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.

Maternal type 1collagen N-terminal telopeptide levels in severe hyperemesis gravidarum.

BACKGROUND: Nausea and vomiting occur 50-90% during the first trimester of pregnancy. However, patients with hyperemesis gravidarum (HG) may be hospitalized at an incidence rate of 0.8-2% before the 20th week of gestational age. The symptoms generally start during the 5-6th gestational weeks, reaching the highest degree during the 9th week, and decline after the 16-20th weeks of gestation. Clinical findings are proportional to the severity of the disease and severe HG is characterized with dehydration, electrolyte imbalance, and nutritional deficiency as a result of vomiting. METHODS: The study population consisted of two groups of pregnant volunteers at 5-12 weeks of gestation: a severe HG group and a control group. The HG severity was scored using the Pregnancy-Unique Quantification of Emesis (and nausea) (PUQE).The serum levels of the maternal Ca, parathyroid hormone (PTH), Na, K, blood urea nitrogen(BUN), creatinine, vitamin D(25OHD3), and the maternal urine NTx levels were compared between the groups. RESULTS: In total, 40 volunteers were enrolled in this study: 20 healthy pregnant volunteers and 20 with severe HG. There were no statistically significant differences between the maternal characteristics. The first trimester weight loss of ≥5 kg was significantly higher in the severe HG group (p < 0.001), while the control group had a significantly higher sunlight exposure ratio than the severe HG group (p = 0.021). The urine NTx levels were significantly higher in the severe HG group (39.22 ± 11.68NTx/Cre) than in the control group(32.89 ± 8.33NTx/Cre) (p = 0.028).The serum Ca, PTH, Na, K, BUN, and creatinine levels were similar between the groups (p = 0.738, p = 0.886, p = 0.841, p = 0.957, p = 0.892, and p = 0.824, respectively). In the severe HG group, the serum 25OHD3 levels were significantly lower than in the control group (p < 0.001). CONCLUSIONS: The data from this study indicated that severe HG is associated with increased urine NTx levels. However, large-scale studies are required to understand the clinical significance of this finding, as well as the long-term consequences of elevated urine NTx levels and the underlying mechanisms. TRIAL REGISTRATION: NCT02862496 Date of registration: 21/07/2016.

[PR-EMPTIVE TREATMENT FOR HYPEREMESIS GRAVIDARUM].

BACKGROUND: Hyperemesis gravidarum (HG) affects around 1% of pregnant women. The experience is traumatic, and many women hesitate to start a subsequent pregnancy in view of the tendency of HG to re-occur. OBJECTIVES: A 25 year old woman who experienced HG in her previous pregnancy was very afraid to start a second pregnancy, as she considered the termination of the first, traumatic pregnancy. She was advised to use pre- emptive antiemetic therapy with an anti emetic drug before any symptom appeared. The pregnancy passed with only mild nausea and vomiting. DISCUSSION: Several controlled randomized studies have shown the effectiveness of pre emptive therapy in preventing a repeat of HG symptoms.

Variation in hyperemesis gravidarum definition and outcome reporting in randomised clinical trials: a systematic review.

BACKGROUND: Hyperemesis gravidarum (HG) is a common cause of hospital admission in early pregnancy. There is no international consensus on the definition of HG, or on outcomes that should be reported in trials. Consistency in definition and outcome reporting is important for the interpretation and synthesis of data in meta-analyses. OBJECTIVE: To identify which HG definitions and outcomes are currently in use in trials. SEARCH STRATEGY: We searched the following sources: (1) Cochrane Central Register of Controlled Trials, (2) Embase and (3) Medline for published trials and the WHO-ICTRP database for ongoing trials (27 October 2017). SELECTION CRITERIA: All randomised clinical trials reporting on any intervention for HG were eligible. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial eligibility and extracted data on HG definition and outcomes. MAIN RESULTS: We included 31 published trials reporting data from 2511 women and three ongoing trials with a planned sample size of 360 participants. We identified 11 definition items. Most commonly used definition items were vomiting (34 trials) and nausea (30 trials). We identified 34 distinct outcomes. Most commonly reported outcomes were vomiting (29 trials), nausea (26 trials), need for hospital treatment (14 trials) and duration of hospital (re)admission(s) (14 trials). CONCLUSION: There is substantial variation of HG definition and outcome reporting in trials. This hampers meaningful aggregation of trial results in meta-analysis and implementation of evidence in guidelines. To overcome this, international consensus on a definition and a core outcome set for HG trials should be developed. TWEETABLE ABSTRACT: There is a wide variation of definitions and outcomes reported in trials on hyperemesis gravidarum.

