CurrentDevelopment ofPrenatal CareProfessor Hassan Nasrat FRCS, FRCOGThe Fetal Medicine ClinicThe First ClinicTuesday, Jun...
oMost	  complications	  occur	  toward	  the	  end	  of	  pregnancy.oAdverse	  outcomes	  cannot	  be	  predictedMinistry ...
Major Complications•Hemorrhagic complications•Abnormal presentation and•Abnormal Lie•-----•--Tuesday, June 18, 13
•Changes Of The Nature Of ObstetricComplications•Current Obstetric Challenges❖ Fetal Anueploidy and other fetal Anomalies❖...
How Can We Predict Complications ?Tuesday, June 18, 13
Background Risk (PRIORI RISK)AgeRacePrevious PTLPrevious PETPrevious AnomaliesUnderlying Medial DisordersOther Maternal Ch...
Background Risk (PRIORI RISK)LOW RISK PATIENT HIGH RISK PATIENTTuesday, June 18, 13
Background Risk (PRIORI RISK)LOW RISK PATIENT HIGH RISK PATIENT❖ Most OfThose Complications Develop Late❖ Same Standard Of...
Define Patient Specific RiskHow Can We Predict Complications ?Individualized Patient CareTuesday, June 18, 13
Background Risk (PRIORI RISK)Tuesday, June 18, 13
DATA FROM ULTRASOUND SCANNING+Background Risk (PRIORI RISK)Tuesday, June 18, 13
DATA FROM ULTRASOUND SCANNINGFINDINGS OF BIOPHYSICALAND BIOCHEMICALTESTS++Background Risk (PRIORI RISK)Tuesday, June 18, 13
DATA FROM ULTRASOUND SCANNINGFINDINGS OF BIOPHYSICALAND BIOCHEMICALTESTS++➧Patient Specific RiskBackground Risk (PRIORI RIS...
 For	  Every	  Disorder	  There	  is	  background	  risk	  	  (Priori	  Risk)	  Calculation	  of	  Patient	  Specific	  RI...
Screening	  for	  Risk	  FactorsImportant	  proper+es	  of	  a	  screening	  test	  are	  its	  sensi+vity,	  specificity,	...
Screening	  for	  Risk	  FactorsImportant	  proper+es	  of	  a	  screening	  test	  are	  its	  sensi+vity,	  specificity,	...
Screening	  for	  Risk	  FactorsImportant	  proper+es	  of	  a	  screening	  test	  are	  its	  sensi+vity,	  specificity,	...
Screening	  for	  Risk	  FactorsImportant	  proper+es	  of	  a	  screening	  test	  are	  its	  sensi+vity,	  specificity,	...
The	  likelihood	  ra(o	  Indicate by how much a given test resultincreases or decreases the probability ofdevelopinga con...
Calculation	  of	  Patient	  Specific	  RISK	  “Using	  Positive	  &	  Negative	  Likelihood	  Ratio”The	  Background“Prior...
Calculation	  of	  Patient	  Specific	  RISK	  “Using	  Positive	  &	  Negative	  Likelihood	  Ratio”×The	  Background“Prio...
Calculation	  of	  Patient	  Specific	  RISK	  “Using	  Positive	  &	  Negative	  Likelihood	  Ratio”×The	  Likelihood	  ra...
Calculation	  of	  Patient	  Specific	  RISK	  “Using	  Positive	  &	  Negative	  Likelihood	  Ratio”×The	  Likelihood	  ra...
Calculation	  of	  Patient	  Specific	  RISK	  “Using	  Positive	  &	  Negative	  Likelihood	  Ratio”×The	  Likelihood	  ra...
0.6 0.4 2.0LR=1.7 LR=10.6 LR=2.0AFP(MOM) UE3(MOM) hCG(MOM)Age Risk30 years1:900Likelihood RatioAFP UE3 hCG1.7 × 10.4 × 2.0...
 Every woman has a background or apriori risk for any given disorder/complication. A new individual “patient-specific”ri...
CurrentDevelopment inPrenatal CareTuesday, June 18, 13
Individualized Patient CarePrediction of Fetal Complications ?What Is The Role of Feto-Maternal ServiceTuesday, June 18, 13
❖FetalAnueploidy and other fetalAnomalies❖Pre-eclampsia❖Fetal Growth Restriction❖Preterm Labor❖Fetal Macrosomia❖Gestationa...
The	  11–13+6	  weeks	  Scan	  PackageWhat Is The Role ofFeto-Maternal ServiceTuesday, June 18, 13
Screening	  AneuploidyTuesday, June 18, 13
Maternal Characteristics“A Priori Risk”Biophysical MarkersBiochemical MarkersEarly Screening for PETAdjusted Risk++Tuesday...
cteduE3(MoM)UnaffectedDown’s syndromeDown’s syndromeUnaffectedfectedDown’s syndrome UnaffectedAFP (MoM) uE3(MoM)Unaffected...
THREE SCREENING OPTIONS2nd TrimesterQuad1st TrimesterCombined Test1st and 2nd TrimesterFully Integrated TestSerum Integrat...
First Trimester Screening “The Combined Test”Maternal Age NT+ + B-hCG& PAPP-ATuesday, June 18, 13
1...9 10 11 12 13 14 15 16 17 18 19 20......4015 to 20wksBlood DrawQuadAFPhCGUe3InhibinSecond Trimester Screening “The QUA...
THREE SCREENING OPTIONS2nd TrimesterQuad1st TrimesterCombined Test1st and 2nd TrimesterFully Integrated TestSerum Integrat...
FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
0255075100FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
025507510075FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
02550751007585NT NT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“FirstTrimesterSecondTrimester1st & 2ndTrimester...
02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June ...
02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“95NT+PAPP-A&β-hCG“QUAD”FirstTrimesterSecondTrimester1st & 2nd...
02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“95NT+PAPP-A&β-hCG“QUAD”What	  if	  NT	  is	  Not	  Available?...
