Late first-trimester ultrasound findings can alter management after high-risk NIPT result.

OBJECTIVE: To evaluate the impact of detailed late first-trimester ultrasound (LFTU) on the positive predictive value (PPV) of a high-risk non-invasive prenatal test (NIPT) result for various chromosomal abnormalities. METHODS: This was a retrospective study of all cases undergoing invasive prenatal testing from three tertiary providers of obstetric ultrasound over 4 years, each using NIPT as a first-line screening test. Data were collected from pre-NIPT ultrasound, NIPT, LFTU, placental serology and later ultrasound examinations. Prenatal testing for chromosomal abnormalities was performed by microarray, initially using array comparative genomic hybridization and then single nucleotide polymorphism (SNP) array for the last 2 years. Uniparental disomy testing was performed by SNP array during all 4 years. The majority of NIPT tests were analyzed using the Illumina platform, initially confined to the assessment of the common autosomal trisomies, sex chromosome aneuploidies and rare autosomal trisomies (RAT), then extending to genome-wide analysis for the last 2 years. RESULTS: Amniocentesis or chorionic villus sampling (CVS) was performed on 2657 patients, 1352 (51%) of whom had undergone prior NIPT, with 612 (45%) of these returning a high-risk result and meeting the inclusion criteria for the study. LFTU findings significantly affected the PPV of the NIPT result for trisomies 13 (T13), 18 (T18) and 21 (T21), monosomy X (MX) and RAT but not for the other sex chromosomal abnormalities or segmental imbalances (> 7 Mb). Abnormal LFTU increased the PPV close to 100% for T13, T18, T21, MX and RAT. The magnitude of the change in PPV was highest for the most severe chromosomal abnormalities. When LFTU was normal, the incidence of confined placental mosaicism (CPM) was highest in those with a high-risk NIPT result for T13, followed by T18 and T21. After normal LFTU, the PPV for T21, T18, T13 and MX decreased to 68%, 57%, 5% and 25%, respectively. CONCLUSIONS: LFTU after a high-risk NIPT result can alter the PPV for many chromosomal abnormalities, assisting counseling regarding invasive prenatal testing and pregnancy management. The high PPVs of NIPT for T21 and T18 are not sufficiently modified by normal LFTU findings to alter management. These at-risk patients should be offered CVS for earlier diagnosis, particularly given the low rate of CPM associated with these aneuploidies. Patients with a high-risk NIPT result for T13 and normal LFTU findings often wait for amniocentesis or avoid invasive testing altogether given the low PPV and higher rate of CPM in this context. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Central blood pressure in children and adolescents: non-invasive development and testing of novel transfer functions.

Central blood pressure can be estimated from peripheral pulses in adults using generalised transfer functions (TF). We sought to create and test age-specific non-invasively developed TFs in children, with comparison to a pre-existing adult TF. We studied healthy children from two sites at two time points, 8 and 14 years of age, split by site into development and validation groups. Radial and carotid pressure waveforms were obtained by applanation tonometry. Central systolic pressure was derived from carotid waveforms calibrated to brachial mean and diastolic pressures. Age-specific TFs created in the development groups (n=50) were tested in the validation groups aged 8 (n=137) and 14 years (n=85). At 8 years of age, the age-specific TF estimated 82, 99 and 100% of central systolic pressure values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF overestimated central systolic pressure by 2.2 (s.d. 3.7) mm Hg, compared to being underestimated by 5.6 (s.d. 3.9) mm Hg with the adult TF. At 14 years of age, the age-specific TF estimated 60, 87 and 95% of values within 5, 10 and 15 mm Hg of their measured values, respectively. This TF underestimated central systolic pressure by 0.5 (s.d. 6.7) mm Hg, while the adult TF underestimated it by 6.8 (s.d. 6.0) mm Hg. In conclusion, age-specific TFs more accurately predict central systolic pressure measured at the carotid artery in children than an existing adult TF.

m-Diabete in Senegal. "Be He@lthy Be Mobile", a program initiated by WHO and the ITU.

