Case Series of Diabetic Ketoacidosis in Late Pregnancy with Normal Glucose Tolerance.

Diabetic ketoacidosis (DKA) is rare in pregnancy, especially in pregnant women with normal glucose tolerance examined in early pregnancy. Once DKA occurs in pregnancy, the disease progresses rapidly and can be life-threatening for both mother and fetus. We concluded three cases of DKA in late pregnancy. The clinical manifestations, progression, and prognosis of the three cases are different, but all of the cases have normal glucose tolerance. We summarized the characteristics of pregnant women with DKA and analyzed and discussed them in conjunction with literature for reference by clinical doctors.

Platelet aggregation in normal pregnancy.

It was recently shown that abnormal platelet aggregation (PA) had played a critical role in some adverse pregnancies. Till now reference range for PA in normal pregnancy has not been determined. Furthermore, few study has been conducted to explore the factors related to PA. Our study was performed to assess the reference range of PA in normal pregnancy (150 participants in the second trimester), and to determine whether it differs from that of the controls (38 nonpregnant participants). In addition, this study explored the factors related to PA. The results showed that PA was significantly higher in normal pregnancy than that in the controls (84.40% vs. 80.7%, respectively, P = 0.013). The reference interval for PA in normal pregnancy was 74.75%-94.77%. Hemoglobin (Hb), platelet counts (PLT) and albumin (Alb) were significant lower in normal pregnancy than those in the control group. Moreover, it was found that PA was positively correlated with PLT (r = 0.263, P < 0.001), and negatively correlated with platelet distribution width (PDW) (r = -0.342, P < 0.001) and mean platelet volume (r = -0.296, P < 0.001). Linear correlations between PA and Alb, PDW were proved by linear regression model (LRM). In conclusion, PA was enhanced in normal pregnancy, and Alb and PDW might be the possible contributing factors to PA.

Paternal body mass index before conception associated with offspring's birth weight in Chinese population: a prospective study.

Whether paternal epigenetic changes resulting from nutrition might be inherited by their offspring remains unknown. This study evaluated the relationship between preconception paternal body weight and their offspring's birth weight in 1,810 Chinese mother-father-baby trios. Information on paternal and maternal preconception body weight and height was collected via a self-reported questionnaire. Birth weight was collected from medical records. Paternal preconception body weight was associated with offspring's birth weight (p trend = .02) after multivariate adjustment. Each standard deviation increment of paternal body mass index was associated with an additional 29.6 g increase of birth weight (95% confident interval: 5.7 g, 53.5 g). The association was more pronounced in male neonates, and neonates with overweight mothers, and with mothers who gained excessive gestational weight, compared to their counterparts (all p interaction < .05). Sensitivity analyses showed similar pattern to that of the main analysis. Paternal preconception body weight was associated with birth weight of their offspring.Impact statementWhat is already known on this subject? More efforts have previously been put on the maternal contribution to birth weight, however, it is uncertain whether paternal pre-conceptional body weight, an indicator for epigenetic information, might be inherited by their offspring.What do the results of this study add? In the current study that included 1,810 Chinese mother-father-baby trios, a small but significant association was observed between paternal preconception body weight and offspring's birth weight (p trend =.02).What are the implications of these findings for clinical practice and/or further research? Paternal epigenetic information of nutrition could be inherited by their offspring.

Transcriptomic Profiling in Human Decidua of Severe Preeclampsia Detected by RNA Sequencing.

Maternal decidua plays a critical role in implantation and placentation. Impaired decidualization causes failed intravascular trophoblast invasion and inadequate placentation and then increases the risk of preeclampsia (PE). RNA sequencing (RNA-Seq) has achieved great advances in the characterization and quantification of transcriptomes; is a powerful tool for new transcript discovery, genome annotation, and expression profiling. In the present study, we conducted a RNA-Seq analysis to compare gene expression between decidua of PE (n = 3, early-onset severe PE, EOSPE; n = 3, late-onset severe PE, LOSPE) and normal pregnancies (n = 3). We revealed that decidual gene transcription profile was altered in severe PE and identified 293 key PE-related genes involved in 19 differentially regulated pathways relevant for the pathogenesis of PE, among which ENO2, PGK1, and HK2 involved in glycolysis/gluconeogenesis and HIF-1 signaling pathway which are all highly related with tumorigenesis and are significantly upregulated in cancer cells were severely inhibited in the decidua of PE. Moreover, we identified 22 core regulatory genes, including the newly identified pseudogenes BNIP3P1, HK2P1, and PGK1P1 that encode long non-coding RNA (lncRNA); interestingly, BNIP3/BNIP3P1, HK2/HK2P1, and PGK1/PGK1P1 appear in pairs in core genes. Subsequent analyses using quantitative PCR validated a portion of these results. This study may provide further insight into the mechanisms of PE and function as preventive, predictive, and therapeutic measures. Future functional studies are needed in order to accomplish a greater understanding of the mechanisms involved. J. Cell. Biochem. 119: 607-615, 2018. © 2017 Wiley Periodicals, Inc.

