HYPERTENSIVE DISORDERS DURING PREGNANCY ppsx

The mildest form of the process is gestational hypertension, which consists of systolic blood pressure .140 with a rise of .30 mmHg and/or diastolic blood pressure of .90 mmHg with a ris

CLASSIFICATION

The hypertensive disorders of pregnancy have been variously sified without consensus being achieved as to a lasting classifica-tion A practical classification may be achieved by modification ofthe system proposed by the American Committee on Maternal Wel-fare (1985)

clas-I Pregnancy Induced Hypertension (Preeclampsia-eclampsia,toxemia, EPH, and gestosis)

II Chronic hypertension

● Primary (essential, idiopathic)

● Secondary (to some known cause)

1 Renal: e.g., parenchymal (glomerulonephritis, chronicpyelonephritis, interstitial nephritis, and polycystic kid-ney disease), renovascular nephritis

2 Adrenal: cortical-Cushing’s disease, hyperaldosteronism,medullary-pheochromocytoma

3 Other: coarctation of the aorta, thyrotoxicosis, etc III Chronic hypertension with superimposed preeclampsia

IV Transient (atypical, undiagnosed) hypertension (a nebulous group

of patients who develop hypertension in labor or immediatelypostpartum)

13

HYPERTENSIVE DISORDERS

DURING PREGNANCY

* Modifications

etiol-maternal and perinatal morbidity and mortality both in developing

as well as industrialized nations Currently, it is not possible to

dict who will acquire the processes There are no strategies for vention This group of conditions are progressive, but with variable presentations and rates of progression Moreover, after clinical

pre-symptoms have occurred, there are only symptomatic therapeutic

options One or another of the hypertensive disorders will

compli-cate approximately 10% of pregnancies.

The mildest form of the process is gestational hypertension,

which consists of systolic blood pressure 140 with a rise of 30

mmHg and/or diastolic blood pressure of 90 mmHg with a rise of

.15 mmHg Only 15%–25% of women having gestational

hyper-tension will develop preeclampsia This progression is more likelywith earlier presentation or if the woman has had a prior sponta-neous abortion Women with gestational hypertension
36 weekshave⬃10% risk of developing preeclampsia

Preeclampsia is characterized by hypertension (as previously

de-fined), plus generalized edema, and/or proteinuria occurring after the 20th week of pregnancy (usually in the last trimester or early puer-

perium) Any two of the three signs are diagnostic The only tion to the 20th week for onset is when pregnancy-induced hyper-tension (PIH) is associated with trophoblastic disease Preeclampsia

excep-is divided into mild and severe, based on blood pressure and

labora-tory abnormalities (see below)

Although up to 40% of patients with preeclampsia will havesome hemostatic abnormalities, for reasons yet unknown, some

preeclamptic patients will develop the HELLP syndrome This

includes the signs of preeclampsia (as above) plus hemolysis (H),elevated liver enzymes (EL), and low platelets (LP, see below).These gravidas deserve even more special consideration because

of the potential for poor perinatal and maternal prognosis

with-out early diagnosis and proper therapy, including expeditiousdelivery

Eclampsia, the most fulminating degree of PIH, is

character-ized by convulsions or coma, in addition to the other signs and

symptoms of preeclampsia Uncontrolled preeclampsia may progress

to eclampsia, with resultant permanent disability or death

Chronic hypertension (CH) alone or with superimposed

pre-eclampsia (SIPE) must be differentiated from PIH The risks of

chronic hypertension in pregnancy (abruptio placenta, fetal growth restriction and prematurity) are worsened by the superimposition of preeclampsia Additionally, the maternal and perinatal risk increase

in relation to the severity of the preexisting chronic hypertension

About 8% (recent reports range from 5%–10%) of all pregnant

women in the United States develop preeclampsia; however, there

is great geographic variation in incidence Approximately 5% ofthese cases progress to eclampsia, and about 5% of women with

eclampsia die of the disease or its complications At least 95% of

cases of PIH occur after the 32nd week, and about 75% of these

patients are primigravidas The incidence is at least doubled withmultiple pregnancy, hydatidiform mole, and polyhydramnios Prim-igravidas of all ages are affected PIH is more prevalent amongblacks and Native Americans than whites

