Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys.

OBJECTIVE: Hyperechogenic kidneys are a relatively rare antenatal finding, which can generate significant parental anxiety due to uncertain prognosis. We report on the perinatal and infant outcomes of a large cohort of fetuses with antenatally diagnosed hyperechogenic kidneys. METHODS: This was a retrospective analysis of all cases diagnosed prenatally with hyperechogenic kidneys between 2002 and 2017 in a large tertiary fetal medicine unit. Hyperechogenicity was defined as kidney parenchyma with greater echogenicity than that of the liver. Pregnancy, pathological and postnatal outcomes were collected from hospital and general practitioner records up to 1 year of age. Abnormal renal outcome was defined as elevated creatinine beyond 6 months of age, hypertension requiring medication or major kidney surgery, such as nephrectomy. Severe abnormal renal outcome was defined as the need for dialysis or kidney transplant at any stage. RESULTS: Three-hundred and sixteen fetuses with hyperechogenic kidneys were identified at a mean gestational age of 21 (range, 13-37) weeks. The majority of cases (97%) had bilateral hyperechogenic kidneys. In the 265 cases with available follow-up data, other associated renal tract abnormalities were identified prenatally in 36%, concomitant extrarenal structural abnormalities in 39% and abnormal karyotype in 15% of cases. Of the 316 included cases, 139 did not survive, including 105 terminations of pregnancy, five intrauterine deaths and 29 early neonatal deaths. Only 4.3% (6/139) of these fetuses had isolated hyperechogenic kidneys while 28.1% (39/139) had associated multiple renal tract abnormalities alongside hyperechogenic kidneys and over two-thirds (67.6%; 94/139) had concomitant extrarenal abnormalities. Of the 177 cases that survived beyond 1 month of age, outcome data were available in 126. Of these, based on the antenatal findings, 60 (47.6%) cases had isolated hyperechogenic kidneys, 56 (44.4%) had associated renal structural abnormalities and 10 (7.9%) had additional extrarenal abnormalities. Considering renal outcome alone, kidney function was abnormal in 13 (21.7%), 10 (17.9%) and 0 (0%) infants in these three groups, respectively, although concurrent pathology clearly affected global outcome in the more complex cases. Neonatal mortality of 1.6% was observed in the isolated renal hyperechogenicity group. The presence of oligohydramnios or abnormal renal volume was not associated significantly with abnormal renal function (odds ratio (OR), 2.32 (99% CI, 0.54-10.02) and OR, 0.74 (99% CI, 0.21-2.59), respectively) in this group. CONCLUSIONS: Hyperechogenic kidneys are often complicated by associated renal tract and extrarenal abnormalities, aberrant karyotype and genetic disease, and these factors have a greater effect on overall outcome than does kidney echogenicity. The renal outcome of fetuses with isolated hyperechogenic kidneys is good generally, with over 70% of cases having normal renal function postpartum. Importantly, for prognostic counseling, all of the fetuses in this non-selected series with isolated hyperechogenic kidneys and normal amniotic fluid levels had normal renal outcome in infancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Crash sign: new first-trimester sonographic marker of spina bifida.

