Human trapezius muscle development during the early fetal period.

This study aimed to observe human trapezius muscle (TpzM) development during early fetal period and apply diffusion tensor imaging (DTI) analysis to describe the muscle architecture that leads to physiological functions. Human embryonic and early fetal specimens were selected for this study. TpzM was first detected at Carnegie stage 20. The position of the TpzM changed with the formation of the scapula, clavicle, and vertebrae, which are its insertions and origins. DTI revealed the fiber orientation from each vertebral level to dissect each muscle. Fiber orientation in the ventral view gradually changed from the cervical to thoracic vertebrae, except for the middle part at which the insertions changed, which was almost similar in all early fetal specimens. The TpzM volume increased from C1 to C7 in the upper part, reached local maxima at C6 and C7 in the middle, and then decreased. These muscles can be categorized into three parts according to their insertions and presented with the features of each part. The fiber orientation and distribution of the three parts at the vertebral level were almost constant during the early fetal period. The border between the upper and middle parts was mainly located around the C6 and C7 vertebral levels, whereas the middle and lower parts were between the Th1 and Th2 vertebral levels. A three-dimensional change in the fiber orientation in the upper part of the TpzM according to the vertebral level was noticeable. Our data will help to elucidate the developmental processes of TpzM.

Formation of tendinous intersections in the human fetal rectus abdominis.

Previous studies have poorly described the initial development process of the tendinous intersections of the rectus abdominis muscle (RAM). The present study aimed to observe the formation of tendinous intersections in the RAM during the early fetal period using diffusion tensor imaging (DTI). Fifteen human fetal specimens (crown-rump length [CRL]: 39.5-93.7 mm) were selected. Three-dimensional measurements revealed that Zone-4 (i.e., the zone between the pubic symphysis and the caudal base of the umbilical ring in the RAM) had a smaller width and was thicker than Zone-1 and Zone-2 (i.e., the zones between the costal arch and the cranial base of the umbilical ring) and Zone-3 (i.e., the zone at the umbilical ring). Characteristics of tendinous intersections in the RAM during the early fetal period were assessed according to number, size, type, laterality, and sex. The mean number of tendinous intersections on both sides was 3.1 (range: 2.0-4.0), and 21% of specimens had only two tendinous intersections, which was higher than that reported in previous adult studies. The present data suggest that the formation of tendinous intersections was still in progress in specimens with two tendinous intersections in the RAM and that the third tendinous intersection was formed in Zone-2. Ordinal logistic regression via generalized estimating equations revealed that the odds for a higher type of tendinous intersections in Zone-1 and Zone-2 were significantly higher than those in Zone-4 (adjusted odds ratio: 14.85, 8.84). The odds for the presence of incomplete types (tendinous intersections that could not completely transverse the RAM) in Zone-3 were significantly higher than those in Zone-1 (adjusted odds ratio: 7.4). The odds for missing tendinous intersections in Zone-4 were significantly higher than those in Zone-1 (adjusted odds ratio: 20.5). These zonal differences in the formation of tendinous intersections were consistent with those observed in previous adult studies. In this study, DTI detected tendinous intersections in a sample with a CRL of 45.8 mm (approximately 11 weeks of gestation), which is earlier than that in previous histological findings, indicating that the RAM does not have mature tendinous intersections until the 17th week of gestation. In conclusion, DTI could detect the premature differentiation of tendinous intersection formation. Our data may aid in elucidating the developmental processes of tendinous intersections in the RAM.

Morphogenesis of the pulmonary vein and left atrial appendage in human embryos and early fetuses.

