[The changes of LCHAD in preeclampsia with different clinical features and the correlation with NADPH P47-phox, p38MAPK-α, COX-2 and serum FFA and TG].

OBJECTIVE: To investigate the changes of fatty acid oxidase in the placenta of preeclampsia cases with different clinical features, and the relationship with oxidative stress and inflammatory response. To study the correlation of serum free fatty acid (FFA) and triglycerides (TG) level in early second trimester with the molecular changes of the long-chain fatty acid oxidase in the third trimester. METHODS: This was prospective cohort study, in which cases with singleton pregnancies who archived in Haidian Maternal and Children's Hospital, Beijing, from January 1st 2012 to May 31st, with regular prenatal care were included. Doppler ultrasound was used for screening for the presence of early diastolic notch of uterine artery at 22-24 weeks of gestation. All the 101 cases with the early diastolic notch of uterine artery were included as the notch group, and 377 cases without the early diastolic notch of uterine artery were included as the non-notch group. The perinatal outcomes and the incidence of hypertensive disorders in pregnancy of the two groups were observed. The serum level of FFA and TG was tested, and the mRNA and protein expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), P47-phox subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, p38 mitogen-activated protein kinase a (p38MAPK-α) and cyclooxygenase-2 (COX-2) were detected using real-time quantitative PCR and western blot. The relationship between serum level of FFA and TG and the mRNA and protein expression of LCHAD, NADPH P47-phox, p38MAPK-α and COX-2 of the placental tissue specimens were analyzed. RESULTS: (1) In the notch group, there were 9 cases of early-onset preeclampsia, 15 cases of late-onset preeclampsia and 10 cases of gestational hypertension;and there were 8 cases of late-onset preeclampsia and 18 cases of gestational hypertension in the non-notch group. 15 cases with normal blood pressure in each group were randomly selected as the control group. (2)The serum level of TG of cases of early-onset preeclampsia, late-onset preeclampsia and gestational hypertension in the notch group were (2.0 ± 0.8), (1.8 ± 0.6)and (1.9 ± 0.7)mmol/L, and that of FFA were(0.68 ± 0.26), (0.52 ± 0.10) and (0.52 ± 0.17)mmol/L, respectively. The serum level of TG of cases of late-onset preeclampsia and gestational hypertension in the non-notch group were (1.6 ± 0.6) and (1.4 ± 0.4)mmol/L, and that of FFA were (0.49 ± 0.11) and (0.48 ± 0.05)mmol/L, respectively. The serum level of TG and FFA in the control group were (1.4 ± 0.5) and (0.52 ± 0.06)mmol/L, respectively. The TG level of the notch group was higher than that of the control group, and the difference was statistically significant (P < 0.05). The FFA level of the early-onset preeclampsia in the notch group was higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group, and the difference was statistically significant (P < 0.05). (3) The mRNA expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of the late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of NADPH P47-phox of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of p38MAPK-α of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). The mRNA expression of COX-2 of the early-onset preeclampsia in the notch group were significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and the control group (P < 0.01). (4)The protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group and gestational hypertension in the notch group were significantly lower than that of the control group (P < 0.01); and the protein expression of LCHAD in the placenta of early-onset preeclampsia in the notch group was significantly lower than that of late-onset preeclampsia in the non-notch group (P < 0.01). The protein expression of NADPH P47-phox in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the non-notch group and control group (P < 0.05). The protein expression of p38MAPK-α in the placenta of early-onset preeclampsia in the notch group was significantly higher than that of late-onset preeclampsia in the notch group, late-onset preeclampsia in the non-notch group and control group (P < 0.01). The protein expression of COX-2 in the placenta of early-onset preeclampsia in the notch group, late-onset preeclampsia in the notch group, gestational hypertension in the notch group, late-onset preeclampsia in the non-notch group, and gestational hypertension in the non-notch group, were significantly higher than that of control group (P < 0.01). (5)The blood concentration of maternal FFA in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA and protein expression of placental LCHAD (r = -0.810, -0.932, P < 0.01). There was no correlation between maternal TG level and the mRNA and protein expression of placental LCHAD in each group(P > 0.05). (6)The mRNA expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the mRNA expression of placental NADPH P47-phox and COX-2 (r = - 0.877, -0.762, P < 0.05). The mRNA expression of placental LCHAD in the control group was significantly negatively correlated with the mRNA expression of placental COX-2 (r = -0.565, P < 0.01). The protein expression of placental LCHAD in the early-onset preeclampsia in the notch group was significantly negatively correlated with the protein expression of NADPH P47-phox (r = -0.818, P < 0.01). The protein expression of placental LCHAD in the control group was significantly negatively correlated with the protein expression of COX-2 (r = -0.502, P < 0.01). CONCLUSIONS: The placental mRNA and protein expression of long-chain fatty acid oxidation enzymes were different in different clinical features of preeclampsia, which were reduced more obviously in the early-onset preeclampsia in the notch group than that of the late-onset preeclampsia in the notch group, and were negatively correlated with the elevated serum FFA level, significantly enhanced oxidative stress and inflammatory response, but with no correlation with serum TG level.

