Hypertensive disorders in pregnancy Dr. Wael Al,Halaki Professor in Qasyoun Private university Hama University 2017

Hypertensive disorders in pregnancy

Hypertensive disorders are the most common and yet serious conditions seen in obstetrics

INTRODUCTION Incidence is 5-10%. The most frequent cause of iatrogenic prematurity. Preterm delivery Intrauterine growth restriction (IUGR) Perinatal death Maternal cerebrovascular accidents ( CVA). Placental abruption.

Normal Blood Pressure changes in Pregnancy Decreases during the first trimester, Reaching its lowest point at 20 weeks, Returns to pre-pregnancy levels during the third trimester.

Classification Pre-eclampsia Eclampsia Gestational hypertension Preeclampsia superimposed on chronic hypertension Chronic hypertension with pregnancy Gestational hypertension

GESTATIONAL HYPERTENSION Blood Pressure ≥ 140/90mmHg on two or more occasions - In a previously normotensive patient - After 20 weeks gestation - Without proteinuria - Returning to normal 12 weeks after delivery Almost half of these develop preeclampsia syndrome

GESTATIONAL HYPERTENSION SUSTAINED HYPERTENSION ( ≥ 140/90) GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION ( ≥ 140/90) No proteinuria

GESTATIONAL HYPERTENSION Sustained B.P No proteinuria DEFINITION SYMPTOMS NONE EXAMINATION Unremarkable

Preeclampsia It is defined as hypertension of at least 140/90mm Hg recorded on two separate occasions at least 4 hours apart and in the presence of at least 300mg protein in a 24 hour collection of urine, arising after the 20th week of gestation in a previously normotensive woman and resolving completely by the 6th postpartum week.

Gestational Hypertension Preeclampsia Preeclamsia Gestational Hypertension Proteinuria

RISK FACTORS for PREECLAMPSIA NULLIPARA (Age extremes <20yrs , >35yrs ) DEMOGRAPHIC Multiple gestation Molar pregnancy Non-immune hydrops OBSTETRICS Diabetes mellitus Chronic HTN Renal disease SLE MEDICAL

Genetic Age &Parity Partner Factors Genetic Predisposition Family History Race & Ethnicity More Common in black & Asians Pregnancy by ovum donation Age &Parity Teenage pregnancy <18 yrs Age>35 yrs Long interval between pregnancy >10 years Nulliparity Partner Factors Change of partner Limited sperm exposure Pregnancy by donor insemination Partner fathered an eclamptic pregnancy

Pregnancy Factors Underlying Medical Diseae Others Multiple pregnancy Hydatiform mole Hydrops fetalis Fetal chromosomal anomaly (trisomy 13) Underlying Medical Diseae Chronic hypertension Diabetes mellitus Renal Disease Cardiovascular disease Hyperthyroidism Metabolic Syndrome Others Obesity BMI> 35 kg/m2 Psychological stress & strain Smoking Previous history of preeclamsia insulin resistance, obesity, atherogenic dyslipidemia and hypertension.  Hyperhomocysteinemia , Autoimmune disease Antiphospholipid antibodies, Thrombophilia

SUSTAINED HYPERTENSION (≥ 140/90) MILD PREECLAMPSIA GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION (≥ 140/90) Proteinuria (≥300mg /24 hr)

MILD PREECLAMPSIA LABORATORY FINDINGS Proteinuria (1-2+) Hemoconcentration < 36 wks Conservative >36 wks MgSO4 and Delivery MANAGEMENT

GESTATIONAL HYPERTENSION GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION (≥ 140/90) NO PROTEINURIA MILD PREECLAMPSIA GESTATION ≥ 20 WEEKS SUSTAINED HYPERTENSION ( ≥ 140/90) Proteinuria ( ≥ 300mg /24 hr)

CRITERIA: SEVERE PREECLEMPSIA ≥ 170/110 GREEN TOP GUIDELINE 2010 BLOOD PRESSURE ≥ 5grams GREEN TOP GUIDELINE 2010 PROTEINURIA Headache Epigastric pain Visual changes SYMPTOMS

ECLAMPSIA New onset of seizures or unexplained coma during pregnancy in patients with pre-existing preeclampsia and without pre-existing neurological disorder.

