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This document discusses the development of near-miss criteria for stillbirth research as part of the "In Utero" program. The criteria aim to identify live births at high risk of stillbirth and focus on placental insufficiency as a common cause. The document acknowledges limitations in the consensus procedure used to develop the criteria but concludes that they are a step closer to recognizing and addressing the issue of stillbirth. The criteria can be applied in both high-income and low- and middle-income countries. [Extracted from the article]

Background and Objective: Over the past 2 years, several drugs have been approved for coronavirus disease 2019 (COVID-19) treatment, but their safety during pregnancy remains poorly understood. This study aims to assess the relative risk of obstetric, neonatal, and infant outcomes associated with the use of drugs specifically indicated for the treatment of COVID-19 compared with other drug treatment strategies. The purpose of this article is to present elements of the study protocol. Methods: The COVID-19 International Drug Pregnancy Registry (COVID-PR) is a noninterventional, postmarketing cohort study. Pregnant women receiving treatment with monoclonal antibodies (mAbs) or antiviral drugs for mild, moderate, or severe COVID-19 are matched 1:1 with pregnant women not receiving these study-specific drugs, based on calendar time, country, gestational age at enrollment, and COVID-19 severity. Participants complete online questionnaires at enrollment, during pregnancy, and for 12 months after delivery of liveborn infants. The study began enrolling participants on 1 December 2021 and is set to span 5 years for each drug of interest. Discussion: The COVID-PR is designed to evaluate the safety profile of each studied drug. Additionally, it may allow for an analysis of the effects of COVID-19 drug exposure during relevant gestational periods on specific neonatal outcomes. Although the sample size will be too small to detect associations with rare outcomes, the study has the potential to generate hypotheses for future research. Ultimately, these data can provide valuable insights for evidence-based decisions about COVID-19 treatment during pregnancy. Trial registration: ClinicalTrials.gov: NCT05013632. EU PAS EUPAS42517. [ABSTRACT FROM AUTHOR]

Professor Christopher Redman, a pioneering obstetrician and professor, has passed away at the age of 82. He made significant contributions to the field of maternal and fetal medicine, particularly in the study of preeclampsia. Professor Redman conducted groundbreaking research on the role of extracellular vesicles released from the placenta in the development of preeclampsia. He also co-founded Action on Preeclampsia, a charity that has improved care and awareness of the disease. Professor Redman's legacy includes his medical innovations, his dedication to patient care, and his warm and engaging personality. He is survived by his wife, five children, and 13 grandchildren. [Extracted from the article]

Editor‐in‐Chief, Dr Aris Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/November‐editorial‐2022 [ABSTRACT FROM AUTHOR]

Editor‐in‐Chief, Dr Aris Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/November‐editorial‐2022 [ABSTRACT FROM AUTHOR]

