Abstract Introduction The randomized control Trial (RCT) of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE study) established its clinical efficacy for monitoring preterm fetal growth restriction (FGR). The objective of this study was to assess the clinical effectiveness of this protocol in a routine clinical setting with regards to the clinical outcomes, both overall and stratified by gestational age at FGR diagnosis. Material and Methods This is a retrospective cohort study of singleton pregnancies with preterm FGR between January 2013 and July 2024 in a tertiary Fetal Medicine Unit. FGR was defined as an estimated fetal weight or abdominal circumference <10th centile with an elevated umbilical artery pulsatility index >95th centile. Main outcomes collected included perinatal survival, interval from diagnosis to delivery, and delivery indications. Results 171 pregnancies met inclusion criteria. The median (IQR) gestation at FGR diagnosis and birth was 27+6 (25+5–29+4) and 30+3 (28+0–32+4) weeks, respectively. Overall intact neonatal survival was 90.6%, with the rate of stillbirth and neonatal death being 2.9% and 5.8%, respectively. FGR diagnosis prior to 26 weeks was associated with a three‐fold longer interval to birth compared with FGR diagnosis at 26+0–29+6 and ≥30 weeks (median of 31.0 vs. 10.0 and 14.0 days; p < 0.001). Below 32 weeks, the predominant indication for elective birth was abnormal computerized CTG with low short‐term variation (STV). Beyond 32 weeks' gestation, abnormal umbilical artery Doppler and maternal indications such as preeclampsia were more frequent. Conclusions The TRUFFLE monitoring protocol is clinically effective in managing early‐onset FGR outside a trial environment, achieving comparable perinatal outcomes to the original RCT. Routine integration of both Doppler and cCTG monitoring is crucial for optimal timing of birth with early FGR. Further research is needed to explore the benefits of more frequent or remote fetal monitoring.

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research, related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has the remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG ([email protected]). The incidence of multiple pregnancy has increased over the years, mainly due to delayed childbirth and advanced maternal age at conception and the resultant widespread use of assisted reproduction techniques1. In addition to often involving the transfer of more than one embryo, in-vitro fertilization increases the frequency of monozygotic twinning2. The twin birth rate was reported to have increased in the USA by just under 70% between 1980 (19 per 1000 live births) and 2020 (31 per 1000 live births)3, though other reports demonstrated a decline in the twin birth between 2014 and 2018 in both the USA and UK4. Twin pregnancy is associated with a high risk of perinatal mortality and morbidity5-8. There is also an increased risk of maternal complications, such as hypertensive disorders of pregnancy9. In 2019, the stillbirth rate was 7.6 per 1000 twin births compared with 3.8 per 1000 singleton births10. Preterm birth prior to 37 weeks' gestation occurs in up to 60% of multiple pregnancies, while the risk of very preterm birth prior to 32 weeks is 10 times higher in twin compared with singleton pregnancies (10% vs 1%), contributing to the increased risk of neonatal mortality and long-term morbidity11-14. Compared with singleton pregnancies, twin pregnancies are at increased risk of iatrogenic preterm birth due to the greater incidence of maternal and fetal complications. This risk is significantly higher in monochorionic compared with dichorionic pregnancy5-8. Yet, multiple pregnancies are often excluded from research studies, with only 8% of trials on fetal growth restriction (FGR), 17% of those on pre-eclampsia and 2% of those on diabetes including multiple pregnancies15. Moreover, the majority of recommendations in national and international guidelines for the management of multiple pregnancy lack high-quality robust supporting evidence16. Ultrasound assessment of chorionicity, fetal biometry, anatomy, Doppler velocimetry and amniotic fluid volume is used to identify and monitor twin pregnancies at risk of adverse outcomes, such as twin-to-twin transfusion syndrome (TTTS) and FGR. As in singletons, impaired fetal growth can be assessed in twins by comparing biometry and Doppler velocimetry parameters against standards for uncomplicated pregnancy. This guidance will address the role of ultrasound in the care of uncomplicated twin pregnancies and those complicated by TTTS, selective FGR (sFGR), twin anemia–polycythemia sequence (TAPS), twin reversed arterial perfusion (TRAP) sequence, conjoined twins and single intrauterine death (IUD). The document provides guidance on the methods used to determine gestational age and chorionicity, screening for chromosomal and structural abnormalities, and screening for TTTS, TAPS, TRAP sequence, growth abnormalities and the risk of preterm birth. The management of higher-order multiple pregnancy will be covered in a separate document. The Cochrane Library and Cochrane Register of Controlled Trials were searched for relevant randomized controlled trials (RCTs), systematic reviews and meta-analyses, and a search of MEDLINE from 1966 to 2022 was carried out. The date of the last search was 31 December 2022. In addition, relevant conference proceedings and abstracts were searched. Databases were searched using the relevant MeSH terms, including all subheadings. This was combined with a keyword search using 'twin', 'multiple', 'pregnancy', 'ultrasound', 'twin-to-twin transfusion syndrome', 'fetal growth restriction', 'twin anemia polycythemia sequence', 'twin reversed arterial perfusion', 'acardiac twin', 'monochorionic monoamniotic', 'conjoined' and 'demise'. The National Library for Health and the National Guidelines Clearing House were also searched for relevant guidelines and reviews. Gray (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections and clinical trial registries. The search was limited to the English language. When possible, recommendations are based on, and explicitly linked to, the evidence that supports them, while areas lacking evidence are annotated as 'good practice points'. Details of the grades of recommendation and levels of evidence used in these Guidelines are given in Appendix 1. The most common practice for dating twin pregnancies is to use the CRL of the larger twin in the first trimester. Some studies have recommended the use of the smaller CRL or the mean CRL, which takes into account both fetuses17-20, as studies of pregnancies conceived via assisted reproductive technology have shown that the CRL of the smaller twin correlates best with the known gestational age. The disadvantage of using the smaller CRL is the potential for the operator to believe that, in CRL-discordant pairs, the larger twin is large-for-gestational age, therefore being falsely reassured that the smaller twin is growing appropriately. One study showed that using the larger CRL did not increase the proportion of neonates classified as small-for-gestational age (SGA)20. Recommending the use of the smaller CRL would entail a significant change in practice. Generally, it would alter the due date by only a few days, and it is uncertain whether this would result in any improvement in clinical outcomes. Therefore, pending further evidence to inform this question, the recommendation is to continue with the current practice of using the CRL of the larger twin to date twin pregnancies in the first trimester. If the woman presents after 14 weeks' gestation, the head circumference of the larger twin should be used to date the pregnancy. Every effort should be made to determine the chorionicity of a twin pregnancy. Chorionicity should be determined before 13 + 6 weeks of gestation using the ultrasound features of the intertwin septum (Figure 1). It is important to examine the entire intertwin septum carefully. In dichorionic diamniotic (DCDA) twin pregnancy, the twins are separated by a thick layer of fused chorionic membranes, with two thin amniotic layers, one on each side, giving the appearance of a 'full lambda' or 'twin peak sign', compared with only two thin amniotic layers separating the two fetuses in monochorionic diamniotic (MCDA) twin pregnancy (T-sign or empty lambda sign). In women presenting for the first time after 14 weeks of gestation, chorionicity is best determined using the same ultrasound signs, in particular by counting the membrane layers, and noting whether the fetal sex is discordant. The reliability of the number of placental masses is questionable, as dichorionic placentae are commonly adjacent to each other, appearing as a single mass, and 