Risk factors for placenta accreta spectrum without prior cesarean section: A case-control study in China.

OBJECTIVE: To identify the risk factors for placenta accreta spectrum (PAS) disorders in women without prior cesarean section (CS). METHODS: This retrospective case-control study investigated patients without prior CS who gave birth at Peking University Third Hospital between January 1, 2015 and December 31, 2021. Patients diagnosed with PAS according to the clinical diagnostic criteria of the 2019 International Federation of Gynecology and Obstetrics (FIGO) classification were included as the study group. Patients were matched as the control group according to delivery date and placenta previa, in a 1:2 allocation ratio. Maternal characteristics were compared between the two groups. RESULTS: The study included 348 patients in the study group and 696 in the control group. The multivariate analysis showed that the independent risk factors of PAS consisted of operative hysteroscopy (once: adjusted odds ratio [aOR] 2.38, 95% CI 1.28-4.24, P = 0.006; twice or more: aOR 5.43, 95% CI 1.04-28.32, P = 0.045), uterine curettage (once: aOR 2.54, 95% CI 1.80-3.58, P < 0.001; twice: aOR 3.01, 95% CI 1.81-5.02, P < 0.001; three or more times: aOR 9.18, 95% CI 4.64-18.18, P < 0.001), multifetal pregnancy (aOR 5.64, 95% CI 3.01-10.57, P < 0.001), adenomyosis (aOR 2.77, 95% CI 1.23-6.22, P = 0.014), in vitro fertilization (aOR 1.51, 95% CI 1.04-2.20, P = 0.030) and pre-eclampsia (aOR 2.72, 95% CI 1.36-5.45, P = 0.005), and the independent protective factor was being multiparous (aOR 0.37, 95% CI 0.25-0.54, P < 0.001). CONCLUSION: After controlling the effect of placenta previa, we found that patients with PAS without prior CS had unique maternal characteristics. Classification and quantification of the intrauterine surgeries they have undergone is essential for identifying high-risk patients. Early identification of high-risk groups by risk factors has the potential to improve the prognosis considerably.

Characteristics and treatment for severe postpartum haemorrhage in different midwifery hospitals in one district of Beijing in China: an institution-based, retrospective cohort study.

OBJECTIVE: To identify the characteristics and treatment approaches for patients with severe postpartum haemorrhage (SPPH) in various midwifery institutions in one district in Beijing, especially those without identifiable antenatal PPH high-risk factors, to improve regional SPPH rescue capacity. DESIGN: Retrospective cohort study. SETTING: This study was conducted at 9 tertiary-level hospitals and 10 secondary-level hospitals in Haidian district of Beijing from January 2019 to December 2022. PARTICIPANTS: The major inclusion criterion was SPPH with blood loss ≥1500 mL or needing a packed blood product transfusion ≥1000 mL within 24 hours after birth. A total of 324 mothers with SPPH were reported to the Regional Obstetric Quality Control Office from 19 midwifery hospitals. OUTCOME MEASURES: The pregnancy characteristics collected included age at delivery, gestational weeks at delivery, height, parity, delivery mode, antenatal PPH high-risk factors, aetiology of PPH, bleeding amount, PPH complications, transfusion volume and PPH management. SPPH characteristics were compared between two levels of midwifery hospitals and their association with antenatal PPH high-risk factors was determined. RESULTS: SPPH was observed in 324 mothers out of 106 697 mothers in the 4 years. There were 74.4% and 23.9% cases of SPPH without detectable antenatal PPH high-risk factors in secondary and tertiary midwifery hospitals, respectively. Primary uterine atony was the leading cause of SPPH in secondary midwifery hospitals, whereas placental-associated disorders were the leading causes in tertiary institutions. Rates of red blood cell transfusion over 10 units, unscheduled returns to the operating room and adverse PPH complications were higher in patients without antenatal PPH high-risk factors. Secondary hospitals had significantly higher rates of trauma compared with tertiary institutions. CONCLUSION: Examining SPPH cases at various institutional levels offers a more comprehensive view of regional SPPH management and enhances targeted training in this area.

Longitudinal Cervical Length Measurements and Spontaneous Preterm Birth in Singleton and Twin Pregnancies.

