Analysis of the prenatal ultrasound diagnostic value and prognostic factors of fetal mediastinal cysts.

Background: A prenatal fetal mediastinal cyst is a benign disease. However, if a cyst enlargement grows, it may compress the adjacent organs and affect the fetal cardiopulmonary function. This study aimed to compare and analyze the prenatal ultrasound characteristics of different mediastinal cysts, and to evaluate the pregnancy outcome of the fetus and the factors affecting the prognostic of the fetus. To compare and analyze the prenatal ultrasound characteristics of different types of mediastinal cysts, and to evaluate the fetal pregnancy outcome and the influencing factors of fetal prognosis. Methods: A retrospective analysis of patients with prenatal diagnoses of mediastinal cysts was conducted to evaluate the ultrasound characteristics and to monitor the pregnancy outcomes to identify prognostic influences and provide a reliable basis for patient prognosis. Results: In total, 30 patients were diagnosed with mediastinal cysts [including bronchogenic cysts (n=12), esophageal cysts (n=9), pericardial cysts (n=5), and thymic cysts (n=4)] on prenatal ultrasonography. The diagnostic accuracy rate was 93.33%; two cases of esophageal cysts were misdiagnosed as bronchial cysts. In total, 4 (44.44%) of 9 esophageal cysts and 4 thymic cysts were located in the anterior mediastinum, 10 (83.33%) of 12 bronchogenic cysts and 5 pericardial cysts were located in the middle mediastinum, and 2 (16.67%) of 12 bronchogenic cysts and 5 (55.56%) of 9 esophageal cysts were located in the posterior mediastinum. There were significant differences in the distribution of the cyst location, morphology, and cyst wall thickness (P<0.05). After delivery, 17 patients had clinical symptoms. There was a significant difference in the clinical symptoms between patients with a maximum diameter of postpartum cysts <5 and ≥5 cm (P<0.05), and children with a low gestational age and birth weight were more likely to have clinical symptoms. Conclusions: The prenatal ultrasound features of fetal mediastinal cysts were similar. However, the ultrasound characteristics related to the cyst location, morphology, and cyst wall thickness were helpful in providing an accurate diagnosis. In addition, the postpartum cyst size, location, adjacent relationship with the surrounding tissues, volume, gestational age, and weight were related to patient prognosis.

Advancements in medical research using fetal sheep: Implications for human health and treatment methods.

Sheep are typically considered as industrial animals that provide wool and meals. However, they play a significant role in medical research in addition to their conventional use. Notably, sheep fetuses are resistant to surgical invasions and can endure numerous manipulations, such as needle puncture and cell transplantation, and surgical operations requiring exposure beyond the uterus. Based on these distinguishing characteristics, we established a chimeric sheep model capable of producing human/monkey pluripotent cell-derived blood cells via the fetal liver. Furthermore, sheep have become crucial as human fetal models, acting as platforms for developing and improving techniques for intrauterine surgery to address congenital disorders and clarifying the complex pharmacokinetic interactions between mothers and their fetuses. This study emphasizes the significant contributions of fetal sheep to advancing human disease understanding and treatment strategies, highlighting their unique characteristics that are not present in other animals.

Outcome of fetal congenital pulmonary malformations: a systematic review and meta-analysis.

OBJECTIVES: To report the outcome of fetuses with a prenatal diagnosis of congenital lung malformation (CLM) diagnosed on ultrasound by performing a comprehensive assessment of these outcomes through a systematic review and meta-analysis. CONTENT: CLMs are a heterogeneous group of anomalies that involve the lung parenchyma and its bronchovascular structures. Their presentation and evolution are variable, from entirely asymptomatic lesions with sonographic regression in utero to hydropic fetuses requiring fetal therapy, intrauterine death or neonatal morbidity. A systematic review was conducted in Medline, Embase and Cochrane databases including studies on fetuses with CLM diagnosed prenatally in order to report the in-utero natural history of these lesions. Thirty-nine studies (2,638 fetuses) were included in the final review. SUMMARY: Regression/reduction in size of the lung lesion during pregnancy was reported in 31 % of cases, while its increase in 8.5 % of cases. Intra-uterine death complicated 1.5 % of pregnancies with fetal CLM, while neonatal and perinatal death were 2.2 and 3 %, respectively. Neonatal morbidity occurred in 20.6 % of newborns with CLM; 46 % had surgery, mainly elective. In fetuses with CLM and hydrops, fetal/perinatal loss occurred in 42 %. Assessment of the role of fetal therapy in improving the outcomes of pregnancies complicated by CLM was hampered by the small number of included cases and heterogeneity of type of interventions. OUTLOOK: Fetuses with CLM prenatally diagnosed have a generally favorable outcome. Conversely, there is a low quality of evidence on the actual role of fetal therapy in improving the outcome of fetuses presenting with these anomalies.

