Fetal Limb Research Articles

MEDIAN EPISIOTOMY APPROACH IN A MINIATURE POMERANIAN WITH VULVAL HYPOPLASIA: A CASE REPORT

This case report details the episiotomy approach employed in managing vulval hypoplasia in a two year old Miniature Pomeranian bitch. The animal was presented to the Teaching Veterinary Clinical Complex, Veterinary Gynaecology and Obstetrical Unit, Madras Veterinary College, displaying a history of greenish black discharge and continuous straining for two hours. The animal was bred before 64 days. Physical examination revealed a small vaginal opening, measuring approximately 1.5 cm in length. Digital examination indicated fetal hind limbs and tail extending into the vaginal passage, while all other vital parameters were within the normal range. Attempts to induce uterine contractions using Inj. Oxytocin and 10 % Calcium gluconate in 5 % DNS proved unsuccessful. Therefore, under local anesthesia (2 % Lignocaine injection), median episiotomy was made and a single live male puppy was successfully delivered with mild traction. Closure of the incision site was accomplished using PGA 1/0 with a simple interrupted suture pattern. The patient had uneventful recovery after 5 day treatment regimen, involving a single dose of subcutaneous Inj. Cefovecin (antibiotic) and anti-inflammatory drugs, along with meticulous wound management.

Antenatal unilateral upper limb acromesomelic dysplasia.

Acromesomelic dysplasia (AMD) is an umbrella term given to a heterogeneous group of progressive skeletal disorders characterized by short limbed dwarfism associated with disproportionate shortening of middle and distal segments of the upper as well as lower limbs. Although specific skeletal anomalies are difficult to diagnose antenatally, but because of their antenatal and postnatal implications and a possibility of reoccurrence in following pregnancies, such skeletal anomalies need to be actively addressed. A combination of radiologic, pathologic, genetic and molecular investigation prenatally as well as postnatally is required to classify a specific congenital skeletal dysplasia. Once the genetic make-up of fetal skeletal dysplasia is deciphered, a meaningful genetic counselling could be offered for future pregnancies of affected families. We describe a case of primigravida diagnosed with fetal unilateral upper limb AMD on antenatal ultrasound done at early second trimester. The radius and ulna of left upper limb were abnormally short (less than 5th centile of the mean for that gestational age). The left hand was also hypoplastic. Rest of the sonographic anomaly scan was normal. To the best of our knowledge, AMD limited to unilateral upper limb diagnosed antenatally as an isolated finding is not described in the medical literature so far.

Development of fetal magnetic resonance imaging (MRI) phantom.

Anthropomorphic phantoms play an important role in routine clinical practice. They can be used to calibrate magnetic resonance imaging (MRI) scanners, control the diagnostic equipment quality, and reduce the acquisition time. The latter is especially critical for diagnosing fetal anomalies, which requires optimal image quality within the shortest possible time. This paper aims to develop an MRI fetal phantom and determine the materials that best mimic the magnetic resonance (MR) characteristics of its internal organs. Future phantom features will include simulations of fetal limb movements. A single MRI study of a pregnant woman at 20 weeks 3 days of gestation was used as a reference and for image segmentation. Anonymized Digital Imaging and Communication in Medicine (DICOM) files were imported into 3D Slicer v. 5.2.1 for segmentation of the uterus, fetus, and internal organs. Based on the performed segmentation, a three-dimensional model was obtained for printing on a 3D printer. The mold was 3D printed on an Anycubic Photon M3 Max printer. The paper showcases the selection and manufacturing of compositions to simulate the relaxation times of the fetal organs. Formulations for emulsions and carrageenan- and agar-based hydrogels are presented. The selected compositions were used to fill the 3D printed model. Statistical analysis showed no significant differences in absolute and relative signal values obtained from scans of a pregnant woman at 20 weeks and 3 days and a fetal phantom. During the study, an anthropomorphic fetal phantom was constructed, filled with compositions with relaxation times T1 and T2 similar to the control values of the corresponding tissues. The phantom can be used to set up and optimize fetal MRI protocols, train and educate medical students, residents, graduate students, and X-ray technicians, as well as to timely control image quality and equipment serviceability.

