The association between human chorionic gonadotropin and adverse pregnancy outcomes: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to evaluate the association between human chorionic gonadotropin and adverse pregnancy outcomes. DATA SOURCES: Medline, Embase, PubMed, and Cochrane were searched in November 2021 using Medical Subject Headings (MeSH) and relevant key words. STUDY ELIGIBILITY CRITERIA: This analysis included published full-text studies of pregnant women with serum human chorionic gonadotropin testing between 8 and 28 weeks of gestation, investigating fetal outcomes (fetal death in utero, small for gestational age, preterm birth) or maternal factors (hypertension in pregnancy: preeclampsia, pregnancy-induced hypertension, placental abruption, HELLP syndrome, gestational diabetes mellitus). METHODS: Studies were extracted using REDCap software. The Newcastle-Ottawa scale was used to assess for risk of bias. Final meta-analyses underwent further quality assessment using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) method. RESULTS: A total of 185 studies were included in the final review, including the outcomes of fetal death in utero (45), small for gestational age (79), preterm delivery (62), hypertension in pregnancy (107), gestational diabetes mellitus (29), placental abruption (17), and HELLP syndrome (2). Data were analyzed separately on the basis of categorical measurement of human chorionic gonadotropin and human chorionic gonadotropin measured on a continuous scale. Eligible studies underwent meta-analysis to generate a pooled odds ratio (categorical human chorionic gonadotropin level) or difference in medians (human chorionic gonadotropin continuous scale) between outcome groups. First-trimester low human chorionic gonadotropin levels were associated with preeclampsia and fetal death in utero, whereas high human chorionic gonadotropin levels were associated with preeclampsia. Second-trimester high human chorionic gonadotropin levels were associated with fetal death in utero and preeclampsia. CONCLUSION: Human chorionic gonadotropin levels are associated with placenta-mediated adverse pregnancy outcomes. Both high and low human chorionic gonadotropin levels in the first trimester of pregnancy can be early warning signs of adverse outcomes. Further analysis of human chorionic gonadotropin subtypes and pregnancy outcomes is required to determine the diagnostic utility of these findings in reference to specific cutoff values.

Use of therapeutic apheresis methods during pregnancy.

This review will focus on the current application of TA in pregnancy and possible aspects for future studies. It seems that scientific interest and field for further research in pregnancy is lately focused in specific removal of pathogens implicated in the physiologic mechanism of pre-eclampsia/HELLP syndrome as well as recurrent pregnancy failure.

Corticosteroids for improving patient-relevant outcomes in HELLP syndrome: a systematic review and meta-analysis.

BACKGROUND: We conducted this updated systematic review to assess the effects of corticosteroids vs. placebo or no treatment for improving patient-relevant outcomes in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. METHODS: CENTRAL, MEDLINE/PubMed, Web of Science, and Scopus, from the date of inception of the databases to February 3, 2024 were searched. Reference lists of included studies and systematic reviews were thoroughly searched. We included RCTs that enrolled women with HELLP syndrome, whether antepartum or postpartum, to receive any corticosteroid versus placebo or no treatment. No language or publication date restrictions were made. We used a dual independent approach for screening titles and abstracts, full text screening, and data extraction. Risk of bias was assessed in the included studies using Cochrane's RoB 2 tool. Pairwise meta-analyses were conducted, where two or more studies met methodological criteria for inclusion. GRADE approach was used to assess certainty of evidence for the pre-specified outcomes. RESULTS: Fifteen trials (821 women) compared corticosteroids with placebo or no treatment. The effect of corticosteroids is uncertain for the primary outcome i.e., maternal death (risk ratio [RR] 0.77, 95% confidence interval [CI] 0.25 to 2.38, very low certainty evidence). Out of 6 studies reporting maternal death, 5 were judged overall to have "low risk" of bias. The effect of corticosteroids is also uncertain for other important outcomes including pulmonary edema (RR 0.70, 95% CI 0.23 to 2.09), dialysis (RR 3, 95% CI 0.13 to 70.78), liver morbidity (hematoma, rupture, and failure; RR 0.22, 95% CI 0.03 to 1.83), or perinatal death (0.64, 95% CI 0.21 to 1.97) because of very low certainty evidence. Low certainty evidence suggests that corticosteroids have little or no effect on the need for platelet transfusion (RR 0.98, 95% CI 0.60 to 1.60) and may result in a slight reduction in acute renal failure (RR 0.67, 95% CI 0.40 to 1.12). Subgroup and sensitivity analyses showed results that were similar to the primary synthesis. CONCLUSIONS: In women with HELLP syndrome, the effect of corticosteroids vs. placebo or no treatment is uncertain for patient-relevant outcomes including maternal death, maternal morbidity, and perinatal death. These uncertainties regarding this critical question should be addressed by adequately powered rigorous trials. SYSTEMATIC REVIEW REGISTRATION: Center for Open Science, osf.io/yzku5.

