Preterm birth (PTB), predominantly induced by intraamniotic inflammation, stands as the foremost contributor to neonatal morbidity and mortality globally. Fetal inflammatory response syndrome, stemming from the activation of the innate immune system, signifies the occurrence of funisitis or chorionic vasculitis. Maternal-fetal complications associated with infection-related PTB encompass maternal sepsis, fetal demise, neonatal sepsis, neonatal neurological impairment, and chronic lung disease. The inflammatory cascade is initiated when Toll-like receptors present on immune cells within the fetal membranes and the female reproductive tract encounter pathogen-associated molecular patterns derived from infectious agents. Subsequently, the nuclear factor kappa-light-chain-enhancer of activated B cells facilitates the transcription of cytokines. The accumulation of neutrophils compromises the tissue integrity of the fetal membranes, leading to membrane rupture via the secretion of matrix metalloproteinases. Elevated prostaglandin levels prompt uterine contractions and cervical remodeling, resulting in progressive cervical effacement and dilation, ultimately culminating in fetal delivery. The diagnosis of PTB should encompass three pivotal criteria: gestational age, uterine activity, and the consequences of that uterine activity. The diagnosis of chorioamnionitis is established through a combination of clinical manifestations, laboratory findings, identification of infectious microorganisms, and placental pathology. Fetal monitoring involves antenatal ultrasonography and non-stress testing. The management of infection-related PTB involves controlling and treating the infection, timing delivery to coincide with optimal fetal lung maturity, and optimizing outcomes for both the mother and neonate. Current preventive strategies for PTB primarily focus on inhibiting myometrial contractions that arise from the inflammatory cascade initiating PTB. An understanding of these pathways serves as the cornerstone for the development of therapeutic interventions aimed at preventing PTB.

Preterm birth (PTB), predominantly induced by intraamniotic inflammation, stands as the foremost contributor to neonatal morbidity and mortality globally. Fetal inflammatory response syndrome, stemming from the activation of the innate immune system, signifies the occurrence of funisitis or chorionic vasculitis. Maternal-fetal complications associated with infection-related PTB encompass maternal sepsis, fetal demise, neonatal sepsis, neonatal neurological impairment, and chronic lung disease. The inflammatory cascade is initiated when Toll-like receptors present on immune cells within the fetal membranes and the female reproductive tract encounter pathogen-associated molecular patterns derived from infectious agents. Subsequently, the nuclear factor kappa-light-chain-enhancer of activated B cells facilitates the transcription of cytokines. The accumulation of neutrophils compromises the tissue integrity of the fetal membranes, leading to membrane rupture via the secretion of matrix metalloproteinases. Elevated prostaglandin levels prompt uterine contractions and cervical remodeling, resulting in progressive cervical effacement and dilation, ultimately culminating in fetal delivery. The diagnosis of PTB should encompass three pivotal criteria: gestational age, uterine activity, and the consequences of that uterine activity. The diagnosis of chorioamnionitis is established through a combination of clinical manifestations, laboratory findings, identification of infectious microorganisms, and placental pathology. Fetal monitoring involves antenatal ultrasonography and non-stress testing. The management of infection-related PTB involves controlling and treating the infection, timing delivery to coincide with optimal fetal lung maturity, and optimizing outcomes for both the mother and neonate. Current preventive strategies for PTB primarily focus on inhibiting myometrial contractions that arise from the inflammatory cascade initiating PTB. An understanding of these pathways serves as the cornerstone for the development of therapeutic interventions aimed at preventing PTB.

