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CMAJ : Canadian Medical Association... Jun 2024
Review
Topics: Humans; Hyperemesis Gravidarum; Pregnancy; Female; Antiemetics
PubMed: 38830681
DOI: 10.1503/cmaj.221502-f -
BMJ Case Reports Feb 2020Hyperparathyroidism is a rare disease during pregnancy, which has increased risks, including miscarriage and fetal growth restriction. However, the diagnosis of...
Hyperparathyroidism is a rare disease during pregnancy, which has increased risks, including miscarriage and fetal growth restriction. However, the diagnosis of hyperparathyroidism is frequently not recognised or delayed as symptoms are non-specific and calcium is not routinely measured. With a thorough medical history and clinical suspicion, early diagnosis and treatment can reduce the risk of some pregnancy complications. A 35-year-old woman presented at 13/40 with hyperemesis gravidarum. She had elevated serum calcium and a parathyroid lesion on ultrasound. She underwent a parathyroidectomy with rapid normalisation of her calcium. Histopathology confirmed a parafibromin-deficient parathyroid tumour, suggestive of hyperparathyroidism jaw tumour syndrome. At 30/40, she presented with pre-eclampsia (hypertension, hyper-reflexia, proteinuria and intrauterine growth restriction) and had a caesarean section at 30+1/40, delivering a male infant, 897 g (fifth percentile). She had a prior 12-month history of chronic constipation and nephrolithiasis but was not investigated further despite elevated calcium (2.82 mmol/L).
Topics: Adult; Calcium; Cesarean Section; Diagnosis, Differential; Female; Humans; Hyperemesis Gravidarum; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Parathyroidectomy; Pregnancy; Pregnancy Complications; Pregnancy Outcome
PubMed: 32066577
DOI: 10.1136/bcr-2019-232653 -
Placenta Apr 2023Cannabis use during pregnancy is increasing. The improvement of pregnancy-related symptoms including morning sickness and management of mood and stress are among the... (Review)
Review
Cannabis use during pregnancy is increasing. The improvement of pregnancy-related symptoms including morning sickness and management of mood and stress are among the most reported reasons for its use. Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) are the most abundant cannabinoids found within the cannabis flower. The concentration of these components has drastically increased in the past 20 years. Additionally, many edibles contain only one cannabinoid and are marketed to achieve a specific goal, meaning there are an increasing number of pregnancies that are exposed to isolated cannabinoids. Both Δ9-THC and CBD cross the placenta and can impact the fetus directly, but the receptors through which cannabinoids act are also expressed throughout the placenta, suggesting that the effects of in-utero cannabinoid exposure may include indirect effects from the placenta. In-utero cannabis research focuses on short and long-term fetal health and development; however, these studies include little to no placenta analysis. Prenatal cannabinoid exposure is linked to small for gestational age and fetal growth-restricted babies. Compromised placental development is also associated with fetal growth restriction and the few studies (clinical and animal models) that included placental analysis, identify changes in placental vasculature and function in these cannabinoid-exposed pregnancies. In vitro studies further support cannabinoid impact on cell function in the different populations that comprise the placenta. In this article, we aim to summarize how phytocannabinoids can impact placental development and function. Specifically, the cannabinoids and their actions at the different receptors are described, with receptor localization throughout the human and murine placenta discussed. Findings from studies that included placental analysis and how cannabinoid signaling may modulate critical developmental processing including cell proliferation, angiogenesis and migration are described. Considering the current research, prenatal cannabinoid exposure may significantly impact placental development, and, as such, identifying windows of placental vulnerability for each cannabinoid will be critical to elucidate the etiology of fetal outcome studies.
Topics: Female; Humans; Mice; Animals; Pregnancy; Cannabinoids; Dronabinol; Placenta; Cannabidiol; Signal Transduction; Fetal Growth Retardation
PubMed: 36965349
DOI: 10.1016/j.placenta.2023.03.002 -
Acta Obstetricia Et Gynecologica... Jan 2024Hyperemesis gravidarum affects 0.3%-3% of pregnant women each year and is the leading cause of hospitalization in early pregnancy. Previous systematic reviews of...
