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Purpose Fetal growth restriction (FGR) management and delivery planning is based on a multimodal approach. This meta-analysis aimed to evaluate the prognostic accuracies of the aortic isthmus Doppler to predict adverse perinatal outcomes in singleton pregnancies with FGR. Methods PubMed, EMBASE, the Cochrane Library, ClinicalTrials.gov and Google scholar were searched from inception to May 2021, for studies on the prognostic accuracy of anterograde aortic isthmus flow compared with retrograde aortic isthmus flow in singleton pregnancy with FGR. The meta-analysis was registered on PROSPERO and was assessed according to PRISMA and Newcastle–Ottawa Scale. DerSimonian and Laird’s random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2 statistics. Results A total of 2933 articles were identified through the electronic search, of which 6 studies (involving 240 women) were included. The quality evaluation of studies revealed an overall acceptable score for study group selection and comparability and substantial heterogeneity. The risk of perinatal death was significantly greater in fetuses with retrograde Aortic Isthmus blood flow, with a RR of 5.17 (p value 0.00001). Similarly, the stillbirth rate was found to have a RR of 5.39 (p value 0.00001). Respiratory distress syndrome had a RR of 2.64 (p value = 0.03) in the group of fetuses with retrograde Aortic Isthmus blood flow. Conclusion Aortic Isthmus Doppler study may add information for FGR management. However, additional clinical trial are required to assess its applicability in clinical practice.

Background Discoid meniscus (DM) is a rare variant of regular knee anatomy. Compared to standard meniscus it is thicker and abnormal in shape; these characteristics make it more prone to tear. It is a congenital defect whose correct etiology is still debated and far from being clarified. The purpose of this systematic review is to evaluate evidences of DM in human fetuses in order to assess whether embryological development may have a role. Methods A systematic review was performed on PubMed, Scopus, and Embase with different combinations of the keywords “discoid meniscus”, “embryology”, “fetus”, “neonatal”. Search yielded 1013 studies, on which we performed a primary evaluation. Results Seven studies were considered including a total of 1378 fetal menisci specimens, from 396 different fetuses. Discoid shape was not found represented as a normal stage of prenatal development. From 782 lateral menisci analyzed, only 86 (10.86%) were discoid (13 complete, 73 incomplete type). None of medial menisci was found to be discoid. Lateral meniscus was observed to cover a larger surface of tibial plateau than medial one until 28th gestational week. Conclusion Lateral meniscus seems to be more prone to discoid shape for its natural tendency of covering a larger surface of the tibial plateau during fetal stages. However the fact that a discoid shape was not found in the majority of fetuses suggests that it is not a normal stage of fetal development. To support a single etiological factor it will be appropriate to have further morphological and morphometric studies.

The aim of this mini-review is to present the current knowledge on iodine requirements in developmental age, from conception to adolescence. It is based on the analysis of updated national and international guidelines on iodine intake and the prevention of iodine deficiency. Health policy initiatives carried out in industrialized countries in previous decades have led to a dramatic improvement in nutritional iodine status in the general population. However, the prevention of iodine deficit continues to be a concern, especially for vulnerable categories, like adolescents and pregnant women.

Purpose of review Fetal central nervous system malformations are among the most common congenital anomalies. Whereas simple axial views are sufficient for basic fetal brain examination, other important views are essential for a more detailed examination, which are sometimes challenging to obtain. Three-dimensional ultrasound can be helpful in obtaining standardized and reproducible images of many difficult fetal brain views. The aim of the present review is to explore the most recent evidence on the utility and technique of three-dimensional ultrasound in the examination of the fetal brain, with particular emphasis on the brain views that benefit from three-dimensional ultrasound. Recent findings The article describes the various techniques of acquisition and analyses of three-dimensional ultrasound volumes of the fetal brain and their usefulness in the assessment of normal and abnormal fetal brain anatomy. Three-dimensional ultrasound has also permitted the application of many new technologies, such as artificial intelligence and deep machine learning. Recently, thanks to high-quality three-dimensional ultrasound, fetal cortical development can be assessed quantitatively and reliably. Summary Three dimensional ultrasound can help as a complementary tool to two-dimensional ultrasound in the assessment of the fetal brain development and malformations. In addition, it paves the way for the application of promising technologies in the evaluation of fetal brain. Video abstract A video summarizing the findings of the article. The video illustrates the various approaches and techniques applied for the examination of the fetal brain using three-dimensional ultrasound. Furthermore, the advantages and future perspectives of the application of three-dimensional ultrasound in the examination of the fetal brain are discussed, http://links.lww.com/COOG/A74.

