Neonatal screening of ABO/RhD blood group and direct antiglobulin Coombs test. Experience of a single institution.

BACKGROUND: Evaluating the ABO/RhD blood group and the direct antiglobulin Coombs test (DAT) at birth is recommended good practice, but there is variability in its universal implementation. This study aims to show the comparative results in various variables of clinical impact during the hospital stay of neonates with positive DAT compared with those with negative DAT, based on the systematic detection of the ABO/RhD group and DAT at birth. METHODS: Newborns between 2017 and 2020 in a high-risk pregnancy care hospital were included. The ABO/RhD and DAT group was determined in umbilical cord samples or the first 24 hours of life. Demographic, maternal, and neonatal variables were recorded. The association between the variables was estimated using the odds ratio (OR). RESULTS: 8721 pairs were included. The DAT was positive in 239 newborns (2.7%), with the variables associated with positive PDC being maternal age > 40 years (OR: 1.5; 95% CI: 1.0 to 2.3), birth by cesarean section (1.4; 1.1-2.0), mother group O (6.4; 3.8-11.8), prematurity (3.6; 2.6-5.0), birth weight < 2500 g (2.1; 1.6-2.8), newborn group A (15.7; 10.7-23.1) and group B (17.6; 11.4-27.2), hemoglobin at birth < 13.5 g/dl (4.5; 2.8-7.1) and reticulocytosis > 9% (1.9; 1.2 to 3.1). DISCUSSION: The frequency of neonatal positive PDC was 2.7%, with a significant association with maternal/neonatal incompatibility to the ABO and RhD group, with a substantial impact on various neonatal variables. These results support the policy of universal implementation at the birth of the ABO/RhD and DAT determination.

INTRODUCCIÓN: La determinación del grupo sanguíneo ABO/RhD y la prueba directa de Coombs (PDC) al nacimiento son una práctica recomendada, pero existe variabilidad en su implementación universal. Se presentan los resultados de la determinación al nacimiento del grupo ABO/RhD y la PDC en una cohorte institucional. MÉTODOS: Se incluyeron los recién nacidos entre 2017 y 2020 en un hospital de atención a embarazos de alto riesgo. Se determinó el grupo ABO/RhD y se realizó la PDC en muestras de cordón umbilical o en las primeras 24 horas de vida. Se registraron las variables demográficas, maternas y neonatales. Se estimó la asociación entre las variables mediante la razón de probabilidad (OR). RESULTADOS: Se incluyeron 8721 binomios. La PDC fue positiva en 239 recién nacidos (2.7%), siendo las variables asociadas a la PDC positiva la edad materna > 40 años (OR: 1.5;IC95%: 1.0-2.3), el nacimiento por vía cesárea (1.4; 1.1-2.0), la madre del grupo O (6.4; 3.8-11.8), la prematuridad (3.6; 2.6-5.0); el peso al nacer < 2500 g (2.1; 1.6-2.8); el neonato del grupo A (15.7; 10.7-23.1) o del grupo B (17.6; 11.4-27.2), la hemoglobina al nacer < 13.5 g/dl (4.5; 2.8-7.1) y la reticulocitosis > 9% (1.9; 1.2 a 3.1). DISCUSIÓN: La frecuencia de PDC positiva neonatal es del 2.7%, con asociación significativa la incompatibilidad materna/neonatal al grupo ABO y RhD, con impacto significativo en diversas variables neonatales. Estos resultados apoyan la política de implementación universal al nacimiento de la determinación de ABO/RhD y PDC.

The RhoA guanine exchange factor ABR: a glucose-sensitive mediator of actin reorganization in feto-placental arterial endothelial cells altered by gestational diabetes mellitus.

