Lower-dose corticosteroid therapy in severe immune thrombocytopenia during pregnancy: The comparable efficacy and lower incidence of maternal complications.

Background: This study assessed the clinical efficacy of oral prednisone at low dose (LD) versus the previous high-dose (HD) study in patients with severe immune thrombocytopenia during pregnancy and its side effects on maternal and neonatal outcomes. Study design: Pregnant patients with ITP were enrolled in the study (platelet count <30×109/L) between January 2015 and 2019. A total of 43 patients received LD oral prednisone (0.25-0.5 mg/kg) as the initial treatment and were compared retrospectively with the 31 patients in the HD (1 mg/kg) study. The primary clinical endpoint was the response rate, and the secondary endpoint was maternal hemorrhagic events, complications, and neonatal outcomes. Results: In total, 35% of patients responded (15/43) to the LD cortico-therapy, including four patients with a complete response which was no less than HD therapy (35.5%). The bleeding symptoms of 10 (30%) patients were ameliorated after 14 days of LD prednisone treatment. Preeclampsia occurred in three cases (7% of total) of which the incidence was obviously lower than that of the previous study at HD (18%). No stillbirth or miscarriage occurred in the LD group, and neonatal outcomes had no significant differences between the two studies. Conclusion: LD prednisone therapy for severe ITP patients during pregnancy had equal efficacy to HD treatment. In addition, the decrease in dosage significantly reduced the incidence of hypertension.

Prednisone plus IVIg compared with prednisone or IVIg for immune thrombocytopenia in pregnancy: a national retrospective cohort study.

Background: The responses of intravenous immunoglobulin (IVIg) or corticosteroids as the initial treatment on pregnancy with ITP were unsatisfactory. This study aimed to assess the safety and effectiveness of prednisone plus IVIg versus prednisone or IVIg in pregnant patients with immune thrombocytopenia (ITP). Methods: Between 1 January 2010 and 31 December 2020, 970 pregnancies diagnosed with ITP at 19 collaborative centers in China were reviewed in this observational study. A total of 513 pregnancies (52.89%) received no intervention. Concerning the remaining pregnancies, 151 (33.04%) pregnancies received an initial treatment of prednisone plus IVIg, 105 (22.98%) pregnancies received IVIg alone, and 172 (37.64%) pregnancies only received prednisone. Results: Regarding the maternal response to the initial treatment, no differences were found among the three treatment groups (41.1% for prednisone plus IVIg, 33.1% for prednisone, and 38.1% for IVIg). However, a significant difference was observed in the time to response between the prednisone plus IVIg group (4.39 ± 2.54 days) and prednisone group (7.29 ± 5.01 days; p < 0.001), and between the IVIg group (6.71 ± 4.85 days) and prednisone group (p < 0.001). The median prednisone duration in the monotherapy group was 27 days (range, 8-195 days), whereas that in the combination group was 14 days (range, 6-85 days). No significant differences were found among these three treatment groups in neonatal outcomes, particularly concerning the neonatal platelet counts. The time to response in the combination treatment group was shorter than prednisone monotherapy. The duration of prednisone application in combination group was shorter than prednisone monotherapy. The combined therapy showed a lower predelivery platelet transfusion rate than IVIg alone. Conclusion: These findings suggest that prednisone plus IVIg may represent a potential combination therapy for pregnant patients with ITP.

Prediction of postpartum hemorrhage in pregnant women with immune thrombocytopenia: Development and validation of the MONITOR model in a nationwide multicenter study.

Globally, postpartum hemorrhage (PPH) is the leading cause of maternal death. Women with immune thrombocytopenia (ITP) are at increased risk of developing PPH. Early identification of PPH helps to prevent adverse outcomes, but is underused because clinicians do not have a tool to predict PPH for women with ITP. We therefore conducted a nationwide multicenter retrospective study to develop and validate a prediction model of PPH in patients with ITP. We included 432 pregnant women (677 pregnancies) with primary ITP from 18 academic tertiary centers in China from January 2008 to August 2018. A total of 157 (23.2%) pregnancies experienced PPH. The derivation cohort included 450 pregnancies. For the validation cohort, we included 117 pregnancies in the temporal validation cohort and 110 pregnancies in the geographical validation cohort. We assessed 25 clinical parameters as candidate predictors and used multivariable logistic regression to develop our prediction model. The final model included seven variables and was named MONITOR (maternal complication, WHO bleeding score, antepartum platelet transfusion, placental abnormalities, platelet count, previous uterine surgery, and primiparity). We established an easy-to-use risk heatmap and risk score of PPH based on the seven risk factors. We externally validated this model using both a temporal validation cohort and a geographical validation cohort. The MONITOR model had an AUC of 0.868 (95% CI 0.828-0.909) in internal validation, 0.869 (95% CI 0.802-0.937) in the temporal validation, and 0.811 (95% CI 0.713-0.908) in the geographical validation. Calibration plots demonstrated good agreement between MONITOR-predicted probability and actual observation in both internal validation and external validation. Therefore, we developed and validated a very accurate prediction model for PPH. We hope that the model will contribute to more precise clinical care, decreased adverse outcomes, and better health care resource allocation.

