AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

Preeclampsia is defined as gestational blood pressure (BP) elevation with proteinuria that develops after 20 weeks' gestation. Preeclampsia is one of 4 major hypertensive disorders of pregnancy. The other 3 conditions that comprise the hypertensive complications of pregnancy include gestational hypertension, chronic hypertension, and chronic hypertension with superimposed preeclampsia. Preeclampsia occurs in 5-8% of pregnancies. Although its pathogenesis is incompletely understood, it is a major cause of maternal and neonatal morbidity and mortality.

Eclampsia; the occurrence of seizures, coma, or both in the setting of preeclampsia; and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are manifestations of severe preeclampsia. The outcome for infants born to women with preeclampsia depends on the infant's gestational age and condition at delivery, the severity of the maternal hypertensive disease, end-organ involvement, and any other associated comorbid maternal conditions. Preterm birth is more common among pregnancies complicated by preeclampsia, which accounts for up to 15% of preterm deliveries.

As the understanding of the hypertensive disorders of pregnancy has grown, the term pregnancy-induced hypertension (PIH) is no longer recommended to describe preeclampsia. Although preeclampsia is primarily a disease of primigravidas, multiple clinical risk factors that increase the predisposition to develop this disease have been identified. Risk factors include black race, past obstetric history, genetic predisposition, obesity, BP at the initiation of pregnancy, multifetal gestation, advanced maternal age, and preexisting vascular insufficiency, insulin resistance, or thrombophilia. Preeclampsia is a multisystem disorder that affects the fetus because of uteroplacental insufficiency. Fetal outcomes include stillbirth, intrauterine growth restriction, low birth weight, and prematurity.

Pathophysiology

The current concepts regarding the pathophysiology of preeclampsia recognize that preeclampsia is a multisystem disorder characterized by vasoconstriction, metabolic changes, endothelial dysfunction, and activation of the coagulation cascade in conjunction with an inflammatory response. A 2-stage model of preeclampsia has been proposed in which failure of placental vascular remodeling results in reduced placental perfusion and initiates a cascade of events that result in serious maternal illness with the potential for significant perinatal morbidity and death. Women with underlying microvascular disease, such as diabetes, hypertension, and collagen vascular disease, have a higher incidence of preeclampsia.

Normal placental development involves progressive loss of the musculoelastic tissue in the spiral arteries that feed the vessels of the intervillous spaces, which results in uterine blood flow increases of nearly 25% during the first trimester. This process of remodeling the maternal spiral arteries that branch from the uterine artery is typically completed by 18-20 weeks' gestation.

In women destined to develop preeclampsia (and in infants who are small for gestational age or whose mothers have diabetes mellitus), this physiologic dilatation of the spiral arteries does not occur because the placental trophoblast cells do not invade the spiral arteries, resulting in maintenance of narrow vessels with resultant placental hypoperfusion and ischemia. In severe cases, not only do the spiral arteries maintain their muscular structure, but other pathologic changes also occur. Accumulation of fat-laden macrophages with fibrinoid necrosis (ie, acute atherosis), disruption of the basement membranes, platelet deposition, mural thrombi, and proliferation of intimal and smooth muscle cells all decrease the luminal diameter.

The narrowed and damaged spiral arteries become thrombosed, resulting in placental infarction and necrosis. Uteroplacental blood flow is then reduced by 50-75%. The anatomical reduction in blood flow may be complicated by vasospasm of the uteroplacental bed.

The primary defect in preeclampsia appears to originate at the maternal-fetal interface (the placenta). Decreased placental perfusion is thought to lead to fetoplacental ischemia. The ischemic placenta may produce circulating antiangiogenic factors that promote generalized maternal vascular endothelium dysfunction, leading to systemic manifestations of preeclampsia. Associated abnormalities in clotting and platelet function contribute to vasoconstriction and platelet adhesion and aggregation, as well as to the activation of coagulation factors that increase the risk of thromboembolic formation.