3% of monochorionic twin pregnancies have two placental masses on ultrasound, the presence of which does not preclude the presence of vascular anastomoses21. Conversely, approximately 5% of apparently monochorionic twins were reported to be dizygotic in a Danish series22, and this phenomenon is more common in conceptions after assisted reproduction23. It is likely that using a combination of ultrasound features, rather than a single feature, would be more accurate1. If it is not possible to determine chorionicity by transabdominal ultrasound imaging, this should be attempted using transvaginal sonography. If it is still not possible to determine chorionicity, a second opinion should be sought from a tertiary referral center. If the center is uncertain about the chorionicity, it is safest to classify the pregnancy as monochorionic1 (EVIDENCE LEVEL: 3). In monochorionic twin pregnancies, amnionicity (i.e. whether or not the twins share the same amniotic sac) can be determined from 8 weeks onwards, when the amniotic sac becomes visible on ultrasound scan. In case of doubt, absence of the intertwin membrane is best confirmed by transvaginal scan. Another useful finding is demonstration of cord entanglement, which is almost universal in MCMA twin pregnancy, using color and pulsed-wave Doppler ultrasound. Using pulsed-wave Doppler, two distinct arterial waveform patterns with different heart rates are seen within the same sampling gate (EVIDENCE LEVEL: 4). Pseudo- or partial monoamnionicity is a term used to describe MCDA twin pregnancy in which the intertwin membrane has ruptured spontaneously. The term iatrogenic monoamnionicity is used when the intertwin septum in MCDA twin pregnancy is disrupted as a complication of amniocentesis or other invasive fetal procedure24, 25. All MCMA twin pregnancies should be referred to a tertiary center with expertise in their management1. It is recommended that an ultrasound image of the intertwin septum demonstrating the chorionicity is stored electronically and that a hard copy is added to the medical records. As determination of chorionicity and amnionicity is most accurate in the first trimester, when the amnion and chorion have not yet fused, the first-trimester scan is paramount in twin pregnancy (EVIDENCE LEVEL: 4). It is important to follow a reliable, consistent strategy for antenatal twin labeling. Options include: labeling according to their site, either right and left, or lower and upper; or mapping in the first trimester according to the insertion of their cords relative to the placental edges and membrane insertion. In some healthcare settings, Twin A is the fetus on the right side, while Twin B is the one on the left. Categorical information, i.e. different sex or discordance for structural anomalies, can also be used when present, as they are not likely to change with advancing gestation. This information should be documented clearly in the woman's notes in order to ensure consistent labeling during follow-up scans26. Overall, it is advisable to describe each twin using as many features as possible, so as to enable others to identify them accurately; e.g. 'Twin A (female) is on the maternal right with a posterior placenta and marginal cord insertion'. For pregnancies with discordance, the labeling should be accompanied by a description such as 'Twin A, potential recipient'. It is important to acknowledge that labeling is less accurate (or not possible) in MCMA twin pregnancy, particularly in the absence of discordance. It should be borne in mind that the twins labeled as 'Twin A' and 'Twin B' during antenatal ultrasound scans may not necessarily be delivered in that order, particularly if the mode of delivery is Cesarean section27. It is important to alert parents and healthcare professionals attending the birth to this fact, especially in pregnancies in which the twins are discordant for structural abnormalities that are not obvious on external examination, for example congenital diaphragmatic hernia or cardiac defects. In such cases, an ultrasound scan should be performed just prior to delivery and also before instigating any specific neonatal intervention. In an uncomplicated dichorionic twin pregnancy, ultrasound imaging should be performed in the first trimester, again at around 20 weeks' gestation (second-trimester anomaly scan) and every 4 weeks thereafter, unless a complication is detected which might require more frequent scans (Figure 2)1. In an uncomplicated monochorionic twin pregnancy, an ultrasound scan should be performed in the first trimester, followed by scans every 2 weeks from 16 weeks onwards, as timely detection of TTTS has been shown to improve perinatal outcome (Figure 3)28, 29 (EVIDENCE LEVEL: 4). Currently, the optimal gestational age for delivery of uncomplicated dichorionic twins is considered to be between 37 + 0 and 37 + 6 weeks, and that for uncomplicated monochorionic twins between 36 + 0 and 36 + 6 weeks, as prolongation of pregnancy beyond this stage may increase the risk of perinatal mortality30. At each ultrasound assessment, the following should be evaluated: fetal biometry, amniotic fluid volume and umbilical artery (UA) Doppler (the latter from 20 weeks' gestation in monochorionic and from 24 weeks' gestation in dichorionic twin pregnancies) for both twins. Discordance in estimated fetal weight (EFW) should be calculated and documented at each scan from 20 weeks onwards. In monochorionic twin pregnancy, middle cerebral artery (MCA) peak systolic velocity (PSV) should be recorded from 20 weeks onwards, in order to screen for TAPS. In MCDA twins, the amniotic fluid volume (deepest vertical pocket (DVP)) should be assessed and documented at each ultrasound scan, to screen for TTTS. In twin pregnancy, screening for trisomy 21 can be performed in the first trimester using the combined test, which includes maternal age, NT measurement and serum free β-hCG and PAPP-A levels1. An alternative is the combination of maternal age and the NT recorded between 11 + 0 and 13 + 6 weeks of gestation, depending on the clinical context and/or healthcare setting. The phenomenon of a vanishing twin occurs in around one in five of all twin pregnancies and is more common in those conceived via assisted reproductive technology31, 32. In a retrospective study comparing maternal serum free β-hCG and PAPP-A levels at 11–13 weeks' gestation in dichorionic pregnancies with a vanishing twin (an empty gestational sac or a dead embryo) with those in normal singleton pregnancies matched for method of conception and gestational age at examination, the levels of maternal serum free β-hCG were similar, while the PAPP-A levels were higher33. Using a modeling approach, similar performance of screening for trisomy 21 could be achieved in pregnancies with, compared to those without, a vanishing twin, provided that appropriate adjustments were made to the level of PAPP-A to account for the interval between embryonic demise and blood sampling. The researchers proposed that screening in twin pregnancies with a vanishing twin could potentially rely on a combination of maternal age, NT measurement and serum free β-hCG, as in singleton pregnancy, without the use of serum PAPP-A, and that maternal serum PAPP-A level could be included only after appropriate adjustment for the interval between embryonic demise and blood sampling33. Prospective validation of this approach is needed before its routine implementation in clinical practice. The risk of trisomy 21 in monochorionic and thus monozygotic twin pregnancy is calculated per pregnancy based on the average risk of both fetuses, whereas in dichorionic twin pregnancy the risk is calculated per fetus, because around 90% are dizygotic. It has been assumed previously that monochorionic twins would have the same chance of having Down syndrome as singletons, and dichorionic twins would have double the risk of at least one twin being affected34. However, this does not appear to be the case. It has been found that the observed-to-expected ratio of Down syndrome in twins is lower than that in singletons: 33.6% for monozygotic, 75.2% for dizygotic and 70.0% for all twins35, 36 (EVIDENCE LEVEL: 2++). The DR of the combined first-trimester test for Down syndrome may be lower in twin compared with singleton pregnancy1. However, a meta-analysis reported similar performance (89% for singletons, 86% for dichorionic twins and 87% for monochorionic twins, at a false-positive rate (FPR) of 5%)37 (EVIDENCE LEVEL: 2++). The likelihood of being offered invasive testing on the basis of a combined screening result is greater in twin compared with singleton pregnancy1. Moreover, invasive testing may carry a greater risk in twins38-40. A meta-analysis showed that the overall procedure-related loss rate