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Gene therapy is an important tool for treating fetal diseases that allows for the delivery and integration of therapeutic genes into the genome of cells carrying mutations. Nanomolecules, like PAMAM dendrimers, have recently come into wider use for carrying vectors as they have several advantages over viral vectors. Namely, (1) tunable size and surface chemistry, (2) uniform size, (3) the ability to target specific tissues, and (4) the ability to carry large biomolecules and drugs. Recently, we demonstrated that 4th generation (G4) PAMAM dendrimer with a cystamine core and a non-toxic surface having 90% –OH and 10% –NH2 groups (D-Cys) could cross the blood–brain barrier following injection into the bloodstream. In the current study, as a proof of concept, we delivered the dendrimers alone (D-Cys) tagged with Cy5.5 (D-Cys-cy5.5) to healthy pregnant C57BL/6J mice to determine the fate of these dendrimers in the pregnant mice as well as in the fetus. Systematic diffusion of the D-Cys-cy5.5 was evaluated on gestational day 17 (3 days after injection) using in vivo imaging. This revealed that the dendrimer was taken up into circulation and away from the injection site. Analysis of sections by fluorescence microscopy showed that D-Cys-cy5.5 was able to successfully cross the maternal blood–brain barrier. However, analysis of the fetal brains failed to detect dendrimers in the central nervous system (CNS). Instead, they appeared to be retained in the placenta. This is one of the first studies to analyze the distribution of surface-modified PAMAM dendrimer in the pregnant mouse and fetus following systemic injection. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the accuracy of combined models of maternal biophysical factors, ultrasound, and biochemical markers for predicting stillbirths.A retrospective cohort study of pregnant women undergoing first‐trimester pre‐eclampsia screening at 11–13 gestational weeks was conducted. Maternal characteristics and history, mean arterial pressure (MAP) measurement, uterine artery pulsatility index (UtA‐PI) ultrasound, maternal ophthalmic peak ratio Doppler, and placental growth factor (PlGF) serum were collected during the visit. Stillbirth was classified as placental dysfunction‐related when it occurred with pre‐eclampsia or birth weight <10th percentile. Combined prediction models were developed from significant variables in stillbirths, placental dysfunction‐related, and controls. We used the area under the receiver‐operating‐characteristics curve (AUC), sensitivity, and specificity based on a specific cutoff to evaluate the model's predictive performance by measuring the capacity to distinguish between stillbirths and live births.There were 13 (0.79%) cases of stillbirth in 1643 women included in the analysis. The combination of maternal factors, MAP, UtA‐PI, and PlGF, significantly contributed to the prediction of stillbirth. This model was a good predictor for all (including controls) types of stillbirth (AUC 0.879, 95% CI: 0.799–0.959, sensitivity of 99.3%, specificity of 38.5%), and an excellent predictor for placental dysfunction‐related stillbirth (AUC 0.984, 95% CI: 0.960–1.000, sensitivity of 98.5, specificity of 85.7).Screening at 11–13 weeks' gestation by combining maternal factors, MAP, UtA‐PI, and PlGF, can predict a high proportion of stillbirths. Our model has good accuracy for predicting stillbirths, predominantly placental dysfunction‐related stillbirths. [ABSTRACT FROM AUTHOR]

Objectives: Artificial intelligence (AI) has shown promise in improving the performance of fetal ultrasound screening in detecting congenital heart disease (CHD). The effect of giving AI advice to human operators has not been studied in this context. Giving additional information about AI model workings, such as confidence scores for AI predictions, may be a way of further improving performance. Our aims were to investigate whether AI advice improved overall diagnostic accuracy (using a single CHD lesion as an exemplar), and to determine what, if any, additional information given to clinicians optimized the overall performance of the clinician–AI team. Methods: An AI model was trained to classify a single fetal CHD lesion (atrioventricular septal defect (AVSD)), using a retrospective cohort of 121 130 cardiac four‐chamber images extracted from 173 ultrasound scan videos (98 with normal hearts, 75 with AVSD); a ResNet50 model architecture was used. Temperature scaling of model prediction probability was performed on a validation set, and gradient‐weighted class activation maps (grad‐CAMs) produced. Ten clinicians (two consultant fetal cardiologists, three trainees in pediatric cardiology and five fetal cardiac sonographers) were recruited from a center of fetal cardiology to participate. Each participant was shown 2000 fetal four‐chamber images in a random order (1000 normal and 1000 AVSD). The dataset comprised 500 images, each shown in four conditions: (1) image alone without AI output; (2) image with binary AI classification; (3) image with AI model confidence; and (4) image with grad‐CAM image overlays. The clinicians were asked to classify each image as normal or AVSD. Results: A total of 20 000 image classifications were recorded from 10 clinicians. The AI model alone achieved an accuracy of 0.798 (95% CI, 0.760–0.832), a sensitivity of 0.868 (95% CI, 0.834–0.902) and a specificity of 0.728 (95% CI, 0.702–0.754), and the clinicians without AI achieved an accuracy of 0.844 (95% CI, 0.834–0.854), a sensitivity of 0.827 (95% CI, 0.795–0.858) and a specificity of 0.861 (95% CI, 0.828–0.895). Showing a binary (normal or AVSD) AI model output resulted in significant improvement in accuracy to 0.865 (P < 0.001). This effect was seen in both experienced and less‐experienced participants. Giving incorrect AI advice resulted in a significant deterioration in overall accuracy, from 0.761 to 0.693 (P < 0.001), which was driven by an increase in both Type‐I and Type‐II errors by the clinicians. This effect was worsened by showing model confidence (accuracy, 0.649; P < 0.001) or grad‐CAM (accuracy, 0.644; P < 0.001). Conclusions: AI has the potential to improve performance when used in collaboration with clinicians, even if the model performance does not reach expert level. Giving additional information about model workings such as model confidence and class activation map image overlays did not improve overall performance, and actually worsened performance for images for which the AI model was incorrect. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. Linked article: There is a comment on this article by Drukker. Click here to view the Editorial. [ABSTRACT FROM AUTHOR]

Abstract Gene therapy is an important tool for treating fetal diseases that allows for the delivery and integration of therapeutic genes into the genome of cells carrying mutations. Nanomolecules, like PAMAM dendrimers, have recently come into wider use for carrying vectors as they have several advantages over viral vectors. Namely, (1) tunable size and surface chemistry, (2) uniform size, (3) the ability to target specific tissues, and (4) the ability to carry large biomolecules and drugs. Recently, we demonstrated that 4th generation (G4) PAMAM dendrimer with a cystamine core and a non-toxic surface having 90% –OH and 10% –NH2 groups (D-Cys) could cross the blood–brain barrier following injection into the bloodstream. In the current study, as a proof of concept, we delivered the dendrimers alone (D-Cys) tagged with Cy5.5 (D-Cys-cy5.5) to healthy pregnant C57BL/6J mice to determine the fate of these dendrimers in the pregnant mice as well as in the fetus. Systematic diffusion of the D-Cys-cy5.5 was evaluated on gestational day 17 (3 days after injection) using in vivo imaging. This revealed that the dendrimer was taken up into circulation and away from the injection site. Analysis of sections by fluorescence microscopy showed that D-Cys-cy5.5 was able to successfully cross the maternal blood–brain barrier. However, analysis of the fetal brains failed to detect dendrimers in the central nervous system (CNS). Instead, they appeared to be retained in the placenta. This is one of the first studies to analyze the distribution of surface-modified PAMAM dendrimer in the pregnant mouse and fetus following systemic injection.

