Copy number variation sequencing for diagnosis of cytomegalovirus infection based low-depth whole-genome sequencing technology in fetus:Three cases and literature review

Objective:To summarize the application value of copy number variant sequencing(CNV-seq)in the detection of fetal chromosome and cytomegalovirus load.Methods:The study analyzed the clinical basic data,relevant laboratory tests,treatment process,and outcomes of three patients with positive cytomegalovirus load detected by CNV-seq for fetal chromosomes and cytomegalovirus load,and literature review was done simutaneoubly.Results:In all three cases,the amniotic fluid cytomegalovirus load was less than 105 Copies/ml,and there were no significant neurological abnormalities observed during pregnancy or postpartum follow-up.There is no literature review on the application of CNV-seq technology in the detection of cytomegalovirus infection,only literature reports on genome analysis of CMV-DNA in confirmed patients were available.Conclusion:CNV-seq can be used to detect cytomegalovirus load,which may have a certain degree of predictive value for fetal outcome.CNV-seq can simultaneously detect fetal chromosomes and pathogenic microorganisms,which is of great significance for the prevention and control of birth defects.

正常胎儿脐静脉血流量Z评分模型的构建及其对小于胎龄儿围生期不良结局的预测价值

目的构建正常胎儿脐静脉血流量(Quv)Z评分模型,并探讨该模型对小于胎龄儿(SGA)围生期不良结局的预测价值。方法(1)纳入862例18~40周正常胎儿建立模型。以腹部超声测量的腹内段Quv作为因变量,孕周为自变量,采用回归分析获得Quv均数及标准差的最佳拟合方程后,根据公式[Z评分=(实际Quv测值-拟合Quv均值)/拟合Quv标准差]建立正常胎儿Quv Z评分模型。(2)另纳入53例正常胎儿(正常组)和109例SGA,并根据围生期有无不良结局将SGA分为不良结局组(n=50)、无不良结局组(n=59)。利用所建立的模型获得3组的胎儿Quv Z评分。通过绘制受试者工作特征曲线分析正常胎儿Quv Z评分预测SGA围生期不良结局的效能。结果(1)正常胎儿的Quv与孕周呈正相关(P<0.05),Quv的均数及标准差相对孕周的最佳拟合方程均为线性方程。根据公式获得正常胎儿Quv Z评分模型:Z评分=(Quv+346.069-20.754×孕周)(/-51.320+4.075×孕周)。正常组胎儿Quv的Z评分呈正态分布,且不随孕周而改变。(2)不良结局组、无不良结局组、正常组的胎儿Quv Z评分依次增加(P<0.05)。(3)正常胎儿Quv Z评分预测SGA围生期不良结局的曲线下面积为0.843,基于最佳截断值-2.06的预测敏感度、特异度、阳性预测值、阴性预测值分别为74.0%、86.4%、82.2%、76.4%。结论所建立的正常胎儿Quv Z评分模型可消除孕周的影响,具有较好的临床适用性。正常胎儿Quv Z评分是预测SGA围生期不良结局较敏感的指标。

Evidence supporting the relationship between maternal asthma and risk for autism spectrum disorders

During pregnancy,maternal immune activation(MIA),due to infection,chronic inflammatory disorders,or toxic exposures,can result in lasting health impacts on the developing fetus.MIA has been associated with an increased risk of neurodevelopmental disorders,such as autism spectrum disorder(ASD)in the offspring.ASD is characterized by increased repetitive and stereotyped behaviors and decreased sociability.As of 2020,1 in 36 children are diagnosed with ASD by the age of 8 years,with ASD rates continuing to increase in prevalence in USA(Tamayo et al.,2023).Post-mortem brain studies,biomarker and transcriptomic studies,and epidemiology studies have provided compelling evidence of immune dysregulation in the circulation and brain of individuals diagnosed with ASD.Currently,the etiology of ASD is largely unknown,however,genetic components and environmental factors can contribute to increased susceptibility.Maternal allergic asthma(MAA),a form of MIA,has been identified as a potential risk factor for developing neurodevelopmental disorders(Patel et al.,2020).Asthma is a chronic inflammatory condition driven by a T-helper type(TH)2 immune response.

