Preeclampsia

HELLP syndrome, a life-threatening complication of gestational hypertension, was first described by Weinstein in 1982 (Baltzer 2004).

Preeclampsia is defined as any new and any preexisting hypertension with blood pressure values ≥ 140 / 90 mmHg during pregnancy with at least one new-onset organ manifestation that cannot be attributed to any other cause (Scharl 2019).

Hypertensive disorders of pregnancy (HES) include:

- Chronic hypertension.

In this case, hypertension already exists before conception or in the 1st trimester (Scharl 2019).

- Gestational hypertension (SIH).

This first occurs in pregnancy after 20 weeks gestation and does not last longer than 12 weeks post partum (Rath 2005).

- Preeclampsia

In this case, in addition to SIH, other new-onset abnormalities are found, such as proteinuria, renal insufficiency, liver involvement, uteroplacental dysfunction, and hematologic or neurologic complications (Herold 2022).

In preeclampsia, one differentiates between a

- mild hypertensive disease:

- Blood pressure values between 140- 159 mmHg systolic and 90 - 109 mmHg diastolic.

- proteinuria between 0.5 - 5 g / l / 24h.

- severe hypertensive disease

- blood pressure values > 160 mmHg systolic and > 110 mmHg diastolic

- Oliguria < 400 ml / 24 h

- hyperreflexia

- pulmonary edema

- cyanosis

- upper abdominal discomfort (Dudenhausen 2011)

- impending eclampsia

- headache

- visual disturbances (Dudenhausen 2011)

- severe hypertensive disease (eclampsia)

- tonic-clonic convulsions

- apnea

- coma (Dudenhausen 2011)

Hypertensive disorders of pregnancy are a leading cause of both maternal and perinatal mortality worldwide (Gestational Hypertension and Preeclampsia 2020).

Preeclampsia develops in approximately 5% of all pregnant women (Herold 2022).

Preeclampsia is caused by the pregnancy itself (Schwenger 2021).

Risk factors are:

- nulliparity

- anamnestically known:

- renal disease

- diabetes mellitus

- preeclampsia in previous pregnancy

- chronic hypertension

- obesity

- maternal age < 15 years or > 35 years

- multiple pregnancy

- Antiphospholipid antibody syndrome (Kasper 2015)

- Hydrops fetalis

- trisomy

- In vitro fertilization (IVF)

- Bladder mole (Scharl 2019)

In preeclampsia, the following symptoms exist:

- Blood pressure elevation > 135 / 85 mmHg

- edema

- proteinuria (Dudenhausen 2011)

In the further course of pregnancy, complications can lead to the following symptoms:

- Renal dysfunction with

- oliguria or a creatinine value > 1.5 mg / dl

- hepatocellular damage with

- increase of the serum alanine aminotransferase level to more than twice the normal level

- pulmonary edema

- hematological dysfunction with e.g.

- platelets < 100,000 / l

- disseminated intravascular coagulation

- CNS dysfunction with

- headache

- blurred vision

- seizures (Dudenhausen 2011)

In the 1st trimester, the mother should first be assessed for risk.

In the 2nd and 3rd trimesters, blood pressure measurement and proteinuria are particularly important in screening for preeclampsia during regular examinations according to the maternity guidelines (Scharl 2019).

Estimation of the risk of preeclampsia can be done by Doppler sonography of the uterine artery and determination of angiogenic factors (Scharl 2019).

Other examinations

Blood pressure measurement

These should always be performed with cuffs adapted to the circumference of the upper arm, the primary measurement always on both sides and always after an appropriate rest period in the sitting pregnant woman (Scharl 2019).

24 h blood pressure measurement

This examination is used for differential diagnostic clarification of hypertension, in particular to exclude "white coat hypertension". Furthermore, conclusions can be drawn about a possible loss of the circadian rhythm, which is a prognostically unfavorable sign. In addition, the success of any antihypertensive therapy can be assessed (Scharl 2019).