Other factors predisposing to PIH include age 20 and
35,vascular or renal disease, diabetes mellitus, gestational diabetes mel-litus, obesity, chronic hypertension, pheochromocytoma, systemiclupus erythematosus, nonimmune fetal hydrops, malnutrition, andlow socioeconomic status

Interestingly, if a multigravida remarries, her chance of havingPIH with her next pregnancy is similar to what it would be as a nul-lipara Pregnancies achieved through assisted reproductive tech-nology with a male donor to whom the gravida has not previouslybeen exposed have the same risk as a primigravida, even if they are

a multipara In preliminary data, donated gametes further increasethe risk of preeclampsia (to
18%) All of these conditions con-tribute to maternal and perinatal morbidity and mortality; however,given the spectrum of the processes, the amount and type of risk isvariable This information is summarized as follows

Although many associations have been detailed (see previousdiscussion), the cause of preeclampsia-eclampsia remains unknownand speculation has been so rife that this disorder has been called

a disease of theories Currently there are four popular hypotheses:

● Placental ischemia Increased trophoblast deportation, as a

consequence of ischemia, may inflict endothelial cell function Certainly evidence for endothelial involvement inthis condition abounds

dys-● Preeclampsia is the manifestation of a toxic reaction At least two areas are being investigated: Very low density lipopro-

tein toxicity prevention In pregnancy, nonesterified fatty

acids are mobilized to compensate for increased energy mands Albumin, which has a specific antitoxic activity, alsotransports the nonesterified fatty acids from adipose tissues

de-to the liver Low albumin concentrations may allow an

ex-pression of very low density lipoprotein toxicity Impaired

antioxidant activity and the reduction of antioxidant levels,

which increase the level of lipid peroxidation products, maycause peroxidative damage of vascular endothelium

● Immune maladaptation The immune interaction between

mother and invading cytotrophoblast may be aberrant, ing to shallower endovascular cytotrophoblastic cell inva-sion of spiral arteries This dysfunction may lead to in-creased decidual release of cytokines, proteolytic enzymes,and free radial species Preeclampsia is associated withwidespread apoptosis of placental cytotrophoblasts with theuterine wall

lead-● Genetic imprinting Genetic imprinting for pregnancy

in-duced hypertension could be based on a single recessive gene

or a dominant gene with incomplete penetrance (depending

on fetal genotype) Preeclampsia during the pregnancy of amother is a risk factor for development of preeclampsia dur-ing the pregnancy of her daughters

PATHOLOGIC PHYSIOLOGY

VASOSPASM

Arteriolar spasm, consistently observed in the retinas, kidneys, brain,

and splanchnic region, promotes hypertension Furthermore, the mal refractoriness to angiotensin II (A-II) is lost weeks before theonset of preeclampsia In contrast, normal pregnant women lose theirrefractoriness to A-II after receiving prostaglandin synthetase in-hibitors (e.g., aspirin, which implicates prostaglandin as a mediator

nor-of vascular reactivity to A-II during pregnancy) Moreover, A-II fractoriness can be restored to preeclamptic individuals by drugs thatincrease levels of cyclic AMP (cAMP) (e.g., theophylline) An im-balance between prostacyclin (PGI2), a vasodilator and inhibitor ofplatelet aggregation, and thromboxane (TXA2), a vasoconstrictor andplatelet aggregator in preeclampsia, also occurs because PGI2pro-duction is decreased months before the clinical onset of preeclamp-sia Mild preeclampsia is associated with lower systemic daytimeproduction of prostacycline, elevated plasma norepinephrine levels,and blunting of the normal diurnal variations of brain natriuretic pep-tide, atrial natriuretic peptide, norepinephrine, and aldosterone

re-SODIUM AND WATER RETENTION

Sodium retention is an adjunct of growth and is normal during

preg-nancy, but sodium retention, particularly intracellular, is

exagger-ated in PIH Nonetheless, sodium retention does not cause this

dis-order However, an alteration at the cellular membrane level mayinhibit the usual exchange of sodium Reduced serum levels of al-bumin and globulin resulting from proteinuria account for the di-minished oncotic pressure of the blood despite hemoconcentration.Increased excretion of corticosteroids (including aldosterone) andvasopressin in certain patients suggests increased tissue concentra-tions of these substances This results in enhanced sodium and wa-ter retention