The ontogeny of human fetal trabecular bone architecture occurs in a limb-specific manner

Gestational growth and development of bone is an understudied process compared to soft tissues and has implications for lifelong health. This study investigated growth and development of human fetal limb bone trabecular architecture using 3D digital histomorphometry of microcomputed tomography data from the femora and humeri of 35 skeletons (17 female and 18 male) with gestational ages between 4 and 9 months. Ontogenetic data revealed: (i) fetal trabecular architecture is similar between sexes; (ii) the proximal femoral metaphysis is physically larger, with thicker trabeculae and greater bone volume fraction relative to the humerus, but other aspects of trabecular architecture are similar between the bones; (iii) between 4 and 9 months gestation there is no apparent sexual or limb dimorphism in patterns of growth, but the size of the humerus and femur diverges early in development. Additionally, both bones exhibit significant increases in mean trabecular thickness (and for the femur alone, bone volume fraction) but minimal trabecular reorganisation (i.e., no significant changes in degree of anisotropy, connectivity density, or fractal dimension). Overall, these data suggest that in contrast to data from the axial skeleton, prenatal growth of long bones in the limbs is characterised by size increase, without major reorganizational changes in trabecular architecture.

Identification of four TTN variants in three families with fetal akinesia deformation sequence

BackgroundTTN is a complex gene with large genomic size and highly repetitive structure. Pathogenic variants in TTN have been reported to cause a range of skeletal muscle and cardiac disorders. Homozygous or compound heterozygous mutations tend to cause a wide spectrum of phenotypes with congenital or childhood onset. The onset and severity of the features were considered to be correlated with the types and location of the TTN variants.MethodsWhole-exome sequencing was performed on three unrelated families presenting with fetal akinesia deformation sequence (FADS), mainly characterized by reduced fetal movements and limb contractures. Sanger sequencing was performed to confirm the variants. RT-PCR analysis was performed.ResultsTTN c.38,876–2 A > C, a meta transcript-only variant, with a second pathogenic or likely pathogenic variant in trans, was observed in five affected fetuses from the three families. Sanger sequencing showed that all the fetal variants were inherited from the parents. RT-PCR analysis showed two kinds of abnormal splicing, including intron 199 extension and skipping of 8 bases.ConclusionsHere we report on three unrelated families presenting with FADS caused by four TTN variants. In addition, our study demonstrates that pathogenic meta transcript-only TTN variant can lead to defects which is recognizable prenatally in a recessive manner.

Analysis of the Efficacy of Prenatal B-Ultrasound in Diagnosing Fetal Abnormalities

Objective: To explore the positive significance of using prenatal B-ultrasound in diagnosing fetal abnormalities. Methods: A total of 200 pregnant women who visited Shaanxi Provincial People’s Hospital between January 2023 and January 2024 were recruited as the research subjects. All pregnant women received prenatal examinations. A retrospective analysis was carried out to analyze the positive significance of prenatal B-ultrasound examination in the diagnosis of fetal abnormalities. Results: Prenatal B-ultrasound examination detected 10 cases of fetal abnormalities, with a detection rate of 5.00%. When compared with the postnatal examination results of 5.50%, the difference was insignificant (P > 0.05). Moreover, comparing the fetal limb abnormalities and cardiovascular abnormalities in prenatal B-ultrasound examination and postnatal examination, one case of congenital heart disease was missed in the prenatal B-ultrasound examination, and the others were consistent with the postnatal examination results, with a coincidence rate of 90.91%, indicating a high compliance rate. Conclusion: Fetal abnormalities have a great impact on mothers, babies, and families, and it is particularly important to strengthen diagnosis during this process. Prenatal B-ultrasound examination can improve the accuracy of diagnosis of fetal abnormalities and can be promoted in clinical practice as a basis for screening fetal abnormalities.

Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography

BackgroundA major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of two-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established two-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. ObjectiveThe Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by three-dimensional ultrasonography and compare growth trajectories with conventional two-dimensional measures where applicable. Study DesignThe NICHD Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to five scans per fetus (N=1,730 fetuses). Abdominal subcutaneous tissue thickness was measured from two-dimensional images and fetal limb soft tissue parameters extracted from three-dimensional multiplanar views. Cerebellar, lung, liver and kidney volumes were measured using virtual organ computer aided analysis (VOCAL). Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (5th, 50th, 95th percentiles) were derived from 15-41 weeks’ using linear mixed models for repeated measures with cubic splines. ResultsSubcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27-29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29-30 weeks. In contrast, growth patterns for two-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the 2nd trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid arm and thigh circumferences were more linear with some decelerations. Cerebellar two-dimensional diameter increased linearly, whereas cerebellar three-dimensional volume growth gradually accelerated until 32 weeks and then decelerated. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26-27 weeks for kidneys, and 29 weeks for liver. ConclusionGrowth patterns and timing of maximal growth for three-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional two-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic or environmental influences and pregnancy complications, in ways not identifiable using corresponding two-dimensional measures. Further investigation into the relationships of these three-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

USING FOETAL SKELETOGENESIS TO EVALUATE AND IMPROVE IN VITRO CHONDROGENESIS PROTOCOLS

The reliable production of _in vitro_ chondrocytes that faithfully recapitulate _in vivo_ development would be of great benefit for orthopaedic disease modelling and regenerative therapy(1,2). Current efforts are limited by off-target differentiation, resulting in a heterogeneous product, and by the lack of comparison to human tissue, which precludes detailed evaluation of _in vitro_ cells(3,4).We performed single-cell RNA-sequencing of long bones dissected from first-trimester fetal limbs to form a detailed ‘atlas’ of endochondral ossification. Through 100-gene in-situ sequencing, we placed each sequenced cell type into its anatomical context to spatially resolve the process of endochondral ossification. We then used this atlas to perform deconvolution on a series of previously published bulk transcriptomes generated from _in vitro_ chondrogenesis protocols to evaluate their ability to accurately produce chondrocytes.We then applied single-nuclear RNA-sequencing to cells from the best performing protocol collected at multiple time points to allow direct comparison between the differentiation of _in vitro_ and _in vivo_ cells.We captured 275,000 single fetal cells, profiling the development of chondrocytes from multipotent mesenchymal progenitors to hypertrophic cells at full transcriptomic breadth. Using this atlas as the ground truth for evaluating _in vitro_ cells, we found substantial variability in cell states produced by each protocol, with many showing little similarity to _in vivo_ cells, and all exhibiting off-target differentiation.Trajectory alignment between _in vivo_ and _in vitro_ single-cell data revealed key differences in gene expression dynamics between _in vitro_ and _in vivo cells,_ with several osteoblastic transcription factors erroneously unregulated _in vitro,_ including _FOXO1._Using this information, we inhibited _FOXO1_ in culture to successfully increase chondrocyte yield _in vitro._This study presents a new framework for evaluating tissue engineering protocols, using single-cell data to drive improvement and bring the prospect of true engineered cartilage closer to reality.

Compensatory growth and recovery of cartilage cytoarchitecture after transient cell death in fetal mouse limbs

A major question in developmental and regenerative biology is how organ size and architecture are controlled by progenitor cells. While limb bones exhibit catch-up growth (recovery of a normal growth trajectory after transient developmental perturbation), it is unclear how this emerges from the behaviour of chondroprogenitors, the cells sustaining the cartilage anlagen that are progressively replaced by bone. Here we show that transient sparse cell death in the mouse fetal cartilage is repaired postnatally, via a two-step process. During injury, progression of chondroprogenitors towards more differentiated states is delayed, leading to altered cartilage cytoarchitecture and impaired bone growth. Then, once cell death is over, chondroprogenitor differentiation is accelerated and cartilage structure recovered, including partial rescue of bone growth. At the molecular level, ectopic activation of mTORC1 correlates with, and is necessary for, part of the recovery, revealing a specific candidate to be explored during normal growth and in future therapies.

