Genome-wide association study of nausea and vomiting during pregnancy in Japan: the TMM BirThree Cohort Study.

BACKGROUND: Nausea and vomiting during pregnancy (NVP) and hyperemesis gravidarum (HG), common conditions affecting most pregnant women, are highly heritable and associated with maternal and fetal morbidity. However, the pathologies underlying NVP and HG and their associated loci are scarce. METHODS: We performed genome-wide association studies (GWAS) of NVP in pregnant women (n = 23,040) who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study in Japan from July 2013 to March 2017. Participants were divided into discovery (n = 9,464) and replication (n = 10,051) stages based on the platform used for their genotyping. Loci that achieved the genome-wide significance level (p < 5.0 × 10- 8) in the discovery stage were selected for genotyping in the replication stage. A meta-analysis integrating the discovery and replication stage results (n = 19,515) was conducted. NVP-related variables were identified as categorical or continuous. RESULTS: GWAS analysis in the discovery phase revealed loci linked to NVP in two gene regions, 11q22.1 (rs77775955) and 19p13.11 (rs749451 and rs28568614). Loci in these two gene regions have also been shown to be associated with HG in a White European population, indicating the generalizability of the GWAS analyses conducted in this study. Of these, only rs749451 and rs28568614 at 19p13.11 reached the genome-wide suggestive level (p < 1.0 × 10- 5) in the replication stage; however, both loci were significant in the meta-analysis. CONCLUSIONS: NVP-related loci were identified in the Japanese population at 11q22.1 and 19p13.11, as reported in previous GWAS. This study contributes new evidence on the generalizability of previous GWAS on the association between genetic background and NVP.

Suicidal ideation and associated factors among pregnant women attending antenatal care at public hospitals of Harari regional state, eastern Ethiopia: A cross-sectional study.

BACKGROUND: Suicide is a global issue. It is the third responsible for death among the reproductive age group. Pregnancy is a complicated event and crucial in the life of a woman with considerable physiological, hormonal changes, social, and mental changes. However, third-world countries like Ethiopia have not been investigated well. Therefore, the study planned to assess the magnitude and factors associated with suicidal ideation. Furthermore, it will identify the role of hyperemesis gravidarum on suicidal ideation. METHOD: A Cross-sectional study was employed for 543 pregnant participants attending antenatal care at Hiwot Fana Specialized University Hospital and Jugal General Hospital, Harari regional state, eastern Ethiopia from June 1 to August 1, 2022. The recruited participants were selected by systematic random sampling method. Suicide was assessed using Composite International Diagnostic by interview methods data collection. Epi data and STATA version 14.1 were used for data entry and analysis respectively. Candidate variables were entered into a multivariate logistic regression then those variables that have p-value < 0.05 were considered as significantly associated. RESULTS: The magnitude of suicidal ideation in this study was found to be 11.15% at (95% CI: 8.75-14.11). Regarding the associated factor, unwanted pregnancy (AOR = 3.39: at 95% CI = 1.58-7.27), Hyperemesis gravidarum (AOR = 3.65: at 95% CI = 1.81-7.34), having depressive symptoms (AOR = 2.79: at 95% CI = 1.49-5.23), having anxiety symptoms (AOR = 3.37; at 95% CI = 1.69-6.68), experiencing intimate partner violence (AOR = 2.88: at 95% CI = 1.11-7.46), and having stress (AOR = 3.46; at 95% CI = 1.75-6.86) were significantly associated variable with suicidal ideation among pregnant women. CONCLUSION AND RECOMMENDATION: This study revealed that suicidal ideation is common among pregnant women. Regarding the associated factors unwanted pregnancy, hyperemesis gravidarum, having depressive and anxiety symptoms, experiencing intimate partner violence, and stress were significantly associated with suicidal ideation. Thus, giving awareness and early screening and interferences for antenatal suicide should be warranted.

Offspring of women with hyperemesis gravidarum are more likely to have cardiovascular abnormalities.

