Comparison of orexigenic and anorexigenic neuropeptide levels in hyperemesis gravidarum patients with normal pregnant women: A prospective cohort study.

BACKGROUND: The aim of this study was to determine whether orexigenic neuropeptides, orexin and galanin, and anorexigenic neuropeptides, alpha-melanocyte-stimulating hormone (α-MSH) and cocaine- and amphetamine-regulated transcript (CART), are implicated in hyperemesis gravidarum (HG). METHODS: Fifty pregnant women who had been diagnosed with HG between April 2022 and February 2023 at the Siirt University Faculty of Medicine Training and Research Hospital (tertiary center) were recruited for this study. An equal number of pregnant women without an HG diagnosis were included in the study as the control group. Participants' age, pregnancy history, medical history, thyroid function test results, complete blood count results, and electrolyte levels were recorded, and their orexin, galanin, α-MSH, and CART serum levels were analyzed using an enzyme-linked immunosorbent assay. RESULTS: No statistically significant differences in orexigenic neuropeptides (orexin and galanin) were observed between the HG and control groups. A statistical difference was found between an anorexigenic neuropeptide (α-MSH) and the control group (P = .012). Based on a receiver operating characteristic analysis, the α-MSH parameter was statistically significant for distinguishing between participants with an HG diagnosis and those without, with a sensitivity of 63.6%, specificity of 65.9%, and cutoff value of 11769.3 pg/mL (P = .012, area under curve: 0.655). Based on the severity classification of ketonuria (ketonuria levels of +1 or +2 were classified as mild, whereas levels of +3 or +4 were classified as moderate to severe), the anorexigenic CART neuropeptide was found to be a statistically significant diagnostic indicator of severe ketonuria (P = .020). CONCLUSION: α-MSH and CART levels were found to be related in HG patients and in HG patients with severe ketonuria.

Investigation of serum spexin concentrations in pregnant women diagnosed with hyperemesis gravidarum.

OBJECTIVE: We aimed to investigate the serum concentration of the spexin, which has been shown to have an anorexic effect in animal models, in pregnant women with hyperemesis gravidarum (HG). METHODS: This case-control study was conducted with 80 pregnant women who applied to the Umraniye Training and Research Hospital Gynecology and Obstetrics Clinic between April 2022 and September 2022. The HG group consisted of 40 pregnant women who were diagnosed with HG in the first 14 weeks of pregnancy, and the control group consisted of 40 healthy pregnant women matched with the HG group in terms of age, BMI, and gestational week. RESULTS: Both groups were similar in terms of demographic characteristics and gestational age at blood sampling for spexin (p > 0.05). While maternal serum spexin concentration was 342.4 pg/ml in the HG group, it was 272.8 pg/ml in the control group (p = 0.003). ROC analysis was performed to determine the value of maternal serum spexin concentration in terms of predicting HG. AUC analysis of maternal serum spexin for HG estimation was 0.693 (p = 0.003, 95% CI =0.577 - 0.809). The optimal cutoff value for maternal serum spexin concentration was determined as 305.90 pg/ml with 65% sensitivity and 65% specificity. CONCLUSIONS: High serum spexin concentration is thought to play a role in the etiopathogenesis of HG, and this should be supported by demonstrating changes in serum spexin concentrations in pregnant women with HG whose symptoms alleviated and weight regain started after treatment.

An evaluation of serum blood parameters and amyloid-A levels in women with hyperemesis gravidarum; A prospective observational study.

This study aimed to investigate whether serum amyloid A (AA) level can be used as a biomarker in women with hyperemesis gravidarum (HEG). This prospective observational study was conducted at the Antalya Training and Research Hospital Gynecology and Obstetrics Clinic, Türkiye, between July and December 2023. Forty women diagnosed with HEG and 40 healthy women were included. No statistically significant differences were observed between the groups in terms of sociodemographic data such as age, body mass index, family history, educational status, economic level, place of residence, occupation, smoking and alcohol use, or drug habits. However, obstetric characteristics such as number of miscarriages, number of dilatation curettages, and gestational age and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocyte, platelet, free T4, albumin, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, hs-C-reactive protein, and sodium (P > .05) all differed significantly. In addition, significant differences were observed between the HEG and healthy groups in terms of numbers of gravidities (2 [1-3] vs 1 [0-1], respectively, P < .001), numbers of parities (1 [0-1] vs 1 [0-1], P < .001), numbers of living children (1 [0-2] vs 1 [0-1], P < .001), presenting complaints (nausea 0 [0%], nausea + vomiting 0 [0%], none 40 [100.0%] vs nausea 27 [67.5%], nausea + vomiting 13 [32.5%], none 0 [0%], P < .001), serum thyroid-stimulating hormone (1.16 ±â€…0.56 vs 1.81 ±â€…0.624, P = .004), potassium (4.1 ±â€…0.7 vs 3.8 ±â€…0.2, P = .001), and AA values (7.29 ±â€…2.61 vs 10.74 ±â€…3.04, P < .001). At receiver operating characteristic analysis, the area under the curve (AUC: 0.881) was statistically significant for serum AA (P: <.001), with a cutoff value of ≥ 8.79 ([95% confidence interval] 0.743-0.919, sensitivity 87.4%, specificity 80.2%). The positive predictive value of serum AA was 81.1% and the negative predictive value was 80.4%. The study results showed that serum AA can be used as a diagnostic biomarker in HEG. Prospective studies involving more participants are now required to confirm our results.