Association of maternal obesity with growth of fetal fractional limb volume

BackgroundMaternal obesity influences birth weight and newborn adiposity. Fetal fractional limb volume has recently been introduced as a useful parameter for the proxy of fetal adiposity. However, the association between maternal adiposity and the growth of fetal fractional limb volume has not been examined. AimsTo investigate the association of maternal pre-pregnancy BMI with the growth of fetal fractional limb volume. Study designProspective cohort study. SubjectsWomen with singleton uncomplicated pregnancies enrolled between July 2017 and June 2020. Outcome measuresFetal fractional limb volume was assessed between 20 and 40 weeks' gestation, measured as cylindrical limb volume based on 50 % of the total diaphysis length. The measured fractional limb volume at each gestational week were converted to z-scores based on a previous report. The association between pre-pregnancy BMI and fetal fractional limb volume was examined. Maternal age, parity, gestational weight gain and fetal sex were considered as potential confounding variables. ResultsUltrasound scans of 455 fractional arm volume and thigh volume were obtained. Fractional limb volume increased linearly until the second trimester of gestation, then increased exponentially in the third trimester. Maternal pre-pregnancy BMI was significantly correlated with z-scores of fractional arm volume and thigh volume across gestation. The post-hoc analysis showed the association between pre-pregnancy BMI and fractional arm volume was significant especially between 34 and 40 weeks. ConclusionsMaternal obesity influences the growth pattern of fetal fractional limb volume. Fractional arm volume may potentially provide a useful surrogate marker of fetal nutritional status in late gestation.

Case report of congenital myotonic dystrophy with multiple prenatal sonographic findings

Abstract Objectives Myotonic dystrophy 1 (DM1) is an autosomal dominant inherited neuromuscular disorder. The most severe form is congenital myotonic dystrophy (cDM). Prenatal diagnosis is complicated and sonographic findings of cDM that are not pathognomonic occur in the late second or early third trimester of pregnancy. Case presentation It is the case of prenatally diagnosed cDM. In 32 weeks of pregnancy multiple sonographic findings such as severe polyhydramnios, bilateral talipes, fetal legs akinesia, macrocephaly with mild bilateral ventriculomegaly, right-sided pleural effusion and diaphragmatic pathology were observed by fetal medicine specialist. As the patient complained of weakness in her limbs, she was consulted by a neurologist. The neurological examination revealed a pathognomonic sign of DM1 – grip myotonia. The amniotic fluid and the mother’s blood sample were further tested for DM1. This identified >150 repeats in one copy of the DMPK gene of the both, which is consistent with the diagnosis DM1. Conclusions The sonographic findings of fetal limb abnormalities with progressive polyhydramnios is an indication for maternal neurological examination and genetic testing due to myotonic dystrophy.

Nomogram for fetal limb bones in Chinese ethnicity

Objective To construct fetal limb bone nomograms in the Chinese ethnic population. Methods This was a prospective cross-sectional study on singleton pregnancies between 12 and 37 weeks of gestation. Femur, tibia, fibula, humerus, ulna, radius, and foot length were measured in a standardized manner by one of the three sonographers. Each fetus’s measurements were only included once and those who developed maternal or fetal complications were excluded. Fractional polynomial regression model was used to obtain the 3rd, 10th, 50th, 90th, and 97th centiles for each of the limb measurement. Z-score for the 50th centile of each fetal limb measurement was then compared with published nomograms derived from other populations. Results Of the 843 scans performed, 775 were included in analysis after excluding conditions such as pre-eclampsia, chromosomal abnormalities, single umbilical artery and skeletal dysplasia. Comparison with other populations showed that Chinese had shorter fetal limb bone lengths than the Caucasian and Afro-Caribbean populations. Conclusion This study established nomograms for all the fetal limb bones in the Chinese ethnic population, which showed lengths comparatively shorter than Caucasian and Afro-Caribbean nomograms. This would reduce the false alarm of short fetal limb bone lengths and its consequent anxiety and intervention.

