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Objective: To evaluate twin survival stratified by Quintero stage in patients with twin‐to‐twin transfusion syndrome (TTTS) after Solomon laser treatment. Methods: This was a single‐center study at Johns Hopkins Center for Fetal Therapy, investigating a cohort of consecutive twin pregnancies treated with the Solomon laser technique for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were investigated in relation to neonatal survival of the recipient and donor twins at discharge. Determinants of twin survival were evaluated using univariate logistic regression and cumulative survival probability analyses. Results: Of 402 pregnancies with TTTS that underwent Solomon laser treatment, 80 (19.9%) were diagnosed with Quintero Stage‐I TTTS, 126 (31.3%) with Stage II, 169 (42.0%) with Stage III and 27 (6.7%) with Stage IV. Post‐laser twin anemia polycythemia sequence or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser surgery. Preterm prelabor rupture of membranes occurred in 150 (37.3%) patients and median gestational age at delivery was 32 + 1 weeks. In 303 (75.4%) patients, both twins were alive at discharge; 67/80 (83.8%) were Stage I, 101/126 (80.2%) were Stage II, 113/169 (66.9%) were Stage III and 22/27 (81.5%) were Stage IV (P = 0.062). Donor twin survival was lower than that of recipients in cases with Stage‐III TTTS (118/169 (69.8%) vs 145/169 (85.8%) (χ2 = 26.076, P < 0.0001)). Higher intertwin size discordance and absent or reversed umbilical artery (UA) end‐diastolic velocity (EDV) were associated with donor demise (Nagelkerke R2, 0.38; P < 0.001). Overall, spontaneous post‐laser donor demise occurred in 53 (39.6%) patients, accounting for the majority of all losses. Cumulative donor survival decreased from 92% to 65% when intertwin size discordance was >30% and to 48% when UA‐EDV was absent or reversed (P < 0.001). Conclusions: The Solomon laser technique achieves TTTS resolution and double twin survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant intertwin size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in Stage‐III TTTS, is the primary factor preventing double survival due to a higher rate of donor demise. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We aimed to provide a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe setup. Procedural characteristics and outcomes as well as the accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9–6.0]). One pET was stopped due to fetal deceleration. The patients were delivered at 33.0 weeks [IQR 31.9–33.3] with two survivors and no neonatal transfusion requirements. The IUT volume was 48 mL [IQR 39–63 mL] and the pET volume was 32 mL [IQR 20–50], utilizing aliquots of 5–20 mL for the latter (p = 0.021). For the IUTs, the assumption of a fetal blood volume below 150 mL/kg underestimated the required transfusion volume. For the pETs, all formulas required adjustment of the dilution volume based on bedside testing (p < 0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy continue to be significant contributors to adverse perinatal outcome and maternal mortality, as well as inducing life-long cardiovascular health impacts that are proportional to the severity and frequency of pregnancy complications. The placenta is the interface between the mother and fetus and its failure to undergo vascular maturation in tandem with maternal cardiovascular adaptation by the end of the first trimester predisposes to hypertensive disorders and fetal growth restriction. While primary failure of trophoblastic invasion with incomplete maternal spiral artery remodeling has been considered central to the pathogenesis of preeclampsia, cardiovascular risk factors associated with abnormal first trimester maternal blood pressure and cardiovascular adaptation produce identical placental pathology leading to hypertensive pregnancy disorders. Outside pregnancy blood pressure treatment thresholds are identified with the goal to prevent immediate risks from severe hypertension >160/100 mm Hg and long-term health impacts that arise from elevated blood pressures as low as 120/80 mm Hg. Until recently, the trend for less aggressive blood pressure management during pregnancy was driven by fear of inducing placental malperfusion without a clear clinical benefit. However, placental perfusion is not dependent on maternal perfusion pressure during the first trimester and risk-appropriate blood pressure normalization may provide the opportunity to protect from the placental maldevelopment that predisposes to hypertensive disorders of pregnancy. Recent randomized trials set the stage for more aggressive risk-appropriate blood pressure management that may offer a greater potential for prevention for hypertensive disorders of pregnancy. Key Points Optimal management of maternal blood pressure to prevent preeclampsia and its risks is undefined. Early gestational rheological damage to the intervillous space predisposes to preeclampsia and FGR. First trimester blood pressure management may need to aim for normotension to prevent preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. Objectives: To assess the performance of existing pre-eclampsia prediction models and to develop and validate models for pre-eclampsia using individual participant data meta-analysis. We also estimated the prognostic value of individual markers. Design: This was an individual participant data meta-analysis of cohort studies. Setting: Source data from secondary and tertiary care. Predictors: We identified predictors from systematic reviews, and prioritised for importance in an international survey. Primary outcomes: Early-onset (delivery at

