Serum lipids and lipoproteins in pregnancies associated with emesis gravidarum

Nausea and/or vomiting in pregnancy (emesis gravidarum) is a very common event. The specific etiology of this disorder is still unknown. In this study we examined serum lipid and lipoprotein concentrations in 98 healthy pregnant women in early and late pregnancy. Sixty of these women complained of emesis gravidarum. Compared to non-pregnant controls the pregnancy values of serum cholesterol, triglycerides and phospholipids were elevated in all subjects due to an increase in all lipoprotein classes. In addition, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were enriched in triglycerides relative to other components. Differences in serum lipids and lipoproteins between the emetic and non-emetic subjects were found. The lipid contents of LDL and HDL were significantly higher and lower, respectively, in the emetic women in early pregnancy. During late pregnancy the total lipid content in all fractions was higher in previously emetic subjects. Thus, a metabolic difference between the groups persisted throughout pregnancy. It is suggested that an altered influence of estrogen on the liver might be responsible for these dissimilarities.     

Steroid hormones in emetic and non-emetic pregnancy

Nausea and/or vomiting in early pregnancy is common enough to be generally accepted as normal or 'physiological'. The specific etiology of these complaints is still obscure. One possibility is that endocrine factors may play some part. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy and the circulating levels of cortisol, testosterone, dehydroepiandrosterone sulphate (DHEA-S), progesterone, oestradiol and total and free oestriol were measured. In early pregnancy, serum levels of cortisol and progesterone were significantly lower in emetic subjects. In the last trimester, significantly higher DHEA-S concentrations and lower testosterone values were found in women who had suffered from nausea and vomiting in early pregnancy compared to asymptomatic subjects. Overt differences were found between emetic and non-emetic pregnancy and it is concluded that endocrine factors are of etiological importance in emesis gravidarum.     

Serum bile acids, gamma-glutamyltransferase and routine liver function tests in emetic and nonemetic pregnancies

The etiology of nausea and vomiting in pregnancy is still unknown. One possibility is that ovarian and placental hormones may play some part. The liver is the major site of metabolic inactivation of steroid hormones. In this study, 102 healthy pregnant women, of whom 62 complained of nausea, were followed throughout pregnancy. Liver function tests were performed to ascertain whether emesis gravidarum is related to impaired hepatic function. In this series, all values were within the normal ranges. Serum levels of total bilirubin and gamma-glutamyl-transferase were significantly decreased and those of total serum bile acids significantly increased in emetic women compared to nonemetic subjects. Furthermore, the metabolic load on the liver seems to follow a biphasic course as there is an apparent minimum in liver function variables in the second trimester. It is concluded that a slow adaptation to the increased hormonal load on the liver might be responsible for the condition of emesis gravidarum.     

Does position and size of corpus luteum have any effect on nausea of pregnancy?

It is a puzzling fact that emesis might occur in one pregnancy, whereas other pregnancies in the same woman could be either free or again associated with nausea. Pregnancy-associated hormones are believed to cause nausea, possibly through effects mediated via the liver. In 43 women who applied for a legal abortion in early pregnancy the occurrence of nausea was recorded and the position and size of the corpus luteums were measured by means of ultrasound. It was found that emesis was associated with corpus luteum located predominantly on the right side, while the non-emetic pregnancy often had a left-sided corpus luteum. It is suggested that the venous drainage, which differs between the right and the left side, may be responsible for the fact that the same woman can either suffer from or be free from nausea during pregnancy. Ovarian vein insufficiency, being more common in multigravidity, may also explain why nausea is more common in multigravidae.     

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.     

Nausea and vomiting in pregnancy: a review

Throughout pregnancy, women with nausea and vomiting in early pregnancy showed a different metabolic pattern compared to asymptomatic pregnancies. Women suffering from nausea and vomiting seem to have a low "functional reserve" of their liver capacity and could tentatively be described as hypersensitive to estrogens or their metabolites, e.g., catecholestrogens. These steroids have "emetic" properties, which might be explained by their direct stimulation of area postrema. It is known that estrogens increase the brain's excitability. Another possible mechanism could be by interacting with liver metabolism, resulting in the production of irregular metabolites, which in turn possess "emetic" qualities.     