The association between maternal smoking and hyperemesis gravidarum: a meta-analysis.

BACKGROUND: The majority of studies have not found hyperemesis to be a protective and some others have not. To date, no meta-analysis has quantitatively assessed the association between smoking and risk of hyperemesis gravidarum. To help close that research gap, we performed meta-analysis of the association between smoking and risk of hyperemesis gravidarum. METHODS: A literature search was carried out in PubMed, Web of Science, and Scopus from the earliest possible year to January 2016. The heterogeneity across studies was explored by Q-test and I2 statistic. The possibility of publication bias was assessed using Begg's and Egger's tests. The results were reported using odds ratio (OR) estimate with its 95% confidence intervals (CI) using a random-effects model. RESULTS: The literature search yielded 607 publications until January 2016 with 1 400 000 participants. Based on the random-effects model, compared to nonsmoker people, the estimated OR of hyperemesis gravidarum was 0.40 (95% CI: 0.24, 0.56). CONCLUSIONS: We showed based on reports in epidemiological studies that smoking before and during pregnancy is not a risk factor for hyperemesis gravidarum but also can reduce the risk of it.

Incidence of pregnancy-related discomforts and management approaches to relieve them among pregnant women.

AIMS AND OBJECTIVES: To determine the incidence of pregnancy-related physical symptoms in healthy pregnant women and their management strategies. BACKGROUND: In normal progression of pregnancy, many symptoms were experienced. Pregnancy-related physical symptoms may have a negative effect on pregnant women's quality of life. However, pregnant women avoid taking medications from the fear that the medication they use may have a harmful effect on the foetus. Therefore, they practise nonpharmacological methods to help them manage their pregnancy-related physical symptoms. DESIGN: This study used a comparative and descriptive design. METHODS: The study population comprised of pregnant women who were visiting for routine check-up and/or examination in the obstetrics gynaecology outpatient clinics of three hospitals in Erzurum, Turkey. The data were collected via a questionnaire including socio-demographic items and questions to identify the pregnancy-related physical symptoms that they experienced and their management strategies. RESULTS: The top three most reported complaints were nausea-vomiting (87·8%), fatigue (77·9%) and breast pain-tenderness (76·2%) during the first trimester, whereas polyuria (79·9%, 88·4%), fatigue (75·6%, 88·4%) and heart burn (71·3%, 81·8%) during the second and third trimesters. Depending on the symptoms, the pregnant women either did nothing or took correct, incorrect or empirical actions to manage their problems. Data revealed that the major source of knowledge was based on their previous experience and that of close relatives. As their education level increased, the percentage of women taking scientifically proven action to correct the problem increased. CONCLUSIONS: Various physical symptoms were experienced by women in each trimester of pregnancy. The majority of the women did not do anything to alleviate their physical symptoms. RELEVANCE TO CLINICAL PRACTICE: Midwives and nurses should question the strategies used by pregnant women. In this way, the inappropriate and incorrect practices can be determined, and education on the appropriate practices can be provided.

Pregnancy nausea and vomiting--the role of the midwife.

Seventy five-80 per cent of pregnant women get some degree of nausea and vomiting of pregnancy (NVP) and it becomes severe in about 30 per cent of women with symptoms. Calling it 'morning sickness' is both inaccurate and damaging as it can be seen to trivialise the condition. Severe NVP can cause depression, feelings of inadequacy, loss of time at work, admission to hospital and termination of pregnancy. It is important for midwives to treat women with NVP with understanding and empathy, and for midwives to be able to assess women with NVP and refer for admission those developing hyperemesis gravidarm.

Diet before pregnancy and the risk of hyperemesis gravidarum.