Pregnancy is a physiological state that predisposes women to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a disease that can cause adverse maternal and perinatal outcomes. The severity of coronavirus disease 2019 (COVID-19) disease is known to vary by viral strain; however, evidence for the effects of this virus in pregnant women has yet to be fully elucidated. In this review, we describe maternal and perinatal outcomes, vaccination, and vertical transmission, among pregnant women infected with the different SARS-CoV-2 variants identified to date. We also summarize existing evidence for maternal and perinatal outcomes in pregnant women with specific information relating to SARS-CoV-2 variants. Our analysis showed that Omicron infection was associated with fewer severe maternal and perinatal adverse outcomes while the Delta variant was associated with worse pregnancy outcomes. Maternal deaths arising from COVID-19 were found to be rare (<1.0%), irrespective of whether the virus was a wild-type strain or a variant. Severe maternal morbidity was more frequent for the Delta variant (10.3%), followed by the Alpha (4.7%), wild-type (4.5%), and Omicron (2.9%) variants. The rates of stillbirth were 0.8%, 4.1%, 3.1%, and 2.3%, respectively, in pregnancies infected with the wild-type strain, Alpha, Delta, and Omicron variants, respectively. Preterm birth and admission to neonatal intensive care units were more common for cases with the Delta infection (19.0% and 18.62%, respectively), while risks were similar for those infected with the wild-type (14.7% and 11.2%, respectively), Alpha (14.9% and 13.1%), and Omicron variants (13.2% and 13.8%, respectively). As COVID-19 remains a global pandemic, and new SARS-CoV-2 variants continue to emerge, research relating to the specific impact of new variants on pregnant women needs to be expanded.

Pregnancy is a physiological state that predisposes women to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, a disease that can cause adverse maternal and perinatal outcomes. The severity of coronavirus disease 2019 (COVID-19) disease is known to vary by viral strain; however, evidence for the effects of this virus in pregnant women has yet to be fully elucidated. In this review, we describe maternal and perinatal outcomes, vaccination, and vertical transmission, among pregnant women infected with the different SARS-CoV-2 variants identified to date. We also summarize existing evidence for maternal and perinatal outcomes in pregnant women with specific information relating to SARS-CoV-2 variants. Our analysis showed that Omicron infection was associated with fewer severe maternal and perinatal adverse outcomes while the Delta variant was associated with worse pregnancy outcomes. Maternal deaths arising from COVID-19 were found to be rare (<1.0%), irrespective of whether the virus was a wild-type strain or a variant. Severe maternal morbidity was more frequent for the Delta variant (10.3%), followed by the Alpha (4.7%), wild-type (4.5%), and Omicron (2.9%) variants. The rates of stillbirth were 0.8%, 4.1%, 3.1%, and 2.3%, respectively, in pregnancies infected with the wild-type strain, Alpha, Delta, and Omicron variants, respectively. Preterm birth and admission to neonatal intensive care units were more common for cases with the Delta infection (19.0% and 18.62%, respectively), while risks were similar for those infected with the wild-type (14.7% and 11.2%, respectively), Alpha (14.9% and 13.1%), and Omicron variants (13.2% and 13.8%, respectively). As COVID-19 remains a global pandemic, and new SARS-CoV-2 variants continue to emerge, research relating to the specific impact of new variants on pregnant women needs to be expanded.

Objective : To explore the role and molecular mechanism of Supervillin in zebrafish embryo development. Methods : Clustal Omega and DNAman software were used to analyze and compare the homology of amino acid sequences of Svil and SVIL in zebrafish and human. The expression pattern of Svila (subtype of Svil protein in zebrafish) during early embryonic development was analyzed by RT⁃PCR and in situ hybridization. Svila expression in zebrafish was inhibited by injecting morphinos ( MO) , and morphological changes of embryos were observed. The expression and nuclear localization of β ⁃catenin protein were detected by Western blot , and the expression of Wnt/β⁃catenin target gene was detected by RT⁃PCR. Results : During the early embryonic development of zebrafish , Svila was maternally expressed and showed an upward trend with the development process. The expression of Svila was reduced by MO , and the development of zebrafish embryos was distorted and the body axis was bent , which might be related to the blocked movement of concentrated extension of embryos. Further studies showed that Svila expression affected β⁃catenin nuclear transport and Wnt/β⁃catenin signaling pathway activation. Conclusion Svila regulates the concentrated extension movement of zebrafish embryos by activating the Wnt/β⁃catenin signaling pathway.

