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.

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.

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.

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.

Long-term health outcomes of children born to mothers with hyperemesis gravidarum: a systematic review and meta-analysis.

OBJECTIVE: Hyperemesis gravidarum is characterized by severe nausea and vomiting in pregnancy, frequently resulting in severe maternal nutritional deficiency. Maternal undernutrition is associated with adverse offspring health outcomes. Whether hyperemesis gravidarum permanently affects offspring health remains unclear. This review aimed to evaluate the effects of maternal hyperemesis gravidarum on offspring health. DATA SOURCES: MEDLINE and Embase were searched from inception to September 6, 2021. STUDY ELIGIBILITY CRITERIA: Studies reporting on health at any age beyond the perinatal period of children born to mothers with hyperemesis gravidarum were included. METHODS: Two reviewers independently selected studies and extracted data. The Newcastle-Ottawa Quality Assessment Scale was used to assess risk of bias. We conducted a narrative synthesis and meta-analysis where possible. In meta-analyses with high heterogeneity (I2>75%), we did not provide a pooled odds ratio. RESULTS: Nineteen studies were included in this systematic review (n=1,814,785 offspring). Meta-analysis (n=619, 2 studies: 1 among adolescents and 1 among adults) showed that hyperemesis gravidarum was associated with anxiety disorder (odds ratio, 1.74; 95% confidence interval, 1.04-2.91; I2, 0%) and sleep problems in offspring (odds ratio, 2.94; 95% confidence interval, 1.25-6.93; I2, 0%). Hyperemesis gravidarum was associated with testicular cancer in male offspring aged up to 40 years on meta-analysis (5 studies, n=20,930 offspring), although heterogeneity was observed on the basis of a wide 95% prediction interval (odds ratio, 1.60; 95% confidence interval, 1.07-2.39; I2, 0%; 95% prediction interval, 0.83-3.08). All 6 studies reporting on attention deficit (hyperactivity) disorder and autism spectrum disorder reported an increase among children of mothers with hyperemesis gravidarum in comparison with children of unaffected mothers. Meta-analysis showed high heterogeneity, precluding us from reporting a pooled odds ratio. Most studies reporting on cognitive and motor problems found an increase among hyperemesis gravidarum-exposed children. One study investigated brain structure and found smaller cortical volumes and areas among children from hyperemesis gravidarum-affected pregnancies than among those from unaffected pregnancies. Studies evaluating anthropometry and cardiometabolic disease risk of hyperemesis gravidarum-exposed children had inconsistent findings. CONCLUSION: Our systematic review showed that maternal hyperemesis gravidarum is associated with small increases in adverse health outcomes among children, including neurodevelopmental disorders, mental health disorders, and possibly testicular cancer, although evidence is based on few studies of low quality.

Readmissions due to hyperemesis gravidarum: a nation-wide Finnish register study.

PURPOSE: To evaluate the burden of illness caused by hyperemesis gravidarum (HG) and association of readmissions due to HG with maternal, environmental and pregnancy-related factors, and different pregnancy outcomes. METHODS: Data of women with HG diagnosis in Finland, 2005-2017, were retrieved from health-care registers. Associations between readmissions due to HG and age, gravidity, parity, pre-pregnancy body mass index (BMI), smoking, marital status, socioeconomic status, municipality population, assisted reproductive technology (ART), and number and sex of fetuses were analyzed in pregnancies resulting in delivery. Admissions and readmissions due to HG in deliveries, gestational trophoblastic disease, ectopic pregnancies, miscarriages and pregnancy terminations were calculated. RESULTS: 10,381 pregnancies with HG diagnosis were identified: 9518 live births, 31 stillbirths, 8 cases of gestational trophoblastic disease, 16 ectopic pregnancies, 299 miscarriages, and 509 pregnancy terminations. Both outpatients and inpatients were included. Readmission occurred in 60% of pregnancies, inpatient readmission in 17%. Parity of ≥ 5, multiple gestation and female sex of fetus were associated with higher odds of readmission, maternal age 36-40 years, BMI ≥ 35 kg/m2, smoking and ART with lower odds of readmission. Of the 9549 pregnancies resulting in delivery, 33% involved at least one outpatient visit or inpatient episode after the first trimester, and 8% in the third trimester. CONCLUSION: The majority of women suffering from HG needed repeated medical care, often persisting after the first trimester. Our results provide practical information allowing clinicians to prepare for symptom duration beyond the first trimester and emphasize the importance of planning for eventual long-term treatment.