Ultrasound blood flow characteristics changes in fetal umbilical artery thrombosis:A retrospective analysis

BACKGROUND Umbilical artery thrombosis(UAT)is extremely uncommon and leads to adverse perinatal outcomes.Hypercoagulation of blood in pregnant women is suspected to be an important risk for UAT.Ultrasound is an effective way to detect thrombosis.The mother can monitor her own fetal health using ultrasound,which enables her to take preventative action in case of emergency.AIM To investigate ultrasonic blood signal after UAT in the umbilical artery,and evaluate the relationship between hypercoagulability and UAT.METHODS We described a case of a newly formed UAT with markedly altered ultrasonic indices of umbilical artery blood flow,and retrospectively studied it with 18 UAT patients confirmed by histopathology from October 2019 and March 2023 in Xiamen Women and Children's Hospital.Patients’information was collected from medical archives,including maternal clinical data,neonatal outcomes,pathological findings and ultrasonic indices of umbilical artery blood flow,such as systolic-diastolic duration ratio(S/D),resistance index(RI),pulsatility index(PI)and peak systolic velocity(PSV).Ultrasound and coagulation indices were analyzed with matched samples t-test and Wilcoxon rank sum test using the statistical packages in R(version 4.2.1)including car(version 3.1-0)and stats(version 4.2.1),and visualized by ggplot2 package(version 3.3.6).RESULTS A patient with normal findings in second and third-trimester routine ultrasound scan developed UAT with severe changes in ultrasonic indices of umbilical artery blood flow(within 2.5th of reference ranges)in a short period of time.Statistical analysis of umbilical artery blood flow ultrasound indices for 19 patients with UAT showed that the decrease in S/D,RI,and PI and increase of PSV during the disease process was greater than that of non-UAT.All 18 patients delivered in our hospital showed characteristic manifestations of UAT on histological examination after delivery,most of which(16/18)showed umbilical cord abnormalities,with 15 umbilical cord torsion and 1 pseudoknot.Coagulation parameters were not significantly changed in UAT patients compared with normal pregnancy women.CONCLUSION Significant changes in ultrasound indicators after UAT were demonstrated.PSV can play important roles in the diagnosis of UAT.Hypercoagulability alone is not sufficient for the occurrence of UAT.

Cardiovascular Cast Model Fabrication and Casting Effectiveness Evaluation in Fetus with Severe Congenital Heart Disease or Normal Heart

To investigate the application and effectiveness of vascular corrosion technique in preparing fetal cardiovascular cast models, 10 normal fetal heart specimens with other congenital disease（control group） and 18 specimens with severe congenital heart disease（case group） from induced abortions were enrolled in this study from March 2013 to June 2015 in our hospital. Cast models were prepared by injecting casting material into vascular lumen to demonstrate real geometries of fetal cardiovascular system. Casting effectiveness was analyzed in terms of local anatomic structures and different anatomical levels（including overall level, atrioventricular and great vascular system, left-sided and right-sided heart）, as well as different trimesters of pregnancy. In our study, all specimens were successfully casted. Casting effectiveness analysis of local anatomic structures showed a mean score from 1.90±1.45 to 3.60±0.52, without significant differences between case and control groups in most local anatomic structures except left ventricle, which had a higher score in control group（P=0.027）. Inter-group comparison of casting effectiveness in different anatomical levels showed no significant differences between the two groups. Intra-group comparison also revealed undifferentiated casting effectiveness between atrioventricular and great vascular system, or left-sided and right-sided heart in corresponding group. Third-trimester group had a significantly higher perfusion score in great vascular system than second-trimester group（P=0.046）, while the other anatomical levels displayed no such difference. Vascular corrosion technique can be successfully used in fabrication of fetal cardiovascular cast model. It is also a reliable method to demonstrate three-dimensional anatomy of severe congenital heart disease and normal heart in fetus.