In utero exposure to gestational diabetes mellitus (GDM) programs the fetus, increasing offspring risk for endothelial dysfunction and cardiovascular disease later in life. Hyperglycaemia is widely recognized as the driving force of diabetes-induced programming. We have previously shown that GDM exposure alters DNA methylation and gene expression associated with actin remodelling in primary feto-placental arterial endothelial cells (fpEC). Thus, we hypothesized that hyperglycaemic insults underlie programmed changes in fpEC morphology and actin organization by GDM. Therefore, arterial fpECs isolated after normal and GDM pregnancy, as well as normal fpECs that were exposed to hyperglycaemia in vitro, were analysed for the effect of GDM and hyperglycaemia on actin organization and network formation. Integration of gene expression and DNA methylation data identified the RhoA activator active BCR-related (ABR) as programmed by GDM and altered by in vitro hyperglycaemia. ABR silencing in GDM-exposed cells reduced RhoA activity by 34 ± 26% (P = 0.033) and restored normal fpEC phenotype. In fact, in vitro hyperglycaemia induced a similar fpEC phenotype as intrauterine exposure to GDM, i.e. round morphology and increased network formation on Matrigel by 34 ± 33% (P = 0.022) vs. 22 ± 20% for GDM (P = 0.004). Thus, we identified ABR as a novel glucose sensitive regulator of actin organization and cell shape, programmed by GDM and upregulated by hyperglycaemia. Identification of mechanisms induced by hyperglycaemia and affecting endothelial function in the long term will contribute to understanding GDM-induced programming of offspring endothelial dysfunction and cardiovascular disease. Future studies could focus on investigating the prevention or reversal of such malprogramming. KEY POINTS: In utero exposure to gestational diabetes mellitus (GDM) affects future health of the offspring, with an increased risk for endothelial dysfunction and cardiovascular disease in later life. GDM alters DNA methylation and expression of ABR in feto-placental arterial endothelial cells (fpEC), a model for endothelial cells exposed to the intrauterine environment of the fetus. GDM phenotype of fpECs is also induced by hyperglycaemia in vitro, and is characterized by altered actin organization and cell shape, which can be restored by ABR silencing. Revealing the cellular mechanisms induced by GDM and hyperglycaemia is important for understanding the mechanisms of how these conditions disturb endothelial function in the offspring.

Management advances for congenital diaphragmatic hernia: integrating prenatal and postnatal perspectives.

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Bovine placental extracellular vesicles carry the fusogenic syncytin BERV-K1.

Syncytins are endogenous retroviral envelope proteins which induce the fusion of membranes. A human representative of this group, endogenous retrovirus group W member 1 envelope (ERVW-1) or syncytin-1 is present in trophoblast-derived extracellular vesicles and supports the incorporation of these extracellular vesicles into recipient cells. During pregnancy, placenta-derived extracellular vesicles participate in feto-maternal communication. Bovine fetal binucleate trophoblast cells express the syncytin, bovine endogenous retroviral envelope protein K1 (BERV-K1). These cells release extracellular vesicles into the maternal stroma, but it is unclear whether BERV-K1 is included in these extracellular vesicles. Here, extracellular vesicles were isolated from bovine placental tissue using collagenase digestion, ultracentrifugation, and size exclusion chromatography. They were characterized with transmission electron microscopy, nanoparticle tracking analysis, immunoblotting and mass spectrometry. Immunohistochemistry and immunoelectron microscopy were used to localize BERV-K1 within the bovine placental tissue. The isolated extracellular vesicles range between 50 and 300 nm, carrying multiple extracellular vesicle biomarkers. Proteomic analysis and immunoelectron microscopy confirmed BERV-K1 presence on the isolated extracellular vesicles. Further, BERV-K1 was localized on intraluminal vesicles in secretory granules of binucleate trophoblast cells. The presence of BERV-K1 on bovine placental extracellular vesicles suggests their role in feto-maternal communication and potential involvement of BERV-K1 in uptake of extracellular vesicles by target cells.

A Comprehensive Review on Serum Lactate Dehydrogenase (LDH) and Uric Acid in Preeclampsia: Implications for Maternal Health and Disease Severity.

Preeclampsia, a hypertensive disorder unique to pregnancy, remains a significant cause of maternal and fetal morbidity and mortality worldwide. Serum lactate dehydrogenase (LDH) and uric acid have garnered attention as potential biomarkers in understanding preeclampsia's pathophysiology and clinical management. Elevated LDH and uric acid levels have been associated with disease severity and adverse outcomes, highlighting their potential utility in risk stratification and guiding management strategies. This comprehensive review explores the roles of LDH and uric acid in preeclampsia, summarizing current evidence regarding their diagnostic, prognostic, and therapeutic implications. Future research directions are also discussed, including understanding and validation studies. Integrating LDH and uric acid measurements into routine clinical practice may facilitate early detection and intervention, ultimately improving outcomes for preeclamptic pregnancies. This review underscores the importance of serum biomarkers in enhancing our understanding and managing preeclampsia, aiming to optimize maternal and fetal health.

An Application of a Physiologically Based Pharmacokinetic Approach to Predict Ceftazidime Pharmacokinetics in a Pregnant Population.