The left atrium wall has several origins, including the body, appendage, septum, atrial-ventricular canal, posterior wall, and venous component. Here, we describe the morphogenesis of left atrium based on high-resolution imaging (phase-contrast X-ray computed tomography and magnetic resonance imaging). Twenty-three human embryos and 19 fetuses were selected for this study. Three-dimensional cardiac images were reconstructed, and the pulmonary veins and left atrium, including the left atrial appendage, were evaluated morphologically and quantitatively. The positions of the pericardial reflections were used as landmarks for the border of the pericardial cavity. The common pulmonary vein was observed in three specimens at Carnegie stages 17-18. The pericardium was detected at the four pulmonary veins (left superior, left inferior, right superior, and right inferior pulmonary veins) at one specimen at Carnegie stage 18 and all larger specimens, except the four samples. Our results suggest that the position of the pericardial reflections was determined at two pulmonary veins (right and left pulmonary vein) and four pulmonary veins almost simultaneously when the dorsal mesocardial connection between the embryo and heart regressed. The magnetic resonance images and reconstructed heart cavity images confirmed that the left atrium folds were present at the junction between the body and venous component. Three-dimensional reconstruction showed that the four pulmonary veins entered the dorsal left atrium tangentially from the lateral to the medial direction. More specifically, the right pulmonary veins entered at a greater angle than the left pulmonary veins. The distance between the superior and inferior pulmonary veins was shorter than that between the left and right pulmonary veins. Three-dimensional reconstruction showed that the venous component increased proportionally with growth. No noticeable differences in discrimination between the right and left parts of the venous component emerged, while the junction between the venous component and body gradually became inconspicuous but was still recognizable by the end of the observed early fetal period. The left superior pulmonary vein had the smallest cross-sectional area and most flattened shape, whereas the other three were similar in area and shape. The left atrial appendage had a large volume in the center and extended to the periphery as a lobe-like structure. The left atrial appendage orifice increased in the area and tended to become flatter with growth. The whole left atrium volume^(1/3) increased almost proportionally with growth, parallel to the whole heart volume. This study provided a three-dimensional and quantitative description of the developmental process of the left atrium, comprising the venous component and left atrial appendage formation, from the late embryonic to the early fetal stages.

Growth patterns of facial muscles at the angle of the mouth: A histological study using midterm and near-term human fetuses.

At the angle of the mouth, spoke-like muscle bundles converge at the "modiolus," which is believed to appear in utero. The aim of this study was to investigate the growth of the modiolus histologically. We studied frontal histological sections of the face from 12 midterm and six near-term fetuses. At midterm, a convergence of the levator anguli oris (LAOM) and depressor anguli oris (DAOM) was frequently present, and another convergence of the LAOM with the platysma (PM) or orbicularis oris (OOM) was also often evident. At near-term, muscle fiber merging or interdigitation was classified into nine combinations, five of which were frequently seen: LAOM-PM, LAOM-DAOM, zygomaticus major (ZMM)-orbicularis oris (OOM), buccinator (BM)-LAOM, and BM-PM. These combinations existed at slightly different depths and/or sites, thus allowing the angle of the mouth to receive multiple muscles. Notably, tissues interposed between the muscle fibers were limited to a thin epimysium at each crossing or interdigitation. Therefore, the LAOM, DAOM, OOM, BM, and PM appear to form a basic configuration at birth, but the development and growth were much delayed than the classical description. The modiolus is not a specific fibromuscular structure but simply represents a cluster of muscle convergence sites. Even at meeting between an elevator and depressor, a specific fibrous structure seems unlikely to connect the epimysium for the muscle convergence. Instead, the central nervous system appears to regulate the activity of related muscles to minimize tension or friction stress at the meeting site.

Three-dimensional visualization and quantitative analysis of embryonic and fetal thigh muscles using magnetic resonance and phase-contrast X-ray imaging.

The musculoskeletal system around the human hip joint has acquired a suitable structure for erect bipedal walking. However, little is known about the process of separation and maturation of individual muscles during the prenatal period, when muscle composition is acquired. Understanding the maturation process of the normal musculoskeletal system contributes to elucidating the acquisition of bipedal walking in humans and to predicting normal growth and detecting congenital muscle disorders and anomalies. In this study, we clarify the process of thigh muscle maturation from the embryonic stage to the mid-fetal stage using serial sections, phase-contrast X-ray computed tomography, and magnetic resonance imaging. We also provide a 4D atlas of human thigh muscles between 8 and 23 weeks of gestation. As a result, we first show that muscle separation in the lower thigh tends to progress from the superficial to the deep layers and that all musculoskeletal components are formed by Carnegie Stage 22. Next, we show that femur and muscle volume grow in correlation with crown-rump length. Finally, we show that the anterior, abductor, and posterior muscle groups in the thigh contain a high percentage of monoarticular muscle volume by the end of the embryonic period. This ratio approaches that of adult muscle composition during normal early fetal development and is typical of bipedal walking. This study of fetal muscle composition suggests that preparation for postnatal walking may begin in early fetal period.

