Eclampsia is a severe, life-threatening manifestation of preeclampsia. While long-term neurologic damage is rare, there is risk of maternal hypoxia and death. Most women will experience signs such as headaches or visual changes prior to a seizure.
Eclampsia
Defined as convulsions during pregnancy and/or postpartum
Tonic-clonic, focal, or multifocal
New onset
Unexplained by other neurologic pathology
Consider other underlying cerebral conditions when
Seizures occur 2 to 3 days postpartum
Patient on magnesium sulfate
Note: Not all women will demonstrate classic features of preeclampsia (hypertension, proteinuria)
Magnesium Sulfate – How to Use
Magnesium sulfate is the treatment of choice for seizure prophylaxis (ACOG recommended dosing)
Loading dose of 4–6 g of magnesium sulfate administered per infusion pump over 20–30 minutes (i.e., slowly) followed by a maintenance dose of 1-2 g per hour as a continuous intravenous infusion
Continue 24 hours postpartum
Recurrent seizures
Additional dose of 2-4 g can be infused over 5 minutes
Refractory seizures
Sodium amobarbital: 250 mg IV in 3 minutes
Thiopental or phenytoin: 1,250 mg IV at a rate of 50 mg/minute
Patient should be managed in ICU
Consider neuroimaging
IM option
10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
Use if IV access limited
Mix with 1 mL xylocaine 2% to alleviate pain
Note: Magnesium sulfate should not be considered an antihypertensive agent
Magnesium Sulfate – When to Use
Severe features of preeclampsia
Administer to all women
No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg
There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy”
Delivery and Postpartum
Vaginal delivery
Continue infusion 24 hours postpartum
Cesarean
Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended
Prevention of Magnesium Sulfate toxicity
Place Foley to monitor renal function (hourly output)
Confirm normal serum creatinine
Serial evaluation of patellar deep tendon reflexes
Monitor respiratory rate
Serum magnesium levels not routinely required
Monitor serum magnesium levels in setting of renal dysfunction and/or absence of patellar reflexes
Maintain serum concentrations 5 to 9 mg/dL (4–7 mEq/L) range
Predictive symptoms of magnesium sulfate toxicity
Loss of deep tendon reflexes >9 mg/dL (greater than 7 mEq/L)
Respiratory depression >12 mg/dL (greater than 10 mEq/L)
Cardiac arrest >30 mg/dL (greater than 25 mEq/L)
Pending toxicity
Notify appropriate health care provider
Discontinue magnesium infusion
Administer supplemental oxygen
Obtain a serum magnesium level
Reverse magnesium
10 mL of 10% calcium gluconate IV (1 g total) and over 3 min (i.e., slowly) to avoid hypotension and/or bradycardia
Calcium effect (competitively inhibits magnesium at neuromuscular junction) can wear off if magnesium level stays high
Furosemide may help increase urinary excretion
Respiratory arrest: Intubation and assisted ventilation as indicated
Other Prophylactic Agents
Magnesium sulfate is superior to diazepam, phenytoin and lytic cocktail (chlorpromazine, promethazine, pethidine) in reducing significantly the risk of seizure recurrence
Cochrane Review 2010: Magnesium sulfate reduced eclampsia compared to phenytoin (relative risk 0.08, 95% CI 0.01 to 0.60)
Morbidity related to pneumonia, mechanical ventilation and admission to an intensive care unit are significantly reduced with the use of magnesium sulfate compared with phenytoin
Magnesium sulfate does not cause maternal or newborn CNS depression
Diazepam or lorazepam does stop or shorten seizures, but risk of maternal apnea and/or cardiac arrest
ACOG Preeclampsia Guidelines: Antenatal Management and Timing of Delivery
SUMMARY:
Recommendations for prenatal assessment and perinatal management, including delivery, are included in the ACOG preeclampsia and gestational hypertension guidelines.
