Diagnostic markers for hyperemesis gravidarum: a systematic review and metaanalysis

Am J Obstet Gynecol. 2014 Aug;211(2):150.e1-15. doi: 10.1016/j.ajog.2014.02.012. Epub 2014 Feb 13.


Objective: Currently, there is no consensus on the definition of hyperemesis gravidarum (HG; protracted vomiting in pregnancy) and no single widely used set of diagnostic criteria for HG. The various definitions rely on symptoms, sometimes in combination with laboratory tests. Through a systematic review, we aimed to summarize available evidence on the diagnostic value of biomarkers for HG. This could assist diagnosis and may shed light on the, as yet, not understood cause of the disorder.

Study design: We searched Medline and Embase for articles about diagnostic biomarkers for either the presence or severity of HG or nausea and vomiting of pregnancy. We defined HG as any combination of nausea, vomiting, dehydration, weight loss, or hospitalization for nausea and/or vomiting in pregnancy, in the absence of any other obvious cause for these complaints.

Results: We found 81 articles on 9 biomarkers. Although 65% of all studies included only HG cases with ketonuria, we did not find an association between ketonuria and presence or severity of HG in 5 studies reporting on this association. Metaanalysis, with the use of the hierarchical summary receiver operating characteristics model, yielded an odds ratio of 3.2 (95% confidence interval, 2.0-5.1) of Heliobacter pylori for HG, as compared with asymptomatic control subjects (sensitivity, 73%; specificity, 55%). Studies on human chorionic gonadotropin and thyroid hormones, leptin, estradiol, progesterone, and white blood count showed inconsistent associations with HG; lymphocytes tended to be higher in women with HG.

Conclusion: We did not find support for the use of ketonuria in the diagnosis of HG. H pylori serology might be useful in specific patients.

Keywords: biomarker; diagnosis; hyperemesis gravidarum; nausea and vomiting; pregnancy.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Biomarkers / analysis
  • Chorionic Gonadotropin / blood
  • Estradiol / blood
  • Female
  • Helicobacter pylori / isolation & purification
  • Humans
  • Hyperemesis Gravidarum / diagnosis*
  • Ketosis / complications
  • Leptin / blood
  • Leukocyte Count
  • Lymphocytes / metabolism
  • Pregnancy
  • Progesterone / blood
  • Severity of Illness Index
  • Thyroid Hormones / blood


  • Biomarkers
  • Chorionic Gonadotropin
  • Leptin
  • Thyroid Hormones
  • Progesterone
  • Estradiol