Obstetrics 3.1 Dra.

Padolina
Hypertensive Disorders Sept. 4, 2014

OUTLINE PREECLAMPSIA-ECLAMPSIA SYNDROME

I. Pregnancy Hypertension  Leading cause of maternal and perinatal morbidity and mortality
II. Classification of hypertension  50,000-60,000 preeclampsia-related deaths/year worldwide
a. Gestational hypertension o Top 1 cause of maternal mortality in the Philippines
b. Preeclampsia-eclampsia syndrome  Referred to as a syndrome because organs that are connected to the
c. Chronic Hypertension blood vessel will be affected which is why as of recent studies,
d. Chronic Hypertension with superimposed pre eclampsia diagnosis for preeclampsia should include multiorgan affectation
III. Management of Pregnancy HPN  Amount of proteinuria does not affect the maternal and fetal outcome,
IV. Antihypertensive Agents prognosis and severity of the disease
V. Preeclampsia without Severe Symptoms  Negative proteinuria is usually the cause of delayed intervention of
VI. Severe Preeclampsia acutely ill patients with multiple organ dysfunctions
VII. Chronic HPN before 38weeks AOG
VIII. Research Recommendations PREECLAMPSIA
 Preeclampsia is best described as a pregnancy-specific syndrome that
REFERENCES can affect virtually every organ system.
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1. PPT/Lecture o Evidence of multiorgan involvement may include

th
2. Williams 24 thrombocytopenia, renal dysfunction, liver involvement, cerebral
3. 2015a Trans symptoms, and pulmonary edema.
4. ACOG 2013 Guidelines for Hypertension in Pregnancy  Diagnosis of proteinuria is not absolutely required as a criteria.
 Appearance of proteinuria still remains an important diagnostic
PREGNANCY HYPERTENSION criterion (it is an objective marker and reflect system-wide endothelial
 Hypertension is diagnosed empirically when blood pressure exceeds leak) but overt proteinuria may not be a feature in some women with
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140 mm Hg systolic or 90 mm Hg diastolic. preeclampsia syndrome.
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 In the past, it had been recommended that an incremental increase  Criteria required:
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from midpregnancy values by 30 mm Hg systolic or 15 mm Hg diastolic MINIMUM CRITERIA:

pressure be used as diagnostic criteria, even when absolute values o Systolic blood pressure of ≥140mmHg and/or diastolic of
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were below 140/90 mm Hg. ≥90mmHg
o These criteria are no longer recommended because evidence o Proteinuria
shows that such women are not likely to experience increased  Excretion of ≥ 300mg protein in a 24 hour urine protein
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adverse pregnancy outcomes collection
 Women who have a rise in pressure of 30 mm Hg systolic or 15 mm Hg  Protein/creatinine ratio of ≥3.9 (ratio of protein to creatinine
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diastolic should be seen more frequently. in a single voided urine)
 Eclamptic seizures develop in some women whose blood pressures  Dipstick of +1
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have been below 140/90 mm Hg  the only problem with this is the objectivity and
 Edema is also no longer used as a diagnostic criterion because it is too consistency of the results
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common in normal pregnancy to be discriminant.  Not recommended due to variability of results
 Many false positives and false negatives findings
CLASSIFICATION OF HYPERTENSION OTHER CRITERIA:
 Four types of hypertensive disease complicating pregnancy: o Thrombocytopenia
o Gestational Hypertension  Platelets < 100,000/µL
o Preeclampsia-eclampsia o Renal insufficiency
o Chronic hypertension  Creatinine >1.1 mg/dL or doubling of baseline
o Chronic hypertension with superimposed preeclampsia o Liver involvement
 Serum transaminase levels twice normal
Table 1. Comparison between gestational and chronic hypertension o Cerebral symptoms
PROTEINURIA ONSET OF POST PARTUM  Headache, visual disturbances, convulsions
HYPERTENSION o Pulmonary edema
GESTATIONAL absent >20 weeks age Resolves <12  Diagnosis requires 2 determination at least 4-6 hours apart. If it is a
HYPERTENSION of gestation weeks severe case, shorten the period of observation to 4 hours.
postpartum
CHRONIC absent <20 weeks age Persistent >12 ETIOLOGY & PATHOGENESIS
HYPERTENSION of gestation weeks  Natural history would dictate that the fetus would be at an advantage if
postpartum there would be a direct increase of food and oxygen delivery from the
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mother to the baby.
GESTATIONAL HYPERTENSION o Thus during normal implantation, endovascular trophoblasts
 women whose blood pressures reach ≥140/90 mm Hg for the first time replace the vascular endothelial and muscular linings to enlarge
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after midpregnancy, but in whom proteinuria is not identified the diameter of the spiral arteries. (Fig. 1)
 Criteria:  In some cases of preeclampsia, there may be incomplete trophoblastic
o Occurs >20 weeks AOG, often near term invasion. With this, decidual vessels, but not myometrial vessels,
o Systolic BP ≥ 140 mmHg or diastolic BP ≥ 90mmHg become lined with endovascular trophoblasts. The deeper myometrial
o Previously normotensive women arterioles do not lose their endothelial lining and musculoelastic tissue,
o Resolves <12 weeks postpartum and their mean external diameter is only half that of corresponding
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o May have epigastric discomfort or thrombocytopenia vessels in normal placentas.