The primary feature of preeclampsia, development of hypertension, occurs when normally extreme vasodilatation does not occur. Although cardiac output increases 30-50%, the decreased peripheral vascular resistance (PVR) results in decreased BP, even in women with chronic hypertension. Women who develop preeclampsia experience an increase in PVR and alterations in vascular sensitivity to endogenous hormones (eg, angiotensin II, catecholamines, vasopressin). This increase in vascular reactivity to pressor hormones may be mediated, at least in part, through damage to vascular endothelial cells, disrupting the normal prostaglandin balance.

The normal expansion of blood volume by 50% that occurs with pregnancy is decreased by 15-20% in patients with preeclampsia. This is the result of diminished plasma volume, leading to the relative hemoconcentration observed in preeclampsia. The plasma volume abnormality involves a redistribution of extracellular fluid, such that interstitial fluid volume is increased while the plasma volume is decreased. The hematocrit increases as the severity of preeclampsia increases. Circulating blood volume is maintained by the increased vascular tone. Whether the vasospasm is the cause or effect of the vascular endothelial injury is not known. Regardless, this injury likely results in the microangiopathic hemolysis and disseminated intravascular coagulation that accompanies severe preeclampsia.

The increased circulating blood volume and cardiac output of normal pregnancy results in increased renal blood flow and glomerular filtration rates (GFRs). Women with preeclampsia have markedly decreased renal blood flow and GFRs. Renal biopsies of these women show a constellation of lesions, termed glomerular capillary endotheliosis. Some consider glomerular capillary endothelial swelling that is accompanied by deposits of fibrinogen degradation products within and under the endothelial cells as pathognomonic of the disease. These lesions resolve within a month of delivery.

Frequency

United States

Hypertensive disorders affect 12-22% of pregnancies; 70% of these pregnancies are hypertensive secondary to preeclampsia or the preeclampsia-eclampsia syndrome. Preeclampsia is primarily a disease of primigravidas. The disease is mild in 75% of cases.

The recurrence rate of preeclampsia in future pregnancies varies based on the prior obstetric history. Women who were normotensive in their first pregnancy are at lowest risk. Among women who experienced uncomplicated hypertension during their first pregnancy, the risk of preeclampsia during the second pregnancy is reported to be 5-7%. Pregnancy complicated by early severe preeclampsia increases the recurrence risk to 60-80%.

The frequency of preeclampsia complicating pregnancy is further influenced by genetic factors, with studies reporting higher rates of preeclampsia among primiparous siblings. Paternal genes may also have a role in abnormal placentation and the genesis of preeclampsia.

International

Preeclampsia-eclampsia syndrome accounts for 90% of maternal pregnancy-related deaths in developing countries. Although the exact prevalence is unknown, approximately 2-4% of pregnancies (4 million women) are estimated to be complicated by preeclampsia annually; 2% of these women develop eclampsia. Among nulliparous women, the incidence of preeclampsia is reported to be 5-7%. The actual incidence varies by country, with reported rates up to 18% in parts of Africa. In the United Kingdom, 15% of maternal deaths are related to preeclampsia-eclampsia syndrome. High rates of neonatal mortality are reported in pregnancies complicated by preeclampsia (11.5%) and eclampsia (30%).

Mortality/Morbidity

Maternal morbidity includes severe bleeding from placental abruption, coagulopathy, pulmonary edema, acute renal failure, cerebral hemorrhage, liver rupture, and retinal detachment.