Inpatient vs Outpatient Management
Ambulatory management (outpatient) appropriate for the following
Gestational hypertension without severe features or
Preeclampsia without severe features
Inpatient management appropriate for the following
Severe preeclampsia or
Poor adherence to monitoring recommendations
How to Measure BP
Recommended technique for BP monitoring
Appropriate cuff size: 1.5 times upper arm circumference
Avoid tobacco or caffeine: Use in the 30 minutes preceding the measurement may lead to temporary rise in blood pressure
Patient should be upright after a 10-minute rest period
Inpatient setting: Measurement may be taken either
Sitting up or
Left lateral recumbent with arm at the level of the heart
Fetal and Maternal Assessment (Outpatient – No Severe Features)
Fetal Assessment
Fetal growth assessment every 3-4 weeks
Amniotic fluid assessment weekly
Antenatal testing 1-2 times per week
Maternal Assessment
Labs weekly (more frequently if concern that patient status is deteriorating)
Serum creatinine | Liver enzymes | Platelet count
Gestational hypertension: Include proteinuria
Note: If proteinuria is present, additional proteinuria measurements are not necessary
Clinical evaluation: At least one visit per week in-clinic
Obtain BP and evaluate for severe features (see ‘Related ObG Topics’ below)
Combination ambulatory and in-clinic assessment
BP and symptom assessment are recommended “serially”, using a combination of in-clinic and ambulatory approaches, with at least one visit per week in-clinic
sFlt-1/PlGF ratio to predict progression to preeclampsia with severe features
FDA approved | Studied in population of hospitalized patients between 23 and 35 weeks
ACOG states
There are insufficient data to recommend management strategies after a positive or negative test result
The sFlt-1:PlGF ratio alone should not replace current clinical criteria for diagnosing or excluding a diagnosis of preeclampsia with severe features
KEY POINTS:
Delivery vs Expectant Management
Decision regarding management based on gestational age and results from the following evaluation
Maternal: CBC | Creatinine | LDH, AST, ALT | Proteinuria | Uric acid if superimposed preeclampsia suspected
ISUOG Recommendations: Fetal Ultrasound Follow-Up for Women with Established Preeclampsia
SUMMARY:
The ISUOG Clinical Standards Committee has released practice guidelines reviewing the latest evidence and provides recommendations regarding the role of ultrasound in follow-up for women diagnosed with preeclampsia.
KEY POINTS:
Close fetal surveillance is warranted as deteriorating fetal status may be an indication for earlier delivery
Sonographic follow up of PE should include
Fetal growth
Biophysical profile
Fetal Doppler assessments
Frequency and impact of sonographic follow up has yet to be determined by large-scale clinical trials
Role of B-mode Ultrasound
Ultrasound assessment should include
Fetal growth
Rule out impaired growth
Biophysical profile
BPP of >8: Normal – manifestation of fetal wellbeing
BPP of 6: Inconclusive – repeat test
BPP of ≤4: Non-reassuring – consider delivery
Amniotic fluid volume
Ensure presence of MVP >2 cm and/or AFI >5 cm
Evidence that MVP may result in fewer interventions (see ‘Related ObG Topics’ below)
Placental edema and diffuse echogenicity due to edema
Thick placenta and reduced vascularization
Cystic regions (infarctions/ hematomas)
Abruption (poor sensitivity with 50 to 75% missed on ultrasound
Hematoma (preplacental and retroperitoneal) | Subchorionic and marginal blood | Increased placental thickness and echogenicity
Role of Doppler Studies
4 major Doppler exams
Umbilical artery (UA)
Fetal middle cerebral artery (MCA)
Fetal ductus venosus
Uterine arteries
Especially in the presence of maternal headache, abdominal pain, bleeding and/or reduced fetal movements consider
*UA
absent or reversed end-diastolic flow is strongly associated with poor perinatal outcomes
Increased resistance in the uterine arteries is not a useful indicator for timing of delivery
*Fetal MCA PI
Reduced MCA-PI <10th percentile (cephalization) may precede abnormal UA indices, and warrants close fetal surveillance
*Cerebroplacental ratio (CPR)
CPR: MCA PI / UA PI
CPR<10th percentile may represent hemodynamic redistribution
Warrants close fetal surveillance
Fetal ductus venosus
Unlike the above 3 indices (marked with *), ductus venosus is not included in ultrasound recommendation list (‘Good Practice Points’) for preeclampsia follow up
However, the guideline does point out that a reversed a-wave is strongly association with fetal cardiac deterioration
Note: ISUOG states that the above tests should also “be considered for women admitted for PE or with suspected PE, as well as for those with severe PE or HELLP syndrome” as a ‘Good Practice Point’.
