Hyperemesis Gravidarum

Author: Elisabetta Corvetto
Date: 11/07/2012


Nausea with or without vomiting is experienced by up to 90% of pregnant women. It begins early and usually ceases by the beginning of the second trimester, although a few women may experience symptoms throughout the whole of gestation. Despite common usage of the term ‘morning sickness’, only 17% of pregnant women experience nausea solely in the morning. In general, however, NVP tends to be mild and self-limited, and is not associated with adverse pregnancy outcome. More informations at Interventions for nausea and vomiting in early pregnancy. 2003

Hyperemesis gravidarum, however, is a severe, intractable form of nausea and vomiting that affects approximately 0.3–2.0% of pregnancies. It is associated with both maternal and perinatal morbidity. Indeed, in the years 1931–1940 hyperemesis had a recorded mortality in the UK of 159 per million pregnancies.
Women with hyperemesis gravidarum often require hospital admission as the continual nausea and frequent vomiting that causes dehydration and imbalances of fluid and electrolyte, disturbs nutritional intake and metabolism, causes physical and psychological debilitation.
Maternal and fetal outcomes in hyperemesis gravidarum. 1996


Patients with hyperemesis are more likely to be younger, non-smokers, and non-Caucasian.
Several studies have found that smoking is associated with a reduction in the risk of hyperemesis.
Relationship between vitamin use, smoking, and nausea and vomiting of pregnancy.2003
Maternal smoking before pregnancy is a significant protective factor against nausea and vomiting, even after consideration of maternal age and parity. This happened because nausea and vomiting in pregnancy is an expression of a well-functioning placenta, so the negative association with smoking may reflect the negative effect of maternal smoking on early placenta development as the maternal age.


The pathophysiology of nausea and vomiting in pregnancy has not yet been clearly elucidated. Hyperemesis involves a complex interaction of biological, psychological, and sociocultural factors. Various putative mechanisms have been proposed:

1. The cause of hyperemesis gravidarum is thought being due to the effects of rising hCG levels because levels of serum hCG was significantly higher in hyperemesis patients than in controls Hyperemesis gravidarum, a literature review.2005. It is postulated that hCG causes hyperemesis via a stimulating effect on the secretory processes in the upper gastrointestinal tract. Alternatively, hCG is structurally similar to thyroid-stimulating hormone (TSH) and possibly causes hyperemesis by stimulation of the TSH receptor.
Thyrotropic action of human chorionic gonadotropin.1995

2.The role of oestradiol (E2), oestriol (E3), progesterone and prolactin was also analised by Lagiou et al Nausea and vomiting in pregnancy in relation to prolactin, estrogens, and progesterone: a prospective study.2003. They found that maternal serum prolactin levels are higher in patients without hyperemesis gravidarum. Contrariwise they reported a positive association between nausea and vomiting and maternal serum E2 levels. It has been proposed that elevated maternal serum levels of steroid hormones cause a decrease in intestinal motility and gastric emptying. This in turn alters gastrointestinal pH and encourages the development of subclinical Helicobacter pylori infection, which could be related to gastrointestinal symptoms (see below).

3.In early pregnancy, physiological stimulation of the thyroid gland occasionally leads to gestational transient thyrotoxicosis (GTT). GTT has been observed in up to two-thirds of women suffering from hyperemesis. In prospective studies was showed significantly higher T4 and TSH levels in the hyperemesis group. The production of thyroid-binding globulin increases under oestrogenic influence, and T4metabolism is slowed. The transient decrease in free T4 level and higher renal iodine clearance causes stimulation of the thyroid to compensate for a relative iodine deficiency. Furthermore, hCG shares a common α-subunit with TSH, and the structural similarity can cause excessive stimulation of the thyroid gland. Transient hyperthyroidism and hyperemesis gravidarum:Clinical aspects.1992

4.Eleven prospective case–control studies have reported a significant increase in H. pylori infection in hyperemesis patients. Is also significantly higher H. pylori densities in the gastric antrum and corpus in hyperemesis patients. Positive serology for Helicobacter pylori and vomiting in the pregnancy.2004.

5.Various psychological stresses have been linked with hyperemesis, including emotional immaturity, strong mother-dependence, and anxiety and tension related to the pregnancy. More recent investigators argue that the psychological symptoms are a result of stress arising from the physical burden of hyperemesis rather than a cause. Psychological health in early pregnancy: relationship with nausea and vomiting.2004.

6.Pregnancy is associated with a fall in lower oesophageal pressure, decreased gastric peristalsis and delayed gastric emptying. These factors may well exacerbate the symptoms of hyperemesis, but are unlikely to be causative in isolation.

7.Others tests analyse the theory that nausea and vomiting of pregnancy protects women from ingesting certain vegetables and other foods that produce congenital anomalies and other adverse outcomes of pregnancy, but is not demonstrate. Profet, profits, and proof: Do nausea and vomiting of early pregnancy protect women from “harmful” vegetables?1997

8.Hyperemesis gravidarum is associated with overactivation of sympathetic nerves and enhanced production of tumor necrosis factor (TNF)-alpha. Increased adenosine levels have also been noted; since adenosine is an established suppressor of excessive sympathetic nerves activation and cytokine production, the increase in plasma adenosine in hyperemesis gravidarum may be modulatory.
Substances regulating hCG production include trophoblast-derived cytokines, such as interleukin-1, interleukin-6 and TNF-α. Trophoblast-derived interleukin-1 stimulates interleukin-6 production by trophoblasts, and the produced interleukin-6 stimulates hCG production by activating the interleukin-6 receptor system in the placenta.
Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy.2003
High doses of TNF-α have been reported to increase hCG release by 7 to 9 weeks normal human trophoblasts, whereas lower amounts of TNF-α have been reported to inhibit hCG secretion by normal chorionic villi at 6 weeks’ gestation and by the choriocarcinoma cell line. Trophoblast-derived tumor necrosis factor-α induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6-receptor-dependent system in the healthy human trophoblasts.1992.


Hyperemesis is a diagnosis of exclusion to the other causes of nausea and vomiting as the most commonly urinary tract infection, gastrointestinal diseases (Gastritis Reflux oesophagitis Enteric infection Peptic ulceration Bowel obstruction Hepatitis), Diabetes, Hyperthyroidism, Addison's disease, Hypercalcaemia, Drug-induced vomiting, Neurovestibular disease and Psychiatric illness.
There is no single diagnostic investigation, these can usually reveal hyponatraemia, hypokalaemia, a low serum urea, a metabolic hypochloraemic alkalosis and ketonuria. The haematocrit is raised and specific gravity of the urine increased. There may be associated thyroid function and liver function tests abnormalities.
To help the diagnosis exist the Fairweather criteria that define hyperemesis gravidarum as vomiting more than three times a day, weight loss, ketonaemia, electrolyte imbalance and volume depletion, with typical onset at 4–8 weeks of pregnancy and continuing through to weeks 14–16 of pregnancy. Review on hyperemesis gravidarum.2007


The first treatement in case of hyperemesis gravidarum is the complication prevent, water and vitaminic supply to avoid nutritional leak and dehydration.
Secondly the use of drugs to relieve the symptoms, for example Pyridoxine (vitamin B6), which has proved to be functioning on nausea but not on vomiting, antiemetics such as H1 receptor antagonists (antihistamines) and phenothiazines, and newly developed drugs such as extract from ginger that would act on the serotonin 5HT3 receptors.
Ginger treatment of hyperemesis gravidarum.1991
Mode of action of gingerols and shogaols on 5-HT3 receptors: Binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum.2006

Elisabetta Corvetto

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