Background and Objectives: Shoulder dystocia (ShD) is one of most dangerous obstetric complication. The objective of this study was to determine if the ultrasonographic fetal biacromial diameter (BA) and derived parameters could predict ShD in uncomplicated term pregnancies. Materials and Methods: We conducted a prospective observational study in a tertiary care university hospital from March 2021 to February 2022. We included all full-term pregnancies accepted for delivery that received an accurate ultrasonography (USG) scan before delivery. USG biometry and estimated fetal weight (EFW) were collected. Therefore, we evaluated the diameter of the mid-arm, the transverse thoracic diameter (TTD) and the biacromial diameter (BA). BA was estimated using Youssef’s formula: TTD + 2 mid-arm diameters. The primary outcome was the evaluation of BA and its related parameters (BA/biparietal diameter (BPD), BA/head circumference (HC) and BA–BPD in fetuses with ShD versus fetuses without ShD. Diagnostic accuracy for ShD of BA, BA/BPD, BA/HC and BA–BPD was evaluated using receiver operator curve (ROC) analysis. Results: 90 women were included in the analysis, four of these had ShD and required extra maneuvers after head delivery. BA was increased in fetuses with ShD (150.4 cm; 95% CI 133.2 cm to 167.6 cm) compared to no-ShD (133.5 cm; 95% CI 130.1 cm to 137.0 cm; p = 0.04). Significant differences were also found between ShD and no-ShD groups for BA/BPD (1.66 (95% CI 1.46 to 1.86) vs. 1.44 (95% CI 1.41 to 1.48); p = 0.04), BA/HC (0.45 (95% CI 0.40 to 0.49) vs. 0.39 (95% CI 0.38 to 0.40); p = 0.01), BA–BPD (60.0 mm (95% CI 42.4 to 77.6 cm) vs. 41.4 (95% CI 38.2 to 44.6); p = 0.03), respectively. ROC analysis showed an overall good accuracy for ShD, with an AUC of 0.821 (p = 0.001) for BA alone and 0.881 (p = 0.001), 0.857 (p = 0.016) and 0.867 (p = 0.013) for BA/BPD, BA–BPD and BA/HC, respectively. Conclusions: BA alone, as well as BA/BPD, BA/HC and BA–BPD might be useful predictors of ShD in uncomplicated term pregnancies. However, such evidence needs extensive confirmation by means of additional studies with large sample sizes, especially in case of pregnancies at high risk for ShD (i.e., gestational diabetes).

Les problématiques retenues Cette étude porte sur l’histoire du royaume de Fetu des débuts du commerce atlantique sur la Côte de l’Or (1471) à la constitution de la fédération Fanti (années 1720). Fetu, petite monarchie côtière, société étatique constituée et endogène, va se trouver confrontée à l’altérité européenne dès l’arrivée des Portugais sur cette côte. La construction du château de Saint Georges de la Mine sur sa frontière occidentale, l’afflux des concurrents européens des Portugais,...

L’histoire du royaume de Fetu est l’histoire d’un micro-Etat maritime, déjà puissant et intégré aux réseaux commerciaux longue-distance avant l’arrivée des Portugais. Le commerce transsaharien apportait à l’aristocratie du pays les produits de prestige qui lui servaient à matérialiser son prestige et son pouvoir, et contribuait à son enrichissement. L’arrivée des Européens – qui proposent leurs tissus et leurs minerais contre l’or abondant que produit la zone forestière – à la fin du XV° sièc...

A.N.T.T. Arquivo Nacional de Torre do Tombo A.R.A. Algemeen Rijks Archief (Archives nationales de La Haye) B.N. Bibliothèque Nationale C.E. A Cahiers d’Etudes Africaines G.N.Q. Ghana Notes and Queries J.A.H. Journal of African History J.A.S. Journal of African Studies P.R.O. Public Record Office R.A.C. Royal Africa Company T.H.S.G. Transactions of the Historical Society of Ghana W.I.C. West Indische Compagnie

1. LA GUERRE A FETU ET EN PAYS FANTI (LA GUERRE ENTRE AKAN) La guerre en pays Fanti est réglée par un ensemble de pratiques, de codes qu’on ne saurait transgresser sans se déshonorer, se ridiculiser, voire même attirer la colère des ancêtres et des dieux. Les acteurs des guerres en pays Fanti sont tenus de reproduire une série d’attitudes convenues, de rituels, par lesquels la société parle d’elle-même. Emmanuel Terray, dans un article paru en 1982, souligne que le type de guerre que l’on mèn...

1. ASHANTI, FANTI, ANGLAIS ET HOLLANDAIS : LE JEU DES GRANDS En 1699, le Denkyira est défait par l’Ashanti aux batailles d’Adunku et Feyiassé. Anglais et Hollandais s’empressent de gagner les faveurs du nouveau géant de l’intérieur, tandis que sur la côte, les Fanti commencent à contracter des alliances pour faire face à la puissance Ashanti. Quant à Fetu, les Anglais tentent d’y conforter leur position chèrement acquise en 1694 et de renforcer leur emprise sur ce royaume. Sir Dalby Thomas, A...

Plusieurs catégories de sources ont été utilisées ici. D’Eustache de La Fosse (sur la Côte de l’Or en 1479-1480) à P.E. Isert (sur la Côte de l’Or en 1783-1786 et 1788-1789), 19 relations de voyage ont été étudiées, ainsi que divers rapports rédigés par des commandants de forts ou des commercants. Des archives publiées (de forts et de compagnies commerciales) portugaises, anglaises, hollandaises et suédoises ont également été consultées. En ce qui concerne les archives portugaises et anglaise...

1. EUROPEENS ET AFRICAINS : les premiers contacts L’arrivée des Européens sur la Côte de l’Or En janvier 1471, Joao de Santarem et Pero Escobar, chevaliers de la maison du roi du Portugal, découvrent sur la Côte de Guinée pour le compte de Fernao Gomes (à qui le roi du Portugal, Dom Atfonso V, a affermé le commerce de la Côte de Guinée), le village de Samma et l’endroit qui sera plus tard connu sous le nom d’Elmina. Très vite, la nouvelle se répand en Europe que les "Côtes de Guinée" sont ric...

1. LE CADRE REGIONAL La Côte de l’Or était, à l’arrivée des Portugais, quadrillée par des Etats aux frontières très précisément délimitées. Le meilleur exemple en est "Aldea de Duas Partes’’, village dont une moitié appartenait au royaume de Komendo, l’autre à Fetu. Cette région se caractérisait par une grande fragmentation politique, c’est-à-dire par la présence d’un grand nombre de micro-Etats dont Fetu était, avec l’Etat d’Asebu, un des plus petits. Ces Etats entretenaient entre eux des re...

