CASE A

CASE A Farah is 16 and at school. She was on the COCP for contraception but missed some and discovered she was pregnant at 18 weeks. At 30 weeks pregnant she attends her antenatal check with her midwife who checks her blood pressure and finds that it is high 140/95. She also notes that on abdominal palpation the symphysis fundal height is 25 cm. Consider the issues relevant to her pregnancy and presenting complaintWhat are the issues here?Age 16 ( teenage pregnancy)Discovery of pregnancy at 18 week ( late booker)BP high 140/95 @ 30 week pregnancySFH measured 25cm @ 30 week of pregnancyHypertension affects 10-15% of all pregnanciesMild pre-eclampsia affects 10% of primigravid womenSevere pre-eclampsia affects 1% of primigravid womenEclampsia affects 1/2000 pregnanciesDeath from eclampsia = 2%Pre-eclampsia is the commonest cause of iatrogenic prematurityUp to 25% of antenatal admissions are due to hypertension

3What problem could she have?Pre-existing hypertension

Pregnancy Induced Hypertension (PIH)

Pre-eclampsiaNormal BPBlood pressure (BP) proportional to systemic vascular resistance and cardiac outputPregnancy VasodilatationBP falls in early pregnancyNadir reached at 22-24 weeksSteady rise until TermBP falls after delivery but subsequently rises and peaks at day 3-4 P/N

4Hypertension140/90 mmHg on 2 occasions

DBP >110 mmHg

ACOG - >30/15 mmHg compared to booking BP

Pre-existing HypertensionDiagnosis prior to pregnancyLikely if hypertension in early pregnancy (PET / PIH diseases of second half of pregnancy)May be retrospective diagnosis if BP has not returned to normal within 3 months of deliveryConsider secondary causes - renal / cardiac, Cushings, Conns, PhaeochromocytomaRisks include PET (X2), IUGR and abruptionPIHSecond half of pregnancyResolves within 6/52 of deliveryNo proteinuria or other features of pre-eclampsiaBetter outcomes than pre-eclampsia15% progression to pre-eclampsia - depends on gestationRate of recurrence is highPre-eclampsiaHypertension

Proteinuria (0.3g/l or 0.3g/24h)

Oedema

Absence does not exclude the diagnosisPre-eclampsiaA pregnancy-specific multi-system disorder with unpredictable, variable and widespread manifestations May be asymptomatic at time of first presentationDiffuse vascular endothelial dysfunction widespread circulatory disturbanceRenal / Hepatic / Cardiovascular / Haematology / CNS / PlacentaPathogenesisGenetic predisposition

Stage 1 - abnormal placental perfusionBefore 20 weeksStage 2 - maternal syndrome After 20 weeksPathogenesisAbnormal placentation and trophoblast invasion failure of normal vascular remodelling Spiral arteries fail to adapt to become high capacitance, low resistance vesselsPlacental ischaemia widespread endothelial damage and dysfunctionMechanism unclear (??oxidative stress / PGI2 : TXA2 imbalance / NO)Endothelial Activation Capillary Permeability Expression of CAM Prothrombotic Factors Platelet aggregrationVasoconstrictionNormal PlacentationPre-eclampsia

Non- Pregnant12A Multi-system DisorderCNSRenalHepaticHaematological PulmonaryCardiovascularPlacentalCNS DiseaseEclampsiaHypertensive encephalopathyIntracranial haemorrhageCerebral OedemaCortical BlindnessCranial Nerve Palsy

Renal disease GFRProteinuria serum uric acid (also placental ischaemia) creatinine / potassium / ureaOliguria /anuriaAcute renal failureacute tubular necrosisrenal cortical necrosis

Liver DiseaseEpigastric/ RUQ painAbnormal liver enzymesHepatic capsule rupture

HELLP SyndromeHaemolysis, Elevated Liver Enzymes, Low Plateletshigh morbidity/ mortalityHaematological Disease Plasma VolumeHaemo-concentrationThrombocytopeniaHaemolysisDisseminated Intravascular CoagulationCardiac / Pulmonary DiseasePulmonary oedema ARDSiatrogenicdisorder related

Pulmonary Embolus

High mortalityPlacental DiseaseIntrauterine growth restriction (IUGR)

Placental Abruption

Intrauterine Death

SymptomsHeadache Visual disturbanceEpigastric / RUQ painNausea / vomitingRapidly progressive oedema

Considerable variation in timing, progression and order of symptomsSignsHypertensionProteinuriaOedemaAbdominal tendernessDisorientationSGAIUDHyper-reflexia / involuntary movements / clonusInvestigationsUrea & ElectrolytesSerum UrateLiver Function TestsFull Blood CountCoagulation ScreenCTGUltrasound - biometry, AFI, DopplerManagementAssess risk at bookingHypertension < 20 weeks - look for secondary causeAntenatal screening - BP, urine, MUADTreat hypertensionMaternal & fetal surveillanceTiming of DeliveryPIH can be managed as O/P in Day Care UnitRisk FactorsMaternal Age (>40 years 2X)Maternal BMI (>30 2X) Family History (20-25% if mother affected, up to 40% if sister)Parity (first pregnancy 2-3X)Multiple pregnancy (Twins 2X)Previous PET (7X)Molar Pregnancy / Triploidy