The health-care systems of Africa must adapt to the exponential progression of nontransmissible diseases, diabetes in particular. How can we accelerate population awareness of the risk factors? How can we provide the minimal education necessary to all people with diabetes to limit its complications? The "Be He@lthy Be Mobile" initiative of WHO and the ITU (International Telecommunications Union) and its "m-Diabete" app in Senegal explore the conditions for establishing a large-scale patient-education program using texting and its potential health impact.

Insights on the host associations and geographic distribution of Hymenolepis folkertsi (Cestoda: Hymenolepididae) among rodents across temperate latitudes of North America.

Synoptic data and an understanding of helminth parasite diversity among diverse rodent assemblages across temperate latitudes of North America remain remarkably incomplete. Renewed attention to comprehensive survey and inventory to establish the structure of biodiverse faunas is essential in providing indicators and proxies for identifying the outcomes of accelerating change linked to climate warming and anthropogenic forcing. Subsequent to the description of Hymenolepis folkertsi in the oldfield mouse, Peromyscus polionotus, additional specimens of hymenolepidids were collected or discovered in archived museum repositories from multiple species of deer mice (Peromyscus maniculatus, Peromyscus leucopus), the golden mouse (Ochrotomys nuttalli), chipmunks (Tamias striatus, Tamias amoenus), the 13-lined ground squirrel (Ictidomys tridecemlineatus), and tree squirrels (Sciurus carolinensis, Sciurus niger) from disjunct localities in the USA spanning southern Georgia, Virginia, Pennsylvania, Connecticut, the Upper Peninsula of Michigan, Wisconsin, and central Idaho. Specimens were largely consistent morphologically with the original description of H. folkertsi. Initial DNA sequence data, from a portion of the mitochondrial NADH dehydrogenase subunit 1, demonstrated intraspecific variation among three apparently geographically isolated populations attributed to H. folkertsi (uncorrected genetic distances of 2.7 % (Idaho and Michigan), 2.4 % (Virginia + Pennsylvania and Michigan), and 1.89 % (VA + PA and ID). Geography rather than host association explains the distribution and occurrence of H. folkertsi, and host colonization among deer mice, chipmunks, and other sciurids within regional sites is indicated. Genetic divergence revealed across localities for H. folkertsi suggests historically isolated populations, consistent with extended evolutionary and biogeographic trajectories among hymenolepidids and species of Peromyscus and Tamias in North America. Field inventory, that revealed these parasite populations, substantially alters our understanding of the distribution of diversity and provides insights about the nature of the complex relationships that serve to determine cestode faunas in rodents.

Sonographic spectrum of first-trimester fetal cephalocele: review of 35 cases.

OBJECTIVE: To describe the sonographic features of fetal cephalocele diagnosed at the time of first-trimester ultrasound screening for aneuploidy. METHODS: This was a retrospective review of cases of cephalocele diagnosed in the first trimester at four fetal medicine referral centers. Once diagnosis was suspected, a transvaginal ultrasound examination was offered to improve depiction of the cranial defect and enhance examination of fetal anatomy, with special attention given to the location, size and content of defects. To assure consistency in diagnosis, representative pictures and videoclip sequences of the cranial defect were obtained and reviewed by at least two authors. Cases were classified and compared with the assessment made at diagnosis. RESULTS: Of the 35 affected fetuses identified, 33 were of a singleton pregnancy and two were of twin pregnancies in which the other fetus was unaffected. The lesion was classified as a cranial meningocele in 13 (37%) cases and as an encephalocele in 22 (63%). The bone defect was occipital in 27 (77%), frontal in three (9%), parietal in three (9%) and non-classifiable in two (6%). Twelve (34%) were considered as small in size, 11 (31%) as medium and 12 (34%) as large. There were no reported cases of aneuploidy; however, four (11%) cases were associated with Meckel-Gruber syndrome, two (6%) with a disruptive syndrome and one (3%) with skeletal dysplasia. Eight (23%) pregnancies were lost to follow-up. Parents opted for termination of pregnancy in 21 of the 27 remaining cases and, of the six ongoing pregnancies, four patients miscarried or the fetus died in utero during the second trimester, one liveborn infant died shortly after delivery and one underwent neonatal surgery for an isolated cranial meningocele and is currently doing well. CONCLUSIONS: First-trimester sonographic diagnosis of cephalocele is accomplished easily with a detailed examination of the skull contour at the time of routine assessment of the axial and sagittal views of the head for measurement of the biparietal diameter and nuchal translucency, respectively. However, the sonographic features are highly variable. A significant proportion of cases are associated with genetic or disruptive syndromes. Prenatal diagnosis of cephalocele in the first trimester was associated with a high rate of termination of pregnancy and early intrauterine fetal demise. Only one fetus in this series survived and is neurologically intact; therefore, the prognosis of this condition remains poor.

