Neuromesodermal specification during head-to-tail body axis formation.

The anterior-to-posterior (head-to-tail) body axis is extraordinarily diverse among vertebrates but conserved within species. Body axis development requires a population of axial progenitors that resides at the posterior of the embryo to sustain elongation and is then eliminated once axis extension is complete. These progenitors occupy distinct domains in the posterior (tail-end) of the embryo and contribute to various lineages along the body axis. The subset of axial progenitors with neuromesodermal competency will generate both the neural tube (the precursor of the spinal cord), and the trunk and tail somites (producing the musculoskeleton) during embryo development. These axial progenitors are called Neuromesodermal Competent cells (NMCs) and Neuromesodermal Progenitors (NMPs). NMCs/NMPs have recently attracted interest beyond the field of developmental biology due to their clinical potential. In the mouse, the maintenance of neuromesodermal competency relies on a fine balance between a trio of known signals: Wnt/ß-catenin, FGF signalling activity and suppression of retinoic acid signalling. These signals regulate the relative expression levels of the mesodermal transcription factor Brachyury and the neural transcription factor Sox2, permitting the maintenance of progenitor identity when co-expressed, and either mesoderm or neural lineage commitment when the balance is tilted towards either Brachyury or Sox2, respectively. Despite important advances in understanding key genes and cellular behaviours involved in these fate decisions, how the balance between mesodermal and neural fates is achieved remains largely unknown. In this chapter, we provide an overview of signalling and gene regulatory networks in NMCs/NMPs. We discuss mutant phenotypes associated with axial defects, hinting at the potential significant role of lesser studied proteins in the maintenance and differentiation of the progenitors that fuel axial elongation.

Regulatory changes associated with the head to trunk developmental transition.

BACKGROUND: Development of vertebrate embryos is characterized by early formation of the anterior tissues followed by the sequential extension of the axis at their posterior end to build the trunk and tail structures, first by the activity of the primitive streak and then of the tail bud. Embryological, molecular and genetic data indicate that head and trunk development are significantly different, suggesting that the transition into the trunk formation stage involves major changes in regulatory gene networks. RESULTS: We explored those regulatory changes by generating differential interaction networks and chromatin accessibility profiles from the posterior epiblast region of mouse embryos at embryonic day (E)7.5 and E8.5. We observed changes in various cell processes, including several signaling pathways, ubiquitination machinery, ion dynamics and metabolic processes involving lipids that could contribute to the functional switch in the progenitor region of the embryo. We further explored the functional impact of changes observed in Wnt signaling associated processes, revealing a switch in the functional relevance of Wnt molecule palmitoleoylation, essential during gastrulation but becoming differentially required for the control of axial extension and progenitor differentiation processes during trunk formation. We also found substantial changes in chromatin accessibility at the two developmental stages, mostly mapping to intergenic regions and presenting differential footprinting profiles to several key transcription factors, indicating a significant switch in the regulatory elements controlling head or trunk development. Those chromatin changes are largely independent of retinoic acid, despite the key role of this factor in the transition to trunk development. We also tested the functional relevance of potential enhancers identified in the accessibility assays that reproduced the expression profiles of genes involved in the transition. Deletion of these regions by genome editing had limited effect on the expression of those genes, suggesting the existence of redundant enhancers that guarantee robust expression patterns. CONCLUSIONS: This work provides a global view of the regulatory changes controlling the switch into the axial extension phase of vertebrate embryonic development. It also revealed mechanisms by which the cellular context influences the activity of regulatory factors, channeling them to implement one of several possible biological outputs.

Annelid functional genomics reveal the origins of bilaterian life cycles.

Indirect development with an intermediate larva exists in all major animal lineages1, which makes larvae central to most scenarios of animal evolution2-11. Yet how larvae evolved remains disputed. Here we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head12. Notably, this also occurs in the so-called 'head larvae' of other bilaterians13-17, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option9,10 or innovation11 of gene regulatory programmes to explain larva and adult origins.

Novel artificial intelligence approach for automatic differentiation of fetal occiput anterior and non-occiput anterior positions during labor.

