OBSTETRICS AND GYNECOLOGY 2.
At ≥20 weeks of gestation
Pending Topics:
 Menstruation
 AUB
 Tanner stage
 Pre-eclampsia
 Gestational Hypertension
 Gestational Diabetes Mellitus
HYPERTENSION IN PREGNANCY
HEADS UP!
Hypertension After 20 weeks AOG:
A. Gestational hypertension – Gestational hypertension refers to hypertension without proteinuria or
other signs/symptoms of preeclampsia that develops after 20 weeks of gestation.
 It should resolve by 12 weeks postpartum.
 If hypertension persists beyond 12 weeks postpartum, the diagnosis is "revised" to chronic/pre-
existing hypertension that was masked by the physiologic decrease in blood pressure that occurs
in early pregnancy. If hypertension resolves postpartum, and if signs and symptoms of
preeclampsia have not developed, the diagnosis can be "revised" to transient hypertension of
pregnancy.
B. Preeclampsia – Preeclampsia refers to the new onset of hypertension and proteinuria or hypertension
and end-organ dysfunction with or without proteinuria after 20 weeks of gestation in a previously
normotensive woman. It may also develop postpartum. Severe hypertension or signs/symptoms of end-
organ injury represent the severe end of the disease spectrum.
 In 2013, the American College of Obstetricians and Gynecologists removed proteinuria as an
essential criterion for diagnosis of preeclampsia. They also removed massive proteinuria
(5 g/24 hours) and fetal growth restriction as possible features of severe disease because massive
proteinuria has a poor correlation with outcome and fetal growth restriction is managed similarly
whether or not preeclampsia is diagnosed. Oliguria was also removed as a characteristic of severe
disease.
C. Eclampsia refers to the development of grand mal seizures in a woman with preeclampsia, in the
absence of other neurologic conditions that could account for the seizure. (See "Eclampsia".)
 HELLP syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets) probably represents a severe
form of preeclampsia, but this relationship remains controversial; HELLP may be an independent
disorder.
Hypertension Before 20 weeks AOG:
A. Chronic/pre-existing hypertension – Chronic/pre-existing hypertension is defined as systolic pressure
≥140 mmHg and/or diastolic pressure ≥90 mmHg that antedates pregnancy or is present on at least two
occasions before the 20th week of gestation or persists longer than 12 weeks postpartum. It can be
primary (primary hypertension, formerly called "essential hypertension") or secondary to a variety of
medical disorders.
B. Preeclampsia superimposed upon chronic/pre-existing hypertension – Superimposed preeclampsia is
defined by the new onset of proteinuria, end-organ dysfunction, or both after 20 weeks of gestation in a
woman with chronic/pre-existing hypertension. For women with chronic/pre-existing hypertension who
have proteinuria prior to or in early pregnancy, superimposed preeclampsia is defined by worsening or
resistant hypertension (especially acutely) in the last half of pregnancy or development
of signs/symptoms of the severe end of the disease spectrum.
A. Gestational Hypertension
Is a clinical diagnosis defined by:
1. New onset of hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90
mmHg)
3. In the absence of proteinuria or new signs of end-organ dysfunction.
4. The blood pressure readings should be documented on at least two occasions at least four hours
apart. Gestational hypertension is severe when systolic blood pressure is ≥160
mmHg and/or diastolic blood pressure is ≥110 mmHg.
- Gestational hypertension is a temporary diagnosis for hypertensive pregnant women who do not meet
criteria for preeclampsia.
- Gestational hypertension is the most common cause of hypertension during pregnancy.
- prevalence is highest in women with preeclampsia in a previous pregnancy, women with multi-fetal
gestation, and overweight/obese women
 Risk Factors (Same as Pre-eclampsia)
 Diagnostic Evaluation - The main goals in the initial evaluation of pregnant women with newly developed
hypertension are to distinguish gestational hypertension from preeclampsia, which has a different course
and prognosis, and to determine whether hypertension is severe, which affects management and
outcome.
o Measure protein excretion — Urinary protein excretion should be determined since the presence or
absence of proteinuria is the key clinical criterion that determines whether the patient will be given a
diagnosis of gestational hypertension or preeclampsia.