Today, prenatal diagnosis of congenital urogenital malformations is mostly dependent on anatomical variations found on imaging. However, these findings can mislead us in telling us when to intervene, and about post-natal prognosis. Since many findings are dependent on multiple assessments, delayed diagnosis can occur, leading to less optimal outcomes compared to early intervention. Analyses of fetal urinary biomarkers have been proposed as a method of finding biological changes that are predictive for diagnosis and prognosis in fetuses at risk of kidney disease. We interviewed a group of researchers that have demonstrated that by combining multiple omics traits extracted from fetal urine, the biological variability found in single omics data can be circumvented. By analyzing multiple fetal urine peptides and metabolites at single time point, the prognostic power of postnatal renal outcome in fetuses with lower urinary tract obstruction is significantly increased. In this interview, we inquired about the technical aspects of the tests, challenges, and limitations the research group have come across, and how they envision the future for multi-omics fetal analysis in the clinic. [ABSTRACT FROM AUTHOR]

Objective: To evaluate perinatal outcome in a selected group of fetuses with a prenatal diagnosis of isolated echogenic bowel or bowel dilation or both to improve perinatal management and family counselling. Methods: A retrospective study conducted at the Reference Center for Perinatal Medicine and Surgery from 2011 to 2022. The study population was divided into three groups: hyperechogenicity; dilation; contemporary presence of hyperechogenicity and dilation, without other structural or genetic anomalies. The perinatal outcomes studied were: regression rate of prenatal ultrasound data, gestational age at delivery, birth weight and the need for postnatal surgery. Results: A total of 174 fetuses were included in the study (83 hyperechogenicity, 31 dilations and 60 hyperechogenicity + dilation of the loops).Survival to birth was 100%, with a median gestational age at delivery of 38.5 weeks (range 30.4 – 41.5) and an incidence of delivery <36 weeks of 13.4% and <34 weeks of 2.3%.The median birth weight was at the 33rd percentile and 17.7% of newborns had a weight <3rd percentile. For both outcomes there was no significant difference between the three groups.9.8% of newborns underwent surgery within the first week of life. The surgery rate was significantly higher in the dilation group than in the hyperechogenicity group and in the hyperechogenicity + dilation cases than in the hyperechogenicity alone.Analyzing the group of surgical versus non-surgical newborns, there were no significant differences in terms of birth weight and growth restriction, while a higher rate of birth <36 weeks occurred in the surgical group (p 0.03).The ultrasound regression rate was significant in the hyperechogenicity group (75%, p <0.0001) and in the hyperechogenicity + dilation cases (19.5%, p <0.0043).In the group of surgical newborns, no regression of the ultrasound data was observed compared to the non-surgical ones in which the regression was >50% (p<0.0001). Conclusion: Fetal bowel dilatation and echogenicity are important US findings in prenatal care that warrant careful evaluation and follow-up. Recognizing the clinical significance of these ultrasound markers and offering appropriate counselling and diagnostic tests can help to guide expectant parents and healthcare providers in making decisions regarding the health of the neonate. [ABSTRACT FROM AUTHOR]

Key Clinical Message Pituitary apoplexy is a medical and surgical emergency requiring prompt diagnosis and often urgent treatment to manage symptoms and prevent further complications. Abstract This report describes the successful management of a 37‐year‐old pregnant woman with a history of pituitary macroadenoma and apoplexy during a twin pregnancy. Presenting with bitemporal vision loss, a common pituitary adenoma symptom, she showed no other alarming signs despite a twin pregnancy. Successful endoscopic resection improved her vision, and postoperative recovery was uneventful. The discussion underscores significance of the diagnostic utility of contrast MRI. The patient's favorable outcome supports endoscopic resection feasibility in pregnant individuals with pituitary apoplexy.

Key Clinical Message: Pituitary apoplexy is a medical and surgical emergency requiring prompt diagnosis and often urgent treatment to manage symptoms and prevent further complications. This report describes the successful management of a 37‐year‐old pregnant woman with a history of pituitary macroadenoma and apoplexy during a twin pregnancy. Presenting with bitemporal vision loss, a common pituitary adenoma symptom, she showed no other alarming signs despite a twin pregnancy. Successful endoscopic resection improved her vision, and postoperative recovery was uneventful. The discussion underscores significance of the diagnostic utility of contrast MRI. The patient's favorable outcome supports endoscopic resection feasibility in pregnant individuals with pituitary apoplexy. [ABSTRACT FROM AUTHOR]

PurposeExposures early in life, beginning in utero, have long-term impacts on mental and physical health. The ECHO prenatal and early childhood pathways to health consortium (ECHO-PATHWAYS) was established to examine the independent and combined impact of pregnancy and childhood chemical exposures and psychosocial stressors on child neurodevelopment and airway health, as well as the placental mechanisms underlying these associations.ParticipantsThe ECHO-PATHWAYS consortium harmonises extant data from 2684 mother-child dyads in three pregnancy cohort studies (CANDLE [Conditions Affecting Neurocognitive Development and Learning in Early Childhood], TIDES [The Infant Development and Environment Study] and GAPPS [Global Alliance to Prevent Prematurity and Stillbirth]) and collects prospective data under a unified protocol. Study participants are socioeconomically diverse and include a large proportion of Black families (38% Black and 51% White), often under-represented in research. Children are currently 5-15 years old. New data collection includes multimodal assessments of primary outcomes (airway health and neurodevelopment) and exposures (air pollution, phthalates and psychosocial stress) as well as rich covariate characterisation. ECHO-PATHWAYS is compiling extant and new biospecimens in a central biorepository and generating the largest placental transcriptomics data set to date (N=1083).Findings to dateEarly analyses demonstrate adverse associations of prenatal exposure to air pollution, phthalates and maternal stress with early childhood airway outcomes and neurodevelopment. Placental transcriptomics work suggests that phthalate exposure alters placental gene expression, pointing to mechanistic pathways for the developmental toxicity of phthalates. We also observe associations between prenatal maternal stress and placental corticotropin releasing hormone, a marker of hormonal activation during pregnancy relevant for child health. Other publications describe novel methods for examining exposure mixtures and the development of a national spatiotemporal model of ambient outdoor air pollution.Future plansThe first wave of data from the unified protocol (child age 8-9) is nearly complete. Future work will leverage these data to examine the combined impact of early life social and chemical exposures on middle childhood health outcomes and underlying placental mechanisms.

