COPO - Trans CPG HPN
COPO - Trans CPG HPN
COPO - Trans CPG HPN
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Preeclampsia:
Maternal Medical Risk Factors
Preeclampsia complicates about 3% of
pregnancies, and all hypertensive disorders 1. Underlying medical conditions:
affect about 5-10% of pregnancies. a. Diabetes mellitus - Among 462 women with
- etiology is multifactorial pregestational diabetes mellitus, Sibai, et al.
demonstrated a 20% occurrence of
Material Personal Risk Factors preeclampsia.
1. Primiparity - based study in Norway covering b. Antiphospholipid antibody syndrome - Two
all births since 1967 (about 1.5 million women), meta-analyses and a number of case-control
the risk of preeclampsia in first pregnancies was and cohort studies have found associations
3%, decreased to 1.7% in the second pregnancy. between preeclampsia and lupus anticoagulant,
Primiparity is associated with approximately 2.4- anticardiolipin, and/or anti-P2 glycoprotein. The
fold elevated risk of preeclampsia. presence of antiphospholipid antibodies
significantly increases the risk of developing
2. Primipaternity - The role of the father has
preeclampsia
long been hypothesized to be central in the
primipaternity model which can be interpreted c. Systemic lupus erythematosus - Maternal
by an immunogenetic hypothesis. This may be complications included lupus flare (25.6%),
interpreted as an immunological habituation to hypertension (16.3%), nephritis (16.1%),
paternal antigens through contact between the preeclampsia (7.6%) and eclampsia.
sperm and the female genital tract. Moreover, if d. Renal disease - Davies, et al. found that the
a woman becomes pregnant by a man who has prevalence of renal disease was higher in
fathered a preeclamptic pregnancy in a different women who developed preeclampsia compared
woman, her risk of developing is 1.8%. with those that did not (5.3% vs 1.8%)
3. History of Preeclampsia - The risk of 2. Maternal Infection - The risk of preeclampsia
recurrence is about 14%. The recurrence risk was increased in patients with urinary tract
was reported even higher in a study based on infection (OR 1.57, 95% CI 1.45-1.70) and
hospital records, with a 20-fold increase in the periodontal disease (OR 1.76, 95% CI 1.43-2.18).
preeclampsia risk compared with parous women
with no previous preeclampsia. Moreover,
severe preeclamptic women in an initial Placental/Fetal Risk Factors
pregnancy have a recurrence rate of as high as 1. Multiple Pregnancies - In women with twin
50%. gestations compared with those with singletons,
4. Obesity - The relationship between maternal the incidence o fgestational hypertension and
weight and the risk of preeclampsia is preeclampsia are both significantly increased,
progressive. It increases from 4.3% to 13.3% to 13% in singletons and 5-6% in twins. When a
BMI >35kg/m2 woman is pregnant with twins, her risk triples.
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“This Task Force report changes the paradigm Preeclampsia- In its absence, preeclampsia is
that we use in diagnosing preeclampsia from diagnosed as hypertension in association with
one that is dependent on new onset other multi-organ involvement such as
hypertension and proteinuria. The problem is thrombocytopenia, impaired liver function, new
that many patients with preeclampsia don't development of renal insufficiency, pulmonary
have enough proteinuria to meet the former edema, or new-onset cerebral or visual
criteria, so their diagnosis and treatment is disturbances
delayed." - This quote, perhaps, underlines the
reason for the changes recommended by the
most recent Task Force Report on Hypertension
in Pregnancy by the American College of
Obstetricians and Gynecologists (ACOG)
submitted last November 2013 and adopted by
many obstetrical bodies worldwide.
Four categories by ACOG Task Force:
I. Preeclampsia-eclampsia
2. Chronic hypertension (of whatever cause)
3. Chronic hypertension with superimposed
preeclampsia
4. Gestational hypertension
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Summary of biomarkers and their accuracy 1. Should aspirin be given to all women for
prevention of hypertensive disorders of
pregnancy?