Importance: Changes in cervical length in twin pregnancies exhibit various patterns, but it is unclear whether the mechanism underlying spontaneous preterm birth (sPTB) is consistent. The existence of detailed phenomena in singleton pregnancies is also unclear. Objectives: To explore the different patterns in cervical length trajectories in singleton and twin pregnancies and to analyze whether the immunological mechanisms of sPTB are consistent among these cervical length patterns. Design, Setting, and Participants: This cohort study recruited pregnant individuals who received antenatal care and delivered at Peking University Third Hospital in Beijing, China, between January 1, 2014, and December 31, 2022. Individuals with singleton and twin pregnancies were included. Exposures: Cervical length measurements and white blood cell (WBC) indicators. Main Outcomes and Measures: The primary outcome was sPTB. Longitudinal trajectory cluster analysis was used to identify patterns of changes in cervical length in singleton and twin pregnancies. A random-effects model with cubic spline was used to fit and compare the longitudinal trajectory of WBC indicators among early preterm birth, moderate to late preterm birth, and term birth. Results: A total of 43 559 pregnant individuals were included; of these, 41 706 had singleton pregnancies (mean [SD)] maternal age, 33.0 [4.0] years) and 1853 had twin pregnancies (mean [SD] maternal age, 33.3 [3.6] years). Two distinct patterns of cervical length changes were observed in both singleton and twin pregnancies: shortened (21 366 singletons and 546 twins) and stable (20 340 singletons and 1307 twins). In singleton pregnancies, WBC count was associated with early sPTB in individuals with both shortened cervix (odds ratio [OR], 1.35; 95% CI, 1.00-1.82) and stable cervix (OR, 1.64; 95% CI, 1.07-2.50). However, for twin pregnancies, the association of WBC count (OR, 3.13; 95% CI, 1.58-6.18) with the risk of early sPTB was observed only in individuals with a shortened cervix. Conclusions and Relevance: This study identified 2 distinct cervical length patterns: shortened and stable. These patterns revealed 2 preterm birth mechanisms in twin pregnancies, with the immunopathogenesis of sPTB found only in the shortened cervix pattern; in singleton pregnancies, maternal immune response was associated with a higher risk of sPTB regardless of a shortened or stable cervix.

Optimal starting dosing regimen of intravenous oxytocin for labor induction based on the population kinetic-pharmacodynamic model of uterine contraction frequency.

BACKGROUND: Intravenous oxytocin is commonly used for labor induction. However, a consensus on the initial dosing regimen is lac with conflicting research findings and varying guidelines. This study aimed to develop a population kinetic-pharmacodynamic (K-PD) model for oxytocin-induced uterine contractions considering real-world data and relevant influencing factors to establish an optimal starting dosing regimen for intravenous oxytocin. METHODS: This retrospective study included pregnant women who underwent labor induction with intravenous oxytocin at Peking University Third Hospital in 2020. A  population K-PD model was developed to depict the time course of uterine contraction frequency (UCF), and covariate screening identified significant factors affecting the pharmacokinetics and pharmacodynamics of oxytocin. Model-based simulations were used to optimize the current starting regimen based on specific guidelines. RESULTS: Data from 77 pregnant women with 1095 UCF observations were described well by the K-PD model. Parity, cervical dilation, and membrane integrity are significant factors influencing the effectiveness of oxytocin. Based on the model-based simulations, the current regimens showed prolonged onset times and high infusion rates. This study proposed a revised approach, beginning with a rapid infusion followed by a reduced infusion rate, enabling most women to achieve the target UCF within approximately 30 min with the lowest possible infusion rate. CONCLUSION: The K-PD model of oxytocin effectively described the changes in UCF during labor induction. Furthermore, it revealed that parity, cervical dilation, and membrane integrity are key factors that influence the effectiveness of oxytocin. The optimal starting dosing regimens obtained through model simulations provide valuable clinical references for oxytocin treatment.

The changing Doppler patterns and perinatal outcomes of monochorionic diamniotic twins with selective fetal growth restriction.

OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66 %) type I cases were stable, whereas 25/100 (25 %) cases changed to type II and 9/100 (9 %) changed to sFGR complicated TTTS. A total of 48.9 % (22/45) sFGR cases were complicated with polyhydramnios and 30.4 % (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3 %, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.