[Interaction mechanism and influence between fatty acid oxidation in trophoblast cells and p38MAPK signal transduction pathway of severe preeclampsia].

OBJECTIVE: To investigate the effects of expression of mitochondria long-chain fatty acid oxidative enzyme (long-chain 3 hyroxyacyl CoA dehydrogenase, LCHAD) and p38 mitogen activated protein kinase (p38MAPK) signal transduction pathway in severe preeclampsia. METHODS: Serum-free trophoblast cells cultured in vitro were stimulated by early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group), HELLP syndrome serum (HELLP group), and normal pregnancy serum (NP group) respectively; each group was added DMEM/F12 medium, reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (NADPH-I) and p38MAPK inhibitor (p38-I) to stimulate cells. Expression of mRNA and protein of LCHAD in trophoblast cells were detected by real-time PCR and western blot. RESULTS: (1)The expression of mRNA of LCHAD: the level of mRNA of LCHAD in NP+DMEM, E-PE+DMEM, E-PE+NADPH-I, E-PE+p38-I, L-PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+DMEM, HELLP+NADPH-I, HELLP+p38-I groups were 1.00 ± 0.03, 0.14 ± 0.08, 0.95 ± 0.20, 1.43 ± 1.02, 0.37 ± 0.18, 1.51 ± 0.36, 1.60 ± 0.31, 0.10 ± 0.04, 0.49 ± 0.10, 0.44 ± 0.21, respectively. The relative expressions of mRNA of LCHAD were significantly reduced in E-PE+DMEM, L-PE+DMEM and HELLP+DMEM groups compared with the NP+DMEM group (P < 0.05). Compared with the NP groups, the relative expressions of mRNA of LCHAD were significantly increased in L-PE+NADPH-I and L-PE+p38-I group (P < 0.05), while reduced in HELLP groups(P < 0.05). (2) The expression of protein of LCHAD: the relative expressions of protein of LCHAD in NP+DMEM, E-PE+DMEM, E-PE+NADPH-I, E-PE+p38-I, L-PE+DMEM, L-PE+NADPH-I, L-PE+p38-I and HELLP+ DMEM, HELLP+NADPH-I, HELLP+p38-I groups were 19.4 ± 2.2, 10.7 ± 1.1, 17.9 ± 3.3, 19.1 ± 2.9, 16.4 ± 2.3, 20.3 ± 2.3, 20.9 ± 4.3, 12.4 ± 2.3, 17.6 ± 2.6, 17.7 ± 2.0 respectively. Compared with the NP groups, the protein expressions of LCHAD were significantly remarkably reduced in E-PE+DMEM, L-PE+DMEM and HELLP groups (P < 0.05). Compared with the DMEM groups, the protein expressions of LCHAD were significantly increased in NADPH-I and p38-I groups of E-PE, L-PE and HELLP groups (P < 0.05). CONCLUSIONS: These studies demonstrate that long chain fatty acid oxidation was involved in the pathogenesis and development of preeclampsia. The expressions of gene and protein of LCHAD were remarkably affected by early onset severe preeclampsia and HELLP syndrome. NADPH-I and p38-I may allay the disorder of fatty acid oxidation. p38MAPK signal transduction pathway may contributed in this process.

[Interaction mechanism and influence between fatty acid oxidation and p38MAPK signal transduction pathway in trophoblast cells incubated with fatty acids].

