Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis.

Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.

DDX58 variant triggers IFN-ß-induced autophagy in trabecular meshwork and influences intraocular pressure.

Singleton-Merten syndrome (SMS) is a rare immunogenetic disorder affecting multiple systems, characterized by dental dysplasia, aortic calcification, glaucoma, skeletal abnormalities, and psoriasis. Glaucoma, a key feature of both classical and atypical SMS, remains poorly understood in terms of its molecular mechanism caused by DDX58 mutation. This study presented a novel DDX58 variant (c.1649A>C [p.Asp550Ala]) in a family with childhood glaucoma. Functional analysis showed that DDX58 variant caused an increase in IFN-stimulated gene expression and high IFN-ß-based type-I IFN. As the trabecular meshwork (TM) is responsible for controlling intraocular pressure (IOP), we examine the effect of IFN-ß on TM cells. Our study is the first to demonstrate that IFN-ß significantly reduced TM cell viability and function by activating autophagy. In addition, anterior chamber injection of IFN-ß remarkably increased IOP level in mice, which can be attenuated by treatments with autophagy inhibitor chloroquine. To uncover the specific mechanism underlying IFN-ß-induced autophagy in TM cells, we performed microarray analysis in IFN-ß-treated and DDX58 p.Asp550Ala TM cells. It showed that RSAD2 is necessary for IFN-ß-induced autophagy. Knockdown of RSAD2 by siRNA significantly decreased autophagy flux induced by IFN-ß. Our findings suggest that DDX58 mutation leads to the overproduction of IFN-ß, which elevates IOP by modulating autophagy through RSAD2 in TM cells.

Preterm birth in singleton pregnancies conceived by in vitro fertilization or intracytoplasmic sperm injection: an overview of systematic reviews.

BACKGROUND: The rate of preterm birth of singletons conceived through in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) is increased, being as high as 15% to 16% across Europe and the United States. However, the underlying etiology, phenotype, and mechanisms initiating preterm birth (PTB) are poorly understood. OBJECTIVE: To quantify the PTB risk and examine supposed etiology in IVF/ICSI singleton pregnancies compared to naturally conceived. STUDY DESIGN: Overview of reviews including all available systematic reviews with meta-analysis comparing PTB risk in IVF/ICSI and naturally conceived singletons. A comprehensive search of PubMed/MEDLINE, Embase, Scopus, and Cochrane Library databases was performed up to December 31, 2023. Information available on etiology, phenotype, initiation of PTB, and relevant moderators was retrieved and employed for subgroup analyses. Random-effects meta-analysis models were used for pooling effect measures. Estimates were presented as odds ratios (ORs) with 95% confidence intervals (CIs). The extent of overlap in the original studies was measured using the corrected covered area assessment. The quality of the included reviews was evaluated with the AMSTAR 2 tool. The Grading of Recommendations Assessment, Development and Evaluation approach was applied to rate evidence certainty. The protocol was registered on PROspective Register of Systematic Reviews (CRD42023411418). RESULTS: Twelve meta-analyses (16,522,917 pregnancies; ˃433,330 IVF/ICSI) were included. IVF/ICSI singletons showed a significantly higher PTB risk compared to natural conception (PTB ˂37 weeks: OR: 1.72, 95% CI: 1.57-1.89; PTB<32 weeks: OR: 2.19, 95% CI: 1.82-2.64). Influential analysis reinforced the strength of this association. Subgroup analyses investigating supposed etiology revealed a comparable risk magnitude for spontaneous PTB (OR: 1.79, 95% CI: 1.56-2.04) and a greater risk for iatrogenic PTB (OR: 2.28, 95% CI: 1.72-3.02). PTB risk was consistent in the subgroup of conventional IVF (OR: 1.95, 95% CI: 1.76-2.15) and higher in the subgroup of fresh only (OR: 1.79, 95% CI: 1.55-2.07) vs frozen-thawed embryo transfers (OR: 1.39, 95% CI: 1.34-1.43). There was minimal study overlap (13%). The certainty of the evidence was graded as low to very low. CONCLUSION: Singletons conceived through IVF/ICSI have a 2-fold increased risk of PTB compared to natural conception, despite the low certainty of the evidence. There is paucity of available data on PTB etiology, phenotype, or initiation. The greater risk increase is observed in fresh embryo transfers and involves iatrogenic PTB and PTB ˂32 weeks, likely attributable to placental etiology. Future studies should collect data on PTB etiology, phenotype, and initiation. IVF/ICSI pregnancies should undertake specialistic care with early screening for placental disorders, cervical length, and growth abnormalities, allowing appropriate timely follow-up, preventive measures, and therapeutic interventions strategies.

SMFM Consult Series #70: Management of short cervix in individuals without a history of spontaneous preterm birth.