Heavy metals and trace elements in maternal blood and prevalence of congenital limb abnormalities among newborns: the Japan Environment and Children's Study.

Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children's Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid-late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.

LCN2 inhibits the BMP9-induced osteogenic differentiation through reducing Wnt/β-catenin signaling via interacting with LRP6 in mouse embryonic fibroblasts.

Due to its effective osteogenic ability, BMP9 is a promising candidate for bone regeneration medicine. Whereas, BMP9 can also induce adipogenesis simultaneously. LCN2 is a cytokine associated with osteogenesis and adipogenesis. Reducing the adipogenic potential may be a feasible measure to enhance the osteogenic capability of BMP9. The objective of the study was to explore the role of LCN2 in regulating the BMP9-initialized osteogenic and adipogenic differentiation in mouse embryonic fibroblasts (MEFs), and clarify the possible underlying mechanism. Histochemical stain, western blot, real-time PCR, laser confocal, immunoprecipitation, cranial defect repair, and fetal limb culture assays were used to evaluate the effects of LCN2 on BMP9-induced osteogenic and adipogenic differentiation, as well as Wnt/β-catenin signaling. LCN2 was down-regulated by BMP9. The BMP9-induced osteogenic markers were inhibited by LCN2 overexpression, but the adipogenic markers were increased; LCN2 knockdown exhibited opposite effects. Similar results were found in bone defect repair and fetal limb culture tests. The level of β-catenin nucleus translocation was found to be reduced by LCN2 overexpression, but increased by LCN2 knockdown. The inhibitory effect of LCN2 overexpression on the osteogenic capability of BMP9 was reversed by β-catenin overexpression; whereas, the effect of LCN2 knockdown on promoting BMP9 osteogenic potential was almost eliminated by β-catenin knockdown. LCN2 could bind with LRP6 specifically, and the inhibitory effect of LCN2 on the osteogenic potential of BMP9 could not be enhanced by LRP6 knockdown. LCN2 inhibits the BMP9-induced osteogenic differentiation but promotes its adipogenic potential in MEFs, which may be partially mediated by reducing Wnt/β-catenin signaling via binding with LRP6.

EP15.24: Association of maternal serum adipokine levels in mid‐gestation with growth of fetal fractional limb volume

EP15.24: Association of maternal serum adipokine levels in mid‐gestation with growth of fetal fractional limb volume

EP15.26: Association of maternal pregravid body mass index with growth of fetal fractional limb volume

EP15.26: Association of maternal pregravid body mass index with growth of fetal fractional limb volume

Klippel–Trenaunay–Weber Syndrome—Case Report: Diagnostic Role of Fetal Autopsy and Histopathology

Abstract Objectives The aim of this study was to evaluate a case of Klippel–Trenaunay–Weber Syndrome (KTWS) diagnosed at 15 weeks of gestation. Materials and Methods A 30-year-old G4P1L1A2 at 15 weeks gestation was detected with abnormal fetal right lower limb thickness and hypervascularity in both thighs. Multiseptated hypoechoic areas were detected involving skin and subcutaneous tissue of the left shoulder region, axilla, chest wall, and lower back region posteriorly extending into both lower limbs associated with cortical thickening of long bones of the lower limb. Significant subcutaneous thickening was present in the right foot along with a slow flow vascular malformation. The couple did not opt for any prenatal testing and continued the pregnancy. Results The patient received routine antenatal care and at 27 weeks of gestation there was polyhydramnios with fetal demise. She delivered a macerated stillborn baby girl weighing 2.5 kg (>99th centile). Consent was obtained for external autopsy, fetal photographs, and tissue biopsy. The fetus was grossly macerated. The skin was hypertrophied and subcutaneous tissue along with bluish discoloration was present over the affected areas. Histopathology of fetal thigh tissue was suggestive of arteriovenous malformation compatible with a diagnosis of KTWS. Conclusions KTWS has unique sonographic features. Confirmation can be done by clinical exome sequencing of amniotic fluid or fetal tissue.

