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Objectives: To reach an international expert consensus on the diagnosis, prognosis and management of fetal lower urinary tract obstruction (LUTO) by means of a Delphi procedure, and to use this to define a core outcome set (COS). Methods: A three‐round Delphi procedure was conducted among an international panel of experts in fetal LUTO. The panel was provided with a list of literature‐based parameters to consider for the diagnosis, prognosis, management and outcomes of LUTO. A parallel procedure was conducted with patient groups during the development of the COS. Results: A total of 168 experts were approached, of whom 99 completed the first round and 80/99 (80.8%) completed all three rounds of the study questionnaires. Consensus was reached that, in the first trimester, an objective measurement of longitudinal bladder diameter of ≥ 7 mm should be used to suspect LUTO. In the second trimester, imaging parameters suggestive of LUTO could include enlarged bladder, keyhole sign, bladder wall thickening, bilateral hydronephrosis, bilateral hydroureteronephrosis and male sex. There was 79% agreement that the current prognostic scoring systems in the literature should not be used clinically. However, experts agreed on the value of amniotic fluid volume (at < 24 weeks) to predict survival and that the value of fetal intervention is to improve the chance of neonatal survival. Experts endorsed sonographic parameters suggestive of renal dysplasia, at least one vesicocentesis, and renal biochemistry for prognosis and counseling, but these items did not reach a consensus for determining candidacy for fetal intervention. On the other hand, imaging parameters suggestive of LUTO, absence of life‐limiting structural or genetic anomalies, gestational age of ≥ 16 weeks and oligohydramnios (defined as deepest vertical pocket < 2 cm) should be used as candidacy criteria for fetal intervention based on expert consensus. If bladder refill was evaluated, it should be assessed subjectively. Vesicoamniotic shunt should be the first line of fetal intervention. In the presence of suspected fetal renal failure, serial amnioinfusion should be offered only as an experimental procedure under research protocols. A COS for future LUTO studies was agreed upon. Conclusion: International consensus on the diagnosis, prognosis and management of fetal LUTO, as well as the COS, should inform clinical care and research to optimize perinatal outcomes. © 2024 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

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]

Objectives: The placental dysfunction underlying fetal growth restriction (FGR) may result in severe adverse perinatal outcome (SAPO) related to fetal hypoxia. Traditionally, the diagnostic criteria for FGR have been based on fetal size, an approach that is inherently flawed because it often results in either over‐ or underdiagnosis. The anomaly ultrasound scan at 20 weeks' gestation may be an appropriate time at which to set a benchmark for growth potential of the individual fetus. We hypothesized that the fetal growth trajectory from that point onwards may be informative regarding third‐trimester placental dysfunction. The aim of this study was to investigate the predictive value for SAPO of a slow fetal growth trajectory between 18 + 0 to 23 + 6 weeks and 32 + 0 to 36 + 6 weeks' gestation in a large, low‐risk population. Methods: This was a post‐hoc data analysis of the IUGR Risk Selection (IRIS) study, a Dutch nationwide cluster‐randomized trial assessing the (cost‐)effectiveness of routine third‐trimester sonography in reducing SAPO. In the current analysis, for the first ultrasound examination we used ultrasound data from the routine anomaly scan at 18 + 0 to 23 + 6 weeks' gestation, and for the second we used data from an ultrasound examination performed between 32 + 0 and 36 + 6 weeks' gestation. Using multilevel logistic regression, we analyzed whether SAPO was predicted by a slow fetal growth trajectory, which was defined as a decline in abdominal circumference (AC) and/or estimated fetal weight (EFW) of more than 20 percentiles or more than 50 percentiles or as an AC growth velocity (ACGV) < 10th percentile (p10). In addition, we analyzed the combination of these indicators of slow fetal growth with small‐for‐gestational age (SGA) (AC or EFW < p10) and severe SGA (AC/EFW < 3rd percentile) at 32 + 0 to 36 + 6 weeks' gestation. Results: Our sample included the data of 6296 low‐risk singleton pregnancies, among which 82 (1.3%) newborns experienced at least one SAPO. Standalone declines in AC or EFW of > 20 or > 50 percentiles or ACGV < p10 were not associated with increased odds of SAPO. EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation combined with a decline in EFW of > 20 percentiles was associated with an increased rate of SAPO. The combination of AC or EFW < p10 between 32 + 0 and 36 + 6 weeks' gestation with ACGV < p10 was also associated with increased odds of SAPO. The odds ratios of these associations were higher if the neonate was SGA at birth. Conclusions: In a low‐risk population, a slow fetal growth trajectory as a standalone criterion does not distinguish adequately between fetuses with FGR and those that are constitutionally small. This absence of association may be a result of diagnostic inaccuracies and/or post‐diagnostic (e.g. intervention and selection) biases. We conclude that new approaches to detect placental insufficiency should integrate information from diagnostic tools such as maternal serum biomarkers and Doppler ultrasound measurements. © 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 FROM AUTHOR]

