Treatment resistant hyperemesis gravidarum in a patient with type 1 diabetes mellitus: neonatal withdrawal symptoms after successful antiemetic therapy with mirtazapine

Here we present the case of a 30-year-old woman with type I diabetes mellitus, preeclampsia and treatment resistant persistent hyperemesis gravidarum in her 25th week of gestation who was successfully treated with the antidepressant mirtazapine (Remergil). Nausea and vomiting resolved within 5 days. After discharge from the hospital in 28 weeks of gestation and discontinuation of the medication on her own initiative a relapse occurred, once again with good response to mirtazapine. The drug was continued until birth. At 34 + 0 weeks a cesarean section was performed due to fetal growth restriction and deteriorating preeclampsia. During the second and fourth day postnatal age the child temporarily developed hyperarousal which could be explained by mirtazapine withdrawal.     

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.     

The impact of total parenteral nutrition support on pregnancy outcome in women with hyperemesis gravidarum

Abstract

Objective: To assess pregnancy outcome among women with hyperemesis gravidarum (HEG) with and without total parenteral nutrition (TPN) support.

Study design: A retrospective study of all pregnant women with singleton pregnancies who were hospitalized due to HEG between 1997 and 2011. Pregnancy outcome was compared with a control group without HEG matched by maternal age and parity in a 3:1 ratio.

Results: Overall 599 women were admitted during the study period with the diagnosis of HEG and subsequently delivered in our center. Of those, 122 (20.4%) received TPN support. Women in the HEG group were characterized by a higher rate of severe preeclampsia (1.3% versus 0.5%, p?=?0.04), and a higher rate of preterm delivery at less than 37 and 34 weeks (10.9% versus 6.9%, p?<?0.001 and 4.7% versus 1.6%, p?<?0.001, respectively). Neonates in the HEG group were characterized by a lower birth weight (3074?±?456?g versus 3248?±?543?g, p?<?0.001), higher rate of birth weight?<?10th percentile (12.7% versus 6.8%, p?<?0.001), and a higher rate of neonatal morbidity (8.7% versus 3.8%, p?<?0.001). These associations persisted after adjustment for potential confounders, and were of most notable among women with HEG who did not receive TPN support.

Conclusion: HEG is an independent risk factor for adverse pregnancy outcome. TPN support during early pregnancy is associated with a decreased risk for perinatal morbidity.     

Use of diazepam for hyperemesis gravidarum

Objective. To evaluate the efficacy and safety of intravenous (IV) fluid and diazepam therapy compared with the IV-fluid only therapy for the resistant hyperemesis gravidarum (HG) cases.

Methods. Medical records of 74 HG cases who were refractory to standard management were reviewed. All patients hospitalised were administered IV fluid and multivitamin combination as the first-step therapy. Patients who were refractory to first-step therapy were given IV fluid (Group 1, n = 43) or IV fluid and diazepam (Group 2, n = 31) depending on the patients' desire. Groups were matched for demographic characteristics, rehospitalisation requirement, patient satisfaction and neonatal outcomes.

Results. Thirteen of the 74 patients were excluded from the study because of unknown maternal and fetal outcome. The mean gestational age was 10.4 ± 2.4 year. Age, parity, body mass index and educational level were similar between the two groups. Mean diazepam dose was 62.8 ± 24.5 mg (range 40–160) in Group 2 (n = 31). The number of hospitalisation was significantly lower, and patient satisfaction was significantly higher in Group 2. There were no differences for the obstetrics outcomes between the groups.

Conclusions. The addition of diazepam to IV fluids was associated with less hospitalisation in women with hyperemesis gravidarum. Safety of diazepam therapy in early pregnancy deserves further study.     

Adjusted leptin level (ALL) is a predictor for hyperemesis gravidarum

OBJECTIVE: To compare the maternal serum leptin level according to the gestational week and to assess the relationship between the adjusted serum leptin level and thyroid hormones. In order to obtain this objective a new parameter is developed: adjusted leptin level (ALL: maternal serum leptin level/gestational week). STUDY DESIGN: A prospective study was carried out at the early prenatal care unit, SSK Ankara Women's Health and Teaching Hospital. Fifty-four women with hyperemesis gravidarum (HG) and 42 pregnant women without HG as a control group were included to the study. The groups were compared for age, parity, body mass index, fasting serum TSH, free T3, free T4 and leptin levels. A new parameter; ALL was also calculated in each case. RESULTS: Gestational age and body mass index (BMI) were found significantly lower in the HG group than in the control group (p=0.001). ALL was significantly high in the HG group (p=0.009). Serum TSH, free T3, free T4 levels were significantly different in the HG group than in the control group (p=0.003, 0.013, 0.012, respectively). A significant positive correlation was found between ALL and BMI in the HG group (r=0.449 p=0.001). The maternal leptin level was also positively correlated with BMI in the HG group (r=0.313 p=0.025). CONCLUSION: Etiology of the hyperemesis gravidarum is multifactorial. However we can postulate the adjusted leptin level is a good predictor for hyperemesis gravidarum.     