HEMATOLOGIC ALTERATIONS

The Hgb and Hct are elevated due to hemoconcentration

Preeclamp-sia is a hypercoagulative status that may be explained by a rangement of the platelet L-arginine-nitric oxide pathway Severepreeclampsia-eclampsia shares similarities with the disorders ofcoagulation because disseminated intravascular coagulation (DIC)

de-of varying degrees so frequently occurs The magnitude de-of thecoagulation defect does not always correlate with the severity ofpreeclampsia-eclampsia The alterations may include thrombocy-topenia, decreased coagulation factors (especially reduced fibrino-gen), and the presence of fibrin split products Microfibrin embolimay occur in the lungs, liver, or kidneys Occasionally, hemolysis(e.g., microangiopathic hemolytic anemia, deformed red bloodcells), elevated liver enzymes, and thrombocytopenia occur in pa-tients with preeclampsia-eclampsia This combination is termed theHELLP syndrome

BLOOD CHEMISTRY

ABNORMALITIES

Uric acid levels are generally 6 mg/dL Serum creatinine is most

often normal but may be elevated in severe cases Some serum

albumin and globulin are lost via the urine, but blood proteins mustalso be lost or destroyed in other ways, since proteinuria alone isnot sufficient to explain the abnormally low protein levels in severecases Acidosis occurs after convulsions Elevated levels of hepaticenzymes indicate hepatic dysfunction Placental clearance of dehy-droepiandosterone sulfate (DHEAS), as a measure of placental per-fusion, decreases before the onset of preeclampsia

In summary, PIH is marked by vasospasm Whereas normal pregnancy is marked by sodium and water retention, together with increased blood volume, in preeclampsia, there is enhanced sodium and water retention with a contracted plasma volume Swan-Ganz catheter studies in preeclampsia reveal normal wedge pressures and normal or elevated cardiac output

PATHOLOGY KIDNEY

In severe preeclampsia and eclampsia, the only typical lesion is

glomerular capillary endotheliosis (i.e., swelling of the glomerular

capillary endothelium, narrowing of the capillary lumen, and dothelial fibrinoid deposition) These abnormalities are totally re-versible and disappear by 6 weeks postpartum In patients withthe clinical diagnosis of preeclampsia, renal biopsy reveals glomeru-lar capillary endotheliosis in ⬃70% of primigravidas 25 years,and⬃25% have unsuspected renal disease Other electron micro-scopic abnormalities include massive subendothelial and mesan-gial deposits of lipids and fibrillar fibrins, monocyte invasion inthe mesangium, and rupture and duplication of the glomerular cap-illary wall

suben-CARDIOPULMONARY

Pulmonary edema may occur with severe preeclampsia or eclampsia

from cardiogenic or noncardiogenic causes It is most common partum and also may be related to fluid overload and decreasedplasma colloid oncotic pressure Preeclampsia is usually character-ized as a hyperdynamic state, with increased cardiac output, normalwedge pressure, and normal or slightly elevated systemic vascular re-

post-sistance Aspiration of gastric contents may occur as a complication

of eclamptic seizures Death may result from particulate matterobstructing airways or from chemical pneumonitis, leading to the

adult respiratory distress syndrome

In the liver, chronic passive congestion and subcapsular rhages may develop

hemor-FETUS

As a result of the poor intervillous blood flow, intrauterine growth

retardation may be marked Fetal death may follow hypoxia or

aci-dosis This is further compounded by both severe hypertension andmaternal multiple organ involvement, which may necessitate earlydelivery