Association of Paternal Age Alone and Combined with Maternal Age with Perinatal Outcomes: A Prospective Multicenter Cohort Study in China.

Maternal and paternal age at birth is increasing globally. Maternal age may affect perinatal outcomes, but the effect of paternal age and its joint effect with maternal age are not well established. This prospective, multicenter, cohort analysis used data from the University Hospital Advanced Age Pregnant Cohort Study in China from 2016 to 2021, to investigate the separate association of paternal age and joint association of paternal and maternal age with adverse perinatal outcomes. Of 16,114 singleton deliveries, mean paternal and maternal age (± SD) was 38.0 ± 5.3 years and 36.0 ± 4.1 years. In unadjusted analyses, older paternal age was associated with increased risks of gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy, preeclampsia, placenta accreta spectrum disorders, placenta previa, cesarean delivery (CD), and postpartum hemorrhage, preterm birth (PTB), large-for-gestational-age, macrosomia, and congenital anomaly, except for small-for-gestational-age. In multivariable analyses, the associations turned to null for most outcomes, and attenuated but still significant for GDM, CD, PTB, and macrosomia. As compare to paternal age of < 30 years, the risks in older paternal age groups increased by 31-45% for GDM, 17-33% for CD, 32-36% for PTB, and 28-31% for macrosomia. The predicted probabilities of GDM, placenta previa, and CD increased rapidly with paternal age up to thresholds of 36.4-40.3 years, and then plateaued or decelerated. The risks of GDM, CD, and PTB were much greater for pregnancies with younger paternal and older maternal age, despite no statistical interaction between the associations related to paternal and maternal age. Our findings support the advocation that paternal age, besides maternal age, should be considered during preconception counseling.Trial Registration NCT03220750, Registered July 18, 2017-Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT03220750 .

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

Amniotic fluid metabolic fingerprinting contributes to shaping the unfavourable intrauterine environment in monochorionic diamniotic twins.

BACKGROUND & AIMS: Amniotic fluid (AF) is the primary intrauterine environment for fetal growth throughout gestation. Selective fetal growth restriction (sFGR) is an adverse complication characterized by unequal growth in twins with nearly identical genetic makeup. However, the influence of AF-mediated intrauterine environment on the development and progression of sFGR remains unexplored. METHODS: High-throughput targeted metabolomics analysis (G350) was performed on AF samples collected from sFGR (n = 18) and MCDA twins with birth weight concordance (MCDA-C, n = 20) cases. Weighted correlation network analysis (WGCNA) was used to identify clinical features that may influence the metabolite composition in AF. Subsequently, partial least-squares discriminant analysis (PLS-DA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to compare the different types of sFGR and MCDA-C twins. Receiver operating characteristic (ROC) and multivariate ROC curves were utilized to explore potential AF markers in twins with sFGR. RESULTS: In our study, 182 metabolites were quantified in 76 AF samples. WGCNA indicated that the metabolite composition in late AF may not be influenced by gestational age. PLSDA demonstrated distinct variations between the metabolite profiles of AF in the sFGR and MCDA-C twins, with a significant emphasis on amino acids as the primary differential metabolite. The dissimilarities observed in sFGR twins were predominantly attributed to lipid metabolism-related metabolites. In particular, the KEGG enrichment metabolic pathway analysis revealed significant associations of both types of sFGR twins with central carbon metabolism in cancer. The multivariate ROC curves indicated that the combination of carnosine, sarcosine, l-alanine, beta-alanine, and alpha-n-phenylacetylglutamine significantly improved the AUC to 0.928. Notably, the ROC curves highlighted creatine (AUC:0.934) may be a potential biomarker for severe sFGR. CONCLUSION: The data presented in this study offer a comprehensive metabolic map of the AF in cases of sFGR, shedding light on potential biomarkers associated with fetal growth and development in MCDA twins.

Deep Learning Model Based on Multisequence MRI Images for Assessing Adverse Pregnancy Outcome in Placenta Accreta.