Eclampsia addition of convulsions in a woman with preeclampsia occurs in 0.5-4% of deliveries 25% have eclamptic seizures before labour, 50% during labour, and 25% after delivery. Eclampsia Preeclampsia Seizure/ Convulsion/ Coma

ECLAMPSIA Same as Preeclampsia RISK FACTORS PATHO -PYSIOLOGY Cerebral vasospasm , ischemia and edema Generalized tonic-clonic SEIZURES SYMPTOMS

ECLAMPSIA Proteinuria Hemoconcentration LABORATORY FINDINGS MANAGEMENT DIC Elevated Liver enzymes Stop convulsions with MgSO4 Prompt delivery at any gestational age Lower diastolic BP 90-100mm/Hg MANAGEMENT

MANAGEMENT IV MgSO4 – To prevent convulsions ( continue 24 hrs post-partum ) LOWER B.P ( hydralazine or labetalol) INDUCE LABOR (IV oxytocin and amniotomy )

CHRONIC HYPERTENSION OR Blood pressure ≥ 140/90 before 20 weeks of gestation. OR persistence of hypertension beyond 12 weeks after delivery.

CHRONIC HYPERTENSION GESTATION < 20 WEEKS OR Prepragnancy SUSTAINED HYPERTENSION (≥140/90) +/- PROTEINURIA

CHRONIC HTN PREGNANCY PROGNOSIS B.P 140/90 to 179/109 No end organ damage GOOD PROGNOSIS KIDNEYS: Renal disease EYES : Retinopathy HEART : Left Ventricular Hypertrophy (B.P >180/110) POOR PROGNOSIS Uncontrolled HTN Chronic HTN +Superimposed Pre-eclampsia WORST PROGNOSIS

MANAGEMENT OF CHRONIC HYPERTENSION antihypertensive meds (if B.P >100 mm Hg diastolic) If antihypertensive meds needed - Methyl dopa is drug of choice (or labetalol) Serial ultrasounds (increase risk of IUGR >30 weeks ) Serial B.P and urine protein (watch for superimposed preeclampsia) Induce labor at term

SUPERIMPOSED PREECLAMPSIA (on Chronic Hypertension) New-onset proteinuria > 300 mg/24 hrs in hypertensive women but no proteinuria before 20 wks gestation. A sudden increase in proteinuria or blood pressure or platelet count < 100,000/ cu mm in women with hypertension and proteinuria before 20 wks gestation.

CHRONIC HTN SUPERIMPOSED PRE-ECLAMPSIAS CHRONIC HYPERTENSION Worsening BLOOD PRESSURE Worsening proteinuria

MANAGEMENT of Chronic HTN and superimposed PRE-ECLAMPSIA MgSO4 – To prevent convulsions ( continue 24 hrs post-partum ) LOWER B.P - Diastolic 90-100 mm Hg ( hydralazine or labetalol) INDUCE LABOR (IV oxytocin and amniotomy )

HELLP Syndrome HTN patients with hemolysis (H), elevated liver enzymes (EL), low platelet count (LP) 4-12% of pt. with severe preeclampsia and eclampsia develop HELLP syndrome

HELLP Syndrome Cardiovascular stabilization, correction of coagulation abnormalities, and delivery PLT transfusion before or after delivery if PLT count is <20,000/mm3 (advised at <50,000/mm3 before cesarean) <32 weeks gestation; steroid therapy may help stabilize maternal PLT count

PATHOPHYSIOLOGY Complex disease Appears to be triggered by the placenta Can occur in molar pregnancies where fetus absent Can also occur in abdominal pregnancy (pregnancy not in uterus)

Poor Immunoregulation Clinical manifestation Mechanisms Stage 0 3-8 weeks Stage 1 8-18 weeks Stage 2 20 weeks to birth Poor Immunoregulation Inadequate tolerance to feto-paternal antigens during conception and implantation Poor Placentation Deficient trophoblast invasion and spiral artery remodelling Clinical manifestation Over activation of maternal endothelium and systemic inflammatory network Oxidative Stress Endoplasmic reticulum Stress Inflammatory Stress Abnormal placentation (stage 1), particularly lack of dilatation of the uterine spiral arterioles, is the common starting point in the genesis of pre-eclampsia, which compromises blood flow to the maternal–fetal interface. Reduced placental perfusion activates placental factors and induces systemic hemodynamic changes. The maternal syndrome (stage 2) is a function of the circulatory disturbance caused by systemic maternal endothelial cell dysfunction resulting in vascular reactivity, activation of coagulation cascade and loss of vascular integrity. Pre-eclampsia has effects on most maternal organ systems, but predominantly on the vasculature of the kidneys, liver and brain.