This document explores the potential of AI language models in the field of fetal medicine. It discusses how these models can assist specialists in assessing fetal anomalies, determining imaging protocols, and aiding in research and training. However, it also emphasizes the need for caution and recognition of limitations, as biases and inaccuracies can impact patient care. The document provides a comparison of different AI language models and their features, advantages, and disadvantages. It concludes by emphasizing the importance of a comprehensive evaluation process for AI language models in fetal medicine. [Extracted from the article]

Objective: To investigate associations between maternal testosterone status and offspring birth anthropometrics. Design: Population‐based prospective cohort study. Setting: University Hospital. Population: 1486 mother–child dyads from Odense Child Cohort. Methods: Maternal blood samples were collected at gestational weeks 27–30 and free testosterone (FT) levels were calculated using the Vermeulen equation from total testosterone (TT) analysed by mass spectrometry and sex hormone binding globulin. Associations between FT or TT levels and birth anthropometrics were analysed with multiple linear regression models according to offspring sex with adjustment for maternal age, parity, smoking and educational level. Analyses were repeated with polycystic ovary syndrome as exposure for offspring birth anthropometrics. Main outcome measures: Offspring birth weight (BW), birth length, abdominal and head circumferences. Results: Maternal mean (SD) age was 30.2 (4.5) years and pre‐pregnancy body mass index was 23.5 (5.3) kg/m2. In boys (n = 787), higher FT was associated with lower birth weight (adjusted doubling constant = −65.53, P = 0.010), shorter birth length (adjusted doubling constant = −0.43, P < 0.001), and lower abdominal circumference (adjusted doubling constant = −0.39, P < 0.001); Higher TT was associated with lower abdominal circumference (adjusted doubling constant = −0.25, P = 0.028). In girls, no associations were found between maternal FT or TT and offspring anthropometrics. Conclusions: Higher maternal free testosterone exposure was linked to reduced birth weight, length and abdominal circumference in boys, whereas girls were not susceptible to maternal testosterone exposure. [ABSTRACT FROM AUTHOR]

• Fetal growth restriction (FGR) requires individualised care, with patients often required to assimilate large volumes of information rapidly in response to a changing clinical situation. • Women are more likely to look online for healthcare information than they are to seek advice from a clinician. • This systematic review of healthcare information available on Google regarding FGR demonstrates low credibility, generally poor quality (although one high quality source was identified), and a median accuracy score of 9/24; websites all had a reading complexity above the national average reading age. • Women cannot rely on Google for information relating to FGR. Healthcare professionals have a responsibility both to provide reliable information and to discuss any information a woman has accessed via other means. To review systematically the quality, readability and credibility of English language webpages offering patient information on fetal growth restriction. A systematic review of patient information was undertaken on Google with location services and browser history disabled. Websites from the first page were included providing they gave at least 300 words of health information on fetal growth restriction aimed at patients. Validated assessment of readability, credibility and quality were undertaken. An accuracy assessment was performed based on international guidance. Characteristics were tabulated. Thirty-one websites including 30 different texts were included. No pages had a reading age of 11 years or less, none were credible, and only one was of high quality. Median accuracy rating was 9/24. Patients cannot rely on Google as a source of information on fetal growth restriction. As well as being difficult to read, information tends to be low quality, low accuracy and not credible. Healthcare professionals must consider how to enable access to high-quality patient information and give time for discussion of information patients have found: failure to do so may disenfranchise patients. [ABSTRACT FROM AUTHOR]

Vasa previa occurs when fetal vessels lie above the cervical os. A novel type of vasa previa, known as type III, is characterized by an abnormal branching of fetal vessels from the placenta in the absence of velamentous cord insertion (as seen in type I) or multilobed placenta (as seen in type II). Here, we present a case of a type III vasa previa after a resolution of a low-lying placenta. The presence of any known risk factors of vasa previa, including low-lying placenta, should prompt screening for vasa previa in the third trimester. Accurate and timely diagnosis of vasa previa will confer significant survival benefit for the neonate.

We are living in a golden age of medicine in which the availability of prenatal diagnosis, fetal therapy, and gene therapy/editing make it theoretically possible to repair almost any defect in the genetic code. Furthermore, the ability to diagnose genetic disorders before birth and the presence of established surgical techniques enable these therapies to be delivered safely to the fetus. Prenatal therapies are generally used in the second or early third trimester for severe, life-threatening disorders for which there is a clear rationale for intervening before birth. While there has been promising work for prenatal gene therapy in preclinical models, the path to a clinical prenatal gene therapy approach is complex. We recently held a conference with the University of California, San Francisco-Stanford Center of Excellence in Regulatory Science and Innovation, researchers, patient advocates, regulatory (members of the Food and Drug Administration), and other stakeholders to review the scientific background and rationale for prenatal somatic cell gene therapy for severe monogenic diseases and initiate a dialogue toward a safe regulatory path for phase 1 clinical trials. This review represents a summary of the considerations and discussions from these conversations.

Introduction: Maternal perception of fetal movements during pregnancy are reassuring; however, the perception of a reduction in movements are concerning to women and known to be associated with increased odds of late stillbirth. Prior to full term, little evidence exists to provide guidelines on how to proceed unless there is an immediate risk to the fetus. Increased strength of movement is the most commonly reported perception of women through to full term, but perception of movement is also hypothesized to be influenced by fetal size. The study aimed to assess the pattern of maternal perception of strength and frequency of fetal movement by gestation and customized birthweight quartile in ongoing pregnancies. A further aim was to assess the association of stillbirth to perception of fetal movements stratified by customized birthweight quartile. Material and methods: This analysis was an individual participant data meta‐analyses of five case–control studies investigating factors associated with stillbirth. The dataset included 851 cases of women with late stillbirth (>28 weeks' gestation) and 2257 women with ongoing pregnancies who then had a liveborn infant. Results: The frequency of prioritized fetal movement from 28 weeks' gestation showed a similar pattern for each quartile of birthweight with increased strength being the predominant perception of fetal movement through to full term. The odds of stillbirth associated with reduced fetal movements was increased in all quartiles of customized birthweight centiles but was notably greater in babies in the lowest two quartiles (Q1: adjusted OR: 9.34, 95% CI: 5.43, 16.06 and Q2: adjusted OR: 6.11, 95% CI: 3.11, 11.99). The decreased odds associated with increased strength of movement was present for all customized birthweight quartiles (adjusted OR range: 0.25–0.56). Conclusions: Increased strength of fetal movements in late pregnancy is a positive finding irrespective of fetal size. However, reduced fetal movements are associated with stillbirth, and more so when the fetus is small. [ABSTRACT FROM AUTHOR]

Fetoscopic laser coagulation (FLC) has been widely used in clinical treatment of patients with twin to twin transfusion syndrome (TTTS) by Ⅱ-Ⅳ stage and has achieved certain results. The perinatal survival rate of TTTS is significantly improved, and the incidence rate of the surviving fetal nervous system is significantly reduced. Meanwhile, it is widely recognized and carried out in the field of minimally invasive fetal medicine because of its advantages such as direct vision operation, small incision, less maternal blood loss, and less interference to pregnancy. However, due to the limitations of FLC technology, which requires a high level of operator skill and special equipment such as their own endoscope and laser, FLC technology can not achieve better results. Pregnant women who receive FLC treatment still face serious perioperative complications, postoperative recurrence, and the risk of reoperation. This article reviews the application and research progress of FLC in TTTS treatment both domestically and internationally, comprehensively elaborates on the development history, operational methods, shortcomings, and future development direction of FLC technology, in order to provide certain reference for the future development of fetal medicine. [ABSTRACT FROM AUTHOR]

Background Induction of labor is performed for either maternal or fetal indications to reduce perinatal morbidity and mortality without increasing maternal morbidity. The aim of this study was to review the scientific literature regarding induction of labor in patients with full-term pregnancy and create a systematic review of the literature to answer the question: “In patients with full-term gestation - does combining the Foley balloon with dinoprostone for the artificial induction of labor - offer better perinatal results over time from the application of the labor induction method until birth?”. Methods A literature search was performed on 23/08/2023 in the PubMed database; only articles published within the past 5 years were considered. We included articles in which labor was triggered with a vaginal device with dinoprostone, oxytocin, and/or a Foley catheter in full-term patients who met the following criteria: monofetal pregnancy, cranial presentation, intact membranes, and no history of uterine scar. We used the keywords “induction,” “labour,” “term,” “Foley,” “dinoproston,” “oxytocin.” Results The Pubmed database currently has approximately 20,000 scientific papers about labor induction. Only two studies met the proposed criteria. Considering the small volume of eligible data for the proposed research, the main meta-analysis addressing the topic was also considered. Conclusions The use of dinoprostone and oxytocin infusion is effective for triggering labor under conditions of compliance with obstetrical indications and pharmacological characteristics. Studies that compare the success of artificial induction of labor with Foley balloon and Foley+dinoprostone in patients with full term gestation are limited, but nevertheless, the association of Foley balloon with artificial induction with dinoprostone seems to be a cost-effective method. The limited number of scientific studies on this topic determines a risk of bias, inconsistency and imprecision, and for the future, we propose to carry out a randomized prospective study to study the topic.

