Obstetrics 3.

Dra. Padolina
Sept. 4, 2014

Hypertensive Disorders
OUTLINE
I.
Pregnancy Hypertension
II.
Classification of hypertension
a. Gestational hypertension
b. Preeclampsia-eclampsia syndrome
c. Chronic Hypertension
d. Chronic Hypertension with superimposed pre eclampsia
III.
Management of Pregnancy HPN
IV.
Antihypertensive Agents
V.
Preeclampsia without Severe Symptoms
VI.
Severe Preeclampsia
VII.
Chronic HPN before 38weeks AOG
VIII.
Research Recommendations
REFERENCES
1. PPT/Lecture
th
2. Williams 24
3. 2015a Trans
4. ACOG 2013 Guidelines for Hypertension in Pregnancy

PREGNANCY HYPERTENSION
Hypertension is diagnosed empirically when blood pressure exceeds
2
140 mm Hg systolic or 90 mm Hg diastolic.
In the past, it had been recommended that an incremental increase
from midpregnancy values by 30 mm Hg systolic or 15 mm Hg diastolic
pressure be used as diagnostic criteria, even when absolute values
2
were below 140/90 mm Hg.
o These criteria are no longer recommended because evidence
shows that such women are not likely to experience increased
2
adverse pregnancy outcomes
Women who have a rise in pressure of 30 mm Hg systolic or 15 mm Hg
2
diastolic should be seen more frequently.
Eclamptic seizures develop in some women whose blood pressures
2
have been below 140/90 mm Hg
Edema is also no longer used as a diagnostic criterion because it is too
2
common in normal pregnancy to be discriminant.

CLASSIFICATION OF HYPERTENSION
Four types of hypertensive disease complicating pregnancy:
o Gestational Hypertension
o Preeclampsia-eclampsia
o Chronic hypertension
o Chronic hypertension with superimposed preeclampsia

Table 1. Comparison between gestational and chronic hypertension

PROTEINURIA
ONSET OF
POST PARTUM
HYPERTENSION
GESTATIONAL
absent
>20 weeks age
Resolves <12
HYPERTENSION
of gestation
weeks
postpartum
CHRONIC
absent
<20 weeks age
Persistent >12
HYPERTENSION
of gestation
weeks
postpartum

GESTATIONAL HYPERTENSION
women whose blood pressures reach 140/90 mm Hg for the first time
after midpregnancy, but in whom proteinuria is not identified
Criteria:
o Occurs >20 weeks AOG, often near term
o Systolic BP 140 mmHg or diastolic BP 90mmHg
o Previously normotensive women
o Resolves <12 weeks postpartum
o May have epigastric discomfort or thrombocytopenia

Group 26 | Valera, Vallester, Velasco, Velasquez, Verdejo

PREECLAMPSIA-ECLAMPSIA SYNDROME
Leading cause of maternal and perinatal morbidity and mortality
50,000-60,000 preeclampsia-related deaths/year worldwide
o Top 1 cause of maternal mortality in the Philippines
Referred to as a syndrome because organs that are connected to the
blood vessel will be affected which is why as of recent studies,
diagnosis for preeclampsia should include multiorgan affectation
Amount of proteinuria does not affect the maternal and fetal outcome,
prognosis and severity of the disease
Negative proteinuria is usually the cause of delayed intervention of
acutely ill patients with multiple organ dysfunctions
PREECLAMPSIA
Preeclampsia is best described as a pregnancy-specific syndrome that
2
can affect virtually every organ system.
o Evidence
of
multiorgan
involvement
may
include
thrombocytopenia, renal dysfunction, liver involvement, cerebral
symptoms, and pulmonary edema.
Diagnosis of proteinuria is not absolutely required as a criteria.
Appearance of proteinuria still remains an important diagnostic
criterion (it is an objective marker and reflect system-wide endothelial
leak) but overt proteinuria may not be a feature in some women with
2
preeclampsia syndrome.
2
Criteria required:
MINIMUM CRITERIA:
o Systolic blood pressure of 140mmHg and/or diastolic of
90mmHg
o Proteinuria

Excretion of 300mg protein in a 24 hour urine protein

collection

Protein/creatinine ratio of 3.9 (ratio of protein to creatinine

in a single voided urine)

Dipstick of +1
the only problem with this is the objectivity and
consistency of the results
Not recommended due to variability of results
Many false positives and false negatives findings
OTHER CRITERIA:
o Thrombocytopenia

Platelets < 100,000/L

o Renal insufficiency

Creatinine >1.1 mg/dL or doubling of baseline

o Liver involvement

Serum transaminase levels twice normal

o Cerebral symptoms

Headache, visual disturbances, convulsions

o Pulmonary edema
Diagnosis requires 2 determination at least 4-6 hours apart. If it is a
severe case, shorten the period of observation to 4 hours.

