultrasound  Based  on  Risk  Factors  

   

•  Singleton  births,  all  French  maternity  units  in  2010,  over  1  week   period   •  Rou>ne  US  between  30  and  35  weeks   •  22%  of  SGA  infants  were  suspected  of  FGR  (but  outcome  was   not  beger  if  FGR  was  suspected)   •  50%  of  infants  suspected  of  FGR  were  not  SGA  (increased  risk   of  provider-­‐ini>ated  early  delivery  in  this  group)    

•  A  risk  factor  or  lagging  fundal  height  may   be  present  in  about  20%     •  As  a  group,  risk  factors  confer  about  a  2  to   3-­‐fold  risk  for  SGA   •  Detec>on  of  SGA  is  higher  in  the  semng  of   a  risk  factor,  about  50%   •  However,  the  majority  of  SGA  infants  do   not  have  risk  factors  

 

Fetal  Growth  Restric>on

Screening  -­‐  Summary  

Prenatal  detec3on:  

 

• Undetected  in  30  -­‐  50%  of  cases   • Incorrectly  diagnosed  in  50%  of  cases  

ACOG  IUGR  bulle>n  2000.  Reaffirmed  2010   Acta  Obstet  Gynecol  Scand  1998;77:643   J  Obstet  Gynecol  1996;16:77  

Diagnosis   • Fetal  biometry   – Screening  tool  in  high  risk  popula>on  and   gold  standard  in  diagnosis  of  FGR   – Different  formulas  used  to  calculate  SEFW   – Inaccurate  da>ng  may  lead  to  false   diagnosis    

Diagnosis  

• Fetal  biometry  

– BPD,  HC,  AC,  FL  

– Transverse  cerebellar  diameter   between  14  and  24  weeks  correlates   with  GA  in  weeks  (it  is  unchanged  in   FGR)   – Fetuses  with  abdominal  wall  defect   are  ooen  over-­‐diagnosed  with  FGR    

Goldstein  I,  Am  J  Obstet  Gynecol,  1987  

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Formulas  for  SEFW  

Formulas  for  SEFW  

•  No  consistently  superior  method  of  assessment  emerged   •  Similar  systema>c  and  random  errors  between  formulas   •  Wide  intra  and  inter-­‐observer  variability  iden>fied     •  Use  average  of  mul>ple  measurements   •  Improvement  in  image  quality  

•  Review  of  studies  employing  7  different   regression  equa>ons  for  EFW    

•  Uniform  calibra>on  of  equipment   •  Regular  audits  for  quality  assurance     Dudley  N,  UOG  2005  

Weight  Percen>les   o Popula>on  Norms   • “one  size  fits  all   • Unadjusted  for  factors  that  affect  fetal   size  

o Customized  Norms   • “one  size  does  not  fit  all”   • Adjusted  for  factors  that  affect  fetal  size   (fetal  gender,  ethnicity,  parity,  parental   size,  al>tude,  maternal  co-­‐morbidity)  

FGR: Morbidity and Mortality •  IUFD (risk correlates with SEFW percentile) – > 10% - 0.7% – < 10% - 1.5% – < 5% - 2.5%

•  Neonatal death •  Cognitive delay in childhood •  Diseases in adulthood (DM2, obesity, CAD, stroke)

Intergrowth-­‐21   •  Mul>center  interna>onal  study  –  7  countries   •  Longitudinal  growth  4321  low-­‐risk  pregnant   women  from  14  weeks  to  42  weeks   •  Biometric  charts  for  BPD,  HC,OFD,  AC  and  FL  were   developed   •  Goal  is  to  describe  how  fetuses  SHOULD  grow,  as   opposed  to  tradi>onal  charts  that  describe  how   fetuses  DO  grow   •  Ques>on:  outcome  studies  to  confirm  superiority   over  current  exis>ng  charts    

Papageorghiou  AT,  Lancet,  2014  

Fetal  Growth  Restric>on Outcome:  

 