Mechanisms Normal Pregnancy invasive cytotrophoblasts of fetal origin invade the maternal spiral arteries transforms them from small-caliber resistance vessels to high-caliber capacitance vessels capable of providing placental perfusion adequate to sustain the growing fetus Normal Pregnancy process of vascular invasion, the cytotrophoblasts differentiate from an epithelial phenotype to an endothelial phenotype, a process referred to as "pseudovasculogenesis" 

cytotrophoblasts fail to adopt an invasive endothelial phenotype Mechanisms Preeclampsia cytotrophoblasts fail to adopt an invasive endothelial phenotype invasion of the spiral arteries is shallow and they remain small caliber, resistance vessels placental ischemia

Pre-eclampsia is two stage disease Maternal Syndrome Fetal Syndrome

Organ Specific Changes associated with Pre-eclampsia Cardiovascular Renal Generalized vasospasm Increased peripheral resistance Reduced central venous/ pulmonary pressure Proteinuria Decreased glomerular filtration rate Decreased urate excretion Hepatic Organ Specific Changes associated with Pre-eclampsia Periportal necrosis Subscapular hematoma Hematological Central Nervous System Platelet activation and depletion Coagulopathy Decreased plasma volume Increased blood viscosity Cerebral oedema Cerebral haemorrhages

Treatment of Hypertension: Antihypertensive drugs used in pregnancy are Methyldopa Hydralazine labetalol

Seizure Prophylaxis Routinely used in severe PE. Magnesium sulphate: most commonly used. Initiated with onset of labor till 24h postpartum. For caesarean, started 2hrs before the section till 12hrs postpartum.

Recommended regime for MgSO4 it can be given either IV or IM. IV has good prognosis. Loading dose for IV is 4g. i.e. 8 ml diluted in 12ml normal saline. This 20 ml is given in 20 minutes. Maintenance dose is 20 g i.e. 40ml diluted in 60ml normal saline and given at rate of 1g/hr.

Recommended regime for MgSO4 IM is also used. Loading dose is as IV. Maintenance dose is 5g every 4 hrs in alternate buttocks for 24hrs. Mgso4 acts on NM junction and inhibit entry of Ca++ ions thus inhibiting excitability of neurons.

Management of MgSO4 Toxicity Calcium gluconate is antagonist for MgSO4. it is usually given as 10 ml of 10% Calcium gluconate in 10 minutes

Delivery The only definitive treatment Preeclamptic patients divided into 3 categories A- Preeclampsia features fully subside B- partial control, but BP maintains a steady high level C- persistently increasing BP to severe level or addition of other features

Management: A: can wait till spontaneous onset of labor don’t exceed Expected Date of Delivery B: >37wk terminate without delay <37wk, expectant management at least till 34wks C: terminate irrespective of POG start seizure prophylaxis and steroids if<34wks

Delivery in Eclampsia Unless contraindicated: Eclamptic women should undergo normal vaginal delivery Indications for caesarean section - Fetal distress Placental abruption Unfavourable cervix Failed induction of labour Recurrent seizures

Investigations Urine: 24 hour urine, Proteinuria. Kidney functions: serum creatinine, urea, creatinine clearance and uric acid. Liver functions: bilirubin, Enzymes Blood: CBC, HCt , Hemolysis and Platelet count (Thrombocytopenia). Coagulation Profile: Bleeding and clotting time

PREVENTION Regular Antenatal checkup: Rapid gain in weight Rising blood pressure Edema Proteinuria/Deranged liver or renal profile Low dose Aspirin in High risk group: ↑PGs and↓TXA2 (nice guideline) Calcium supplementation: no effects unless women are calcium deficient Antioxidants- Vitamin C and E Nutritional supplementation: zinc, magnesium, fish oil, low salt diet

Uterine Artery Doppler Velocimetry (abnormal flow resistance/ diastolic notch in 2nd/ 3rd trimester) is most promising, but currently, none of them is completely suitable for clinical use. (Conde-Agudelo, 2014; Kleinrouweler, 2012; Myatt, 2012a). These have value for fetal-growth restriction but not preeclampsia (ACOG, 2013a). As a result of these trials, some methods to prevent Preeclampsia have been theorized…

uterine artery DOPPLER at 24 weeks of pregnancy: Flow velocity waveform from the uterine artery at 24 weeks of gestation in a pregnancy with impaired placentation; in early diastole there is a notch (yellow arrow) and in late diastole there is decreased flow (orange arrow). In preeclamptic mother: Showing early diastolic NOTCH Decreased EDF (due to high resistance) In normal mother