BACKGROUND: Preoperative assessment of adverse outcomes risk in placenta accreta spectrum (PAS) disorders is of high clinical relevance for perioperative management and prognosis. PURPOSE: To investigate the association of preoperative MRI multisequence images and adverse pregnancy outcomes by establishing a deep learning model in patients with PAS. STUDY TYPE: Retrospective. POPULATION: 323 pregnant women (age from 20 to 46, the median age is 33), suspected of PAS, underwent MRI to assess the PAS, divided into the training (N = 227) and validation datasets (N = 96). FIELD STRENGTH/SEQUENCE: 1.5T scanner/fast imaging employing steady-state acquisition sequence and single shot fast spin echo sequence. ASSESSMENT: Different deep learning models (i.e., with single MRI input sequence/two sequences/multisequence) were compared to assess the risk of adverse pregnancy outcomes, which defined as intraoperative bleeding ≥1500 mL and/or hysterectomy. Net reclassification improvement (NRI) was used for quantitative comparison of assessing adverse pregnancy outcome between different models. STATISTICAL TESTS: The AUC, sensitivity, specificity, and accuracy were used for evaluation. The Shapiro-Wilk test and t-test were used. A P value of <0.05 was considered statistically significant. RESULTS: 215 cases were invasive placenta accreta (67.44% of them with adverse outcomes) and 108 cases were non-invasive placenta accreta (9.25% of them with adverse outcomes). The model with four sequences assessed adverse pregnancy outcomes with AUC of 0.8792 (95% CI, 0.8645-0.8939), with ACC of 85.93% (95%, 84.43%-87.43%), with SEN of 86.24% (95% CI, 82.46%-90.02%), and with SPC of 85.62% (95%, 82.00%-89.23%) on the test cohort. The performance of model with four sequences improved above 0.10 comparing with that of model with two sequences and above 0.20 comparing with that of model with single sequence in terms of NRI. DATA CONCLUSION: The proposed model showed good diagnostic performance for assessing adverse pregnancy outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Association of maternal age with adverse pregnancy outcomes: A prospective multicenter cohort study in China.

Background: Although maternal age might affect pregnancy outcomes, it remains unclear whether this relationship is linear or curvilinear and if it differs between nulliparous and multiparous women. We aimed to characterize the relationship between maternal age and risks of pregnancy outcomes in a diverse sample of Chinese singleton pregnant women and to evaluate whether the relationship varied by parity. Methods: We based this prospective multicenter cohort study on data from 18 495 singleton pregnant women who participated in the University Hospital Advanced Age Pregnant Cohort Study, conducted in eight Chinese public hospitals from 2016 to 2021. We used restricted cubic splines to model nonlinear relationships between maternal age continuum and adverse outcomes, and performed multivariable log-binomial regression to estimate the adjusted relative risk (RR) and 95% confidence interval (CI). Results: Among 18 495 singleton pregnant women (mean age 35.7, standard deviation (SD) = 4.2 years), maternal age was not related to postpartum hemorrhage or small for gestational age, but showed a positive, nonlinear relationship to gestational diabetes mellitus, hypertensive disorders of pregnancy, preeclampsia, placenta accreta spectrum, placenta previa, cesarean delivery, preterm birth, large for gestational age, macrosomia, and fetal congenital anomaly, with inflection points around 35.6-40.4 years. Compared to women younger than 35 years, older women had higher risks of adverse pregnancy outcomes, except for postpartum hemorrhage and small for gestational age. The risks of placenta accreta spectrum, placenta previa, large for gestational age, and macrosomia were highest for women aged 40-44 years, and risks of gestational diabetes mellitus, hypertensive disorders of pregnancy, preeclampsia, cesarean delivery, preterm birth and congenital anomaly were highest for those aged ≥45 years. Most risks were more pronounced in nulliparous than multiparous women (P for interaction <0.02). Conclusions: Delayed childbirth was related to increased risks of adverse pregnancy outcomes, especially for nulliparous women. Appropriate childbearing age, generally before 35 years, is recommended for optimising pregnancy outcomes.

A study on the correlation of placental anastomosis and superficial vascular branches of selective fetal growth restriction in monochorionic diamniotic twins.