OBJECTIVES: To describe a new first-trimester sonographic sign, the 'crash sign', associated with fetal open spina bifida, and to evaluate its clinical usefulness in the first-trimester diagnosis of spina bifida. METHODS: This was a retrospective review of patients referred to three fetal medicine centers in the first trimester (11 + 0 to 13 + 6 weeks) with suspected spina bifida. Spina bifida was confirmed by direct visualization of the spinal defect on ultrasound by two experts and, when possible, by fetal postmortem examination. Ultrasound images were reviewed for the presence of the crash sign, which is the posterior displacement of the mesencephalon and deformation against the occipital bone in the axial view. The first-trimester ultrasound images of a mixed group of 10 cases and 40 control fetuses without spina bifida were assessed for the presence of the crash sign by two assessors blinded to the diagnosis. RESULTS: The crash sign was present in 48 out of 53 confirmed cases of spina bifida. Of these, 27 had isolated spina bifida and 21 had an associated anomaly. Of the five cases without the crash sign, one had isolated spina bifida and four had an associated anomaly. The crash sign was not reported in any of the control fetuses. CONCLUSIONS: We have described a new first-trimester sonographic marker for the diagnosis of spina bifida. Our results suggest that the crash sign may be a useful tool in the first-trimester detection of spina bifida. Prospective evaluation of the crash sign would be beneficial, ideally in a routine clinical screening ultrasound setting. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Increased first-trimester nuchal translucency as a prenatal manifestation of salt-wasting congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that results from a deficiency in one or other of the five enzymes of cortisol biosynthesis. The most common form of CAH is 21-hydroxylase deficiency (21-OHD) and this may be manifest clinically in the neonatal period as a life threatening salt-wasting condition along side genital ambiguity. Prenatal diagnosis is available for CAH, however, there is poor correlation between the specific genotype and the phenotypic expression of the condition. We report two cases of severe salt-wasting CAH in one family that presented in both pregnancies with increased nuchal translucency (NT) in the first trimester. This is the first report of the association, between increased NT and CAH 21-OHD.

Outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation.

The aim of this study was to determine the outcome of chromosomally normal livebirths with increased fetal nuchal translucency at 10-14 weeks' gestation. Clinical follow up of 89 chromosomally normal livebirths that in fetal life had a minimum nuchal translucency thickness of 3.5 mm and a comparison group of 302 infants whose fetal nuchal translucency thickness at 10-14 weeks of gestation was less than 3.5 mm was performed. Major abnormalities, mainly structural defects of the cardiovascular or skeletal systems, were found in 10.1% (nine of 89) of the group with increased translucency, compared to 2% (five of 302) in those with translucency of less than 3.5 mm (chi2=11.9, p<0.001). Delay in achievement of developmental milestones was observed in one of the infants with increased translucency and in one of the comparison group. The findings of this study show that in chromosomally normal fetuses increased nuchal translucency thickness at 10-14 weeks of gestation is a marker for fetal abnormalities including structural defects and genetic syndromes.

Ultrasound screening for fetal abnormalities in the first trimester.

There has been an increase in the use of fetal ultrasound in the first trimester over the last few years. This paper will review the published literature on first trimester ultrasound screening programmes for both aneuploidy and fetal structural abnormalities.

The prevalence of non-viable pregnancy at 10-13 weeks of gestation.

In an ultrasound screening study at 10-13 weeks of gestation involving 17,870 women, the prevalence of early pregnancy failure was 2.8% (501 cases), including 313 (62.5%) missed abortions and 188 (37.5%) anembryonic pregnancies. Lower gestation and higher maternal age were associated with a higher prevalence (chi 2 = 143.5; p < 0.001 and chi 2 = 53.3; p < 0.0001, respectively). The prevalence was higher in women with a history of vaginal bleeding (chi 2 = 141.5; p < 0.0001), but there was no significant association with previous pregnancy losses (chi 2 = 2.8), parity (chi 2 = 0.6) or cigarette smoking (chi 2 = 0.0). Recent evidence suggests that the most effective method of screening for chromosomal abnormalities is measurement of fetal nuchal translucency thickness at 10-13 weeks, and therefore ultrasound examination at this gestation is likely to become universally available. As shown in this study, an additional advantage of such a scan is the diagnosis of early pregnancy failure, which will be found in about 3% of patients examined. Elective evacuation of retained products of conception is likely to be more cost effective and potentially safer than emergency surgery in a patient presenting during miscarriage.

Screening for fetal trisomies by maternal age and fetal nuchal translucency thickness at 10 to 14 weeks of gestation.

