Die Bedeutung der Hyperhomocysteinämie für Embryonalentwicklung und Schwangerschaftskomplikationen

U. Hübner; I. Koch; U. Retzke; W. Herrmann

doi:10.1055/s-2003-42733

Geburtshilfe und Frauenheilkunde, Table of Contents

Geburtshilfe Frauenheilkd 2003; 63(10): 990-998
DOI: 10.1055/s-2003-42733

Übersicht

Georg Thieme Verlag Stuttgart · New York

Die Bedeutung der Hyperhomocysteinämie für Embryonalentwicklung und Schwangerschaftskomplikationen

The Role of Hyperhomocysteinemia in the Development of the Embryo and the Etiology of Complications of PregnancyU. Hübner¹ , I. Koch² , U. Retzke² , W. Herrmann¹

¹Institut für Klinische Chemie/Zentrallabor, Universitätskliniken des Saarlandes, Homburg/Saar
²Frauenklinik im Zentralklinikum Suhl, Suhl

Abstract

Zusammenfassung

Die Hyperhomocysteinämie resultiert aus einem gestörten Methioninmetabolismus. Leichte und mäßige Hyperhomocysteinämien sind häufig auf ein Vitamindefizit an Folsäure, Vitamin B₁₂ und/oder B₆ zurückzuführen. Die seltenen schweren Hyperhomocysteinämien beruhen auf homozygoten Enzymmutationen.

Die Hyperhomocysteinämie ist ein unabhängiger Risikofaktor für arteriosklerotische Erkrankungen. Viele neuere Studien zeigen, dass Homocystein auch mit geburtshilflichen Erkrankungen wie Präeklampsie, HELLP-Syndrom, habituellen Aborten und angeborenen kindlichen Fehlbildungen wie Neuralrohrdefekten assoziiert ist.

Beim habituellen Abort wurde die Assoziation sowohl mit der Folatdefizienz als auch mit der Hyperhomocysteinämie beschrieben. Zur Prophylaxe kindlicher Neuralrohrdefekte wird eine Supplementation mit Folsäure spätestens bei der Planung einer Schwangerschaft empfohlen. Die prophylaktische Wirksamkeit einer Folsäuresupplementierung und tierexperimentelle Untersuchungen weisen auf die Bedeutung des Homocysteins für die Pathogenese von Neuralrohrdefekten hin.

Bei der Präeklampsie wird angenommen, dass oxidativer Stress an der Pathogenese der Endotheldysfunktion beteiligt ist. Sowohl in der präeklamptischen Plazenta als auch im mütterlichen Plasma wurden erhöhte Konzentrationen stabiler Oxidationsprodukte und verminderte Antioxidanzienkonzentrationen gefunden. Homocystein kann oxidativen Stress auslösen und direkt zytotoxisch auf Endothelzellen wirken. In der normalen Schwangerschaft sinkt die Plasmahomocysteinkonzentration. Bei der Präeklampsie wurden in mehreren, jedoch nicht in allen Studien erhöhte Plasmahomocysteinkonzentrationen im Vergleich zu normalen Schwangerschaften gefunden. Der Plasmahomocysteinanstieg bei Präeklampsie ist relativ niedrig und kann auf der Nierenbeteiligung und einer Reaktion des Methioninstoffwechsels auf oxidativen Stress beruhen. Daher ist eine direkte ätiologische Bedeutung des Homocysteins für die Endotheldysfunktion bei der Präeklampsie nicht sicher.

Abstract

Hyperhomocysteinemia is a result of disturbed methionine metabolism. Mild and moderate forms are commonly caused by deficiency of folic acid and vitamins B₁₂ and B₆. Rare severe forms of hyperhomocysteinemia are due to homozygotic enzyme mutations. Hyperhomocysteinemia is an independent risk factor for the development of atherosclerotic vascular disease. Recent studies also indicate an association with preeclampsia, HELLP syndrome, recurrent early pregnancy loss, and congenital anomalies such as neural tube defects. Several studies of recurrent early pregnancy loss have documented an association with folic acid deficiency and hyperhomocysteinemia. Folic acid supplementation to prevent neural tube defects is recommended for women attempting to conceive (and during early pregnancy). The efficacy of folic acid supplementation and the results of animal studies support a role of homocysteine in the pathogenesis of neural tube defects.

The pathogenesis of endothelial dysfunction in preeclampsia involves oxidative stress. Elevated levels of stable oxidation products and decreased levels of antioxidants are found in the preeclamptic placenta and maternal plasma. Homocysteine induces oxidative stress and is toxic to endothelial cells. Plasma homocysteine levels decrease during normal pregnancy. Several studies have reported increased plasma homocysteine levels in pregnancies complicated by preeclampsia, but this has been disputed. The increase of plasma homocysteine in preeclampsia is small and may result from disturbed renal function and alterations of methionine metabolism due to oxidative stress. Thus it is not clear whether hyperhomocysteinemia is involved in the etiology of preeclampsia.

Schlüsselwörter

Homocystein - Neuralrohrdefekte - Schwangerschaftskomplikationen - Folsäure - oxidativer Stress

Key words

Homocysteine - neural tube defects - pregnancy complications - folic acid - oxidative stress

Full Text

References

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Prof. Dr. Wolfgang Herrmann

Institut für Klinische Chemie · Universitätskliniken des Saarlandes · Gebäude 40

66421 Homburg/Saar

Email: kchwher@uniklinik-saarland.de