INTRODUCTION: The main purpose of the present study was to investigate the correlation between placental anastomosis and superficial vascular branches in selective fetal growth restriction (sFGR) in monochorionic diamniotic twins. MATERIALS AND METHODS: This was a retrospective analysis of the pregnancy data and placental perfusion of 395 patients with monochorionic diamniotic (MCDA) twin pregnancies delivered at our hospital from April 2013 to April 2020. We divided the patients into two groups and compared the number of placental superficial vascular branches in sFGR twins and normal MCDA twins. The correlation between the placental anastomosis and the number of superficial vascular branches in sFGR and normal MCDA twins was also investigated. RESULTS: The number of umbilical arterial branches and umbilical venous branches was less than larger twins in sFGR, larger twins in normal MCDA and smaller twins in normal MCDA. (11.83 [4-44], 21.82 [7-50], 19.72 [3-38], 14.85 [0-31], p < 0.001, 6.08 [1-18], 9.60 [3-22], 9.96 [2-22], 8.38 [1-20], p < 0.00) For smaller twins in the sFGR group, the number of umbilical venous branches was positively associated with AA anastomosis overall diameter, AV anastomosis overall diameter and all anastomosis overall diameter. (r = 0.194, 0.182 and 0.211, p < 0.05) CONCLUSIONS: The risk of sFGR may arise when the placenta from MCDA twins shows a poor branching condition of placental superficial vessels. For the smaller twin of sFGR, regular ultrasound examination of the number of the umbilical venous branches may help to predict artery-to-artery (AA) overall diameter, artery-to-vein (AV) overall diameter and all anastomosis overall diameter.

Thick artery-artery anastomoses delay the onset of selective fetal growth restriction in monochorionic diamniotic twins: a 7-year single-center cohort study.

Objective: This study aimed to investigate differences in placental characteristics between early- and late-onset selective fetal growth restriction (sFGR) in monochorionic diamniotic twins. Methods: A total of 253 patients with sFGR between April 2013 and April 2020 were retrospectively analyzed. Placental characteristics of early- and late-onset sFGR were compared. Results: The gestational age at diagnosis and delivery in the early-onset group was significantly less than that in the late-onset group [22.0 (16.9-23.9) and 28.4 (24.0, 36.3) weeks, P < 0.001; 33.1 ± 2.2 and 33.7 ± 2.5 weeks, P = 0.025]. The birth weight of normal growth and growth-restricted fetuses in the early-onset group was less than the late-onset group [1,990 ± 422 and 2,162 ± 525 g, P = 0.044; 1,320 ± 409 and 1,595 ± 519 g, P = 0.001]. The birthweight discordance ratio in the early-onset group was greater than the late-onset group (0.34 ± 0.12 and 0.29 ± 0.13, P = 0.001). The early-onset group had a significantly lower prevalence of sFGR type I than the late-onset group (37.5 and 62.0%, P = 0.018). The early-onset group had a significantly higher prevalence of sFGR type III than the late-onset group (30.4 and 12.7%, P = 0.048). The early-onset group had a lower prevalence of thick artery-artery anastomoses than the late-onset group (37.5 and 62.0%, P = 0.006). The placental territory discordance ratio in the early-onset group was higher than in the late-onset group [0.60 (0.01, 0.80) and 0.50 (0.01, 0.88), P = 0.018]. Conclusion: Unequal placental territory is the cause for most of the late-onset sFGR. Thick artery-artery anastomoses may delay the onset time of these cases of sFGR.

Metabolic dynamics and prediction of sFGR and adverse fetal outcomes: a prospective longitudinal cohort study.