Evaluation of glucocorticoid compared with immunoglobulin therapy of severe immune thrombocytopenia during pregnancy: Response rate and complication.

PROBLEM: Evaluate the response rate of glucocorticoid (GC) and/or immunoglobulin (IVIg) therapy in severe thrombocytopenia of immune thrombocytopenia (ITP) pregnant patients and the influence on maternal and neonatal outcomes. METHOD OF STUDY: This is a prospective observational cohort study. Pregnant ITP patients with platelet count less than 30 × 109 /L and their newborn infants participated in this research. Over a 3-year period, 87 patients were allocated to 4 groups: group 1 (n = 18) were treated by oral prednisone, group 2 (n = 20) with IVIg, group 3 (n = 22) with prednisone/methlyprednisone plus IVIg, and group 4 were non-treatment controls (n = 27). Diagnosis and therapy were based on guideline from the 2011 American Society of Hematology criteria, and the initial dose of prednisone was 1 mg/kg day. Their newborns were followed up to 1 year old. RESULTS: The response rate among patients who ever received prednisone therapy was 35.5% (11/31) overall, while the IVIg response rate was 55.9% (19/34). The incidence of pregnancy induced hypertension in GC therapy group was significantly higher than controls (22.2% and 13.6% vs 0%). There was no significant difference in neonatal outcomes in treatment groups in comparison with controls. The rate of Neonatal follow-up within 1 year old was 63%, and there is no evidence indicated intrauterine GC exposure influence the growth and development. CONCLUSION: GC therapy of 1 mg/kg for ITP patients during pregnancy is less efficiency than non-pregnant population and increases the incidence of hypertensive disorders. The use of lower starting doses of prednisone may be suggested for use in pregnancy.

Clinical features of new-onset systemic lupus erythematosus in pregnant patients.

AIM: This study was conducted to examine the clinical characteristics of new-onset systemic lupus erythematosus (SLE) during pregnancy. METHODS: We performed a retrospective study of all pregnancies in patients with SLE managed at The People's Hospital of Peking University from 2008 to 2015. In total, 97 pregnancies were identified and studied, 22 of which were first diagnosed with SLE during pregnancy or puerperium. RESULTS: New-onset SLE mainly occurred during the first and second pregnancy trimesters. Blood and multi-organ involvement were detected in 95.45% and 45.45% of new-onset patients, respectively, and both had a higher incidence than in active patients. Thrombocytopenia was the most common blood involvement in new-onset patients. All three maternal deaths occurred in new-onset patients. There were nine (40.91%) fetal losses, three (13.64%) low birth weight infants, one (4.54%) fetal malformation and two (9.09%) cases of neonatal lupus in new-onset patients. CONCLUSION: New-onset pregnant SLE patients were characterized with blood system involvement and generally experienced more adverse maternal outcomes than active patients with SLE history. However, adverse fetal outcomes in new-onset patients were the same as those of active patients with an SLE history.

Clinical features and outcome of pregnancy with SLE-associated thrombocytopenia.

OBJECTIVE: To analyze the course of maternal diseases and compare pregnancy outcomes in patients with systemic lupus erythematosus (SLE)-associated thrombocytopenia to patients without. METHODS: Medical charts of 77 pregnancies in 73 SLE patients were systematically reviewed. Patients were divided into two groups according to the presence or absence of thrombocytopenia. Patients who are new onset SLE during pregnancy were also been studied. RESULT: Thrombocytopenia was found in 18 (23.3%) of the pregnancies. SLE patients with thrombocytopenia during pregnancy had higher percentage of disease flaring (11/18 versus 14/59, p = 0.003) and SLE-Pregnancy Disease Activity Index (7.89 ± 6.192 versus 2.41 ± 3.3.89, p = 0.001) compared to patients without. Also, patients with thrombocytopenia had a higher percentage of pulmonary, cardiac and multiple organ system involvement. There was a statistically significant difference in preeclampsia and early onset hypertensive disorder induced before 34 weeks as well as the rate of live birth less than 34 weeks (33.3% versus 6.8%, p = 0.003 & 38.9% versus 13.6%, p = 0.018 & 16.7% versus 1.7%, p = 0.038). Patients with thrombocytopenia suffered from higher rate of pregnancy loss (22.2% versus 3.4%, p = 0.024) and neonatal death (33.3% versus 1.7%, p = 0.000). In our study there were 17 patients with new-onset of SLE during pregnancy. The hematological system manifestation occurred in all of them and there was a significant increase in the incidence of thrombocytopenia (n = 12, 70.6%). CONCLUSION: Thrombocytopenia in SLE during pregnancy indicates higher disease activity, severe organ damage, early onset preeclampsia and higher pregnancy loss.

[Analysis of risk factors for preeclampsia in pregnancies complicated with chronic aplastic anemia].