Impact of Medications on Ultrasound Indices
Antihypertensives
Not associated with changes in maternal and fetal Doppler indices
Antenatal steroids
Associated with a transient decrease in vascular resistance in the UA and ductus venosus
ISUOG Recommendations for Preeclampsia Prevention: Combined Screening and the Role of Ultrasound
SUMMARY:
The ISUOG Clinical Standards Committee, based on the latest evidence, has released practice guidelines that provide recommendations regarding the role of ultrasound in screening for and follow-up of preeclampsia. Preventative strategies (such as low-dose aspirin) for preeclampsia are effective if started in the first trimester and should begin as soon as high-risk status is identified.
Given the superiority of combined screening, the use of Doppler cut-offs as a standalone screening modality should be avoided if combined screening is available (GRADE OF RECOMMENDATION: B)
Note: Screening refers to identification of at risk cases that may lead to prevention | Prediction refers to ability to identify at risk cases, but no evidence available regarding improved outcomes
Combined Screening (10-13 weeks) – Preferred where available
ASPRE trial results with a 10% FPR (see ASPRE summary in ‘Related ObG Topics’ below)
100% detection rate for preeclampsia <32 weeks
75% detection rate for preeclampsia <37 weeks
43% detection rate for preeclampsia ≥37 weeks
Combined screening approach is preferred over ultrasound alone and includes the following (see summary of ASPRE algorithm details in ‘Related ObG Topics’ below)
Maternal factors
History | Demographics | CVD and metabolic profile
Maternal arterial BP
Placental growth factor (PlGF)
Pulsatility index (PI) should be used to assess uterine artery resistance
Transabdominal approach preferred as used for most studies
Transabdominal: Use color flow mapping on a mid-sagittal view of the uterus at the level of the cervical internal os (transabdominal approach)
Transvaginal: Also obtain mid-sagittal view of the uterus, with lateral movement until paracervical vascular plexus is seen and uterine artery is also at the level of the internal cervical os
Identify an ascending or descending branch of the uterine arteries
Narrow Doppler sampling gate (2 mm)
Insonation angle <30 degrees
Peak systolic velocity of a uterine artery should be greater than 60 cm/s
PI measurement obtained when 3 identical waveforms are captured
95th percentile uterine artery mean PI (11-13 weeks)
Transabdominal: 2.35
Transvaginal 3.10 for CRL up to 65 mm
Uterine artery PI may be affected by
Ethnicity: African origin has higher PI
Obesity: Decreasing PI with increasing BMI
History of preeclampsia: Increased PI
Note: Placental volume and vascularization indices are not recommended | Combined screening in the second trimester compares favorably to first trimester, but aspirin intervention is ineffective if initiated >20 weeks
Ultrasound Screening Only
First Trimester Ultrasound Screening (10-13 weeks)
Due to maternal effects and lesser performance, uterine artery PI is not preferred as a stand-alone test based on cut-offs, but should preferably be incorporated into a combined, multifactorial screening model (see above)
Uterine artery PI >90th percentile in the first trimester detects
47.8% of women who will develop early PE (7.9% FPR)
26.4% of women who will develop any PE (6.6% FPR)
PI is superior to resistance index (RI) or uterine artery notching as a preeclampsia predictive tool
PI is more stable than RI, and may still be used in cases of absent or reversed diastolic values
Uterine artery notching is a subjective measure with low specificity
Associated with 22-fold increased risk for preeclampsia and 9-fold increased risk for an SGA neonate
However, may be observed in up to 50% of patients at 11-13th weeks
Second Trimester Ultrasound Screening
Uterine artery PI may be performed at time of the second trimester scan (10% FPR)
85% detection of early-onset preeclampsia
48% detection of late-onset preeclampsia
95th percentile uterine artery mean PI (23 weeks)
Transabdominal: 1.44
Transvaginal: 1.58
Third Trimester Ultrasound Screening
Use of PI during this period is not recommended due to insufficient outcomes data
Multifetal Pregnancies
Use twin-specific reference ranges
Increased placental mass and lower mean uterine artery resistance seen in multiple gestation
Results from the SPREE Trial: How Does First Trimester Preeclampsia Screening Compare to Current Guidelines?