OBJECTIVE: To explore the interaction mechanism and influence between fatty acids oxidation and p38MAPK signal transduction pathway in trophoblast cells stimulated by fatty acids of different chain lengths. METHODS: Serum-free trophoblast cells cultured in vitro were divided into 5 groups, i.e. incubation with DMEM/F12 medium without FFA (F-FFA), short-chain fatty acids (SC-FFA), medium-chain fatty acids (MC-FFA), long-chain fatty acids (LC-FFA) and very long-chain fatty acids (VLC-FFA). Then cells in each group were stimulated by DMEM/F12 medium, NADPH oxidase inhibitor (Apocynin) and p38MAPK inhibitor (SB203580) and were subdivided into FFA plus-DMEM group, plus-NADPH-I and plus-p38MAPK-I groups. Expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. RESULTS: (1) mRNA expression of LCHAD: the Δct of mRNA of LCHAD in F-FFA+DMED, SC-FFA+DMEM, MC-FFA+DMEM, LC-FFA+DMEM, LC-FFA+NADPH-I, LC-FFA+p38MAPK-I and VLC-FFA+DMEM, VLC-FFA+NADPH-I, VLC-FFA+p38MAPK-I groups were 4.57 ± 0.12, 4.36 ± 0.09, 4.55 ± 0.10, 6.84 ± 0.42, 4.45 ± 0.24, 5.08 ± 0.36, 2.23 ± 0.15, 3.90 ± 0.32, 3.81 ± 0.41. Compared with the F-FFA groups, the relative mRNA expressions of LCHAD significantly decreased in LC-FFA+DMEM/p38MAPK-I groups (P < 0.05) while increased in VLC-FFA groups (P < 0.05). Compared with the LC-FFA+DMEM groups, the relative mRNA expressions of LCHAD increased in LC-FFA+NADPH-I/p38MAPK-I groups (P < 0.05). The relative mRNA expressions of LCHAD in VLC-FFA+NADPH-I/p38MAPK-I groups significantly decreased versus VLC-FFA+DMEM group (P < 0.05). (2) Protein expression of LCHAD: The relative protein expressions of LCHAD in F-FFA+DMED, SC-FFA+DMEM, MC-FFA+DMEM, LC-FFA+DMEM, LC-FFA+NADPH-I, LC-FFA+p38MAPK-I and VLC-FFA+DMEM, VLC-FFA+NADPH-I, VLC-FFA+p38MAPK-I groups were 23.6 ± 13.0, 21.2 ± 10.2, 19.7 ± 1.9, 10.6 ± 2.6, 14.0 ± 1.8, 14.0 ± 2.8, 29.3 ± 1.9, 35.8 ± 3.2 and 35.2 ± 4.5 respectively. Compared with the F-FFA groups, the protein expressions of LCHAD significantly decreased in LC-FFA groups (P < 0.05) while increased in VLC-FFA+NADPH-I/p38MAPK-I groups (P < 0.05). CONCLUSION: Free fatty acids affect the gene and protein expressions of mitochondrial ß-oxidation enzyme of LCHAD in trophoblastic cells. Fatty acid ß-oxidation is impaired in trophoblast cells incubated with long-chain fatty acid. NADPH oxidase and p38MAPK inhibitors may alleviate such an effect. Thus p38MAPK signal transduction pathway may participate in this process. The correlation between very long chain fatty acids and fatty acid ß-oxidation is confirmed. But their interactions require further explorations.

[Effects of expression of mitochondria long-chain fatty acid oxidative enzyme with different chain lengths of free fatty acids in trophoblast cells].

OBJECTIVE: To explore the interacting mechanisms and influences of different chain lengths of fatty acids and the expression of mitochondria long-chain 3 hydroxyacyl CoA dehydrogenase (LCHAD) in trophoblast cells. METHODS: The serum-free trophoblast cells cultured in vitro were divided into 5 groups to receive the stimulations of DMEM/F12 medium without FFA (F-FFA), short-chain fatty acids (SC-FFA), medium-chain fatty acids (MC-FFA), long-chain fatty acids (LC-FFA), very long-chain fatty acids (VLC-FFA). The expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. RESULTS: Compared with the F-FFA, SC-FFA and MC-FFA groups, the expressions of gene and protein of LCHAD significantly decreased (P < 0.05) in the LC-FFA group. The expression of gene of LCHAD increased significantly in the VLC-FFA group (P < 0.05). But no difference existed in protein expression between the VLC-FFA group and other three groups (P > 0.05). Gene expression of LCHAD had no difference among the F-FFA, SC-FFA, MC-FFA groups (P > 0.05). Compared with the LC-FFA group, the expression of gene of LCHAD increased significantly in the VLC-FFA group (P < 0.05). CONCLUSION: Free fatty acids may affect the expression of mitochondrial ß-oxidation enzyme of LCHAD in trophoblast cells. Long-chain fatty acid alters the LCHAD gene protein expression. The correlation between very long chain fatty acids and the gene expression of LCHAD has been detected and their interactions needs further explorations. Short or medium chain fatty acids have no significant effect on the mitochondrial metabolism of fatty acid ß-oxidation in trophoblast cells.