02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“9585NT+PAPP-A&β-hCG“QUAD”PAPP-A&β-hCGWhat	  if	  NT	  is	  No...
Nasal BoneTricuspid RegurgitationDuctus VenoususFigure 3 Four-chamber view illustrating an endocardial cushiondefect in wh...
Screening	  Pre-­‐eclampsiaTuesday, June 18, 13
Pathophysiology of PETImpaired Trophoblastic Invasion ofMaternal Spiral ArteriesPlacental hypoxiaRelease of Inflammatory cy...
782 Section VI Pregnancy and Coexisting Diseasehypertension and approaches 50% whtension develops before 32 weeks’these ca...
Figure 1. Trophoblasts are the first cells to differentiate from the fertilized egg in early pregnancy,becoming the outer ...
DecidualAreteriolopathyPlacental Pathology, Fetal, Neonatal and MaternalComplications in early and late onset PEFGRPerinat...
Maternal Characteristics“A Priori Risk”Biophysical MarkersBiochemical MarkersEarly Screening for PETAdjusted Risk++Tuesday...
Candidate screening tests for preeclampsia and IUGR5. Markers of insulin resistance•Tumor necrosis factor•Sex hormone–bind...
Early Screening for PETIndependentVariable Adjusted OR (95% CI)Adjusted OR (95% CI)Adjusted OR (95% CI)Adjusted OR (95% CI...
32history, uterine artery pulsatility index (UAPI), maternal mean arterial pressure(MAP), maternal serum pregnancy-associa...
Early Screening for PETBlood Pressure at 11-13 weeks9149 Pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%Mean Arterial Bloo...
Early Screening for PETHistoryMaternal AgeBMI (Kg/m2)Racial Origin•White•Black•Indian or PakistaniParous•No Previous PE•Pr...
ImpairedTrophoblasticInvasionPre-eclampsiaEarly Screening for PETPlacental Growth Factor,PAPP-A,PP13 at 11-13 wksTuesday, ...
Early Screening for PETCell-free Fetal DNA in Maternal BloodRelease of necroticplacental fragmentsImpairedTrophoblasticInv...
Early Screening for PETUaD mBP32centation is less advanced, the chance of any future preventative steps succeedingis incre...
HistoryMaternal AgeBMI (Kg/m2)Racial Origin•White•Black•Indian or PakistaniParous•No Previous PE•Previous PE•Maternal Hist...
Objective: to develop algorithms based on acombination of maternal factors, uterineartery PI, MAP and serum biomarkers toe...
Maternal	  age	  years	   	   	  Maternal	  weight	   kg	   	   	  Maternal	  height	   cm	   	   	  Racial	  origin	   	 ...
Receiver	  operating	  characteristic	  (ROC)	  curves	  in	  the	  prediction	  of	  early	  (left),	  intermediate	  (mi...
PREECLAMPSIAIn PET the incidence of adverse fetal and maternal short-term and long-term consequences are inversely relate...
Tuesday, June 18, 13
Kozer et al., First Trimester aspirin = 2.37 Oddsratio for GastroschisisAJOG 2002Tuesday, June 18, 13
❖FetalAnueploidy and other fetalAnomalies❖Pre-eclampsia❖Fetal Growth Restriction❖Preterm Labor❖Fetal Macrosomia❖Gestationa...
SMALL FOR GESTATIONALAGE FETUSES GA include constitutionally small and growth restricted FGR due to impaired placentatio...
PRETERM DELIVERYThe patient-specific risk for spontaneousdelivery before 34 weeks can be determinedby an algorithm combinin...
GESTATIONAL DIABETESMELLITUS Traditional screening at the end of the second trimester by aseries of independent maternal ...
FETAL MACROSOMIAScreening for macrosomia (birth weight abovethe 90th centile for gestational age at delivery)by a combinat...
Individualized Patient CareWhat Is The Role of Feto-Maternal ServiceTuesday, June 18, 13
An integrated first first trimester scan (11 – 13 weeks)combining data from maternal characteristics andhistorywithfinding...
THE NEW PYRAMID OFPRENATALCARETuesday, June 18, 13
oMost	  complications	  occur	  toward	  the	  end	  of	  pregnancy.oAdverse	  outcomes	  cannot	  be	  predictedTuesday, ...
Tuesday, June 18, 13
o Early estimation of patient-specific complications riskso Individualized patient and disease-specific approachTuesday, Jun...