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 In preeclampsia, vasoconstriction of the spiral arteries (Fig. 2 yellow o Signifies platelet activation and aggregation as well as
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arrow) result in diminution of the nutrients and oxygen from the microangiopathic hemolysis.
mother to the baby. Impact of which would be the syndrome of  Imparied liver function
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preeclampsia o Epigastric or right upper quadrant pain frequently accompanies
o Diminished perfusion and a hypoxic environment eventually lead hepatocellular necrosis, ischemia, and edema that ostensibly
to release of placental debris or microparticles that incite a stretches Glisson capsule. This characteristic pain is frequently
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systemic inflammatory response. accompanied by elevated serum hepatic transaminase levels.
o Antiangiogenic and metabolic factors and other inflammatory  Progressive renal insufficiency
mediators are thought to provoke endothelial cell injury, which  Pulmonary edema
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modify their nitric oxide production and interfere with  Criteria eliminated as severe feature
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prostaglandin balance. o Proteinuria >5g
 Loss of maternal immune tolerance to paternally derived placental and o IUGR
fetal antigens is another theory cited to account for preeclampsia  Preferred terminology: Preeclampsia with severe features or
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syndrome. preeclampsia without severe features instead of using “mild” or
 From a hereditary viewpoint, preeclampsia is a multifactorial, polygenic “severe”
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disorder. The hereditary predisposition for preeclampsia likely is the  The differentiation between nonsevere and severe gestational
result of interactions of literally hundreds of inherited genes—both hypertension or preeclampsia can be misleading because what might
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maternal and paternal—that control myriad enzymatic and metabolic be apparently mild disease may progress rapidly to severe disease.
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functions throughout every organ system.
 Any satisfactory theory concerning the etiology and pathogenesis of Table 2. Indicators of Severity of Preeclampsia
preeclampsia must account for the observation that gestational CRITERIA NONSEVERE SEVERE
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hypertensive disorders are more likely to develop in women who: Systolic BP ≤160mmHg ≥160mmHg
o Are exposed to chorionic villi for the first time
 Diastolic BP <100 mmHg ≥110mmHg
o Are exposed to a superabundance of chorionic villi, as with twins Proteinuria
a
None to positive None to positive
or hydatidiform mole
 Headache Absent Present
o Have preexisting renal or cardiovascular disease
 Visual disturbances Absent Present
o Are genetically predisposed to hypertension developing during Upper abdominal pain Absent Present
pregnancy. Oliguria Absent Present
Convulsion (Eclampsia) Absent Present
Serum creatinine Normal Elevated
Thrombocytopenia Absent Present
Liver enzyme elevation Minimal Marked
Pulmonary edema Absent Present
a
Most disregard degrees of proteinuria as being severe or nonsevere