Biochemical and molecular characterization of Campylobacter fetus isolates from bulls subjected to bovine genital campylobacteriosis diagnosis in Spain.

BACKGROUND: Bovine genital campylobacteriosis (BGC) is caused by Campylobacter fetus subsp. venerealis (Cfv) including its biovar intermedius (Cfvi). This sexually transmitted disease induces early reproductive failure causing considerable economic losses in the cattle industry. Using a collection of well-characterized isolates (n = 13), C. fetus field isolates (n = 64) and saprophytic isolates resembling Campylobacter (n = 75) obtained from smegma samples of breeding bulls, this study evaluated the concordance of the most used phenotypic (H2S production in cysteine medium and 1% glycine tolerance) and molecular (PCR) methods for the diagnosis of BGC and assessed possible cross-reactions in the molecular diagnostic methods. RESULTS: Characterization at the subspecies level (fetus vs. venerealis) of C. fetus isolated from bull preputial samples using phenotypic and molecular (PCR targeting nahE and ISCfe1) methods showed moderate concordance (κ = 0.462; CI: 0.256-0.669). No cross-reactions were observed with other saprophytic microaerophilic species or with other Campylobacter species that can be present in preputial samples. Whole genome sequencing (WGS) of discrepant isolates showed 100% agreement with PCR identification. For the differentiation of Cfv biovars, comparison of the H2S test (at 72 h and 5 days of incubation) and a PCR targeting the L-cysteine transporter genes showed higher concordance when H2S production was assessed after 5 days (72 h; κ = 0.553, 0.329-0.778 CI vs. 5 days; κ = 0.881, 0.631-1 CI), evidencing the efficacy of a longer incubation time. CONCLUSIONS: This study confirmed the limitations of biochemical tests to correctly identify C. fetus subspecies and biovars. However, in the case of biovars, when extended incubation times for the H2S test (5 days) were used, phenotypic identification results were significantly improved, although PCR-based methods produced more accurate results. Perfect agreement of WGS with the PCR results and absence of cross-reactions with non-C. fetus saprophytic bacteria from the smegma demonstrated the usefulness of these methods. Nevertheless, the identification of new C. fetus subspecies-specific genes would help to improve BGC diagnosis.

ASSESSMENT OF HUMAN FETUSES UNDERGOING ACUTE PAIN: VALIDATION OF THE FETAL-7 SCALE.

Improvements in fetal ultrasound have allowed for the diagnosis and treatment of fetal diseases in the uterus, often though surgery. However, little attention has been drawn to the assessment of fetal pain. To address this gap, a fetal pain scoring system, known as the Fetal-7 scale, was developed. The present study is a full validation of the Fetal-7 scale. The validation involved two steps: i. four fetuses with indication of surgery were evaluated in three conditions perioperatively: acute pain, rest, and under loud sound stimulation. Facial expressions were assessed by 30 raters using screenshots from 4D high-definition ultrasound films; ii., assessment of sensitivity and specificity of the Fetal-7 scale in 54 healthy fetuses and two fetuses undergoing acute pain after preoperative anesthetic intramuscular injection. There was high internal consistency with Cronbach's alpha (α) of 0.99. Intra-rater reliability of the Fetal-7 scale (test-retest) calculated by intraclass correlation coefficient (ICC) was 0.95, and inter-rater reliability was 0.99. The scale accurately differentiated between healthy fetuses at rest and those experiencing acute pain (sensitivity of 100% and specificity of 94.4%). The Fetal-7 scale is a valid tool for assessing acute pain-related behavior in third trimester fetuses and may be of value in guiding analgesic procedures efficacy in these patients. Further research is warranted to explore the presence of post-operative pain in fetuses and its effects afterbirth. PERSPECTIVE: Recordings with three-dimension ultrasound of human fetuses undergoing pre-operative anesthetic injections revealed complex facial expressions during acute pain, similar to those collected in newborns. This study presented the validation process and cut-off value of the Fetal-7 scale, paving the way for the study of pain before birth in humans.