 A urine dipstick of negative to trace should not be used to definitively exclude significant
proteinuria since false negative results occur with low specific gravity (<1.010), high salt
concentration, highly acidic urine, or with nonalbumin proteinuria.
 A positive urine dipstick value, especially if only +1, also requires confirmation since false
positives occur.
 Urine protein can be quantitated using a urine protein-to-creatinine ratio ≥0.26
mg protein/mg creatinine (30 mg/mmol) on a random urine sample or with a 24-hour urine
collection. We prefer the latter, as it conforms to the most widely accepted diagnostic criteria
for preeclampsia.
o Evaluate for features of severe disease — Patients should be questioned about the presence of
severe features of preeclampsia, such as the new onset of cerebral or visual disturbances or
epigastric or right upper quadrant pain. The chest should be auscultated to assess for pulmonary
edema. The presence of any of these findings upgrades the diagnosis to preeclampsia with severe
features.
o Perform laboratory evaluation — Laboratory evaluation helps to determine whether there is end
organ involvement, which occurs with preeclampsia but not gestational hypertension. Changes
consistent with preeclampsia with severe features include:
 Thrombocytopenia
 Increase in creatinine concentration to >1.1 mg/dL
 Doubling of hepatic transaminases
 o Determine the severity of hypertension — Hypertension is defined as systolic blood pressure ≥140
mmHg and/or diastolic blood pressure ≥90 mmHg. Hypertension in pregnancy is considered severe
when systolic blood pressure is ≥160 mmHg and/or diastolic blood pressure is ≥110 mmHg.
o Assess fetal well-being — As with all hypertensive pregnancies, fetal well-being should be assessed
with a biophysical profile or nonstress test with amniotic fluid estimation. We also obtain a sonographic
estimation of fetal weight; umbilical artery Doppler velocimetry is reserved for fetuses with growth
restriction
 RISK OF PROGRESSION TO PREECLAMPSIA
o Ten to 50 percent of women initially diagnosed with gestational hypertension go on to develop
preeclampsia in one to five weeks
o It is not clear whether gestational hypertension and preeclampsia are independent diseases with a
similar phenotype (hypertension) or if gestational hypertension is an early mild stage of
preeclampsia.
o There is consistent evidence that preeclampsia develops in a substantial proportion of women
initially diagnosed with gestational hypertension, and that women who progress to preeclampsia
have characteristics different from those who continue to have nonproteinuric hypertension.
o Clinical characteristics at presentation of gestational hypertension that predict an increased risk for
progression to preeclampsia include:
 Gestational age less than 34 weeks at diagnosis (sensitivity 85 percent, specificity 60 percent)
 Mean systolic blood pressure >135 mmHg on 24 hour blood pressure monitoring (sensitivity 61
percent, specificity 76 percent)
 Abnormal uterine artery Doppler velocimetry (sensitivity 86 percent, specificity 90 percent)
 Elevated serum uric acid level (>5.2 mg/dL [309 mmol/L]) (sensitivity 88 percent, specificity 93
percent)
o Other characteristics have been reported to be predictive, but are not readily measureable:
 elevated serum levels of anti-angiogenic markers (eg, sFlt- 1)
 reduced levels of proangiogenic placental growth factor
 higher total vascular resistance (>1340 dyne seconds/cm5)
 Management
o The decision to deliver women with preterm gestational hypertension attempts to balance three
competing factors:
1) The fetal benefits from expectant management (ie, further growth and maturation)
2) The maternal and fetal benefits from early intervention (ie, avoidance of complications from
progression of hypertensive disease over the remainder of pregnancy)
3) The maternal and fetal risks from expectant management (eg, progression of hypertensive
disease and possible sequelae, including stillbirth or asphyxia).
o We believe close surveillance of pregnancies with non-severe gestational hypertension managed
expectantly can mitigate the risk of development of serious sequelae of gestational hypertension;
therefore, we manage these patients expectantly and deliver them when their clinical situation
deteriorates or at term.
o For Blood pressure less than 160/110 mmHg
 Site of care — Most women with gestational hypertension without severe blood pressure
elevation (ie, systolic blood pressure is ≥160 mmHg and/or diastolic blood pressure is ≥110
mmHg) can be managed safely as outpatients with weekly or twice weekly antepartum visits
to measure blood pressure and protein excretion. Home blood pressure monitoring can be
useful to determine the patient’s average and peak blood pressure during usual activity.