OBJECTIVE: To investigate the risk factors for preeclampsia(PE) in pregnancies complicated with chronic aplastic anemia (CAA) by analyzing the obstetric management and pregnancy outcome. METHODS: Retrospectively review the clinical data including the obstetric management, the laboratory findings and the pregnancy outcome of 41 pregnant women complicated with CAA, all of whom were hospitalized in Peking University People's Hospital from May 2002 to February 2011. Multiple logistic regression was used to explore the risk factors associated with PE. RESULTS: (1) Twenty-eight patients were diagnosed before conception while 13 were diagnosed during gestation. Eleven patients including all the 7 who were categorized as severe CAA presented with mild bleeding in the third trimester. (2) The medians of white blood cell counts, hemoglobin concentrations and platelet counts were 5.0×109/L, 66.0 g/L and 12.0×109/L respectively. (3) The obstetric management consisted of strict assessment, intensive surveillance and follow-up, appropriate supportive measures, timely recognition of complications, and delivery when necessary. Twenty-one patients received supportive transfusions. Ten patients developed PE, all of whom were diagnosed as severe PE (SPE). Twelve patients suffered postpartum hemorrhage, and 3 of them had blood loss more than 1000 ml. All were conservatively treated in success. (4) The median gestational age of delivery was 37 weeks. Sixteen cases delivered before 37 weeks and 5 delivered before 34 weeks. Two patients developed SPE at 29 weeks and 30 weeks respectively, and both of the neonates died for severe asphyxia. The birth weight of the live neonates ranged from 1500 to 3660 g. (5) The postpartum follow-up period ranged from 6 months to 7 years. Thirty-three patients got improvement without dependence on transfusions. Four achieved no remission and still needed intermittent transfusions. Four were lost in follow-up. (6) Significant differences were found in the bleeding tendency, the platelet counts and the delivery weeks when comparing the patients developing PE and those without PE. No differences were found with regard to the age, the gestational age of first visit, the percentage of patients diagnosed before conception, the percentage of severe CAA, the choice of treatment, the white blood cell counts and the hemoglobin level. The Multiple logistic regression showed that the platelet count less than 10×109/L was an independent risk factor for CAA patients developing PE (P = 0.006). CONCLUSIONS: Most pregnancies complicated with CAA could achieve good maternal and fetal outcome, when intensive prenatal care and supportive management are provided. SPE is the most common complication. The platelet count less than 10×109/L is perhaps an independent risk factor for CAA patients developing PE.

Bilateral interhemispheric subdural hematoma after inadvertent lumbar puncture in a parturient.

PURPOSE: Interhemispheric subdural hematomas (ISH) are rare in adults and occur most often after cranial trauma. We describe a parturient who developed bilateral acute ISH after inadvertent dural puncture associated with placement of an epidural catheter for labour analgesia. We discuss the features, pathophysiology, and management of this type of subdural hematoma. CLINICAL FEATURES: A 38-yr-old woman requested epidural analgesia for relief of labour pain. An inadvertent dural puncture occurred during placement of a 17G Tuohy needle. After labour and delivery, the patient developed symptoms of a postdural puncture headache, which responded only partially to an epidural blood patch. The patient's headache subsequently became less position-dependent and was associated with episodes of sharp pain radiating down her legs and paresthesias on the left side of her body. A computed tomography (CT) scan showed right frontal and left parietal acute ISH without an intracranial mass effect. The patient was monitored in the intensive care unit and treated conservatively because of the relatively small size of the ISH and the absence of progressive neurological deficits on serial examinations. Daily CT scans showed gradual decreases in the size of the ISH concomitant with improvement of the headache. CONCLUSIONS: Rupture of bridging veins between the cerebral cortex and the superior sagittal sinus is the usual mechanism by which ISH occur. Nearly one-quarter of patients with ISH do not survive, although those with smaller hematomas have a better outcome. If the hematoma is < 1 cm in thickness, a conservative approach to ISH is recommended in the absence of mental status changes, seizure activity, or focal deficits, but with larger ISH or evidence of progressive neurological deterioration, surgical evacuation is most often required to prevent mortality.

[Etiology and clinical characteristics of pregnancy-emerged thrombocytopenia].