BACKGROUND AND PURPOSE:
Current NICE guidelines use maternal characteristics and medical history to identify women at high risk for preeclampsia (PE) who could benefit from aspirin
NICE guideline considers a pregnant woman at high risk if
Any one major factor
History of hypertensive disease in previous pregnancy
Chronic kidney disease
Autoimmune disease
Diabetes mellitus
Chronic hypertension
OR any two moderate factors
First pregnancy at age ≥ 40 years
Interpregnancy interval > 10 years
BMI at first visit ≥ 35 kg/m2
Family history of PE
Using more traditional approach of professional committees, each factor is considered separately
Tan et al. (Ultrasound in Obstetrics & Gynecology, 2018) compared the above NICE approach to screening PE to a method that uses Bayes’ theorem that combines maternal factors with biomarkers
METHODS:
Prospective multicenter cohort study
Screening program for pre-eclampsia (SPREE) study
Participants: Singleton pregnancies at 11–13 weeks’ gestation had recording of maternal characteristics and medical history and measurements of
The performance of screening for PE by the Bayes’ theorem‐based method was compared with that of the NICE method
Primary outcome
Detection rate (DR) using NICE method vs mini‐combined test (maternal factors, MAP and PAPP‐A) in the prediction of PE at any gestational age (all‐PE) for the same screen‐positive rate determined by the NICE method
Secondary comparisons
DR of screening recommended by the NICE guidelines vs 3 Bayes’ theorem‐based methods for prediction of preterm PE (requiring delivery <37weeks)
Maternal factors, MAP and PAPP‐A
Maternal factors, MAP and PlGF
Maternal factors, MAP, UtA‐PI and PlGF
RESULTS:
17,051 women were eligible and outcome data were obtained from 16,747
All-PE developed in 2.8% of the 16,747 pregnancies and preterm PE developed in 0.8%
NICE method for PE
Screen positive rate: 10.3%
DR for all‐PE: 30.4%
DR for preterm PE: 40.8%
There was only 23% compliance with aspirin recommendation
Mini-combined method for PE
DR of the mini‐combined test for all‐PE was 42.5%
Superior to that of the NICE method by 12.1% (95% CI, 7.9–16.2%)
Screening for preterm PE compared to NICE
Maternal factors, MAP and PlGF: DR was 69.0%, which was superior to NICE method by 28.2% (95% CI, 19.4–37.0%)
Maternal factors, MAP, UtA‐PI and PlGF: DR was 82.4%, which was to NICE method by 41.6% (95% CI, 33.2–49.9%)
CONCLUSION:
NICE detection rates and compliance were lower than using a Bayesian approach that incorporates serum markers
The authors state that a PE methodology that combines biomarkers with maternal factors is a substantial improvement over current recommendations
ASPRE Trial: A Combined Risk Algorithm and Use of Aspirin to Prevent Preterm Preeclampsia
BACKGROUND AND PURPOSE:
Multiple studies have demonstrated beneficial effects of low dose aspirin for prevention of preeclampsia
ACOG supports the key USPSTF findings and recommends considering the use of low dose aspirin (81 mg/day) between 12 and 28 weeks’ gestation in women with known clinical risk factors including
History of preeclampsia, especially if accompanied by an adverse outcome
Multifetal gestation
Chronic hypertension
Diabetes (Type 1 or Type 2)
Renal disease
Autoimmune disease (for example, systematic lupus erythematosus, antiphospholipid syndrome)
An alternative Bayesian risk algorithm that combines multiple clinical, biochemical and fetal sonographic (functional) findings at 11 to 13 weeks has been well studied an appears to have superior performance characteristics when compared to clinical factors alone
Applicable to general pregnant population, not just high risk
Previous studies have found that (1) starting aspirin ≤ 16 weeks provides greater preventative benefit; (2) prevention is limited to preterm preeclampsia; (3) there is a positive dose-dependent benefit effect beyond 81 mg/day; (4) taking aspirin in the evening may be beneficial
Purpose: The goal of the Aspirin for Evidence-Based Preeclampsia Prevention (ASPRE) trial (Rolnik, NEJM 2017) was to determine if 150 mg of aspirin at night could reduce the incidence of preterm preeclampsia in women identified at high risk using the combined Bayesian model approach