 Patient education and counseling — are important components of management since these
patients are at increased risk of developing preeclampsia and other pregnancy complications.
 We instruct patients to promptly report any symptoms suggestive of preeclampsia
(headache, visual changes, epigastric or right upper quadrant pain).
 We also review signs suggestive of possible fetal impairment, such as decreased fetal
movement and vaginal bleeding, and signs of preterm labor.
 Patients should be given appropriate telephone numbers to call care providers for
questions and emergencies.
 Level of physical activity — Women may maintain most of their normal physical activities.
Bedrest at home or in the hospital does not prevent progression to preeclampsia or improve
maternal or fetal outcome, but reduces the frequency of worsening hypertension. The decision
to place a patient on bedrest should be individualized and should take into consideration her
blood pressures, comorbidities, and social factors. Prolonged bedrest should be avoided
because it increases the risk of venous thromboembolism.
 We advise against strength training and pure isometric exercise, such as weight lifting, as
these activities can acutely raise blood pressure to severe levels.
 Aerobic exercise can cause a modest rise in systolic pressure, usually with no change or
a slight reduction in diastolic pressure. In the absence of information about a woman’s
blood pressure response to her usual aerobic exercise activities, we advise against
aerobic exercise.
 Whether and how many hours the patient continues to work outside her home depends
on multiple factors, particularly her blood pressure at work. These decisions should be
made on a case-by-case basis.
 Low dose aspirin — Whether low dose aspirin prevents progression of gestational hypertension
to preeclampsia is unclear.
 We do not begin aspirin for prevention of preeclampsia after 20 weeks of gestation and
therefore do not prescribe it for women with gestational hypertension.
 Meta-analyses have shown that beginning low dose aspirin in the second trimester to
pregnant women at average or high risk of developing preeclampsia is associated with
a modest reduction in preeclampsia and its sequelae (growth restriction, preterm birth).
However, the included trials had a wide variety of inclusion and exclusion criteria, with
some including and others excluding women with gestational hypertension. Most women
in these trials began low dose aspirin before 20 weeks of gestation.
 Practice guidelines consistently recommend initiating low dose aspirin before 20 weeks
for this reason and because preeclampsia is known to affect placental development
early in pregnancy
 Maternal blood pressure and laboratory monitoring — American College of Obstetricians and
Gynecologists (ACOG) guidelines that suggest monitoring blood pressure once or twice weekly
in the office and weekly assessment of proteinuria, platelet count, and liver enzymes.
Proteinuria, thrombocytopenic, or elevated liver enzymes change the diagnosis to
preeclampsia, and these patients should be managed accordingly.
 Fetal assessment — In our practice, we ask patients with gestational hypertension to monitor
fetal movement daily and call if it is decreased or absent.
 Nonstress test with sonographic estimation of the amniotic fluid index or a biophysical
profile weekly. Testing is begun at 32 weeks of gestation, or earlier if an increased risk of
fetal demise is identified and delivery for perinatal benefit would be considered if test
results are abnormal.
 Serial ultrasound examinations to monitor fetal growth every three to four weeks, as
hypertension of any etiology may be associated with placental insufficiency. The need for,
type, and frequency of fetal assessment in women with gestational hypertension that is not
severe are controversial. There is no evidence from large randomized trials that any routine
surveillance method results in a decreased risk of fetal death or neonatal morbidity in these
patients.
 Antihypertensive therapy — We do not prescribe antihypertensive drugs for antepartum
treatment of gestational hypertension, unless hypertension is severe or approaching the severe
range or the patient has preexisting end organ dysfunction (eg, renal, cardiac) that may be
worsened by hypertension. Data from randomized trials show that drug therapy of mild
hypertension does not improve maternal or neonatal outcome. These data are reviewed
separately.
 For most women undergoing treatment of severe hypertension, the blood pressure goal is
130 to 150 mmHg systolic and 80 to 100 mmHg diastolic, similar to that in preeclampsia.
  Antenatal corticosteroids — If the clinician believes that an individual patient is at increased risk
for delivery within seven days and before 34 weeks of gestation (eg, coexistent pregnancy
complications, development of preeclampsia), then corticosteroids should be administered.