OBJECTIVE: To investigate the etiology and clinical characteristics of pregnancy-emerged thrombocytopenia. METHODS: A retrospective analysis was conducted on clinical data of 159 pregnancies with thrombocytopenia, who were admitted to Peking University People's Hospital from January 2000 to January 2010. All the patients recruited in this study had no history of blood or immune system disease before pregnancy, and thrombocytopenia was the predominate clinical manifestation during pregnancy, with platelet counts less than 100 × 10(9)/L at least twice during pregnancy. The thrombocytopenia should not be induced by drugs, viral infections, preeclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome (HELLP). All cases were followed up. The general condition, the onset time of thrombocytopenia, platelet changes, accompany symptoms, maternal and perinatal outcomes as well as follow-up conditions were compared based on the etiology. RESULTS: (1) ETIOLOGY: among the 159 cases, 101 (63.5%) were diagnosed gestational thrombocytopenia (GT); 43 (27.0%) were idiopathic thrombocytopenic purpura (ITP); 9 (5.7%) were blood system diseases, including 4 cases of megaloblastic anemia (MA), 2 cases of aplastic anaemia (AA), and 3 cases of myelodysplastic syndrome (MDS). Six cases (3.8%) were diagnosed immune system diseases, including 3 cases of systemic lupus erythematosus (SLE), 2 cases of antiphospholipid syndrome (APS), and 1 case of Evans syndrome. (2) Maternal and perinatal outcomes:pregnancy induced hypertension was diagnosed in 21 cases (13.2%), abnormal glucose metabolism in 13 cases (8.2%), anemia in 44 cases (27.7%) and preterm delivery in 18 cases (11.3%). Twenty-nine cases (18.2%) were treated with corticosteroids or gamma globulin during pregnancy. The average gestational week was 38 weeks. Fifty-five cases (34.6%) underwent vaginal delivery, 104 cases (65.4%) received cesarean section. Postpartum hemorrhage was observed in 34 cases (21.4%), and puerperal infection happened in 2 cases (1.3%). No maternal death was found. In a total of 160 fetuses (including twins), there were 157 live births. Three cases of fetal death and 2 cases of early neonatal deaths were observed. Fetal growth restriction was observed in 4 cases, and neonatal thrombocytopenia was seen in 6 cases. No intracranial hemorrhage was detected. (3) The onset time of thrombocytopenia: among the 159 cases, 29 cases (18.2%), 67 cases (42.1%), 63 cases (43.6%) of thrombocytopenia were detected in the first, second and third trimester, respectively. There was a significant difference of the onset time of thrombocytopenia between GT and ITP groups (P < 0.05). Patients with GT tended to have a later onset of thrombocytopenia, which mainly happened in the second and third trimester, while patients with ITP tended to happen in the first and second trimester. (4) The degree of thrombocytopenia: the cases with the minimum platelets level of (51 - 100) × 10(9)/L, (31 - 50) × 10(9)/L, (10 - 30) × 10(9)/L, < 10 × 10(9)/L during pregnancy were 75 (47.2%), 39 (24.5%), 31 (19.5%), 14 (8.8%) respectively. There was a significant difference between GT and ITP groups in the lowest platelets level (P < 0.01). (5) Thrombocytopenia accompany with anemia: among the 159 cases, there were 44 cases (27.7%) accompanied with anemia. The proportion was 9.9% (10/101) in GT group, 58.1% (25/43) in ITP group, with significant difference (P < 0.01). Anemia was also found in 5 cases in blood system disease group (5/9), and 1 case in immune system disease group (Evans syndrome, 1/6). Pancytopenia was observed in 2 cases with ITP (4.7%, 2/43) and 3 cases with blood system disease (AA: 1 cases, MA: 2 cases, 3/9). (6) The recovery of the platelets counts postpartum: the postpartum follow-up periods were 7 months to 10 years. Patients recovered within 1 week, 6 weeks, 6 months postpartum were 66 cases (41.5%), 43 cases (27.0%), 17 cases (10.7%) respectively. The platelets counts did not recover within 6 months postpartum in 33 cases (45.7%). CONCLUSIONS: GT is the leading cause of pregnancy-emerged thrombocytopenia followed by ITP. There are significant differences between GT and ITP in the onset time of thrombocytopenia, the lowest platelets level, the proportion of anemia accompanied and the postpartum recovery. Other etiologies including immune and blood system diseases are rare. The relevant examinations should be taken for etiology and differential diagnosis.

[Clinical analysis about the management and the perinatal outcomes of pregnancy with chronic myeloid leukemia].

OBJECTIVE: to investigate the perinatal outcomes of pregnancy with chronic myeloid leukemia (CML) and how to manage it during pregnancy. METHODS: to retrospectively analyse the clinical datas about the perinatal outcome and the obstetric management of the 16 cases of pregnancy with CML during the last 30 years in a single center. RESULTS: (1) management ang perinatal outcomes: among the 16 pregnancies nine ended with therapeutic abortion during the first or second trimester and no CML complications were observed. The average gestation week was 7 weeks (5 - 13 weeks) when they came to our hospital. Seven pregnancies gave birth, among which CML was diagnosed during pregnancy in four patients and pregnancy was confirmed during CML in three patients. The average gestation week was 36 weeks (27 - 40 weeks(+2)) when they came to our hospital. Among the seven women three were treated with hydroxyurea (one became pregnant while she was on hydroxyurea and she elected to continue her pregnancy and continued to use hydroxyurea), one with leukapheresis twice after her 40 weeks of gestation, one with plateletpheresis and three hadn't any treatment. In the seven pregnacies three developed severe pre-eclampsias, including the two had hydroxyurea during the gestation. The average delivery gestational week was 38 weeks (33 weeks(+4) - 41 weeks), two were premature birth. Two caesarean sections, three vaginal deliveries and two forceps deliveries. There were two postpartum hemorrhage, during the 24 hours the amount of bleeding was 1500 - 1800 ml and secondary disseminated intravascular coagulation happened. Seven patients gave birth to seven infants whose average birth weight was 2469 g (1820 - 2810 g), of whom two were premature infants, two low birth weight infants, one had congenital malformation and two had abnormal blood routine examinations. (2) Management after delivery and prognosis: during the nine patients who ended pregnancy with therapeutic abortion during the first or second trimester four withdraw, one died whose course of disease was 3 years and the other four were alive during 5 months to 72 months, among which one had stem cell transplantation, two are taking imatinib mesylate and one takes hydroxyurea. Among the seven patients who deliveried two withdraw, two died and three are alive. Among the seven infants two withdraw, the other five have normal development following 4 months to 9 years. CONCLUSIONS: CML patient may have successful pregnancy and delivery, and it is not the absolute indication for terminating pregnancy. On the other hand, CML and the treatment during pregnancy can have side effect on the mother and the fetus, so the patients should be monitored and treated in tertiary hospitals.