Objectives: To determine the rate of emergency delivery for presumed fetal compromise after epidural analgesia (EDA) compared with that after alternative analgesia or no analgesia, and to assess whether this rate is increased in pregnancies with reduced placental reserve. Methods: This was a nationwide registry‐based cohort study of 629 951 singleton pregnancies delivered at 36 + 0 to 42 + 0 weeks of gestation that were recorded in the Dutch national birth registry between 2014 and 2018, including 120 426 cases that received EDA, 86 957 that received alternative analgesia and 422 568 that received no analgesia during labor. Pregnancies with congenital anomaly, chromosomal abnormality, fetal demise, planned Cesarean delivery, non‐cephalic presentation at delivery and use of multiple forms of analgesia were excluded. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included delivery characteristics and neonatal outcome. Negative binomial regression analysis was stratified by parity and results are presented according to birth‐weight centile, after adjusting for confounding. Results: Among women who received EDA, 13.2% underwent emergency delivery for presumed fetal compromise, compared with 4.1% of women who had no analgesia (relative risk (RR), 3.23 (95% CI, 3.16–3.31)) and 7.0% of women who received alternative analgesia (RR, 1.72 (95% CI, 1.67–1.77)). Independent of birth weight, the RR of presumed fetal compromise after EDA vs no analgesia was higher in parous women (adjusted RR (aRR), 2.15 (95% CI, 2.04–2.27)) compared with nulliparous women (RR, 1.88 (95% CI, 1.84–1.94)). Stratified for parity, the effect of EDA was modified significantly by birth‐weight centile (interaction P‐value, < 0.001 for nulliparous and 0.004 for parous women). The emergency delivery rate following EDA was highest in those with a birth weight < 5th centile (25.2% of nulliparous and 16.6% of parous women), falling with each increasing birth‐weight centile category up to the 91st–95th centile (11.8% of nulliparous and 7.2% of parous women). Conclusions: Intrapartum EDA is associated with a higher risk of emergency delivery for presumed fetal compromise compared with no analgesia and alternative analgesia, after adjusting for relevant confounding. The highest rate of emergency delivery for presumed fetal compromise was observed at the lowest birth‐weight centiles. RRs of emergency delivery for presumed fetal compromise after EDA were modestly but consistently modified by birth‐weight centile, supporting the hypothesis that the adverse effects of EDA are exacerbated by reduced placental function. While EDA provides effective pain relief during labor, alternative strategies for pain management may be preferable in pregnancies with a high background risk of fetal compromise. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked articles: There are comments on this article by Cavoretto et al., Verheggen et al., Papazova et al. and Rongen et al. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between epidural analgesia (EDA) vs patient‐controlled remifentanil analgesia (PCRA) and emergency delivery for presumed fetal compromise, in relation to birth‐weight quintile. Methods: This was a post‐hoc per‐protocol analysis of the RAVEL multicenter equivalence randomized controlled trial. Non‐anomalous singleton pregnancies between 36 + 0 and 42 + 6 weeks' gestation were randomized at the time of requesting pain relief to receive EDA or PCRA. The primary outcome was emergency delivery for presumed fetal compromise. Secondary outcomes included mode of delivery and neonatal outcomes. Analysis was performed according to birth‐weight quintile and was corrected for relevant confounding variables. Results: Of 619 pregnant women, 336 received PCRA and 283 received EDA. Among women receiving EDA, 14.8% had an emergency delivery for presumed fetal compromise, compared with 8.3% of women who received PCRA. After adjusting for parity, women receiving EDA had higher odds of presumed fetal compromise compared to those receiving PCRA (odds ratio, 1.69 (95% CI, 1.01–2.83)). A statistically significant linear‐by‐linear association was observed between presumed fetal compromise and birth‐weight quintile (P = 0.003). The incidence of emergency delivery for presumed fetal compromise was highest in women receiving EDA and delivering a neonate with a birth weight in the lowest quintile. Conclusions: Intrapartum EDA is associated with a higher rate of emergency delivery for presumed fetal compromise compared to treatment with PCRA. Birth‐weight quintile is a strong predictor of this outcome, independent of pain management method. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked articles: There are comments on this article by Cavoretto et al., Rongen et al. and van den Bosch et al. [ABSTRACT FROM AUTHOR]

