Use of Thiamine Supplementation in Pregnant Women Diagnosed With Hyperemesis Gravidarum and Wernicke Encephalopathy.

Hyperemesis gravidarum is the most common condition requiring hospital care for women during the first 20 weeks of pregnancy and may lead to malnutrition, dehydration, and vitamin deficiencies. Depletion of vitamins such as thiamine may result in the development of Wernicke encephalopathy, a severe neurological disorder that can increase the risk for mortality and morbidity for the mother and fetus. A lack of awareness regarding the relationship of hyperemesis gravidarum and Wernicke encephalopathy may result in delayed treatment and disease management. Glucose administration in the presence of thiamine deficiency may induce Wernicke encephalopathy; protocols are needed to ensure dextrose is used for women with hyperemesis gravidarum in times of prolonged vomiting and poor oral intake only after first administering thiamine. This article includes a discussion of best practices for thiamine supplementation with hyperemesis gravidarum and Wernicke encephalopathy.

Hyperemesis gravidarum and the risk of childhood cancer - A case-control study in Denmark.

OBJECTIVE: Only a few studies have reported on the association between hyperemesis gravidarum and the risk of childhood cancer. We examined possible associations in this population-based study in Denmark. METHODS: Pediatric cancer cases (n = 6420) were ascertained from the Denmark Cancer Registry among children born between 1977 and 2013. Twenty-five controls were matched to each case by sex and birth date from the Central Person Registry (n = 160500). Mothers with hyperemesis gravidarum were ascertained from the National Patient Register. The risk of childhood cancer was estimated using conditional logistic regression. In a separate analysis, we examined pregnancy prescription of antinauseant medications, ascertained from the National Pharmaceutical Register, to determine associations with childhood cancers. RESULTS: In Denmark, hyperemesis gravidarum was associated with an increased risk of childhood cancer [all types combined; Odds Ratio (OR) = 1.43, 95% confidence interval (CI) 1.12, 1.81; n = 73 exposed cases). Hyperemesis gravidarum was also associated with an increased risk of neuroblastoma (OR = 2.52, 95% CI 1.00, 6.36; n = 5 exposed cases), acute lymphoblastic leukemia (OR = 1.63, 95% CI 0.98, 2.72; n = 16 exposed cases), and non-Hodgkin's lymphoma (OR = 2.41, 95% CI 0.95, 6.08; n = 5 exposed cases). We observed no childhood cancer risk increase from antinauseant prescriptions (OR = 1.05, 95% CI 0.84, 1.30; n = 91 exposed cases). CONCLUSION: Our results are suggestive of an association between hyperemesis gravidarum and the overall cancer risk in offspring, particularly for neuroblastoma. Mothers with hyperemesis gravidarum should be closely monitored and receive appropriate treatment during pregnancy.

Reorganising and improving quality of care for hyperemesis gravidarum in a Danish hospital: a quality improvement project.

BACKGROUND: Hyperemesis gravidarum (HG) is a pregnancy complication comprising severe nausea and vomiting in pregnancy. It is associated with adverse outcomes for both mother and child. Treatment consists primarily of antiemetics and intravenous fluids; however, support from healthcare professionals is also important. LOCAL PROBLEM: At the department of obstetrics at Nordsjællands Hospital, an increasing workload caused challenges regarding patient care and organisation for patients with HG, and exploring possibilities of reorganising HG care to release midwife resources was warranted. METHODS: Through input from staff and patients, possible improvements were identified. Plan-do-study-act cycles were conducted with staff and patients, resulting in adjustments in care and organisation and thus use of resources. The specific, measurable, attainable, realistic and timely aims included patient satisfaction and number of follow-ups conducted via phone. INTERVENTIONS: HG care was relocated to the department of gynaecology, where it was managed primarily by nurses. Staff and patients were actively involved in the process. RESULTS: HG care was successfully relocated without compromising patient satisfaction. Additionally, an option of patient-administered home treatment for selected patients was established. CONCLUSION: This quality improvement project describes the relocation and set-up of hospital care provided to patients with HG, resulting in high patient satisfaction. This project might serve as an inspiration to other departments of obstetrics and gynaecology.

Diplopia after Sleeve Gastrectomy: The Canary in the Coal Mine.