BACKGROUND: Selective fetal growth restriction (sFGR) is an extreme complication that significantly increases the risk of perinatal mortality and long-term adverse neurological outcomes in offspring, affecting approximately 15% of monochorionic diamniotic (MCDA) twin pregnancies. The lack of longitudinal cohort studies hinders the early prediction and intervention of sFGR. METHODS: We constructed a prospective longitudinal cohort study of sFGR, and quantified 25 key metabolites in 337 samples from maternal plasma in the first, second, and third trimester and from cord plasma. In particular, our study examined fetal growth and brain injury data from ultrasonography and used the Ages and Stages Questionnaire-third edition subscale (ASQ-3) to evaluate the long-term neurocognitive behavioral development of infants aged 2-3 years. Furthermore, we correlated metabolite levels with ultrasound data, including physical development and brain injury indicators, and ASQ-3 data using Spearman's-based correlation tests. In addition, special combinations of differential metabolites were used to construct predictive models for the occurrence of sFGR and fetal brain injury. RESULTS: Our findings revealed various dynamic patterns for these metabolites during pregnancy and a maximum of differential metabolites between sFGR and MCDA in the second trimester (n = 8). The combination of L-phenylalanine, L-leucine, and L-isoleucine in the second trimester, which were closely related to fetal growth indicators, was highly predictive of sFGR occurrence (area under the curve [AUC]: 0.878). The combination of L-serine, L-histidine, and L-arginine in the first trimester and creatinine in the second trimester was correlated with long-term neurocognitive behavioral development and showed the capacity to identify fetal brain injury with high accuracy (AUC: 0.94). CONCLUSIONS: The performance of maternal plasma metabolites from the first and second trimester is superior to those from the third trimester and cord plasma in discerning sFGR and fetal brain injury. These metabolites may serve as useful biomarkers for early prediction and promising targets for early intervention in clinical settings.

Relationship between one-carbon metabolism and fetal growth in twins: A cohort study.

We investigated the associations of one-carbon metabolism (OCM)-related metabolites, including choline, betaine, dimethylglycine (DMG), and methionine with fetal growth of twins. This hospital-based cohort study included dichorionic twin gestations. Blood samples were collected at a median of 14.7 weeks of gestation. Blood plasma metabolite levels were measured using high-performance liquid chromatography-triple quadrupole mass spectrometry. Generalized estimating equations and mixed effects models were used to explore associations between plasma metabolite levels and fetal growth. In total, 115 women with dichorionic diamniotic pregnancies were included. The maternal plasma DMG level was negatively correlated with fetal birth weight (ß = -43.5, 95% confidence interval [CI] = -74.1 to -12.8, p < .05) and head circumference (ß = -0.23, 95% CI = -0.39 to -0.07, p < .05). Other metabolites were not significantly associated with birth weight, body length, head circumference (HC), or chest circumference. Analysis of the relationships between plasma metabolite levels and fetal biological parameters on ultrasound revealed that the maternal choline level was negatively correlated with fetal abdominal circumference (AC) (ß = -0.12, 95% CI = 0.24 to -0.004, p < .05); the maternal DMG level was negatively correlated with fetal AC (ß = -0.17, 95% CI = 0.28-0.07, p < .05), femur length (ß = 0.02, 95% CI = 0.04-0.003, p < .05), and estimated fetal weight (ß = 26.4, 95% CI = -41.6 to -11.2, p < .05), but not with HC. The maternal methionine level was negatively correlated with HC (ß = -0.08, 95% CI = -0.14 to -0.02, p < .05). The plasma level of the OCM-related metabolite DMG during the second trimester was negatively correlated with fetal intrauterine growth and birth weight. However, further studies with larger samples are needed.

Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta.

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0 ) synthesis, reduced estradiol (E2 ), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2 , but not T0 , actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17ß-HSD3 and 3ß-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.

Outcomes of fetal reduction versus expectant management in dichorionic triamniotic triplets.

OBJECTIVE: To compare the outcomes of dichorionic triamniotic (DCTA) triplets who underwent fetal reduction (FR) to singletons or twins with those managed expectantly. METHODS: We conducted a retrospective study of DCTA triplets with three living fetuses at 11-14 weeks over a 7-year period. Pregnancy outcomes were compared following different management strategies. RESULTS: Of 108 included patients, 22 underwent expectant management (EM), 28 were reduced to dichorionic diamniotic twins, and 58 to singletons. The median gestational age at birth for EM, FR to twins, and singletons was 33.1 weeks, 37.0 weeks, and 38.6 weeks, respectively (P < 0.001). Prematurity before 37 and 34 weeks was less common following FR to singletons and twins than in ongoing triplets (18.9%, 46.2% and 90.5%, P < 0.001; 13.2%, 26.9% and 57.1%, P < 0.001). Neonatal birth weight was higher in triplets reduced to singletons and twins compared with EM cases (3140g, 2315g, and 1860g, P < 0.001). However, rates of miscarriage, pregnancies with ≥1 survivor, maternal complications, and adverse neonatal outcomes were comparable among the three groups. CONCLUSIONS: In our experience, FR in DCTA triplets could reduce prematurity risk compared to EM, but it confers no survival advantage. Fetal reduction to singletons may result in more favorable outcomes than those reduced to dichorionic twins.