Objective: To determine, by expert consensus using a Delphi procedure, a minimum reporting set of study variables for fetal growth restriction (FGR) research studies.Methods: A panel of experts, identified based on their publication record as lead or senior author of studies on FGR, was asked to select a set of essential reporting study parameters from a literature-based list of variables, utilizing the Delphi consensus methodology. Responses were collected in four consecutive rounds by online questionnaires presented to the panelists through a unique token-secured link for each round. The experts were asked to rate the importance of each parameter on a five-point Likert scale. Variables were selected in the three first rounds based on a 70% threshold for agreement on the Likert-scale scoring. In the final round, retained parameters were categorized as essential (to be reported in all FGR studies) or recommended (important but not mandatory).Results: Of the 100 invited experts, 87 agreed to participate and of these 62 (71%) completed all four rounds. Agreement was reached for 16 essential and 30 recommended parameters including maternal characteristics, prenatal investigations, prenatal management and pregnancy/neonatal outcomes. Essential parameters included hypertensive complication in the current pregnancy, smoking, parity, maternal age, fetal abdominal circumference, estimated fetal weight, umbilical artery Doppler (pulsatility index and end-diastolic flow), fetal middle cerebral artery Doppler, indications for intervention, pregnancy outcome (live birth, stillbirth or neonatal death), gestational age at delivery, birth weight, birth-weight centile, mode of delivery and 5-min Apgar score.Conclusions: We present a list of essential and recommended parameters that characterize FGR independent of study hypotheses. Uniform reporting of these variables in prospective clinical research is expected to improve data quality, study consistency and ultimately our understanding of FGR. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To assess clinical variability in the management of small-for-gestational-age (SGA) fetuses according to different published Doppler reference charts for umbilical artery (UA) and fetal middle cerebral artery (MCA) Doppler indices and cerebroplacental ratio (CPR).Methods: We performed a systematic search of MEDLINE, EMBASE, CINAHL and the Web of Science databases from 1954 to 2018 for studies with the sole aim of creating fetal Doppler reference values for UA, MCA and CPR. The top cited articles for each Doppler parameter were included. Variability in Doppler values at the following clinically relevant cut-offs was assessed: UA-pulsatility index (PI) > 95th percentile; MCA-PI < 5th percentile; and CPR < 5th percentile. Variability was calculated for each week of gestation and expressed as the percentage difference between the highest and lowest Doppler value at the clinically relevant cut-offs. Simulation analysis was performed in a cohort of SGA fetuses (n = 617) to evaluate the impact of this variability on clinical management.Results: From a total of 40 studies that met the inclusion criteria, 19 were analyzed (13 for UA-PI, 10 for MCA-PI and five for CPR). Wide discrepancies in reported Doppler reference values at clinically relevant cut-offs were found. MCA-PI showed the greatest variability, with differences of up to 51% in the 5th percentile value at term. Variability in the 95th percentile of UA-PI and the 5th percentile of CPR at each gestational week ranged from 21% to 41% and 15% to 33%, respectively. As expected, on simulation analysis, these differences in Doppler cut-off values were associated with significant variation in the clinical management of SGA fetuses, despite using the same protocol.Conclusions: The choice of Doppler reference chart can result in significant variation in the clinical management of SGA fetuses, which may lead to suboptimal outcomes and inaccurate research conclusions. Therefore, an attempt to standardize fetal Doppler reference ranges is needed. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: To assess the diagnostic accuracy of two‐dimensional ultrasound at 11–14 weeks' gestation as a screening test for individual fetal anomalies and to identify factors impacting on screening performance. Methods: This was a systematic review and meta‐analysis that was developed and registered with PROSPERO (CRD42018111781). MEDLINE, EMBASE, Web of Science Core Collection and the Cochrane Library were searched for studies evaluating the diagnostic accuracy of screening for 16 predefined, non‐cardiac, congenital anomalies considered to be of interest to the early anomaly scan. We included prospective and retrospective studies from any healthcare setting conducted in low‐risk, mixed‐risk and unselected populations. The reference standard was the detection of an anomaly on postnatal or postmortem examination. Data were extracted to populate 2 × 2 tables and a random‐effects model was used to determine the diagnostic accuracy of screening for the predefined anomalies (individually and as a composite). Secondary analyses were performed to determine the impact on detection rates of imaging protocol, type of ultrasound modality, publication year and index of sonographer suspicion at the time of scanning. Post‐hoc secondary analysis was conducted to assess performance among studies published during or after 2010. Risk of bias assessment and quality assessment were undertaken for included studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. Results: From 5684 citations, 202 papers underwent full‐text review, resulting in the inclusion of 52 studies comprising 527 837 fetuses, of which 2399 were affected by one or more of the 16 predefined anomalies. Individual anomalies were not equally amenable to detection on first‐trimester ultrasound: a high (> 80%) detection rate was reported for severe conditions, including acrania (98%), gastroschisis (96%), exomphalos (95%) and holoprosencephaly (88%); the detection rate was lower for open spina bifida (69%), lower urinary tract obstruction (66%), lethal skeletal dysplasias (57%) and limb‐reduction defects (50%); and the detection rate was below 50% for facial clefts (43%), polydactyly (40%) and congenital diaphragmatic hernia (38%). Conditions with a low (< 30%) detection rate included bilateral renal agenesis (25%), closed spina bifida (21%), isolated cleft lip (14%) and talipes (11%). Specificity was > 99% for all anomalies. Secondary analysis showed that detection improved with advancing publication year, and that the use of imaging protocols had a statistically significant impact on screening performance (P < 0.0001). Conclusions: The accurate detection of congenital anomalies using first‐trimester ultrasound is feasible, although detection rates and false‐positive rates depend on the type of anomaly. The use of a standardized protocol allows for diagnostic performance to be maximized, particularly for the detection of spina bifida, facial clefts and limb‐reduction defects. Highlighting the types of anomalies amenable to diagnosis and determining factors enhancing screening performance can support the development of first‐trimester anomaly screening programs. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Health is not bought with a chemist's pills. The authors took advantage of data available from the Medicaid system to examine cervical screening practices, and in particular to assess adherence to evidence-based screening recommendations. [Extracted from the article]

Depending on the methods, many NIPT tests undertake analysis of the whole genome, but reporting is limited to the common trisomies. From the perspective of screening for common fetal aneuploidies, important advantages of NIPT are higher detection rates and much lower false-positive rates than from traditional screening methods, such as maternal age, combined screening or maternal serum screening. While screening for segmental copy number variants is technically possible (and indeed undertaken privately and in some public health settings), there are important aspects that should be considered: offering screening for these conditions increases the screen positive rate (and therefore the invasive testing rate), eradicating one of the major benefits of moving from more traditional screening approaches to NIPT. [Extracted from the article]

Objective: Accurate gestational-age (GA) estimation, preferably by ultrasound measurement of fetal crown-rump length before 14 weeks' gestation, is an important component of high-quality antenatal care. The objective of this study was to determine how GA can best be estimated by fetal ultrasound for women who present for the first time late in pregnancy with uncertain or unknown menstrual dates.Methods: INTERGROWTH-21st was a large, prospective, multicenter, population-based project performed in eight geographically defined urban populations. One of its principal components, the Fetal Growth Longitudinal Study, aimed to develop international fetal growth standards. Each participant had their certain menstrual dates confirmed by first-trimester ultrasound examination. Fetal head circumference (HC), biparietal diameter (BPD), occipitofrontal diameter (OFD), abdominal circumference (AC) and femur length (FL) were measured every 5 weeks from 14 weeks' gestation until delivery. For each participant, a single, randomly selected ultrasound examination was used to explore all candidate biometric variables and permutations to build models to predict GA. Regression equations were ranked based upon minimization of the mean prediction error, goodness of fit and model complexity. An automated machine learning algorithm, the Genetic Algorithm, was adapted to evaluate > 64 000 potential polynomial equations as predictors.Results: Of the 4607 eligible women, 4321 (94%) had a pregnancy without major complications and delivered a live singleton without congenital malformations. After other exclusions (missing measurements in GA window and outliers), the final sample comprised 4229 women. Two skeletal measures, HC and FL, produced the best GA prediction, given by the equation loge (GA) = 0.03243 × (loge (HC))2 + 0.001644 × FL × loge (HC) + 3.813. When FL was not available, the best equation based on HC alone was loge (GA) = 0.05970 × (loge (HC))2 + 0.000000006409 × (HC)3 + 3.3258. The estimated uncertainty of GA prediction (half width 95% interval) was 6-7 days at 14 weeks' gestation, 12-14 days at 26 weeks' gestation and > 14 days in the third trimester. The addition of FL to the HC model led to improved prediction intervals compared with using HC alone, but no further improvement in prediction was afforded by adding AC, BPD or OFD. Equations that included other measurements (BPD, OFD and AC) did not perform better.Conclusions: Among women initiating antenatal care late in pregnancy, a single set of ultrasound measurements combining HC and FL in the second trimester can be used to estimate GA with reasonable accuracy. We recommend this tool for underserved populations but considerable efforts should be implemented to improve early initiation of antenatal care worldwide. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