Outcomes of severely injured pregnant trauma patients: a multicenter analysis.

Nearly 10% of pregnant women suffer traumatic injury. Clinical outcomes for pregnant trauma patients (PTPs) with severe injuries have not been well studied. We sought to describe outcomes for PTPs presenting with severe injuries, hypothesizing that PTPs with severe injuries will have higher rates of complications and mortality compared to less injured PTPs. A post-hoc analysis of a multi-institutional retrospective study at 12 Level-I/II trauma centers was performed. Patients were stratified into severely injured (injury severity score [ISS] > 15) and not severely injured (ISS < 15) and compared with bivariate analyses. From 950 patients, 32 (3.4%) had severe injuries. Compared to non-severely injured PTPs, severely injured PTPs were of similar maternal age but had younger gestational age (21 vs 26 weeks, p = 0.009). Penetrating trauma was more common in the severely injured cohort (15.6% vs 1.4%, p < 0.001). The severely injured cohort more often underwent an operation (68.8% vs 3.8%, p < 0.001), including a hysterectomy (6.3% vs 0.3%, p < 0.001). The severely injured group had higher rates of complications (34.4% vs 0.9%, p < 0.001), mortality (15.6% vs 0.1%, p < 0.001), a higher rate of fetal delivery (37.5% vs. 6.0%, p < 0.001) and resuscitative hysterotomy (9.4% vs. 0%, p < 0.001). Only approximately 3% of PTPs were severely injured. However, severely injured PTPs had a nearly 40% rate of fetal delivery as well as increased complications and mortality. This included a resuscitative hysterotomy rate of nearly 10%. Significant vigilance must remain when caring for this population.

Contribution of the serotonergic system to developmental brain abnormalities in autism spectrum disorder.

This review highlights a key role of the serotonergic system in brain development and in distortions of normal brain development in early stages of fetal life resulting in cascades of abnormalities, including defects of neurogenesis, neuronal migration, neuronal growth, differentiation, and arborization, as well as defective neuronal circuit formation in the cortex, subcortical structures, brainstem, and cerebellum of autistic subjects. In autism, defects in regulation of neuronal growth are the most frequent and ubiquitous developmental changes associated with impaired neuron differentiation, smaller size, distorted shape, loss of spatial orientation, and distortion of cortex organization. Common developmental defects of the brain in autism include multiregional focal dysplastic changes contributing to local neuronal circuit distortion, epileptogenic activity, and epilepsy. There is a discrepancy between more than 500 reports demonstrating the contribution of the serotonergic system to autism's behavioral anomalies, highlighted by lack of studies of autistic subjects' brainstem raphe nuclei, the center of brain serotonergic innervation, and of the contribution of the serotonergic system to the diagnostic features of autism spectrum disorder (ASD). Discovery of severe fetal brainstem auditory system neuronal deficits and other anomalies leading to a spectrum of hearing deficits contributing to a cascade of behavioral alterations, including deficits of social and verbal communication in individuals with autism, is another argument to intensify postmortem studies of the type and topography of, and the severity of developmental defects in raphe nuclei and their contribution to abnormal brain development and to the broad spectrum of functional deficits and comorbid conditions in ASD.

Intestinal alterations and mild glucose homeostasis impairments in the offspring born to overweight rats.

