Objective To investigate the relationship between potential maternal risk factors between potential maternal risk factors in different level hospitals as well as different prenatal care patterns and characteristics of preeclampsia. Methods A retrospective study of 300 preeclamptic singleton patients delivered in Peking University Third Hospital was performed.Patients were divided into three groups:regular prenatal care in tertiary hospitals (n =100),regular prenatal care in primary hospitals (n=81) and without prenatal care (n=119). The onset of preeclampsia and incidence of severe preeclampsia of different groups were analyzed. Non-parametric and Chi-square test were adopted for continuous and categorical variables respectively. Results (1) In total cases of preeclampsia subgroup (I-PE subgroup) and with chronic hypertension (CH subgroup),the diagnosis of preeclampsia was later in patient with regular prenatal care in tertiary hospital (patient-TH)[100,64 and 14 cases,37.1 (4.1),37.3 (1.7) and 36.3 (2.5) weeks respectively] than those with regular prenatal care in primary hospital (patient-PH) [81,54 and 9 cases,32.9 (6.7),33.8 (6.1)and 27.9(6.3) weeks respectively] (Z=72.29,51.30 and 14.58 respectively,P＜0.05) or the patient without regular prenatal care (patient-NP) [119,85 and 19 cases,31.6(6.6),31.9(6.7) and 30.3(4.7) weeks respectively] (Z=86.69,58.83 and 11.33 respectively,P＜0.05).The proportion of severe preeclampsia occurred earlier than 32 weeks [13.0％ (13/100) vs 55.5％ (66/119),9.4％(6/64) vs 50.6％(43/85),and 35.7％(5/14) vs 89.5％(17/19); x2=43.95,29.42 and 10.17respectively,P＜0.05] or earlier than 34 weeks [17.0％ (17/100) vs 65.5％ (78/119),14.1％(9/64) vs 61.2％(52/85) and 42.9％(6/14) vs 94.7％(18/19); x2 =47.71,31.18 and 10.61 respectively,P＜0.05] were lower in patient-TH than in patient-NP.(2) In patient-NP and patientPH,onset of preeclampsia was earlier in CH subgroup compared with I-PE subgroup (Z=26.61 and 22.82,P＜ 0.05). In patient-NP,the proportion of severe preeclampsia occurred earlier than 32 weeks (x2 =9.11,P＜0.05) or earlier than 34 weeks (x2 =7.95,P＜0.05) was higher in CH subgroup than in I-PE subgroup. Conclusions Regular prenatal care in tertiary hospital might effectively delay the onset of preeclampsia or severe preeclampsia,especially in patients with risk factors for preeclampsia. Assessment of risk factors for preeclampsia in early trimester should be strengthened and individualized prenatal care plan should be established.

Objective To investigate the oxidative stress and inflammation in trophoblast cells stimulated by different chain length fatty acids.MethodsSerum-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 conrelation in the mRNA expression between p38MAPK and COX-2 in the F-FFA,SC-FFA,MC-FFA,VLC-FFA groups (P ＞ 0.05).ConclusionsThe 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.

Objective To investigate the risk factors for severe and mild preeclampsia (PE) in women with irregular prenatal care,and to identify practical measures to reduce the occurrence of severe PE.Methods A retrospective study of 222 PE patients with irregular prenatal care,who delivered in Peking University Third Hospital from January 2007 to December 2011,was performed.The risk factors for PE and the status of prenatal care were analyzed.The non-parametric test,Chi-square test,Fisher's exact test,trendy Chi-square test and Logistic regression analysis were used for statistical analysis.Results There were 207 (93.2％) cases of severe PE and 15 (6.8％) cases of mild PE.In 207 severe PE patients,there were 95 cases (45.9％) of early-onset PE (diagnosed before 32 gestational weeks) and 112 cases (54.1％) of late-onset PE.In the 15 mild PE patients,there were two early-onset cases and 13 late-onset cases.The percentage of early-onset cases in severe PE patients was higher than that in mild PE patients [45.9％ (95/207) vs 2/15,x2=6.027,P=0.015].After excluding 9 cases without any prenatal care,213 PE patients were analyzed,and it was found that the proportion of severe PE diagnosed in hospitals of grade 3,2 and 1 were significantly different [5/9,94.2％ (131/139) vs 96.9％ (63/65),x2=8.600,P=0.003].Compared with mild PE patients,the prenatal care interval for PE diagnosis in severe PE patients was longer [M(Q),8.0(4.0) vs 4.8(4.4) weeks,Z=2.695,P=0.007];the frequency of prenatal care after 20 gestational weeks was less [1(1) vs 3(3) times,Z=-4.195,P=0.000];the gestational week of PE diagnosis and referral to grade 3 hospitals were earlier [32.4(5.6) vs 35.4(4.3) weeks,Z=-3.075,P=0.002;33.1(5.3) vs 35.4(3.9) weeks,respectively,Z=-2.608,P=0.009];and the interval between PE diagnosis and referral was longer [0.1 (0.7) vs 0.0(0.0) weeks,respectively,Z=2.904,P=0.004].Multivariate logistic regression showed that the frequency of prenatal care after 20 gestational weeks was an independent risk factor for severe PE (OR=0.115,95％CI:0.046-0.285,P=0.000).Conclusion In women without regular prenatal care,the onset of severe PE is related to low-level prenatal hospital care,lack of prenatal care after 20 gestational weeks and longer prenatal care intervals as well as referral to grade 3 hospitals.

