Profiling cortical morphometric similarity in perinatal brains: Insights from development, sex difference, and inter-individual variation.

The topological organization of the macroscopic cortical networks important for the development of complex brain functions. However, how the cortical morphometric organization develops during the third trimester and whether it demonstrates sexual and individual differences at this particular stage remain unclear. Here, we constructed the morphometric similarity network (MSN) based on morphological and microstructural features derived from multimodal MRI of two independent cohorts (cross-sectional and longitudinal) scanned at 30-44 postmenstrual weeks (PMW). Sex difference and inter-individual variations of the MSN were also examined on these cohorts. The cross-sectional analysis revealed that both network integration and segregation changed in a nonlinear biphasic trajectory, which was supported by the results obtained from longitudinal analysis. The community structure showed remarkable consistency between bilateral hemispheres and maintained stability across PMWs. Connectivity within the primary cortex strengthened faster than that within high-order communities. Compared to females, male neonates showed a significant reduction in the participation coefficient within prefrontal and parietal cortices, while their overall network organization and community architecture remained comparable. Furthermore, by using the morphometric similarity as features, we achieved over 65 % accuracy in identifying an individual at term-equivalent age from images acquired after birth, and vice versa. These findings provide comprehensive insights into the development of morphometric similarity throughout the perinatal cortex, enhancing our understanding of the establishment of neuroanatomical organization during early life.

Amniocentesis in pregnancies at or beyond 24 weeks: an international multicenter study.

BACKGROUND: Amniocentesis for genetic diagnosis is most commonly done between 15 and 22 weeks of gestation but can be performed at later gestational ages. The safety and genetic diagnostic accuracy of amniocentesis have been well-established through numerous large-scale multicenter studies for procedures before 24 weeks, but comprehensive data on late amniocentesis remain sparse. OBJECTIVE: To evaluate the indications, diagnostic yield, safety, and maternal and fetal outcomes associated with amniocentesis performed at or beyond 24 weeks of gestation. STUDY DESIGN: We conducted an international multicenter retrospective cohort study examining pregnant individuals who underwent amniocentesis for prenatal diagnostic testing at gestational ages between 24w0d and 36w6d. The study, spanning from 2011 to 2022, involved 9 referral centers. We included singleton or twin pregnancies with documented outcomes, excluding cases where other invasive procedures were performed during pregnancy or if amniocentesis was conducted for obstetric indications. We analyzed indications for late amniocentesis, types of genetic tests performed, their results, and the diagnostic yield, along with pregnancy outcomes and postprocedure complications. RESULTS: Of the 752 pregnant individuals included in our study, late amniocentesis was primarily performed for the prenatal diagnosis of structural anomalies (91.6%), followed by suspected fetal infection (2.3%) and high-risk findings from cell-free DNA screening (1.9%). The median gestational age at the time of the procedure was 28w5d, and 98.3% of pregnant individuals received results of genetic testing before birth or pregnancy termination. The diagnostic yield was 22.9%, and a diagnosis was made 2.4 times more often for fetuses with anomalies in multiple organ systems (36.4%) compared to those with anomalies in a single organ system (15.3%). Additionally, the diagnostic yield varied depending on the specific organ system involved, with the highest yield for musculoskeletal anomalies (36.7%) and hydrops fetalis (36.4%) when a single organ system or entity was affected. The most prevalent genetic diagnoses were aneuploidies (46.8%), followed by copy number variants (26.3%) and monogenic disorders (22.2%). The median gestational age at delivery was 38w3d, with an average of 59 days between the procedure and delivery date. The overall complication rate within 2 weeks postprocedure was 1.2%. We found no significant difference in the rate of preterm delivery between pregnant individuals undergoing amniocentesis between 24 and 28 weeks and those between 28 and 32 weeks, reinforcing the procedure's safety across these gestational periods. CONCLUSION: Late amniocentesis, at or after 24 weeks of gestation, especially for pregnancies complicated by multiple congenital anomalies, has a high diagnostic yield and a low complication rate, underscoring its clinical utility. It provides pregnant individuals and their providers with a comprehensive diagnostic evaluation and results before delivery, enabling informed counseling and optimized perinatal and neonatal care planning.

Maternal vascular indices at 36 weeks' gestation in the prediction of preeclampsia.