Analysis of characteristic features in ultrasound diagnosis of fetal limb body wall complex during 11-13+6 weeks.

Limb body wall complex (LBWC) is a fatal malformation characterized by major defects in the fetal abdominal or thoracic wall, visceral herniation, significant scoliosis or spina bifida, limb deformities, craniofacial deformities, and umbilical cord abnormalities (short or absent umbilical cord). Early diagnosis of this condition is of great clinical significance for clinical intervention and pregnancy decision-making. With the rapid development of fetal ultrasound medicine, early pregnancy (11-13+6 wk) standardized prenatal ultrasound examinations have been widely promoted and applied. To explore the value of prenatal ultrasound in the diagnosis of fetal LBWC syndrome during early pregnancy. The ultrasonographic data and follow-up results of 18 cases of fetal LBWC diagnosed by prenatal ultrasound during early pregnancy (11-13+6 wk) were retrospectively analyzed, and their ultrasonographic characteristics were analyzed. Among the 18 fetuses with limb wall abnormalities, there were spinal dysplasia (18/18, 100%), varying degrees of thoracoschisis and gastroschisis (18/18, 100%), limb dysplasia in 6 cases (6/18, 33%), craniocerebral malformations in 4 cases (4/18, 22%), thickening of the transparent layer of the neck in 5 cases (5/18, 28%), and umbilical cord abnormalities in 18 cases (18/18, 100%), single umbilical artery in 5 cases. Prenatal ultrasound in early pregnancy can detect LBWC as early as possible, and correct prenatal evaluation provides important guidance value for pregnancy decision-making and early intervention.

Maternal Cigarette Smoking and Congenital Upper and Lower Limb Differences: A Systematic Review and Meta-Analysis.

Maternal smoking during pregnancy has been associated with adverse effects on foetal development, including congenital limb anomalies. This systematic review aimed to provide an updated assessment of the association between maternal smoking during pregnancy and the risk of congenital limb anomalies. A systematic search was conducted to identify relevant studies published up to February 2023. Studies reporting on the relationship between maternal smoking during pregnancy and congenital digital anomalies or congenital limb reduction defects were included. Two independent reviewers screened the studies, extracted data, and assessed the quality of the included studies. Meta-analyses were performed to estimate the pooled odds ratios with 95% confidence intervals using fixed and random-effects models. In total, 37 publications comprising 11 cohort and 26 case-control studies were included in the systematic review. The meta-analysis demonstrated a significant increased risk of congenital limb reduction defects (pooled OR: 1.27, 95% CI: 1.18-1.38) in infants born to mothers who smoked during pregnancy. Similarly, a significant relationship was observed for the development of polydactyly/syndactyly/adactyly when considered as a single group (pooled OR: 1.32, 95% CI: 1.25-1.40). Yet, in contrast, no significant association was observed when polydactyly (pooled OR: 1.06, 95% CI: 0.88-1.27) or syndactyly (pooled OR: 0.91, 95% CI: 0.77-1.08) were considered individually. This systematic review provides updated evidence of a significant relationship between maternal smoking during pregnancy and increased risk of congenital limb anomalies. These findings highlight the potential detrimental effects of smoking on foetal limb development and underscore the importance of smoking cessation interventions for pregnant women to mitigate these risks.

Technique for Surgical Dissection and Histological Investigation of the Anterolateral Ligament in the Fetal Knee

There is growing evidence into the structure and function of the anterolateral ligament (ALL) of the knee. However, debate still exists about the anatomical characteristics, biomechanical role, and even the existence of the ALL, despite numerous cadaveric, biomechanical, and clinical studies. This article describes, with video illustration, the surgical dissection of the ALL in human fetal lower limbs, including determination of detailed anatomical and histological features of the ALL during fetal development. The ALL was clearly identified in dissected fetal knees, and histologic analysis shows well-organized, dense collagenous tissue fibers with elongated fibroblasts, consistent with the properties of a ligament.