BMAL1 facilitates trophoblast migration and invasion via SP1-DNMT1/DAB2IP pathway in recurrent spontaneous abortion.

The underlying mechanism about rhythms and epigenetics leading to aberrant trophoblast migration and invasion in recurrent spontaneous abortion (RSA) remains unknown. Brain and muscle ARNT-like protein 1 (BMAL1) is considered as a crucial role in fertility, and polymorphism of BMAL1 gene has been reported to be associated with risk of miscarriage. However, the functional role of BMAL1 in RSA is not fully understood. Previous study shows the descended expression of DNA 5'-cytosine-methyltransferases 1 (DNMT1) in the villous of early pregnancy loss. Thus, understanding of the regulation of DNMT1 expression may be of significance for the elucidation of the process of RSA. Using HTR-8/SVneo and JEG-3 cell lines, we certified the induction of specificity protein 1 (SP1) to DNMT1 and DAB2 interaction protein (DAB2IP), respectively, both of which further activated matrix metallo-proteinase 2/9 (MMP2/9), bringing out changes in trophoblast migration and invasion. Notably, BMAL1 functioned as a positive upstream factor of SP1 only in HTR-8/SVneo cells but not in JEG-3 cells, inducing SP1-DNMT1/DAB2IP pathway and facilitating migration and invasion of trophoblasts. In addition, progesterone might restore the down-regulation of BMAL1 and downstream pathway in a dose-dependent manner. Last but not least, the decreased abundance of BMAL1 was correlated positively with that of SP1, DNMT1, DAB2IP, MMP2 and MMP9 in human villous specimens of RSA. Our results demonstrate that the induction of BMAL1 to SP1 contributes to the expression of DNMT1 and DAB2IP, respectively, activating trophoblast migration and invasion. The deregulation of the BMAL1-mediated pathway in RSA can be rescued by progesterone.

Notch2 and Notch3 suppress the proliferation and mediate invasion of trophoblast cell lines.

Notch signaling pathways play important roles in cell fate and many diseases, including preeclampsia, the dysregulation of which may be the main cause of maternal mortality. This study aimed to investigate the roles of Notch2 and Notch3 in proliferation and invasion in trophoblast cell lines (BeWo and JAR). Small hairpin RNAs targeting Notch2/Notch3 and Notch2/Notch3-overexpression vectors were designed, constructed and transfected into BeWo and JAR cells. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were then used to detect Notch2 and Notch3 mRNA and protein levels, and confirm the efficiency of silence and overexpression. Flow cytometry assays were conducted to evaluate the cell cycle of the two cell lines, and transwell assays were used to detect migration and invasion. Western blot analysis was also performed to show the alteration of the cell lines' physiological activities at protein level.When Notch2 was downregulated in BeWo cells, proliferation was dramatically promoted, while migration and invasion were significantly inhibited. When Notch2 was upregulated in JAR cells, proliferation was inhibited, but migration and invasion were promoted. After overexpression of Notch3 in BeWo cells, proliferation was downregulated, but migration and invasion were both upregulated. By contrast, the silencing of Notch3 expression in JAR cells significantly enhanced proliferation, but suppressed migration and invasion. These data indicated that Notch2 and Notch3 mediate the invasion and migration of BeWo and JAR cells, and may play a potential role in early onset severe preeclampsia.

Accuracy of sonographic fetal weight estimation prior to delivery in a Chinese han population.

OBJECTIVE: To compare the sonographic-estimated fetal weights (EFW) calculated with the Hadlock formula and with the Woo formula in a group of Chinese pregnant women. METHODS: We prospectively recruited term pregnancies for sonographic biometric examination. EFWs were calculated according to two formulas and compared with the corresponding birth weight (BW). We also assessed the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of EFW for the diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) neonates. RESULTS: A total of 374 subjects who delivered within 7 days after the sonographic examinations was recruited. Using the Hadlock formula, the median absolute difference between EFW and BW was 182 g (15-308 g) and the median percentage difference was 5.3% (0.5-9.1%), whereas it was 230 g (62-367) and 7.1% (2.1-10.4%) for the Woo formula (p < 0.001). Several factors, namely the fetal presentation, gender, and high amniotic quantity, showed no evident impact on this predictive difference. Among the 175 women who delivered within 2 days after ultrasound, the sensitivity and specificity of Hadlock EFW were 100% and 97.1% for the detection of SGA and 48.1% and 97.3% for the detection of LGA, respectively. The PPV and NPV were 44.4% and 100.0% for the detection of SGA and 76.5% and 91.1% for the detection of LGA, respectively. CONCLUSIONS: EFWs calculated using the Hadlock formula for our research subjects were as accurate as those reported for other populations. The predictive performance showed a high NPV for the diagnosis of SGA and a relatively acceptable PPV for the diagnosis of LGA. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:465-471, 2017.