Abstract Background Selective fetal growth restriction in monochorionic twin pregnancies is associated with an increased risk of perinatal mortality and morbidity and represents a clinical dilemma. Interventions include expectant management with early preterm delivery if there are signs of fetal compromise, selective termination of the compromised twin, fetoscopic laser coagulation of the communicating placental vessels or termination of the whole pregnancy. Previous studies evaluating interventions have reported many different outcomes and outcome measures. Such variation makes comparing, contrasting, and combining results challenging, limiting ongoing research on this uncommon condition to inform clinical practice. We aim to produce, disseminate, and implement a core outcome set for selective fetal growth restriction research in monochorionic twin pregnancies. Methods An international steering group, including professionals, researchers, and lay experts, has been established to oversee the development of this core outcome set. The methods have been guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. Potential core outcomes will be developed by undertaking a systematic review of studies evaluating interventions for selective fetal growth restriction in monochorionic twin pregnancies. Potential core outcomes will be entered into a three-round Delphi survey and key stakeholders including clinical professionals, researchers, and lay experts will be invited to participate. Repeated reflection and rescoring of individual outcomes should encourage group and individual stakeholder convergence towards consensus outcomes which will be entered into a modified Nominal Group Technique to finalize the core outcome set. Once core outcomes have been agreed, we will establish standardized definitions and recommend high-quality measurement instruments for each outcome. Discussion The development, dissemination, and implementation of a core outcome set for selective fetal growth restriction should ensure that future research protocols select, collect, and report outcomes and outcome measures in a standardized manner. Data synthesis will be possible on a broad level and rigorous implementation should advance the quality of research studies and their effective use in order to guide clinical practice, improve patient care, maternal, short-term perinatal outcomes, and long-term neurodevelopmental outcomes. Trial registration Core Outcome Measures in Effectiveness Trials (COMET) registration number: 998. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42018092697. 18th April 2018.

Abstract Background Foetal growth restriction (FGR) refers to a foetus that does not reach its genetically predetermined growth potential. It is well recognised that growth-restricted foetuses are at increased risk of stillbirth, foetal compromise, early neonatal death and neonatal morbidity. Later in life, they are prone to health problems, including increased risk of cardiovascular diseases and neurodevelopmental disorders. Interventions for preventing and treating FGR have been studied in many trials, but evidence is often difficult to synthesise and compare because of differences in the selection and definition of outcomes. To enable future trials to measure similar, meaningful outcomes, we are developing two core outcome sets (COS) – one for prevention and the other for treatment of FGR. Methods We will review the literature to identify previously reported outcomes. An international panel of relevant stakeholders who have experience of FGR (parent or carer of a baby that was growth restricted, health professional involved in the care of mothers and babies affected by FGR, a person with expertise in FGR research) will rate the importance of each of those outcomes in a series of three sequential online rounds of a Delphi study. Participants will be able to add items to the proposed list in round 1. A final face-to-face consensus meeting will be held with representatives of each stakeholder group at which a final list of outcomes for inclusion in the COS will be agreed. Discussion The development of COSs in FGR will ensure the collection and reporting of a minimum dataset agreed by stakeholder consensus and will reduce inconsistencies in the reporting of outcomes across relevant trials. Such standardisation in the reporting of outcomes will improve synthesis of evidence and generalisability of knowledge in the future by reducing heterogeneity in outcomes between trials and thus improve the results of systematic reviews and meta-analyses. Ultimately, we hope that the COSs will lead to an improvement in the quality of evidence-based clinical practice, enhance patient care, and improve the quality and consistency of research. Trial registration Not applicable. This study is registered in the Core Outcome Measures for Effectiveness (COMET) database.

