A randomized, placebo-controlled trial of corticosteroids for hyperemesis due to pregnancy

OBJECTIVE: Hyperemesis gravidarum, a severe form of nausea and vomiting due to pregnancy for which there is no proven pharmacological treatment, is the third leading cause for hospitalization during pregnancy. Corticosteroids are commonly used for the treatment of nausea and vomiting due to cancer chemotherapy-induced emesis and might prove useful in hyperemesis gravidarum. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 126 women who previously had not responded to outpatient therapy for hyperemesis gravidarum during the first half of pregnancy. Intravenous methylprednisolone (125 mg) was followed by an oral prednisone taper (40 mg for 1 day, 20 mg for 3 days, 10 mg for 3 days, 5 mg for 7 days) versus an identical-appearing placebo regimen. All women also received promethazine 25 mg and metoclopramide 10 mg intravenously every 6 hours for 24 hours, followed by the same regimen administered orally as needed until discharge. The primary study outcome was the number of women requiring rehospitalization for hyperemesis gravidarum. RESULTS: A total of 110 women delivered at our hospital and had pregnancy outcomes available for analysis; 56 were randomized to corticosteroids and 54 were administered placebo. Nineteen women in each study group required rehospitalization (34% versus 35%, P =.89, for corticosteroids versus placebo, respectively). CONCLUSION: The addition of parenteral and oral corticosteroids to the treatment of women with hyperemesis gravidarum did not reduce the need for rehospitalization later in pregnancy.     

Helicobacter pylori seropositivity in patients with hyperemesis gravidarum.

OBJECTIVE: The aim of this study was to analyze the hypothesis that there was an association between hyperemesis gravidarum (HG) and Helicobacter pylori (HP) infection. METHODS: The study group consisted of 95 pregnant women with HG and 116 asymptomatic pregnant women who were admitted to our hospital between January 1997 and October 1998. Specific serum immunoglobulin G for HP was assayed in the sera of the study group after informed consent was obtained. Chi-square and Student's t-test were used accordingly for statistical analysis of the data. RESULTS: Serologically positive HP infection was detected in 87 of the 95 patients with HG (91.5%) whereas 52 of the 116 asymptomatic gravidas (44.8%) serving as the control group had positive antibody concentrations against HP. The ratio of HP positivity in pregnant women with HG was significantly higher than asymptomatic pregnant women (P < 0.001). The mean index percentages of IgG titers were 73.8 +/- 9.7% in the hyperemesis gravidarum and 25.8 +/- 5.6% control group (P < 0.01). CONCLUSION: HP infection seemed to be significantly associated with hyperemesis gravidarum in our pregnant patient population with hyperemesis gravidarum.     

Relation between plasma adenosine and serum TSH levels in women with hyperemesis gravidarum

Introduction: This study investigated the relation between adenosine and thyroid function associated with hyperemesis gravidarum. Methods: We examined 84 Japanese singleton pregnant women with an average age of 33.0±5.8 years at 9–12 weeks gestation being managed at our hospital. The patients were divided into three groups according to the severity of emesis: (1) those with hyperemesis gravidarum (nausea and vomiting with weight loss >5%, n=13), (2) those with emesis (nausea and vomiting with weight loss <5%, n=31), and (3) those with no symptoms as a control (n=40). Results: The average serum TSH levels in the emesis and hyperemesis groups were significantly higher than that in the control group (P<0.05). The average plasma adenosine level in the hyperemesis group was significantly higher than those in the control pregnant and emesis groups (P<0.05). There were no significant differences in plasma adenosine levels between the control pregnant and emesis groups. The serum TSH level showed significant correlations with weight loss (%) and plasma adenosine levels (P<0.05). Conclusions: Our findings support the possible role of adenosine in counteracting the further progression of hyperemesis gravidarum associated with gestational thyrotoxicosis.     

The function of the anterior pituitary-adrenal cortex axis in hyperemesis gravidarum.