The gut plays a crucial role in metabolism by regulating the passage of nutrients, water and microbial-derived substances to the portal circulation. Additionally, it produces incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1, encoded by gcg gene) in response to nutrient uptake. We aimed to investigate whether offspring from overweight rats develop anomalies in the barrier function and incretin transcription. We observed pro-inflammatory related changes along with a reduction in Claudin-3 levels resulting in increased gut-permeability in fetuses and offspring from overweight rats. Importantly, we found decreased gip mRNA levels in both fetuses and offspring from overweight rats. Differently, gcg mRNA levels were upregulated in fetuses, downregulated in female offspring and unchanged in male offspring from overweight rats. When cultured with high glucose, intestinal explants showed an increase in gip and gcg mRNA levels in control offspring. In contrast, offspring from overweight rats did not exhibit any response in gip mRNA levels. Additionally, while females showed no response, male offspring from overweight rats did exhibit an upregulation in gcg mRNA levels. Furthermore, female and male offspring from overweight rats showed sex-dependent anomalies when orally challenged with a glucose overload, returning to baseline glucose levels after 120 min. These results open new research questions about the role of the adverse maternal metabolic condition in the programming of impairments in glucose homeostasis, enteroendocrine function and gut barrier function in the offspring from overweight mothers and highlight the importance of a perinatal maternal healthy metabolism.

Congenital bronchogenic cyst: From prenatal diagnosis to postnatal management.

OBJECTIVE: Bronchogenic cysts are rare congenital abnormalities, and usually asymptomatic until adulthood. We present a fetus prenatally diagnosed with a bronchogenic cyst, experiencing compression symptoms immediately after birth and underwent thoracoscopic surgery at 14 days old. CASE REPORT: A 33-year-old primigravida had a suspicion of fetal tracheal cyst. Prenatal ultrasound scan revealed a cyst near the trachea at 23 weeks' gestation. Fetal MRI defined a cystic lesion in the upper mediastinum, displacing surrounding vessels. A 3,940 g girl was delivered vaginally at 38 weeks' gestation. Shortly after birth, she developed respiratory distress, and imaging revealed a mediastinal cyst compressing the trachea and esophagus. The cyst was successfully removed through video-assisted thoracoscopic surgery at 14 days old, and pathology confirmed it as a bronchogenic cyst. Follow-up images demonstrated well-aerated lungs. At present, this 1-year-old girl develops normally without respiratory symptoms. CONCLUSION: Early detection in utero, accurate diagnosis, and timely management are crucial for bronchogenic cysts in neonates.

Complete hydatidiform mole with concurrent fetus: Two cases of live, term birth coupled with spontaneous resolution of molar tissue.

Pregnancies with a complete hydatidiform mole and co-existing fetus (CMCF) are rare, but increasingly common due to the rising prevalence of assisted reproductive technology. They are frequently associated with adverse obstetric outcomes, providing women with the challenge of pregnancy termination or continuing the pregnancy at the risk of maternal-fetal morbidity and fetal mortality. This report demonstrates two cases of CMCF pregnancy with excellent maternal-fetal outcomes, including spontaneous resolution of the molar tissue antenatally. It is helpful in counselling women who are diagnosed with this rare and frequently morbid condition in considering how to proceed with their pregnancy.

Regression of Cardiac Rhabdomyomas Producing a Severe Aortic Stenosis: Case Report and Discussion of the Literature.

We describe a case of a voluminous rhabdomyoma (R) detected by fetal echocardiography at 32 weeks' gestation (w.g.) obstructing the left ventricular inflow and aortic outflow tract, with a moderate aortic gradient at birth, not needing immediate surgery. At follow-up, the mass progressively regressed, leaving the aortic valve partly damaged, with a gradient that increased to a maximum of 100 mmHg at 9 years. The girl was then operated on successfully by a plasty of the aortic valve. The literature regarding R is discussed.

Estrogen promotes fetal skeletal muscle mitochondrial distribution and ATP synthase activity important for insulin sensitivity in offspring.

PURPOSE: We previously showed that offspring delivered to baboons in which levels of estradiol (E2) were suppressed during the second half of gestation exhibit insulin resistance. Mitochondria are essential for the production of ATP as the main source of energy for intracellular metabolic pathways, and skeletal muscle of type 2 diabetics exhibit mitochondrial abnormalities. Mitochondria express estrogen receptor ß and E2 enhances mitochondrial function in adults. Therefore, the current study ascertained whether exposure of the fetus to E2 is essential for mitochondrial development. METHODS: Levels of ATP synthase and citrate synthase and the morphology of mitochondria were determined in fetal skeletal muscle obtained near term from baboons untreated or treated daily with the aromatase inhibitor letrozole or letrozole plus E2. RESULTS: Specific activity and amount of ATP synthase were 2-fold lower (P < 0.05) in mitochondria from skeletal muscle of E2 suppressed letrozole-treated fetuses and restored to normal by treatment with letrozole plus E2. Immunocytochemistry showed that in contrast to the punctate formation of mitochondria in myocytes of untreated and letrozole plus E2 treated animals, mitochondria appeared to be diffuse in myocytes of estrogen-suppressed fetuses. However, citrate synthase activity and levels of proteins that control mitochondrial fission/fusion were similar in estrogen replete and suppressed animals. CONCLUSION: We suggest that estrogen is essential for fetal skeletal muscle mitochondrial development and thus glucose homeostasis in adulthood.