 However, a course of antenatal corticosteroids is not routinely administered to women
with non-severe gestational hypertension because preterm birth <34 weeks is uncommon.
 Timing of delivery — We recommend delivery at term for women with gestational hypertension,
in general agreement with guidelines from multiple major societies. The optimum gestational
age between 37 and 40 weeks for intervention (induction, cesarean delivery) because of
gestational hypertension is controversial. We individualize these cases based on the degree of
hypertension, presence of comorbidities, and the presence of risk factors for adverse
pregnancy outcome.
 For uncomplicated pregnancies with only an occasional blood pressure ≥140/90 mmHg
and <160/110 mmHg - we deliver at 38 to 39 weeks, since neonatal morbidity is lower than
at 37 to 38 weeks
 For pregnancies with frequent blood pressures ≥140/90 mmHg and <160/110 mmHg,
comorbidities, or other risk factors for adverse outcome - we deliver at 37 weeks.
 A consensus opinion from a workshop held by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development and the Society for Maternal-Fetal
Medicine suggested delivery at 370/7ths to 386/7ths weeks for all women with any degree of
gestational hypertension because of the risk of progression to preeclampsia
 The ACOG Task Force on Hypertension in Pregnancy suggests delivery rather than
expectant management for women with uncomplicated gestational hypertension at ≥37
weeks.
 Intrapartum management — During labor, we monitor women with gestational hypertension for
development of:
 Proteinuria
 Worsening hypertension
 Symptoms of severe disease since preeclampsia can manifest intrapartum.
 We do not administer magnesium sulfate seizure prophylaxis unless the patient develops
severe hypertension or symptoms or laboratory abnormalities associated with severe
preeclampsia.
o Blood pressure greater than 160/110 mmHg — Systolic blood pressure ≥160 mmHg or diastolic blood
pressure ≥110 mmHg should be treated with antihypertensive drugs to reduce the risk of stroke:
 Although there are no data that severe gestational hypertension is associated with
cerebrovascular regulatory defects (as seen in preeclampsia) or that these women are at
increased risk of stroke. A reasonable blood pressure goal is 130 to 150 mmHg systolic and 80 to
100 mmHg diastolic.
 Women who develop severe gestational hypertension have rates of pregnancy complications
comparable with those with preeclampsia with severe features, and thus are managed similarly.
 For >34 weeks, We suggest delivery for pregnancies
 For pregnancies <34 weeks, administration of a course of antenatal corticosteroids and
frequent blood pressure, laboratory, and fetal monitoring in the hospital is a reasonable
approach. If the patient's blood pressure is easily controlled with medication, she does not
develop preeclampsia, and the fetus remains healthy, we favor delivery at 34 to 36 weeks.
o Patients who develop preeclampsia or have abnormal results on antepartum fetal testing are
managed according to usual standards for these pregnancy complications.
o We administer magnesium sulfate for peripartum seizure prophylaxis to women with gestational
hypertension at this blood pressure level because eclampsia has been reported in these patients
and consistent with expert opinion.
 Maternal Prognosis:
o Postpartum course — Most women with gestational hypertension become normotensive within the
first postpartum week.
 If blood pressure returns to normal by 12 weeks postpartum, their diagnosis is changed to
transient hypertension of pregnancy.
 If they remain hypertensive at the 12th postpartum week, they are given the diagnosis of chronic
hypertension
o The mean time to normalization of blood pressure postpartum after preeclamptic pregnancies is
about two weeks. The slower rate of recovery in preeclampsia may reflect the time required for
resolution of the endothelial injury, which may not be present in gestational hypertension.
o The decision to use nonsteroidal antiinflammatory agents for postpartum analgesia should be
individualized, as these drugs are known to cause elevations in blood pressure in non-pregnant
individuals with hypertension. If blood pressure is elevated in the postpartum period, we recommend
avoiding these drugs.
o Recurrence risk — A 2015 meta-analysis of individual patient data from almost 24,000 women with
gestational hypertension who became pregnant again reported that 22 percent developed
hypertension in a subsequent pregnancy (gestational hypertension: 15 percent, preeclampsia: 7
percent). Given these data and other data that women with a high risk factor or several moderate
risk factors for preeclampsia may benefit from low dose aspirin therapy in pregnancy, we offer
women with a history of gestational hypertension and blood pressures ≥160/110 mmHg low dose
aspirin in future pregnancies to reduce their risk of developing preeclampsia.
o Long-term prognosis — Gestational hypertension is associated with development of hypertension
later in life, and also with development of diseases related to hypertension (cardiovascular disease,
hyperlipidemia, chronic kidney disease, diabetes mellitus).