Nausea and vomiting associate with increasing maternal androgen levels in otherwise uncomplicated pregnancies

BACKGROUND: The objective of the present study was to investigate the hypothesis that maternal androgen levels associate with nausea and vomiting in otherwise uncomplicated pregnancies. METHODS: One hundred and twenty-nine women with uncomplicated pregnancies, reported nausea and vomiting in weeks 17, 25, 33, 37, and when admitted for delivery. Maternal levels of androstenedione, dehydroepiandrosterone sulfate (DHEAS), testosterone, and sex hormone binding globulin (SHBG) were measured and the free testosterone index calculated in weeks 17 and 33 of pregnancy. RESULTS: Maternal levels of androstenedione and DHEAS associated positively with nausea and vomiting in week 17. In week 33, testosterone and DHEAS associated positively with nausea and vomiting, as well as androstenedione. A calculated emesis score associated positively with increasing average levels of both androstenedione and testosterone during pregnancy, as well as the free testosterone index. CONCLUSIONS: Nausea and vomiting associate with increasing maternal androgen levels during otherwise uncomplicated pregnancies. Whether androgens are causally related to emesis gravidarum remains unknown.     

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.     

Plasma anandamide and related n-acylethanolamide levels are not elevated in pregnancies complicated by hyperemesis gravidarum

Abstract

Objectives: Cannabinoids are effective antiemetics and the “endogenous cannabinoids” (endocannabinoids) are thought to modulate emesis in both humans and animal models. Endocannabinoids, their receptors and their metabolising enzymes are present in peripheral blood and a reduction in blood endocannabinoid concentration has been observed in individuals with excessive nausea and vomiting following parabolic flight manoeuvres. We tested the hypothesis that plasma endocannabinoid levels are similarly perturbed in women with hyperemesis gravidarum (HG), a condition where the aetiopathogenesis is still unknown, compared to normal pregnant controls.

Methods: Plasma N-arachidonoylethanolamine (anandamide), N-oleoylethanolamide and N-palmitoylethanolamide were quantified in women with HG (n?=?15) and matched normal pregnant controls (n?=?30) using UHPLC-ESI-MS/MS utilising an isotope dilution method and selective ion monitoring.

Results: No significant differences in anandamide, oleoylethanolamide and palmitoylethanolamide levels were observed between the two groups. There were no significant correlations between these endocannabinoids and plasma haematocrit and serum urea or sodium concentrations.

Conclusions: These results would suggest that either the circulating endocannabinoids quantified may not be key modulating factors in HG or that the expected endocannabinoid system response to the stress induced by nausea and vomiting of early pregnancy remain unchanged in women with HG.     

Survey of medicinal cannabis use among childbearing women: patterns of its use in pregnancy and retroactive self-assessment of its efficacy against 'morning sickness'

A majority of women experience some nausea and/or vomiting during pregnancy. This condition can range from mild nausea to extreme nausea and vomiting, with 1-2% of women suffering from the life-threatening condition hyperemesis gravidarum. Cannabis (Cannabis sativa) may be used therapeutically to mitigate pregnancy-induced nausea and vomiting. This paper presents the results of a survey of 84 female users of medicinal cannabis, recruited through two compassion societies in British Columbia, Canada. Of the seventy-nine respondents who had experienced pregnancy, 51 (65%) reported using cannabis during their pregnancies. While 59 (77%) of the respondents who had been pregnant had experienced nausea and/or vomiting of pregnancy, 40 (68%) had used cannabis to treat the condition, and of these respondents, 37 (over 92%) rated cannabis as 'extremely effective' or 'effective.' Our findings support the need for further investigations into cannabis therapy for severe nausea and vomiting during pregnancy.     

Helicobacter pylori and severe nausea and vomiting during pregnancy

Helicobacter pylori is a bacterial infection of the stomach, which may aggravate nausea and vomiting in pregnancy. Studies have found conflicting evidence of the role of H. pylori in severe nausea and vomiting in pregnancy and hyperemesis gravidarum. Several women suffering from weight loss and experiencing continued nausea and vomiting were tested for H. pylori antibody during their pregnancy. This article reviews the outcomes of women with both positive and negative H. pylori tests, the treatment of H. pylori, and its controversial role in managing severe nausea and vomiting in pregnancy.     