Most deliveries before 34 weeks of gestation occur in individuals with no previous history of preterm birth. Midtrimester cervical length assessment using transvaginal ultrasound is one of the best clinical predictors of spontaneous preterm birth. This Consult provides guidance for the diagnosis and management of a short cervix in an individual without a history of preterm birth. The following are Society for Maternal-Fetal Medicine recommendations: (1) we recommend that all cervical length measurements used to guide therapeutic recommendations be performed using a transvaginal approach and in accordance with standardized procedures as described by organizations such as the Perinatal Quality Foundation or the Fetal Medicine Foundation (GRADE 1C); (2) we recommend using a midtrimester cervical length of ≤25 mm to diagnose a short cervix in individuals with a singleton gestation and no previous history of spontaneous preterm birth (GRADE 1C); (3) we recommend that asymptomatic individuals with a singleton gestation and a transvaginal cervical length of ≤20 mm diagnosed before 24 weeks of gestation be prescribed vaginal progesterone to reduce the risk of preterm birth (GRADE 1A); (4) we recommend that treatment with vaginal progesterone be considered at a cervical length of 21 to 25 mm based on shared decision-making (GRADE 1B); (5) we recommend that 17-alpha hydroxyprogesterone caproate, including compounded formulations, not be prescribed for the treatment of a short cervix (GRADE 1B); (6) in individuals without a history of preterm birth who have a sonographic short cervix (10-25 mm), we recommend against cerclage placement in the absence of cervical dilation (GRADE 1B); (7) we recommend that cervical pessary not be placed for the prevention of preterm birth in individuals with a singleton gestation and a short cervix (GRADE 1B); and (8) we recommend against routine use of progesterone, pessary, or cerclage for the treatment of cervical shortening in twin gestations outside the context of a clinical trial (GRADE 1B).

Maternal and Paternal Preconception Serum Concentrations of Per and Polyfluoroalkyl Substances in Relation to Birth Outcomes.

Prenatal per and polyfluoroalkyl substances (PFAS) exposure is associated with adverse birth outcomes. There is an absence of evidence on the relationship between maternal and paternal preconception PFAS exposure and birth outcomes. This study included 312 mothers and 145 fathers with a singleton live birth from a preconception cohort of subfertile couples seeking fertility treatment at a U.S. clinic. PFAS were quantified in serum samples collected before conception. Gestational age (GA) and birthweight (BW) were abstracted from delivery records. We also assessed low birthweight (BW < 2500 g) and preterm birth (GA < 37 completed weeks). We utilized multivariable linear regression, logistic regression, and quantile-based g computation to examine maternal or paternal serum concentrations of individual PFAS and mixture with birth outcomes. Maternal serum concentrations of perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), and the total PFAS mixture were inversely associated with birthweight. Maternal PFOS concentration was associated with a higher risk of low birthweight. Conversely, paternal PFOS and PFHxS concentrations were imprecisely associated with higher birthweight. No associations were found for gestational age or preterm birth. The findings have important implications for preconception care. Future research with larger sample sizes would assist in validating these findings.

Major postpartum haemorrhage after frozen embryo transfer: A population-based study.

OBJECTIVE: To investigate the effect on major postpartum haemorrhage (PPH) of mode of conception, differentiating between naturally conceived pregnancies, fresh embryo in vitro fertilisation (fresh-IVF) and frozen embryo transfer (frozen-IVF). DESIGN: Retrospective cohort study. SETTING: The French Burgundy Perinatal Network database, including all deliveries from 2006 to 2020, was linked to the regional blood centre database. POPULATION OR SAMPLE: In all, 244 336 women were included, of whom 240 259 (98.3%) were singleton pregnancies. METHODS: The main analyses were conducted in singleton pregnancies, including 237 608 naturally conceived, 1773 fresh-IVF and 878 frozen-IVF pregnancies. Multivariate logistic regression models adjusted on maternal age, body mass index, smoking, parity, induction of labour, hypertensive disorders, diabetes, placenta praevia and/or accreta, history of caesarean section, mode of delivery, birthweight, birth place and year of delivery, were used. MAIN OUTCOME MEASURES: Major PPH was defined as PPH requiring blood transfusion and/or emergency surgery and/or interventional radiology. RESULTS: The prevalence of major PPH was 0.74% (n = 1749) in naturally conceived pregnancies, 1.92% (n = 34) in fresh-IVF pregnancies, and 3.30% (n = 29) in frozen-IVF pregnancies. The risk of major PPH was higher in frozen-IVF pregnancies than in both naturally conceived pregnancies (adjusted odds ratio [aOR] 2.63, 95% CI 1.68-4.10) and fresh-IVF pregnancies (aOR 2.78, 95% CI 1.44-5.35). CONCLUSIONS: We found that frozen-IVF pregnancies have a higher risk of major PPH and they should be subject to increased vigilance in the delivery room.

Longitudinal evaluation of cervical length and shear wave elastography in women with spontaneous preterm birth.