OBJECTIVE: To evaluate screening for chromosomal defects by a combination of fetal nuchal translucency thickness and maternal age. DESIGN: A prospective multicentre screening study where fetal nuchal translucency thickness was measured at 10 to 14 weeks of gestation. SUBJECTS: 20,804 women with singleton pregnancies screened at 10 to 14 weeks of gestation from 1 September 1992 to 28 October 1994. MAIN OUTCOME MEASURES: Trisomy 21 and other chromosomal defects identified by increased nuchal translucency thickness and by a combination of nuchal translucency thickness and maternal age. RESULTS: In normal fetuses nuchal translucency thickness increased significantly with crown-rump length. The nuchal translucency was above the 95th centile in 77% (66 of 86) of fetuses with trisomy 21 and in 78% (61 of 78) of those with other chromosomal defects. On the basis of the distribution of nuchal translucency measurements in normal fetuses and those with trisomy 21, a new method of screening is proposed which involves assessment of individual risk based on the combination of fetal nuchal translucency, crown-rump length and maternal age. The minimum risk was 1/100 in 4.9% of the normal pregnancies, in 80% of those with trisomy 21 and in 77% of those with other chromosomal defects. CONCLUSION: Screening for fetal trisomy 21 can be carried out effectively during the first trimester of pregnancy.

Nuchal translucency thickness and crown-rump length in twin pregnancies with chromosomally abnormal fetuses.

We retrospectively examined the crown-rump length and nuchal translucency thickness of each fetus in eight twin pregnancies in which karyotyping at 10 to 14 weeks' gestation demonstrated that at least one of the fetuses was chromosomally abnormal. Eight fetuses had trisomy 21 and two had trisomy 18. The nuchal translucency thickness was more than 2.5 mm in nine (90%) of the trisomic fetuses and in one of the chromosomally normal ones. In contrast, the crown-rump length was below the fifth percentile in only one of the fetuses with trisomy 18; all other measurements were within the normal range.

Natural history of trisomy 21 fetuses with increased nuchal translucency thickness.

Increased fetal nuchal translucency thickness at 10-14 weeks of gestation can identify 80% of trisomy 21 pregnancies. However, a potential disadvantage of screening in the first trimester of pregnancy is that earlier screening preferentially identifies those chromosomally abnormal pregnancies that are destined to miscarry. In this study, we report on the outcome of six fetuses with increased nuchal translucency thickness and trisomy 21 whose parents chose to continue with the pregnancy. During the second trimester, the nuchal translucency resolved in five of the cases and in one it evolved into nuchal edema. Therefore, resolution of translucency with advancing gestation is not indicative of a normal karyotype. All pregnancies resulted in live births, suggesting that increased nuchal translucency does not necessarily identify those trisomic fetuses that are destined to die in utero.

Repeatability of measurement of fetal nuchal translucency thickness.

The aim of this prospective study was to assess the repeatability of measurement of fetal nuchal translucency thickness at 10-14 weeks' gestation. The nuchal translucency was measured by two of four operators in 200 pregnant women attending the Harris Birthright Research Centre for Fetal Medicine at 10-14 weeks' gestation. To assess repeatability of different components of variability, six measurements of nuchal translucency were made on each fetus, with a total of 1200 measurements. The data of this study demonstrate that 95% of the time the intraobserver, interobserver and caliper placement repeatability of measuring fetal nuchal translucency were less than 0.54 mm, 0.62 mm and 0.58 mm, respectively. In addition, the repeatability was unrelated to the size of the nuchal translucency. The findings of this study demonstrate that, when the nuchal translucency thickness is measured by well-trained operators, the measurement is highly reproducible.

First trimester fetal nuchal translucency.

This review examines the development of a new method of screening for Down's syndrome based on the combination of fetal nuchal translucency thickness, maternal age and maternal serum biochemistry at 10-14 weeks of gestation. This method can potentially identify more than 80% of affected fetuses for a false-positive rate of less than 5%.

Crown-rump length in chromosomally abnormal fetuses at 10 to 13 weeks' gestation.