BACKGROUND: Epidemiological studies have shown that women with preeclampsia (PE) are at increased long term cardiovascular risk. This risk might be associated with accelerated vascular ageing process but data on vascular abnormalities in women with PE are scarce. OBJECTIVE: This study aimed to identify the most discriminatory maternal vascular index in the prediction of PE at 35 to 37 weeks' gestation and to examine the performance of screening for PE by combinations of maternal risk factors and biophysical and biochemical markers at 35 to 37 weeks' gestation. STUDY DESIGN: This was a prospective observational nonintervention study in women attending a routine hospital visit at 35 0/7 to 36 6/7 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices, and hemodynamic parameters obtained by a noninvasive operator-independent device (pulse wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressures, total peripheral resistance, and fetal heart rate), mean arterial pressure, uterine artery pulsatility index, and serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1. The performance of screening for delivery with PE at any time and at <3 weeks from assessment using a combination of maternal risk factors and various combinations of biomarkers was determined. RESULTS: The study population consisted of 6746 women with singleton pregnancies, including 176 women (2.6%) who subsequently developed PE. There were 3 main findings. First, in women who developed PE, compared with those who did not, there were higher central systolic and diastolic blood pressures, pulse wave velocity, peripheral vascular resistance, and augmentation index. Second, the most discriminatory indices were systolic and diastolic blood pressures and pulse wave velocity, with poor prediction from the other indices. However, the performance of screening by a combination of maternal risk factors plus mean arterial pressure was at least as high as that of a combination of maternal risk factors plus central systolic and diastolic blood pressures; consequently, in screening for PE, pulse wave velocity, mean arterial pressure, uterine artery pulsatility index, placental growth factor, and soluble fms-like tyrosine kinase-1 were used. Third, in screening for both PE within 3 weeks and PE at any time from assessment, the detection rate at a false-positive rate of 10% of a biophysical test consisting of maternal risk factors plus mean arterial pressure, uterine artery pulsatility index, and pulse wave velocity (PE within 3 weeks: 85.2%; 95% confidence interval, 75.6%-92.1%; PE at any time: 69.9%; 95% confidence interval, 62.5%-76.6%) was not significantly different from a biochemical test using the competing risks model to combine maternal risk factors with placental growth factor and soluble fms-like tyrosine kinase-1 (PE within 3 weeks: 80.2%; 95% confidence interval, 69.9%-88.3%; PE at any time: 64.2%; 95% confidence interval, 56.6%-71.3%), and they were both superior to screening by low placental growth factor concentration (PE within 3 weeks: 53.1%; 95% confidence interval, 41.7%-64.3%; PE at any time: 44.3; 95% confidence interval, 36.8%-52.0%) or high soluble fms-like tyrosine kinase-1-to-placental growth factor concentration ratio (PE within 3 weeks: 65.4%; 95% confidence interval, 54.0%-75.7%; PE at any time: 53.4%; 95% confidence interval, 45.8%-60.9%). CONCLUSION: First, increased maternal arterial stiffness preceded the clinical onset of PE. Second, maternal pulse wave velocity at 35 to 37 weeks' gestation in combination with mean arterial pressure and uterine artery pulsatility index provided effective prediction of subsequent development of preeclampsia.

Fasting blood glucose as a screening measure for late-onset gestational diabetes in the third trimester.

OBJECTIVE: To investigate the positive rate of late-onset gestational diabetes mellitus (GDM) by additional fasting blood glucose (FBG) screening at 32-34 gestational weeks (GW) and analyse the perinatal outcomes of late-onset GDM after standard treatment. DESIGN: An Prospective cohort study. SETTING: Single centre in China. POPULATION: 1130 singleton pregnancies with negative GDM screening in their first and second trimester. METHODS: Additional FBG testing was performed at 32-34 GW. Pregnancies with FBG ≥5.1 mmol/L were diagnosed as GDM and received standardized treatment. Perinatal outcomes were collected and compared. MAIN OUTCOME MEASURES: Diagnosis of late-onset GDM, obstetric and neonatal outcomes. RESULTS: 6.3% (71/1130) of participants had FBG values ≥5.1 mmol/L and were diagnosed with late-onset GDM. Sixty-five (91.5%) were treated by dietary therapy and 6 (8.5%) by insulin therapy. The perinatal outcomes of full-term delivery were compared. The incidence of macrosomia (22.7% vs. 5.1%, adjusted odds ratio (aOR) 5.51, 95% confidence interval (CI) 1.83-16.61, p = 0.002) and NICU transferring (18.3% vs. 10.1%, aOR 1.94, 95% CI 1.01-3.74, p = 0.046) was significantly higher in late-onset GDM group than that in FBG <5.1 mmol/L group. Elevated FBG was associated with overweight or obesity during pregnancy (54.9% vs. 34.9%, OR 2.27, 95% CI 1.40-3.68, p = 0.001). CONCLUSIONS: 6.3% of singleton pregnancies with normal GDM screening results in the first and second trimester were found to have late-onset GDM by additional FBG screening at 32-34 GW, and their risk of macrosomia during a full-term pregnancy remains significantly higher after standard treatment.

Prenatal diagnosis and postnatal outcome of Type-III vasa previa: systematic review of literature.