The incidence of postoperative nausea and vomiting after caesarean section in patients with hyperemesis gravidarum: a retrospective cohort study.

BACKGROUND: Postoperative nausea and vomiting is one of the most common anaesthetic complications of caesarean section. This study examined the association between hyperemesis gravidarum during pregnancy and nausea and vomiting after caesarean section. METHODS: A single-centre, retrospective cohort study, using electronic databases of patients with and without hyperemesis gravidarum, undergoing caesarean section from 2015 to 2019. The incidence and severity of postoperative nausea and vomiting were established by a review of the documentation of administration of postoperative anti-emetics within the 24-h period after surgery, and examined using univariable, multivariable binary and ordered logistic regression models. RESULTS: Data were compared for 76 patients with hyperemesis gravidarum and 315 patients without the condition. The incidence of postoperative nausea and vomiting in the hyperemesis group versus the non-hyperemesis group was 43.4% vs 29.6%, respectively. The odds of experiencing postoperative nausea and vomiting was 1.95 times higher in women with hyperemesis gravidarum than in those without (aOR 1.95, 95% CI 1.13 to 3.36, P=0.016). The odds of having more severe postoperative nausea and vomiting were greater in the hyperemesis gravidarum group (aOR 1.91, 95% CI 1.14 to 3.20, P=0.014). CONCLUSION: Patients with hyperemesis gravidarum are more likely to develop nausea and vomiting after caesarean section, and this is likely to be of greater severity than in those without the condition. This finding should assist the effective provision of intra-operative and postoperative anti-emetics for patients with hyperemesis gravidarum undergoing caesarean section.

Early maternal weight gain as a risk factor for SGA in pregnancies with hyperemesis gravidarum: a 15-year hospital cohort study.

BACKGROUND: Inadequate maternal weight gain increases the risk of small-for-gestational age (SGA) infants. Women with hyperemesis gravidarum (HG) are at risk of significant early pregnancy weight loss and insufficient total pregnancy weight gain. Recent studies have implied that weight gain during the first half of pregnancy is more crucial to pregnancy outcome than total weight gain. The aim of this study was to investigate whether not regaining prepregnancy weight by 13-18 weeks of gestation contributed to not reaching minimum body mass index (BMI)-specific total pregnancy weight gain and influenced the risk of SGA outcome in HG pregnancies. METHODS: In this retrospective 15-year cohort (2002-2016) of women hospitalized due to hyperemesis gravidarum, we reviewed individual patient hospital files and corresponding outpatient maternity records to collect prepregnancy BMI and weight, pregnancy weight gain (spanning 3-week intervals), delivery weight and foetal outcomes. BMI and total pregnancy weight gain goals were categorized according to the Institute of Medicine (IOM) 2009 guidelines: BMI < 18,5 kg/m2: 12.5-18 kg, 18.5-24.9 kg/m2: 11.5-16 kg, 25-29.9 kg/m2: 7-11.5 kg and > 30 kg/m2: 5-9 kg. Birth weight was categorized as SGA if less than the 10th percentile of sex- and gestational length-specific Norwegian neonatal weight charts. Nonparametric tests were used to compare weight categories, and logistic regression was used to predict the odds ratio (OR) of inadequate total pregnancy weight gain or SGA delivery. RESULTS: Out of 892 women hospitalized for HG during 2002-2016, 784 had a pregnancy lasting > 24 weeks, of which 746 were singleton pregnancies with follow-up until delivery. Among these women, 42 were classified as underweight, 514 as normal weight, 230 as overweight and 102 as obese before pregnancy. Not regaining prepregnancy weight by week 13-18 was an independent predictor of inadequate total gestational weight gain with an OR of 7.05 (95% CI 4.24-11.71) and an independent predictor for SGA outcome with an OR of 2.66 (95% CI 1.11-6.34), even when adjusted for total pregnancy weight gain, prepregnancy BMI, parity, age and smoking status. CONCLUSION: Inadequate total maternal weight gain and not regaining prepregnancy weight by week 13-18 may be considered independent risk factors for delivering a baby that is small for gestational age in pregnancies with hyperemesis gravidarum. Achieving adequate weight gain during the first trimester in HG pregnancies is important for the foetal outcome, underscoring the importance of nutritional treatment during this period.

