Liver pathology in pregnancy.

Liver dysfunction occurs in up to 3% of pregnancies and can be due to pregnancy-associated liver injury, exacerbation of pre-existing liver disease, or co-incident with pregnancy. The most common form of pregnancy-associated liver injury is intrahepatic cholestasis of pregnancy (ICP). This condition is typically benign and self-limited, but is associated with fetal morbidity and mortality with high levels of serum bile acids. Acute fatty liver of pregnancy (AFLP) and the hypertensive disorders of pregnancy (including pre-eclampsia, eclampsia, and hemolysis, elevated liver enzymes, and low platelets [HELLP] syndrome) are more commonly associated with maternal and fetal complications and may necessitate expedient delivery. Histologically, ICP shows nonspecific features of cholestasis, while AFLP and the hypertensive disorders have more characteristic histologic findings. While not a true liver disease, hyperemesis gravidarum can cause elevated liver enzymes. Pregnant patients are at increased risk of developing severe hepatitis E and herpesvirus infections, Budd-Chiari syndrome, and gallstones, and they may also experience worsening of known chronic liver disease. Mass lesions in pregnancy including hemangiomas, focal nodular hyperplasia, and hepatocellular adenomas and carcinomas can present unique challenges for diagnosis and management. This review will explore the pathophysiology, presentation, histologic features, and management of these conditions.

Relapse of Human Chorionic Gonadotropin-Induced Hyperthyroidism and Severe Hyperemesis Gravidarum Secondary to Twin-Twin Transfusion Syndrome, With Rapid Recovery Following Fetoscopic Laser Coagulation: Case Report.

Background: Limited data have shown that, compared to uncomplicated twin pregnancies, pregnancies complicated by twin-twin transfusion syndrome (TTTS), a life-threatening condition, are associated with higher maternal serum levels of both human chorionic gonadotropin (hCG) and thyroid hormones. With the continuing expansion of assisted reproductive technologies, the rate of twin pregnancies, including those complicated by TTTS and associated hyperemesis gravidarum, is expected to increase further. Therefore, detailed descriptions of the maternal and fetal clinical outcomes of maternal thyrotoxicosis linked to TTTS can be useful for timely diagnosis and management. However, such descriptions are currently lacking in the literature. Case Presentation: We report the case of a 30-year-old woman carrying a monochorionic twin pregnancy complicated by TTTS that induced a relapse of severe hyperemesis gravidarum with overt non-autoimmune hyperthyroidism at 17 weeks of gestation. Following fetoscopic laser coagulation (FLC), both hyperemesis and hyperthyroidism improved within 1 week. Conclusions: The present experience contributes to the knowledge base on maternal thyrotoxicosis linked to TTTS and can be useful in the diagnosis and treatment of future cases; it also emphasizes the need for a high degree of clinical suspicion and for close collaboration between endocrinologists and obstetricians. Another key point is that TTTS-associated hyperemesis gravidarum and maternal hyperthyroidism should be considered in the differential diagnosis of refractory or relapsing hyperemesis gravidarum in women with monochorionic twin pregnancy, because this condition may require more stringent supportive treatment before and during the FLC procedure when the mother is overtly hyperthyroid.

Determinants of disease course and severity in hyperemesis gravidarum.

OBJECTIVE: We aimed to identify determinants that predict hyperemesis gravidarum (HG) disease course and severity. STUDY DESIGN: For this study, we combined data of the Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding (MOTHER) randomized controlled trial (RCT) and its associated observational cohort with non-randomised patients. Between October 2013 and March 2016, in 19 hospitals in the Netherlands, women hospitalised for HG were approached for study participation. In total, 215 pregnant women provided consent for participation. We excluded women enrolled during a readmission (n = 24). Determinants were defined as patient characteristics and clinical features, available to clinicians at first hospital admission. Patient characteristics included i.e. age, ethnicity, socio-economic status, history of mental health disease and HG and gravidity. Clinical features included weight loss compared to pre-pregnancy weight and symptom severity measured with Pregnancy Unique Quantification of Emesis (PUQE-24) questionnaire and the Nausea and Vomiting in Pregnancy specific Quality of Life questionnaire (NVPQoL). Outcome measures were measures of HG disease severity present at 1 week after hospital admission, including weight change, PUQE-24 and NVPQoL scores. Total days of admission hospital admission and readmission were also considered outcome measures. RESULTS: We found that high PUQE-24 and NVPQoL scores at hospital admission were associated with those 1 week after hospital admission (difference (ß) 0.36, 95 %CI 0.16 to 0.57 and 0.70,95 %CI 0.45-1.1). PUQE-24 and NVPQoL scores were not associated with other outcome measures. None of the patient characteristics were associated with any of the outcome measures. CONCLUSION: Our findings suggest that the PUQE-24 and NVPQoL questionnaires can identify women that maintain high symptom scores a week after admission, but that patient characteristics cannot be used as determinants of HG disease course and severity.