• Eclampsia represents one of several clinical manifestations of severe preeclampsia and may manifest as early as the second trimester. The reported incidence is 4-5 per 10,000 live births. The risk of occurrence is 4-fold higher in women with severe preeclampsia than in women with mild preeclamptic disease. Eclampsia is more common among nonwhite primiparous women with low socioeconomic status. Peak incidences occur among young women in their teens and early third decade of life and in women with advanced maternal age (>35 y). The reported maternal mortality rate is 2-4% in eclampsia or when HELLP syndrome complicates preeclampsia. It rises to 10% in patients with pulmonary edema. Whether HELLP syndrome is solely a manifestation of severe preeclampsia or if it actually represents a separate microangiopathic disorder remains controversial.
• The fetal morbidity and mortality rates are increased in the presence of preeclampsia, which is the result of prolonged uteroplacental insufficiency, the risk of placental abruption, declining maternal health, and the frequent need for premature delivery. Worsening maternal condition or the inability of the fetus to tolerate the in utero environment may necessitate preterm delivery.
• Fetal growth restriction imposes an additional risk to the infant. Eclampsia and HELLP syndrome develop prior to 37 weeks' gestation in approximately 50% and 80% of cases, respectively. Perinatal death is commonly due to prematurity, growth restriction, placental abruption, and intrauterine asphyxia.
• Intrauterine growth restriction is usually disproportionate or asymmetric because head growth and length are closer to what is expected than weight. In these cases, fetal growth is restricted because of malnutrition rather than decreased growth potential.
• The sparing of head growth is thought to result from circulatory changes in the fetus that redistribute blood flow to the brain and heart. Although nutritional constraints on growth are unusual before the 24th week of gestation, severe reductions in uteroplacental blood flow may affect head growth. This is observed most commonly in patients with class D diabetes but may occur in severe preeclampsia or when preeclampsia complicates other maternal conditions (eg, systemic lupus erythematosus).
• The incidence and severity of fetal growth restriction increases as maternal plasma volume decreases. It is not understood how this inequity in plasma and interstitial volume correlates with fetal growth.

Race

Relating the frequency of preeclampsia to race is difficult. However, the spectrum of preeclampsia-eclampsia is observed more commonly in black women and is thought to be related to a higher prevalence of hypertensive disorders found in the black population. This is exaggerated by cases of preeclampsia in nulliparous women. Some studies note up to a 3-fold higher risk among black women, while other studies have not found an increased risk in black women.

Individual maternal and paternal genetic factors that appear to increase the risk for development of preeclampsia have been identified. These include conditions under which maternal fetal genotypic concordance changes, such as with differing paternity in multiparous pregnancies and paternal family history of preeclampsia. Genetic variations further influence susceptibility to preeclampsia and the other hypertensive disorders of pregnancy.

Data have shown that rates of preeclampsia are lower among Asians, with both maternity and paternity contributing to a lower rate of disease. Among the Hispanic population, results are more varied, in large part because of the diversity in racial and genetic makeup among women and men of Hispanic origin. Emerging data suggest that Hispanic women may be at an increased risk for preeclampsia (independent of confounding factors such as baseline BP, obesity, diabetes, and multiple gestation), although the risk for gestational hypertension appears to be low among Hispanic women who are not obese or hypertensive.

Sex

By definition, preeclampsia is a disease of pregnant women.

Age

Maternal age of younger 20 years and older than 35-40 years are among the clinical risk factors for the development of preeclampsia. The increased incidence of preeclampsia noted among patients older than 35 years probably reflects undiagnosed chronic hypertension with superimposed PIH.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

The onset of preeclampsia rarely occurs before 20 weeks' gestation. Hypertension is typically the first clinical sign that preeclampsia is developing. Most women typically experience gradual development of hypertension, proteinuria (>0.3 g protein in a 24-h urine specimen), and edema in the latter part of the third trimester. The clinical presentation includes sudden weight gain with the development of edema, particularly of the face and upper extremities.

In women with preexisting chronic hypertension and proteinuria before 20 weeks' gestation, the preeclampsia can be diagnosed when the BP is exacerbated BP (systolic >160 mm Hg or diastolic >110 mm Hg) during the last half of pregnancy or when proteinuria significantly increases.

Gestational hypertension is the occurrence of hypertension, typically mild, without proteinuria or other signs of preeclampsia, that develops in late pregnancy. It may be transient in nature, resolving by 12 weeks postpartum or may represent underlying chronic hypertension. Among women with the onset of gestational hypertension before 30 weeks' gestation, the risk for development of preeclampsia is increased.