Hyperemesis gravidarum in relation to estradiol levels, pregnancy outcome, and other maternal factors: a seroepidemiologic study

Two studies were conducted to assess factors associated with increased risk of hyperemesis gravidarum during pregnancy with data and serum samples collected from participants in the Collaborative Perinatal Study. In the case-control study, 419 pregnant women with hyperemesis gravidarum were matched on medical center, date of study registration, and race with 836 pregnant women who did not vomit during the index pregnancy. Younger age, nulliparity, and high body weight were significantly associated with increased risk of hyperemesis. Women with hyperemesis had significantly reduced risk of fetal loss; however, their infants had higher risk of central nervous system malformations. In the second study, first-trimester pregnancy hormones were measured in the serum of 35 women with hyperemesis and 35 control women who were individually matched to cases on age, parity, and medical center. After adjusting for length of gestation, mean levels of total estradiol were 26% higher and mean levels of sex hormone binding-globulin binding capacity were 37% higher in patients with hyperemesis gravidarum than in control subjects. These differences were statistically significant. Although human chorionic gonadotropin concentrations were higher in control pregnancies, the differences were not statistically significant. The average amount of estradiol that was nonprotein bound (adjusted for length of gestation) was also higher in patients than in control subjects. These results are consistent with the hypothesis that elevated estrogen levels are responsible for excessive vomiting in pregnancy.     

Serum chorionic gonadotrophin (hCG), schwangerschaftsprotein 1 (SP1), progesterone and oestradiol levels in patients with nausea and vomiting in early pregnancy

Serum concentrations of human chorionic gonadotrophin (hCG), schwangerschaftsprotein 1(SP1), progesterone and oestradiol were measured in 116 pregnant women experiencing varying degrees of nausea and vomiting or no nausea at all at between 9 and 16 weeks gestation. The patients were categorized into four groups, namely asymptomatic, nausea alone, nausea and vomiting and hyperemesis gravidarum. The distribution of levels for each group were examined in relation to the calculated normal ranges. Statistically higher hCG levels were found in out-patients with nausea alone or nausea and vomiting than in the asymptomatic women. No significant differences were found between the groups for any of the other measured variables, including the progesterone/oestradiol concentration ratio.     

Recall bias of the symptoms of nausea and vomiting of pregnancy

OBJECTIVE: Nausea and vomiting of pregnancy is the most common medical condition in pregnancy. Relatively little research has been conducted on this condition, and much of it is based on women's reports. Determinants that affect women's reports of their nausea and vomiting of pregnancy symptoms have not been elucidated. The purpose of this study was to assess the accuracy of recall by women of their symptoms of nausea and vomiting of pregnancy. STUDY DESIGN: Two hundred women who called the Motherisk nausea and vomiting of pregnancy counseling line in Toronto were asked about the severity of their nausea and vomiting of pregnancy symptoms with the use of the pregnancy unique quantification of emesis and nausea system (PUQE). The patients were asked the same questions again during a follow-up call, which took place up to 16 weeks later. RESULTS: There was a recall (or reporting) bias for nausea and vomiting, with women reporting significantly more severe symptoms during their follow-up call than they had reported originally. Multivariate analysis revealed that the severity of the symptoms affected the accuracy of recall positively, whereas the time that has elapsed affected it negatively. CONCLUSION: Retrospective evaluation of nausea and vomiting of pregnancy symptoms may produce a recall bias, which may distort the evaluation of the therapeutic effectiveness of antiemetics.     

Nausea and vomiting in early pregnancy: its role in placental development

Nausea and emesis in early pregnancy is a common phenomenon affecting between 50% and 70% of pregnant women, but little is known about the etiology and possible function of this common and often incapacitating condition. Morning sickness has been reported to have a positive effect on pregnancy outcome and is associated with a decreased risk of miscarriage, preterm birth, low birth weight (LBW), and perinatal death. Both human and animal studies have shown that reduced energy intakes in early pregnancy are associated with increased placental weight. Based on evidence from the literature, a hypothesis is proposed that suggests a functional role for the nausea and emesis of pregnancy in stimulating early placental growth. It is suggested that morning sickness, resulting from secretion of hCG and thyroxine, reduces maternal energy intake. As a result, maternal levels of the anabolic hormones, insulin, and insulin growth factor-1 (IGF-1) are lowered. By suppressing maternal tissue synthesis in early pregnancy, we propose that nausea and vomiting in pregnancy helps ensure that nutrient partitioning favors the developing placenta. Evidence is also presented that suggests there may be a positive relationship between morning sickness and preconceptional body mass index (BMI), such that women who are underweight will experience less severe symptoms of morning sickness compared with women with normal preconceptional BMIs.     

