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Pharmacology 2017In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for... (Review)
Review
BACKGROUND
In the United States, hyperemesis gravidarum is the most common cause of hospitalization during the first half of pregnancy and is second only to preterm labor for hospitalizations in pregnancy overall. In approximately 0.3-3% of pregnancies, hyperemesis gravidarum is prevalent and this percentage varies on account of different diagnostic criteria and ethnic variation in study populations. Despite extensive research in this field, the mechanism of the disease is largely unknown. Although cases of mortality are rare, hyperemesis gravidarum has been associated with both maternal and fetal morbidity. The current mainstay of treatment relies heavily on supportive measures until improvement of symptoms as part of the natural course of hyperemesis gravidarum, which occurs with progression of gestational age. However, studies have reported that severe, refractory disease manifestations have led to serious adverse outcomes and to termination of pregnancies.
SUMMARY
Despite extensive research in the field, the pathogenesis of hyperemesis gravidarum remains unknown. Recent literature points to a genetic predisposition in addition to previously studied factors such as infectious, psychiatric, and hormonal contributions. Maternal morbidity is common and includes psychological effects, financial burden, clinical complications from nutritional deficiencies, gastrointestinal trauma, and in rare cases, neurological damage. The effect of hyperemesis gravidarum on neonatal health is still debated in literature with conflicting results regarding outcomes of birth weight and prematurity. Available therapy options remain largely unchanged in the past several decades and focus on parenteral antiemetic medications, electrolyte repletion, and nutritional support. Most studies of therapeutic options do not consist of randomized control studies and cross-study analysis is difficult due to considerable variation of diagnostic criteria. Key Messages: Hyperemesis gravidarum carries a significant burden on maternal health and US health care. Most published research on pathogenesis is observational and suggests multifactorial associations with hyperemesis gravidarum. Precise, strictly defined criteria for clinical diagnosis are likely to benefit meta-analyses of further research studies regarding pathogenesis as well as therapeutic options.
Topics: Antiemetics; Female; Humans; Hyperemesis Gravidarum; Pregnancy
PubMed: 28641304
DOI: 10.1159/000477853 -
Archives of Women's Mental Health Jun 2017Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3-2% of pregnancies and is defined by dehydration,... (Comparative Study)
Comparative Study Review
Hyperemesis gravidarum (HG) is a severe and prolonged form of nausea and/or vomiting during pregnancy. HG affects 0.3-2% of pregnancies and is defined by dehydration, ketonuria, and more than 5% body weight loss. Initial pharmacologic treatment for HG includes a combination of doxylamine and pyridoxine. Additional interventions include ondansetron or dopamine antagonists such as metoclopramide or promethazine. The options are limited for women who are not adequately treated with these medications. We suggest that mirtazapine is a useful drug in this context and its efficacy has been described in case studies. Mirtazapine acts on noradrenergic, serotonergic, histaminergic, and muscarinic receptors to produce antidepressant, anxiolytic, antiemetic, sedative, and appetite-stimulating effects. Mirtazapine is not associated with an independent increased risk of birth defects. Further investigation of mirtazapine as a treatment for HG holds promise to expand treatment options for women suffering from HG.
Topics: Adrenergic alpha-Antagonists; Adult; Antiemetics; Dopamine Agonists; Female; Humans; Hyperemesis Gravidarum; Mianserin; Mirtazapine; Pregnancy
PubMed: 28070660
DOI: 10.1007/s00737-016-0707-4 -
Canadian Family Physician Medecin de... Feb 2020To help obstetric care providers, including family physicians, nurse practitioners, midwives, and obstetricians, educate patients on the risks of cannabis use in... (Review)
Review
OBJECTIVE
To help obstetric care providers, including family physicians, nurse practitioners, midwives, and obstetricians, educate patients on the risks of cannabis use in pregnancy and postpartum and its relationship to nausea and vomiting in pregnancy.
SOURCES OF INFORMATION
The Ovid MEDLINE database was searched using the MeSH terms and in various combinations. The relevant articles were reviewed and further sources were found within the references of these articles.
MAIN MESSAGE
In utero exposure to cannabis has been associated with long-term neurodevelopmental outcomes that persist into young adulthood. Cannabis should not be used to treat nausea and vomiting in pregnancy and its chronic use might lead to the development of cannabinoid hyperemesis syndrome.