Incidence and risk factors of hyperemesis gravidarum: A national register-based study in Finland, 2005-2017.

INTRODUCTION: Hyperemesis gravidarum is the most common reason for hospitalization in early pregnancy in pregnancies resulting in delivery. Several associative factors indicate that the etiology is likely to be multifactorial. To assess this, we used a unique procedure to compare hyperemetic pregnancies with non-hyperemetic pregnancies both in different women and in the same women's different pregnancies. MATERIAL AND METHODS: Data about all pregnancies resulting in delivery in Finland in 2005-2017 were retrieved from healthcare registers. Women who had a diagnosis of hyperemesis gravidarum in any pregnancy in the Finnish Hospital Discharge Register were chosen as cases (n = 9315) and other women (n = 428 150) as the reference group. The incidence of hyperemesis gravidarum was calculated and associations between hyperemesis and maternal, environmental and pregnancy-related factors were analyzed in a novel setting by comparing case women's pregnancies diagnosed with hyperemesis to (1) reference group women's pregnancies and (2) case women's non-hyperemetic pregnancies. RESULTS: Of the 437 465 women who had at least one pregnancy resulting in delivery during the study period, 9315 women had at least one hyperemetic pregnancy. The total number of pregnancies resulting in delivery was 741 387 and 9549 of those were diagnosed with hyperemesis gravidarum; thus the incidence of hyperemesis gravidarum was 1.3%. In comparison (1), case women's hyperemetic pregnancies vs reference group's pregnancies, younger maternal age, higher gravidity, underweight and overweight were associated with increased risk of hyperemesis; in contrast, in comparison (2), case women's hyperemetic pregnancies vs their non-hyperemetic pregnancies, higher age and obesity were associated with higher risk of hyperemesis, whereas the risk was lower as gravidity and parity increased. In both comparisons, smoking was associated with lower risk, whereas higher municipality population, assisted reproductive technology, multiple gestation and female sex of the fetus were associated with increased risk of hyperemesis. CONCLUSIONS: Our novel study setting provided new insights about risk factors: hyperemetic pregnancies differ both from pregnancies of women who had never been diagnosed with hyperemesis and from hyperemetic women's non-hyperemetic pregnancies. The incidence of hyperemesis gravidarum in Finland was comparable to that in other countries.

Nausea and vomiting of pregnancy and hyperemesis gravidarum.

Nausea and vomiting of pregnancy (NVP) is a common condition that affects as many as 70% of pregnant women. Although no consensus definition is available for hyperemesis gravidarum (HG), it is typically viewed as the severe form of NVP and has been reported to occur in 0.3-10.8% of pregnant women. HG can be associated with poor maternal, fetal and child outcomes. The majority of women with NVP can be managed with dietary and lifestyle changes, but more than one-third of patients experience clinically relevant symptoms that may require fluid and vitamin supplementation and/or antiemetic therapy such as, for example, combined doxylamine/pyridoxine, which is not teratogenic and may be effective in treating NVP. Ondansetron is commonly used to treat HG, but studies are urgently needed to determine whether it is safer and more effective than using first-line antiemetics. Thiamine (vitamin B1) should be introduced following protocols to prevent refeeding syndrome and Wernicke encephalopathy. Recent advances in the genetic study of NVP and HG suggest a placental component to the aetiology by implicating common variants in genes encoding placental proteins (namely GDF15 and IGFBP7) and hormone receptors (namely GFRAL and PGR). New studies on aetiology, diagnosis, management and treatment are under way. In the next decade, progress in these areas may improve maternal quality of life and limit the adverse outcomes associated with HG.

Leisure-time physical activity before pregnancy and risk of hyperemesis gravidarum: a population-based cohort study.