Introduction: Perinatal palliative care services are increasingly available globally, offering a range of clinical and psychological support services to families during pregnancy, in the neonatal period and following the death of a baby with a life‐limiting or life‐threatening condition. Little is understood about the role of children's hospice care and how it contributes to effective perinatal palliative care. Design: The study aims to answer the question "what is the role of children's hospices in the provision of perinatal palliative care and advance care planning in the United Kingdom?" Methods: An electronic survey was sent to all 54 children's hospices in the United Kingdom between May and June 2022. Results: Thirty hospices responded, representing 54% of the sector. All regions of all four counties are represented. Numbers of referrals to hospices for perinatal palliative care have increased significantly over the last 5 years. Hospices provide a range of services for families and babies, usually from the point of diagnosis or recognition of a life‐limiting or life‐threatening condition, underpinned with counseling and emotional support. Hospices worked with a range of professionals and services, most commonly fetal medicine and neonatal services. Advance care plans were an important element of effective perinatal palliative care, strengthening parent–professional and interprofessional relationships. Conclusion: Children's hospice services play an important and growing role in the perinatal care of babies and families following the diagnosis or recognition of a life‐limiting or life‐threatening condition. The family‐centered approach to care, from a broad, biopsychosocial perspective means that hospices make a unique and meaningful contribution to both the clinical and psychological needs of families. Clinical relevance: The family‐centered approach to care, from a broad, biopsychosocial perspective means that hospices make an important contribution to both the clinical needs of babies, and psychological needs of families antenatally, in the neonatal period and after death. [ABSTRACT FROM AUTHOR]

Prenatal screening has come a long way from the discovery of fetal ultrasound markers for Down syndrome followed by improved ultrasound skills where genetic syndromes and major congenital malformations can be diagnosed right in the first trimester itself. The outcome is a key factor for the couple to make informed decision on the future of the high risk pregnancy. Prenatal screening,diagnosis,management and subsequent prevention is now an established practice in fetal medicine. The first trimester screening (at 11-13+6 weeks) includes evaluating markers for common aneuploidies (trisomies) such as Down syndrome along with a detailed fetal anatomy review. This is followed by a genetic sonogram or anomaly scan at around 20 weeks. Any signs of “high risk” for trisomies or malformations prompt invasive testing for precision diagnosis, either a chorion villous sampling (CVS) or an amniocentesis (AC). The fetal sample is used for various genetic tests, such as chromosome microarray analysis (CMA), targeted clinical exome sequencing (CES), or whole exome sequencing (WES) depending upon the abnormality noted or the suspected genetic condition. Non Invasive prenatal screening (NIPS) is now available as a screening tool for Down syndrome (99%accuracy for Down syndrome) if the couple choose to defer invasive testing. Apart from aneuploidies, prenatal screening for non-structural disorders, such as Beta thalassemia (both parents carriers) or investigating any other genetic disorder can also be offered. In addition, Carrier Screening can be considered especially by consanguineous couples who are known to be at increased risk for having an affected baby. The option for NIPS is now preferred by most parents undergoing pre-conception genetic counselling and confirmed to be carriers for an autosomal recessive genetic disease. The prenatal screening is the best choice for secondary prevention of genetic condition. The option for preimplantation genetic diagnosis (PGD) offers primary prevention by specific wild embryo selection and implantation in an in vitro fertilization cycle, following exclusion of affected embryo for aneuploidy (PGD-A), structural chromosome aberration (PGD-A), and a monogenic Mendelian genetic disease (PGD-M). The prenatal screening or diagnosis by the Fetal Medicine Team remains the mainstay for identification and management of pregnancies at high risk of genetic disorders.

Objective: The Accelerating Innovation for Mothers project established a new database of candidate medicines under development between 2000 and 2021 for five pregnancy‐related conditions, including fetal growth restriction. The objective was to assess medicines for fetal growth restriction and their potential for clinical use globally. Design: Landscape analysis. Setting: Global (focus on low‐ and middle‐income countries, LMICs). Sample: Drugs, dietary supplements and biologics under investigation for prevention or treatment of fetal growth restriction. Methods: A research pipeline database of medicines was created through searching AdisInsight, PubMed and various grant and clinical trial databases. Analysis of clinical and preclinical candidates were descriptive. Main Outcomes Measures Fetal growth restriction candidates in clinical development were identified and ranked as high, medium or low potential based on prespecified criteria, including efficacy, safety and accessibility. Results: Of the 444 unique candidates in the database across all five pregnancy‐related conditions, 63 were for fetal growth restriction. Of these, 31 were in clinical development (phases I, II or III) and 32 were in preclinical development. Three candidates, aspirin, l‐arginine and vitamin D, were ranked as having high potential as preventive agents. There were no high‐potential candidates for treating fetal growth restriction, although five candidates were ranked as having medium potential: allylestrenol, dalteparin, omega‐3 fatty acids, tadalafil, and United Nations International Multiple Micronutrient Antenatal Preparation (UNIMMAP). Conclusions: l‐Arginine, aspirin and vitamin D are promising, high‐potential preventative agents for fetal growth restriction. Based on the medicines pipeline, new pharmacological agents for fetal growth restriction are unlikely to emerge in the near future. [ABSTRACT FROM AUTHOR]