• The classic triad of hypertension (systolic BP >140 mm Hg or diastolic BP >90 mm Hg in a women who was previously normotensive prior to 20 weeks' gestation), proteinuria, and edema seems to result from suppression of the normal physiologic responses to pregnancy. Elements of increased BP, increased vascular permeability, disordered intravascular coagulation, and decreased perfusion of certain organs produce the clinical effects. Initiation of the disease requires only a placenta because cases of preeclampsia in women with molar pregnancies have been reported. Definitive treatment is the delivery of the placenta, although disease progression may occur for a time.
• Preeclampsia renders kidneys highly susceptible to endothelial injury as a result of decreased renal blood flow and GFR. Pulmonary edema may also develop; its cause is felt to be multifactorial.
• Hematological findings include abnormalities in clotting and platelet function. In severe preeclampsia, thrombocytopenia due to microthrombi formation and a mild consumptive coagulopathy are frequent findings.
• HELLP syndrome may accompany severe cases of preeclampsia. In these patients, hepatic subcapsular hematomas may occur and result in life-threatening capsular rupture. Periportal hemorrhagic necrosis in the periphery of the liver lobule probably results in the elevation of liver enzymes and the site of hemorrhage. Once again, the endothelial damage is considered the underlying etiology.
• CNS effects of headache, dizziness, tinnitus, altered mental status, visual changes, and seizures are thought to result from the increased vascular resistance and vasospasm of preeclampsia. Although total cerebral blood flow and cerebral oxygen metabolism generally are not altered in preeclampsia, regional changes certainly do occur. One third of patients who died from eclampsia experienced cerebral hemorrhages of varying degrees. The visual changes may result from vasospasm, ischemia, and hemorrhage in the occipital cortex, or from retinal artery spasm, edema, or retinal detachment.
• Fetal consequences of preeclampsia vary with the time of onset and severity of maternal disease. Early onset and severe preeclampsia are important contributors to fetal growth restriction and preterm birth. The risk for abruptio placenta triples with the increasing severity of the maternal disease.

Physical

Preeclampsia is a disease of the pregnant woman.

• Maternal findings upon examination may include edema, hypertension, retinal-vascular changes, hyperreflexia, and hepatic enlargement and tenderness. Severe preeclampsia may result in anasarca and disseminated intravascular coagulopathy (DIC) with purpura.
• Infants who experienced fetal growth restriction exhibit variable effects on growth parameters, weight, length, and head circumference. The time of onset, severity of disease, and genetic, environmental, and behavioral factors, as well as the presence of underlying maternal vascular disease, influence the fetal growth processes. Oligohydramnios and abnormalities in Doppler studies of the umbilical artery and the fetal middle cerebral artery develop in the presence of severe disease.
• Neonates born to mothers with preeclampsia may have low birth weight or be premature. Maternal treatment with magnesium sulfate also may confer generalized hypotonia on the newborn, with or without apnea or respiratory compromise.

Causes

The cause of preeclampsia has not been fully elucidated. Current evidence suggests an important role of reduced placental perfusion leading to maternal disease that is characterized in reduced systemic blood flow, endothelial dysfunction, and the potential for multiple organ injury.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Neonates born to mothers with preeclampsia-eclampsia may warrant laboratory investigation if affected by prematurity, low birth weight (<2.5 kg) or very low birth weight ( <1.5 kg). Laboratory investigation also is indicated if intrauterine growth restriction, hypotonia, apnea, or an infectious disease risk is present.
• Neonatal lab studies may include a serum calcium, magnesium, complete blood count with differential and platelets, arterial blood gas, and blood culture. Common findings include low WBC, elevated hematocrit, and low platelet count. Glucose monitoring may also be appropriate for infants with growth restriction, transitional difficulties, or moderate prematurity.
• Additional lab studies may be collected as indicated by the newborn's condition.

Imaging Studies

• No specific neonatal imaging studies are indicated by the presence of maternal preeclampsia.

Histologic Findings

Placental histology reveals abnormal syncytiotrophoblast with increased mitotic activity. Trophoblast basement membrane thickening also is observed.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

Incomplete understanding of the genesis and underlying pathophysiology in preeclampsia has impeded attempts at prevention. Empiric approaches of dietary manipulations, low-dose aspirin, use of diuretics or antihypertensives, and manipulations of mineral and electrolyte concentrations have not produced consistent results. Resolution of the disease only occurs after delivery of the placenta. Antepartum management is fraught with controversies before 37 weeks' gestation. In mild cases, fetal and maternal surveillance may allow pregnancy to proceed toward maturity, while prevention of CNS effects, control of hypertension, and management of fluid balance is attempted. Timing and mode of delivery are obstetrical decisions generally based on the maternal and fetal condition.