• Low  Apgar  scores  &  cord  pH  <  7.0   • Increased  NICU  admissions  &  sepsis   • Increased  s>llbirth  and  neonatal  mortality   • Increased  learning  disabili>es     • Increased  adult  onset  cardiovascular      disease   ACOG  IUGR  bulle>n  2000.  Reaffirmed  2010  

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SGA:  Morbidity  and  Mortality   • Hypoglycemia   • Hyperbilirubinemia   • Hypothermia   • IVH   • NEC   • Seizures   • Sepsis   • RDS  

• Cerebral  Palsy   • Neonatal  death  

•  Medical  Birth  Registry  in   Norway   •  Singletons,  born  1996-­‐2006   •  398  children  with  CP,   490,022  normally   developed   •  Low  birth  weight  and  HC   correlates  with  increased   risk  of  CP    

   

Fetal  Assessment   Non-­‐invasive  tests:   •  Fetal  kick  counts   •  Non-­‐stress  test   •  Biophysical  profile   •  Doppler  assessment     Invasive  tests:   •  Amniocentesis   •  Cordocentesis   No  ideal  test  for  all  growth  restricted  fetuses.  

Cardiovascular   Adapta>on  of  FGR  

Biophysical  Profile   •  Normal  BPP  is  associated  with  decreased  rate  of   fetal  death  within  1  week  of  tes>ng   •  Not  reliable  in  premature  fetuses  (ve  results   •  BPP  only  compared  to  “no  tes>ng  strategy”  results   in:   –  60%  reduc>on  of  IUFD   –  59%  reduc>on  of  neonatal  death   –  92%  reduc>on  of  neonatal  disability  

Early  Changes  /  FGR   Arterial Redistribution

Brain  Sparing  Reflex   • £  impedance  in  UA  (£S/D)   • ¤  impedance  in  MCA  (¤  PI)     Value  of  CPR  

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Fetal  Hypoxemia  

Umbilical  Arteries  

Blood Flow Redistribution Brain Sparing Reflex

Increased • Heart • Brain • Adrenal • Spleen

Decreased • Lungs • GI • Skeletal • Other

Umbilical  Arteries  

Normal  Waveform  

Abnormal  Waveform  

Fetal  Hypoxemia    /  FGR  

Umbilical  Artery  

AEDF

REDF

Fetal  Hypoxemia  /  FGR  

UA ↑ Impedance

UA ↑ Impedance

• Oblitera>on  of  small  muscular          arteries  in  ter>ary  stem  villi   • For  A/REDF,  need  >  70  %            placental  oblitera>on  

• Meta-­‐analysis  of  18  trials      (>  10,000  women),  concluded  that  use  of    UA  Doppler  in  high-­‐risk  women  reduced      perinatal  death  &  obstetric  interven>ons    

Ultrasound  Obstet  Gynecol  1997;9:271   AJOG  1989;161:1055  

Syst  Rev  2010;(1):CD007529  

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Should  Doppler  be  performed  in  low-­‐ risk  women  as  a  screening  test?   Meta-­‐analysis  of  4  trials  found     no  difference  in  outcome  

Cerebral  Vasculature   Middle Cerebral Artery • Most  accessible  cerebral  vessel   • Carries  80  %  of  cerebral  flow   • Constant  3%  -­‐  7%  of  CO   • Excellent  reproducibility   AJOG  1993;169:1393  

Circle  of  Willis  

Middle  Cerebral  Artery  

MCA

Normal  Waveform  

Abnormal  Waveform  

Cerebral  Placental  Ra>o  (CPR)   •  Ra>o  of  MCA  PI  to  UA  PI   •  Used  to  assess  brain  sparing     •  Blood  flow  centraliza>on  present  if  CPR  <  5%  for  GA   or  <  1.08  (similar  accuracy)  –  associated  with   adverse  perinatal  outcome   •  Can  iden>fy  FGR  fetuses  at  risk  of  cesarean  sec>ons   for  NRFHR   Bahado-­‐Singh  RO,  AJOG,  1999   Cruz-­‐Mar>nez  R,  Obstet  Gynecol,  2011   Odibo  A,  JUM,  2005  

