Hypertensive disorders of pregnancy

Spectrum/categories of HDP:

1. pre-existing HTN (prior to 20 weeks GA)
2. GHTN (after 20 weeks GA)
3. Transient HTN (single measurement)
4. de novo preeclampsia (new or worsening hypertension with adverse conditions, usually after 20 weeks)

HTN Definitions in Pregnancy

Classification	Definition
Hypertension	Office measurement ≥140/90, ambulatory measurement ≥135/85
Severe hypertension	≥160/110
Resistant hypertension	≥3 anti-hypertensives

BP Targets in Pregnancy

1. Hypertension Canada: DBP < 85 mmHg
2. CHIPS (NEJM 2015) trial: "less tight" (target DBP 100 mm Hg) vs "tight" (target DBP 85 mm Hg) BP control in women with nonproteinuric pre-existing or gestational HTN.
   1. No difference in maternal or fetal outcomes
   2. Higher severe hypertension in the less tight group (40 vs 28%) and had more laboratory features of HELLP

BP Medications in Pregnancy

Preeclampsia

This is a multi system disorder in pregnancy that is mediated by the placenta, that results in systemic vascular and endothelial dysfunction, resulting in maternal and fetal morbidity and mortality.

Risk factors: first pregnancy, new partner, IVF, family history, age <20 or >35. Maternal risk factors: prior pre-eclampsia, chronic HTN, DM, renal disease, autoimmune disorders, obesity. Fetal risk factors: multiple gestation, hydrops fetalis, molar pregnancy.

Diagnosis/Definition

1. Hypertension as above.
2. Gestational age > 20 weeks
3. Adverse conditions with end-organ damage or severe complications that warrant delivery and IV MgSO4 (see below)

System	Adverse condition	Severe Complications
CNS	HA/visual symptoms	eclampsia, PRES, cortical blindness, GCS <13, stroke, TIA, RIND
Cardiorespiratory	Chest pain or dyspnea, SpO2 < 97%	Uncontrolled severe HTN, frank hypoxia or respiratory failure, infarction, pulmonary edema and heart failure
Hematologic	Leukocytosis, coagulopathy, thrombocytopenia	Plt < 50, blood product transfusion
Renal	Elevated Cr, hyperuricemia	AKI, dialysis
Hepatic	N/V, RUQ or epigastric pain, elevated liver enzymes or decreased liver synthetic function	liver dysfunction (INR > 2), hepatic hematoma or capsular rupture
Feto-placental	AbN FHR, IUGR, oligohydramnios, absent or reversed end-diastolic flow (Dopplers)	placental abruption, reverse ductus venosus A wave

Prevention of Pre-eclampsia

• ASA 81-162 mg daily
  • this was examined in the ASPREE trial (NEJM 2017) which randomized women to ASA 150 mg vs placebo, and showed that this intervention reduced pre-eclampsia <37 weeks (1.6% vs 4.3%)
  • start 12-16 weeks and continue until 36 weeks
  • Indications per the USPTF: prior pre-eclampsia, chronic HTN, DM1 or DM2, CKD, SLE, APLA, multiple gestation, two or more minor factors (such as nulliparous or new partner, IVF, Age > 35, BMI > 30, first-degree family history of pre-eclampsia)
• Calcium 1000 mg daily supplementation recommend ed if low dietary intake (<600 mg)
• APLA testing
  • diagnostic criteria
    • obstetric event: 3 pregnancy losses <10 weeks, 1 pregnancy loss > 10 week, 1 preterm pre-eclampsia <34 weeks
    • arterial or venous thrombosis
    • laboratory criteria
  • if obstetric criteria, treat with ASA +/- prophylactic dose LMWH

Treatment of Pre-eclampsia

1 - Hypertension Management

• Note: this doesn't prevent progression of pre-eclampsia.
• See above for BP management in pregnancy.

2 - Eclampsia Prevention

• IV magnesium sulfate is the medication of choice
  • Informed by the Magpie (Lancet 2002) trial which randomized 10,000 women with pre-eclampsia to Mg vs placebo. It showed a 58% RRR NNT 91 reduction in eclampsia, and trend towards decreased mortality.
  • Therefore IV MgSO4 is indicated for the prevention and treatment of eclampsia.
    • Preventative indications: severe pre-eclampsia, severe HTN, headache, vision changes, RUQ plain, thrombocytopenia, elevated liver enzymes, AKI
    • Treatment indications: first-line for seizures in pregnancy which are related to eclampsia.
  • Regimen: 4g IV loading dose then 1-2 g/hr for at least 24 hours after delivery. Requires a Foley (everyone) and a monitored setting
  • Toxicity of IV MgSO4:
    • Symptoms: respiratory suppression, bradycardia, hypotension, reduced GCS and CNS suppression
    • Monitoring: decreased tendon reflexes, decreased UOP. NOT by monitoring Mg levels.
    • Treatment: stop Mg, IV calcium gluconate, and consider RRT

3 - Delivery

• decision is made by the OB (involve them early!)
• indications for delivery are generally
  • severe pre-eclampsia
  • refractory maternal symptoms (resistant HTN, persistent symptoms, and end-organ damage)
  • fetal complications: IGUR, Doppler abnormalities, fetal distress
  • women at term: >37 weeks GA
• antenatal corticosteroids for fetus <35 weeks GA (betamethasone). Per the ACOG:
  • A single course of corticosteroids is recommended for pregnant women between 24 0/7 weeks and 33 6/7 weeks of gestation who are at risk of preterm delivery within 7 days, including for those with ruptured membranes and multiple gestations. It also may be considered for pregnant women starting at 23 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, based on a family’s decision regarding resuscitation, irrespective of membrane rupture status and regardless of fetal number
  • Administration of corticosteroids for pregnant women during the periviable period who are at risk of preterm delivery within 7 days is linked to a family’s decision regarding resuscitation and should be considered in that context
  • A single course of betamethasone is recommended for pregnant women between 34 0/7 weeks and 36 6/7 weeks of gestation at risk of preterm birth within 7 days, and who have not received a previous course of antenatal corticosteroids.
  • Regularly scheduled repeat courses or serial courses (more than two) are not currently recommended.
  • A single repeat course of antenatal corticosteroids should be considered in women who are less than 34 0/7 weeks of gestation who are at risk of preterm delivery within 7 days, and whose prior course of antenatal corticosteroids was administered more than 14 days previously. Rescue course corticosteroids could be provided as early as 7 days from the prior dose, if indicated by the clinical scenario.
• pre-eclampsia is not a contraindication for vaginal delivery
• epidurals are safe when Plt > 75 and without coagulopathy

Post-Partum Care

1. BP tends to rise 3-6 days post-partum
2. Pre-eclampsia puts women at 4x increased risk of chronic HTN, 2x increased risk of heart disease, stroke, VTE, and diabetes. Make sure to counsel the patient about future pregnancy risk, CVD risk, and to quit smoking, lose weight, and support breastfeeding
3. ACE inhibitors are safe in breast feeding

References

1. IMR Slides (2021)
2. CHIPS trial
3. Magpie trial