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.

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.

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.

[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.

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.

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.

Use of Thiamine Supplementation in Pregnant Women Diagnosed With Hyperemesis Gravidarum and Wernicke Encephalopathy.

Hyperemesis gravidarum is the most common condition requiring hospital care for women during the first 20 weeks of pregnancy and may lead to malnutrition, dehydration, and vitamin deficiencies. Depletion of vitamins such as thiamine may result in the development of Wernicke encephalopathy, a severe neurological disorder that can increase the risk for mortality and morbidity for the mother and fetus. A lack of awareness regarding the relationship of hyperemesis gravidarum and Wernicke encephalopathy may result in delayed treatment and disease management. Glucose administration in the presence of thiamine deficiency may induce Wernicke encephalopathy; protocols are needed to ensure dextrose is used for women with hyperemesis gravidarum in times of prolonged vomiting and poor oral intake only after first administering thiamine. This article includes a discussion of best practices for thiamine supplementation with hyperemesis gravidarum and Wernicke encephalopathy.

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.

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

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

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

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

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

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

Oral rehydration therapy versus intravenous rehydration therapy in the first 12 h following hospitalization for hyperemesis gravidarum: A randomized controlled trial.

OBJECTIVE: To evaluate oral rehydration therapy (ORT) compared with intravenous rehydration therapy (IVT) in the early inpatient management of hyperemesis gravidarum (HG). METHODS: A total of 124 women hospitalized for HG from February 10, 2021 till January 6, 2023 were randomized to ORT (n = 61) or IVT (n = 63) for an initial 12 h. Inclusion criteria includes women older than 18 years, with a viable intrauterine pregnancy less than 14 weeks at their first hospitalization for HG with ketonuria of at least 2+. Primary outcomes were (1) satisfaction score with allocated intervention, (2) weight change, and (3) ketonuria change at 12 h. Secondary outcomes included vomiting frequency, nausea score, serial vital signs, hematocrit and electrolyte levels at 12 h, deviation from treatment protocol (cross-over therapy), participant recommendation of allocated treatment to a friend, and length of hospital stay. RESULTS: Primary outcomes of (1) participant satisfaction score (on a 0-10 visual numerical rating scale) was 7 (interquartile range [IQR] 5-8) versus 9 (IQR 8-10), P < 0.001; (2) weight gain was 293 ± 780 g versus 948 ± 758 g, P < 0.001; and (3) ketonuria improvement was 50/61 (82.0%) versus 49/63 (77.8%) (relative risk [RR] 1.05, 95% confidence interval [CI] 0.88-1.26, P = 0.561) for ORT versus IVT, respectively. For secondary outcomes, vomiting frequency was 2.6 ± 2.7 versus 1.1 ± 1.4 episodes (P < 0.001), participant cross-over rate to opposing treatment 20/61 (32.8%) versus 0/63 (0%) (P < 0.001) (in the 12-h study period) and participant recommendation of allocated treatment to a friend rate 24/61 (39.3%) versus 61/63 (96.8%) (RR 0.41, 95% CI 0.30-0.56, P < 0.001) for ORT versus IVT, respectively. By hospital discharge, 31/61 (50.8%) of women allocated to ORT had required IVT. Other secondary outcomes of serial assessments of nausea score and vital signs, hematocrit and electrolyte levels, and length of hospital stay were not different. CONCLUSIONS: ORT was inferior to IVT in two primary outcomes and three secondary outcomes. Cross-over rate to intravenous therapy from oral therapy was 50.8% by hospital discharge. Intravenous rehydration therapy should remain as first-line rehydration therapy in the early inpatient treatment of HG. CLINICAL TRIAL REGISTRATION: The present study was registered in ISRCTN registry on December 6, 2020 with trial identification number: ISRCTN 40152556 (https://doi.org/10.1186/ISRCTN40152556). The first participant was recruited on February 10, 2021.

The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

Inpatient Management of Hyperemesis Gravidarum.

Hyperemesis gravidarum has a reported incidence of approximately 0.3-3% of pregnancies. Without treatment, refractory hyperemesis gravidarum can result in dehydration, electrolyte deficiencies, and severe nutritional deficiencies, resulting in significant maternal morbidity. The overall goals of inpatient management of refractory hyperemesis gravidarum are the resumption of oral intake to an adequate level to maintain hydration and nutrition, including the ability to tolerate oral pharmacotherapy. Patients initially are stabilized with rehydration and electrolyte repletion. There are numerous pharmacotherapeutics available that can be administered intravenously to control symptoms when oral intake is not an option. However, despite maximizing typical antiemetics, there will be cases refractory to these medications, and alternative pharmacotherapeutics and nutrition-support modalities must be considered. Mirtazapine, olanzapine, corticosteroids, and gabapentin are examples of alternative pharmacotherapeutics, and enteral and parenteral nutrition are alternative therapies that can be used when oral intake is not tolerated for prolonged time periods with ongoing weight loss. In refractory cases of hyperemesis gravidarum, the risks and benefits of these alternative forms of management must be considered, along with the risks of undertreated hyperemesis gravidarum and the overall effect of hyperemesis gravidarum on patients' quality of life.

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

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

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

GDF15, a hormone acting on the brainstem, has been implicated in the nausea and vomiting of pregnancy, including its most severe form, hyperemesis gravidarum (HG), but a full mechanistic understanding is lacking1-4. Here we report that fetal production of GDF15 and maternal sensitivity to it both contribute substantially to the risk of HG. We confirmed that higher GDF15 levels in maternal blood are associated with vomiting in pregnancy and HG. Using mass spectrometry to detect a naturally labelled GDF15 variant, we demonstrate that the vast majority of GDF15 in the maternal plasma is derived from the feto-placental unit. By studying carriers of rare and common genetic variants, we found that low levels of GDF15 in the non-pregnant state increase the risk of developing HG. Conversely, women with ß-thalassaemia, a condition in which GDF15 levels are chronically high5, report very low levels of nausea and vomiting of pregnancy. In mice, the acute food intake response to a bolus of GDF15 is influenced bi-directionally by prior levels of circulating GDF15 in a manner suggesting that this system is susceptible to desensitization. Our findings support a putative causal role for fetally derived GDF15 in the nausea and vomiting of human pregnancy, with maternal sensitivity, at least partly determined by prepregnancy exposure to the hormone, being a major influence on its severity. They also suggest mechanism-based approaches to the treatment and prevention of HG.