OBJECTIVE: Our purpose was to investigate whether fetuses with aneuploidies demonstrate evidence of growth retardation during the first trimester. STUDY DESIGN: This was a retrospective, cross-sectional study of singleton pregnancies undergoing fetal karyotyping at 10 to 13 weeks' gestation. Measurements of crown-rump length in 135 chromosomally abnormal fetuses were compared with those in 700 chromosomally normal fetuses. RESULTS: The median crown-rump length of fetuses with trisomy 18 (n = 32) was significantly reduced. In contrast, in fetuses with trisomy 21 (n = 72), trisomy 13 (n = 11), 47,XXX (n = 6), 47,XXY (n = 6), 45,X (n = 5), and triploidy (n = 3) the crown-rump length was not lower than normal. CONCLUSION: At 10 to 13 weeks' gestation fetuses with trisomy 18 are growth retarded, whereas in trisomy 21, trisomy 13, and sex chromosome aneuploidy growth is normal.

Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency.

In 1015 fetuses undergoing first-trimester karyotyping because of increased nuchal translucency thickness, the incidence of chromosomal abnormalities increased with both maternal age and nuchal translucency thickness. The observed numbers of trisomies 21, 18 and 13 in fetuses with nuchal translucency thicknesses of 3 mm, 4 mm, 5 mm and > or = 6 mm were approximately 3 times, 18 times, 28 times and 36 times higher than the respective numbers expected on the basis of maternal age. The incidences of Turner syndrome and triploidy were 9-fold and 8-fold higher but the incidence of other sex chromosome aneuploidies was similar to that of an unselected population of women undergoing first-trimester fetal karyotyping for maternal age. In the chromosomally normal group, the incidence of structural defects, mainly cardiac, diaphragmatic, renal and abdominal wall, was approximately 4%, which is higher than would be expected in an unselected population. The rates of fetal loss in the groups with nuchal translucency thickness of 3 mm and 4 mm were 2% and 4%, respectively, which is similar to the 2.3% rate of fetal loss observed in a group of fetuses with normal nuchal translucency thickness undergoing chorion villus sampling. For fetal nuchal translucency thickness of > or = 5 mm, the rate of fetal loss was 13%.

The implementation of first-trimester scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in two maternity units.

The aim of this prospective screening study was to evaluate the implementation of an additional ultrasound examination, incorporating the measurement of fetal nuchal translucency thickness, at 10-13 weeks' gestation in two maternity units providing routine antenatal care. During the 1 year prior to the introduction of the first-trimester scan, the major indication for fetal karyotyping was maternal age > or = 35 years and only two out of the total of 11 cases of trisomy 21 were identified. In the first 5 months of the study, 70% of the women delivering in these hospitals attended for measurement of fetal nuchal translucency thickness and the measurement was obtained in all cases. This was achieved without an increase in the number of sonographers or ultrasound machines. The incidence of fetal nuchal translucency thickness > or = 2.5 mm was 3.6% (63 of 1763), and this group included three of the four fetuses with trisomy 21. The findings of this study demonstrate the feasibility of introducing scanning at 10-13 weeks' gestation and the measurement of fetal nuchal translucency thickness in routine maternity units. The sensitivity and specificity of this method of screening are at present being evaluated in a large multicenter study.

Rapid determination of fetal sex in coelomic and amniotic fluid by fluorescence in situ hybridisation.

Coelomic fluid (n = 32), amniotic fluid (n = 26) and placental tissue were obtained from 32 women undergoing termination of pregnancy at 7-11 weeks of gestation. Fluorescence in situ hybridisation (FISH) was performed to determine fetal sex using a heterochromatic Y probe and an alpha satellite repeat probe for chromosome X. In each case there was concordance in the fetal sex from the three compartments. However, no result could be obtained from 4 of the 32 coelomic fluids and 4 of the 26 amniotic fluid samples. The hybridisation efficiency was significantly lower in coelomic and amniotic fluid compared with placental tissue.

First-trimester fetal nuchal translucency thickness and risk for trisomies.