ETIOLOGY & PATHOGENESIS

Natural history would dictate that the fetus would be at an advantage if

there would be a direct increase of food and oxygen delivery from the
1
mother to the baby.
o Thus during normal implantation, endovascular trophoblasts
replace the vascular endothelial and muscular linings to enlarge
2
the diameter of the spiral arteries. (Fig. 1)

In some cases of preeclampsia, there may be incomplete trophoblastic

invasion. With this, decidual vessels, but not myometrial vessels,
become lined with endovascular trophoblasts. The deeper myometrial
arterioles do not lose their endothelial lining and musculoelastic tissue,
and their mean external diameter is only half that of corresponding
2
vessels in normal placentas.
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OBSTETRICS 3.1

In preeclampsia, vasoconstriction of the spiral arteries (Fig. 2 yellow

arrow) result in diminution of the nutrients and oxygen from the
mother to the baby. Impact of which would be the syndrome of
1
preeclampsia
o Diminished perfusion and a hypoxic environment eventually lead
to release of placental debris or microparticles that incite a
2
systemic inflammatory response.
o Antiangiogenic and metabolic factors and other inflammatory
mediators are thought to provoke endothelial cell injury, which
modify their nitric oxide production and interfere with
2
prostaglandin balance.
Loss of maternal immune tolerance to paternally derived placental and
fetal antigens is another theory cited to account for preeclampsia
2
syndrome.
From a hereditary viewpoint, preeclampsia is a multifactorial, polygenic
disorder. The hereditary predisposition for preeclampsia likely is the
result of interactions of literally hundreds of inherited genesboth
maternal and paternalthat control myriad enzymatic and metabolic
2
functions throughout every organ system.
Any satisfactory theory concerning the etiology and pathogenesis of
preeclampsia must account for the observation that gestational
2
hypertensive disorders are more likely to develop in women who:
o Are exposed to chorionic villi for the first time
o Are exposed to a superabundance of chorionic villi, as with twins
or hydatidiform mole
o Have preexisting renal or cardiovascular disease
o Are genetically predisposed to hypertension developing during
pregnancy.

Table 2. Indicators of Severity of Preeclampsia

CRITERIA
NONSEVERE
SEVERE
Systolic BP
160mmHg
160mmHg
Diastolic BP
<100 mmHg
110mmHg
a
Proteinuria
None to positive
None to positive
Headache
Absent
Present
Visual disturbances
Absent
Present
Upper abdominal pain
Absent
Present
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

Figure 1. Natural events that usually happen during pregnancy.

Figure 2. Incomplete trophoblastic invasion

INDICATORS OF SEVERE PREECLAMPSIA

BP 160/110 mmHg determined at least 4 hours apart
Thrombocytopenia

Group 26 | Valera, Vallester, Velasco, Velasquez, Verdejo

Signifies platelet activation and aggregation as well as

2
microangiopathic hemolysis.
Imparied liver function
o Epigastric or right upper quadrant pain frequently accompanies
hepatocellular necrosis, ischemia, and edema that ostensibly
stretches Glisson capsule. This characteristic pain is frequently
2
accompanied by elevated serum hepatic transaminase levels.
Progressive renal insufficiency
Pulmonary edema
1
Criteria eliminated as severe feature
o Proteinuria >5g
o IUGR
Preferred terminology: Preeclampsia with severe features or
preeclampsia without severe features instead of using mild or
1
severe
The differentiation between nonsevere and severe gestational
hypertension or preeclampsia can be misleading because what might
2
be apparently mild disease may progress rapidly to severe disease.

