Perinatal and neonatal outcomes of high-risk asymptomatic women from a specialist preterm birth surveillance clinic.

OBJECTIVES: To report the perinatal outcomes of high-risk asymptomatic women who attended a specialist preterm surveillance clinic (PSC) to undergo screening for spontaneous preterm birth (PTB) in Ireland. METHODS: Single center, retrospective cohort study of asymptomatic high risk women who attended the PSC between January 2019 and December 2022. A comprehensive database of all patients who attended the clinic during the study period was constructed and analyzed. Overall outcomes were reported, and stratified per the occurrence of preterm or term birth. Iatrogenic PTBs were included in the outcome data. RESULTS: Following exclusions for loss-to-follow-up, 762 cases were analyzed, constituting 2262 PSC visits. Of those, 183 women were prescribed progesterone (24.0 %), and 100 women underwent cervical cerclage (13.1 %) to prevent spontaneous PTB. Overall, 2.4 %, 6.2 % and 18.6 % of participants gave birth prior to 30 weeks, 34 weeks, and 37 weeks, respectively. The median gestational age at birth for the entire cohort was 38.6 weeks (inter-quartile range (IQR) 37.2-39.6 weeks). Women who delivered < 37 weeks were significantly more likely to be smokers (p = 0.030), have a previous spontaneous PTB (p = 0.016), have multiple pregnancies (p < 0.001), type 1 or 2 diabetes (p = 0.044), or have a previous full dilatation caesarean section birth (p = 0.024). Infants born prior to 37 weeks were more likely to have a lower median birthweight (2270 vs 3300 g, p < 0.001), be admitted to a neonatal intensive care unit (53.8 % vs 2.3 %, p < 0.001) or experience short-term morbidity, including respiratory support (38.0 % vs 1.6 %, p < 0.001). CONCLUSIONS: Over 80% of women deemed to be at high risk of PTB gave birth at term gestations following attendance at a PSC during pregnancy. Most women can be successfully managed without interventions, instead employing a policy of serial cervical surveillance, to identify those at greatest risk of PTB.

Performance of QUiPP App v.2 tool for prediction of preterm birth in asymptomatic high-risk women attending preterm specialist clinic: external validation study.

OBJECTIVE: To validate externally the QUiPP App v.2 algorithms in an independent cohort of high-risk asymptomatic women attending a preterm birth (PTB) surveillance clinic in Ireland. METHODS: This was a retrospective, single-center, observational study assessing discrimination and calibration of the QUiPP App v.2 at six predetermined clinical timepoints (PTB at < 30, < 34 and < 37 weeks of pregnancy and PTB within 1, 2 and 4 weeks of testing). Discrimination was assessed by estimating the area under the receiver-operating-characteristics curve (AUC) and sensitivity at fixed false-positive rates of 5%, 10% and 20%. Model calibration was assessed to evaluate the concordance between expected and observed outcomes. P-values < 0.05 were considered statistically significant. No adjustments for treatment effects were made. RESULTS: Overall, 762 women with 1660 PTB surveillance clinic visits using the QUiPP App v.2 between 2019 and 2022 were analyzed. The study population included 142 (18.6%) patients who later experienced PTB. The QuiPP App's performance in the prediction of short-term outcomes, such as birth within 1 week (AUC, 0.866 (95% CI, 0.755-0.955)), 2 weeks (AUC, 0.721 (95% CI, 0.569-0.854)) and 4 weeks (AUC, 0.775 (95% CI, 0.699-0.842)), and delivery at < 30 weeks (AUC, 0.747 (95% CI, 0.613-0.865)), was superior to its ability to predict longer-term outcomes (PTB at < 37 weeks: AUC, 0.631 (95% CI, 0.596-0.668)). Calibration was generally good for low-risk results, as the predicted risk in these patients tended to match the observed incidence. However, in women deemed to be at greater risk of PTB, the predicted probability superseded the observed incidence of PTB. CONCLUSIONS: The QUiPP App v.2 accurately discriminates women who are at short-term risk of PTB. A 'treatment paradox' may influence calibration in high-risk women. Further research is needed to ascertain if QuiPP treatment thresholds can be safely adjusted in women receiving prophylactic treatment to prevent PTB, and whether this improves the outcome. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Cell free DNA screening for fetal aneuploidy in Ireland: An observational study of outcomes following insufficient fetal fraction.

