Pre-eclampsia

doi:10.1016/S0140-6736(00)02800-2

The Lancet

Volume 356, Issue 9237, 7 October 2000, Pages 1260-1265

https://doi.org/10.1016/S0140-6736(00)02800-2 Get rights and content

Summary

Pre-eclampsia is associated with significant morbidity and mortality for mother and baby, but it resolves completely post partum. Despite a steady reduction in maternal mortality from the disorder in more developed countries, it remains one of the most common reasons for a woman to die during pregnancy. The disorder starts with a placental trigger followed by a maternal systemic response. Because both this systemic response and the woman's reaction to it are inconsistent, the clinical presentation varies in time and substance, with many different organ systems affected. With the increasing understanding of the disease process, there have been advances in management, such as antihypertensive therapy, magnesium sulphate, and fluid restriction.

Section snippets

Epidemiology

The epidemiology of pre-eclampsia is complicated by differences in definitions and inaccuracy of diagnosis. A single blood-pressure reading of 140/90 mm Hg or above is not uncommon in pregnancy and was reported in nearly 40% of pregnant women in one study.⁶ Such a finding carries little risk to the mother or fetus. Persistent hypertension is diagnosed if a high reading is found on two occasions at least 4 h apart. Persistent hypertension occurs in around 12–22% of pregnancies,7, 8, 9 depending

Pathophysiology

Pre-eclampsia is the result of an initial placental trigger, which has no adverse effect on the mother, and a maternal systemic reaction that produces the clinical signs and symptoms of the disorder.¹⁷

Placental trigger

Pre-eclampsia occurs only in the presence of a placenta. Although it is associated with a failure of the normal invasion of trophoblast cells, leading to maladaptation of maternal spiral arterioles,¹⁸ it can also be associated with hyperplacentation disorders such as diabetes, hydatidiform mole, and multiple pregnancy. The maternal arterioles are the source of blood supply to the fetus (figure 2), and maladaptation of these vessels can interfere with normal villous development. In some cases,

Maternal response

Although pre-eclampsia is said to be a vascular endothelial disorder,²¹ it is a multisystem disorder with various forms. This variation could be due to different vascular beds being affected to varying degrees, but later research has shown that there is a strong maternal inflammatory response.¹⁷ Although this response has been described in the placental bed,²² there is far broader immunological systemic activity.¹⁷ These changes may explain many of the clinical signs, including the

Hereditary factors

Pre-eclampsia can be familial,²³ but various groups have studied the genetic basis of this disorder and no persistent results have been obtained with obvious population differences. A single pre-eclampsia gene is unlikely; there are probably several modifier genes along with environmental factors.²⁴ There have been conflicting results for the genes that encode angiotensinogen, superoxide dismutase, tumour necrosis factor α, methylene-tetrahydrofolate reductase, factor V Leiden, and endothelial

Diagnosis and assessment

Hypertension is the most common diagnostic sign, although some women present with convulsions, abdominal pain, or general malaise. Because there are no specific diagnostic investigations, the initial diagnosis of pre-eclampsia remains clinical. The classification of severity is mainly based on the blood-pressure value and the presence of proteinuria; further characterisation is based on the other accompanying signs.²⁵

Management

The management of pre-eclampsia is complicated by the presence of the fetus. Delivery is the ultimate cure, but management aimed at benefiting the mother may be detrimental to the fetus because premature birth is a significant cause of morbidity and mortality.⁴⁰ Therefore, the management of pre-eclampsia is based on a stepwise protocol: pregnant women are screened; those at risk are monitored; the maternal condition is stabilised; monitoring is continued; and the delivery is initiated at the

Planning of delivery

Delivery is the ultimate cure for pre-eclampsia but most maternal deaths occur post partum.¹ The timing of delivery is critical. A rushed delivery in an unstable patient or a delay in delivery in a sick patient can add to the maternal risk rather than reducing it.

If delivery has been decided upon before 32 weeks of gestation, the practice in the UK is to deliver by elective caesarean section⁴¹ although many centres throughout the world would attempt a vaginal delivery with varied results.⁴⁰

Postpartum care

Continued close monitoring is required after delivery. An initial improvement with a relapse is commonly seen within 24 h of delivery. The woman should be cared for in a high-dependency area and should not be transferred to the postnatal ward until the test results begin to return to the normal range.