[Clinical analysis of pregnancy complicated with severe thrombocytopenia].

OBJECTIVE: To investigate the etiology and perinatal outcome of pregnancies complicated with extremely severe thrombocytopenia [at least two times of platelets count (PLT) < 10 × 10(9)/L during pregnancy]. METHODS: Clinical data, including basic information, etiology, management and outcomes of pregnant women with extremely severe thrombocytopenia, admitted to Peking University People's Hospital from January 2004 to March 2009, were retrospectively collected. The management of these cases varied according to different etiology and the symptoms: (1) PLT were maintained > 20 × 10(9)/L and hemoglobulin > 70 g/L in those women without spontaneous bleeding; (2) PLT transfusion would be required when PLT < 10 × 10(9)/L or bleeding occur and RBC would be supplied when hematocrit < 25% and hemoglobulin < 70 g/L; (3) Hemoglobulin should be > 70 g/L and PLT > 30 × 10(9)/L before cesarean section or delivery; (4) Predinisone and/or intravenous immunoglobulin G (IVIG) would be given in women complicated with idiopathic thrombocytopenic purpura (ITP) when PLT < (20 - 30) × 10(9)/L or bleeding. PLT would be given if all the above management were failed, or PLT < 10 × 10(9)/L, or bleeding. Women without bleeding would be closely monitored and delivery would be planned. RESULTS: (1) Twenty-six cases were identified among 9302 deliveries during the study period (0.28%), with an average of maternal age of 29. Seventeen were diagnosed before conception and 9 during pregnancy. Among the 26 women, half received regular prenatal check in our hospital and the average gestations at diagnosis was 24 weeks and the other half without regular prenatal visits and the average gestations at diagnosis was 32 weeks. Etiology was identified in 24 out of the 26 women, including 14 (54%) ITP, 5 myelodysplastic syndrome (MDS), 4 chronic aplastic anaemia (CAA) and 1 systemic lupus erythematosus (SLE). (2) MANAGEMENT: All of the 26 women received blood products. Among the 14 ITP cases, 6 received predinisone and IVIG and 8 only took predinisone. Nine of the 26 patients (35%) had pregnant complications, among which 6 (6/9) were preeclampsia. The overall average gestation at delivery was 36 weeks. Only 2 delivered vaginally with the average blood loss of 83 ml and 23 cesarean sections were performed with the average blood loss of 410 ml. (3) Perinatal outcomes: There were 26 perinatal babies, among which 1 died intrauterine and 25 were born alive (12 preterm infants). The average birth weight was 2877 g. Neonatal severe thrombocytopenia presented in 2 newborns whose mother complicated with ITP. CONCLUSIONS: The main cause of extremely severe thrombocytopenia during pregnancy is ITP, managed mainly by predinisone and IVIG, followed by CAA and MDS, which may require supportive treatment. Pregnancy complicated with extremely severe thrombocytopenia is not an indication of termination. Better maternal and fetal outcomes can be achieved through proper treatment based on the etiology, intensive care in prevention and management of complications and cesarean section.

Prenatal cytogenetic diagnosis study of 2782 cases of high-risk pregnant women.

BACKGROUND: Prenatal diagnoses are extremely advantageous for pregnant women with high-risk indicators and can help prevent the birth of malformed infants. However, no large-scale statistical study analyzing the correlation between fetal chromosome disorders and abnormal indicators during pregnancy has been done in China. The objectives of this study were to diagnose and analyze fetal chromosome abnormalities, determine the feasibility of the various prenatal test methods and establish diagnostic guidelines for the early, middle, and late trimesters. METHODS: From January 2004 to May 2009, 2782 pregnant women at high-risk underwent prenatal diagnoses. Categorized data expressed as either actual counts or percentages were analyzed by the chi-square or Fisher's exact test. Chorionic villus sampling was performed in the early-trimester (10 - 12 weeks of gestation), amniocentesis in mid-trimester (16 - 28 weeks of gestation), and umbilical cord blood collection in mid- or late-trimester (16 - 37 weeks of gestation). In 51 cases either autopsy samples from intrauterine fetal deaths or placental tissues from aborted fetuses were tested. RESULTS: Chromosomal abnormalities were observed in 3.99% (111/2782) of the samples. Overall, the success rate of cytogenetic analysis for high-risk pregnancy groups was 98.17% (2731/2782). It was significantly less successful when used to analyze data from the chorionic villus sampling compared with that from amniocentesis and umbilical cord blood (P = 0.000). Abnormal chromosome carriers had the highest percentage of abnormal chromosomes (67.86%) when compared with chromosomal abnormalities in patients with ultra-sonographic "soft markers" (11.81%), advanced maternal age (4.51%) and those who had positive serum screening results (P = 0.000). CONCLUSIONS: Invasive prenatal diagnostic techniques are feasible tools for confirming fetal chromosomal abnormalities. Abnormal chromosomes detected in one of the parents carrying abnormal chromosome, ultrasound soft markers, advanced maternal age or positive serum screening results were associated with a higher frequency of fetal genetic diseases.

