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.

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.

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.

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.

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.

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.

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.

Hyperemesis gravidarum: Associations with personal and family history of nausea.

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.

Risk of Cardiovascular Disease in Women With a History of Hyperemesis Gravidarum, With and Without Preeclampsia.

Background Hyperemesis gravidarum is associated with preeclampsia, but it is unclear whether hyperemesis gravidarum is a risk factor for cardiovascular disease. We assessed the long-term risk of cardiovascular disease in women who experienced hyperemesis gravidarum with or without preeclampsia. Methods and Results We analyzed a longitudinal cohort of 1 413 166 pregnant women in Quebec between 1989 and 2021. Women were followed from their first pregnancy up to 3 decades later. We computed hazard ratios (HRs) and 95% CIs for the association of hyperemesis gravidarum, preeclampsia, or both conditions with subsequent risk of cardiovascular hospitalization using Cox regression models adjusted for baseline characteristics. Among 1 413 166 women, 16 288 (1.2%) had hyperemesis gravidarum only, 69 645 (4.9%) preeclampsia only, and 1103 (0.08%) had both conditions. After 32 years of follow-up, cardiovascular disease incidence was 17.7 per 100 women with hyperemesis gravidarum only, 28.2 per 100 women with preeclampsia only, 30.9 per 100 women with both exposures, and 14.0 per 100 women with neither exposure. Compared with no exposure, women with both hyperemesis and preeclampsia had the greatest risk of cardiovascular hospitalization (HR, 3.54 [95% CI, 3.03-4.14]), followed by women with preeclampsia only (HR, 2.58 [95% CI, 2.51-2.64]) and hyperemesis only (HR, 1.46 [95% CI, 1.38-1.54]). Having both hyperemesis gravidarum and preeclampsia was strongly associated with valve disease (HR, 3.38 [95% CI, 1.69-6.75]), heart failure (HR, 3.43 [95% CI, 1.79-6.59]), and cardiomyopathy (HR, 4.17 [95% CI, 1.99-8.76]). Conclusions Hyperemesis gravidarum is associated with the development of cardiovascular disease, whether preeclampsia is present or not.

Placenta-associated adverse pregnancy outcomes in women experiencing mild or severe hyperemesis gravidarum - a systematic review and meta-analysis.

BACKGROUND: Nausea and vomiting in pregnancy (NVP) affects 50-80% of pregnant women and is correlated to the level of human chorionic gonadotropin (hCG). Hyperemesis gravidarum (HG) is a severe condition, with an incidence of 0.2-1.5%, characterized by consistent nausea, vomiting, weight loss and dehydration continuing after the second trimester. AIM: The aim of this systematic review was to investigate a potential correlation between NVP or HG with adverse pregnancy outcomes and hCG levels. METHOD: A systematic search in PubMed, Embase and CINAHL Complete was conducted. Studies on pregnant women with nausea in the first or second trimester, reporting either pregnancy outcomes or levels of hCG were included. The primary outcomes were preterm delivery (PTD), preeclampsia, miscarriage, and fetal growth restriction. Risk of bias was assessed using ROBINS-I. The overall certainty of evidence was assessed using GRADE. RESULTS: The search resulted in 2023 potentially relevant studies; 23 were included. The evidence was uncertain for all outcomes, however women with HG had a tendency to have an increased risk for preeclampsia [odds ratio (OR) 1.18, 95% confidence of interval (CI) 1.03 to 1.35], PTD [OR 1.35, 95% CI 1.13 to 1.61], small for gestational age (SGA) [OR 1.24, 95% CI 1.13 to 1.35], and low birth weight (LBW) [OR 1.35, 95% CI 1.26 to 1.44]. Further, a higher fetal female/male ratio was observed [OR 1.36, 95% CI 1.15 to 1.60]. Meta-analyses were not performed for women with NVP; however, most of these studies indicated that women with NVP have a lower risk for PTD and LBW and a higher risk for SGA, and a higher fetal female/male ratio. CONCLUSION: There may be an increased risk in women with HG and a decreased risk in women with NVP for adverse placenta-associated pregnancy outcomes, however the evidence is very uncertain. TRIAL REGISTRATION: PROSPERO: CRD42021281218.

