Low-molecular-weight heparin and preeclampsia - does the sword cut both ways? Three case reports and review of literature.

BACKGROUND: Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants during pregnancy. It is considered to be the drug of choice due to its safety in not crossing placenta. Considering the beneficial effect in the improvement of microcirculation, prophylactic application of LMWH in patients with preeclampsia became a trend. However, the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated. This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia. CASE SUMMARY: Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy. All the cases experienced catastrophic hemorrhagic events. After reviewing the twenty-one meta-analyses, the bleeding risk related with LMWH seems ignorable. Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH. Other studies reported minor bleeding risks, none of these were serious enough to stop LMWH treatment. Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored. Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial. CONCLUSION: Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

[Relationship Between ABO Blood Group and Pregnancy Complications].

ABO blood group system is the most commonly used blood group classification system in clinic practice. The relevant antigens, A, B and H determinants, are complex carbohydrate molecules that are expressed in red blood cells and other cell lines and tissues. These antigens are determined by the ABO locus located on chromosome 9 (9q34.1-q34.2). ABO blood group is associated with the development of many human diseases, e.g., cardiovascular diseases, infectious diseases, and tumors. The relationship between the ABO blood group of pregnant women and various pregnancy complications, including preeclampsia (PE) and the related diseases, pregnancy associated venous thromboembolism (PA-VTE), gestational diabetes mellitus (GDM), and postpartum hemorrhage (PPH), have become the focus of obstetricians' recent research interest. Herein, we reviewed the relationship between ABO blood group and these pregnancy complications, and found that most of the reported findings supported the following views: 1) Blood type O is a protective factor for PE, while blood type AB increases the risk of PE; 2) blood types other than O are more prone to PA-VTE than blood type O; 3) blood type O or blood type AB may be related to the pathogenesis of GDM; 4) women of blood type O are at higher risks for PPH than those of other blood types. More in-depth epidemiological and genetic studies are needed to confirm these findings in the future. These findings can provide new ideas for researching into the pathogenesis of obstetric diseases and form the theoretical basis for obstetricians to prevent and treat related diseases.

Hyperthyroid heart disease in pregnancy: Retrospective analysis of a case series and review of the literature.

BACKGROUND: Hyperthyroidism in pregnancy may pose a great threat to maternal and fetal health. The risk of hyperthyroid heart disease (HHD), even heart failure, is significantly elevated in pregnant women. AIM: To investigate the clinical characteristics, prognosis, and therapy of HHD in pregnant women. METHODS: We searched the patient registry data at West China Second University Hospital of Sichuan University in Chengdu, China, following the approval by the Ethics Committee. We retrospectively analyzed the clinical characteristics of pregnant women diagnosed with HHD. The medical records of women with HHD during pregnancy from January 2012 to December 2017 were obtained from the electronic medical records system. All the included patients were followed in outpatient clinics and by telephone interviews until October 2018. RESULTS: A total of 155 patients were diagnosed with thyrotoxicosis, of whom six were diagnosed with HHD. Three of them had regular antenatal care. Two patients were complicated with acute heart failure attacks, and one of them had a stillbirth. Both of these patients had a long history of Graves' disease with poor treatment compliance. Treatments of precipitating factors such as the control of infection could relieve the symptoms and prolong gestation for a better prognosis. Hyperthyroid heart failure could be controlled with aggressive diuretics and management of the coexisting complications. Intense monitoring and timely anti-heart failure treatment were crucial in patients with severe cardiac damage. Our findings indicated the importance of regular antenatal care and treatment adherence in patients with hyperthyroidism. CONCLUSION: The timely and accurate diagnosis of HHD and the implementation of effective management are important for a better prognosis in pregnant women with HHD. Improvement in patients' awareness of thyrotoxicosis is needed.

Pregnancy Outcomes in Women of Advanced Maternal Age: a Retrospective Cohort Study from China.

This retrospective cohort study attempts to investigate pregnancy complications and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were extracted from electronic medical records system at West China Second University Hospital of Sichuan University from January 2013 to July 2016. The study cohort consisted 8 subgroups of women on 4 different age levels (20-29 years, 30-34 years, 35-39 years and ≥40 years) and 2 different parities (primiparity and multiparity). In the study period, 38811 women gave birth at our hospital, a randomized block was used to include 2800 women of singleton pregnancy >28 gestational weeks, with 350 patients in each subgroup. Maternal complications and fetal outcomes were collected and defined according to relevant guidelines. Confounding factors representing maternal demographic characteristics were identified from previous studies and analysed in multivariate analysis. There was an increasing trend for the risks of adverse pregnancy outcomes with increasing age, especially in AMA groups. Our study showed that AMA, primiparity, maternal overweight or obesity, lower educational level and residence in rural area increased pregnancy complications and adverse fetal outcomes. Increased professional care as well as public concern is warranted.

[Placental PHLDA2 gene imprinting in patients with pre-eclampsia].