Effects of Notch2 and Notch3 on Cell Proliferation and Apoptosis of Trophoblast Cell Lines.

AIMS: To investigate the effect of Notch2 and Notch3 on cell proliferation and apoptosis of two trophoblast cell lines, BeWo and JAR. METHODS: Notch2 and Notch3 expression in BeWo and JAR cells was upregulated or downregulated using lentivirus-mediated overexpression or RNA interference. The effect of Notch2 and Notch3 on cell proliferation was assessed by the CCK-8 assay. The effect of Notch2 and Notch3 on the apoptosis of BeWo and JAR cells was evaluated by flow cytometry using the Annexin V-PE Apoptosis kit. Lentivirus-based overexpression vectors were constructed by cloning the full-length coding sequences of human Notch2 and Notch3 C-terminally tagged with GFP or GFP alone (control) into a lentivirus-based expression vector. Lentivirus-based gene silencing vectors were prepared by cloning small interfering sequences targeting human Notch2 and Notch3 and scrambled control RNA sequence into a lentivirus-based gene knockdown vector. The effect of Notch2 and Notch3 on cell proliferation was assessed by the CCK-8 assay. And the effect of Notch2 and Notch3 on the apoptosis of BeWo and JAR cells was evaluated by flow cytometry using the Annexin V PE Apoptosis kit. RESULTS: We found that the downregulation of Notch2 and Notch3 gene expression in BeWo and JAR cells resulted in an increase in cell proliferation, while upregulation of Notch3 and Notch2 expression led to a decrease in cell proliferation. Moreover, the overexpression of Notch3 and Notch2 in BeWo and JAR cells reduced apoptosis in these trophoblast cell lines, whereas apoptosis was increased in the cells in which the expression of Notch3 and Notch2 was downregulated. CONCLUSIONS: Notch2 and Notch3 inhibited both cell proliferation and cell apoptosis in BeWo and JAR trophoblast cell lines.

Expression of notch family proteins in placentas from patients with early-onset severe preeclampsia.

OBJECTIVES: This study is aimed to identify the expression of Notch family proteins in placentas from patients with early-onset severe preeclampsia. STUDY DESIGN: The expression of Notch family proteins in placentas was investigated by immunohistochemistry, Western blotting, and real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The profile of distribution of all Notch family proteins in placentas from patients with early-onset severe preeclampsia is similar to that in normal placentas. All Notch family proteins are expressed in placental trophoblasts. Moreover, Notch1 and Jagged1 (Jag1) are detected in placental endothelial cells. Real-time RT-PCR showed that messenger RNA levels of Notch2 and Delta-like4 (Dll4) in placentas from patients with early-onset severe preeclampsia are lower than that of normal placentas. Western blotting showed a significant increase in Notch3 expression and a significant decrease in Notch2 expression in placentas from patients with early-onset severe preeclampsia relative to those in normal placentas. CONCLUSION: The results suggest that Notch2 and Notch3 may play some roles in the pathogenesis of preeclampsia.

Pregnancy outcomes and relative risk factors among Chinese women with congenital heart disease.

OBJECTIVE: To summarize pregnancy outcomes among a cohort of Chinese women with congenital heart disease (CHD) and to identify predictive risk factors for maternal, fetal, and neonatal complications. METHODS: A retrospective analysis of 529 women with CHD who gave birth at the Shanghai Obstetrical Cardiology Intensive Care Center, Shanghai, China, between January 1, 1993, and September 30, 2010. Maternal, fetal, and neonatal complications were evaluated for these women. RESULTS: Maternal cardiac complications were reported in 33 (6.2%) of the women, whereas fetal and neonatal complications were reported in 145 (27.4%). The factors found to be significantly predictive for maternal cardiac complications were cardiac events before pregnancy (odds ratio [OR] 36.811), New York Heart Association functional class greater than II (OR 27.702), oxygen saturation below 90% (OR 7.506), and left ventricular obstruction (aorta stenosis) (OR 2.408). Factors significantly predictive for fetal and neonatal complications were New York Heart Association functional class greater than II (OR 20.12), oxygen saturation below 90% (OR 3.78), and pulmonary arterial hypertension (systolic pressure ≥ 50 mm Hg) (OR 3.42). CONCLUSION: Identification of maternal, fetal, and neonatal complications among women with CHD may guide medical intervention and therefore reduce pregnancy-associated risk for these patients.