Determinants of hyperemesis gravidarum among pregnant women attending antenatal care at public and private hospitals in Bahir Dar City, North-West Ethiopia, 2022: a multicenter unmatched case control study.

INTRODUCTION: Hyperemesis gravidarum is a severe form of nausea and vomiting during pregnancy characterized by more than 5% weight loss and ketonuria. Although there are cases in Ethiopia, there is still insufficient information regarding the determinant factors of hyperemesis gravidarum.This finding helps to decrease maternal as well as fetal complications of hyperemesis gravidarum by early identification of pregnant mothers who are at high risk. This study aimed to assess determinants of hyperemesis gravidarum among pregnant women attending antenatal care at public and private hospitals in Bahir Dar, North-West Ethiopia, 2022. METHOD: A multicenter, facility-based, unmatched case-control study was conducted on 444 pregnant women (148 cases and 296 controls) from January 1 to May 30. Women with a documented diagnosis of hyperemesis gravidarum on the patient chart were considered as cases, and women who attended antenatal care service without hyperemesis gravidarum were assigned as controls. Cases were selected using a consecutive sampling technique, whereas controls were selected using systematic random sampling technique. Data were collected using an interviewer-administered structured questionnaire. The data were entered into EPI-Data version 3 and exported into SPSS version 23 for analysis. Multivariable logistic regression was performed to identify determinants of hyperemesis gravidarum at a p-value of less than 0.05. An adjusted odds ratio with a 95% confidence interval was used to determine the direction of association. RESULTS: Living in urban (AOR = 2.717, 95% CI : 1.693,4.502), primigravida (AOR = 6.185, 95% CI: 3.135, 12.202), first& second trimester of pregnancy (AOR = 9.301, 95% CI: 2.877,30.067) & (AOR = 4.785, 95% CI: 1.449,15.805) respectively, family history of hyperemesis gravidarum (AOR = 2.929, 95% CI: 1.268,6.765), helicobacter pylori (AOR = 4.881, 95% CI: 2.053, 11.606) & Depression (AOR = 2.195, 95% CI: 1.004,4.797) were found to be determinants of hyperemesis gravidarum. CONCLUSION: Living in an urban area, primigravida woman, being in the first and second trimester, having family history of hyperemesis gravidarum, Helicobacter pylori infection, and having depression were the determinants of hyperemesis gravidarum. Primigravid women, those living in urban areas, and women who have a family history of hyperemesis gravidarum should have psychological support and early treatment initiation if they develop nausea and vomiting during pregnancy. Routing screening for Helicobacter pylori infection and mental health care for a mother with depression at the time of preconception care may decreases hyperemesis gravidarum significantly during pregnancy.

Perinatal outcomes of infants born to mothers with hyperemesis gravidarum: A systematic review and meta-analysis.