Objectives: First, to compare published Doppler reference charts of the ratios of flow in the fetal middle cerebral and umbilical arteries (i.e. the cerebroplacental ratio (CPR) and umbilicocerebral ratio (UCR)). Second, to assess the association of thresholds of CPR and UCR based on these charts with short-term composite adverse perinatal outcome in a cohort of pregnancies considered to be at risk of late preterm fetal growth restriction.Methods: Studies presenting reference charts for CPR or UCR were searched for in PubMed. Formulae for plotting the median and the 10th percentile (for CPR) or the 90th percentile (for UCR) against gestational age were extracted from the publication or calculated from the published tables. Data from a prospective European multicenter observational cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks' gestation, in which fetal arterial Doppler measurements were collected longitudinally, were used to compare the different charts. Specifically, the association of UCR and CPR thresholds (CPR < 10th percentile or UCR ≥ 90th percentile and multiples of the median (MoM) values) with composite adverse perinatal outcome was analyzed. The association was also compared between chart-based thresholds and absolute thresholds. Composite adverse perinatal outcome comprised both abnormal condition at birth and major neonatal morbidity.Results: Ten studies presenting reference charts for CPR or UCR were retrieved. There were large differences between the charts in the 10th and 90th percentile values of CPR and UCR, respectively, while median values were more similar. In the gestational-age range of 28-36 weeks, there was no relationship between UCR or CPR and gestational age. From the prospective observational study, 856 pregnancies at risk of late-onset preterm fetal growth restriction were included in the analysis. The association of abnormal UCR or CPR with composite adverse perinatal outcome was similar for percentile thresholds or MoM values, as calculated from the charts, and for absolute thresholds, both on univariable analysis and after adjustment for gestational age at measurement, estimated fetal weight MoM and pre-eclampsia. The adjusted odds ratio for composite adverse perinatal outcome was 3.3 (95% CI, 1.7-6.4) for an absolute UCR threshold of ≥ 0.9 or an absolute CPR threshold of < 1.11 (corresponding to ≥ 1.75 MoM), and 1.6 (95% CI, 0.9-2.9) for an absolute UCR threshold of ≥ 0.7 to < 0.9 or an absolute CPR threshold of ≥ 1.11 to < 1.43 (corresponding to ≥ 1.25 to < 1.75 MoM).Conclusions: In the gestational-age range of 32 to 36 weeks, adjustment of CPR or UCR for gestational age is not necessary when assessing the risk of adverse outcome in pregnancies at risk of fetal growth restriction. The adoption of absolute CPR or UCR thresholds, independent of reference charts, is feasible and makes clinical assessment simpler than if using percentiles or other gestational-age normalized units. The high variability in percentile threshold values among the commonly used UCR and CPR reference charts hinders reliable diagnosis and clinical management of late preterm fetal growth restriction. © 2021 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]

At the 50 SP th sp centile, most fetuses will be at their ideal size, but some should have been at a higher centile (e.g. the 80 SP th sp centile) and thus have been constrained, with the associated perinatal and long-term risks. We interpret the uniformity of findings that the best outcomes are at the 80 SP th sp -90 SP th sp birth-weight centiles slightly differently from Prof. Visser, who states that 'optimal fetal weight at birth is not at the 50 SP th sp centile, but close to the 90 SP th sp centile'. Reduced placental function and the associated relative constraint on oxygen and nutrients impairs growth and brain development and puts fetuses at risk of perinatal mortality, most notably at the lowest centile categories. [Extracted from the article]