1. L’IMPLANTATION DES NATIONS EUROPEENNES CONCURRENTES Les Fetu, acteurs de l’implantation des Européens En 1637, les Hollandais alliés aux Komendo prennent Elmina après plusieurs tentatives infructueuses ; dès 1642, les Portugais ne possèdent plus un fort sur la Côte de l’Or. Les années 1640, 1650 et 1660 sont des années d’intense concurrence entre les compagnies anglaise, hollandaise, danoise et suédoise, qui toutes, tentent de s’implanter sur le littoral de Fetu et y parviennent, au moins ...

1. LA MONTEE EN PUISSANCE DES ETATS AKAN DE L’INTERIEUR ET SES CONSEQUENCES POLITIQUES Les dernières décennies du XVII° siècle voient la montée en puissance des Etats forestiers de l’hinterland Akan. Alors que la carte politique est restée stable sur la côte tout au long de la période traitée ici, les Etats de l’intérieur connaissent au contraire de profondes mutations et il se crée, par regroupements, de puissants Etats aux sources de l’or Akan. Le Denkyira, qui a vaincu l’Adanse en 1659, s’...

Les guerres Komenda que nous avons rapidement résumées, tout comme la guerre de 1694 opposant Fetu à Asebu, s’inscrivent en rupture totale avec les pratiques de la guerre traditionnelle Akan. On assiste en effet à la mise en place, à l’initiative des Européens, de vastes coalitions impliquant des royaumes côtiers et des royaumes de l’intérieur. Ces coalitions ont pour lien l’or qu’Anglais et Hollandais proposent aux Adom, Denkyira, Twifo, Cabesterra, Sabu, Fanti et Akani afin de gagner le con...

1. AGRICULTURE ET DEMOGRAPHIE La conséquence la plus immédiate de l’instauration du commerce atlantique est un renversement de la situation géopolitique de Fetu. En effet, avant l’arrivée des Européens, Fetu se trouvait à l’extrémité méridionale des routes du commerce longue distance qui reliaient la Côte de l’Or à la zone soudanaise ; le commerce atlantique confère à Fetu, en raison de son ouverture sur la mer et de sa proximité avec Elmina, une position stratégique. On a vu avec quel succès...

Dans la seconde moitié du XVII° siècle, tandis que le contexte politique régional se modifie, les pratiques guerrières des Fanti évoluent. Plusieurs facteurs entrent en jeu, en ce qui concerne la cause de ces évolutions. Nous proposons ici en premier lieu de souligner quelles sont ces évolutions puis de les mettre en relation avec l’évolution du contexte régional. 1. LE SYSTEME DES ASAFO Le rôle et l’organisation des asafo Un asafo est "l’organisation des hommes valides capables de combattre"...

Objective: This study aims to assess accuracy and clinical utility of postmortem radiological exams [Magnetic Resonance Imaging (MRI), Computed Tomography (CT) and Radiography (XR)] after termination of pregnancy at

Objectives: To investigate the umbilical vein and uterine arteries blood flow volume (UV-Q, UtA-Q) in late-term pregnancies.& nbsp;Study design: This was a prospective observational cohort study of singleton pregnancies > 40 + 0 weeks in which UV-Q and UtA-Q, both absolute and normalized for estimated fetal weight (EFW) values, were evaluated in relation to AC drop of > 20 percentiles from 20 weeks to term, Doppler signs of fetal cerebral blood flow redistribution and composite adverse perinatal outcome. The presence of neonatal hypoglycaemia and the need of formula milk supplementation were also examined.& nbsp;Results: The study population comprised 200 women. Fetuses with AC drop (n = 34) had a significantly lower UV-Q and UV-Q/EFW than fetuses without AC drop (n = 166): median UV-Q 184 ml/min (IQR 143-225) vs 233 ml/min (IQR 181-277), p = 0.0006; median UV-Q/EFW 55 ml/min/kg (IQR 42-66) vs 63 ml/min/kg (IQR 48-74), p = 0.03. Fetuses with cerebral blood flow redistribution (n = 48) had a significantly lower UV-Q and UV-Q/EFW than those without (n = 134): median UV-Q 210 ml/min (IQR 155-263) vs 236 ml/min (IQR 184-278), p = 0.04; median UV-Q/EFV 58 ml/min/kg (IQR 45-70) vs 65 ml/min/kg (IQR 50-76), p = 0.04. There was a significant moderate correlation between middle cerebral artery pulsatility index (MCA-PI) and UV -Q and UV-Q/EFW (Spearman Rho-0.20 and-0.20; p = 0.008 and p = 0.006).& nbsp;Conclusions: The umbilical vein blood flow volume might have a potential role to identify fetuses with stunted growth in late-term pregnancies.

Background Congenital malformations of the central nervous system (CNS) consist of a wide range of birth defects of multifactorial origin. Methods Concentrations of 44 metals were determined by Inductively Coupled Plasma Mass Spectrometry in serum of 111 mothers in the second trimester of pregnancy who carried a malformed fetus and compared them with serum concentrations of the same metals in 90 mothers with a normally developed fetus at the same week of pregnancy. Data are reported as means ± standard deviations. Results We found a direct relationship between congenital defects of the CNS and maternal serum concentration of aluminum: it was statistically higher in women carrying a fetus with this class of malformation, compared both to mothers carrying a fetus with another class of malformation (6.45 ± 15.15 μg/L Vs 1.44 ± 4.21 μg/L, p Conclusion CAluminum may play a role in the onset of central nervous system malformations, although the exact Aluminum species and related specific type of malformation needs further elucidation.

Bisphenol A (BPA) is an organic chemical compound widely used for manufacturing plastics. BPA exposure originates principally from the diet, but it can also originate from dermal contact. In over 90% of individuals, including pregnant women, BPA is detectable in several body fluids. The effects of this exposure on the fetus are under active investigation in several research laboratories. The aim of our work was to study the impact of prenatal exposure to BPA in the liver of rat fetuses from a sex-dependent point of view. We particularly investigated the effects of prenatal BPA exposure on hepatic lipids because of their crucial role, not only for the liver, but also for the whole-body functions. Our results demonstrate that the liver of rat fetuses, in utero exposed to a very low dose of BPA (2.5 µg/kg/day), displays significant modulations with regard to proteins involved in cholesterol and fatty acid biosynthesis and trafficking. Moreover, an impact on inflammatory process has been observed. All these effects are dependent on sex, being observable only in female rat fetuses. In conclusion, this work demonstrates that maternal exposure to BPA compromises hepatic lipid metabolism in female offspring, and it also reveals the perspective impact of BPA on human health at doses currently considered safe.

Objective To assess the differential diagnostic significance of a series of quantitative and qualitative variables of the cerebellar vermis in fetuses with posterior fossa cystic malformation, including Dandy-Walker malformation (DWM), vermian hypoplasia (VH) and Blake's pouch cyst (BPC). Methods This was a retrospective study of confirmed cases of DWM, VH and BPC, diagnosed at the Fetal Medicine and Surgery Unit of the Federico II University between January 2005 and June 2013 or the Fetal Medicine and Surgery Unit of G. Gaslini Hospital between July 2013 and September 2017. All included cases had good-quality three-dimensional (3D) volume datasets of the posterior fossa, acquired by transvaginal ultrasound through the posterior fontanelle. The midsagittal view of the posterior fossa was the reference view for the study. We assessed brainstem-tentorium angle and brainstem-vermis angle (BVA), as well as craniocaudal (CCVD) and anteroposterior (APVD) vermian diameters and vermian area (VA), which were normalized by biparietal diameter (BPD) to take into account gestational age (CCVD/BPD × 100, APVD/BPD × 100 and VA/BPD × 100, respectively). Finally, the position of the fourth ventricular choroid plexus (4VCP) was defined as normal ('up') or abnormal ('down'), relative to the roof/cyst inlet of the fourth ventricle. Results We analyzed 67 fetuses with posterior fossa malformations (24 cases of DWM, 13 of VH and 30 of BPC). The mean gestational age at diagnosis was 23.6 weeks. Regardless of gestational age, the BVA differed significantly between the three groups, and the VA/BPD was able to differentiate between VH and BPC. In differentiating between VH and BPC, the greatest areas under the receiver-operating characteristics curve were those for VA/BPD ratio. The 4VCP position was down in all cases of DWM and VH, while it was up in all cases of BPC. Conclusions Our data support the concept that VA/BPD ratio and 4VCP position may be used to differentiate between DWM, VH and BPC in the fetus. In our series, the position of the 4VCP had the highest accuracy, but a larger number of VH cases should be evaluated to confirm that an up position of the 4VCP indicates BPC while a down position indicates DWM or VH. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normalcholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p-value

Background: Occiput posterior position is the most frequent cephalic malposition, and its persistence at delivery is associated with a higher risk of maternal and perinatal morbidity. Diagnosis and management of occiput posterior position remain a clinical challenge. This is partly caused by our inability to predict fetuses who will spontaneously rotate into occiput anterior from those who will have persistent occiput posterior position. The angle of progression, measured with transperineal ultrasound, represents a reliable tool for the evaluation of fetal head station during labor. The relationship between the persistence of occiput posterior position and fetal head station in the second stage of labor has not been previously assessed. Objective: This study aimed to evaluate the role of fetal head station, as measured by the angle of progression, in the prediction of persistent occiput posterior position and the mode of delivery in the second stage of labor. Study Design: We recruited a nonconsecutive series of women with posterior occiput position diagnosed by transabdominal ultrasound in the second stage of labor. For each woman, a transperineal ultrasound was performed to measure the angle of progression at rest. We compared the angle of progression between women who delivered fetuses in occiput anterior position and those with persistent occiput posterior position at delivery. Receiver operating characteristics curves were performed to evaluate the accuracy of the angle of progression in the prediction of persistent occiput posterior position. Finally, we performed a multivariate logistic regression to determine independent predictors of persistent occiput posterior position. Results: Overall, 63 women were included in the analysis. Among these, 39 women (62%) delivered in occiput anterior position, whereas 24 (38%) delivered in occiput posterior position (persistent occiput posterior position). The angle of progression was significantly narrower in the persistent occiput posterior position group than in women who delivered fetuses in occiput anterior position (118.3°±12.2° vs 127.5°±10.5°; P=.003). The area under the receiver operating characteristics curve was 0.731 (95% confidence interval, 0.594–0.869) with an estimated best cutoff range of 121.5° (sensitivity of 72% and specificity of 67%). On logistic regression analysis, the angle of progression was found to be independently associated with persistence of occiput posterior position (odds ratio, 0.942; 95% confidence interval, 0.889–0.998; P=.04). Finally, women who underwent cesarean delivery had significantly narrower angle of progression than women who had a vaginal delivery (113.5°±8.1 vs 128.0°±10.7; P