INTRODUCTION: Women who experience severe nausea and vomiting in early pregnancy are less likely to participate in leisure-time physical activity (LTPA) during pregnancy. Whether LTPA before pregnancy is associated with hyperemesis gravidarum (HG) has not yet been studied. The aim of the study was to estimate associations between prepregnancy LTPA and HG in pregnancy. METHODS: We present data from 37,442 primiparous women with singleton pregnancies enrolled in The Norwegian Mother and Child Cohort Study. Prepregnancy LTPA was self-reported by questionnaire in pregnancy week 17. HG was reported in week 30 and defined as prolonged nausea and vomiting in pregnancy requiring hospitalisation before the 25th gestational week. We estimated the crude and adjusted associations between LTPA and HG using multiple logistic regression. We assessed effect modification by prepregnancy BMI or smoking by stratified analysis and interaction terms. RESULTS: A total of 398 (1.1%) women developed HG. Before pregnancy 56.7% conducted LTPA at least 3 times weekly, while 18.4% of women conducted LTPA less than once a week. Compared to women reporting LTPA 3 to 5 times weekly, women reporting no LTPA before pregnancy had an increased odds of HG (adjusted odds ratio (aOR) 1.69; 95% confidence interval (CI), 1.20 to 2.37). LTPA-HG associations differed by prepregnancy BMI but not by prepregnancy smoking. DISCUSSION: Lack of LTPA before pregnancy was associated with an increased odds of HG. Due to few cases of HG and thereby low statistical power, one need to be cautious when interpreting the results of this study.

Recurrence patterns of hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum, excessive vomiting in pregnancy, affects approximately 0.3-3.0% of all pregnancies, but the risk is considerably higher in pregnancies following a hyperemetic pregnancy. The reported recurrence rate of hyperemesis gravidarum is wide, ranging from 15-81%, depending on study settings. Factors affecting recurrence of hyperemesis gravidarum are as yet insufficiently studied. OBJECTIVE: We sought to evaluate the recurrence rate of hyperemesis gravidarum in subsequent pregnancies, to elucidate chronological patterns of recurrence of the condition, and to analyze maternal, environmental, and pregnancy-related factors associated with recurring hyperemesis gravidarum. STUDY DESIGN: Out of all pregnancies ending in delivery in Finland from 2004 through 2011, data of women who had at least 1 pregnancy ending in delivery following a pregnancy diagnosed with hyperemesis gravidarum were retrieved from hospital discharge register and medical birth register (1836 women, 4103 pregnancies; 1836 index pregnancies and 2267 subsequent pregnancies). The first pregnancy with hyperemesis gravidarum diagnosis was chosen as the index pregnancy, and recurrence rate was calculated by comparing the number of hyperemetic pregnancies that followed the index pregnancy to the total number of pregnancies that followed the index pregnancy. Recurrence patterns of hyperemesis gravidarum were illustrated by presenting the chronological order of the women's pregnancies beginning from the index pregnancy to the end of the follow-up period. The associations between recurring hyperemesis and age, parity, prepregnancy body mass index, smoking, marital and socioeconomic status, domicile, month of delivery, assisted reproductive technology, sex, and number of fetuses were analyzed in both the index pregnancies and in pregnancies following the index pregnancy. RESULTS: There were 544 pregnancies with a hyperemesis diagnosis and 1723 pregnancies without a hyperemesis diagnosis following the index pregnancies. The overall recurrence rate of hyperemesis gravidarum in pregnancies following the index pregnancy was 24%. In case of >1 subsequent pregnancy, 11% of women were diagnosed with hyperemesis in all of their pregnancies. In the index pregnancies, recurrence of hyperemesis gravidarum was more common among women with parity of 2 than parity of 1 (adjusted odds ratio, 1.33, P = .046). Overweight women (adjusted odds ratio, 0.58, P = .036) or women who smoked after the first trimester (adjusted odds ratio, 0.27, P < .001) had lower recurrence of hyperemesis. In the comparison of the subsequent pregnancies, quitting smoking in the first trimester (adjusted odds ratio, 0.32, P = .010) and smoking continued after the first trimester (adjusted odds ratio, 0.38, P = .002) were associated with lower odds of recurring hyperemesis. Female sex of the fetus was associated with higher odds of recurring hyperemesis (adjusted odds ratio, 1.29, P = .012). CONCLUSION: In the majority of pregnancies following an earlier hyperemetic pregnancy, hyperemesis gravidarum does not recur, but hyperemetic pregnancies occur in the next pregnancies with little predictability. Only few factors associated with recurring hyperemesis could be identified. Although estimating the probability of recurrence of hyperemesis gravidarum in a subsequent pregnancy based on a woman's first hyperemetic pregnancy turned out not to be feasible, it is reassuring to know that hyperemesis does not appear to become more likely with each pregnancy and that after 1 pregnancy with hyperemesis, the following pregnancy may be different.