OBJECTIVE: To observe the imprinting status of maternally expressed gene pleckstrin homology-like domain, family A, member 2 (PHLDA2) in placental tissues from patients with pre-eclampsia. METHODS: Samples of placental tissues were collected from women with normal pregnancy (n=21) and pre-eclampsia (n=19). We examined two single nucleotide polymorphism (SNPs) which are prone to variation in PHLDA2: the C/T polymorphism in exon 1 and the G/A polymorphism in exon 2, corresponding to rs13390 (PHLDA2-1) and rs1056819 (PHLDA2-2), respectively. DNA PCR-direct sequencing and cDNA RT-PCR-direct sequencing were applied to detect the special-allelic imprinting status of PHLDA2. RESULTS: No heterozygote was found in placental tissues in relation to C/T polymorphism in PHLDA2 exon 1. Differences in heterozygote in relation to G/A polymorphism in PHLDA2 exon 2 were found between pre-eclampsia (4/19) and normal pregnancy(5/21), but without statistical significance. PHLDA2 cDNA from heterozygotes (PHLDA2-2) were all exclusively monoallelically expressed. CONCLUSION: Similargene polymorphism of PHLDA2 (PHLDA2-1 and PHLDA2-2) in placental tissues was found between pre-eclampsia and normal pregnancies. No loss of imprinting (LOI) of PHLDA2 was found in this study.

REDD1 expression in placenta during human gestation.

The aim of the study was to detect the regulated in development and DNA responses (REDD1) in human placentas throughout different gestational ages (GAs) and to correlate REDD1 with preeclampsia (PE). In experiments, REDD1 messenger RNA and protein expression levels throughout the gestation were determined using immunohistochemistry, quantitative reverse transcriptase polymerase chain reaction, and Western blot. Furthermore, REDD1 protein levels in placenta were also compared between normal outcome pregnancies (n = 20, GA >37 weeks) and PE pregnancies (n = 29), which includes early onset PE; n = 15, GA: 24-33 weeks) and late onset PE (n = 14, GA: 34-39 weeks) by Western blot. As a result, REDD1 protein was predominantly observed in the cytoplasm of trophoblasts. Moreover, higher levels of REDD1 were found not only at earlier gestational stage but also in the PE groups (P < .05). In conclusion, REDD1 may play an important role in maintaining the normal function of placenta during various stages of gestation and predicted that the increase in REDD1 is related to the pathogenesis of PE.

[Expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the expression of HIF-1alpha mRNA and HIF-2alpha mRNA in placentas of pregnant women with intrahepatic cholestasis of pregnancy(ICP). METHODS: Twenty samples of placentas from pregnant women with ICP and 20 samples of normal term placentas were selected. The expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA were measured by RT-PCR. RESULTS: There was no statistically significant difference in respect to the expression levels of HIF-1alpha mRNA and HIF-2alpha mRNA between the two groups of samples (P > 0.05). CONCLUSION: Under hypoxic conditions, HIF-1alpha and HIF-2alpha proteins are not transcriptionally regulated at the mRNA level but are probably regulated at the post-mRNA level.

[The relationship between P53 and hypoxia-inducible transcription factor-1alpha in the placenta of patient with intrahepatic cholestasis of pregnancy under acute hypoxic condition].

OBJECTIVE: Owing to the molecular mechanisms unexplored yet to fetal hypoxia signaling in the intrahepatic cholestasis of pregnancy (ICP), and therefore we intend to investigate the significant expression of the hypoxia-inducible transcription factor-1alpha (HIF-1alpha) in placenta of pregnant women with ICP during hypoxia. METHODS: The villous placenta tissues were in vitro cultured under hypoxia condition. The immuno-histochemistry technique was applied to probe the HIF-1alpha and P53 expressions in placentas of pregnant women and patient with ICP. RESULTS: Under the condition of normal concentration oxygen, P53 was highly expressed in the placenta of pregnant women with ICP (P < 0.01), however the HIF-1alpha expression was not up to higher than in normal control. Under the condition of lower concentration oxygen (2% O2), the HIF-1alpha and P53 expressions were detected from the placental villous tissues cultured for 4 h of normal control and patient with ICP, and with HIF-1alpha and P53 proteins increased in the placenta of pregnant women with ICP (P < 0.05 and P < 0.001 respectively). Whatever was hypoxia condition, P53 protein got always a high expression, and had a positive correlation with HIF-1alpha expression in ICP (P < 0.01). CONCLUSION: Under hypoxic conditions, high increase of HIF-1alpha may influence the increase of P53 directly, which may be one of the hypoxia pathogenesis factors in ICP. The fetal hypoxia and stillbirth may be the results of unbalance of HIF-1alpha and P53 which induced apoptosis under hypoxia condition.

[Design and field calculation of coil array for functional magnetic stimulation].

OBJECTIVE: To locate the activation point in functional magnetic stimulation (FMS). METHOD: Coil arrays were applied to establish the magnetic field distribution with ideal focusing capability. Models of hemispherical and plane coil arrays were established. Then an improved adaptive genetic algorithm (GA) was applied in the optimization of value and phase of the electric current infused into each coil. RESULT: Based on the calculated results of the optimized current configurations, ideal focusing capability was drawn as contour lines and 3-D mesh charts of the magnitude of magnetic and electric field within the calculated area. CONCLUSION: It was shown that the coil arrays have good capability to establish the magnetic distribution in focused shape. In addition, it was also shown that the coil arrays have the capability of focusing on two or more targets simultaneously.