Wernicke's encephalopathy (WE) is a neurologic emergency requiring timely intravenous thiamine supplementation to prevent permanent neurologic deficits. Historically, the WE diagnosis was limited to individuals with alcohol use disorder. However, it is now widely recognized to occur in patients who are chronically malnourished, post-bariatric surgery, pregnant with hyperemesis gravidarum, and with severe anorexia nervosa. Here we present a young woman who developed WE after undergoing a recent sleeve gastrectomy followed by protracted emesis for several days. This case underscores the importance of performing a thorough neurological review of systems and physical exam in high-risk patients and having a low clinical threshold to initiate appropriate thiamine treatment.

Ondansetron Use During Pregnancy: Birth Defects and Obstetric Outcomes.

Ondansetron is a widely administered medication for nausea and vomiting of pregnancy. Further examination of its teratogenic capacity is necessary. This study examines the association between ondansetron treatment during pregnancy and birth defects and adverse obstetric outcomes. Patient data were extracted from Clalit Health Services, Israel. A propensity-score analysis was performed matching those exposed to ondansetron with those who were not. Findings identified 774 women exposed to ondansetron, matched 1:1 with unexposed control patients. No significant differences were found between the groups for: cleft palate, cardiovascular congenital abnormalities, spina bifida occulta, preterm delivery, or small for gestational age. Ondansetron may be a useful and safe alternative as treatment for women who suffer from hyperemesis gravidarum and do not respond to other antiemetic drugs. Notwithstanding, additional prospectively designed research is needed to establish the safety of ondansetron treatment during pregnancy.

Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy.

BACKGROUND: Nausea and vomiting in pregnancy often require pharmacotherapy for symptom management. Serotonin syndrome is a rare clinical entity that can be precipitated by the medications used to treat nausea and vomiting in pregnancy. CASE: A 35-year-old pregnant individual with a history of hyperemesis gravidarum in an earlier pregnancy requiring prolonged hospitalization presented with nausea and vomiting at 7 weeks of gestation. She was incidentally found to have severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection when she was universally screened at the time of admission. She required pharmacotherapy, including prochlorperazine and ondansetron for treatment of nausea as well as sumatriptan for migraine. She developed acute spasticity, autonomic dysfunction, and temperature rise, precipitated by antiemetic therapy, consistent with serotonin syndrome. The syndrome resolved with supportive care and benzodiazepines. CONCLUSION: Serotonin syndrome is a serious clinical entity that can be provoked by the pharmacotherapy given to treat nausea and vomiting in pregnancy. This medical emergency requires early recognition and prompt management.

Effect of Acupressure at P6 on Nausea and Vomiting in Women with Hyperemesis Gravidarum: A Randomized Controlled Trial.

Hyperemesis gravidarum is characterized by severe nausea and vomiting. This study aims to illustrate the efficacy of acupressure at P6 in treating nausea and vomiting in hyperemesis gravidarum. This parallel randomized controlled trial was conducted from 2016-2017 in a tertiary hospital. Hospitalized women with ≤16 weeks of gestation and moderate to severe nausea and vomiting classified using a modified PUQE score were randomly assigned in a 1:1 ratio to either apply an acupressure wristband at the P6 point three times daily or to receive regular doses of intravenous antiemetics. The primary outcome was differences in modified PUQE scores among the groups. The secondary outcomes were differences in the rate of urine ketone clearance and the frequency of requiring rescue antiemetics. Ninety women were equally randomized into two groups, with no dropout. There was a statistically significant difference in the degrees of nausea and vomiting between the groups at 8, 16, and 24 hours post-admission (p8hours= 0.001, p16hours = 0.006, and p24hours = 0.001). The requirement of antiemetics and the rate of urine ketone clearance between the two groups were also statistically significant, at p = 0.001 and p = 0.02 respectively. There were no side effects in either group. The P6 acupressure was efficacious in alleviating nausea and vomiting among hyperemesis gravidarum women. The trial was retrospectively registered on ClinicalTrials.gov (NCT05175079).

A potential role for olanzapine in the treatment of hyperemesis gravidarum.

Hyperemesis gravidarum is a rare but potentially serious complication of pregnancy. Some women with severe symptoms and possibly psychiatric comorbidities remain symptomatic despite the use of currently available treatments. Due to its favorable safety profile, antiemetic efficacy in other conditions, and 5-HT3 antagonism, olanzapine may be a potentially useful addition to the armamentarium for management of hyperemesis gravidarum resistant to standard- of-care treatment.