(a) When the ultrasound beam was perpendicular to the direction of swing of the fetal heart during contraction and relaxation, with the heart appearing to swing left and right, the motion would be captured by the beam intermittently, and an M-mode tracing would show a dashed line (arrows). The earliest article published on fetal echocardiography in German was by Kratochwil and Eisenhut in 19671, and that in English was by Fred Winsberg in 19722. In 1963, they used an M-mode ultrasound device made by Wuhan Radio Equipment Company (c) to display the earliest M-mode fetal echocardiograms (Figure 2). gl In the early 1960s, they first observed "flashing dots" above the pelvic area of pregnant women using an A-mode ultrasound device, made by a Shanghai shipyard. [Extracted from the article]

A unified protocol is essential to ensure that fetal ultrasound measurements taken in multicentre research studies are accurate and reproducible. This paper describes the methodology used to take two-dimensional, ultrasound measurements in the longitudinal, fetal growth component of the INTERGROWTH-21(st) Project. These standardised methods should minimise the systematic errors associated with pooling data from different study sites. They represent a model for carrying out similar research studies in the future. [ABSTRACT FROM AUTHOR]

Key content: There are currently more than 100 different population‐based and customised charts in use, hence definitions of small‐for‐gestational‐age (SGA) are inconsistent.Over 130 countries have adopted the World Health Organization Child Growth Standards. These standards recognise that all children can achieve similar growth if environment, nutrition and health are optimal.The INTERGROWTH‐21st Project was a large‐scale, multicountry study that measured fetal growth of babies in utero and at birth in mothers in whom environmental, social, medical and pregnancy conditions were optimal.International standards for fetal measurement and the assessment of newborn size at birth will enable continuity of measurement from the pregnancy to childhood. Learning objectives: Understand that 97% of variation in fetal growth is caused by factors unrelated to ethnicity.When conditions for growth are optimal, fetal growth is strikingly similar around the world. Ethical issues: Consider poor fetal growth as a human rights issue: what is the legacy for individuals and societies where undernutrition has occurred in the first 1000 days of life?Recognise that, as obstetricians, we have a duty to help the most disadvantaged. The practice of ‘customising’ for ethnicity could normalise suboptimal growth. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical accuracy of the IONA® test for aneuploidy screening.Methods: This was a multicenter blinded study in which plasma samples from pregnant women at increased risk of trisomy 21 underwent cell-free DNA analysis utilizing the IONA test. For each sample, the IONA software generated a likelihood ratio and a maternal age-adjusted probability risk score for trisomies 21, 18 and 13. All results from the IONA test were compared against accepted diagnostic karyotyping.Results: A total of 442 maternal samples were obtained, of which 437 had test results available for analysis and assessment of clinical accuracy. The IONA test had a detection rate of 100% for trisomies 21 (n = 43; 95% CI, 87.98-100%), 18 (n = 10; 95% CI, 58.72-100%) and 13 (n = 5; 95% CI, 35.88-100%) with cut-offs applied to likelihood ratio (cut-off > 1 considered high risk for trisomy) and probability risk score incorporating adjustment for maternal age (cut-off ≥ 1/150 considered high risk for trisomy). The false-positive rate (FPR) was 0% for trisomies 18 and 13 with both analysis outputs. For trisomy 21, a FPR of 0.3% was observed for the likelihood ratio, but became 0% with adjustment for maternal age.Conclusion: This study indicates that the IONA test is suitable for trisomy screening in a high-risk screening population. The result-interpretation feature of the IONA software should facilitate wider implementation, particularly in local laboratories, and should be a useful addition to the current screening methods for trisomies 21, 18 and 13. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Prof Aris T. Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/December‐editorial‐2021 [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Prof Aris T. Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/September-editorial-2021 [ABSTRACT FROM AUTHOR]

An abstract of the article "Only seeing what you look for: use of a detailed ultrasound protocol is associated with increased anomaly detection rates in the first trimester" by J. Karim and others is presented.

ABSTRACT Objectives There are no international standards for relating fetal crown-rump length (CRL) to gestational age (GA), and most existing charts have considerable methodological limitations. The INTERGROWTH-21st Project aimed to produce the first international standards for early fetal size and ultrasound dating of pregnancy based on CRL measurement. Methods Urban areas in eight geographically diverse countries that met strict eligibility criteria were selected for the prospective, population-based recruitment, between 9 + 0 and 13 + 6 weeks' gestation, of healthy well-nourished women with singleton pregnancies at low risk of fetal growth impairment. GA was calculated on the basis of a certain last menstrual period, regular menstrual cycle and lack of hormonal medication or breastfeeding in the preceding 2 months. CRL was measured using strict protocols and quality-control measures. All women were followed up throughout pregnancy until delivery and hospital discharge. Cases of neonatal and fetal death, severe pregnancy complications and congenital abnormalities were excluded from the study. Results A total of 4607 women were enrolled in the Fetal Growth Longitudinal Study, one of the three main components of the INTERGROWTH-21st Project, of whom 4321 had a live singleton birth in the absence of severe maternal conditions or congenital abnormalities detected by ultrasound or at birth. The CRL was measured in 56 women at < 9 + 0 weeks' gestation; these were excluded, resulting in 4265 women who contributed data to the final analysis. The mean CRL and SD increased with GA almost linearly, and their relationship to GA is given by the following two equations (in which GA is in days and CRL in mm): mean CRL = −50.6562 + (0.815118 × GA) + (0.00535302 × GA2); and SD of CRL = −2.21626 + (0.0984894 × GA). GA estimation is carried out according to the two equations: GA = 40.9041 + (3.21585 × CRL0.5) + (0.348956 × CRL); and SD of GA = 2.39102 + (0.0193474 × CRL). Conclusions We have produced international prescriptive standards for early fetal linear size and ultrasound dating of pregnancy in the first trimester that can be used throughout the world. © 2014 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Dr Aris T. Papageorghiou, discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/june-editors-choice-2021. [ABSTRACT FROM AUTHOR]

Background: In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21(st) Project, aimed to develop international growth and size standards for fetuses.Methods: The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth--head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length--were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study.Findings: We screened 13,108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2·25 mm (SD 3·0), 0·02 mm (3·0), and -2·69 mm (3·2) for head circumference; 0·83 mm (0·9), -0·05 mm (0·8), and -0·84 mm (1·0) for biparietal diameter; 0·63 mm (1·2), 0·04 mm (1·1), and -1·05 mm (1·3) for occipitofrontal diameter; 2·99 mm (3·1), 0·25 mm (3·2), and -4·22 mm (3·7) for abdominal circumference; and 0·62 mm (0·8), 0·03 mm (0·8), and -0·65 mm (0·8) for femur length. We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth.Interpretation: We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations.Funding: Bill & Melinda Gates Foundation. [ABSTRACT FROM AUTHOR]

Background. In 2006, WHO produced international growth standards for infants and children up to age 5 years on the basis of recommendations from a WHO expert committee. Using the same methods and conceptual approach, the Fetal Growth Longitudinal Study (FGLS), part of the INTERGROWTH-21st Project, aimed to develop international growth and size standards for fetuses. Methods. The multicentre, population-based FGLS assessed fetal growth in geographically defined urban populations in eight countries, in which most of the health and nutritional needs of mothers were met and adequate antenatal care was provided. We used ultrasound to take fetal anthropometric measurements prospectively from 14 weeks and 0 days of gestation until birth in a cohort of women with adequate health and nutritional status who were at low risk of intrauterine growth restriction. All women had a reliable estimate of gestational age confirmed by ultrasound measurement of fetal crown-rump length in the first trimester. The five primary ultrasound measures of fetal growth—head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length—were obtained every 5 weeks (within 1 week either side) from 14 weeks to 42 weeks of gestation. The best fitting curves for the five measures were selected using second-degree fractional polynomials and further modelled in a multilevel framework to account for the longitudinal design of the study. Findings. We screened 13108 women commencing antenatal care at less than 14 weeks and 0 days of gestation, of whom 4607 (35%) were eligible. 4321 (94%) eligible women had pregnancies without major complications and delivered live singletons without congenital malformations (the analysis population). We documented very low maternal and perinatal mortality and morbidity, confirming that the participants were at low risk of adverse outcomes. For each of the five fetal growth measures, the mean differences between the observed and smoothed centiles for the 3rd, 50th, and 97th centiles, respectively, were small: 2-25 mm (SD 3 • 0), 0 • 02 mm (3 • 0), and -2•69 mm (3 • 2) for head circumference; 0 • 83 mm (0 • 9), -0 • 05 mm (0 • 8), and -0 •84 mm (10) for biparietal diameter; 0 -63 mm (1 • 2), 0• 04 mm (1 • 1), and -1 • 05 mm (1 • 3) for occipitofrontal diameter; 2 • 99 mm (3 • 1), 0 • 25 mm (3 • 2), and -4-•22 mm (3 • 7) for abdominal circumference; and 0-62 mm (0 • 8), 0 • 03 mm (0 • 8), and -0 • 65 mm (0 • 8) for femur length We calculated the 3rd, 5th 10th, 50th, 90th, 95th and 97th centile curves according to gestational age for these ultrasound measures, representing the international standards for fetal growth. Interpretation. We recommend these international fetal growth standards for the clinical interpretation of routinely taken ultrasound measurements and for comparisons across populations. [ABSTRACT FROM AUTHOR]

Objective Recent studies suggest that phase-rectified signal averaging ( PRSA), measured in antepartum fetal heart rate ( FHR) traces, may sensitively indicate fetal status; however, its value has not been assessed during labour. We determined whether PRSA relates to acidaemia in labour, and compare its performance to short-term variation ( STV), a related computerised FHR feature. Design Historical cohort. Setting Large UK teaching hospital. Population All 7568 Oxford deliveries that met the study criteria from April 1993 to February 2008. Methods We analysed the last 30 minutes of the FHR and associated outcomes of infants. We used computerised analysis to calculate PRSA decelerative capacity (DCPRSA), and its ability to predict umbilical arterial blood pH ≤ 7.05 using receiver operator characteristic (ROC) curves and event rate estimates (EveREst). We compared DCPRSA with STV calculated on the same traces. Main outcome measure Umbilical arterial blood pH ≤ 7.05. Results We found that PRSA could be measured in all cases. DCPRSA predicted acidaemia significantly better than STV: the area under the ROC curve was 0.665 (95% CI 0.632-0.699) for DCPRSA, and 0.606 (0.573-0.639) for STV ( P = 0.007). EveREst plots showed that in the worst fifth centile of cases, the incidence of low pH was 17.75% for DCPRSA but 11.00% for STV ( P < 0.001). DCPRSA was not highly correlated with STV. Conclusions DCPRSA of the FHR can be measured in labour, and appears to predict acidaemia more accurately than STV. Further prospective evaluation is warranted to assess whether this could be clinically useful. The weak correlation between DCPRSA and STV suggests that they could be combined in multivariate FHR analyses. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Aris T Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/march-editors-choice-2021. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Aris T Papageorghiou, highlights articles from this themed issue in an audio podcast available at: https://soundcloud.com/bjog/fetalmedicine-issue. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Dr Aris T Papageorghiou, discusses his top articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/december-editorial-2020. [ABSTRACT FROM AUTHOR]

A unified protocol is essential to ensure that fetal ultrasound measurements taken in multicentre research studies are accurate and reproducible. This paper describes the methodology used to take two-dimensional, ultrasound measurements in the longitudinal, fetal growth component of the INTERGROWTH-21st Project. These standardised methods should minimise the systematic errors associated with pooling data from different study sites. They represent a model for carrying out similar research studies in the future. [ABSTRACT FROM AUTHOR]

Background Several biomarkers for predicting intrauterine growth restriction ( IUGR) have been proposed in recent years. However, the predictive performance of these biomarkers has not been systematically evaluated. Objective To determine the predictive accuracy of novel biomarkers for IUGR in women with singleton gestations. Search strategy Electronic databases, reference list checking and conference proceedings. Selection criteria Observational studies that evaluated the accuracy of novel biomarkers proposed for predicting IUGR. Data collection and analysis Data were extracted on characteristics, quality and predictive accuracy from each study to construct 2 × 2 tables. Summary receiver operating characteristic curves, sensitivities, specificities and likelihood ratios ( LRs) were generated. Main results A total of 53 studies, including 39 974 women and evaluating 37 novel biomarkers, fulfilled the inclusion criteria. Overall, the predictive accuracy of angiogenic factors for IUGR was minimal (median pooled positive and negative LRs of 1.7, range 1.0-19.8; and 0.8, range 0.0-1.0, respectively). Two small case-control studies reported high predictive values for placental growth factor and angiopoietin-2 only when IUGR was defined as birthweight centile with clinical or pathological evidence of fetal growth restriction. Biomarkers related to endothelial function/oxidative stress, placental protein/hormone, and others such as serum levels of vitamin D, urinary albumin : creatinine ratio, thyroid function tests and metabolomic profile had low predictive accuracy. Conclusions None of the novel biomarkers evaluated in this review are sufficiently accurate to recommend their use as predictors of IUGR in routine clinical practice. However, the use of biomarkers in combination with biophysical parameters and maternal characteristics could be more useful and merits further research. [ABSTRACT FROM AUTHOR]

Background Fetal ultrasound scanning is considered vital for routine antenatal care with first trimester scans recommended for accurate estimation of gestational age (GA). A reliable estimate of gestational age is key information underpinning clinical care and allows estimation of expected date of delivery. Fetal crown-rump length (CRL) is recommended over last menstrual period for estimating GA when measured in early pregnancy i.e. 9+0-13+6 weeks. Methods The INTERGROWTH-21st Project is the largest prospective study to collect data on CRL in geographically diverse populations and with a high level of quality control measures in place. We aim to develop a new gestational age estimation equation based on the crown-rump length (CRL) from women recruited between 9+0-13+6 weeks. The main statistical challenge is modelling data when the outcome variable (GA) is truncated at both ends, i.e. at 9 and 14 weeks. We explored three alternative statistical approaches to overcome the truncation of GA. To evaluate these strategies we generated a data set with no truncation of GA that was similar to the INTERGROWTH-21st Project CRL data, which we used to explore the performance of different methods of analysis of these data when we imposed truncation at 9 and 14 weeks of gestation. These 3 methods were first tested in a simulation based study using a previously published dating equation by Verburg et al. and evaluated how well each of them performed in relation to the model from which the data were generated. After evaluating the 3 approaches using simulated data based on the Verburg equations, the best approach will be applied to the INTERGROWTH-21st Project data to estimate GA from CRL. Results Results of these rather "ad hoc" statistical methods correspond very closely to the "real data" for Verburg, a data set that is similar to the INTERGROWTH-21st project CRL data set. Conclusions We are confident that we can use these approaches to get reliable estimates based on INTERGROWTH-21st Project CRL data. These approaches may be a solution to other truncation problems involving similar data though their application to other settings would need to be evaluated. [ABSTRACT FROM AUTHOR]

Background: Intermittent preventive treatment (IPT), the main strategy to prevent malaria and reduce anaemia and low birthweight, focuses on the second half of pregnancy. However, intrauterine growth restriction may occur earlier in pregnancy. The aim of this study was to measure the effects of malaria in the first half of pregnancy by comparing the fetal biparietal diameter (BPD) of infected and uninfected women whose pregnancies had been accurately dated by crown rump length (CRL) before 14 weeks of gestation. Methodology/Principal Findings: In 3,779 women living on the Thai-Myanmar border who delivered a normal singleton live born baby between 2001-10 and who had gestational age estimated by CRL measurement <14 weeks, the observed and expected BPD z-scores (<24 weeks) in pregnancies that were (n = 336) and were not (n = 3,443) complicated by malaria between the two scans were compared. The mean (standard deviation) fetal BPD z-scores in women with Plasmodium (P) falciparum and/or P.vivax malaria infections were significantly lower than in non-infected pregnancies; -0.57 (1.13) versus -0.10 (1.17), p<0.001. Even a single or an asymptomatic malaria episode resulted in a significantly lower z-score. Fetal female sex (p<0.001) and low body mass index (p = 0.01) were also independently associated with a smaller BPD in multivariate analysis. Conclusions/Significance: Despite early treatment in all positive women, one or more (a)symptomatic P.falciparum or P.vivax malaria infections in the first half of pregnancy result in a smaller than expected mid-trimester fetal head diameter. Strategies to prevent malaria in pregnancy should include early pregnancy. [ABSTRACT FROM AUTHOR]

Background Being able to predict preterm birth is important, as it may allow a high-risk population to be selected for future interventional studies and help in understanding the pathways that lead to preterm birth. Objective To investigate the accuracy of novel biomarkers to predict spontaneous preterm birth in women with singleton pregnancies and no symptoms of preterm labour. Search strategy Electronic searches in PubMed, Embase, Cinahl, Lilacs, and Medion, references of retrieved articles, and conference proceedings. No language restrictions were applied. Selection criteria Observational studies that evaluated the accuracy of biomarkers proposed in the last decade to predict spontaneous preterm birth in asymptomatic women. We excluded studies in which biomarkers were evaluated in women with preterm labour. Data collection and analysis Two reviewers independently extracted data on study characteristics, quality, and accuracy. Data were arranged in 2 × 2 contingency tables and synthesised separately for spontaneous preterm birth before 32, 34, and 37 weeks of gestation. We used bivariate meta-analysis to estimate pooled sensitivities and specificities, and calculated likelihood ratios (LRs). Main results A total of 72 studies, including 89 786 women and evaluating 30 novel biomarkers, met the inclusion criteria. Only three biomarkers (proteome profile and prolactin in cervicovaginal fluid, and matrix metalloproteinase-8 in amniotic fluid) had positive LRs > 10. However, each of these biomarkers was evaluated in only one small study. Four biomarkers had a moderate predictive accuracy (interleukin-6 and angiogenin, in amniotic fluid; human chorionic gonadotrophin and phosphorylated insulin-like growth factor binding protein-1, in cervicovaginal fluid). The remaining biomarkers had low predictive accuracies. Conclusions None of the biomarkers evaluated in this review meet the criteria to be considered a clinically useful test to predict spontaneous preterm birth. Further large, prospective cohort studies are needed to evaluate promising biomarkers such as a proteome profile in cervicovaginal fluid. [ABSTRACT FROM AUTHOR]

The article presents a study on the natural history, intrauterine management, and outcome of pregnancies associated with giant placental chorioangioma. The study made a retrospective analysis to 19 cases of prenatally detected placental chorioangioma from January 2001 to December 2007. Results show that 18 cases are associated with various fetal complications including growth restriction, anemia, and cardiomegaly and found that specialized fetal therapy resulted to successful pregnancy.

The article discusses the guidance issued by the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) for ultrasound for Zika virus (ZIKV) infection during pregnancy. Topics covered include the steps needed for fetal abnormalities to occur due to congenital infection, the methods used for ZIKV testing and the importance of accurate estimation of gestational age (GA). Also mentioned are the processed involved in a baseline ultrasound scan.

Background: The aim was to evaluate the role of serum inhibin A and activin A in the prediction of the outcome of women with 'pregnancies of unknown location' (PULs). Methods: Serum human chorionic gonadotrophin (hCG), progesterone, inhibin A and activin A levels were measured at 0 and 48 h. Differences in the mean levels and the change in levels over 48 h expressed as a ratio (48/0 h) were examined between the three outcome groups--failing PUL, intrauterine pregnancy (IUP) or ectopic pregnancy. Variables were incorporated into logistic regression models to predict the pregnancy outcomes, which were evaluated using receiver operator characteristic curves. Results: One hundred and forty-one women were classified as PULs: 67 failing PULs (47.5%), 58 IUPs (41.1%) and 16 ectopic pregnancies (11.4%). Activin A levels were not significantly different between the three outcome groups. Inhibin A levels were significantly lower in failing PULs. The logistic regression model based on serum inhibin levels gave an area under the curve (AUC) of 0.88 for failing PUL, 0.87 for IUP and 0.60 for ectopic pregnancy. The model based on serum activin levels gave an AUC of 0.61 for failing PUL, 0.64 for IUP and 0.51 for ectopic pregnancy, and the model based on serum hCG levels gave an AUC of 0.95 for failing PUL, 0.97 for IUP and 0.67 for ectopic pregnancy. Conclusions: Serum activin A levels at 0 and 48 h are not helpful in predicting the outcome of PULs. Although serum inhibin A levels may be of use in the prediction of failing PULs and IUPs in the PUL populations, they do not perform as well as serum hCG levels. [ABSTRACT FROM AUTHOR]

For instance, pre-eclampsia is a very common condition in Obstetrics and can lead to multiple long-term maternal and neonatal complications. Systematic reviews and accompanying meta-analyses of high-quality studies are at the top of the evidence pyramid. Data availability Data sharing is not applicable to this article as no new data were created or analysed in this commentary. [Extracted from the article]

The article explores birth weight in dichorionic and monochorionic twins and trichorionic triplets. It also estimates the importance on growth of fetal number, chorionicity and gestational age. Results suggest that monochorionic twins were of lower adjusted birth weight than dichorionic twins. The effect of fetal number independent of chorionicity is revealed by the lower birth weight of trichorionic triplets compared with dichorionic twins.

