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/ [email protected]