Notch signaling pathway and human placenta.

Notch signaling was evolutionarily conserved and critical for cell-fate determination, differentiation and many other biological processes. Growing evidences suggested that Notch signaling pathway played an important role in the mammalian placental development. All of the mammalian Notch family proteins had been identified in human placenta except Delta-like 3, which appeared to affect the axial skeletal system. However the molecular mechanisms that regulated the Notch signaling pathway remained largely unknown in human placenta. Therefore, additional research was needed to investigate expression pattern of Notch family members and the mechanisms for activation of Notch signaling pathway in human placenta, which might help elucidate the roles of Notch signaling pathway in human placentation. This review would focus on the roles of Notch receptors and ligands in the human placental trophoblasts function and placental angiogenesis. It might hopefully provide perspectives for future research about human placentation of pregnancy complicated by preeclampsia and other placenta associated diseases.

Pregnancy outcomes in women with Ebstein's anomaly.

OBJECTIVES: To evaluate whether women with Ebstein's anomaly can tolerate pregnancy and whether the perinatal outcomes are influenced by the severity of Ebstein's anomaly. METHODS: Data of four women with Ebstein's anomaly delivered in our unit were collected and analyzed retrospectively. RESULTS: (1) Two women with Ebstein's anomaly had uneventful pregnancies, cesarean section and puerperium. (2) The patient with the most serious Ebstein's anomaly (with central cyanosis and clubbing) had an episode of paroxysmal ventricular tachycardia and spontaneous cardioversion to sinus rhythm on day 4 postpartum. She developed intracerebral hemorrhage on day 25 postpartum. (3) One of them suffered from atrial flutter on 38 + 3 weeks of gestation which was restored to sinus rhythm after being treated with verapamil and remained stable afterward. (4) All neonatal birth weights were more than 2,500 g, and all neonatal Apgar scores were 10 at 1 min. (5) The gestational age at delivery of our cases was from week 36 + 4 to week 38 + 4. The mean duration of follow-up was 56 days postpartum. CONCLUSIONS: (1) The clinical features of pregnant women with Ebstein's anomaly vary. They might have good perinatal outcomes when given appropriate treatment. (2) Those with cyanosis should be given more attention, as they can have more complications during pregnancy, delivery and puerperium. (3) All women with Ebstein's anomaly should be offered fetal echocardiography during pregnancy. (4) Vaginal delivery is advised for most cases with Ebstein's anomaly.

[Perinatal management and pregnancy outcome in pregnant women with pulmonary hypertension complicating cardiac disease].

OBJECTIVE: To evaluate the pregnancy outcome of women with pulmonary hypertension complicating cardiac disease. METHODS: Clinical data of 61 cases of pregnant women with pulmonary hypertension from Jan 1996 to Aug 2004 were analyzed and they were divided into three groups: 32 cases of slight group [pulmonary hypertension from 30 mm Hg (1 mm Hg = 0.133 kPa) to 49 mm Hg], 23 cases of moderate group (pulmonary hypertension from 50 mm Hg to 79 mm Hg) and 6 cases of severe group (pulmonary hypertension equal to or higher than 80 mm Hg). The types of heart disease, cardiac functional status (New York heart association, NYHA), gestational weeks of pregnancy termination, mode of delivery and outcomes of infants were compared between the groups. RESULTS: (1) The occurrence rate of NYHA class III - IV was 5/6 in severe group. The rate of NYHA class I - II was 72% (23/32) in slight group. (2) The rate of moderate and severe pulmonary hypertension was 53% (11/21) and of NYHA class IV 43% (9/21) in rheumatic heart disease. The rate of slight pulmonary hypertension was 97% (35/36) and NYHA class I - II 81% (29/36) in congenital heart disease. (3) The rate of term delivery was 75% (24/32) and the birth weight was 2744 g on average in slight group. The rate of term delivery was 48% (11/23), preterm labor 35% (8/23), abortion 17% (4/23) in moderate group. The rate of term delivery was 1/6, preterm labor occurred in 3 cases, and abortion in 2 cases in severe group. The rates of neonatal complications between the three groups had no significant difference. (4) Caesarean section rate was 79% (48/61) among all patients. (5) Overall maternal mortality was 2% (1/61). CONCLUSIONS: The rate of heart failure increases gradually with the severity of pulmonary hypertension. The severity of pulmonary hypertension in rheumatic heart disease is higher than in congenital heart disease. The rate of maternal mortality and fetal loss increases in pregnant women with pulmonary hypertension complicating cardiac disease. Perinatal morbidity is higher than normal. Cesarean section is more suitable for those women.