Patient with antiphospholipid syndrome accompanied by pre-eclampsia who developed hellp syndrome and eclampsia after abortion.

Antiphospholipid syndrome (APS) refers to a group of clinical symptoms and signs caused by antiphospholipid antibody (aPLA). We reported a rare case of poor outcome of a pregnant woman with APS. The pregnant woman had APS, hemolytic anemia, elevated liver function and low platelet count (HELLP) syndrome, and eclampsia and had a poor outcome from a second pregnancy. She was treated with antispasmodics, sedatives, and anti-hypertensive agents, along with anticoagulant therapy and infusion of immunoglobulin. APS during pregnancy often makes pregnancy even more complex and risky. Obstetricians should carry out anticoagulation treatment throughout the perinatal period.

[Study on clinical risk of maternal underlying medical conditions and onset of preeclampsia].

OBJECTIVE: To investigate the effect of clinical risk factors including maternal underlying medical conditions on the development of preeclampsia (PE) in order to improve and strengthen the early assessment of high clinical risk population of PE. METHODS: Clinical observational data of patients with PE in Peking University Third Hospital from November 2008 to January 2011 were analyzed. Comparative analysis was made among medical conditions with PE (M-PE) sub-group and isolated PE (I-PE) sub-group and non-PE pregnancy with or without medical conditions (control group). RESULTS: Totally 159 cases, 43.09% (159/369) of total cases of PE had high clinical risk factors (multiple pregnancy and medical conditions) and 32.3% (97/300) of singleton PE accompanied with medical conditions. The incidence of PE in singleton pregnancies with medical conditions was significantly higher than those without medical conditions [15.0% (97/646) versus 4.45% (210/4719), P < 0.05]. In M-PE sub-group, the average age [(31.7 ± 4.5) versus (29.3 ± 5.2) year-old] and body mass index (BMI) in first trimester [(26.0 ± 5.6) versus (23.3 ± 3.7) kg/m(2)], the proportion with previous preeclampsia [11% (11/97) versus 4.9% (10/203)] and pregnancy loss in third trimester [11% (11/97) versus 3.0% (6/203)], were higher than those of I-PE sub-group (all P < 0.05). The onset of preeclampsia in M-PE sub-group was earlier than I-PE (32.9 versus 34.4 gestation weeks, P < 0.05). The proportion serious cases of PE occurring before 32 gestational weeks were higher in M-PE than that of I-PE sub-group [45% (44/97) versus 34.0% (69/203), P < 0.05]. Multivariate regression analysis showed that previous history of late pregnancy loss and irregular prenatal care were clinical risk factors for early-onset PE whether early-onset was defined as < 34 or < 32 gestational weeks respectively (all P < 0.05); medical conditions were risk factors for PE if early-onset was defined as < 32 gestational weeks (OR = 1.718, 95%CI: 1.005 - 2.937, P = 0.048). CONCLUSIONS: Multiple pregnancies and pregnancies with medical conditions exceed one-third of total subjects of PE. The onset of PE in subjects with maternal underlying medical conditions was earlier which is the subgroup should not be ignored. The difference of early pregnancy BMI may show the maternal heterogeneity in early onset and late onset of preeclampsia. Assessment of clinical risk factors including the underlying medical disorders for preeclampsia in early trimester should be strengthened.

[Study on the oxidative stress and inflammation in trophoblast cells stimulated by different chain length fatty acids].