Maternal inflammation regulates fetal emergency myelopoiesis.

Neonates are highly susceptible to inflammation and infection. Here, we investigate how late fetal liver (FL) mouse hematopoietic stem and progenitor cells (HSPCs) respond to inflammation, testing the hypothesis that deficits in the engagement of emergency myelopoiesis (EM) pathways limit neutrophil output and contribute to perinatal neutropenia. We show that fetal HSPCs have limited production of myeloid cells at steady state and fail to activate a classical adult-like EM transcriptional program. Moreover, we find that fetal HSPCs can respond to EM-inducing inflammatory stimuli in vitro but are restricted by maternal anti-inflammatory factors, primarily interleukin-10 (IL-10), from activating EM pathways in utero. Accordingly, we demonstrate that the loss of maternal IL-10 restores EM activation in fetal HSPCs but at the cost of fetal demise. These results reveal the evolutionary trade-off inherent in maternal anti-inflammatory responses that maintain pregnancy but render the fetus unresponsive to EM activation signals and susceptible to infection.

Twin pregnancy with one normal fetus and one complete hydatidiform mole: Outcome of expectant management.

Twin pregnancy with one fetus and one complete mole falls amongst extremely rare obstetric situations. The spectrum of complications associated with it is wide. Once diagnosed, the choice between continuation and termination of pregnancy depends upon couple's preference and readiness to accept possible complications. Key to success lies in clinical vigilance and tailoring management according to emerging needs during pregnancy and follow up. We present a case of twin pregnancy with complete hydatidiform mole and coexisting normal fetus diagnosed at 25 weeks. Pregnancy was complicated by anemia, gestational diabetes mellitus, recurrent vaginal bleeding, intrauterine growth restriction and iatrogenic preterm delivery. She was followed for development of GTN, none occurred.

Prenatal ultrasound diagnosis and prognosis of fetus with isolated filar cyst: a retrospective analysis.

Objective: This study aimed to investigate the prenatal ultrasonographic diagnosis and prognosis of fetuses with isolated filar cysts (FCs). Methods: The ultrasonographic features, reasons for missed diagnosis, and prognosis of eight isolated FCs diagnosed using ultrasound were analyzed retrospectively through follow-up. Results: Eight isolated FCs showed round or fusiform cystic anechoic areas at the end of the conus medullaris. Among them, six cases were prenatally diagnosed and the other two cases were diagnosed after birth. Of the six cases diagnosed prenatally, four (66.7%) disappeared during pregnancy, and the shortest time to disappearance was 1 month after the first diagnosis. All patients were followed up without any clinical symptoms or functional abnormalities. Conclusion: Isolated FCs may exhibit physiological variations that disappear spontaneously during pregnancy and usually have no clinical symptoms. They are usually benign and have a good prognosis. Ultrasonography is helpful for the diagnosis and follow-up of FCs.

Retrospective analysis of the prognostic factors of fetal corpus callosum dysplasia.