Physiological changes during pregnancy can alter maternal and fetal drug exposure. The objective of this work was to predict maternal and umbilical ceftazidime pharmacokinetics during pregnancy. Ceftazidime transplacental permeability was predicted from its physicochemical properties and incorporated into the model. Predicted concentrations and parameters from the PBPK model were compared to the observed data. PBPK predicted ceftazidime concentrations in non-pregnant and pregnant subjects of different gestational weeks were within 2-fold of the observations, and the observed concentrations fell within the 5th-95th prediction interval from the PBPK simulations. The calculated transplacental clearance (0.00137 L/h/mL of placenta volume) predicted an average umbilical cord-to-maternal plasma ratio of 0.7 after the first dose, increasing to about 1.0 at a steady state, which also agrees well with clinical observations. The developed maternal PBPK model adequately predicted the observed exposure and kinetics of ceftazidime in the pregnant population. Using a verified population-based PBPK model provides valuable insights into the disposition of drug concentrations in special individuals that are otherwise difficult to study and, in addition, offers the possibility of supplementing sparse samples obtained in vulnerable populations with additional knowledge, informing the dosing adjustment and study design, and improving the efficacy and safety of drugs in target populations.

The 'communicatome' of pregnancy: spotlight on cellular and extravesicular chimerism.

Communication via biological mediators between mother and fetus are key to reproductive success and offspring's future health. The repertoire of mediators coding signals between mother and fetus is broad and includes soluble factors, membrane-bound particles and immune as well as non-immune cells. Based on the emergence of technological advancements over the last years, considerable progress has been made toward deciphering the "communicatome" between fetus and mother during pregnancy and even after birth. In this context, pregnancy-associated chimerism has sparked the attention among immunologists, since chimeric cells-although low in number-are maintained in the allogeneic host (mother or fetus) for years after birth. Other non-cellular structures of chimerism, e.g. extracellular vesicles (EVs), are increasingly recognized as modulators of pregnancy outcome and offspring's health. We here discuss the origin, distribution and function of pregnancy-acquired microchimerism and chimeric EVs in mother and offspring. We also highlight the pioneering concept of maternal microchimeric cell-derived EVs in offspring. Such insights expand the understanding of pregnancy-associated health or disease risks in mother and offspring.

From Conception to Delivery: A Comprehensive Review of Thyroid Disorders and Their Far-Reaching Impact on Feto-Maternal Health.

This comprehensive review delves into the multifaceted landscape of thyroid disorders during pregnancy, exploring their impact from conception to postpartum considerations. Key findings highlight the intricate interplay between maternal thyroid health and fetal development, emphasizing the critical importance of timely screening and targeted interventions. The evolving landscape of research and technology suggests a paradigm shift toward personalized approaches in clinical practice, emphasizing integrated care models and the integration of telehealth platforms. Postpartum considerations, including postpartum thyroiditis, underscore the necessity for ongoing monitoring and intervention for maternal well-being. Implications for clinical practice encompass healthcare provider education, public awareness campaigns, and policy advocacy for standardized screening guidelines. The call to action resonates for increased research funding to advance understanding and improve outcomes. By fostering awareness, education, and collaborative efforts, this review aims to navigate the complexities of thyroid disorders during pregnancy, ensuring a healthier start for both mothers and their infants.

Fetal magnetic resonance imaging, ultrasound, and echocardiography findings in twin reversed arterial perfusion sequence.

BACKGROUND: Twin reversed arterial perfusion (TRAP) sequence is a rare complication of monochorionic multiple gestation pregnancies, in which the pump twin provides hemodynamic support to a nonviable co-twin (acardius). Fetal magnetic resonance imaging (MRI) is used to detect pump twin abnormalities, particularly brain ischemia, prior to fetal intervention to interrupt umbilical blood flow to the acardius. OBJECTIVE: To summarize the imaging findings of TRAP sequence pregnancies in a large series. MATERIALS AND METHODS: A single-center retrospective review was performed of all TRAP sequence pregnancies referred for fetal MRI (2004-2021). Fetal MRI, ultrasound, and echocardiography data were collected. RESULTS: Eighty-eight TRAP sequence pregnancies with MRI were included (mean gestational age, 19.8±2.8 weeks). Demise of the pump twin was noted in two pregnancies at the time of MRI. By MRI, 12% (10/86) of live pump twins had abnormalities, including 3% (3/86) with brain abnormalities and 9% (8/86) with extra-cranial abnormalities. By echocardiography, 7% (6/86) of pump twins had structural cardiac abnormalities. Three acardius morphological subtypes were identified by MRI: acephalus (55%, 48/88), anceps (39%, 34/88), and amorphous (7%, 6/88). The mean ultrasound acardius to pump twin ratio A/P ratio, calculated for each twin pair as the ratio of the acardius trunk (and head, if present) plus limb volume to the pump twin estimated fetal weight) differed among the three acardius subtypes (P=.03). The mean A/P ratio moderately correlated with pump twin cardiothoracic ratio and combined cardiac output (Pearson's r=0.45 and 0.48, respectively, both P<.001). CONCLUSION: Fetal MRI of TRAP sequence pregnancies found anomalies in a substantial number of pump twins. The three acardius subtypes differed in A/P ratio, which moderately correlated with the pump twin cardiothoracic ratio and combined cardiac output.