Blood Lead Dynamics of Lead-Exposed Pregnant Women and Its Effects on Fetus Development

The dynamics of blood lead (Pb-B) and blood zinc protoporphyrin (ZPP-B) of women in early pregnancy and parturient women with lead exposure and the effects on fetus development were investigated. Pb-B of lead-exposed women was high: 0.984 μmol/L (20.38 μg/dl) and ZPP was 84.52μg/dl. Cord blood Pb-B was 0.896 μmol/L(18.56μg/dl)and cord blood ZPP was 69.24μg/dl. In the control group, Pb-B was 0.261μmol/L(5.41μg/dl), ZPP-B, 37.59 μg/dl, cord blood, Pb-B 0.34 μmol/L (7.93 μg/dl), and cord ZPP-B 49.0μg/dl. There was a significant correlation between blood lead and blood ZPP, maternal Pb-B and cord Pb-B, maternal Pb-B and cord ZPP-B. The significance of the consistency of high level Pb-B and the effects on fetus development is discussed.

CLINICAL OBSERVATION ON CORRECTING MALPOSITION OF FETUS BY ELECTRO-ACUPUNCTURE

Forty-eight cases of malposition of fetus were treated by electro-acupuncture, using Zhiyin (UB 67) points. 39 cases were corrected with a rate of 81.3%, the average session of treatment being 1.41. Two control groups were set up: moxibustion and blank control group. Statistical analysis shows that efficacy of electro-acupuncture is markedly superior to that of the blank. Sessions of electro-acupuncture were less than that of moxibustion and the difference was statistically significant, though there is no significant difference of efficacy between the two groups.

Prognosis of 591 Fetuses with Ultrasonic Soft Markers during Mid-Term Pregnancy

The present study aimed to examine the value of ultrasonic soft markers in prenatal screening by analyzing the clinical outcome of fetuses with ultrasonic soft markers during the second trimester of pregnancy. A retrospective analysis was performed to evaluate the outcome of 591 fetuses with ultrasonic soft markers from January 2015 to August 2016 in Zhongnan Hospital of Wuhan University, China. It was found that 591 fetuses showed ultrasonic soft markers in 4927 cases with the occurrence rate being 12.0%. Among them, 564 fetuses（95.4%） were delivered and the remaining 27 cases（4.6%） were aborted. Five hundred and sixty-seven cases had single ultrasonic soft marker, including echogenic intracardiac focus（n=343）, mild renal pelvis dilatation（n=116）, short long bones（n=72）, single umbilical artery（n=31）, mild lateral ventriculomegaly（n=21）, choroid plexus cysts（n=19）, and echogenic bowel（n=13）, with the disappearing rates in pregnancy being 97.1%（333/343）, 77.6%（90/116）, 0%（0/72）, 0%（0/31）, 57.1%（12/21）, 89.5%（17/19） and 61.5%（8/13） respectively. The rate of pregnancy termination due to single ultrasonic soft marker was 3.4%（19/567）, and that was 33.3%（8/24） due to two ultrasonic soft markers with the difference being statistically significant（P〈0.05）. The reasons of pregnancy termination included malformations（polycystic kidney, cleft lip and palate, congenital heart diseases, pcromphalus, hypospadias, hydrocephalus）, chromosome abnormality, and stillbirth. It was concluded that single ultrasonic soft marker is usually transient manifestation in pregnancy. Without the other structural defects, single ultrasonic soft marker usually disappears spontaneously with favorable prognosis in a low-risk population. It is suggested that ultrasonic soft markers should be appropriately interpreted to avoid unnecessary invasive examination.

Study of concentration of amniotic fluid Alpha-fetal protein in thalassemia fetus