OBJECTIVES: To determine maternal factors associated with low fetal fraction (FF). To determine the proportion of women who receive a result from repeat non-invasive prenatal testing (NIPT) testing. To identify any significant associations between pregnancy interventions or outcomes and low FF. STUDY DESIGN: Retrospective observational study of 4465 women undergoing antenatal screening by targeted cell free DNA (cfDNA) testing at an Irish tertiary maternity hospital between January 2017 and December 2022. Patients who failed to obtain a result after the first NIPT were analyzed in two cohorts; those who received a result on a repeat sample and those who failed to ever achieve a result despite a second, third or fourth cfDNA test. RESULTS: Risk of insufficient FF significantly increased with elevated maternal BMI (OR 1.07; 95% CI 1.01-1.13, p = 0.03) and in-vitro fertilization (IVF) (OR 3.4; 95% CI 1.19-9.4, p = 0.02). Women with no result were more likely to have diagnostic invasive testing (p < 0.01), but had no increased risk of aneuploidy. Repeated failed NIPT attempts due to low FF were significantly associated with the subsequent development of hypertensive diseases of pregnancy (p = 0.03). Greater than 70% of patients who were unsuccessful in a first or second attempt at NIPT due to low FF yielded a result following a second or third sample. CONCLUSIONS: High BMI and IVF conceptions are greater contributors to low FF than fetal aneuploidy. Repeating NIPT yields a result in greater than 70% of cases. WHAT'S ALREADY KNOWN ABOUT THIS TOPIC?: Fetal fraction (FF) in prenatal cfDNA testing is influenced by maternal and pregnancy factors including body mass index (BMI) and IVF. Low FF has been associated with adverse pregnancy outcomes including fetal aneuploidy and hypertensive diseases of pregnancy. WHAT DOES THIS STUDY ADD?: In a large Irish population, increasing maternal BMI and in-vitro fertilization are the most significant contributors to repeated test failures due to low FF. Greater than 70% of patients with test failure due to low FF will receive a result on 2nd and 3rd NIPT attempts. Patients with no result from NIPT were more likely to undergo diagnostic invasive testing but the risk of aneuploidy was not significantly increased.

A cross-sectional survey of women's views and preferences for preterm birth screening and treatment.

OBJECTIVES: Primary outcomes were to determine; 1) the desire for more patient information from healthcare professionals on preterm birth (PTB) prevention 2) the desire for PTB screening surveillance or participation in research or 3) the acceptability of transvaginal ultrasound (TVUS) or vaginal examinations to predict spontaneous PTB. METHODS: A 19-question, piloted, self-administered survey was completed by unselected pregnant women in a tertiary maternity hospital in Dublin, Ireland. Data was collected to include maternal socio-demographics, past obstetric history, and current pregnancy details, in addition to views and preferences on PTB screening and preventative treatments. Statistical analysis to include binary and multinomial regression was performed by IBM SPSS Statistics for Windows (Version 29.0). RESULTS: 277 women completed the study survey. 9.4% of women had attended the preterm birth surveillance clinic (PSC). 75.1% of respondents indicated a preference for more information from healthcare professionals about PTB. 65% reported that TVUS and vaginal examinations were acceptable in pregnancy. The acceptability of antenatal examinations was significantly influenced by ethnicity; white European (OR 2.58, CI 1.12-5.95, p = 0.003) and Asian (OR 3.39, CI 1.18-9.67, p = 0.02). Discomfort (25.3%) and vaginal bleeding (11.9%) were the most frequently reported concerns about TVUS. 95.7% of unselected women indicated that they would accept treatment to prevent PTB. Vaginal progesterone (53.8%) was preferred treatment compared to cervical cerclage (15.9%) or cervical pessary (16.6%). 55.6% of respondents stated they attend or wish to attend for additional appointments or research opportunities for PTB screening. Women with a previous PTB or second trimester miscarriage were more likely to attend or wish to attend for PTB screening (OR 3.23, CI 1.34-7.79, p = 0.009). CONCLUSION: PTB is an important healthcare priority for pregnant women in Ireland. However, women require more information, counselling and reassurance about the utility and safety of TVUS in PSCs.

