检测STR多态位点作为非性别依赖胎儿标记的探讨

本研究探讨检测孕妇血浆中游离胎儿DNA短串联重复序列（short tandem repeat,STR）多态位点作为内对照进行遗传病产前基因诊断的可行性。用QIAamp DNA Kit抽提孕妇血浆DNA,应用AmpFlSTR profiler试剂盒扩增9个（D3S1358,VWA,FGA,D5S818,D13S317,D7S820,D8S1179,D21S11,D18S51）具有高度多态性的STR位点,以多重荧光PCR方法对不同孕期的36份孕妇血浆标本中胎儿DNA进行STR等位基因扩增,同时扩增孕妇及丈夫外周血来源DNA的STR位点。PCR产物经ABI Prism 377序列分析仪电泳后,用基因扫描软件进行分析,以在孕妇血浆中胎儿DNA检出父源性STR等位基因来确认胎儿DNA存在。结果表明：其中孕早期4份（4/6）、孕中期19份（19/20）、孕晚期9份（9/10）样本中检出胎儿父源性等位基因,即胎儿DNA。4份样本未检到胎儿DNA。结论：应用多重荧光PCR方法对孕妇血浆中胎儿DNA进行STR多态位点的复合扩增,可获得男性及女性胎儿性别DNA信息,作为非性别依赖胎儿标记,从而用于无创伤性产前诊断。     

Development of the Fetal Spinal Cord

Objective. The purpose of this study was to perform high‐resolution sonographic examinations to determine the normal anatomic relationship of the conus medullaris (CM) of the spinal cord with the vertebral column during different stages of gestation. Methods. In this prospective study, fetal sonographic evaluations were performed between 13 and 40 weeks' gestation. Transvaginal probes (7.5–8 MHz) or abdominal probes (5–8 MHz) were used, depending on gestational age and position of the fetus. The CM was located in coronal longitudinal sections. The positions of the kidneys and lumbosacral junction and the origin of the ribs determined the location of the vertebrae. The locations of the CM were divided into 5 groups according to their positions relative to the vertebrae. Results. A total of 110 fetuses between 13 and 40 weeks' gestation were studied. Between 13 and 18 weeks' gestation, the CM was situated at the level of the L4 vertebra, or more caudally, in 100% of the fetuses. At term, all fetuses showed the CM above L2. A distinct ascent of the CM was detected between 13 and 40 weeks' gestation. The results were statistically significant (P <.0001). Conclusions. A distinguishable ascent of the CM in relation to the vertebral column during fetal life was detected.     

产前超声检测胎儿心脏功能的研究进展

超声仪器对胎儿心脏功能的检测有重要作用.产前超声在诊断胎儿心脏病方面发挥了不可替代的作用,随着计算机和超声仪器的发展进步,超声心功能测定方法也得到进一步完善,一些测量指标的变化规律可以反映胎儿心脏的收缩、舒张及全心功能.文章针对胎儿心动图评价胎儿心功能的各种检测方法及测量指标作一综述.     

Fetal echocardiographic diagnosis of vascular rings.

OBJECTIVE: The purpose of this series is to describe the prenatal echocardiographic findings of vascular rings. METHODS: The 3-vessel and trachea view consists of the axial view of the upper mediastinum. The normal left aortic arch appears as a V-shaped confluence of the ductus arteriosus and aortic arch, with the trachea situated posterior and to the right. No vessel should encircle the trachea. The diagnoses of vascular rings were made prenatally and were confirmed in all patients postnatally. RESULTS: Six fetuses had diagnoses of vascular rings. The mean gestational age at diagnosis was 23.3 weeks (range, 18-31 weeks). The indications for fetal echocardiography were family history of congenital heart disease, echogenic focus in the left ventricle, and abnormal 4-chamber view. There were 2 fetuses with a double aortic arch; 3 fetuses with a right aortic arch, an aberrant left subclavian artery, and a left ductus arteriosus; and 1 with a right circumflex aortic arch with a left ductus arteriosus and an aberrant left subclavian artery. Two fetuses had associated structural cardiac defects, 1 with an unbalanced atrioventricular septal defect and trisomy 21 and the other with a double-outlet right ventricle, pulmonary atresia, and multiple other congenital anomalies. CONCLUSIONS: Vascular rings can be accurately diagnosed prenatally with recognition of a vascular structure that courses around the trachea and absence of the usual V-shaped relationship of the aortic and ductal arches. The color Doppler findings and the presence of a ductus arteriosus aid in identifying various components of the vascular ring.     

