Hypertensive Disorders in Pregnancy

Nawal M. Nour, MD, MPH Director, Global Ob/Gyn Health

Assoc. Prof, Harvard Medical School

May 15, 2012

Overview

• Pre-eclampsia – Mild – Severe – Gestational hypertension – HELLP

• Diagnosis and management of PET • Indications for delivery • Management of Eclampsia • Postpartum PET

Epidemiology

• PET: 6-8% of all pregnancy • 2nd most common cause of maternal

mortality • 70 maternal mortality per yr in US and

50,000 worldwide • Significant perinatal mortality and

morbidity due to prematurity

Causes

• Increased production of anti-angiogenics, placental growth factors.

• Circulating syncytiotropholasts causing maternal inflammation

• Placental ischemia: chronic htn, DM, SLE, thrombophilias, hydrops and molar pregnancy

• Low-calcium intake • Increased sensitivity to angiotensin • Genetics

Risks Factors for Preeclampsia • Pregnancy-associated factors

Chromosomal abnormalities Hydatidiform mole Hydrops fetalis Multifetal pregnancy Oocyte donation or donor insemination Structural congenital anomalies Urinary tract infection

• Maternal-specific factors Age greater than 35 years Age less than 20 years Black race Family history of preeclampsia Nulliparity Preeclampsia in a previous pregnancy Specific medical conditions: gestational diabetes, type I diabetes, obesity, chronic hypertension, renal disease, thrombophilias Stress

• Paternal-specific factors First-time father Previously fathered a preeclamptic pregnancy in another woman

Mild Pre-eclampsia

• Incidence 5-6% • 75% develop at >37 weeks’ gestation • Minimal impact on mother and baby • Management variable and not evidence

based

Definition Mild PET

• SBP> 140mm Hg, DBP >90mm Hg • Onset after 20 weeks • UProtein +1 on dipstick on 2 occasions 6h

apart • UProtein >300mg/24 hr • Spot urine protein/creatine ratio >0.19

Severe PET

• SBP>160mm Hg, DBP >110 mmHg, twice at least 6 hours apart (sitting)

• Proteinuria >5gms, 3+ dip 4 hrs apart • Oliguria <500mg in 24 hrs • Other symptoms – visual changes,

epigastric pain, IUGR and lab changes

HELLP • H- Hemolysis, EL – Elevated liver

enzymes, LP – Low platelets – Pritchard et al. NEJM 1954;250:89-98 – Weinstein, L. Am J Ob Gyn 1982;142:159-67

• Prevalence – 26% of all pregnancies have 1 manifestation – 12% have 2 manifestations – 10% have 3 manifestations

• 1/3 of cases occur ppartum Sibai BM. Am J Obstet Gynecol. 1990;162:311-6

Gestational Hypertension

• SBP >140mm Hg, DBP >90mm Hg • First detected >20 weeks • No proteinuria

Evaluate patient

• Exclude other disorders characterized by hypertension and proteinuria

• Assess the severity of the disease • Assess fetal well-being

Signs and symptoms

• Unremitting headache (“worst headache of life”) • Visual disturbances (spots) • Epigastric/RUQ pain (N/V) • Brisk DTRs/clonus • Edema • Chest pain • Shortness of breath – pulmonary edema • Oliguria <500cc/24hr • Seizure!

Lab tests

• Elevated hct – hemoconcentration • Proteinuria – 300mg/5gms • Thrombocytopenia – <100K • Elevated liver enzymes – 2 x normal • Uric Acid – not specific but first to increase • Elevated PT/PTT – severe disease • Hypofibrinogenimia – severe disease • Elevated LDH – severe disease • Schistocytes – severe disease

Fetal Assessment

• Fetal heart rate monitoring • Fetal growth restriction • Decreased amniotic fluid volume • Diminished, absent or reversed umbilical

artery doppler studies

Complications of PET • Eclampsia • Liver capsule rupture • Kidney damage • Placental abruption • Preterm delivery • Brain injury (CVA) • Fetal/neonatal demise • Maternal demise

Management of Mild PET

• If preterm, should you deliver? • In the past, admit and observe – now, we

manage as outpatient

Patients Managed Expectantly

• Monitor BP • Twice-weekly CBC and LFTs • Document symptoms • Serial U/S every 3 weeks – EFW and AFV • NST or BPP every week • Daily fetal movement counts

Management of Severe PET: Weigh Risks • Weigh Risks:

– Maternal Complications: Stroke, Blindness, Liver rupture, Death

– Fetal complications: Cerebral Palsy, IVH, RDS, NEC etc.