“we should learn the past andresearch the present to predict thefuture”HippocratesTuesday, June 18, 13
ThanksThe studies and some of the slides are found on FMF webpage (k Nicholides)Tuesday, June 18, 13
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Current development in prenatal care - Hassan Nasrat

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Current development in Prenatal Care (JUCOG Jan 2013 meeting)

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Current development in prenatal care - Hassan Nasrat

  1. 1. CurrentDevelopment ofPrenatal CareProfessor Hassan Nasrat FRCS, FRCOGThe Fetal Medicine ClinicThe First ClinicTuesday, June 18, 13
  2. 2. oMost  complications  occur  toward  the  end  of  pregnancy.oAdverse  outcomes  cannot  be  predictedMinistry of Health Report, 1929- UKTuesday, June 18, 13
  3. 3. Major Complications•Hemorrhagic complications•Abnormal presentation and•Abnormal Lie•-----•--Tuesday, June 18, 13
  4. 4. •Changes Of The Nature Of ObstetricComplications•Current Obstetric Challenges❖ Fetal Anueploidy and other fetal Anomalies❖ Pre-eclampsia❖ Fetal Growth Restriction❖ Preterm Labor❖ Fetal Macrosomia❖ Gestational Diabetes❖ Others.....Tuesday, June 18, 13
  5. 5. How Can We Predict Complications ?Tuesday, June 18, 13
  6. 6. Background Risk (PRIORI RISK)AgeRacePrevious PTLPrevious PETPrevious AnomaliesUnderlying Medial DisordersOther Maternal CharacteristicsThe First Ante-NatalVisit+Tuesday, June 18, 13
  7. 7. Background Risk (PRIORI RISK)LOW RISK PATIENT HIGH RISK PATIENTTuesday, June 18, 13
  8. 8. Background Risk (PRIORI RISK)LOW RISK PATIENT HIGH RISK PATIENT❖ Most OfThose Complications Develop Late❖ Same Standard Of Care Regardless Of PotentialRisks❖ Complications Occur More Among Women WhoHas No Historical Risk Factors❖ The Importance Of Rationalizing Prenatal CareTuesday, June 18, 13
  9. 9. Define Patient Specific RiskHow Can We Predict Complications ?Individualized Patient CareTuesday, June 18, 13
  10. 10. Background Risk (PRIORI RISK)Tuesday, June 18, 13
  11. 11. DATA FROM ULTRASOUND SCANNING+Background Risk (PRIORI RISK)Tuesday, June 18, 13
  12. 12. DATA FROM ULTRASOUND SCANNINGFINDINGS OF BIOPHYSICALAND BIOCHEMICALTESTS++Background Risk (PRIORI RISK)Tuesday, June 18, 13
  13. 13. DATA FROM ULTRASOUND SCANNINGFINDINGS OF BIOPHYSICALAND BIOCHEMICALTESTS++➧Patient Specific RiskBackground Risk (PRIORI RISK)Tuesday, June 18, 13
  14. 14.  For  Every  Disorder  There  is  background  risk    (Priori  Risk)  Calculation  of  Patient  Specific  RISK   The  risk  may  increase  or  decrease  based  on  the  presence  (or  absence)  of  certain  marker  (s)E.g.❖Maternal Age > 35 Predict 20-30 % of DS❖Maternal Characteristics can Predict 30% of PETTuesday, June 18, 13
  15. 15. Screening  for  Risk  FactorsImportant  proper+es  of  a  screening  test  are  its  sensi+vity,  specificity,  and  predic+ve  values  nega+ve  and  posi+ve.Tuesday, June 18, 13
  16. 16. Screening  for  Risk  FactorsImportant  proper+es  of  a  screening  test  are  its  sensi+vity,  specificity,  and  predic+ve  values  nega+ve  and  posi+ve.The  sensi(vity   and  specificity   cannot   be  used  to  es+mate  the  probability  of  the  disease  in  an  individual.Tuesday, June 18, 13
  17. 17. Screening  for  Risk  FactorsImportant  proper+es  of  a  screening  test  are  its  sensi+vity,  specificity,  and  predic+ve  values  nega+ve  and  posi+ve.The  sensi(vity   and  specificity   cannot   be  used  to  es+mate  the  probability  of  the  disease  in  an  individual.Posi(ve   and   nega(ve   predic(ve   are   dependent   on   the  prevalence  of  the  diseaseTuesday, June 18, 13
  18. 18. Screening  for  Risk  FactorsImportant  proper+es  of  a  screening  test  are  its  sensi+vity,  specificity,  and  predic+ve  values  nega+ve  and  posi+ve.The  sensi(vity   and  specificity   cannot   be  used  to  es+mate  the  probability  of  the  disease  in  an  individual.Posi(ve   and   nega(ve   predic(ve   are   dependent   on   the  prevalence  of  the  diseaseThe  likelihood  ra(o  are  independent  of  disease  prevalence  and   integrate   the   sensi+vity   and   specificity   of   screening  tests  Tuesday, June 18, 13
  19. 19. The  likelihood  ra(o  Indicate by how much a given test resultincreases or decreases the probability ofdevelopinga condition.Tuesday, June 18, 13
  20. 20. Calculation  of  Patient  Specific  RISK  “Using  Positive  &  Negative  Likelihood  Ratio”The  Background“Priori  Risk”Tuesday, June 18, 13
  21. 21. Calculation  of  Patient  Specific  RISK  “Using  Positive  &  Negative  Likelihood  Ratio”×The  Background“Priori  Risk”Tuesday, June 18, 13
  22. 22. Calculation  of  Patient  Specific  RISK  “Using  Positive  &  Negative  Likelihood  Ratio”×The  Likelihood  ratio  as  Calculated  from  a  given  markerThe  Background“Priori  Risk”Tuesday, June 18, 13
  23. 23. Calculation  of  Patient  Specific  RISK  “Using  Positive  &  Negative  Likelihood  Ratio”×The  Likelihood  ratio  as  Calculated  from  a  given  markerThe  Background“Priori  Risk”Tuesday, June 18, 13
  24. 24. Calculation  of  Patient  Specific  RISK  “Using  Positive  &  Negative  Likelihood  Ratio”×The  Likelihood  ratio  as  Calculated  from  a  given  markera  new  priori  Posterior    Risk    For  the  next  test  The  Background“Priori  Risk”Tuesday, June 18, 13
  25. 25. 0.6 0.4 2.0LR=1.7 LR=10.6 LR=2.0AFP(MOM) UE3(MOM) hCG(MOM)Age Risk30 years1:900Likelihood RatioAFP UE3 hCG1.7 × 10.4 × 2.0× =AdjustedRisk1:25NormalDSCalculations  of  LRs  for  three  analytes.  At  a  MSAFP  level  of  0.6  MoM,  approximately  twice  as  many  fetuses  with  Down  syndrome  are  at  this  level  than  chromosomally  normal  fetuses.  Therefore,  the  LR  for  Down  syndrome  at  a  MSAFP  level  of  0.6  MoM  is  1.7.Patients  Specific  Risk  for  DSTuesday, June 18, 13