OBJECTIVES: To describe a newly developed machine-learning (ML) algorithm for the automatic recognition of fetal head position using transperineal ultrasound (TPU) during the second stage of labor and to describe its performance in differentiating between occiput anterior (OA) and non-OA positions. METHODS: This was a prospective cohort study including singleton term (> 37 weeks of gestation) pregnancies in the second stage of labor, with a non-anomalous fetus in cephalic presentation. Transabdominal ultrasound was performed to determine whether the fetal head position was OA or non-OA. For each case, one sonographic image of the fetal head was then acquired in an axial plane using TPU and saved for later offline analysis. Using the transabdominal sonographic diagnosis as the gold standard, a ML algorithm based on a pattern-recognition feed-forward neural network was trained on the TPU images to discriminate between OA and non-OA positions. In the training phase, the model tuned its parameters to approximate the training data (i.e. the training dataset) such that it would identify correctly the fetal head position, by exploiting geometric, morphological and intensity-based features of the images. In the testing phase, the algorithm was blinded to the occiput position as determined by transabdominal ultrasound. Using the test dataset, the ability of the ML algorithm to differentiate OA from non-OA fetal positions was assessed in terms of diagnostic accuracy. The F1 -score and precision-recall area under the curve (PR-AUC) were calculated to assess the algorithm's performance. Cohen's kappa (κ) was calculated to evaluate the agreement between the algorithm and the gold standard. RESULTS: Over a period of 24 months (February 2018 to January 2020), at 15 maternity hospitals affiliated to the International Study group on Labor ANd Delivery Sonography (ISLANDS), we enrolled into the study 1219 women in the second stage of labor. On the basis of transabdominal ultrasound, they were classified as OA (n = 801 (65.7%)) or non-OA (n = 418 (34.3%)). From the entire cohort (OA and non-OA), approximately 70% (n = 824) of the patients were assigned randomly to the training dataset and the rest (n = 395) were used as the test dataset. The ML-based algorithm correctly classified the fetal occiput position in 90.4% (357/395) of the test dataset, including 224/246 with OA (91.1%) and 133/149 with non-OA (89.3%) fetal head position. Evaluation of the algorithm's performance gave an F1 -score of 88.7% and a PR-AUC of 85.4%. The algorithm showed a balanced performance in the recognition of both OA and non-OA positions. The robustness of the algorithm was confirmed by high agreement with the gold standard (κ = 0.81; P < 0.0001). CONCLUSIONS: This newly developed ML-based algorithm for the automatic assessment of fetal head position using TPU can differentiate accurately, in most cases, between OA and non-OA positions in the second stage of labor. This algorithm has the potential to support not only obstetricians but also midwives and accoucheurs in the clinical use of TPU to determine fetal occiput position in the labor ward. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Expression of Sonic Hedgehog and pathway components in the embryonic mouse head: anatomical relationships between regulators of positive and negative feedback.

OBJECTIVE: The Hedgehog pathway is a fundamental signaling pathway in organogenesis. The expression patterns of the ligand Sonic Hedgehog (Shh) and key pathway components have been studied in many tissues but direct spatial comparisons across tissues with different cell compositions and structural organization are not common and could reveal tissue-specific differences in pathway dynamics. RESULTS: We directly compared the expression characteristics of Shh, and four genes with functional roles in signaling and whose expression levels serve as readouts of pathway activity in multiple tissues of the embryonic mouse head at embryonic day 15.5 by serial in situ hybridization. The four readout genes were the positive feedback regulator Gli1, and three negative feedback regulators, Patched1, Patched2, and Hedgehog Interacting Protein. While the relative abundance of Gli1 was similar across tissues, the relative expression levels and spatial distribution of Shh and the negative feedback regulators differed, suggesting that feedback regulation of hedgehog signaling is context dependent. This comparative analysis offers insight into how consistent pathway activity could be achieved in tissues with different morphologies and characteristics of ligand expression.

Rspo2 inhibits TCF3 phosphorylation to antagonize Wnt signaling during vertebrate anteroposterior axis specification.