Fetal Polydactyly

Records of 24 pregnancies with fetal polydactyly were reviewed for the type of polydactyly, family history, associated sonographic findings, genetic testing, and postnatal/postmortem examination findings. The importance of fetal polydactyly can be mainly elucidated by the family history and absent or associated anomalies on a specialized malformation scan. Fetal karyotyping diagnoses frequent chromosomal anomalies in about half of cases with additional malformations, and array comparative genomic hybridization may be a future means of detecting cryptic chromosomal aberrations. Syndromic disorders of monogenic origin demand a careful interdisciplinary clinical assessment for establishing a clinical diagnosis and prognosis for the outcome of the child.     

Fetal breasts in normal and down syndrome fetuses

To assess the validity of fetal breast size measurement as a sonographic marker in fetuses with Down syndrome. Methods: Fetal breasts were studied in 26 fetuses with trisomy 21 and 78 fetuses with normal chromosomes. Breasts were identified and measured in a cross-sectional plane of the fetal chest at the level of the four-chamber view of the heart. Normal fetuses had a mean breast size of 3.8 mm ± 1.1 mm. Fetuses with Down syndrome had a mean breast size of 1.9 mm ± 0.7 mm (p ⩽ 0.0001). Diminished breast size measured by ultrasound in the second trimester may be helpful in identifying fetuses with Down syndrome. © 1996 John Wiley & Sons, Inc.     

Prenatal Sonographic Abnormal Appearances of the Fetal Hyaloid Artery: From Normal Variants to Pathology

This is a case series on the abnormal sonographic appearance and outcome of the fetal hyaloid artery (HA) detected during between 1987 and 2015 at one medical center. Fifteen cases were detected during fetal anatomy scans, usually performed at 14 to 16 weeks’ gestation. Three other cases were diagnosed following referral for a second opinion. In nine fetuses, the HA regressed normally throughout pregnancy. Of them, eight neonates had normal outcomes and one had cataract at the same eye. All nine other cases ended with adverse outcomes. Failure of the HA to regress in the third trimester appears to be an indicator of congenital blindness.     

Fetal Lateral Ventricular Width: What Should Be Its Upper Limit?

OBJECTIVE: The upper limit of the fetal atrial width in normal fetuses is debated. This was a prospective cohort evaluation of the lateral ventricular width with special regard to the upper limit of its size. METHODS: Measurements of fetal atrial ventricular size were obtained by abdominal ultrasonography in 427 male and female fetuses between 20 and 40 weeks' gestation of normal singleton pregnancies. In addition, reanalysis of previous data (8 studies) and the current data was performed to produce a pooled mean and SD. RESULTS: The mean ventricular width +/- SD was 6.2 +/- 1.2 mm. The ventricular width did not show significant modification throughout gestation. Reanalysis of the current and previous studies (8216 cases) yielded a pooled mean of 6.4 +/- 1.2. CONCLUSIONS: According to the current and previous studies, the upper cutoff of fetal ventricular atrium width should be 10 mm. This cutoff represents a range of approximately 3 SDs above the pooled mean, corresponding to a 99.74% confidence interval.     

Fetal facial expression in response to intravaginal music emission

This study compared fetal response to musical stimuli applied intravaginally (intravaginal music [IVM]) with application via emitters placed on the mother’s abdomen (abdominal music [ABM]). Responses were quantified by recording facial movements identified on 3D/4D ultrasound. One hundred and six normal pregnancies between 14 and 39 weeks of gestation were randomized to 3D/4D ultrasound with: (a) ABM with standard headphones (flute monody at 98.6 dB); (b) IVM with a specially designed device emitting the same monody at 53.7 dB; or (c) intravaginal vibration (IVV; 125 Hz) at 68 dB with the same device. Facial movements were quantified at baseline, during stimulation, and for 5 minutes after stimulation was discontinued. In fetuses at a gestational age of >16 weeks, IVM-elicited mouthing (MT) and tongue expulsion (TE) in 86.7% and 46.6% of fetuses, respectively, with significant differences when compared with ABM and IVV (p = 0.002 and p = 0.004, respectively). There were no changes from baseline in ABM and IVV. TE occurred ≥5 times in 5 minutes in 13.3% with IVM. IVM was related with higher occurrence of MT (odds ratio = 10.980; 95% confidence interval = 3.105–47.546) and TE (odds ratio = 10.943; 95% confidence interval = 2.568–77.037). The frequency of TE with IVM increased significantly with gestational age (p = 0.024). Fetuses at 16–39 weeks of gestation respond to intravaginally emitted music with repetitive MT and TE movements not observed with ABM or IVV. Our findings suggest that neural pathways participating in the auditory–motor system are developed as early as gestational week 16. These findings might contribute to diagnostic methods for prenatal hearing screening, and research into fetal neurological stimulation.     