PLACENTA

Grossly, no specific placental lesions are typical of

preeclampsia-eclampsia, although the placenta is often smaller than normal, and

intervillous fibrin deposits (red infarcts) are common Increased and

more severe endarteritis and periarteritis, a thinned and broken cytium, and calcium and intervillous fibrin deposition may appear(grossly, microscopically, and sonographically) as premature aging.There are two very serious microscopic placental alterations in pa-

syn-tients with preeclampsia: the spiral arteries in the myometrium fail

to lose their musculoelastic structure, and acute atherosis develops

in the myometrial segment of the spiral arteries This leads to

in-creased vascular resistance and a compromise of the vessel lumen.Thus, the fetus receives less intervillous blood flow

SYMPTOMS AND SIGNS

Except for an abnormal blood pressure, patients with gestational

hypertension are usually asymptomatic Preeclampsia-eclampsia is characterized by hypertension, generalized edema, and proteinuria

in the absence of vascular or renal disease The manifestations

de-velop from the 20th week of pregnancy through the 6th week after

delivery.

HYPERTENSION

Hypertension is the key sign in the diagnosis of PIH Gestational

hypertension is a rise in systolic blood pressure of 30 mm Hg,

a rise in diastolic pressure of 15 mm Hg, or a blood pressure

of140/90 Some (Canadian Hypertension Society Consensus

Conference) consider only the diastolic blood pressure Except for

very high diastolic readings (.110), it is recommended that all diastolic readings be confirmed after 4 hours Hypertension also

exists with a mean arterial pressure rise of 20 mm Hg The levelsdescribed must occur at least twice, 6 h or more apart, and be based

on previously recorded blood pressures Occasional patients withhypertension during pregnancy must remain unclassified until stud-ies can be evaluated after the puerperium

EDEMA

Edema is the least precise sign of PIH because dependent edema is normal in pregnancy and up to 40% of patients with PIH do not have

edema However, the following criteria may facilitate the diagnosis

● Generalized accumulation of fluid in tissues (i.e.,
2 ting edema after 1 h bedrest)

pit-● A weight gain of 2 pounds/wk because of the influence ofpregnancy

● Nondependent edema of the hands and face present on ing in the morning

aris-PROTEINURIA

Gestational proteinuria is often the last sign to develop and is fined as $0.3 g/liter in a 24-h specimen or 1 g/liter (1 to 2 bydipstick methods) with urinalysis on random midstream or catheterspecimens Up to 30% of patients with eclampsia will not have pro-teinuria, but when present, proteinuria signals increased fetal risk(more SGA infants and enhanced perinatal mortality) If only thenoted criteria for preeclampsia are present, it is classified as mildpreeclampsia The criteria for severe preeclampsia follow

de-● Blood pressure
160 systolic or
110 diastolic (at bedrest,

on two occasions at least 6 h apart)

preeclampsia Scintillating scotomas and partial or complete

blind-ness are due to edema of the retina, retinal hemorrhage, or retinal

detachment Epigastric pain, nausea, and liver tenderness are the

result of congestion or thrombosis of the periportal system and capsular hepatic hemorrhages.

sub-There are no consistent symptoms of the HELLP syndrome This

nonspecificity is problematic for early diagnosis Similarly, sia may occur with little or no warning

eclamp-COMPLICATIONS

Maternal complications are related directly to progression fromgestational hypertension to preeclampsia, the HELLP syndrome oreclampsia The fetal complications are related to acute and chronicuteroplacental insufficiency (e.g., asymmetric or symmetric SGAfetus, stillbirth, or intrapartum fetal compromise) and early deliv-ery (complications of prematurity)