OBJECTIVE: To evaluate longitudinal changes in cervical length (CL) and mean cervical shear wave elastography (CSWE) score in women with a singleton or twin pregnancy who undergo spontaneous preterm birth (sPTB) compared with those who deliver at term. METHODS: This was a prospective longitudinal study of unselected women with a singleton or twin pregnancy attending a dedicated research clinic for screening for sPTB at four timepoints during pregnancy: 11 + 0 to 15 + 6 weeks, 16 + 0 to 20 + 6 weeks, 21 + 0 to 24 + 6 weeks and 28 + 0 to 32 + 6 weeks. At each visit, a transvaginal ultrasound scan was conducted to measure the CL and the CSWE scores in six regions of interest (ROI) (inner, middle and external parts of anterior and posterior cervical lips). The mean CSWE score from the six ROIs was calculated for analysis. Log10 transformation was applied to data to produce a Gaussian distribution prior to statistical analysis. A multilevel mixed-effects analysis was performed to compare longitudinally CL and CSWE between the sPTB and term-delivery groups. RESULTS: The final cohort consisted of 1264 women, including 1143 singleton pregnancies, of which 57 (5.0%) were complicated by sPTB, and 121 twin pregnancies, of which 33 (27.3%) were complicated by sPTB. Compared to those who delivered at term, women with sPTB had a lower CL across gestation when controlling for history of cervical surgery, number of fetuses, gestational age (GA) at cervical assessment and the interaction between GA at cervical assessment and sPTB (P < 0.001). Specifically, CL in the sPTB group was significantly lower at 21 + 0 to 24 + 6 weeks (P = 0.039) and 28 + 0 to 32 + 6 weeks (P < 0.001). Twin pregnancies had significantly greater CL throughout pregnancy compared with singleton pregnancies (regression coefficient, 0.01864; P < 0.001). After adjusting for maternal age, weight, height, body mass index and GA at cervical assessment, CSWE score in the sPTB group was significantly lower compared with that in the term-delivery group across gestation (P = 0.013). However, on analysis of individual visits, CSWE score in the sPTB group was significantly lower than that in the term-delivery group only at 11 + 0 to 15 + 6 weeks (P = 0.036). There was no difference in CSWE score between singleton and twin pregnancies throughout gestation (regression coefficient, -0.00128; P = 0.937). CONCLUSIONS: Women with sPTB have a shorter and softer cervix across gestation compared with those who deliver at term. A shorter cervix in the sPTB group is observed from the late second trimester onwards, while lower cervical stiffness in the sPTB group is observed primarily in the first trimester. CL is significantly lower in singleton pregnancies compared with twin pregnancies, while cervical stiffness does not differ between the two. Our findings indicate that the cervix tends to undergo a softening process prior to shortening in sPTB cases. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Association between fetal growth restriction and stillbirth in twin compared with singleton pregnancies.

OBJECTIVES: Twin pregnancies are at higher risk of stillbirth compared to singletons. Fetal growth restriction (FGR) is a major cause of perinatal mortality, but its impact on twins vs singletons remains unclear. The primary objective of this study was to investigate the association of FGR and small-for-gestational age (SGA) with stillbirth in twin compared with singleton pregnancies. A secondary objective was to assess these associations stratified by gestational age at delivery. Furthermore, we aimed to compare the associations of FGR and SGA with stillbirth in twin pregnancies using twin-specific vs singleton birth-weight charts, stratified by chorionicity. METHODS: This was a retrospective cross-sectional study of pregnancies receiving obstetric care and giving birth between 1999 and 2022 at St George's Hospital, London, UK. The exclusion criteria included triplet and higher-order pregnancies, those resulting in miscarriage or live birth at ≤ 23 + 6 weeks, termination of pregnancy and missing data regarding birth weight or gestational age at birth. Birth-weight data were collected and FGR and SGA were defined as birth weight <5th and <10th centiles, respectively. While standard logistic regression was used for singleton pregnancies, the association of FGR and SGA with stillbirth in twin pregnancies was investigated using mixed-effects logistic regression models. For twin pregnancies, intercepts were allowed to vary for twin pairs to account for intertwin dependency. Analyses were stratified by gestational age at delivery and chorionicity. Statistical significance was set at P ≤ 0.001. RESULTS: The study included 95 342 singleton and 3576 twin pregnancies. There were 494 (0.52%) stillbirths in singleton and 41 (1.15%) stillbirths in twin pregnancies (17 dichorionic and 24 monochorionic). SGA and FGR were associated significantly with stillbirth in singleton pregnancies across all gestational ages at delivery: the odds ratios (ORs) for SGA and FGR were 2.36 ((95% CI, 1.78-3.13), P < 0.001) and 2.67 ((95% CI, 2.02-3.55), P < 0.001), respectively, for delivery before 32 weeks; 2.70 ((95% CI, 1.71-4.31), P < 0.001) and 2.82 ((95% CI, 1.78-4.47), P < 0.001), respectively, for delivery between 32 and 36 weeks; and 3.85 ((95% CI, 2.83-5.21), P < 0.001) and 4.43 ((95% CI, 3.16-6.12), P < 0.001), respectively, for delivery after 36 weeks. In twin pregnancies, when stratified by gestational age at delivery, both SGA and FGR determined by twin-specific birth-weight charts were associated with increased odds of stillbirth for those delivered before 32 weeks (SGA: OR, 3.87 (95% CI, 1.56-9.50), P = 0.003 and FGR: OR, 5.26 (95% CI, 2.11-13.01), P = 0.001), those delivered between 32 and 36 weeks (SGA: OR, 6.67 (95% CI, 2.11-20.41), P = 0.001 and FGR: OR, 9.54 (95% CI, 3.01-29.40), P < 0.001) and those delivered beyond 36 weeks (SGA: OR, 12.68 (95% CI, 2.47-58.15), P = 0.001 and FGR: OR, 23.84 (95% CI, 4.62-110.25), P < 0.001). However, the association of stillbirth with SGA and FGR in twin pregnancies was non-significant when diagnosis was based on singleton charts (before 32 weeks: SGA, P = 0.014 and FGR, P = 0.005; 32-36 weeks: SGA, P = 0.036 and FGR, P = 0.008; after 36 weeks: SGA, P = 0.080 and FGR, P = 0.063). CONCLUSION: Our study demonstrates that SGA and, especially, FGR are associated significantly with an increased risk of stillbirth across all gestational ages in singleton pregnancies, and in twin pregnancies when twin-specific birth-weight charts are used. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Incidence of neonatal morbidity in small-for-gestational-age twins based on singleton and twin charts.