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]

Introduction: Birth weight to placenta weight (BWPW)-ratio is an indicator of the ability of the placenta to maintain adequate nutrient supply to the fetus. We sought to investigate the relationship between BWPW-ratio with fetal growth, utero-placental Doppler and neonatal and maternal morbidity.Methods: We studied a group of 3311 women recruited to a prospective cohort study of nulliparous women (Rosie Hospital, Cambridge, UK) who delivered a live born infant at term and whose placental weight and birth weight were known. Ultrasonic indices and BWPW ratio were converted to gestational age adjusted z scores. Analysis of continuous variables was by multivariable linear regression. BWPW ratio was also categorized (lowest or highest quintile, both referent to quintiles 2 to 4) and associations with adverse outcomes analyzed using multivariable logistic regression.Results: Lowest quintile of BWPW-ratio was associated (adjusted odds ratio [95% CI], P) with both neonatal morbidity (1.55 [1.12-2.14], 0.007) and maternal diabetes (1.75 [1.18-2.59], 0.005). Highest quintile of BWPW ratio was associated with a reduced risk of maternal obesity (0.71 [0.53 to 0.95], 0.02) and preeclampsia (0.51 [0.31 to 0.84], 0.008), but higher (adjusted z score [95% CI], P) uterine artery Doppler mean pulsatility index (PI) at 20 weeks of gestation (0.09 [0.01-0.18], 0.04) and umbilical artery Doppler PI at 36 weeks of gestation (0.16 [0.07-0.25], <0.001).Conclusion: BWPW-ratio is related to ultrasonic measurements and both neonatal and maternal morbidity. Therefore, this ratio may be an indicative marker of immediate and longer term health risks for an individual. [ABSTRACT FROM AUTHOR]

The article offers a commentary from the authors to a paper published within the issue about core outcome sets (COS) for postpartum haemorrhage (PPH). They specifically addressed the issue about the role of COS as barrier to research as it drives researchers to abandon their preferred study design, arguing that COS facilitates focused and relevant research. The standardisation of baseline characteristics for optimal comparability of studies is suggested.

A letter to the editor is presented in response to an article on the use of delphi consensus method in diagnosing fetal growth restriction.