Prenatal screening has come a long way from the discovery of fetal ultrasound markers for Down syndrome followed by improved ultrasound skills where genetic syndromes and major congenital malformations can be diagnosed right in the first trimester itself. The outcome is a key factor for the couple to make informed decision on the future of the high risk pregnancy. Prenatal screening, diagnosis, management and subsequent prevention is now an established practice in fetal medicine. The first trimester screening (at 11-13+6 weeks) includes evaluating markers for common aneuploidies (trisomies) such as Down syndrome along with a detailed fetal anatomy review. This is followed by a genetic sonogram or anomaly scan at around 20 weeks. Any signs of "high risk" for trisomies or malformations prompt invasive testing for precision diagnosis, either a chorion villous sampling (CVS) or an amniocentesis (AC). The fetal sample is used for various genetic tests, such as chromosome microarray analysis (CMA), targeted clinical exome sequencing (CES), or whole exome sequencing (WES) depending upon the abnormality noted or the suspected genetic condition. Non Invasive prenatal screening (NIPS) is now available as a screening tool for Down syndrome (99%accuracy for Down syndrome) if the couple choose to defer invasive testing. Apart from aneuploidies, prenatal screening for non-structural disorders, such as Beta thalassemia (both parents carriers) or investigating any other genetic disorder can also be offered. In addition, Carrier Screening can be considered especially by consanguineous couples who are known to be at increased risk for having an affected baby. The option for NIPS is now preferred by most parents undergoing pre-conception genetic counselling and confirmed to be carriers for an autosomal recessive genetic disease. The prenatal screening is the best choice for secondary prevention of genetic condition. The option for preimplantation genetic diagnosis (PGD) offers primary prevention by specific wild embryo selection and implantation in an in vitro fertilization cycle, following exclusion of affected embryo for aneuploidy (PGD-A), structural chromosome aberration (PGD-A), and a monogenic Mendelian genetic disease (PGD-M). The prenatal screening or diagnosis by the Fetal Medicine Team remains the mainstay for identification and management of pregnancies at high risk of genetic disorders. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has stressed patients and healthcare givers alike and challenged our practice of antenatal care, including fetal diagnosis and therapy. This document aims to review relevant recent information to allow us to optimize prenatal care delivery. We discuss potential modifications to obstetric management and fetal procedures in SARS-CoV2-negative and SARS-CoV2-positive patients with fetal anomalies or disorders. Most fetal therapies are time sensitive and cannot be delayed. If personnel and resources are available, we should continue to offer procedures of proven benefit, acknowledging any fetal and maternal risks, including those to health care workers. There is, to date, minimal, unconfirmed evidence of spontaneous vertical transmission, though it may theoretically be increased with some procedures. Knowing a mother's preoperative SARS-CoV-2 status would enable us to avoid or defer certain procedures while she is contagious and to protect health care workers appropriately. Some fetal conditions may alternatively be managed neonatally. Counseling regarding fetal interventions which have a possibility of additional intra- or postoperative morbidity must be performed in the context of local resource availability. Procedures of unproven benefit should not be offered. We encourage participation in registries and trials that may help us to understand the impact of COVID-19 on pregnant women, their fetuses, and neonates.

Amniotic fluid volume assessment has become standard in the surveillance of fetal well-being, especially in high-risk pregnancies. Amniotic fluid disorders are a frequent and important topic in fetal and perinatal medicine. However, although important advances have been achieved, many important and challenging questions remain unanswered to date. An abnormally low amniotic fluid volume, referred to as oligohydramnios, has been traditionally considered a possible indicator of placental insufficiency or fetal compromise and is associated with an increased rate of obstetric interventions. An excess of amniotic fluid, referred to as polyhydramnios, may be secondary to fetal or maternal conditions and has been associated with a variety of adverse pregnancy outcomes, especially when it is severe. The ultrasonographic detection of an amniotic fluid disorder should prompt a proper workup to identify the underlying etiology. Data on the association of isolated oligohydramnios or idiopathic polyhydramnios with adverse obstetric and perinatal outcomes are conflicting. While the management of secondary oligohydramnios is usually guided by the underlying condition, the management of isolated oligohydramnios is poorly defined. Similarly, the management of idiopathic and secondary polyhydramnios is not yet standardized. There is an urgent need for randomized clinical trials to provide stronger recommendations on the management of these two common conditions. [ABSTRACT FROM AUTHOR]

The experience of diagnosis, decision-making and management in critical congenital heart disease is layered with complexity for both families and clinicians. We synthesise the current evidence regarding the family and healthcare provider experience of critical congenital heart disease diagnosis and management. A systematic integrative literature review was conducted by keyword search of online databases, MEDLINE (Ovid), PsycINFO, Cochrane, cumulative index to nursing and allied health literature (CINAHL Plus) and two journals, the Journal of Indigenous Research and Midwifery Journal from 1990. Inclusion and exclusion criteria were applied to search results with citation mining of final included papers to ensure completeness. Two researchers assessed study quality combining three tools. A third researcher reviewed papers where no consensus was reached. Data was coded and analysed in four phases resulting in final refined themes to summarise the findings. Of 1817 unique papers, 22 met the inclusion criteria. The overall quality of the included studies was generally good, apart from three of fair quality. There is little information on the experience of the healthcare provider. Thematic analysis identified three themes relating to the family experience: (1) The diagnosis and treatment of a critical congenital heart disease child significantly impacts parental health and wellbeing. (2) The way that healthcare and information is provided influences parental response and adaptation, and (3) parental responses and adaptation can be influenced by how and when support occurs. The experience of diagnosis and management of a critical congenital heart disease child is stressful and life-changing for families. Further research is needed into the experience of minority and socially deprived families, and of the healthcare provider, to inform potential interventions at the healthcare provider and institutional levels to improve family experience and support. [ABSTRACT FROM AUTHOR]

In this work, a novel multimodal learning approach for early prediction of birth weight is presented. Fetal weight is one of the most relevant indicators in the assessment of fetal health status. The aim is to predict early birth weight using multimodal maternal–fetal variables from the first trimester of gestation (Anthropometric data, as well as metrics obtained from Fetal Biometry, Doppler and Maternal Ultrasound). The proposed methodology starts with the optimal selection of a subset of multimodal features using an ensemble-based approach of feature selectors. Subsequently, the selected variables feed the nonparametric Multiple Kernel Learning regression algorithm. At this stage, a set of kernels is selected and weighted to maximize performance in birth weight prediction. The proposed methodology is validated and compared with other computational learning algorithms reported in the state of the art. The obtained results (absolute error of 234 g) suggest that the proposed methodology can be useful as a tool for the early evaluation and monitoring of fetal health status through indicators such as birth weight.

ObjectivesOur objective was to investigate if an increased nuchal translucency (NT) was associated with higher mortality in chromosomally normal children with congenital heart defects (CHD).MethodsIn a nationwide cohort using population-based registers, we identified 5,633 liveborn children in Denmark with a pre- or postnatal diagnosis of CHD from 2008 to 2018 (incidence of CHD 0.7%). Children with chromosomal abnormalities and non-singletons were excluded. The final cohort compromised 4,469 children. An increased NT was defined as NT > 95th-centile. Children with a NT > 95th-centile vs. NT 95th-centile to those with a NT 95th centile. Complex CHD had no differences in mortality rate between a NT > 95th-centile and NT 99th centile (>3.5 mm) could not be assessed. Adjustment for mediating (preeclampsia, preterm birth, small for gestational age) and confounding variables (extracardiac anomalies, cardiac intervention) did not alter the associations significantly, except for extracardiac anomalies in simple CHD.ConclusionAn increased NT > 95th-centile is correlated with higher mortality in children with simple CHD, but the underlying cause is unknown and undetected abnormal genetics might explain the correlation rather than the increased NT itself, hence further research is warranted.

Abstract Background Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked overgrowth syndrome. The main clinical manifestations are overgrowth and multiple malformations. Case presentation A 38-year-old Chinese woman was pregnant with dichorionic-diamniotic (DCDA) twins after in-vitro fertilization. Series of ultrasound examinations indicated that the measurements (abdominal circumference and estimated foetal weight) of one twin were significantly greater than those of the other one. The genetic testing results of the larger baby indicated of Simpson-Golabi-Behmel syndrome. Conclusion SGBS is difficult to diagnose due to different clinical manifestations. Clinicians need to be more aware of typical SGBS’s clinical findings and choose genetic testing methods individually to improve its prenatal diagnosis.