In order to study the function of the pituitary-adrenal axis, serum ACTH and cortisol levels were estimated before and after insulin induced hypoglycaemia in nine women with hyperemesis gravidarum, seven women in normal early pregnancy and in eight non-pregnant controls. Before hypoglycaemia, the basal ACTH level in the hyperemesis group (102-4+/-62-9 pg/ml) was higher than in normal early pregnancy (67-5+/-19-2 pg/ml; p less than 0-05) or in non-pregnant controls (54-8+/-25-2 pg/ml; less than 0-01). Correspondingly, the mean cortisol value in hyperemesis (0-47+/-0-16 mumol/l) was higher than in normal early pregnancy (0-39+/-0-10 mumol/l; p greater than 0-05) or in non-pregnant controls (0-32+/-0-13 mumol/l; p less than 0-01). After insulin the elevation of ACTH (p greater than 0-05) and cortisol (p less than 0-01) was observed in every group. The level of ACTH and cortisol was highest in hyperemesis group. Our results do not support the idea that hypofunction of the pituitary-adrenal axis contributes to the aetiology or pathogenesis of hyperemesis gravidarum. The high ACTH level might be evidence of the psychia instability of hyperemesis gravidarum patients.     

The efficacy low dose of prednisolone in the treatment of hyperemesis gravidarum

BACKGROUND: To determine whether low dosages of prednisolone are effective in the treatment of outpatients with hyperemesis gravidarum. METHODS: Eighty pregnant women with gestational ages of 6 to 12 weeks and persistent nausea and vomiting participated. The women were assigned by simple randomization to receive prednisolone 5 mg daily or promethazine 75 mg daily by oral route for 10 days. The severity of nausea, frequency of vomiting per day, sickness and the drugs' side-effects were compared (Fisher's exact test, Mann-Whitney U-test, Odds Ratio test). RESULTS: The women who received promethazine responded better in the first 48 h (p = 0.02). With continuation of the treatment, the difference decreased, and one week after completion of the treatment, the subjects who had received prednisolone had less symptoms. CONCLUSION: Promethazine reduces the symptoms of hyperemesis gravidarum faster than prednisolone, but during prolonged treatment, prednisolone has at least the same effects on the symptoms and less drug side-effects.     

Correlations between interscapular deep temperature and plasma free fatty acid levels in pregnant women with hyperemesis gravidarum

OBJECTIVES: The aim of the present study was to investigate whether deep temperature directly reflects underlying pathology in pregnant women with hyperemesis gravidarum. SUBJECTS. We studied 24 women at first trimester hospitalized for hyperemesis gravidarum who had lost a mean of 4.3 kg since becoming pregnant and 20 pregnant controls who did not experience hyperemesis gravidarum and were matched for weeks of gestation and pre-conception weight and height. METHODS: Serum free T(3), T(4), and plasma free fatty acid levels were determined, and deep temperatures of the interscapular tissues were measured. Measurements were compared at admission and after symptoms improved. RESULTS: Free fatty acid, free T(3), and T(4) levels at admission were appreciably higher in the hyperemesis gravidarum group than in the control group (p<0.05). After symptoms improved, free fatty acid levels in patients had decreased by 29% and free T(4) levels by 28% (p<0.05). A significant relationship was observed between reductions in free fatty acid level accompanying improvement in patient status and decreases in both free T(3) and free T(4) levels (p<0.05). Interscapular deep temperatures at admission (36.4 +/- 0.5 C degrees ) significantly decreased to 35.8 +/- 0.9 C degrees after symptoms improved (p<0.05). Reductions in interscapular temperature as a result of improvements in patient status were significantly correlated with reductions in free fatty acid level (p<0.001). CONCLUSIONS: Deep temperatures of the interscapular region in hyperemesis gravidarum change in association with lipolysis as a result of transient hyperthyroidism. This phenomenon can be used as an indicator for evaluating improvements in the pathologic features of hyperemesis gravidarum.     