LABORATORY STUDIES

All patients with PIH may need the following studies (additional

studies or repetition may also be necessary): Hct, or Hgb, WBC;

urinalysis, urine culture and sensitivity; serum protein and min/globulin ratio; and serum uric acid and creatinine Also, de-

albu-pending on the gestational age and seriousness of the situation, it

may be useful to determine fetal physiologic maturity by centesis and appropriate tests A 24-h urine collection is collected for total protein, creatinine clearance, and vanillylmandelic acid (if BP varies greatly) Baseline coagulation studies usually include

amnio-a plamnio-atelet count, totamnio-al fibrinogen, prothrombin, pamnio-artiamnio-al

thrombo-plastin time, and split fibrin products (if DIC is suspected) A liver function profile is usually added to rule out HEELP syndrome This

includes bilirubin and liver enzymes (lactate dehydrogenase,

as-partate aminotransferase, alanine amniotransferase).

Recently, some have recommended that the laboratory tion of patients suspected of preeclampsia may be abbreviated incertain circumstances Specifically, if there is no evidence of bleed-ing or of a condition that could produce coagulopathy and if theplatelet count and lactate dehydrogenase level are both normal, a

evalua-PT, a PTT, or fibrinogen test is not necessary

IMAGING

Sonography is useful in detailing the fetal size and position and in

estimation of well-being Additionally, Doppler evaluation of the uterine artery velocimetry may be useful in predicting adverse preg-

nancy outcomes from compromised fetuses

If the patient is stable and not severely preeclamptic or eclamptic,

general diet without sodium restriction may be appropriate, as isunrestricted fluid intake (but with recorded intake and output) The

lateral recumbent position increases renal blood flow, which assists

in resolving edema Therefore, the patient is encouraged to assumeright or left lateral recumbency as much as possible High-risk ob-stetric care and treatment of complications is required to optimize

outcomes The keys to treatment are bedrest and delivery at a time

of fetal maturity.

Those who have gestational hypertension may be followed der close supervision as outpatients Such supervision usually in- volves bedrest (lateral recumbent position as much as possible),

un-blood pressure evaluation (while awake) every 4 h, a daily urine dipstick evaluation for proteinuria, a minimum of twice weekly physician visits, weekly nonstress testing (or other evaluation of fe-

tal well-being), and maternal fetal motion counting.

Careful patient education is necessary concerning signs that would require immediate hospitalization: proteinuria, increasing

blood pressure, severe headache, and epigastric pain.

In some circumstances, for gestational hypertension and in all

preeclamptic women, maternal hospitalization may help prevent

premature delivery and thus be less expensive (compared to

pre-mature neonatal care) An example of hospital care includes bedrest (again, in the lateral recumbent position), daily weights, blood pres-

sures every 4 h (because the highest pressures of the day occur at 3–5 AM , it is worthwhile to screen these occasionally); daily urine dipstick for proteinuria, and 24-h urine once or twice weekly (for creatinine clearance and total protein) On admission and weekly

thereafter, the following laboratory studies may be employed:

hemogram, liver function studies, uric acid and creatinine, trolytes, serum albumin, and a coagulation profile.

elec-Sonography for gestational age is usually obtained on

admis-sion and every 2 weeks thereafter Weekly testing for fetal well-being

may be performed by serial BPPs, or NSTs Should an

abnormal-ity arise, a CST may be necessary Glucose tolerance testing is

indicated after 20 weeks gestation if the patient has hyperglycemia

or multiple pregnancy A vanillylmandelic acid study is effective in

ruling out pheochromocytoma if wide blood pressure fluctuationsoccur

Criteria to allow nonhospital care for the patient commonly

in-clude an environment where bedrest is possible, BP reduction to

120/80, proteinuria 150 mg/24 h and normal renal function,

and no evidence of CNS irritability Any relapse or complications require readmission to the hospital If possible, delivery is delayed

until physiologic maturity (
36 weeks amniocentesis and testing)occurs If early delivery is required, induction is attemped Whenthe cervix is not favorable (Bishop score 6–7), a prostaglandinripening agent may be useful If induction is not a good option, iflabor is delayed, or if fetal compromise develops, cesarean sectionmay be a better option