BACKGROUND: Hyperemesis gravidarum is the severe form of nausea and vomiting during pregnancy and can lead to undernutrition and low maternal weight gain. Previous epidemiologic and animal studies have shown that undernutrition and low maternal weight gain in pregnancy can increase the risk of unfavorable perinatal outcomes, like shorter gestational age, small for gestational age and lower weight at birth. OBJECTIVE: To evaluate the effect of hyperemesis gravidarum on perinatal outcomes. SEARCH STRATEGY: OVID Medline and Embase were searched from inception to February 9th, 2022. STUDY ELIGIBILITY: Studies reporting on perinatal outcomes of infants born to mothers with hyperemesis gravidarum or severe nausea and vomiting in pregnancy were included. Case reports, case series, animal studies, reviews, editorials and conference abstracts were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected and extracted data. Risk of bias was assessed by the Newcastle-Ottawa Quality Assessment Scale. We conducted meta-analyses where possible. RESULTS: Our search yielded 1387 unique papers, of which 61 studies (n = 20,532,671 participants) were included in our systematic review. Meta-analyses showed that hyperemesis gravidarum was associated with preterm birth < 34 weeks (2 studies n = 2,882: OR 2.81, 95 %CI: 1.69-4.67), birth weight < 1500 g (2 studies, n = 489,141: OR 1.43, 95 %CI: 1.02-1.99), neonatal resuscitation (2 studies, n = 4,289,344: OR 1.07, 95 %CI: 1.05-1.10), neonatal intensive care unit admission (7 studies, n = 6,509,702: OR 1.20, 95 %CI: 1.14-1.26) and placental abruption (6 studies, n = 9,368,360: OR 1.15, 95 %CI: 1.05-1.25). Hyperemesis gravidarum was associated with reductions in birthweight > 4000 g (2 studies, n = 5,503,120: OR 0.74, 95 %CI: 0.72-0.76) and stillbirth (9 studies, n = 3,973,154: OR 0.92, 95 %CI: 0.85-0.99). Meta-analyses revealed no association between hyperemesis gravidarum and Apgar scores < 7 at 1 and 5 min; fetal loss, perinatal deaths and neonatal deaths. CONCLUSION: Hyperemesis gravidarum is associated with several adverse perinatal outcomes including low birth weight and preterm birth. We also found that pregnancies complicated by hyperemesis gravidarum less frequently were complicated by macrosomia and stillbirth. We were unable to investigate underlying mechanisms.

Proportion of hyperemesis gravidarum and associated factors among pregnant women admitted into the obstetrics ward at Akesta general hospital, North East Ethiopia.

INTRODUCTION: Hyperemesis gravidarum is a condition of intractable vomiting during pregnancy that leads to fluid and electrolyte imbalance, nutrition deficiency and weight loss often requiring hospital admission. Approximately 0.3%-10.8% of pregnant women experience nausea and vomiting during the first trimester of pregnancy. It has been associated with both maternal and fetal morbidity. There is limited evidence about the proportion of hyperemesis gravidarum and associated factors in the study area. OBJECTIVE: The aim of this study was to determine the proportion of hyperemesis gravidarum and associated factors among pregnant women admitted into the obstetric ward at Akesta General Hospital, South Wollo Zone, Ethiopia. METHODS: This is hospital-based cross-sectional study of 355 pregnant mothers in Akesta general hospital in northeast Ethiopia from September 1/2018- to August 30 /2020. A simple random sampling technique was used to select the patient card from the whole admission of pregnant women cards during the study period. The diagnosis of hyperemesis gravidarum include persistent vomiting not related to other causes, an objective measure of acute starvation, electrolyte abnormalities and acid-base disturbances, as well as weight loss. The data analysis was done using SPSS version 25. Bivariable and multivariable binary logistic regression analysis was conducted to identify factors associated with hyperemesis gravidarum. Adjusted odds ratio (AOR) with 95% confidence intervals (CI) was reported to show the strength of the association. Statistical significance was stated at P-value < 0.05. RESULTS: The proportion of hyperemesis gravidarum was 11.3%. Women with previous history of hyperemesis gravidarum AOR (95%CI) = 10.9[2.46, 48.44], previous history of urinary tract infection AOR (95%CI) = 4.32[1.58, 11.86], previous history of gastrointestinal disease AOR (95% CI) = 4.12[1.40, 12.65], history of abortion AOR (95% CI) = 6.23[2.24, 17.52] were factors significantly associated with hyperemesis gravidarum. CONCLUSION: In this study, the overall hospital proportion of hyperemesis gravidarum was high. History of gastrointestinal disease, previous history of urinary tract infection, history of hyperemesis gravidarum, and history of abortion were the major risk factors.

Association between Hyperemesis Gravidarum in pregnancy on postnatal ability of infants to attend to a play task with their mother.