INTRODUCTION
Hyperemesis gravidarum affects 0.3%-3% of pregnant women each year and is the leading cause of hospitalization in early pregnancy. Previous systematic reviews of available treatments have found a lack of consistent evidence, and few studies of high quality. Since 2016, no systematic review has been conducted and an up-to date review is requested. In a recent James Lind Alliance collaboration, it was clear that research on effective treatments is a high priority for both patients and clinicians.
MATERIAL AND METHODS
Searches without time limits were performed in the AMED, CINAHL, Cochrane Library, EMBASE, Medline, PsycINFO, and Scopus databases until June 26, 2023. Studies published before October 1, 2014 were identified from the review by O'Donnell et al., 2016. Selection criteria were randomized clinical trials and non-randomized studies of interventions comparing treatment of hyperemesis gravidarum with another treatment or placebo. Outcome variables included were: degree of nausea; vomiting; inability to tolerate oral fluids or food; hospital treatment; health-related quality of life, small-for-gestational-age infant; and preterm birth. Abstracts and full texts were screened, and risk of bias of the studies was assessed independently by two authors. Synthesis without meta-analysis was performed, and certainty of evidence was assessed using the GRADE approach. PROSPERO (CRD42022303150).
RESULTS
Twenty treatments were included in 25 studies with low or moderate risk of bias. The certainty of evidence was very low for all treatments except for acupressure in addition to standard care, which showed a possible moderate decrease in nausea and vomiting, with low certainty of evidence.
CONCLUSIONS
Several scientific knowledge gaps were identified. Studies on treatments for hyperemesis gravidarum are few, and the certainty of evidence for different treatments is either low or very low. To establish more robust evidence, it is essential to use validated scoring systems, the recently established diagnostic criteria, clear descriptions and measurements of core outcomes and to perform larger studies.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Hyperemesis Gravidarum; Nausea; Pregnant Women; Premature Birth; Quality of Life
PubMed: 37891710
DOI: 10.1111/aogs.14706 -
CMAJ : Canadian Medical Association... Apr 2024
Review
Topics: Pregnancy; Female; Humans; Hyperemesis Gravidarum; Risk Factors
PubMed: 38621783
DOI: 10.1503/cmaj.221502 -
Cells Mar 2019In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this... (Review)
Review
In the sanctity of pure drug discovery, objective reasoning can become clouded when pursuing ideas that appear unorthodox, but are spot on physiologically. To put this into historical perspective, it was an unorthodox idea in the 1950's to suggest that warfarin, a rat poison, could be repositioned into a breakthrough drug in humans to protect against strokes as a blood thinner. Yet it was approved in 1954 as Coumadin and has been prescribed to billions of patients as a standard of care. Similarly, no one can forget the horrific effects of thalidomide, prescribed or available without a prescription, as both a sleeping pill and "morning sickness" anti-nausea medication targeting pregnant women in the 1950's. The "thalidomide babies" became the case-in-point for the need of strict guidelines by the U.S. Food & Drug Administration (FDA) or full multi-species teratogenicity testing before drug approval. More recently it was found that thalidomide is useful in graft versus host disease, leprosy and resistant tuberculosis treatment, and as an anti-angiogenesis agent as a breakthrough drug for multiple myeloma (except for pregnant female patients). Decades of diabetes drug discovery research has historically focused on every possible angle, except, the energy-out side of the equation, namely, raising mitochondrial energy expenditure with chemical uncouplers. The idea of "social responsibility" allowed energy-in agents to be explored and the portfolio is robust with medicines of insulin sensitizers, insulin analogues, secretagogues, SGLT2 inhibitors, etc., but not energy-out medicines. The primary reason? It appeared unorthodox, to return to exploring a drug platform used in the 1930s in over 100,000 obese patients used for weight loss. This is over 80-years ago and prior to Dr Peter Mitchell explaining