Cardiovascular risk profile at the age of 40-45 in women with previous hyperemesis gravidarum or hypertensive disorders in pregnancy: A population-based study.

OBJECTIVE: To assess midlife cardiovascular risk profiles in women with a history of hyperemesis or hypertensive disorders in pregnancy compared to women with none of the studied pregnancy complications. STUDY DESIGN: Population-based study. Cardiovascular risk factors at the age of 40-45 among women with previous singleton births only were studied through linkage of the Norwegian Birth Registry and a Norwegian screening program (the Age 40 Program). MAIN OUTCOME MEASURES: Family history of coronary heart disease, body mass index, smoking, physical activity, systolic and diastolic blood pressure, heart rate, cholesterol, triglycerides, antihypertensive treatment and diabetes. RESULTS: Among 178,231 women participating in the Age 40 Program with previous singleton births; 2140 (1.2%) had experienced hyperemesis and 13,348 (7.5%) hypertensive disorders in pregnancy. Women who had suffered from hyperemesis were less physically active. The differences in mean systolic blood pressure and body mass index were probably clinically irrelevant. In women with a history of hypertensive disorders in pregnancy, systolic and diastolic blood pressure and body mass index were higher, and they were more likely to report diabetes in midlife. Women who had suffered from hyperemesis or hypertensive disorders in pregnancy were less likely to be daily smokers. CONCLUSION: Women with hypertensive disorders in pregnancy seemed to have an unfavorable cardiovascular risk profile in midlife compared to women with uncomplicated pregnancies. In contrast there was no consistent evidence of increased risk subsequent to hyperemesis gravidarum. The proportion of daily smokers was lower in women with either of the two pregnancy complications.

Breast cancer risk in relation to history of preeclampsia and hyperemesis gravidarum: Prospective analysis in the Generations Study.

Preeclampsia and hyperemesis gravidarum are pregnancy complications associated with altered sex hormone levels. Previous studies suggest preeclampsia may be associated with a decreased risk of subsequent breast cancer and hyperemesis with an increased risk, but the evidence remains unclear. We used data from the Generations Study, a large prospective study of women in the United Kingdom, to estimate relative risks of breast cancer in relation to a history of preeclampsia and hyperemesis using Cox regression adjusting for known breast cancer risk factors. During 7.5 years average follow-up of 82,053 parous women, 1,969 were diagnosed with invasive or in situ breast cancer. Women who had experienced preeclampsia during pregnancy had a significantly decreased risk of premenopausal breast cancer (hazard ratio (HR) =0.67, 95% confidence interval (CI): 0.49-0.90) and of HER2-enriched tumours (HR = 0.33, 95% CI: 0.12-0.91), but there was no association with overall (HR = 0.90, 95% CI: 0.80-1.02) or postmenopausal (HR = 0.97, 95% CI: 0.85-1.12) breast cancer risk. Risk reductions among premenopausal women were strongest within 20 years since the last pregnancy with preeclampsia. Hyperemesis was associated with a significantly increased risk of HER2-enriched tumours (HR = 1.76, 95% CI: 1.07-2.87), but not with other intrinsic subtypes or breast cancer risk overall. These results provide evidence that preeclampsia is associated with a decreased risk of premenopausal and HER2-enriched breast cancer and that hyperemesis, although not associated with breast cancer risk overall, may be associated with raised risk of HER2-enriched tumours.

Hospital admission for hyperemesis gravidarum in women at increased risk of spontaneous preterm birth.

BACKGROUND: Progesterone administration prevents spontaneous preterm birth (sPTB) in women at increased risk. Progesterone concentration is lower in women with subsequent sPTB. Conversely, high concentrations of progesterone are implicated in the pathogenesis of hyperemesis gravidarum (HG). We hypothesized that women at increased risk of sPTB or spontaneous late miscarriage would be less likely to have a diagnosis of HG. To explore this hypothesis, we compared the incidence of HG in women at increased risk of sPTB and women with no identifiable risk factors. METHODS: Women at increased risk of sPTB were identified from a specialist Preterm Birth Clinic (PTBC) database where criteria for PTBC attendance are previous cervical surgery, previous sPTB <34 weeks, previous spontaneous late miscarriage, incidental sonographic cervical shortening, and uterine anomaly. Hospital antenatal booking and coding records for the same time period were examined to identify HG admissions. Women with multiple gestations, trophoblastic disease, or pre-existing abnormal thyroid function were excluded. The incidence of HG among PTBC (n=394) and non-PTBC attendees (n=4762) was calculated. RESULTS: The incidence of HG was lower in women at increased risk of sPTB (1.52%, n=6) compared with women with no identifiable risk factor for sPTB (3.33%, n=159; P=.049). CONCLUSION: Hospital admission for HG is reduced in women with risk factors for sPTB compared with those without risk factors. Exploration of the pathogenesis of HG may improve understanding of the mechanisms underlying sPTB.