Hyperemesis gravidarum (hyperemesis), characterised by severe nausea and vomiting in early pregnancy, has an unknown aetiology. The aim of the present study was to investigate food and nutrient intake before pregnancy and the risk of developing hyperemesis in women participating in the Norwegian Mother and Child Cohort Study. From 1999 to 2002, a total of 7710 pregnant women answered a FFQ about their diet during the 12 months before becoming pregnant and a questionnaire about illnesses during pregnancy, including hyperemesis. Only women who were hospitalised for hyperemesis were included as cases. Nutrient intakes during the year before pregnancy did not differ between the ninety-nine women who developed hyperemesis and the 7611 who did not. However, the intake of seafood, allium vegetables and water was significantly lower among women who developed hyperemesis than among women in the non-hyperemesis group. Relative risks of hyperemesis were approximated as OR, and confounder control was performed with multiple logistic regression. Women in the upper tertile of seafood consumption had a lower risk of developing hyperemesis than those in the lower tertile (OR 0·56, 95 % CI 0·32, 0·98), and women in the second tertile of water intake had a lower risk of developing hyperemesis than those in the first tertile (OR 0·43, 95 % CI 0·25, 0·73). The findings suggest that a moderate intake of water and adherence to a healthy diet that includes vegetables and fish are associated with a lower risk of developing hyperemesis.

Recurrence risk of hyperemesis gravidarum.

INTRODUCTION: The purpose of this study is to describe the recurrence risk for hyperemesis gravidarum (HG). METHODS: Women who registered on a Web site sponsored by the Hyperemesis Education and Research Foundation as having had one HG-complicated pregnancy were contacted to follow-up on a subsequent pregnancy. Participants completed an online survey. RESULTS: One hundred women responded. Fifty-seven had become pregnant again, 2 were trying to conceive, 37 were not willing to get pregnant again because of HG, and 4 did not have a second pregnancy for other reasons. Among the 57 women who responded that they had become pregnant again, 81% reported having severe nausea and vomiting in their second pregnancy. Among the women reporting recurrent HG, 98% reported losing weight and taking prescribed medication for HG, 83% reported treatment with intravenous fluids, 20% reported treatment with total parenteral nutrition or nasogastric tube feeding, and 48% reported hospitalization for HG. DISCUSSION: This study demonstrates both a high recurrence rate of HG and a large percentage of women who change reproductive plans because of their experiences with HG.

Blood tests for investigating maternal wellbeing. 4. When nausea and vomiting in pregnancy becomes pathological: hyperemesis gravidarum.

Nausea and vomiting in pregnancy (NVP) is commonplace, with many midwives frequently counselling women in their care. But how do midwives know when NVP becomes pathological? Although hyperemesis gravidarum (HEG) is less common, midwives must be able to recognise and differentiate between these two conditions, especially as HEG has the potential to have a detrimental effect on maternal and fetal wellbeing. The physiological impact of HEG is well documented but what often goes unacknowledged is the psychological, social, occupational and familial impact it also has on a woman's life. Knowledge about the aetiology of HEG and treatment options available is essential but a timely initial diagnosis is paramount. For this to occur the midwife must be skilled in history taking, clinical examination and utilisation of serum blood tests--specifically electrolytes and urea. An understanding of how electrolyte levels can cause pathology is vital if the midwife wishes to interpret blood tests for women with this condition.

Symptoms and pregnancy outcomes associated with extreme weight loss among women with hyperemesis gravidarum.

OBJECTIVE: To report the weight loss and associated symptoms experienced by a large cohort of women with hyperemesis gravidarum (HG). METHODS: Data were obtained from an HG website registry, where women with HG were recruited on-line. Respondents were included if they experienced at least 1 live birth>27 weeks' gestation. Extreme weight loss was defined as a loss of >15% of prepregnancy weight. RESULTS: Of the 819 women surveyed, 214 (26.1%) met criteria for extreme weight loss. These women were twice as likely to be Hispanic or nonwhite. Extreme weight loss (p<0.001) was associated with indicators of the severity of HG, such as hospitalization and use of parenteral nutrition, and with multiple symptoms during pregnancy, such as gallbladder and liver dysfunction, renal failure, and retinal hemorrhage. Among all women surveyed, 22.0% reported that symptoms lasted throughout pregnancy; this finding was nearly twice as likely among women with extreme weight Loss: 63 of 214 (29.4%) vs. 117 of 605 (19.3%) (OR=1.73, 95% CI 1.2-2.5, p=0.003). For some women, symptoms continued postpartum and included food aversions, muscle pain, nausea, and posttraumatic stress. Approximately 16% of babies were born prematurely, and 8% reportedly weighed <2500 g. Among women with extreme weight loss, 9.3% reported having a child with a behavioral disorder. CONCLUSIONS: Extreme weight loss is common among women with HG, suggesting that HG is a form of prolonged starvation in pregnancy and that the long-term effects of this condition on women and their offspring warrant further investigation.