Rightward convexity of the great vessel arising from the anterior ventricle: a novel fetal marker for transposition of the great arteries.

OBJECTIVES: Traditionally transposition of the great arteries (TGA) is suggested by bifurcation of the great vessel arising from the posterior ventricle and the parallel course of the great vessels as they leave the heart. These findings may be difficult to demonstrate, requiring additional fetal echocardiographic features to indicate TGA. In this study, we investigated a new marker of TGA, namely rightward convexity of the great vessel arising from the anterior ventricle. METHODS: We reviewed fetal studies from 2006 to 2010 in which an antenatal diagnosis of TGA was confirmed postnatally. We specifically viewed images obtained by scanning the great vessel arising from the anterior ventricle cranially to the superior mediastinum at the level of the three vessels and trachea view and compared them with similar views in normal hearts. RESULTS: In 21 cases of confirmed TGA, the great vessel arising from the anterior ventricle (aorta) coursing cranially demonstrated an abnormal convexity to the right. This was in contrast to convexity to the left or lack of convexity of the great vessel (pulmonary artery) arising from the anterior ventricle in fetuses with a normal heart. In two fetuses rightward vessel convexity from the anterior ventricle was the clue on the initial scan suggesting TGA, which was subsequently confirmed. In addition, only two vessels, the superior vena cava and aorta, were demonstrated in fetuses with TGA, the pulmonary artery and ductus arteriosus lying below (caudal to) the transverse arch. CONCLUSIONS: Noting the rightward convexity of the great vessel arising from the anterior ventricle may aid in the prenatal diagnosis of TGA. Furthermore, the relative simplicity of this sign may make it valuable in fetal screening for this cardiac defect.

The aqueduct of Sylvius: a sonographic landmark for neural tube defects in the first trimester.

OBJECTIVES: To describe a new first-trimester sonographic landmark, posterior displacement of the midbrain and aqueduct of Sylvius, which may be useful in early screening for neural tube defects. METHODS: This was a prospective study of 457 normal fetuses at 11 + 0 to 13 + 6 weeks' gestation. We measured the distance from the posterior border of the aqueduct of Sylvius to the anterior border of the occiput (AOS-to-occiput distance) in the axial plane and created a reference range. In the nine fetuses with abnormal midbrain position identified in the first trimester and with neural tube defect subsequently confirmed, we analyzed ultrasound images to determine the position of the aqueduct of Sylvius. RESULTS: The lower limit of normal AOS-to-occiput distance (mean minus 2 SD) ranged from 1.7 mm at a crown-rump length (CRL) of 45 mm to 3.7 mm at a CRL of 84 mm. In the nine cases with abnormal position of the midbrain and confirmed neural tube defect, juxtaposition of the midbrain to the occiput was the clue to diagnosis of the spinal abnormality. In all nine cases, the AOS-to-occiput distance was below the established normal range. CONCLUSIONS: Examination of the midbrain in an axial plane may prove a reliable marker for the first-trimester diagnosis of neural tube defects. In contrast to recently reported subtle changes in the mid-sagittal view of the posterior cranial fossa, axial imaging of the midbrain reveals striking displacement of this structure, with virtual juxtaposition to the occiput, in fetuses with confirmed open spina bifida. This anatomical distortion of the midbrain can be quantified by measurement of the AOS-to-occiput distance.

Association between lumbar epidural injection and development of acute paraparesis in patients with spinal dural arteriovenous fistulas.