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
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
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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OBSTETRICS 3.1

o Other severe features

Over-diagnosis is preferred to increase surveillance

MANAGEMENT
Delivery is the only effective treatment
Table 3. Complications of Preeclampsia
MATERNAL
FETAL
COMPLICATIONS
COMPLICATIONS
Abruptio placenta
IUGR
HELLP

NEONATAL
COMPLICATIONS
Respiratory Distress
Syndrome
Bronchopulmonary
dysplasia
Retinopathy of
prematurity
Hypoglycemia

Fetal death in utero

DIC
Ischemic or
hemorrhagic stroke
Myocardial Infarction

Necrotizing
Enterocolitis (NEC)
Neurodevelopmental
problems/
Developmental delay

ANTEPARTUM MANAGEMENT
Maternal Evaluation
Laboratory Examination
o CBC with platelet count
o Serum Creatinine
o LDH
o Liver enzymes
o 24 hour urine proteins
Assessment of symptoms
o Severe headache
o Visual disturbances
o Epigastric pain
o
Shortness of breath
Fetal Evaluation
o Daily kick count
o Biometry
o Amniotic fluid
o Non stress test (NST)
o Gestational Hypertension
o Preeclampsia without severe features
Biophysical Profile
o Indirect way of looking into the fetal development
HOSPITALIZATION
Indicated for pregnant women with:
o Gestational hypertension or preeclampsia without severe features

surveillance is continued in the hospital

o New signs or symptoms of severe preeclampsia
o Severe hypertension (160/110 mmHg or higher)
o Evidence of fetal growth restriction
o Increased liver enzymes or thrombocytopenia
o Chronic hypertension with superimposed pre-eclampsia
o Worsening disease or severe features
o Concern for fetal well being
ANTIHYPERTENSIVE AGENTS
ANTIHYPERTENSIVE MEDICATIONS
Antihypertensive therapy recommended in:
o Preeclampsia with severe HPN - sustained systolic BP of 160 or
diastolic BP of 110

Group 26 | Valera, Vallester, Velasco, Velasquez, Verdejo

Chronic HPN: persistent systolic BP 160 or higher or diastolic BP at

least 105 or higher
Objectives in treatment of severe HPN:
o No consensus in the management of HPN in pregnant patients if
BP is NOT severely elevated.
o Non pregnant adults:

Anti HPN med for BP >/= 140/90

Supported by large trials showing benefits in treatment

Doppler Flow Analysis helps determine when the optimum time is to
deliver the baby
Close monitoring of women with gestational hypertension or
preeclampsia without severe features with assessment of:
o Maternal symptoms
o Fetal movement (daily)
o BP monitoring
o Platelet count and liver enzymes (weekly)

Table 4. Summary table for Pregnancy-related HPN requiring medications

CLASSIFICATION OF
HYPERTENSION
Gestational
preeclampsia
Preeclampsia
with severe
hypertension
Chronic
Hypertension
Chronic
Hypertension

BP

MEDICATION
No

QUALITY
OR
EVIDENCE
Moderate

STRENGTH OF
RECOMMENDATION
Qualified

<160/110
Sustained BP
160/110

Yes

Moderate

Strong

Sustained BP
160/105
BP < 160/105,
no end organ
damage

Yes

Moderate

Strong

No

Low

Qualified

IDEAL TARGET BP ON ANTIHYPERTENSIVE MEDICATIONS

Insufficient evidence to determine the optimal BP control on

antihypertensive therapy to improve maternal and fetal or neonatal
outcome

In a Cochrane review (256 participants):

o No significant difference in the adverse outcome between Tight
control (BP <130/80) and Loose control (BP <140/90)

No difference in both groups with regards to development of

severe preeclampsia, fetal distress, IUGR, NICU admission,
perinatal deaths, induction of labor and CS
Table 5. Medications for urgent BP Control during Pregnancy
DRUG
DOSE
COMMENTS
Labetalol
10-20mg IV then 20First line agent
80mg every 20-30 mins
Tachycardia less
to a max dose of
common with fewer
300mg
adverse effects
Constant infusion 1-2
Contraindications:
mg/min IV
asthma, heart disease
Hydralazine
5mg or IM then 5-10
Maternal HYPOtension,
mg IV every 20-40 min
headaches and fetal
OR Constant infusion
distress with higher or
0.5-10 mg/hr
frequent dosage may
be more common than
other agents
Nifedipine
10-20 mg orally, repeat Reflex tachycardia and
in 30 min if needed;
headache
then 10-20 mg every
2-6 hours
Table 6. Oral antihypertensive medications in pregnancy
DRUG
DOSE
COMMENTS
Labetalol
200-2400 mg/day
Well tolerated
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OBSTETRICS 3.1

Nifedipine

Methyldopa

orally in 2-3 divided

doses
30-120 mg/day orally
of a slow release
preparation
0.5-3 g/day in 2-3
divided doses

Do NOT use sublingual

form
Reflex tachycardia and
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 2 adrenergic agonist)
Cochrane analysis: less effective in preventing severe HPN compared to
-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
Short-acting nifedipine capsules are associated with maternal
Hypotension and fetal distress
No adverse effect in uterine and umbilical blood flow
There are theoretical concerns like excessive hypotension and
neuromuscular blockade with combined use of Nifedipine and
MgSO4.