Objective:To test the hypothesis that concentration of amniotic fluid alpha-fetal protein(AFAFP) is increased in thalassemia fetus.Methods:A total of 135 cases of amniocentesis admitted from July 2013 to December 2014 were included in this study.Among them 98 cases of normal fetuses were assigned into control group and 37 cases of thalassemia fetus were included as thalassemia fetus group.Alpha-fetoprotein levels detected by enzyme linked immunosorbent assay and the alpha-fetoprotein concentration were compared between the two groups.There is no significant difference in gestrational age between the two groups.Results:1.AFP concentration in thalassemia fetus group was significantly higher than that of normal control group [(1541.65±734.78) μg/mL vs.(2728.84± 1539.97) μg/mL ],and amniotic fluid AFP concentration was related to fetal thalassemia.2.AFAFP concentration in pureα-thalassemia fetus was higher than that of β thalassemia fetus or mixed αand was not significant.Conclusions:Concentration of a β thalassemia fetus,but the difference mniotic fluid alpha-fetal protein is increased in thalassemia fetus.AFP concentration inα-thalassemia fetus was higher than that of β thalassemia or mixed αand lore β thalassemia fetus but difference was not significance.Further studies are needed to exp the possible correlation between Down syndrome and biochemical markers of Thalassemia.

Proteomic analysis of adipose tissue during the last weeks of gestation in pure and crossbred Large White or Meishan fetuses gestated by sows of either breed

Background: The degree of adipose tissue development at birth may influence neonatal survival and subsequent health outcomes. Despite their lower birth weights, piglets from Meishan sows(a fat breed with excellent maternal ability) have a higher survival rate than piglets from Large White sows(a lean breed). To identify the main pathways involved in subcutaneous adipose tissue maturation during the last month of gestation, we compared the proteome and the expression levels of some genes at d 90 and d 110 of gestation in purebred and crossbred Large White or Meishan fetuses gestated by sows of either breed.Results: A total of 52 proteins in fetal subcutaneous adipose tissue were identified as differential y expressed over the course of gestation. Many proteins involved in energy metabolism were more abundant, whereas some proteins participating in cytoskeleton organization were reduced in abundance on d 110 compared with d 90. Irrespective of age,24 proteins differed in abundance between fetal genotypes, and an interaction effect between fetal age and genotype was observed for 13 proteins. The abundance levels of proteins known to be responsive to nutrient levels such as aldolase and fatty acid binding proteins, as wel as the expression levels of FASN, a key lipogenic enzyme, and MLXIPL, a pivotal transcriptional mediator of glucose-related stimulation of lipogenic genes, were elevated in the adipose tissue of pure and crossbred fetuses from Meishan sows. These data suggested that the adipose tissue of these fetuses had superior metabolic functionality, whatever their paternal genes. Conversely, proteins participating in redox homeostasis and apoptotic cel clearance had a lower abundance in Meishan than in Large White fetuses. Time-course differences in adipose tissue protein abundance were revealed between fetal genotypes for a few secreted proteins participating in responses to organic substances, such as alpha-2-HS-glycoprotein, transferrin and albumin.Conclusions: These results underline the importance of not only fetal age but also maternal intrauterine environment in the regulation of several proteins in subcutaneous adipose tissue. These proteins may be used to estimate the maturity grade of piglet neonates.

TREATMENT OF 80 CASES OF MALPOSITION OF FETUS BY MOXIBUSTION COMBINED WITH CHINESE DRUGS

On 80 patients with abnormal fetal position, we observed the effects of moxibustioncombined with Chinese herbs on the position of fetus. The results suggest this therapy is practical andeffective.

Termination of a partial hydatidiform mole and coexisting fetus: A case report

BACKGROUND We describe the treatment strategy for a patient who was found to have a partial hydatidiform mole and coexisting fetus(PHMCF)during the second trimester.The patient was a 38-year-old Chinese woman who had become pregnant following in vitro fertilization and embryo transplantation.We wanted to determine the safest therapeutic strategy to terminate the PHMCF during the second trimester.CASE SUMMARY In this case,we present a patient who was found to have a PHMCF complicated with serious continuous vaginal bleeding and pre-eclampsia during the second trimester.After careful evaluation,the pregnancy was considered to be unsustainable and was terminated via caesarean section(CS).An infant with weak vital signs and a partially cystic placenta measuring 110 mm×95 mm×35 mm were delivered by CS.The patient was discharged after 4 d.The serum levels ofβ-human chorionic gonadotropin decreased to within a normal range 5 wk after the operation,and no evidence of persistent trophoblastic disease or lung metastases was noticed at the 6-mo follow-up.CONCLUSION CS termination of PHMCF during the second trimester may be a relatively safe therapeutic strategy.