Research indicates a higher prevalence of attention deficits in children exposed to HG in utero compared to controls with some claiming that the deficit is due to prenatal effects of malnutrition in HG mothers and others that it is due to maternal mental health after birth. The current study examines the effect of hyperemesis gravidarum (HG) diagnosis during pregnancy on infant attention controlling for maternal stress, depression anxiety and attachment. Thirty-eight infants mean age 4 months were videotaped with their mothers (19 mothers with a hyperemesis diagnosis and 19 controls) during play with a soft toy and looking at a picture book. Infant attention was operationalized as gaze direction towards the play activity, mother, and 'distracted' (indicated by looking away from play or mother). Mothers completed stress, depression, anxiety, and attachment questionnaires. HG exposed infants attended for significantly less time during play with a book or soft toy compared to controls. Maternal stress, depression, anxiety, and attachment did not differ in HG mothers and controls. Infant ability to attend to the toy, book, mother or being distracted did not relate to maternal postnatal attachment, or mental health. These results suggest that the prenatal environment, especially exposure to HG might be associated with reduced infant attention abilities independent of maternal postnatal health.

Hyperemesis Gravidarum: Risk of Recurrence in Subsequent Pregnancies.

This study aimed to examine whether the recurrence risk of hyperemesis gravidarum (HG) is modified by the timing of diagnosis, the severity of illness, and interpregnancy interval. The Kaiser Permanente Southern California 1998-2020 longitudinally linked medical records were used to examine the recurrence risk of HG in the first two (n = 93,444) and first three (n = 17,492) successive pregnancies. The timing of diagnosis- and the severity of illness-specific recurrence risks were examined by estimating the adjusted relative risks (aRR). The risks of HG in the second pregnancy among patients with and without previous HG were 23.8% and 3.4%, respectively (aRR: 8.20; 95% confidence interval [CI]: 7.52, 8.94). The recurrence risk persisted regardless of the trimester at diagnosis and the gestational age of delivery in the first pregnancy. The recurrence risk was greater for patients with metabolic disturbances requiring in-hospital treatment (30.0%) than those managed on an outpatient basis (18.6%) in the first pregnancy (aRR: 10.84 95% CI: 9.66, 12.16). Although Asian/Pacific Islander (RR = 12.9) and White (RR = 8.9) patients had higher HG recurrence risk regardless of the gestational age at delivery in the first pregnancy, all patients had significant recurrence risk only if their first pregnancy was delivered after 32 weeks of gestation. African American patients had the highest recurrence rate (34.4%). HG recurrence risk was unaffected by interpregnancy interval and correlated with the number of previous pregnancies complicated by HG. There is an increased recurrence risk of HG in subsequent pregnancies that is influenced by race/ethnicity and gestational age at delivery. The number of pregnancies complicated by HG synergistically adds to the recurrence risk.

Hospitalizaciones por hiperémesis gravídica durante el 2018-2021 en Chile / Hospitalizations for hyperemesis gravidarum during 2018-2021- in Chile

Introducción: La hiperémesis gravídica (HG) se caracteriza por más de 3 episodios diarios de vómitos persistentes y baja de peso. Frente a un puntaje PUQE mayor a 12 requerirá manejo intrahospitalario. El objetivo de esta investigación es calcular la tasa de egreso hospitalario (TEH) por HG, en el periodo 2018 a 2021 en Chile. Metodología: Estudio observacional, descriptivo. Sobre egresos hospitalarios por HG entre los años 2018-2021 en Chile (n=4.515) según grupo etario y días de estadía, datos del Departamento de Estadística e Información de Salud. Se calculó TEH, No se requirió comité de ética. Resultados: La TEH para el periodo seleccionado fue de 16,93/100.000 habitantes, con una disminución a través de los años de estudio, siendo el menor el año 2020 con 14,11/100.000 habitantes mujeres. El grupo etario con mayor TEH fue el de 20-44 años con 30,8. El promedio de estadía hospitalaria fue de 3,65 días. Discusión: La disminución de hospitalizaciones el año 2020 puede deberse a la pandemia por COVID-19, en la que se reporta una disminución de hospitalizaciones en patologías no respiratorias. Con respecto al grupo etario con mayor TEH, puede deberse a que se trata del periodo fértil de las mujeres, generando más embarazos y casos de HG a diferencia de las edades extremas de este estudio. No hay diferencia significativa en días de estadía hospitalaria según grupo etario. Conclusión: Es importante estudiar y educar sobre esta patología para su prevención y continuar disminuyendo posibles hospitalizaciones y complicaciones por HG.

