Evaluation of relationship between inflammatory markers and hyperemesis gravidarum in patients admitted to emergency department.

BACKGROUND: Hyperemesis gravidarum (HG) is defined as severe nausea and vomiting in pregnancy and considered as one of the most frequent causes to emergency department (ED) admissions. Previous research has shown that HG is associated with systemic inflammation, but there have been no prospective studies to explore this link. The objective of this study was to assess the impact of inflammation in HG pathophysiology and to investigate the association between severity of HG and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and CRP in patients who were admitted to ED with nausea and vomiting. METHODS: This prospective study has been conducted in a tertiary clinic between 2015 and 2016. A total of 162 patients with <16 weeks gestation with singleton pregnancies and without any chronic diseases enrolled in the study. The study group consisted of 113 patients with HG and the control group included 49 healthy subjects. PUQE Index and VAS were used to evaluate the severity of symptoms. RESULTS: Demographical data were similar between both groups. The study group demonstrated significantly higher NLR, PLR and CRP levels (NLR 3.39 vs 2.5, p = 0.001; PLR 134.3 vs 111.2, p = 0.005; CRP 0.85 mg/dL vs 0.19 mg/dL, p = 0.001). While NLR and PLR levels were not correlated with severity of HG, CRP levels were associated with severity of disease (p = 0.001) regarding to PUQE index. CONCLUSION: NLR and PLR are easily obtained and routinely used diagnostic tools for various inflammatory diseases. Measurement of this markers might provide useful information in HG pathogenesis and diagnosis.

A meta-analysis of the association between Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum remains a common, distressing, and significant yet poorly understood disorder during pregnancy. The association between maternal Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum has been increasingly recognized and investigated. This study thus aimed to provide an updated review and meta-analysis of the topic. METHODS: Using the search terms (H. pyloriOR Helicobacter ORHelicobacter pyloriOR infection) AND (pregnancy OR emesis OR hyperemesis gravidarum OR nausea OR vomiting), a preliminary search on the PubMed, Ovid, Web of Science, Google Scholar, and WanFang database yielded 372 papers published in English between January 1st, 1960 and June 1st, 2017. RESULTS: A total of 38 cross-sectional and case-control studies, with a total of 10 289 patients were eligible for review. Meta-analysis revealed a significant association between H. pylori infection and hyperemesis gravidarum during pregnancy, with a pooled odds ratio of 1.348 (95% CI: 1.156-1.539, P < .001). Subgroup analysis found that serologic and stool antigen tests were comparable methods of detecting H. pylori as they yielded similar odds ratios. LIMITATIONS: Although the studies did not have high heterogeneity (I2  = 28%), publication bias was observed, and interstudy discrepancies in the diagnostic criteria adopted for hyperemesis gravidarum limit the reliability of findings. Also, 15 of the included studies were from the same country (Turkey), which could limit the generalizability of current findings. The prevalence of H. pylori infection varies throughout the world, and there may also be pathogenic differences as most strains of H. pylori in East Asia carry the cytotoxin-associated gene A gene. CONCLUSION: H. pylori infection was associated with an increased likelihood of hyperemesis gravidarum during pregnancy. Given the high prevalence of H. pylori infections worldwide, detecting H. pylori infection and the eradication of maternal H. pylori infection could be part of maternal hyperemesis gravidarum management. Further confirmation with robust longitudinal studies and mechanistic investigations are needed.

Relation of inflammatory markers with both presence and severity of hyperemesis gravidarum.