BACKGROUND: Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China. METHODS: A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed. RESULTS: In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P  < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further. CONCLUSIONS The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.
Adult ; Blood Glucose/metabolism* ; China/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Diabetes, Gestational ; Female ; Fetal Macrosomia ; Glucose Intolerance ; Humans ; Male ; Pregnancy ; Retrospective Studies

Objective::To investigate the safety and efficacy of internal electronic fetal heart rate (FHR) monitoring during labor.Methods::This was a retrospective case-control study, which was an analysis of monitoring FHR with a fetal scalp electrode or a Doppler probe (94 pregnant women per group). In the internal monitoring group, when the opening of the uterine orifice was ≥3 cm, the fetal scalp electrode was placed after natural or artificial rupture of the membrane. FHR was simultaneously monitored using a Doppler probe. In the external monitoring group, continuous FHR monitoring was performed using an ultrasound Doppler transducer fixed on the maternal abdomen. The toco transducer was used to record uterine contractions. Pathological examination of the placenta was performed prospectively in 49 and 48 cases in the internal electronic FHR monitoring group and control group, respectively. Maternal-infant outcomes (e.g. fever, puerperal infection, puerperal morbidity, delivery mode, Apgar score, and scalp injury) were recorded. Umbilical artery blood was extracted for blood gas analysis. Differences between the two groups were compared using the paired t-test, χ2 test, Yates corrected χ2 test or Fisher exact test. Results::Non-statistically significant differences between the internal and external monitoring groups were observed in the incidence of neonatal acidosis (1/94 (1.06%) vs. 3/94 (3.19%), respectively; χ2= 0.255, P= 0.613), cesarean section/operative vaginal delivery (8/94 (8.51%) vs. 15/94 (15.96%), respectively; χ2 = 2.427, P= 0.181), fever during labor (18/94 (19.15%) vs. 15/94 (15.96%), respectively; χ2=0.331, P= 0.565), puerperal morbidity (2/94 (2.13%) vs. 3/94 (3.19%), respectively; χ2= 0.000, P= 1.000), chorioamnionitis (9/49 (18.37%) vs. 7/48(14.58%), respectively; χ2= 0.252, P= 0.616), and neonatal asphyxia (0/94 (0.00%) vs. 1/94 (1.06%), respectively; χ2= 0.000, P= 1.000). There were no puerperal infections, neonatal scalp injuries, or scalp abscesses found in either group. Using the internal monitoring value as reference, the incidence of FHR false deceleration in external FHR monitoring was 20.21% (19/94 women). Conclusion::Internal FHR monitoring during labor does not increase the incidence of adverse perinatal outcomes. External monitoring was associated with FHR false decelerations.

Objective::To investigate the efficacy of in-phase and quadrature (IQ) demodulation in electronic fetal heart rate monitoring (EFM) to reduce false reports of fetal heart rate (FHR) doubling or halving.Methods::This is a prospective cohort study. A total of 263 full-term pregnant women who delivered at Peking University Shenzhen Hospital between August 2019 and July 2020 were prospectively enrolled in the study. FHR monitoring began when the cervix was dilated to 2-3 cm and continued until delivery. Raw fetal Doppler audio signals and internal and external cardiotocography curves from internal electrode monitoring, EFM with conventional demodulation (external), and EFM with IQ demodulation (external) were acquired to compare FHR doubling and halving time. In cohort 1, FHR was compared between IQ demodulation and conventional demodulation. In cohort 2, FHR was compared between IQ demodulation, conventional demodulation, and internal FHR monitoring. Count data were statistically analyzed using the Chi-squared test, and measurement data were statistically analyzed using t-test for correlation coefficients, and Bland-Altman analysis for concordance ranges. Results::To compare IQ demodulation and conventional demodulation, 225 pregnant women were monitored for a total of 835,870 seconds. The beat-to-beat interval of FHRs in raw fetal Doppler audio signals was used as the reference. The results showed a doubling time of 3401 seconds (0.407%, 3401/835,870) and a halving time of 2918 seconds (0.349%, 2918/835,870) with conventional demodulation, compared to 241 seconds (0.029%, 241/835,870) and 589 seconds (0.070%, 589/835,870), respectively, with IQ demodulation. IQ demodulation reduced FHR doubling by approximately 93% (3160/3401) and FHR halving by approximately 80% (2329/2918) compared to conventional demodulation ( P < 0.01). Conclusion::EFM with IQ demodulation significantly reduces false FHR doubling and halving, with an efficacy similar to that of internal FHR monitoring.