Population: Women undergoing their routine prenatal visit at 11 weeks 0 days through 13 weeks 6 days
Screening tool: Bayesian risk algorithm which assesses the following factors
Age
Weight and height (BMI)
Racial/ethnic origin (white, Afro-Caribbean, South Asian, East Asian, and mixed)
Medical History
Chronic hypertension
Systemic lupus erythematosus or antiphospholipid syndrome
Diabetes mellitus type 1 or 2
Mode of conception – spontaneous vs. assisted
Obstetrical history
Parity ( ≥ 24 weeks)
Previous preeclampsia
Gestational age and weight at delivery in the last pregnancy
Interval since last pregnancy
Family history of preeclampsia in the patient’s mother
Biomarkers
Mean arterial pressure (MAP)
Uterine artery pulsatility index (UtA-PI)
Pregnancy associated plasma protein-A (PAPP-A)
Placental growth factor (PlGF)
Intervention: 150 mg dose/day of aspirin or placebo from 11 to 14 weeks until 36 weeks
2971 women out of 26,941 women (11.0%) were ‘screen positive’ for risk of preterm preeclampsia
Following exclusion, withdrawal and loss to follow up, 798 participants remained in the aspirin group and 822 in the placebo group
RESULTS:
Delivery with preeclampsia < 37 weeks: Definition of preeclampsia based on International Society for the Study of Hypertension in Pregnancy criteria
1.6% in the aspirin group had preterm preeclampsia vs. 4.3% in the placebo group (odds ratio 0.38; 95% CI 0.20 to 0.74; P=0.004)
Secondary Outcomes: Such as abruption, stillbirth, miscarriage, neonatal morbidity and mortality
No statistical differences found but study not powered to draw definitive conclusions
Adverse Events: Including maternal, fetal and neonatal
No statistical differences between groups overall, including anemia, vaginal, nasal and other bleeding
CONCLUSION:
Aspirin did not reduce the incidence of term preeclampsia
In singleton pregnancies, using a combined Bayesian risk assessment tool, 150 mg of aspirin nightly from 11-14 weeks until 36 weeks led to a 62% reduction in the rate of preterm preeclampsia compared to placebo
Gestational Thrombocytopenia – a Diagnosis of Exclusion
Thrombocytopenia is a common finding which occurs in 7-12% of pregnant women. The cause of isolated thrombocytopenia may be differentiated by history, physical examination, laboratory investigation, and medical imaging.
CLINICAL ACTIONS:
When evaluating a patient for gestational thrombocytopenia (GT), consider the following
≥Use platelet count <150 x 109/L to define thrombocytopenia in pregnancy
Normal platelet range in nonpregnant women is 165-415 x 109/L
Expect lower platelet counts in pregnant women, especially 3rd trimester
Order the following tests to assist with diagnosis/underlying cause
Based on clinical context, may require medical imaging to evaluate splenic size
Diagnose GT in the absence of historical, clinical, hematological and biochemical findings that would suggest another underlying condition
Transfuse platelets to achieve minimum platelet counts if
<10 x 109/L even without surgery and/or procedures
<50 x 109/L if active bleeding present unless undergoing cesarean in which case prophylactic platelet transfusion is recommended (or other major surgery as per AABB guidance)
Epidural and spinal “are considered acceptable” if ≥70 x 109/L prior to epidural and
Platelet level stable | No coagulopathy | Platelet function normal | No antiplatelet or anticoagulant therapy
Limited evidence regarding low-dose aspirin combined with thrombocytopenia and neuraxial blockade
SYNOPSIS:
GT is the most common cause of thrombocytopenia in pregnancy and accounts for 80% of such cases. GT may be a result of hemodilution and enhanced platelet clearance. The low platelet counts associated with GT are seen during the second and third trimesters with the nadir rarely lower than 70 x 109/L. The diagnosis of GT is made by the presence of a decreased platelet count during pregnancy and should be considered a diagnosis of exclusion. GT usually resolves within days to two months postpartum.