BACKGROUND: Hyperemesis gravidarum (HG) is a severe form of pregnancy-related nausea and vomiting affecting 0.3-2.3% of pregnancies, which can lead to fluid, electrolyte, and acid-base imbalances, nutritional deficiencies, and weight loss, and is usually severe enough to require hospitalization. Abnormally elevated urinary ketones are commonly seen in patients with HG, and ketone bodies are free to pass through the placenta, and maternal hyperketonemia, with or without acidosis, is associated with an increased rate of stillbirth, an increased incidence of congenital anomalies, and impaired neurophysiologic development of the infant. This study investigates the obstetric outcomes of patients with HG and whether HG increases the incidence of cardiovascular disease in the offspring. METHODS: This study included 1020 pregnant women who were hospitalized in our hospital for HG and ultimately delivered in our hospital as well as pregnant women without HG in early gestation and delivered in our hospital from January 2019-January 2020, and we collected and followed up the clinical information of the pregnant women and their offspring. RESULTS: Pregnant women with HG were more likely to have severe urinary ketones, the rate of early miscarriage and mid-term miscarriage was significantly higher in women with HG compared to pregnant women without HG. Fetal and neonatal head and abdominal circumferences were smaller in HG group than in control group. Neonatal birth weight and length were also lower in the HG group and cardiovascular anomalies were more likely to occur in the offspring of women with HG when all births were followed up for 3 years. CONCLUSIONS: HG may cause poor obstetric outcomes and was associated with the development of cardiovascular disease in the offspring of women with HG.

Mediating Factors in the Association of Maternal Educational Level With Pregnancy Outcomes: A Mendelian Randomization Study.

Importance: Lower educational attainment is associated with increased risk of adverse pregnancy outcomes, but it is unclear which pathways mediate this association. Objective: To investigate the association between educational attainment and pregnancy outcomes and the proportion of this association that is mediated through modifiable cardiometabolic risk factors. Design, Setting, and Participants: In this 2-sample mendelian randomization (MR) cohort study, uncorrelated (R2 < 0.01) single-nucleotide variants (formerly single-nucleotide polymorphisms) associated with the exposure (P < 5 × 10-8) and mediators and genetic associations with the pregnancy outcomes from genome-wide association studies were extracted. All participants were of European ancestry and were largely from Finland, Iceland, the United Kingdom, or the US. The inverse variance-weighted method was used in the main analysis, and the weighted median, weighted mode, and MR Egger regression were used in sensitivity analyses. In mediation analyses, the direct effect of educational attainment estimated in multivariable MR was compared with the total effect estimated in the main univariable MR analysis. Data were extracted between December 1, 2022, and April 30, 2023. Exposure: Genetically estimated educational attainment. The mediators considered were genetically estimated type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure. Main Outcomes and Measures: Ectopic pregnancy, hyperemesis gravidarum, gestational diabetes, preeclampsia, preterm birth, and offspring birth weight. Results: The analyses included 3 037 499 individuals with data on educational attainment, and those included in studies on pregnancy outcomes ranged from 141 014 for ectopic pregnancy to 270 002 with data on offspring birth weight. Each SD increase in genetically estimated educational attainment (ie, 3.4 years) was associated with an increased birth weight of 42 (95% CI, 28-56) g and an odds ratio ranging from 0.53 (95% CI, 0.46-0.60) for ectopic pregnancy to 0.81 (95% CI, 0.71-0.93) for preeclampsia. The combined proportion of the association that was mediated by the 5 cardiometabolic risk factors ranged from -17% (95% CI, -46% to 26%) for hyperemesis gravidarum to 78% (95% CI, 10%-208%) for preeclampsia. Sensitivity analyses accounting for pleiotropy were consistent with the main analyses. Conclusions and Relevance: In this MR cohort study, intervening for type 2 diabetes, body mass index, smoking, high-density lipoprotein cholesterol level, and systolic blood pressure may lead to reductions in several adverse pregnancy outcomes associated with lower levels of education. Such public health interventions would serve to reduce health disparities attributable to social inequalities.

Treatments for hyperemesis gravidarum: A systematic review.

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.

The association between Helicobacter pylori and gastrointestinal disorders during pregnancy: A Multicenter retrospective study.

BACKGROUND: Some gastrointestinal disorders may be associated with Helicobacter pylori infection, which not only affect maternal health, but may also lead to adverse pregnancy outcomes. We aim to explore the association between H. pylori and gastrointestinal disorders in pregnant women. MATERIALS AND METHODS: In total, 503 patients were retrospectively analyzed and divided into the H. pylori-uninfected group, the H. pylori-infected group, or the H. pylori-eradicated group. We analyzed the influence of H. pylori on gastrointestinal diseases during pregnancy among the groups, as well as the severity, symptoms, laboratory tests of the H. pylori-related diseases. RESULTS: Pregnant women with H. pylori infection had higher risk of nausea and vomiting of pregnancy (NVP) (p < 0.001), severe NVP(p = 0.012), hyperemesis gravidarum (p = 0.027), hematemesis (p = 0.018), hyponatremia (p = 0.033), as well as functional dyspepsia symptoms including epigastric pain (p = 0.004), bloating (p = 0.024), and feeling full quickly in a meal (p = 0.031) compared with those without H. pylori infection. While the prevalence of NVP (p = 0.024), severe NVP (p = 0.009), epigastric pain (p = 0.037), and bloating (p = 0.032) were lower in H. pylori-eradicated pregnant women than in H. pylori-infected women. In addition, pregnant women with H. pylori infection had higher risk of spontaneous preterm birth than whom without H. pylori infection (p = 0.033). CONCLUSIONS: Helicobacter pylori infection was associated with higher risks of NVP, severe NVP, hyperemesis gravidarum, functional dyspepsia, and spontaneous preterm birth in pregnant women.

Hyperemesis gravidarum and eating disorders before and after pregnancy: A register-based study.

OBJECTIVE: Hyperemesis gravidarum (HG) is a severe form of excessive vomiting during pregnancy. The connection between psychiatric morbidity and HG has been debated, but only a few studies have focused on eating disorders (EDs). The objective of this study was to evaluate the association between HG and both pre-pregnancy and new post-pregnancy EDs. METHODS: A register-based controlled study. HG diagnoses were retrieved from healthcare registers between 2005 and 2017. Women with HG in their first pregnancy resulting in delivery were chosen as cases (n = 4265; the HG group) and women with no HG as controls (n = 302,663; the non-HG group). The associations between EDs and HG were analyzed by binary logistic regression, adjusted with age, body mass index, smoking, socioeconomic status, and pre-pregnancy psychiatric diagnoses. RESULTS: In the HG group, 1.6% and in the non-HG group, 0.2% had a pre-pregnancy ED. Women with ED were more likely to have HG in their first pregnancy compared with women with no history of EDs (adjusted odds ratio [AOR] 9.4, 95% CI 6.52-13.66, p < .0001). Moreover, 0.4% of the women in the HG group and 0.1% of the women in the non-HG group had a new ED diagnosis after pregnancy, and thus the women in the HG group were more likely to have an ED diagnosis after pregnancy (AOR I 3.5, 95% CI 1.71-7.15, p < .001, AOR II 2.7, 95% CI 1.30-5.69, p = .008). DISCUSSION: We found a bidirectional association between ED and HG, suggesting a shared etiology or risk factors between these disorders. This finding emphasizes the importance of collaboration across various specialties when treating these patients. PUBLIC SIGNIFICANCE: Our findings suggest a bidirectional association between HG and EDs before and after pregnancy. This finding provides essential information for healthcare professionals working with pregnant women. As both of these disorders are known to have far-reaching effects on the lives of both the mother and her offspring, our results help clinicians to target special attention and interventions to the patients suffering from these disorders.

GDF15 linked to maternal risk of nausea and vomiting during pregnancy.

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 lacking1-4. 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 ß-thalassaemia, a condition in which GDF15 levels are chronically high5, 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.

The impact of maternal hyperemesis gravidarum on early childhood respiratory morbidity.

BACKGROUND: Lung maldevelopment due to in-utero events may potentially cause respiratory morbidity during childhood. Maternal nutritional status during pregnancy is critical for lung development. This study is contributing to the understanding of the interplay between maternal nutrition status during pregnancy, fetal lung development and the risk for respiratory diseases in early life. RESEARCH QUESTION: To investigate the association between maternal hyperemesis gravidarum (HG) during pregnancy and respiratory morbidity in the offspring's early childhood. STUDY DESIGN AND METHODS: This is a retrospective population-based cohort study that included all singleton term deliveries at Soroka University Medical Center (SUMC) between 1991 and 2021. Preterm deliveries (<37 gestational week), perinatal deaths, multiple gestations, and children with congenital malformations or chromosomal abnormalities were excluded. The main outcomes measured were offspring's hospitalizations due to pneumonia, acute bronchiolitis, asthma, or wheezing. RESULTS: Overall 232,476 deliveries were included in the study, of which 3227 women (1.4%) were diagnosed with HG. Offspring in the HG group exhibited significantly higher rates of respiratory morbidity, including asthma (OR = 1.36, 95% CI 1.22-1.36, p < .001), acute bronchiolitis (OR = 1.38, 95% CI 1.21-1.59, p < .001), and pneumonia (OR = 1.2, 95% CI 1.12-1.48, p < .001). An inverse correlation between multivariate adjusted-hazard ratios for asthma and pneumonia with offspring's age was noted. INTERPRETATION: This study provides evidence of a potential association between maternal HG during pregnancy and increased risk of respiratory morbidity in offspring's early childhood. Maternal nutritional status during pregnancy plays a crucial role in lung development, affecting respiratory health in childhood.

Análise dos efeitos em fetos expostos à hiperêmese gravídica durante a gravidez / Analysis of the effects on fetuses exposed to hyperemesis gravidarum during pregnancy

INTRODUÇÃO: De etiologia desconhecida, a hiperêmese gravídica é um quadro caracterizado por vômitos persistentes, perda de 5% ou mais do peso, cetonúria, hipocalemia e desidratação. Acredita-se que a gonadotrofina coriônica humana (hCG) provoque aumento das náuseas e vômitos por meio de seu estímulo à produção de estrogênio pelo ovário, provocando a exacerbação dos sintomas do "enjoo matinal". OBJETIVO: Logo, essa revisão narrativa tem como objetivo analisar as repercussões fetais do quadro de hiperêmese gravídica. MÉTODOS: Foram realizadas buscas em Sistema Online de Busca e Análise de Literatura Médica - MEDLINE®. Sendo utilizadas os Medical Subject Headings (MeSh terms) e seus sinônimos: "hyperemesis gravidarum", "fetal risks", sendo selecionados ao todo 13 artigos. RESULTADOS: Os estudos demonstraram que a hiperêmese gravídica pode trazer malefícios para mãe e feto. A gestante pode apresentar distúrbios eletrolíticos, encefalopatia de Wernicke, fraqueza muscular, disfunções emocionais como depressão, ansiedade e estresse pós-traumático. DISCUSSÃO: Os estudos revelaram que a patologia pode estar relacionada ao risco aumentado para desfechos adversos no nascimento, como baixo peso ao nascer, nascimento prematuro e pequena estatura para idade gestacional. Ademais, alguns estudos relataram os riscos prejudiciais no neurodesenvolvimento do recém-nascido, como problemas psicológicos e comportamentais na idade adulta, redução à sensibilidade à insulina, e comorbidades (obesidade e doenças cardiovasculares) além de distúrbios de desenvolvimento neuropsicomotor. CONCLUSÃO: Gestantes que apresentam o quadro de hiperêmese gravídica devem ser regularmente acompanhadas com consultas entre 1 a 2 semanas, conforme a gravidade do caso e o mais precocemente possível tratadas, a fim de evitar maiores complicações tanto maternas quanto fetais.

INTRODUCTION: Of unknown etiology, hyperemesis gravidarum is a condition characterized by persistent vomiting, 5% or more weight loss, ketonuria, hypokalemia and dehydration. Human chorionic gonadotropin (hCG) is believed to cause increased nausea and vomiting through its stimulation of estrogen production by the ovary, causing exacerbation of "morning sickness" symptoms. OBJECTIVE: Thus, this narrative review aims to analyze the fetal repercussions of hyperemesis gravidarum. METHODS: Searches were performed in the Online Medical Literature Analysis and Search System - MEDLINE®. The Medical Subject Headings (MeSh terms) and their synonyms were used: "hyperemesis gravidarum", "fetal risks", being selected a total of 13 articles. RESULTS: The studies showed that hyperemesis gravidarum can bring harm to mother and fetus. The pregnant woman may present electrolyte disturbances, Wernicke's encephalopathy, muscle weakness, emotional dysfunctions such as depression, anxiety, and post-traumatic stress. DISCUSSION: The studies revealed that hyperemesis gravidarum may be associated with increased risk of adverse outcomes. Furthermore, some studies reported harmful risks in neurodevelopment of the newborn, such as psychological and behavioral problems in adulthood, reduced sensitivity to insulin, and comorbidities (obesity and cardiovascular diseases) and neurodevelopmental disorders. CONCLUSION: Pregnant women who present with hyperemesis gravidarum should be followed up with consultations between 1 to 2 weeks, according to the severity of the case and treated as early as possible in order to avoid further complications both maternal and fetal.

Survivors' Experiences of Hyperemesis Gravidarum.

Hyperemesis gravidarum can result in life-threatening physical and psychological maternal morbidity, including severe dehydration, weight loss, electrolyte imbalance, depression, and suicidal ideation. The reported prevalence of hyperemesis gravidarum ranges from 0.3% to 3.6%. The purpose of this qualitative study was to investigate what blogs can tell us about women's experiences of hyperemesis gravidarum. Thirty-three blogs written by hyperemesis gravidarum survivors posted on Hyperemesis Australia's website were analyzed using Krippendorff's qualitative content analysis method. Clustering was used and yielded 6 themes: (1) debilitating physical and mental health problems: digging deep to persevere, (2) heartbreaking choices, (3) lack of understanding and dismissed, (4) so much guilt surrounding their unborn infant, (5) it takes a village to support women with hyperemesis gravidarum, and (6) warriors and survivors: giving back. Infusion nurses are in a perfect position to provide support and compassionate care for women who are repeatedly coming to the hospital for rehydration treatment. Infusion nurses can validate women's physical and emotional struggles with hyperemesis gravidarum and help to no longer make women feel stigmatized.

Correlation between serum beta-human chorionic gonadotropin levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum.

As previously demonstrated, serum beta-human chorionic gonadotropin (ß-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum ß-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum ß-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum ß-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between ß-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and ß-hCG levels for HG. Versus those in the control group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum ß-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum ß-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that ß-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum ß-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, ß-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

Vitamin D and hyperemesis gravidarum: A mendelian randomization study.

BACKGROUND: The causality between vitamin D and hyperemesis gravidarum remains unknown. Our aim was to investigate the causal effect of vitamin D on hyperemesis gravidarum using the two-sample Mendelian randomization method. METHODS: Independent single nucleotide polymorphisms significantly associated with serum 25-hydroxyvitamin D levels served as instrumental variables. The corresponding effect estimates for hyperemesis gravidarum were obtained from the Finngen Biobank. For Mendelian randomization analysis, inverse variance weighting was used as the primary method. We also used weighted median, MR-Egger regression, simple mode, and weighted mode as complementary methods to inverse variance weighting. The MR-Egger intercept test, Cochran's Q test, and "leave-one-out" sensitivity analysis were performed to assess the horizontal pleiotropy, heterogeneity, and stability of the causal association between 25-hydroxyvitamin D levels and hyperemesis gravidarum. RESULTS: We found that an increase in 25-hydroxyvitamin D level was associated with a lower risk of hyperemesis gravidarum [odds ratio (OR): 0.568, 95 % CI: 0.403-0.800, p = 0.001]. The result demonstrates the causal relationship between 25-hydroxyvitamin D level and the risk of hyperemesis gravidarum in the European population. CONCLUSIONS: The large Mendelian randomization analysis suggests that vitamin D may be causally associated with risk of hyperemesis gravidarum.

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.

Relationship between combined systemic inflammatory indices with presence and severity of hyperemesis gravidarum.

OBJECTIVE: Our study aims to determine the levels of systemic inflammation markers and the combined systemic inflammation indices in hyperemesis gravidarum (HG) patients and to investigate the association between the severity of the disease. PATIENTS AND METHODS: The study population consisted of 83 pregnant women with HG and 100 healthy pregnant women matched for gestational age as a control group. We grouped the HG patients according to the Modified Pregnancy Unique Quantification of Emesis/Nausea (PUQE) scoring system as mild, moderate, and severe. We calculated the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), MPV-to-lymphocyte ratio (MPVLR), RDW-to-platelet ratio (RPR), Systemic immune-inflammation index (SII), Systemic Inflammation Response Index (SIRI), and Aggregate Systemic Inflammation Index (AISI). RESULTS: NLR, PLR, SII, SIRI, and AISI levels were significantly higher in the HG group. These indices tended to increase as the severity of the disease increased. We found NLR, PLR, SII, SIRI, and AISI indices as the independent risk factors for the presence and severity of HG. The SIRI index, which has the highest area under the curve (AUC), sensitivity, and specificity values, was determined as the most powerful diagnostic tool in the diagnostic evaluation of the presence (AUC: 0.695; p < 0.001; sensitivity: 54%; specificity: 75%; cut-off: 3.14) and severity (AUC: 0.785; p < 0.001, sensitivity: 82%; specificity: 68%; cut-off: 2.74) of HG. CONCLUSIONS: Our study results showed that combined systemic inflammatory indices (NLR, PLR, SII, SIRI, and AISI) are associated and correlated with the presence and severity of HG. These indices are independent risk factors for the presence and severity of HG. Combined systemic inflammatory indices are diagnostic in determining the severity of HG. The SIRI index has the best diagnostic power for both the diagnosis of HG and the determination of the severity of HG.

[A case of very long chain acyl-CoA dehydrogenase deficiency diagnosed due to a trigger of hyperemesis gravidarum during pregnancy].

A 25-year-old Japanese woman with a history of repeated episodes of rhabdomyolysis since the age of 12 presented with rhabdomyolysis caused by hyperemesis gravidarum. Blood tests showed an elevated serum CK level (11,755 |IU/l; normal: 30-180 |IU/l). Carnitine fractionation analysis revealed low levels of total carnitine (18.3 |µmol/l; normal: 45-91 |µmol/l), free carnitine (13.1 |µmol/l; normal: 36-74 |µmol/l), and acylcarnitine (5.2 |µmol/l; normal: 6-23 |µmol/l). Tandem mass spectrometry showed high levels of C14:1 acylcarnitine (0.84 |nmol/ml: normal: <0.4 |nmol/ml) and a high C14:1/C2 ratio of 0.253 (normal: <0.013), indicating a potential diagnosis of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Enzyme activity measurement in the patient's peripheral blood lymphocytes confirmed the diagnosis of VLCAD deficiency, with low palmitoyl-CoA dehydrogenase levels (6.5% of normal control value). With the patient's informed consent, acyl-CoA dehydrogenase very long-chain (ACADVL) gene analysis revealed compound heterozygous mutations of c.1332G>A in exon 13 and c.1349G>A (p.R450H) in exon 14. In Japan, neonatal mass screening is performed to detect congenital metabolic diseases. With the introduction of tandem mass screening in 2014, fatty acid metabolism disorders, including VLCAD deficiency, are being detected before the onset of symptoms. However, it is important to note that mass screening cannot detect all cases of this disease. For patients with recurrent rhabdomyolysis, it is essential to consider congenital diseases, including fatty acid metabolism disorders, as a potential diagnosis.