Objective. To evaluate uterine balloon tamponade in the management of postpartum hemorrhage (PPH). Method and study design. Prospective audit. Setting. St George's Hospital, London. Population. Twenty-seven women with intractable PPH managed by uterine balloon tamponade using a Sengstaken-Blakemore Oesophageal Catheter (SBOC) when medical management was not effective, and prior to surgical intervention. Main outcome measures. Success rate of the SBOC in arresting hemorrhage. The need for additional measures, use of anesthesia and complication rates is reported. Results. During the study period there were 27 women who had placement of the catheter. In 22 cases (81%) hemostasis was achieved, while in five cases (19%) the SBOC failed in arresting hemorrhage. Of the five failures, hysterectomy was required in four cases and in the remaining case the failure was associated with expulsion of the balloon, but hemostasis was achieved with further conservative measures. Among the failed cases there was one maternal death due to amniotic fluid embolism with cardiac arrest and PPH secondary to coagulopathy. In cases where the balloon was successful it was removed around 24 hours later. In these cases no further bleeding was observed, and no complications occurred from the procedure. Conclusions. Placement of a SBOC successfully treats atonic PPH refractory to medical management in around 80% of cases. It is simple, inexpensive and in those with successful placement no surgical morbidity was observed. The potential for it to be used by inexperienced operators in areas with limited resources makes it a useful adjunct in management of PPH. [ABSTRACT FROM AUTHOR]

The article investigates the outcome of fetuses diagnosed with short femur length at the time of the routine anomaly scan. The finding of isolated short femur at 18-24 weeks in a population previously screened by first-trimester fetal nuchal translucency measurement is unlikely to be due to aneuploidy. Severe intrauterine growth restriction (IUGR) related to high mortality occurs in 40%, making uterine artery Doppler evaluation a useful clinical tool.

The article comments on developments related to diagnosis, treatment and prevention of pre-eclampsia. Pre-eclampsia has been reported to complicate about two percent of pregnancies and account for at least 5,000 maternal deaths per year worldwide. Antenatal care was originally developed to detect pregnancy complications at an early stage. Uterine artery Doppler may be used to assess women's risk for preterm preeclampsia.

Objective To assess the impact of introduction of the STAN monitoring system. Study design Prospective observational study. Setting Tertiary referral labour ward, St George’s Hospital, London. Population High-risk term pregnancies. Methods We report all consecutive cases of intrapartum monitoring using the STAN S 21 fetal heart monitor. Cases with adverse neonatal outcome were evaluated in relation to the ST waveform analysis and cardiotocography (CTG). Main outcome measures Cord artery metabolic acidosis, neonatal encephalopathy (NNE) and reasons behind cases with poor outcome. Results Between 2002 and 2005, there were 1502 women monitored by STAN. Based on combined STAN analysis in the 1502 women, action was indicated in 358 women (23.8%), while in 1108 women (73.8%) no action was indicated. Traces were not interpretable in 36 women (2.4%). Of the 836 cases (55.7%) where cord blood gases were available, there were 23 cases (2.8%) of metabolic acidosis and 16 of these (70%) were identified by STAN. Overall, there were 14 cases of NNE monitored by STAN. Retrospective analysis of these highlights human errors, such as poor CTG interpretation, delay in taking appropriate action and not following the guidelines. Conclusions Our experience suggests the need for more intense training on interpretation of CTG and strict adherence to guidelines. [ABSTRACT FROM AUTHOR]

Two different categories of high-order numerical methods are adopted for the electro-hydrodynamic modeling of the streamer: the finite-element method (FEM) with flux-corrected-transport (FCT) technique and the finite-volume method (FVM) with monotonic upwind-centered scheme for conservation-law (MUSCL) algorithm. Specific numerical tests on the transport equation are used to investigate the efficiency of the two methods to propagate sharp density gradients in stationary uniform and nonuniform velocity fields. The streamer simulations are performed in a positive point-to-plane electrodes filled with air at room temperature and atmospheric pressure. The influence of the numerical schemes on the 2-D streamer modeling is analyzed. Both FVM-MUSCL and FEM-FCT accurately describe the streamer propagation and the morphology of the discharge channel, thereby giving similar axial and radial density profiles. Furthermore, the computational cost is higher for the FEM-FCT solver as compared to the FVM-MUSCL one, which is at least twice as fast. However, the unstructured-grid approach adopted by FEM-FCT proves to be very efficient in describing nonuniform geometries. [ABSTRACT FROM AUTHOR]