following chorionic villus sampling (CVS) in twin pregnancy was 3.8%, and following amniocentesis it was 3.1%38. Other reports have cited lower loss rates: 2% following CVS and 1.5–2% following amniocentesis41. The risk was found to be similar for transabdominal vs transcervical approaches, use of a single-needle vs double-needle system, and single vs double uterine entry23, and may be attributable more to background risk factors rather than to the procedure itself42, 43 (See also 'Invasive prenatal diagnosis in twin pregnancy' section, below.) (EVIDENCE LEVEL: 2++). Screening and diagnostic testing for trisomies is more complex in twin compared with singleton pregnancy. It is important, therefore, that counseling prior to testing is provided by healthcare professionals with expertise in this area1. It is important to inform in advance women and their partners regarding the potentially complex decisions that they will need to make on the basis of the results of combined screening, bearing in mind the increased risk of invasive testing in twins, the possible discordance between dichorionic twins for fetal aneuploidy, and the risks of selective fetal reduction1. NIPT of fetal cfDNA in maternal blood for risk assessment for fetal trisomy 21 is now commonly used in clinical practice. It has the potential to overcome many of these complex issues, because it has a much higher DR and lower FPR than does the combined test44. In singletons, NIPT has a DR of > 99% for trisomy 21, with a FPR of 0.04%45. Several factors can affect the use of NIPT in twin pregnancy. First, in dichorionic twins, aneuploidy is usually discordant; if the normal twin contributes a greater fetal fraction to the cfDNA in the maternal blood, this can lead to a false-negative result46, 47. Second, NIPT has a higher failure rate in twin pregnancy, with dichorionicity, conception by in-vitro fertilization and greater maternal weight having been identified as significant predictors of failure of NIPT46, 48. Third, single-twin demise can render unreliable the results of NIPT. These early deaths are more likely to occur in an aneuploid fetus, and this can lead to unreliable results due to the continued release of cfDNA from the demised twin into the maternal circulation49, 50. Several studies have investigated the performance of NIPT in twin pregnancy. For trisomy 21, the reported DR ranges from 94% to 100%, with a failure rate of 2.9% to 9.4%45-47, 51. For trisomies 18 and 13, the DR was 60% in twins47, compared with 97.9% and 99%, respectively, in singletons45. A recent study that recruited over 1000 twin pregnancies concluded that NIPT using cfDNA testing is the most accurate screening test for trisomy 21 in twin pregnancy, with a DR of 100% and a FPR of 0%, and a low failure rate of 0.3% (lower than that reported in other studies)52. However, the performance of this test for trisomies 18 and 13 was less accurate52. An updated meta-analysis on this topic included 137 twin pregnancies with trisomy 21, 50 with trisomy 18 and 11 with trisomy 13, and over 7500 twin pregnancies unaffected by these three trisomies53. The pooled weighted DR and FPR for trisomy 21 were 99.0% and 0.02%, respectively; the equivalent figures for trisomy 18 were 93% and 0.01%, respectively, and those for trisomy 13 were 95% and 0.10%, respectively. In summary, NIPT using cfDNA is the most accurate screening test for trisomies in twin pregnancy. Nevertheless, the number of reported cases of a trisomy in twin pregnancy diagnosed using cfDNA testing remains low, and further evidence is needed (EVIDENCE LEVEL: 2++). When invasive testing for chromosomal or genetic analysis of twins is indicated or desired, it should be carried out by a fetal medicine expert. CVS is preferred in dichorionic twin pregnancy because it can be performed earlier than amniocentesis. Earlier diagnosis of any aneuploidy is particularly important in dichorionic twin pregnancy, given the lower risk of selective termination in the first compared with the second trimester54, 55. It is important to map carefully the position of the twins within the uterus. During amniocentesis in monochorionic twins, if monochorionicity has been confirmed before 14 weeks' gestation and the fetuses appear concordant for growth and anatomy, it is acceptable to sample only one amniotic sac. Otherwise, both amniotic sacs should be sampled because of the possibility of rare discordant chromosomal anomalies in monochorionic pregnancy. CVS in monochorionic pregnancy will sample only the single placenta, so will miss these rare discordant chromosomal anomalies. Discordance for most of the common human aneuploidies (trisomies 13, 18 and 21, Turner syndrome and triploidy) has been reported in monochorionic twin pairs56. In the event of heterokaryotypic monochorionic pregnancy, selective reduction by umbilical cord occlusion can be offered from 16 weeks onwards, with a survival rate of more than 80% for the healthy twin57, 58. When monochorionic twins are discordant for an abnormality, prior to invasive testing a discussion should take place regarding the complexity of selective termination, should this become necessary58 (EVIDENCE LEVEL: 3). A 2012 meta-analysis38 of amniocentesis in twin pregnancies reported a pooled 3.07% pregnancy loss rate, and a 2.54% loss rate before 24 weeks; for case–control studies, the pooled loss rates for twin pregnancies undergoing amniocentesis and for control twins were 2.59% vs 1.53% (relative risk, 1.81 (95% CI, 1.02–3.19)). No difference was found between single vs double uterine entry (EVIDENCE LEVEL: 2+). The same meta-analysis38, albeit with limited data for CVS, reported a pooled loss rate of 3.84% after CVS in twins. There were no significant differences between the transabdominal and transcervical approach, use of a single-needle system vs a double-needle system, or single uterine entry vs double uterine entry (EVIDENCE LEVEL: 2+). No significant differences in loss rates have been reported between CVS and amniocentesis in retrospective studies comparing the two methods. A study including twin pregnancy data from the years 1984–1990 reported a 3.2% loss rate after CVS vs 2.9% after amniocentesis59 (EVIDENCE LEVEL 2+). A more recent study found a non-significant difference, reporting loss rates of 3.85% and 4.0% after CVS and amniocentesis, respectively60 (EVIDENCE LEVEL: 2+). There are insufficient data to compare the loss rate related to CVS with the background risk in twins. A meta-analysis published in 202061 compared directly outcomes between women with twin pregnancy undergoing amniocentesis and those not undergoing amniocentesis, and between women undergoing CVS and those not undergoing CVS. It was found that, compared to the background rate of fetal loss, in pregnancies undergoing amniocentesis, there was no significant difference in the rate of fetal loss before 24 weeks of gestation (odds ratio (OR), 1.59; P = 0.06) or within 4 weeks after the procedure (OR, 1.38, P = 0.3). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4–3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9–4.6%) in those not undergoing amniocentesis. Similarly, there was no significant difference compared with the background rate in either overall fetal loss (OR, 1.61; P = 0.5) or fetal loss before 24 weeks of gestation (OR, 1.61; P = 0.5) following CVS. Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0–6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3–4.2%) in those not undergoing CVS. Those undergoing invasive testing may represent a selected population already at increased risk of miscarriage; two recent multicenter studies attempted to control for this while assessing the CVS procedure-related risk of miscarriage in twin pregnancy42, 43. The first study42 used multivariable logistic regression analysis with backward stepwise elimination, adjusting for maternal and pregnancy characteristics, including maternal age, racial origin and weight, method of conception, smoking status, parity, chorionicity, intertwin discordance in CRL, fetal NT ≥ 95th percentile and free β-hCG and PAPP-A multiples of the median (MoM). The authors reported that, after adjustment for maternal and pregnancy characteristics, CVS did not contribute significantly to the risk of fetal loss. They also found no significant association between fetal loss and the number of intrauterine needle insertions or needle size (LEVEL OF EVIDENCE 2++). The second of these studies43, from the same group, assessed the risk of death of at least one fetus in twin pregnancies that had CVS and those that did not, after propensity score matching (1:1 ratio) which created two comparable groups by balancing the maternal and pregnancy characteristics that led to CVS being performed. The authors reported that