CPR = MCA PI / UA PI Am J Obstet Gynecol 2014;211:288

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Late  Changes  /  FGR  

Ductus  Venosus  

Elevated Central Venous Pressure Cardiac  Decompensa>on  

• £  EDP  in  RV  (£  aoerload)   • £  Cardiac  s>ffness     Ultrasound  Obstet  Gynecol  1996;7:401  

Ductus  Venosus  

Ductus  Venosus  

Abnormal  Waveforms  

Fetal  Hypoxemia  /  FGR  

FGR  

Early Changes • Biometric  changes   • Arterial  Doppler  

Late Changes • Venous  Doppler   • Heart  rate  tracing   Ultrasound  Obstet  Gynecol  2002;19:140  

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FGR  /  Late  Gesta>on   •  Mul>ple  poten>al  pathways  of   Doppler  deteriora>on  in  IUGR   •  UA→  MCA  →  DV  is  no  more  common   than  other  pathways   •  Abnormal  UA  and  MCA  Doppler  are   strongest  predictors  of  adverse   perinatal  outcome   •  Only  marginal  added  benefit  to  DV   and  cardiac  indices   Unterscheider  J,  Am  J  Obstst  Gynecol,  2013  

• Normal  UA  Doppler  is  common  in  IUGR    fetuses  in  late  gesta>ons   • Cerebroplacental  ra>o  has  poor  correla>on    in  IUGR  fetuses  >  34  weeks   • Sequen>al  deteriora>on  is  rare  in  fetuses    beyond  32  -­‐  34  weeks   Eur  J  Obstet  Gynecol  Reprod  Biol  1993;73:23   AJOG  1999;180:750   Ultrasound  Obstet  Gynecol  2000;15:209  

Hypoxia Placental Effects

Early Gestations • Inhibits  angiogenesis  

Late Gestations • S>mulates  angiogenesis  

Br  Med  J  1987;294:1641   Eu  J  Obstet  Gynecol  &  Repro  Bio  2000;92:35  

•  In  high-­‐risk  pregnancies  with  suspected  FGR  UA   Doppler  assessment  significantly  decreases   likelihood  of  IOL,  cesarean  delivery  and  perinatal   death   •  UA  Doppler  surveillance  should  be  started  when   fetus  is  viable  and  FGR  suspected   •  DV,  MCA  and  other  vessels  Dopplers  have  some   prognos>c  value  for  FGR  fetuses,  but  currently  lack   of  RCT  showing  benefit  and  they  should  be   reserved  for  research  protocols  

•  •  • 

Am J Obstet Gynecol 2014;211:288

Fetal  outcome  was  beger  than  expected   Perinatal  death  was  uncommon  (8%)   70%  survived  without  severe  neonatal   morbidity.    

Ultrasound  Obstet  Gynecol  2013;  42:  400–408  

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Timing  of  Delivery   Poor  Prognos>c  Factors:   -­‐  Presence  and  severity  of  maternal     hypertensive  condi>ons   age  at  diagnosis   -­‐  Gesta>onal   Gesta>onal   age  at  delivery   -­‐ 

Stillbirth Neonatal morbidity and mortality

Ultrasound  Obstet  Gynecol  2013;  42:  400–408  

•  Retrospec>ve  cohort  study   •  Data  from  Na>onal  Center  for  Health   Sta>s>cs  (NCHS)   •  3,399,816  singleton  non-­‐anomalous   neonates  born  in  US  in  2005   •  compared  risk  of  IUFD  within  4  growth  strata     Pilliod  R,  AJOG,  2012  

•  Cumula>ve  risk  of  s>llbirth   increases  for  each  week  aoer   37  weeks   •  The  increased  risk  becomes   significant  at  39  weeks  for  FGR   <  10%     •   FGR  llbirth  at   38  weeks  compared  to  37   weeks   Pilliod  R,  AJOG,  2012  

