PREGNANCY-RELATED HYPERTENSIONFRANS O H PRASETYADI

SUBDEPT. OF OBSTETRICS & GYNECOLOGYDR. RAMELAN INDONESIAN NAVAL HOSPITALS U R A B A Y A

INTRODUCTIONOne of the deadly triad maternal morbidity & mortalityUS incidence in 2001 : 3.7% of pregnancies16% pregnancy-related deaths ( US, 2003 )Challenge the medical & obstetrical skills of the health care teamunderstanding the patophysiology of the HT disorders disease of theoriesrecognition of the pharmacokinetic changes occuring during pregnancy & the possible fetal effects of therapeutic agents

Management & impact on the mother & fetus depend on whether :HT antedated the pregnancy, orHT as the marker of pregnancy-specific vasospastic syndrome several systems of nomenclature and classification

TERMINOLOGY AND CLASSIFICATIONThe NIH working group on hypertension in pregnancy ( 2000 ):Gestational hypertensionPreeclampsia-eclampsiaSuperimposed PE on chronic hypertensionChronic hypertension

GESTATIONAL HYPERTENSIONBP 140/90 For the 1st time during pregnancyNo proteinuriaBP returns to normal < 12 weeks postpartumFinal diagnosis made only postpartumMay have other signs or symptoms of PE, i.e. :epigastric discomfort or thrombocytopenia

PREECLAMPSIAMinimum criteriaBP 140/90 after 20 weeks of gestationProteinuria 300 mg/24 hr or 1+ dipstickIncreased certainty of preeclampsiaBP 160/110Proteinuria 2.0 g/24 hr or 2+ dipstickSerum creatinine > 1.2 mg/dL unless known to be previously elevatedPlatelets < 100,000/mm3Microangiopathic hemolysis ( LDH )Elevated ALT or ASTPersistent headache or other cerebral or visual disturbancePersistent epigastric pain

ECLAMPSIASeizures that cannot be attributed to other causes in a woman with preeclampsia

SUPERIMPOSED PREECLAMPSIANew onset proteinuria 300 mg/24 hr in hypertensive women but no proteinuria before 20 weeks gestationA sudden increase in proteinuria or blood pressure or platelet count < 100,000/mm3 in women with hypertension and proteinuria before 20 weeks gestation

CHRONIC HYPERTENSIONBP 140/90 before pregnancy or diagnosed before 20 weeks gestation not attributable to gestational trophoblastic disease, orHypertension first diagnosed after 20 weeks gestation and persistent after 12 weeks postpartum

PREECLAMPSIAMajor cause of - Maternal mortality ( 15-20% in developed countries ) and morbidities ( acute and long-term)- Perinatal deaths- Preterm birth- IUGR, oligohydramnios, abnormal oxygenationThose morbidities & mortalities are in women who :-develop the disorder before 33 weeks gestation-in those w/ pre-existing medical disorders-in those from developing countries

Etiology and pathophysiology ?

Likely to develop in women who :1. are exposed to chorionic villi for the first time2. are exposed to a superabundance of chprionic villi, as with twins or hydatidiform mole3. have preexisting vascular disease4. are genetically predisposed to hypertension developing during pregnancy

PREECLAMPSIAIs a multisystem disorder of unknown cause that is unique to human pregnancyCharacterised by abnormal vascular response to placentation that is associated with :- systemic vascular resistance- enhanced platelet aggregation- activation of the coagulation system, and- endothelial dysfunctionClinical manifestations :maternal syndromefetal syndrome

Maternal and fetal complications in severe preeclampsia

Maternal complications

abruptio placentae ( 1-4% )DIC / HELLP syndr ( 10-20%)Pulmonary oedema/aspiration (2-5%)ARF (1-5%)Eclampsia (

DIAGNOSIS PEHT + proteinuria, >20 weeks gestation, normotensive beforehand

BP measurements : 2 occasions, 4-6 h apart &

RISK FACTORS

-Limited sperm exposure-Primipaternity-Pregnancy after donor insemination, oocyte donation, embryo donation-Protective effectof partner change in the case of previous PE pregnancy-Maternal or pregnancy-related risk factors-Extremes of maternal age-Multifetal gestation-PE in a previous pregnancy-Chronic HT or renal disease-Rheumatic disease-Maternal low birthweight-Obesity & insulin resistance-Pregestational DM-Maternal infections-Pre-existing thrombophilia-Maternal susceptibility genes-Family history of PE-Smoking ( reduced risk )-Hydropic degeneration of placenta-PCOS, recurrent abortions

Epidemiology & risk factors2% - 7% in healthy nulliparous women

Generally regarded as a disease of first pregnancy

Importance of paternal factors : dangerous father

Primipaternity concept ? >< women w/ no previous PE ~ risk of PE with increasing time interval between births

Concept : healthy pregnancy is a state of systemic inflammation, at least in the 3rd trimester PE is the extreme end of a range of maternal systemic inflammatory responses engendered by the pregnancy itself