BACKGROUND: Abnormal sulcation of the brain is frequently associated with severe malformations, but the prenatal diagnosis is challenging, especially in early pregnancy. OBJECTIVE: Our study aimed to investigate the value of Sylvian fossa sonographic biometry in the diagnosis of cerebral malformation in the second trimester of gestation. STUDY DESIGN: We prospectively established the normal values of the Sylvian fossa depth in a cohort of nonconsecutive patients, with singleton pregnancies and normal fetuses between 18+0 and 23+0 weeks’ gestation. For each patient, a coronal view of the fetal brain, with a clear visualization of the anterior complex and the Sylvian fissure, was acquired by 1 sonologist, who also measured the depth of the fossa. Reproducibility for each parameter was assessed by a second sonologist using stored images. We also retrospectively acquired the same measurements in second trimester fetuses with central nervous system anomalies. RESULTS: In 103 fetuses with a normal sonogram, the mean depth of the Sylvian fossa was 3.9±0.8 mm Interobserver reproducibility analysis demonstrated good results. Notably, 11 of 31 fetuses with cerebral malformations had a Sylvian fossa depth of

Background: Pregnant women are usually more susceptible to infection due to typical physiological and mechanical changes, such as increased heart rate, stroke volume and pulmonary residual capacity. The aim of this study was to evaluate an innovative anesthesiologic opioid-free management protocol in symptomatic pregnant women, with COVID-19 and with oxygen therapy, undergoing cesarean delivery with spinal anesthesia. Methods: With the patient in the sitting position, spinal anesthesia was performed at the L1-L2 level. Vertebral level has been identified starting from the sacrum, we counted the laminae in the caudal-to-cephalad direction, which was then marked with a surgical pen. The technique was performed in asepsis, in the subarachnoid space after vision of clear Cephalo-Spinal Fluid (CSF) in the spinal needle 27 Gauge, without letting out the CSF, bupivacaine 0.5% 10 mg, dexmedetomidine 10 μg and dexamethasone 4 mg was injected. Results: During the study period, 40 pregnant women with one or more symptoms and supplemental oxygen (FiO2 35-40%) who underwent cesarean delivery were included in the study. All pregnant women had pain visual analog scale (VAS)

Objective: To assess the feasibility and reliability of transperineal ultrasound in the assessment of fetal breech descent in the birth canal, by measuring the breech progression angle (BPA). Methods: Women with a singleton pregnancy with the fetus in breech presentation between 34 and 41 weeks' gestation were recruited. Transperineal ultrasound images were acquired in the midsagittal view for each woman, twice by one operator and once by another. Each operator measured the BPA after anonymization of the transperineal ultrasound images. BPA was defined as the angle between a line running along the long axis of the pubic symphysis and another line extending from the most inferior portion of the pubic symphysis tangentially to the lowest recognizable fetal part in the maternal pelvis. Each operator was blinded to all other measurements performed for each woman. Intra- and interobserver reproducibility of BPA measurement was evaluated using the intraclass correlation coefficient (ICC). To investigate the presence of any bias, intra- and interobserver agreement was also analyzed using Bland–Altman analysis. Student's t-test and Levene's W0 test were used to investigate whether a number of different clinical factors had an effect on systematic differences and homogeneity, respectively, between BPA measurements. Results: Overall, 44 women were included in the analysis. BPA was measured successfully by both operators on all images. Both intra- and interobserver agreement analyses showed excellent reproducibility in BPA measurement, with ICCs of 0.88 (95% CI, 0.80–0.93) and 0.83 (95% CI, 0.71–0.90), respectively. The mean difference between measurements was 0.4° (95% CI, −1.4 to 2.2°) for intraobserver repeatability and −0.4° (95% CI, −2.6 to 1.8°) for interobserver repeatability. The upper limits of agreement were 12.0° (95% CI, 8.9–15.1°) and 13.6° (95% CI, 9.9–17.3°) for intra- and interobserver repeatability, respectively. The lower limits of agreement were −11.2° (95% CI, −14.3 to −8.1°) and −14.4° (95% CI, −18.2 to −10.7°) for intra- and interobserver repeatability, respectively. No systematic difference between BPA measurements was found on either intra- or interobserver agreement analysis. None of the clinical factors examined (maternal body mass index, maternal age, gestational age at the ultrasound scan and parity) showed a statistically significant effect on intra- or interobserver reliability. Conclusions: BPA represents a new feasible and highly reproducible measurement for the evaluation of fetal breech descent in the birth canal. Future studies assessing its usefulness in the prediction of successful external cephalic version and breech vaginal delivery are needed. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increasing evidence suggests that maternal cholesterol represents an important risk factor for atherosclerotic disease in offspring already during pregnancy, although the underlying mechanisms have not yet been elucidated. Eighteen human fetal aorta samples were collected from the spontaneously aborted fetuses of normal cholesterolemic and hypercholesterolemic mothers. Maternal total cholesterol levels were assessed during hospitalization. DNA methylation profiling of the whole SREBF2 gene CpG island was performed (p value