Managing nausea and vomiting of pregnancy: a survey of obstetrician-gynecologists.

OBJECTIVE: To assess obstetrician-gynecologists' treatment of nausea and vomiting of pregnancy and to compare it with recommendations in an American College of Obstetricians and Gynecologists (ACOG) evidence-based practice bulletin on the topic. STUDY DESIGN: A survey questionnaire was mailed to the 1075 ACOG fellows who constitute the Collaborative Ambulatory Research Network (CARN). RESULTS: The most frequently recommended treatments for a patient with moderate to severe nausea with occasional vomiting were: eat frequent, small meals (93%); snack on soda crackers (68.5%); and take vitamin B6 plus doxylamine (67.1%). Two of 3 (66.7%) respondents had read the ACOG practice bulletin; most of those who had read it found it helpful (67.0%) or very helpful (29.5%). Respondents who read the practice bulletin were generally more willing to treat nausea and vomiting of pregnancy aggressively. They were more likely to be aware that early treatment is recommended to prevent progression to hyperemesis gravidarum and more likely to recommend the use of ginger (59.7% vs. 47.9%, p = 0.014), and to prescribe vitamin B6 (84.1% vs. 73.8%, p = 0.005) and vitamin B6 plus doxylamine (70.9% vs. 59.3%, p = 0.009). CONCLUSION: Obstetrician-gynecologists' treatment and prescribing practices generally follow ACOG recommendations; the ACOG practice bulletin appears to have affected practice and knowledge.

All day long. Interview by Carol Davis.

Hyperemess, severe and excessive vomiting during pregnancy, is a distressing condition that can require hospital treatment. One hospital has set up a dedicated, midwife-led day unit for these women.

Acupuncture for nausea and vomiting: an update of clinical and experimental studies.

The objective of this overview is to summarize existing knowledge about the effects of acupuncture-point stimulation on nausea and vomiting. Systematic reviews on postoperative nausea and vomiting, chemotherapy-induced nausea and vomiting, and pregnancy-related nausea and vomiting exist. Several randomised trials, but no reviews, exist for motion sickness. For postoperative nausea and vomiting, results from 26 trials showed acupuncture-point stimulation was effective for both nausea and vomiting. For chemotherapy-induced nausea and vomiting, results of 11 trials differed according to modality with acupressure appearing effective for first-day nausea, electroacupuncture appearing effective for first-day vomiting, and noninvasive electrostimulation appearing no more effective than placebo for any outcome. For pregnancy-related nausea and vomiting, results were mixed. Experimental studies showed effects of P6-stimulation on gastric myoelectrical activity, vagal modulation and cerebellar vestibular activities in functional magnetic resonance imaging. There is good clinical evidence from more than 40 randomised controlled trials that acupuncture has some effect in preventing or attenuating nausea and vomiting. A growing number of experimental studies suggest mechanisms of action.

Experience of Taiwanese women living with nausea and vomiting during pregnancy.

Two common symptoms of pregnancy are nausea and vomiting, which, for some women, cause great discomfort and profoundly impact daily life. A descriptive phenomenological method was used to understand how Taiwanese women deal with nausea and vomiting during pregnancy. A purposive sample of 10 expectant mothers participated in the study. A transcription of each informant's verbal description of her nausea and vomiting experience was made and analyzed using Colaizzi's phenomenological methodology. Four themes emerged from the interview data after inductively analyzing the narrative content concerning nausea and vomiting: 1) understanding nausea and vomiting, 2) finding coping strategies, 3) psychosocial adaptation, and 4) needing support. The results also indicated the importance of social support to pregnant women's health, including instrumental and emotional forms of support. Health professionals, however, were not mentioned in the mothers' narratives as a source of support. The issues of social support, language translation, and western and eastern perspectives on nausea and vomiting and cultural differences in perceptions of their severity are discussed.