KEY POINTS:
Primary immune thrombocytopenia (ITP) may be difficult to distinguish from GT
ITP induces development of platelet autoantibodies that may cross the placenta
Features that may help distinguish GT from ITP
GT usually mid-late 2nd & 3rd trimester / ITP all trimesters
GT only in pregnancy / ITP may occur outside pregnancy
GT will resolve postpartum / ITP may not resolve
GT does not affect fetus or neonate / ITP may cause neonatal thrombocytopenia
If the diagnosis thrombocytopenia is unclear at the time of delivery, assume ITP and manage accordingly due to fetal/newborn risk for thrombocytopenia
Mode of delivery in ITP should be based on obstetric indications alone
ITP treatment options comparable to non-pregnant management – corticosteroids and intravenous immune globulin (IVIG)
In pregnancy, may start at lower end of prednisone dose (10-20 mg daily) and titrate up
Both GT and ITP may recur
Other disorders resulting in non-isolated thrombocytopenia that will present with other related findings include
ACOG Guidance: Emergency Treatment for Severe Hypertension in Pregnancy
Summary:
Severe hypertension can be a life-threatening event during pregnancy and requires special vigilance in the postpartum period, particularly following hospital discharge. The goal of treatment is to control hypertension and prevent seizures. Uncontrolled hypertension can lead to heart failure, myocardial ischemia, renal injury and stroke.
When to Treat:
Urgently treat acute onset severe hypertension in pregnancy or postpartum period
SBP ≥160 and and/or DBP ≥110 mm Hg persisting for 15 minutes
systolic BP a predictor of maternal morbidity/mortality
Note: ACOG states that “any of these agents can be used to treat acute severe hypertension in pregnancy” | An approach detailed in ACOG guidance uses “an initial regimen of labetalol at 200 mg orally every 12 hours and increase the dose up to 800 mg orally every 8–12 hours as needed (maximum total 2,400 mg/d). If the maximum dose is inadequate to achieve the desired blood pressure goal, or the dosage is limited by adverse effect, then short-acting oral nifedipine can be added gradually”
Seizure Prophylaxis: Magnesium Sulfate
Remains drug of choice for seizure prophylaxis
Magnesium sulfate should not be used to reduce blood pressure
See more on magnesium sulfate in ‘Related ObG Topics’
When to Use
Severe features of preeclampsia
Administer to all women
No severe features of preeclampsia and systolic BP > 140 and < 160 mm Hg or diastolic BP > 90 and < 110 mm Hg
There is no consensus on this matter as prophylaxis will reduce eclampsia but 1 in 100 to 129 women need to be treated and side effects (although not life threatening) will increase
ACOG states that the decision to use magnesium sulfate when severe features are not present should be the decision of the “physician or institution, considering patient values or preferences, and the unique risk-benefit trade-off of each strategy”
Delivery and Postpartum
Vaginal delivery
Continue infusion 24 hours postpartum
Cesarean
Begin infusion (if not yet running) before surgery and continue 24 hours postpartum
Discontinuing prior to operative vaginal birth or cesarean section to avoid uterine atony or anesthetic drug interactions is not recommended
Administration
Loading dose of 4 to 6 g administered per infusion pump over 20 to 30 minutes (i.e., slowly) followed by a maintenance dose of 1 to 2 g per hour as a continuous intravenous infusion
IM option if IV access limited
10 g initially as a loading dose (5 g IM in each buttock) followed by 5 g every 4 hours
Diagnosing Preeclampsia – Key Definitions and ACOG Guidelines
WHAT IS IT?