Severe hemolysis, elevated liver enzymes, and low platelet syndrome requiring differentiation of thrombotic microangiopathy: Four cases from a nationwide survey in Japan.

Severe cases of hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome requiring plasma exchange or dialysis should be differentiated from other thrombotic microangiopathy (TMA) and treated appropriately. To evaluate the prevalence and clinical characteristics of such cases in Japan, a questionnaire-based survey was conducted among obstetricians who are members of the Perinatal Research Network Group in Japan. There were a total of 335 cases of HELLP syndrome over a 3-year period in the 48 facilities that responded to the survey. Four patients required plasma exchange or dialysis, of which two were diagnosed with atypical hemolytic uremic syndrome and two with TMA secondary to systemic lupus erythematosus. Although such severe HELLP syndrome is rare, identifying the clinical features and making accurate differential diagnosis are critical for optimal clinical outcomes for mothers and neonates.

Pregnancy-Associated Liver Diseases.

The liver disorders unique to pregnancy include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy, and preeclampsia-associated hepatic impairment, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome (HELLP). Their importance lies in the significant maternal and fetal/neonatal morbidity and mortality. Expeditious diagnosis and clinical evaluation is critical to ensure timely, appropriate care and minimize risks to the pregnant woman and her fetus/baby. A multidisciplinary approach is essential, including midwives, maternal-fetal-medicine specialists, anesthetists, neonatologists, and hepatologists.

Segmental hair metabolomics analysis in pregnant women with pregnancy complications.

INTRODUCTION: Pregnancy complications, as preeclampsia (PE) and HELLP syndrome, occurring with similar pathophysiological mechanisms, have adverse effects on the health of both mother and fetus during pregnancy and thereafter, they are leading causes of maternal and fetal morbidity and mortality. The hair metabolome has been recognized as a valuable source of information in pregnancy research, as it provides stable metabolite information to be able to assist with studying biomarkers or metabolic mechanisms of pregnancy and its complications. OBJECTIVE: The aim of this study was to investigate the hair metabolome profile of pregnant women with PE, HELLP syndrome and healthy women. METHOD: Hair samples of new-borns' mothers (patients and controls) were investigated segmentally relevant to each trimester using a proper sample preparation and gas chromatography-mass spectrometry (GC-MS) to identify robust biomarkers that can be useful for screening, early detection, follow-up and treatment of PE and HELLP syndrome, the etiology of which are still unknown. RESULTS: The results showed a significant change in the metabolome profiles of the patient and control groups regarding the trimesters. A striking decrease was observed in all 100 metabolites investigated in the patient group (p < 0.000). The metabolic pathways associated with significant metabolites have also been investigated, and the most affected pathways were observed to be the urea cycle, glycine, serine, aspartate, methionine and purine metabolism, ammonia cycle, and phosphatidylethanolamine biosynthesis. CONCLUSION: The found metabolites provide us with extensive data on the ability to establish biomarkers for predicting, early detection and monitoring of PE.

HELLP syndrome at <23 weeks' gestation: a systematic literature review.

OBJECTIVE: We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. DATA SOURCES: PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution. STUDY ELIGIBILITY CRITERIA: Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria. METHODS: Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692). RESULTS: A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system-related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases. CONCLUSION: Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system-related, and respiratory. Fetal outcomes are poor.

The correlation between pregnancy, disease activity and adverse pregnancy outcomes in patients with systemic lupus erythematosus.