OBJECTIVE: Type-III vasa previa (VP) is a rare form of VP, not necessarily associated with other placental or vascular anomalies, in which aberrant vessels run from the placenta to the amniotic membranes, near the internal cervical os, before returning to the placenta. Early diagnosis of Type-III VP is important but technically challenging. The objective of this study was to gather the current available evidence on the perinatal diagnosis and outcome of Type-III VP. METHODS: A systematic review of the literature on the perinatal diagnosis of atypical Type-III VP was carried out in PubMed, MEDLINE and EMBASE accordingto PRISMA guidelines from inception to March 2023. Data extraction and tabulation were performed by two operators and checked by a third senior author. The quality of the included studies was evaluated using the National Institutes of Health tool for the quality assessment of case-series studies. Our local ultrasound database was searched for previously unreported recent cases. Characteristics of prenatally and postnatally diagnosed Type-III VP, including clinical features and perinatal outcomes, were summarized using descriptive statistics. RESULTS: Eighteen cases of Type-III VP were included, of which 16 were diagnosed prenatally (14 cases were retrieved from 10 publications and two were unpublished cases from our center) and two were diagnosed postnatally (retrieved from two publications). All prenatal cases were diagnosed on transvaginal ultrasound at a mean gestational age of 29 weeks (median, 31 weeks; range, 19-38 weeks). Conception was achieved with in-vitro fertilization in 4/16 (25.0%) cases. There were no prenatal symptoms in 15/18 (83.3%) cases, while in two (11.1%) cases there was vaginal bleeding and in one (5.6%) preterm labor occurred. In 15/18 (83.3%) cases, at least one placental abnormality was observed, including low-lying insertion (9/17), succenturiate or accessory lobe (1/17), velamentous cord insertion (3/18) and marginal insertion (9/18). All prenatally diagnosed cases were liveborn and were delivered by Cesarean section before rupture of membranes at a median gestational age of 35 weeks (range, 32-38 weeks) without neonatal complications. Emergency Cesarean section was performed in 2/16 (12.5%) cases with a prenatal diagnosis and 1/2 (50.0%) cases with a postnatal diagnosis (P = 0.179). Among those with data available, an Apgar score of ≤ 7 was observed in the prenatally vs postnatally diagnosed group in 5/13 vs 1/1 cases, respectively, at the 1-min evaluation and 3/13 vs 1/1 cases, respectively, at the 5-min evaluation. CONCLUSIONS: The prenatal diagnosis of Type-III VP is challenging, with few cases reported in the literature; however, it is crucial for minimizing the risk of adverse outcome by enabling early-term elective Cesarean delivery prior to rupture of membranes. Given that clinical manifestations and risk factors are non-specific, and that Type-III VP cannot be excluded when there is a normal cord insertion or a singular placental mass, systematic screening by transvaginal ultrasound in the general pregnant population is recommended, particularly in those with a low-lying or morphologically abnormal placenta and those who conceived using assisted reproductive technology. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Trimester-specific diagnostic accuracy of ultrasound for detection of placenta accreta spectrum: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second- and third-trimester ultrasound examination in pregnancies at risk for PAS. METHODS: PubMed, EMBASE and Web of Science databases were searched to identify relevant studies published from inception until 10 March 2023. Inclusion criteria were cohort, case-control or cross-sectional studies that evaluated the accuracy of ultrasound examination performed at < 14 weeks of gestation (first trimester) or ≥ 14 weeks of gestation (second/third trimester) for the diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was the diagnostic accuracy of sonography in detecting PAS in the first trimester, compared with the accuracy of ultrasound examination in the second and third trimesters. The secondary outcome was the diagnostic accuracy of each sonographic marker individually across the trimesters of pregnancy. The reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio and positive and negative likelihood ratios. RESULTS: A total of 37 studies, including 5764 pregnancies at risk of PAS, with 1348 cases of confirmed PAS, were included in our analysis. The meta-analysis demonstrated that ultrasound had a sensitivity of 86% (95% CI, 78-92%) and specificity of 63% (95% CI, 55-70%) during the first trimester, and a sensitivity of 88% (95% CI, 84-91%) and specificity of 92% (95% CI, 85-96%) during the second/third trimester. Regarding sonographic markers examined in the first trimester, lower uterine hypervascularity exhibited the highest sensitivity (97% (95% CI, 19-100%)), and uterovesical interface irregularity demonstrated the highest specificity (99% (95% CI, 96-100%)). In the second/third trimester, loss of clear zone had the highest sensitivity (80% (95% CI, 72-86%)), and uterovesical interface irregularity exhibited the highest specificity (99% (95% CI, 97-100%)). CONCLUSIONS: First-trimester ultrasound examination has similar accuracy to second- and third-trimester ultrasound examinations for the diagnosis of PAS. Routine first-trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal vascular indices at 36 weeks' gestation in small and growth restricted fetuses.

OBJECTIVE: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation, in pregnancies complicated by small for gestational age (SGA) fetuses and those with fetal growth restriction (FGR). METHODS: This was a prospective observational non-intervention study in women with singleton pregnancies attending for a routine hospital visit at 35+0 to 36+6 weeks' gestation. The visit included recording of maternal demographic characteristics and medical history, vascular indices and hemodynamic parameters obtained by a non-invasive operator independent device, including pulse wave velocity, augmention index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and fetal heart rate. Hypertensive disorders of pregnancy were excluded and the values in the SGA and FGR groups were compared between them and with unaffected pregnancies. Diagnosis of SGA was based on the birth of a baby with birthweight below the 10th percentile for gestational age. In FGR, in addition to a birthweight below the 10th percentile, at the 35-37 weeks scan Doppler studies had shown that the uterine artery or umbilical artery pulsatility index (PI) was above the 95th percentile for gestational age or the fetal middle cerebral artery PI was below the 5th percentile. RESULTS: In the 6,413 women included in the study there were 605 (9.4%) cases of SGA, 133 (2.1%) of FGR and 5,675 (88.5%) unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were also increased, whereas aortic stiffness assessed by pulse wave velocity and augmentation index did not differ between affected and unaffected pregnancies. In the FGR, compared to the SGA group, central systolic and diastolic blood pressure were higher, whereas, heart rate was lower. CONCLUSIONS: In SGA and FGR pregnancies there are deranged maternal hemodynamic responses when these are compared to normal pregnancies. Mothers with FGR babies have higher central blood pressure compared to SGA ones, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. This article is protected by copyright. All rights reserved.

Ophthalmic artery Doppler and biomarkers of impaired placentation at 36 weeks' gestation in pregnancies with small fetuses.