CONCLUSION
There is no known safe level of cannabis use during pregnancy or lactation. Pregnant women should be counseled regarding the risks of in utero exposure and encouraged to abstain from use in pregnancy and while breastfeeding.
Topics: Cannabis; Child; Child, Preschool; Dronabinol; Female; Humans; Hyperemesis Gravidarum; Infant; Infant, Newborn; Marijuana Use; Neurodevelopmental Disorders; Postpartum Period; Pregnancy; Prenatal Exposure Delayed Effects; Substance-Related Disorders; Young Adult
PubMed: 32060189
DOI: No ID Found -
Frontiers in Medicine 2021Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP,... (Review)
Review
Nausea and vomiting of pregnancy (NVP) is a common condition that affects up to 70% of pregnant women. Hyperemesis gravidarum (HG) is considered the serious form of NVP, which is reported in 0.3-10.8% of pregnant women. NVP has a relatively benign course, but HG can be linked with some poor maternal, fetal, and offspring outcomes. The exact causes of NVP and HG are unknown, but various factors have been hypothesized to be associated with pathogenesis. With the advance of precision medicine and molecular biology, some genetic factors such as growth/differentiation factor 15 (GDF15) have become therapeutic targets. In our review, we summarize the historical hypotheses of the pathogenesis of NVP and HG including hormonal factors, , gastrointestinal dysmotility, placenta-related factors, psychosocial factors, and new factors identified by genetics. We also highlight some approaches to the management of NVP and HG, including pharmacological treatment, complementary treatment, and some supporting treatments. Looking to the future, progress in understanding NVP and HG may reduce the adverse outcomes and improve the maternal quality of life during pregnancy.
PubMed: 35083256
DOI: 10.3389/fmed.2021.809270 -
Autonomic Neuroscience : Basic &... Jan 2017Nausea and vomiting of pregnancy (NVP) is one of the most common disorders of pregnancy. The symptoms occur predominantly during the first trimester, although in a... (Review)
Review
Nausea and vomiting of pregnancy (NVP) is one of the most common disorders of pregnancy. The symptoms occur predominantly during the first trimester, although in a subgroup of patients they can continue throughout the entire pregnancy and can affect the woman's quality of life. A small percentage of women develop a severe form of NVP called hyperemesis gravidarum (HG) that if left untreated may lead to significant maternal morbidity and adverse birth outcomes. Overall, the morbidity in pregnant women with NVP is significant, although it tends to be underestimated. The pathogenesis of NVP remains unclear, but there is consensus that the disorder is multifactorial and that various genetic, endocrine and infectious factors may be involved. The treatment of NVP can be challenging as the optimal targets for therapy are not known. Currently, the therapy used depends on the severity of the disorder and it is focused on improving the symptoms while minimizing risks to mother and fetus. Therapies range from dietary changes, pharmacologic treatment or hospitalization with intravenous fluid replacement and nutrition therapy. The aims of this review are 1) to provide an overview of NVP, 2) to present possible links between the most important factors associated with the pathogenesis of NVP and 3) to discuss the effectiveness and safety of the pharmacologic and non-pharmacologic options available to treat this disorder.
Topics: Female; Humans; Nausea; Pregnancy; Pregnancy Complications; Vomiting
PubMed: 27209471
DOI: 10.1016/j.autneu.2016.05.002 -
Health Technology Assessment... Oct 2016Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are... (Review)
Review
BACKGROUND
Nausea and vomiting in pregnancy (NVP) affects up to 85% of all women during pregnancy, but for the majority self-management suffices. For the remainder, symptoms are more severe and the most severe form of NVP - hyperemesis gravidarum (HG) - affects 0.3-1.0% of pregnant women. There is no widely accepted point at which NVP becomes HG.
OBJECTIVES
This study aimed to determine the relative clinical effectiveness and cost-effectiveness of treatments for NVP and HG.
DATA SOURCES
MEDLINE, EMBASE, Cumulative Index to Nursing and Allied Health Literature, Cochrane Central Register of Controlled Trials, PsycINFO, Commonwealth Agricultural Bureaux (CAB) Abstracts, Latin American and Caribbean Health Sciences Literature, Allied and Complementary Medicine Database, British Nursing Index, Science Citation Index, Social Sciences Citation Index, Scopus, Conference Proceedings Index, NHS Economic Evaluation Database, Health Economic Evaluations Database, China National Knowledge Infrastructure, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from inception to September 2014. References from studies and literature reviews identified were also examined. was hand-searched, as were websites of relevant organisations. Costs came from NHS sources.