Management of Severe PET

• If >34 wks, deliver • If <34 wks, admit to L+D

– Antenatal glucocortoids – Seizure prophylaxis - magnesium sulfate – Blood pressure control – labetolol, hydralazine – Strict fluid intake and output – Follow lab tests – Monitor fetus (NST, U/S, dopplers)

Expectant Management of Severe PET <34 wks • Odendaal (1990) 28-34 wks

– Randomized delivery after Beta vs exp mgmt – No difference in maternal mortality – Decrease composite neonatal morbidity/mort

• Sabai (1994) 28-32 wks – Randomized delivery after Beta vs exp mgmt – Dec RDS, NICU admission, NEC

Treating hypertension

• Hydralazine (Apresoline) – 5 mg IV bolus q 10 min x 2 doses (then q 20 minutes) or 10 mg IM until BP <150/100

• Labetolol – 20 mg IV q 10-20 min (max 80mg per dose, 300mg total)

• Nifedipine – 10 mg po q 30 min x 2 doses, 10-20 mg po q 4-6 hrly

Grossman et al. JAMA. 1996; 276:1328-31

Long Term Drug Therapy

• Methyldopa: 250 mg tid (max. 4gms/day) • Nifedipine: 10 mg tid (max. 120mg/day) • Labetalol: 100mg tid (max 2400 mg/day)

Indications for delivery • Fetal indications

– Severe intrauterine growth restriction – Nonreassuring fetal surveillance – Oligohydramnios

• Maternal indications – Platelet count below 100 X 103 per mm – Progressive deterioration of hepatic or renal fxn – Suspected placental abruption – Persistent severe headache or visual changes – Persistent severe epigastric pain, nausea, or vomiting – Eclampsia – Pulmonary Edema

Seizure Prophylaxis

• 75% of seizures at time occur either in labor or 48 hours after delivery

• Severe PET: Intrapartum and 24 hrs ppartum

• Mild PET: Intrapartum and 12-24 hrs ppartum

• Hypertension only: Not recommended

Post-Partum PET

• PET can develop in healthy women • At risk of pulmonary edema • BP medication for >155/105 mmHg • Discharge home with visiting nurse or

follow up visit within a week

Prognosis of HELLP

• Maternal mortality rate: 0-24% – Due to liver rupture, DIC, renal failure,

pulmonary edema, CVA.

• Perinatal mortality rate: 8-60% – Related to complications of prematurity,

placental abruption, IUGR.

– Weinstein, L. Am J Ob Gynecol 1982;142:159-67 – Sibai BM. Am J Obstet Gynecol. 1990;162:311-6 – Sibai BM et al. Am J Obstet Gynecol. 1995;172-125-9

Diagnosis of HELLP

• Hemolysis – Abnormal peripheral smear – Total bilirubin >1.2 mg/dL – Serum LDH > 600 U/L

• Elevated liver enzymes – Serum ALT > 70 U/L

• Low platelets – <100,000 platelets/mm3

Differential Diagnosis of HELLP • Thrombotic microgangiopathies

– Thrombotic Thrombocytopenic Purpura – Hemolytic Uremic Syndrome

• Disseminated intravascular coagulation – Abruption, hemorrhage, sepsis

• Severe folate deficiency – GI & hematologic manifestations (dx bone

marrow biopsy)

• Acute fatty liver of pregnancy

Treatment of HELLP

• Steroids – A total of 132 women over 20 weeks of

gestation with HELLP syndrome (60 antepartum, 72 ppartum) randomized to dexamethasone 10mg q 12 v placebo

– No difference in duration of hospitalization, the rate of platelet or FF plasma transition, or maternal complications

– Fonseca JE et al. Am J Obstet Gynecol 2005; 193:1591-8

Eclampsia

• Greek: ekampsis – sudden flash • Generalized seizure and/or coma in setting

of PET and absence of neurologic disorders – ACOG Technical Bulletin #219, 1996 – ACOG Practice Bulletin #33, 2002

Etiology of Eclampsia

• Unknown • Hypothesis:

– Central vasospasm with ischemic injury – Hypertensive encephalopathy with cerebral

hyperperfusion – Endothelial injury – Vasogenic edema

• Douglas & Redman. BMJ 1994,309:1385-400. • Morris et al. Obstet Gynecol 1997;89:561-8.

Management of Eclampsia

• Airway!! • Control convulsion

– Seizures are self-limiting – MgS04: 2 gm IV to max 6 gm. IM dosing. – Diazipam 0.1-0.3 mg/kg over 60 seconds,

max 20 mg (only if MgSO4 is unavailable)

• Prevent recurrent Sz: Mg/S04 • Control hypertension • Evaluate delivery

Prediction and Prevention

• Early, severe PET: risk of recurrence 25-65% • Mild PET: risk of recurrence 7% • First pregnancy normal: risk of PET 1% • No reliable predictive test • No effective prophylaxis

Prevention

• ACOG: Cochran database – Low dose ASA: no use in low-risk women – Calcium: no benefit in low-risk women with

normal dietary intake

Conclusion

• Differentiate between PET and PIH • Outpatient management of mild PET

acceptable • Severe PET or HELLP needs admission,

assessment and management on L+D

Result of Severe Pre-eclampsia