Low-density lipoprotein cholesterol and the risk of hyperemesis gravidarum: a Mendelian randomization study.

OBJECTIVE: The inconsistency in conclusions from early observational studies has sparked our interest in elucidating the relationship between lipid levels and susceptibility to hyperemesis gravidarum (HG). This study wishes to employed Mendelian randomization analysis to investigate the causal relationship between low-density lipoprotein cholesterol (LDL-C) and HG. METHODS: We employed Tow-Sample MR analysis to investigate the causal associations between LDL-C and HG. Specific variables were selected from GWAS database for MR analysis, using single nucleotide polymorphisms (SNPs) as our instruments. The threshold for significant SNPs as genetic instruments has been set at 5 × 10-8. F-statistic was employed to validate the strength of exposure instruments. The causality was mainly evaluated by Inverse Variance Weighted method (IVW). To address potential bias from the selection of genetic variants with pleiotropic effects, sensitivity analysis was performed by Cochrane Q-test, MR Egger, weighted median, MR-PRESSO and Leave-one-out methods. To validate the directionality of causal relationships, we employed Steiger test to filter SNPs. At last, we conducted reverse MR to exclude the causal impact of HG on LDL-C levels. RESULTS: Our MR results identified the effect of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG (OR:1.30; 95%CI:1.03-1.65; p = 0.028). In reverse MR analyses, no evidence was found for causal effect of HG on LDL-C levels (OR:1.00; 95%CI:1.00-1.01; p = 0.163). Sensitivity analyses were used to confirm reliability. CONCLUSION: This study may have provided evidence of genetically predicted increased LDL-C levels on increased genetic susceptibility to HG. Appropriate lowering LDL-C levels may serve as a preventive and treatment measure for HG.

Association between Dietary Inflammatory Index and Hyperemesis Gravidarum.

(1) Background: Diet holds a pivotal position in exacerbating or ameliorating chronic inflammation, which has been implicated in the pathogenesis of hyperemesis gravidarum (HG). However, no study has explored the association between dietary inflammatory potential and HG. This study aimed to investigate the potential correlation between following a pro-inflammatory diet and the likelihood of developing HG. (2) Methods: A total of 2033 Chinese pregnant women (mean age: 31.3 ± 3.4 years) were included in this cross-sectional study from April 2021 to September 2022 as part of the China Birth Cohort Study (CBCS). Dietary inflammatory index (DII) scores with 23 food components were constructed through dietary intakes collected via a reliable 108-item semi-quantitative food frequency questionnaire. HG was defined as a pregnancy-unique quantification of emesis (PUQE) score ≥13 points, severe nausea and vomiting leading to weight loss ≥5%, or being hospitalized for treatment due to the disease. The relationship between DII and HG was conducted utilizing binary logistic regression and restricted cubic spline regression. (3) Results: Overall, 8.2% (n = 167) of study participants had HG. The DII scores ranged from -4.04 to 3.82. After adjusting for potential confounders, individuals with the highest tertile of DII score had a higher risk of HG (OR = 1.65, 95% CI: 1.04, 2.62, Ptrend = 0.032). Such an association was stronger in those with pre-pregnancy overweight/obesity (Pinteraction = 0.018). (4) Conclusions: A higher DII score, which serves as a marker for a diet promoting inflammation, is correlated with an elevated risk of developing HG. This finding suggests that dietary recommendations for HG should focus on minimizing the DII through incorporating foods abundant in anti-inflammatory components.

Hyperemesis gravidarum and the risk of offspring morbidity: a longitudinal cohort study.