OBJECTIVE: To compare morbidity, as measured by length of stay in the neonatal intensive care unit (NICU), in twin and singleton gestations classified as small-for-gestational age (SGA) according to estimated fetal weight < 10th percentile on twin or singleton growth charts. METHODS: NICU length of stay was compared in 1150 twins and 29 035 singletons that underwent ultrasound assessment between 35 + 0 and 36 + 6 weeks' gestation. Estimated fetal weight was obtained from measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Gestational age was derived from the first-trimester crown-rump length measurement, using the larger of the two twins. Singletons and twins were compared in terms of NICU admission rate and length of stay according to classification as SGA by the Fetal Medicine Foundation singleton and twin reference distributions. RESULTS: The overall proportions of twins and singletons admitted to NICU were similar (7.3% vs 7.4%), but twins tended to have longer lengths of stay in NICU (≥ 7 days: 2.4% vs 0.8%; relative risk (RR), 3.0 (95% CI, 1.6-4.4)). Using the singleton chart, a higher proportion of twins were classified as SGA compared with singletons (37.6% vs 7.0%). However, the proportion of SGA neonates entering NICU was similar (10.2% for twins and 10.1% for singletons) and the proportion of SGA neonates spending ≥ 7 days in NICU was substantially higher for twins compared with singletons (3.7% vs 1.4%; RR, 2.6 (95% CI, 1.4-4.7)). CONCLUSIONS: When singleton charts are used to define SGA in twins and in singletons, there is a greater degree of growth-related neonatal morbidity amongst SGA twins compared with SGA singletons. Consequently, singleton charts do not inappropriately overdiagnose fetal growth restriction in twins and they should be used for monitoring fetal growth in both twins and singletons. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Fetal Medicine Foundation charts for fetal growth in twins.

OBJECTIVE: To derive reference distributions of estimated fetal weight (EFW) in twins relative to singletons. METHODS: Gestational-age- and chorionicity-specific reference distributions for singleton percentiles and EFW were fitted to data on 4391 twin pregnancies with two liveborn fetuses from four European centers, including 3323 dichorionic (DC) and 1068 monochorionic diamniotic (MCDA) twin pregnancies. Gestational age was derived using the larger of the two crown-rump length measurements obtained during the first trimester of pregnancy. EFW was obtained from ultrasound measurements of head circumference, abdominal circumference and femur length using the Hadlock formula. Singleton percentiles were obtained using the Fetal Medicine Foundation population weight charts for singleton pregnancies. Hierarchical models were fitted to singleton Z-scores with autoregressive terms for serial correlations within the same fetus and between twins from the same pregnancy. Separate models were fitted for DC and MCDA twins. RESULTS: Fetuses from twin pregnancies tended to be smaller than singletons at the earliest gestational ages (16 weeks for MCDA and 20 weeks for DC twins). This was followed by a period of catch-up growth until around 24 weeks. After that, both DC and MCDA twins showed reduced growth. In DC twins, the EFW corresponding to the 50th percentile was at the 50th percentile of singleton pregnancies at 23 weeks, the 43rd percentile at 28 weeks, the 32nd percentile at 32 weeks and the 22nd percentile at 36 weeks. In MCDA twins, the EFW corresponding to the 50th percentile was at the 36th percentile of singleton pregnancies at 24 weeks, the 29th percentile at 28 weeks, the 19th percentile at 32 weeks and the 12th percentile at 36 weeks. CONCLUSIONS: In DC and, to a greater extent, MCDA twin pregnancies, fetal growth is reduced compared with that observed in singleton pregnancies. Furthermore, after 24 weeks, the divergence in growth trajectories between twin and singleton pregnancies becomes more pronounced as gestational age increases. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Triglyceride-glucose index in early pregnancy predicts the risk of gestational diabetes: a prospective cohort study.

OBJECTIVE: This study aimed to investigate the association between the triglyceride-glucose (TyG) index in early pregnancy and the development of gestational diabetes mellitus (GDM) in the second trimester. The primary objectives were to evaluate the predictive potential of the TyG index for GDM, determine the optimal threshold value of the TyG index for GDM assessment, and compare the predictive performance of the TyG index alone versus its combination with maternal age and pre-pregnancy body mass index on GDM. Moreover, the study explored the association between the TyG index in early pregnancy and the risk of other pregnancy-related complications (PRCs), such as placental abruption and gestational hypertension. PATIENTS AND METHODS: This prospective cohort study recruited 1,624 pregnant women who underwent early pregnancy antenatal counseling and comprehensive assessments with continuous monitoring until delivery. To calculate the TyG index, health indicators, including maternal triglycerides and fasting plasma glucose, were measured in early pregnancy (< 14 weeks of gestation). The predictive power of the TyG index for evaluating GDM in Chinese pregnant women was determined using multifactorial logistic regression to derive the odds ratios and 95% confidence interval (CI). Subgroup analyses were conducted, and the efficacy of the TyG index in predicting PRCs was assessed via receiver operating characteristic (ROC) curve analysis and restricted cubic spline, with the optimal cutoff value calculated. RESULTS: Logistic regression analyses revealed a 2.10-fold increase in the GDM risk for every 1-unit increase in the TyG index, after adjusting for covariates. The highest GDM risk was observed in the group with the highest TyG index compared with the lowest quintile group (odds ratios: 3.25; 95% CI: 2.23-4.75). Subgroup analyses indicated that exceeding the recommended range of gestational weight gain and an increased GDM risk were significantly associated (P = 0.001). Regarding predictive performance, the TyG index exhibited the highest area under the curve (AUC) value in the ROC curve for GDM (AUC: 0.641, 95% CI: 0.61-0.671). The optimal cutoff value was 8.890, with both sensitivity and specificity of 0.617.The combination of the TyG index, maternal age, and pre-pregnancy body mass index proved to be a superior predictor of GDM than the TyG index alone (AUC: 0.672 vs. 0.641, P < 0.01). After adjusting for multiple factors, the analyses indicated that the TyG index was associated with an increased risk of gestational hypertension. However, no significant association was noted between the TyG index and the risk of preeclampsia, placental abruption, intrauterine distress, or premature rupture of membranes. CONCLUSION: The TyG index can effectively identify the occurrence of GDM in the second trimester, aligning with previous research. Incorporating the TyG index into routine clinical assessments of maternal health holds significant practical implications. Early identification of high-risk groups enables healthcare providers to implement timely interventions, such as increased monitoring frequency for high-risk pregnant women and personalized nutritional counseling and health education. These measures can help prevent or alleviate potential maternal and infant complications, thereby enhancing the overall health outcomes for both mothers and babies.