Comparison of Single Versus Multiple Echogenic Foci in the Fetal Heart Regarding Risk of Aneuploidy

Objective. The purpose of this study was to investigate whether multiple echogenic cardiac foci (ECF) are associated with an increased risk of fetal trisomy 21 in our patient population. Methods. During a span of 38 months, all women found to have an ECF on obstetric sonography were identified as study patients and grouped into single‐ and multiple‐ECF groups. Age‐ and race‐matched patients were identified as a control group. Fetal anatomic sonographic examinations were assessed for other markers of aneuploidy and major abnormalities. The baseline risk for trisomy 21 was assessed by maternal serum screening or age alone if no serum screening had been performed. Trisomy 21 was assessed by amniocentesis or clinically at birth. Both univariate and multivariate analyses were used to assess for associations with trisomy 21. Results. Six of 71 patients (8.5%) with multiple ECF and 1 of 171 patients (0.6%) with a single ECF had trisomy 21. One of 242 control patients (0.4%) had trisomy 21. Logistic regression found multiple ECF (P < .008), the presence of a major finding or multiple minor findings (P = .0012), and a baseline risk for trisomy 21 of greater than 1 in 100 (P = .003) as independent associations with trisomy 21. Conclusions. Our results suggest that finding multiple ECF is a stronger predictor of trisomy 21 than what is described for a single ECF.     

孕妇血浆中胎源性RASSF1A基因在无损性产前诊断中的应用研究

本研究旨在探讨运用非性别依赖的甲基化表观遗传学标记RASSF1A基因作为孕妇血浆中循环游离胎儿DNA存在的通用性标志的可行性.采用2种方法提取孕妇血浆游离DNA,选用其中效果较好的用磁珠法提取20例标本的游离DNA;采用RT-PCR方法扩增SRY基因以及甲基化酶处理后的RASSF1A基因,且对酶处理后RASSF1A基因的扩增体系进行条件优化.结果表明,在20例标本中11例检测有SRY基因,且与胎儿出生后性别相符;选用优化后的PCR体系扩增甲基化酶处理后的RASSF1A基因,在18例标本中检测有RASSF1A基因,在2例标本中未检测到此基因.结论：甲基化RASSF1A基因与SRY基因相比,不受胎儿性别限制,可作为广泛性胎儿特异性表观遗传学标记物,用于临床无损性产前诊断.     

Prenatal Diagnosis of the Fetal Retroesophageal Left Brachiocephalic Vein: Case Series and Review of the Literature

A retroesophageal left brachiocephalic vein (LBCV) is a highly rare anomaly. We retrospectively analyzed 7 cases of a retroesophageal LBCV that were prenatally diagnosed from a database of fetal echocardiogram of 31,356 cases. The 3-vessel view and the long-axis view are the main views for confirming a fetal retroesophageal LBCV. An isolated retroesophageal LBCV is rare, and it is typically associated with congenital heart defects, especially conotruncal defects and a right aortic arch. An isolated fetal retroesophageal LBCV has a good prognosis and does not need surgical treatment.     