A retrospective observational study of labour ward work Intensity: The challenge of maternity staffing.

BACKGROUND: The UK and Ireland are facing significant challenges in the recruitment and retention of midwifery staff. Deficiencies in staffing, training and leadership have been cited as contributory factors to substandard care in both regional and global independent maternity safety reports. Locally, workforce planning is critical to maintaining 'one to one' care for all women in labor and to meet the peaks of daily birthing suite activity. OBJECTIVES: Analyze the variation in work intensity, defined by the mean number and range of births per midwifery working hours. METHODS: Retrospective observational study of birthing suite activity between 2017 and 2020. 30,550 singleton births were reported during the study period; however, 6529 elective Cesarean sections were excluded as these were performed during normal working hours by a separate operating theatre team. The times of 24,021 singleton births were organized into five proposed midwifery working rosters lasting eight or 12 h; A (00.00-07.59), B (08.00-15.59), C (16.00-23.59), D (20.00-0.759) and E (0.800-19.59). RESULTS: The number of births was comparable between the eight-hour and 12-hour work periods with a mean of five to six babies born per roster (range zero to 15). Work periods D and E lasting 12-hours both recorded a mean of eight births (range zero to 18). Hourly births ranged from a minimum of zero to a maximum of five births per hour (greater than seven times the mean), a number that was achieved 14 times during the study period. CONCLUSIONS: The mean number of births is consistent between normal working hours and unsociable 'on-call' periods, however there is an extreme range of activity within each midwifery roster. Prompt escalation plans remain essential for maternity services to manage unexpected increases in demand and complexity. WHAT IS ALREADY KNOWN ON THIS TOPIC: Shortfalls in staffing and inadequate workforce planning have been frequently cited in recent maternity safety reports as barriers to sustainable and safe maternity care. WHAT THIS STUDY ADDS: Our study shows that the mean number of births in a large tertiary center are consistent across day and night rosters. However, there are large fluctuations in activity during which births can exceed the number of available midwives. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY: Our study reflects the sentiments of the Ockenden review and APPG report on safe maternity staffing. Investment in services and the workforce to aid recruitment and reduce attrition is essential to establish robust escalation plans, including the deployment of additional staff in the event of extreme service pressures.

ASPRE trial: effects of aspirin on mean arterial blood pressure and uterine artery pulsatility index trajectories in pregnancy.

OBJECTIVES: The mechanism by which aspirin prevents pre-eclampsia is poorly understood, and its effects on biomarkers throughout pregnancy are unknown. We aimed to investigate the effects of aspirin on mean arterial pressure (MAP) and mean uterine artery pulsatility index (UtA-PI) using repeated measures from women at increased risk of preterm pre-eclampsia. METHODS: This was a longitudinal secondary analysis of the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Pre-eclampsia Prevention (ASPRE) trial using repeated measures of MAP and UtA-PI. In the trial, 1620 women at increased risk of preterm pre-eclampsia were identified using the Fetal Medicine Foundation algorithm at 11 + 0 to 13 + 6 weeks, of whom 798 were randomly assigned to receive 150 mg/day aspirin and 822 were assigned to receive placebo daily from 11-14 weeks to 36 weeks of gestation or delivery, whichever came first. MAP and UtA-PI were measured at baseline and follow-up visits at 19-24, 32-34 and 36 weeks of gestation. Generalized additive mixed models with treatment by gestational age interaction terms were used to investigate the effects of aspirin on MAP and UtA-PI trajectories over time. RESULTS: Among 798 participants in the aspirin group and 822 in the placebo group, there were 5951 MAP and 5942 UtA-PI measurements. Trajectories of raw and multiples of the median (MoM) values of MAP did not differ significantly between the two groups (MAP MoM analysis: P-value for treatment by gestational age interaction, 0.340). In contrast, trajectories of raw and MoM values of UtA-PI showed a significantly steeper decline in the aspirin group than in the placebo group, with the difference mainly driven by a more pronounced reduction before 20 weeks of gestation (UtA-PI MoM analysis: P-value for treatment by gestational age interaction, 0.006). CONCLUSIONS: In women at increased risk of preterm pre-eclampsia, 150 mg/day aspirin initiated in the first trimester does not affect MAP but is associated with a significant decrease in mean UtA-PI, particularly before 20 weeks of gestation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

The duration of labor in spontaneous preterm deliveries: A retrospective observational study in a tertiary Irish maternity hospital.