Association between graded subchorionic hematoma and adverse pregnancy outcomes in singleton pregnancies: a prospective observational cohort study.

OBJECTIVE: To investigate whether different grades of subchorionic hematoma (SCH) are involved in the timing of birth and the development of adverse pregnancy outcomes in singleton pregnant women. METHODS: A total of 171 women with singleton pregnancies, 72 of whom had SCH before 20 weeks and between 12 and 20 weeks of gestational age (GA), were included in this study conducted between January 2018 and December 2021. These patients were divided into three subgroups based on the size of the subchorionic hematoma on ultrasound imaging. Baseline demographic data, obstetric outcomes, and risk factors for subchorionic hematoma were compared for the two groups. RESULTS: A higher number of pregnancies from the SCH group resulted in miscarriage (30.56% versus 2.02%, p < 0.0001), early preterm birth (8.33% versus 1.01%, p = 0.0035), premature rupture of membranes (15.28% versus 4.04%, p = 0.0103), fetal growth restriction (9.72% versus 0%, p = 0.0015), and delivery 13.18 days earlier (274.34 ± 11.25 versus 261.16 ± 29.80, p = 0.0013) than those from the control group. Compared with SCH detected before 12 weeks of GA, the rate of miscarriage increased, and the live birth rate decreased significantly in patients with SCH caught between 12 and 20 weeks of GA. With the increase in hematoma size, the likelihood of miscarriage increased significantly. Further analysis found that delivery occurred earlier in the medium/large SCH group (271.49 ± 23.61 versus 253.28 ± 40.68/261.77 ± 22.11, p = 0.0004/0.0073) but not in the small SCH group (274.34 ± 11.25 versus 267.85 ± 21.01, p = 0.2681) compared to the control group. Our results also showed that the anterior placenta (52.04% versus 33.33%, p = 0.0005, OR = 0.3137, 95% CI [0.1585, 0.601]) is a protective factor for subchorionic hematoma. CONCLUSION: Our study shows that women with SCH are at a higher risk of adverse pregnancy outcomes and are independently associated with miscarriage, early preterm birth, premature rupture of membranes, and fetal growth restriction. A subchorionic hematoma, especially detected between 12 and 20 weeks of GA, is very likely to cause miscarriage or preterm birth in women with a medium or large subchorionic hematoma.

Analysis of perinatal outcomes for emergency cervical cerclage in singleton pregnancies at 24-28 weeks of gestation.

BACKGROUND: Cervical cerclage is the only effective treatment for cervical insufficiency, effectively preventing late miscarriage and preterm birth. The effectiveness and safety of emergency cervical cerclage (ECC) as an emergency treatment when the cervix is already dilated or when there is protrusion of the fetal membranes into the vagina remain controversial, especially in pregnancies at 24-28 weeks when the fetus is viable. There is still no consensus on whether emergency cervical cerclage should be performed in such cases. PURPOSE: To investigate the effectiveness and safety of emergency cervical cerclage in singleton pregnant women at 24-28 weeks of gestation. METHODS: This study employed a single-center prospective cohort design, enrolling singleton pregnant women at 24-28 weeks of gestation with ultrasound or physical examination indicating cervical dilation or even membrane protrusion. Emergency cervical cerclage was compared with conservative treatment. The primary endpoints included a comprehensive assessment of perinatal pregnancy loss, significant neonatal morbidity, and adverse neonatal outcomes. Secondary endpoints included prolonged gestational age, preterm birth, neonatal hospitalization rate, premature rupture of membranes, and intrauterine infection/chorioamnionitis. RESULTS: From June 2021 to March 2023, a total of 133 pregnant women participated in this study, with 125 completing the trial, and were allocated to either the Emergency Cervical Cerclage (ECC) group (72 cases) or the conservative treatment group (53 cases) based on informed consent from the pregnant women. The rate of adverse neonatal outcomes was 8.33% in the ECC group and 26.42% in the conservative treatment (CT) group, with a statistically significant difference (P = 0.06). There were no significant differences between the two groups in terms of perinatal pregnancy loss and significant neonatal morbidity. The conservative treatment group had a mean prolonged gestational age of 63.0 (23.0, 79.5) days, while the ECC group had 84.0 (72.5, 89.0) days, with a statistically significant difference between the two groups (P < 0.001). Compared with CT group, the ECC group showed a significantly reduced incidence of preterm birth before 28 weeks, 32 weeks, and 34 weeks, with statistical significance (P = 0.046, 0.007, 0.001), as well as a significantly decreased neonatal hospitalization rate (P = 0.013, 0.031). Additionally, ECC treatment did not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis, with no statistically significant differences (P = 0.406, 0.397). CONCLUSION: In singleton pregnant women with cervical insufficiency at 24-28 weeks of gestation, emergency cervical cerclage can reduce adverse neonatal pregnancy outcomes, effectively prolong gestational age, decrease preterm births before 28 weeks, 32 weeks, and 34 weeks, lower neonatal hospitalization rates, and does not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis.

