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Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

Objective: We have previously established that a logistic regression model, based on maternal demographic characteristics and blood pressure measured at 11–13 weeks' gestation, can identify about 70% of women who develop future chronic hypertension (CH) in the 3 years following pregnancy, at a screen‐positive rate of 10%. Furthermore, in midgestation, women who subsequently develop hypertensive disorders of pregnancy (HDP) have increased peripheral vascular resistance and mild cardiac functional and morphological alterations and these cardiovascular abnormalities persist for at least 2 years after delivery. In this study, we set out to examine whether use of the first‐trimester risk model for subsequent development of CH can help to identify women at high risk for cardiovascular maladaptation in midgestation. Methods: This was a prospective observational study of 3812 women with singleton pregnancy attending for a routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation and again at 19 + 1 to 23 + 3 weeks at King's College Hospital, London, UK, between December 2019 and August 2020. The first‐trimester visit included recording of maternal demographic characteristics and medical history and measurement of systolic and diastolic blood pressure. In midgestation, detailed maternal cardiovascular assessment was carried out. The association between risk for development of CH, determined from first‐trimester assessment, and cardiovascular indices in midgestation was examined. Results: Women who were at high risk for development of future CH, compared to those at low risk, had a higher incidence of HDP. In addition, high‐risk women had reduced systolic and diastolic function in midgestation. Among women with HDP, those who were at high risk for future CH, compared to those at low risk, had worse cardiac function in midgestation. Conclusions: Use of a model for first‐trimester prediction of subsequent development of CH can identify women who show evidence of cardiac maladaptation in midgestation. Further studies are needed to clarify whether women who screen as high risk for future CH, compared to those at low risk, have reduced cardiac function beyond pregnancy. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

The first-trimester prediction of spontaneous preterm birth (sPTB) has been elusive, and current screening is heavily dependent on obstetric history. However, nullipara lack a relevant history and are at higher risk for spontaneous (s)PTB ≤ 32 weeks compared to multipara. No available objective first-trimester screening test has proven a fair predictor of sPTB ≤ 32 weeks. We questioned whether a panel of maternal plasma cell-free (PCF) RNAs (PSME2, NAMPT, APOA1, APOA4, and Hsa-Let-7g) previously validated at 16–20 weeks for the prediction of sPTB ≤ 32 weeks might be useful in first-trimester nullipara. Sixty (60) nulliparous women (40 with sPTB ≤ 32 weeks) who were free of comorbidities were randomly selected from the King’s College Fetal Medicine Research Institute biobank. Total PCF RNA was extracted and the expression of panel RNAs was quantitated by qRT-PCR. The analysis employed, primarily, multiple regression with the main outcome being the prediction of subsequent sPTB ≤ 32 weeks. The test performance was judged by the area under the curve (AUC) using a single threshold cut point with observed detection rates (DRs) at three fixed false positive rates (FPR). The mean gestation was 12.9 ± 0.5 weeks (range 12.0–14.1 weeks). Two RNAs were differentially expressed in women destined for sPTB ≤ 32 weeks: APOA1 (p < 0.001) and PSME2 (p = 0.05). APOA1 testing at 11–14 weeks predicted sPTB ≤ 32 weeks with fair to good accuracy. The best predictive model generated an AUC of 0.79 (95% CI 0.66–0.91) with observed DRs of 41%, 61%, and 79% for FPRs of 10%, 20%, and 30%, including crown–rump length, maternal weight, race, tobacco use, and age.

Skills training for teachers is of major importance in order to improve the relationship between teachers and students and at the same time has the potential to improve and develop all other educational processes. A psychoeducational training program for primary and secondary school teachers was implemented in schools in Greece with the main goal to improve teachers' self-reported characteristics relating to self-efficacy and work involvement, and teacher-student relationships. Self-report measures were completed by two groups of teachers (intervention and control groups) before and immediately after the implementation of the training program to assess work engagement, core self-evaluations, and relationships with students. ANCOVA analyses showed significant improvement between the two groups in terms of core-self evaluations and student-teacher relationships after the training program. The implications of these findings as potentially protective factors for teachers' performance and prevention of other school-related distressing phenomena, and the limitations of the study are discussed.

