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PARIS — The understanding and management of nausea, vomiting, and hyperemesis gravidarum are progressing. "Improving hyperemesis gravidarum treatment begins with recognizing the symptoms and suffering of the affected women," according to Philippe Deruelle, MD, PhD, coordinator of the first French consensus on behalf of the French National College of Obstetricians and Gynecologists (CNGOF), Paris, France.

Recent developments have brought attention to an often overlooked but relatively common condition: A consensus of experts and recent fundamental research results have shed light on nausea, vomiting, and hyperemesis gravidarum, which are common pathologies in the first trimester of pregnancy or later. The physical and psychological distress caused by these conditions is often trivialized.

It is often forgotten that among the 50%-90% of women experiencing nausea and vomiting in early pregnancy, around 35% find these manifestations highly disabling, affecting all aspects of their daily lives. For 0.3%-3.6% of pregnant women, these uncontrollable vomiting episodes become the main cause of hospitalization in the first trimester.

Nausea and vomiting are so severe that women lose weight or become dehydrated and sometimes both. "Nausea and vomiting in pregnancy and its ultimate stage, hyperemesis gravidarum, need to be addressed," emphasized Deruelle, professor of obstetrics and gynecology at Montpellier University Hospital, Montpellier, France. "Even though we face significant challenges in relieving these women, it starts with making a diagnosis."

Beyond stress, anxiety or depressive disorders, and suicidal thoughts, hyperemesis gravidarum can be associated with distress that leads some women to consider abortion or to forgo future pregnancies.

Regarding the diagnosis, a consensus definition, albeit imperfect due to the lack of literature on the subject, has been included in the consensus.

Relevant Criteria

According to the formalized CNGOF consensus, hyperemesis gravidarum is distinguished from nausea and vomiting in pregnancy by specific criteria, namely, weight loss of at least 5%, signs of dehydration, or a Pregnancy Unique Quantification of Emesis and Nausea (PUQE) score > 7. The "modified" PUQE score is calculated from information obtained during the interview and covers 24-hour periods.

Clinical signs of dehydration include a strong feeling of thirst, the presence of a persistent skin fold, orthostatic hypotension, and decubitus with compensatory reflex tachycardia.

In extreme cases, hospitalization is recommended if at least one of the following criteria is observed: Weight loss of at least 10%, clinical signs of dehydration, PUQE score > 13, hypokalemia below 3.0 mmol/L, hyponatremia below 120 mmol/L, an elevation of creatinine exceeding 100 mmol/L, or resistance to treatment.

Symptoms Often Alleviated

First, it is recommended to discontinue prenatal vitamins and iron supplementation, except for folic acid, which can be continued. Women are free to adjust their diet and lifestyle based on their preferences, as no dietary modification has demonstrated proven efficacy in managing nausea and vomiting. The use of aromatherapy is not advised.

The doxylamine-pyridoxine combination can be considered the first-line treatment, with a response rate of approximately 60%, especially as it appears to expose patients to fewer side effects.

Neuroleptics, particularly dopamine antagonists, including phenothiazines (such as chlorpromazine and prochlorperazine), are also therapeutic options, although they are associated with an increased risk for extrapyramidal symptoms.

As a second-line option for hyperemesis gravidarum, ondansetron, a potent selective 5-HT3 serotonin receptor antagonist, is recommended, although its exposure during the organogenesis period is associated with a minimal increase in the absolute risk for cleft lip/palate (about three additional cases per 10,000 live births exposed).

Due to potential side effects and uncertain efficacy, steroids are considered a last resort, only in cases of hyperemesis gravidarum. Systematic thiamine supplementation is recommended in cases of hyperemesis gravidarum requiring parenteral rehydration to prevent Wernicke's encephalopathy.

Psychological Support Crucial

"It is important to actively promote psychological support and direct women to support groups," said Deruelle, emphasizing the importance of a proactive approach to prevent worsening without waiting for 48-72 hours. Practices "inherited from the past," as mentioned in the consensus, often supported by psychoanalytic beliefs and now considered unacceptable, persist today, and "they need to be identified," Deruelle warned. These ideas include removing basins or isolating women with hyperemesis gravidarum (confinement in darkness or deprivation of visits and communication). No psychosomatic etiology has ever been established.

Identifying women at an increased risk of developing nausea and vomiting in pregnancy is challenging, given the lack of identified risk factors (such as carrying Helicobacter pylori, fetal sex, etc.).

The underlying mechanisms of hyperemesis gravidarum remain poorly understood. It is likely influenced by multiple factors, including genetic predisposition, overall health status, and hormonal changes (human chorionic gonadotropin; thyroid hormones; steroid hormones, such as cortisol, estrogen, and progesterone in early pregnancy; ghrelin and leptin; as well as growth differentiation factor 15 [GDF15] or insulin-like growth factor-binding protein [IGFBP7], which are markers of cachexia and influence appetite and taste perception).

However, these hormonal changes alone do not explain the clinical symptomatology associated with hyperemesis gravidarum.

Focus on GDF15

Recent research published in late 2023 in Nature and conducted by a team from the Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit at the University of Cambridge, Cambridge, England, revealed that sensitivity to a hormone abundantly produced early in pregnancy, GDF15, influences the risk of developing symptoms associated with pregnancy-related nausea. GDF15 is known to inhibit appetite in mice, primarily acting on a small group of cells located at the base of the brain that previously were identified as inducing nausea and vomiting.

"GDF15 is present in large quantities in the human placenta and found at high concentrations in the blood of healthy pregnant women," said the researchers. "We observed that women experiencing these pregnancy discomforts indeed had higher concentrations of GDF15. However, the levels of this hormone in each group overlapped, suggesting that factors other than the absolute amount of GDF15 produced early in pregnancy would play a role in the symptoms."

In further research, they realized that reduced levels of GDF15 before pregnancy led to women's hypersensitivity to high concentrations of GDF15 released during pregnancy. Therefore, they concluded, two therapeutic approaches emerge: Desensitizing women to GDF15 by increasing levels before pregnancy or blocking its action during pregnancy.

Deruelle provides oral presentations for Exeltis Santé and Nordine laboratories.

This article was translated from the Medscape French edition.