OBJECTIVES: First, to compare ophthalmic artery peak systolic velocity (PSV) ratio and biomarkers of impaired placentation at 36 weeks' gestation in women who delivered a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate, in the absence of hypertensive disorder, with those of women who developed pre-eclampsia (PE) or gestational hypertension (GH) and of women unaffected by SGA, FGR, PE or GH. Second, to examine the associations of PSV ratio, uterine artery pulsatility index (UtA-PI), placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) with birth-weight Z-score or percentile. METHODS: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, and measurement of maternal ophthalmic artery PSV ratio, UtA-PI, PlGF and sFlt-1. Values of PSV ratio, UtA-PI, PlGF and sFlt-1 were converted to multiples of the median (MoM) or delta values. Median MoM or deltas of these biomarkers in the SGA, FGR, PE and GH groups were compared with those in the unaffected group. Regression analysis was used to examine the relationship of PSV ratio delta, UtA-PI MoM, PlGF MoM and sFlt-1 MoM with birth-weight Z-score, after exclusion of PE and GH cases. RESULTS: The study population of 9033 pregnancies included 7696 (85.2%) that were not affected by FGR, SGA, PE or GH, 182 (2.0%) complicated by FGR in the absence of PE or GH, 698 (7.7%) with SGA in the absence of FGR, PE or GH, 236 (2.6%) with PE and 221 (2.4%) with GH. Compared with unaffected pregnancies, in the FGR and SGA groups, the PSV ratio delta and sFlt-1 MoM were increased and PlGF MoM was decreased; UtA-PI MoM was increased in the FGR group but not the SGA group. The magnitude of the changes in biomarker values relative to the unaffected group was smaller in the FGR and SGA groups than that in the PE and GH groups. In non-hypertensive pregnancies, there were significant inverse associations of PSV ratio delta and UtA-PI MoM with birth-weight Z-score, such that the values were increased in small babies and decreased in large babies. There was a quadratic relationship between PlGF MoM and birth-weight Z-score, with low PlGF levels in small babies and high PlGF levels in large babies. There was no significant association between sFlt-1 MoM and birth-weight Z-score. CONCLUSIONS: Ophthalmic artery PSV ratio, reflective of peripheral vascular resistance, and UtA-PI, PlGF and sFlt-1, biomarkers of impaired placentation, are altered in pregnancies complicated by hypertensive disorder and, to a lesser extent, in non-hypertensive pregnancies delivering a SGA or FGR neonate. The associations between the biomarkers and birth-weight Z-score suggest the presence of a continuous physiological relationship between fetal size and peripheral vascular resistance and placentation, rather than a dichotomous relationship of high peripheral resistance and impaired placentation in small compared to non-small fetuses. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal serum glycosylated fibronectin and angiogenic markers at 36 weeks' gestation.

OBJECTIVES: First, to examine the predictive performance of maternal serum glycosylated fibronectin (GlyFn) at 35 + 0 to 36 + 6 weeks' gestation in screening for delivery with pre-eclampsia (PE) and delivery with gestational hypertension (GH) at ≥ 37 weeks' gestation, both within 3 weeks and at any time after the examination. Second, to compare the predictive performance for delivery with PE and delivery with GH of various combinations of biomarkers, including GlyFn, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1). Third, to compare the predictive performance for delivery with PE and delivery with GH by serum PlGF concentration, sFlt-1/PlGF concentration ratio and the competing-risks model with different combinations of biomarkers as above. Fourth, to compare the predictive performance of screening at 11 + 0 to 13 + 6 weeks vs 35 + 0 to 36 + 6 weeks for delivery with PE and delivery with GH at ≥ 37 weeks' gestation. METHODS: This was a case-control study in which maternal serum GlyFn was measured in stored samples from a non-intervention screening study in singleton pregnancies at 35 + 0 to 36 + 6 weeks' gestation using a point-of-care device. We used samples from women who delivered at ≥ 37 weeks' gestation, including 100 who developed PE, 100 who developed GH and 600 controls who did not develop PE or GH. In all cases, MAP, UtA-PI, PlGF and sFlt-1 were measured during the routine visit at 35 + 0 to 36 + 6 weeks. We used samples from patients that had been examined previously at 11 + 0 to 13 + 6 weeks' gestation. Levels of GlyFn were transformed to multiples of the expected median (MoM) values after adjusting for maternal demographic characteristics and elements from the medical history. Similarly, the measured values of MAP, UtA-PI, PlGF and sFlt-1 were converted to MoM. The competing-risks model was used to combine the prior distribution of the gestational age at delivery with PE, obtained from maternal risk factors, with various combinations of biomarker MoM values to derive the patient-specific risks of delivery with PE. The performance of screening of different strategies was estimated by examining the detection rate (DR) at a 10% fixed false-positive rate (FPR) and McNemar's test was used to compare the DRs between the different methods of screening. RESULTS: The DR, at 10% FPR, of screening by the triple test (maternal risk factors plus MAP, PlGF and sFlt-1) was 83.7% (95% CI, 70.3-92.7%) for delivery with PE within 3 weeks of screening and 80.0% (95% CI, 70.8-87.3%) for delivery with PE at any time after screening, and this performance was not improved by the addition of GlyFn. The performance of screening by a combination of maternal risk factors, MAP, PlGF and GlyFn was similar to that of the triple test, both for delivery with PE within 3 weeks and at any time after screening. The performance of screening by a combination of maternal risk factors, MAP, UtA-PI and GlyFn was similar to that of the triple test, and they were both superior to screening by low PlGF concentration (PE within 3 weeks: DR, 65.3% (95% CI, 50.4-78.3%); PE at any time: DR, 56.0% (95% CI, 45.7-65.9%)) or high sFlt-1/PlGF concentration ratio (PE within 3 weeks: DR, 73.5% (95% CI, 58.9-85.1%); PE at any time: DR, 63.0% (95% CI, 52.8-72.4%)). The predictive performance of screening at 35 + 0 to 36 + 6 weeks' gestation for delivery with PE and delivery with GH at ≥ 37 weeks' gestation was by far superior to screening at 11 + 0 to 13 + 6 weeks. CONCLUSION: GlyFn is a potentially useful biomarker in third-trimester screening for term PE and term GH, but the findings of this case-control study need to be validated by prospective screening studies. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of angiogenic factors in prediction of growth-related neonatal morbidity at term and comparison with competing-risks model.