Droperidol and diphenhydramine in the management of hyperemesis gravidarum

OBJECTIVE: Hyperemesis gravidarum is a common pregnancy complication requiring hospitalization. Continuous droperidol infusion and bolus intravenous diphenhydramine were instituted as treatment. We compared the number and length of hospitalizations for hyperemesis gravidarum, readmissions for this diagnosis, and pregnancy outcome in patients receiving this treatment protocol with a historic group of patients receiving other forms of parenteral therapy for hyperemesis gravidarum. STUDY DESIGN: All patients hospitalized with a diagnosis of hyperemesis gravidarum between January 1992 and January 1994 were offered the droperidol-diphenhydramine protocol. These patients were compared with patients admitted between January 1990 and January 1992 with a diagnosis of hyperemesis gravidarum but who were not treated with droperidol at any time or with diphenhydramine as primary therapy for the control of severe nausea and vomiting. Data regarding the number and length of hospitalizations and readmissions for hyperemesis gravidarum were compared, as were maternal and perinatal outcomes. RESULTS: Patients treated with the droperidol-diphenhydramine protocol had significantly shorter hospitalizations (3.1 ± 1.9 vs 3.8 ± 2.4 days, p = 0028), fewer days per pregnancy hospitalized for hyperemesis (3.5 ± 2.3 days vs 4.8 ± 4.3 days, p = 0018), and fewer readmissions with this diagnosis (15.0% vs 31.5%, p = 0015). There were no significant differences in maternal or perinatal outcomes. CONCLUSION: Droperidol and diphenhydramine infusion is a beneficial, cost-effective therapy for the treatment of hyperemesis gravidarum. (Am J Obstet Gynecol 1996;174:1801-6.)     

High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals

Objective

The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals.

Study design

Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006.

Results

Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s).

Conclusion

There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy.     

Leptin and leptin receptor levels in pregnant women with hyperemesis gravidarum

OBJECTIVE: To investigate the association between the leptin, leptin receptor and hormone levels and hyperemesis gravidarum, and to determine whether these two parameters may be early markers for hyperemesis gravidarum. METHODS: The study group consisted of 18 pregnant women with hyperemesis gravidarum and the control group consisted of 18 healthy pregnant women. Demographic characteristics were recorded and body mass index (BMI) values were calculated for all the pregnant women. Serum leptin, leptin receptor, insulin, cortisol, thyroid hormone and human chorionic gonadotrophin (hCG) levels were measured. RESULTS: When the two groups were compared with respect to leptin levels, the group with hyperemesis gravidarum was found to have significantly higher leptin levels (P = 0.037). No intergroup differences were observed in serum cortisol, insulin, hCG, thyroid hormone levels or BMI values. In the group with hyperemesis gravidarum, an inverse correlation was detected between cortisol and leptin (r = -0.762, P < 0.01), and hCG and thyroid-stimulating hormone (r = -0.503, P < 0.05), whereas a significant correlation was detected between insulin and leptin (r = 0.538, P < 0.05), leptin and BMI (r = 0.711, P < 0.01), and between TT3 and hCG (r = 0.605, P < 0.01). CONCLUSION: It was concluded that leptin could play a role in, and be defined as, a marker of hyperemesis gravidarum.     

Understanding the Stigma of Hyperemesis Gravidarum: Qualitative Findings from an Action Research Study