Objective To analyze the heterogeneous variation of serum free fatty acid (FFA) and lipids during early second trimester in women with or without uterine artery notch in pre-eclampsia (PE).Methods This is a prospective cohort study of 4 000 women with singleton pregnancies registered in early pregnancy and in whom regular check-ups were performed in Haidian Maternal & Child Health Hospital.Blood specimens were collected at gestational age 14-18 weeks at the same time of screening for Down's syndrome.One hundred and one cases with early diastolic notch of the uterine artery were included in the N+ group,and 172 cases without notch but at high risk of PE were included in the N-group at 22-24 weeks.In addition,205 women who were selected randomly at a ratio of 1 ∶ 5,without notch or PE high-risk factors,were also included in the N group.Both groups were subgrouped according to the outcomes of pregnancy complications:early-onset PE group EPE,late-onset PE (LPE),gestational hypertension (GH) group,gestational diabetes mellitus (GDM) group with normal blood pressure,and no complications (NC) group.The variation in FFA and other lipid metabolism indicators in the PE subgroups were compared and analyzed by two independent-sample t-test,one-factor analysis of variance,Chi-square test (or Fisher's exact) and Logistic regression.Results History of PE and pre-hypertension at first visit differed significantly between the N+ and N-groups [3.9％ (4/101) vs.0.8％ (3/377),x2=5.52,P＜0.05; pre-hypertension at first visit,42.2％ (43/101) vs.25.7％ (97/377),x2=10.91,P＜0.05].In the N+ group,23.8％ (n=24) of women had PE,of which 37.5％ (n=8) were early onset.In the N group,2.1％ (n=8) had PE,and all were late onset.The incidence of PE differed significantly between the N+ and N-groups (x2=59.72,P＜0.05).In the N+ group,FFA gradually decreased among the ePE,IPE,GH and NC groups [(0.68±0.27),(0.58±0.21),(0.57±0.21) and (0.49±0.19) mmol/L,F=2.78,P＜0.05]; Multivariate regression analysis showed that FFA (OR=135.68,95％CI:3.78-4 873.00) and PE history (OR=123.25,95％CI:9.27-i 638.00) were risk factors of ePE.Pre-hypertension at registration (OR=4.69,95％CI:2.08-10.58) and pre-pregnancy body mass index (BMI) 24-28 (OR=3.69,95％CI:1.26-10.83) were risk factors ofGH.FFA (OR=9.08,95％CI:2.49-33.01) and pre-pregnancy BMI ≥ 28 (OR=5.08,95％CI:2.16-11.92) were risk factors for GDM.Conclusions Serum FFA and TG levels in early second trimester are correlated with PE,especially the early-onset PE.The onset of PE is heterogeneous and affected by many factors,and occurs in patients with or without early diastolic notch of the uterine artery in the second trimester.Patients with notch are more likely to have early-onset PE,which is correlated with blood FFA and TG levels.

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 α (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.