Objective: To determine whether serum placental growth factor (PlGF) at 19–23 weeks of gestation can improve the identification of risk for adverse outcomes. Design: Prospective observational cohort study. Setting: Two English maternity units. Population: Unselected singleton pregnancies attending routine ultrasound at 19–23 weeks of gestation. Methods: Outcomes ascertained by health record review. Diagnostic test properties evaluated clinical risk factors for pre‐eclampsia (according to National Institute of Care Excellence) or fetal growth restriction (according to Royal College of Obstetricians and Gynaecologists), low PlGF at 19–23 weeks of gestation (<5th percentile) or both. Main outcome measures: Pre‐eclampsia, gestational hypertension, stillbirth, birthweight below third percentile or neonatal intensive care unit (NICU) admission for ≥48 h. Results: In 30 013 pregnancies, risk factors were present in 9941 (33.1%), low PlGF was present in 1501 (5.0%) and both ('two‐stage' screening) were present in 547 (1.8%) pregnancies. Risk factors detected 41.7%–54.7% of adverse outcomes, and could not meaningfully revise the risk (all positive likelihood ratios, +LR, <5.0; all negative likelihood ratios, −LR, ≥0.2). Low PlGF detected 8.5%–17.4% of adverse outcomes, but meaningfully increased risks (other than NICU admission) associated with delivery <37 weeks of gestation (+LR = 5.03–15.55); all −LRs were ≥0.2. 'Two‐stage' screening detected 4.2%–8.9% of adverse outcomes, with meaningful +LRs (6.28–18.61) at <37 weeks of gestation, except for NICU admission of ≥48 h, which had an +LR of 7.56 at <34 weeks of gestation; all −LRs were ≥0.2. No screening strategy meaningfully increased or decreased the detection of adverse outcome risk at term. Conclusions: Clinical risk factor screening has a high screen‐positive rate and a poor detection of adverse outcomes. False positives cannot be reduced by PlGF testing at 19–23 weeks of gestation; therefore, this cannot be recommended as a useful strategy on its own. [ABSTRACT FROM AUTHOR]