OBJECTIVE: In this study, our pregnant systemic lupus erythematosus (SLE) cohort, which was under medical surveillance of both our Rheumatology and Obstetrics departments, was analyzed. We intended to determine the effects of pregnancy on disease activity and the correlation between disease flares and adverse pregnancy outcomes. METHODS: One hundred sixty eight pregnancy data involving 136 patients with SLE were examined. Cumulative clinical, laboratory, and serological parameters were described. Disease activity and flares were calculated using the systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) in the pre/postpartum periods and the SLEPDAI in the three trimesters of pregnancy. Patients with a SLEDAI-2K or SLEPDAI ≥ 4 were classified as "active." Patients with lupus low disease activity state (LLDAS) during each of these periods were identified.Fetal/neonatal death, premature birth due to pre-eclampsia, eclampsia or hemolysis, elevated Liver enzymes (HELLP) syndrome, and neonates small for gestational age were determined as adverse pregnancy outcomes (APO). RESULTS: Out of 168 pregnancies, there were 60 (35.7%) pregnancies with flares covering the pregnancy and 6 months of postpartum period. The mean SLEDAI in the 6 months postpartum period was significantly higher compared to mean disease activity during pregnancy (p < .05). Of all pregnancies, 132 (78.6%) were in LLDAS during pregnancy. Comparison of the frequency of severe postpartum flares in patients who were in LLDAS during pregnancy revealed a lower percentage of flares compared to those who were not in the LLDAS group (11 vs 29%, p < .05). APO was observed in 33.9% of 168 pregnancies. The mean SLEPDAI score was significantly higher in APO+ pregnancies than in APO- pregnancies (4.9 ± 6.1 vs 2.8 ± 4.9, p = .002). Comparison of SLICC damage score between APO - and + pregnancies revealed a significantly higher score in APO+ pregnancies (1.8 ± 2.1 vs 0.8 ± 1.3, p = .001). CONCLUSION: Postpartum six-month period appears to have the highest risk for disease flares during SLE pregnancies. Disease activity during pregnancy increases the risk of APO. In order to achieve a positive pregnancy outcome and lower maternal morbidity, regular follow-up of patients is necessary.

Advanced tubal pregnancy at 34 weeks with eclampsia and HELLP syndrome: a case report and literature re.

BACKGROUND: Tubal ectopic pregnancies in the late stages of pregnancy are uncommon, and reports on their complications are scarce. We present the case of a woman who had a tubal ectopic pregnancy at around 34 weeks and developed severe pre-eclampsia complications. CASE: A 27-year-old woman presented to our hospital several times with vomiting and convulsions. A physical exam revealed hypertension, scattered ecchymosis, and a large abdominal mass. A computed tomography (CT) scan performed in an emergency revealed an empty uterus, a stillbirth baby in the abdominal cavity, and a crescent-shaped placenta. Blood tests revealed that the patient had a low platelet count and clotting dysfunction. Laparotomy confirmed advanced right fallopian tube pregnancy without rupture, and salpingectomy was performed. Pathological examination revealed a significantly thickened tubal wall, adhesion of the placenta, and poor placental perfusion. CONCLUSION: The unusually thickened muscular layer of the tube may be one of the reasons for tubal pregnancy progressing to an advanced stage. Placenta adhesion and the special site to which it is attached reduce the risk of rupture. The detection of a crescent-shaped placenta on imaging may aid in the accurate diagnosis, distinguishing between abdominal and tubal pregnancy. Women with advanced ectopic pregnancy are more likely to develop pre-eclampsia and have poorer maternal-fetal outcomes. These negative outcomes may be influenced by abnormal artery remodeling, villous dysplasia, and placental infarction.

Value of proteinuria in evaluating the severity of HELLP and its maternal and neonatal outcomes.