Wernicke's encephalopathy in women with hyperemesis gravidarum - Case series and literature review.

Whilst nausea affects around 80% of pregnant women, hyperemesis gravidarum, an extreme form of the same, affects only 0.5% to 3%, but may lead to severe nutritional deficiency. Wernicke's encephalopathy is an acute neuropsychiatric disorder which occurs due to thiamine deficiency and needs emergency treatment to prevent neurological morbidity and mortality. Wernicke's encephalopathy is characterised by a clinical triad of oculomotor abnormalities, cerebellar dysfunction and altered mental state. Korsakoff's psychosis is a chronic condition and consequence of Wernicke's encephalopathy, resulting from its delayed treatment. Wernicke's encephalopathy is a well-known complication of chronic alcohol abuse. Not many are aware of its association with hyperemesis gravidarum. Although it is a rare complication, if not diagnosed and treated promptly, it may result in permanent and irreversible neurological sequelae. The objective of our retrospective observational study was to analyse the clinical profile and outcome (short and long term) in a rare yet preventable complication of pregnancy.

Pregnant women report being denied medications to treat severe nausea and vomiting of pregnancy or hyperemesis gravidarum - findings from an Australian online survey.

We conducted an online survey of 249 Australian women who currently or previously experienced severe nausea and vomiting of pregnancy (NVP) or hyperemesis gravidarum (HG) and examined their experiences in being denied medications during pregnancy. One in four women reported being denied medications for NVP/HG, which most commonly involved doxylamine and encounters with community pharmacists. Women's experiences reflected that lack of awareness of guidelines and unfavourable risk-benefit assessments appeared to be key barriers to facilitating medication access. Approaches towards identifying and effectively addressing barriers to the provision of effective treatments for severe NVP and HG are urgently needed.

Effect of gabapentin on hyperemesis gravidarum: a double-blind, randomized controlled trial.

BACKGROUND: Hyperemesis gravidarum is a disabling disease of nausea, vomiting, and undernutrition in early pregnancy for which there are no effective outpatient therapies. Poor weight gain in hyperemesis gravidarum is associated with several adverse fetal outcomes including preterm delivery, low birthweight, small for gestational age, low 5-minute Apgar scores, and neurodevelopmental delay. Gabapentin is most commonly used clinically for treating neuropathic pain but also substantially reduces chemotherapy-induced and postoperative nausea and vomiting. Pregnancy registry data have shown maternal first-trimester gabapentin monotherapy to be associated with a 1.2% rate of major congenital malformations among 659 infants, which compares favorably with the 1.6% to 2.2% major congenital malformation rate in the general population. Open-label gabapentin treatment in hyperemesis gravidarum was associated with reduced nausea and vomiting and improved oral nutrition. OBJECTIVE: This study aimed to determine whether gabapentin is more effective than standard-of-care therapy for treating hyperemesis gravidarum. STUDY DESIGN: A double-blind, randomized, multicenter trial was conducted among patients with medically refractory hyperemesis gravidarum requiring intravenous hydration. Patients were randomized (1:1) to either oral gabapentin (1800-2400 mg/d) or an active comparator of either oral ondansetron (24-32 mg/d) or oral metoclopramide (45-60 mg/d) for 7 days. Differences in Motherisk-pregnancy-unique quantification of nausea and emesis total scores between treatment groups averaged over days 5 to 7, using intention-to-treat principle employing a linear mixed-effects model adjusted for baseline Motherisk-pregnancy-unique quantification of nausea and emesis scores, which served as the primary endpoint. Secondary outcomes included Motherisk-pregnancy-unique quantification of nausea and emesis nausea and vomit and retch subscores, oral nutrition, global satisfaction of treatment, relief, desire to continue therapy, Nausea and Vomiting of Pregnancy Quality of Life, and Hyperemesis Gravidarum Pregnancy Termination Consideration. Adjustments for multiple comparisons were made employing the false discovery rate. RESULTS: A total of 31 patients with hyperemesis gravidarum were enrolled from October 2014 to May 2019. Among the 21 patients providing primary outcome data (12 assigned to gabapentin and 9 to the active comparator arm), 18 were enrolled as outpatients and all 21 were outpatients from days 5 to 7. The study groups' baseline characteristics were well matched. Gabapentin treatment provided a 52% greater reduction in days 5 to 7 baseline adjusted Motherisk-pregnancy-unique quantification of nausea and emesis total scores than treatment with active comparator (95% confidence interval, 16-88; P=.01). Most secondary outcomes also favored gabapentin over active comparator treatment including 46% and 49% decreases in baseline adjusted Motherisk-pregnancy-unique quantification of nausea and emesis nausea (95% confidence interval, 19-72; P=.005) and vomit and retch subscores (95% confidence interval, 21-77; P=.005), respectively; a 96% increase in baseline adjusted oral nutrition scores (95% confidence interval, 27-165; P=.01); and a 254% difference in global satisfaction of treatment (95% confidence interval, 48-459; P=.03). Relief (P=.06) and desire to continue therapy (P=.06) both showed trends favoring gabapentin treatment but Nausea and Vomiting of Pregnancy Quality of Life (P=.68) and Hyperemesis Gravidarum Pregnancy Termination Consideration (P=.58) did not. Adverse events were roughly equivalent between the groups. There were no serious adverse events. CONCLUSION: In this small trial, gabapentin was more effective than standard-of-care therapy for reducing nausea and vomiting and increasing oral nutrition and global satisfaction in outpatients with hyperemesis gravidarum. These data build on previous findings in other patient populations supporting gabapentin as a novel antinausea and antiemetic therapy and support further research on gabapentin for this challenging complication of pregnancy.