BACKGROUND: Preterm deliveries account for 10% of all births, and are the most important cause of neonatal mortality globally. Despite their frequency, there is a paucity of information known about usual patterns of preterm labor, as previous studies which critically defined the normal progression of labor excluded preterm gestations. OBJECTIVE: To compare the durations of the first, second and third stages of spontaneous preterm labor in nulliparous and multiparous women at varying preterm gestations. METHODS: A retrospective observational study was undertaken of women admitted in spontaneous preterm labor from January 2017 to December 2020 with viable singleton gestations between 24 and 36 + 6 weeks' gestation who then proceeded to have a vaginal delivery. There were 512 cases following exclusion of preterm inductions of labor, instrumental vaginal deliveries, provider-initiated pre-labor Caesarean sections and emergency intrapartum Caesarean sections. The data was then examined to determine our outcomes of interest including the durations of the first, second and third stages of preterm labor, analyzing results by parity and gestation. For comparison, we reviewed data of term spontaneous labors and spontaneous vaginal deliveries during the same study period, identifying 8339 cases. FINDINGS: 97.6% of participants achieved a spontaneous cephalic vaginal delivery with the remainder undergoing an assisted breech birth. 5.7% of gestations delivered spontaneously between 24 + 0 and 27 + 6 weeks, with most births at gestations greater than 34 weeks (74%). The second stage duration (mean 15 vs 32 vs 32 mins respectively) was significantly different across the three gestation periods (p < 0.05), but was notably much quicker in extremely preterm labors. The first and third stage durations were similar between all gestational age groups with no statistically significant differences in results. There was a significant influence of parity on the first and second stages of labor, with multiparous women progressing more quickly than nulliparae (p < 0.001). CONCLUSION: The duration of spontaneous preterm labor is described. Multiparous women progress more quickly in the first and second stages of preterm labor than nulliparous women.

Heterogeneity in defining fetal corpus callosal pathology: systematic review.

OBJECTIVE: Fetal anomalies of the corpus callosum (CC) have been reported in the prenatal imaging literature since 1985, and, especially when isolated, pose challenges for both the patient and fetal medicine specialist. The purpose of this study was to review systematically the literature on prenatally diagnosed abnormalities of the CC, focusing on the terminology used to describe abnormalities other than complete agenesis of the CC, and to assess the heterogeneity of the nomenclature and definitions used. METHODS: This study was conducted in accordance with the PRISMA statement for reporting systematic reviews. A literature search was performed to identify prospective or retrospective case series or cohort studies, published in English, French, Italian, German or Spanish, reporting fetal imaging findings and describing anomalies of the CC. Quality and risk of bias of the studies were evaluated using the Newcastle-Ottawa scale and a modification of the scale developed by Conde-Agudelo et al. for other fetal imaging studies. The data extracted included the number of patients, the number of different anomalies identified, the descriptive names of the anomalies, and, where applicable, the definitions of the anomalies, the number of cases of each type of anomaly and the biometric charts used. Secondary tests used to confirm the diagnosis, as well as the postnatal or post-termination tests used to ascertain the diagnosis, were also recorded. RESULTS: The search identified 998 records, and, after review of titles and abstracts and full review of 45 papers, 27 studies were included initially in the review, of which 24 were included in the final analysis. These 24 studies had a broad range of quality and risk of bias and represented 1135 cases of CC anomalies, of which 49% were complete agenesis and the remainder were described using the term partial agenesis or nine other terms, of which five had more than one definition. CONCLUSIONS: In comparison to the postnatal literature, in the prenatal literature there is much greater heterogeneity in the nomenclature and definition of CC anomalies other than complete agenesis. This heterogeneity and lack of standard definitions in the prenatal literature make it difficult to develop large multicenter pooled cohorts of patients who can be followed in order to develop a better understanding of the genetic associations and neurodevelopmental and psychological outcomes of patients with CC anomalies. As this information is important to improve counseling of these patients, a good first step towards this goal would be to develop a simpler categorization of prenatal CC anomalies that matches better the postnatal literature. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prediction of pre-eclampsia in twin pregnancy by maternal factors and biomarkers at 11-13 weeks' gestation: data from EVENTS trial.