Abstract: Background: Severe nausea and vomiting in pregnancy (hyperemesis gravidarum) can be a distressing and debilitating condition when it is uncontrolled. For all concerned, hyperemesis gravidarum can be difficult to treat satisfactorily, and women tend to be admitted to a hospital several times during early pregnancy. Our research objectives were to describe the experience of hyperemesis gravidarum from the perspective of affected women and to explore with health care professionals the barriers and facilitators to caring for women with the condition. Methods: A qualitative research design was used. A total of 18 women were interviewed, of whom 8 had two or more interviews. Seven focus groups were conducted with health care professionals. Thematic data analysis was undertaken. Results: The main themes emerging from the women’s data were the effect and burden of the symptoms of the condition and feeling unpopular with staff. From the practitioner data, the main themes were the validity (or invalidity) of hospitalization for women, skepticism of the severity of symptoms, the psychological and social dimensions of the condition, and inadequate primary care services. Conclusions: The main findings revealed that hyperemesis gravidarum is a debilitating condition and that the unhelpful attitudes of practitioners may affect whether women access timely and appropriate care. Many women appear to be unsupported by primary care services and are distressed when perceived either as “time wasters” or someone else’s responsibility. We propose that a tailored assessment and care plan for each woman is needed to help them control their symptoms, which ideally should be delivered in the community. (BIRTH 37:3 September 2010)     

Recurrence risk of hyperemesis gravidarum

Introduction: The purpose of this study is to describe the recurrence risk for hyperemesis gravidarum (HG). Methods: Women who registered on a Web site sponsored by the Hyperemesis Education and Research Foundation as having had one HG‐complicated pregnancy were contacted to follow‐up on a subsequent pregnancy. Participants completed an online survey. Results: One hundred women responded. Fifty‐seven had become pregnant again, 2 were trying to conceive, 37 were not willing to get pregnant again because of HG, and 4 did not have a second pregnancy for other reasons. Among the 57 women who responded that they had become pregnant again, 81% reported having severe nausea and vomiting in their second pregnancy. Among the women reporting recurrent HG, 98% reported losing weight and taking prescribed medication for HG, 83% reported treatment with intravenous fluids, 20% reported treatment with total parenteral nutrition or nasogastric tube feeding, and 48% reported hospitalization for HG. Discussion: This study demonstrates both a high recurrence rate of HG and a large percentage of women who change reproductive plans because of their experiences with HG.     

Helicobacter pylori seropositivity in patients with hyperemesis gravidarum.

OBJECTIVES: To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. METHODS: From November 1999 to February 2001, we enrolled 54 pregnant women with hyperemesis gravidarum and 53 asymptomatic pregnant women in a prospective study. Specific serum immunoglobulin G for Helicobacter pylori was assayed in the sera of the study group and compared with the asymptomatic group. Chi-square and Student's t-test were used accordingly for statistical analysis of the data. RESULTS: Serologically positive Helicobacter pylori infection was detected in 44 out of 54 patients with hyperemesis gravidarum (81.5%) whereas 29 out of 53 asymptomatic gravidas (54.7%) had positive antibody titers for Helicobacter pylori. The ratio of Helicobacter pylori seropositivity in pregnant women with hyperemesis gravidarum was significantly higher than asymptomatic pregnant women (P<0.01). The mean (+/-S.D.) of the IgG titer was 69.7 (+/-77.5) in the hyperemesis gravidarum group and 34.5 (+/-47.8) in the control group (P<0.01). CONCLUSIONS: There is a significant association between Helicobacter pylori infection and hyperemesis gravidarum in our hyperemetic pregnant patients.     

Hormone profile of Kuwaiti women with hyperemesis gravidarum

OBJECTIVE: To evaluate the incidence of hyperemesis gravidarum among pregnant women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of patients with hyperemesis gravidarum compared with a control group of women. METHODOLOGY: During a 6-month period all patients admitted to Maternity Hospital with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were enlisted into the study. In fifty of these patients and their fifty normal controls, the status of serum total (beta)hCG, TSH, total T4 and freeT4 were evaluated with AXSYM micro particle enzyme immunoassay. RESULTS: The incidence of hyperemesis in the maternity population was 45 per 1000 deliveries. Total (beta)hCG and Total T4 and FreeT4 were significantly higher in the hyperemesis patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively). TSH levels were significantly lower in hyperemesis patients than in their normal controls (p<0.0001). There was a strong positive correlation between the total (beta)hCG and the gestational age (r=0.8). CONCLUSION: There is a high incidence of hyperemesis gravidarum in the Kuwaiti population. Total (beta)hCG, Total T4 and Free T4 titers were significantly higher in patients with hyperemesis gravidarum, but none of the patients showed signs of hyperthyroidism.     