BACKGROUND: HELLP syndrome refers to a group of clinical syndromes characterized by hemolysis, elevated liver enzymes and low platelet, and the evidence on the association between proteinuria and the severity of HELLP and its maternal and neonatal outcomes is rare. METHODS: 106 pregnant women were assigned to the proteinuric group (24-hUPro ≥ 0.3 g, 79 cases) and the non-proteinuric group (24-hUPro < 0.3 g, 27 cases). The proteinuric group was further divided into three subgroups: mild group (24-hUPro:0.3-2.0 g, 33 cases), moderate group (24-hUPro:2.0-5.0 g, 21 cases) and severe group (24-hUPro: ≥5.0 g, 25 cases). The general clinical data, laboratory indexes, complications and pregnancy outcome and adverse neonatal outcomes of HELLP with or without proteinuric were analyzed. RESULTS: Compared with proteinuric group, the non-albuminuric group or in the three proteinuric subgroups of HELLP pregnant women's, increased proteinuria was associated with earlier onset gestations, higher incidence of abdominal pain, skin jaundice, headache, blurred vision (p < 0.05 respectively), and also the higher levels of ALT, AST, LDH, Fib, APTT, ATII, proportions of tubular urine and lower levels of ALB, PLT (p < 0.05 respectively). In the three subgroups of the proteinuric group, the ratio of fetal growth restriction, cesarean section and postpartum hemorrhage were compared, and the difference was statistically significant (p < 0.05 respectively). Compared with the proteinuric group, the non-proteinuric group had higher birth weight, birth length, and lower SGA, admission rate in NICU (p < 0.05 respectively). In the three subgroups of the proteinuric group, significant differences were identified in the adverse outcomes of newborns (p < 0.05 respectively), and the incidence of adverse outcomes in neonates tended to be higher. Significant differences were identified in birth weight, birth length, and lower SGA and NICU occupancy rate among the three subgroups (p < 0.05 respectively). CONCLUSIONS: HELLP syndrome is a severe complication of pregnancy, involving multiple systems of the whole body. It has posed a great challenge to obstetricians for its acute onset, dangerous condition, rapid progress, and great harm. Thus, insights into HELLP syndrome should be gained, and early diagnosis, early treatment and timely termination of pregnancy should be conducted to reduce the incidence of maternal and fetal adverse outcomes and improve maternal and fetal prognosis.

HELLP syndrome, intracerebral hemorrhage, and hemophagocytic syndrome after cesarean section in a pregnant patient with severe preeclampsia: a case report.

BACKGROUND: Pregnancy-related intracranial hemorrhage (ICH) is a rare but potentially life-threatening event with complex and varied cause, such as HELLP syndrome and hemophagocytic syndrome. CASE PRESENTATION: A 33-year-old patient underwent a cesarean section with a preliminary diagnosis of "severe preeclampsia and class3 HELLP syndrome ". The patient had poor response to language before surgery, and the catheter drainage fluid was hematuria. Later, the surgeon reported severe bleeding in the operation. Following thromboelastography (TEG) result and postoperative laboratory tests confirmed class1 HELLP syndrome and ICH occurred on the second day after the surgery, and hemophagocytic syndrome was diagnosed during subsequent treatments. CONCLUSION: For patients with HELLP syndrome, we should pay attention to their coagulation condition. The coagulation tests and platelet counts should be repeated if their clinical presentation changed. Those with neurological alarm signs should receive CT or MRI scan. If a pregnant woman had prolonged hemocytopenia and thrombocytopenia, not only the HELLP but also the hemophagocytic syndrome should be considered.

Expression of insulin-like growth factor binding protein-3 in HELLP syndrome.