Flavor Sensing in Utero and Emerging Discriminative Behaviors in the Human Fetus.

The diet of pregnant women exposes fetuses to a variety of flavors consisting of compound sensations involving smell, taste, and chemesthesis. The effects of such prenatal flavor exposure on chemosensory development have so far been measured only postnatally in human infants. Here, we report the first direct evidence of human fetal responsiveness to flavors transferred via maternal consumption of a single-dose capsule by measuring frame-by-frame fetal facial movements. Pregnant women and their fetuses based in the northeast of England were involved in this study from 32 to 36 weeks' gestation. Fetuses exposed to carrot flavor (n = 35) showed "lip-corner puller" and "laughter-face gestalt" more frequently, whereas fetuses exposed to kale flavor (n = 34) showed more "upper-lip raiser," "lower-lip depressor," "lip stretch," "lip presser," and "cry-face gestalt" in comparison with the carrot group and a control group not exposed to any flavors (n = 30). The complexity of facial gestalts increased from 32 to 36 weeks in the kale condition, but not in the carrot condition. Findings of this study have important implications for understanding the earliest evidence for fetal abilities to sense and discriminate different flavors.

Comparison of postmortem whole-body contrast-enhanced microfocus computed tomography and high-field magnetic resonance imaging of human fetuses.

OBJECTIVE: Although fetal autopsy is generally recommended to confirm or refute the antemortem diagnosis, parental acceptance of the procedure has fallen over time, mainly due to its invasiveness. Contrast-enhanced microfocus CT (micro-CT) and high-field magnetic resonance imaging (HF-MRI, ≥ 3 Tesla) have both been suggested as non-invasive alternatives to conventional fetal autopsy for fetuses < 20 weeks of gestation. The aim of this study was to compare these two modalities in postmortem whole-body fetal imaging. METHODS: In this study, the imaging process and quality of micro-CT and HF-MRI were compared using both qualitative and quantitative assessments. For the qualitative evaluation, fetal anatomy experts scored 56 HF-MRI and 56 micro-CT images of four human fetuses aged 13-18 gestational weeks on two components: overall image quality and the ability to recognize and assess 21 anatomical structures. For the quantitative evaluation, participants segmented manually three organs with increasing complexity to assess interobserver variability. In addition, the signal-to-noise and contrast-to-noise ratios of five major organs were determined. RESULTS: Both imaging techniques were able to reach submillimeter voxel size. The highest resolution of micro-CT was 22 µm (isotropic), while the highest resolution of HF-MRI was 137 µm (isotropic). The qualitative image assessment form was sent to 45 fetal anatomy experts, of whom 36 (80%) responded. It was observed that micro-CT scored higher on all components of the qualitative assessment compared with HF-MRI. In addition, the quantitative assessment showed that micro-CT had lower interobserver variability and higher signal-to-noise and contrast-to-noise ratios. CONCLUSIONS: Our findings show that micro-CT outperforms HF-MRI in postmortem whole-body fetal imaging in terms of both quantitative and qualitative outcomes. Combined, these findings suggest that the ability to extract diagnostic information is greater when assessing micro-CT compared with HF-MRI images. We, therefore, believe that micro-CT is the preferred imaging modality as an alternative to conventional fetal autopsy for early gestation and is an indispensable tool in postmortem imaging services. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Delayed development of vacuoles and recanalization in the duodenum: a study in human fetuses to understand susceptibility to duodenal atresia/stenosis.