OBJECTIVES: The aim of our study is to determine the newly introduced systemic inflammation marker, neutrophil lymphocyte ratio (NLR) in hyperemesis gravidarum (HG) patients and to investigate the association between severity of the disease and NLR. METHOD: The study population consisted of 55 pregnant patients with HG and 50 pregnant women without complaints matched for gestational age as a control group. The HG patients were grouped as mild (n = 16), moderate (n = 19) and severe (n = 20) according to Modified Pregnancy- Unique Quantification of Emesis and Nausea Scoring Index Questionnaire. Furthermore, hsCRP, neutrophils, lymphocytes, and NLR were evaluated with complete blood count. RESULTS: The HG group had significantly higher NLR values compared to the control group (2.69 +/- 1.81 vs 1.97 +/- 1.34, p = 0.004). HsCRP levels were significantly higher among HG patients compared to the control group (1.95 +/- 2.2 vs 0.56 +/- 0.30, p < 0.001). The subgroup analysis revealed statistically significant increases in NLR and hsCRP values with increased HG severity (p < 0.001, p = 0.002). The correlation analysis demonstrated a strong correlation between NLR and hsCRP levels (r: 0.703, p < 0.001). CONCLUSION: Our study results showed that NLR and hsCRP levels are increased in HG disease compared to gestational age matched control group subjects. Furthermore, NLR and hsCRP values are correlated with severity of disease. NLR could be used as a marker for both presence and severity of hyperemesis gravidarum.

Serum levels of adenosine deaminase and pregnancy-related hormones in hyperemesis gravidarum.

OBJECTIVES: We investigated the correlation between pregnancy-related hormones and serum adenosine deaminase (indicator of cellular immunity) level in women with hyperemesis gravidarum. MATERIALS AND METHODS: Twenty patients with hyperemesis gravidarum and 20 normal pregnancies were included in this prospective, case-control study. Serum adenosine deaminase levels, hematological parameters (white blood cells, neutrophil, monocyte and lymphocyte counts) and hormone levels (prolactin, progesterone, thyroid stimulating hormone, human chorionic gonadotropin beta subunit, estradiol (E2)) were measured in all women. Interrelations of blood cell counts and hormone levels with serum adenosine deaminase levels were also investigated. RESULTS: Serum adenosine deaminase, human chorionic gonadotropin beta subunit, thyroid stimulating hormone, E2, progesterone and prolactin levels, and lymphocyte and monocyte counts in women with hyperemesis gravidarum were significantly higher than in controls but white blood cells, neutrophil, T3 and T4 levels were not different. Serum adenosine deaminase level correlated with E2, progesterone, lymphocyte, and monocyte levels for all patients. CONCLUSION: Elevated serum adenosine deaminase in patients with hyperemesis gravidarum may relate to high levels of E2 and progesterone.

Hyperemesis gravidarum, a literature review.

Hyperemesis gravidarum (HG) is a condition causing severe nausea and vomiting in early pregnancy often resulting in hospital admission. The incidence of HG is approximately 0.5% of live births, said to be higher in multiple pregnancies, hydatidiform mole and other conditions associated with increased pregnancy hormone levels. Both the aetiology and pathogenesis of HG remain unknown. We conducted a literature review (1966-now) to summarize the current evidence on the aetiology and pathogenesis of HG. The potential role of pregnancy-related hormones such as progesterone, estrogen and HCG has been widely studied; however, various other hormones such as leptin, placental growth hormone, prolactin, thyroid and adrenal cortical hormones have been implicated in the aetiology of HG. In addition to endocrinological hypotheses, the rationale and evidence considering infectious, immunological, psychological, metabolic and anatomical causes for HG have been analysed here. Many studies suffer from the low number of patients included, the variable definition used for HG and varying assay methodology used in studies of hormone measurement. This review highlights the need for more extensive studies addressing the pathogenesis and aetiology of HG.

Serum adenosine deaminase activity in women with hyperemesis gravidarum.