In pregnancy, the spiral arteries are remodeled by extravillous trophoblast cells and NK cells. The left panel shows the nonpregnant endometrium in the secretory phase of the menstrual cycle just before menstruation. The right panel shows the endometrium in the second half of normal pregnancy when the spiral arteries are remodeled to a depth that penetrates the myometrium. The middle panel shows the situation in preeclampsia where the extent and depth of remodeling is less than in normal pregnancy. These vascular changes are effected by extravillous trophoblast cells (EVT) with the help of activated NK cells. In the process, the enlarged vessels become lined with endovascular trophoblast cells (ENVT)

Noris M et al. (2005) Mechanisms of Disease: pre-eclampsiaNat Clin Pract Neprol 1: 98114 doi:10.1038/ncpneph0035Figure 4Unifying hypothesis of pre-eclampsia pathophysiology

Maternal Vasculer diseaseFaulty PlacentationExcessive TrophoblastsGenetic, immunologic, or inflamatory factors

Endothelial ActivationActivation of CoagulationCapillary leakVasospasmHypertensionSeizuresOliguriaLiver ischemiaAbruptionEdemaHemoconcentrationProteinuriaTrombocytopeniaNoxious agents:Cytokines, Lipid PeroxidasesVasoactive agents:Prostaglandins, nitric Oxide, Endothelins

Berhubungan dengan:Tekanan afterloadTekanan PreloadEkstravasasi cairanCO meningkat CO menurun + resitensi perifer meningkatHemokonsentrasiHati-hati pada perdarahan waktu persalinanAktivasi, agregasi, konsumsi + volume dan usia platelet trombositopeniaWaktu thrombin meningkatDefisiensi faktor pembekuan karena penyakit penyertaFibronectin cenderung meningkatHemolisis LDH, perubahan bentuk eritrosit.Akibat gangguan endotelhemolisis mikroangiopati

RAA system menurun akibat retensi air + NaVasopressin tetapAtrial natriuretik peptide menurunKerusakan endotel retensi cairan edema generalisataElektrolit cenderung tetap normalPada kejang eklamsia pH dan bicarbonat

Perdarahan akibat ruptur arteriEdema, iskemi, hyperemia,trombosis, perdarahan serebralHiperperfusiKehilangan autoregulasi aliran darahInfark arteri retinaAblasio retinaEdema korteks dan defek visualKlirens plasenta menurunLaju aliran darah plasenta menurun

Prediction of PENo known biomarkers

No efective predictors

Doppler velocimetry of uterine artery blood flow in 2nd trimester might be useful ( RI or early diastolic notch uni- or bilateral ) for those at very high risk

Fetal Velocity Waveforms

Medical Physiology Lippincott Williams & Wilkins, 2nd edition 2004

Prevention of PELevels of evidence (I IV) as outlined by the US Preventive Task Force. *Insufficient evidence - small

Diet and exercise (I)Protein or salt (II)restrictionMg or Zn supplementation (I)Fish-oil supplementation & other sources of fatty acids (I)Calcium supplementation (I)

Low-dose aspirin (I)

Heparin or low-molecular-weight heparin (III)Antioxidant vitamins (C,E) (II)Anti-HT medications in women w/ chronic HTPregnancy outcomeNo reduction in PE

No reduction in PENo effect in low-risk or high-risk populationsReduced PE in those at high-risk & with low baseline dietary calcium intakeNo effect on perinatal outcome19% reduction in risk of PE16% reduction in fetal or neonatal deathsReduced PEin women w/ renal dis. & in women w/ thrombophiliaReduced PE in one trialRisk of women developing severe HT reduced by half, but not risk of PERecommendationInsuff. evidence to recommend

Not recommended*Insufficient evidence to recomm.*

Recommended for women at high risk of gestational HT, & in communities w/ low dietary calcium intakeConsider in high-risk populations

Lack of randomised trials, not recommendedInsufficient evidence to recomm.No evidence to recommend for prevention

Management of PEAdequate & proper prenatal care is most important ( identification of women at high risk, early detection by the recognition of clinical signs & symptoms, progression of the condition to severe state )

The main objective : safety of the mother

Delivery or expectant? ~ fetal gestational age, fetal status, severity of maternal condition at time of assessment

Management of PEPreeclampsiaMaternal & fetal assessmentGestational age 38 weeksAt 34 weeks gestation: - Severe PE - Labour or rupture of membranes - Abnormal fetal testing - Severe oligihydramnios or fetal growth restrictionDeliverMild diseaseSevere disease Hospital or office management Maternal and fetal assessment22 32 weeks< 23 weeks33 34 weeks Worsening maternal or fetal condition 38 weeks Labour or rupture of membranes Steroids Anti-HT Daily assessment of maternal-fetal conditions Delivery at 34 weeks Steroids Delivery after 48 hYESNO

**Fig 34-3, (Friedman and Lindheimer, 1999)Pathophysiological considerations in the development of hypertensive disorder due to pregnancy****