there was at least one fetal loss in 29 (11.2%) cases in the CVS group and in 35 (13.6%) cases in the matched non-CVS group (OR, 0.81; 95% CI, 0.48–1.35; P = 0.415). However, there was a significant interaction between the risk of fetal loss after CVS and the background risk of fetal loss: when the background risk was higher, the risk of fetal loss after CVS was lower (OR, 0.46; 95% CI, 0.23–0.90), while, in pregnancies with a lower background risk of fetal loss, the risk of fetal loss after CVS was higher (OR 2.45; 95% CI, 0.95–7.13) (LEVEL OF EVIDENCE 2++). In summary, the current evidence suggests that the contribution of amniocentesis or CVS to the risk of fetal loss in twin pregnancy is likely to be small, with procedure-related loss rates of less than 1% (though, paradoxically, the risk might be a little greater in pregnancies at lower background risk of fetal loss). The technique for amniocentesis and CVS in twin pregnancies is described in more detail in the ISUOG Practice Guidelines for invasive procedures for prenatal diagnosis62. In a dichorionic twin pregnancy, sampling of both amniotic sacs is recommended. There is a small (1.8%) risk of sampling the same sac twice with the two-puncture technique (one per sac). Using the single-puncture technique with intertwin membrane passage, the first 1–2 mL of amniotic fluid sampled after intertwin membrane passage should be discarded to avoid contamination from the first twin. If sampling of two sacs is clinically indicated, as in the case of monochorionic twin pregnancy, the two-puncture technique is recommended to avoid iatrogenic monoamnionicity (EVIDENCE LEVEL: 4). When performing CVS, it is recommended to sample the placenta near the cord insertion and to avoid the area around the dividing membrane in order to avoid unreliable or inaccurate results (which have been reported in 3–4% of cases) (EVIDENCE LEVEL: 4). A single-sampling approach around the amniotic equator is a reasonable option in monochorionic twin pregnancy (EVIDENCE LEVEL: 4). Determination of zygosity should be recommended for the laboratory analysis. It is preferred that the same operator performs the invasive diagnosis and the selective termination procedure, if needed, taking into account local protocols and the resources available. Although some studies have reported an association between first-trimester intertwin discordance in NT or CRL, or reversed a-wave in the ductus venosus (DV), and the development of TTTS, their predictive value is poor26, 63-66. NT discordance of 20% had a sensitivity of 52–64%, specificity of 78–80%, positive predictive value of 50% and negative predictive value of 86% for the development of TTTS67, 68. Discordance in NT of ≥ 20% is found in around 25% of monochorionic twin pregnancies, and the risk of early IUD or development of severe TTTS in these cases is more than 30%68. The risk of complications is less than 10% if the NT discordance is <20%68. An abnormal DV (reversed a-wave in at least one of the fetuses) will pick up only 38% of all monochorionic twin pregnancies that will subsequently develop TTTS, and, of those predicted to be at high risk, only 30% will ultimately develop TTTS65. Similarly, although intertwin discordance in CRL at 11–13 weeks' gestation is significantly associated with the risk of pregnancy loss ≥ 24 weeks, birth-weight discordance and preterm birth prior to 34 weeks' gestation, again, the predictive value is poor69, 70. Nevertheless, the management of twin pregnancy with CRL discordance ≥ 10% or NT discordance ≥ 20% should be discussed with a fetal medicine expert in accordance with local guidelines and depending on resource availability, and in these pregnancies there should be detailed ultrasound assessment and possibly testing for aneuploidy if fetal abnormalities are identified. The risk of fetal abnormality was found to be 25% in dichorionic twin pregnancies with CRL discordance ≥ 10%, compared with 4% in pregnancies with CRL discordance < 10%71. Also, CRL discordance at 7 + 0 to 9 + 6 weeks' gestation is a predictor of the risk of single fetal demise in the first trimester (DR, 74% for a FPR of 5%)72 (EVIDENCE LEVEL: 2++). At the first-trimester scan (between 11 + 0 and 13 + 6 weeks' gestation), twin fetuses should be assessed for the presence of a

OBJECTIVE:To assess whether combining estimated fetal weight (EFW) and fetal Doppler ultrasound parameters would provide information to optimize the timing of birth in monochorionic twin pregnancies and prevent adverse perinatal outcomes. STUDY DESIGN:Retrospective multicentre cohort study. SETTING:Three tertiary centres in the UK, Italy and Belgium. POPULATION:624 monochorionic twin pregnancies managed between 2013 and 2023. METHODS:Univariable and multivariable analyses assessed the association between EFW and Doppler indices taken within 2 weeks of birth. MAIN OUTCOME MEASURES:Stillbirth at any gestation or iatrogenic preterm birth before 34 weeks for suspected fetal compromise. RESULTS:The primary outcome occurred in 143 (22.9%) pregnancies with 70 cases of early PTB for fetal reasons and 73 cases of at least one IUD. Significant associations between biometric and Doppler parameters and adverse perinatal outcomes were found. The best-performing prediction models incorporated EFW discordance and umbilical artery pulsatility index (UA PI) discordance, achieving an AUC of 0.85 (95% CI 0.78-0.91) and EFW discordance and absent or reverse end diastolic flow of UA PI with an AUC of 0.86 (95% CI 0.80-0.92). The model incorporating EFW and UA PI discordance could be applied to the largest proportion of pregnancies and outperformed the currently clinical sFGR classification in predicting adverse outcomes. CONCLUSION:A model incorporating intertwin EFW discordance and UA PI discordance outperforms the current clinical classification for prediction of adverse perinatal outcomes in monochorionic pregnancies. If confirmed by further external validation studies, these findings could contribute to building a tailored risk assessment in these pregnancies.

BACKGROUND: Placenta accreta spectrum is a serious condition associated with signi ficant maternal morbidity and even mortality. The recommended treatment is hysterectomy. An alternative is 1 -step conservative surgery, which involves the en bloc resection of the myometrium affected by placenta accreta spectrum along with the placenta, followed by uterine reconstruction. Currently, there are no studies comparing the 2 techniques in the setting of a randomized controlled trial. OBJECTIVE: We performed a prospectively registered multicenter randomized controlled trial comparing hysterectomy with 1 -step conservative surgery. The aim was to collect feasibility and clinical outcomes of the 2 techniques in women assigned to hysterectomy or 1step conservative surgery. In addition to assessing participants ' willingness to be randomized, we also collected data on intraoperative blood loss, transfusion requirement, serious adverse event, and other clinical outcomes. STUDY DESIGN: Sixty women with strong antenatal suspicion of placenta accreta spectrum were assigned randomly to either hysterectomy (n=31) or 1 -step conservative surgery (n=29). RESULTS: During a 20 -month period, 60 of the 64 eligible patients (93.7%) underwent randomization. Intention -to -treat analysis showed that the clinical outcomes for 1 -step conservative surgery were comparable to those of hysterectomy (median intraoperative blood loss, 1740 mL [interquartile range, 1010 -2410] vs 1500 mL [interquartile range, 1122 - 2753]; odds ratio, 1 [1-1]; P=.942; median duration of surgery, 135 minutes [interquartile range, 111 -180] vs 155 minutes [interquartile range, 120 -185]; odds ratio, 0.99 [0.98 -1]; P=.151; transfusion rate, 58.6% vs 61.3%; odds ratio, 0.96 [0.83 -1.76]; P=.768; and adverse event rate, 17.2% vs 9.7%; odds ratio, 1.77 [0.43 -10.19]; P=.398; respectively). In the subgroup of women with type 1 class on topographic classification, all participants allocated to 1-step surgery had successful outcomes, which were superior to those of hysterectomy. This was evidenced by the shorter surgery duration (median, 125 [interquartile range, 98 -128] vs 180 [129 - 226] minutes; P=.002), lower transfusion rates (46.2% vs 82.4%), and fewer units of red blood cells transfused (median, 1 [interquartile range, 1 - 1.8] vs 3 [interquartile range, 2 -4] units; P=.007). CONCLUSION: A randomized controlled trial comparing 2 surgical techniques for the treatment of placenta accreta spectrum is feasible. One-step conservative repair is a valid alternative to hysterectomy in the large majority of cases, but this can only be ascertained following intraoperative surgical staging. El resumen esta y disponible en Espanol al final del articulo.