Placental Trophoblast Cell Isolation from the Term Placenta.

Multiple cell lines have been utilized over time in studying placental biology. Still, most of them rely on choriocarcinoma cells or immortalized trophoblast cells that may not be entirely comparable with actual human placental trophoblast cells. Term placentas can be a source of primary villous trophoblasts. However, challenges remain in isolating them and maintaining them in extended culture. This manuscript describes our three-phase protocol utilizing enzymatic/mechanical digestion, modified Percoll gradient density separation, and immunopurification using magnetic beads. The resulting trophoblast culture remains viable for an extended period and highly pure after initial passaging.

Feto-Maternal Interface Organ-on-Chip: A New Technology to Study Ascending Infection.

Modeling human pregnancy is challenging as two subjects, the mother and fetus, must be evaluated in tandem. To understand pregnancy, parturition, and adverse pregnancy outcomes, the two feto-maternal interfaces (FMi) that form during gestation (i.e., the placenta and fetal membrane) need to be investigated to understand their biological roles, and organ dysfunction can lead to adverse outcomes. Adverse pregnancy outcomes such as preterm rupture of the membranes, spontaneous preterm birth, preeclampsia, intra-uterine growth restriction, and gestational diabetes rates are on the rise worldwide, highlighting the need for future studies and a better understanding of molecular and cellular pathways that contribute to disease onset. Current in vivo animal models nor in vitro cell culture systems can answer these questions as they do not model the function or structure of human FMis. Utilizing microfabrication and soft-lithography techniques, microfluidic organ-on-chip (OOC) devices have been adapted by many fields to model the anatomy and biological function of complex organs and organ systems within small in vitro platforms.These techniques have been adapted to recreate the fetal membrane FMi (FMi-OOC) using immortalized cells and collagen derived from patient samples. The FMi-OOC is a four-cell culture chamber, concentric circle system, that contains both fetal (amniochorion) and maternal (decidua) cellular layers and has been validated to model physiological and pathological states of pregnancy (i.e., ascending infection, systemic oxidative stress, and maternal toxicant exposure). This platform is fully compatible with various analytical methods such as microscopy and biochemical analysis. This protocol will outline this device's fabrication, cell loading, and utility to model ascending infection-related adverse pregnancy outcomes.

Sex and fetal genome influence gene expression in pig endometrium at the end of gestation.

BACKGROUND: A fine balance of feto-maternal resource allocation is required to support pregnancy, which depends on interactions between maternal and fetal genetic potential, maternal nutrition and environment, endometrial and placental functions. In particular, some imprinted genes have a role in regulating maternal-fetal nutrient exchange, but few have been documented in the endometrium. The aim of this study is to describe the expression of 42 genes, with parental expression, in the endometrium comparing two extreme breeds: Large White (LW); Meishan (MS) with contrasting neonatal mortality and maturity at two days of gestation (D90-D110). We investigated their potential contribution to fetal maturation exploring genes-fetal phenotypes relationships. Last, we hypothesized that the fetal genome and sex influence their endometrial expression. For this purpose, pure and reciprocally crossbred fetuses were produced using LW and MS breeds. Thus, in the same uterus, endometrial samples were associated with its purebred or crossbred fetuses. RESULTS: Among the 22 differentially expressed genes (DEGs), 14 DEGs were differentially regulated between the two days of gestation. More gestational changes were described in LW (11 DEGs) than in MS (2 DEGs). Nine DEGs were differentially regulated between the two extreme breeds, highlighting differences in the regulation of endometrial angiogenesis, nutrient transport and energy metabolism. We identified DEGs that showed high correlations with indicators of fetal maturation, such as ponderal index at D90 and fetal blood fructose level and placental weight at D110. We pointed out for the first time the influence of fetal sex and genome on endometrial expression at D90, highlighting AMPD3, CITED1 and H19 genes. We demonstrated that fetal sex affects the expression of five imprinted genes in LW endometrium. Fetal genome influenced the expression of four genes in LW endometrium but not in MS endometrium. Interestingly, both fetal sex and fetal genome interact to influence endometrial gene expression. CONCLUSIONS: These data provide evidence for some sexual dimorphism in the pregnant endometrium and for the contribution of the fetal genome to feto-maternal interactions at the end of gestation. They suggest that the paternal genome may contribute significantly to piglet survival, especially in crossbreeding production systems.