The Wnt pathway activates target genes by controlling the ß-catenin-T-cell factor (TCF) transcriptional complex during embryonic development and cancer. This pathway can be potentiated by R-spondins, a family of proteins that bind RNF43/ZNRF3 E3 ubiquitin ligases and LGR4/5 receptors to prevent Frizzled degradation. Here we demonstrate that, during Xenopus anteroposterior axis specification, Rspo2 functions as a Wnt antagonist, both morphologically and at the level of gene targets and pathway mediators. Unexpectedly, the binding to RNF43/ZNRF3 and LGR4/5 was not required for the Wnt inhibitory activity. Moreover, Rspo2 did not influence Dishevelled phosphorylation in response to Wnt ligands, suggesting that Frizzled activity is not affected. Further analysis indicated that the Wnt antagonism is due to the inhibitory effect of Rspo2 on TCF3/TCF7L1 phosphorylation that normally leads to target gene activation. Consistent with this mechanism, Rspo2 anteriorizing activity has been rescued in TCF3-depleted embryos. These observations suggest that Rspo2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling.

Intrapulmonary artery Doppler to predict mortality and morbidity in fetuses with mild or moderate left-sided congenital diaphragmatic hernia.

OBJECTIVES: In fetuses with isolated left-sided congenital diaphragmatic hernia (LCDH), prenatal detection of severe pulmonary hypoplasia is important, as fetal therapy can improve survival. Cases with mild or moderate lung hypoplasia still carry a considerable risk of mortality and morbidity, but there has been less interest in the accurate prediction of outcome in these cases. In this study of fetuses with mild or moderate isolated LCDH, we aimed to investigate: (1) the association between intrapulmonary artery (IPA) Doppler findings and mortality at discharge; (2) whether adding IPA Doppler findings improves the prediction of mortality based on lung size and liver herniation; and (3) the association between IPA Doppler findings and early neonatal morbidity. METHODS: This was a retrospective study of all consecutive fetuses assessed at the BCNatal and UZ Leuven hospitals between 2008 and 2020 with a prenatal diagnosis of isolated, non-severe LCDH, defined as observed-to-expected lung-to-head ratio (o/e-LHR) > 25%, that were managed expectantly during pregnancy followed by standardized neonatal management. An additional inclusion criterion was the availability of IPA Doppler measurements. The primary outcome was the association between IPA Doppler findings and mortality at discharge. Other predictors included o/e-LHR, liver herniation and gestational age at birth. Secondary outcomes were the association between IPA Doppler findings and the presence of pulmonary hypertension (PHT), need for supplemental oxygen at discharge and need for extracorporeal membrane oxygenation. IPA pulsatility index (PI) values were converted into Z-scores. Logistic regression analysis was performed to investigate the associations between predictor variables and outcome, and the best model was chosen based on the Nagelkerke R2 . RESULTS: Observations for 70 non-severe LCDH cases were available. Fifty-four (77%) fetuses survived until discharge. On logistic regression analysis, higher IPA-PI was associated with an increased risk of mortality (odds ratio (OR), 3.96 (95% CI, 1.62-9.70)), independently of o/e-LHR (OR, 0.87 (95% CI, 0.79-0.97)). An IPA-PI Z-score cut-off of 1.8 predicted mortality with a detection rate of 69% and specificity of 93%. Adding IPA-PI to o/e-LHR improved significantly the model's performance (Nagelkerke R2 , 46% for o/e-LHR + IPA-PI vs 28% for o/e-LHR (P < 0.002)), with a detection rate of 81% at a 10% false-positive rate. IPA-PI was associated with PHT (OR, 2.20 (95% CI, 1.01-4.59)) and need for oxygen supplementation at discharge (OR, 1.90 (95% CI, 1.10-3.40)), independently of lung size. CONCLUSIONS: In fetuses with mild or moderate LCDH, IPA-PI was associated with mortality and morbidity, independently of lung size. A model combining o/e-LHR with IPA-PI identified up to four in five cases that eventually died, despite being considered to have non-severe pulmonary hypoplasia. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Automatic quality assessment for 2D fetal sonographic standard plane based on multitask learning.