OBJECTIVES: First, to validate a previously developed model for screening for pre-eclampsia (PE) by maternal characteristics and medical history in twin pregnancies; second, to compare the distributions 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) in twin pregnancies that delivered with PE to those in singleton pregnancies and to develop new models based on these results; and, third, to examine the predictive performance of these models in screening for PE with delivery at < 32 and < 37 weeks' gestation. METHODS: Two datasets of prospective non-intervention multicenter screening studies for PE in twin pregnancies at 11 + 0 to 13 + 6 weeks' gestation were used. The first dataset was from the EVENTS (Early vaginal progesterone for the preVention of spontaneous prEterm birth iN TwinS) trial and the second was from a previously reported study that examined the distributions of biomarkers in twin pregnancies. Maternal demographic characteristics and medical history from the EVENTS-trial dataset were used to assess the validity of risks from our previously developed model. The combined data from the first and second datasets were used to compare the distributional properties of log10 multiples of the median (MoM) values of UtA-PI, MAP, PlGF and PAPP-A in twin pregnancies that delivered with PE to those in singleton pregnancies and develop new models based on these results. The competing-risks model was used to estimate the individual patient-specific risks of delivery with PE at < 32 and < 37 weeks' gestation. Screening performance was measured by detection rates (DR) and areas under the receiver-operating-characteristics curve. RESULTS: The EVENTS-trial dataset comprised 1798 pregnancies, including 168 (9.3%) that developed PE. In the validation of the prior model based on maternal characteristics and medical history, calibration plots demonstrated very good agreement between the predicted risks and the observed incidence of PE (calibration slope and intercept for PE < 32 weeks were 0.827 and 0.009, respectively, and for PE < 37 weeks they were 0.942 and -0.207, respectively). In the combined data, there were 3938 pregnancies, including 339 (8.6%) that developed PE and 253 (6.4%) that delivered with PE at < 37 weeks' gestation. In twin pregnancies that delivered with PE, MAP, UtA-PI and PlGF were, at earlier gestational ages, more discriminative than in singleton pregnancies and at later gestational ages they were less so. For PAPP-A, there was little difference between PE and unaffected pregnancies. The best performance of screening for PE was achieved by a combination of maternal factors, MAP, UtA-PI and PlGF. In screening by maternal factors alone, the DR, at a 10% false-positive rate, was 30.6% for delivery with PE at < 32 weeks' gestation and this increased to 86.4% when screening by the combined test; the respective values for PE < 37 weeks were 24.9% and 41.1%. CONCLUSIONS: In the assessment of risk for PE in twin pregnancy, we can use the same prior model based on maternal characteristics and medical history as reported previously, but in the calculation of posterior risks it is necessary to use the new distributions of log10 MoM values of UtA-PI, MAP and PlGF according to gestational age at delivery with PE. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

OBJECTIVE: To examine the performance of screening for early, preterm and term pre-eclampsia (PE) at 11-13 weeks' gestation by maternal factors and combinations of mean arterial pressure (MAP), uterine artery (UtA) pulsatility index (PI), serum placental growth factor (PlGF) and serum pregnancy-associated plasma protein-A (PAPP-A). METHODS: The data for this study were derived from three previously reported prospective non-intervention screening studies at 11 + 0 to 13 + 6 weeks' gestation in a combined total of 61 174 singleton pregnancies, including 1770 (2.9%) that developed PE. Bayes' theorem was used to combine the prior distribution of gestational age at delivery with PE, obtained from maternal characteristics, with various combinations of biomarker multiples of the median (MoM) values to derive patient-specific risks of delivery with PE at < 37 weeks' gestation. The performance of such screening was estimated. RESULTS: In pregnancies that developed PE, compared to those without PE, the MoM values of UtA-PI and MAP were increased and those of PAPP-A and PlGF were decreased, and the deviation from normal was greater for early than late PE for all four biomarkers. Combined screening by maternal factors, UtA-PI, MAP and PlGF predicted 90% of early PE, 75% of preterm PE and 41% of term PE, at a screen-positive rate of 10%; inclusion of PAPP-A did not improve the performance of screening. The performance of screening depended on the racial origin of the women; on screening by a combination of maternal factors, MAP, UtA-PI and PlGF and using a risk cut-off of 1 in 100 for PE at < 37 weeks in Caucasian women, the screen-positive rate was 10% and detection rates for early, preterm and term PE were 88%, 69% and 40%, respectively. With the same method of screening and risk cut-off in women of Afro-Caribbean racial origin, the screen-positive rate was 34% and detection rates for early, preterm and term PE were 100%, 92% and 75%, respectively. CONCLUSION: Screening by maternal factors and biomarkers at 11-13 weeks' gestation can identify a high proportion of pregnancies that develop early and preterm PE. © 2018 Crown copyright. Ultrasound in Obstetrics & Gynecology © 2018 ISUOG.