Society for Maternal-Fetal Medicine Statement: RhD immune globulin after spontaneous or induced abortion at less than 12 weeks of gestation.

Guidelines for the management of first-trimester spontaneous and induced abortion vary in terms of rhesus factor D (RhD) testing and RhD immune globulin (RhIg) administration. These existing guidelines are based on limited data that do not convincingly demonstrate the safety of withholding RhIg for first-trimester abortions or pregnancy losses. Given the adverse fetal and neonatal outcomes associated with RhD alloimmunization, prevention of maternal sensitization is essential in RhD-negative patients who may experience subsequent pregnancies. In care settings in which RhD testing and RhIg administration are logistically and financially feasible and do not hinder access to abortion care, we recommend offering both RhD testing and RhIg administration for spontaneous and induced abortion at <12 weeks of gestation in unsensitized, RhD-negative individuals. Guidelines for RhD testing and RhIg administration in the first trimester must balance the prevention of alloimmunization with the individual- and population-level harms of restricted access to abortion.

Surfactant Therapy in Congenital Diaphragmatic Hernia and Fetoscopic Endoluminal Tracheal Occlusion.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population. METHODS: A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression. RESULTS: Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use. CONCLUSIONS: Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO.

Effect of cannula insertion site during fetal endoscopic tracheal occlusion for congenital diaphragmatic hernia on preterm prelabor rupture of membranes.

OBJECTIVE: To assess whether the cannula insertion site on the maternal abdomen during fetal endoscopic tracheal occlusion (FETO) for congenital diaphragmatic hernia (CDH) was associated with preterm prelabor rupture of membranes (PPROM) before balloon removal. METHODS: This was a multicenter retrospective study of consecutive pregnancies with isolated left- or right-sided CDH that underwent FETO in four centers between January 2009 and January 2021. The site for balloon insertion was categorized as above or below the umbilicus. One propensity score was analyzed in both groups to calculate an average treatment effect (ATE) by inverse probability of treatment weighting. Logistic regression and Cox proportional hazard regression including the ATE weights were performed to examine the effect size of entry point on the frequency and timing of PPROM before balloon removal. RESULTS: A total of 294 patients were included. The mean ± SD gestational age at PPROM was 33.45 ± 2.01 weeks and the mean rate of PPROM before balloon removal was 25.9% (76/294). Gestational age at FETO was later in the below-umbilicus group (mean ± SD, 29.47 ± 1.29 weeks vs 29.00 ± 1.25 weeks; P = 0.002) and the duration of FETO was longer in the above-umbilicus group (median, 14.49 min (interquartile range (IQR), 8.00-21.00 min) vs 11.00 min (IQR, 7.00-14.49 min); P = 0.002). After balancing for possible confounding factors, trocar entry point below the umbilicus did not increase the risk of PPROM before balloon removal (adjusted odds ratio, 1.56 (95% CI, 0.89-2.74); P = 0.120) and had no effect on the timing of PPROM before balloon removal (adjusted hazard ratio, 1.56 (95% CI, 0.95-2.55); P = 0.080). CONCLUSION: There was no evidence that uterine entry site for FETO was correlated with the risk of PPROM before balloon removal. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Displasia mesenquimal placentaria

La displasia mesenquimal placentaria es una entidad poco frecuente, confundida al ultrasonido y macroscopía con mola parcial por las lesiones vesiculares y la presencia de feto. La microscopía revela vellosidades troncales hidrópicas con gran hiperplasia mesenquimal y lesiones vasculares prominentes, pero sin hiperplasia del epitelio trofoblástico. El feto, generalmente femenino, puede ser normal o presentar retardo del crecimiento intrauterino, malformaciones, tumores o cromosomopatías. Presentamos el estudio de cuatro casos de displasia mesenquimal placentaria; tres primigestas de 39 y 20 años de edad, y una segundigesta de 26 años. La mayor, del tercer trimestre, cursó con preeclampsia y mortinato de sexo femenino con anomalías pulmonar y esplénica, las otras dos presentaron sangrado vaginal y dolor pélvico y un caso fue un hallazgo en el control prenatal a las 8 semanas de gestación. En tres casos se observaron feto y embrion, dos de ellos tuvieron necropsia.