OBJECTIVE: To investigate the oxidative stress and inflammation in trophoblast cells stimulated by different chain length fatty acids. METHODS: Serum-free trophoblast cells cultured in vitro were divided into five groups, which were incubated with DMEM medium without free fatty acid (F-FFA), short chain fatty acids (SC-FFA), medium chain fatty acids (MC-FFA), long chain fatty acids (LC-FFA), very long chain fatty acids (VLC-FFA). Then cells in each group were stimulated by DMEM medium, reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor (apocynin) and p38 mitogen-activated protein kinases (p38MAPK) inhibitor (SB203580) and were subdivided as each FFA plus-DMEM group, plus-NADPH-I and plus-p38MAPK-I groups. Expressions of mRNA and protein of p38MAPK and cyclooxygenase 2 (COX-2) in trophoblast cells were detected by real-time PCR and western blot. RESULTS: (1) The mRNA expression of p38MAPK in LC-FFA + DMEM, VLC-FFA + DMEM, LC-FFA + NADPH-I, LC-FFA + p38MAPK-I, VLC-FFA + NADPH-I, VLC-FFA + p38MAPK-I group were 4.56 ± 0.28, 22.65 ± 2.40, 0.87 ± 0.06, 1.02 ± 0.15, 19.87 ± 1.93, 10.22 ± 0.75 separately, and the protein expressions were 0.79 ± 0.02, 0.93 ± 0.10, 0.43 ± 0.06, 0.44 ± 0.19, 0.79 ± 0.10, 0.81 ± 0.14. Compared with other groups, the mRNA and protein expressions of p38MAPK in LC-FFA + DMEM, VLC-FFA + DMEM group were increased (P < 0.05). Compared with LC-FFA + DMEM group, mRNA and protein expressions of p38MAPK in LC-FFA + NADPH-I and LC-FFA + p38MAPK-I group were significantly decreased (P < 0.05). Compared with VLC-FFA + DMEM group, mRNA and protein expressions of p38MAPK had no difference in VLC-FFA + NADPH-I group (P > 0.05), mRNA expression of p38MAPK in VLC-FFA + p38MAPK-I group was significantly decreased (P < 0.05), but there was no difference in protein expression (P > 0.05). (2) The mRNA expression of COX-2 in LC-FFA + DMEM, VLC-FFA + DMEM, LC-FFA + NADPH-I, LC-FFA + p38MAPK-I, VLC-FFA + NADPH-I, VLC-FFA + p38MAPK-I group were 3.97 ± 0.03, 39.08 ± 0.63, 0.99 ± 0.13, 0.98 ± 0.18, 20.93 ± 3.70, 13.46 ± 2.31 separately, and the protein expressions were 1.32 ± 0.20, 1.33 ± 0.25, 0.59 ± 0.13, 0.58 ± 0.30, 0.88 ± 0.18, 0.91 ± 0.24. Compared with other groups, mRNA and protein expressions of COX-2 in LC-FFA + DMEM and VLC-FFA + DMEM group were significantly increased (P < 0.05). Compared with LC-FFA + DMEM group, mRNA and protein expressions of COX-2 in LC-FFA + NADPH-I and LC-FFA + p38MAPK-I group were decreased (P < 0.05). Compared with VLC-FFA + DMEM group, mRNA and protein expressions of COX-2 in VLC-FFA + NADPH-I and VLC-FFA + p38MAPK-I group were all decreased (P < 0.05). (3) The correlation analysis showed that there were significantly positive correlations between the mRNA and protein expressions of p38MAPK and COX-2 in LC-FFA group (P < 0.05). There were significantly positive correlations in protein expression (P < 0.05), but no correlation in the mRNA expression between p38MAPK and COX-2 in the F-FFA, SC-FFA, MC-FFA, VLC-FFA groups (P > 0.05). CONCLUSIONS: The oxidative stress and inflammation may exist in trophoblast cells which were stimulated by LC-FFA and VLC-FFA. p38MAPK signal transduction pathway may contributed in this process.

[Correlation between severe preeclampsia and abnormal expression of long-chain fatty acid oxidative enzyme].

OBJECTIVE: To explore the correlation between severe preeclampsia and abnormal expression of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD). METHODS: Serum-free trophoblast cells cultured in vitro were divided into 4 groups under the stimulations of normal pregnancy serum (NP group), early onset severe preeclampsia serum (E-PE group), late onset severe preeclampsia serum (L-PE group) and HELLP (hemolysis, elevated liver enzymes & low platelets) syndrome serum (HELLP group) respectively. The expressions of mRNA and protein of LCHAD in trophoblast cells were detected by real-time polymerase chain reaction (PCR) and Western blot. RESULT: (1) Expression of LCHAD mRNA: the relative expressions of mRNA of LCHAD in NP, E-PE, L-PE and HELLP groups were 1.00 ± 0.00, 3.08 ± 0.22, 1.62 ± 0.23 and 3.36 ± 0.18 respectively. The relative expressions of LCHAD mRNA were significantly reduced in the E-PE, L-PE and HELLP groups versus the NP group (P < 0.05). Compared with the L-PE group, the gene expressions of LCHAD significantly decreased in the E-PE and HELLP groups (P < 0.05) while no significant difference was found between the E-PE and HELLP groups (P > 0.05). (2) Expression of LCHAD protein: the relative expressions of LCHAD protein were 4.94 ± 0.02, 2.93 ± 0.13, 4.14 ± 0.06 and 2.80 ± 0.09 in the NP, E-PE, L-PE and HELLP groups respectively. The protein expressions of LCHAD were remarkably reduced in the E-PE, L-PE and HELLP groups versus the NP group (P < 0.05). The expressions of LCHAD protein remarkably decreased in the E-PE and HELLP groups versus the L-PE group (P < 0.05) while no significant difference was found between the E-PE and HELLP groups (P > 0.05). CONCLUSION: Long chain fatty acid oxidation is involved in the pathogenesis and development of preeclampsia. The expressions of LCHAD gene and protein are remarkably affected by early onset severe preeclampsia and HELLP syndrome. The interacting mechanism and influence between fatty acid oxidation and the development of preeclampsia are worth further exploring.