Uterocervical angle and cervical length measurements for spontaneous preterm birth prediction in low-risk singleton pregnant women: a prospective cohort study.

PURPOSE: Preterm birth is the leading cause of early neonatal morbidity and mortality. Strategies to predict preterm birth risk can help improve pregnancy outcomes. Even pregnant women without known risk factors for preterm birth can also experience it. This study aimed to evaluate the ability of the uterocervical angle and cervical length to predict spontaneous preterm birth in low-risk singleton pregnant women. METHODS: A prospective study on 1107 singleton pregnant women between 16+0 and 23+6 weeks gestation at low risk for spontaneous preterm birth who were treated at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, between September 2020 and September 2021 was conducted. A single sonographer assessed the cervical length and the uterocervical angle using transvaginal ultrasonography. The patients were followed up until delivery to determine the main pregnancy outcome (spontaneous preterm birth before 37 weeks gestation). The cut-off points for the uterocervical angle and cervical length were established by analyzing the receiver operating characteristic curve. The sensitivity, specificity, likelihood ratio, positive and negative predictive values, and accuracy of the uterocervical angle and cervical length for predicting spontaneous preterm birth were determined. RESULTS: A uterocervical angle ≥ 99° predicted spontaneous preterm birth at < 37 weeks, with a sensitivity and specificity of 91% and 76%, respectively. A cervical length ≤ 33.8 mm predicted preterm birth at < 37 weeks with a sensitivity and specificity of 25% and 66%, respectively. A uterocervical angle ≥ 99° combined with a cervical length ≤ 33.8 mm yielded the sensitivity, specificity, positive predictive value, likelihood ratio, and accuracy of spontaneous preterm birth prediction of 66%, 93%, 36%, 9, and 91%, respectively; thus provided a significant increase of specificity with an acceptable reduction of sensitivity as compared to cervical length alone. CONCLUSION: Besides the cervical length, the uterocervical angle can be considered a valuable ultrasound parameter for predicting spontaneous preterm birth in low-risk singleton pregnant women. Combining the uterocervical angle and cervical length yielded stronger spontaneous preterm birth prediction values.

Assessing hospital differences in low-risk cesarean delivery metrics in Florida.

BACKGROUND: Unnecessary cesarean deliveries lead to increased maternal and neonatal morbidities and mortalities. In 2020, Florida had a cesarean delivery rate of 35.9%, the third highest in the nation. An effective quality improvement strategy to reduce overall cesarean delivery rates is to decrease primary cesarean deliveries in low-risk births (nulliparous, term, singleton, vertex). Of note, 3 nationally accepted hospital measures of low-risk cesarean delivery rates include the nulliparous, term, singleton, vertex; Joint Commission; and Society for Maternal-Fetal Medicine metrics. Comparing metrics is necessary because accurate and timely measurement is essential to support multihospital quality improvement efforts to reduce low-risk cesarean delivery rates and improve the quality of maternal care. OBJECTIVE: This study aimed to assess differences in hospital low-risk cesarean delivery rates in Florida using 5 different metrics of low-risk cesarean delivery rate based on (1) risk methodology, nulliparous, term, singleton, vertex; Joint Commission; and Society for Maternal-Fetal Medicine metrics, and (2) data source, linked birth certificate and hospital discharge records and hospital discharge records only. STUDY DESIGN: This was a population-based study of live Florida births from 2016 to 2019 to compare 5 approaches to calculating low-risk cesarean delivery rates. Analyses were performed using linked birth certificate data and inpatient hospital discharge data. The 5 low-risk cesarean delivery measures were defined as follows: nulliparous, term, singleton, vertex birth certificate; Joint Commission-linked used Joint Commission exclusions; Society for Maternal-Fetal Medicine-linked used Society for Maternal-Fetal Medicine exclusions; Joint Commission hospital discharge with Joint Commission exclusions; and Society for Maternal-Fetal Medicine hospital discharge with Society for Maternal-Fetal Medicine exclusions. Nulliparous, term, singleton, vertex birth certificate was based on data from birth certificates and not using linked hospital discharge data. Designated as nulliparous, term, singleton, vertex, it does not exclude other high-risk conditions. The second and third measures (Joint Commission-linked used Joint Commission exclusions and Society for Maternal-Fetal Medicine-linked used Society for Maternal-Fetal Medicine exclusions) use data elements from the full-linked dataset to designate nulliparous, term, singleton, vertex and excluded several high-risk conditions. The last 2 measures (Joint Commission hospital discharge with Joint Commission exclusions; and Society for Maternal-Fetal Medicine hospital discharge with Society for Maternal-Fetal Medicine exclusions) were based on data from hospital discharge data only and not using linked birth certificate data. These measures generally reflect term, singleton, and vertex because parity could not be assessed adequately on hospital discharge data. Hospital differences between these 5 measures were calculated overall and by neonatal intensive care unit level. RESULTS: Overall, the median of hospital low-risk cesarean rates decreased across the measures, from NTSV-BC 30.7%, to Joint Commission linked 29.1%, and Society for Maternal Fetal Medicine hospital discharge 29.2% with a large decrease to Joint Commission hospital discharge 19.4% and Society for Maternal Fetal Medicine hospital discharge 18.1%. A similar trend was seen by neonatal intensive care unit level. For each of the measures, level II had the highest median low-risk cesarean rates (nulliparous. term, singleton, vertex birth certificate) 32.7%, Joint Commission linked (31.4%), Society for Maternal Fetal Medicine linked: 31.1%, Society for Maternal Fetal Medicine hospital discharge 19.3%), except for level III Joint Commission hospital discharge (20.0%). A comparison of the median number of low-risk births overall and by neonatal intensive care unit level showed a decreasing number across the linked and hospital discharge measures. Again, a wide gap in low-risk cesarean delivery rates was identified between linked measures and hospital discharge measures. However, this gap narrowed as hospital rates increased. CONCLUSION: Quality monitoring of low-risk cesarean delivery rates measured by the nulliparous, term, singleton, vertex metric using the birth certificate was fairly accurate and provided timely assessment for use by Florida hospitals. The nulliparous, term, singleton, vertex birth certificate rates were comparable with low-risk metrics using the linked data source. Overall, metrics used within the same data source had similar rates, with the Society for Maternal-Fetal Medicine metric having the lowest rates. Across data sources, metrics using hospital discharge data only resulted in substantially underestimated rates because of the inclusion of multiparous women and should be interpreted with caution.

