Hyperemesis gravidarum

Definition

• Hyperemesis gravidarum is the severe end of the spectrum of nausea and vomiting of pregnancy and is characterised by persistent vomiting, significant weight loss (typically at least 5% of pre-pregnancy weight), dehydration and metabolic disturbances.
• The common, milder nausea of pregnancy, by contrast, peaks between 8 and 12 weeks of gestation and improves in the second trimester.

Occurrence & epidemiology

Epidemiology

• Nausea and vomiting affect the majority of pregnant women, on average about 70% according to one meta-analysis; reported frequencies of hyperemesis range from 0.3% to 10.8%.
• Nausea and vomiting usually begin at 6 to 8 weeks of gestation and resolve by 16 to 20 weeks; hyperemesis commonly recurs in subsequent pregnancies.

Aetiopathogenesis

Aetiology and risk factors

• The cause is not fully understood and is probably multifactorial; meta-analyses show an inconsistent association with hCG concentration.
• GDF15, produced in the early trophoblast and binding to receptors in the area postrema, is now regarded as a key factor; genome-wide studies identified risk loci containing GDF15 and IGFBP7.
• Risk factors include hyperemesis in a previous pregnancy, a positive family history, young maternal age, a female fetus, multiple and molar pregnancy, thyroid and parathyroid dysfunction, type 1 diabetes and Helicobacter pylori infection.

Clinical features

Clinical features and complications

• Affected women cannot eat and drink sufficiently, leading to weight loss and dehydration and severely impairing daily life.
• Complications include Wernicke encephalopathy due to vitamin B1 deficiency, coagulopathy due to vitamin K deficiency, acute liver and kidney failure, cardiac arrhythmias resulting from electrolyte disturbances and oesophageal rupture.
• In one prospective study, 57.4% of affected women met the criteria for depression or anxiety.

Diagnosis

• The diagnosis is clinical after exclusion of other causes and is supported by ketonuria, orthostatic hypotension and electrolyte disturbances.
• According to the international Windsor definition (2021), severe nausea or vomiting, inability to eat or drink normally, a strong impact on daily living and onset before 16 weeks are decisive; ketonuria is not required for the diagnosis.
• Ultrasound identifies multiple and molar pregnancy; some affected women develop self-limiting gestational transient thyrotoxicosis caused by hCG stimulation of the thyroid.
• Severity can be assessed with the PUQE score (up to 6 mild, 7 to 12 moderate, 13 or more severe).

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Further reading (selection)

1. StatPearls: Hyperemesis Gravidarum (NCBI Bookshelf)
2. Front Med 2021: Emerging Progress in Nausea and Vomiting of Pregnancy and Hyperemesis Gravidarum (PMC, open access)

Cross-references