Severe hyperemesis gravidarum caused by Helicobacter pylori

32-year-old female, 9 + 3 weeks pregnant with earlier diagnosis of antiphospholipid syndrome, gestational hypothyroidism and four miscarriages, undergoing treatment with folic acid, levothyroxine, progesterone, acetylsalicylic acid and enoxaparin. She was admitted from the emergency department with a diagnosis of hyperemesis gravidarum, in spite of being treated with oral doxylamine/pyridoxine and metoclopramide. Despite symptomatic management with intravenous metoclopramide and methylprednisolone, the patient was unable to tolerate oral fluids and solids for 9 days after being admitted and parenteral nutrition was required. After this time, despite partial relief of symptoms, the patient continued to vomit 3–4 times a day. Given her poor progress, a Helicobacter pylori antigen stool test was ordered, with positive results. Eradication treatment was initiated in week 11 + 3. A regimen of amoxicillin 1 g/12 h, metronidazole 500 mg/12 h and omeprazole 20 mg/12 h was prescribed for 14 days. Following treatment, at her 15 + 5 week obstetrics appointment, the patient reported a clear improvement in her general health with no nausea or vomiting. A breath test and an antigen stool test were performed one month after completing treatment, with negative results. All ultrasounds and blood tests performed throughout the rest of the pregnancy were normal. The patient had a spontaneous vaginal delivery in week 39 + 5. The newborn had an APGAR score of 9/10, a birth weight of 3.275 g and did not need to be admitted or resuscitated. All post-natal check-ups were normal.

Hyperemesis gravidarum is characterised by more than 3 vomiting episodes a day, ketonuria and weight loss of 3 kg or more or 5% of the patient's pre-pregnancy weight.¹ It affects 0.3%–2% of pregnancies² and is associated with poor weight gain during pregnancy, low birth weight, restricted intrauterine growth, preterm delivery and low 5-min APGAR scores.³

Helicobacter pylori (H. pylori) is a spiral-shaped, gram-negative bacterium that colonises the human stomach thanks to its mobility and acid resistance. The prevalence of H. pylori infection in Spain is higher than 50%.⁴

A recent meta-analysis shows a significant association between H. pylori infection and hyperemesis gravidarum (OR: 1.348; 95% CI: 1.156–11.539; P < .001).² This association opens up the way for improved diagnosis and management of the disease, allowing the cause and not only the symptoms to be treated. The physiological immunosuppression caused by pregnancy probably contributes largely to susceptibility to H. pylori infection or its reactivation. Once the pregnant patient has the infection, it colonises the antral gastric mucosa, releases toxins that damage the mucosa and produces localised inflammation, increasing nausea and vomiting.⁵

H. pylori is also associated with other complications of pregnancy: preeclampsia (OR: 2.51; 95% CI: 1.88–3.34; P < .001), foetal growth restriction (OR: 2.28; 95% CI: 1.21–4.32; P = .01), gestational diabetes (OR: 2.03; 95% CI: 1.56–2.64; P < .001), miscarriage (OR: 1.5; 95% CI: 1.05–2.54; P = .03) and birth defects (OR: 1.63; 95% CI: 1.05–2.54; P = .03).⁶

The use of non-invasive methods is preferred for diagnosing pregnant patients. The C¹³ urea breath test is the recommended non-invasive test,⁷ although this may give false negative results in patients taking proton pump inhibitors,⁸ which are common during pregnancy. Therefore, antigen stool tests may be more useful in pregnant women. This test is recommended as an alternative to the breath test⁷ and is also the non-invasive method most commonly used in Spain.⁴ Serological tests are not routinely recommended.

Very few studies suggest specific eradication therapy regimens during pregnancy. It is important to consider the possible teratogenicity or foetal toxicity of treatments and whether pregnant women with severe symptoms are candidates. The most commonly used therapy is combination therapy or monotherapy with erythromycin, clarithromycin, metronidazole and amoxicillin, proton pump inhibitors and antihistamines.⁹ The duration of treatment is 5–14 days. Clarithromycin should not be used during the first trimester due to the increased risk of miscarriage (OR 1.56; 95% CI: 1.14–2.13).¹⁰

As in our case, H. pylori infection should be investigated in patients with severe hyperemesis gravidarum that is refractory to symptomatic treatment as this allows the cause to be treated and may prevent other adverse effects during pregnancy. Screening for H. pylori infection at the patient's antenatal appointment may be of interest provided that the usual eradication therapy poses no risk to the foetus.

Funding

This study received no specific funding from public, private or non-profit organisations.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Acknowledgements

We would like to thank Dr Constanza Gabriela Caliendo (Obstetrics and Gynaecology Department, Hospital Quirónsalud San José, Madrid, Spain) and Dr Laura Ibarra Veganzones (resident of the Internal Medicine Department, Hospital 12 de Octubre, Madrid, Spain) for their collaboration, suggestions and professional support.?