REVIEW METHODS
A systematic review of randomised and non-randomised controlled trials (RCTs) for effectiveness, and population-based case series for adverse events and fetal outcomes. Treatments: vitamins B6 and B12, ginger, acupressure/acupuncture, hypnotherapy, antiemetics, dopamine antagonists, 5-hydroxytryptamine receptor antagonists, intravenous (i.v.) fluids, corticosteroids, enteral and parenteral feeding or other novel treatment. Two reviewers extracted data and quality assessed studies. Results were narratively synthesised; planned meta-analysis was not possible due to heterogeneity and incomplete reporting. A simple economic evaluation considered the implied values of treatments.
RESULTS
Seventy-three studies (75 reports) met the inclusion criteria. For RCTs, 33 and 11 studies had a low and high risk of bias respectively. For the remainder ( = 20) it was unclear. The non-randomised studies ( = 9) were low quality. There were 33 separate comparators. The most common were acupressure versus placebo ( = 12); steroid versus usual treatment ( = 7); ginger versus placebo ( = 6); ginger versus vitamin B6 ( = 6); and vitamin B6 versus placebo ( = 4). There was evidence that ginger, antihistamines, metoclopramide (mild disease) and vitamin B6 (mild to severe disease) are better than placebo. Diclectin [Duchesnay Inc.; doxylamine succinate (10 mg) plus pyridoxine hydrochloride (10 mg) slow release tablet] is more effective than placebo and ondansetron is more effective at reducing nausea than pyridoxine plus doxylamine. Diclectin before symptoms of NVP begin for women at high risk of severe NVP recurrence reduces risk of moderate/severe NVP compared with taking Diclectin once symptoms begin. Promethazine is as, and ondansetron is more, effective than metoclopramide for severe NVP/HG. I.v. fluids help correct dehydration and improve symptoms. Dextrose saline may be more effective at reducing nausea than normal saline. Transdermal clonidine patches may be effective for severe HG. Enteral feeding is effective but extreme method treatment for very severe symptoms. Day case management for moderate/severe symptoms is feasible, acceptable and as effective as inpatient care. For all other interventions and comparisons, evidence is unclear. The economic analysis was limited by lack of effectiveness data, but comparison of costs between treatments highlights the implications of different choices.
LIMITATIONS
The main limitations were the quantity and quality of the data available.
CONCLUSION
There was evidence of some improvement in symptoms for some treatments, but these data may not be transferable across disease severities. Methodologically sound and larger trials of the main therapies considered within the UK NHS are needed.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42013006642.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Antiemetics; Clinical Trials as Topic; Complementary Therapies; Cost-Benefit Analysis; Female; Fluid Therapy; Humans; Hyperemesis Gravidarum; Nausea; Pregnancy
PubMed: 27731292
DOI: 10.3310/hta20740 -
Nature Jan 2024GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a...
GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with β-thalassaemia, a condition in which GDF15 levels are chronically high, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.
Topics: Animals; Female; Humans; Mice; Pregnancy; beta-Thalassemia; Fetus; Growth Differentiation Factor 15; Hormones; Hyperemesis Gravidarum; Nausea; Placenta; Vomiting
PubMed: 38092039
DOI: 10.1038/s41586-023-06921-9 -
American Journal of Obstetrics and... Sep 2022Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health.
DATA SOURCES
MEDLINE and Embase were searched from inception to September 6, 2021.
STUDY ELIGIBILITY CRITERIA
Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included.
METHODS
Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I>75%), we did not provide a pooled odds ratio.
RESULTS
Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04-2.91; I, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25-6.93; I, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07-2.39; I, 0%; 95% prediction interval, 0.83-3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings.
CONCLUSION
Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.
Topics: Adolescent; Adult; Aged; Autism Spectrum Disorder; Child; Female; Humans; Hyperemesis Gravidarum; Male; Neoplasms, Germ Cell and Embryonal; Outcome Assessment, Health Care; Pregnancy; Testicular Neoplasms
PubMed: 35367190
DOI: 10.1016/j.ajog.2022.03.052 -
Journal of the Chinese Medical... Sep 2018
Topics: Female; Humans; Hyperemesis Gravidarum; Interleukin-6; Pregnancy; Receptors, Urokinase Plasminogen Activator; Signal Transduction
PubMed: 28969993
DOI: 10.1016/j.jcma.2017.09.001