Background: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. Objectives: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non‐adherence to these guidelines will probably contribute to its failure. Search Strategy and Selection Criteria: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. Data Collection and Analysis: We analyzed the implications of 14 criteria each accounting for 0–2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk–benefit ratio of medical devices. Main Results: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre‐registration, but mainly non‐adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12–0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13–0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10–0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35–0.82) after a pessary as compared with controls. Conclusion: Non‐audited RCTs and meta‐analyses mixing studies of different clinical quality as pre‐defined by a CEP and the MDR pose the risk for erroneous conclusions. Synopsis: Our findings underline the importance of clinical audit procedures for randomized trials and specifically for the effect of cervical pessaries. [ABSTRACT FROM AUTHOR]

Abstract Background Twin–Twin Transfusion Syndrome (TTTS) is associated with an increased risk of perinatal mortality and morbidity. Several treatment interventions have been described for TTTS, including fetoscopic laser surgery, amnioreduction, septostomy, expectant management, and pregnancy termination. Over the last decade, fetoscopic laser surgery has become the primary treatment. The literature to date reports on many different outcomes, making it difficult to compare results or combine data from individual studies, limiting the value of research to guide clinical practice. With the advent and ongoing development of new therapeutic techniques, this is more important than ever. The development and use of a core outcome set has been proposed to address these issues, prioritising outcomes important to the key stakeholders, including patients. We aim to produce, disseminate, and implement a core outcome set for TTTS. Methods An international steering group has been established to oversee the development of this core outcome set. This group includes healthcare professionals, researchers and patients. A systematic review is planned to identify previously reported outcomes following treatment for TTTS. Following completion, the identified outcomes will be evaluated by stakeholders using an international, multi-perspective online modified Delphi method to build consensus on core outcomes. This method encourages the participants towards consensus ‘core’ outcomes. All key stakeholders will be invited to participate. The steering group will then hold a consensus meeting to discuss results and form a core outcome set to be introduced and measured. Once core outcomes have been agreed, the next step will be to determine how they should be measured, disseminated, and implemented within an international context. Discussion The development, dissemination, and implementation of a core outcome set in TTTS will enable its use in future clinical trials, systematic reviews and clinical practice guidelines. This is likely to advance the quality of research studies and their effective use in order to guide clinical practice and improve patient care, maternal, short-term perinatal outcomes and long-term neurodevelopmental outcomes. Trial registration Core Outcome Measures in Effectiveness Trials (COMET), 921 Registered on July 2016. International Prospective Register of Systematic Reviews (PROSPERO), CRD42016043999 . Registered on 2 August 2016.

The use of fetoscopic endoluminal tracheal occlusion in severe left-sided congenital diaphragmatic hernia may improve morbidity but did not reduce overall mortality in a North American cohort. OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%). [ABSTRACT FROM AUTHOR]

Objective: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long‐term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. Method: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. Results: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk‐benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. Conclusion: Considering these points may advance the interests of fetuses, future children, and their families. Key points: What's already known about this topic? After an initial clinical study, the risks and benefits of an experimental fetal therapy can remain uncertain.While further research is still needed to justify the integration of such therapies into standard of care, clinicians may be asked to provide them outside research. What does this study add? We propose points for consideration when deciding whether and how to offer experimental fetal therapies outside research following initial clinical studies. [ABSTRACT FROM AUTHOR]

Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.