PURPOSE: Hyperemesis gravidarum has the potential to affect the long-term health of offspring. We examined whether maternal hyperemesis gravidarum was associated with the risk of hospitalization for childhood morbidity. METHODS: We conducted a longitudinal cohort study of 1,189,000 children born in Quebec, Canada, between April 2006 and March 2021. The main exposure measure was maternal hyperemesis gravidarum requiring hospitalization in the first or second trimester. The outcome was any pediatric admission between birth and 16 years of age, with follow-up ending in March 2022. We used Cox regression models adjusted for maternal and socioeconomic factors to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between maternal hyperemesis gravidarum and childhood hospitalization. RESULTS: Among 1,189,000 children, 6904 (0.6%) were exposed to maternal hyperemesis gravidarum. Hospitalization rates at age 16 years were higher for children exposed to hyperemesis gravidarum than unexposed children (47.6 vs 43.9 per 100 children). Relative to no exposure, hyperemesis gravidarum was associated with a 1.21 times greater risk of any hospitalization before 16 years (95% CI 1.17-1.26). Hyperemesis gravidarum was associated with hospitalization for neurologic (HR 1.50, 95% CI 1.32-1.71), developmental (HR 1.51, 95% CI 1.29-1.76), digestive (HR 1.40, 95% CI 1.30-1.52), and allergic disorders (HR 1.39, 95% CI 1.24-1.56). When contrasted with preeclampsia, hyperemesis gravidarum was a stronger risk factor for these outcomes. CONCLUSIONS: Maternal hyperemesis gravidarum is associated with an increased risk of childhood hospitalization, especially for neurologic, developmental, digestive, and atopic disorders. WHAT IS KNOWN: • Hyperemesis gravidarum is associated with neurodevelopmental disorders in offspring. • However, the effect of hyperemesis gravidarum on other childhood morbidity is unclear. WHAT IS NEW: • In this longitudinal cohort study of 1.2 million children, maternal hyperemesis gravidarum was associated with a greater risk of hospitalization before age 16 years. • Exposure to hyperemesis gravidarum was associated with developmental, neurologic, atopic, and digestive morbidity in childhood.

Primary achalasia diagnosed during pregnancy: rare cause of nausea and vomiting.

Nausea and vomiting during pregnancy are very common; however, when persistent symptoms lead to severe malnutrition, other conditions should be considered. We present a patient with severe postprandial nausea and vomiting resulting in 120 lb weight loss. She was treated for presumed hyperemesis gravidarum but diagnosed with achalasia type 1 upon further work-up. The pregnancy was further complicated by fetal growth restriction, shortened cervix and preterm premature rupture of membranes, and resulted in delivery at 26 weeks of gestation. Postpartum, she underwent a peroral endoscopic myotomy procedure and has returned to normal body mass index.The differential for nausea/vomiting is broad, and major medical conditions can manifest for the first time during pregnancy. Severe malnutrition adversely affects maternal and fetal health. Further work-up should be pursued when symptoms cannot otherwise be explained.

The Effect of Hyperemesis Gravidarum on Macular Thickness, Corneal Thickness, and Intraocular Pressure in Pregnancy.

AIM: Physiological changes in intraocular pressure as well as in the cornea and macula may occur during pregnancy. Therefore, we decided to investigate the effect of hyperemesis gravidarum on macular thickness, corneal thickness and intraocular pressure (IOP). MATERIAL AND METHODS: A total of 110 people, 55 of whom were diagnosed with hyperemesis gravidarum and 55 of whom were in the control group, were included in the study. The inclusion criteria for the study were as follows: first trimester (8-14 weeks of gestation) pregnancy with positive fetal heartbeat and no history of systemic disease, no continuous use of medication, diagnosis of hyperemesis gravidarum (ketonuria and weight loss of more than 3 kilograms or 5% of body weight), body mass index (BMI) within normal limits, age between 18 and 40, no alcohol use or smoking. RESULTS: In the HG group compared to the control group, there was a difference between the CCT values of both the right and left eyes (p<0.01). There was a difference in both right and left IOP values in patients in the HG group compared to the control group (p<0.05), and there was no correlation between ketonuria scores and right and left eye CCT values, right and left eye macular thickness, and right and left eye pressure in patients diagnosed with HG (p>0.05). CONCLUSION: In hyperemesis gravidarum, changes occur in IOP, corneal thickness, and macular thickness. In ophthalmic examinations in the pregestational period, especially for women with systemic disease, it may be important for clinicians to take the necessary precautions in this regard.

Hyperemesis gravidarum theories dispelled by recent research: a paradigm change for better care and outcomes.