ECLAMPSIA
 Seizures or convulsions that cannot be attributed to other causes in a
woman with preeclampsia
 New onset grand mal seizures in preeclampsia
 Premonitory events of severe headaches
 May also occur in the absence of warning signs and symptoms
 Differential diagnosis: AV malformation, ruptured aneurysm, idiopathic
Figure 1. Natural events that usually happen during pregnancy. seizure disorder
 Case: A woman 22 weeks AOG in OPD, Systolic BP is 200mmHg, with a
history of loss of consciousness in the ER. You later notice that the
patient is having a seizure. If it cannot be attributed to any seizure
disorders, suspect eclampsia.
 If not managed, patient can have stroke or may die
 Fetus may also die due to vasoconstriction of vessels

CHRONIC HYPERTENSION
 Criteria:
o BP ≥140/90 mmHg before pregnancy or diagnosed before 20
weeks gestation not attributable to gestational trophoblastic
disease
o Hypertension first diagnosed after 20 weeks gestation and
persistent after 12 weeks postpartum

Figure 2. Incomplete trophoblastic invasion
INDICATORS OF SEVERE PREECLAMPSIA
 BP ≥ 160/110 mmHg determined at least 4 hours apart
 Thrombocytopenia
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CHRONIC HYPERTENSION WITH SUPERIMPOSED PRE ECLAMPSIA
 Proteinuria develops after 20 weeks
 Proteinuria present before 20 weeks with:
o Sudden exacerbation of hypertension or increased anti-HPN drug
dose
o Sudden substantial, sustained increase in protein excretion
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o Other severe features o Chronic HPN: persistent systolic BP 160 or higher or diastolic BP at
 Over-diagnosis is preferred to increase surveillance least 105 or higher
 Objectives in treatment of severe HPN:
MANAGEMENT o No consensus in the management of HPN in pregnant patients if
 Delivery is the only effective treatment BP is NOT severely elevated.
o Non pregnant adults:
Table 3. Complications of Preeclampsia  Anti HPN med for BP >/= 140/90
MATERNAL FETAL NEONATAL  Supported by large trials showing benefits in treatment
COMPLICATIONS COMPLICATIONS COMPLICATIONS  Doppler Flow Analysis – helps determine when the optimum time is to
Abruptio placenta IUGR Respiratory Distress deliver the baby
Syndrome  Close monitoring of women with gestational hypertension or
HELLP Fetal death in utero Bronchopulmonary preeclampsia without severe features with assessment of:
dysplasia o Maternal symptoms
DIC Retinopathy of o Fetal movement (daily)
prematurity o BP monitoring
Ischemic or Hypoglycemia o Platelet count and liver enzymes (weekly)
hemorrhagic stroke
Myocardial Infarction Necrotizing Table 4. Summary table for Pregnancy-related HPN requiring medications
Enterocolitis (NEC) CLASSIFI- BP MEDICA- QUALITY STRENGTH OF
Neurodevelopmental CATION OF TION OR RECOMMEN-
problems/ HYPERTENSION EVIDENCE DATION
Gestational <160/110 No Moderate Qualified
Developmental delay
preeclampsia
Preeclampsia Sustained BP≥ Yes Moderate Strong
ANTEPARTUM MANAGEMENT with severe 160/110
 Maternal Evaluation hypertension
 Laboratory Examination Chronic Sustained BP Yes Moderate Strong
o CBC with platelet count Hypertension ≥160/105
o Serum Creatinine Chronic BP < 160/105, No Low Qualified
Hypertension no end organ
o LDH
damage
o Liver enzymes
o 24 hour urine proteins
IDEAL TARGET BP ON ANTIHYPERTENSIVE MEDICATIONS
 Assessment of symptoms
 Insufficient evidence to determine the optimal BP control on
o Severe headache
antihypertensive therapy to improve maternal and fetal or neonatal
o Visual disturbances
outcome
o Epigastric pain
 In a Cochrane review (256 participants):
o Shortness of breath
o No significant difference in the adverse outcome between “Tight
 Fetal Evaluation
control” (BP <130/80) and “Loose control” (BP <140/90)
o Daily kick count
 No difference in both groups with regards to development of
o Biometry
severe preeclampsia, fetal distress, IUGR, NICU admission,
o Amniotic fluid
perinatal deaths, induction of labor and CS
o Non stress test (NST)
o Gestational Hypertension
Table 5. Medications for urgent BP Control during Pregnancy
o Preeclampsia without severe features
DRUG DOSE COMMENTS
 Biophysical Profile
o Indirect way of looking into the fetal development Labetalol 10-20mg IV then 20- First line agent
80mg every 20-30 mins Tachycardia less
HOSPITALIZATION to a max dose of common with fewer
 Indicated for pregnant women with: 300mg adverse effects
o Gestational hypertension or preeclampsia without severe features Constant infusion 1-2 Contraindications:
 surveillance is continued in the hospital mg/min IV asthma, heart disease
o New signs or symptoms of severe preeclampsia Hydralazine 5mg or IM then 5-10 Maternal HYPOtension,
o Severe hypertension (160/110 mmHg or higher) mg IV every 20-40 min headaches and fetal
o Evidence of fetal growth restriction OR Constant infusion distress with higher or
o Increased liver enzymes or thrombocytopenia 0.5-10 mg/hr frequent dosage may
o Chronic hypertension with superimposed pre-eclampsia be more common than
o Worsening disease or severe features other agents
o Concern for fetal well being Nifedipine 10-20 mg orally, repeat Reflex tachycardia and
in 30 min if needed; headache
ANTIHYPERTENSIVE AGENTS then 10-20 mg every
ANTIHYPERTENSIVE MEDICATIONS 2-6 hours
 Antihypertensive therapy recommended in:
o Preeclampsia with severe HPN - sustained systolic BP of ≥ 160 or Table 6. Oral antihypertensive medications in pregnancy
diastolic BP of ≥ 110 DRUG DOSE COMMENTS
Labetalol 200-2400 mg/day Well tolerated
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orally in 2-3 divided  Significant decrease in adverse maternal outcome