Hyperemesis gravidarum and the risk of emotional distress during and after pregnancy.

Hyperemesis gravidarum (HG) is a pregnancy condition characterised by severe nausea and vomiting. Previous studies have shown an association between HG and depressive symptoms during pregnancy, but little is known about the risk of maternal psychological distress following an HG pregnancy. The objective of the current study was therefore to assess the association between HG and emotional distress during and after pregnancy. This was a population-based pregnancy cohort study using data from the Norwegian Mother and Child Cohort Study. A total of 851/92,947 (0.9%) had HG. Emotional distress was measured by the Hopkins Symptom Checklist (SCL-5) in gestational weeks 17 and 32 and 6 and 18 months postpartum. The generalised estimating equations model was estimated for assessing time trends in emotional distress. Adjustments were made for previous HG, lifetime history of depression, maternal age, parity, BMI, smoking before pregnancy, physical activity, length of education, and pelvic girdle pain. Women with HG had higher odds for emotional distress than women without HG at the 17th (p < 0.001) and 32nd gestational weeks (p = 0.001) in addition to 6 months postpartum (p = 0.005) but not 18 months postpartum (p = 0.430). Adjusted odds for emotional distress varied significantly over time for women with and without HG (p = 0.035). Women with HG were more likely to report emotional distress compared to women without HG during pregnancy and 6 months postpartum, but the difference between the groups disappeared 18 months after birth. The results suggest that the increased risk of developing emotional distress may primarily be a consequence of HG.

Are early pregnancy complications more common in women with hyperemesis gravidarum?

Ultrasound evaluation is usually requested for women presenting with hyperemesis gravidarum (HG) in early pregnancy. This is to check viability as well as to diagnose multiple pregnancies and exclude gestational trophoblastic disease (GTD). The aim of this retrospective case control study was to evaluate the early pregnancy outcomes in women with HG and to compare them with an asymptomatic control group. 790 women referred with HG between 2002 and 2014 were matched for gestational age and maternal age with an asymptomatic patient attending for a reassurance or dating scan. A higher proportion of women with HG had ongoing pregnancies compared with controls and conversely, embryonic demise was less frequent in the HG group. The risk of twin pregnancy was doubled in the HG group compared to controls. There was no evidence of an increase in the prevalence of GTD. There appears to be a limited role for ultrasound in women who present with HG alone.

Hospital admission for hyperemesis gravidarum: a nationwide study of occurrence, reoccurrence and risk factors among 8.2 million pregnancies.