Evaluation of right ventricular volume and systolic function in normal fetuses using intelligent spatiotemporal image correlation

BACKGROUND Heart defects are the most common congenital malformations in fetuses.Fetal cardiac structure and function abnormalities lead to changes in ventricular volume.As ventricular volume is an important index for evaluating fetal cardiovascular development,an effective and reliable method for measuring fetal ventricular volume and cardiac function is necessary for accurate ultrasonic diagnosis and effective clinical treatment.The new intelligent spatiotemporal image correlation(iSTIC)technology acquires high-resolution volumetric images.In this study,the iSTIC technique was used to measure right ventricular volume and to evaluate right ventricular systolic function to provide a more accurate and convenient evaluation of fetal heart function.AIM To investigate the value of iSTIC in evaluating right ventricular volume and systolic function in normal fetuses.METHODS Between October 2014 and September 2015,a total of 123 pregnant women received prenatal ultrasound examinations in our hospital.iSTIC technology was used to acquire the entire fetal cardiac volume with off-line analysis using QLAB software.Cardiac systolic and diastolic phases were defined by opening of the atrioventricular valve and the subsequent closure of the atrioventricular valve.The volumetric data of the two phases were measured by manual tracking and summation of multiple slices and recording of the right ventricular end-systolic volume and the right ventricular end-diastolic volume.The data were used to calculate the right stroke volume,the right cardiac output,and the right ejection fraction.The correlations of changes between the above-mentioned indices and gestational age were analyzed.The right ventricular volumes of 30 randomly selected cases were measured twice by the same sonographer,and the intraobserver agreement measurements were calculated.RESULTS Among the 123 normal fetuses,the mean right ventricular end-diastolic volume increased from 0.99±0.34 mL at 22 wk gestation to 3.69±0.36 mL at 35+6 wk gestation.The mean right ventricular end-systolic volume increased from 0.43±0.18 mL at 22 wk gestation to 1.36±0.22 mL at 35+6 wk gestation.The mean right stroke volume increased from 0.62±0.29 mL at 22 wk gestation to 2.33±0.18 mL at 35+6 wk gestation.The mean right cardiac output increased from 92.23±40.67 mL/min at 22 wk gestation to 335.83±32.75 mL/min at 35+6 wk gestation.Right ventricular end-diastolic volume,right ventricular end-systolic volume,right stroke volume,and right cardiac output all increased with gestational age and the correlations were linear(P<0.01).Right ejection fraction had no apparent correlation with gestational age(P>0.05).CONCLUSION Fetal right ventricular volume can be quantitatively measured using iSTIC technology with relative ease and high repeatability.iSTIC technology is expected to provide a new method for clinical evaluation of fetal cardiac function.

THE EFFECT OF HBsAg ANTIGENEMIA IN PREGNANT WOMEN ON FETUSES AND INFANTS

We followed up 1576 pennant women prospectively from less than 24 weeks of pregnancy,in order to investigate the effect of HBsAg antigenemia on fetuses and infants.The resultsshowed that there was no difference between HBsAg-positive and negative pregnant women in the incidence of fetal distress,Premature labor,asphyxia neonatorum, perinatal death,low birth weight,and congenital malformation,P= 0. 6035, 0.2177,0.8722,0.4673,0.9508,and 0.7892,respectively.

THE DISTRIBUTION OF ATRIONATRIURETIC POLYPEPTIDE （ANP）－LIKE SUBSTANCE IN THE HEART OF THE HUMAN FETUS AND RAT－AN IMMUNOHISTOC

human fetuses and 15 SD rats were used in this study. The distribution of theANPlike substance in the hearts of human fetuses and rats was studied. The results were as follows:①In human fetus ANP-like substance was found throughout in the atrial wall, but more intensely in the inner layer. It lacked in the ventricular wall. ②In young rat atrum, ANP-like substance wasdistributed over the whole wall, but richer in the cells beneath the endocardium and epicardium. In adult rat atrium, distribution of ANP-like substance was more intensely beneath the epicardium than that near the lumen. In the ventricle, ANP-like substance was found only in the young rat, especially on the left side of interventricular septum (IVS). So the distribution of ANP in rat hearts changes with age. ③In the sinus node (SAN) and atrioventricular node (AVN) of both human fetuses and rats showed a small amount of ANP-like substance, and more in peripheral part of the nodes, but thereactive intensity was weaker than that of the atrial wall. The presence of ANP in conduction system may have some functional significance to influence the pulse conduction.