Nausea and vomiting (NVP) affect most pregnant women. At the severe end of the clinical spectrum, hyperemesis gravidarum (HG) can be life-threatening. The condition is fraught with misconceptions that have slowed progress and left women undertreated. Herein, recent scientific advances are presented that dispel common myths associated with HG related to maternal/offspring outcomes, etiology, and evolution. There is now strong evidence that (i) HG is associated with poor outcomes, (ii) a common cause of NVP and HG has been identified, and (iii) NVP is likely a protective evolutionary mechanism that occurs throughout the animal kingdom but is no longer necessary for human survival. Therefore, it is encouraging that we are finally on the cusp of testing treatments that may put an end to unnecessary suffering.

"Navigating in a maze without a map". Partners' experiences of hyperemesis gravidarum- a qualitative study.

OBJECTIVE: A supportive environment for women with Hyperemesis Gravidarum is crucial but not always provided. There is a lack of research regarding Hyperemesis Gravidarum, its impact on the family, and the partner's perception of supporting their spouse. Thus, this study aims to explore partners' experiences of Hyperemesis Gravidarum during their spousés pregnancy. METHODS: Data were gathered through 13 individual, semi-structured, in-depth, digital interviews with partners of women who had experienced Hyperemesis Gravidarum and analysed with Qualitative Content Analysis. The partners were recruited through advertisement on a social media platform and were exclusively males, representing 8 of 21 Swedish regions. The mean age was 34, and they had, on average, 1 previous child. The mean time from the experience to the interview was 12 months. FINDINGS: The main theme, "Navigating in a maze without a map", explains partners' situation as stressful and demanding when their spouse suffers from Hyperemesis Gravidarum, with insufficient support and guidance from healthcare providers. The analysis resulted in three themes: "Standing alone with a demanding responsibility", "Being in a lottery when facing healthcare", and "Climbing the mountain together." The themes display challenges within everyday life and healthcare, as well as strained relations within the family. CONCLUSION: Partners experience a need to support their spouse in every aspect of daily life and advocate for adequate healthcare. Healthcare professionals must support and acknowledge the partners' struggles during the demanding situation with Hyperemesis Gravidarum.

[Nausea and vomiting in pregnancy]. / Nausées et vomissements gravidiques.

NAUSEA AND VOMITING IN PREGNANCY. Nausea and vomiting during pregnancy are common symptoms experienced by pregnant women. In more severe cases, known as hyperemesis gravidarum, these symptoms can become a pathological condition that can lead to significant complications in both the short and long term. Short-term complications include hydro-electrolyte imbalances, pregnancy termination, and growth retardation. Long-term complications may include anxiety disorders, depression, and post-traumatic stress disorder. Mild cases can often be alleviated through lifestyle and dietary adjustments or non-pharmacological treatments like ginger, acupuncture, or acupressure. However, moderate to severe cases require specific psychological support, anti-emetic treatments, and sometimes hospitalization with intravenous treatment and parenteral rehydration. Managing these cases is complex and challenging because it does not guarantee the complete disappearance of symptoms, which can pose difficulties for caregivers.

NAUSÉES ET VOMISSEMENTS GRAVIDIQUES. Les nausées et vomissements de la grossesse sont un symptôme classique chez la femme enceinte. Le plus souvent sans gravité, les formes modérées à sévères, appelées hyperémèse gravidique, constituent une pathologie qui peut être invalidante, source de complications de la grossesse à court terme (troubles hydroélectrolytiques, arrêt de grossesse, retard de croissance) mais aussi à long terme (troubles anxiodépressifs, état de stress post-traumatique). Les formes minimes peuvent être atténuées par des règles hygiénodiététiques ou des traitements non médicamenteux (gingembre, acupuncture, acupression). Les formes modérées à sévères nécessitent un accompagnement psychologique spécifique, des traitements antiémétiques et, parfois, une hospitalisation avec traitement par voie intraveineuse et réhydratation parentérale. Leur prise en charge est complexe et difficile car elle ne permet pas toujours une disparition des symptômes, ce qui peut mettre en difficulté les soignants.

Visual loss and encephalopathy in a pregnant patient with hyperemesis gravidarum.

A pregnant woman in her 20s at 17 weeks of gestation, presented with symptoms of painless diminution of vision preceded by 8 weeks history of hyperemesis gravidarum. On examination, she was confused, disoriented and had gait ataxia with complete loss of vision in both eyes. Fundus examination revealed grade 4 disc oedema with superficial retinal haemorrhages. Possibilities kept were cerebral venous sinus thrombosis, neuromyelitis optica spectrum disorder, posterior reversible encephalopathy syndrome and Wernicke's encephalopathy (WE). Thiamine levels were low. MRI brain with MR venography revealed symmetrical areas of hyperintensities in bilateral medial thalami, hypothalamus, mammillary body and area postrema. She was managed as a case of WE with intravenous thiamine with complete clinical and radiological resolution within 2 weeks of treatment. Therefore, we conclude that a high index of suspicion of WE in appropriate clinical settings leading to early treatment can potentially reverse its grave clinical symptoms and complications.