Maternal treatment often includes magnesium sulfate infusions. Depending on the duration of infusion and maternal blood levels, this may result in symptomatic neonatal hypermagnesemia. Although the hypotonia and apnea are transient, they may result in the need for respiratory support in the infant.

Among infants born to women with preeclampsia who exhibited absent or reverse end-diastolic umbilical artery Doppler flow velocity on fetal monitoring, an increased frequency of hypoglycemia and polycythemia that is independent of the degree of gestational age and fetal growth restriction has been found.

Surgical Care

Preeclampsia is not a surgical disease of the mother or affected newborn. However, cesarean delivery may be required to address increasing maternal disease severity and minimize maternal and fetal-neonatal morbidity and mortality.

Consultations

Consultation with a neonatologist may be appropriate when caring for a newborn with low birth weight who was delivered to a mother with preeclampsia. Problems such as hypotonia, apnea, hypoglycemia, infection, hyperviscosity, and difficulties with thermoregulation may require a neonatologist's management.

Diet

• Neonate
• • Initial IV fluids with dextrose 10% in water and additional calcium may be sufficient. The early use of a protein-containing parenteral alimentation solution is advocated for infants with very low birth weight.
  • Infants with reverse end-diastolic umbilical artery Doppler flow should be monitored for hypoglycemia and polycythemia. Interventions are predicated on screening results and infant symptomatology.
  • The ability to enterally feed the newborn who is delivered to a mother with preeclampsia is determined by associated findings, such as the presence or degree of any perinatal distress, asphyxia, or acidemia; presence of hypotonia/hypermagnesemia; problems with respiratory embarrassment or apnea and need for ventilatory assistance; or other concerns (eg, infection, need for central venous or arterial access). When appropriate to initiate feedings, breast milk or a formula for premature infants is recommended. Breastfeeding in the first few days also is dependent on the maternal postpartum condition.

Activity

Recommendations for activity vary, depending on the presence of associated problems of prematurity or, perhaps, hypotonia.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug therapy is not applicable to this discussion, with the exception of the medication safety considerations among women choosing to breastfeed their infants. Preeclampsia is a maternal disease that affects the fetus. No specific drug therapy for the fetus exists.

Breastfeeding is permissible if the mother has received treatment with magnesium sulfate or certain beta-blockers and calcium channel blockers. Labetalol and propranolol are preferred for initial maternal antihypertensive therapy because these drugs are not concentrated in breast milk, unlike other beta-blockers. Sustained-release nifedipine or verapamil are acceptable alternatives. Diuretics may reduce milk volume and should be avoided.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• The clinical care needs of the neonate born to a mother with preeclampsia are based on the infant's associated findings (eg, prematurity, low birth weight) and clinical symptomatology rather than solely based on maternal preeclampsia.

Further Outpatient Care

• No further outpatient concerns are conferred on the newborn of the mother with preeclampsia. Among infants born prematurely or with significant growth restriction, attention to the adequacy of nutrient intake, postnatal weight gain, and overall growth is important. Periodic developmental surveillance may be necessary for infants with very low birth weight and infants who experienced complications at birth.
• Note that an infant's low weight at birth and history of pregnancy complicated by preeclampsia are risk factors for later onset of metabolic syndrome (hypertension, insulin resistance, and hyperlipidemia) and appear to increase the risk for development of preeclampsia among women born of pregnancies complicated by hypertensive disorders of pregnancies.

Transfer

• Neonates who have very low birth weight or are premature may require transfer to a center with neonatal intensive care capabilities if born in a level I center. This is especially true if the neonate has extreme prematurity, a need for respiratory support, or prolonged intravenous nutrition. Support in transport should be focused on routinely recognized conditions and vital signs (see Transport of the Critically Ill Newborn).