Serum chorionic gonadotrophin (hCG), schwangerschaftsprotein 1(SP1), progesterone and oestradiol levels in patients with nausea and vomiting in early pregnancy

Summary. Serum concentrations of human chorioni gonadotrophin (hCG). schwangerschaftsprotein l(SPl), progesterone and oestradiol were measured in 116 pregnant women experiencing varying degrees of nausea and vomiting or no nausea at all at between 9 and 16 weeks gestation. The patients were categorized into four groups, namely asymptomatic, nausea alone, nausea and vomiting and hyperemesis gravidarum. The distribution of levels for each group were examined in relation to the calculated normal ranges. Statistically higher hCG levels were found in out-patients with nausea alone or nausea and vomiting than in the asymptomatic women. No significant differences were found between the groups for any of the other measured variables, including the progesterone/oestradiol concentration ratio.     

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.     

Interventions for treating hyperemesis gravidarum: a Cochrane systematic review and meta-analysis

Introduction: While nausea and vomiting in early pregnancy are very common, affecting approximately 80% of the pregnancies, hyperemesis gravidarum is a severe form affecting 0.3–1.0% of the pregnancies. Although hyperemesis gravidarum is rarely a source of mortality, it is a significant source of morbidity. It is one of the most common indications for hospitalization in pregnancy. Beyond the maternal and fetal consequences of malnutrition, the severity of hyperemesis symptoms causes a major psychosocial burden leading to depression, anxiety, and even pregnancy termination. The aim of this meta-analysis was to examine all randomized controlled trials of interventions specifically for hyperemesis gravidarum and evaluate them based on both subjective and objective measures of efficacy, maternal and fetal/neonatal safety, and economic costs.

Material and methods: Randomized controlled trials were identified by searching electronic databases. We included all randomized controlled trials for the treatment of hyperemesis gravidarum. The primary outcome was intervention efficacy as defined by severity, reduction, or cessation in nausea/vomiting; number of episodes of emesis; and days of hospital admission. Secondary outcomes included other measures of intervention efficacy, adverse maternal/fetal/neonatal outcomes, quality of life measures, and economic costs.

Results: Twenty-five trials (2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. Selected comparisons reported below: No primary outcome data were available when acupuncture was compared with placebo. There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (risk ratio (RR) 1.40, 95% CI 0.79–2.49 and RR 1.51, 95% CI 0.92–2.48, respectively). Midwife-led outpatient care was associated with fewer hours of hospital admission than routine inpatient admission (mean difference (MD)???33.20, 95% CI ?46.91 to ?19.49) with no difference in pregnancy-unique quantification of emesis and nausea (PUQE) score, decision to terminate the pregnancy, miscarriage, small-for-gestational age infants, or time off work when compared with routine care. Women taking vitamin B6 had a slightly longer hospital stay compared with placebo (MD 0.80 days, 95% CI 0.08–1.52). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI ?0.40–1.40) or side effects. A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI ?0.15–3.55, and MD ?0.10, 95% CI ?1.63–1.43; one study, 83 women, respectively). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23–4.69, and RR 2.38, 95% CI 1.10–5.11, respectively). There were no clear differences between groups for other side effects. In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (risk ratio (RR) 0.70, 95% CI 0.56–0.87, RR 0.48, 95% CI 0.34–0.69, and RR 0.31, 95% CI 0.11–0.90, respectively). There were no clear differences between groups for other important outcomes including quality of life and other side effects. In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (mean difference (MD) 0.00, 95% CI ?1.39–1.39), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00–0.94). Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD ?0.30, 95% CI ?0.70–0.10), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50–0.94; 4 studies, 269 women). For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00–1.28; one study, 40 women). In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48?h (RR 2.00, 95% CI 1.08–3.72), but not at 17 days (RR 0.81, 95% CI 0.58–1.15). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting.

Conclusions: While there were a wide range of interventions studied, both pharmaceutical and otherwise, there were a limited number of placebo controlled trials. In comparing the efficacy of the commonly used antiemetics, metoclopramide, ondansetron, and promethazine, the results of this review do not support the clear superiority of one over the other in symptomatic relief. Other factors such as side effect profile medication safety and healthcare costs should also be considered when selecting an intervention.     

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.     

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)