STATIN trial: predictive performance of competing-risks model in screening for pre-eclampsia at 35-37 weeks' gestation.

OBJECTIVE: To examine the predictive performance of a previously reported competing-risks model of screening for pre-eclampsia (PE) at 35-37 weeks' gestation by combinations of maternal risk factors, 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) in a validation dataset derived from the screened population of the STATIN study. METHODS: This was a prospective third-trimester multicenter study of screening for PE in singleton pregnancies by means of a previously reported algorithm that combines maternal risk factors and biomarkers. Women in the high-risk group were invited to participate in a trial of pravastatin vs placebo, but the trial showed no evidence of an effect of pravastatin in the prevention of PE. Patient-specific risks of delivery with PE were calculated using the competing-risks model, and the performance of screening for PE by maternal risk factors alone and by various combinations of risk factors with MAP, UtA-PI, PlGF and sFlt-1 was assessed. The predictive performance of the model was examined by, first, the ability of the model to discriminate between the PE and no-PE groups using the area under the receiver-operating-characteristics curve (AUC) and the detection rate at a fixed false-positive rate of 10%, and, second, calibration by measurements of calibration slope and calibration-in-the-large. RESULTS: The study population of 29 677 pregnancies contained 653 that developed PE. In screening for PE by a combination of maternal risk factors, MAP, PlGF and sFlt-1 (triple test), the detection rate at a 10% false-positive rate was 79% (95% CI, 76-82%) and the results were consistent with the data used for developing the algorithm. Addition of UtA-PI did not improve the prediction provided by the triple test. The AUC for the triple test was 0.923 (95% CI, 0.913-0.932), demonstrating very high discrimination between affected and unaffected pregnancies. Similarly, the calibration slope was 0.875 (95% CI, 0.831-0.919), demonstrating good agreement between the predicted risk and observed incidence of PE. CONCLUSION: The competing-risks model provides an effective and reproducible method for third-trimester prediction of term PE. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Retrospective observational RT-PCR analyses on 688 babies born to 843 SARS-CoV-2 positive mothers, placental analyses and diagnostic analyses limitations suggest vertical transmission is possible.

RESEARCH QUESTION: Is there vertical transmission (from mother to baby antenatally or intrapartum) after SARS-CoV-2 (COVID-19) infected pregnancy? STUDY DESIGN: A systematic search related to SARS-CoV-2 (COVID-19), pregnancy, neonatal complications, viral and vertical transmission. The duration was from December 2019 to May 2020. RESULTS: A total of 84 studies with 862 COVID positive women were included. Two studies had ongoing pregnancies while 82 studies included 705 babies, 1 miscarriage and 1 medical termination of pregnancy (MTOP). Most publications (50/84, 59.5%), reported small numbers (<5) of positive babies. From 75 studies, 18 babies were COVID-19 positive. The first reverse transcription polymerase chain reaction (RT-PCR) diagnostic test was done in 449 babies and 2 losses, 2nd RT-PCR was done in 82 babies, IgM tests were done in 28 babies, and IgG tests were done in 28 babies. On the first RT-PCR, 47 studies reported time of testing while 28 studies did not. Positive results in the first RT-PCR were seen in 14 babies. Earliest tested at birth and the average time of the result was 22 hours. Three babies with negative first RT-PCR became positive on the second RT-PCR at day 6, day 7 and at 24 hours which continued to be positive at 1 week.Four studies with a total of 4 placental swabs were positive demonstrating SARS-CoV-2 localised in the placenta. In 2 studies, 10 tests for amniotic fluid were positive for SARS-CoV-2. These 2 babies were found to be positive on RT-PCR on serial testing. CONCLUSION: Diagnostic testing combined with incubation period and placental pathology indicate a strong likelihood that intrapartum vertical transmission of SARS-CoV-2 (COVID-19) from mother to baby is possible.

Prediction and prevention of small-for-gestational-age neonates: evidence from SPREE and ASPRE.

OBJECTIVES: To examine the effect of first-trimester screening for pre-eclampsia (PE) on the prediction of delivering a small-for-gestational-age (SGA) neonate and the effect of prophylactic use of aspirin on the prevention of SGA. METHODS: The data for this study were derived from two multicenter studies. In SPREE, we investigated the performance of screening for PE by a combination of maternal characteristics and biomarkers at 11-13 weeks' gestation. In ASPRE, women with a singleton pregnancy identified by combined screening as being at high risk for preterm PE (> 1 in 100) participated in a trial of aspirin (150 mg/day from 11-14 until 36 weeks' gestation) compared to placebo. In this study, we used the data from the ASPRE trial to estimate the effect of aspirin on the incidence of SGA with birth weight < 10th , < 5th and < 3rd percentile for gestational age. We also used the data from SPREE to estimate the proportion of SGA in the pregnancies with a risk for preterm PE of > 1 in 100. RESULTS: In SPREE, screening for preterm PE by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor identified a high-risk group that contained about 46% of SGA neonates < 10th percentile born at < 37 weeks' gestation (preterm) and 56% of those born at < 32 weeks (early); the overall screen-positive rate was 12.2% (2014 of 16 451 pregnancies). In the ASPRE trial, use of aspirin reduced the overall incidence of SGA < 10th percentile by about 40% in babies born at < 37 weeks' gestation and by about 70% in babies born at < 32 weeks; in babies born at ≥ 37 weeks, aspirin did not have a significant effect on incidence of SGA. The aspirin-related decrease in incidence of SGA was mainly due to its incidence decreasing in pregnancies with PE, for which the decrease was about 70% in babies born at < 37 weeks' gestation and about 90% in babies born at < 32 weeks. On the basis of these results, it was estimated that first-trimester screening for preterm PE and use of aspirin in the high-risk group would potentially reduce the incidence of preterm and early SGA by about 20% and 40%, respectively. CONCLUSION: First-trimester screening for PE by the combined test identifies a high proportion of cases of preterm SGA that can be prevented by the prophylactic use of aspirin. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Comparison of diagnostic accuracy of early screening for pre-eclampsia by NICE guidelines and a method combining maternal factors and biomarkers: results of SPREE.