Objective:To explore the feasibility and key point of improvement in preventing and postponing the onset of severe pre-eclampsia (SPE) and its severe complications in the tertiary referral system by analyzing the clinical characteristics of SPE in a single tertiary referral center.Methods:The clinical data of 217 patients with SPE who were hospitalized and terminated pregnancy in Peking University Third Hospital from January 2020 to December 2020 were retrospectively analyzed. The risk factors, clinical characteristics and severe complications of SPE between the patients referred from primary hospitals (referral group) and the patients received regular prenatal care in the tertiary referral center (central group) were compared, as well as the influence of the referral timing on the characteristics and perinatal outcome.Results:(1) Clinical characteristics: among the 217 cases of SPE, 84 cases were in the referral group and 133 cases were in the central group. The gestational ages at SPE clinical diagnosis [31.5 weeks (28.1-34.6 weeks) vs 35.6 weeks (33.3-37.2 weeks); Z=-6.547, P<0.01], termination of pregnancy [32.3 weeks (29.5- 35.1 weeks) vs 36.3 weeks (34.4-37.5 weeks); Z=-6.554, P<0.01] and onset of SPE severe complications [30.6 weeks (26.4-32.7 weeks) vs 34.9 weeks (32.7-36.5 weeks); Z=-4.040, P<0.01] in the referral group were significantly earlier than those in the central group, the rates of ICU [10.7% (9/84) vs 3.8% (5/133); χ2 =4.126, P=0.042] and neonatal ICU hospitalization [72.9% (51/70) vs 54.7% (70/128); χ2 =6.286, P=0.012] were higher than those in the central group, while the live birth rate [83.3% (70/84) vs 96.2% (128/133); χ2 =10.736, P=0.001] was lower than that of the central group. (2) Analysis of risk factors: for the patient whose risk factors were obesity, advanced age or pre-eclampsia history, the gestational ages at SPE clinical diagnosis and termination of pregnancy in the referral group were significantly earlier than those in the central group ( P<0.05). For those with chronic hypertension, the gestational ages at severe complications onset in the referral group were significantly later than those in the central group ( P<0.05). For those without obvious risk factors, the gestational ages at SPE clinical diagnosis, termination of pregnancy and onset of SPE severe complications in the referral group were earlier than those in the central group ( P<0.05). (3) Analysis of severe complications: the top three severe complications in the referral group and the central group were hypertensive encephalopathy/cerebrovascular accident [20.2% (17/84) vs 7.5% (10/133)], HELLP syndrome [7.1% (6/84) vs 8.3% (11/133)] and placental abruption [8.3% (7/84) vs 7.5% (10/133)]. The rate of hypertensive encephalopathy/cerebrovascular accident in the referral group was significantly higher than that in the central group ( χ2 =7.645, P=0.006). (4) Analysis of referral timings: the timings included referral after onset of SPE severe complications (8.3%, 7/84), referral after onset of SPE (67.9%, 57/84), referral after detection of SPE early warning signs (14.3%, 12/84) and referral after detection of SPE risk factors in the 2nd and 3rd trimester (9.5%, 8/84). The earlier the referral, the longer the interval from clinical diagnosis to onset of severe complications, from referral to termination of pregnancy, and from referral to severe complications onset ( P<0.05). The earlier the referral, the lower the NICU hospitalization rates, the higher the live birth rates. The ICU hospitalization rate of referrals after severe complications onset was significantly higher than those of the other three referral timing groups ( P<0.05). Conclusions:SPE occurs in hospitals of different levels. Although tertiary referral center may postpone the onset of SPE and its severe complications, reduce the severity of SPE and prolong the gestational age, its awareness of prevention and control still needs to be further improved. Early identification of the risk of SPE and timely referral are important parts of improving SPE adverse outcomes in primary medical institutions. The significance and value of referral system need to be brought into full play.

Objective:To investigate the clinical features and perinatal outcomes of twin pregnancies with complete placenta previa (CPP).Methods:We conducted a retrospective study on 266 women with CPP, including 62 twin pregnancies (twins group) and 204 singleton pregnancies (singleton group), who gave birth in Peking University Third Hospital from January 2012 to December 2020. T-test, nonparametric test and Chi-square test were adopted for univariate analysis. Differences between the two groups regarding clinical features and perinatal outcomes were compared using multivariate logistic regression or multivariate linear regression. Results:The incidence of twin pregnancy with CPP was 2.11% (62/2 937). Placenta accreta spectrum disorders (PAS) accounted for 48.4% (30/62) and 53.9% (110/204) in the twin and singleton group, respectively, but the difference was not statistically significant ( χ 2=0.58, P>0.05). In terms of antepartum hemorrhage, the proportion of women affected, those with first onset <29 weeks, amount of bleeding ≥200 ml, and the number of episodes of bleeding ≥3 were significantly higher in the twin group than those in the singletons [56.5% (35/62) vs 39.7% (81/204); 35.5% (22/62) vs 12.7% (26/204); 17.7% (11/62) vs 4.9% (10/204); and 21.0% (13/62) vs 10.3% (21/204), χ 2=5.42, 16.62, 10.78, and 4.86, respectively, all P<0.05]. Multivariate Logistic regression analysis showed that compared with the singleton group, the twin group was at higher risk of antepartum hemorrhage volume >200 ml, the number of antepartum hemorrhage episodes ≥3, preterm delivery before 34 weeks and 32 weeks, emergency cesarean section, and emergency cesarean section caused by antepartum hemorrhage [a OR(95% CI)=4.36(1.17-16.30), 3.15(1.01-9.79), 17.24(5.36-55.46), 9.85(2.32-41.77), 3.98(1.72-9.20), and 3.10(1.22-7.85), respectively, all P<0.05]. Multivariate linear regression analysis showed that the gestational week at the emergency cesarean section in the twins group was about 2.22 weeks (0.17-4.27 weeks) earlier than that in the singletons. The postpartum hemorrhage amount and the risk of postpartum hemorrhage after cesarean section, infusion of red blood cells, and hysterectomy did not differ significantly between the two groups. Conclusions:Compared with singleton pregnancies, the proportion of preterm delivery, cesarean sections, especially those caused by antepartum hemorrhage, is significantly higher among twin pregnancies combined with CPP. Accordingly, preterm delivery should be actively prevented, and the timing of cesarean section should be individualized according to the condition of the mothers and babies, and early delivery may be considered.