Congenital anomalies of the umbilical cord are associated with an increased risk of pregnancy and perinatal complications. Some anomalies of the cord have a higher prevalence than other fetal structural anomalies. The most common anomalies are the absence of an umbilical artery and velamentous insertion of the cord (with or without vasa previa). These anomalies, even when not associated with fetal structural defects, increase the risk of adverse perinatal outcome including, fetal growth restriction and stillbirth. In the absence of prenatal diagnosis, vasa previa is associated with the highest perinatal morbidity and mortality of all congenital anomalies of the umbilical cord. Most cases can be detected by ultrasound from the beginning of the second trimester and should be included in the routine mid-pregnancy ultrasound examination. Documentation should include cord insertion site, number of vessels in the cord, and if other pathologies have been detected. Pregnancies at increased risk of velamentous cord insertion should be screened for vasa previa using transvaginal ultrasound and colour Doppler imaging. If a velamentous cord insertion or isolated single umbilical artery is detected, individualised follow-up during pregnancy and tailored obstetric management are indicated.

BACKGROUND:Preeclampsia is a common condition associated with significant maternal and foetal complications. The diagnosis of preeclampsia is based on clinical criteria, with recent introduction of angiogenic markers as an aid to clinical triage. Several biomarkers are now available in a point-of-care test format, which provide swift results to support clinical decision-making. OBJECTIVES:To determine sensitivity and specificity of available point-of-care tests used for preeclampsia prediction. SEARCH STRATEGY:Systematic searches of databases (PubMed/Medline, Ovid Embase) from inception till May 2024 were done to identify relevant studies. SELECTION CRITERIA:we included studies reporting on the diagnostic test accuracy of any point-of-care test for short-term prediction of preeclampsia in the second or third trimester. DATA COLLECTION AND ANALYSIS:Data were extracted using pre-designed template, and statistical analysis was performed to pool sensitivity and specificity and a hierarchal summary receiver operating characteristic curve model was used. Quality of included studies and risk of bias were assessed following the QUADAS-2 tool. MAIN RESULTS:We identified 17 studies that met the inclusion criteria, six of which described the use of glycosylated fibronectin, five with Congo red, two with placental growth factor (PlGF) and one study each investigated nephrin, misfolded protein, CD44/FKBPL ratio and inositol phosphoglycan-P. Meta-analysis was possible only for glycosylated fibronectin with a pooled sensitivity of 0.80 (95% CI: 0.51-0.94) and a specificity of 0.84 (95% CI: 0.71-0.93). Five studies were included in meta-analysis, all of which had a low risk of bias on the QUADAS assessment. CONCLUSIONS:These findings suggest that the point-of-care glycosylated fibronectin testing might be beneficial in clinical triage for preeclampsia in an at-risk population.

Fetal heart rate (FHR) monitoring is one of the central parts of obstetric care. Ultrasound-based technologies such as cardiotocography (CTG) remain the most common method for FHR monitoring. The CTG's limitations, including subjective interpretation, high interobserver variability, and the need for skilled professionals, led to the development of computerized CTG (cCTG). While cCTG demonstrated advantages, its superiority over visual interpretation remains inconclusive. This has prompted the exploration of alternatives like noninvasive fetal electrocardiography (NIFECG). This review explores the landscape of antenatal FHR monitoring and the need for remote FHR monitoring in a patient-centered care model. Additionally, FHR monitoring needs to evolve from the traditional approach to incorporate artificial intelligence and machine learning. The review underscores the importance of aligning fetal monitoring with modern healthcare, leveraging artificial intelligence algorithms for accurate assessments, and enhancing patient engagement. The physiology of FHR variability (FHRV) is explained emphasizing its significance in assessing fetal well-being. Other measures of FHRV and their relevance are described. It delves into the promising realm of NIFECG, detailing its history and recent technological advancements. The potential advantages of NIFECG are objective FHR assessment, beat-to-beat variability, patient comfort, remote prolonged use, and less signal loss with increased maternal body mass index. Despite its promise, challenges such as signal loss must be addressed. The clinical application of NIFECG, its correlation with cCTG measures, and ongoing technological advancements are discussed. In conclusion, this review explores the evolution of antenatal FHR monitoring, emphasizing the potential of NIFECG in providing reliable, home-based monitoring solutions. Future research directions are outlined, urging longitudinal studies and evidence generation to establish NIFECG's role in enhancing fetal well-being assessments during pregnancy.

ABSTRACT Objective Antenatal growth assessment using ultrasound aims to identify small fetuses that are at higher risk of perinatal morbidity and mortality. This study explored whether the association between suboptimal fetal growth and adverse perinatal outcome varies with different definitions of fetal growth restriction (FGR) and different weight charts/standards. Methods This was a retrospective cohort study of 17 261 singleton non‐anomalous pregnancies at ≥ 24 + 0 weeks' gestation that underwent routine ultrasound at a tertiary referral hospital. Estimated fetal weight (EFW) and Doppler indices were converted into percentiles using a reference standard (INTERGROWTH‐21 st (IG‐21)) and various reference charts (Hadlock, Fetal Medicine Foundation (FMF) and Swedish). Test characteristics were assessed using the consensus definition, Society for Maternal–Fetal Medicine (SMFM) definition and Swedish criteria for FGR. Adverse perinatal outcome was defined as perinatal death, admission to the neonatal intensive care unit at term, 5‐min Apgar score < 7 and therapeutic cooling for neonatal encephalopathy. The association between FGR according to each definition and adverse perinatal outcome was compared. Multivariate logistic regression analysis was used to test the strength of association between ultrasound parameters and adverse perinatal outcome. Ultrasound parameters were also tested for correlation. Results IG‐21, Hadlock and FMF fetal size references classified as growth‐restricted 1.5%, 3.6% and 4.6% of fetuses, respectively, using the consensus definition and 2.9%, 8.8% and 10.6% of fetuses, respectively, using the SMFM definition. The sensitivity of the definition/chart combinations for adverse perinatal outcome varied from 4.4% (consensus definition with IG‐21 charts) to 13.2% (SMFM definition with FMF charts). Specificity varied from 89.4% (SMFM definition with FMF charts) to 98.6% (consensus definition with IG‐21 charts). The consensus definition and Swedish criteria showed the highest specificity, positive predictive value and positive likelihood ratio in detecting adverse outcome, irrespective of the reference chart/standard used. Conversely, the SMFM definition had the highest sensitivity across all investigated growth charts. Low EFW, abnormal mean uterine artery pulsatility index (UtA‐PI) and abnormal cerebroplacental ratio were significantly associated with adverse perinatal outcome and there was a positive correlation between the covariates. Multivariate logistic regression showed that UtA‐PI > 95 th percentile and EFW < 5 th percentile were the only parameters consistently associated with adverse outcome, irrespective of the definitions or fetal growth chart/standard used. Conclusions The apparent prevalence of FGR varies according to the definition and fetal size reference chart/standard used. Irrespective of the method of classification, the sensitivity for the identification of adverse perinatal outcome remains low. EFW, UtA‐PI and fetal Doppler parameters are significant predictors of adverse perinatal outcome. As these indices are correlated with one other, a prediction algorithm is advocated to overcome the limitations of using these parameters in isolation. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Non-invasive fetal electrocardiography (NIFECG) has potential benefits over the computerized cardiotocography (cCTG) that may permit its development in remote fetal heart-rate monitoring. Our study aims to compare signal quality and heart-rate detection from a novel self-applicable NIFECG monitor against the cCTG, and evaluate the impact of maternal and fetal characteristics on both devices. This prospective observational study took place in a university hospital in London. Women with a singleton pregnancy from 28 + 0 weeks’ gestation presenting for cCTG were eligible. Concurrent monitoring with both NIFECG and cCTG were performed for up to 60 minutes. Post-processing of NIFECG produced signal loss, computed in both 0.25 (E240)- and 3.75 (E16)-second epochs, and fetal heart-rate and maternal heart-rate values. cCTG signal loss was calculated in 3.75-second epochs. Accuracy and precision analysis of 0.25-second epochal fetal heart-rate and maternal heart-rate were compared between the two devices. Multiple regression analyses were performed to assess the impact of maternal and fetal characteristics on signal loss. ClinicalTrials.gov Identifier: NCT04941534. 285 women underwent concurrent monitoring. For fetal heart-rate, mean bias, precision and 95% limits of agreement were 0.1 beats per minute (bpm), 4.5 bpm and −8.7 bpm to 8.8 bpm, respectively. For maternal heart-rate, these results were −0.4 bpm, 3.3 bpm and −7.0 to 6.2 bpm, respectively. Median NIFECG E240 and E16 signal loss was 32.0% (interquartile range [IQR] 6.5%–68.5%) and 17.3% (IQR 1.8%–49.0%), respectively. E16 cCTG signal loss was 1.0% (IQR 0.0%–3.0%). For NIFECG, gestational age was negatively associated with signal loss (beta = −2.91, 95% CI −3.69 to −2.12, P  < 0.001). Increased body mass index, fetal movements and lower gestational age were all associated with cCTG signal loss (beta = 0.30, 95% CI 0.17–0.43, P  < 0.001; beta = 0.03, 95% CI 0.01–0.05 , P  = 0.014; and beta = −0.28, 95% CI −0.51 to −0.05, P  = 0.017, respectively). Although NIFECG is complicated by higher signal loss, it does not appear to be influenced by increased body mass index or fetal movement. NIFECG signal loss varies according to method of computation, and standards of signal acceptability need to be defined according to the ability of the device to produce clinically reliable physiological indices. The high accuracy of heart-rate indices is promising for NIFECG usage in the remote setting.