OBJECTIVES: First, to describe the distribution of biomarkers of impaired placentation in small-for-gestational-age (SGA) pregnancies with neonatal morbidity; second, to examine the predictive performance for growth-related neonatal morbidity of a high soluble fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF) ratio or low PlGF; and, third, to compare the performance of a high sFlt-1/PlGF ratio or low PlGF with that of the competing-risks model for SGA in predicting growth-related neonatal morbidity. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, an ultrasound scan and measurement of serum PlGF and sFlt-1. The primary outcome was delivery within 4 weeks after assessment and at < 42 weeks' gestation of a SGA neonate with birth weight < 10th or < 3rd percentile, combined with neonatal unit (NNU) admission for ≥ 48 h or a composite of major neonatal morbidity. The detection rates in screening by PlGF < 10th percentile, sFlt-1/PlGF ratio > 90th percentile, sFlt-1/PlGF ratio > 38 and the competing-risks model for SGA, using combinations of maternal risk factors and Z-scores of estimated fetal weight (EFW) with multiples of the median values of uterine artery pulsatility index, PlGF and sFlt-1, were estimated. The detection rates by the different methods of screening were compared using McNemar's test. RESULTS: In the study population of 29 035 women, prediction of growth-related neonatal morbidity at term provided by the competing-risks model was superior to that of screening by low PlGF concentration or a high sFlt-1/PlGF concentration ratio. For example, at a screen-positive rate (SPR) of 13.1%, as defined by the sFlt-1/PlGF ratio > 38, the competing-risks model using maternal risk factors and EFW predicted 77.5% (95% CI, 71.7-83.3%) of SGA < 10th percentile and 89.3% (95% CI, 83.7-94.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 71.4% (95% CI, 56.5-86.4%) and 90.0% (95% CI, 76.9-100%). These were significantly higher than the respective values of 41.0% (95% CI, 34.2-47.8%) (P < 0.0001), 48.8% (95% CI, 39.9-57.7%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.035) achieved by the application of the sFlt-1/PlGF ratio > 38. At a SPR of 10.0%, as defined by PlGF < 10th percentile, the competing-risks model using maternal factors and EFW predicted 71.5% (95% CI, 65.2-77.8%) of SGA < 10th percentile and 84.3% (95% CI, 77.8-90.8%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered within 4 weeks after assessment. The respective values for SGA with major neonatal morbidity were 68.6% (95% CI, 53.1-83.9%) and 85.0% (95% CI, 69.4-100%). These were significantly higher than the respective values of 36.5% (95% CI, 29.8-43.2%) (P < 0.0001), 46.3% (95% CI, 37.4-55.2%) (P < 0.0001), 37.1% (95% CI, 21.1-53.2%) (P = 0.003) and 55.0% (95% CI, 33.2-76.8%) (P = 0.021) achieved by the application of PlGF < 10th percentile. CONCLUSION: At 36 weeks' gestation, the prediction of growth-related neonatal morbidity by the competing-risks model for SGA, using maternal risk factors and EFW, is superior to that of a high sFlt-1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Ophthalmic artery Doppler at 36 weeks' gestation in prediction of pre-eclampsia: validation and update of previous model.

OBJECTIVE: To validate and extend a model incorporating maternal ophthalmic artery Doppler at 35-37 weeks' gestation in the prediction of subsequent development of pre-eclampsia (PE). METHODS: This was a prospective validation study of screening for PE (defined according to the 2019 American College of Obstetricians and Gynecologists criteria) by maternal ophthalmic artery peak systolic velocity (PSV) ratio in 6746 singleton pregnancies undergoing routine care at 35 + 0 to 36 + 6 weeks' gestation (validation dataset). Additionally, the data from the validation dataset were combined with those of 2287 pregnancies that were previously used for development of the model (training dataset), and the combined data were used to update the original model parameters. The competing-risks model was used to estimate the individual patient-specific risk of delivery with PE at any time and within 3 weeks from assessment by a combination of maternal demographic characteristics and medical history with PSV ratio alone and in combination with the established PE biomarkers of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum soluble fms-like tyrosine kinase-1 (sFlt-1). We evaluated the predictive performance of the model by examining, first, the ability to discriminate between the PE and non-PE groups using the area under the receiver-operating-characteristics curve and the detection rate (DR) at fixed screen-positive (SPR) and false-positive rates of 10% and, second, calibration by measuring the calibration slope and calibration-in-the-large. McNemar's test was used to compare the performance of screening by a biophysical test (maternal factors, MAP, UtA-PI and PSV ratio) vs a biochemical test (maternal factors, PlGF and sFlt-1), low PlGF concentration (< 10th percentile) or high sFlt-1/PlGF concentration ratio (> 90th percentile). RESULTS: In the validation dataset, the performance of screening by maternal factors and PSV ratio for delivery with PE within 3 weeks and at any time after assessment was consistent with that in the training dataset, and there was good agreement between the predicted and observed incidence of PE. In the combined data from the training and validation datasets, good prediction for PE was achieved in screening by a combination of maternal factors, MAP, UtA-PI, PlGF, sFlt-1 and PSV ratio, with a DR, at a 10% SPR, of 85.0% (95% CI, 76.5-91.4%) for delivery with PE within 3 weeks and 65.7% (95% CI, 59.2-71.7%) for delivery with PE at any time after assessment. The performance of a biophysical test was superior to that of screening by low PlGF concentration or high sFlt-1/PlGF concentration ratio but not significantly different from the performance of a biochemical test combining maternal factors with PlGF and sFlt-1 for both PE within 3 weeks and PE at any time after assessment. CONCLUSION: Maternal ophthalmic artery PSV ratio at 35-37 weeks' gestation in combination with other biomarkers provides effective prediction of subsequent development of PE. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Body image perception and social support as predictors of psychological distress among third trimester pregnant women in Nigeria.