Doppler sonography

The examination should be performed in the 2nd trimester. Here, the mean pulsatility index (PI) is determined as the best marker for the prediction of preeclampsia. The sensitivity is up to 93% (Scharl 2019).

- renal dysfunction with a creatinine value > 1.5 mg / dl.

- Increase in

- alanine aminotransferase levels in serum

- bilirubin

- ALT and AST(GPT and GOT, respectively) by ≥ 2 times the reference range

- LDH by ≥ 2 times the reference range

- Hematologic dysfunction with, for example, platelets < 100,000 / l.

- proteinuria:

In the context of SIH, proteinuria is defined as a 24-hr urinary protein > 300 mg / 24 h

or a protein- creatinine ratio ≤ 0.3 (Kasper 2015). If proteinuria occurs before the 20th SSW, this is considered an indication of preexisting renal disease (Scharl 2019).

Repeated urine tests for protein are not necessary, as the level of proteinuria is not predictive (Scharl 2019).

- HELLP syndrome (haemolysis, elevated liver enzymes, low platelet count)

This is found in approx. 0.5% of SIH sufferers (Herold 2022). This is primarily characterized by pain in the right upper abdomen due to capsular tension of the liver as well as nausea and vomiting (Baltzer 2004). This is a life-threatening complication (Baltzer 2004 / Schölmerich 2005).

- Eclampsia

Eclampsia is found in approx. 0.1 % of those affected by SIH (Herold 2022). Generalized tonic-clonic convulsions occur (Schölmerich 2005).

Eclampsia is also a life-threatening complication (Baltzer 2004 / Schölmerich 2005).

- Apoplexy

The occurrence of coagulation disorders or disorders of platelet function increases the risk of apoplexy (Kasper 2015).

- Developmental disorders in children

These occur as part of SIH due to degenerative processes in the placenta (Dellas 2022).

Although SIH is self-limited and disappears without treatment within a few weeks post partum, early treatment is essential due to the morbidity and mortality for mother and child (Kasper 2015).

Indications for hospitalization are:

- clinically confirmed pre-eclampsia

- Blood pressure values ≥ 160 mmHg systolic or ≥ 110 mmHg diastolic

- Especially HELLP syndrome (especially with persistent pain in the upper abdomen)

In case of dyspnea, hypertensive crisis and severe neurological prodromal symptoms, immediate transport to hospital by ambulance is required (Scharl 2019).

Mild pre-eclampsia:

Conservative treatment with limitation of physical activity, close monitoring of blood pressure, kidney function and the fetus is recommended here (Kasper 2015).

Severe pre-eclampsia:

With blood pressure values ≥ 160 / 110 mm Hg, there is a significantly increased risk of eclampsia, premature birth or apoplexy (Scharl 2019).

In this case, pregnant women are often recommended to have a (premature) delivery (Kasper 2015).

Drug therapy should be given starting at blood pressure values of 150 - 160 / 100 - 110 mmHg. For blood pressure values ≥ 160 / 110 mm Hg, blood pressure adjustment under stationary conditions is recommended (Scharl 2019).

However, elevated arterial blood pressure should be lowered slowly, otherwise cerebrovascular adverse events may occur (Kasper 2015). Lowering it too drastically also decreases placental perfusion and thus poses an acute fetal impairment (Scharl 2019).

Oral medications available include:

- Alpha- methyldopa

This represents the drug of 1st choice. Dosage recommendation: 250 - 500 mg 2 - 4 x / d p. o., maximum dose 2 g / d (Scharl 2019).

- Nifedipine ret.

Dosage recommendation: 20 - 60 mg orally, maximum dose 120 mg / d (Scharl 2019).

- Labetalol (Kasper 2015).

Dosage recommendation: Initial 3 x 200 mg / d, maximum dose is 4 x 300 mg / d (Scharl 2019).