Objective To assess the performance of fetal magnetic resonance imaging (MRI) in detecting associated anomalies in fetuses diagnosed with isolated corpus callosal (CC) anomaly on multiplanar ultrasound evaluation of the fetal brain (neurosonography). Methods This was a multicenter, retrospective cohort study involving 14 fetal medicine centers in Italy, UK, Portugal, Canada, Austria and Spain. Inclusion criteria were fetuses with an apparently isolated CC anomaly, defined as an anomaly of the CC and no other additional central nervous system (CNS) or extra-CNS abnormality detected on expert ultrasound, including multiplanar neurosonography; normal karyotype; maternal age >= 18 years; and gestational age at diagnosis >= 18 weeks. The primary outcome was the rate of additional CNS abnormalities detected exclusively on fetal MRI within 2 weeks following neurosonography. The secondary outcomes were the rate of additional abnormalities according to the type of CC abnormality (complete (cACC) or partial (pACC) agenesis of the CC) and the rate of additional anomalies detected only on postnatal imaging or at postmortem examination. Results A total of 269 fetuses with a sonographic prenatal diagnosis of apparently isolated CC anomalies (207 with cACC and 62 with pACC) were included in the analysis. Additional structural anomalies of the CNS were detected exclusively on prenatal MRI in 11.2% (30/269) of cases, with malformations of cortical development representing the most common type of anomaly. When stratifying the analysis according to the type of CC anomaly, the rate of associated anomalies detected exclusively on MRI was 11.6% (24/207) in cACC cases and 9.7% (6/62) in pACC cases. On multivariate logistic regression analysis, only maternal body mass index was associated independently with the likelihood of detecting associated anomalies on MRI (odds ratio, 1.07 (95% CI, 1.01-1.14); P = 0.03). Associated anomalies were detected exclusively after delivery and were missed on both types of prenatal imaging in 3.9% (8/205) of fetuses with prenatal diagnosis of isolated anomaly of the CC. Conclusion In fetuses with isolated anomaly of the CC diagnosed on antenatal neurosonography, MRI can identify a small proportion of additional anomalies, mainly malformations of cortical development, which are not detected on ultrasound. (c) 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Fertility in mammals is controlled by hypothalamic neurons that secrete gonadotropin-releasing hormone (GnRH). These neurons differentiate in the olfactory placodes during embryogenesis and migrate from the nose to the hypothalamus before birth. Information regarding this process in humans is sparse. Here, we adapted new tissue-clearing and whole-mount immunohistochemical techniques to entire human embryos/fetuses to meticulously study this system during the first trimester of gestation in the largest series of human fetuses examined to date. Combining these cutting-edge techniques with conventional immunohistochemistry, we provide the first chronological and quantitative analysis of GnRH neuron origins, differentiation and migration, as well as a 3D atlas of their distribution in the fetal brain. We reveal not only that the number of GnRH-immunoreactive neurons in humans is significantly higher than previously thought, but that GnRH cells migrate into several extrahypothalamic brain regions in addition to the hypothalamus. Their presence in these areas raises the possibility that GnRH has non-reproductive roles, creating new avenues for research on GnRH functions in cognitive, behavioral and physiological processes.

Death was a common factor during pregnancy and childbirth in both past and recent societies. Nevertheless, the recording of women from archaeological contexts still featuring a fetus in the pelvic cavity or dystocia is very rare. Even less frequent are cases of post mortem fetal extrusion. At the archaeological site of San Genesio (San Miniato, Pisa), a stoppage point along the Via Francigena, the cemetery phases dating from the 6th to the 13th century were investigated. In one of the phases dating to the Early Medieval period, the skeleton of a female individual of about thirty years of age, deceased during the 32nd week of pregnancy, was documented. The fetus was positioned between the femurs, in the opposite orientation to that of the mother. Taphonomic analysis, comparative review of other forensic and archaeological cases and the anthropological study of the recorded skeletons suggest that, due to the accumulation of gas during the emphysematous phase of decomposition, the fetus would have been expelled from the mother’s pelvic cavity before the bodies were completely covered by soil. We can define this finding as one of those rare cases of “coffin birth” in an archaeological context.

Objectives: The aims of this study were to review systematically literature on and describe the sonographic features and associated anomalies of total (TAPVC) and partial (PAPVC) anomalous pulmonary venous connection and scimitar syndrome (SS). Methods: A retrospective cohort study was carried out of cases of TAPVC, PAPVC and SS that underwent comprehensive ultrasound examination, seen over a 20-year period at two tertiary referral centers. Assessed variables included TAPVC subtype, gestational age at diagnosis, area behind the left atrium, ventricular disproportion, vertical vein, pulmonary venous obstruction, mode of diagnosis, association with cardiac and extracardiac conditions, and pregnancy and fetoneonatal outcomes. The outcome was considered favorable if the individual was alive and well (no functional impairment from surgery or cardiac or extracardiac conditions). Cases associated with right isomerism were excluded from the analysis, as TAPVC in these cases was only one of several major cardiac anomalies affecting sonographic signs. A systematic review was performed in order to obtain a synthesis of characteristics associated with TAPVC, PAPVC and SS. The literature search of PubMed and EMBASE (1970–2016) included reviews, case series and case reports. A meta-analysis was conducted only for TAPVC. Random-effects models were used to obtain pooled estimates of the frequencies of clinical characteristics and sonographic features. Results: For TAPVC, a total of 15 studies involving 71 patients (including 13 from the current cohort study) were included in the systematic review and meta-analysis. The pooled estimate for the association of TAPVC with congenital heart disease was 28.3% (95% CI, 18.1–41.3%) and with extracardiac anomalies it was 18.5% (95% CI, 10.5–30.6%). Of TAPVC cases, obstructed venous return was observed in 34.1% (95% CI, 22.7–47.7%), a favorable outcome in 43.8% (95% CI, 24.0–65.8%), ventricular disproportion in 59.2% (95% CI, 45.1–72.0%), increased area behind the left atrium in 58.1% (95% CI, 41.1–73.5%) and a vertical vein in 59.3% (95% CI, 41.1–75.3%). Diagnosis was established by using color or power Doppler in 84.9% (95% CI, 67.3–93.9%) of cases. For SS, there were only three studies describing eight cases, to which the current study added another five. Ventricular disproportion was present in three out of nine SS cases for which data were available, but for two of these, there was a concurrent heart anomaly. Color Doppler was used for all SS diagnoses, and four-dimensional echocardiography was useful in two out of six cases in which it was used. Outcome for SS cases was generally good. For PAPVC, there were only five studies describing five cases, to which the current study added another two. Major cardiac anomalies were associated in four out of seven of these cases, and extracardiac anomalies in three out of six cases for which data were available. Conclusions: TAPVC can be associated with other cardiac and extracardiac anomalies in a significant percentage of cases. Leading sonographic signs are ventricular disproportion, increased area behind the left atrium and the finding of a vertical vein. Color/power Doppler is the key mode for diagnosis of TAPVC. Obstructed venous return can be expected in roughly one-third of cases of TAPVC and outcome is favorable in less than half of cases. Data for SS and PAPVC are too few to synthesize. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