- Aspirin should be given to patients at high risk
for development of hypertensive disorders of
pregnancy. (Level I; HIGH GRADE)
In a study by Duley, et al. which included 22
randomized trials, patients in the low risk
population given aspirin had a significant
decrease in the risk of preeclampsia, preterm
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birth and small for gestational age babies. evaluate its efficacy. (Level 1B; MODERATE
However, no significant difference was seen GRADE)
with gestational hypertension, eclampsia and In a study done last 2010, it was shown that bed
neonatal death. rest results in a statistically significant reduction
2. When should aspirin be started to prevent of in the risk of preeclampsia and gestational
hypertensive disorders of pregnancy? hypertension. However, the sample size is
- Aspirin should be given starting 16 weeks age relatively small and there is unclear risk of bias
of gestation. (Level I; HIGH GRADE) in the manner of randomization of the patients.
The study by Buold, et al. determined the 6. Should folic acid be used to prevent
optimal timing of initiation of aspirin in patients hypertensive disorders of pregnancy?
at high risk for hypertensive disorders of - The use of folic acid could not be
pregnancy.Gestational hypertension, recommended as this time. More studies are
preeclampsia, severe preeclampsia, preterm needed to evaluate its role In the prevention of
birth were significantly reduced when aspirin hypeflensive disorders of pregnancy. (Level 1B;
was started at 16 weeks. However, it did not LOW GRADE)
affect the Incidence of abruptio placenta. In a cohort study done last 2013 where folic acid
Aspirin given after 16 weeks age of gestation supplementation was given to all patients,
decreased gestational hypertension, various outcomes were noted. In patients who
preeclampsia, and preterm birth but did not are at least 70% compliant with the folic acid,
affect the occurrence of severe preeclampsia, they noted that 9.6% had gestational
intrauterine growth restriction (IUGR) and hypertension and 2.4% had preeclampsia. In this
abruptio placenta. study they computed a RR of 1.00 (95% Cl 0.93-
3. Should high dose calcium be used in the 1.08) for preeclampsia and 1.11 (95% Cl 1.08-
prevention of hypertensive disorders? 1.14) for gestational hypertension, negating the
- High dose calcium is recommended for role of folic acid for the prevention of
patients with adequate and inadequate calcium hypertensive disorders of pregnancy.
intake. (Level 1; HIGH GRADE) 7. Should marine oil supplementation be given
In a meta-analysis by Hofmeyr, et al. in 2014, for the prevention of hypertensive disorders of
the use of high dose calcium supplementation of pregnancy?
1500-2000 mg/day in patients with adequate - Fish oil or marine oil supplementation is not
and calcium deficient diet showed that there recommended for the prevention of
was statistically significant reduction in hypertensive disorders of pregnancy. (Level IA;
hypertension with or without proteinuria in HIGH GRADE)
pregnancy with a RR of 0.90 (95% Cl 0.81-0.99) In a meta-analysis published last 2006 regarding
and RR of 0.44 (95% Cl 0.28-0.70). Preeclampsia the role of marine oil supplementation, it was
was also reduced based on the 4 studies with a noted that fish oil supplementation did not
RR of 0.62 (95% CI 0.32-1.2) in patients with reduce the incidence of preeclampsia (RR 0.86,
adequate calcium intake versus a RR of 0.36 95% CI 0.59-1.27), gestational hypertension (RR
(95% CI 0.20-0.65) in calcium deficient 1.09, 95% CI 0.90-1.33), and eclampsia (RR 0.14,
individuals. 95% Cl 0.01-2.7)
4. Should regular aerobic exercise versus normal
physical activity be used for prevention of
hypertensive disorders of pregnancy? V. GESTATIONAL HPN AND PREECLAMPSIA
- Exercise does not decrease the risk for Gestational hypertension and preeclampsia
hypertensive disorders of pregnancy. More without severe features is blood pressure (BP)
studies are needed to evaluate its effect in elevation after 20 weeks of gestation in the
pregnant patients. (Level IA; MODERATE absence of proteinuria (gestational
GRADE) hypertension) or the other various systemic
findings which would qualify as preeclampsia
In nonpregnant women moderate exercise has with severe features.
been shown to reduce hypertension and
cardiovascular disease. It is currently Antihypertensives
recommended that 30 minutes of moderate 1. Use of antihypertensives in mild to moderate
exercise be done during normal pregnancy. It hypertension in pregnancy decreases the risk of
was hypothesized that this will improve severe HPN (Level I. MODERATE GRADE)
maternal endothelial dysfunction and stimulate
placental angiogenesis.