[Preterm birth and preterm infants in Beijing regional district].

OBJECTIVE: To investigate the incidence and relevant information of preterm birth and the outcomes of preterm infants delivered at various gestational weeks and for different causes. METHODS: Totally 955 women, who ended their pregnancies before term, and 1066 neonates of the previous mothers were enrolled in this survey, among 15,197 deliveries at Peking University First Hospital, Beijing Gynecological and Obstetric Hospital, Women's and Children's Hospital of Haidian District and Peking University Third Hospital, respectively, from December 1(st), 2006 to May 31(st), 2007. RESULTS: (1) Incidence of preterm birth: the overall incidence of preterm birth of the 4 hospitals was 6.3% (955/15 197), and it was 8.1% (125/1549) in Peking University First Hospital, 13.1% (150/1142), which was the highest (P < 0.01), in Peking University Third Hospital, 5.5% (369/6656) in Beijing Gynecological and Obstetric Hospital and 34.0% (311/5850) in Women's and Children's Hospital of Haidian District. The preterm birth rate at the two comprehensive hospitals was significantly higher than that of the two specialized hospitals [10.2% (275/2691) vs 5.4% (680/12 506), P < 0.01]. (2) Gestational weeks at delivery: the incidence of preterm birth before 34 weeks was 28.5% (272/954) and the number changed to 71.5% (682/954) for those preterm deliveries after 34 weeks. However, this number varied among the 4 hospitals. Peking University First Hospital had the highest incidence of preterm birth before 34 weeks (P < 0.05), and the lowest was found in Women's and Children's Hospital of Haidian District (P < 0.01), but no difference was found between Peking University Third Hospital and Beijing Gynecological and Obstetric Hospital. (3) Etiology of preterm birth: preterm premature rupture of membranes (PPROM) accounted for the most proportion of all preterm birth cases, followed by iatrogenic preterm birth and spontaneous preterm birth. But the causes of preterm birth in the 4 hospitals were different. Peking University Third Hospital had a higher incidence of iatrogenic preterm birth than the others (P < 0.01), and Peking University First Hospital had a higher incidence of preterm birth caused by PPROM and lower incidence of spontaneous preterm birth. The first four reasons of iatrogenic preterm birth were preeclampsia (143, 42.0%), fetal distress (58, 17.1%), placenta previa (43, 12.6%) and placenta abruption (33, 9.7%). (4) Neonatal outcomes in different hospitals: the neonatal outcomes were quite different among the 4 hospitals due to different causes and different delivery weeks. The highest neonatal mortality rate was found in Beijing Gynecological and Obstetric Hospital (5.4%, 22/408) compared to that in Women's and Children's Hospital of Haidian District (1.3%, 4/320) and Peking University Third Hospital (0.6%, 1/170) (P < 0.01), but without any difference when compared to that in Peking University First Hospital (2.4%, 3/124) (P > 0.05). (5) Neonatal outcomes at different gestational age: the recovery rate of preterm infants delivered at < 32 weeks was lower than those delivered > or = 32 weeks (P < 0.01), and this number rose to 99.6% in those delivered > or = 34 weeks. More infants delivered < 32 weeks were given up for treatment or died during the perinatal period than those delivered > or = 32 weeks, with the neonatal mortality rate of 22.1% for those delivered at < 32 weeks and only 0.3% for those delivered at > or = 34 weeks (P < 0.01). (6) Neonatal outcomes for various causes: the premature neonatal mortality rate for iatrogenic preterm births was higher than that of PPROM (4.9% vs 1.6%, P < 0.05). But the neonatal recovery rates were similar among the PPROM, spontaneous and iatrogenic preterm birth group (P > 0.05). CONCLUSIONS: Preterm birth is associated with high perinatal mortality rate, especially for those delivered before 32 weeks which would be highlighted in prevention. Reduction of the iatrogenic preterm birth, combined with proper prevention of PPROM, is an important issue in decreasing the prevalence of preterm birth.

[Early warning signs of severe preeclampsia].