• Outcomes are better for late second trimester selective termination than third trimester selective termination. • Late second and third trimester selective termination have similar rates of preterm birth. • A cervical length of 35 mm of less at the procedure increases the risk of preterm birth. • Reduction of the presenting twin increases the risk of preterm birth. Do perinatal outcomes of selective termination performed in the late second versus third trimester differ and what risk factors are associated with subsequent preterm birth? This is a retrospective cohort study of late selective terminations performed in dichorionic twins between 2009 and 2021. Perinatal outcomes were compared between two groups: group A, late second trimester (20.2 to 24.2 weeks, n = 26), and group B, third trimester (≥28.2 weeks, n = 55) selective terminations. Univariate and multivariate analyses were conducted to identify factors associated with post-procedure preterm birth. In total, 81 dichorionic twin pregnancies were included. There were no pregnancy losses but 16% (13/81) of cases experienced complications. Group A had a higher median birthweight centile (36.5th versus 15th centile, P = 0.002) and lower rates of intrauterine growth restriction (IUGR) and Caesarean delivery (11.5% versus 32.7%, P = 0.04; and 26.9% versus 61.8%, P = 0.003) than group B. Preterm birth rates were similar (46.2% versus 63.6%, P = 0.15). Multiple regression revealed that reduction of the presenting twin and cervical length ≤35 mm were independently associated with post-procedure preterm birth (odds ratio [OR] 8.7, P = 0.001, 95% confidence interval [CI] 2.5–29.8; OR 3.8, P = 0.015, 95% CI 1.3–11). Late second trimester selective termination is associated with a higher birthweight centile and lower rates of IUGR and Caesarean delivery, compared with third trimester selective termination. Cervical length 35 mm or less and reduction of the presenting twin are independent risk factors for post-procedural preterm birth. These findings may help determine the optimal time to perform a late selective termination. [ABSTRACT FROM AUTHOR]

Background: There are few studies on the detection rate by chromosomal microarray analysis (CMA) of the prenatal diagnosis of talipes equinovarus (TE) compared to conventional karyotyping. We aimed to explore the molecular etiology of fetal TE and examine the detection rate by CMA, which provides more information for the clinical screening and genetic counseling of TE. Methods: In this retrospective study, pregnancies diagnosed with fetal TE were enrolled and clinical data for all cases were retrieved from our medical record database, including demographic data for pregnancies, ultrasound findings, karyotype/CMA results, and pregnant and perinatal outcomes. Results: Among the 164 patients, 17 (10.4%) clinically significant variants were detected by CMA. In 148 singleton pregnancies, the diagnostic rate of clinically significant variants was significantly higher in the non-isolated TE group than in the isolated TE group (10/37, 27.0% vs. 6/111, 5.4%, P < 0.001). In twin pregnancies, 1 (6.3%) pathogenic copy number variant was present in the other 16 twin pregnancies. Conclusions: This study demonstrates that CMA is useful for the prenatal genetic diagnosis of fetal TE. Fetal TE with the associated structural malformation correlates with a higher probability of clinically significant variants. This data may aid prenatal diagnosis and genetic counseling for fetal TE. [ABSTRACT FROM AUTHOR]

Rationale: Pulmonary hypoplasia secondary to congenital diaphragmatic hernia is characterized by reduced branching morphogenesis, which is responsible for poor clinical outcomes. Administration of amniotic fluid stem cell extracellular vesicles (AFSC-EVs) rescues branching morphogenesis in rodent fetal models of pulmonary hypoplasia. Herein, we hypothesized that AFSC-EVs exert their regenerative potential by affecting autophagy, a process required for normal lung development. Objectives: To evaluate autophagy in hypoplastic lungs throughout gestation and establish whether AFSC-EV administration improves branching morphogenesis through autophagy-mediated mechanisms. Methods: EVs were isolated from c-kit+ AFSC-conditioned medium by ultracentrifugation and characterized for size, morphology, and EV markers. Branching morphogenesis was inhibited in rat fetuses by nitrofen administration to dams and in human fetal lung explants by blocking RAC1 activity with NSC23766. The expression of autophagy activators (BECN1 and ATG5) and adaptor (SQSTM1/p62) was analyzed in vitro (rat and human fetal lung explants) and in vivo (rat fetal lungs). Mechanistic studies on rat fetal primary lung epithelial cells were conducted using inhibitors for microRNA-17 and -20a contained in the AFSC-EV cargo and known to regulate autophagy. Measurements and Main Results: Rat and human models of fetal pulmonary hypoplasia showed reduced autophagy mainly at pseudoglandular and canalicular stages. AFSC-EV administration restored autophagy in both pulmonary hypoplasia models by transferring miR-17∼92 cluster members contained in the EV cargo. Conclusions: AFSC-EV treatment rescues branching morphogenesis partly by restoring autophagy through microRNA cargo transfer. This study enhances our understanding of pulmonary hypoplasia pathogenesis and creates new opportunities for fetal therapeutic intervention in congenital diaphragmatic hernia babies. [ABSTRACT FROM AUTHOR]

To evaluate maternal serum pregnancy-associated plasma protein-A (PAPP-A) levels at 11-14 weeks of gestation and preeclampsia risk in women with common congenital anatomic uterine abnormalities (AUAs). First trimester screening markers were compared between 12 AUA pregnancies, 60 age matched controls and 12 cases of early preeclampsia. PAPP-A level and birth weight were significantly lower in AUA compared to control and early preeclampsia group (p<.001). Preeclampsia was absent in the AUAs pregnancies group. Birth weight were similar in AUA group when we compared AUA and control group regarding weeks of gestation at delivery and lower but not significantly, when we compared AUA and early preeclampsia group. Our findings suggest that AUA pregnancies are associated with low first trimester maternal serum PAPP-A concentrations not predictive of susceptibility to preeclampsia.Impact statementWhat is already known on this subject? During first trimester screening for preeclampsia based on maternal pregnancy-associated plasma protein A (PAPP-A) levels, various parameters are used, such as the somatometric characteristics of pregnant woman, single or multiple pregnancy, smoking status, family history, diabetes, hypertension and measurement of blood pressure and uterine artery Dopplers.What do the results of this study add? Our pioneer study revealed that there is drastic difference in PAPP-A concentration in women with common anatomic uterine abnormalities (AUAs), in comparison with their age matched control women with normal uterus.What are the implications of these findings for clinical practice and further research? Based on our results, uterine anatomical deviations, is another factor which must be taken in account for preeclampsia risk calculation and further clinical consultation and follow up in those pregnancies. Lower PAPP-A levels in AUA cases is a weak predictor of susceptibility to preeclampsia and could be associated to smaller placental size rather than poor placentation and in future research the calculation of the uterine cavity functional dimension may lead to a more accurate clinical assessment. [ABSTRACT FROM AUTHOR]

Summary: Most cases of fetal and neonatal thrombocytopenia (FNAIT) are caused by maternal anti‐human platelet antigen‐1a antibodies (anti‐HPA‐1a). Anti‐HPA‐5b antibodies are the second most common antibodies in suspected FNAIT cases. Given the high prevalence of anti‐HPA‐5b antibodies in pregnant women delivering healthy newborns, the association with FNAIT may be coincidental. This review of the literature related to FNAIT using the MEDLINE database was conducted according to PRISMA guidelines. A retrospective analysis of a single‐centre cohort of 817 suspected FNAIT cases was conducted. The pooled prevalence of anti‐HPA‐5b antibodies in unselected pregnant women of European descent was 1.96% (n = 3113), compared with 3.4% (n = 5003) in women with suspected FNAIT. We found weak evidence that a small proportion of pregnant women presenting with anti‐HPA‐5b antibodies will give birth to a newborn with mild thrombocytopenia. The neonatal platelet counts were not different between suspected FNAIT cases (n = 817) with and without maternal anti‐HPA‐5b antibodies. The prevalence of maternal anti‐HPA‐5b antibodies was not different between neonates with intracranial haemorrhage and healthy controls. The current experimental and epidemiological evidence does not support the hypothesis that anti‐HPA‐5b antibodies cause severe thrombocytopenia or bleeding complications in the fetus or newborn. [ABSTRACT FROM AUTHOR]