In the UK, the main cause of maternal mortality in pre-eclampsia is pulmonary oedema (table).¹ This complication occurs in about 6% of cases in severe disease.⁵⁸ It is aggravated by exogenous fluid

References (60)

BM Sibai
Prevention of preeclampsia: a big disappointment
Am J Obstet Gynecol
(1998)
BM Sibai et al.
Pregnancies complicated by HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets): subsequent pregnancy outcome and long-term prognosis
Am J Obstet Gynecol
(1995)
CW Redman et al.
Preeclampsia: an excessive maternal inflammatory response to pregnancy
Am J Obster Gynecol
(1999)
L Macara et al.
Structural analysis of placental terminal villi from growth-restricted pregnancies with abnormal umbilical artery doppler waveforms
Placenta
(1996)
JM Roberts et al.
Endothelial dysfunction yes, cytotoxicity no
Am J Obstet Gynecol
(1995)
R Pijnenborg et al.
Immunolocalization of tumour necrosis factor-alpha (TNF-alpha) in the placental bed of normotensive and hypertensive human pregnancies
Placenta
(1998)
JN Martin et al.
Early risk assessment of severe preeclampsia: admission battery of symptoms and laboratory tests to predict likelihood of subsequent signifiant maternal morbidity
Am J Obstet Gynecol
(1999)
MA Brown et al.
Randomised trial of management of hypertensive pregnancies by Korotkoff phase IV or phase V
Lancet
(1998)
PM Bosio et al.
Maternal central hemodynamics in hypertensive disorders of pregnancy
Obstet Gynecol
(1999)
HV Gartner et al.
Preeclamptic nephropathy–an endothelial lesion: a morphological study with a review of the literature
Eur J Obstet Gynecol Reprod Biol
(1998)

Why mothers die. Report on confidential inquiries into maternal deaths in the United Kingdom 1994–96

(1999)

CR Leitch et al.

The changing pattern of eclampsia over a 60 year period

Br J Obstet Gynaecol

(1997)

L Duley

Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean

Br J Obstet Gynaecol

(1992)

JJ Walker

Day-care obstetrics

Br J Hosp Med

(1993)

PF Plouin et al.

Incidence and fetal impact of hypertension in pregnancy: study of 2996 pregnancies

Arch Mal Coeur Vaiss

(1982)

Cited by (562)