Maternal characteristics largely explain poor pregnancy outcome after hyperemesis gravidarum

Objective

To describe the characteristics of women who suffer from hyperemesis gravidarum, and explore the independent effect of hyperemesis gravidarum on pregnancy outcome.

Study design

In The Netherlands Perinatal Registry, we used all data on singleton pregnancies of at least 24 weeks and 500 g without congenital anomalies in the years 2000-2006. We examined the characteristics of women who suffered from hyperemesis gravidarum and their children.

Results

Women who suffered from hyperemesis gravidarum were slightly younger; more often primiparous, of lower socio-economic status, of non-Western descent and substance abusers; had more often conceived through assisted reproduction techniques and more often had pre-existing hypertension, diabetes mellitus and psychiatric diseases than women who did not suffer from hyperemesis gravidarum. Also, their pregnancies were more often complicated by hypertension and diabetes and they more often carried a female fetus. Pregnancies complicated by hyperemesis gravidarum significantly more often had an adverse outcome (prematurity or birth weight below the 10th percentile). The increased risk of adverse pregnancy outcomes after hyperemesis gravidarum was largely explained by the differences in maternal characteristics (crude OR 1.22 (95% CI 1.10-1.36), adjusted OR was 1.07 (95% CI 0.95-1.19)).

Conclusion

Hyperemesis gravidarum is associated with adverse pregnancy outcomes. This is largely explained by differences in maternal characteristics. Given the impact of the early environment on later health (which is independent of size at birth), studies that aim to assess the long-term consequences of hyperemesis gravidarum need to be given high priority.     

Helicobacter pylori seropositivity in patients with hyperemesis gravidarum.

OBJECTIVES: To test the hypothesis that infection with Helicobacter pylori is associated with hyperemesis gravidarum. METHODS: From November 1999 to February 2001, we enrolled 54 pregnant women with hyperemesis gravidarum and 53 asymptomatic pregnant women in a prospective study. Specific serum immunoglobulin G for Helicobacter pylori was assayed in the sera of the study group and compared with the asymptomatic group. Chi-square and Student's t-test were used accordingly for statistical analysis of the data. RESULTS: Serologically positive Helicobacter pylori infection was detected in 44 out of 54 patients with hyperemesis gravidarum (81.5%) whereas 29 out of 53 asymptomatic gravidas (54.7%) had positive antibody titers for Helicobacter pylori. The ratio of Helicobacter pylori seropositivity in pregnant women with hyperemesis gravidarum was significantly higher than asymptomatic pregnant women (P<0.01). The mean (+/-S.D.) of the IgG titer was 69.7 (+/-77.5) in the hyperemesis gravidarum group and 34.5 (+/-47.8) in the control group (P<0.01). CONCLUSIONS: There is a significant association between Helicobacter pylori infection and hyperemesis gravidarum in our hyperemetic pregnant patients.     

High prevalence of severe nausea and vomiting of pregnancy and hyperemesis gravidarum among relatives of affected individuals

Objective

The goal of this study was to determine the prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of affected individuals.

Study design

Family history data were obtained on 1224 self-reported cases of hyperemesis gravidarum. Cases completed an online survey administered by the Hyperemesis Education and Research Foundation between 2003 and 2006.

Results

Approximately 28% of cases reported their mother had severe nausea and vomiting or hyperemesis gravidarum while pregnant with them. Of the 721 sisters with a pregnancy history, 137 (19%) had hyperemesis gravidarum. Among the most severe cases, those requiring total parenteral nutrition or nasogastric feeding tube, the proportion of affected sisters was even higher, 49/198 (25%). Nine percent of cases reported having at least two affected relatives including sister(s), mother, grandmother, daughters, aunt(s), and cousin(s).

Conclusion

There is a high prevalence of severe nausea and vomiting of pregnancy/hyperemesis gravidarum among relatives of hyperemesis gravidarum cases in this study population. Because the incidence of hyperemesis gravidarum is most commonly reported to be 0.5%, this study provides strong but preliminary evidence for a genetic component to extreme nausea and vomiting of pregnancy.     

Antihistamines and other prognostic factors for adverse outcome in hyperemesis gravidarum

Objective

The purpose of this study is to determine the frequency of adverse perinatal outcome in women with hyperemesis gravidarum and identify prognostic factors.