OBJECTIVE: To define the relation between fetal nuchal translucency thickness at 10-13 weeks' gestation and the risk for fetal trisomies and pregnancy outcome. METHODS: Five hundred sixty fetuses with nuchal translucency thickness of 3-9 mm at 10-13 weeks' gestation were karyotyped. The ratio of the observed number of fetal trisomies to that expected on the basis of maternal age was calculated. RESULTS: The incidence of trisomies 21, 18, or 13 was 18% (102 of 560 cases) and was significantly associated with both maternal age (r = 0.97) and fetal nuchal translucency thickness (r = 0.75). In 383 fetuses with nuchal translucency of 3 mm, the observed number of fetal trisomies was 23, in contrast to the frequency of 6.0 expected on the basis of maternal age. In 177 fetuses with nuchal translucency of 4 mm or more, 79 cases were observed, compared with 2.7 expected on the basis of maternal age. In fetuses with nuchal translucency of 4 mm or more and normal karyotype, there was a high association with other defects and the prognosis was often poor, whereas the translucency resolved for those with 3 mm and the pregnancy outcome was usually normal. CONCLUSION: At 10-13 weeks' gestation, fetal nuchal translucency of 3 mm is associated with a fourfold increase, and translucency of greater than 3 mm with a 29-fold increase, in the maternal age-related risk for trisomies 21, 18, and 13. Fetal nuchal translucency of 4 mm or more is associated with poor pregnancy outcome even when the fetal karyotype is normal.

Rapid detection of chromosome aneuploidies in fetal blood and chorionic villi by fluorescence in situ hybridisation.

OBJECTIVE: Evaluation of fluorescence in situ hybridisation in the detection of numerical aberrations involving chromosomes X, Y, 13, 18 and 21. SETTING: Harris Birthright Research Centre for Fetal Medicine. SUBJECTS AND METHODS: Chorionic villi (n = 45) or fetal blood (n = 34) were obtained from 79 pregnancies undergoing fetal karyotyping at 10 to 39 weeks of gestation because of ultrasonographic markers of fetal chromosomal abnormality. Karyotyping was performed by both traditional cytogenetics and fluorescence in situ hybridisation, using commercially available kits which utilise a heterochromatic Y probe and the alpha satellite repeat probes for chromosomes X, 18, and 13/21. The frequency distributions of the number of signals obtained by fluorescence in situ hybridisation in the chromosomally normal and abnormal fetuses were compared. RESULTS: Traditional cytogenetic analysis demonstrated that the fetal karyotype was normal in 47 cases and abnormal in 32 (including 24 with trisomies 21, 18 or 13, three with triploidy, one with Turner's syndrome and four with translocations, deletions or mosaicism). With fluorescence in situ hybridisation it was possible to obtain accurate diagnosis of trisomy 18, Turner's or triploidy within six hours of sampling; signal distributions with these chromosomal abnormalities were very different from those of normals. However, for trisomies 21 and 13 there was an overlap in values with those from normals. CONCLUSIONS: In detection of fetal numerical chromosomal abnormalities the use of the combined 13/21 probe cannot provide sufficiently accurate results to justify abandonment of traditional cytogenetics in favour of fluorescence in situ hybridisation.

Stage at presentation and survival of white and black patients with prostate carcinoma.

BACKGROUND: Black men are known to have a higher incidence and mortality from prostate carcinoma than white men and are more likely to have a more advanced stage or grade of disease diagnosed. METHODS: In a Veterans Administration Medical Center where black and white men have the same eligibility for medical care, the authors reviewed the stage at presentation of 861 consecutive cases of prostate carcinoma diagnosed from 1969-1990. In addition, survival, stratified by race, stage, and grade, was determined on all men in whom prostate cancer was diagnosed from 1969-1985 (525 patients). RESULTS: It was found that 26% of white and 52% of black men with prostate carcinoma presented with Stage D disease. Similar proportions of white and black men with prostate carcinoma presented with Stage D disease between 1969-73 as between 1986-90. The overall survival was poorer for black men because of their higher proportion of Stage D disease, but stratified for grade and stage, survival was similar in both races. CONCLUSIONS: This study suggests that factors other than eligibility for medical care may be responsible for the higher proportion of black men with prostate carcinoma presenting with Stage D prostate carcinoma.