STUDY QUESTION: What are the maternal risk factors for hyperemesis gravidarum (HG) hospital admission, readmission and reoccurrence in a following pregnancy? SUMMARY ANSWER: Young age, less socioeconomic deprivation, nulliparity, Asian or Black ethnicity, female fetus, multiple pregnancy, history of HG in a previous pregnancy, thyroid and parathyroid dysfunction, hypercholesterolemia and Type 1 diabetes are all risk factors for HG. WHAT IS KNOWN ALREADY: Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with a history of HG were previously reported to be at higher risk of developing HG; however, most evidence is from small studies. Little is known about associations with other comorbidities and there is controversy over other risk factors such as parity. Estimates of HG prevalence vary and there is a little understanding of the risks of HG readmission in a current pregnancy and reoccurrence rates in subsequent pregnancies, all of which are needed for planning measures to reduce onset or worsening of the condition. STUDY DESIGN, SIZE, DURATION: We performed a population-based cohort study of pregnancies ending in live births and stillbirths using prospectively recorded secondary care records (Hospital Episode Statistics) from England. We analysed those computerized and anonymized clinical records from over 5.3 million women who had one or more pregnancies between 1997 and 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS: We obtained 8 215 538 pregnancies from 5 329 101 women of reproductive age, with a total of 186 800 HG admissions occurring during 121 885 pregnancies. Multivariate logistic regression with generalized estimating equations was employed to estimate odds ratios (aOR) to assess sociodemographic, pregnancy and comorbidity risk factors for HG onset, HG readmission within a pregnancy and reoccurrence in a subsequent pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: Being younger, from a less socioeconomically deprived status, of Asian or Black ethnicity, carrying a female fetus or having a multiple pregnancy all significantly increased HG and readmission risk but only ethnicity increased reoccurrence. Comorbidities most strongly associated with HG were parathyroid dysfunction (aOR = 3.83, 95% confidence interval 2.28-6.44), hypercholesterolemia (aOR = 2.54, 1.88-3.44), Type 1 diabetes (aOR = 1.95, 1.82-2.09), and thyroid dysfunction (aOR = 1.85, 1.74-1.96). History of HG was the strongest independent risk factor (aOR = 4.74, 4.46-5.05). Women with higher parity had a lower risk of HG compared with nulliparous women (aOR = 0.90, 0.89-0.91), which was not explained by women with HG curtailing further pregnancies. LIMITATIONS, REASONS FOR CAUTION: Although this represents the largest population-based study worldwide on the topic, the results could have been biased by residual and unmeasured confounding considering that some potential important risk factors such as smoking, BMI or prenatal care could not be measured with these data. Underestimation of non-routinely screened comorbidities such as hypercholesterolemia or thyroid dysfunction could also be a cause of selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The estimated prevalence of 1.5% from our study was similar to the average prevalence reported in the literature and the representativeness of our data has been validated by comparison to national statistics. Also the prevalence of comorbidities was mostly similar to other studies estimating these in the UK and other developed countries. Women with Black or Asian ethnicity, of young age, carrying multiple babies or singleton females, with Type 1 diabetes or with history of HG were confirmed to be at higher risk of HG with an unprecedented higher statistical power. We showed for the first time that socioeconomic status interacts with maternal age, that hypercholesterolemia is a potential risk factor for HG and that carrying multiple females increases risk of hyperemesis compared with multiple males. We also provided robust evidence for the association of parity with HG. Earlier recognition and management of symptoms via gynaecology day-case units or general practitioner services can inform prevention and control of consequent hospital admissions. STUDY FUNDING/COMPETING INTERESTS: The work was founded by The Rosetrees Trust and the Stoneygate Trust. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. C.N.-P. reports personal fees from Sanofi Aventis, Warner Chilcott, Leo Pharma, UCB and Falk, outside the submitted work and she is one of the co-developers of the RCOG Green Top Guideline on HG; all other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: Not applicable.

Hyperemesis gravidarum and maternal cancer risk, a Scandinavian nested case-control study.

Reproductive factors have been shown to influence cancer risk. Several pathological conditions during pregnancy have also been associated with subsequent altered cancer risk in the mother. Hyperemesis gravidarum (hyperemesis) is an early pregnancy condition characterized by severe nausea and vomiting resulting in weight loss and metabolic disturbances. Studies have reported associations between hyperemesis and cancer, but results are inconsistent. In this nested case-control study we linked the population-based medical birth registries and cancer registries in Norway, Sweden and Denmark in order to examine overall cancer risk and risk of specific cancer types in women with a history of hyperemesis, using conditional logistic regression. In total, 168,501 cases of cancer in addition to up to 10 cancer-free controls per case were randomly sampled, matched on year of birth and birth registry (n = 1,721,626). Hyperemesis was defined through the International Classification of Diseases. Analyses were adjusted for potential confounders. Hyperemesis was inversely associated with overall cancer risk with adjusted relative risk (aRR) of 0.93 (95% CI: 0.88-0.99), with cancer in the lungs (aRR: 0.60, 95% CI: 0.44-0.81), cervix (aRR: 0.66, 95% CI: 0.49-0.91) and rectum (aRR: 0.48, 95% CI: 0.29-0.78). Thyroid cancer was positively associated with hyperemesis (aRR 1.45, 95% CI: 1.06-1.99) and risk increased with more than one hyperemetic pregnancy (aRR 1.80, 95% CI: 1.23-2.63). Hormonal factors, in particular human chorionic gonadotropin, are likely to be involved in mediating these effects. This study is the first to systematically address these associations and provides valuable knowledge on potential long-term consequences of hyperemesis.