 A prospective study of over 15,000 women with a first singleton birth observed that women with
gestational hypertension in three consecutive pregnancies had significantly higher blood
pressure later in life than women who remained normotensive (systolic pressure 27 mmHg
higher, diastolic pressure 12 mmHg higher).
 They also had more unfavorable lipid and glycemic profiles, but these differences appeared to
be due to higher body mass index at follow-up in women with a history of hypertension in
pregnancy. Clinical monitoring, risk factor evaluation, and early intervention might benefit
women with a history of hypertension of any etiology in pregnancy.
 Perinatal Outcome:
 Non-severe hypertension -- Pregnancy outcomes of patients with non-severe gestational
hypertension are generally favourable.
o Most studies report that the mean birth weight and rates of fetal growth restriction,
preterm birth, abruption, and perinatal death are similar to those in the general
obstetrical population.
 o However, one population-based cohort study reported that the risk of delivering a
small for gestational age newborn at term increased by 2 percent for each mmHg rise
in diastolic blood pressure from early to late pregnancy, even in the absence of overt
hypertension
 Severe hypertension -- Pregnancies associated with severe gestational hypertension appear
to be at increased risk of maternal and perinatal morbidity. These pregnancies have rates of:
o Preterm delivery
o Small for gestational age (SGA) infants
o Abruptio placentae
B. Pre-eclampsia
- is a multi-system progressive disorder characterized by the new onset of hypertension and proteinuria, or
hypertension and end-organ dysfunction with or without proteinuria, in the last half of pregnancy or
postpartum.
- The disorder is caused by placental and maternal vascular dysfunction and always resolves after
delivery. Although most affected pregnancies deliver at term or near term with good maternal and fetal
outcomes, these pregnancies are at increased risk for maternal and/or fetal mortality or serious
morbidity. In addition, women with preeclampsia are at increased risk for future cardiovascular disease.
a. Risk Factors:
o A past history of preeclampsia increases the risk of developing preeclampsia in a subsequent
pregnancy sevenfold compared with women without this history
o The severity of preeclampsia strongly impacts this risk. Women with severe features of
preeclampsia in the second trimester are at greatest risk of developing preeclampsia in a
subsequent pregnancy
o First pregnancy (nulliparity) - It is unclear why the nulliparous state is consistently found to be a
significant predisposing factor for preeclampsia.
o One theory is that the immune system of nulliparous women has had limited exposure to
paternal antigens, and this lack of desensitization may play a role in the pathogenesis of the
disease. Epidemiologic data support this theory: Protection from preeclampsia in subsequent
pregnancies is either reduced or eliminated if there is a change in paternity, women using
barrier methods of contraception are at increased risk, and risk is reduced with increased
duration of sexual activity before pregnancy. However, the notion that the risk of
preeclampsia is increased in a second pregnancy with a new partner has been challenged
by data suggesting that a longer interval between pregnancies may be the reason for the
increased risk with a new partner.
o A family history of preeclampsia in a first-degree relative, a heritable mechanism in some cases. The
occurrence and severity of the disease appears to be influenced primarily by maternal factors, but
the paternal contribution to fetal genes may have a role in defective placentation and subsequent
preeclampsia.
o Pre-existing medical conditions:
 Pregestational diabetes - This increase has been related to a variety of factors, such as
underlying renal or vascular disease, high plasma insulin levels/insulin resistance, and
abnormal lipid metabolism.
 Blood pressure ≥130/80 mmHg at the first prenatal visit. The risk of superimposed preeclampsia
is highest in women with diastolic blood pressure ≥110 mmHg (RR 5.2) and ≥100 mmHg (RR 3.2)
before 20 weeks of gestation.