MUTAGENIC EFFECT OF TNT ON BODY-CELL OF PREGNANT RATS AND FETUS

The micronucleus rate of PCE in bone marrow for 800mg/kg,50mg/kg TNT.positive and negative controlgroups were 4.8‰,2.4‰,4.4‰ and 1.3‰,respectively,The difference between higher dose group and negativecontrol group had statistical significance(p【0.01).Themicronucleus rates of PCE in fetus liver were,

Aka Canturk Oral Autopsy Method for the Dental Identification of Fetus and Infant Cases

Forensic research requires the application of reliable identification methods for unidentified individuals, among which the dental analysis has prime importance. The most significant source of dental evidence is oral autopsy applications, which consist of an examination and evidence collection from the oral cavity of a deceased individual. Oral autopsies show variations depending on the age of the person due to rigor mortis. The oral autopsy of a child may require an easier operation than adults, and thus, the procedures are usually simpler for fetus or infant cases. The aim of this study is to propose the theoretical and experimental aspects of an oral autopsy protocol for a special age group of fetus or infant cases, which is a method for extracting tooth germs in their developmental stages for identification purposes and entitled by the authors’ names as the “Aka-Canturk Oral Autopsy Method”.

Relationship between the development of sphenoid bone in human embryo and fetus and adult morphology

The developing sphenoid bone is considered to be a median cartilage mass(basilar sphenoid bone)with three cartilaginous processes(orbital wing or orbital pterygoid process,temporal wing and nasal pterygoid process).The relationship between this initial morphology and adult morphology is difficult to determine because of extensive membranous ossification along the cartilaginous elements.We examined the sagittal sections of 25 embryos and fetuses aged 6-34 weeks,and compared them with the horizontal and frontal sections of the other 25 late fetuses(217-340 mm).At 7-8 weeks,the optic nerve was sandwiched between bars of the orbitosphenoid.The superior rectus originates from a bar different from the other three recti.

Prenatal Diagnosis of Fetus in Fetu with a Well Formed Skull: A Rare Case Report

Fetus in fetu is an extremely rare condition embryologically arising in monozygotic diamniotic twins with an incidence of 1:500,000 births. To the best of our knowledge, number of reported cases should not be more than 100 with majority of cases presenting in post natal life with only 5 cases detected prenatally. We are presenting a case diagnosed at 24 weeks of gestation on ultrasound with presence of well formed skull, facial skeleton and bony orbit.

The Expression of Surfactant Proteins A and D in the Intestines and Pancreas of Murine Fetuses

Purpose: Surfactant proteins exist in the digestive tract and may play an important role in the host defense. However, the expression of surfactant proteins in the premature digestive system remains unclear. The aim of this study was to investigate the expression of surfactant proteins in the intes-tines and pancreas of murine fetuses. Methods: Immunostaining for SP-A and SP-D was assessed in the small intestine and pancreas of ICR murine fetuses on days 15, 16, 17 and 18 of gestation (normal duration of pregnancy: 19 - 21 days). RT-PCR was performed to detect the expression of spa and spd mRNA in the small intestine and pancreas on day 16, 17 and 18 of gestation. Results: Immunoreactivity for SP-A and SP-D in the acinar cells of pancreas and intestinal mucosal surface were positive on day 16 of gestation onward. RT-PCR revealed that the expression of spa and spd mRNA was significant in the pancreas but weak in the small intestine. Conclusions: Our data revealed that surfactant proteins are present in the fetal intestines and pancreas and that a significant expression of spa and spd mRNA is detected in the fetal pancreas. Pancreas may be a possible organ involved in the synthesis and secretion of surfactant proteins into the intestinal lumen.