Hyperemesis gravidarum: outcomes and complications with and without total parenteral nutrition

OBJECTIVE: To evaluate the obstetric and medical complications with hyperemesis gravidarum, comparing those who were supported with total parenteral nutrition (TPN group) and those who did not receive TPN (non-TPN group). STUDY DESIGN: The medical records of women with a diagnosis of hyperemesis gravidarum (ICD-9 code 643) admitted to Crouse Hospital, Syracuse, New York, between January 1995 and December 1998, were reviewed. A total of 166 subjects were identified and 192 admissions reviewed. Information was gathered for age, gestational age, gravity and parity, marital status, length of stay and number of admissions, and a review of electrolyte, albumin and thyroid function was performed. An assessment of pregnancy complications and outcomes was undertaken. RESULTS: Of the cases reviewed, 16% (27/166) were treated with TPN. The 2 groups were similar regarding incidence of pregnancy-related and maternal medical complications. The groups were similar when comparing objective measures, such as serum potassium, bicarbonate, albumin and thyroid function. The TPN group had a significantly increased incidence of complications directly attributable to parenteral therapy. Among multiparous patients in both groups, 69% had a prior pregnancy that had ended in spontaneous or induced abortion. CONCLUSION: The TPN group had a marked and significant increase in serious complications directly related to TPN use. These data suggest that great care should be taken to assess the need for parenteral therapy in patients with hyperemesis gravidarum. A history of loss in the antecedent pregnancy may be a risk factor for a subsequent pregnancy complicated by hyperemesis gravidarum.     

Mirtazapine use in resistant hyperemesis gravidarum: report of three cases and review of the literature

{\it Background}: Hyperemesis gravidarum is a serious health problem for the fetus and the mother. Effective treatment regimens are obscure in patients with severe symptoms. Our aim was to use mirtazapine in hyperemesis gravidarum patients who failed to respond to conventional anti-emetic drugs. Cases: Three pregnant women who had severe hyperemesis gravidarum. All patients had dehydration, ketonuria, hypokalemia, and weight loss. All failed to respond to conventional anti-emesis treatment regimens, such as metoclopramide and promethazine. Al patients had mirtazapine 30 mg/day within the intravenous fluid support approximately for 1 week. All responded to mirtazapine within 24 h and were able to resume diet within a few days after the initiation of treatment. None of these pregnant women had any disturbing symptoms of emesis throughout the pregnancy and had healthy newborns. Conclusion: Mirtazapine seems to be an effective treatment modality in patients with severe hyperemesis gravidarum who do not respond to conventional anti-emesis treatment regimens. Larger-scaled studies should be performed to show the effectiveness of mirtazapine in pregnant women with severe hyperemesis gravidarum who may request pregnancy termination. Mirtazapine and severe hyperemesis gravidarum. Mirtazapine is an effective treatment regimen in severe hyperemesis gravidarum     

Hyperemesis gravidarum: current aspect

An advanced state of nausea and vomiting, which are common symptoms of early pregnancy, is known as hyperemesis gravidarum and may result in dehydration, ketonuria, catabolism and require hospitalisation. Aetiological factors include increased hCG and steroids, multiple pregnancy and vitamin deficiency. Differential diagnosis of nausea and vomiting should be made and supportive treatment as well as antiemetic therapy is recommended. This review discusses aetiology and management modalities of hyperemesis gravidarum including fluid therapy, antiemetics, vitamins, psychological support and non-pharmacological measures.     

Hyperemesis gravidarum presenting as jaundice and transient hyperthyroidism complicated with acute pancreatitis.