OBJECTIVE: To investigate the expression of insulin-like growth factor binding protein-3(IGFBP-3) in HELLP syndrome and its possible role in the pathogenesis of this disease. METHODS: 1) 87 subjects were enrolled, including 29 patients with HELLP syndrome, 29 patients with pre-eclampsia (PE), and 29 healthy gravidae as control. The levels of IGFBP-3, IGF-1, TGF-ß1, and VEGF in maternal and umbilical blood of them were detected using ELISA. Correlation analysis was used to observe the correlation between IGFBP-3 and IGF-1/TGF-ß1/VEGF in maternal and umbilical blood, as well as that between maternal serum IGFBP-3 and clinical diagnostic indicators of HELLP syndrome. 2) Human hepatic sinusoid endothelial cells (HLSEC) and human umbilical vein endothelial cells (HUVEC) were cultured with different concentrations of IGFBP-3. After 72 h of culture, cell apoptosis and the normal living cells rate were detected and compared. RESULTS: 1) In both maternal and umbilical blood of HELLP group, levels of IGFBP-3 and TGF-ß1 were higher than control and PE group, IGF-1was lower than control group, VEGF was lower than control and PE group. IGFBP-3 in maternal blood was correlated with IGF-1/TGF-ß1/ VEGF, while IGFBP-3 in umbilical blood was linked to IGF-1/TGF-ß1. In maternal blood, there was a negative correlation between PLT and IGFBP-3, and a positive correlation between ALT/AST/LDH and IGFBP-3. 2) After cultured with IGFBP-3, the total apoptosis rate of either HLSEC or HUVEC was considerably elevated, while the normal living rate was decreased. CONCLUSION: The expression of IGFBP-3 is elevated in HELLP syndrome, which may subsequently promote cell apoptosis by affecting the expression and function of IGF-1, VEGF, and TGFß1 in the IGF/PI3K/Akt, TGF-ß1/Smad3, and VEGF/eNOS/NO pathways. IGFBP-3 aggravates inflammatory reactions of the vascular endothelium and liver under hypoxia, affects the normal function of cells, and plays a role in the pathogenesis of diseases.

Assessing the Impact of the Zero Mother Mortality Preeclampsia Program on Maternal Mortality Rates at a Single Center in Bandung, West Java (2015-2022): A Retrospective Study.

BACKGROUND The Zero Mother Mortality Preeclampsia (ZOOM) program was adopted as an accelerated initiative to curb mortality related to hypertensive disorders in pregnancy, including preeclampsia. This single-center, retrospective study in Bandung, West Java, aims to evaluate the impact of the ZOOM program implemented from 2015 to 2022. MATERIAL AND METHODS We analyzed 19,176 childbirths and associated maternal deaths due to hypertension in pregnancy. Diagnoses were validated using blood pressure measures, lab tests including urine protein, liver function, blood profiles, platelets, X-ray, echocardiography, and COVID-19 testing. The case fatality rate (CFR) was assessed to evaluate the impact of the ZOOM program. RESULTS Hypertension in pregnancy was identified in 25.1% of cases, with 9.8% and 1.4% attributed to preeclampsia and eclampsia, respectively. Maternal deaths associated with hypertension accounted for 36.6%, with the majority linked to eclampsia. Heart failure (45.5%) and Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP) syndrome (22%) were the most common complications. The CFR decreased from 61% in 2018 to 10% in 2022. The overall CFR from 2015 to 2022 was 1.3%, with the highest fatality rate observed in eclampsia cases (9.4%). However, a declining trend was seen since 2018, reaching a low of 0.2% in 2021. CONCLUSIONS The implementation of the ZOOM program, which includes preeclampsia re-education, early detection, prompt intervention, protocol adjustments, and a refined referral system, led to a marked reduction in maternal deaths from hypertensive pregnancy disorders.

Optimizing Delivery Strategies in Eclampsia: A Comprehensive Review on Seizure Management and Birth Methods.

Eclampsia seizure is an always serious and potentially fatal obstetric condition. Safe delivery in women with pregnancies complicated by eclampsia seizures is still one of the greatest challenges in perinatal medicine. Pregnancy should be terminated (childbirth) in the safest and least traumatic way possible. Attempting vaginal delivery can take place only exceptionally, in the event of possibly quick completion of childbirth with a stable state of the mother and the fetus. However, immediate labor via cesarean section is most often recommended. It is essential to maintain left lateral patient positioning during cesarean section. Regional anesthesia can be used only in conscious patients who are free from coagulopathy and from HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome to decrease the risk of aspiration and failed intubation attempts in preeclamptic or eclamptic women. For sudden, unexpected interventions, when a patient arrives at the hospital with an eclampsia seizure without lab results, general anesthesia can be the best option and should be performed by an experienced medical team of anesthesiologists, ready to perform difficult intubation. Magnesium sulfate is the drug that should be used first to stop eclamptic convulsions and prevent their recurrence. Intravenous antihypertensive drugs can stabilize elevated blood pressure (BP), preventing multiorgan failure and recurrent eclampsia seizure, and thus the prevention of maternal death. This article aims to review the management of seizures during pregnancy in women with eclampsia to ensure safe delivery.