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GRIT  Trial  

GRIT  Trial  

•  Growth  Restric>on  Interven>on  Trial  

•  Growth  Restric>on  Interven>on  Trial  

 

 

•  Mul>center  RCT  

•  Mul>center  RCT  

 

 

•  548  mothers  randomized  to  immediate          delivery  (48hrs)  vs.  delayed  delivery  

•  548  mothers  randomized  to  immediate          delivery  (48hrs)  vs.  delayed  delivery     •  MOD  at  discre>on  of  the  provider  

– Obstetrician  was  uncertain  whether  to  deliver   between  24-­‐36  weeks  

•   MOD  at  discre>on  of  the  provider   GRIT  Group,  BJOG,  2003  

GRIT  Trial  

GRIT  Group,  BJOG,  2003  

GRIT  Trial  

•  If  choose  to  delay  delivery  on  average  most   physicians  will  delay  by  4  days   •  There  is  no  difference  in  perinatal  mortality     –  S>llbirths  are  counterbalanced  by  neonatal  deaths    

•   Two-­‐year  follow  up   –  No  difference  in  mortality  or  severe  disability   –  All  severe  disability  observed  was  in  neonates   delivered  <  31  weeks  

•  Long-­‐term  outcome  (mean  9  yrs)   –  No  significant  differences  in  cogni>on,  language,   motor  performance,  behavior   GRIT  Group,  BJOG,  2003  

GRIT  Group,  BJOG,  2003  

 

•  The  Dispropor>onate  Intrauterine  Growth   Interven>on  Trial  at  Term   •  Randomized  trial  (650  women  randomized  to  IOL  or   expectant  management)   •  36+0  weeks  to  41+0  weeks   –  Singleton,  cephalic,  suspected  IUGR   –  Included  normal  and  abnormal  Dopplers  

 

DIGITAT  Trial  

•  No  significant  differences   – Primary  composite  adverse  neonatal  outcome   – Rate  of  opera>ve  delivery  or  cesarean   – MAIN  scores   •  No  fetal  or  neonatal  deaths  in  either  group   •  No  difference  in  developmental  or  behavioral   outcomes  at  2-­‐year  follow  up   •  IOL  before  38  weeks  associated  with  >  NICU  admit   •  Either  strategy  acceptable    Boers  KE,  AJOG,  2012   Van  Wyk  L,  AJOG,  2012    

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Delivery  Timing  with  Abnormal  Dopplers  

Summary:  Delivery  Timing   Uncomplicated  FGR  (nl  UA  Dopplers)   1.  EFW  5  -­‐10%  -­‐    delivery  at  39  weeks   2.  EFW  <  5%  -­‐  delivery  at  37  weeks     Complicated  FGR  (abnormal  UA  Dopplers)   1.  Elevated  UA  Dopplers  (DEDF)  -­‐  37  weeks   2.  AEDF:  cor>costeroids  à    delivery  if  >  34  weeks   3.  REDF:  cor>costeroids  à    delivery  if  >  32  weeks  

FGR  –  Mode  of  Delivery  

Recurrence  Risk  of  SGA  

•  No  RCTs  for  MOD  for  FGR   •  Several  small  observa>onal  studies   –  Demonstrate  that  FGR  is  a  risk  factor  for  cesarean  

•  No  evidence  to  suggest  VD  (or  IOL)  is  contra-­‐ indicated  for  FGR   •  Even  with  abnormal  UA  Dopplers,  a  reasonable   chance  for  VD   Horowitz,  KM  et  al.  J  MFNM  2014   Li,  H  et  al.  Acta  Obstet  Gynecol  Scand  2003   Chavakula,  PR  et  al.  Int  J  Gynecol  Obstet  2015   Maslovitz,  S  et  al.  Arch  Gyn  Obstet  2009   Ben-­‐Haroush,  A  et  al.  Acta  Obstet  Gynecol  Scand  2004   Visen>n,  S  et  al.    J  U  Med  2014      

 

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