KATP channel subunits in rat dorsal root ganglia: alterations by painful axotomy.

BACKGROUND: ATP-sensitive potassium (KATP) channels in neurons mediate neuroprotection, they regulate membrane excitability, and they control neurotransmitter release. Because loss of DRG neuronal KATP currents is involved in the pathophysiology of pain after peripheral nerve injury, we characterized the distribution of the KATP channel subunits in rat DRG, and determined their alterations by painful axotomy using RT-PCR, immunohistochemistry and electron microscopy. RESULTS: PCR demonstrated Kir6.1, Kir6.2, SUR1 and SUR2 transcripts in control DRG neurons. Protein expression for all but Kir6.1 was confirmed by Western blots and immunohistochemistry. Immunostaining of these subunits was identified by fluorescent and confocal microscopy in plasmalemmal and nuclear membranes, in the cytosol, along the peripheral fibers, and in satellite glial cells. Kir6.2 co-localized with SUR1 subunits. Kir6.2, SUR1, and SUR2 subunits were identified in neuronal subpopulations, categorized by positive or negative NF200 or CGRP staining. KATP current recorded in excised patches was blocked by glybenclamide, but preincubation with antibody against SUR1 abolished this blocking effect of glybenclamide, confirming that the antibody targets the SUR1 protein in the neuronal plasmalemmal membrane. In the myelinated nerve fibers we observed anti-SUR1 immunostaining in regularly spaced funneled-shaped structures. These structures were identified by electron microscopy as Schmidt-Lanterman incisures (SLI) formed by the Schwann cells. Immunostaining against SUR1 and Kir6.2 colocalized with anti-Caspr at paranodal sites.DRG excised from rats made hyperalgesic by spinal nerve ligation exhibited similar staining against Kir6.2, SUR1 or SUR2 as DRG from controls, but showed decreased prevalence of SUR1 immunofluorescent NF200 positive neurons. In DRG and dorsal roots proximal to axotomy SLI were smaller and showed decreased SUR1 immunofluorescence. CONCLUSIONS: We identified Kir6.2/SUR1 and Kir6.2/SUR2 KATP channels in rat DRG neuronal somata, peripheral nerve fibers, and glial satellite and Schwann cells, in both normal state and after painful nerve injury. This is the first report of KATP channels in paranodal sites adjacent to nodes of Ranvier and in the SLI of the Schwann cells. After painful axotomy KATP channels are downregulated in large, myelinated somata and also in SLI, which are also of smaller size compared to controls.Because KATP channels may have diverse functional roles in neurons and glia, further studies are needed to explore the potential of KATP channels as targets of therapies against neuropathic pain and neurodegeneration.

[Clinical analysis of eleven patients with chronic myeloproliferative disorders complicating pregnancy].

OBJECTIVE: To investigate the clinical characteristics, the antenatal management, the outcome and prognosis of chronic myeloproliferative disorders(CMPD) complicating pregnancy. METHODS: Retrospectively analyze the clinical data of eleven patients with CMPD complicating pregnancy hospitalized in Peking University People's Hospital from 2000 to 2009, including five patients with essential thrombocythemia, one with primary myelofibrosis and five with chronic myeloid leukemia. RESULTS: (1) Five pregnancies had periodic antenatal care and laboratory monitorings like full blood count. Reasonable anti-coagulation therapy was given to prevent the complications. One patient with PMF diagnosed before conception had her first pregnancy ended with mild pre-eclampsia and intrauterine death at the gestational age of 32 weeks. During the first trimester of her second pregnancy two years later, the test for anti-ß2 glycoprotein antibody was positive. She received low-dose aspirin and low-molecular-weight heparin as anti-coagulants. An uneventful course was obtained and she delivered a healthy term infant. (2) Five pregnancies had occasional antenatal examination, including two patients with ET and three patients with CML. One patient with ET developed severe pre-eclampsia at the gestational age of 25 weeks. Umbilical artery Doppler showed reversed end-diastolic velocity. The management with anti-convulsants, anti-hypertensives and anti-coagulants showed no effect. An emergency cesarean section had to be performed because of the aggressive hypertension and placental abruption, with still birth as a result. Two pregnancies never had an antenatal care. Both of them were admitted on labor and the diagnoses of CML were made. (3) Four pregnancies developed oligohydramnios and three developed preelampsia (two severe pre-eclampsia and one mild pre-eclampsia). There was no other hemorrhage and thrombosis event. (4) Eight pregnancies reached full-term with four cesarean sections and four vaginal births. Two preterm cesarean sections were performed because of a progressive oligohydramnios. The ten live neonates weighed 1820 - 3600 g. All were appropriate for gestational age, except one fetal growth retardation (FGR) developed in one patient with severe pre-eclampsia. (5) As for the CMPD, the eleven patients were all in stable conditions. Three patients with CML received hydroxyurea in the third trimester, four with ET and one with CML had platelet-pheresis before delivery with favorable effect. All patients were uneventful postpartum, except one with CML who died in 5 months after childbirth. CONCLUSIONS: The pregnancy outcomes for patients with CMPD are mostly good. However, antenatal care should pay more attention to the complications such as thromboembolic accidents, pre-eclampsia, still birth and fetal growth retardation. Management including reasonable anti-coagulation therapy should be considered, which may help improve the prognosis.