BACKGROUND:Antenatal fetal heart rate (FHR) monitoring is currently limited by hospital-based accessibility as well as the availability of relevant equipment and expertise required to position device electrodes. Ambulatory FHR monitoring in the form of noninvasive fetal electrocardiography (NIFECG) is currently an area of research interest, particularly during the era of the COVID-19 pandemic, and the potential to improve maternity care and reduce hospital attendances need to be evaluated. OBJECTIVES:To assess the feasibility, acceptability, and signal success of ambulatory NIFECG monitoring and identify research areas required to facilitate clinical utilization of this method of monitoring. METHODS:Medline, EMBASE, and PubMed databases were searched from January 2005 to April 2021 using terms relevant to antenatal ambulatory or home NIFECG. The search was compliant with PRISMA guidelines, and was registered with the PROSPERO database (CRD42020195809). All studies reporting the clinical utilization of NIFECG inclusive of its use in the ambulatory setting performed in the antenatal period, human studies, and those in the English language were included. Those reporting novel technological methods and electrophysiological algorithms, satisfaction surveys, intrapartum studies, case reports and reviews, and animal studies were excluded. Study screening and data extraction were conducted in duplicate. Risk of bias was appraised using the Modified Downs and Black tool. Due to the heterogeneity of the reported findings, a meta-analysis was not feasible. RESULTS:The search identified 193 citations, where 11 studies were deemed eligible for inclusion. All studies used a single NIFECG system with a duration of monitoring ranging from 5.6 to 21.4 h. Predefined signal acceptance threshold ranged from 34.0-80.0%. Signal success in the study populations was 48.6-95.0% and was not affected by maternal BMI. Good signals were achieved in the 2nd trimester, but less so in the early 3rd trimester. NIFECG was a well-accepted method of FHR monitoring, with up to 90.0% of women's satisfaction levels when worn during outpatient induction of labor. Placement of the acquisition device needed input from healthcare staff in every report. CONCLUSIONS:Although there is evidence for the clinical feasibility of ambulatory NIFECG, the disparity in the literature limits the ability to draw firm conclusions. Further studies to establish repeatability and device validity, whilst developing standardized FHR parameters and set evidence-based standards for signal success for NIFECG are required to ascertain the clinical benefit and potential limitations of ambulatory outpatient FHR monitoring.

Data S1. Data S2. Data S3. Data S4. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ABSTRACTObjectivesTo establish the correlation between phase‐rectified signal averaging (PRSA) outputs obtained from a novel self‐applicable non‐invasive fetal electrocardiography (NIFECG) monitor with those from computerized cardiotocography (cCTG). A secondary objective was to evaluate the potential for remote assessment of fetal wellbeing by determining the relationship between PRSA and short‐term variation (STV).MethodsThis was a prospective observational study of women with a singleton pregnancy over 28 + 0 weeks' gestation attending a London teaching hospital for cCTG assessment. Participants underwent concurrent cCTG and NIFECG monitoring for up to 60 min. Averaged accelerative (AAC) and decelerative (ADC) capacities and STV were derived by postprocessing and filtration of signals, generating fully (F) and partially (P) filtered results. Linear correlation and accuracy and precision analysis were performed to assess the relationship between PRSA outputs from cCTG and NIFECG, using varying anchor thresholds, and their association with STV.ResultsA total of 306 concurrent cCTG and NIFECG traces were collected from 285 women. F‐filtered NIFECG PRSA (eAAC/eADC) results were generated from 65% of traces, whereas cCTG PRSA (cAAC/cADC) outputs were generated from all. Strong correlations were observed between cAAC and F‐filtered eAAC (r = 0.879, P < 0.001) and between cADC and F‐filtered eADC (r = 0.895, P < 0.001). NIFECG anchor detection decreased significantly with increasing signal loss, and NIFECG PRSA indices showed considerable deviation from those of cCTG when derived from traces in which fewer than 100 anchors were detected. Removing anchor filters from NIFECG traces to generate P‐filtered PRSA outputs weakened the correlation (AAC: r = 0.505, P < 0.001; ADC: r = 0.560, P < 0.001). Lowering the anchor threshold to 100 increased the yield of eAAC and eADC outputs to approximately 74%, whilst maintaining strong correlation with cAAC (r = 0.839, P < 0.001) and cADC (r = 0.815, P < 0.001), respectively. Both cAAC and cADC showed a very strong linear relationship with cCTG STV (r = 0.928, P < 0.001 and r = 0.911, P < 0.001, respectively). Similar findings were observed with eAAC (r = 0.825, P < 0.001) and eADC (r = 0.827, P < 0.001).ConclusionsPRSA appears to be a method of fetal assessment equivalent to STV, but, due to its innate ability to eliminate artifacts, it generates interpretable NIFECG traces with high accuracy at a higher rate. These findings raise the possibility of self‐applied at‐home or remote fetal heart‐rate monitoring with automated reporting, thus enabling increased surveillance in high‐risk women without impacting on service demand. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

In February 2018, the World Health Organization published a set of recommendations for a positive childbirth experience.1 In their own words, the guideline, when delivered as a package will ensure the delivery of good-quality and evidence-based care irrespective of the setting or level of health care. In 2020, a user's manual was published to help health personnel to successfully use the Labor Care Guide (LCG).2 The usability, acceptability, and feasibility of the LCG have been tested in South America, Asia and Africa but not in high-income settings.3 How did we manage to land up in this situation? Women have been giving birth since time immemorial. Are we to take it that mankind is still unsure how to look after women in childbirth or that childbirth experience is not so positive for a significant proportion of women? A summary list of all the recommendations appears at the beginning of the documents.1, 2 We will discuss the prominent ones below. The recommendations about providing care that is respectful and with dignity is undisputed. However, the fact that this needs to be spelt out underscores the reality that there are times when women feel that they are not respected or dealt with dignity. It is recommended that women's views be taken into account when looking after the labor process. This means different things to different people. While the accoucheurs should not be reduced to doing as they are told (by the pregnant women or her partner/relatives), they should also not be making unilateral decisions thought to be in the best interest of the woman and the baby. The extent to which women wish to make decisions about their own care is variable. Apart from personal preferences it is also driven in some parts by the culture. All clinicians have been faced with this question from the patients: ‘What would you do if you were in my situation?’ This is not an unreasonable question and difficult to respond to. The guideline authors acknowledge this diversity of expectations. Exploring the extent to which the women wish to make decisions about their care would achieve a congruity between women's expectations and their actual experience. The difficulty in diagnosing onset of labor (latent as well as active phase) is well-known to practicing obstetricians and midwives. There have been attempts by WHO to remedy this by increasing the threshold of cervical dilation from 3 cm to 4 cm in the past4 and to 5 cm now in LCG1 to diagnose active phase. Some have suggested ignoring that the latent phase exists. One would expect that the new definitions of the onset of the latent and active phase are based on outcomes such as morbidity or achievement of vaginal birth. In reality, these definitions are still based on consensus of published studies, or healthcare resource use rather than either objective health outcomes or patient reported measures. The WHO suggests avoiding using the Partograph to monitor maternal and fetal condition altogether before the onset of active phase.1 The idea behind it is to avoid diagnosing active phase too early and prevent interventions due to overdiagnosis of slow or lack of progress of labor. However, neither there is a consensus nor there are clear guidelines for the management of pregnant women during the period from the onset of regular painful uterine contractions until the cervix is 5 cm dilated. With the new definition, a fairly large proportion of women can be expected to be in the latent phase, who will require some monitoring and care. Therefore, clearer recommendations are desirable for the management of latent phase of labor. We have learned from studies that the ‘normal’ rate of labor progress can be variable. Definitions held until very recently may be too stringent and can result in an excess of intervention without good justification.5, 6 A slow progress of labor is often a marker of problems, although the evidence that intervention leads to improved outcomes is difficult to come by. The new recommendations acknowledge this variability in duration of the first and the second stages of labor. Rates of progress that would be considered too slow by previously held beliefs are deemed acceptable now,7-9 and dynamic rather than static definitions are used to diagnose slow progress. Digital vaginal examination at 4-hourly intervals is recommended for routine assessment of active first stage of labor in low-risk women, and alert time threshold for each cervical dilatation are set as