the mechanism of how mitochondrial uncouplers, like 2,4-dinitrophenol (DNP) even worked by three decades later in 1961. Although there is a clear application for metabolic disease, it was not until recently that this platform was explored for its merit at very low, weight-neutral doses, for treating insidious human illnesses and completely unrelated to weight reduction. It is known that mitochondrial uncouplers specifically target the entire organelle's physiology non-genomically. It has been known for years that many neuromuscular and neurodegenerative diseases are associated with overt production of reactive oxygen species (ROSs), a rise in isoprostanes (biomarker of mitochondrial ROSs in urine or blood) and poor calcium (Ca) handing. It has also been known that mitochondrial uncouplers lower ROS production and Ca overload. There is evidence that elevation of isoprostanes disease onset, in Alzheimer's Disease (AD). It is also curious, why so many neurodegenerative diseases of known and unknown etiology start at mid-life or later, such as Multiple Sclerosis (MS), Huntington Disease (HD), AD, Parkinson Disease, and Amyotrophic Lateral Sclerosis (ALS). Is there a relationship to a buildup of mutations that are sequestered over time due to ROSs exceeding the rate of repair? If ROS production were managed, could disease onset due to aging be delayed or prevented? Is it possible that most, if not all neurodegenerative diseases are manifested through mitochondrial dysfunction? Although DNP, a historic mitochondrial uncoupler, was used in the 1930s at high doses for obesity in well over 100,000 humans, and so far, it has never been an FDA-approved drug. This review will focus on the application of using DNP, but now, repositioned as a potential disease-modifying drug for a legion of insidious diseases at much lower and paradoxically, weight doses. DNP will be addressed as a treatment for "metabesity", an emerging term related to the global comorbidities associated with the over-nutritional phenotype; obesity, diabetes, nonalcoholic steatohepatitis (NASH), metabolic syndrome, cardiovascular disease, but including neurodegenerative disorders and accelerated aging. Some unexpected drug findings will be discussed, such as DNP's induction of neurotrophic growth factors involved in neuronal heath, learning and cognition. For the first time in 80's years, the FDA has granted (to Mitochon Pharmaceutical, Inc., Blue Bell, PA, USA) an open Investigational New Drug (IND) approval to begin rigorous clinical testing of DNP for safety and tolerability, including for the first ever, pharmacokinetic profiling in humans. Successful completion of Phase I clinical trial will open the door to explore the merits of DNP as a possible treatment of people with many truly unmet medical needs, including those suffering from HD, MS, PD, AD, ALS, Duchenne Muscular Dystrophy (DMD), and Traumatic Brain Injury (TBI).
Topics: 2,4-Dinitrophenol; Adenosine Triphosphate; Animals; Calcium; Cognition; Humans; Medicine; Reactive Oxygen Species
PubMed: 30909602
DOI: 10.3390/cells8030280 -
Acta Obstetricia Et Gynecologica... Sep 2023The pathogenesis and risk factors for hyperemesis gravidarum, excessive nausea and vomiting of pregnancy, are not adequately recognized. In our previous study, we found...
INTRODUCTION
The pathogenesis and risk factors for hyperemesis gravidarum, excessive nausea and vomiting of pregnancy, are not adequately recognized. In our previous study, we found that women with a personal history of nausea in different situations and a family history of nausea and vomiting of pregnancy (NVP) were more likely to have severe NVP. The present study focuses on these themes in association with hyperemesis gravidarum in a hospital setting.
MATERIAL AND METHODS
Women with hyperemesis gravidarum (n = 102) were recruited from among patients hospitalized due to hyperemesis gravidarum in Turku University Hospital, Finland. Our control group (Non-NVP group, n = 138) consisted of pregnant women with no NVP. Personal history of nausea in different situations was inquired about in relation to "motion sickness", "seasickness", "migraine", "other kind of headache", "after anesthesia", "during the use of contraception", and "other kinds of nausea". Relatives with NVP were divided into first-degree (mother and sisters) and second-degree (more distant) relatives.
RESULTS
In univariate analysis, a personal history of motion sickness, seasickness, nausea related to migraine, nausea with other headache and nausea in other situations were associated with hyperemesis gravidarum. After adjusting for age, parity, pre-pregnancy body mass index, marital status, and smoking, motion sickness (adjusted odds ratio [aOR] 5.24, 95% confidence interval [CI] 2.67-10.31, p < 0.0001), seasickness (aOR 4.82, 95% CI 2.32-10.03, p < 0.0001), nausea related to migraine (aOR 3.00, 95% CI 1.58-5.70, p < 0.001), and nausea in other situations (aOR 2.65, 95% CI 1.13-6.20, p = 0.025) remained significant. In multivariable analysis with all history of nausea variables, motion sickness (OR 2.76, 95% CI 1.29-5.89, p = 0.009) and nausea related to migraine (OR 3.10, 95% CI 1.40-6.86, p = 0.005) were associated with hyperemesis gravidarum. Having any affected relative (OR 3.51, 95%CI 1.84-6.73, p = 0.0002), especially a first-degree relative (OR 3.06, 95% CI 1.62-5.79, p = 0.0006), was also associated with hyperemesis gravidarum. Adjustment did not change the results.
CONCLUSIONS
Women with a personal history of nausea or a family history of NVP are more likely to suffer from hyperemesis gravidarum. These results are beneficial to better identify and help women at risk for hyperemesis gravidarum.
Topics: Humans; Female; Adult; Hyperemesis Gravidarum; Nausea; Pregnant Women; Finland; Case-Control Studies; Headache
PubMed: 37431247
DOI: 10.1111/aogs.14629 -
Journal of Cannabis Research Jun 2023Cannabis use during pregnancy is increasing, with 19-22% of patients testing positive at delivery in Colorado and California. Patients report using cannabis to alleviate... (Review)
Review
BACKGROUND
Cannabis use during pregnancy is increasing, with 19-22% of patients testing positive at delivery in Colorado and California. Patients report using cannabis to alleviate their nausea and vomiting, anxiety, and pain. However, preclinical and clinical data highlight harmful effects to offspring physiology and behavior following fetal cannabis exposure. This narrative review identifies potential areas for intervention to decrease cannabis consumption during pregnancy.
METHODS
A combination of keywords, including "cannabis", "cannabis", "weed", "pregnancy", "morning sickness", "child protective services", and "budtender" were searched in databases such as PubMed and Google Scholar, as well as in social media forums, governmental webpages, and other publicly available sources.
RESULTS
The literature search identified several areas for intervention to reduce cannabis use during pregnancy, including physician and pharmacist training, engagement with pregnant patients, regulation of dispensary workers, and the role of child protective services.
DISCUSSION
This comprehensive review identifies multiple areas for improvement to benefit pregnant patients. Recommendations are independent and can be implemented simultaneously by the identified groups. Limitations of this research includes the relatively limited availability of data focused specifically on cannabis consumption during pregnancy and the complexity of the sociopolitical field of substance use during pregnancy.
CONCLUSIONS
Cannabis consumption during pregnancy is increasing and causes harm to the developing fetus. To educate pregnant patients about these risks, we must address the gaps in education from multiple contact points.
PubMed: 37330589
DOI: 10.1186/s42238-023-00184-x -
Disability and Health Journal Apr 2018In the late 1950s and early 1960s the drug Thalidomide was given to thousands of pregnant women across the world to relieve morning sickness. The drug caused severe... (Review)
Review
BACKGROUND
In the late 1950s and early 1960s the drug Thalidomide was given to thousands of pregnant women across the world to relieve morning sickness. The drug caused severe birth defects. Much has been written about the drug, its teratogenic effects, and the nature of the damage it caused. There is however, little literature exploring ageing with Thalidomide damage.
OBJECTIVES
The aim of the review was to bring together, for the first time, the evidence about the Thalidomide-related health problems Thalidomide survivors are experiencing, as they grow older.
METHODS
A systematised review of published and grey literature, in which grounded theory provided a heuristic for the evidence synthesis.
RESULTS
Twenty-five relevant papers were found. They included biomedical papers focusing on specific health problems, alongside surveys and mixed method accounts exploring the health of Thalidomide survivors. Most studies had physical health as their primary focus.
CONCLUSIONS
The two most frequently reported groups of health problems were musculoskeletal and mental health conditions. There was little discussion about the social consequences of secondary damage being layered onto lifelong impairments or of the implications of co-morbidities. Future research needs a stronger connection to more social models of disability and critical disability studies.
Topics: Aging; Comorbidity; Congenital Abnormalities; Disabled Persons; Female; Health Status; Humans; Mental Disorders; Musculoskeletal Diseases; Pregnancy; Survivors; Teratogens; Thalidomide
PubMed: 29109034
DOI: 10.1016/j.dhjo.2017.09.004 -
JAMA Network Open May 2023It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
It is unknown whether olanzapine combined with triplet antemetic therapy is effective for all patients undergoing highly emetogenic chemotherapy. A secondary analysis of randomized clinical trials using olanzapine may provide insight into the effectiveness of olanzapine for chemotherapy-induced nausea and vomiting (CINV), including cisplatin.
OBJECTIVE
To examine the add-on effect of olanzapine according to risk factors for CINV.
DESIGN, SETTING, AND PARTICIPANTS
This preplanned secondary analysis evaluated results of the J-FORCE trial, a large double-blind, placebo-controlled phase 3 randomized clinical trial conducted in Japan from February 9, 2017, to July 18, 2018. Participants were enrolled from 26 participating hospitals across Japan and included patients aged 20 to 75 years who had a malignant tumor and were cisplatin-naive. The efficacy analysis population of the J-FORCE trial was analyzed according to allocation adjustment factors (sex [male or female], age [≥55 years or <55 years], and cisplatin dose [≥70 mg/m2 or <70 mg/m2]) and patient-related risk factors (history of motion sickness, drinking habit [defined as alcoholic drinks consumption in excess of occasional drinking], and history of morning sickness during pregnancy). Statistical analysis was performed from February 18 to April 18, 2020.
INTERVENTIONS
Patients were randomized 1:1 to receive 5 mg of olanzapine or placebo combined with standard triplet antiemetic therapy.
MAIN OUTCOMES AND MEASURES
The primary end point was complete response (CR, defined as no vomiting and no use of rescue medication) in the delayed phase (24-120 hours after cisplatin-based chemotherapy administration). Secondary end points were CR, complete control, and total control in the acute, delayed, and overall phases for 6 CINV risk factors as well as time to treatment failure. The CR point estimates and 95% CIs of the differences between groups were calculated, and a Mantel-Haenszel test was performed.
RESULTS
Of the 705 patients (mean [SD] age, 63.0 [9.2] years; 471 males [66.8%]) included in the efficacy analysis population; 581 patients (82.4%) were 55 years or older, and 526 (74.6%) were treated with a cisplatin dose of 70 mg/m2 or more. Risk difference (RD) for a CR in the delayed phase was significantly greater in the olanzapine group than the placebo group in males (RD, 12.6% [95% CI, 5.0%-20.1%]; P = .001); in females (RD, 14.5% [95% CI, 2.2%-26.3%]; P = .02); in those 55 years or older (RD, 11.1% [95% CI, 3.9%-18.2%]; P = .003) or younger than 55 years (RD, 23.6% [95% CI, 7.3%-38.3%]; P = .005); for a cisplatin dose of 70 mg/m2 or more (RD, 13.5% [95% CI, 5.9%-21.0%]; P < .001); for those without a history of motion sickness (RD, 13.9% [95% CI, 6.9%-20.6%]; P < .001); for those with a drinking habit (RD, 14.9% [95% CI, 6.1%-23.4%]; P = .001) or without a drinking habit (RD, 12.0% [95% CI, 2.5%-21.3%]; P = .01); and for those with a history of morning sickness during pregnancy (RD, 27.2% [9.7%-42.6%]; P = .002). In other subgroups, a delayed CR was higher in the olanzapine group than the placebo group, although not significantly higher.
CONCLUSIONS AND RELEVANCE
Results of this study suggest a benefit of using 5 mg of olanzapine plus triplet antiemetic therapy to counter CINV regardless of the presence or absence of risk factors.
TRIAL REGISTRATION
University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000024676.
Topics: Humans; Male; Female; Pregnancy; Middle Aged; Antiemetics; Olanzapine; Cisplatin; Vomiting; Nausea; Motion Sickness; Morning Sickness
PubMed: 37129897
DOI: 10.1001/jamanetworkopen.2023.10894