Midwifery care during labor and birth in the United States.

The intrapartum period is a crucial time in the continuum of pregnancy and parenting. Events during this time are shaped by individuals' unique sociocultural and health characteristics and by their healthcare providers, practice protocols, and the physical environment in which care is delivered. Childbearing people in the United States have less opportunity for midwifery care than in other high-income countries. In the United States, there are 4 midwives for every 1000 live births, whereas, in most other high-income countries, there are between 30 and 70 midwives. Furthermore, these countries have lower maternal and neonatal mortality rates and have consistently lower costs of care. National and international evidences consistently report that births attended by midwives have fewer interventions, cesarean deliveries, preterm births, inductions of labor, and more vaginal births after cesarean delivery. In addition, midwifery care is consistently associated with respectful care and high patient satisfaction. Midwife-physician collaboration exists along a continuum, including births attended independently by midwives, births managed in consultation with a physician, and births attended primarily by a physician with a midwife acting as consultant on the normal aspects of care. This expert review defined midwifery care and provided an overview of midwifery in the United States with an emphasis on the intrapartum setting. Health outcomes associated with midwifery care, specific models of intrapartum care, and workforce issues have been presented within national and international contexts. Recommendations that align with the integration of midwifery have been suggested to improve national outcomes and reduce pregnancy-related disparities.

Incidence of stillbirth: effect of deprivation.

OBJECTIVES: To examine the relationship between the English index of multiple deprivation (IMD) and the incidence of stillbirth and assess whether IMD contributes to the prediction of stillbirth provided by the combination of maternal demographic characteristics and elements of medical history. METHODS: This was a prospective, observational study of 159 125 women with a singleton pregnancy who attended their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation in two maternity hospitals in the UK. The inclusion criterion was delivery at ≥ 24 weeks' gestation of a fetus without major abnormality. Participants completed a questionnaire on demographic characteristics and obstetric and medical history. IMD was used as a measure of socioeconomic status, which takes into account income, employment, education, skills and training, health and disability, crime, barriers to housing and services, and living environment. Each neighborhood is ranked according to its level of deprivation relative to that of other areas into one of five equal groups, with Quintile 1 containing the 20% most deprived areas and Quintile 5 containing the 20% least deprived areas. Logistic regression analysis was used to determine whether IMD provided a significant independent contribution to stillbirth after adjustment for known maternal risk factors. RESULTS: The overall incidence of stillbirth was 0.35% (551/159 125), and this was significantly higher in the most deprived compared with the least deprived group (Quintile 1 vs Quintile 5). The odds ratio (OR) in Quintile 1 was 1.57 (95% CI, 1.16-2.14) for any stillbirth, 1.64 (95% CI, 1.20-2.28) for antenatal stillbirth and 1.89 (95% CI, 1.23-2.98) for placental dysfunction-related stillbirth. In Quintile 1 (vs Quintile 5), there was a higher incidence of factors that contribute to stillbirth, including black race, increased body mass index, smoking, chronic hypertension and previous stillbirth. The OR of black (vs white) race was 2.58 (95% CI, 2.14-3.10) for any stillbirth, 2.62 (95% CI, 2.16-3.17) for antenatal stillbirth and 3.34 (95% CI, 2.59-4.28) for placental dysfunction-related stillbirth. Multivariate analysis showed that IMD did not have a significant contribution to the prediction of stillbirth provided by maternal race and other maternal risk factors. In contrast, in black (vs white) women, the risk of any and antenatal stillbirth was 2.4-fold higher and the risk of placental dysfunction-related stillbirth was 2.9-fold higher after adjustment for other maternal risk factors. CONCLUSIONS: The incidence of stillbirth, particularly placental dysfunction-related stillbirth, is higher in women living in the most deprived areas in South East England. However, in screening for stillbirth, inclusion of IMD does not improve the prediction provided by race, other maternal characteristics and elements of medical history. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Singleton effect decreases under time pressure: An fNIRS study.