SUMMARY: We report 3 patients with previously undiagnosed spinal dural arteriovenous fistulas (SDAVFs), who developed acute paraparesis following lumbar epidural steroid injection. MR imaging demonstrated spinal cord T2 hyperintensity, edema and/or enhancement of the conus, and intradural enlarged vascular flow voids. Spinal angiography confirmed SDAVFs arising from pedicles remote from the sites of the epidural steroid injection. Fistulas were eliminated with either endovascular or combination endovascular and open surgical approaches, with subsequent partial resolution of paraparesis.

The roles of magnetic resonance and endoscopic retrograde cholangiopancreatography (MRCP and ERCP) in the diagnosis of patients with suspected sclerosing cholangitis: a cost-effectiveness analysis.

BACKGROUND AND STUDY AIMS: The optimal approach for diagnosing sclerosing cholangitis remains unclear in the face of competing imaging technologies. We aimed to determine the most cost-effective strategy. PATIENTS AND METHODS: A decision model compared three approaches in the work-up of patients with suspected sclerosing cholangitis; all included an initial test, with, if unsuccessful, performance of a second cholangiographic method. They were magnetic resonance cholangiopancreatography (MRCP) and endoscopic retrograde cholangiopancreatography (ERCP), termed "MRCP_ERCP", ERCP and MRCP ("ERCP_MRCP"), or ERCP and a repeat ERCP ("ERCP_ERCP"). The implications of true and false positive and negative results with regard to costs and procedural complications were considered, including that of a liver biopsy, if indicated as a result of a negative work-up in the face of persistent clinical suspicion. The unit of effectiveness adopted was that of a correct diagnosis. Probability assumptions were derived from published literature, while cost estimates were derived from time-motion microanalyses or a national database, and expressed in Canadian dollars at 2004 values. Sensitivity analyses, including clinically relevant threshold analyses, were carried out. RESULTS: The average cost-effectiveness ratios were $414 for MRCP_ERCP, $1101 for ERCP_MRCP and $1123 for ERCP_ERCP, per correct diagnosis. The ERCP_MRCP strategy was dominated (more expensive and less effective) by MRCP_ERCP, while ERCP_ERCP was more effective and more costly than MRCP_ERCP, at $289,292 per additional correct diagnosis. Sensitivity and threshold analyses confirmed the robustness of these findings. CONCLUSIONS: Based on the model assumptions, a strategy of initial MRCP, followed, if negative, by ERCP is currently the most cost-effective approach to the work-up of patients with suspected sclerosing cholangitis.

Anatomical flow phantoms of the nonplanar carotid bifurcation, part I: computer-aided design and fabrication.

Doppler ultrasound is widely used in the diagnosis and monitoring of arterial disease. Current clinical measurement systems make use of continuous and pulsed ultrasound to measure blood flow velocity; however, the uncertainty associated with these measurements is great, which has serious implications for the screening of patients for treatment. Because local blood flow dynamics depend to a great extent on the geometry of the affected vessels, there is a need to develop anatomically accurate arterial flow phantoms with which to assess the accuracy of Doppler blood flow measurements made in diseased vessels. In this paper, we describe the computer-aided design and manufacturing (CAD-CAM) techniques that we used to fabricate anatomical flow phantoms based on images acquired by time-of-flight magnetic resonance imaging (TOF-MRI). Three-dimensional CAD models of the carotid bifurcation were generated from data acquired from sequential MRI slice scans, from which solid master patterns were made by means of stereolithography. Thereafter, an investment casting procedure was used to fabricate identical flow phantoms for use in parallel experiments involving both laser and Doppler ultrasound measurement techniques.

Anatomical flow phantoms of the nonplanar carotid bifurcation, part II: experimental validation with Doppler ultrasound.

