Effect of routine first-trimester combined screening for pre-eclampsia on small-for-gestational-age birth: secondary interrupted time series analysis.

OBJECTIVE: To evaluate the impact of a first-trimester combined screening program for pre-eclampsia, based on the Fetal Medicine Foundation (FMF) algorithm, on the rate of small-for-gestational age (SGA) at birth and adverse pregnancy outcome. METHODS: This was a retrospective cohort study of data obtained from a London tertiary hospital between January 2017 and March 2019. The data were derived from a secondary analysis of the cohort evaluated in a clinical-effectiveness study on the implementation of a first-trimester screening program for pre-eclampsia. The cohort included 7720 women screened according to the UK National Institute for Health and Care Excellence (NICE) risk-based approach and 4841 women screened by the FMF multimodal approach, which combines maternal risk factors, blood pressure, pregnancy-associated plasma protein-A and uterine artery Doppler indices. The care package for the FMF-screened group included 150-mg aspirin prophylaxis, ultrasound scans at 28 and 36 weeks' gestation and scheduled delivery at 40 weeks. Outcome measures included the rates of SGA neonates at birth, admission to the neonatal unit, intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy assessed by interrupted time series analysis (ITSA). RESULTS: There was no significant difference in the rates of intrauterine demise, neonatal death and hypoxic-ischemic encephalopathy between the FMF-screened and NICE-screened cohorts. ITSA showed a significant reduction in the rate of term SGA birth < 10th percentile at 21 months following implementation of the FMF screening program, with a relative effect reduction of 45.1% (P = 0.004). However, there was no significant relative effect reduction in term SGA birth < 5th or < 3rd percentile. CONCLUSIONS: First-trimester combined screening for pre-eclampsia based on the FMF algorithm accompanied by a care package including serial ultrasound scans for growth evaluation and elective birth from 40 weeks' gestation resulted in a significant 45% relative effect reduction in term SGA birth < 10th percentile but did not affect term SGA birth < 5th or < 3rd percentile. Further screening strategies to detect and improve the outcome of cases with SGA birth < 5th percentile need to be considered. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Implementation of routine first trimester combined screening for pre-eclampsia: a clinical effectiveness study.

OBJECTIVE: Evaluate clinical effectiveness of the first trimester combined (FMF) pre-eclampsia screening programme when implemented in a public healthcare setting. DESIGN: Retrospective cohort study. SETTING: London tertiary hospital from January 2017 to March 2019. METHODS: 7720 women screened for pre-eclampsia according to National Institute for Health and Care Excellence (NICE) risk-based guidance and 4841 by the Fetal Medical Foundation (FMF) algorithm which combined maternal risk factors, blood pressure, PAPP-A and uterine artery Doppler indices in the first trimester. High risk was defined by standard NICE criteria in the pre-intervention cohort (prescribed 75 mg aspirin) or a risk of ≥1:50 for preterm pre-eclampsia from the FMF algorithm in the post-intervention cohort (prescribed 150 mg aspirin). MAIN OUTCOME MEASURES: Screening effectiveness, rates of pre-eclampsia. RESULTS: The FMF screening programme resulted in a significant reduction in the screen-positive rate (16.1 versus 8.2%, odds ratio [OR] 0.50, 95% confidence interval [CI] 0.41-0.53) with a concurrent increase in targeted aspirin use in women classified as high risk for pre-eclampsia (28.9 versus 99.0%, OR 241.6, 95% CI 89.6-652.0). Screening indices were uniformly improved for the FMF algorithm with receiver operating characteristic (ROC) analysis demonstrating excellent discrimination for preterm pre-eclampsia (area under the curve [AUC] = 0.846, 95% CI 0.778-0.915, P value <.001). Interrupted time series analysis showed that the FMF screening programme resulted in a significant 21-month relative effect reduction of 80% (P = .025) and 89% (P = .017), for preterm and early pre-eclampsia, respectively. CONCLUSIONS: First trimester combined screening for pre-eclampsia is both feasible and effective in a public healthcare setting. Such an approach results in a two-fold de-escalation of risk, doubling of pre-eclampsia detection, near total physician compliance of aspirin use and a significant reduction in the prevalence of preterm pre-eclampsia. TWEETABLE ABSTRACT: Implementation of 1st trimester combined pre-eclampsia screening effectively reduces prevalence of the disorder.

Routine first-trimester combined screening for pre-eclampsia: pregnancy-associated plasma protein-A or placental growth factor?