Fetal intra-abdominal umbilical vein varix: retrospective cohort study and systematic review and meta-analysis.

OBJECTIVE: To investigate the ultrasound characteristics and outcome of pregnancies with fetal intra-abdominal umbilical vein varix (FIUVV). METHODS: Cases of FIUVV managed at our tertiary university hospital over an 8-year period were reviewed. Information retrieved included gestational age and diameter of the umbilical varix at diagnosis, increase in varix diameter, associated ultrasound or chromosomal anomalies and pregnancy outcome. Furthermore, a systematic review and meta-analysis of series of FIUVV in the literature was performed to assess the incidence of chromosomal anomalies, small-for-gestational age infants and intrauterine fetal demise (IUFD), and to pool odds ratio (OR) estimates on the relationship between the incidence of these outcomes and the presence of additional associated ultrasound anomalies. RESULTS: Thirteen cases of FIUVV were included in the cohort study. Additional ultrasound anomalies were found in two (15.4%) of 13 cases. One case of IUFD was observed and no case of chromosomal anomaly or thrombosis of varix was recorded. A total of five studies comprising 254 cases met the inclusion criteria of the systematic review. FIUVV was associated with additional ultrasound anomalies (non-isolated FIUVV) in 19% (95% CI, 10.9-29.1%) of cases. No case of chromosomal abnormality or IUFD was reported in fetuses with isolated FIUVV. In contrast, in the group of non-isolated FIUVV, the incidence of chromosomal anomalies was 19.6% and that of IUFD was 7.3%, with ORs of 14.8 (95% CI, 2.9-73.0) and 8.2 (95% CI, 1.05-63.1), respectively, when compared with the group of isolated FIUVV. CONCLUSION: When isolated, the outcome of cases affected by FIUVV is usually favorable. In about 20% of cases, additional ultrasound anomalies are found, which are associated with an increased risk for chromosomal abnormalities and IUFD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

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.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

OBJECTIVE: To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. METHODS: This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11-13 weeks' gestation. A previously published FMF 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 derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. 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. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80-100%) of PE < 32 weeks, 75% (95% CI, 62-85%) of PE < 37 weeks and 43% (95% CI, 35-50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18-67%) of PE < 32 weeks, 39% (95% CI, 27-53%) of PE < 37 weeks and 34% (95% CI, 27-41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71-100%) of PE < 32 weeks, 90% (95% CI, 79-96%) of PE < 37 weeks and 89% (95% CI, 84-94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1-27%) of PE < 32 weeks, 5% (95% CI, 2-14%) of PE < 37 weeks and 2% (95% CI, 0.3-5%) of PE ≥ 37 weeks, at 0.2% FPR. CONCLUSION: Performance of screening for PE at 11-13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. 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.

Uterine artery pulsatility index at 12, 22, 32 and 36 weeks' gestation in screening for pre-eclampsia.