Objective::To investigate the safety and efficacy of internal electronic fetal heart rate (FHR) monitoring during labor.Methods::This was a retrospective case-control study, which was an analysis of monitoring FHR with a fetal scalp electrode or a Doppler probe (94 pregnant women per group). In the internal monitoring group, when the opening of the uterine orifice was ≥3 cm, the fetal scalp electrode was placed after natural or artificial rupture of the membrane. FHR was simultaneously monitored using a Doppler probe. In the external monitoring group, continuous FHR monitoring was performed using an ultrasound Doppler transducer fixed on the maternal abdomen. The toco transducer was used to record uterine contractions. Pathological examination of the placenta was performed prospectively in 49 and 48 cases in the internal electronic FHR monitoring group and control group, respectively. Maternal-infant outcomes (e.g. fever, puerperal infection, puerperal morbidity, delivery mode, Apgar score, and scalp injury) were recorded. Umbilical artery blood was extracted for blood gas analysis. Differences between the two groups were compared using the paired t-test, χ2 test, Yates corrected χ2 test or Fisher exact test. Results::Non-statistically significant differences between the internal and external monitoring groups were observed in the incidence of neonatal acidosis (1/94 (1.06%) vs. 3/94 (3.19%), respectively; χ2= 0.255, P= 0.613), cesarean section/operative vaginal delivery (8/94 (8.51%) vs. 15/94 (15.96%), respectively; χ2 = 2.427, P= 0.181), fever during labor (18/94 (19.15%) vs. 15/94 (15.96%), respectively; χ2=0.331, P= 0.565), puerperal morbidity (2/94 (2.13%) vs. 3/94 (3.19%), respectively; χ2= 0.000, P= 1.000), chorioamnionitis (9/49 (18.37%) vs. 7/48(14.58%), respectively; χ2= 0.252, P= 0.616), and neonatal asphyxia (0/94 (0.00%) vs. 1/94 (1.06%), respectively; χ2= 0.000, P= 1.000). There were no puerperal infections, neonatal scalp injuries, or scalp abscesses found in either group. Using the internal monitoring value as reference, the incidence of FHR false deceleration in external FHR monitoring was 20.21% (19/94 women). Conclusion::Internal FHR monitoring during labor does not increase the incidence of adverse perinatal outcomes. External monitoring was associated with FHR false decelerations.

Objective::To investigate the efficacy of in-phase and quadrature (IQ) demodulation in electronic fetal heart rate monitoring (EFM) to reduce false reports of fetal heart rate (FHR) doubling or halving.Methods::This is a prospective cohort study. A total of 263 full-term pregnant women who delivered at Peking University Shenzhen Hospital between August 2019 and July 2020 were prospectively enrolled in the study. FHR monitoring began when the cervix was dilated to 2-3 cm and continued until delivery. Raw fetal Doppler audio signals and internal and external cardiotocography curves from internal electrode monitoring, EFM with conventional demodulation (external), and EFM with IQ demodulation (external) were acquired to compare FHR doubling and halving time. In cohort 1, FHR was compared between IQ demodulation and conventional demodulation. In cohort 2, FHR was compared between IQ demodulation, conventional demodulation, and internal FHR monitoring. Count data were statistically analyzed using the Chi-squared test, and measurement data were statistically analyzed using t-test for correlation coefficients, and Bland-Altman analysis for concordance ranges. Results::To compare IQ demodulation and conventional demodulation, 225 pregnant women were monitored for a total of 835,870 seconds. The beat-to-beat interval of FHRs in raw fetal Doppler audio signals was used as the reference. The results showed a doubling time of 3401 seconds (0.407%, 3401/835,870) and a halving time of 2918 seconds (0.349%, 2918/835,870) with conventional demodulation, compared to 241 seconds (0.029%, 241/835,870) and 589 seconds (0.070%, 589/835,870), respectively, with IQ demodulation. IQ demodulation reduced FHR doubling by approximately 93% (3160/3401) and FHR halving by approximately 80% (2329/2918) compared to conventional demodulation ( P < 0.01). Conclusion::EFM with IQ demodulation significantly reduces false FHR doubling and halving, with an efficacy similar to that of internal FHR monitoring.