OBJECTIVES To compare the efficiency of electronic spatiotemporal image correlation (eSTIC) with that of conventional STIC to acquire four-dimensional (4D) fetal cardiac volumes of diagnostic quality. METHODS This was a randomized controlled trial of 100 patients in mid-gestation with normal sonograms. In half of the cases, STIC volumes of the fetal heart were obtained with a conventional mechanical 4D probe and in the remaining cases eSTIC volumes were obtained with an electronic 4D probe. Examinations were kept within the timeframe allotted for a standard examination of fetal anatomy, and a maximum of two attempts were made at obtaining a 4D cardiac volume. Datasets were stored on a computer and subsequently analyzed and categorized as being of optimal, satisfactory or inadequate quality, depending on whether or not it was possible to perform an extended basic cardiac examination, including obtaining a three vessels and trachea view, as well as a clear reconstruction of both the aortic and ductal arches in the sagittal plane. RESULTS The eSTIC volume datasets were more frequently of optimal or satisfactory diagnostic quality compared with conventional STIC (94% vs 76%, P < 0.0001). Failure to obtain an eSTIC volume of adequate quality was in all cases the consequence of an unfavorable position of the fetus. CONCLUSIONS Compared with a standard mechanical probe, the electronic 4D probe facilitates acquisition of sonographic cardiac volumes in mid-trimester fetuses. In our hands, eSTIC volumes of optimal or satisfactory diagnostic quality, allowing a detailed offline evaluation of the fetal heart, were obtained in more than 90% of cases within the time frame of a standard examination of fetal anatomy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The final stages of restriction to the T cell lineage occur in the thymus after the entry of thymus-seeding progenitors (TSPs). The identity and lineage potential of TSPs remains unclear. Because the first embryonic TSPs enter a non-vascularized thymic rudiment, we were able to directly image and establish the functional and molecular properties of embryonic thymopoiesis-initiating progenitors (T-IPs) before their entry into the thymus and activation of Notch signaling. T-IPs did not include multipotent stem cells or molecular evidence of T cell-restricted progenitors. Instead, single-cell molecular and functional analysis demonstrated that most fetal T-IPs expressed genes of and had the potential to develop into lymphoid as well as myeloid components of the immune system. Moreover, studies of embryos deficient in the transcriptional regulator RBPJ demonstrated that canonical Notch signaling was not involved in pre-thymic restriction to the T cell lineage or the migration of T-IPs.

Purpose: The aim of our study was to evaluate the postmortem micro-CT anatomy of early fetal human fetal brains, either in situ or isolated. Methods: We studied 12 ex vivo specimens, 9 whole human fetuses (9–18 GW), and 3 isolated samples (16–26 GW). Specimens were fixed in formalin, then immersed in Lugol solution. Images were evaluated by two neuroradiologists. The depiction of CNS structures was defined based on the comparison between micro-CT images and a reference histologic anatomical Atlas of human brain development. Results: Micro-CT provided informative high-resolution brain images in all cases, with the exception of one case (9weeks) due to advanced maceration. All major CNS structures (i.e., brain hemispheres, layering, ventricles, germinal neuroepithelium, basal ganglia, corpus callosum, major cranial nerves, and structures of the head and neck) were recognizable. Conclusions: Micro-CT imaging of the early fetal brain is feasible and provides high-quality images that correlate with the histological Atlas of the human brain, offering multiplanar and volumetric images that can be stored and shared for clinical, teaching, and research purposes.

Objective: To evaluate whether changes in the cerebroplacental Doppler and birth weight (BW) suggestive of chronic fetal hypoxemia, precede the development of late-onset placental abruption (PA) after 32 weeks. Methods: In a multicenter retrospective study, the Doppler examinations of the fetal umbilical artery (UA) and middle cerebral artery (MCA) recorded after 32 weeks were collected in pregnancies subsequently developing PA. The BW centiles were calculated and the MCA pulsatility indices (PI), and UA PI were converted into multiples of the median (MoM). Afterwards, a comparison was made with a group of fetuses, which did not develop PA. Logistic regression was used to adjust for potential confounders and evaluate the feasibility of the prediction model. Results: Pregnancies complicated by late-onset PA (n = 31) presented lower MCA PI (p = 0.015) and were smaller (p < 0.001) than those who did not (n = 1294). Logistic regression analysis indicated that cerebral vasodilation was more important than umbilical flow in the explanation of PA (MCA PI OR = 0.106, p = 0.014 and UA PI OR 1.901, p = 0.32). In addition, the influence of BW exerted was residual (BW centile OR = 0.989, p = 0.15). Conclusions: Fetuses developing late-onset PA demonstrate significant cerebral vasodilation with scarce placental dysfunction, suggesting the existence of some kind of chronic hypoxemia that follows the late-onset pattern.