Severity of Hyperemesis Gravidarum and Associated Maternal factors.

BACKGROUND: Hyperemesis gravidarum is the most severe form of nausea and vomiting in pregnancy. It is one of the most common cause of early pregnancy admissions and associated with various maternal risk factors . Very few studies have been conducted among Nepalese women with hyperemesis gravidarum. This study aims to identify various maternal risk factors among Nepalese women and its severity using pregnancy unique quantification of emesis scoring. METHODS: This is a cross sectional observational study conducted at Paropakar Maternity and Women's Hospital. Total duration of the study period was for one year from February 2018 to Janurary 2019. A total of 144 patients meeting the inclusion criteria were included in the study.The severity of the hyperemesis gravidarum was assessed and classified using pregnancy unique quantification of emesis scoring. Various maternal demographic, obstetric and personal factors were studied in relation to the incidence and severity of hyperemesis gravidarum. RESULTS: Moderate (49.30%) to severe(50.69%) hyperemesis gravidarum were admitted in the hospital. Most women were nulliparous from 20-24 years age group. Among all categories of BMI, underweight had more severe hyperemesis gravidarum (63.63%) and overweight patient had increased incidence of moderate hyperemesis gravidarum (66.66%). Women with previous dysmenorrhea had severe hyperemesis gravidarum (54.05%) and non-smoker had severe hyperemesis gravidarum (52.03%) while smoker had moderate hyperemesis gravidarum (57.14%). CONCLUSIONS: Pregnant women of age group of 20-24 years, nulliparity and underweight were associated with severe hyperemesis gravidarum.

Early nasogastric tube feeding in optimising treatment for hyperemesis gravidarum: the MOTHER randomised controlled trial (Maternal and Offspring outcomes after Treatment of HyperEmesis by Refeeding).

BACKGROUND: Hyperemesis gravidarum (HG), or intractable vomiting during pregnancy, is the single most frequent cause of hospital admission in early pregnancy. HG has a major impact on maternal quality of life and has repeatedly been associated with poor pregnancy outcome such as low birth weight. Currently, women with HG are admitted to hospital for intravenous fluid replacement, without receiving specific nutritional attention. Nasogastric tube feeding is sometimes used as last resort treatment. At present no randomised trials on dietary or rehydration interventions have been performed. Small observational studies indicate that enteral tube feeding may have the ability to effectively treat dehydration and malnutrition and alleviate nausea and vomiting symptoms. We aim to evaluate the effectiveness of early enteral tube feeding in addition to standard care on nausea and vomiting symptoms and pregnancy outcomes in HG patients. METHODS/DESIGN: The MOTHER trial is a multicentre open label randomised controlled trial ( www.studies-obsgyn.nl/mother ). Women ≥ 18 years hospitalised for HG between 5 + 0 and 19 + 6 weeks gestation are eligible for participation. After informed consent participants are randomly allocated to standard care with intravenous rehydration or early enteral tube feeding in addition to standard care. All women keep a weekly diary to record symptoms and dietary intake until 20 weeks gestation. The primary outcome will be neonatal birth weight. Secondary outcomes will be the 24-h Pregnancy Unique Quantification of Emesis and nausea score (PUQE-24), maternal weight gain, dietary intake, duration of hospital stay, number of readmissions, quality of life and side-effects. Also gestational age at birth, placental weight, umbilical cord plasma lipid concentration and neonatal morbidity will be evaluated. Analysis will be according to the intention to treat principle. DISCUSSION: With this trial we aim to clarify whether early enteral tube feeding is more effective in treating HG than intravenous rehydration alone and improves pregnancy outcome. TRIAL REGISTRATION NUMBER: NTR4197 . Date of registration: October 2(nd) 2013.

Is hyperemesis gravidarum associated with placental weight and the placental weight-to-birth weight ratio? A population-based Norwegian cohort study.