Introduction: We sought to characterize the current workforce and training for fetal intervention procedures at fetal centers in North America. Methods: An anonymous electronic survey was developed to query the 34 centers in the North American Fetal Treatment Network regarding the demographics and training of their faculty. Telephone surveys were conducted with directors of known fetal intervention fellowships. Results: More than 50% of maternal-fetal medicine (MFM) faculty at fetal centers were female; more than two-thirds of pediatric surgical faculty were male. Most of the training of faculty was undertaken by visiting more experienced centers or having new faculty work with more experienced ones at the same center. Current fetal intervention fellowships appear to achieve levels of competency for intrauterine transfusions and laser therapy for twin-twin transfusion syndrome. Two-thirds of centers stated that they would be able to offer a position to an MFM who completed a formal fellowship in fetal intervention. Conclusion: A collaborative effort should be undertaken to establish formal fellowships in fetal medicine and intervention. [ABSTRACT FROM AUTHOR]

Isolated restrictive foramen ovale (rFO) without complex heart defects is a rare pathology. There may be difficulties in managing this situation, which can lead to right heart enlargement, tricuspid regurgitation and hydrops findings in the foetus. We conducted a retrospective analysis of 8451 foetuses. 7883 (93.2%) had a structurally normal heart or minor heart disease, 18 (0.22%) of which had a diagnosis of isolated rFO. Nine patients with neonatal echocardiographic examination were included in the study. In 8 (88.8%) patients, it was stated that a decision to give birth should be made at the time of presentation. Evaluating postpartum echocardiographic examinations, 7 (77.7%) patients had normal or minor defects. The decision of delivery made at the right time during follow-up is critical to determine the prognosis. What is already known on this subject? The data about the prenatal diagnosis of isolated rFO is limited. What the results of this study add? We conducted a retrospective analysis of 8451 foetuses. 7883 (93.2%) foetuses had a structurally normal heart or minor heart disease, 18 (0.22%) of which had a diagnosis of rFO. Nıne patients with foetal and postnatal follow-up and echocardiographic findings were examined in the study. The group's median gestational age at admission was 35.0 weeks (range: 27.0–39.0 weeks). The delivery decision was made in 8 (88.8%) patients at the time of admission. Evaluating postpartum echocardiographic examinations, 7 (77.7%) patients had normal or minor defects. Additionally, one patient was diagnosed with cardiomyopathy, and the other patient was diagnosed with functional pulmonary atresia. No death occurred in any foetus during follow-up. What the implications are of these findings for clinical practice and/or further research? Isolated rFO, a rare condition in the foetus, is generally well-tolerated in foetal life. However, the right heart enlargement, tricuspid regurgitation, or hydrops findings can be seen in patients. The decision of delivery made at the right time during follow-up is critical to determine the prognosis. [ABSTRACT FROM AUTHOR]

Background: In the United States, patients with monochorionic diamniotic twins who undergo in utero fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS) may travel great distances for care. After delivery, many parents cannot return to study sites for formal pediatric evaluation due to geographic location and cost., Objective: The aim of this study was to collect long-term pediatric outcomes in patients who underwent FLP for TTTS., Methods: We assessed the feasibility of using a web-based survey designed in REDCap (Research Electronic Data Capture; Vanderbilt University) to collect parent-reported outcomes in children treated for TTTS at a single center during 2011-2019. Patients with ≥1 neonatal survivor were invited via email to complete 5 possible questionnaires: the child status questionnaire (CSQ); fetal center questionnaire (FCQ); Ages & Stages Questionnaires, Third Edition (ASQ-3); Modified Checklist for Autism in Toddlers, Revised With Follow-Up (M-CHAT-R/F); and thank you questionnaire (TYQ). The R programming language (R Foundation for Statistical Computing) was used to automate survey distribution, scoring, and creation of customized reports. The survey was performed in 2019 and repeated after 12 months in the same study population in 2020., Results: A total of 389 patients in 26 different states and 2 international locations had an email address on file and received an invitation in 2019 to complete the survey (median pediatric age 48.9, IQR 1.0-93.6 months). Among surveyed mothers in 2019, the overall response rate was 37.3% (145/389), and the questionnaire completion rate was 98% (145/148), 87.8% (130/148), 71.1% (81/100), 86.4% (19/22), and 74.3% (110/148) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively. In 2020, the overall response rate was 57.8% (56/97), and the questionnaire completion rate was 96.4% (54/56), 91.1% (51/56), 86.1% (31/36), 91.7% (11/12), and 80.4% (45/56) for the CSQ, FCQ, ASQ-3, M-CHAT-R/F, and TYQ, respectively., Conclusions: This is the first study to use both REDCap and computer automation to aid in the dissemination, collection, and reporting of surveys to collect long-term pediatric outcomes in the field of fetal medicine., (© Eric Bergh, Kimberly Rennie, Jimmy Espinoza, Anthony Johnson, Ramesha Papanna. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org).)