Noninvasive continuous blood pressure measurement from the finger: Optimal measurement conditions and factors affecting reliability

We recorded finger arterial blood pressure (FINAP) in 50 male patients during various types of surgical operations. Three different types of cuffs were used on four fingers of each patient. Measurements were made by the arterial volume-clamp method of Penaz. The FINAP measurements were compared with pressure data obtained ipsilaterally from a radial artery catheter-transducer system (intraarterial pressure [IAP]) to find optimal recording conditions and to document factors affecting FINAP readings. The thumb, with a specially designed cuff, gave the most accurate results. The mean FINAP- IAP difference for the thumb was –4.8 mm Hg for systolic pressure, 1.49 mm Hg for diastolic pressure, and 0.29 mm Hg for mean pressure. The differences were statistically significant for systolic and diastolic pressure but not for mean pressure. The regression slope for thumb systolic FINAP/IAP was 0.979, that for thumb diastolic FINAP/IAP was 0.963, and that for mean thumb FINAP/IAP was 0.996, whereas the intercepts were 7.499 for systolic pressure, 0.802 for diastolic pressure, and 0.083 for mean pressure. The correlation coefficients were 0.945 (systolic), 0.884 (diastolic), and 0.949 (mean). The correlation coefficients with the other fingers ranged from 0.502 to 0.922 for systolic pressure, 0.757 to 0.932 for diastolic pressure, and 0.767 to 0.892 for mean pressure. The slopes for the various finger-cuff combinations ranged from 0.537 to 0.996, and the intercepts ranged from 0.083 to 32.387 from mean pressure. In 3 patients (6%) the FINAP measurement was not possible because of insufficient peripheral circulation. In 9 other patients (18%) the FINAP measurements were not accurate during some periods of time.In 5 of those 9 patients the difficulties were related to arterial cannulation and began immediately after cannulation. In 1 of those 5 patients the FINAP subsequently decreased dramatically after the onset of phenylephrine infusion because of peripheral vasoconstriction and diminished blood flow. In the 4 other patients the FINAP readings were accurate at the beginning of anesthesia but later decreased out of proportion to changes in IAP. These periods were associated with one-lung ventilation. The FINAP accurately reflects systemic arterial pressure. Measurements from the thumb fitted with a specially designed cuff approximate IAP best. Factors affecting peripheral circulation must be taken into consideration when this device is used in the monitoring of FINAP.     

Fetal sex assignment by sonographic evaluation of the pelvic organs in the second and third trimesters of pregnancy.

OBJECTIVE: The purpose of this study was to determine the feasibility and reliability of fetal sex assignment by prenatal sonography of the pelvic organs in the second and third trimesters. METHODS: A prospective study, on an axial pelvic image with the umbilical arteries in cross section at the midpoint of the bladder, measured the distance between the posterior wall of the bladder and the anterior wall of the rectum. The bladder interface was scored as concave, flat, or convex. Endometrium visualization was recorded. A video loop of the pelvis was obtained. Each case was read by a second reader aware of only the gestational age. RESULTS: The study population included 205 fetuses. The primary reader was 98.8% accurate in identifying true female fetuses and 100% accurate in identifying true male fetuses. The intraclass correlation coefficient for axial measurement was 0.99. Video loop analysis achieved 96% inter-reader concordance. In the second trimester, measurements in 100% of male fetuses were less than 3.3 mm, and those in 94% of female fetuses were greater than 3.3 mm. In the third trimester, measurements in 96% of male fetuses were less than 4.7 mm, and those in 100% of female fetuses were greater than 4.7 mm. Ninety-eight percent of all fetuses with concave interfaces were female. The endometrium was visualized in 74%. The additional time per examination was less than 5 minutes in 87.7%. CONCLUSIONS: Internal pelvic fetal sex assignment is a reliable additional method for fetal sex determination. A numerical discriminatory level can be used to distinguish between male and female internal genitalia. Larger numbers will be required to further refine these values.     

First‐Trimester Assessment of the Fetal Palate

We describe a new technique that can facilitate the first‐trimester examination of the fetal palate using the Volume NT algorithm (Samsung Medison, Seoul, Korea), a program that automatically detects the exact midsagittal plane of the head and is primarily designed for semiautomatic measurement of the nuchal translucency thickness. Three‐dimensional (3D) data sets from the fetal face were captured with Volume NT and subsequently reformatted with the Oblique View software to obtain orthogonal views of the primary and secondary palate in coronal and axial planes, respectively. By testing this method in selected 3D data sets obtained retrospectively (n = 12) and prospectively (n = 28), we were able to extract clinically acceptable views of the fetal palate in all cases. This preliminary report shows that with this new 3D automation development, early evaluation of the fetal palate is feasible and reproducible and could be easily incorporated into the first‐trimester sonographic protocol once its ability to detect abnormal cases is demonstrated.