OBJECTIVE: To identify the early warning signs of severe preeclampsia (SPE). METHODS: A case-control (1:2) observational study was conducted. Forty-seven pregnant women with SPE, who attended the prenatal clinics of Peking University Third Hospital regularly from Jan. 2002 to Dec. 2007, were selected as the study group, including 12 early onset and 35 late onset ones. The control group consisted of 94 healthy singleton pregnant women at the same period. Clinical data were collected and analyzed. RESULTS: (1) The basal body mass index (BMI) showed no difference between the study and control group [(23.27 +/- 4.31) kg/m(2) vs (21.52 +/- 3.09) kg/m(2), P > 0.05]. (2) The net increase of BMI in the study group before the onset of SPE was higher than that in the control [(5.60 +/- 2.17) kg/m(2) vs (4.85 +/- 1.52) kg/m(2), P < 0.05] and the increase of BMI per week was also higher [(0.74 +/- 0.41) kg/(m(2).w)(-1) vs (0.23 +/- 0.18) kg/(m(2).w)(-1), P < 0.01]. The sensitivity and specificity of BMI increase per week in predicting SPE was 84% and 81% at a cut-off value of 0.39 kg/(m(2).w)(-1), respectively, and 79% and 91% at 0.41 kg/(m(2).w)(-1) correspondingly. (3) During the third trimester and before the onset of SPE, the weight gain per week in the study group was higher than that of the control [(0.93 +/- 0.70) kg vs (0.63 +/- 0.20) kg, P < 0.01]. Significant difference was also found in the net weight gain between the two groups (P < 0.01), but not in the percentage of women with excessive weight gain (> 0.50 kg/w) [60% (25/42) in the study group vs 63% (53/84) in the control group, P > 0.05]. (4) Higher percentage of women experienced pre-hypertension in the study group than in the controls [17% (8/47) vs 5% (5/94), P < 0.01]. (5) In the study group, 53% (25/47) of the women had edema before SPE onset, but the figure dropped to 18% (17/94) in the controls (P < 0.01). (6) Eight women in the study group and one in the control group suffered from hypoproteinemia before SPE onset with the average level of plasma albumin of (32.6 +/- 1.6) g/L and (38.4 +/- 2.1) g/L (P < 0.01), respectively. (7) Proteinuria was reported in 10 cases (21%) in the study group and 4 (4%) in the controls (P < 0.01). (8) Logistic regression analysis showed that the risk factors for SPE included edema (OR = 6.16, 95%CI: 2.29 - 16.57), pre-hypertension (OR = 6.21, 95%CI: 1.56 - 24.77), proteinuria (OR = 9.68, 95%CI: 1.86 - 50.30), and weight gain > 0.85 kg/w during the third trimester (OR = 11.60, 95%CI: 3.54 - 37.97). CONCLUSIONS: Edema, excessive weight gain, pre-hypertension and hypoproteinemia are early warning signs of SPE. Pregnant women with the above signs required close monitoring during prenatal care.

[Interaction among abnormal fatty acid oxidation, endothelial function disorder, and oxidative stress in the onset of severe preeclampsia].

OBJECTIVE: To investigate the association of abnormal fatty acid oxidation (FAO), endothelial function activation, and oxidative stress in pathogenesis of severe preeclampsia ( S-PE). METHODS: Placenta tissues were obtained from 70 S-PE patients with onset in different gestational weeks with or without liver damage. The protein expression of long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD), tumor necrosis factor (TNF)-alpha, vascular cell adhesion molecule (VCAM)-1, and peroxisome proliferator activated receptor (PPAR) gamma were analyzed using immunohistochemistry. 54 samples from normal pregnancy in first, second and third trimester were collected as controls. RESULTS: Protein expression of LCHAD, TNF-alpha, VCAM-1, and PPARgamma could be seen in both placenta of normal pregnancy and S-PE. The protein expression on level of LCHAD of the cases of S-PE that came down of the disease before 32 gestational weeks, especially of the cases complicated with liver damage, was significantly lower than that of the controls (P < 0.05). However, no differences in the LCHAD protein expression were found between the S-PE patients with the onset after and 32 gestational weeks and the controls. The TNF-alpha protein expression levels of the S-PE patients with different onset weeks were all significantly higher than those of the controls (all P < 0.05). The VCAM-1 protein expression levels of the S-PE patients with the onset after 34 gestational weeks was significantly higher than that of the controls (P < 0.05). There was no significant difference in the PPARgamma protein expression between the S-PE patients and the controls. The placental LCHAD protein expression of the S-PE patients with the onset before 32 gestational weeks, especially of the cases with liver function damage, was dramatically decreased in comparison with the controls, and the placental TNF-alpha protein expression was dramatically increased, however, there was no linear correlation between LCHAD and TNF-alpha expression. There was no significant difference in expression of PPARgamma and VCAM-1 between the S-PE patients and the controls. There was no linear correlation among the expression levels of LCHAD, TNF-alpha, VCAM-1, and PPARgamma between the S-PE patients with the onset before and after 32 gestation weeks. CONCLUSION: Abnormal FAO may be one of the factors related to some cases of PE with the onset before 32 gestational-weeks, especially those with liver damage. The correlation among LCHAD, TNF-alpha, VCAM-1, and PPARgamma are complicated.