INTRODUCTION: Studies have suggested a link between placental weight, placental weight-to-birth weight ratio (PW/BW) and adult health. Hyperemesis gravidarum (HG) may also have implications for adult health. No studies on HG and placental characteristics have been identified. We therefore explored the relationship between HG, placental weight and the PW/BW-ratio in a population-based cohort. METHODS: Singleton births to primiparous women between 1999 and 2009 with data on HG, placental weight and birth weight in the Medical Birth Registry of Norway (MBRN) comprised the study base (n = 200,390). HG was defined through ICD-10 code 021.0, 021.1 and 021.9. Gender and gestational age specific percentile curves for placenta weight and PW/BW ratio were used to define those below the 10th and above the 90th percentile of both outcomes. Associations between HG and dichotomous outcomes were studied by multiple logistic regression. Multiple linear regression was applied to study placental weight as a continuous variable. Male and female offspring were analyzed separately. RESULTS: The prevalence of HG was 1.2%. Women with HG and female offspring had significantly higher risk of a PW/BW-ratio above the 90th percentile (OR = 1.17, 95% CI: 1.03-1.34). HG and PW/BW-ratio below the 10th percentile were inversely associated (OR = 0.70, 95% CI: 0.56-0.89). For male offspring no association was observed for HG and PW/BW-ratio below the 10th or above the 90th percentile. DISCUSSION/CONCLUSIONS: We observed positive associations between HG and high PW/BW ratio limited to female offspring only. The high PW/BW-ratio suggests that there may be a possible link between HG and adult health.

Neurological complications in hyperemesis gravidarum.

Hyperemesis gravidarum can impair correct absorption of an adequate amount of thiamine and can cause electrolyte imbalance. This study investigated the neurological complications in a pregnant woman with hyperemesis gravidarum. A 29-year-old pregnant woman was admitted for hyperemesis gravidarum. Besides undernutrition, a neurological examination disclosed weakness with hyporeflexia, ophthalmoparesis, multidirectional nystagmus and optic disks swelling; the patient became rapidly comatose. Brain MRI showed symmetric signal hyperintensity and swelling of periaqueductal area, hypothalamus and mammillary bodies, medial and posterior portions of the thalamus and columns of fornix, consistent with Wernicke encephalopathy (WE). Neurophysiological studies revealed an axonal sensory-motor polyneuropathy, likely due to thiamine deficiency or critical illness polyneuropathy. Sodium and potassium supplementation and parenteral thiamine were administered with improvement of consciousness state in a few days. WE evolved in Korsakoff syndrome. A repeat MRI showed a marked improvement of WE-related alterations and a new hyperintense lesion in the pons, suggestive of central pontine myelinolysis. No sign or symptom due to involvement of the pons was present.

Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum.

PURPOSE: To evaluate the role of Helicobacter pylori (H. pylori) in the pathogenesis of hyperemesis gravidarum (HG) and the value of adding a non teratogenic regimen for its treatment in intractable cases. METHODS: Eighty hyperemesis gravidarum cases were recruited from Ain Shams University out patient clinics. A complete history was taken including history of medical disorders and chronic medications intake as non steroidal anti-inflammatory drugs. After general and local examination, ultrasound was done for all cases to exclude obstetric causes of hyperemesis. Eighty normal pregnant women acted as control. Serum test for H. pylori IgG antibody titre was done for all patients and controls. RESULTS: Seventy-one cases among the 80 HG cases and twenty-four out of the 80 controls were H. pylori positive. Eight HG cases developed severe intractable vomiting. Three of them developed attacks of hematemesis. Gastroscopy done for the eight cases revealed antral gastritis and duodenitis. Gastric and duodenal erosions were found in two cases. The eight patients received a non teratogenic regimen for treatment. Attacks of vomiting decreased and pregnancy continued till delivery of healthy newborns. CONCLUSION: Screening for H. pylori should be added to the investigations of hyperemesis gravidarum cases. Non teratogenic treatment can be considered in intractable cases.

Third trimester fetal intracranial hemorrhage owing to vitamin K deficiency associated with hyperemesis gravidarum.

In rare cases, severe fetal vitamin K deficiency bleeding may occur in utero as a result of insufficient vitamin K placental transfer. We present a case of a 32-week-preterm infant born with severe intracranial hemorrhage to a pregnant woman who suffered from hyperemesis gravidarum. Neonatal hematologic status was compatible with vitamin K deficiency whereas the maternal coagulation function was normal. This case emphasizes the potential risk of fetal bleeding owing to vitamin K deficiency in pregnancies complicated with hyperemesis gravidarum. These women should be closely monitored and vitamin K prophylaxis might be considered.

