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This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery.

Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

Objective To predict birth weight at various potential gestational ages of delivery based on data routinely available at the first antenatal visit.Design Individual participant data meta-analysis.Data sources Individual participant data of four cohorts (237 228 pregnancies) from the International Prediction of Pregnancy Complications (IPPIC) network dataset.Eligibility criteria for selecting studies Studies in the IPPIC network were identified by searching major databases for studies reporting risk factors for adverse pregnancy outcomes, such as pre-eclampsia, fetal growth restriction, and stillbirth, from database inception to August 2019. Data of four IPPIC cohorts (237 228 pregnancies) from the US (National Institute of Child Health and Human Development, 2018; 233 483 pregnancies), UK (Allen et al, 2017; 1045 pregnancies), Norway (STORK Groruddalen research programme, 2010; 823 pregnancies), and Australia (Rumbold et al, 2006; 1877 pregnancies) were included in the development of the model.Results The IPPIC birth weight model was developed with random intercept regression models with backward elimination for variable selection. Internal-external cross validation was performed to assess the study specific and pooled performance of the model, reported as calibration slope, calibration-in-the-large, and observed versus expected average birth weight ratio. Meta-analysis showed that the apparent performance of the model had good calibration (calibration slope 0.99, 95% confidence interval (CI) 0.88 to 1.10; calibration-in-the-large 44.5 g, −18.4 to 107.3) with an observed versus expected average birth weight ratio of 1.02 (95% CI 0.97 to 1.07). The proportion of variation in birth weight explained by the model (R2) was 46.9% (range 32.7-56.1% in each cohort). On internal-external cross validation, the model showed good calibration and predictive performance when validated in three cohorts with a calibration slope of 0.90 (Allen cohort), 1.04 (STORK Groruddalen cohort), and 1.07 (Rumbold cohort), calibration-in-the-large of −22.3 g (Allen cohort), −33.42 (Rumbold cohort), and 86.4 g (STORK Groruddalen cohort), and observed versus expected ratio of 0.99 (Rumbold cohort), 1.00 (Allen cohort), and 1.03 (STORK Groruddalen cohort); respective pooled estimates were 1.00 (95% CI 0.78 to 1.23; calibration slope), 9.7 g (−154.3 to 173.8; calibration-in-the-large), and 1.00 (0.94 to 1.07; observed v expected ratio). The model predictions were more accurate (smaller mean square error) in the lower end of predicted birth weight, which is important in informing clinical decision making.Conclusions The IPPIC birth weight model allowed birth weight predictions for a range of possible gestational ages. The model explained about 50% of individual variation in birth weights, was well calibrated (especially in babies at high risk of fetal growth restriction and its complications), and showed promising performance in four different populations included in the individual participant data meta-analysis. Further research to examine the generalisability of performance in other countries, settings, and subgroups is required.Trial registration PROSPERO CRD42019135045

Introduction Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin

Background Fetal growth restriction is associated with perinatal morbidity and mortality. Early identification of women having at-risk fetuses can reduce perinatal adverse outcomes. Objectives To assess the predictive performance of existing models predicting fetal growth restriction and birthweight, and if needed, to develop and validate new multivariable models using individual participant data. Design Individual participant data meta-analyses of cohorts in International Prediction of Pregnancy Complications network, decision curve analysis and health economics analysis. Participants Pregnant women at booking. External validation of existing models (9 cohorts, 441,415 pregnancies); International Prediction of Pregnancy Complications model development and validation (4 cohorts, 237,228 pregnancies). Predictors Maternal clinical characteristics, biochemical and ultrasound markers. Primary outcomes fetal growth restriction defined as birthweight 32 weeks). To assess if the performance of the prediction models is generalisable for various definitions of FGR, and assess the association between various birthweight centiles calculated using customised and population-based standards and perinatal morbidity and mortality. To estimate the net benefit (clinical utility) of the developed prediction models using decision curve analysis (DCA). To assess the costs and outcomes and the potential impact of resource use of the prediction models. Methods We followed existing recommendations for prediction model development and validation and reported in line with guidelines for prognostic research and IPD meta-analysis. Our meta-analysis utilised IPD within the IPPIC Network database. IPPIC is a living data repository of cleaned and harmonised data of pregnant women from large birth or population-based cohorts, study cohort data, registries or unpublished data from hospital records. The primary outcomes were (1) FGR defined as birthweight