Headaches Attributed to Disorders of Homeostasis
2024, Neurologic Clinics
Investigation of the effects of gestational diabetes and hypertension on retinal and choroidal microvascular circulation using swept-source optical coherence tomography angiography
2024, Microvascular Research
The aim of this study was to investigate the microvascular changes in the retina and choroid in gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH) and to compare the results with those of healthy pregnant subjects.
Twenty-nine pregnant subjects with coexisting GDM and PIH (group 1) and 36 healthy pregnant subjects (group 2) were enrolled in the study. All subjects were examined by optical coherence tomography (OCT) and angiography (OCTA). The retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), choroidal thickness (CT), superficial capillary plexus (SCP), deep capillary plexus (DCP), choriocapillaris (CC) vascular density (VD), and foveal avascular zone (FAZ) were measured.
We observed that the values of CT and VD were lower in group 1 than in group 2. No significant difference was found between groups in RT, FAZ area and CC VD. SCP and DCP VD values were higher in group 2 in all quadrants. We observed a significant increase in FAZ area and CC VD with increasing systolic blood pressure. No correlation was observed between diastolic blood pressure and FBS with other parameters. In group 1, FAZ area was significantly higher in the diet-treated group than in the insulin-treated group.
Monitoring and treatment of pregnant women with PIH and GDM is important because of the risks that may occur during pregnancy. We believe that changes in microvascular circulation can be detected noninvasively with OCTA, even in the absence of clinical or retinal findings.
Maldistribution of fluid in preeclampsia: a secondary kinetic analysis
2024, International Journal of Obstetric Anesthesia
Hypovolemia and peripheral edema are frequent components of preeclampsia. The level of the dysregulation of the body fluid distribution is unclear, which complicates the choice of infusion fluid during surgery. The present fluid kinetic study challenges whether the maldistribution of fluid is due to increased capillary leakage or to poor return of already distributed fluid, which occurs via lymphatic pathways.
Ringeŕs solution was infused in 10 awake non-pregnant women, eight healthy pregnant women, and in eight women with mild-to-moderately severe preeclampsia. Distribution and redistribution of the infused fluid was calculated with mixed models kinetics based on the excreted urine volumes and 675 measurements of hemodilution. Differences in fluid kinetics between the three groups were studied with covariance analysis.
The return flow of fluid volume to the plasma after distribution (rate parameter k₂₁) was almost zero in women with preeclampsia, while the rate was normal in the other two groups (P< 0.001). By contrast, the capillary leakage rate of fluid in response to the infusion (k₁₂) was normal. The urinary excretion (k₁₀) was moderately accelerated.
Decreased flow of extravascular fluid to the plasma was the key disturbance in women with preeclampsia. Such decreased flow alone promotes hypovolemia, peripheral edema, and hypoalbuminemia, and may be explained by inhibition of lymphatic pumping and/or a decreased interstitial hydrostatic pressure due to the presence of vasoactive and inflammatory signal molecules. The moderately accelerated urine flow may be due to “pressure diuresis” in response to hypertension.
The significance of mitochondrial haplogroups in preeclampsia risk
2023, Pregnancy Hypertension
To determine whether mitochondrial haplogroups function as disease-modifiers or as susceptibility factors in preeclampsia using a traditional haplogroup association model.
This retrospective study haplotyped 235 control and 78 preeclamptic pregnancies from Denmark using either real-time PCR or Sanger sequencing depending on the rarity of the haplogroup.
No significant association between haplogroups and the risk of preeclampsia was found, nor was any role for haplogroups in disease severity uncovered.
Mitochondrial haplogroups are not associated with preeclampsia or the severity of preeclampsia in the Danish population. However, this study cannot exclude a role for less common mtDNA variation. Models that can examine these should be applied in preeclamptic patients.
Obstetric Events That Affect Cardiac Patients
2022, Maternal Cardiac Care: A Guide to Managing Pregnant Women with Heart Disease
Pregnancy represents a potential significant stressor for women with underlying cardiac disease. Physiologic adaptations to pregnancy pose alterations to the cardiac preload, afterload, output demands, and chamber sizes, and such adaptations may not be tolerated in the setting of underlying cardiac disease. Additional noncardiovascular physiologic adaptations to pregnancy can exacerbate the risk for cardiac compromise or pose noncardiac risks such as venous thromboembolism. Anticipated pregnancy-specific events such as those experienced during the intrapartum and immediate postpartum periods may serve as triggers for many cardiac complications.
Do frozen embryo transfers modify the epigenetic control of imprinted genes and transposable elements in newborns compared with fresh embryo transfers and natural conceptions?
2021, Fertility and Sterility