BACKGROUND: Body image perception and social support during pregnancy can impact the psychological distress levels experienced by pregnant women. As a result, the purpose of this study was to examine the relationship between various components of social support and body image perception on psychological distress levels among pregnant women in their third trimester in Nigeria. METHOD: A cross-sectional study was conducted among 246 pregnant women who were in the third trimester and attending selected health care facilities in Ogbomoso, a semiurban city in Oyo State, Nigeria. Body image perception, social support, and psychological distress scales were used to collect the data. Data were analyzed and summarized using descriptive and inferential statistics (ANOVA and multiple regression), with significance set at p < 0.05. RESULTS: Regression analysis showed that 44% of the variation in psychological distress among pregnant women was explained by the background variables, marital status, body image perception, appraisal support, tangible support, belonging support, interaction between body image perception and appraisal support, belong support and tangible support. CONCLUSION: Intervention programs focusing on bolstering tangible support, belonging support and appraisal support are recommended at reducing the psychological distress due to body image perception among pregnant women at third trimester.

Third-Trimester Ultrasound Diagnosis of Large for Gestational Age and Risk of Cesarean Delivery.

OBJECTIVE: Determine if knowledge of a third-trimester ultrasound diagnosis of large for gestational age (LGA) independently increases the risk of cesarean delivery (CD). STUDY DESIGN: Historical cohort comparing CD rate among patients diagnosed with an LGA fetus on a clinically indicated ultrasound from January 2017 to July 2021 with those without an LGA diagnosis at 34 weeks or later. LGA was defined as an ultrasound-estimated fetal weight greater than or equal to the 90th percentile for the gestational age. Univariate analysis was performed to identify significant confounding variables and was utilized as covariates for binary regression with CD rate as the primary outcome, and adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated. Nulliparous term singleton vertex (NTSV) and multiparous CD rates were also compared. RESULTS: There were 447 patients diagnosed with an LGA fetus and 1971 patients without an LGA diagnosis on third-trimester ultrasound. The positive predictive value of LGA diagnosis was 50.1% and the false positive rate was 10.6%. Patients with a diagnosis of LGA had higher AOR of CD (OR 2.11, 95% CI 1.56-2.83), and higher AOR of NTSV CD (OR 1.88, 95% CI 1.14-3.13) compared with those without an LGA diagnosis. There was no difference in the rates of non-medically indicated CD, multiparous primary CD, and attempted and successful TOLAC. CONCLUSION: Our results suggest third-trimester ultrasound diagnosis of LGA independently increases odds of CD, specifically among nulliparous patients, and the potential bias may be one factor contributing to excessive CDs and NTSV CDs.

TU-LESS procedure for acute abdomen in late pregnancy: a retrospective study.

BACKGROUND: Acute abdominal conditions during pregnancy are significant risks to maternal and fetal health, necessitating timely diagnosis and intervention. The choice of surgical approach is a major concern for obstetricians. OBJECTIVE: To evaluate the safety and efficacy of the TU-LESS procedure for acute abdomen in late pregnancy. METHODS: We retrospectively analyzed 12 patients who underwent TU-LESS for acute abdominal conditions in the third trimester from 2020 to 2023. We reviewed medical records for clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes. RESULTS: The study included patients with a median age of 27 (range 20-35) and a BMI of 24.33 kg/m2 (range 21.34-31.96). The median gestational age at surgery was 30 weeks (range, 28 + 3-32 + 4 weeks), with surgeries lasting an average of 60 min (range, 30-163 min). Blood loss was 2-20 mL, and the median hospital stay post-surgery was 6 days (range, 2-16 days). There were no significant complications. The median time to delivery after TU-LESS was 56 days (range, 26-66 days), resulting in 8 full-term deliveries, 2 preterm cesareans, and 2 preterm vaginal deliveries. All newborns were healthy, with no fetal losses or neonatal deaths. CONCLUSION: TU-LESS, performed by experienced obstetricians and gynecologists with proper preoperative preparation, is safe and effective for managing acute abdomen in late pregnancy, without the need to delay surgery due to gestational age.

Assessing the Clinical Significance of Third-Trimester Post-Coital Bleeding.

INTRODUCTION: This study aimed to evaluate the impact of third-trimester post-coital bleeding (PCB) on pregnancy outcomes. METHODS: A retrospective cohort study was conducted at two tertiary medical centers, including all pregnant women between 24 and 34 weeks of gestation referred due to vaginal bleeding over an 11-year period. The study population includes all singleton deliveries; within this population, women were further classified into three groups: those admitted due to vaginal bleeding related to PCB, those admitted due to vaginal bleeding not related to PCB, and those who did not report vaginal bleeding. The primary outcome measure was delivery prior to 37 weeks of gestation, while secondary outcome measures included maternal and neonatal complications. Baseline characteristics of the two groups were compared. RESULTS: During the study period, there were a total of 51,698 deliveries. Among these, 230 cases involved bleeding between 24 and 34 weeks of gestation, 34 (14.8%) were identified as PCB, and 196 as bleeding unrelated to intercourse. In addition, 51,468 pregnancies without bleeding were analyzed as the general population for comparison. The incidence of preterm labor before 37 weeks of gestation was notably higher in both women with PCB (14.7%) and those with bleeding unrelated to coitus (20.9%) compared to the general population (5.6%); however, there was no statistically significant difference between the two bleeding groups (p = 0.403) while both were significantly different from the general population (p < 0.001). The odds ratio for preterm birth before 37 weeks of gestation after PCB was 3.29 (95% CI: 1.26-8.56, p = 0.0149). There were no significant differences between the PCB and bleeding unrelated to intercourse groups in terms of maternal and neonatal complications. CONCLUSION: This study found that third-trimester PCB is a risk factor for preterm delivery, with rates similar to other causes of third-trimester bleeding but significantly higher than the general population without bleeding. These findings challenge the assumption that PCB is benign.