Fetal therapies undertaken to improve fetal outcome or to optimize transition to neonate life often entail some level of maternal, fetal, or neonatal risk. A fetal therapy center needs access to resources to carry out such therapies and to manage maternal, fetal, and neonatal complications that might arise, either related to the therapy per se or as part of the underlying fetal or maternal condition. Accordingly, a fetal therapy center requires a dedicated operational infrastructure and necessary resources to allow for appropriate oversight and monitoring of clinical performance and to facilitate multidisciplinary collaboration between the relevant specialties. Three care levels for fetal therapy centers are proposed to match the anticipated care complexity, with appropriate resources to achieve an optimal outcome at an institutional and regional level. A level I fetal therapy center should be capable of offering fetal interventions that may be associated with obstetric risks of preterm birth or membrane rupture but that would be very unlikely to require maternal medical subspecialty or intensive care, with neonatal risks not exceeding those of moderate prematurity. A level II center should have the incremental capacity to provide maternal intensive care and to manage extreme neonatal prematurity. A level III therapy center should offer the full range of fetal interventions (including open fetal surgery) and be able manage any of the associated maternal complications and comorbidities, as well as have access to neonatal and pediatric surgical intervention including indicated surgery for neonates with congenital anomalies.

Normal neuronal cell differentiation and migration is critical to brain formation, is rapidly occurring as the fetal brain develops, and peaks at the time of the routine ultrasound anatomic survey. Abnormalities in cortical migration can signify an underlying genetic abnormality or other fetal injury that can have a profound impact on future development. Although cortical migration peaks at 20–22 weeks, cortical migration abnormalities are rarely diagnosed at the time of the anatomic survey. We describe three cases of fetal cortical abnormalities in which prenatal ultrasound imaging was instrumental to making a prompt and accurate diagnosis in the mid-trimester and for guiding clinical counseling.

Heterotopic cesarean scar pregnancy is an extremely rare form of pregnancy and is defined as an intrauterine pregnancy coexisting with an ectopic pregnancy implanted in the cesarean scar. Cesarean scar ectopic pregnancy can also be a precursor for placenta accreta spectrum, a potentially life-threatening condition in which the placenta is abnormally adherent to the uterine myometrium and possibly adjacent organs. Although cesarean scar ectopic pregnancies are rare, there has been an increase in their incidence due to the rise in cesarean deliveries. We present the case of a 35-year-old patient with a heterotopic pregnancy with ectopic implantation in a cesarean scar and associated placenta increta, as well as the radiologic evaluation of placenta accreta spectrum and subsequent management.