  26. 26.  Every woman has a background or apriori risk for any given disorder/complication. A new individual “patient-specific”risk is calculated by multiplying thepriori risk with a series of likelihoodratios obtained from screening tests.SummaryTuesday, June 18, 13
  27. 27. CurrentDevelopment inPrenatal CareTuesday, June 18, 13
  28. 28. Individualized Patient CarePrediction of Fetal Complications ?What Is The Role of Feto-Maternal ServiceTuesday, June 18, 13
  29. 29. ❖FetalAnueploidy and other fetalAnomalies❖Pre-eclampsia❖Fetal Growth Restriction❖Preterm Labor❖Fetal Macrosomia❖Gestational Diabetes❖ Others.....Tuesday, June 18, 13
  30. 30. The  11–13+6  weeks  Scan  PackageWhat Is The Role ofFeto-Maternal ServiceTuesday, June 18, 13
  31. 31. Screening  AneuploidyTuesday, June 18, 13
  32. 32. Maternal Characteristics“A Priori Risk”Biophysical MarkersBiochemical MarkersEarly Screening for PETAdjusted Risk++Tuesday, June 18, 13
  33. 33. cteduE3(MoM)UnaffectedDown’s syndromeDown’s syndromeUnaffectedfectedDown’s syndrome UnaffectedAFP (MoM) uE3(MoM)UnaffectedDown’s syndromeNuchal translucency (MoM)Down’s syndromeUnaffectedDown’s syndromePAPP-A (MoM)UnaffectedDown’s syndrome UnaffectedAFP (MoM) uE3(MoM)UnaffectedDown’s syndromeNuchal translucency (MoM)Down’s syndromeUnaffectedDown’s syndromePAPP-A (MoM)UnaffectedNuchal traUnaffectedUnaffectedInhibin-A (MoM)Down’s syndromePAPP-A (MoM)UnaffectedUnaffected Down’ssyndromefree ß9DownssyndromeUnaffectedInhibin-A (MoM)Unaffected Down’ssyndromefree ß-hCG (MoM)Down’s syndrome UnaffectedAFP (MoM) uE3(MoM)UnaffectedDown’s syndromeNuchal translucency (MoM)Down’s syndromeUnaffectedDownssyndromeUnaffectedDown’s syndromePAPP-A (MoM)UnaffectedUnaffected Down’ssyndromeUnaffectedD SyndromeUnaffectedD SyndromeD SyndromeUnaffectedUnaffected UnaffectedUnaffected D SyndromeD Syndrome D SyndromeTuesday, June 18, 13
  34. 34. THREE SCREENING OPTIONS2nd TrimesterQuad1st TrimesterCombined Test1st and 2nd TrimesterFully Integrated TestSerum IntegratedStepwise Sequential ContingentSequential ScreenTuesday, June 18, 13
  35. 35. First Trimester Screening “The Combined Test”Maternal Age NT+ + B-hCG& PAPP-ATuesday, June 18, 13
  36. 36. 1...9 10 11 12 13 14 15 16 17 18 19 20......4015 to 20wksBlood DrawQuadAFPhCGUe3InhibinSecond Trimester Screening “The QUAD Test”Tuesday, June 18, 13
  37. 37. THREE SCREENING OPTIONS2nd TrimesterQuad1st TrimesterCombined Test1st and 2nd TrimesterFully Integrated TestSerum IntegratedSequential ScreenContingent ScreenTuesday, June 18, 13
  38. 38. FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  39. 39. 0255075100FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  40. 40. 025507510075FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  41. 41. 02550751007585NT NT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  42. 42. 0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  43. 43. 0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCGFirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  44. 44. 0255075100758575NTAFP+Ue3&β-hCGNT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  45. 45. 02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  46. 46. 02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“95NT+PAPP-A&β-hCG“QUAD”FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  47. 47. 02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“95NT+PAPP-A&β-hCG“QUAD”What  if  NT  is  Not  Available?FirstTrimesterSecondTrimester1st & 2ndTrimesterTuesday, June 18, 13
  48. 48. 02550751007585NT NT+PAPP-A&β-hCG85AFP+Ue3&β-hCG&Inhibin“QUAD“9585NT+PAPP-A&β-hCG“QUAD”PAPP-A&β-hCGWhat  if  NT  is  Not  Available?FirstTrimesterSecondTrimester1st & 2ndTrimester“QUAD”Tuesday, June 18, 13
  49. 49. Nasal BoneTricuspid RegurgitationDuctus VenoususFigure 3 Four-chamber view illustrating an endocardial cushiondefect in which a ventricular (VSD) and atrial (ASD) septal defectare present. LA, left atrium; LV, left ventricle; RA, right atrium;RV, right ventricle.SUGGESTED USE OF FETALECHOCARDIOGRAPHY AS PART OF THEGENETIC SONOGRAM GIVEN CURRENTSCREENING TECHNOLOGIESAt present, common screening tests for trisomy 21 mayinclude any of the following: (1) first-trimester combinedNT and serum screening, (2) first-trimester combinedNT and serum screening plus second-trimester QUADscreening, (3) first-trimester serum and second-trimesterGenetic sonography as an adjunct to first-trimester NTand serum and/or second-trimester serum screeningWhen genetic sonography was first introduced in theearly 1990s it was an option for screening for trisomy21 in women less than 35 years of age for two reasons:(1) the detection rate was similar to or higher than thatusing MSAFP screening, and (2) the ultrasound exam onlyrequired measurements of the biparietal diameter, femurlength and nuchal skin fold (Table 1). However, as moreanalytes were added, second-trimester maternal serum(triple and QUAD) screening increased the detectionrate for trisomy 21, was easier to use, and did notrequire the specialized ultrasound skills needed to keepthe genetic sonogram comparable in terms of detectionrates (Table 2).Investigators have reported the use of genetic sono-graphy as an adjunct to other screening protocols.In 2001, Roberto Romero and I11reported offer-ing genetic sonography to women considered to beat moderate risk (1 : 190–1 : 1000) for trisomy 21Figure 4 Four-chamber view illustrating a ventricular septal defect (VSD) at the level of the inflow tracts. (a) B-mode image; (b) powerDoppler image confirming flow at the level of the VSD. LV, left ventricle; RV, right ventricle.Tuesday, June 18, 13