Introduction: Hyperemesis gravidarum is characterized by more than 3 daily episodes of persistent vomiting and weight loss. Patients with a PUQE score more than 12 points will require intrahospital treatment. The objective of this study is to calculate the Hyperemesis gravidarum hospital discharge rate during the years 2018 to 2021 in Chile. Methodology: It is an observational-descriptive study about Hyperemesis gravidarum hospital discharge rate during the years 2018 to 2021 in Chile (n=4.515) according to age rate and days of hospital stay, the data was taken from Departamento de Estadística e Información de Salud. The Ethics Committee was not needed. Results: The hospital discharge rate during the selected period was 16,93/100.000 habitants, decreasing through the years, being the year 2020 the one with the lower rate 14,11/100.000 women, the age group with the highest rate was 20 - 44 years with 30,8. The average of hospital stay was 3,65 days. Discussion: The decrease in the number of hospitalizations during 2020 may be due to the COVID-19 pandemic in which it was reported a decrease of hospitalization in non respiratory pathologies. According to the age group with the highest rate it may be explain because it is the fertile period of women, causing more number of pregnancy and cases of Hyperemesis gravidarum, unlike the other grupo of ages There is no significant difference in days of hospital stay according to age group Conclusion: It is important to study and educate about this pathology for its prevention and to continue reducing HG hospitalizations and complications.

Hyperemesis Gravidarum and the Potential for Cancer: A Longitudinal Cohort Study over Three Decades.

BACKGROUND: Our objective was to assess whether hyperemesis gravidarum is associated with the risk of endodermal, mesodermal, and ectodermal human chorionic gonadotropin (hCG) receptor+ cancer in women. METHODS: We performed a longitudinal cohort study of 1,343,040 women who were pregnant between 1989 and 2019 in Quebec, Canada. We identified women with and without hyperemesis gravidarum and followed them over time to capture incident cancers, grouped by embryonic germ cell layer of origin and organ hCG receptor positivity. We used time-varying Cox regression to model hazard ratios (HR) and 95% confidence intervals (CI) for the association between hyperemesis gravidarum and cancer onset, adjusted for maternal age, comorbidity, multiple gestation, fetal congenital anomaly, socioeconomic deprivation, and time period. RESULTS: Women with hyperemesis gravidarum had a greater risk of endodermal cancer compared with no hyperemesis gravidarum (5.8 vs. 4.8 per 10,000 person-years; HR, 1.36; 95% CI, 1.17-1.57), but not mesodermal or ectodermal cancer. Severe hyperemesis with metabolic disturbance was more strongly associated with cancer from the endodermal germ layer (HR, 1.97; 95% CI, 1.51-2.58). The association between hyperemesis gravidarum and endodermal cancer was driven by bladder (HR, 2.49; 95% CI, 1.37-4.53), colorectal (HR, 1.41; 95% CI, 1.08-1.84), and thyroid (HR, 1.43; 95% CI, 1.09-1.64) cancer. CONCLUSIONS: Women with hyperemesis gravidarum have an increased risk of cancers arising from the endodermal germ cell layer, particularly bladder, colorectal, and thyroid cancers. IMPACT: Future studies identifying the pathways linking hyperemesis gravidarum with endodermal tumors may help improve the detection and management of cancer in women.

Antiemetic treatment of hyperemesis gravidarum in 1,064 Norwegian women and the impact of European warning on metoclopramide: a retrospective cohort study 2002-2019.