ObjectiveWe compared the cross-sectional areas of the duodenum to the distal small intestine during early gestation to determine if there is a difference in age for recanalization.MethodsSerial sagittal sections of six fetuses of gestational age (GA) 8-10 weeks were examined morphologically to compare the degree of recanalization of the duodenum with to the more distal small intestine.ResultsAt GA 8-9 weeks, the duodenum had more epithelial plugs and vacuoles with no or narrower spaces compared to the distal small bowel. Quantitative assessment at GA 10 weeks showed that the cross-sectional area of the duodenal cavity was significantly less than the distal small bowel.ConclusionThe development and recanalization of vacuoles in the duodenum occurs later than the jejunum and ileum may be involved in the more frequent development of atresia/stenosis of the duodenum compared to more distal gastrointestinal tract.

Quantitative MRI Analyses of Regional Brain Growth in Living Fetuses with Down Syndrome.

Down syndrome (DS) is the most common liveborn autosomal chromosomal anomaly and is a major cause of developmental disability. Atypical brain development and the resulting intellectual disability originate during the fetal period. Perinatal interventions to correct such aberrant development are on the horizon in preclinical studies. However, we lack tools to sensitively measure aberrant structural brain development in living human fetuses with DS. In this study, we aimed to develop safe and precise neuroimaging measures to monitor fetal brain development in DS. We measured growth patterns of regional brain structures in 10 fetal brains with DS (29.1 ± 4.2, weeks of gestation, mean ± SD, range 21.7~35.1) and 12 control fetuses (25.2 ± 5.0, range 18.6~33.3) using regional volumetric analysis of fetal brain MRI. All cases with DS had confirmed karyotypes. We performed non-linear regression models to compare fitted regional growth curves between DS and controls. We found decreased growth trajectories of the cortical plate (P = 0.033), the subcortical parenchyma (P = 0.010), and the cerebellar hemispheres (P < 0.0001) in DS compared to controls. This study provides proof of principle that regional volumetric analysis of fetal brain MRI facilitates successful evaluation of brain development in living fetuses with DS.

Human orbital muscle in adult cadavers and near-term fetuses: its bony attachments and individual variation identified by immunohistochemistry.

PURPOSE: To compare fetal and adult morphologies of the orbital muscle (OM) and to describe the detailed topographical anatomy in adults. METHODS: Using unilateral orbits from 15 near-term fetuses and 21 elderly cadavers, semiserial horizontal or sagittal paraffin sections were prepared at intervals of 20-100 µm. In addition to routine histology, we performed immunohistochemistry for smooth muscle actin. RESULTS: At near term, the OM consistently extended widely from the zygomatic bone or the greater wing of the sphenoid to the maxilla or ethmoid. Thus, it was a large sheet covering the future inferior orbital fissure. In contrast, the adult OM was a thin and small muscle bundle connecting (1) the greater wing of the sphenoid to the maxilla (11/19 cadavers), (2) the lesser wing of the sphenoid to the maxilla (5/19) or the greater wing (3/19). The small OM was likely to be restricted within the greater wing (5/19 cadavers) or the maxilla (3/19). Two of these five types of OM coexisted in eight orbits. OM attachment to the lesser wing was not seen in fetuses, whereas ethmoid attachment was absent in adults. CONCLUSIONS: The lesser wing attachment of the OM seemed to establish after birth. A growing common origin of the three recti was likely involved in "stealing" the near-term OM attachment from the ethmoid. The strong immunoreactivity of remnant-like OM in the elderly suggests that OM contraction is still likely to occur against the increased flow through a thin vein. However, the contraction might have no clinical significance.

Fetal development and growth of the human erector spinae with special reference to attachments on the surface aponeurosis.