  50. 50. Screening  Pre-­‐eclampsiaTuesday, June 18, 13
  51. 51. Pathophysiology of PETImpaired Trophoblastic Invasion ofMaternal Spiral ArteriesPlacental hypoxiaRelease of Inflammatory cytokinesPlatelets and endothelial cellactivation and damageClinical symptoms of preeclampsiaFigure 1. Trophoblasts are the first cells to differentiate from the febecoming the outer layer of a blastocyst. They further differentiatephoblast and the outer syncytiotrophoblast. Trophoblast cells protimmune system.clear sugar from the blood and is often a precursor todemonstrated in active PE, and women with insulin reof developing PE during pregnancy.[66] It is also suggments of insulin resistance based on a single determinglucose could predict pre-eclampsia at least as well asfor prediction of pre-eclampsia, uterine artery DoppleSibai have proposed that pregnancies complicated witmetabolic syndrome (e.g. adiposity, increased insulin rexcess thrombin generation) and inflammatory signalsdeveloping pre-eclampsia.[99]Tuesday, June 18, 13
  52. 52. 782 Section VI Pregnancy and Coexisting Diseasehypertension and approaches 50% whtension develops before 32 weeks’these cases result in preterm deliverTherefore, such women require closedetection of preeclampsia (frequenserial evaluation of platelets and livegrowth (serial ultrasound).Preeclampsia should also be contional hypertension is severe becaupreterm delivery.11,20Preeclampsia is clearly a heteroge-neous condition for which the pathogenesis could bedifferent in women with various risk factors.11,20,21Thepathogenesis of preeclampsia in nulliparous women maybe different than that in women with preexisting vasculardisease, multifetal gestation, diabetes mellitus, or previousFIGURE 35-2. Various clinical and laboratory findings in women withpreeclampsia or atypical preeclampsia. CNS, Central nervous system;DIC, disseminated intravascular coagulopathy; HELLP, hemolysis,elevated liver enzymes, and low platelets.Excessiveweight gainCapillaryleakBloodpressureSymptomsFibrinolysisHemolysisDICLow platelets↑ Liver enzymesNausea/vomitingBleedingCNSEpigastricpainSevereMildNormalProteinuriaFacial edemaPulmonaryedemaAscitesPleuraleffusionsHELLPRenalfailure• Gestational hypertension plus ofollowing:• Symptoms of preeclampsia• Hemolysis• Thrombocytopenia (<100,000/mm• Elevated liver enzymes: two timthe normal value for aspartateand alanine transaminase (ALT)• Gestational proteinuria plus onfollowing:• Symptoms of preeclampsia• Hemolysis• Thrombocytopenia• Elevated liver enzymes• Early signs and symptoms of preeat <20 weeks• Late postpartum preeclampsia-ecpostpartum)CRITERIA FOR ATYPICAL PRTuesday, June 18, 13
  53. 53. Figure 1. Trophoblasts are the first cells to differentiate from the fertilized egg in early pregnancy,becoming the outer layer of a blastocyst. They further differentiate into two layers, the inner cytotro-phoblast and the outer syncytiotrophoblast. Trophoblast cells protect the fetus against the maternalimmune system.SyncytiotrophoblastCytotrophoblastUterine epitheliumof developing PE during pregnancy.[66] It is also suggested that simple assess-ments of insulin resistance based on a single determination of fasting insulin andglucose could predict pre-eclampsia at least as well as the current gold standardfor prediction of pre-eclampsia, uterine artery Doppler velocimetry.[103] Ness andSibai have proposed that pregnancies complicated with IUGR lack the maternalmetabolic syndrome (e.g. adiposity, increased insulin resistance, hyperlipidemia,excess thrombin generation) and inflammatory signals which prevent patients fromdeveloping pre-eclampsia.[99]SyncytrophoblastCytotrophoblastUterineepithelium•Maternal syndrome:BP with or withoutsystem dysfunction•Fetal syndrome:(FGR, reduced amnioticfluid, and abnormaloxygenation).Clinically can manifest as either a:The pathophysiology of early- onset PE may bedifferent than that of PE developing at termTuesday, June 18, 13
  54. 54. DecidualAreteriolopathyPlacental Pathology, Fetal, Neonatal and MaternalComplications in early and late onset PEFGRPerinatalDeathMaternal DeathTuesday, June 18, 13
  55. 55. Maternal Characteristics“A Priori Risk”Biophysical MarkersBiochemical MarkersEarly Screening for PETAdjusted Risk++Tuesday, June 18, 13
  56. 56. Candidate screening tests for preeclampsia and IUGR5. Markers of insulin resistance•Tumor necrosis factor•Sex hormone–binding globulin (SHBG) Adiponectin•Leptin1. Maternal Characteristics “Clinical risk factors screening”2. Placenta perfusion dysfunction–related tests• Uterine artery Doppler ultrasonography• Two-dimensional (2D) placenta imaging Three-dimensional (3D) placenta imaging• Placental volume• Placenta quotient• Placenta vascular indices3. Maternal serum analytes•Down syndrome markers•a-Fetoprotein (AFP)•Human chorionic gonadotropin (hCG) Estriol•Inhibin A•disintegrin and metalloproteases (ADAM) Placental protein 134. Endothelial dysfunction–related tests “Circulated angiogenic factors”•Placental growth factor (PlGF)•Soluble fms-like tyrosine kinase 1•Vascular endothelial growth factor (VEGF) Soluble endoglin (sEng)•Entholial cell adhesion molecules•Selectin6. Genomics and proteomicsTuesday, June 18, 13