Hyperemesis gravidarum is an extreme form of nausea and vomiting during pregnancy. Its presenting symptoms include vomiting, disturbed nutrition, electrolyte imbalance, ketosis, extreme weight loss, renal and/or liver damage. It is rare for a hyperemesis gravidarum patient to present with jaundice, hyperthyroidism and idiopathic acute pancreatitis during the same hospitalization period. Here, we report such a case. A 25-year-old pregnant woman without underlying liver or thyroid disease was admitted due to jaundice noted for 2 days at 8 weeks of gestational age. Hyperthyroidism symptoms of tachycardia and finger tremor also bothered her. After treatment with parenteral fluid and antithyroid agents, her clinical condition improved. However, an episode of idiopathic pancreatitis occurred after nausea and vomiting subsided. Bowel rest with parenteral fluid and nutrition supplement was given and the increased pancreatic enzyme level gradually subsided. Follow-up liver and thyroid function were normal after gestational age of 26 weeks. She delivered a healthy female baby without low birth body weight at gestational age of 39 weeks. Rapid diagnosis and supportive care are important for the hyperemesis gravidarum patient with the complication of acute pancreatitis.     

Hyperemesis gravidarum. A comparison of single and multiple admissions

Recurrent hyperemesis gravidarum is a frustrating and poorly studied complication of early pregnancy. Between 1979 and 1987, 140 women with emesis severe enough to require parenteral fluid and electrolyte replacement were admitted to the Medical University of South Carolina Hospital, Charleston, on 220 occasions. Thirty-nine of the 140 women were admitted on multiple occasions. A comparison of clinical characteristics of women with single and multiple admissions revealed no significant differences except that women admitted repeatedly for hyperemesis gravidarum were more likely to be nulliparous (P less than .05). Ptyalism (59% vs. 9%) and persistent vomiting for greater than 24 hours after admission (69% vs. 23%) were significantly more common among women who were admitted repeatedly (P less than .05). Despite published reports that hyperemesis gravidarum has no impact on ultimate perinatal outcome, this study indicated that women admitted repeatedly have a more severe nutritional disturbance, associated with significantly reduced maternal weight gain and neonatal birth weight. These risks argue for more aggressive antenatal treatment and increased fetal surveillance in pregnancies complicated by recurrent hyperemesis gravidarum.     

The T-helper 1/T-helper 2 balance in peripheral blood of women with hyperemesis gravidarum

OBJECTIVE: The purpose of this study was to evaluate the T-helper 1/T-helper 2 balance and its relation with pregnancy-related hormones in hyperemesis gravidarum. STUDY DESIGN: The T-helper 1/T-helper 2 ratio and plasma progesterone and estrogen levels were examined in the peripheral blood of 22 women with hyperemesis gravidarum and normal pregnancies. The proportion of CD4-positive cells that expressed intracellular cytokines (interferon gamma and interleukin-4) were analyzed by blood flow cytometry. The ratio of interferon gamma-secreting cells to interleukin-4-secreting cells was taken as the T-helper 1/T-helper 2 ratio. RESULTS: In hyperemesis gravidarum, the proportions of interleukin-4-secreting cells increased, and the T-helper 1/T-helper 2 ratio averaged 8.4 +/- 0.9, which was significantly lower than in normal pregnancy (11.6 +/- 1.1, P <.05). The changes in the T-helper 1/T-helper 2 ratio in hyperemesis gravidarum were accompanied by the elevation of progesterone and estrogen levels. CONCLUSION: A further shift of the T-helper 1/T-helper 2 balance to the T-helper 2 dominance in hyperemesis gravidarum may be related to the increase of progesterone and estrogen levels.     

Low birth weight and hyperemesis gravidarum

A group of patients suffering from severe hyperemesis gravidarum is defined. In contrast to what is reported in the literature, these women gave birth to babies with lower birth weight when compared to the hospital population and also to women who had a milder degree of hyperemesis gravidarum. This indicates that the metabolic disturbance created by hyperemesis may have an adverse effect on the growth potential of the fetus.