OBJECTIVE: To test the hypothesis that the performance of first-trimester screening for pre-eclampsia (PE) by a method that uses Bayes' theorem to combine maternal factors with biomarkers is superior to that defined by current National Institute for Health and Care Excellence (NICE) guidelines. METHODS: This was a prospective multicenter study (screening program for pre-eclampsia (SPREE)) in seven National Health Service maternity hospitals in England, of women recruited between April and December 2016. Singleton pregnancies at 11-13 weeks' gestation had recording of maternal characteristics and medical history and measurements of mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). The performance of screening for PE by the Bayes' theorem-based method was compared with that of the NICE method. Primary comparison was detection rate (DR) using NICE method vs mini-combined test (maternal factors, MAP and PAPP-A) in the prediction of PE at any gestational age (all-PE) for the same screen-positive rate determined by the NICE method. Key secondary comparisons were DR of screening recommended by the NICE guidelines vs three Bayes' theorem-based methods (maternal factors, MAP and PAPP-A; maternal factors, MAP and PlGF; and maternal factors, MAP, UtA-PI and PlGF) in the prediction of preterm PE, defined as that requiring delivery < 37 weeks. RESULTS: All-PE developed in 473 (2.8%) of the 16 747 pregnancies and preterm PE developed in 142 (0.8%). The screen-positive rate by the NICE method was 10.3% and the DR for all-PE was 30.4% and for preterm PE it was 40.8%. Compliance with the NICE recommendation that women at high risk for PE should be treated with aspirin from the first trimester to the end of pregnancy was only 23%. The DR of the mini-combined test for all-PE was 42.5%, which was superior to that of the NICE method by 12.1% (95% CI, 7.9-16.2%). In screening for preterm PE by a combination of maternal factors, MAP and PlGF, the DR was 69.0%, which was superior to that of the NICE method by 28.2% (95% CI, 19.4-37.0%) and with the addition of UtA-PI the DR was 82.4%, which was higher than that of the NICE method by 41.6% (95% CI, 33.2-49.9%). CONCLUSIONS: The performance of screening for PE as currently recommended by NICE guidelines is poor and compliance with these guidelines is low. The performance of screening is substantially improved by a method combining maternal factors with biomarkers. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

ASPRE trial: performance of screening for preterm pre-eclampsia.

OBJECTIVE: To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. METHODS: This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11-13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11-14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). RESULTS: The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). CONCLUSION: The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11-13 weeks' gestation. METHODS: This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm. RESULTS: In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80-100%) for PE < 32 weeks, 75% (95% CI, 62-85%) for PE < 37 weeks and 43% (95% CI, 35-50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79-96%) for PE < 32 weeks, 75% (95% CI, 70-80%) for PE < 37 weeks and 47% (95% CI, 44-51%) for PE ≥ 37 weeks. CONCLUSION: Assessment of a combination of maternal factors and biomarkers at 11-13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Work-related repetitive strain injuries amongst practitioners of obstetric and gynaecological ultrasound worldwide.

OBJECTIVES: The aims of this study were to determine the prevalence of work-related musculoskeletal disorders amongst practitioners of obstetric and gynaecology ultrasound worldwide, and to establish relevant aetiological factors. METHODS: A questionnaire survey was conducted amongst the participants at the 2010 ISUOG world congress held in Prague, Czech Republic. All pain complaints were evaluated in relation to the gender, operator experience, average workload and the background prevalence of obesity in the patient population scanned. Joint (neck, shoulder, elbow, wrist) or back pain was considered as repetitive strain injury (RSI). RESULTS: The response rate obtained was 49 %, with 407 questionnaires returned out of a total of 830. Female operators reported more RSI than their male counterparts (70.1 vs. 59.6 %, p = 0.03). We found no significant relationship between the grade of the operator, the number of years of scanning experience, orientation in ergonomics and the occurrence of symptoms. Rest breaks in between cases revealed positive benefit (61.4 % RSI with rest vs. 71 % without rest, p = 0.041). The incidence of the reported RSI in the practitioners who had less than 30 % of their population classified as obese (body mass index of 30 or more) when compared with those who had more than 30 % of their case load classified as obese, was similar (65.3 vs. 64 %, p = 0.83). CONCLUSIONS: Operator-dependant factors except gender, had little correlation with symptoms suffered, whilst the number of days worked per week, not taking regular breaks each day, revealed positive correlation. The results suggest that symptoms are both operator and workplace dependent. Though 65.6 % respondents suffered from RSI, less than half (30.5 %) resorted to supportive measures like physiotherapy.