[Clinical analysis of bicytopenia and pancytopenia during pregnancy].

OBJECTIVE: To investigate the diagnosis, management, pregnancy outcome and prognosis of bicytopenia or pancytopenia during pregnancy. METHODS: Retrospective chart review was conducted on 24 pregnancies who were found bicytopenia or pancytopenia during pregnancy for the first time. The diagnoses were reconfirmed. The management and pregnancy outcome were collected. And the prognoses were followed. RESULTS: According to the clinical data and laboratory findings, the latter including complete blood cell count, reticulocyte count, peripheral smear, serum folate and vitamin B12 level, autoimmune antibody screening, bone marrow smear and biopsy, thirteen patients were diagnosed as having chronic aplastic anemia (CAA), six as having myelodysplastic syndromes (MDS), two as having megaloblastic anemia (MA), one as having paroxysmal nocturnal hemoglobinuria (PNH), one as having Evan's syndrome and one as having acute leukemia. The management basically consisted of supportive transfusions. Six patients suffered pregnancy complications including four with severe preeclampsia (one with intracranial hemorrhage and one with intrauterine death concomitantly) and two with gestational diabetes. The delivery ages of the 21 patients were term or nearly term with all good neonatal outcomes. Postpartum follow-up showed the two patients with MA achieved complete remission, the one with PNH had mild anemia and that with Evan's syndrome had mild thrombocytopenia. The patient with acute leukemia died of recurrence six months postpartum. Of the thirteen patients with CAA, two achieved complete remission, six partial remission, four no remission and one was lost follow-up. Of the 6 patients with MDS, one achieved partial remission, four no remission, and one transformed into acute monocytic leukemia, then refused chemotherapy and was lost follow-up. CONCLUSIONS: CAA may be one of the most common causes of bicytopenia or pancytopenia during pregnancy, MDS may be the second. Diagnosis should be made as soon as possible through appropriate and reasonable laboratory examinations. Most patients could achieve good pregnancy outcomes through supportive management. The maternal prognosis may vary widely depending on the causes.

Suppressed Ca2+/CaM/CaMKII-dependent K(ATP) channel activity in primary afferent neurons mediates hyperalgesia after axotomy.

Painful axotomy decreases K(ATP) channel current (IK(ATP)) in primary afferent neurons. Because cytosolic Ca(2+) signaling is depressed in injured dorsal root ganglia (DRG) neurons, we investigated whether Ca(2+)-calmodulin (CaM)-Ca(2+)/CaM-dependent kinase II (CaMKII) regulates IK(ATP) in large DRG neurons. Immunohistochemistry identified the presence of K(ATP) channel subunits SUR1, SUR2, and Kir6.2 but not Kir6.1, and pCaMKII in neurofilament 200-positive DRG somata. Single-channel recordings from cell-attached patches revealed that basal and evoked IK(ATP) by ionomycin, a Ca(2+) ionophore, is activated by CaMKII. In axotomized neurons from rats made hyperalgesic by spinal nerve ligation (SNL), basal K(ATP) channel activity was decreased, and sensitivity to ionomycin was abolished. Basal and Ca(2+)-evoked K(ATP) channel activity correlated inversely with the degree of hyperalgesia induced by SNL in the rats from which the neurons were isolated. Inhibition of IK(ATP) by glybenclamide, a selective K(ATP) channel inhibitor, depolarized resting membrane potential (RMP) recorded in perforated whole-cell patches and enhanced neurotransmitter release measured by amperometry. The selective K(ATP) channel opener diazoxide hyperpolarized the RMP and attenuated neurotransmitter release. Axotomized neurons from rats made hyperalgesic by SNL lost sensitivity to the myristoylated form of autocamtide-2-related inhibitory peptide (AIPm), a pseudosubstrate blocker of CaMKII, whereas axotomized neurons from SNL animals that failed to develop hyperalgesia showed normal IK(ATP) inhibition by AIPm. AIPm also depolarized RMP in control neurons via K(ATP) channel inhibition. Unitary current conductance and sensitivity of K(ATP) channels to cytosolic ATP and ligands were preserved even after painful nerve injury, thus providing opportunities for selective therapeutic targeting against neuropathic pain.

Nitric oxide activates ATP-sensitive potassium channels in mammalian sensory neurons: action by direct S-nitrosylation.