  57. 57. Early Screening for PETIndependentVariable Adjusted OR (95% CI)Adjusted OR (95% CI)Adjusted OR (95% CI)Adjusted OR (95% CI)Adjusted OR (95% CI)Early PEEarly PE Late-PELate-PELate-PEMaternal Age -- 1.04 (1.00-1.07)1.04 (1.00-1.07)1.04 (1.00-1.07)BMI -- 1.10 (1.07-1.13)1.10 (1.07-1.13)1.10 (1.07-1.13)Racial Origin•White•Black•Indian or Pakistani•White•Black•Indian or Pakistani3.64(1.84-7.21)3.64(1.84-7.21) 2.97(1.98-4.46)2.97(1.98-4.46)2.97(1.98-4.46)•White•Black•Indian or Pakistani -- 2.66 (1.29-5.48)2.66 (1.29-5.48)2.66 (1.29-5.48)ParousParous•No Previous PE•Previous PE•Maternal Historyof PE0.31(0.14-0.71)0.31(0.14-0.71) 0.24(0.15-0.38)0.24(0.15-0.38)0.24(0.15-0.38)•No Previous PE•Previous PE•Maternal Historyof PE4.02(1.58-10.24)4.02(1.58-10.24) 2.18(1.24-3.83)2.18(1.24-3.83)2.18(1.24-3.83)•No Previous PE•Previous PE•Maternal Historyof PE8.70(2.77-27.33)8.70(2.77-27.33) ---Ovulation drugs 4.75(1.55-14.53)4.75(1.55-14.53) ---0102030405060708090100Early-PE Late-PE28.0034.00Detection Rate for FPR 5%9149 Pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%Maternal Characteristics“Priori Risk”RaceTuesday, June 18, 13
  58. 58. 32history, uterine artery pulsatility index (UAPI), maternal mean arterial pressure(MAP), maternal serum pregnancy-associated plasma protein-A levels (PAPP-A),and maternal serum placental growth factor levels (PlGF) in screening for pre-ec-lampsia in the first trimester.[39, 107, 108, 110] The specific maternal factors thatappear to play the most significant role in adjusting the risk of pre-eclampsia arematernal BMI, age, ethnicity, smoking and parity. In a study, which included 7,797patients, the combination of these parameters predicted early severe pre-eclamp-sia in 93% cases, late pre-eclampsia in 36% of the cases, and 18% of the casesof gestational hypertension with a 5% false positive rate.In comparison, using maternal history alone predicts only 30% of early severe pre-eclampsia and 20% of late pre-eclampsia for a 5% false positive rate.Measuring uterine artery PI using Doppler at 11-13+6 weeks’ gestationIdentification of the uterine arteries begins by obtaining a sagittal view of the loweruterine segment and the cervix. The cervical canal is visualized and the endocervixis identified at thejunction of the canaland the lower uterinesegment. The uterineartery is generally foundin the paracervical tissueat the level of the endo-cervix. Therefore, thetransducer is directed tothis region and the uter-ine artery may be foundthere with the aid ofcolor Doppler.Figure 4. Color Doppler ofuterine arteries (upper) anduterine artery waveform(lower) obtained using theconditions described in thetext. Images courtesy ofCathy Downing, Fetal Medi-cine Foundation, USA.32centation is less advanced, the chance of any future preventative steps succeedingis increased.The Fetal Medicine Foundation has evaluated the utility of combining maternalhistory, uterine artery pulsatility index (UAPI), maternal mean arterial pressure(MAP), maternal serum pregnancy-associated plasma protein-A levels (PAPP-A),and maternal serum placental growth factor levels (PlGF) in screening for pre-ec-lampsia in the first trimester.[39, 107, 108, 110] The specific maternal factors thatappear to play the most significant role in adjusting the risk of pre-eclampsia arematernal BMI, age, ethnicity, smoking and parity. In a study, which included 7,797patients, the combination of these parameters predicted early severe pre-eclamp-sia in 93% cases, late pre-eclampsia in 36% of the cases, and 18% of the casesof gestational hypertension with a 5% false positive rate.In comparison, using maternal history alone predicts only 30% of early severe pre-eclampsia and 20% of late pre-eclampsia for a 5% false positive rate.Measuring uterine artery PI using Doppler at 11-13+6 weeks’ gestationIdentification of the uterine arteries begins by obtaining a sagittal view of the loweruterine segment and the cervix. The cervical canal is visualized and the endocervixis identified at thejunction of the canaland the lower uterinesegment. The uterineartery is generally foundin the paracervical tissueat the level of the endo-cervix. Therefore, thetransducer is directed tothis region and the uter-ine artery may be foundthere with the aid ofcolor Doppler.Figure 4. Color Doppler ofuterine arteries (upper) anduterine artery waveform(lower) obtained using theconditions described in thetext. Images courtesy ofCathy Downing, Fetal Medi-cine Foundation, USA.Early Screening for PETUterine Artery 11-13 weeks9149 Pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%Tuesday, June 18, 13
  59. 59. Early Screening for PETBlood Pressure at 11-13 weeks9149 Pregnancies; Early-PE 0.5% Late-PE 1.5% GH 1.7%Mean Arterial Blood Pressure =Diastolic BP+ (Systolic BP- Diastolic BP)/334In clinical practice MAP measurement in the first trimester may not make a clinicalimpact in isolation but could be suitable for use with other markers, including ma-ternal serum markers, to improve the accuracy for estimating risk of pre-eclampsia.Already it has been shown following a large prospective study that maternal vari-ables such as ethnic origin, body mass index, and personal history of PE, combinedwith MAP at 11+0 to 13+6 weeks is able to identify a group at high risk for pre-eclampsia.[105]How MAP is measuredThe Fetal Medicine Foundation recommends the following protocol for themeasurement of blood pressure (see also the FMF’s automatic calculator onhttps://courses.fetalmedicine.com/calculator/map?locale=en). The measurementshould be made when the gestational age is between 11 and 13+6 weeks andwhen the crown rump length is between 45 and 84 mm.Figure 5. Measurement ofmean arterial pressure (MAP).Tuesday, June 18, 13