Study design

This is a case–control study in which outcomes of first pregnancies were compared between 254 women with hyperemesis gravidarum treated with intravenous fluids and 308 controls. Prognostic factors were identified by comparing the clinical profile of patients with hyperemesis gravidarum with a normal and an adverse pregnancy outcome. Binary responses were analyzed using either a Chi-square or Fisher exact test and continuous responses were analyzed using a t-test.

Results

Women with hyperemesis gravidarum have over a 4-fold increased risk of poor outcome including preterm birth and lower birth weight (p < 0.0001). Among maternal characteristics, only gestational hypertension had an influence on outcome (p < 0.0001). Treatment as an outpatient and/or by alternative medicine (acupuncture/acupressure/Bowen massage) was associated with a positive outcome (p < 0.0089). Poor outcomes were associated with early start of symptoms (p < 0.019), and treatment with methylprednisolone (p < 0.0217), promethazine (p < 0.0386), and other antihistamines [diphenhydramine (Benadryl), dimenhydrinate (Gravol), doxylamine (Unisom), hydroxyzine (Vistaril/Atarax), doxylamine and pyridoxine (Diclectin/Bendectin)] (p < 0.0151) independent of effectiveness. Among these medications, only the other antihistamines were prescribed independent of severity: they were effective in less than 20% of cases and were taken by almost 50% of patients with an adverse outcome.

Conclusion

Poor outcomes are significantly greater in women with HG and are associated with gestational hypertension, early symptoms, and antihistamine use. Given these results, there is an urgent need to address the safety and effectiveness of medications containing antihistamines in women with severe nausea of pregnancy.     

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.     

Maternal serum cytokine levels in women with hyperemesis gravidarum in the first trimester of pregnancy

OBJECTIVE: To compare serum cytokine levels in patients with hyperemesis gravidarum with levels in healthy pregnant and nonpregnant women. DESIGN: Case-control study. SETTING: Clinical and academic research center. PATIENT(S): Thirty women with hyperemesis gravidarum, 30 healthy women in the first trimester of pregnancy, and 30 healthy nonpregnant women. MAIN OUTCOME MEASURE(S): Serum levels of interleukin-1beta, interleukin-2 receptor, interleukin-6, interleukin-8, and tumor necrosis factor (TNF)-alpha. RESULT(S): Median serum levels of interleukin-2 receptor and interleukin-8 did not differ significantly among the three groups. Serum levels of interleukin-1beta and interleukin-6 were significantly higher in healthy pregnant women than in healthy nonpregnant women. Median TNF-alpha levels were significantly higher in women with hyperemesis (25.8 pg/mL [range, 4.9-140 pg/mL]) than in healthy pregnant and nonpregnant women (10.85 pg/mL [range, 4.1-35.8 pg/mL] and 12 pg/mL [4.3-68.2 pg/mL], respectively). CONCLUSION(S): Levels of TNF-alpha were significantly higher in patients with hyperemesis gravidarum than in healthy pregnant and nonpregnant women. Thus, TNF-alpha may be involved in the etiology of hyperemesis gravidarum.     

Anxiety and depression in hyperemesis gravidarum: prevalence,risk factors and correlation with clinical severity

Objective

To evaluate prevalence, risk factors and clinical severity correlates of anxiety and depression caseness in hyperemesis gravidarum (HG).

Study design

A prospective study of self-assessment using the Hospital Anxiety and Depression Scale (HADS) was performed. Women at their first hospitalization for HG were recruited as soon as possible after hospital admission. Cut-off at the score of 7/8 was used for both the anxiety and depression subscales of HADS to denote anxiety and depression caseness respectively. Risk factors for anxiety and depression caseness were identified using Chi-square test, Fisher's exact test, Mann–Whitney's U-test or the Student's t-test. Multivariable logistic regression analysis incorporating all co-variables with crude P < 0.1 was performed to identify independent risk factors. Bivariate analyses were performed to identify associations between clinical markers of severity and anxiety and depression caseness. Prolonged hospitalization and a number of biochemical and hematological abnormalities were used as clinical markers of HG severity.

Results

Criteria for anxiety and depression caseness were fulfilled in 98/209 (46.9%) and 100/209 (47.8%) women respectively. 78 (37.3%) participants fulfilled the criteria for both anxiety and depression caseness, 89 (42.6%) neither, 20 (9.6%) anxiety caseness only and 22 (10.5%) depression caseness only. Gestational age at commencement of vomiting, duration of vomiting leading up to hospitalization and paid employment status had crude P < 0.1 in association with anxiety caseness. After adjustment, only paid employment was independently associated with anxiety caseness (AOR 2.9 95% CI 1.3–6.5; P = 0.009). Previous miscarriage, gestational age at commencement of vomiting and duration of vomiting leading up to hospitalization all had P < 0.1 in association with depression caseness. After adjustment, only previous miscarriage was negatively associated with depression caseness (AOR 0.4 95% CI 0.2–0.9; P = 0.022). There was no marker of HG severity associated with anxiety caseness on bivariate analysis. High hematocrit was associated with depression caseness (OR 2.1 95% CI 1.1–3.9; P = 0.027).