ABSTRACT: The quality control of fetal sonographic (FS) images is essential for the correct biometric measurements and fetal anomaly diagnosis. However, quality control requires professional sonographers to perform and is often labor-intensive. To solve this problem, we propose an automatic image quality assessment scheme based on multitask learning to assist in FS image quality control. An essential criterion for FS image quality control is that all the essential anatomical structures in the section should appear full and remarkable with a clear boundary. Therefore, our scheme aims to identify those essential anatomical structures to judge whether an FS image is the standard image, which is achieved by 3 convolutional neural networks. The Feature Extraction Network aims to extract deep level features of FS images. Based on the extracted features, the Class Prediction Network determines whether the structure meets the standard and Region Proposal Network identifies its position. The scheme has been applied to 3 types of fetal sections, which are the head, abdominal, and heart. The experimental results show that our method can make a quality assessment of an FS image within less a second. Also, our method achieves competitive performance in both the segmentation and diagnosis compared with state-of-the-art methods.

Craniofacial transitions: the role of EMT and MET during head development.

Within the developing head, tissues undergo cell-fate transitions to shape the forming structures. This starts with the neural crest, which undergoes epithelial-to-mesenchymal transition (EMT) to form, amongst other tissues, many of the skeletal tissues of the head. In the eye and ear, these neural crest cells then transform back into an epithelium, via mesenchymal-to-epithelial transition (MET), highlighting the flexibility of this population. Elsewhere in the head, the epithelium loses its integrity and transforms into mesenchyme. Here, we review these craniofacial transitions, looking at why they happen, the factors that trigger them, and the cell and molecular changes they involve. We also discuss the consequences of aberrant EMT and MET in the head.

Cephalochordates: A window into vertebrate origins.

How vertebrates evolved from their invertebrate ancestors has long been a central topic of discussion in biology. Evolutionary developmental biology (evodevo) has provided a new tool-using gene expression patterns as phenotypic characters to infer homologies between body parts in distantly related organisms-to address this question. Combined with micro-anatomy and genomics, evodevo has provided convincing evidence that vertebrates evolved from an ancestral invertebrate chordate, in many respects resembling a modern amphioxus. The present review focuses on the role of evodevo in addressing two major questions of chordate evolution: (1) how the vertebrate brain evolved from the much simpler central nervous system (CNS) in of this ancestral chordate and (2) whether or not the head mesoderm of this ancestor was segmented.

Single-cell reconstruction with spatial context of migrating neural crest cells and their microenvironments during vertebrate head and neck formation.

The dynamics of multipotent neural crest cell differentiation and invasion as cells travel throughout the vertebrate embryo remain unclear. Here, we preserve spatial information to derive the transcriptional states of migrating neural crest cells and the cellular landscape of the first four chick cranial to cardiac branchial arches (BA1-4) using label-free, unsorted single-cell RNA sequencing. The faithful capture of branchial arch-specific genes led to identification of novel markers of migrating neural crest cells and 266 invasion genes common to all BA1-4 streams. Perturbation analysis of a small subset of invasion genes and time-lapse imaging identified their functional role to regulate neural crest cell behaviors. Comparison of the neural crest invasion signature to other cell invasion phenomena revealed a shared set of 45 genes, a subset of which showed direct relevance to human neuroblastoma cell lines analyzed after exposure to the in vivo chick embryonic neural crest microenvironment. Our data define an important spatio-temporal reference resource to address patterning of the vertebrate head and neck, and previously unidentified cell invasion genes with the potential for broad impact.

Accuracy of automated three-dimensional ultrasound imaging technique for fetal head biometry.

OBJECTIVES: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition. METHODS: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics. RESULTS: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique. CONCLUSIONS: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Training the trainees: a pilot study of inter-observer discrepancy and learning curve in the maternal foetal unit of a tertiary centre.