Regulating Abortion Later in Pregnancy: Fetal-Centric Laws and the Erasure of Women's Subjectivity.

CONTEXT: In the United States, fetal development markers, including "viability" and the point when a fetus can "feel pain", have permeated the social imaginary of abortion, affecting public support and the legality and availability of care, but the extent to which they describe and orient the experience of abortion at later gestations is unclear. METHODS: Using interviews with 30 cisgender women in the U.S. who obtained an abortion after 24 weeks of pregnancy, we investigate whether and how notions of fetal viability and/or pain operated in their lived experiences of pregnancy and abortion. FINDINGS: By respondents' accounts, fetal development-based laws restricting abortion based in purported points of fetal development operated as gestational limits, privileged the viability and pain status of the fetus over that of the prospective neonate, and failed to account for the viability and pain of the pregnant person. CONCLUSIONS: The discursive practice of centering fetal development in regulating abortion access makes denial of abortion care because of the status of the fetus conceptually available-even at the point of fertilization-and naturalizes the erasure of the subjectivity of women and others who can become pregnant.

Correlation of amniotic fluid inflammatory markers with preterm birth: a meta-analysis.

BACKGROUND: The relationship between amniotic fluid inflammatory biomarkers and preterm birth in second- or third-trimester pregnancy has been a focus, and understanding the correlation between these markers and preterm birth is important for early identification and intervention in preterm birth. The aim of this study was to explore potential inflammatory biomarkers in second- or third-trimester pregnancy amniotic fluid associated with preterm birth. METHODS: On November 30, 2023, we searched literature involved the influence of second- or third-trimester pregnancy amniotic fluid inflammatory biomarkers on preterm birth through PubMed, Web of Science, Embase, Scope, CNKI, WanFang, VIP and China Biomedical Databases. The search languages were Chinese and English. Included outcomes indexes were combined utility analysis via R software. RESULTS: A total of 11 articles were included in the combined utility analysis. This combined analysis revealed significant differences in several inflammatory biomarkers in amniotic fluid between the two groups (MD = 6.87, 95%CI: 0.26 - 13.47, P < 0.01); the difference in amniotic fluid IL-6 between the two groups (MD = 5.73, 95%CI: 3.13-8.32, P < 0.01); the difference in amniotic fluid IL-10 between the two groups (MD = 0.11, 95%CI: -3.26-3.48, P < 0.01); the difference in amniotic fluid CRP between the two groups (MD = 21.34, 95%CI: 11.69-30.89, P < 0.01); the difference in amniotic fluid MCP-1 between the two groups (MD = 312.14, 95%CI: 211.34-412.97, P < 0.01); the difference in the amniotic fluid MMP-9 between the two groups (MD = 0.86, 95%CI: -0.10-1.82, P < 0.01); and the difference in TNF-α in amniotic fluid between the two groups (MD = 22.78, 95%CI: -5.05-50.61, P < 0.01). CONCLUSIONS: The inflammatory biomarkers IL-1ß, IL-6, IL-10, CRP, TNFα, MCP-1 and MMP-9 in the amniotic fluid of patients in the second- or third-trimester pregnancy were all correlated with preterm birth.

The premature foetus has many serious complications in the near and long term because of the immature organs, which is related to the long-term incidence of cerebral palsy, developmental delay and retinopathy of prematurity, which is the main cause of perinatal foetal death. Preterm birth cases are accompanied by infection of pathogenic microorganisms in amniotic cavity, which then leads to inflammatory reaction in amniotic cavity. However, research on the correlation between inflammatory markers and preterm birth has shown certain complexity and differences. The results of this meta-analysis show that the inflammatory biomarkers interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and interleukin-10 (IL-10), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in amniotic fluid of patients in the second- or third-trimester pregnancy are significant between the preterm birth group and the control group, and the expression level of inflammatory factors in amniotic fluid of patients in the preterm birth group is elevated, thus suggesting that these inflammatory factors may be able to predict preterm birth.

Vascular phenotype at 35-37 weeks' gestation in women with gestational diabetes mellitus.

OBJECTIVES: To examine the vascular phenotype at 35-37 weeks' gestation of women with gestational diabetes mellitus (GDM) and compare it to that in women without GDM, using ophthalmic artery Doppler and carotid-femoral pulse-wave velocity. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 37 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ophthalmic artery Doppler for calculation of the peak systolic velocity (PSV) ratio and assessment of cardiac output, stroke volume, total peripheral resistance, central systolic and diastolic blood pressure, carotid-femoral pulse-wave velocity and augmentation index. All measurements were standardized to remove the effects of maternal characteristics and elements from the medical history, and the adjusted values in the GDM group were compared with those in the non-GDM group. RESULTS: The study population of 2018 pregnancies contained 218 (10.8%) that developed GDM, including 78 (35.8%) that were treated with diet alone, 81 (37.2%) treated with metformin and 59 (27.1%) treated with insulin with or without metformin. In the GDM group, compared with the non-GDM group, there were significantly higher ophthalmic artery PSV ratio, carotid-femoral pulse-wave velocity and central systolic blood pressure, but there was no significant difference in cardiac output, stroke volume, total peripheral resistance, central diastolic blood pressure or augmentation index. In the GDM group, women treated with metformin or insulin had a higher ophthalmic artery PSV ratio compared with those treated with diet alone. Additionally, compared with the diet group, the metformin group had higher central systolic blood pressure and the insulin group had a higher carotid-femoral pulse-wave velocity. CONCLUSION: Women with GDM have evidence of early vascular disease, and this may contribute to their long-term cardiovascular risk. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Implication of third-trimester screening accuracy for small-for-gestational age and additive value of third-trimester growth-trajectory indicators in predicting severe adverse perinatal outcome in low-risk population: pragmatic secondary analysis of IRIS study.