The study aimed to develop structured, expert-based clinical guidance on the prenatal and postnatal management of hemolytic disease of the fetus and newborn. A Delphi procedure was conducted among an international panel of experts in fetal medicine, neonatology, and hematology. Experts were selected based on their expertise, relevant publications, and affiliations. The domains were (i) prenatal workup, (ii) prenatal monitoring and management, (iii) intrauterine transfusion (IUT), (iv) delivery, and (v) postnatal management. The predefined cut-off for consensus was ≥70% agreement. One hundred-seven experts representing 25 countries across 6 continents completed the first round, and 100 (93.5%) completed the subsequent rounds. 75.3% agreed on using cfDNA to determine fetal antigen status, particularly for RhD, Kell, and Rhc antigens. The critical titer, requiring fetal monitoring via ultrasound, is considered when the threshold of ≥16 is for non-Kell antigens. 70.0% agreed on the use of maternal IVIg in pregnancies with prior IUT <24 weeks or fetal/neonatal death due to HDFN. The minimum GA for IUT is 16 to 18 weeks, and the maximum is 350/7 to 356/7 weeks. Postnatal management consensus was reached for the following: anemia labs should be investigated in the affected neonates before hospital discharge (92.0% agreement), and if they received IUT, the labs should be repeated within 1 week of discharge (84.0% agreement). 96.0% agreed that exchange transfusions should be centralized in hospitals with sufficient exposure and experience, and 92.0% agreed that the hemoglobin cut-off level to consider transfusion following hospital discharge is 7 g/dL, and the newborns need to be monitored until 2 to 3 months of age (96.0% agreement). [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To determine if the resolution of fetal growth discordance after laser surgery in pregnancies with twin‐to‐twin transfusion syndrome (TTTS) and coexisting selective fetal growth restriction (sFGR) can be predicted by estimated fetal weight (EFW) discordance recorded prior to the development of TTTS (pre‐TTTS). Methods: This was a single‐center, retrospective analysis of prospectively collected data on monochorionic twins with concurrent TTTS and sFGR that underwent laser surgery and had available growth ultrasound records from a pre‐TTTS ultrasound evaluation. Maternal demographics, pregnancy characteristics and birth outcomes were compared between three outcome groups: double twin survival with resolved sFGR determined by birth weight discordance (BWD) < 20%; double twin survival with ongoing sFGR determined by BWD ≥ 20%; and single or double fetal demise after laser surgery. One‐way analysis of variance or the Kruskal–Wallis test was used for continuous variables. The chi‐square test or Fisher's exact test was used for categorical variables. A multivariate logistic regression model was constructed based on univariate associations. Results: Ninety‐seven patients with TTTS and concurrent sFGR underwent same‐ or next‐day laser surgery after a TTTS staging ultrasound at a median gestational age of 19.4 (interquartile range (IQR), 18.0–22.3) weeks, with a median EFW discordance of 28.8% (IQR, 22.9–34.0%). At delivery, 34 (35.1%) patients had resolved sFGR with a median BWD of 7.7% (IQR, 3.5–13.0%), 34 (35.1%) had ongoing sFGR with a median BWD of 30.6% (IQR, 24.4–43.9%) and 29 (29.9%) had a single or double fetal demise. Although some characteristics available at the time of TTTS diagnosis, such as the donor umbilical artery end‐diastolic velocity (P = 0.0087) and donor umbilical artery pulsatility index (P = 0.0061), also correlated with growth outcome, multivariate logistic regression analysis identified EFW discordance at the pre‐TTTS ultrasound as the primary determinant of the odds of resolved growth discordance at birth (P = 0.0063). Conclusions: In patients undergoing laser surgery for TTTS with coexisting sFGR, a history of concordant growth at the pre‐TTTS scan prior to the development of TTTS was associated with the resolution of fetal growth discordance at birth. These findings suggest that TTTS pathophysiology can contribute to growth discordance noted at the time of TTTS diagnosis. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Objective: To determine consensus, using Delphi methodology, on the critical procedural steps for intravascular intrauterine transfusion (IUT) for the treatment of fetal anemia. Methods: We conducted a two‐part Delphi survey of international experts in fetal intervention. The first round of the survey proposed 32 potentially critical steps for the IUT procedure. Participants were asked to rate all steps on a Likert scale ranging from 1 (not important) to 5 (absolutely essential). We calculated the mean Likert score and 95% CI for all steps. Procedural steps were determined to be critical if the lower bound of the 95% CI was ≥ 3.0 and were excluded if the upper bound of the 95% CI was ≤ 3.5. In the second round of the survey, participants were asked specific questions regarding parameters associated with the procedural steps determined to be critical in the first round. Results: Overall, 49 individuals from 24 different countries (six continents) participated in both rounds of the Delphi survey. The median length of experience in fetal medicine was 21 (range, 4–38) years. The median number of IUT procedures performed annually per respondent was 20 (range, 2–80). Of the 32 proposed procedural steps, 20 were determined to be critical and 12 non‐critical procedural steps were excluded. Respondents indicated that an individual should perform a median of 20 (range, 10–50) IUT procedures during training to attain competency, and that the median number of IUT procedures required annually to maintain competency was 10 (range, 5–20). There was marked variation between respondents in how they performed the following critical IUT procedural steps: preparation of donor blood, preoperative medication, maternal anesthesia, site chosen for cordocentesis, use of fetal paralysis, method for determining fetal hematocrit, postoperative care and decision to schedule a subsequent IUT. Conclusions: The findings of this international Delphi survey can be used to standardize the approach to performing IUT. An experienced fetal interventionist should perform the procedure, and in centers in which IUT is performed infrequently, referral to a more experienced center should be considered. Calculating the specific volume of blood to transfuse at the start of the procedure and undertaking continuous fetal heart‐rate monitoring once the gestational‐age threshold for viability is reached were ranked highest in the intra‐ and postoperative phases of the procedure, respectively. © 2024 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

IntroductionWe performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC.Material and methodsOn May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409).Conclusion and discussionThis review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.

Objectives: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. Study design: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. Results: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. Conclusion: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes. [ABSTRACT FROM AUTHOR]

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]

Normal neuronal cell differentiation and migration is critical to brain formation, is rapidly occurring as the fetal brain develops, and peaks at the time of the routine ultrasound anatomic survey. Abnormalities in cortical migration can signify an underlying genetic abnormality or other fetal injury that can have a profound impact on future development. Although cortical migration peaks at 20–22 weeks, cortical migration abnormalities are rarely diagnosed at the time of the anatomic survey. We describe three cases of fetal cortical abnormalities in which prenatal ultrasound imaging was instrumental to making a prompt and accurate diagnosis in the mid-trimester and for guiding clinical counseling. [ABSTRACT FROM AUTHOR]