A nonplanar wall-less anatomical flow phantom of a healthy human carotid artery is described, the construction of which is based on a lost-core technique described in the companion paper (Part I) by . The core was made by rapid prototyping of an idealized three-dimensional computer model of the carotid artery. Flow phantoms were built using these idealized non planar carotid artery bifurcations. Physiologically realistic flow waveforms were produced with resistance index values of 0.75, 0.72 and 0.63 in the common, external and internal carotid artery branches, respectively. Distension of the common carotid using M-mode imaging was found to be at 10% of diameter. Although differences in vessel diameter between the phantom and that of the original computer model were statistically significant (p < 0.05), there was no difference (p > 0.05) in measurements made on the lost-cores and those obtained by B-mode ultrasound on the resulting flow phantoms. In conclusion, it was possible to reliably reproduce geometrically similar anatomical flow phantoms that are capable of producing realistic physiological flow patterns and distensions.

Design and characterisation of a wall motion phantom.

Arterial wall motion is an essential feature of a healthy cardiovascular system and it is known that wall motion is affected by age and disease. In recent years, methods have been developed for measurement of wall motion with the intention of providing diagnostically useful information. An issue with all of these techniques is the accuracy and variability of both wall motion and derived quantities such as elasticity, which requires the development of suitable test tools. In this paper, a vessel wall phantom is described for use in ultrasound studies of wall motion. The vessel was made from polyvinyl alcohol (PVA) subjected to a freeze-thaw process to form a cryogel (PVA-C). The elastic modulus, acoustic velocity and attenuation coefficient varied from 57 kPa, 1543 m s(-1) and 0.18 dB cm(-1) MHz(-1) for one freeze-thaw cycle to 330 kPa, 1583 m s(-1) and 0.42 dB cm(-1) MHz(-1) for 10 freeze-thaw cycles. Wall motion was effected by the use of pulsatile flow produced from a gear pump. The use of a downstream flow resistor removed gross distortions in the wall motion waveform, possibly by removal of reflected pressure waves. However, a low amplitude 20 Hz oscillation remained, which is unphysiologic and thought to be caused by the vibration of the distended PVA-C vessel.

The effect of image size on screen-positive rates for nuchal translucency screening.

It has been shown previously that the absolute measurement of nuchal translucency (NT) thickness, one of the most effective screening tests for fetal Down syndrome, significantly decreases with increasing image size. We undertook a prospective study to assess whether this effect materially alters the NT-derived risk estimation for fetal Down syndrome. In 350 women, NT was measured at both 100 and 200% image sizes. The median NT measurement at 200% was 8% smaller than at 100%. The screen-positive rates at 100 and 200% image sizes were 5.1% (18/350) and 2.3% (8/350), respectively (P= 0.048). Altering the image magnification settings is likely to decrease the sensitivity of NT-derived Down syndrome risk estimation. Further study is required to test the effect of our finding on the sensitivity of NT screening and to assess whether adjustments in gain settings mitigate the effect.

Determining zygosity in early pregnancy by ultrasound.

OBJECTIVES: First-trimester ultrasound can reliably determine chorionicity but not zygosity. We set out to investigate whether it may be possible to determine zygosity using ultrasound by noting the number of corpora lutea (CLs), structures which reflect ovulation. In the presence of a dichorionic twin pregnancy, the identification of one CL would suggest that twins are monozygotic whereas two CLs implies dizygosity. METHODS: This was a retrospective analysis of predominantly spontaneous twin pregnancies presenting for an early pregnancy ultrasound at 5-8-completed weeks of gestation. Placentation was correlated with presumed zygosity as predicted by the number of CLs present. RESULTS: Of 33 twin gestations, chorionicity was compatible in all cases with the predicted zygosity. In 15 cases one CL was seen and these were designated monozygotic. Of these, four were of monochorionic placentation and 11 dichorionic. The remaining 18 cases had two CLs and were presumed dizygotic; all were of dichorionic placentation. CONCLUSION: We propose a novel technique of zygosity determination during very early pregnancy which may have implications both clinically and in genetic research involving twins. However, this study requires further verification by comparing ultrasound results with DNA evidence taken after birth.

Ultrasound prediction of risk of spontaneous miscarriage in live embryos from assisted conceptions.