 Antiphospholipid antibodies
 Body mass index ≥26.1
 Chronic kidney disease (CKD)- In one study, the combination of treated hypertension and
proteinuria in early pregnancy appeared to increase the risk for superimposed preeclampsia
above that for hypertension alone. In other studies, as many as 40 to 60 percent of women
with advanced CKD (stages 3, 4, 5) were diagnosed with preeclampsia in the latter half of
pregnancy.
 Twin pregnancy- Preeclampsia is even more frequent with multi-order gestations (triplets,
quadruplets)
 Advanced maternal age (maternal age ≥40: RR 1.96, 95% CI 1.34-2.87 for multiparas and RR
1.68, 95% CI 1.23-2.29 for primiparas). Older women tend to have additional risk factors, such
as diabetes mellitus and chronic hypertension that predispose them to developing
preeclampsia.
o Of note, women who smoke cigarettes have a lower risk of preeclampsia than nonsmokers.
b. Pathophysiology - The pathophysiology of preeclampsia likely involves both maternal
and fetal/placental factors.
1) Abnormal trophoblast invasion of the spiral arteries of the decidua and myometrium early in
pregnancy, weeks to months before development of clinical manifestations of the disease, has
been well documented.
2) Failure to establish an adequate uteroplacental blood flow can result in relatively hypoxic
trophoblast tissue, which may promote an exaggerated state of oxidative stress in the placenta. This
may further attenuate trophoblast invasion and appears to alter placental villous angiogenesis,
leading to poor development of the fetoplacental vasculature and abnormal vascular reactivity.
3) Placental secretion of angiogenic factors (soluble flt1 and endoglin) that bind vascular endothelial
growth factor and placental growth factor in the maternal circulation appears to result in
widespread maternal vascular dysfunction, leading to hypertension, proteinuria, and the other
clinical manifestations of preeclampsia.
4) Some authorities have characterized preeclampsia as early-onset (<34 weeks of gestation) and late-
onset (≥34 weeks of gestation). The clinical features overlap, but the spectrum of disease and
outcomes differ: Early-onset disease has been associated with more severe placental
and maternal/fetal clinical findings and, in turn, poorer maternal/fetal outcomes. For this reason, it
has been hypothesized that the two phenotypes have different origins and pathophysiologies.
However, these differences can also be explained by biological variation in the disease process.
c. Screening - Screening for traditional risk factors for preeclampsia is of value at the first prenatal visit to
identify women at high risk of developing the disease, as these women are offered low-
dose aspirin therapy to reduce their risk of developing the disease.
 o All pregnant women are at risk for preeclampsia, and evidence supports routinely screening for the
disorder by measuring blood pressure at all provider visits throughout pregnancy. The value of any
laboratory or imaging test for screening has not been established
o It is customary to test for proteinuria at each prenatal visit; however, this practice has not been
rigorously evaluated and proven to improve outcomes.
o We suggest performing a urinalysis to test for proteinuria at the first prenatal visit to establish a baseline
and, given the possibility for false-positives and false-negatives, repeating the test in asymptomatic
normotensive patients on at least one subsequent prenatal visit. In contrast, testing for proteinuria
should be performed in women with hypertension as proteinuria changes the diagnosis to
preeclampsia.
o Once a diagnosis of preeclampsia is established, testing for proteinuria is no longer diagnostically or
prognostically useful.
d. Clinical Presentation - Most patients are nulliparous and present with new-onset hypertension and
proteinuria at ≥34 weeks of gestation, sometimes during labor. Approximately 10 percent of affected
women develop these signs and symptoms at <34 weeks of gestation (ie, early-onset preeclampsia) and
rarely as early as 20 to 22 weeks. In approximately 5 percent, the signs and symptoms are first recognized
postpartum (ie, postpartum preeclampsia), usually within 48 hours of delivery.
o The degree of maternal hypertension and proteinuria, and the presence/absence of other clinical
manifestations of the disease (described below) are highly variable.
o Approximately 25 percent of affected women develop one or more of the following nonspecific
symptoms, which characterize the severe spectrum of the disease and signify the need for urgent
evaluation and possible delivery:
 Persistent and/or severe headache
 Visual abnormalities (scotomata, photophobia, blurred vision, or temporary blindness [rare])
 Upper abdominal or epigastric pain
 Altered mental status
 Dyspnea, retrosternal chest pain
o Epigastric pain may be the presenting symptom of preeclampsia; thus, a high index of suspicion is
important to make the diagnosis of preeclampsia rather than gastroesophageal reflux, which is
common in pregnant women, especially at night.