Zinc is a key element for growth and development. In this narrative review, we focus on the role of dietary zinc in early life (including embryo, fetus and preterm neonate), analyzing consequences of zinc deficiency and adequacy of current recommendations on dietary zinc. We performed a systematic search of articles on the role of zinc in early life. We selected and analyzed 81 studies. Results of this analysis showed that preservation of zinc balance is of critical importance for the avoidance of possible consequences of low zinc levels on pre- and post-natal life. Insufficient quantities of zinc during embryogenesis may influence the final phenotype of all organs. Maternal zinc restriction during pregnancy influences fetal growth, while adequate zinc supplementation during pregnancy may result in a reduction of the risk of preterm birth. Preterm neonates are at particular risk to develop zinc deficiency due to a combination of different factors: (i) low body stores due to reduced time for placental transfer of zinc; (ii) increased endogenous losses; and (iii) marginal intake. Early diagnosis of zinc deficiency, through the measurement of serum zinc concentrations, may be essential to avoid severe prenatal and postnatal consequences in these patients. Typical clinical manifestations of zinc deficiency are growth impairment and dermatitis. Increasing data suggest that moderate zinc deficiency may have significant subclinical effects, increasing the risk of several complications typical of preterm neonates (i.e., necrotizing enterocolitis, chronic lung disease, and retinopathy), and that current recommended intakes should be revised to meet zinc requirements of extremely preterm neonates. Future studies evaluating the adequacy of current recommendations are advocated.

Aims: Many authors do not recommend hypoglycemic treatment during pregnancy in women affected by monogenic diabetes due to heterozygous glucokinase (GCK) mutations (MODY 2) in case of affected fetus, because maternal hyperglycemia would be necessary to achieve a normal birthweight. We aimed to evaluate differences in birthweight between MODY 2 affected children according to the parent who carried the mutation. Methods: We retrospectively studied 48 MODY 2 affected children, whose mothers did not receive hypoglycemic treatment during pregnancy, divided into two groups according to the presence of the mutation in the mother (group A) or in the father (group B). Data were extracted from the database of the Regional Centre of Pediatric Diabetology of the University of Campania, Naples, collected from 1996 to 2016. We analyzed birthweight and centile birthweight. Results: Percentage of small for gestational age was significantly higher in group B than in group A. We found three large for gestational age in the group that inherited the deficit from the mother, all with the same novel GCK mutation (p.Lys458-Cys461del). Conclusions: We hypothesize that not all MODY 2 affected fetuses need the same levels of hyperglycemia to have an appropriate growth, maybe because different kinds of GCK mutations may result in different phenotypes. Consequently, a “tailored therapy” of maternal hyperglycemia, based on fetal growth frequently monitored through ultrasounds, is essential in MODY 2 pregnancies.

Objectives: To assess the feasibility and reliability of an automated technique for the assessment of the angle of progression (AoP) in labor by using three-dimensional (3D) ultrasound. Methods: AoP was assessed by using 3D transperineal ultrasound by two operators in 52 women in active labor to evaluate intra- and interobserver reproducibility. Furthermore, intermethod agreement between automated and manual techniques on 3D images, and between automated technique on 3D vs 2D images were evaluated. Results: Automated measurements were feasible in all cases. Automated measurements were considered acceptable in 141 (90.4%) out of the 156 on the first assessments and in all 156 after repeating measurements for unacceptable evaluations. The automated technique on 3D images demonstrated good intra- and interobserver reproducibility. The 3D-automated technique showed a very good agreement with the 3D manual technique. Notably, AoP calculated with the 3D automated technique were significantly wider in comparison with those measured manually on 3D images (133 ± 17° vs 118 ± 21°, p = 0.013). Conclusions: The assessment of the angle of progression through 3D ultrasound is highly reproducible. However, automated software leads to a systematic overestimation of AoP in comparison with the standard manual technique thus hindering its use in clinical practice in its present form.

In the last decades, technological development has led to an increasing use of devices and systems based on microwave radiation. The increased employment of these devices has elicited questions about the potential long-term health consequences associated with microwave radiation exposure. From this perspective, biological effects of microwave radiation have been the focus of many studies, but the reported scientific data are unclear and contradictory. The aim of this study is to evaluate the potential genotoxic and cellular effects associated with in vitro exposure of human fetal and adult fibroblasts to microwave radiation at the frequency of 25 GHz. For this purpose, several genetic and biological end points were evaluated. Results obtained from comet assay, phosphorylation of H2AX histone, and antikinetochore antibody (CREST)-negative micronuclei frequency excluded direct DNA damage to human fetal and adult fibroblasts exposed to microwaves. No induction of apoptosis or changes in prosurvival signalling proteins were detected. Moreover, CREST analysis showed for both the cell lines an increase in the total number of micronuclei and centromere positive micronuclei in exposed samples, indicating aneuploidy induction due to chromosome loss.

A major problem in developmental neurotoxicity (DNT) risk assessment is the lack of toxicological hazard information for most compounds. Therefore, new approaches are being considered to provide adequate experimental data that allow regulatory decisions. This process requires a matching of regulatory needs on the one hand and the opportunities provided by new test systems and methods on the other hand. Alignment of academically and industrially driven assay development with regulatory needs in the field of DNT is a core mission of the International STakeholder NETwork (ISTNET) in DNT testing. The first meeting of ISTNET was held in Zurich on 23-24 January 2014 in order to explore the concept of adverse outcome pathway (AOP) to practical DNT testing. AOPs were considered promising tools to promote test systems development according to regulatory needs. Moreover, the AOP concept was identified as an important guiding principle to assemble predictive integrated testing strategies (ITSs) for DNT. The recommendations on a road map towards AOP-based DNT testing is considered a stepwise approach, operating initially with incomplete AOPs for compound grouping, and focussing on key events of neurodevelopment. Next steps to be considered in follow-up activities are the use of case studies to further apply the AOP concept in regulatory DNT testing, making use of AOP intersections (common key events) for economic development of screening assays, and addressing the transition from qualitative descriptions to quantitative network modelling.