BACKGROUND: ATP-sensitive potassium (KATP) channels in neurons regulate excitability, neurotransmitter release and mediate protection from cell-death. Furthermore, activation of KATP channels is suppressed in DRG neurons after painful-like nerve injury. NO-dependent mechanisms modulate both KATP channels and participate in the pathophysiology and pharmacology of neuropathic pain. Therefore, we investigated NO modulation of KATP channels in control and axotomized DRG neurons. RESULTS: Cell-attached and cell-free recordings of KATP currents in large DRG neurons from control rats (sham surgery, SS) revealed activation of KATP channels by NO exogenously released by the NO donor SNAP, through decreased sensitivity to [ATP]i. This NO-induced KATP channel activation was not altered in ganglia from animals that demonstrated sustained hyperalgesia-type response to nociceptive stimulation following spinal nerve ligation. However, baseline opening of KATP channels and their activation induced by metabolic inhibition was suppressed by axotomy. Failure to block the NO-mediated amplification of KATP currents with specific inhibitors of sGC and PKG indicated that the classical sGC/cGMP/PKG signaling pathway was not involved in the activation by SNAP. NO-induced activation of KATP channels remained intact in cell-free patches, was reversed by DTT, a thiol-reducing agent, and prevented by NEM, a thiol-alkylating agent. Other findings indicated that the mechanisms by which NO activates KATP channels involve direct S-nitrosylation of cysteine residues in the SUR1 subunit. Specifically, current through recombinant wild-type SUR1/Kir6.2 channels expressed in COS7 cells was activated by NO, but channels formed only from truncated isoform Kir6.2 subunits without SUR1 subunits were insensitive to NO. Further, mutagenesis of SUR1 indicated that NO-induced KATP channel activation involves interaction of NO with residues in the NBD1 of the SUR1 subunit. CONCLUSION: NO activates KATP channels in large DRG neurons via direct S-nitrosylation of cysteine residues in the SUR1 subunit. The capacity of NO to activate KATP channels via this mechanism remains intact even after spinal nerve ligation, thus providing opportunities for selective pharmacological enhancement of KATP current even after decrease of this current by painful-like nerve injury.

[Effect of general anesthesia used in cesarean section on maternal-neonatal outcome of pregnancy complicated with severe thrombocytopenia].

OBJECTIVE: To investigate the effect of general anesthesia on pregnancy women with thrombocytopenia and neonate during cesarean section (CS). METHODS: Sixty-five singleton pregnant women with low platelet count (< 50 x 10(9)/L) and gestation>35 weeks were allocated into general anesthesia group (35 cases) and local anesthesia group (30 cases) randomly. The time from skin incision to fetal delivery, the oxyhemoglobin saturation (SO2) before and after anesthesia, the blood loss during operation, Apgar scores at 1 min, birth weight,umbilical cord blood gas analysis were recorded. RESULTS: The mean time from anesthesia induction to fetal delivery was (9.7 +/- 3.5) minutes in general anesthesia group. The time from skin incision to fetal delivery in general anesthesia group [(7.7 +/- 2.5) minutes] was shorter than that in local anesthesia group [(12.5 +/- 3.0) minutes, P < 0.01], while the operation time had no significant differences. There were no significant difference for the value of SO2 before and after general anesthesia or local anesthesia (P > 0.05). There was no significant difference for the blood loss [(471 +/- 245) ml vs. (452 +/- 213) ml, P > 0.05], Apgar scores at 1 minute, birth weight and umbilical cord blood gas analysis between the two groups (P > 0.05). There had two infants with blue asphyxia in local anesthesia group while no infant with asphyxia in general anesthesia group. CONCLUSION: General anesthesia is safe to pregnant women with thrombocytopenia during CS.

[Prenatal diagnosis and treatment of fetal choroid plexus cysts].

OBJECTIVE: To discuss the clinical management and significance of the prenatal diagnosis of Fetal Choroid Plexus Cysts (CPC). METHODS: From May 2004 to March 2007, 55 cases of fetal CPC diagnosed by B-ultrasound during second trimester were prospectively studied. Each case was studied regarding fetal chromosome karyotype, disappearance weeks of the cyst, the clinical outcome and follow-up results respectively. RESULT: The cases were diagnosed during 16 - 25 gestational weeks. The diameters of the cysts varied from 0.2 cm to 2.4 cm. There were 25 cases of bilateral cysts and 30 cases of unilateral or 50 cases of isolated CPC and 5 cases of complicated CPC. The cysts of all cases who continued pregnancy disappeared before 28 weeks. Fetal chromosome karyotypes were obtained in 50 cases. Among them, two cases were 18-trisomy, and one case was 21-trisomy. Five cases were terminated pregnancy because of abnormal chromosome karyotype or malformation during second trimester. One neonate was diagnosed as ventricular septal defect among 50 cases of follow up. Among these six cases, three were from advanced-age pregnant women, five cases were with abnormal fetal structure and five cases were with the diameter of bilateral or unilateral cysts more than 1.0 cm. CONCLUSION: (1) Fetal CPC can be diagnosed during second trimester, and the majority disappear before 28 gestational weeks. (2) High risk factors for fetal abnormal chromosome karyotype may be: advanced-age pregnant women, abnormal structure of fetus, and the diameter of bilateral or unilateral cyst more than 1.0 cm. It is suggested that fetal CPC with the high risks should receive fetal chromosome karyotype test during pregnancy.