  60. 60. Early Screening for PETHistoryMaternal AgeBMI (Kg/m2)Racial Origin•White•Black•Indian or PakistaniParous•No Previous PE•Previous PE•Maternal History of PEHistory of BPOvulation drugs32Moving screening for pre-eclampsia to the first trimester appears to improve thedetection rate. Furthermore, since this is done at a time when the process of pla-centation is less advanced, the chance of any future preventative steps succeedingis increased.The Fetal Medicine Foundation has evaluated the utility of combining maternalhistory, uterine artery pulsatility index (UAPI), maternal mean arterial pressure(MAP), maternal serum pregnancy-associated plasma protein-A levels (PAPP-A),and maternal serum placental growth factor levels (PlGF) in screening for pre-ec-lampsia in the first trimester.[39, 107, 108, 110] The specific maternal factors thatappear to play the most significant role in adjusting the risk of pre-eclampsia arematernal BMI, age, ethnicity, smoking and parity. In a study, which included 7,797patients, the combination of these parameters predicted early severe pre-eclamp-sia in 93% cases, late pre-eclampsia in 36% of the cases, and 18% of the casesof gestational hypertension with a 5% false positive rate.In comparison, using maternal history alone predicts only 30% of early severe pre-eclampsia and 20% of late pre-eclampsia for a 5% false positive rate.Measuring uterine artery PI using Doppler at 11-13+6 weeks’ gestationIdentification of the uterine arteries begins by obtaining a sagittal view of the loweruterine segment and the cervix. The cervical canal is visualized and the endocervixis identified at thejunction of the canaland the lower uterinesegment. The uterineartery is generally foundin the paracervical tissueat the level of the endo-cervix. Therefore, thetransducer is directed tothis region and the uter-ine artery may be foundthere with the aid ofcolor Doppler.Figure 4. Color Doppler ofuterine arteries (upper) anduterine artery waveform(lower) obtained using theconditions described in thetext. Images courtesy ofCathy Downing, Fetal Medi-cine Foundation, USA.MaternalPriori Risk + UaD mBP+Tuesday, June 18, 13
  61. 61. ImpairedTrophoblasticInvasionPre-eclampsiaEarly Screening for PETPlacental Growth Factor,PAPP-A,PP13 at 11-13 wksTuesday, June 18, 13
  62. 62. Early Screening for PETCell-free Fetal DNA in Maternal BloodRelease of necroticplacental fragmentsImpairedTrophoblasticInvasionPlacental HypoxiaEndothelial cellactivationTuesday, June 18, 13
  63. 63. Early Screening for PETUaD mBP32centation is less advanced, the chance of any future preventative steps succeedingis increased.The Fetal Medicine Foundation has evaluated the utility of combining maternalhistory, uterine artery pulsatility index (UAPI), maternal mean arterial pressure(MAP), maternal serum pregnancy-associated plasma protein-A levels (PAPP-A),and maternal serum placental growth factor levels (PlGF) in screening for pre-ec-lampsia in the first trimester.[39, 107, 108, 110] The specific maternal factors thatappear to play the most significant role in adjusting the risk of pre-eclampsia arematernal BMI, age, ethnicity, smoking and parity. In a study, which included 7,797patients, the combination of these parameters predicted early severe pre-eclamp-sia in 93% cases, late pre-eclampsia in 36% of the cases, and 18% of the casesof gestational hypertension with a 5% false positive rate.In comparison, using maternal history alone predicts only 30 % of early severe pre-eclampsia and 20 % of late pre-eclampsia for a 5% false positive rate.Measuring uterine artery PI using Doppler at 11-13+6 weeks’ gestationIdentification of the uterine arteries begins by obtaining a sagittal view of the loweruterine segment and the cervix. The cervical canal is visualized and the endocervixis identified at thejunction of the canaland the lower uterinesegment. The uterineartery is generally foundin the paracervical tissueat the level of the endo-cervix. Therefore, thetransducer is directed tothis region and the uter-ine artery may be foundthere with the aid ofcolor Doppler.Figure 4. Color Doppler ofuterine arteries (upper) anduterine artery waveform(lower) obtained using theconditions described in thetext. Images courtesy ofCathy Downing, Fetal Medi-cine Foundation, USA.+ PLGP+Tuesday, June 18, 13
  64. 64. HistoryMaternal AgeBMI (Kg/m2)Racial Origin•White•Black•Indian or PakistaniParous•No Previous PE•Previous PE•Maternal History ofPEHistory of BPOvulation drugsEarly Screening for PET10,000 pregnancies600 pregnanciesLate-PE75/150Early-PE45/5020%Screen +ve6%32lampsia in the first trimester.[39, 107, 108, 110] The specific maternal factors thatappear to play the most significant role in adjusting the risk of pre-eclampsia arematernal BMI, age, ethnicity, smoking and parity. In a study, which included 7,797patients, the combination of these parameters predicted early severe pre-eclamp-sia in 93% cases, late pre-eclampsia in 36% of the cases, and 18% of the casesof gestational hypertension with a 5% false positive rate.In comparison, using maternal history alone predicts only 30 % of early severe pre-eclampsia and 20 % of late pre-eclampsia for a 5% false positive rate.Measuring uterine artery PI using Doppler at 11-13+6 weeks’ gestationIdentification of the uterine arteries begins by obtaining a sagittal view of the loweruterine segment and the cervix. The cervical canal is visualized and the endocervixis identified at thejunction of the canaland the lower uterinesegment. The uterineartery is generally foundin the paracervical tissueat the level of the endo-cervix. Therefore, thetransducer is directed tothis region and the uter-ine artery may be foundthere with the aid ofcolor Doppler.Figure 4. Color Doppler ofuterine arteries (upper) anduterine artery waveform(lower) obtained using theconditions described in thetext. Images courtesy ofCathy Downing, Fetal Medi-cine Foundation, USA.Tuesday, June 18, 13