INDICATIONS FOR DELIVERY

While there are few absolutes, given the large number of variables

in fetal states, fetal maturity, intercurrent diseases, maternal status,and so forth, some of the criteria commonly employed for deliveryfollow

Hypertension is the issue that mandates delivery in the vast

ma-jority of patients Blood pressure elevations forcing this deliveryare consistently
100 diastolic for 24 h, and a single BP diastolic

110 despite bedrest Laboratory abnormalities signaling sufficient

risk to warrant delivery consideration include: proteinuria
1 g/24 h,increasing serum creatinine, abnormal liver function studies, and

thrombocytopenia Maternal complications signaling the

consider-ation for delivery comprise the HELLP syndrome, eclampsia, severepreeclampsia (including signs such as epigastric pain and cerebralsymptoms), pulmonary edema, cardiac decompensation, coagu-

lopathies, and renal failure Fetal abnormalities indicative of risk

sufficient to warrant delivery include: fetal compromise by tronic monitoring criteria; abnormal NST, CST, or BPP; and an SGAfetus with growth failure on sonography

elec-SEVERE PREECLAMPSIA

Severe preeclamptics and their offspring are best cared for in tiary centers The goals of management are prevention of convul- sions, control of maternal blood pressure, and delivery

ter-For gestations of ,27 weeks, conservative management

(delay-ing delivery) may be warranted, but maternal complications

(abrup-tio placenta, eclampsia, coagulopathy, renal failure, hypertensiveencephalopathy, and hepatic rupture) are directly related to thelength of time delivery is delayed In some pregnancies distant fromterm, however, attempting to lengthen gestation is the most ration-ale choice to avoid the morbidity and mortality of early preterm de-livery Patient and family participation is necessary

Severe preeclampsia is a high-risk situation that may end in

ma-ternal complications or poor perinatal outcomes despite maximalmedical efforts For those 28 weeks with a tertiary care nurseryavailable, delivery after short-term maternal stabilization is thetreatment of choice Laboratory assessment should be similar to themild preeclamptic, but it may be necessary in extreme cases to addelectrocardiography and hemodynamic monitoring Determination

of fetal pulmonary maturity is necessary to properly time delivery.This may be repeated at weekly intervals to accomplish delivery assoon as survival is likely Corticosteroid therapy for gestations of26–34 weeks is indicated to enhance fetal lung maturity

The severe preeclamptic may be started on magnesium sulfate

to help in preventing seizures (see dosage under “Eclampsia”)

Mag-nesium sulfate prevents seizures by direct central nervous systemaction; however, magnesium sulfate decreases acetylcholine release

at the neuromuscular junction and causes paralysis at a serum level

of⬃15 mg/dL Magnesium sulfate potentiates both depolarizingand nondepolarizing muscle relaxants In patients requiring hyper-tensive control, hydralazine and labetalol have traditionally been

the safest agents Blood pressures of 170/110 are an emergency and

treatment with hydralazine, labetalol, or nifedipine should be ated immediately Although the benefits and risks of antihyperten-

initi-sive treatment should be considered in all cases of hypertension in

pregnancy, it is particularly important to treat those with sustained

systolic BP 160 mm Hg or sustained diastolic BP 100 With

lesser hypertensions, the decision to utilize antihypertensive therapy

may be much more individualized In milder cases (e.g., gestational

hypertension), methyldopa is the treatment of choice Labetalol,

pindolol, oxprenolol, and nifedipine are second-line drugs

Those patients with nausea, vomiting, and epigastric pain are

at particular risk Additionally, these patients may have laboratory findings that indicate a greater maternal risk: lactate dehydroge-

nase level
1400 IU/L, aspartate aminotransferase
150 IU/L, nine aminotransferase
100 IU/L, uric acid level
7.8 mg/dL,serum creatinine
1.0 mg/dL, and 4 urinary protein by dipstick.These factors are independent of the rising maternal risk associatewith the decreased platelet count found in full expression of theHELLP syndrome Prompt delivery must be considered for the in-dications noted previously