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Introduction: Spina bifida (SB) remains one of the most common congenital anomalies and associates with significant comorbidities in the fetus, which may, in part, be driven by placental maldevelopment. We hypothesised that placental pathologies would be more prevalent in fetuses with SB compared to fetuses without congenital anomalies., Methods: Placental pathology and transcriptome were evaluated for fetuses with isolated open SB born preterm (cases; n = 12) and control fetuses without congenital anomalies (n = 22) born at full term (FT) or preterm (PT). We evaluated associations between study group and placental histopathology, and between placental histopathology and gene expression., Results: Placental weight was lower in cases than PT controls (median [IQR]: 263 g [175, 370] vs. 455 g [378, 560], p = 0.001). Placental villi structural phenotype was different in cases, where proportion of immature intermediate villi was higher in cases than PT controls (32.5 % [6.3, 56.3] vs. 10 % [5, 13.8], p = 0.01), but cases and FT controls had similar proportions of mature intermediate (10 % [5, 10] vs. 10 % [8.75, 11.25]) and terminal villi (22.5 % [11.3, 43.8] vs. 30 % [20, 36.3]), and similar odds of having many syncytial knots (adjusted odds ratio [aOR] = 6 [0.2, 369]). Case placentae also had higher odds of having many Hofbauer cells (aOR = 16.2 [1.4, 580], p = 0.02) and a thick syncytial membrane (aOR = 146 [3, 3.46e5], p = 0.007). Gene expression in immune/inflammatory processes, spinal cord injury, and Hedgehog and Wnt signaling pathways were associated with placental maturity in cases., Discussion: Improved knowledge on placental phenotypes in SB increases our understanding of mechanisms that may drive comorbidities, and may ultimately inform efforts to reduce offspring morbidity and mortality., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Neural tube defects (NTDs) are amongst the most common congenital anomalies and are associated with significant postnatal morbidity, but also with a higher incidence of low birthweight and fetal growth restriction. Despite the placenta being a critical determinant of fetal growth, placental development has not been extensively studied in fetuses with NTDs., Methods: We performed a matched case-cohort study using data from the Collaborative Perinatal Project to assess the risk of placental pathology in pregnancies with an isolated fetal NTD (cases; n = 74) compared to those without any congenital anomalies (controls; n = 148). We hypothesised that cases would be at an increased risk of placental pathology compared to controls. Data were analysed using adjusted generalized linear and nominal logistic regression models. Results are presented as adjusted β or adjusted odds ratio (aOR; 95% confidence interval)., Results: Cases had lower placental weight (β = -22.2 g [-37.8 to -6.6]), surface area (β = -9.6 cm 2 [-18.3 to -1.0]) and birth length z-scores (β = -0.4 [-0.7 to -0.001]) compared to controls. Cases were more likely to have a single umbilical artery (vs. two; 6 [8.1%] vs. 1 [0.7%]; aOR = 301 [52.6-1726]), placental hypermaturity (9 [12.2%] vs. 5 [3.4%]; aOR = 6.8 [3.1-14.7]), many (vs. few) Hofbauer cells (9 [12.2%] vs. 7 [4.7%]; aOR = 3.02 [1.2-7.3]), and stromal fibrosis (9 [12.2%] vs. 10 [6.8%]; aOR = 3.0 [1.4-6.3]) in placental terminal villi compared to controls., Conclusions: Fetuses with isolated NTDs may be at increased risk of placental pathology, which could be contributing to poor fetal growth in these pregnancies and subsequent postnatal morbidities., Competing Interests: Declaration of competing interest None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Twin-twin transfusion syndrome (TTTS) complicates 15% of monochorionic twin pregnancies, often being associated with recipient cardiac dysfunction. Untreated, it has a fetal mortality rate of at least 90%; although treatment by fetoscopic laser coagulation significantly improves prognosis. Measurement of recipient amniotic fluid metabolites, such as cardiac Troponin T and atrial natriuretic polypeptide, correlate with cardiac function in this fetus. The aim of this study is to describe the amniotic fluid metabolomic profile in TTTS, relate this to fetal recipient cardiac function and assess the metabolomic changes induced by fetoscopic laser coagulation., Methods: Prospective single centre cohort study. The metabolomics profile of the amniotic fluid from the recipient sac of TTTS pregnancies was assessed using ultra high performance liquid chromatography-mass spectrometry. Profiles were compared pre- and post-laser coagulation and related to fetal recipient cardiac function, as assessed using Doppler ultrasound within 4 h of treatment., Results: Eleven metabolites had significant associations with recipient fetal right and left ventricular myocardial performance index pre-laser. 200 metabolites in recipient amniotic fluid demonstrated a change in relative concentrations when comparing pre- and post-laser coagulation (p < 0.005). The most prominent change is in the balance of carbohydrate and fatty acid metabolic profile contributing to fetal or placental energy metabolism. These changes were also associated with the echocardiographic measures of recipient cardiac function., Discussion: Changes in carbohydrate and fatty acid metabolic profiles are noted in recipients with cardiac dysfunction, and further changes are noted after treatment. Validation and investigation may identify targets for potential pharmacological treatment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)