Helicobacter pylori Exposure in Nausea and Vomiting of Pregnancy Increases Risk of Preterm Delivery.

Background: Hyperemesis gravidarum (HG), a severe form of nausea and vomiting in pregnancy (NVP), is a leading indication for hospitalization in the first trimester. NVP and HG are associated with Helicobacter pylori (HP) infection in non-United States cohorts. How HP exposure and NVP interact to affect metabolic disturbance and pregnancy outcomes is not known. Materials and Methods: We designed a retrospective cohort study relating HP and NVP to serum electrolyte laboratory results, preterm delivery, and infant birth weight. Single academic institution discovery and independent multi-institutional validation cohorts included pregnant subjects with an HP test result. Associations of HP, NVP, and pregnancy outcomes were assessed with odds ratio calculations, Student's t-tests, and multivariate logistic regression. Results: Among subjects with positive HP test results, the prevalence of hyperemesis gravidarum (HG) was 0.025 (66 of 2671) and NVP was 0.27 (710 of 2671). Subjects with negative HP had prevalence of HG 0.015 (165 of 10,960) and NVP 0.22 (2392 of 10,960). History of HP exposure increased risk of NVP, including HG (odds ratio 1.3, 95% CI 1.1-1.4). Patients with HP exposure had lower serum potassium (mean difference 0.1 mEq/L) and bicarbonate (mean difference 0.3 mEq/L) during pregnancy than HP-negative patients (p < 0.01). Serum potassium was lowest in subjects with both NVP and HP exposure (mean 3.5 mEq/L [3.4-3.6], p < 0.0001). HP exposure alone carried increased risk for preterm delivery (OR 1.3 [1.1-1.4]). NVP alone increased risk of preterm delivery (OR 2.8 [2.5-3.1]) including second trimester delivery (OR 2.2 [1.7-2.8]). In multivariate analysis, HP exposure in the setting of NVP further increased risk of preterm delivery (adjusted OR 1.4 [1.0-1.9], p = 0.03). Conclusions: H. pylori exposure and diagnosis of NVP are individually associated with metabolic disturbances and adverse pregnancy outcomes such as preterm labor and delivery, and their combination further increases risk in US populations.

Acute Myositis in a Pregnant Woman Complicated With COVID-19 and Hyperemesis Gravidarum: A Case Report.

Myalgia is the most frequently reported neuromuscular symptom in COVID-19 patients, with a frequency of around 20% in pregnant women. Acute myositis due to COVID-19 is severe and requires medical intervention. There have been some reports of acute myositis due to COVID-19, mostly in elderly men, but rarely in pregnant women. Here we report a case of a pregnant woman who was diagnosed with acute myositis following COVID-19 illness early in her pregnancy. She had been affected by morning sickness since the 6th week of gestation and was diagnosed with COVID-19 at the 12th week. Muscle pain appeared in her limbs 5 days after the diagnosis of COVID-19, with a predominance of pain in the lower limbs, and her gait gradually became unstable. We concluded that it was acute myositis complicated by COVID-19 and hypokalemia, but we could not determine whether hypokalemia or COVID-19 or both were the cause of the muscle damage in this case. Pregnant women diagnosed with COVID-19 often complain of myalgia and fatigue, and when a pregnant woman's symptoms are severe we should keep in mind that they may be suffering from muscle damage that needs medical intervention.