follows: 5 cm ≥6 h, 6 cm ≥5 h, 7 cm ≥3 h, 8 cm ≥2.5 h and 9 cm ≥2 h. Although these thresholds may make sense physiologically, their interpretation may be little more complex compared to a standard 1 cm/h rule in the active phase. Furthermore, use of a new dynamic Partograph was not shown to be more effective in reducing labor dystocia or intrapartum cesarean section rate compared with the use of a traditional static WHO Partograph in a randomized controlled trial.10 One of the most important recommendations of the LCG is perhaps the continuing careful assessment of maternal-fetal condition and progress of labor in the second stage. Whether this logical component, which was lacking in previous WHO Partograph, will have any effect on reducing adverse perinatal outcomes is not known and merits further investigation. The LCG was primarily designed to be used for the care of apparently healthy pregnant women and their babies (i.e. women with low risk pregnancies), and not as a substitute for good clinical practice. Thus, it is still important to diagnose abnormal labor, such as slow progress by regular assessment throughout labor and document care plans (eg intervene or continue monitoring, setting time-limits regarding when an intervention would be considered in consultation and agreement with the woman), as this is important both for good clinical practice and for legal reasons. Dignity, respect and clinically as well as psychologically safe environment are equally important to the care givers and the delivering women. Continuity of care is recommended, and few would disagree. However, the practical difficulties with delivering continuity of care without compromising the personal needs of the caregivers are considerable. We are not aware of any models where both the laboring woman and the accoucheur are completely satisfied. To state that ‘most women want a normal birth with good outcomes for mother and baby’ is a meaningless rhetoric. We cannot think of anyone who would want anything else. The contentious word is ‘good’. A debate is needed about what outcomes are important and to what extent patient-reported outcomes and expectations should drive healthcare practices. This becomes even more complicated because judgment can get clouded in a stressful and emotionally charged situation. Can the woman really decide what is best for the situation when she is faced with extreme distress due to labor contractions? At times, health outcomes are perfect (unharmed mother and a healthy baby) but the woman is left emotionally very traumatized. We need to acknowledge that the drivers for current practice are variable. They include healthcare setting (public/free vs private/paying), availability of resources (labor analgesia for example), differences in culture, the concern for litigation, changes in practice (higher prevalence of labor induction) and changing expectations of the society. Medical interventions during childbirth are generally intended to prevent adverse outcomes, but they may be associated with risk. Therefore, interventions without good indication are not justified. However, one cannot expect to have low intervention rate, at the same time no adverse outcome at all. The new WHO LCG may be considered too prescriptive by some. Although, the integration of items to promote quality of care as well as positive childbirth experience for women is commendable, the caregivers' perspective is not sufficiently addressed. We would argue that the underlying principles are invariant and applicable to all settings. It is the responsibility of us health professionals to test whether the guidelines work in our specific practice environments. We look forward to the completion and subsequent publication of such a study that is at the planning stage.11 The effectiveness of the LCG on objectively measured health outcomes as well as patient reported measures (outcomes and experiences) should be investigated appropriately in diverse healthcare settings.

ABSTRACTObjectivesTo evaluate the prenatal ultrasound features associated with operative complications and to assess the interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of placenta accreta spectrum (PAS) in a cohort of high‐risk patients with detailed intraoperative and histopathologic data.MethodsThis was a retrospective multicenter cohort study of patients at high risk of PAS referred for specialist perinatal care and management between January 2019 and May 2022. Deidentified ultrasound images were reviewed independently by two experienced operators blinded to clinical details, intraoperative features, outcome and histopathologic findings. The diagnosis of PAS was confirmed by failure of detachment of one or more placental cotyledons from the uterine wall at delivery, and the absence of decidua with distortion of the uteroplacental interface by fibrinoid deposition on histologic examination of the accretic areas obtained by guided sampling of partial myometrial resection or hysterectomy specimens. Patients were categorized as having a low or high likelihood of PAS at birth. Interobserver agreement of prenatal ultrasound assessment with histopathologic confirmation of PAS was assessed using the kappa statistic. Primary outcome was major operative morbidity (blood loss ≥ 2000 mL, unintentional injury to the viscera, admission to intensive care unit or death).ResultsA total of 102 women at high risk of PAS were referred, of whom 66 had evidence of PAS at birth and 36 did not. When blinded to other clinical details, the examiners agreed on the low or high probability of PAS, according to ultrasound features, in 75/102 cases (73.5%). The kappa statistic was 0.47 (95% CI, 0.28–0.66), showing moderate agreement. Morbidity was twice as common with concordant prenatal diagnosis of PAS vs concordant diagnosis of not PAS. Concordant assessment of high probability of PAS was associated with the highest morbidity (66.6%) and a very high (97.6%) likelihood of histopathologic confirmation.ConclusionsThe probability of histopathologic confirmation is very high with concordant prenatal assessment suggestive of PAS. The interobserver agreement for preoperative assessment with histopathologic confirmation of PAS is only moderate. Morbidity is associated with both histopathologic diagnosis and concordant antenatal assessment of PAS. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

ABSTRACT Objective To determine, by expert consensus through a modified Delphi process, the role of standardized and new ultrasound signs in the prenatal evaluation of patients at high risk of placenta accreta spectrum (PAS). Methods A systematic review of articles providing information on ultrasound imaging signs or markers associated with PAS was performed before the development of questionnaires for the first round of the Delphi process. Only peer‐reviewed original research studies in the English language describing one or more new ultrasound sign(s) for the prenatal evaluation of PAS were included. A three‐round consensus‐building Delphi method was then conducted under the guidance of a steering group, which included nine experts who invited an international panel of experts in obstetric ultrasound imaging in the evaluation of patients at high risk for PAS. Consensus was defined as agreement of ≥ 70% between participants. Results The systematic review identified 15 articles describing eight new ultrasound signs for the prenatal evaluation of PAS. A total of 35 external experts were approached, of whom 31 agreed and participated in the first round. Thirty external experts (97%) and seven experts from the steering group completed all three Delphi rounds. A consensus was reached that a prior history of at least one Cesarean delivery, myomectomy or PAS should be an indication for detailed PAS ultrasound assessment. The panelists also reached a consensus that seven of the 11 conventional signs of PAS should be included in the examination of high‐risk patients and the routine mid‐gestation scan report: (1) loss of the ‘clear zone’, (2) myometrial thinning, (3) bladder‐wall interruption, (4) placental bulge, (5) uterovesical hypervascularity, (6) placental lacunae and (7) bridging vessels. A consensus was not reached for any of the eight new signs identified by the systematic review. With respect to other ultrasound features that are not specific to PAS but increase the probability of PAS at birth, the panelists reached a consensus for the finding of anterior placenta previa or placenta previa with cervical involvement. The experts were also asked to determine which PAS signs should be quantified and consensus was reached only for the quantification of placental lacunae using an existing score. For predicting surgical outcome in patients with a high probability of PAS at delivery, a consensus was obtained for loss of the clear zone, bladder‐wall interruption, presence of placental lacunae and presence of placenta previa involving the cervix. Conclusions We have confirmed the continued importance of seven established standardized ultrasound signs of PAS, highlighted the role of transvaginal ultrasound in evaluating the placental position and anatomy of the cervix, and identified new ultrasound signs that may become useful in the future prenatal evaluation and management of patients at high risk for PAS at birth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

( BJOG . 2023;130:42–50) When placental villous tissue abnormally attaches to the uterine wall it is known as placenta accreta spectrum (PAS). A large number of PAS cases are seen in the setting of placenta previa and previous cesarean delivery (CD). Removing placental villous tissue at delivery typically results in hemorrhaging. This hemorrhaging has been proven to be reduced when PAS is caught before delivery. Studies show that PAS is missed before delivery in over 50% of cases. This study aimed to determine how preoperative ultrasound can help to detect PAS in patients prior to delivery.