doses  No differences in rates of neonatal complications or cesarean
Nifedipine 30-120 mg/day orally Do NOT use sublingual delivery
of a slow release form
preparation
Methyldopa 0.5-3 g/day in 2-3 Reflex tachycardia and
divided doses headache

METHYLDOPA
 Long history of use in pregnancy
 Mainstay for patients with chronic hypertension with superimposed
preeclampsia
 Maintenance for patients with preeclampsia with severe features
 Gradual BP control in 6-8 hours as a result of the indirect mechanism of
action (centrally acting α2 adrenergic agonist)
 Cochrane analysis: less effective in preventing severe HPN compared to
β-blocker and Calcium channel blocker

NIFEDIPINE
 Most commonly used calcium channel blocker
 Long-acting preparations preferred
 Sublingual route NOT recommended
o Rapid unpredictable decrease in BP that may precipitate ischemic
events Figure 3. Management of Preeclampsia without severe features
 Short-acting nifedipine capsules are associated with maternal
Hypotension and fetal distress SEVERE PREECLAMPSIA
 No adverse effect in uterine and umbilical blood flow  For women with severe preeclampsia at or beyond 34 0/7 weeks AOG,
 There are theoretical concerns like excessive hypotension and and in those with unstable maternal-fetal conditions irrespective of
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neuromuscular blockade with combined use of Nifedipine and AOG
MgSO4. o Recommendation: Delivery soon after maternal stabilization
 For women with severe preeclampsia at less than 34 0/7 AOG with
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MAGNESIUM SULFATE stable maternal and fetal conditions
 Severe preeclampsia o Recommendation: Continued pregnancy be undertaken only at
o Recommendation: administration of intrapartum-postpartum facilities with adequate maternal and NICU resources
MgSO4 to prevent eclampsia  For women with severe preeclampsia receiving expectant
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o MgSO4 decreases the rate of eclampsia by 50% management at 34 weeks AOG or less
 Eclampsia o Recommendation: administration of corticosteroids for fetal lung
o Recommendation: administration of MgSO4 maturity
o MgSO4 superior to phenytoin and diazepam
o Continued for at least 24 hours after the last convulsion SEVERE PREECLAMPSIA BEFORE FETAL VIABILITY
o Quality of evidence: High  Recommendation: Delivery
o Strength of recommendation: Strong o Expectant management: NOT recommended
o IV loading dose of 4-6 grams then 1-2 grams for at least 24 hours o Quality of evidence: Moderate
o Continue IV infusion even if patient delivers with the 24 hours o Strength of recommendation: Strong
 Rare survival rates with expectant management of severe preeclampsia
PREECLAMPSIA WITHOUT SEVERE FEATURES (MILD GESTATTIONAL HPN) at <23-24 weeks
 There has been a change in the management of preeclampsia without  Prenatal mortality 100% associated with severe IUGR
severe features.
o Timing of delivery is at 37 weeks AOG Table 7. Fetal survival rates in severe preeclampsia before 34 weeks AOG
 For mild gestational HPN or preeclampsia without severe features AOG Survival Rates
between 34 to 37 weeks
<23 weeks 0%
o Recommendation: continued monitoring and delivery at 37 0/7