Objective: To examine the natural history and detailed outcome of antenatally diagnosed abdominal wall defects. Methods: This was a retrospective review of the antenatal reports, pediatric surgery records and subsequent follow-up information of all cases of omphalocele and gastroschisis diagnosed in a 10-year period in our tertiary referral center. Results: There were 109 cases of abdominal wall defects, including omphalocele in 67 cases and gastroschisis in 42 cases. Of the 67 cases of omphalocele there were 26 (39%) with chromosomal abnormalities and 22 (33%) underwent termination of pregnancy, mainly for associated structural abnormalities. Of the ongoing 19 cases there were five (26%) in-utero deaths, 12 (63%) survivors and two (11%) neonatal deaths, both associated with prematurity. Excluding chromosomal abnormalities, the survival rate in isolated omphalocele was 7/16 (44%) whilst it was 5/25 (20%) in those with associated abnormalities. Gastroschisis was isolated in 40 (95%) cases. Among these 40 isolated cases there were two (5%) terminations. Of the 38 ongoing cases, there were two (5%) in-utero deaths, and 36 (95%) live births. Four of the 36 liveborn infants (11%) died in the postoperative period owing to complications of small bowel atresia. Conclusions: Although only 18% of infants with antenatally diagnosed omphalocele were alive in the neonatal period, postoperative morbidity was low. The majority (90%) of fetuses with antenatally diagnosed gastroschisis survived to delivery, but the mortality in affected newborns was 11%. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To assess the safety and efficacy of a modified fetoscopic laser ablation technique for the management of severe twin-twin transfusion syndrome (TTTS) in a large series of pregnancies. DESIGN: Prospective cohort study. SETTING: Tertiary referral fetal medicine unit. POPULATION: Women with pregnancies complicated by severe TTTS (Quintero stage III or IV), before 26 weeks of gestation. METHODS: Fetoscopic laser ablation of placental anastomoses was performed. The sonoendoscopic approach was used to identify the placental vascular equator and to photocoagulate crossing vessels. MAIN OUTCOME MEASURES: Overall survival, fetal and perinatal mortalities, gestational age at delivery, birthweight, operating time and recurrence of TTTS. RESULTS: A total of 77 women underwent the procedure. The mean gestational age at treatment was 20 (range 16-26) weeks. On average, four vessels were ablated during each procedure, with a mean operative time of 15 (range 5-25) minutes. None of the women required a repeat fetoscopic laser treatment for recurrence of the TTTS. There was at least one survivor in 74% (57/77) of pregnancies, and the overall survival rate was 57% (88/154). CONCLUSIONS: Fetoscopic laser ablation is a safe and effective form of treatment in the management of severe TTTS. The technique of identifying the common villous district of the placenta by ultrasound and photocoagulating any vessels crossing the vascular equator appears to be an acceptable alternative to both the nonselective and highly selective methods described so far. This approach is associated with a short operating time, low likelihood of TTTS recurrence or fetal anaemia and with survival results that are equivalent to previously reported techniques. [ABSTRACT FROM AUTHOR]

Objective To assess the safety and efficacy of a modified fetoscopic laser ablation technique for the management of severe twin–twin transfusion syndrome (TTTS) in a large series of pregnancies. Design Prospective cohort study. Setting Tertiary referral fetal medicine unit. Population Women with pregnancies complicated by severe TTTS (Quintero stage III or IV), before 26 weeks of gestation. Methods Fetoscopic laser ablation of placental anastomoses was performed. The sonoendoscopic approach was used to identify the placental vascular equator and to photocoagulate crossing vessels. Main outcome measures Overall survival, fetal and perinatal mortalities, gestational age at delivery, birthweight, operating time and recurrence of TTTS. Results A total of 77 women underwent the procedure. The mean gestational age at treatment was 20 (range 16–26) weeks. On average, four vessels were ablated during each procedure, with a mean operative time of 15 (range 5–25) minutes. None of the women required a repeat fetoscopic laser treatment for recurrence of the TTTS. There was at least one survivor in 74% (57/77) of pregnancies, and the overall survival rate was 57% (88/154). Conclusions Fetoscopic laser ablation is a safe and effective form of treatment in the management of severe TTTS. The technique of identifying the common villous district of the placenta by ultrasound and photocoagulating any vessels crossing the vascular equator appears to be an acceptable alternative to both the nonselective and highly selective methods described so far. This approach is associated with a short operating time, low likelihood of TTTS recurrence or fetal anaemia and with survival results that are equivalent to previously reported techniques. [ABSTRACT FROM AUTHOR]

Objective: Previous studies have examined ultrasound findings in histopathologically confirmed cases of hydatidiform mole. The aim of this study was to assess the first-trimester ultrasonographic findings in all women suspected of having hydatidiform mole on ultrasound and those subsequently diagnosed with hydatidiform mole after histological examination of removed products of conception after surgical evacuation of the uterus. The aim was to obtain a true sensitivity and positive predictive value for ultrasound in the diagnosis of hydatidiform mole.Methods: A retrospective analysis was performed of all cases of sonographically suspected hydatidiform mole and histologically proven hydatidiform mole presenting to the Early Pregnancy Unit of an inner city hospital over a 4-year period. The sensitivity and positive predictive value (PPV) of ultrasound in the detection of histologically proven hydatidiform mole was calculated.Results: The study group consisted of 90 women; 56 were suspected of having hydatidiform mole on ultrasound, and of these 27 (48%) had hydatidiform mole confirmed after histopathological examination of the products of conception, while no changes suggestive of hydatidiform mole were present in the other 29 cases. Overall, 61 women had hydatidiform mole confirmed on histology-41 (67%) partial hydatidiform moles (PHM) and 20 (33%) complete hydatidiform moles (CHM). The ultrasound findings in the 34 cases not suspected of hydatidiform mole were an empty sac in 8/34 (24%) women and a delayed miscarriage in the other 26/34 (76%). The overall sensitivity and positive predictive value for the ultrasound diagnosis of hydatidiform mole was 44% and 48%, respectively. For PHMs the respective values were 20% and 22% and for CHMs they were 95% and 40%.Conclusion: Ultrasonography is more reliable for diagnosing CHMs than for PHMs. Overall, the sensitivity of ultrasound for accurately predicting hydatidiform mole is 44%, and one in two women with an abnormal scan will have the disease confirmed on histology. [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief Dr Aris T Papageorghiou discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/sept-editorial-2020 [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Prof Aris T Papageorghiou, discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/june-editorial-2020 [ABSTRACT FROM AUTHOR]

Deputy Editor‐in‐Chief, Prof Aris T. Papageorghiou, discusses the latest thinking in women's health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/march-editorial-2020 [ABSTRACT FROM AUTHOR]