Impact of different referral timing on the pregnancy outcomes of severe pre-eclampsia in the referral system / 中华妇产科杂志

Objective:To explore the impact of different referral timing on postponing early-onset pre-eclampsia (PE), postponing severe pre-eclampsia (SPE), reducing SPE severe complications and improving maternal and neonatal outcomes by analyzing the pregnancy outcomes of SPE patients who were referred from primary hospitals to tertiary referral center in the referral system.Methods:The clinical data of 159 SPE patients who were referred from primary hospitals, treated and then terminated their pregnancy in Peking University Third Hospital from January 2020 to October 2021, were observed and analyzed in this clinical observational study. According to the clinical stage of PE at the time of referral, they were divided into four groups: 38 cases were referred after onset of SPE severe complications (SPE-C group), 72 cases were referred after onset of SPE (a-SPE group), 15 cases were referred after onset of PE (a-PE group) and 34 cases were referred after detection of PE early warning-signs (Warn-s group). And then these 159 cases were divided into different color groups according to the project management system for high-risk pregnant women. Patients of Red color (highest risk) and Orange color (higher risk) were required to be referred to tertiary hospitals (Red-Orange group, 113 cases), and patients of Yellow color (high risk) could be treated under tertiary hospitals (Yellow group, 46 cases). The maternal and neonatal outcomes of different referral timings were analyzed and compared.Results:(1) Pregnancy outcomes of different referral timings grouped by PE clinical stage at the time of referral: the later the referral timing, the higher the rate of SPE severe complications, the shorter the interval from referral to termination of pregnancy. The rate of SPE severe complications in the SPE-C group was significantly higher than those of the other three groups, and the interval from referral to termination of pregnancy in the SPE-C group was significantly shorter than those of the other three groups (all P<0.05). The referral gestational age of Warn-s group was earlier than those of the other three groups (all P<0.05). The average gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications were all after 34 gestational weeks, and were later than those of a-SPE group and SPE-C group; the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, neonatal intensive care unit (NICU) hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group, and its rate of take-home-babies was 100%, significantly higher than those in a-SPE group and SPE-C group (all P<0.05). The gestational ages for onset of SPE and termination of pregnancy in a-PE group were later than those in a-SPE group and SPE-C group, the rates of SPE onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, and NICU hospitalization were lower than those of a-SPE group and SPE-C group, the length of NICU stay was shorter than those of a-SPE group and SPE-C group (all P<0.05). (2) Pregnancy outcomes of different referral timings grouped by the color classification of PE clinical characteristics: among the 159 cases of SPE, 113 cases (71.1%, 113/159) were in the Red-Orange group which were required to be referred to tertiary hospitals, and 46 cases (28.9%, 46/159) were in the Yellow group,which were not in the range of referral requirements, but actually referred to the tertiary hospital and eventually developed SPE. Gestational ages for onset of SPE, termination of pregnancy, and onset of SPE severe complications in the Yellow group were later than those of the Red-Orange group, while the rates of SPE onset before 34 gestational weeks, SPE severe complications onset before 34 gestational weeks, terminating pregnancy before 34 gestational weeks, NICU hospitalization, and pregnancy giving up before 28 gestational weeks were lower than those of the Red-Orange group, the length of NICU stay was shorter than that of the Red-Orange group, and its rate of take-home-babies was higher than that in the Red-Orange group (all P<0.05). (3) Analysis of different clinical referral timings in the Yellow group: among these 159 SPE patients, 46 cases (28.9%, 46/159) would be excluded from the range of referral requirements which belonged to the Yellow color grade, but 6 cases still developed SPE severe complications (4 cases in Warn-s group and 2 cases in a-PE group), 17 cases were terminated pregnancy before 34 weeks of gestation (12 cases in Warn-s group and 5 cases in a-PE group), and 23 cases developed SPE before 34 weeks of gestation (17 cases in Warn-s group and 6 cases in a-PE group). (4) Multivariate analysis: referral after detection of PE early warning signs was the independent protective factor for postponing the onset of SPE severe complications ( P<0.05). Referral after detection of PE early warning signs and referral after onset of PE were both protective factors for postponing the onset of SPE and early-onset PE (all P<0.05). Conclusions:Different referral timing in the referral system is one of the key points that affect the maternal and neonatal outcomes of SPE. Referral after detection of PE early warning signs and timely referral after onset of PE would reduce early-onset PE, postpone the onset of SPE and reduce the severe complications of SPE. The clinical development and evolution of PE is really complicated, and referral based on specific clinical situations is better than referral based on fixed mode.

Preliminary study of human serum albumin level in early warning onset of preeclampsia / 中华妇产科杂志

Objective@#To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) .@*Methods@#Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed.@*Results@#(1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance (P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications (r=-0.19, P<0.01).@*Conclusions@#Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.

Preliminary study of human serum albumin level in early warning onset of preeclampsia / 中华妇产科杂志

Objective:To observe the dynamic changes of human serum albumin (HSA) level during pregnancy and study the early warning significance of HSA level on the onset of preeclampsia (PE) .Methods:Totally 369 PE pregnant women (PE group) and 309 normal pregnant women (control group) without PE who admitted in Haidian Maternal and Child Health Hospital from January 2013 to December 2017 were selected. HSA levels were tested before meeting the criterion of PE in the first trimester, the early-third trimester and the late-third trimester, the difference between the two groups were compared. The relationship between the HSA level and the incidence of complications in PE patients was analyzed.Results:(1)The mean values of HSA level in PE group and control group were (41.9±3.1) versus (40.0±2.2) g/L, (34.2±2.7) versus (35.4±2.7) g/L and (33.7±2.9) versus (36.7±3.3) g/L in the first trimester,the early-third trimester and the late-third trimester respectively,the difference in the first trimester was no significance ( P>0.05), while the differences in the early-third trimester and the late-third trimester were both significant (all P<0.05). (2) The HSA level during pregnancy of PE group showed a continuous downward trend, while the control group was V-shaped trend. The receiver operating characteristic (ROC) curve analysis showed that PE could be early warned by the decrease of HSA level in PE group [area under curve (AUC)=0.742, cut-off value=5.97 g/L, sensitivity 70.8%, specificity 62.8%], the same result was in severe PE (AUC=0.756, cut-off value=6.85 g/L, sensitivity 70.8%, specificity 72.0%). The level of HSA was negatively correlated with the incidence of complications ( r=-0.19, P<0.01). Conclusions:Excessive decrease of HSA level is an early warning factor for PE onset. The higher the baseline of HSA level and the greater the extent of pregnancy decline, the risk of PE in pregnant women is higher. The lower of HSA level in PE, the incidence of complications is higher. The excessive decrease of HSA level may be the first clinical manifestation before the onset of clinical symptoms of PE, so it may be the warning factor and one of the laboratory indicators in the PE sub-clinical stage.

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 / 中华妇产科杂志

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).(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.

Correlation of free fatty acid and blood lipids in early second trimester and uterine artery notch in pre-eclampsia / 中华围产医学杂志

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.