Preeclampsia is a pregnancy specific hypertensive disease with multi-system involvement. It usually occurs after 20 weeks of gestation and can be superimposed on another hypertensive disorder. While preeclampsia was historically defined by the new onset of hypertension in combination with proteinuria, some women will present with hypertension and multisystemic signs in the absence of proteinuria. The presence of multisystemic signs is an indication of disease severity.
SUMMARY:
Diagnostic Criteria
Blood Pressure Criteria
Hypertension – systolic BP > 140 mm hg or diastolic BP > 90 mm hg or both
On two occasions at least 4 hours apart after 20 weeks gestations with previously normal BP
Considered ‘mild’ until diastolic BP > 110mm hg or systolic BP ≥160 mm Hg
Severe Hypertension – systolic BP > 160 mm hg or diastolic BP > 110 mm hg or both
Can confirm using a short time interval (e.g., minutes) to facilitate timely antihypertensive therapy
Note: Gestational Hypertension
ACOG defines gestational hypertension as “hypertension without proteinuria or severe features develops after 20 weeks of gestation and blood pressure levels return to normal in the postpartum period”
Caution and close follow-up is warranted as up to a half of women with gestational hypertension will go on to manifest signs an symptoms consistent with preeclampsia
Women with severe gestational hypertension, even in the absence of proteinuria should be managed similar to women with severe preeclampsia
ACOG states
Women with gestational hypertension with severe range blood pressures (a systolic blood pressure of 160 mm Hg or higher, or diastolic blood pressure of 110 mm Hg or higher) should be diagnosed with preeclampsia with severe features.
Proteinuria Criteria
24 hour urine collection >300 mg protein or
Single voided urine protein/creatinine ratio ≥0.3
Dipstick reading of 2+ (use only if other quantitative methods not available)
Preeclampsia Definitions
Preeclampsia
Hypertension and proteinuria or
In absence of proteinuria, new-onset hypertension with the new onset of any of the following
Thrombocytopenia: Platelets <100 x 109/L
Renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
Impaired liver function: Elevated blood concentrations of liver transaminases to twice normal concentration
Pulmonary edema
Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms
Preeclampsia with severe features
Preeclampsia diagnosis, above, with any of the following
Severe hypertension
On two occasions at least 4 hours apart while on bed rest (unless already on antihypertensive therapy)
Thrombocytopenia: Platelets <100 x 109/L
Impaired liver function (without an alternative diagnosis): Elevated liver transaminases greater than twice upper limit of normal or severe persistent right upper quadrant or epigastric pain not responsive to medications
Progressive renal insufficiency: serum creatinine >1.1 mg/dl or doubling of serum creatinine in the absence of other renal disease
Pulmonary edema
Neuro: Unexplained new-onset headache unresponsive to medication (without an alternative diagnosis) or visual symptoms
Note: The following are not diagnostic criteria for the diagnosis of preeclampsia or preeclampsia with severe features
Clinically evident edema
Rapid weight gain
Massive proteinuria
Does not qualify as a ‘severe feature’
Fetal growth restriction
ACOG states that while it is important to monitor fetal status, FGR in the setting of all other fetal assessment being within normal limits (e.g., AFV, Doppler), expectant management ‘may be reasonable’ if mother and fetus appear stable and no other clinical indication is present that would indicate the need for early delivery
Uric acid
Hyperuricemia in hypertensive pregnancy is not a diagnostic marker, but is an important finding as a risk factor for adverse maternal and fetal outcomes
Small for gestational age (SGA) infant
Prematurity
Risk for adverse maternal outcomes if include patients with preeclampsia and risks increase with increasing concentration of uric acid
May be warranted in the setting of ‘diagnostic dilemmas’ such as diagnosing superimposed preeclampsia in the setting of chronic hypertension
Aspirin Treatment for Women at Risk for Preeclampsia – ACOG, SMFM and USPSTF Recommendations
FINDINGS:
ACOG/SMFM have released guidance aligned with USPSTF regarding the use of low-dose aspirin during pregnancy to prevent preeclampsia. When indicated, low-dose aspirin should be started between 12 to 28 weeks and continued until delivery. Optimally, aspirin usage should begin <16 weeks.