Beckwith-Wiedemann Syndrome in Newborn of Mother with HELLP Syndrome/Preeclampsia: An Analysis of Literature and Case Report with Fetal Growth Restriction and Absence of CDKN1C Typical Pathogenic Genetic Variation.

Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder, which manifests by overgrowth and predisposition to embryonal tumors. The evidence on the relationship between maternal complications such as HELLP (hemolysis, elevated liver enzymes, and low platelet count) and preeclampsia and the development of BWS in offspring is scarce. A comprehensive clinical evaluation, with genetic testing focused on screening for mutations in the CDKN1C gene, which is commonly associated with BWS, was conducted in a newborn diagnosed with BWS born to a mother with a history of preeclampsia and HELLP syndrome. The case study revealed typical clinical manifestations of BWS in the newborn, including hemihyperplasia, macroglossia, midfacial hypoplasia, omphalocele, and hypoglycemia. Surprisingly, the infant also exhibited fetal growth restriction, a finding less commonly observed in BWS cases. Genetic analysis, however, showed no mutations in the CDKN1C gene, which contrasts with the majority of BWS cases. This case report highlights the complex nature of BWS and its potential association with maternal complications such as preeclampsia and HELLP syndrome. The atypical presence of fetal growth restriction in the newborn and the absence of CDKN1C gene mutations have not been reported to date in BWS.

First-Trimester Screening for HELLP Syndrome-Prediction Model Based on MicroRNA Biomarkers and Maternal Clinical Characteristics.

We evaluated the potential of cardiovascular-disease-associated microRNAs for early prediction of HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Gene expression profiling of 29 microRNAs was performed on whole peripheral venous blood samples collected between 10 and 13 weeks of gestation using real-time RT-PCR. The retrospective study involved singleton pregnancies of Caucasian descent only diagnosed with HELLP syndrome (n = 14) and 80 normal-term pregnancies. Upregulation of six microRNAs (miR-1-3p, miR-17-5p, miR-143-3p, miR-146a-5p, miR-181a-5p, and miR-499a-5p) was observed in pregnancies destined to develop HELLP syndrome. The combination of all six microRNAs showed a relatively high accuracy for the early identification of pregnancies destined to develop HELLP syndrome (AUC 0.903, p < 0.001, 78.57% sensitivity, 93.75% specificity, cut-off > 0.1622). It revealed 78.57% of HELLP pregnancies at a 10.0% false-positive rate (FPR). The predictive model for HELLP syndrome based on whole peripheral venous blood microRNA biomarkers was further extended to maternal clinical characteristics, most of which were identified as risk factors for the development of HELLP syndrome (maternal age and BMI values at early stages of gestation, the presence of any kind of autoimmune disease, the necessity to undergo an infertility treatment by assisted reproductive technology, a history of HELLP syndrome and/or pre-eclampsia in a previous gestation, and the presence of trombophilic gene mutations). Then, 85.71% of cases were identified at a 10.0% FPR. When another clinical variable (the positivity of the first-trimester screening for pre-eclampsia and/or fetal growth restriction by the Fetal Medicine Foundation algorithm) was implemented in the HELLP prediction model, the predictive power was increased further to 92.86% at a 10.0% FPR. The model based on the combination of selected cardiovascular-disease-associated microRNAs and maternal clinical characteristics has a very high predictive potential for HELLP syndrome and may be implemented in routine first-trimester screening programs.

Decreased Levels of Soluble Developmental Endothelial Locus-1 Are Associated with Thrombotic Microangiopathy in Pregnancy.

HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets) syndrome is a life-threatening complication of pregnancy, which is often secondary to preeclampsia. To date, there is no biomarker in clinical use for the early stratification of women with preeclampsia who are under increased risk of HELLP syndrome. Herein, we show that the levels of circulating developmental endothelial locus-1 (DEL-1), which is an extracellular immunomodulatory protein, are decreased in patients with HELLP syndrome compared to preeclampsia. DEL-1 levels are also negatively correlated with the circulating levels of kidney injury molecule-1 (KIM-1), which is a biomarker for disorders associated with kidney damage. Receiver-operating characteristic curve analysis for DEL-1 levels and the DEL-1 to KIM-1 ratio demonstrates that these values could be used as a potential biomarker that distinguishes patients with HELLP syndrome and preeclampsia. Finally, we show that placental endothelial cells are a source for DEL-1, and that the expression of this protein in placenta from patients with HELLP syndrome is minimal. Taken together, this study shows that DEL-1 is downregulated in HELLP syndrome both in the circulation and at the affected placental tissue, suggesting a potential role for this protein as a biomarker, which must be further evaluated.

