The human vertebral column has a stable number of vertebrae and ribs, which is presumably the result of evolutionary selection. An association between an abnormal vertebral pattern, especially in the cervical region, and congenital anomalies or adverse fetal outcome has been reported.The aim of this study was to review the current literature concerning an abnormal vertebral pattern and prevalence of cervical ribs in healthy subjects and in subjects with adverse outcome.Scientific databases were searched systematically. Studies assessing the number of vertebrae and/or ribs were included, and data concerning anomalies and outcome were extracted.Thirty-nine studies including 75,018 healthy subjects and 6130 subjects with structural or chromosomal anomalies or adverse outcome were selected. The majority of these studies focused on the prevalence of cervical ribs. The prevalence of cervical ribs was considerably higher in fetuses with adverse outcome, including aneuploidies, compared with healthy individuals in the vast majority of studies. Studies suggest an association between cervical ribs and other structural anomalies.These results demonstrate that detailed assessment of the fetal vertebral column, especially of the cervicothoracic region, could provide valuable information regarding fetal and neonatal prognosis. Based on the available evidence, the application of 3-dimensional (3D) ultrasound to assess the vertebral column and ribs, in particular the cervical region, warrants further research.Prenatal assessment of the ribs and vertebral pattern by 3D ultrasound, which is currently not routinely performed, might be useful in the assessment of the fetus, because this can predict fetal and neonatal outcome in some cases.
What's already known about this topic? In fetuses with an isolated omphalocele, the OC/AC ratio is less than 24 weeks; gestation is of predictive value for postnatal type of closure. What does this study add? The OC/AC ratio is predictive for type of surgical closure and survival in all fetuses with an omphalocele. This report is the first concerning the trend of the OC/AC ratio throughout gestation. The OC/AC ratio best predicts type of closure and survival in the third trimester of pregnancy.
Abstract Objectives To study the methodology and results of studies assessing the relationship between fetal heart rate and specified neonatal outcomes including, heart rate, infection, necrotizing enterocolitis, intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and seizure. Methods Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and CINAHL were searched from inception to October 5, 2023. Results Forty-two studies were included, encompassing 57,232 cases that underwent fetal monitoring and were evaluated for neonatal outcome. Heterogeneity was observed in the timing and duration of fetal heart rate assessment, classification guidelines used, number of assessors, and definition and timing of neonatal outcome assessment. Nonreassuring fetal heart rate was linked to lower neonatal heart rate variability. A significant increase in abnormal fetal heart rate patterns were reported in neonates with hypoxic-ischemic encephalopathy, but the predictive ability was found to be limited. Conflicting results were reported regarding sepsis, seizure and intraventricular hemorrhage. No association was found between necrotizing enterocolitis rate and fetal heart rate. Conclusions There is great heterogeneity in the methodology used in studies evaluating the association between fetal heart rate and aforementioned neonatal outcomes. Hypoxic-ischemic encephalopathy was associated with increased abnormal fetal heart rate patterns, although the predictive ability was low. Further research on developing and evaluating an automated early warning system that integrates computerized cardiotocography with a perinatal health parameter database to provide objective alerts for patients at-risk is recommended.
Abstract Objective To assess the vertebral pattern in a cohort of deceased fetuses and neonates, and to study the possible impact of DNA Copy Number Variations (CNVs) in coding regions and/or disturbing enhancers on the development of the vertebral pattern. Method Radiographs of 445 fetuses and infants, deceased between 2009 and 2015, were assessed. Terminations of pregnancies, stillbirths and neonatal deaths were included. Patients were excluded if the vertebral pattern could not be determined. Copy number profiles of 265 patients were determined using single nucleotide polymorphism array. Results 274/374 patients (73.3%) had an abnormal vertebral pattern. Cervical ribs were present in 188/374 (50.3%) and were significantly more common in stillbirths (69/128 (53.9%)) and terminations of pregnancies (101/188 (53.7%)), compared to live births (18/58, 31.0%, p = 0.006). None of the rare CNVs were recurrent or overlapped candidate genes for vertebral patterning. Conclusion The presence of an abnormal vertebral pattern, particularly in the cervical region, could be a sign of disruption at critical, highly interactive and conserved stages of embryogenesis. The vertebral pattern might provide valuable information regarding fetal and neonatal outcome. CNV analyses did not identify a mutual genetic cause for the occurrence of vertebral patterning abnormalities, indicating genetic heterogeneity.
Objectives. The aim of this study was to determine whether prospective parents, primarily referred for prenatal diagnosis to exclude Down syndrome, prefer to know the fetal sex as part of invasive testing. Methods. In this prospective study 400 pregnant women undergoing amniocentesis were invited to answer a questionnaire, including information about demographic factors, current pregnancy, and previous children. In two open-ended questions they were asked why they wanted to know the fetal sex after amniocentesis or ultrasound investigation. Scores were given for reasons that could have played a role in the wish whether or not to know the sex of their unborn child. Results. A total of 210 (52.5%) questionnaires were completed. Overall, 69.0% was interested to know the fetal sex as part of the diagnostic test result. The most important reasons were curiosity (77.8%), "just want to know" (68.0%), and "because it is possible" (66.8%). The overall knowledge of sex chromosomal disorders appeared low and did not seem to affect the parent's wish to know the fetal sex. Almost all women (96.6%) planned to have a 20-week ultrasound scan and 96.2% thought the scan to be reliable in detecting the fetal sex. A minority (28%) was willing to learn the fetal sex by ultrasound examination, whereas 65% preferred to learn the fetal sex only after the amniocentesis. Conclusion. Personal values affect the parental desire to know or not to know the fetal sex. This does not appear to be affected by invasive prenatal testing and/or genetic knowledge of sex chromosomal disorders.