weeks AOG, if in the absence of abnormal fetal testing or other 23 weeks 18.2%
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severe conditions (PROM, pre-term labor or vaginal bleeding) 24 weeks 57.7%
 For pregnancy at AOG < 37 0/7 weeks and no indication for delivery:
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o Expectant management with maternal and fetal monitoring
PROTEINURIA
 AOG ≥ 37 weeks
 Recommendation: Delivery decision in preeclampsia should NOT be
o Recommendation: Delivery rather than observation
based on the amount or the degree of change in proteinuria.
 Quality of evidence: Moderate
o Quality of evidence: Moderate
 Strength of recommendation: Qualified
o Strength of Recommendation: Strong
 Multicenter trial: 756 women at 36-41 6/7 weeks with Gestational HPN
 Sever preeclampsia categorized according to severity of proteinuria
or preeclampsia without severe features; the women were divided into
o Mild: less than 5g/24 hours
Induction of labor group and an expectant group
o Severe: 5-9.9 g/24 hours
o Induction of labor
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o Massive: more than 10 g/24 hours

 No difference with regards to outcomes: eclampsia, abruption Table 8. Management of CH with superimposed preeclampsia
placenta, pulmonary edema, HELLP, neonatal death or morbidity  Without severe With severe features  Uncontrolled severe
 Proteinuria increases over time during expectant management  this features HPN
change is NOT predictive of pregnancy prolongation or perinatal  With stable  Pulmonary edema
outcomes maternal and fetal Delivery 34 weeks  Abruptio placenta
conditions  DIC
 Non-reassuring fetal
status
Expectant
management until 37
weeks Delivery after maternal
stabilization
irrespective of AOG or
full corticosteroid
benefit

THE STATE OF THE SCIENCE AND RESEARCH RECOMMENDATIONS

 In the past 10 years, the increase in the understanding of the
pathophysiology of preeclampsia concludes that it is a multisystemic
disease that affects all organ systems.
 It is with the delivery of the placenta that preeclampsia begins to
resolve.
 The insult to the placenta is proposed as an immunologically initiated
alteration in the trophoblast function which leads to the reduction in
trophoblast invasion.
o This further leads to failed vascular remodelling of the maternal
spiral arteries that perfuse the placenta which then alters
placental function.
o Altered placental function leads to maternal disease through
putative primary mediators (oxidative and endoplasmic reticulum
stress and inflammation) and secondary mediators (modifiers of
endothelial function and angiogenesis.

Figure 4. Management of severe preeclampsia

CHRONIC HYPERTENSION (CH) BEFORE 38 WEEKS AOG

 Recommendation: Delivery before 38 weeks AOG not warranted in
patients with only isolated and uncomplicated CH
o Quality of evidence: Moderate
o Strength of recommendation: Strong
o No known maternal or fetal benefit
o Risk of microbial complications

CH WITH SUPERIMPOSED PREECLAMPSIA

 Timing of delivery guided by subcategory
 Similar to preeclampsia with or without features
Edited by: Venus Rojas

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