Placental mesenchymal dysplasia is a rare entity, confused with ultrasound and macroscopy with partial mole due to vesicular lesions and the presence of a fetus. Microscopy reveals hydropic trunk villi with great mesenchymal hyperplasia and prominent vascular lesions but without hyperplasia of the trophoblastic epithelium. The fetus, usually female, may be normal or present malformations, tumors or chromosomopathies. We present the study of four cases of placental mesenchymal dysplasia; three first-pregnancies, aged 39 and 20, and a second-pregnancy, aged 26. The oldest in the third trimester presented with preeclampsia and a female stillbirth with pulmonary and splenic anomalies, the other two presented vaginal bleeding and pelvic pain and one case was a finding in prenatal control at 8 weeks of gestation. In three cases, fetus and embryo were observed, two of them had a necropsy.

Desarrollo del dolor fetal y neonatal / Development of fetal and neonatal pain

Resumen: El dolor es el principal síntoma reportado a nivel mundial, es la principal causa de sufrimiento humano. Se considera que para que un individuo sienta dolor deben estar presentes: nociceptores, neurotransmisores del dolor, vías que llevan el estímulo al cerebro, el tálamo y conexión con la corteza. Por un tiempo se consideró que en esta etapa no se contaba con la madurez suficiente del sistema nervioso para sentir dolor; sin embargo, en la actualidad hay evidencia de que el feto presenta dolor; y su presencia altera el desarrollo del sistema nervioso. La presente revisión proporciona una visión actualizada de la ontogenia del dolor fetal y neonatal.

Abstract: Pain is the main symptom reported worldwide, it is the main cause of human suffering. It is considered that for an individual to feel pain, the following must be present: nociceptors, pain neurotransmitters, pathways that carry the stimulus to the brain, the thalamus and connection with the cortex. For a time it was considered that at this stage the nervous system was not mature enough to feel pain, however, there is currently evidence that the fetus has pain; and its presence alters the development of the nervous system. This review provides an updated view of the ontogeny of fetal and neonatal pain.

Case Report: Fetoscopic Laparoschisis (FETO-LAP)-A New Therapeutic Route to Explore for Fetuses with Severe Diaphragmatic Hernias.

BACKGROUND: The purpose of this report is to describe the seminal case of a near-term human fetus with a life-threatening left diaphragmatic hernia that underwent fetoscopic tracheal occlusion (FETO) combined with fetoscopic partial removal of herniated bowel from the fetal chest by fetoscopic laparoschisis (FETO-LAP). CASE SUMMARY: A life-threatening left diaphragmatic hernia (liver-up; o/e LHR of ≤25%; MRI lung volume ≤ 20%) was observed in a human fetus at 34 weeks of gestation. After counselling the mother about the high risks of postnatal demise if left untreated, the expected limitations of fetoscopic tracheal occlusion (FETO), and the previously untested option of combining FETO with fetoscopic laparoschisis, i.e., partial removal of the herniated bowel from the fetal chest (FETO-LAP), she consented to the latter novel treatment approach. FETO-LAP was performed at 36 + 5 weeks of gestation under general maternofetal anesthesia. Mother and fetus tolerated the procedure well. The neonate was delivered and the balloon removed on placental support at 37 + 2 weeks of gestation. On ECMO, a rapid increase in tidal volume was seen over the next eight days. Unfortunately, after this period, blood clots obstructed the ECMO circuit and the neonate passed away. DISCUSSION: This seminal case shows that in a fetus with severe left diaphragmatic hernia, partial removal of the herniated organs from the fetal chest is not only possible by minimally invasive fetoscopic techniques but also well tolerated. As the effect of FETO alone is limited in saving severely affected fetuses, combining FETO with fetoscopic laparoschisis (FETO-LAP) offers a new therapeutic route with multiple, potentially life-saving implications.

Fetal surgery using fetoscopic endoluminal tracheal occlusion for severe congenital diaphragmatic hernia: a single-center experience.

PURPOSE: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center. METHODS: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO. RESULTS: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032). CONCLUSIONS: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers.