Analysis of GDF15 and IGFBP7 in Hyperemesis Gravidarum Support Causality

Abstract

Objective Hyperemesis gravidarum, severe nausea and vomiting in pregnancy, occurs in up to 2% of pregnancies and leads to significant weight loss, dehydration, electrolyte imbalance, and ketonuria. It is associated with both maternal and fetal morbidity. Familial aggregation studies and twin studies suggest a genetic component. In a recent GWAS, we showed that placentation, appetite, and cachexia genes GDF15 and IGFBP7 are linked to hyperemesis gravidarum (HG). The purpose of this study is to determine whether GDF15 and IGFBP7 are upregulated in HG patients.

Methods We compared serum levels of GDF15 and IGFBP7 at 12 and 24 weeksʼ gestation in women hospitalized for HG, and two control groups, women with nausea and vomiting of pregnancy (NVP), and women with no NVP.

Results We show GDF15 and IGFBP7 serum levels are significantly increased in women with HG at 12 weeksʼ gestation. Serum levels of hCG are not significantly different between cases and controls. At 24 weeks gestation, when symptoms have largely resolved, there is no difference in GDF15 and IGFBP7 serum levels between cases and controls.

Conclusion This study supports GDF15 and IGFBP7 in the pathogenesis of HG and may be useful for prediction and diagnosis. The GDF15-GFRAL brainstem-activated pathway was recently identified and therapies to treat conditions of abnormal appetite are under intense investigation. Based on our findings, HG should be included.

Zusammenfassung

Hyperemesis gravidarum – Übelkeit und übermäßiges Erbrechen in der Schwangerschaft – tritt in bis zu 2% aller Schwangerschaften auf und führt zu erheblichem Gewichtsverlust, Austrocknung, Elektrolytentgleisungen und Ketonurie. Sie ist mit mütterlicher sowie fetaler Morbidität assoziiert. Familiäre Aggregationsstudien und Zwillingsstudien deuten auf eine genetische Komponente hin. In einer kürzlich publizierten, genomweiten Assoziationsstudie konnten wir zeigen, dass es einen Zusammenhang zwischen den Plazentations-, Appetit- und Kachexie-Genen GDF-15 und IGFBP-7 und Hyperemesis gravidarum (HG) gibt. Ziel dieser Studie war es, zu prüfen, ob GDF-15 und IGFBP-7 in HG-Patientinnen hochreguliert sind.

Methoden Wir verglichen die GDF-15- und IGFBP-7-Spiegel in SSW 12 und 24 von Frauen, die wegen HG ins Krankenhaus eingewiesen wurden, mit den GDF-15- und IGFBP7-Spiegeln von 2 Kontrollgruppen (Frauen mit normaler Übelkeit und Erbrechen in der Schwangerschaft und Frauen ohne Übelkeit und Erbrechen in der Schwangerschaft).

Ergebnisse Die GDF-15- und IGFBP-7-Spiegel von Frauen mit HG waren in SSW 12 signifikant erhöht. Dagegen unterschied sich der hCG-Serumspiegel nicht wesentlich zwischen Fällen und Kontrollen. In SSW 24 hatten sich die Symptome weitgehend gelegt, und es gab keine Unterschiede in den GDF-15- und IGFBP-7-Spiegeln zwischen Fällen und Kontrollen.

Schlussfolgerung Diese Studie unterstützt die Hypothese, dass GDF-15 und IGFBP-7 eine Rolle bei der Pathogenese von HG spielen und dass sie bei der Vorhersage und Diagnose nützlich sein könnten. Der GDF-15-GFRAL-Hirnstamm-aktivierte Signalweg wurde vor Kurzem identifiziert, und es wird intensiv nach Therapien zur Behandlung von abnormen Essgelüsten geforscht. Vor dem Hintergrund unserer Ergebnisse sollte HG ebenfalls einbezogen werden.

Key words

hyperemesis gravidarum - nausea and vomiting of pregnancy - GDF15 - IGFBP7 - GFRAL

Schlüsselwörter

Hyperemesis gravidarum - Übelkeit und Erbrechen in der Schwangerschaft - GDF-15 - IGFBP-7 - GFRAL

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