Recommended (high risk)
Offer low-dose aspirin (81 mg/day) to women with ≥1 high risk factors
History of preeclampsia, especially if accompanied by an adverse outcome
Multifetal gestation
Chronic hypertension
Diabetes (Type 1 or Type 2)
Renal disease
Autoimmune disease (for example, systematic lupus erythematosus, antiphospholipid syndrome)
Moderate Risk Factors
Offer low-dose aspirin (81 mg/day) to women with ≥2 moderate risk factors
Nulliparity
Obesity (BMI >30)
Personal history
Low birthweight or SGA
Previous adverse pregnancy outcome
>10-year pregnancy interval
Family history of preeclampsia
Sister or mother
Social and demographic characteristics
Black race (as a proxy for underlying racism)
Lower income
Maternal age ≥35 years
IVF
Note: USPSTF does allow for consideration of aspirin prophylaxis if ≥1 moderate risk factor is present and states “Clinicians should use clinical judgment in assessing the risk for preeclampsia and discuss the benefits and harms of low-dose aspirin use with their patients”
Universal Implementation
Evidence supports a risk-based approach
ACOG/SMFM acknowledges that in some settings, a majority of patients will fall in to either high or moderate risk categories, and therefore
In these instances, universal implementation (eg, offering low-dose aspirin to all patients within such practices or institutions) may be medically reasonable
The USPSTF recommends the use of low-dose aspirin (81 mg/d) as preventive medication for preeclampsia after 12 weeks of gestation in persons who are at high risk for preeclampsia as per categories above (B recommendation – offer or provide this service)
Benefits
The most recent systematic evidence review (see ‘Learn More – Primary Sources) provided more precise estimate of the association between aspirin and the prevention of perinatal mortality (4% to 44% reduction in fetal and neonatal deaths)
Otherwise, benefits of low-dose aspirin for women at risk for preeclampsia were similar to previous reviews with lower risks for the following (moderate certainty)
Preeclampsia: Pooled relative risk (RR) 0.85 (95% CI, 0.75-0.95)
Perinatal mortality: Pooled RR 0.79 (95% CI, 0.66-0.96)
Preterm birth: Pooled RR 0.80 (95% CI, 0.67-0.95)
Intrauterine growth restriction: Pooled RR 0.82 (95% CI, 0.68-0.99)
Harms
No significant association was found for
PPH or other bleeding-related harms
Rare perinatal or longer-term harms
Long-term child developmental outcomes in offspring from in utero exposure to low-dose aspirin
Follow-up data from the Collaborative Low-dose Aspirin Study in Pregnancy (CLASP), found no differences in physical or developmental outcomes at 12 to 18 months
KEY POINTS:
Risk factors used for ACOG/SMFM recommendations only include factors obtained from the medical record
Uterine artery Doppler ultrasonography and biochemical markers are not included
ACOG/SMFM acknowledge that other studies, in particular the ASPRE trial (see ‘Related ObG Topics’ below), have incorporated ultrasound and maternal serum markers as well as doses >81 mg, but state
Further, the screening algorithm used includes first-trimester serum markers, including placental growth factor and pregnancy-associated plasma protein-A, as well as uterine artery dopplers, which limits the generalizability to a U.S. population. Therefore, a higher dose or doubling of the available 81-mg dose cannot be recommended at this time.
Screening for Preeclampsia
USPSTF
Recommends that blood pressure measurements should be obtained during each prenatal care visit throughout pregnancy
Does not find evidence to support routine use of point-of-care urine protein tests for preeclampsia screening
Various studies have incorporated not only clinical risk factors but also biochemical markers and ultrasound to determine which women are at risk for early onset preeclampsia and may benefit from aspirin prevention (see ‘Related ObG Topics’)
ACOG/SMFM considers the supporting data for the use of such combined risk assessment algorithms to be limited and without more prospective clinical utility trials, states that
…biomarkers and ultrasonography cannot accurately predict preeclampsia and should remain investigational.
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