PURPOSE: The longissimus (LO) and iliocostalis (IC) of adults consist of myofibers extending from the superolateral to the inferomedial side of the back and, because of the same course, they are fused in the thoracolumbar region. The LO also has a medial attachment to the long myofibers of the transversospinalis (TS) showing a course from the superomedial to the inferolateral side. However, there is apparently no information regarding when and how these similar longitudinal muscles differentiate from a cluster of dorsomedial myotome cells. METHODS: We examined sagittal and horizontal sections of the trunks of 39 human embryos and fetuses (18-330 mm crown-rump length). RESULTS: At 6-7 weeks gestational age (GA), the surface aponeurosis appeared prior to and independent of the thoracolumbar fascia. At 6-9 weeks GA, the LO myofibers had a postero-inferior course, from the transverse process to the initial aponeurosis, whereas the TS myofibers had a postero-superior course, from a lateral extension of the intertransverse ligament to the aponeurosis. However, the IC consisted of supracostal longitudinal myofibers and was distant from the LO until 12 weeks GA. Because of the lack of ligamentous attachments and ribs, myofibers of the TS, LO, and IC took a similar inferior course in the lumbar region. When the early TS was represented by the transverso-aponeurotic muscle, consequently, the LO corresponded to the aponeuro-transversal muscle and was independent from the IC. CONCLUSION: The classical model of TS and LO development does not recognize the essential role of the aponeurosis identified here.

Fetal development of the thoracolumbar fascia with special reference to the fascial connection with the transversus abdominis, latissimus dorsi, and serratus posterior inferior muscles.

PURPOSE: The three-layered thoracolumbar fascia (TLF) encapsulates the erector spinae and the quadratus lumborum and has been a major concern for physical therapists. However, knowledge of its prenatal development and growth is limited. METHODS: Histological examination of 25 embryos and fetuses at 6-37 weeks (CRLs, 15-310 mm). RESULTS: At the posterior end, the abdominal muscles continued toward an initial posterior layer of the TLF (pTLF) at 6 weeks, but the connection became narrow and limited to the obliquus externus aponeurosis until near term. The middle layer of the TLF (mTLF) appeared as a posterior continuation of the transversalis fascia at 9 weeks and, depending on a mechanical demand for the vertebral column extension near term, it grew as a thick intermuscular septum between the iliocostalis and quadratus lumborum. Thus, the mTLF lateral end changed from the abdominal wall to the back or pTLF. The serratus posterior inferior originated from the pTLF after 9 weeks, but a connection of the latissimus dorsi with the fascia was established much later. Near term, the gluteus maximus was attached to an aponeurosis covering the multifidus behind the sacrum. Therefore, the pTLF extended to cover the gluteal muscles. CONCLUSION: We rejected the hypothesis that the mTLF develops as a marginal tissue between the primitive epaxial and hypaxial muscles. This study seemed to be the first report showing a fact that, within prenatal life, a drastic change is likely to occur in interfascial connections and their topographical relation to muscles; the TLF might be the best sample.

PEQULIARITIES OF MORPHOGENESYS AND TOPOGRAPHY OF INFRAHYOID TRIANGLES IN HUMAN PREFETUSES AND FETUSES.

OBJECTIVE: The aim: To investigate morphology and developmental features of anatomical structures in the infrahyoid triangles of human neck during prefetal and fetal periods of human ontogenesis. PATIENTS AND METHODS: Materials and methods: We have studied 30 specimens of human prefetuses from 7th till 12th week (16,0-82,0 mm of parieto-coccygeal length (PCL)) and 30 human fetuses aged from 4th till 10th month (84,0-360,0 mm PCL) of intrauterine development by the means of macro-, microscopy, morphometry, three-dimensional remodeling and statistical analyses. RESULTS: Results: We can observe anterior triangle in human fetuses after the time when common precursor muscular mass splits into two: the anterior and posterior portions which will give rise to the sternocleidomastoid and trapezoid muscles accordingly. The area index of the central triangle in human fetuses 4th - 10th month of intrauterine development shows the increasing tendency with the highest rates at 8th-10th months period - 1100-1200 mm2. The angulated course of omohyoid muscle is visible at late prefetal and early fetal periods (3-4th month; 80,0-130,0 PCL) as well as the presence of intermediate tendon. Peaks of the area of sternocleidomastoid region area evaluation was observed in 190,0-210,0 mm PCL and 260,0-270,0 mm PCL human fetuses; 6th and 7,5th months accordingly. CONCLUSION: Conclusions: The critical periods for the AT and SCM regions should be considered 6th and 8th months of the IUD. Prefetal period shows the presence of AT and border structure for the IH neck - precursor of HB. Fetal period of IUD (4th - 10th months of IUD) should be considered as such that represents an adult-alike morphology of IH neck: presence of IH triangles with fully developed vascular, muscular and fascial content.