Effect of high levels of human chorionic gonadotropin and estradiol on the severity of hyperemesis gravidarum.

BACKGROUND: Serum human chorionic gonadotropin (hCG) and estradiol levels are higher in women with hyperemesis gravidarum (HG) than in unaffected pregnant controls. We postulated that higher levels of these hormones may be associated with clinically more severe HG. The aim of this study was to evaluate the effect of maternal hCG and estradiol levels on the severity of HG. METHODS: A prospective study was performed on 167 first trimester women hospitalized for HG. Venous blood was taken for hCG and estradiol levels. Scattergrams were plotted for hCG or estradiol levels vs. gestational age. A curve of best fit was drawn. Women were categorized into two groups according to their position above or below the curve. Prolonged hospital stay (> or =4 days) was used as a marker for HG severity. Multivariable logistic regression analysis was used to control for differences in characteristics, laboratory results on admission, and treatment received. RESULTS: After adjustment, high hCG level adjusted odds ratio (AOR) (2.2, 95% CI 1.0-4.9, p=0.04) and hyponatremia AOR (2.8, 95% CI 1.2-6.6, p=0.02) were independently associated with prolonged hospital stay. With bivariate analysis, high estradiol level was not associated with prolonged stay. CONCLUSIONS: High hCG but not estradiol is associated with more severe HG.

Clinical utility of esophagogastroduodenoscopy in the management of recurrent and intractable vomiting in pregnancy.

OBJECTIVE: To determine the impact of esophagogastroduodenoscopy (EGD) on the clinical management of pregnancy women with recurrent vomiting and their pregnancy outcome. STUDY DESIGN: Retrospective evaluation of 60 pregnant women who underwent diagnostic EGD in the first trimester of pregnancy. RESULTS: Pregnant women were divided into 2 groups according to the indications for EGD: group 1, intractable vomiting with or without epigastric pain (n = 49) and group 2, vomiting and gastrointestinal bleeding (n = 11). The endoscopic findings found in both groups were esophagitis (43%), gastritis (17%), diaphragmatic hernia (17%) and normal EGD (28%). The diagnostic yield for EGD was 69% for group 1 and 82% for group 2. EGD was helpful for clinical management when performed for suspected gastrointestinal bleeding rather than for other indications. Mean gestational age at delivery, fetal weight and mean Apgar score did not differ by groups. No fetal malformations were observed. CONCLUSION: Recurrent intractable vomiting in pregnancy may be accompanied by esophagitis or peptic disease in a significant proportion of patients. Based on the significant pathologies amenable to medical therapy, a therapeutic trial with a proton pump inhibitor during hyperemesis gravidarum seems warranted. EGD can be safely performed in pregnancy with no maternal or fetal complications.

Hyperemesis gravidarum in Eastern Asian population.

OBJECTIVE: To investigate the clinical features of hyperemesis gravidarum in Eastern Asian women. METHOD: Retrospective cohort study was conducted based on delivery records. Hyperemesis gravidarum was defined as a pregnancy with severe nausea and vomiting necessitating hospitalization with a body weight loss of over 5% from pre-pregnancy weight with ketonuria. The onset is at 10 weeks of gestation or less. Maternal and neonatal variables were compared. RESULT: There were 3,350 singleton deliveries in the study period. All subjects were Eastern Asian women. Hyperemesis gravidarum was observed in 119 cases (3.6%). Hyperemesis gravidarum subjects had a smaller pre-pregnancy body weight (50.5 +/- 0.64 kg vs. 51.8 +/- 0.16 kg, p = 0.046) and a smaller pre-pregnancy body mass index compared to non-hyperemetic subjects (20.2 +/- 0.21 kg/m2 vs. 20.8 +/- 0.06 kg/m2, p = 0.02). CONCLUSION: The Eastern Asian population had a significantly higher incidence of hyperemesis gravidarum. Small pre-pregnancy body habitus increased the risk of hyperemesis gravidarum.

Pregnancy outcome in hyperemesis gravidarum and the effect of laboratory clinical indicators of hyperemesis severity.