[Assessment of thyroid function in women treated for vomiting in early pregnancy]. / Ocena czynnosci gruczolu tarczowego u kobiet leczonych z powodu niepowsciagliwych wymiotów ciezarnych.

OBJECTIVES: Hyperthyroidism does not influence procreation ability significantly, but very often causes complications of the course of pregnancy and increases neonatal morbidity and mortality in newborns. Nausea and vomiting in the first trimester of pregnancy are very common complaints in these patients. DESIGN: The aim of the study was to prove, that assessment of the thyroid hormones in every vomiting woman in the first trimester allows to start the proper treatment of hyperthyreosis as early as possible and improves the prognosis. MATERIALS AND METHODS: Authors analyzed 22 pregnant women treated for vomiting during the first trimester in the Department of Obstetrics and 5 women treated in the Outpatient Clinic. RESULTS: In none of them hormonal dysfunction was diagnosed before pregnancy. In 21 patients free thyroxine (fT4) in serum was assessed. In 8 cases (38%) hyperthyreosis was diagnosed. Except the routine anti vomiting treatment, they received a beta-blocker 30 mg per day. It allowed to avoid hospitalization in three pregnant women treated in the outpatient clinic. Two patients, who had earlier two spontaneous abortions, delivered healthy babies. CONCLUSIONS: 1. The beta-blocker in treatment gives very good results and allows to avoid hospitalization in patients with hyperthyroidism and hyper emesis gravidarum. 2. In some patients vomiting may be the only symptom of sub clinical hyperthyroidism in early pregnancy. Assessment of the thyroid hormones levels and adequate treatment may give these women a chance for a healthy child.

Acupuncture versus pharmacological approach to reduce Hyperemesis gravidarum discomfort.

AIM: Several reports have suggested the use of acupuncture as a useful treatment for hyperemesis gravidarum (HG), in particular the effects on nausea intensity was underlined. The aim of this study was to compare the efficacy of acupuncture sessions plus acupressure with a metoclopramide/vitamin B12 treatment. METHODS: In this study we randomized 88 pregnant patients suffering from HG to receive either acupuncture sessions plus acupressure (acupuncture group) or metoclopramide infusion (metoclopramide group) supplemented by vitamin B12 complex. Somatic symptoms and the ability to achieve the daily routine activity (functioning) were evaluated. Acupuncture sessions were performed at the hospital twice a week for 2 weeks according to the traditional Chinese medicine criteria. Acupression was applied for 6-8 h/day. In the metoclopramide group, patients received at hospital metoclopramide infusion (20 mg/500 mL saline for 60 min) twice a week for 2 weeks. An oral supplementation with vitamin B12 complex (30 mg/day) was also prescribed. RESULTS: Both treatments reduced vomiting episodes and then nausea intensity with a consequent improvement in the rate of food intake. The effect of acupuncture seems to be progressive, increasing at the end of treatment whereas pharmacological approach has a prompt effect in responders remaining stable thereafter. Moreover, acupuncture was significantly more effective than drugs in improving functioning. CONCLUSIONS: In our study for the first time acupuncture, applied accordingly to Chinese formula, was compared to drugs demonstrating the same effect of both treatments on HG symptoms. Interestingly, functioning was significantly improved just by acupuncture. Even if the effect of acupuncture on HG discomfort remains to be confirmed, the reports on the effect of acupuncture on psychosocial variables could represent a further advantage of acupuncture application and provide an incentive to widen the base of the research.

The physiological basis of reflexology and its use as a potential diagnostic tool.

Ill-health changes the anatomy and physiology of affected organs, some of which can be observed visually, elicited through physical examination or confirmed through biomedical analysis. Understanding how anatomical changes contribute to physiological signs and symptoms will help practitioners identify the pathology, appreciate its origin and development and justify prescribed interventions in a way which can be upheld by critical external scrutiny. Reflexology contributes to an holistic approach to care and has recently improved its credibility as a discipline which supports orthodox care. Several research publications have identified possible theories and principles for the mechanism of action of reflexology, but more research to explain its contribution in identifying ill-health and diseases, as well as appropriate treatment modalities, is needed. This paper explores the physiological basis of reflexology, some of the theories for the mechanism of action and its potential as a diagnostic tool.