Our study aims to present the preliminary findings of an ongoing prospective cohort study that assesses the trainees' ability to perform foetal biometry during the third trimester of pregnancy. Sixty-three women with third-trimester singleton pregnancies were included. A biometry scan was performed byboth residents and a foetal medicine specialist in the Third department of Obstetrics and Gynaecology of Attikon University Hospital. For each case, the ultrasonographic measurements of the two operator groups were compared. The mean difference of the resident group compared to the specialist group was: for the biparietal diameter +1.3 mm (CI 95%, range -10.6 to +13,3, ±1.96 SD), for the occipitofrontal diameter -2.6 mm (CI 95%, range -31.5 to +26.2), for the anterior-posterior abdominal diameter -2.6 mm (CI 95%, range -17.9 to +12.8), for the transverse abdominal diameter -0.7 mm (CI 95%, range -17.1 to +15.7) and for the femur length -1.1 mm (CI 95%, range -11.7 to +9.6). We observed that, among all biometric parameters, the most accurate -based on the specialist group were the head circumference measurements. The highest discrepancy was noted for the abdominal assessment. Given that foetal biometry is of utmost importance in obstetrical clinical evaluation and management, a study that highlights the weaknesses of residents in this field could open new horizons in optimising the learning procedure.Impact statementWhat is already known on this subject? After review of the literature, we found only a few studies on inter- and intra-observer discrepancy in foetal biometry measurements among specialists.What the results of this study add? To our knowledge, our study is the first to evaluate residents' capacity of performing a biometry scan, by comparing their measurements to those of MFM specialists.What the implications are of these findings to clinical practice and/or further research? The need for constant evaluation of residents is indisputable. Our study could help to improve their ultrasound skills by giving emphasis on residents' weaknesses. With further research on this subject, a standard system of evaluation could be formed and determine the duration and type of training required for each resident.

Impacted foetal head at caesarean section: a national survey of practice and training.

This is a national survey of UK obstetric trainees and consultant labour ward leads designed to investigate the current practice and training for an impacted foetal head (IFH) at Caesarean Section (CS). An anonymous, on-line survey was disseminated to trainees via Postgraduate Schools and RCOG trainee representatives, and to labour ward leads via their national network. Three hundred and forty-five obstetric trainees and consultants responded. The results show that IFH is variably defined and encountered by most UK obstetricians (98% had encountered IFH and 76% had experienced it before full cervical dilatation). There is significant variation in management strategies, although most respondents would use a vaginal push up to assist delivery prior to reverse breech extraction. Responses revealed a paucity of training and lack of confidence in disimpaction techniques: over one in ten respondents had not received any training for IFH and less than half had received instruction in reverse breech extraction.Impact statementWhat is already known on the subject? IFH is an increasingly recognised, technically challenging complication of intrapartum CS. A recent report suggested that birth injuries associated with IFH are now as common as with shoulder dystocia. However, there is no consensus nor guidelines regarding the best practice for management or training.What do the results of this study add? This study demonstrates that IFH is poorly defined and commonly encountered by UK obstetricians. It highlights that IFH is not restricted to CS at full dilatation and reveals the ubiquity of the vaginal push method in UK practice. We found evidence that UK obstetricians are using techniques which have not been investigated and are not recommended for managing an IFH. Moreover, this survey is an eye-opener as to the paucity of training, highlighting that UK obstetric trainees are not adequately prepared to manage this emergency.What are the implications of these findings for clinical practice and/or further research? There is a pressing need to standardise the definition, guidance and training for IFH at CS. Further research should clarify the appropriate techniques for IFH and establish consensus for the best practice. An evidence-based simulation training package, which allows clinicians to learn and practice recognised disimpaction techniques is urgently required.

Fetal growth velocity standards from the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project.