OBJECTIVE: To determine pregnancy outcome in hyperemesis gravidarum and the effect of metabolic, biochemical, hematological and clinical indicators of disease severity on outcome. STUDY DESIGN: A retrospective study based on 166 women hospitalized for confirmed hyperemesis gravidarum from January 2004 to January 2005. For each woman, three controls matched for age, parity and ethnicity were obtained from our 2004 birth register. The effects of laboratory indicators of hyperemesis severity were separately analyzed within the hyperemesis gravidarum study group. Outcome measures include stillbirths, Apgar score, mode of delivery, low birthweight, preterm delivery, labor induction, pregnancy induced hypertension and gestational diabetes. Analysis was by t-test, Fisher's exact test and multivariable logistic regression analysis. RESULTS: Women with hyperemesis had similar pregnancy outcome compared to controls. In the analysis of laboratory indicators of hyperemesis severity and pregnancy outcomes, hypokalemia (adjusted odds ratio [AOR] 2.7: 95% confidence interval [CI] 1.0-6.8) was associated with emergency operative delivery, high creatinine (odds ratio 4.4: 95% CI 1.3-15) with labor induction and raised gamma glutamyltransferase (AOR 7.5: 95% CI 1.2-46) with the development of gestational diabetes. CONCLUSIONS: Hyperemesis gravidarum per se was not associated adverse pregnancy outcome. Hypokalemia, high creatinine and raised gamma glutamyltransferase in women with hyperemesis gravidarum were associated with adverse pregnancy outcome.

Relationship between adenosine and T-helper 1/T-helper 2 balance in hyperemesis gravidarum.

BACKGROUND: Adenosine modulates the T-helper (Th) 1/T-helper (Th) 2 balance. We evaluated the relationship between changes in plasma adenosine and the T-helper (Th) 1/T-helper (Th) 2 balance in hyperemesis gravidarum. METHODS: Plasma adenosine concentrations and the Th1/Th2 ratio were examined in the peripheral blood of 24 women with hyperemesis gravidarum and normal pregnancies. The proportion of CD4-positive cells that expressed intracellular cytokines (interferon gamma and interleukin 4) was analyzed by flow cytometry. The ratio of interferon-gamma-secreting cells to interleukin-4-secreting cells was taken as the Th1/Th2 ratio in vivo. The change induced by adenosine-receptor blocker 8-sulfophenyltheophylline was also measured in vitro to evaluate the possible role of adenosine in modifying the Th1/Th2 balance. RESULTS: In hyperemesis gravidarum, plasma adenosine and the proportion of interleukin-4-secreting cells were increased significantly, and the Th1/Th2 ratio was significantly lower than in normal pregnancy (p<0.05). The decrease in the proportion of IL-4-secreting cells after adenosine receptor blockade in hyperemesis gravidarum significantly exceeded that of normal pregnancy (p<0.05). CONCLUSIONS: Increased plasma adenosine may be involved in regulating the Th1/Th2 balance in hyperemesis gravidarum.

Pre-emptive therapy for severe nausea and vomiting of pregnancy and hyperemesis gravidarum.

Nausea and vomiting of pregnancy (NVP) affects 80% of pregnancies. Its severe form, hyperemesis gravidarum (HG), results in dehydration, electrolyte imbalance, the need for hospitalisation and can, rarely, be fatal. This was a prospective, open-labelled, controlled, interventional study to evaluate the effectiveness of pre-emptive treatment of NVP symptoms in women who experienced severe NVP or HG in their previous pregnancy. Twenty-five women who reported severe symptoms of NVP with or without HG in their previous pregnancy were recruited and counselled to commence the use of antiemetics as soon as they became aware of the present pregnancy, and no later than the beginning of symptoms. They were followed-up prospectively through the index pregnancy for symptoms of NVP, and were counselled continuously as to how to modify antiemetic doses based on symptoms. A comparison group consisted of randomly selected women also counselled by us for NVP, who had also had severe NVP in the previous pregnancy, but who did not call before a planned pregnancy and thus could not be offered pre-emptive therapy. The recruited women commenced pre-emptive drug therapy for NVP before conception or up to 7 weeks' gestation, before the appearance of NVP symptoms in all cases. In comparison to the previous pregnancy, only eight of these 18 women experienced a HG again in the index pregnancy (P = 0.01). The majority of study the women had an improvement in severity of NVP symptoms compared to the previous pregnancy. In the comparison group (n = 35), symptoms in the index pregnancy remained severe in 28 cases (80%), decreased to moderate in six (16.6%) and decreased to mild in five cases (13.9%). There were five cases of HG in the previous pregnancy and three in the index pregnancy. The pre-emptive group was improved significantly compared to the control group (P = 0.01). Pre-emptive symptom management appears to be effective in preventing severe NVP in general, and HG in particular. Women who have experienced severe NVP in a previous pregnancy may benefit from taking antiemetics before, or immediately at the start of symptoms in a subsequent pregnancy.