Objectives: First, to evaluate the predictive performance for preterm growth‐related neonatal morbidity of a high soluble fms‐like tyrosine kinase‐1 (sFlt‐1)/placental growth factor (PlGF) ratio or low PlGF at midgestation and, second, to compare the performance of a high sFlt‐1/PlGF ratio or low PlGF with that of the competing‐risks model for small‐for‐gestational age (SGA), utilizing a combination of maternal risk factors, sonographic estimated fetal weight and uterine artery pulsatility index. Methods: This was a prospective observational study in women attending for a routine hospital visit at 19–24 weeks' gestation in two maternity hospitals in England. The visit included recording of maternal demographic characteristics and medical history, carrying out an ultrasound scan and measuring serum PlGF and sFlt‐1. The primary outcome was delivery < 32 and < 37 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 and the competing‐risks model for SGA were estimated and then compared using McNemar's test. Results: In the study population of 40 241 women, prediction of preterm growth‐related neonatal morbidity provided by the competing‐risks model for SGA was superior to that of screening by low PlGF concentration or high sFlt‐1/PlGF ratio. For example, at a screen‐positive rate of 10.0%, as defined by the sFlt‐1/PlGF ratio > 90th percentile, the competing‐risks model predicted 70.1% (95% CI, 61.0–79.2%) of SGA < 10th percentile and 76.9% (95% CI, 67.6–86.3%) of SGA < 3rd percentile with NNU admission for ≥ 48 h delivered < 32 weeks' gestation. The respective values for SGA with major neonatal morbidity were 73.8% (95% CI, 64.4–83.2%) and 77.9% (95% CI, 68.0–87.8%). These were significantly higher than the respective values of 35.1% (95% CI, 25.6–44.6%), 35.9% (95% CI, 25.3–46.5%), 38.1% (95% CI, 27.7–48.5%) and 39.7% (95% CI, 28.1–51.3%) achieved by the application of the sFlt‐1/PlGF ratio > 90th percentile (all P < 0.0001). Conclusion: At midgestation, the prediction of growth‐related neonatal morbidity by the competing‐risks model for SGA is superior to that of a high sFlt‐1/PlGF ratio or low PlGF. © 2023 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To report the predictive performance for preterm birth (PTB) of the Fetal Medicine Foundation (FMF) triple test and National Institute for health and Care Excellence (NICE) guidelines used to screen for pre‐eclampsia and examine the impact of aspirin in the prevention of PTB. Design: Secondary analysis of data from the SPREE study and the ASPRE trial. Setting: Multicentre studies. Population: In SPREE, women with singleton pregnancies had screening for preterm pre‐eclampsia at 11–13 weeks of gestation by the FMF method and NICE guidelines. There were 16 451 pregnancies that resulted in delivery at ≥24 weeks of gestation and these data were used to derive the predictive performance for PTB of the two methods of screening. The results from the ASPRE trial were used to examine the effect of aspirin in the prevention of PTB in the population from SPREE. Methods: Comparison of performance of FMF method and NICE guidelines for pre‐eclampsia in the prediction of PTB and use of aspirin in prevention of PTB. Main outcome measure: Spontaneous PTB (sPTB), iatrogenic PTB for pre‐eclampsia (iPTB‐PE) and iatrogenic PTB for reasons other than pre‐eclampsia (iPTB‐noPE). Results: Estimated incidence rates of sPTB, iPTB‐PE and iPTB‐noPE were 3.4%, 0.8% and 1.6%, respectively. The corresponding detection rates were 17%, 82% and 25% for the triple test and 12%, 39% and 19% for NICE guidelines, using the same overall screen positive rate of 10.2%. The estimated proportions prevented by aspirin were 14%, 65% and 0%, respectively. Conclusion: Prediction of sPTB and iPTB‐noPE by the triple test was poor and poorer by the NICE guidelines. Neither sPTB nor iPTB‐noPE was reduced substantially by aspirin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cardiovascular disease is the leading cause of mortality in women. Pregnancy is an ideal period to implement cardiovascular prevention strategies as women seek medical help. We aimed to develop a predictive model to identify women at increased risk for chronic hypertension (CH) based on information collected in the index pregnancy. METHODS: Cohort of 26 511 women seen in 2 consecutive pregnancies. Included were women without CH, with information on maternal characteristics and blood pressure at 11 to 13 weeks' gestation, and the development of preeclampsia or gestational hypertension (GH) in the index pregnancy. Logistic regression models were fitted for the prediction of the development of future CH by the 20th week of the subsequent pregnancy. The performance of screening and risk calibration of the model were assessed. RESULTS: In this study 1560 (5.9%) women developed preeclampsia or GH (index pregnancy), and 215 (0.8%) developed future CH, with a median of 3.0 years later. Predictors of development of future CH were maternal age, weight, and blood pressure; Black and South Asian ethnicity; family history of preeclampsia; parity; and development of preeclampsia or GH. Preeclampsia or GH detected 52.1% (45.2%-58.9%) of future CH. At a screen-positive rate of 10%, a model including maternal characteristics, early pregnancy blood pressure, and development of preeclampsia or GH detected 73.5% (67.1-79.3) of future CH. CONCLUSIONS: Early pregnancy maternal characteristics, blood pressure, and development of preeclampsia or GH identify three-fourths of women at risk for future CH. Our results offer an important preventative strategy for identifying women at increased risk of future CH, which is applicable worldwide. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the incidence of antepartum stillbirth in relation to the distribution of neonatal/fetal weight for different gestational ages. Design: Prospective observational cohort study. Setting: Obstetric ultrasound departments in two UK maternity hospitals. Population: 168 966 women with singleton pregnancies attending for routine antenatal care. Methods: We examined the incidence of antepartum stillbirths, within different birthweight and fetal weight percentile subgroups, conditioning for gestational age. Main outcome measures: Incidence of antepartum stillbirth. Results: The risk of stillbirth progressively increased for lower birthweight. Considering the 25–75th percentile as the reference category, the relative risks for stillbirth at <37 weeks' gestation were 7.6 (95% confidence interval [CI] 5.7–10.2) <1st percentile, 2.6 (95% CI 1.8–3.7) 1 to 10th percentile, 1.4 (95% CI 0.9–2.1) 10 to 25th percentile, 0.8 (95% CI 0.4–1.5) 75 to 90th percentile, 0.8 (95% CI 0.4–1.7) 90 to 99th percentile, 0.9 (95% CI 0.3–2.5) >99th percentile. The respective values for births at ≥37 weeks' gestation were 5.0 (95% CI 2.9–8.9), 2.1 (95% CI 1.4–3.3), 1.4 (95% CI 0.9–2.1), 1.2 (95% CI 0.7–1.8), 1.0 (95% CI 0.6–1.8) and 4.0 (95% CI 1.8–9.3). The incidence of stillbirth in ongoing low‐risk singleton pregnancies gradually increases for smaller fetuses at any gestational point. The higher incidence (5.56%) was evident for fetal weight <1st percentile between 24 and 28 weeks' gestation. Conclusion: Fetal weight and the weight of the stillborn have a continuous association with the incidence of antepartum stillbirth which is affected by gestational age. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]