5. Should bed rest be used for prevention of
hypertensive disorders of pregnancy?
- Bed rest is not recommended to prevent 2. Use of antihypertensives in mild to moderate
preeclampsia. More studies are needed to hypertension in pregnancy does not
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significantly decrease the development of without severe features with serial assessment
preeclampsia (Level 1, MODERATE GRADE) of maternal symptoms and fetal movement
(daily by the woman) and serial measurements
of BP (twice weekly), and assessment of
3. Use of antihypertensives in mild to moderate platelet counts and liver enzymes (weekly) is
hypertension in pregnancy does not show any suggested. (Level III, MODERATE GRADE)
significant difference in the development of
fetal or neonatal death, preterm birth, small 2. Weekly assessment for proteinuria is
for gestational age (SGA) babies. (Level I, LOW recommended. (Level Ill, MODERATE
TO MODERATE GRADE) GRADE)
4. Hydralazine, compared to labetalol, had 3. Fetal growth assessment and antenatal
lower rates of persistent severe hypertension testing is recommended. If evidence of growth
(Level II, MODERATE GRADE) restriction is noted, Doppler studies should be
5.Hydralazine, compared to nifedipine, had done. (Level Ill. MODERATE GRADE)
higher rates of persistent severe hypertension. 4. Uric acid is weak in predicting eclampsia,
(Level Il, LOW GRADE) severe hypertension, poor fetal outcome, (Level
6. Hydralazine, compared to labetalol, was III, VERY LOW GRADE)
associated with more maternal hypotension. 5. Platelet count 100,000, elevated
(Level II. MODERATE GRADE) transaminases, creatinine 110 mmol/L predicts
7. Hydralazine, compared to nifedipine, was adverse maternal but not fetal outcomes.
associated with more maternal hypotension (Level 111, LOW GRADE)
(Level 11, LOW GRADE)
8. For women with mild gestational Proteinuria
hypertension or preeclampsia with a persistent 1. Measurement of protein-to-creatinine ratio
BP 160 mmHg systolic or 110 mmHg diastolic, it has potential diagnostic value for significant
is suggested that antihypertensive medications proteinuria in cases of suspected preeclampsia.
not be administered. (Level III. MODERATE (Level III, LOW GRADE)