Infants with congenital diaphragmatic hernia (CDH) often develop pulmonary hypertension but frequently fail to respond to vasodilator therapy, for instance because of an altered pulmonary vasoreactivity. Investigating such alterations in vivo is impossible. We hypothesised that these alterations are also present in fetoplacental vessels, since both vasculatures are exposed to the same circulating factors (e.g. endothelin-1) and respond similarly to certain stimuli (e.g. hypoxia). As proof-of-concept, we compared fetoplacental vasoreactivity between healthy and CDH-affected placentas.
Interstitial deletions of the chromosome 22q11.2 region are the most common microdeletions in humans. The TBX1 gene is considered to be the major candidate gene for the main features in 22q11.2 deletion syndrome, including congenital heart malformations, (para)thyroid hypoplasia, and craniofacial abnormalities. We report on eight patients with atypical deletions of chromosome 22q11.2. These deletions comprise the distal part of the common 22q11.2 deleted region but do not encompass the TBX1 gene. Ten similar patients with overlapping distal 22q11.2 deletions have been reported previously. The clinical features of these patients are described and compared to those found in the classic 22q11.2 deletion syndrome. We discuss the possible roles of a position effect or haploinsufficiency of distally located genes (e.g., CRKL) in the molecular pathogenesis of the 22q11.2 deletion syndrome.
To evaluate the diagnostic yield of exome sequencing (ES) in fetuses and neonates with prenatally detected congenital diaphragmatic hernia (CDH) and normal copy number variant (CNV) analysis.
<i>Objectives:</i> To evaluate histological changes in an animal model for bladder exstrophy and fetal repair of the bladder defect with a molecular-defined dual-layer collagen biomatrix to induce fetal bladder wall regeneration. <i>Methods:</i> In 12 fetal lambs the abdominal wall and bladder were opened by a midline incision at 79 days’ gestation. In 6 of these lambs an uncorrected bladder exstrophy was created by suturing the edges of the opened bladder to the abdominal wall (group 1). The other 6 lambs served as a repair group, where a dual-layer collagen biomatrix was sutured into the bladder wall and the abdominal wall was closed (group 2). A caesarean section was performed at 140 days’ gestation, followed by macroscopic and histological examination. <i>Results:</i> Group 1 showed inflammatory and maturational changes in the mucosa, submucosa and detrusor muscle of all the bladders. In group 2, bladder regeneration was observed, with urothelial coverage, ingrowth of fibroblasts and smooth muscle cells, deposition of collagen, neovascularization and nerve fibre formation. This tissue replaced the collagen biomatrix. No structural changes of the bladder were seen in group 2. <i>Conclusions:</i> The animal model, as in group 1, for bladder exstrophy shows remarkable histological resemblance with the naturally occurring anomaly in humans. This model can be used to develop new methods to salvage or regenerate bladder tissue in bladder exstrophy patients. Fetal bladder wall regeneration with a collagen biomatrix is feasible in this model, resulting in renewed formation of urothelium, blood vessels, nerve fibres, ingrowth of smooth muscle cells and salvage of the native bladder.
dick oEpkEs 2Spina bifida is one of the most prevalent major birth malformations with a worldwide incidence of approximately 1:2,000 live births 1 .A myelomeningocele (MMC) is the most frequent form of spina bifida, characterized by the extrusion of the spinal cord and/or nerves through a bony defect of the spine into a sac filled with cerebrospinal fluid (CSF).The severity of symptoms is correlated with the level of the defect.Interruption of the spinal cord at the site of the defect can cause lifelong paralysis of the legs, bowel and bladder dysfunction, sensibility disorders of the skin, sexual dysfunction and deformation of the lower extremities and back.Most children with spina bifida are not mentally retarded, but their intelligence quotient can be reduced 2,3 .Although spina bifida can be compatible with independent life, lifelong supportive care is often needed, and only about half of the patients are able to live independently as adults, even with adapted accommodations 3,4 .The majority of children with spina bifida have a Chiari II malformation, which is a combination of hindbrain herniation and hydrocephalus 4 , and is the leading cause of death in patients with spina bifida 5 .In 45% of the fetuses with spina bifida registered within the Dutch registration of Eurocat, the parents decided to terminate pregnancy after prenatal diagnosis.This is consistent with numbers from the USA; however, in some areas of the Netherlands, these figures are considerably higher 2 .With the introduction of the routine second trimester ultrasound scan, the number of prenatal diagnosis of spina bifida increased considerably.The classical prenatal ultrasound findings in spina bifida are typical U-shaped defect of the vertebral column in an open spina bifida, typical lemon shape of the fetal skull and banana shape of cerebellum.The ventriculomegaly occurs in the majority of cases, and club feet are also present in several cases 6 .The current standard of postnatal care is neurosurgical closure of the defect within 48 to 72 hours after birth.However, surgical intervention does not improve neurological function, but prevents further deterioration 7 .After birth, 80 to 90% of children with hydrocephalys will receive a ventriculo-peritoneal shunt placement to prevent additional damage to brain and brainstem 8 .Despite the successes of postnatal neurosurgical repair and medical treatment of spina bifida, mortality still remains approximately 10%, rising to 35% in those children with symptoms of brainstem dysfunction secondary to the Chiari II malformation.