o Atypical presentations:
 Onset <20 weeks — Preeclampsia prior to 20 weeks of gestation is usually associated with a
complete or partial molar pregnancy. Rarely, characteristic signs and symptoms before 20
weeks have been attributed to preeclampsia with severe features after other disorders with
similar findings (eg, lupus nephritis, thrombotic thrombocytopenic purpura, hemolytic-uremic
syndrome, antiphospholipid syndrome, acute fatty liver of pregnancy) were excluded.
 Severe features of preeclampsia without hypertension — It is uncommon for women to exhibit
the severe features of preeclampsia without hypertension, but this may be observed in 15
percent of patients with HELLP syndrome (which some consider a variant of preeclampsia and
others consider a separate disorder) and in some patients with eclampsia (a possible sequelae
of preeclampsia). It is possible that in such patients, blood pressure is increased above a lower
baseline but does not meet diagnostic criteria for hypertension.
 Isolated hypertension — Women with new onset of hypertension but no other criteria for
preeclampsia or an underlying disease associated with hypertension are given the diagnosis
of gestational hypertension. These women should be followed closely, since 15 to 25 percent
will subsequently develop the full diagnostic criteria for preeclampsia.
 Isolated proteinuria — Isolated gestational proteinuria may be an early manifestation of
preeclampsia, although this is not well described and we are unaware of prospective studies
describing this finding. In a retrospective study of 95 pregnant women with new-onset isolated
proteinuria who were followed to term, 13 developed preeclampsia during pregnancy and 8
developed preeclampsia postpartum.
 Onset or exacerbation of symptoms >2 days postpartum — Delayed postpartum
preeclampsia can be defined as signs and symptoms of the disease leading to readmission
more than two days but less than six weeks after delivery, although various other definitions
have been used. Signs and symptoms can be atypical; for example, the patient may have
thunderclap headaches alternating with mild headaches or intermittent hypertension. Other
etiologies for the signs and symptoms should be considered, such as cerebral vasoconstriction
syndrome or impending stroke. Risk factors for delayed postpartum preeclampsia appear to
be similar to those for preeclampsia during pregnancy, but some patients have no risk factors.
e. Clinical Findings:
o Hypertension — All patients with preeclampsia have hypertension (in patients with HELLP, elevations
in blood pressure may be minimal or even absent).
 It is generally the earliest clinical finding of preeclampsia
 Most common clinical clue to the presence of the disease.
 The blood pressure usually rises gradually, reaching the hypertensive range (≥140/90 mmHg)
sometime in the third trimester, often after the 37th week of gestation. Blood pressures are often
around 135/85 mmHg in the one to two weeks before reaching the hypertensive range.
However, in some women, hypertension develops rapidly or before 34 weeks of gestation or
postpartum.
o Epigastric pain — Epigastric pain, when present, is a cardinal symptom of the severe end of the
disease spectrum. It is characterized by severe constant pain that often begins at night, usually
maximal in the low retrosternum or epigastrium, but may radiate to the right hypochondrium or
back. Nausea and vomiting sometimes also occur. On examination, the liver may be tender to
palpation due to stretching of Glisson's capsule from hepatic swelling or bleeding.
 Liver rupture or hemorrhage is rare, but should be suspected when there is sudden onset of right
upper quadrant pain associated with a decrease in blood pressure.
 Acute pancreatitis is a rare complication of preeclampsia and can mimic the epigastric pain
of preeclampsia
o Headache — Headache, when present, is a cardinal symptom of the severe end of the disease
spectrum. It may be temporal, frontal, occipital, or diffuse. The pain usually has a throbbing or
pounding quality, but may be piercing. Although not pathognomonic, a feature that suggests
preeclampsia-related headache rather than another type of headache is that it persists despite
administration of over-the-counter analgesics and it may become severe (ie, incapacitating, "the
worst headache of my life"). However, resolution of the headache with analgesics does not exclude
the possibility of preeclampsia.