  65. 65. Objective: to develop algorithms based on acombination of maternal factors, uterineartery PI, MAP and serum biomarkers toestimate patient-specific risks for PE at:➡Early (< 34Weeks),➡Intermediate (34-37Weeks)And➡Late (>37Weeks)Tuesday, June 18, 13
  66. 66. Maternal  age  years      Maternal  weight   kg      Maternal  height   cm      Racial  origin      Past  Obstetric  and  Medical  History:     Pre-­‐existing  diabetes  mellitus  type  I           Chronic  hypertension           Cigarette  smoker  in  this  pregnancy           Systemic  lupus  erythematosus           Family  history  of  preeclampsia      Current  Obstetric  History      Method  of  conception   Spontaneous          IVF          Ovulation  drugs  without  IVF  Obstetric  history   Parity  &  Previous  history  of  PE  U/S  DataFetal  crown-­‐rump  length   mm      Uterine  artery  PI   MoM      Mean  arterial  pressure   MoM      Maternal  serum  PAPP-­‐A   MoM      Maternal  serum  PlGF  MoM  (placental  growth  factor  )    Biochemical  DataMaternal  serum  PAPP-­‐A   MoM      Maternal  serum  PlGF  MoM  (placental  growth  factor  )    Tuesday, June 18, 13
  67. 67. Receiver  operating  characteristic  (ROC)  curves  in  the  prediction  of  early  (left),  intermediate  (middle)  and  late  pre-­‐eclampsia  (PE)  (right)  by  maternal  factors  only  (  .  .  .  .  .  .  .)  and  by  a  combination  of  maternal  factors,  biochemical  and  biophysical  markers  (____)Early  PE    (<  34  wks)   Intermediate  (PE  34-­‐37  wks) Late  (PE  >37  wks)Detectionrat(%)33.0%24.5%27.8%80%91.0%60.0%Tuesday, June 18, 13
  68. 68. PREECLAMPSIAIn PET the incidence of adverse fetal and maternal short-term and long-term consequences are inversely related tothe gestational age at the onset of the disease.Algorithms which combine maternal characteristics,mean arterial pressure, uterine artery Doppler andbiochemical tests at 11 to 13 weeks could potentiallyidentify about 90, 80 and 60% of pregnancies thatsubsequently develop early (before 34 weeks), intermediate(34–37 weeks) and late (after 37 weeks) preeclampsia, for afalse positive rate of 5% (Akolekar et al., 2011b).Tuesday, June 18, 13
  69. 69. Tuesday, June 18, 13
  70. 70. Kozer et al., First Trimester aspirin = 2.37 Oddsratio for GastroschisisAJOG 2002Tuesday, June 18, 13
  71. 71. ❖FetalAnueploidy and other fetalAnomalies❖Pre-eclampsia❖Fetal Growth Restriction❖Preterm Labor❖Fetal Macrosomia❖Gestational DiabetesTuesday, June 18, 13
  72. 72. SMALL FOR GESTATIONALAGE FETUSES GA include constitutionally small and growth restricted FGR due to impaired placentation, genetic disease orenvironmental damage is associated with increased perinataldeath and handicap Algorithms which combine maternal characteristics, meanarterial pressure, uterine artery Doppler and themeasurement of various placental products in maternalblood at 11 to 13 weeks could potentially identify, at a falsepositive rate of 10%, about 75% of pregnancies withoutpreeclampsia delivering SGA neonates before 37 weeks and45% of those delivering at term(Karagiannis et al., 2011)Tuesday, June 18, 13
  73. 73. PRETERM DELIVERYThe patient-specific risk for spontaneousdelivery before 34 weeks can be determinedby an algorithm combining maternalcharacteristics and obstetric history (Beta et al.,2011).sonographic measurement of cervical length at11 to 13 weeks can modifies the priori risk ofspontaneous early delivery (Greco et al., 2011).Tuesday, June 18, 13
  74. 74. GESTATIONAL DIABETESMELLITUS Traditional screening at the end of the second trimester by aseries of independent maternal characteristics is poor with adetection rate of about 60%, at a false positive rate of 30 to 40%(Waugh et al., 2007). Algorithms which combine maternal characteristics and maternalserum levels of adiponectin, an adipocyte-derived polypeptide, and sexhormone binding globulin, a liver-derived glycoprotein, at 11 to 13weeks could potentially identify about 75% of pregnancies thatsubsequently develop GDM, for a false positive rate of 20% (Nanda etal., 2011). Additionally, the diagnosis of GDM can be made in the first trimester byappropriate adjustments to the traditional criteria of the oral glucosetolerance test (Plasencia et al., 2011).Tuesday, June 18, 13
  75. 75. FETAL MACROSOMIAScreening for macrosomia (birth weight abovethe 90th centile for gestational age at delivery)by a combination of maternal characteristicsand obstetric history with fetal NT andmaternal serum- free ß-hCG and PAPP-A at 11to 13 weeks could potentially identify, at a falsepositive rate of 10%, about 35% of women whodeliver macrosomic neonates (Poon et al., 2011).Tuesday, June 18, 13
  76. 76. Individualized Patient CareWhat Is The Role of Feto-Maternal ServiceTuesday, June 18, 13
  77. 77. An integrated first first trimester scan (11 – 13 weeks)combining data from maternal characteristics andhistorywithfindingsof biophysicalandbiochemicaltestscandefinethepatient-specificriskforawidespectrumofpregnancycomplications.Tuesday, June 18, 13
  78. 78. THE NEW PYRAMID OFPRENATALCARETuesday, June 18, 13
  79. 79. oMost  complications  occur  toward  the  end  of  pregnancy.oAdverse  outcomes  cannot  be  predictedTuesday, June 18, 13
  80. 80. Tuesday, June 18, 13
  81. 81. o Early estimation of patient-specific complications riskso Individualized patient and disease-specific approachTuesday, June 18, 13
  82. 82. “we should learn the past andresearch the present to predict thefuture”HippocratesTuesday, June 18, 13
  83. 83. ThanksThe studies and some of the slides are found on FMF webpage (k Nicholides)Tuesday, June 18, 13

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