BACKGROUND: Women suffering from severe nausea and vomiting during pregnancy, hyperemesis gravidarum, have poor quality of life and increased risk of potentially fatal maternal and fetal complications. There is increasing and reassuring knowledge about safety of antiemetics in pregnancy. In 2013, the European Medical Agency (EMA) issued a warning on metoclopramide limiting treatment to maximum five days. Metoclopramide was the most used antiemetic in pregnancy at the time the warning was implemented in the Norwegian hyperemesis guidelines (2014). We aimed at describing changes in the treatment of hyperemesis over time, including changes associated with the EMA warning. METHODS: Retrospective chart review of all women hospitalized for hyperemesis gravidarum with metabolic disturbances between 01/Jan/2002 and 31/Dec/2019 at a university hospital serving nearly 10% of the pregnant population in Norway. Time-series analysis described changes over time and interrupted time series analysis quantified changes in treatment and clinical outcomes related to the EMA warning. RESULTS: In total, 1,064 women (1.2% of the birthing population) were included. The use of meclizine, prochlorperazine, and ondansetron increased during 2002-2019. This led to a yearly increase in the percentage of women using any antiemetic of 1.5% (95%CI 0.6; 2.4) pre-hospital, 0.6% (95%CI 0.2; 1.1) during hospitalization, and 2.6% (95%CI 1.3; 3.8) at discharge. Overall, only 50% of the women received antiemetics pre-hospital. Following the EMA warning, prehospital use of metoclopramide dropped by 30% (95%CI 25; 36), while use of any antiemetic pre-hospital dropped by 20% (95%CI 5.7; 34). In timely association, we observed a decrease in gestational age (-3.8 days, 98.75%CI 0.6; 7.1) at first admission, as well as indication of increased rate of termination of pregnancy with an absolute increase of 4.8% (98.75%CI 0.9; 8.7) in 2014. CONCLUSION: During 2002-2019, the overall use of antiemetics in treatment of hyperemesis increased. The EMA-warning on metoclopramide in 2013 temporarily limited pre-hospital antiemetic provision associated with hospitalization at lower gestational length and indication of an increase in termination of pregnancy.

Depression, anxiety, and post-traumatic stress disorder symptoms after hyperemesis gravidarum: a prospective cohort study.

OBJECTIVE: To determine the prevalence of depression, anxiety, and posttraumatic stress disorder (PTSD) years after hyperemesis gravidarum (HG) and its association with HG severity. MATERIAL AND METHODS: This prospective cohort study consisted of a follow-up of 215 women admitted for HG, who were eligible to participate in a randomized controlled trial and either declined or agreed to be randomized between 2013 and 2016 in 19 hospitals in the Netherlands. Participants completed the Hospital Anxiety and Depression Scale (HADS) six weeks postpartum and during follow-up and the PTSD checklist for DSM-5 (PCL-5) during follow-up. An anxiety or depression score ≥8 is indicative of an anxiety or depression disorder and a PCL-5 ≥ 31 indicative of PTSD. Measures of HG severity were symptom severity (PUQE-24: Pregnancy Unique Quantification of Emesis), weight change, duration of admissions, readmissions, and admissions after the first trimester. RESULTS: About 54/215 participants completed the HADS six weeks postpartum and 73/215 participants completed the follow-up questionnaire, on average 4.5 years later. Six weeks postpartum, 13 participants (24.1%) had an anxiety score ≥8 and 11 participants (20.4%) a depression score ≥8. During follow-up, 29 participants (39.7%) had an anxiety score ≥8, 20 participants (27.4%) a depression score ≥8, and 16 participants (21.9%) a PCL-5 ≥ 31.Multivariable logistic regression analysis showed that for every additional point of the mean PUQE-24 three weeks after inclusion, the likelihood of having an anxiety score ≥8 and PCL-5 ≥ 31 at follow-up increased with OR 1.41 (95% CI: 1.10;1.79) and OR 1.49 (95% CI: 1.06;2.10) respectively. CONCLUSION: Depression, anxiety, and PTSD symptoms are common years after HG occurred.