Normal human and sheep fetal vessel oxygen saturations by T2 magnetic resonance imaging.

KEY POINTS: Human fetal Doppler ultrasound and invasive blood gas measurements obtained by cordocentesis or at the time of delivery reveal similarities with sheep (an extensively used model for human fetal cardiovascular physiology). Oxygen saturation (SO2 ) measurements in human fetuses have been limited to the umbilical and scalp vessels, providing little information about normal regional SO2 differences in the fetus. Blood T2 MRI relaxometry presents a non-invasive measure of SO2 in the major fetal vessels. This study presents the first in vivo validation of fetal vessel T2 oximetry against the in vitro T2-SO2 relationship using catheterized sheep fetuses and compares the normal SO2 in the major vessels between the human and sheep fetal circulations. Human fetal vessel SO2 by T2 MRI confirms many similarities with the sheep fetal circulation and is able to demonstrate regional differences in SO2 ; in particular the significantly higher SO2 in the left versus right heart. ABSTRACT: Blood T2 magnetic resonance imaging (MRI) relaxometry non-invasively measures oxygen saturation (SO2 ) in major vessels but has not been validated in fetuses in vivo. We compared the blood T2-SO2 relationship in vitro (tubes) and in vivo (vessels) in sheep, and measured SO2 across the normal human and sheep fetal circulations by T2. Singleton pregnant ewes underwent surgery to implant vascular catheters. In vitro and in vivo sheep blood T2 measurements were related to corresponding SO2 measured using a blood gas analyser, as well as relating T2 and SO2 of human fetal blood in vitro. MRI oximetry was performed in the major vessels of 30 human fetuses at 36 weeks (term, 40 weeks) and 10 fetal sheep (125 days; term, 150 days). The fidelity of in vivo fetal T2 oximetry was confirmed through comparison of in vitro and in vivo sheep blood T2-SO2 relationships (P = 0.1). SO2 was similar between human and sheep fetuses, as was the fetal oxygen extraction fraction (human, 33 ± 11%; sheep, 34 ± 7%; P = 0.798). The presence of streaming in the human fetal circulation was demonstrated by the SO2 gradient between the ascending aorta (68 ± 10%) and the main pulmonary artery (49 ± 9%; P < 0.001). Human and sheep fetal vessel MRI oximetry based on T2 is a validated approach that confirms the presence of streaming of umbilical venous blood towards the heart and brain. Streaming is important in ensuring oxygen delivery to these organs and its disruption may have important implications for organ development, especially in conditions such as congenital heart disease and fetal growth restriction.

The incudopetrosal joint of the human middle ear: a transient morphology in fetuses.

In spite of the amount of research on fetal development of the human middle ear and ear ossicles, there has been no report showing a joint between the short limb of incus and the otic capsule or petrous part of the temporal bone. According to observations of serial histological sections from 65 embryos and fetuses at 7-17 weeks of development, the incudopetrosal joint exhibited a developmental sequence similar to the other joints of ossicles, with an appearance of an interzone followed by a trilaminar configuration at 7-12 weeks, a joint cavitation at 13-15 weeks and development of intraarticular and capsular ligaments at 16-17 weeks. These processes occurred at the same time or slightly later than any other joint. Thus, the joint development might coordinate with vibrating ossicles in utero. The growing short limb of incus appeared to accelerate an expansion of the epitympanic recess of the tympanic cavity. Additional observations of five late-stage fetuses demonstrated the incudopetrosal joint located in the fossa incudis joint changing to syndesmosis. Consequently, a real joint with a cavity existed transiently between the human neurocranium and the first pharyngeal arch derivative (i.e. incus) in contrast to the tympanostapedial joint or syndesmosis between the neurocranium and the second arch derivative. The newly described joint might have an effect on the widely accepted primary jaw concept: the mammalian jaw should thus have been created within the first pharyngeal arch, although the connection with neurocranium by the stapes is of a different origin.