Multiparous women develop more severe diseaseMedical Risk FactorsPre-existing renal diseasePre-existing hypertensionDiabetes MellitusConnective Tissue DiseaseThrombophilias (congenital / acquired)Predicting Pre-eclampsia

Normal MUADNotchMaternal Uterine Artery Doppler 20 - 24 weeksAntenatal ScreeningWhen to refer to AN DCU?BP 140/90(++) proteinuria oedemasymptoms - esp persistent headache

For every 1000 Low-risk patients:100 hypertensive60 normal - 20 will return 20 DCU follow up - 10 admitted20 admittedWhen to admit?BP >170/110 OR >140/90 with (++) proteinuria

Significant symptoms - headache / visual disturbance / abdominal pain

Abnormal biochemistry

Significant proteinuria - >300mg / 24h

Need for antihypertensive therapy

Signs of fetal compromiseInpatient AssessmentBlood Pressure - 4 hourly

Urinalysis - daily

Input / output fluid balance chart

24 hour urine collection - if proteinuria on urinalysis

Bloods - FBC, U&Es, Urate, LFTs. Minimum X2 per weekFetal SurveillanceFetal Movements

CTG - daily

UltrasoundBiometryAmniotic Fluid IndexUmbilical Artery Doppler

NormalAEDFREDFTreatment of HypertensionTreat regardless of aetiologyWith MAP 150 mmHg there is significant risk of cerebral haemorrhageMost treat if BP 150/100 mmHgBP 170/110 mmHg requires immediate RxAim for 140-150/90-100 mmHgControl of blood pressure does not reduce the risk of developing pre-eclampsia

Treatment of HypertensionMode of ActionStarting DoseMaximum DoseContra-indicationsBreast FeedingMethyl DopaCentrally acting agonist250mg bd1 gram tdsDepressionYesLabetolol + antagonist100mg bd600mg qidAsthmaYesNifedipine SRCa channel antagonist10mg bd40mg bdYesHydralazineVasodilator25mg tds75mg qidYes(Avoid Diuretics / ACE Inhibitors)When to Deliver?The only cure for pre-eclampsia is deliveryMother must be stablised before deliveryConsider expectant management if pre-termMost women delivered within 2 weeks of diagnosis

Indications for DeliveryTerm gestationInability to control BPRapidly deteriorating biochemistry / haematologyEclampsiaOther CrisisFetal Compromise - REDF, abnormal CTG

Crises in Pre-eclampsiaEclampsiaHELLP syndromePulmonary OedemaPlacental AbruptionCerebral HaemorrhageCortical BlindnessDICAcute Renal FailureHepatic RuptureSteroidsPromote fetal lung surfactant production neonatal respiratory distress syndrome (RDS) by up to 50% if administered 24-48h before delivery

Administer up to 36 weeksOnly significant effects up to 34 weeks. Proven benefit up to 1 weekBetamethasone preferred to Dexamethasone

1 course = 12mg Betamethasone IM X2 injections 24 hours apart36Eclampsia37EclampsiaTonic-clonic (grand mal) seizure occuring with features of pre-eclampsia>1/3 will have seizure before onset of hypertension / proteinuriaAnte-partum (38%) / Intra-partum (16%) / post-partum (44%)More common in teenagersAssociated with ischaemia / vasospasmManagement of Severe PET / EclampsiaControl BP

Stop / Prevent Seizures

Fluid Balance

Delivery39AntihypertensivesIV LabetololIV Hydralazine

Beware hypotension fetoplacental unitSeizure Treatment / ProphylaxisMAGNESIUM SULPHATE

Loading dose: 4g IV over 5 minutes

Maintenance dose:IV infusion 1g/h If further seizures administer 2g Mg SO4

If persistent seizures consider diazepam 10mg IV41Fluid BalanceMain cause of death = pulmonary oedema(Capillary leak / fluid overload / cardiac failure)

Oliguria in 30%. Does not require intervention

Any doubts about renal function urine osmolality

Fluid challenges are potentially dangerous

Safer to run a patient dry - 80 ml/h42Labour and DeliveryAim for vaginal delivery if possibleControl BPEpidural anaesthesiaContinuous electronic fetal monitoringAvoid ergometrineCaution with iv fluids

Postpartum ManagementBreast feedingContraceptionBP managementCounsellingFuture riskDepends on other medical factorsGestation dependent (28/40 - 40%, 32/40 - 30%)Long term CVD riskLow Dose AspirinAspirin - inhibits cyclo-oxygenase prevents TXA2 synthesis75mg Aspirin 15% reduction in PET (NNT=90)May be more beneficial in preventing severe early onset pre-eclampsia (MRC CLASP Trial)SafeUsed for high risk women - Renal, DM, APS, Multiple risk factors, previous PETCommence before 12 weeksNICE Aug 2010

Calcium, Antioxidants & Folic AcidCalcium supplementation (>1gram / day) may reduce risk of hypertension (30%), PET (52%) and maternal death (20%). Did not affect pre-term birth or stillbirth (Hofmeyr et al Cochrane Database 2006)

Antioxidants not effective (Poston et al. VIP Study, Lancet 2006)

Mid trimester folic acid also appears to be effective in preventing pre-eclampsia (73% reduction) (Wen et al AJOG 2008)