We thank these eminent academics for their interest in our work and for acknowledging the importance of stark ethnic health inequalities in maternity outcomes in the UK.1 We welcome open and balanced academic discourse but were disappointed to see the term ‘racial inequalities’ in their communication to the Journal. Race is perceived as inherent in biology, inherited across generations and therefore potentially unmodifiable. In contrast, ethnicity is understood as something we acquire based on factors like where we live, or the culture and interaction we share with others and as such, may be modifiable. The importance of this distinction was recently highlighted in the ethnic health inequalities report from the NHS Race and Health Observatory (NHS RHO).2 The link between race, ethnicity and health is complex, with black and minority ethnic groups paradoxically comparing favourably with white groups for some measures of health. What is evident is that black and minority ethnic groups are disproportionately affected by socio-economic deprivation—a key determinant of health status. This may seem a trivial point, but this type of unconscious bias may lead to a lack of understanding of the causality (and solutions) to the health inequalities that we seek to address. The pregnancy risk assessment prediction model used in our study was developed by the Fetal Medicine Foundation (FMF) and then externally validated in a large head-to-head comparison with the NICE risk assessment checklist in current use, in a study funded by the NIHR.3 The FMF then conducted a randomised trial to demonstrate the efficacy of a screening programme using the risk prediction model, followed by targeted aspirin prophylaxis and serial ultrasound scans; this significantly reduced the prevalence of preterm pre-eclampsia.3 We implemented the protocol from this trial into a routine NHS setting and—using interrupted time series (ITS) analysis—demonstrated its effectiveness, with relative effect reductions in preterm pre-eclampsia by 80% and term small-for-gestational age birth (SGA) birth by 45%.3, 4 In the strengths and limitations section of our manuscript we state the reasons why an ITS analysis would have been optimal, but that the total number of index events in the minimum required time period epochs before and after the intervention precluded this approach. The correspondents raise the important point that the prediction model has not been investigated for its impact on perinatal death, and here the authors overlook two important issues. First, the use of a risk prediction model in isolation is very unlikely to change outcome in the absence of effective interventions. Secondly, pre-eclampsia, SGA birth and stillbirth are outcomes of the overarching disorder of placental dysfunction. SGA and hypertensive disorders of pregnancy alone contribute approximately 30% of the population attributable risk to stillbirth as well as being major causes of preterm birth predisposing to neonatal death.5 Our previous publications on the effect of the screening programme on identifying reducing preterm pre-eclampsia and term SGA birth is consistent with the finding in the current study of a much greater 72% reduction in PND associated with both of these conditions, compared with a 37% reduction in the overall population.4, 6 Pre-eclampsia and SGA birth are more common in black and ethnic minority women, explaining the very specific finding of a three-fold reduction in PND in this group of women compared with white women, in whom the PND rate was unchanged following the implementation of the screening programme. The correspondents also suggest that variable dose of aspirin in the before and after arms of the study may have biased results. To the best of our knowledge there are no studies that demonstrate efficacy of aspirin prophylaxis of any dose in preventing perinatal death, and such bias is therefore unlikely. We do not claim that implementation of the screening test alone accounted for the reduction in perinatal mortality—rather we made clear our hypothesis, namely, that the programme of interventions may have had a beneficial impact. We agree with the authors that post-hoc analysis when performed may be unreliable, but this does not translate as ‘all post-hoc analyses are unreliable’. This is also true of secondary analyses conducted from randomised controlled trials (RCTs) and we are certain that the authors would not claim that all such analyses should be disregarded. We are unsure what groups the correspondents are referring to when they state that we relied on overlapping confidence intervals and non-significant P-values between study groups. We re-iterate that in the (pre-intervention) NICE cohort, the perinatal death rate was significantly higher in non-white than white women (7.95 versus 2.63/1000 births, odds ratio [OR] 3.035, 95% confidence interval [CI] 1.551–5.941). Following the introduction of FMF screening (post-intervention), the perinatal death rate in non-white women was no longer significantly different from white women (3.22 vs. 2.55/1000 births, OR 1.261, 95% CI 0.641–2.483). Finally, they state that they did not find any subgroup effect in their test for interaction in the reported data. Presumably, they tested the difference between perinatal death rates between the NICE and FMF screened groups, adding ethnicity as an interaction term. Not finding a significant effect for this particular subgroup interaction test does not negate our study findings—as the authors themselves state their letter, is ‘a classic case of misinterpreting absence of evidence as evidence of absence’. The problem of ethnic health inequality in maternity care and pregnancy outcomes has been evident for several decades.7 The COVID-19 pandemic has brought such inequity to the fore and a plan of action in this area was proposed this week in the Government’s response to the Commission on Race and Ethnic Disparities report.8 The arbitrary use of screening thresholds in risk assessment has put the pursuit of perfection in the way of progress, leaving maternity services reliant on a checklist-based approach developed 60 years ago. We do, however, acknowledge and understand the complex service/resource balance highlighted by Dr Ash Paul. The RCOG and RCM— funded by Tommy’s Charity—co-developed the Tommy’s National Centre for Maternity Improvement (NCfMI), which is championing the use of digital health technology to produce personalised risk assessment in a collaborative and focused initiative to improve ethnic health inequalities.9 The NCfMI is actively seeking support, independent of current NHS funding, to undertake a study involving 20–30 hospitals. We look forward to working closely with healthcare practitioners, academics and policy makers in tackling the unnecessary and unwanted problem of ethnic and social disparity in maternal healthcare. None declared. Completed disclosure of interest forms are available to view online as supporting information. All authors contributed to the writing of this correspondence. Dr Becky Liu’s post was funded by an unrestricted grant from Biorithm Pte Ltd. The funders were not involved in the drafting of this correspondence. 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