 The mechanism for headache, as well as other cerebrovascular symptoms of preeclampsia, is
poorly understood. Cerebral edema and ischemic/hemorrhagic changes in the posterior
hemispheres observed on computed tomography and magnetic resonance imaging help to
explain, but do not fully account for, the clinical findings. These findings may result from
generalized endothelial cell dysfunction, leading to vasospasm of the cerebral vasculature in
response to severe hypertension, or they may result from loss of cerebrovascular autoregulation,
leading to areas of both vasoconstriction and forced vasodilation. Thus, they could represent
a form of posterior reversible leukoencephalopathy syndrome (PRES). PRES is typically
associated with severe hypertension but can occur with rapid increases in blood pressure in
patients with endothelial damage.
o Visual symptoms — Visual symptoms, when present, are cardinal symptoms of the severe end of
the disease spectrum. They are caused, at least in part, by retinal arteriolar spasm [59]. Symptoms
include blurred vision, flashing lights or sparks (photopsia), and scotomata (dark areas or gaps in
the visual field). Diplopia or amaurosis fugax (blindness in one eye) may also occur. Visual
disturbances in preeclampsia may also be manifestations of PRES.
 Cortical blindness is rare and typically transient. Blindness related to retinal pathology, such as
retinal artery or vein occlusion, retinal detachment, optic nerve damage, retinal artery spasm,
and retinal ischemia, may be permanent.
 o Generalized hyperreflexia — Hyperreflexia is a common finding. Sustained ankle clonus may be
present.

o Peripheral edema — Many pregnant women have edema, whether or not they have
preeclampsia. However, sudden and rapid weight gain (eg, >5 lb/week [2.3 kg]) and facial
edema are more common in women who develop preeclampsia; thus, these findings warrant
diagnostic evaluation for the disease. Peripheral edema in preeclampsia may be due to capillary
leaking or represent "overfill" edema.

o Pulmonary edema — Pulmonary edema is a feature of the severe end of the disease spectrum.
The symptom complex of dyspnea, chest pain, and/or decreased (≤93 percent) oxygen saturation
by pulse oximetry is predictive of adverse maternal outcome (maternal death and hepatic,
central nervous system, renal, cardiorespiratory, and hematological morbidities).The etiology of
pulmonary edema in preeclampsia is multifactorial. Excessive elevation in pulmonary vascular
hydrostatic pressure compared with decreased plasma oncotic pressure may produce pulmonary
edema in some women, particularly in the postpartum period. However, not all preeclamptic
patients with pulmonary edema demonstrate this phenomenon. Other causes of pulmonary
edema are capillary leak, left heart failure, and iatrogenic volume overload.

o Oliguria — Urine output may decrease to <500 mL/24 hours in women at the severe end of the
disease spectrum. Rarely, women with preeclamptic hepatic disease have developed polyuria
due to transient diabetes insipidus of pregnancy. The mechanism in these cases is decreased
degradation of vasopressinase due to hepatic dysfunction.

o Stroke — Stroke leading to death or disability is the most serious complication

of preeclampsia/eclampsia, which is responsible for approximately 36 percent of pregnancy-
associated stroke. Most strokes in this setting are hemorrhagic and preceded by severe headache
and severe and fluctuating blood pressure levels. Eclamptic seizures occur in some, but not all,
cases. Risk factors for hemorrhagic stroke in women with preeclampsia include persistent severe
hypertension associated with significant headache and/or seizures. Lowering blood pressure may
reduce the risk; however, criteria for persistent hypertension and timing of initiation of acute
antihypertensive therapy (after 15 minutes, 30 minutes, or >60 minutes) are unclear.

o Abruptio placentae — Abruption occurs in less than 1 percent of pregnancies with preeclampsia
without severe features but 3 percent of those with severe features.

o Seizure — Seizure in a preeclamptic woman upstages the diagnosis to eclampsia. Eclamptic

seizures develop in 1 in 400 women with preeclampsia without severe features and 1 in 50 women
with preeclampsia with severe features. Histopathologic correlates include brain hemorrhage,
petechiae, edema, vasculopathy, ischemic damage, microinfarcts, and fibrinoid necrosis.
Neuroimaging consistent with posterior reversible encephalopathy syndrome may be seen.
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