Conclusion

Anxiety and depression caseness is common in HG and risk factors can be identified. There is no convincing association between anxiety and depression and more severe illness. Psychological symptoms may be a response to physical illness but further studies are needed.     

Service use data analysis of pre-pregnancy psychiatric and somatic diagnoses in women with hyperemesis gravidarum

Introduction. The purpose of this study was to redress weaknesses in past studies of a psychogenic etiology for hyperemesis gravidarum (HG) by (1) estimating from a known population what proportion of HG cases also have psychiatric diagnoses, (2) determining if psychiatric disorder preceded HG, and (3) re-considering whether non-pregnancy somatic conditions also precede HG.

Methods. We analyzed insurance data for all 11,016 members who gave birth to singletons in 2000–2004, 208 of whom had HG.

Results. Prevalence of HG was 1.8% overall, 3.8% with one psychiatric diagnosis, 5.8% with >1 psychiatric diagnosis. One in 10 HG cases had pre-pregnancy depression, anxiety, or substance abuse diagnoses. One in five HG cases had either a psychiatric or a somatic condition (e.g., chronic pelvic pain, dysmenorrhea) diagnosis prior to pregnancy. Pre-pregnancy psychiatric diagnosis doubled the adjusted odds of HG. Combined psychiatric and somatic diagnoses quadrupled the adjusted odds of HG.

Discussion. Vomiting is a non-specific sign that may have multiple etiologies. For 10–20% of HG sufferers, vomiting may be a physical comorbidity of a psychiatric condition occurring in the context of pregnancy. Psychobiological research with HG cases with past or current psychiatric diagnoses is needed to consider plausible mechanisms.     

Maternal serum ischemia-modified albumin (IMA), total-sulphydryl concentrations,and some subclinic inflammatory markers in hyperemesis gravidarum (HG)

ObjectiveThis study investigates the relationship between Ischemia Modified Albumin and Total-Sulphydryl levels with some subclinical inflammatory markers in patients with hyperemesis gravidarum.Materials and methodsA total of 258 pregnant women, 137 with hyperemesis gravidarum and 121 low-risk pregnancies, were included in this case–control study. The patients were divided into three groups according to the severity of hyperemesis gravidarum as mild (n = 53), moderate (n = 41) and severe (n = 43).ResultsSerum Ischemia Modified Albumin levels were statistically different from the control group (P < 0.001). Among the subgroups, the highest Ischemia Modified Albumin value was observed in the severe hyperemesis gravidarum group, and the highest Total-Sulphydryl level was observed in the mild hyperemesis gravidarum group (P < 0.001). Serum potassium levels were higher in the control group (P < 0.001). While a negative correlation was observed between Ischemia Modified Albumin and Total-Sulphydryl, a positive correlation was observed in Platelet crit, C-reactive protein, and ketonuria. As the severity of the disease increases, Ischemia Modified Albumin, which is an oxidative stress factor, increases, and Total-Sulphydryl levels decrease (p < 0.001). Logistic regression analysis revealed that a one-unit increase in Ischemia Modified Albumin resulted in a statistically significant 1.9-fold increase in the risk of Severe hyperemesis gravidarum (OR 1.92, 95% CI 1.008–1.956; P = 0.01)ConclusionThis study shows that there is a condition in the pathophysiology of hyperemesis gravidarum, with an increase in Ischemia Modified Albumin and a decrease in Total-Sulphydryl levels, and oxidative stress occurs. It was important to detect increased Ischemia Modified Albumin and decreased antioxidant values in relation to the inflammatory factors that were effective in the severe hyperemesis gravidarum group.     

Hyperemesis gravidarum and neonatal outcomes: A systematic review of observational studies

Hyperemesis gravidarum (HG) is associated with adverse somatic and psychological effects. The impact of HG on neonatal outcomes is debatable given that disagreeing research results have appeared. The objective of this study was to systematically review, according to the PRISMA guidelines, and synthesize the available evidence from observational studies on the relationship between HG and neonatal outcomes. The PubMed, Scopus, and Science Direct databases were systematically reviewed, with the last search carried out in April 2020. The quality of the studies was estimated using the Newcastle–Ottawa Scale (NOS) for non-randomized studies. The databases search yielded 516 studies 15 of which (n = 112.372 HG cases) matched eligibility criteria while the majority of the studies were of moderate quality (n = 12). We observed heterogeneity among the studies regarding the definition of HG and characteristics of the samples. The results of this systematic review suggest that it is still uncertain whether HG has an adverse impact on neonatal outcomes, fact that requires more studies to be conducted.