FetalAnaemiaandIntrauterineTransfusion

MrWilliamDennesPhDFRCOGConsultantObstetrician,SpecialistinFetalMedicine

QueenCharlotte’sandChelseaHospital

LondonW120HS

SouthEastCoastRegionalTransfusionCommitteeEducationSymposium

Wednesday26February2020

FetalAnaemia

•  Clinicalpresentation:–  ImmuneFetalHydrops

–  (Non-immuneFetalHydrops)

•  ManagementFetalanaemia

– MCAassessment

–  FetalBloodsampling/IntrauterineTransfusion

•  CaseStudies

Clinicalpresentation–Fetalanaemia:FetalHydrops:

•  Immuneandnon-immuneFetalhydrops

•  Abnormalfluidcollectioninatleasttwodifferentfetal

compartments:

–  Pericardialeffusion–  Pleuraleffusion

–  Ascites–  Skinoedema(>5mm)

–  Polyhydramnios

–  Thickenedplacenta(>6cm)

–  Cardiacfailure

–  IUD

ImmuneFetalHydrops:

ResultofcirculatingmaternalABagainst(fetal)redcellantigens(Red

cellisoimmunization)

•  >100 Red cell antigens, but isoimmunization associated with <30:

–  Typically: •  anti-D, anti-C, anti-Kell, anti-E

–  Rarely: •  anti-M, anti-N, anti-S

Redcelliso-immunization:•  15% of Antenatal population Rh

Negative

•  Routine pregnancy AB screen – 12 and 28 week

•  Rh negative patient – cfDNA for fetal genotype (IBGRL Bristol)

•  If Rh positive fetus: Anti-D prophylaxis at 28 weeks (and after any sensitising event)

•  cfDNA now available for Kell, C, e and C

Redcelliso-immunization:Assessment

Nicolaides et al. Fetal haemoglobin measurement in the assessment of red cell isoimmunisation. Lancet 1988;1:1073-5.

Normal Hb

Hydropic

Moderate anaemia

Redcelliso-immunization:Assessment

•  Fetal Anaemia - decreased blood viscosity •  Increased venous return + preload – increased

cardiac output •  Increased arterial + venous blood flow velocities •  MCA-PSV useful method to assess anaemia •  Low false positive rate

Mari G. Non-invasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloinmunization. N Eng J Med 2000;342:9-14.

Red cell isoimmunization: management

FBS / IUT

>15 IU

Severe Maternal history

MCA Doppler PSV >2 SD’s

Expectant

Rh antibodies

<15 IU (or1:128)

None / Mild

Fetal Rh group

Red cell isoimmunization: management•  FetalBloodsampling/Intra-uterineTransfusion:

–  Cordocentesis,Intrahepaticvein,intracardiac

–  Outpatientprocedure–FetalMedicineUnit

–  Consent-1-2%procedure–relatedloss(PPROM/Fetal

bradycardia)

–  PreoperativeIVAB

–  Ultrasoundguidance

–  Aseptictechnique

–  LocalAnaestheticinfiltration

–  17Gaugeneedle(1.4mmdiameter)

Red cell isoimmunization: management

•  Intra-uterineFetalBloodsample:

–  From16weeksofpregnancy

–  Transplacentalortransamniotic

–  Samplesite:

•  Intrahepaticvein•  UmbilicalCordinsertion

•  Freeloop

•  Intracardiac

–  1mLsample–immediateresultinFetal

MedicineunitbyHaematologyteamor

Haemacue.

Red cell isoimmunization: management•  IntrauterineTransfusion:

–  TransfuseORhNegative,packedcells(HCT

>85%),irradiated,CMVnegative,KellNegative

–  Rate–10-15ml/min

–  MonitorFH

–  Volume–dependentonHCTandfetalHb:

–  RepeatFBSposttransfusion

–  PairedsamplestoHaematologydepartment

forformalFBC.

Gestationalage: Volumetotransfuse:

16-18weeks 5ml

20weeks 20ml

>20weeks 20mL+10ml/weekofgestationtoamaxof100ml

Red cell isoimmunization: timing of subsequent transfusions•  InitialdecisionforIUTbasedon:

–  Hydrops

–  MCAPSV

•  TimingofSubsequentIUT:

–  MCApredictiveofsevereanaemiafor2nd

(butnotthe3rdtransfusion(foraDRof

95%,MCAPSV):FPR

•  1stTransfusion 14%

•  2ndTransfusion 37%

•  3rdTransfusion 90%

–  Anticipaterateofdecreaseof0.4g/dL/day

–  EmpiricallyIUTevery2-3weeks

Nicolaides et al. PredictionofseverefetalanemiainredbloodcellalloimmunizationafterpreviousintrauterinetransfusionsAmJournalofObstetricsandGynecology(2006)195,1550–6