Validating the effect of Ondansetron and Mirtazapine In Treating hyperemesis gravidarum (VOMIT): protocol for a randomised placebo-controlled trial.

INTRODUCTION: Current pharmacological treatment options for hyperemesis gravidarum have been introduced based on scarce evidence and are often not sufficiently effective. Several case reports suggest that mirtazapine, an antidepressant, may be an effective treatment for hyperemesis gravidarum, but so far there are no controlled trials investigating the potential effect of mirtazapine on hyperemesis gravidarum. The antiemetic ondansetron is currently widely used to treat hyperemesis gravidarum despite sparse evidence of effect in pregnant women. This study aims to investigate the effect of mirtazapine on hyperemesis gravidarum while also providing data on the effect of ondansetron. METHODS AND ANALYSIS: This randomised double-blind placebo-controlled multicentre trial will be conducted in eight Danish hospitals. One hundred and eighty pregnant women referred to secondary care for hyperemesis gravidarum will be randomly allocated to 14-day treatment with either mirtazapine, ondansetron or placebo. Main inclusion criterion will be Pregnancy Unique Quantification of Emesis (PUQE-24) score ≥13 or PUQE-24 score ≥7 if accompanied by weight loss >5% of pre-pregnancy weight or hospitalisation. Participants are eligible regardless of whether other antiemetics, including ondansetron, have been tried. The coprimary outcomes are effects of mirtazapine and ondansetron, respectively, on PUQE-24 score tested hierarchically on day 2 and day 14. Secondary outcomes include, but are not limited to, differences between the three groups in number of daily vomiting episodes, dropout due to treatment failure, use of rescue medication, weight change and side effects. ETHICS AND DISSEMINATION: The trial has been approved by the Regional Committees on Health Research Ethics in the Capital Region of Denmark, the Danish Medicines Agency and the Danish Data Protection Agency. Results will be published in peer-reviewed journals and submitted to relevant conferences. TRIAL REGISTRATION NUMBER: NCT03785691.

Hyperemesis Gravidarum: Strategies to Improve Outcomes.

Hyperemesis gravidarum (HG) is a debilitating and potentially life-threatening pregnancy disease marked by weight loss, malnutrition, and dehydration attributed to unrelenting nausea and/or vomiting; HG increases the risk of adverse outcomes for the mother and child(ren). The complexity of HG affects every aspect of a woman's life during and after pregnancy. Without methodical intervention by knowledgeable and proactive clinicians, life-threatening complications may develop. Effectively managing HG requires an understanding of both physical and psychosocial stressors, recognition of potential risks and complications, and proactive assessment and treatment strategies using innovative clinical tools.