Target blood pressure values are between 130 - 150 mmHg systolic and between 80 - 100 mmHg diastolic (Scharl 2019).

Because of the negative effects on fetal development in the 2nd and 3rd trimesters, should be avoided:

- Angiotensin- receptor blockers

- ACE- inhibitors (Kasper 2015).

According to the guideline, although no teratogenic effects have been proven, they are nevertheless contraindicated in the 2nd and 3rd trimesters because they lead to acute renal failure in the newborn (Scharl 2019).

For rapid acute blood pressure lowering, the drugs used are:

- Urapidil

Dosage recommendation: Initial 6.25 mg slowly i. v. (over 2 min), then via perfusor 3 - 24 mg / h (Scharl 2019).

- Dihydralazine

Dosage recommendation: Initial 5 mg i. v., followed by 2 - 20 mg / h via perfusor (Scharl 2019)

- Magnesium sulfate

Since magnesium interacts with N- methyl- D- aspartate receptors in the CNS, they may reduce the risk of seizures in mothers with SIH (Kasper 2015).

The prognosis depends on the extent of hypertension, as this determines the perinatal mortality of mother and child (Herold 2022).

In women with preeclampsia, approximately 10-15% of maternal deaths are related to (pre)eclampsia. These would have been preventable in up to 90% in Europe (Scharl 2019).

In addition, women with Z. n. preeclampsia have a lifelong increased risk of cardiovascular disease (Herold 2022).

The recurrence risk of preeclampsia in subsequent pregnancies is between 14-18%. It depends on the gestational age of the initial manifestation and is lower the more advanced the pregnancy was (Scharl 2019).

Prophylaxis

The risk of developing preeclampsia can be reduced by low-dose aspirin from the end of the 1st trimester (Kasper 2015). According to the guideline, the dosage recommendation is 150 mg / d ASA from the 16th SSW. This can significantly reduce the risk of developing preeclampsia or SIH before the 37th week of gestation by up to 63% (Scharl 2019).

1. Baltzer J, Friese K, Graf M, Wolff F (2004) Praxis der Gynäkologie und Geburtshilfe: Das komplette Praxiswissen in einem Band. Georg Thieme Verlag Stuttgart / New York 244
2. Dellas C (2022) Pharmacology - short textbook. Elsevier Urban und Fischer Verlag Munich 406
3. Dudenhausen J W, Grab D, Obladen M, Pschyrembel W + (2011) Practical obstetrics with obstetric operations. Walter de Gruyter Verlag Berlin / Boston 73
4. Gestational Hypertension and Preeclampsia (2020) ACOG Practice Bulletin Summary, Number 222. obstetrics and gynecology 135 (6) 1492 - 1495 DOI 10.1097/AOG.000000003892.
5. Herold G et al (2022) Internal Medicine. Herold Publ. 299, 521
6. Kasper D L, Fauci A S, Hauser S L, Longo D L, Jameson J L, Loscalzo J et al (2015) Harrison's Principles of Internal Medicine. Mc Graw Hill Education 45 - 46
7. Rath W, Friese K (2005) Diseases in pregnancy. Georg Thieme Verlag Stuttgart 73
8. Scharl A, Ehm D, Kohlberger P, Schlembach D, Stepan H (2019) Hypertensive disorders of pregnancy: diagnosis and therapy. Guideline program of the DGGG, OEGGG andSGG. AWMF- registration number 015 / 018.
9. Schölmerich J, Burdach S, Drexler H, Hallek M, Hiddemann W, Hörl W H, Klein H, Landthaler M, Lenz K, Mann K, Mössner J, Müller- Ladner U, Reichen J, Schmiegel W, Schröder J O, Seeger W, Stremmel W, Suttrop N, Weilemann L S, Wöhrle J C (2005) Medical therapy 2005 / 2006. Springer Verlag Heidelberg New York 1522.
10. Schwenger V (2021) Clinical guide to nephrology. Elsevier, Urban and Fischer Publishers Germany 604