The ex vivo human placenta perfusion model has proven to be clinically relevant to study transfer- and fetal exposure of various drugs. Although the method has existed for a long period, the setup of the perfusion model has not been generalized yet. This review aims to summarize the setups of ex vivo placental perfusion models used to examine drug transfer across the placenta to identify generalized properties and differences across setups. A literature search was carried out in PubMed September 26, 2022. Studies were labeled as relevant when information was reported, between 2000 and 2022, on the setups of ex vivo placental perfusion models used to study drug transfer across the placenta. The placenta perfusion process, and the data extraction, was divided into phases of preparation, control, drug, and experimental reflecting the chronological timeline of the different phases during the entire placental perfusion process. 135 studies describing an ex vivo human placental perfusion experiment were included. Among included studies, the majority (78.5%) analyzed drug perfusion in maternal to fetal direction, 18% evaluated bi-directional drug perfusion, 3% under equilibrium conditions, and one study investigated drug perfusion in fetal to maternal direction. This literature review facilitates the comparison of studies that employ similar placenta perfusion protocols for drug transfer studies and reveals significant disparities in the setup of these ex vivo placental perfusion models. Due to interlaboratory variability, perfusion studies are not readily comparable or interchangeable. Therefore, a stepwise protocol with multiple checkpoints for validating placental perfusion is needed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Intrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polarisation remains unknown. This study analyses macrophage density and distribution in placentas of patients with ICP compared to controls. Clinical parameters were correlated to macrophage distribution and ursodeoxycholic acid use (UDCA)., Methods: This study included routinely collected placental tissue samples of 42 women diagnosed with ICP and of 50 control pregnancies. Immunohistochemical staining was performed on placental tissue using CD68 antibody as a pan-macrophage marker, CD206 antibody as an M2 and HLA-DR antibody as an M1 macrophage marker. Macrophage density (cells/mm 2 ) and distribution (CD206 + /CD68 + or CD206 + /CD68 + HLA-DR + ) in both decidua (maternal tissue) and villous parenchyma (fetal tissue) were compared between groups. Macrophage density and distribution were correlated to clinical parameters for ICP patients., Results: The density of CD68 + macrophages differed significantly between groups in villous parenchyma. In both decidua and villous parenchyma, CD206 + /CD68 + ratio was significantly lower in ICP patients compared to controls (p = 0.003 and p=<0.001, respectively). No difference was found based on UDCA use or in CD68 + HLA-DR +  cell density. Significant correlations were found between macrophage density and peak serum bile acids and liver enzymes., Discussion: In ICP patients, an immune shift was observed in both decidual and villous tissue, indicated by a lower CD206 + /CD68 + ratio. ICP seems to affect placental tissue, however more research is required to understand its consequences., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose:  To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR)., Materials and Methods:  A prospective European multicenter observational study included women with a singleton pregnancy, 32 + 0 -36 + 6 , at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] < 10 th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of > 40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (< 0.9) or abnormal (≥ 0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements., Results:  856 women had 2770 measurements; 696 (81 %) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7 %) a UCR ≥ 0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30 % vs. 9 %, relative risk 3.2; 95 %CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67 % (95 %CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6 % (95 %CI 5-7 %). The risk of composite adverse outcome was similar using the first or subsequent UCR values., Conclusion:  An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7 % when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: To evaluate current practice and outcomes of pregnancy in women previously diagnosed with Budd-Chiari syndrome and/or portal vein thrombosis, with and without concomitant portal hypertension., Design and Setting: Multicentre retrospective cohort study between 2008 and 2021., Population: Women who conceived in the predefined period after the diagnosis of Budd-Chiari syndrome and/or portal vein thrombosis., Methods and Main Outcome Measures: We collected data on diagnosis and clinical features. The primary outcomes were maternal mortality and live birth rate. Secondary outcomes included maternal, neonatal and obstetric complications., Results: Forty-five women (12 Budd-Chiari syndrome, 33 portal vein thrombosis; 76 pregnancies) were included. Underlying prothrombotic disorders were present in 23 of the 45 women (51%). Thirty-eight women (84%) received low-molecular-weight heparin during pregnancy. Of 45 first pregnancies, 11 (24%) ended in pregnancy loss and 34 (76%) resulted in live birth of which 27 were at term (79% of live births and 60% of pregnancies). No maternal deaths were observed; one woman developed pulmonary embolism during pregnancy and two women (4%) had variceal bleeding requiring intervention., Conclusions: The high number of term live births (79%) and lower than expected risk of pregnancy-related maternal and neonatal morbidity in our cohort suggest that Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy. Individualised, nuanced counselling and a multidisciplinary pregnancy surveillance approach are essential in this patient population., Tweetable Abstract: Budd-Chiari syndrome and/or portal vein thrombosis should not be considered as an absolute contraindication for pregnancy., (© 2021 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)

Objective: Selective fetal growth restriction (sFGR) occurs in monochorionic twin pregnancies when unequal placental sharing leads to restriction in the growth of just one twin. Management options include laser separation of the fetal circulations, selective reduction or expectant management, but what constitutes the best treatment is not yet known. New trials in this area are urgently needed but, in this rare and complex group, maximizing the relevance and utility of clinical research design and outputs is paramount. A core outcome set ensures standardized outcome collection and reporting in future research. The objective of this study was to develop a core outcome set for studies evaluating treatments for sFGR in monochorionic twins., Methods: An international steering group of clinicians, researchers and patients with experience of sFGR was established to oversee the process of development of a core outcome set for studies investigating the management of sFGR. Outcomes reported in the literature were identified through a systematic review and informed the design of a three-round Delphi survey. Clinicians, researchers, and patients and family representatives participated in the survey. Outcomes were scored on a Likert scale from 1 (limited importance for making a decision) to 9 (critical for making a decision). Consensus was defined a priori as a Likert score of ≥ 8 in the third round of the Delphi survey. Participants were then invited to take part in an international meeting of stakeholders in which the modified nominal group technique was used to consider the consensus outcomes and agree on a final core outcome set., Results: Ninety-six outcomes were identified from 39 studies in the systematic review. One hundred and three participants from 23 countries completed the first round of the Delphi survey, of whom 88 completed all three rounds. Twenty-nine outcomes met the a priori criteria for consensus and, along with six additional outcomes, were prioritized in a consensus development meeting, using the modified nominal group technique. Twenty-five stakeholders participated in this meeting, including researchers (n = 3), fetal medicine specialists (n = 3), obstetricians (n = 2), neonatologists (n = 3), midwives (n = 4), parents and family members (n = 6), patient group representatives (n = 3), and a sonographer. Eleven core outcomes were agreed upon. These were live birth, gestational age at birth, birth weight, intertwin birth-weight discordance, death of surviving twin after death of cotwin, loss during pregnancy or before final hospital discharge, parental stress, procedure-related adverse maternal outcome, length of neonatal stay in hospital, neurological abnormality on postnatal imaging and childhood disability., Conclusions: This core outcome set for studies investigating the management of sFGR represents the consensus of a large and diverse group of international collaborators. Use of these outcomes in future trials should help to increase the clinical relevance of research on this condition. Consensus agreement on core outcome definitions and measures is now required. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Perinatal death (PD) is a devastating obstetric complication. Determination of cause of death helps in understanding why and how it occurs, and it is an indispensable aid to parents wanting to understand why their baby died and to determine the recurrence risk and management in subsequent pregnancy. Consequently, a perinatal death requires adequate diagnostic investigation. An important first step in the analysis of PD is to identify the case circumstances, including relevant details regarding maternal history, obstetric history and current pregnancy (complications are evaluated and recorded). In the next step, placental examination is suggested in all cases, together with molecular cytogenetic evaluation and fetal autopsy. Investigation for fetal-maternal hemorrhage by Kleihauer is also recommended as standard. In cases where parents do not consent to autopsy, alternative approaches such as minimally invasive postmortem examination, postmortem magnetic resonance imaging, and fetal photographs are good alternatives. After all investigations have been performed it is important to combine findings from the clinical review and investigations together, to identify the most probable cause of death and counsel the parents regarding their loss., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Placental pathology may explain adverse outcomes and reveal likely recurrent lesions. Stratifying women into intervention arms of a perinatal trial on the basis of the placental histopathological findings of the index pregnancy and evaluating the effect of the interventions against the placental findings at conclusion of a trial may enhance the trial. The Cochrane Central Register of Controlled Trials with "obstetrics" or "perinatal" in the Title, Abstract, or Keywords published in 2015 were classified as to whether placental pathological findings from a previous pregnancy could have been used to stratify the women into the trial and placental pathology (findings) at the end of the study trial could have explained differences in the trial results, and whether these were performed. Two hundred and twenty three of the 275 studies were not relevant. Placental pathology was an outcome measure in 2 of the remaining 52 studies. Seven trials could have benefitted by stratifying women based on previous placental pathology findings, and placental pathology findings at the end of the trial could have explained the trial results but in none of them were these performed. There were 30 trials where placental pathology could have provided an explanation for the result but review of the pathology was not undertaken in any. In the remaining 13 trials, placental pathology was unlikely to be an influence before or after the trial; however, placental pathology would have been of interest or be indicated in most of them. Placental pathology appears to be omitted from perinatal clinical trials. Seventy-four percent (37 of 50) could have benefitted by using placental pathology results of a prior pregnancy to stratify women into intervention arms or incorporating placental pathology results in the evaluation of the interventions., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Acute appendicitis during pregnancy may be associated with serious maternal and/or fetal complications. To date, the optimal clinical approach to the management of pregnant women suspected of having acute appendicitis is subject to debate. The purpose of this retrospective study was to provide recommendations for prospective clinical management of pregnant patients with suspected appendicitis., Method: Case records of all pregnant patients suspected of having appendicitis whom underwent appendectomy at our hospital between 1990 and 2010 were reviewed., Results: Appendicitis was histologically verified in fifteen of twenty-one pregnant women, of whom six were diagnosed with perforated appendicitis. Maternal morbidity was seen in two cases. Premature delivery occurred in two out of six cases with perforated appendicitis cases and two out of six cases following a negative appendectomy. Perinatal mortality did not occur., Conclusion: Both (perforated) appendicitis and negative appendectomy during pregnancy are associated with a high risk of premature delivery. Clinical presentation and imaging remains vital in deciding whether surgical intervention is indicated. We recommend to cautiously weigh the risks of delay until correct diagnosis with associated increased risk of appendiceal perforation and the risk of unnecessary surgical intervention. Based upon current literature, we recommend clinicians to consider an MRI following an inconclusive or negative abdominal ultrasound aiming to improve diagnostic accuracy to reduce the rate of negative appendectomies. Accurate and prompt diagnosis of acute appendicitis should be strived for to avoid unnecessary exploration and to aim for timely surgical intervention in pregnant women suspected of having appendicitis., (Copyright © 2015. Published by Elsevier Ltd.)

Different classification systems for the cause of intra-uterine fetal death (IUFD) are used internationally. About two thirds of these deaths are reported as unexplained and placental causes are often not addressed. Differences between systems could have consequences for the validity of vital statistics, for targeting preventive strategies and for counselling parents on recurrence risks. Our objective was to compare use of the Tulip classification with other currently used classification systems for causes of IUFD. We selected the extended Wigglesworth classification, modified Aberdeen and the classifications by Hey, Hovatta, de Galan-Roosen and Morrison. We also selected the ReCoDe system for relevant conditions, comparable to contributing factors in the Tulip classification. Panel classification for 485 IUFD cases in the different systems was performed by assessors after individual investigation of structured patient information. Distribution of cases into cause of death groups for the different systems varied, most of all for the placental and unknown groups. Systems with a high percentage of cases with an unknown cause of death and death groups consisting of clinical manifestations only are not discriminatory. Our largest cause of death group was placental pathology and classification systems without placental cause of death groups or minimal subdivision of this group are not useful in modern perinatal audit as loss of information occurs. The most frequent contributing factor was growth restriction. This illustrates the vital role of the placenta in determination of optimal fetal development. In the Tulip classification, mother, fetus and placenta are addressed together. The system has a clear defined subclassification of the placenta group, a low percentage of unknown causes and is easily applied by a multidisciplinary team. A useful classification aids future research into placental causes of IUFD.

Objective: To introduce the pathophysiological Tulip classification system for underlying cause and mechanism of perinatal mortality based on clinical and pathological findings for the purpose of counselling and prevention., Design: Descriptive., Setting: Tertiary referral teaching hospital., Population: Perinatally related deaths., Methods: A classification consisting of groups of cause and mechanism of death was drawn up by a panel through the causal analysis of the events related to death. Individual classification of cause and mechanism was performed by assessors. Panel discussions were held for cases without consensus., Main Outcome Measures: Inter-rater agreement for cause and mechanism of death., Results: The classification consists of six main causes with subclassifications: (1) congenital anomaly (chromosomal, syndrome and single- or multiple-organ system), (2) placenta (placental bed, placental pathology, umbilical cord complication and not otherwise specified [NOS]), (3) prematurity (preterm prelabour rupture of membranes, preterm labour, cervical dysfunction, iatrogenous and NOS), (4) infection (transplacental, ascending, neonatal and NOS), (5) other (fetal hydrops of unknown origin, maternal disease, trauma and out of the ordinary) and (6) unknown. Overall kappa coefficient for agreement for cause was 0.81 (95% CI 0.80-0.83). Six mechanisms were drawn up: cardio/circulatory insufficiency, multi-organ failure, respiratory insufficiency, cerebral insufficiency, placental insufficiency and unknown. Overall kappa for mechanism was 0.72 (95% CI 0.70-0.74)., Conclusions: Classifying perinatal mortality to compare performance over time and between centres is useful and necessary. Interpretation of classifications demands consistency. The Tulip classification allows unambiguous classification of underlying cause and mechanism of perinatal mortality, gives a good inter-rater agreement, with a low percentage of unknown causes, and is easily applicable in a team of clinicians when guidelines are followed.