Secretagogin-dependent matrix metalloprotease-2 release from neurons regulates neuroblast migration.

The rostral migratory stream (RMS) is viewed as a glia-enriched conduit of forward-migrating neuroblasts in which chemorepulsive signals control the pace of forward migration. Here we demonstrate the existence of a scaffold of neurons that receive synaptic inputs within the rat, mouse, and human fetal RMS equivalents. These neurons express secretagogin, a Ca2+-sensor protein, to execute an annexin V-dependent externalization of matrix metalloprotease-2 (MMP-2) for reconfiguring the extracellular matrix locally. Mouse genetics combined with pharmacological probing in vivo and in vitro demonstrate that MMP-2 externalization occurs on demand and that its loss slows neuroblast migration. Loss of function is particularly remarkable upon injury to the olfactory bulb. Cumulatively, we identify a signaling cascade that provokes structural remodeling of the RMS through recruitment of MMP-2 by a previously unrecognized neuronal constituent. Given the life-long presence of secretagogin-containing neurons in human, this mechanism might be exploited for therapeutic benefit in rescue strategies.

Vermiform Appendix During the Repackaging Process from Umbilical Herniation to Fixation onto the Right Posterior Abdomen: A Study of Human Fetal Horizontal Sections.

The anatomical position of the vermiform appendix varies among adults, and these variations are responsible for differences in the symptoms of appendicitis. However, to date no study has examined how and when these variations occur during fetal development. The present study examined horizontal sections of 27 midterm fetuses (crown rump length [CRL] 38-97 mm, gestational age approximately 8-15 weeks). There were 10 fetuses (CRL 56 mm or more) in which the cecum and appendix were in a posterosuperior site near the right kidney (postmigration phase), and 12 fetuses (CRL 39-72 mm) in which the ileocecal junction and appendix remained on the visceral surface of the liver in the anterior or anterolateral abdominal cavity (migration phase, after physiological umbilical herniation). Analysis of the 12 fetuses in the migration phase indicated that the appendix extended inferiorly in eight fetuses and superiorly in four fetuses. Likewise, a "preileal" appendix (a morphology in which the distal part of the appendix was in front of the terminal ileum) was present in eight of these fetuses. Extension of the appendix superiorly or inferiorly during the migration phase seems unrelated to the topographical relationship of the appendix with the terminal ileum at the postmigration phase in fetuses and in adults. Conversely, it seems likely that a retroileal appendix leads to a coiled appendix behind the ileocecal junction. "Guidance" by the liver surface seemed to be important for posterior migration, which ended with the ascent of the liver. Clin. Anat., 33:667-677, 2020. © 2019 Wiley Periodicals, Inc.

First-Trimester Placental Growth Factor for the Prediction of Preeclampsia in Nulliparous Women: The Great Obstetrical Syndromes Cohort Study.

BACKGROUND: First-trimester maternal serum markers have been associated with preeclampsia (PE). We aimed to evaluate the performance of first-trimester placental growth factor (PlGF) for the prediction of PE in nulliparous women. SUBJECTS AND METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy at 11-13 weeks. Maternal serum PlGF concentration was measured using B·R·A·H·M·S PlGFplus KRYPTOR automated assays and reported in multiple of the median adjusted for gestational age. We used proportional hazard models, along with receiver operating characteristic curves and areas under the curve (AUC). RESULTS: Out of 4,652 participants, we observed 232 (4.9%) cases of PE including 202 (4.3%) term and 30 (0.6%) preterm PE. PlGF was associated with the risk of term (AUC = 0.61, 95% confidence interval [CI] 0.57-0.65) and preterm PE (AUC = 0.73, 95% CI 0.64-0.83). The models were improved with the addition of maternal characteristics (AUC for term PE 0.66, 95% CI 0.62-0.71; AUC for preterm PE 0.81, 95% CI 0.72-0.91; p < 0.01). At a false-positive rate of 10%, PlGF combined with maternal characteristics could have predicted 26% of term and 55% of preterm PE. The addition of pregnancy-associated plasma protein A did not significantly improve the prediction models. CONCLUSION: First-trimester PlGF combined with maternal characteristics is useful to predict preterm PE in nulliparous women.