OBJECTIVE: To compare the screening performance of serum pregnancy-associated plasma protein-A (PAPP-A) vs placental growth factor (PlGF) in routine first-trimester combined screening for pre-eclampsia (PE), small-for-gestational age (SGA) at birth and trisomy 21. METHODS: This was a retrospective study nested in pregnancy cohorts undergoing first-trimester combined screening for PE and trisomy 21 using The Fetal Medicine Foundation (FMF) algorithm based on maternal characteristics, nuchal translucency thickness, PAPP-A, free beta-human chorionic gonadotropin, blood pressure and uterine artery Doppler. Women at high risk for preterm PE (≥ 1 in 50) received 150 mg of aspirin per day, underwent serial fetal growth scans at 28 and 36 weeks and were offered elective birth from 40 weeks of gestation. PlGF was quantified retrospectively from stored surplus first-trimester serum samples. The performance of combined first-trimester screening for PE and SGA using maternal history, blood pressure, uterine artery pulsatility index and either PAPP-A or PlGF was calculated. Similarly, the performance of combined first-trimester screening for trisomy 21 was calculated using either PAPP-A or PlGF in addition to maternal age, nuchal translucency thickness and free beta-human chorionic gonadotropin. RESULTS: Maternal serum PAPP-A was assayed in 1094 women, including 82 with PE, 111 with SGA (birth weight < 10th centile), 53 with both PE and SGA and 94 with fetal trisomy 21. PlGF levels were obtained retrospectively from 1066/1094 women. Median serum PlGF multiples of the median was significantly lower in pregnancies with PE (1.0 (interquartile range (IQR), 0.8-1.4); P < 0.01), SGA (1.0 (IQR, 0.8-1.3); P < 0.001) and trisomy 21 (0.6 (IQR, 0.5-0.9); P < 0.0001) compared to in controls (1.2 (IQR, 0.9-1.5)). There was no significant difference in the performance of first-trimester screening using PAPP-A vs PlGF for either preterm PE (area under the receiver-operating-characteristics curve (AUC), 0.78 vs 0.79; P = 0.55) or term PE (AUC, 0.74 vs 0.74; P = 0.60). These findings persisted even after correction for the effect of targeted aspirin use on the prevalence of PE. Similarly, there were no significant differences in sensitivity and specificity of combined screening for SGA or trisomy 21 when using PAPP-A vs PlGF. CONCLUSIONS: Using either PlGF or PAPP-A in routine first-trimester combined screening based on maternal characteristics, blood pressure and uterine artery Doppler does not make a significant clinical difference to the detection of PE or SGA. Depending on the setting, biomarkers should be chosen to achieve a good compromise between performance and measurement requirements. This pragmatic clinical-effectiveness study suggests that combined screening for PE can be implemented successfully in a public healthcare setting without changing current protocols for the assessment of PAPP-A in the first trimester. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Results of a nationally implemented cardiac screening programme in elite cricket players in England and Wales.

OBJECTIVES: We assessed the diagnostic yield and costs of an electrocardiogram-based national screening programme in elite cricket players and the incremental value of transthoracic echocardiography and periodic evaluation. DESIGN: Cross-sectional study. METHODS: Between 2008 and 2019, 1208 cricketers underwent screening with a health questionnaire, 12-lead electrocardiogram and cardiology consultation. Athletes with concerning findings underwent on-site transthoracic echocardiography and further investigations as necessary. In addition, despite a normal health questionnaire and electrocardiogram, 342 (28.3%) athletes had a transthoracic echocardiogram and 493 (40.8%) underwent repeat evaluations. RESULTS: After initial evaluation, 47 (3.9%) athletes underwent on-site transthoracic echocardiography of whom 35 (2.8%) were referred for further evaluation. Four athletes (0.3%) were diagnosed with major cardiac conditions; hypertrophic cardiomyopathy (n = 1), arrhythmogenic cardiomyopathy (n = 1) and Wolff-Parkinson-White pattern (n = 2). Two athletes were identified with minor valvular abnormalities. Repeat evaluation of 493 athletes identified hypertrophic cardiomyopathy in a 22-year-old athlete, two years after his initial normal screening. During a follow-up of 5.8 ±â€¯2.9 years no additional diagnoses or adverse cardiac events were reported. The cost of the electrocardiogram-based programme was £127,844, translating to £106 per athlete and £25,569 per major cardiac condition identified.Routine transthoracic echocardiography in 342 athletes identified two athletes with major cardiac conditions (bicuspid aortic valve with severe aortopathy and aortic regurgitation and an atrial septal defect associated with right ventricular volume overload) and 10 athletes with minor abnormalities. CONCLUSIONS: An electrocardiogram-based national screening programme identified a major cardiac condition in 0.3% of athletes. Routine transthoracic echocardiography and periodic evaluation increased the diagnostic yield to 0.6%, at an incremental cost.