Objective: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. Design: Cross‐sectional survey. Setting: International. Population: Clinicians involved in the management of MCDA twin pregnancies with sFGR. Methods: A structured, self‐administered survey. Main Outcome Measures: Clinical practices and attitudes to diagnostic criteria and management strategies. Results: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter‐twin EFW discordance of >25% for the diagnosis of sFGR. For early‐onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early‐onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early‐onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early‐onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. Conclusions: There is significant variation in clinician practices and attitudes towards the management of early‐onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high‐level evidence to guide management. [ABSTRACT FROM AUTHOR]

This review describes an in-depth analysis of the neurotoxicity associated with the anesthetic agents used during fetal surgery, intending to highlight the importance of understanding the effects of general anesthetics on the developing brain, particularly in the context of open fetal surgery, where high doses are applied to facilitate surgical access and augment uterine relaxation. We examined evidence from preclinical studies in rodents and primates, along with studies in human subjects, with the results collectively suggesting that general anesthetics can disrupt brain development and lead to long-lasting neurological deficits. Our review underscores the clinical implications of these findings, indicating an association between extensive anesthetic exposure in early life and subsequent cognitive deficits. The current standard of anesthetic care for fetal surgical procedures was scrutinized, and recommendations have been proposed to mitigate the risk of anesthetic neurotoxicity. These recommendations emphasize the need for careful selection of anesthetic techniques to minimize fetal exposure to potentially harmful agents. In conclusion, while the benefits of fetal surgery in addressing immediate risks often outweigh the potential neurotoxic effects of anesthesia, the long-term developmental impacts nevertheless warrant consideration. Our analysis suggests that the use of general anesthetics in fetal surgery, especially at high doses, poses a significant risk of developmental neurotoxicity. As such, it is imperative to explore safer alternatives, such as employing different methods of uterine relaxation and minimizing the use of general anesthetics, to achieve the necessary surgical conditions. Further research, particularly in clinical settings, is essential to fully understand the risks and benefits of anesthetic techniques in fetal surgery. [ABSTRACT FROM AUTHOR]

More than 3 decades ago, a small group of physicians and other practitioners active in what they called "fetal treatment" authored an opinion piece outlining the current status and future challenges anticipated in the field. Many advances in maternal, neonatal, and perinatal care and diagnostic and therapeutic modalities have been made in the intervening years, yet a thoughtful reassessment of the basic tenets put forth in 1982 has not been published. The present effort will aim to provide a framework for contemporary redefinition of the field of fetal treatment, with a brief discussion of the necessary minimum expertise and systems base for the provision of different types of interventions for both the mother and fetus. Our goal will be to present an opinion that encourages the advancement of thoughtful practice, ensuring that current and future patients have realistic access to centers with a range of fetal therapies with appropriate expertise, experience, and subspecialty and institutional support while remaining focused on excellence in care, collaborative scientific discovery, and maternal autonomy and safety.

Abstract Background Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy. Methods A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex. Results While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively). Conclusions Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.

Abstract Background There is growing evidence of sex differences in placental vascular development. The objective of this study was to investigate the effect of fetal sex on uterine artery pulsatility index (PI) throughout gestation in a cohort of normal and complicated pregnancies. Methods A prospective longitudinal study was conducted in 240 pregnant women. Pulsed wave Doppler ultrasound of the proximal uterine arteries was performed at a 4-weekly interval between 14 and 40 weeks of gestation. The patients were classified retrospectively as normal or complicated (one or more of maternal preeclampsia, preterm birth, or small for gestational age). To assess if the change in uterine artery PI during gestation differed between normal and complicated pregnancies and between fetal sexes, the uterine artery PI was modeled using a linear function of gestational age and the rate of change was estimated from the slope. Results While the uterine artery PI did not differ over gestation between females and males for normal pregnancies, the trajectory of this index differed by fetal sex for pregnancies complicated by either preeclampsia, preterm birth, or fetal growth restriction (p < 0.0001). The male fetuses in the complicated pregnancy group had an elevated slope compared to the other groups (p < 0.0001), suggesting a more progressive deterioration in uteroplacental perfusion over gestation. Conclusions The uterine artery PI is widely used to assess uteroplacental function in clinical settings. The observation that this metric changes more rapidly in complicated pregnancies where the fetus was male highlights the importance of sex when interpreting hemodynamic markers of placental maturation.

Abstract Background Pre-eclampsia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-eclampsia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-eclampsia using individual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. Methods IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-eclampsia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-eclampsia as an outcome were included for validation. We reported the model predictive performance as discrimination (C-statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Results Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C-statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. Conclusions The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-eclampsia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. Trial registration PROSPERO ID: CRD42015029349 .