Evaluation of controlling nutritional status (CONUT) score in the prognosis of hyperemesis gravidarum.

OBJECTIVE: To investigate the predictive value of the Controlling Nutritional Status (CONUT) score on hyperemesis gravidarum (HG) severity, hospitalization, and length of stay. MATERIALS AND METHODS: This retrospective cross-sectional study, conducted between December 2022 and June 2023, involved two groups. Group 1 comprised 52 pregnant women diagnosed with HG in the first trimester, receiving hospitalization and treatment. Group 2 included 105 pregnant women diagnosed with HG in the first trimester, managed and treated as outpatients. The CONUT score was calculated with the formula: Serum albumin score + total lymphocyte score + total cholesterol score. This score is calculated with a number of points between 0 and 12. The interpretation of the score involves four categories: normal (0-1), light (2-4), moderate (5-8), and severe (9-12). RESULTS: The CONUT score differed significantly between the hospitalized (4, IQR: 2.25-5) and outpatient groups (2, IQR: 2-3) (p < 0.001). A CONUT score >3 was associated with the need for hospitalization, demonstrating a sensitivity of 60%, a specificity of 84% (p < 0.001). The CONUT score was the parameter with the highest odds ratio (OR) value among the parameters related to the need for hospitalization, and each unit increase in the CONUT score increased the need for hospitalization by 1.683 times [OR = 1.683 (95% CI: 1.042-2.718), p = 0.033]. A positive correlation was found between the CONUT score and the duration of hospital stay (r = 0.316, p = 0.023). CONCLUSIONS: This study suggests CONUT score as a valuable tool for predicting HG severity, hospitalization need, and duration of hospital stay.

Primary hyperparathyroidism in pregnancy: a case report highlighting uncommon complication.

Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After localization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid adenoma. During follow-up, intrauterine growth restriction and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncommon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.

El hiperparatiroidismo primario (HPTP) se caracteriza por niveles elevados de calcio y hormona paratiroidea (PTH). Sin embargo, la interpretación de pruebas diagnósticas, como los niveles de calcio sérico y PTH, es compleja en mujeres embarazadas. El objetivo de este reporte es presentar un caso de HPTP en una adolescente embarazada, con especial hincapié en una complicación infrecuente, así como en las estrategias diagnósticas y de tratamiento. Una mujer embarazada de 17 años presentó hiperémesis gravídica y síntomas neurológicos, lo que llevó al diagnóstico de trombosis venosa cerebral. Posteriores investigaciones revelaron hipercalcemia y niveles persistentemente elevados de PTH, consistentes con HPTP. Tras la realización de estudios de localización, la paciente fue sometida a una paratiroidectomía de emergencia con diagnóstico de adenoma de paratiroides. Durante el seguimiento, se desarrolló restricción del crecimiento intrauterino y preeclampsia grave, lo que resultó en la necesidad de realizar una cesárea de emergencia. Tanto la madre como el neonato evolucionaron favorablemente. El HPTP es una condición infrecuente en la población embarazada y su diagnóstico puede ser desafiante por la superposición de síntomas con los cambios fisiológicos normales del embarazo. La aparición de complicaciones infrecuentes, como fenómenos trombóticos, resalta la necesidad de un abordaje integral para garantizar la detección y el manejo temprano. En la mayoría de los casos, la paratiroidectomía es el tratamiento de elección.

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.

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.

Kikuchi-Fujimoto disease during early pregnancy.

Kikuchi-Fujimoto disease (KFD) is rare during pregnancy. It is characterized by necrotizing lymphadenitis and often occurs in young Asian women. We report a case of KFD during pregnancy, which was difficult to diagnose. A 37-year-old pregnant female (gestational week [GW] 7+5) was admitted to our hospital because of hyperemesis gravidarum. On the eighth day of hospitalization (GW 8+6), she suddenly developed a fever (38.0°C) with skin rash and posterior pharynx redness. Blood tests showed pancytopenia and abnormal liver function. The patient was misdiagnosed with severe Epstein-Barr virus infection and administered with prednisolone. Subsequently, cervical lymphadenopathy was observed, and biopsy results led to the diagnosis of KFD. Thereafter, her symptoms improved, and she was discharged at GW 13+4. KFD must be included as a differential diagnosis for patients with fever, abnormal liver function, and pancytopenia during pregnancy.