OBJECTIVES: To examine the implications of third-trimester small-for-gestational-age (SGA) screening accuracy on severe adverse perinatal outcome (SAPO) and obstetric intervention in a low-risk population. Furthermore, we aimed to explore the additive value of third-trimester sonographic growth-trajectory measurements in predicting SAPO and obstetric intervention. METHODS: This was a secondary analysis of a Dutch national multicenter stepped-wedge-cluster randomized trial among 11 820 low-risk pregnant women. Using multilevel multivariable logistic regression analysis, we compared SAPO and obstetric interventions in SGA neonates with and without SGA suspected prenatally (true positives and false negatives) and non-SGA neonates with and without SGA suspected prenatally (false positives and true negatives). In a subsample (n = 7989), we analyzed the associations of abdominal circumference (AC) and estimated fetal weight (EFW) < 10th centile (p10) and third-trimester growth-trajectory indicators AC and EFW crossing > 20 and AC crossing > 50 centiles and the lowest decile of AC growth-velocity Z-scores (ACGV < 10%) with SAPO and obstetric interventions. RESULTS: SGA infants, i.e. the true-positive and false-negative cases, had an increased risk of SAPO (adjusted odds ratio (aOR), 4.46 (95% CI, 2.28-8.75) and aOR 2.61 (95% CI, 1.74-3.89), respectively), and obstetric intervention (aOR for: induction of labor, 2.99 (95% CI, 2.15-4.17) and 1.38 (95% CI, 1.14-1.66); Cesarean section, 1.82 (95% CI, 1.25-2.66) and 1.27 (95% CI, 1.05-1.54); medically indicated preterm delivery, 2.67 (95% CI, 1.97-3.62) and 1.20 (95% CI, 1.03-1.40)). The false-positive cases did not differ from the true negatives for all outcomes, including obstetric intervention. Of the third-trimester growth-trajectory indicators, only ACGV < 10% was associated moderately with SAPO (aOR, 2.15 (95% CI, 1.17-3.97)), while AC and EFW crossing > 20 and AC crossing > 50 centiles were not. Both EFW < p10 alone (aOR, 1.95 (95% CI, 1.13-3.38)) and EFW < p10 combined with ACGV < 10% (aOR, 4.69 (95% CI, 1.99-11.07)) were associated with SAPO, and they performed equally well in predicting SAPO (area under the receiver-operating-characteristics curve, 0.71 (95% CI, 0.65-0.76) vs 0.72 (95% CI, 0.67-0.77), P = 0.51). CONCLUSION: Neonates who had been suspected falsely of being SGA during pregnancy had no higher rates of obstetric intervention than did those without suspicion of SGA prenatally. Our results do not support that third-trimester low fetal growth velocity (ACGV < 10%) may be of additive value for the identification of fetuses at risk of SAPO in populations remaining at low risk throughout pregnancy. AC and EFW crossing > 20 and AC crossing > 50 centiles performed poorly in identifying abnormal fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of hypertensive disorders after screening at 36 weeks' gestation: comparison of angiogenic markers with competing-risks model.

OBJECTIVE: To compare the performance at 35 + 0 to 36 + 6 weeks' gestation of screening for delivery with pre-eclampsia (PE) at various timepoints, using one of three approaches: placental growth factor (PlGF) concentration, soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio, or the competing-risks model, which combines maternal risk factors with biomarkers to estimate patient-specific risk. METHODS: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation at one of two maternity hospitals in England between 2016 and 2022. During the visit, maternal demographic characteristics and medical history were recorded and serum PlGF, serum sFlt-1 and mean arterial pressure (MAP) were measured. Detection rates (DRs) were evaluated for delivery with PE (defined as per American College of Obstetricians and Gynecologists 2019 criteria) within 1 week, within 2 weeks or at any time after screening, using the following strategies: (i) low PlGF (< 10th percentile); (ii) high sFlt-1/PlGF ratio (> 90th percentile); or (iii) the competing-risks model, in which maternal factors were combined with multiples of the median values of PlGF ('single test'), PlGF and sFlt-1 ('double test') or PlGF, sFlt-1 and MAP ('triple test'). Risk cut-offs corresponded to a screen-positive rate of 10%. DRs were compared between tests. RESULTS: Of 34 782 pregnancies, 831 (2.4%) developed PE. In screening for delivery with PE at any time from assessment, the DR at 10% screen-positive rate was 47% by low PlGF alone, 54% by the single test, 55% by high sFlt-1/PlGF ratio, 61% by the double test and 68% by the triple test. In screening for delivery with PE within 2 weeks from assessment, the respective values were 67%, 74%, 74%, 80% and 87%. In screening for delivery with PE within 1 week from assessment, the respective values were 77%, 81%, 85%, 88% and 91%. For prediction of PE at any time, the DR was significantly higher with the triple test compared to PlGF alone or the sFlt-1/PlGF ratio, with a DR difference (95% CI) of 20.1% (16.7-23.0%) and 12.4% (9.7-15.3%), respectively. Similar results were seen for prediction of PE within 2 weeks (20.6% (14.9-26.8%) and 12.9% (7.7-17.5%), respectively) and prediction of PE within 1 week (13.5% (5.4-21.6%) and 5.4% (0.0-10.8%), respectively). The double test was superior to the sFlt-1/PlGF ratio and the single test was superior to PlGF alone in the prediction of PE within 2 weeks and at any time from assessment, but not within 1 week of assessment. CONCLUSION: At 35 + 0 to 36 + 6 weeks' gestation, the performance of screening for PE by the competing-risks model triple test is superior to that of PlGF alone or the sFlt-1/PlGF ratio for the development of disease within 1 week, within 2 weeks and at any time from screening. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.