[Study on different onset patterns and perinatal outcomes in severe preeclampsia].

OBJECTIVE: To explore the different clinical onset patterns in severe preeclampsia. METHODS: A prospective observational study was conducted in 173 cases of severe preeclampsia. They were divided into two groups according to the onset of gestational age of severe preeclampsia, early onset of severe preeclampsia (S-PE) (onset < or = 34 weeks) and late onset of S-PE (onset > 34 weeks). Then according to the onset pattern they were subdivided into 4 subgroups: early abrupt onset (10) and early onset with gradual progress of severe preeclampsia (87), late abrupt onset (18) and late onset with gradual progress of severe preeclampsia (58). Clinical characteristics in each subgroup were evaluated. RESULTS: Cases with abrupt onset accounted for 16.2% out of 173 cases of severe preeclampsia (28/173). The incidence of abrupt onset or onset with gradual progress between early and late onset groups was not significantly different (P > 0.05). Whether in early onset group or late onset group, the incidence of serious maternal complications was much higher in abrupt onset subgroups than that in gradual progress subgroups [100.0% (10/10) vs 34.5% (30/87) and 100.0% (18/18) vs 29.3% (17/58); P < 0.001]. The incidence of serious maternal complications was not significantly different between early onset and late onset groups (P > 0.05). The perinatal mortality rate was higher in abrupt onset subgroups compared to gradual progress subgroups both in early onset groups and in late onset ones (72.7% vs 24.3%, P < 0.01; 22.2% vs 4.9%, P < 0.05). The perinatal mortality rate was higher in each subgroups in early onset groups than that in late onset ones respectively (P < 0.01, P < 0.05). The gestational age at delivery was closely associated with perinatal outcomes. When a delimitation of early onset of severe preeclampsia was set at 32-week gestation, perinatal outcome was associated with both gestational age at birth and the onset time of severe preeclampsia. If the cut-off point was set at 34-week gestation, perinatal outcome was associated only with gestational age at birth. CONCLUSIONS: Approximately 16% pregnant women with severe preeclampsia were attacked abruptly and complicated by serious complications. The clinical delimitation of early onset of severe preeclampsia set at 32-week gestation is significantly associated with poor maternal and perinatal outcomes.

[Screening for G1528C mutation in mitochondrial trifunctional protein gene in pregnant women with severe preeclampsia and new born infant].

OBJECTIVE: Severe preeclampsia, and hemolysis, elevated liver enzymes, and low platelet syndrome (HELLP) are serious complications of pregnancy, and evidence suggests a genetic basis for these conditions. A G1528C mutation in the alpha-subunit of the mitochondrial trifunctional protein (MTP) gene has been identified in association with these conditions. The aim of this study is to explore the carrier rate of the G1528C mutation in the MTP gene in pregnant women with severe preeclampsia, HELLP syndrome and in their newborns, as well as in a normal pregnant population, so as to determine its association with maternal liver disease among women in Beijing. METHODS: A multicenter, prospective, case control study was carried out. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to screen the G1528C mutations in the MTP gene. One hundred and forty cord blood samples from cases with severe preeclampsia (n = 130) and HELLP syndrome (n = 10) were collected. Ninety maternal peripheral blood samples among them (84 from severe preeclampsia and 6 from HELLP syndrome) were also collected for screening the common disease-causing mutation in Caucasians. Five hundred and sixty cord blood samples and 90 maternal peripheral blood samples obtained from normal pregnant women served as controls. RESULTS: The G1528C mutations in the MTP gene were not found in samples from women with severe preeclampsia and their newborns, from women with HELLP syndrome and their new borns, as well as in samples from the normal pregnant women and their new borns. CONCLUSIONS: The common disease-causing mutation of G1528C in MTP gene in Caucasians is probably not a common mutation in Chinese Han people in Beijing. Further study is needed to expand the sample size among HELLP syndrome and maternal liver diseases in Chinese population.