To determine whether the epigenetic control of imprinted genes (IGs) and transposable elements (TEs) differs at birth between fresh or frozen embryo transfers and natural conceptions.
Prospective study.
University hospital.
A total of 202 singleton births were divided into three groups: 84 natural pregnancies (controls), 66 in vitro fertilization/intracytoplasmic sperm injection with fresh embryo transfers, and 52 vitro fertilization/intracytoplasmic sperm injection with frozen embryo transfers.
None.
Pyrosequencing was used to assess the DNA methylation profiles of three IGs (H19/IGF2:IG-DMR [two sequences], KCNQ1OT1:TSS-DMR, and SNURF:TSS-DMR) and two TEs (LINE-1 and HERV-FRD) in cord blood and placenta. The quantitative reverse transcriptase polymerase chain reaction was used to study the transcription of three IGs (H19, KCNQ1, and SNRPN) and two TEs (LINE-1 and ORF2).
After adjustment, the placental DNA methylation levels of H19/IGF2 were lower in the fresh embryo transfer group than in the control (H19/IGF2-seq1) and frozen embryo transfer (H19/IGF2-seq2) groups. The DNA methylation rate for LINE-1 was lower in placentas from the fresh embryo transfer group than in placentas from the control and frozen embryo transfer groups and for HERV-FRD compared with controls. In cord blood, DNA methylation levels were not significantly associated with the mode of conception. The relative expression of LINE-1 and ORF2 was decreased in both cord blood and placental tissues from fresh embryo transfer conceptions compared with natural conceptions and frozen embryo transfer conceptions.
Compared with natural conceptions and frozen embryo transfers, fresh embryo transfers were associated with methylation and/or transcription changes in some TEs and IGs, mostly in placental samples, which could indicate altered placental epigenetic regulation resulting from ovarian stimulation protocols.
¿Puede La transferencia de embriones congelados modificar el control epigenético de genes impresos y elementos transponibles en los recién nacidos comparado con la transferencia de embriones frescos y concepciones naturales?
Determinar si el control epigenético de genes impresos (IGs) y elementos transponibles (TEs) difiere al nacimiento entre embriones congelados o frescos y concepciones naturales.
Estudio prospectivo.
Hospital universitario.
Un total de 202 nacimientos únicos fueron divididos en tres grupos: 84 embarazos naturales (controles), 66 logrados por fertilización in vitro/inyección intracitoplasmática de espermatozoides con transferencia de embriones frescos, y 52 por fertilización in vitro/inyección intracitoplasmática de espermatozoides con transferencia de embriones congelados.
Ninguna.
Se usó pirosecuenciación para determinar los perfiles de metilación de tres IGs (H19/IGF2:IG-DMR [dos secuencias], KCNQ1OT1:TSS-DMR, y SNURF:TSS-DMR) y dos TEs (LINE-1 y HERV-FRD) en sangre de cordón y placenta. La medición cuantitativa de la polimerasa transcriptasa reversa reaccionada en cadena se usó para estudiar la transcripción de tres IGs (H19, KCNQ1, y SNRPN) y dos TEs (LINE-1 y ORF2).
Post ajustes, los niveles placentarios de metilación de ADN de H19/IGF2 fueron menores en el grupo de transferencias embrionarias frescas que en los grupos control (H19/IGF2-seq1) y de embriones congelados (H19/IGF2-seq2). La tasa de metilación de ADN para LINE-1 fue menor en placentas obtenidas del grupo de transferencia de embriones frescos comparada con placentas del grupo control y de aquellas provenientes de transferencias de embriones congelados y para HERV-FRD comparada con controles. En sangre de cordón, los niveles de metilación de ADN no se asociaron significativamente a la forma de concepción. La expresión relativa de LINE-1 y ORF2 se encontró disminuida tanto en sangre de cordón como en tejidos placentarios en concepciones obtenidas por transferencias embrionarias frescas comparada con concepciones naturales y transferencias de embriones congelados.
Comparado con concepciones naturales y las producidas por transferencia de embriones congelados, las transferencias embrionarias en fresco se asociaron a cambios en la metilación y/o cambios transcripcionales en algunos TEs e IGs, principalmente en muestras placentarias, lo que podría indicar alteraciones en la regulación epigenética placentaria producto de los protocolos de estimulación ovárica.

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SeminarPre-eclampsia

Summary

Section snippets

Epidemiology

Pathophysiology

Placental trigger

Maternal response

Hereditary factors

Diagnosis and assessment

Management

Planning of delivery

Postpartum care

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obster Gynecol

Placenta

Am J Obstet Gynecol

Placenta

Am J Obstet Gynecol

Lancet

Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Am J Obstet Gynecol

Semin Perinatol

Am J Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Clin Perinatol

Am J Hypertens

Am J Obstet Gynecol

Obstet Gynecol

Clin Perinatol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Why mothers die. Report on confidential inquiries into maternal deaths in the United Kingdom 1994–96

The changing pattern of eclampsia over a 60 year period

Br J Obstet Gynaecol

Maternal mortality associated with hypertensive disorders of pregnancy in Africa, Asia, Latin America and the Caribbean

Br J Obstet Gynaecol

Day-care obstetrics

Br J Hosp Med

Incidence and fetal impact of hypertension in pregnancy: study of 2996 pregnancies

Arch Mal Coeur Vaiss

Seminar
Pre-eclampsia