Evaluation of long noncoding RNA (LncRNA) in pathogenesis of HELLP syndrome: diagnostic and future approach.

HELLP syndrome is a disorder during pregnancy which is defined by elevation of liver enzymes, haemolysis, and low platelet count. This syndrome is a multifactorial one and both genetic and environmental components can have a crucial role in this syndrome's pathogenesis. Long noncoding RNAs (lncRNAs), are defined as long non-protein coding molecules (more than 200 nucleotides), which are functional units in most cellular processes such as cell cycle, differentiation, metabolism and some diseases progression. As these markers discovered, there has been some evidence that they have an important role in the function of some organs, such as placenta; therefore, alteration and dysregulation of these RNAs can develop or alleviate HELLP disorder. Although the role of lncRNAs has been shown in HELLP syndrome, the process is still unclear. In this review, our purpose is to evaluate the association between molecular mechanisms of lncRNAs and HELLP syndrome pathogenicity to elicit some novel approaches for HELLP diagnosis and treatment.

Ruptured subcapsular liver hematoma as a rare complication of HELLP syndrome. A therapeutic challenge.

HELLP syndrome (HS), a low-incidence condition of uncertain pathogenesis associated with pregnancy hypertensive syndromes, is characterized by hemolysis, elevated liver enzymes and low platelet count. Ruptured subcapsular liver hematoma complicated with hemoperitoneum is an uncommon but very serious condition where early recognition and multidisciplinary management are key to reduce its associated maternal, infant mortality rate. Symptoms are nonspecific, characterized by por epigastric pain, nausea and vomiting; clinical suspicion and appropriate imaging studies are of crucial importance. We report the case of a 36-year-old primiparous woman at 39 weeks of gestation. She was admitted for early membrane rupture, with delivery complicated by retained placenta. During the immediate puerperium she had blood pressure > 140/90 mmHg, epigastric pain and vomiting, which required respiratory and hemodynamic support. An exploratory laparotomy was performed that revealed a massive hemoperitoneum as well as CR in the RLL with multifocal active bleeding. The left liver lobe was macroscopically normal. The patient underwent hemoperitoneum drainage and hepatic packing (HP); biopsy findings were consistent with necrosis. Polytransfusion was initiated with blood products and antihemorrhagic agents.

Are the serum delta neutrophil index and systemic inflammatory index useful as predictive parameters for preeclampsia and HELLP syndrome?

OBJECTIVE: We aimed to determine whether the serum delta neutrophil index and other systemic inflammatory index parameters can have an auxiliary effect in the diagnosis when used with other bio chemical markers in preeclampsia and HELLP syndrome and to determine the role of inflammation in the pathogenesis of these diseases. MATERIALS AND METHODS: 121 pregnant women who met the inclusion and exclusion criteria were included in the study. 52 pregnant women diagnosed with preeclampsia and 19 pregnant women diagnosed with HELLP syndrome were included in the study group, and 50 healthy pregnant women were included in the control group. Demographic data, hematological and bio chemical parameters, and inflammatory markers (serum delta neutrophil index - DNI - and systemic inflammatory index parameters) of the groups were recorded and compared between groups. RESULTS: In terms of neutrophil lymphocyte ratio, platelet lymphocyte ratio, and DNI, the HELLP group was different from both groups. The control and preeclampsia groups were similar. In terms of monocyte-to-lymphocyte ratio, the preeclampsia group was different from both groups. The control and HELLP groups were similar. In terms of the systemic inflammatory index, all groups were similar. CONCLUSION: In our study, we found that when maternal serum DNI values are used together with other bio chemical parameters, it can help in the diagnosis of preeclampsia and HELLP syndrome, and inflammation may play a role in the pathogenesis of these diseases.