Time pressure affects multiple cognitive processes but how it affects attention capture remains unclear. Two experiments were carried out in the present study to assess whether time pressure prevents attention from capturing by salient distractors and explore the underlying neural mechanisms using functional near-infrared spectroscopy. The results of behavioral tests showed that the singleton effect decreased (Experiment 2) or even disappeared (Experiment 1) when the subject was under time pressure. Neuroimaging data showed that under time pressure, a salient distractor elicited greater activation in the left middle frontal gyrus/inferior frontal gyrus and bilateral superior parietal lobule, brain areas that are thought to be involved in cognitive inhibition and control of spatial attentional shifts. These findings suggest that the reduction or disappearance of the singleton effect under time pressure results from enhanced inhibition of and/or accelerated disengagement from salient distractors.

Birthweight of the subsequent singleton pregnancy following a first twin or singleton pregnancy.

INTRODUCTION: Birthweight is an important pregnancy indicator strongly associated with infant, child, and later adult life health. Previous studies have found that second-born babies are, on average, heavier than first-born babies, indicating an independent effect of parity on birthweight. Existing data are mostly based on singleton pregnancies and do not consider higher order pregnancies. We aimed to compare birthweight in singleton pregnancies following a first twin pregnancy relative to a first singleton pregnancy. MATERIAL AND METHODS: This was a prospective registry-based cohort study using maternally linked offspring with first and subsequent pregnancies registered in the Medical Birth Registry of Norway between 1967 and 2020. We studied offspring birthweights of 778 975 women, of which 4849 had twins and 774 126 had singletons in their first pregnancy. Associations between twin or singleton status of the first pregnancy and birthweight (grams) in subsequent singleton pregnancies were evaluated by linear regression adjusted for maternal age at first delivery, year of first pregnancy, maternal education, and country of birth. We used plots to visualize the distribution of birthweight in the first and subsequent pregnancies. RESULTS: Mean combined birthweight of first-born twins was more than 1000 g larger than mean birthweight of first-born singletons. When comparing mean birthweight of a subsequent singleton baby following first-born twins with those following first-born singletons, the adjusted difference was just 21 g (95% confidence interval 5-37 g). CONCLUSIONS: Birthweights of the subsequent singleton baby were similar for women with a first twin or a first singleton pregnancy. Although first twin pregnancies contribute a greater combined total offspring birthweight including more extensive uterine expansion, this does not explain the general parity effect seen in birthweight. The physiological reasons for increased birthweight with parity remain to be established.

Distribution of uterocervical angles of pregnant women at 16+ 0 to 23+ 6 weeks gestation with low risk for preterm birth: first vietnamese cohort of women with singleton pregnancies.

BACKGROUND: Cervical length (CL) measured by ultrasound in the second trimester is a predictor of spontaneous preterm birth (sPTB). The uterocervical angle (UCA) has recently been suggested as a predictor to identify women at risk of sPTB. The aim of this study was to investigate the UCAs' distribution in singleton pregnant women at 16+ 0 - 23+ 6 weeks of gestation with low risk for sPTB. METHODS: This was a prospective cohort study of 1,051 pregnant women with singleton pregnancies at low risk for preterm delivery. Pregnant women with a viable singleton fetus at 16+ 0 - 23+ 6 weeks of gestation were enrolled in the study conducted at the Haiphong Hospital of Obstetrics and Gynecology, Vietnam, from 09/2019 to 09/2020. CL and the UCA were assessed using transvaginal ultrasonography (TVS) by a single sonographer. Subjects were followed-up until the end of pregnancy, and maternal and neonatal outcomes were recorded. The UCAs' range and their relationship with gestational age were evaluated using regression analysis. P < 0.05 was considered statistically significant. RESULTS: The normal range of the UCA (5th - 95th percentiles) was 46.47° (95% CI, 40.27°-51.81°) to 127.06° (95% CI, 123.02° - 130.71°). The UCAs in the preterm birth (< 37 weeks) and full-term groups were 117.86° ± 20.25° and 83.80° ± 24.18°, respectively (p < 0.001). Linear regression analysis showed a significant change in the UCA range from 16+ 0 to 23+ 6 weeks of gestation (2.51 degrees per week, p < 0.001). The linear function yielded the highest correlation coefficient in the variation rule of the UCA values (r = 0.22). A total of 42/63 (66.7%) patients with preterm birth < 37 weeks had a UCA above the 75th percentile. The majority of women with preterm birth had a UCA ≥ 95° compared with those with full-term delivery (88.9% vs. 31.3%, p < 0.001). CONCLUSIONS: The results of this study present background information about the normal range of UCA values in singleton pregnant women at 16+ 0 to 23+ 6 weeks at low risk for sPTB in this Vietnamese cohort. In this study population at low risk for sPTB, pregnant women with a UCA value ≥ 95o were also considered at risk for preterm birth.