Initial establishment and validation of a predictive model for preeclampsia in twin pregnancies based on maternal characteristics and echocardiographic parameters.

INTRODUCTION: The primary objective of this study was to evaluate the association between maternal echocardiographic changes and the occurrence of preeclampsia (PE) in twin pregnancies. Additionally, we established and validated a prediction model for PE in twin pregnancies. MATERIAL AND METHODS: The first part of this study was retrospective and included data from 854 twin pregnancies that received antenatal care at Peking University Third Hospital from April 2017 to April 2021 (training cohort). Overall, 159 women who underwent transthoracic echocardiography were included in the analysis. To build a predictive model, cardiac findings were compared between normotensive women and those with PE. The model was then validated in a prospective longitudinal cohort (test cohort) that included 109 women with twin pregnancies who underwent two consecutive transthoracic echocardiography examinations during the second and third trimesters. RESULTS: Fifty-four normotensive women and 105 women with PE were analyzed in the retrospective cohort that was used to build the model in which later preeclampsia was associated with higher left ventricular mass index (>61 g/m2 ), interventricular septal thickness (>7.87 mm), left atrial anteroposterior diameter (>33.5 mm), mitral inflow late diastolic velocity (A) (>0.685 m/s), ratio of early diastolic velocity (E) and peak early diastolic myocardial velocity of the lateral mitral annulus (>6.5), and lower peak early diastolic myocardial velocity (<13.1 cm/s). The optimized PE prediction model based on the interventricular septal thickness, left atrial anteroposterior diameter, A, peak early diastolic myocardial velocity and pre-pregnancy bodyweight index was then established (area under the curve [AUC] = 0.840, 95% CI 0.778-0.903, P < 0.001). The model was tested in the prospective cohort including 87 normotensive women and 22 women with PE; the validation test showed that the prediction model in the second (AUC = 0.801) and third (AUC = 0.811) trimesters had high discriminative ability and calibration. CONCLUSIONS: Maternal echocardiographic changes in twin pregnancies are associated with the development of preeclampsia. The model constructed, based on the echocardiographic parameters and body mass index, provides novel ideas for the prediction of PE.

Management strategy for urologic morbidity in surgery of placenta accreta spectrum: stents or catheters?

OBJECTIVE: Surgery for placenta accreta spectrum disorders is known to be associated with urologic morbidity. Although previous studies have shown preoperative ureteral stent placement might be useful for preventing the urologic morbidity, the patient's discomfort caused by it should not be ignored. Whether there is an alternative management strategy remains unknown. This study was to evaluate the effectiveness of ureteral stents and catheters in preventing urologic injury in patients with placenta accreta spectrum undergoing surgery. METHODS: We conducted a retrospective cohort study. All cases with diagnosed placenta accreta spectrum who underwent surgery at Peking University Third Hospital between January 2018 and December 2020 were collected and reviewed. They were divided into two groups according to the different management strategies for preoperative placement of ureteral catheters or stents. The primary outcome was urologic injury, which was defined as the presence of ureteral or bladder injury during and after surgery. Secondary outcomes included urologic complications within the first three months after surgery. The median (interquartile range) or proportions were reported for variables. The Man Whitney U test, chi-square test and multivariate logistic regression were used for analysis. RESULTS: Ultimately, 99 patients were included in this study. Ureteral catheters were placed in 52 patients and ureteral stents were placed in 47 patients. Placenta accreta, placenta increta, and placenta percreta were diagnosed in three, 19, and 77 women, respectively. The hysterectomy rate was 52.53%. Overall, urologic injuries occurred in three patients (3.03%), including one case of combined bladder and ureteral injury (1.01%) and two cases of bladder injuries (2.02%). Only one ureteral injury occurred in a patient with a ureteral stent, which was recognized postoperatively (p = .475). All bladder injuries were vesical rupture which were recognized and repaired intraoperatively; one patient in the catheter group and two patients in the stent group (p = .929). After adjusting for confounding variables, multinomial regression analysis revealed no significant differences between the two groups in the incidence of bladder injuries(aOR: 0.695, 95% CI: 0.035-13.794, p = .811). A lower risk of urinary irritation (aOR: 0.186, 95% CI: 0.057-0.605, p = .005), hematuria (aOR: 0.011, 95% CI: 0.001-0.136, p < .001), and lower back pain (aOR: 0.075, 95% CI: 0.022-0.261, p < .001) was found in patients with ureteral catheters than in those with ureteral stents. CONCLUSION: The ureteral stents didn't confer a protective benefit in the surgical management for placenta accreta spectrum compare with catheters; however, they did result in a higher incidence of postoperative urologic complications. Ureteral temporal catheters may be an alternative strategy for placenta accreta spectrum cases suspected with urinary tract involved prenatally. Moreover, clearly and explicitly reporting "double J stent" or "temporal catheter" is necessary for future researches.