BACKGROUND: To analyze the genetic characteristics and long-term outcomes of fetuses with dysplasia of the corpus callosum (DCC) or partial agenesis of the corpus callosum (PACC). METHODS: A total of 42 fetuses with DCC (n = 36) or PACC (n = 6) were retrospectively analyzed from January 2016 to December 2022 at the Peking University First Hospital. The cohort was categorized into isolated (15/42, 36%) and nonisolated groups (27/42, 64%), and differences in the genetic abnormalities and long-term outcomes between the two groups were analyzed. DCC was subdivided into short CC, thin CC, and thick CC. The outcomes of the three different types of DCC were analyzed and discussed. RESULTS: (1) Thirty-nine of the 42 cases underwent CMA (chromosomal microarray analysis) and CMA + WES (whole exome sequencing), with 13/15 cases in isolated group and 26/27 cases in nonisolated group. Only pathogenic or likely pathogenic (P/LP) variants were considered, identifying P/LP variants in 2/13 cases in isolated group and 12/26 cases in nonisolated group. There was no significant difference between the two groups (χ² = 3.566, P = 0.05897). (2) In the isolated group, 8 cases were terminated, and 7 cases were delivered. Postnatal follow-up detected 1 case of gross motor development delay one year after birth; no obvious abnormalities were found in the other six cases. In the nonisolated group, 21 cases were terminated, and 6 cases were delivered. Postnatal follow-up detected 4 cases of children with different degrees of language, motor and intelligence abnormalities; 1 case died 10 days after birth. No obvious abnormalities were observed in one case. Six cases (86%, 6/7) in the isolated group showed normal development, compared with 1 case (17%, 1/6) in the nonisolated group, with a significant difference (χ² = 6.198, P = 0.01279). (3) In DCC, the delivery rates of short CCs (18 cases), thin CCs (13 cases), and thick CCs (5 cases) were 17% (3/18), 54% (7/13), and 20% (1/5), respectively, with good outcomes observed in 0% (0/3), 71% (5/7), and 0% (0/1), respectively. P/LP variants were found in 6/17 cases of short CC, 3/12 cases of thin CC, and 2/5 cases of thick CC. CONCLUSIONS: Fetuses with DCC or PACC combined with other structural abnormalities had a poor long-term prognosis compared with the isolated group. Patients with thin CCs had a higher probability of a good prognosis than those with short or thick CCs.

The signature of cancer methylation markers in maternal plasma: Factors influencing the development and application of cancer liquid biopsy assay.

BACKGROUND: DNA methylation is highly correlated with cancer and embryo development, and plasma-based methylation markers have been widely used for cancer early detection. However, whether the commonly used cancer methylation markers cause "false positives" in the plasma of pregnant women has not been comprehensively evaluated. METHODS: We conducted a case-control study from February 2021 to March 2023, which included 138 pregnant women and 44 control women. Plasma cell-free DNA (cfDNA) was isolated and bisulfite-converted, and then the methylation levels of eight methylated markers related to gastrointestinal cancer (SEPT9, SDC2, C9orf50, KCNQ5, CLIP4, TFPI2, ELMO1 and ZNF582) and three markers related to lung cancer (SHOX2, RASSF1A and PTGER4) were analyzed. RESULTS: When comparing the plasma of pregnant women to that of control women, SEPT9, CLIP4, ZNF582, SHOX2, RASSF1A and PTGER showed significantly higher levels of methylation (p < 0.05). These positive signals originate from the placenta/fetus rather than the mother. We found no discernible difference in DNA methylation levels between fetal cfDNA fractions of < 10 % and ≥ 10 % in pregnant women (p > 0.05), while CLIP4 and PTGER4 showed high methylation levels in the assisted fertilization group compared to the natural fertilization group (p < 0.05). CONCLUSION: Our study shows that cancer and fetus/placenta exhibit similar DNA methylation patterns, and some gastrointestinal cancer and lung cancer-related methylation markers also show positives in maternal plasma. This is an important consideration in the design and application of plasma-based cancer liquid biopsy assays.

Prenatal diagnosis of well-developed fetus in fetu with spontaneous movement in a resource-limited setting: A case report.

Fetus in fetu (FIF) is a rare congenital anomaly characterized by the presence of a parasitic monozygotic twin encased within the body of its host twin. Because FIF is asymptomatic throughout pregnancy, it is mainly diagnosed in children with an abdominal mass after birth. In the case reported here, at 38-39 weeks of gestation, a 33-year-old woman (gravida 4, para 3) was referred for routine obstetric ultrasonography. Fluid accumulation was identified along with calcification resembling two well-developed legs and trunk with undifferentiated organs inside. Slight spontaneous movement of the legs was observed. The fetus was delivered based on the presumed diagnosis of FIF. Postnatal sonography and computed tomography (CT) supported the diagnosis. The neonate underwent surgical excision of the tumor and was discharged on the eighth postoperative day. Ultrasound can be used to provide accurate prenatal diagnosis of FIF. Early diagnosis is important to improve outcomes.