Red cell isoimmunization: timing and mode of delivery•  Aimtomanage/resolvehydrops

priortodelivery

•  Nocontraindicationtovaginal

delivery(deliveronstandard

obstetricindications)

•  Aimfordelivery34-36weeks

(basedongoodneonatal

outcomes/limitationsofMCA

data)

Non-ImmuneFetalHydrops:•  Structuralabnormalities:

–  Cardiac-HLHS,PA,arrhythmia(SVT,WPW)

–  Pulmonary–CCAM,CDH

•  Chromosomalabnormalities(X-,T13,T18,T21)

•  Geneticsyndromes

–  Arthrogryposis,TS

•  Haematologicaldisorders:

–  FailuretomanufactureHb(a-thalassaemia)

–  Fetalhaemorrhage(ICH)

–  Haemolysis(G6PD)

•  Infection:

–  Bonemarrowdestruction(ParvovirusB19,CMV,Toxoplasmosis)

•  MCDATwins-TTTS

Non-ImmuneFetalHydrops:•  History:

–  FHofMetabolicdisorders

–  Recentinfection/exposure

•  Investigations:

–  MaternalBlood:

•  BloodGroup,KleihauerandAB

•  FBCandelectrophoresis

•  Viralscreen–Toxoplasma,CMV,Rubella,Parvovirus

–  US/S(tertiaryreferral):

•  Detailedultrasoundscan

•  FetalEcho

•  MCADoppler

•  FBS(Fetal-FBC,BloodGroup,karyotype,Viralscreen)

–  Offerkaryotype(10-20%riskofaneuploidy)

Non-ImmuneFetalHydrops:•  Management:

–  Dependentonaetiology–  Cardiacmalformation:verypoorprognosisifhydropssecondarytostructural

(cardiacmalformation).OfferTOP.

–  Cardiacarrhythmia:maternaltherapy(Digoxin/Flecainide)

–  Fetalanaemia-IUT

–  Terminationofpregnancy

–  Timingofdelivery–maybeassociatedwithpretermdelivery(secondaryto

polyhydramnios,oriatrogenic–PET).

–  Modeofdelivery–optimalmoderemainsunclear.AimforSVD.

–  Perinatalmortalityrate–40-90%

Casestudy♯1:•  36yearold

•  G3P2+0

•  AdmittedtoDGH29+6/40:

–  Oedema,hypertension,proteinuria–“feeling

unwell”

–  Investigations:

•  NormalFBC,LFTandrenalfunction

•  ABRhpositive–noatypicalAB(at28weeks)

–  Management:

•  Admitted,routineObs,CTG

•  US/S:Widespreadhydrops,placentamegaly,pleural

andpericardialeffusions,skinoedema.

•  MCA95cm/s(>1.5MoM)

Casestudy♯1:

•  Furtherhistory–recentviralinfection

•  Diagnosis–ParvovirusB19infectionwithmaternal

PET

•  Management:

–  FBS/IUT

–  InitialHb–3.8g/dL(BloodsentforTORCH,Karyotype)

–  Transfusion–120ml.PostprocedureHb–9.5g/dL

–  PlannedrepeatIUT

–  Returnedtoreferringhospital

–  AbnormalCTG–EmergencyLSCS.Neonataladmission

–  ConfirmedParvovirus

–  BW–1980g.

Casestudy♯2:

•  34yearold

•  G1P0

•  LowriskfirsttrimesterCombinedscreening

•  Routineanomalyscan(22weeks):

–  FetalSupraventricularTachycardia–  Noevidenceofhydrops

•  Management:

–  FetalEcho

–  MaternalECG

–  CommencedonDigoxin250μgTDS

Casestudy♯2:•  Followupscan–24weeks

–  PersistentSVT

–  ModerateHydrops

–  (NormalMCA)

•  Followupscan–27weeks

–  Hydropsresolved

–  NormalSR(Rate140bpm)

•  ContinuedonMaternalDigoxin

•  Outcome:

–  IOLat40weeks(MaternalPET)

–  NormalSVD–Femaleinfant3572g(~50th

centile)

–  Neonatal–Propranololto6monthsofage.

AnyQuestions?

FetalAnaemiaSummary:

•  ImmuneHydrops:

–  AssessHistory,MaternalABscreen,DetailedUS/S+MCA

–  FBS/IUTifMCA>1.5MoM

–  FU:IUT2weeks

•  Non-immuneHydrops:

–  Infection:ParvovirusB19,CMV,Toxoplasmosis.

–  MCDATwins–TTTS

–  FBS/IUTifMCA>1.5MoM

www.fetalmedicine.com/fmf/www.kch.nhs.uk/ william.dennes@nhs.net