OBJECTIVE: To examine the distribution of uterine artery pulsatility index (UtA-PI) at 12, 22, 32 and 36 weeks' gestation in singleton pregnancies which develop pre-eclampsia (PE) and examine the performance of this biomarker in screening for PE. METHODS: UtA-PI was measured in 92 712 singleton pregnancies at 11-13 weeks, in 67 605 cases at 19-24 weeks, in 31 741 at 30-34 weeks and in 5523 at 35-37 weeks. Bayes' theorem was used to combine the a-priori risk from maternal characteristics and medical history with UtA-PI. The performance of screening for PE requiring delivery < 32, at 32 + 0 to 36 + 6, < 37 and ≥ 37 weeks' gestation was estimated. The results of combined screening were compared to those of screening by UtA-PI and by maternal factors alone. RESULTS: In pregnancies that developed PE, UtA-PI was increased and the separation in multiples of the median (MoM) values from normal was greater with earlier, compared to later, gestational age at which delivery for PE became necessary. Additionally, the slope of regression lines of UtA-PI MoM with gestational age at delivery in pregnancies that developed PE increased with increasing gestational age at screening. The detection rate (DR), at a 10% false-positive rate (FPR), for PE delivering < 32 weeks was 71% and 88% with combined screening at 11-13 and 19-24 weeks, respectively, and the DR for PE delivering at 32 + 0 to 36 + 6 weeks was 52%, 63% and 71% with screening at 11-13, 19-24 and 30-34 weeks, respectively. However, the DR of PE delivering ≥ 37 weeks was only about 40%, irrespective of the gestational age at screening. The performance of screening by the approach utilizing Bayes' theorem was superior to that of using a percentile cut-off of UtA-PI for gestational age. CONCLUSIONS: The performance of combined screening with maternal factors and UtA-PI is superior for detection of early, compared to late, PE and, to a certain extent, improves with advancing gestational age at screening. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Maternal plasma cell-free DNA in the prediction of pre-eclampsia.

OBJECTIVES: To examine whether maternal plasma concentrations of total cell-free (cf)DNA and fetal fraction at 11-13 and 20-24 weeks' gestation in pregnancies that subsequently develop pre-eclampsia (PE) are different from those without this complication. METHODS: Total cfDNA and fetal fraction were measured in 20 cases of early PE requiring delivery at < 34 weeks, in 20 cases of late PE with delivery at ≥ 34 weeks and in 200 normotensive controls, at 11-13 and 20-24 weeks' gestation. Total cfDNA and fetal fraction measured at 11-13 weeks were converted to multiples of the median (MoM), corrected for maternal characteristics and gestational age. The distributions of total cfDNA and fetal fraction at 20-24 weeks were expressed as MoM of values at 11-13 weeks. The Mann-Whitney U-test was used to determine the significance of differences in the median values in each outcome group relative to that in the controls. RESULTS: In the early-PE group at 11-13 weeks, compared with controls, there was a significant increase in median total cfDNA (2104 genome equivalents (GE)/mL vs 1590 GE/mL) and a decrease in median fetal fraction (6.8% vs 8.7%). In the late-PE group at 20-24 weeks, compared with controls, there was a significant decrease in median fetal fraction (8.2% vs 9.6%). These significant differences between groups were not observed when the values were converted to MoM. CONCLUSION: Measurements of total cfDNA and fetal fraction in maternal plasma at 11-13 and 20-24 weeks are not predictive of PE.

Dermatitis herpetiformis: no evidence of bone disease despite evidence of enteropathy.

The majority of patients with dermatitis herpetiformis (DH) have small intestinal enteropathy that may result in bone loss. The objective of this study was to evaluate bone mineral density (BMD) in DH and to examine whether dietary treatment or degree of the small intestinal lesion correlate with BMD. Twenty-five patients with DH (18 men) were investigated. Detailed dietary assessment and duodenal biopsies were performed on all patients before entry into the study. BMD at lumbar spine and femur was determined by DXA scan. Bone biomarkers, vitamin D, and parathyroid status were assessed. Twenty patients had enteropathy. None of the patients had hypovitaminosis D or secondary hyperparathyroidism. Resorption and formation markers were within normal limits. BMD Z-scores were not significantly different from expected (-0.38; CI, -0.84 to 0.07) and femur (0.46; CI, -0.06 to 0.97). There was no relationship between BMD Z-scores and the severity of the degree of enteropathy. We conclude that enteropathy of differing severity is present in 80% of patients with DH, but this is not associated with bone disease.