Deterrence/Prevention

• Prevention of preeclampsia is unlikely because a causal agent or condition is not known. Nonetheless, infants born to mothers with preeclampsia do best when maternal hypertension is well controlled, activity and weight gain in pregnancy is regulated, and both antepartum and intrapartum assessment and management are optimal.

Complications

• The perinatal mortality rate is increased in pregnancies complicated by preeclampsia, especially with severe disease. Specific neonatal complications from preeclampsia include effects on length of gestation (ie, prematurity), fetal growth, potential hematologic sequelae, and adverse effects from maternal medications (eg, magnesium sulfate). No reported increases in the incidence of congenital anomalies or birth defects exist.

Prognosis

• The prognosis for neonates born to mothers with preeclampsia is best determined by associated problems (eg, prematurity, low birth weight).

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Lack of recognition of the condition in the mother that would preclude appropriate pregnancy management is a pitfall.
• Inattention to maternal medications used to treat preeclampsia and its complications as potential contributors to neonatal hypotonia and apnea and failing to monitor a neonate who is premature or has low birth weight for respiratory problems may lead to unrecognized apnea, hypoxemia, or other problems requiring resuscitation.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• ACOG Committee on Practice Bulletins. Intrauterine growth restriction. ACOG P. B. No. 12. 2000, Jan.
• ACOG Committee on Practice Bulletins--Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol. Jan 2002;99(1):159-67. [Medline].
• Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. 7th ed. Lippincott, Williams & Wilkins; 2005..
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• Duley L, Meher S, Abalos E. Management of pre-eclampsia. BMJ. Feb 25 2006;332(7539):463-8. [Medline].
• Hale TW. Medications and Mother's Milk: A Manual of Lactational Pharmacology. 12th ed. Pharmasoft Medical Pub; 2006..
• Hughes EC. Obstetric-Gynecology Terminology. Philadelphia, Penn: FA Davis; 1972: 422-423..
• Kaufman P, Scheffen I. Placental development. Fetal and Neonatal Physiology. 2nd ed. 1998:59-70.
• Lain KY, Roberts JM. Contemporary concepts of the pathogenesis and management of preeclampsia. JAMA. Jun 26 2002;287(24):3183-6. [Medline].
• Osmanagaoglu MA, Topcuoglu K, Ozeren M, Bozkaya H. Coagulation inhibitors in preeclamptic pregnant women. Arch Gynecol Obstet. Mar 2005;271(3):227-30. [Medline].
• Pridjian G, Puschett JB. Preeclampsia. Part 1: clinical and pathophysiologic considerations. Obstet Gynecol Surv. Sep 2002;57(9):598-618. [Medline].
• Pridjian G, Puschett JB. Preeclampsia. Part 2: experimental and genetic considerations. Obstet Gynecol Surv. Sep 2002;57(9):619-40. [Medline].
• Redman CW, Sargent IL. Latest advances in understanding preeclampsia. Science. Jun 10 2005;308(5728):1592-4. [Medline].
• Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. Dec 2005;46(6):1243-9. [Medline].
• Rosenfield CR. Regulation of the placental circulation. Fetal and Neonatal Physiology. 2nd ed. 1998:70-77.
• Sezik M, Tuncay G, Yapar EG. Prediction of adverse neonatal outcomes in preeclampsia by absent or reversed end-diastolic flow velocity in the umbilical artery. Gynceol Obstet Invest. 2004;57(4):109-13. [Medline].
• Shear RM, Rinfret D, Leduc L. Should we offer expectant management in cases of severe preterm preeclampsia with fetal growth restriction?. Am J Obstet Gynecol. Apr 2005;192(4):1119-25. [Medline].
• Sibai BM. Preeclampsia as a cause of preterm and late term (near term) births. Seminars in Perinatology. 2006;30:16-19. [Medline].
• Skjaerven R, Vatten LJ, Wilcox AJ, et al. Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort. BMJ. Oct 15 2005;331(7521):877. [Medline]. [Full Text].
• Villar J, Carroli G, Wojdyla D, et al. Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions?. Am J Obstet Gynecol. Apr 2006;194(4):921-31. [Medline].

Article Last Updated: Oct 4, 2006