BACKGROUND: Serum adenosine deaminase (ADA) activity increases in diseases where cellular immunity is stimulated. Since hyperemesis gravidarum is characterized by enhanced cell-mediated immunity, serum ADA activity may be altered. The present study evaluated the relation between serum ADA activity and changes in cell-mediated immunity as causes of changes in ADA activity in hyperemesis gravidarum. METHODS: Serum activities of total ADA and its isoenzymes, ADA1 and ADA2, were measured in women with hyperemesis gravidarum (n = 24) and normal pregnancies (n = 24). Peripheral blood lymphocyte and monocyte counts were also measured. RESULTS: In hyperemesis gravidarum, serum total ADA and ADA2 activities averaged 16.8 +/- 0.5 and 13.3 +/- 0.7 U/l, respectively, which were significantly higher than those in normal pregnancies (10.2 +/- 0.5 and 7.8 +/- 0.5 U/l, respectively) (p < 0.05). The mean values for ADA1 activity in women with hyperemesis gravidarum and normal pregnancies were similar. The increase in total ADA activity was accompanied by the increase in lymphocyte and monocyte counts. CONCLUSIONS: These results suggest that increased serum total ADA activity reflects increases in ADA2 activity, which may be at least in part attributed to enhanced cell-mediated immunity in hyperemesis gravidarum.

Immunologic and biochemical factors in hyperemesis gravidarum with or without hyperthyroxinemia.

OBJECTIVE: This study was set up to investigate the relationship between immune process and high levels of human chorionic gonadotropin-beta (betahCG) in hyperemesis patients with or without hyperthyroxinemia. METHODS: betahCG, immune parameters and thyroid related hormones were assayed in hyperemesis patients and in controls. RESULTS: Mean serum betahCG, fT4 and TSH levels were significantly higher in hyperemesis patients than in controls (p<0. 01, p<0.01, p<0.05, respectively). Further, immune parameters regarding IgG, IgM, C3, C4 and lymphocyte count were significantly higher in patients than in controls (p<0.05, p<0.01, p<0.01, p<0.05, p<0.01, respectively). In hyperemesis patients with hyperthyroxinemia, mean serum betahCG, IgG and IgM were significantly higher than in hyperemesis women without hyperthyroxinemia (p<0.001, p<0.05, p<0.05, respectively). BetahCG was positively correlated with fT4 (r = 0.45, p<0.05), with lymphocyte count (r = 0.47, p<0.01), with IgM (r = 0.38, p<0.05) and with C3 (r = 0.40, p<0.05) in hyperemesis patients. A negative correlation between betahCG and TSH (r = -0.43, p<0.05) was noted in the hyperemesis group. Free T4 showed a positive association to IgM (r = 0.49, p<0.01), to IgG (r = 0.40, p<0.05), to lymphocyte count (r = 0.45, p<0.05). CONCLUSION: Immunologic activity in pregnancy may have an effect or role on the stimulatory mechanism of betahCG in hyperemesis patients with or without hyperthyroxinemia.

Thyroid function tests are rarely abnormal in patients with severe hyperemesis gravidarum.

OBJECTIVES: There is considerable controversy in the literature as to the cause of hyperemesis gravidarum. The aim of this project was to measure a range of thyroid hormone levels in a group of hyperemetic pregnant women. PATIENTS: The study was carried out in 10 first trimester pregnant women with hyperemesis gravidarum. All had been admitted to hospital due to the severity of their symptoms. Fifty age matched, healthy first trimester pregnant women were used as controls. MEASUREMENTS: Blood samples from the women were analysed for total T3 (TT3), total T4 (TT4), free T4 (FT4), TSH, thyrotrophin receptor antibodies (TRAb), thyroid stimulating antibodies (TSAb) and thyroid microsomal and thyroglobulin antibodies. Human chorionic gonadotrophin (hCG) levels were also measured. RESULTS: While individual patients were found to have some abnormal thyroid function tests the group as a whole showed no consistent pattern of abnormality and did not differ significantly from a group of healthy first trimester pregnant women. hCG levels were also within the normal range in the hyperemetic patients. DISCUSSION: None of the women in this study received any antithyroid medication and their symptoms improved as the pregnancy progressed. These results would suggest that there is no underlying thyroid abnormality in patients with hyperemesis gravidarum. It would appear that neither thyroid hormones, nor hCG contribute to the pathogenesis of the condition.