Morphometric study of the primary ossification center of the fibular shaft in the human fetus.

PURPOSES: Precise morphometric data on the development of ossification centers in human fetuses may be useful in the early detection of skeletal dysplasias associated with delayed ossification center development and mineralization. The present study was performed to quantitatively examine the primary ossification center of the fibular shaft with respect to its linear, planar and volumetric parameters. MATERIALS AND METHODS: Using methods of CT, digital-image analysis (Osirix 3.9 MD) and statistics (Student's t-test, Shapiro-Wilk, Fisher's test, Tukey's test, Kruskal-Wallis test, regression analysis), the size of the primary ossification center of the fibular shaft in 47 spontaneously aborted human fetuses (25 ♂ and 22 ♀) aged 17-30 weeks was studied. In each fetus, the assessment of linear dimensions (length, transverse diameters for: proximal end, middle part and distal end), projection surface area and volume of the fibular shaft ossification center was carried out. RESULTS: With no sex and laterality differences, the best fit growth dynamics for the primary ossification center of the fibular shaft was modelled by the following functions: y = - 13.241 + 1.567 × age ± 1.556 (R2 = 0.94) for its length, y = - 0.091 + 0.063 × age ± 0.073 (R2 = 0.92) for its proximal transverse diameter, y = - 1.201 + 0.717 × ln(age) ± 0.054 (R2 = 0.83) for its middle transverse diameter, y = - 2.956 + 1.532 × ln(age) ± 0.090 (R2 = 0.89) for its distal transverse diameter, y = - 69.038 + 4.699 × age ± 4.055 (R2 = 0.95) for its projection surface area, and y = - 126.374 + 9.462 × age ± 8.845 (R2 = 0.94) for its volume. CONCLUSIONS: The ossification center in the fibular shaft follows linear functions with respect to its length, proximal transverse diameter, projection surface area and volume, and natural logarithmic functions with respect to its middle and distal transverse diameters. The obtained morphometric data of the fibular shaft ossification center is considered normative for their respective prenatal weeks and may be of relevance in both the estimation of fetal age and the ultrasound diagnostics of congenital defects.

Mathematical models of human cerebellar development in the fetal period.

The evaluation of cerebellar growth in the fetal period forms a part of a widely used examination to identify any features of abnormalities in early stages of human development. It is well known that the development of anatomical structures, including the cerebellum, does not always follow a linear model of growth. The aim of the study was to analyse a variety of mathematical models of human cerebellar development in fetal life to determine their adequacy. The study comprised 101 fetuses (48 males and 53 females) between the 15th and 28th weeks of fetal life. The cerebellum was exposed and measurements of the vermis and hemispheres were performed, together with statistical analyses. The mathematical model parameters of fetal growth were assessed for crown-rump length (CRL) increases, transverse cerebellar diameter and ventrodorsal dimensions of the cerebellar vermis in the transverse plane, and rostrocaudal dimensions of the cerebellar vermis and hemispheres in the frontal plane. A variety of mathematical models were applied, including linear and non-linear functions. Taking into consideration the variance between models and measurements, as well as correlation parameters, the exponential and Gompertz models proved to be the most suitable for modelling cerebellar growth in the second and third trimesters of pregnancy. However, the linear model gave a satisfactory approximation of cerebellar growth, especially in older fetuses. The proposed models of fetal cerebellar growth constructed on the basis of anatomical examination and objective mathematical calculations could be useful in the estimation of fetal development.