Reduced-visit antenatal care model combined with telemedicine for low-risk pregnant women: protocol for a randomised controlled trial.

INTRODUCTION: Antenatal care (ANC) is a critical measure to reduce maternal and perinatal morbidity and mortality. However, there are issues of too many visits and cumbersome procedures of ANC in many maternity hospitals of China. In the past 2 years, reduced-visit ANC models combined with remote monitoring have been recommended and implemented at most hospitals in China during the COVID-19 pandemic. Nevertheless, due to limited evaluations of the cost-effectiveness, policy-makers remain confused on how to appropriately integrate online delivery strategies with routine models to improve ANC quality and efficiency sustainably at scale. This trial aims to evaluate the effectiveness, acceptability and cost of a reduced-visit ANC model combined with telemedicine. METHODS AND ANALYSIS: A single-blind, randomised controlled trial will be conducted among low-risk pregnant women at Peking University Third Hospital in Beijing. 1476 patients (738 in each group) would be required, and they will be randomly assigned in a 1:1 ratio to receive the reduced-visit ANC combined with telemedicine services or the routine ANC. The primary outcome is the composite rate of adverse maternal and perinatal outcomes which will be extracted from the medical records. Secondary outcomes include acceptability of ANC models, which is assessed by satisfaction with ANC, pregnancy-related stress and ANC costs measured from the perspectives of both service providers and demanders. Both intention-to-treat and per-protocol analyses will be performed. Non-inferiority tests will be used to compare the two ANC models for the primary outcome. A cost-effectiveness analysis comparing the two ANC models will be conducted by estimating the incremental cost-effectiveness ratios. ETHICS AND DISSEMINATION: This study was approved by the ethical review committee of the Peking University Third Hospital (Beijing, China). The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences. TRIAL REGISTRATION NUMBER: NCT05290467.

Comparison of the 2009 Institute of Medicine and 2021 Chinese guidelines for gestational weight gain: A retrospective population-based cohort study.

OBJECTIVE: To analyze the associations between gestational weight gain (GWG) and perinatal outcomes based on the GWG guidelines of the Chinese Nutrition Society (CNS) and the Institute of Medicine (IOM). METHODS: This was a retrospective study with 9075 low-risk singleton pregnant women. Logistic regression model was used to analyze associations between GWG categories and perinatal outcomes. Sensitivity analyses were performed based on pre-pregnancy body mass index (calculated as weight in kilograms divided by the square of height in meters). RESULTS: Excessive GWG as defined by the two guidelines was associated with a higher risk of adverse perinatal outcomes. Inadequate GWG was associated with higher risks of small for gestational age (adjusted odds ratio [aOR] 1.34, 95% confidence interval [CI] 1.10-1.64) and preterm birth (aOR 1.70, 95% CI 1.22-2.36), but a lower risk of large for gestational age (LGA) (aOR 0.77, 95% CI 0.63-0.95) according to the IOM guidelines. When using the CNS guidelines, inadequate GWG was associated with only a lower risk of preterm birth (aOR 1.80, 95% CI 1.19-2.70). Sensitivity analyses suggested that excessive GWG was associated with a higher risk of LGA in underweight women. CONCLUSIONS: Both guidelines could demonstrate the relationship between GWG and adverse perinatal outcomes. The CNS guidelines were more suitable for the Chinese population with underweight or normal weight before pregnancy, whereas IOM was more suitable for pregnant women with inadequate GWG.