Figure 3. Management of Preeclampsia without severe features

MAGNESIUM SULFATE

Significant decrease in adverse maternal outcome

No differences in rates of neonatal complications or cesarean
delivery

Severe preeclampsia
o Recommendation: administration of intrapartum-postpartum
MgSO4 to prevent eclampsia
o MgSO4 decreases the rate of eclampsia by 50%
Eclampsia
o Recommendation: administration of MgSO4
o MgSO4 superior to phenytoin and diazepam
o Continued for at least 24 hours after the last convulsion
o Quality of evidence: High
o Strength of recommendation: Strong
o IV loading dose of 4-6 grams then 1-2 grams for at least 24 hours
o Continue IV infusion even if patient delivers with the 24 hours

PREECLAMPSIA WITHOUT SEVERE FEATURES (MILD GESTATTIONAL HPN)

There has been a change in the management of preeclampsia without

severe features.
o Timing of delivery is at 37 weeks AOG

For mild gestational HPN or preeclampsia without severe features

between 34 to 37 weeks
o Recommendation: continued monitoring and delivery at 37 0/7
weeks AOG, if in the absence of abnormal fetal testing or other
4
severe conditions (PROM, pre-term labor or vaginal bleeding)

For pregnancy at AOG < 37 0/7 weeks and no indication for delivery:
4
o Expectant management with maternal and fetal monitoring

AOG 37 weeks
o Recommendation: Delivery rather than observation

Quality of evidence: Moderate

Strength of recommendation: Qualified

Multicenter trial: 756 women at 36-41 6/7 weeks with Gestational HPN
or preeclampsia without severe features; the women were divided into
Induction of labor group and an expectant group
o Induction of labor
Group 26 | Valera, Vallester, Velasco, Velasquez, Verdejo

SEVERE PREECLAMPSIA
For women with severe preeclampsia at or beyond 34 0/7 weeks AOG,
and in those with unstable maternal-fetal conditions irrespective of
4
AOG
o Recommendation: Delivery soon after maternal stabilization
For women with severe preeclampsia at less than 34 0/7 AOG with
4
stable maternal and fetal conditions
o Recommendation: Continued pregnancy be undertaken only at
facilities with adequate maternal and NICU resources
For women with severe preeclampsia receiving expectant
4
management at 34 weeks AOG or less
o Recommendation: administration of corticosteroids for fetal lung
maturity
SEVERE PREECLAMPSIA BEFORE FETAL VIABILITY
Recommendation: Delivery
o Expectant management: NOT recommended
o Quality of evidence: Moderate
o Strength of recommendation: Strong
Rare survival rates with expectant management of severe preeclampsia
at <23-24 weeks
Prenatal mortality 100% associated with severe IUGR

Table 7. Fetal survival rates in severe preeclampsia before 34 weeks AOG

AOG
Survival Rates

<23 weeks

0%

23 weeks

18.2%

24 weeks

57.7%

PROTEINURIA
Recommendation: Delivery decision in preeclampsia should NOT be
based on the amount or the degree of change in proteinuria.
o Quality of evidence: Moderate
o Strength of Recommendation: Strong
Sever preeclampsia categorized according to severity of proteinuria
o Mild: less than 5g/24 hours
o Severe: 5-9.9 g/24 hours
Page 4 of 5

OBSTETRICS 3.1

o Massive: more than 10 g/24 hours

No difference with regards to outcomes: eclampsia, abruption
placenta, pulmonary edema, HELLP, neonatal death or morbidity
Proteinuria increases over time during expectant management this
change is NOT predictive of pregnancy prolongation or perinatal
outcomes

Table 8. Management of CH with superimposed preeclampsia

With severe features

Without severe
Uncontrolled severe
features
HPN

With stable
Pulmonary edema
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

Group 26 | Valera, Vallester, Velasco, Velasquez, Verdejo

Page 5 of 5