BACKGROUND: Human growth is susceptible to damage from insults, particularly during periods of rapid growth. Identifying those periods and the normative limits that are compatible with adequate growth and development are the first key steps toward preventing impaired growth. OBJECTIVE: This study aimed to construct international fetal growth velocity increment and conditional velocity standards from 14 to 40 weeks' gestation based on the same cohort that contributed to the INTERGROWTH-21st Fetal Growth Standards. STUDY DESIGN: This study was a prospective, longitudinal study of 4321 low-risk pregnancies from 8 geographically diverse populations in the INTERGROWTH-21st Project with rigorous standardization of all study procedures, equipment, and measurements that were performed by trained ultrasonographers. Gestational age was accurately determined clinically and confirmed by ultrasound measurement of crown-rump length at <14 weeks' gestation. Thereafter, the ultrasonographers, who were masked to the values, measured the fetal head circumference, biparietal diameter, occipitofrontal diameter, abdominal circumference, and femur length in triplicate every 5 weeks (within 1 week either side) using identical ultrasound equipment at each site (4-7 scans per pregnancy). Velocity increments across a range of intervals between measures were modeled using fractional polynomial regression. RESULTS: Peak velocity was observed at a similar gestational age: 16 and 17 weeks' gestation for head circumference (12.2 mm/wk), and 16 weeks' gestation for abdominal circumference (11.8 mm/wk) and femur length (3.2 mm/wk). However, velocity growth slowed down rapidly for head circumference, biparietal diameter, occipitofrontal diameter, and femur length, with an almost linear reduction toward term that was more marked for femur length. Conversely, abdominal circumference velocity remained relatively steady throughout pregnancy. The change in velocity with gestational age was more evident for head circumference, biparietal diameter, occipitofrontal diameter, and femur length than for abdominal circumference when the change was expressed as a percentage of fetal size at 40 weeks' gestation. We have also shown how to obtain accurate conditional fetal velocity based on our previous methodological work. CONCLUSION: The fetal skeleton and abdomen have different velocity growth patterns during intrauterine life. Accordingly, we have produced international Fetal Growth Velocity Increment Standards to complement the INTERGROWTH-21st Fetal Growth Standards so as to monitor fetal well-being comprehensively worldwide. Fetal growth velocity curves may be valuable if one wants to study the pathophysiology of fetal growth. We provide an application that can be used easily in clinical practice to evaluate changes in fetal size as conditional velocity for a more refined assessment of fetal growth than is possible at present (https://lxiao5.shinyapps.io/fetal_growth/). The application is freely available with the other INTERGROWTH-21st tools at https://intergrowth21.tghn.org/standards-tools/.

Fetal head progression and regression on maternal pushing at term and labor outcome.

OBJECTIVES: The aim of our study was two-fold. First, to evaluate the association between the change in the angle of progression (AoP) on maternal pushing and labor outcome. Second, to assess the incidence and clinical significance of the reduction of AoP on maternal pushing. METHODS: This was a prospective cohort study of nulliparous women with singleton pregnancy at term. AoP was measured at rest and on maximum Valsalva maneuver before the onset of labor, and the difference between AoP on maximum Valsalva and that at rest (ΔAoP) was calculated for each woman. Following delivery and data collection, we assessed the association between ΔAoP and various labor outcomes, including Cesarean section (CS), duration of the first, second and active second stages of labor, Apgar score and admission to the neonatal intensive care unit (NICU). The prevalence of women with reduction of AoP on maximum Valsalva maneuver (AoP-regression group) was calculated and its association with the mode of delivery and duration of different stages of labor was assessed. RESULTS: Overall, 469 women were included in the analysis. Among these, 273 (58.2%) had spontaneous vaginal birth, 65 (13.9%) had instrumental delivery and 131 (27.9%) underwent CS. Women in the CS group were older, had narrower AoP at rest and on maximum Valsalva, higher rate of epidural administration and lower 1-min and 5-min Apgar scores in comparison with the vaginal-delivery group. ΔAoP was comparable between the two groups. On Pearson's correlation analysis, AoP at rest and on maximum Valsalva maneuver had a significant negative correlation with the duration of the first stage of labor. ΔAoP showed a significant negative correlation with the duration of the active second stage of labor (Pearson's r, -0.125; P = 0.02). Cox regression model analysis showed that ΔAoP was associated independently with the duration of the active second stage (hazard ratio, 1.014 (95% CI, 1.003-1.025); P = 0.012) after adjusting for maternal age and body mass index. AoP reduction on maximum Valsalva was found in 73 (15.6%) women. In comparison with women who showed no change or an increase in AoP on maximum Valsalva, the AoP-regression group did not demonstrate significant difference in maternal characteristics, mode of delivery, rate of epidural analgesia, duration of the different stages of labor or rate of NICU admission. CONCLUSIONS: In nulliparous women at term before the onset of labor, narrower AoP at rest and on maximum Valsalva, reflecting fetal head engagement, is associated with a higher risk of Cesarean delivery. The increase in AoP from rest to Valsalva, reflecting more efficient maternal pushing, is associated with a shorter active second stage of labor. Fetal head regression on maternal pushing is present in about 16% of women and does not appear to have clinical significance. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Frontal lobe growth is impaired in fetuses with congenital heart disease.