GRADE) 2. Urine protein-to-creatinine ratio had a
9. Oral nifedipine and intravenous (IV) labetalol sensitivity of 80-94% and specificity of 74-100%.
regimens are similarly effective in the acute (Level III, MODERATE GRADE)
control of severe hypertension in pregnancy. 3. Proteinuric women with preeclampsia, as
(Level I, MODERATE GRADE) compared to those without proteinuria, were
significantly more likely to:
Magnesium Sulfate a. deliver prior to 37 wks (Level III LOW
1. For women with preeclampsia with systolic GRADE)
BP <160 mmHg and a diastolic BP <110 mmHg b. develop severe hypertension (Level Ill, LOW
and no maternal symptoms, it is suggested that GRADE)
magnesium sulfate (MgS04) not be
administered universally for the prevention of c. have a higher perinatal mortality (Level Ill,
eclampsia LOW GRADE)
2. There was no excess in neuromuscular 4. Proteinuric women with preeclampsia, as
weakness or severe maternal hypotension in compared to those without proteinuria, were
patients who received nifedipine with MgS04 as significantly less likely to develop:
compared to controls who received placebo or a. Thrombocytopenia (< 100,000) (level III,
other antihypertensives with MgSO4. LOW GRADE)
(Level IV, VERYLOWGRADE)
3. The lower risk of eclampsia following b. Thrombocytopenia (< 150,000) (Level III,
prophylaxis with MgS04 was not LOW GRADE)
associated with a clear difference In the risk of c. Liver disease (Level III, LOW GRADE)
death or disability for children at 18 months 5. Non-proteinuric women with preeclampsia,
(Level 1, MODERATE GRADE) as compared to those with gestational
hypertension, were significantly more likely:
Antiplatelet Therapy
- Low dose aspirin has not been shown to a. Deliver prior to 37 weeks (Level III LOW
significantly decrease the incidence of GRADE)
preeclampsia in patients with gestational b. Develop severe hypertension (Level Ill. LOW
hypertension (Level III, LOW GRADE). GRADE)
c. To have small for gestational age (SGA)
Workup babies (Level 111, LOW GRADE)
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Maternal Complications
During expectant management, maternal
complications in reported studies include. HELLP
syndrome (4.1-27.1%), pulmonary edema (0
8.5%) and eclampsia and acute renal failure.
Expectant must provide heightened surveillance
to ensure adequate maternal oxygenation,
provide prompt intervention for symptoms of
hepatic dysfunction (HELLP syndrome or
subcapsular hematoma of the liver),
Recommendations
1. For women with severe preeclampsia ≥34
weeks of gestation, and in those with unstable
maternal or fetal conditions irrespective of
gestational age, delivery soon after maternal
stabilization is recommended. (Level Il, Grade
B)
2. For women with severe preeclampsia at <34
weeks of gestation with stable maternal and
fetal conditions, it is recommended that
continued pregnancy be undertaken only at
facilities with adequate maternal and neonatal
intensive care resources. (Level Il, Grade B)
3. For women with severe preeclampsia
receiving expectant management at 34 weeks or
less of gestation, the administration of
corticosteroids for fetal lung maturity benefit is
Perinatal Complications recommended (Level I, Grade A)
During expectant management of patients with 4. It is recommended that corticosteroids be
severe preeclampsia at 24-34 weeks of given if the fetus is viable and 33 weeks or less
gestation, the rate of perinatal death ranged of gestation, but that delivery not be delayed
from 0 to 16.6%. Abruptio placenta is also a after initial maternal stabilization regardless of
reported complication and it ranged from 4.1% gestational age for women with severe
preeclampsia that is complicated further with
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any of the following: (Uncontrolled severe halted. Calcium gluconate 1g (10 ml,) over 10
hypertension, eclampsia, pulmonary edema minutes can be given if there is concern of
Abruptio placenta, DIC, Nonreassuring fetal MgSO4 toxicity.
status, and Fetal death) (Level ll. Grade B) MgS04 is the drug of choice for the prevention
5. It is recommended that corticosteroids be of convulsions among patients with severe
administered and delivery deferred for 48 preeclampsia who are managed expectantly.
hours if maternal and fetal conditions remain These patients should receive MgS04 for 24
stable for women with severe preeclampsia and hours during expectant management. The dose
a viable fetus at 33 6/7 weeks or less of of MgSO4 depends on the patient's body
gestation with any of the following: (PPROM, weight. Two grams per hour is given if the
Labor, thrombocytopenia, IUGR, Severe patient weighs >70 kg. Patients weighing < 70 kg
oligohydramnios, REDF in Doppler and Renal can receive the 1g hour infusion. If BP is
Dysfunction)(Level Il, Grade C) controlled adequately and fetal testing is
6. For women with severe preeclampsia reassuring, MgS04 is discontinued after 24
(sustained systolic BP of at least 160 mmHg or hours. MgSO4 can be given via:
diastolic BP of at least 110 mmHg), the use of a. Continuous IV infusion
anti-hypertensive therapy is recommended. b. Intermittent Intramuscular injection
(Level Il, Grade B)
7. For women with eclampsia, the 11. For women with severe preeclampsia, it is
administration of parenteral MgS04 is suggested that a delivery decision should not be
recommended. Grade A) based on the amount of proteinuria or change
in the amount of proteinuria. (Level 11, Grade B)
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Alternatives to MgSO4
1. Diazepam – may be used with phenytoin in Recommendations
the absence of MgSO4
2. Phenytoin – no consensual dosage regimen 1. Referral to an internist - for investigation and
but dose may be varied according to patient’s management of possible secondary causes as
weight. well as for possible target organ damage. (GPP)
2. Antihypertensive therapy in severe chronic
C. Antihypertensive Therapy - Patients With hypertension - Pregnant women with chronic
severe hypertension should be started on IV hypertension with persistent systolic BP 160
antihypertensive therapy, with the following mmHg or persistent diastolic BP 105 mmHg, or
recommended: those with evidence of target organ damage,
should be given antihypertensive therapy.
1. Hydralazine (drug of choice)- IV bolus of 5 or
10mg, not recommended for drip 3. Antihypertensive therapy for mild to
moderate chronic hypertension. - Those with
2. Clonidine -IM injection of 75-150 mcg is the persistent systolic BP 160 mmHg or persistent
next recommended drug diastolic BP 105 mmHg, and with no evidence of
3. Nifedipine - if given orally at 10 or 20mg, this target organ damage, should not be routinely in
drug takes effect within 15-50 minutes. antihypertensive therapy. (Level I, Grade A)
4. Labetalol - IV bolus Of 10-20 mg as initial 4. Antihypertensive for continuous therapy in
dose. Not given in CHF and asthma chronic hypertension in pregnancy -
Methyldopa, a centrally acting alpha-2
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adrenergic agonist, is the primary oral d. New onset renal insufficiency (sudden
medication recommended for chronic increase in serum creatinine)
hypertension in pregnancy. e. Cerebral or visual disturbances
5. Second line antihypertensives for continuous
therapy in chronic hypertension in pregnancy - Recommendations
Labetalol, a nonselective β-blocker with vascular 1. Where do we manage cases of chronic
alpha receptor-blocking ability, and nifedipine, a hypertension complicated by superimposed
calcium channel blocker, are second line oral preeclampsia? - The antenatal care and delivery
medications that can be used in chronic of women with chronic hypertension with
hypertension. (Level I, Grade 4) superimposed preeclampsia regardless of
gestational age should be done in facilities with
6. Antihypertensive drugs that should not be adequate maternal and neonatal intensive care
used during pregnancy - Angiotensin converting specialists and resources. (GPP)
enzyme inhibitors (ACE inhibitors) and
angiotensin receptor blockers (ARBS) should not 2. Should MgSO4, be given to women with
be given before conception and during the first chronic hypertension with superimposed
trimester of pregnancy because of evidence of preeclampsia with features? – MgSO4, therapy
teratogenicity. Likewise, they should not be is given to prevent eclampsia once there is the
used during the second and third trimesters of need, and is continued to the intrapartum or
pregnancy because of evidence of fetopathy. even postpartum period. (Level l, Grade A)
7. Antihypertensive drugs for use in urgent 3. When do you give antenatal corticosteroids? -
control of severe chronic hypertension in Antenatal steroids to enhance fetal lung
pregnancy - The parenteral form of labetalol maturity is given to those with 34 weeks
and hydralazine and the oral form of nifedipine gestational and who are being managed
are medications that can be safely used in the expectantly (Level I, Grade A)
urgent control of severe chronic hypertension. 4. When do you deliver those with chronic
The choice should be based on availability, hypertension with superimposed preeclampsia?
familiarity and experience with the use of the - Delivery is recommended when any one of
above medications. (Level I. Grade A) these conditions is present. (Uncontrolled HPN,
8. Fetal surveillance for IUGR in chronic Eclampsia, Abruptio Placenta, DIC, non-
hypertension - Serial ultrasonography to screen reassuring fetal status, and Pulmonary edema).
for IUGR is recommended. (Level II-3, Grade B) The delivery is done once the maternal
condition is stabilized regardless of gestational
9. Surveillance for fetal well-being in chronic age or completion of antenatal steroids. (Level I,
hypertension in pregnancy with IUGR - As an Grade A)
adjunct to conventional antenatal testing,
umbilical artery Doppler velocimetry is 5. When do you deliver patient’s with
recommended for cases where IUGR has been superimposed preeclampsia without severe
confirmed. (Level l, Grade A) features? - For women with chronic
hypertension with superimposed preeclampsia
10. Timing of delivery complicated by mild to without severe features, expectant
moderate chronic hypertension- In management up to 37 weeks is suggested.
uncomplicated chronic hypertension, delivery (Level II-1. Grade B).
before 38 weeks is not recommended. (Level I,
Grade A) 6. Can you do conservative management in
pregnancies complicated by chronic
hypertension with superimposed preeclampsia
2. Chronic Hypertension with Superimposed with severe features <34 weeks? - Expectant
Preeclampsia management can be offered to women with
- Chronic hypertension with superimposed chronic hypertension with superimposed
preeclampsia is defined as a sudden increase in preeclampsia with severe features before 34
BP in a pregnant woman with a previously well- weeks provided that both maternal and fetal
controlled chronic hypertension associated with conditions are stable and the patient is admitted
new onset proteinuria. A sudden increase in in a hospital capable of providing intensive
proteinuria in a chronic hypertensive woman maternal and neonatal care. (Level l, Grade A)
who already has preconceptional proteinuria is 7. Can the antihypertensives used during
also a basis for the diagnosis. pregnancy be continued during breastfeeding if
Chronic hypertension with superimposed needed for continuous BP control? - The
preeclampsia plus severe features: antihypertensives used during pregnancy can be
used and lactation if needed for continuous BP
a. Severe hypertension i.e. systolic BP ≥160 control. With the exception of diuretics, other
mmHg or diastolic BP ≥110 mmHg or both. antihypertensives not used for pregnant women
b. Thrombocytopenia (platelets 100,000fuL) can be used as well. (GPP).
c. Elevated liver transaminases (2x upper limit
of normal)
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A. Initial steps - Stabilize the mother, assess F. Postpartum course - Laboratory values may
fetal condition and decided whether prompt initially worsen following delivery. The time
delivery is indicated. course of recovery from HELLP was evaluated in
a series of 158 women with the disease.
B. Timing of Delivery – if HELLP develops before Decreasing platelet counts continued until 24-48
24 weeks, termination of pregnancy is strongly hours after delivery, while serum LDH
considered. Consensus of indication for prompt concentration usually peaked 24-48 hours
delivery: postpartum. In all patients who recovered, a
a. ≥34 weeks of gestation platelet count: 100,000 was achieved
b. Presence of severe maternal disease spontaneously by the postpartum day or within
72 hours of the platelet nadir. An upward trend
c. Non-reassuring fetal status in platelet count and a downward trend in LDH
C. Platelet Transfusion - Platelet count should concentration should be seen by the
be maintained at 20,000 and 40,000 for vaginal postpartum day in the absence of complications.
and cesarean delivery, respectively. In patients
with platelet count 40,000, 4-10 units of
platelets are transfused at the time of 12-STEP TREATMENT APPROACH
intubation. Platelet transfusion is also indicated 1. Anticipate and make the diagnosis
in patients with significant bleeding or platelet 2. Assess the maternal condition
count less than 20,000 irrespective of the 3. Assess the fetal condition: deliver sooner or
intended mode of delivery. later?
4. Control BP
5. Prevent seizures with MgSOr
6. Manage fluid and electrolytes.
7. Exercise judicious hemotherapy.
8. Manage labor and delivery.
9. Optimize perinatal care.
10. Intensively treat the postpartum patient.
11. Remain alert to the development of multiple
organ system failure.
12. Counsel about future pregnancies.
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