OBJECTIVE: An accurate method to predict subsequent miscarriage in live embryos has not yet been established. This pilot study aimed to determine the most discriminatory ultrasound-based model for predicting spontaneous miscarriage after embryonic life was first detected in assisted conceptions. A method for estimating individual risk of miscarriage was developed. METHODS: This was a prospective cross-sectional survey of 322 live singleton embryos in women from an assisted reproductive technology program. Mean sac diameter (MSD), crown-rump length (CRL), embryonic heart rate (EHR), maternal age and gestational age at the first transvaginal scan detecting embryonic life (between 42 and 62 days) were observed. These variables were included in a multivariate model for predicting spontaneous miscarriage occurring prior to 20 weeks. MSD, CRL and MSD minus CRL were assessed in univariate logistic regression analyses. The global diagnostic accuracy of each model was compared directly using receiver-operating characteristics (ROC) curves. RESULTS: The multivariate model demonstrated the best ROC curve for predicting miscarriage (ROC area 0.87; 95% CI, 0.80-0.95). The separate univariate analyses had less diagnostic accuracy. In particular, MSD - CRL had a significantly smaller ROC area (0.65) than did the multivariate model (P < 0.01). CONCLUSIONS: The most discriminatory test for predicting spontaneous miscarriage in live embryos was a multivariate model, which allows estimation of individual risk levels.

First-trimester diagnosis of micrognathia as a presentation of Pierre Robin syndrome.

We describe a case of first-trimester diagnosis of micrognathia. A transvaginal ultrasound scan performed at 13 weeks' gestation revealed an abnormal fetal facial profile consisting of a small mandible and a receding chin. A subsequent amniocentesis at 15 weeks' gestation revealed a normal karyotype. A morphology scan and subsequent postmortem examination at 19 weeks confirmed the first-trimester findings and revealed, in addition to the facial pathology, a complex cardiac abnormality and unilateral talipes equinovarus. These findings are consistent with the diagnosis of Pierre Robin syndrome.

Mid-trimester fetal subdural hemorrhage: prenatal diagnosis.

A routine antenatal ultrasound examination at 20 weeks' gestation revealed a space-occupying lesion in the fetal right cerebral hemisphere. The borders of the mass were indistinct and there was no midline shift. A small collection of echogenic bowel was identified at the right iliac fossa. In an attempt to explain both findings a provisional diagnosis of a fetal blood dyscrasia was made. Fetal cranial magnetic resonance imaging 24 h later confirmed the diagnosis of a subdural hemorrhage. Subsequent fetal blood sampling confirmed severe fetal thrombocytopenia. To our knowledge this is the first report of the antenatal diagnosis of spontaneous mid-trimester fetal subdural hemorrhage.

Size and fluctuating asymmetry of morphometric characters in mice: their associations with inbreeding and t-haplotype.

Fluctuating asymmetry (FA), a ubiquitous type of asymmetry of bilateral characters, often has been used as a measure of developmental instability in populations. FA is expected to increase in populations subjected to genetic stressors such as inbreeding or environmental stressors such as toxins or parasites, although results have not always been consistent. We tested whether FA in four skeletal size characters and mandible shape was greater in a population of wild-derived mice reared in the laboratory and subjected to one generation of inbreeding (F = 0.25) versus that in an outbred group (F = 0.00). FA did not significantly differ between the inbred and outbred groups, despite the fact that these two groups differed dramatically in fitness under seminatural population conditions. As far as we know, this is the first study to evaluate the relationship between FA and inbreeding in wild house mice, and our general conclusion is opposite that of earlier work on laboratory inbred strains of mice and their hybrids. Size for two of the characters was significantly less in inbreds than in outbreds, however, and there was a significant difference between inbreds and outbreds in the signed differences of right and left sides in one character (humerus length). Some of the mice in both groups also were heterozygous or homozygous carriers of the t-complex. Because mice carrying this chromosome 17 variant are known to have reduced fitness, we also tested whether they had greater FA than mice carrying non-t-haplotypes. The overall level of a composite FA index calculated from all four characters was in fact significantly higher in the t-bearing mice. These combined results suggest that FA is not a generally sensitive proxy measure for fitness, but can be associated with fitness reductions for certain genetic stressors.