OBJECTIVES: The primary objective of this study was to assess whether fetuses with congenital heart disease (CHD) have smaller frontal brain areas compared with normal controls. The secondary objective was to evaluate whether there are any differences in frontal brain area between cases with different types of CHD, grouped according to their impact on hemodynamics. METHODS: This was a retrospective cross-sectional study, including 421 normal fetuses and 101 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine and surgery unit in the period January 2016-December 2019. The study group was subdivided, according to the CHD hemodynamics, as follows: (1) hypoplastic left heart syndrome and other forms of functionally univentricular heart defect; (2) transposition of the great arteries; (3) conotruncal defects and other CHDs with large shunts; (4) right ventricular outflow tract obstruction, without a hypoplastic right ventricle; (5) left outflow tract obstruction; (6) others. The transventricular axial view of the fetal head was used as the reference view, on which the frontal lobe anteroposterior diameter (FAPD) and the occipitofrontal diameter (OFD) were measured, assuming the former to be representative of the area of the frontal lobes. The FAPD/OFD ratio was then calculated as FAPD/OFD × 100. These two variables (FAPD and FAPD/OFD ratio) were then evaluated and compared between the study and control groups. Adjustment for gestational age, both via multiple linear regression and by using a-posteriori matching based on the propensity score, was employed. RESULTS: In normal fetuses, FAPD showed a linear positive correlation with gestational age. In fetuses with CHD, the FAPD was shorter than in normal fetuses from the 20th gestational week onwards, with the difference increasing after 30 gestational weeks. FAPD/OFD ratio was significantly smaller in fetuses with CHD than in normal fetuses (P < 0.0001) at all gestational ages, with no apparent differences among the various CHD categories, all of which had smaller FAPD/OFD ratio compared with controls. CONCLUSIONS: Fetuses with CHD have a shorter FAPD and a smaller FAPD/OFD ratio compared with normal fetuses. This impaired growth of the frontal area of the brain seems to occur in all types of CHD, regardless of their impact on hemodynamics. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Transperineal ultrasound assessment of fetal head elevation by maneuvers used for managing umbilical cord prolapse.

OBJECTIVE: To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. METHODS: This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. RESULTS: Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. CONCLUSIONS: To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal diagnosis of fetal microhydranencephaly: a case report and literature review.

BACKGROUND: The prenatal diagnosis of microhydranencephaly is important and needs to be distinguished from anencephaly, because unlike anencephaly, fetuses with microhydranencephaly can survive after birth. Herein, we report a case of microhydranencephaly that was diagnosed and distinguished from anencephaly prenatally. CASE PRESENTATION: The patient was an 18-year-old woman, 2 gravida nullipara, who presented at 15 weeks of gestation. Ultrasonography showed a normal biparietal diameter (BPD) and no major anomalies. At 23 weeks of gestation, an ultrasound examination revealed a BPD of 40 mm (-5.3 standard deviation, SD). At 29 weeks, anencephaly was suspected despite difficulty in visually examining the fetal head above the orbit. At 34 weeks, insertion of a metreurynter made it possible to observe the skull. Three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the fetal skull, a prominent occipital bone, sloping forehead, marked microcephaly, cerebral loss, and excess cerebrospinal fluid. This allowed differentiation between microhydranencephaly and anencephaly. She delivered vaginally at 37 weeks, and the child had a birth weight of 2342 g and a head circumference of 24 cm (-5.4 SD). The baby's head was flat above the forehead, with a suspected partial head defect. The baby received desmopressin acetate due to central diabetes insipidus 6 months after birth. CONCLUSIONS: The use of multiple imaging modalities and physical manipulation of the fetal head are required to accurately differentiate between microhydranencephaly and anencephaly.