Introduction: Undetected high-risk conditions in pregnancy are a leading cause of perinatal mortality in low-income and middle-income countries. A key contributor to adverse perinatal outcomes in these settings is limited access to high-quality screening and timely referral to care. Recently, a low-cost one-dimensional Doppler ultrasound (1-D DUS) device was developed that front-line workers in rural Guatemala used to collect quality maternal and fetal data. Further, we demonstrated with retrospective preliminary data that 1-D DUS signal could be processed using artificial intelligence and deep-learning algorithms to accurately estimate fetal gestational age, intrauterine growth and maternal blood pressure. This protocol describes a prospective observational pregnancy cohort study designed to prospectively evaluate these preliminary findings., Methods and Analysis: This is a prospective observational cohort study conducted in rural Guatemala. In this study, we will follow pregnant women (N =700) recruited prior to 18 6/7 weeks gestation until their delivery and early postpartum period. During pregnancy, trained nurses will collect data on prenatal risk factors and obstetrical care. Every 4 weeks, the research team will collect maternal weight, blood pressure and 1-D DUS recordings of fetal heart tones. Additionally, we will conduct three serial obstetric ultrasounds to evaluate for fetal growth restriction (FGR), and one postpartum visit to record maternal blood pressure and neonatal weight and length. We will compare the test characteristics (receiver operator curves) of 1-D DUS algorithms developed by deep-learning methods to two-dimensional fetal ultrasound survey and published clinical pre-eclampsia risk prediction algorithms for predicting FGR and pre-eclampsia, respectively., Ethics and Dissemination: Results of this study will be disseminated at scientific conferences and through peer-reviewed articles. Deidentified data sets will be made available through public repositories. The study has been approved by the institutional ethics committees of Maya Health Alliance and Emory University., Competing Interests: Competing interests: The bespoke Android App, source code and algorithms developed for this study are open source and will be available through appropriate public repositories on project completion. The authors have no financial interest in the app or source code. PR and GDC receive funding from the Google Nonprofit Foundation for other artificial intelligence projects related to detection of maternal and neonatal conditions in low-resource settings., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Selective fetal growth restriction (sFGR) in monochorionic twin pregnancy, defined as an estimated fetal weight (EFW) of one twin <10th centile and EFW discordance ≥25%, is associated with stillbirth and neurodisability for both twins. The condition poses unique management difficulties: on the one hand, continuation of the pregnancy carries a risk of death of the smaller twin, with a high risk of co-twin demise (40%) or co-twin neurological sequelae (30%). On the other, early delivery to prevent the death of the smaller twin may expose the larger twin to prematurity, with the associated risks of long-term physical, emotional and financial costs from neurodisability, such as cerebral palsy.When there is severe and early sFGR, before viability, delivery is not an option. In this scenario, there are currently three main management options: (1) expectant management, (2) selective termination of the smaller twin and (3) placental laser photocoagulation of interconnecting vessels. These management options have never been investigated in a randomised controlled trial (RCT). The best management option is unknown, and there are many challenges for a potential RCT. These include the rarity of the condition resulting in a small number of eligible pregnancies, uncertainty about whether pregnant women will agree to participate in such a trial and whether they will agree to be randomised to expectant management or active fetal intervention, and the challenges of robust and long-term outcome measures. Therefore, the main objective of the FERN study is to assess the feasibility of conducting an RCT of active intervention vs expectant management in monochorionic twin pregnancies with early-onset (prior to 24 weeks) sFGR., Methods and Analysis: The FERN study is a prospective mixed-methods feasibility study. The primary objective is to recommend whether an RCT of intervention vs expectant management of sFGR in monochorionic twin pregnancy is feasible by exploring women's preference, clinician's preference, current practice and equipoise and numbers of cases. To achieve this, we propose three distinct work packages (WPs). WP1: A Prospective UK Multicentre Study, WP2A: a Qualitative Study Exploring Parents' and Clinicians' Views and WP3: a Consensus Development to Determine Feasibility of a Trial. Eligible pregnancies will be recruited to WP1 and WP2, which will run concurrently. The results of these two WPs will be used in WP3 to develop consensus on a future definitive study. The duration of the study will be 53 months, composed of 10 months of setup, 39 months of recruitment, 42 months of data collection, and 5 months of data analysis, report writing and recommendations. The pragmatic sample size for WP1 is 100 monochorionic twin pregnancies with sFGR. For WP2, interviews will be conducted until data saturation and sample variance are achieved, that is, when no new major themes are being discovered. Based on previous similar pilot studies, this is anticipated to be approximately 15-25 interviews in both the parent and clinician groups. Engagement of at least 50 UK clinicians is planned for WP3., Ethics and Dissemination: This study has received ethical approval from the Health Research Authority (HRA) South West-Cornwall and Plymouth Ethics Committee (REC reference 20/SW/0156, IRAS ID 286337). All participating sites will undergo site-specific approvals for assessment of capacity and capability by the HRA. The results of this study will be published in peer-reviewed journals and presented at national and international conferences. The results from the FERN project will be used to inform future studies., Trial Registration Number: This study is included in the ISRCTN Registry (ISRCTN16879394) and the NIHR Central Portfolio Management System (CPMS), CRN: Reproductive Health and Childbirth Specialty (UKCRN reference 47201)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objectives: As part of the FERN feasibility study, this qualitative research aimed to explore parents' and clinicians' views on the acceptability, feasibility and design of a randomised controlled trial (RCT) of active intervention versus expectant management in monochorionic (MC) diamniotic twin pregnancies with early-onset (prior to 24 weeks) selective fetal growth restriction (sFGR). Interventions could include laser treatment or selective termination which could lead to the death or serious disability of one or both twins., Design: Qualitative semi-structured interviews with parents and clinicians. Data were analysed using reflexive thematic analysis and considered against the Principles of Biomedical Ethics., Participants and Setting: We interviewed 19 UK parents experiencing (six mothers, two partners) or had recently experienced (eight mothers, three partners) early-onset sFGR in MC twin pregnancy and 14 specialist clinicians from the UK and Europe., Results: Participants viewed the proposed RCT as 'ethically murky' because they believed that the management of sFGR in MC twin pregnancy should be individualised according to the type and severity of sFGR. Clinicians prioritised the gestational age, size, decrease in growth velocity, access to the placental vessels and acceptability of intervention for parents. Discussions and decision-making about selective termination appeared to cause long-term harm (maleficence). The most important outcome for parents and clinicians was 'live birth'. For clinicians, this was the live birth of at least one twin. For parents, this meant the live birth of both twins, even if this meant that their babies had neurodevelopmental impairment or disabilities., Conclusions: All three pregnancy management approaches for sFGR in MC twin pregnancy carry risks and benefits, and the ultimate goal for parents is to receive individualised care to achieve the best possible outcome for both twins. An RCT was not acceptable to parents or clinicians or seen as ethically appropriate. Alternative study designs should be considered to answer this important research question., Competing Interests: Competing interests: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme grant payments were made to the institutions of all authors (except REA, NF and SL). TKM and MP employment roles were funded by the NIHR HTA programme grant payment made to their institution., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Climate change increases not only the frequency, intensity and duration of extreme heat events but also annual temperatures globally, resulting in many negative health effects, including harmful effects on pregnancy and pregnancy outcomes. As temperatures continue to increase precipitously, there is a growing need to understand the underlying biological pathways of this association. This systematic review will focus on maternal, placental and fetal changes that occur in pregnancy due to environmental heat stress exposure, in order to identify the evidence-based pathways that play a role in this association., Methods and Analysis: We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search PubMed and Ovid Embase databases from inception using tested and validated search algorithms. Inclusion of any studies that involve pregnant women and have measured environmental heat stress exposure and either maternal, placental or fetal physiological or biochemical changes and are available in English. Modelling studies or those with only animals will be excluded. The risk of bias will be assessed using the Office of Health Assessment and Translation tool. Abstract screening, data extraction and risk of bias assessment will be conducted by two independent reviewers.Environmental parameters will be reported for each study and where possible these will be combined to calculate a heat stress indicator to allow comparison of exposure between studies. A narrative synthesis will be presented following standard guidelines. Where outcome measures have at least two levels of exposure, we will conduct a dose-response meta-analysis should there be at least three studies with the same outcome. A random effects meta-analysis will be conducted where at least three studies give the same outcome., Ethics and Dissemination: This systematic review and meta-analysis does not require ethical approval. Dissemination will be through peer-reviewed journal publication and presentation at international conferences/interest groups., Prospero Registration Number: CRD42024511153., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The article discusses the study to describe prenatal counselling for surgical anomalies and suggests a list of prenatal abnormalities warranting counselling by a pediatric surgeon. It mentions that prenatal counselling by a pediatric surgeon allows couples to obtain precise information on the pathology of their unborn child, giving them greater autonomy in their decision to continue the pregnancy.

Key content: Fetal cardiac arrhythmias are relatively common and account for up to 20% of referrals to fetal cardiologists.Arrhythmias may occur because of structural abnormalities of the fetal heart, or because of abnormal functioning of the cardiac conduction system in an otherwise structurally normal heart.Arrhythmias may be diagnosed using ultrasound and M‐mode and Doppler echocardiography.Transplacental therapy for tachyarrhythmias has been one of the success stories of fetal cardiology, and good outcomes can be expected in the absence of hydrops.Congenital heart block is most commonly caused by the transplacental passage of anti‐Ro and anti‐La antibodies and transplacental therapy is less successful in managing this. Learning objectives: To enable clinicians to provide better counselling for patients about the prognosis of fetal arrhythmias.To learn how to diagnose fetal arrhythmias and know when to refer to a specialist centre if the diagnosis is suspected.To understand the treatment options available and the evidence‐based antenatal care schedule. [ABSTRACT FROM AUTHOR]