A prospective study of the incidence and significance of fetal choroid plexus cysts

Cysts of the choroid plexus of the lateral ventricle can be detected in the fetus during routine scanning at 16–18 weeks' gestation with an approximate incident of one in every 120 pregnancies. It is likely that in a high percentage of cases cysts are bilateral and that their recent discovery is mainly due to improvements in imaging technology. Although the great majority of cases resolve and do not result in any morbidity, five cases of trisomy 18 and one case of trisomy 21 associated with fetal choroid plexus cysts have been reported. In this prospective study, choroid plexus cysts were detected in 42 fetuses, resulting in 40 normal infants and 2 cases of trisomy 18. It is concluded that there may be a relationship between fetal choroid plexus cysts and trisomy 18. In order to obtain a more precise and accurate result, a multi-centre prospective study is being organized.     

The significance of choroid plexus cysts in fetuses at 18–20 weeks. An indication for amniocentesis?

Over a period of 25 months, all antenatal patients were offered a detailed ultrasound scan at 18–20 weeks' gestation. The lateral cerebral ventricles were scanned for the presence of choroid plexus cysts. Fifty-one patients found to have choroid plexus cysts were offered amniocentesis to exclude chromosomal abnormalities. One pregnancy, in which the only abnormality found was bilateral choroid plexus cysts, was terminated after trisomy 18 was detected on amniocentesis at 19 weeks. The other 50 pregnancies had normal fetal outcomes. The significance of the isolated finding of choroid plexus cysts is reviewed.     

Maternal serum activin A and inhibin A in trisomy 18 pregnancies at 10–14 weeks

In 45 cases of trisomy 18 and 493 control pregnancies at 10–14 weeks of gestation, maternal serum inhibin A, total activin A, free β-hCG and PAPP-A were measured. In the trisomy 18 pregnancies the median values were 0.74 MoM for inhibin A, 1.23 MoM for activin A, 0.38 MoM for free β-hCG and 0.16 MoM for PAPP-A. The degree of deviation from normal in the levels of inhibin and activin is small in comparison with free β-hCG and PAPP-A and they are therefore unlikely to be of value in improving the sensitivity of 90% for a 1% false-positive rate achieved by screening with fetal nuchal translucency and maternal serum free β-hCG and PAPP-A. Copyright © 2001 John Wiley & Sons, Ltd.     

A first trimester trisomy 13/trisomy 18 risk algorithm combining fetal nuchal translucency thickness,maternal serum free β-hCG and PAPP-A

This study examines 45 cases of trisomy 13 and 59 cases of trisomy 18 and reports an algorithm to identify pregnancies with a fetus affected by trisomy 13 or 18 by a combination of maternal age fetal nuchal translucency (NT) thickness, and maternal serum free β-hCG and PAPP-A at 11–14 weeks of gestation. In this mixed trisomy group the median MoM NT was increased at 2.819, whilst the median MoMs for free β-hCG and PAPP-A were reduced at 0.375 and 0.201 respectively. We predict that with the use of the combined trisomy 13 and 18 algorithm and a risk cut-off of 1 in 150 will for a 0.3% false positive rate allow 95% of these chromosomal defects to be identified at 11–14 weeks. Such algorithms will enhance existing first trimester screening algorithms for trisomy 21. Copyright © 2002 John Wiley & Sons, Ltd.     

Minor sonographic signs of trisomy 21 at 15–20 weeks' gestation in fetuses born without malformations: a prospective study

A prospective study was performed on 2119 pregnancies that underwent genetic amniocentesis. Indications for amniocentesis were either maternal age (⩾35) or triple-test results (risk⩾1/380). The study covered a 36-month period and assessed the prevalence of minor ultrasound markers both in fetuses with Down syndrome and normal control fetuses at 15–19 week' gestation. Only fetuses with normal karyotype or trisomy 21 were considered. Six minor sonographic markers were considered: nuchal thickness, pyelectasia, femur observed/expected and humerus observed/expected ratios, bowel echogenicity, and choroid plexus cysts. One or more ultrasound soft markers were present in 23 out of 33 fetuses with Down syndrome (70%) and in 572 out of 2069 normal fetuses (28%). Copyright © 2001 John Wiley & Sons, Ltd.     

Maternal age-specific risks for trisomies at 9—14 weeks' gestation

This study provides data on the incidence of fetal trisomies 21, 18, and 13 at 9–14 weeks' gestation in women aged 35–45 years and estimates of maternal age-specific risks in women aged 20–45 years. Our data from 5814 singleton pregnancies undergoing first-trimester karyotyping for the sole indication of maternal age ⩾ 35 years were combined with those from two previous reports and the incidence of the trisomies was calculated from a total of 15 793 pregnancies. Comparison of incidences at 9–14 weeks' gestation with published data at 15–20 weeks' gestation and in livebirths demonstrated that at birth the maternal age-specific incidence of trisomy 21 is 33 per cent lower than at 15–20 weeks' gestation and 54 per cent lower than at 9–14 weeks' gestation. Furthermore, the relative frequency of trisomies 18 and 13 decreases from 30 per cent at 9–14 weeks to 22 per cent at 15–20 weeks and 14 per cent at birth.     

Maternal platelet size as a marker for fetal trisomies 18 and 13

Maternal and fetal platelet size and glycoprotein expression were measured in 14 pregnancies complicated by fetal aneuploidy between 20 and 24 weeks' gestation. Flow cytometry was used to determine platelet size and surface glycoprotein Ib (GPIb) and GPIIIa expression both before and after stimulation with adenosine diphosphate (ADP). The data were compared with results obtained from 35 normal paired maternal and fetal controls. In fetuses affected with trisomies 18 and 13, but not trisomy 21, the maternal and fetal platelet sizes were significantly higher than those of the normal controls. Furthermore, the increase in fetal platelet size was significantly associated with the increase in maternal platelet size. Increase in maternal platelet size may be of potential value as a marker for fetal trisomies 18 and 13.     

Fetal cholecystomegaly: A prenatal marker of aneuploidy

The fetal gall bladder can now be easily identified during the second and third trimesters using high-resolution ultrasonography. In this report we present eight fetuses with an enlarged gall bladder detected on prenatal ultrasonography at a mean gestational age of 24.6 weeks (range 19–31 weeks). Additional ultrasonographic findings were present in four cases: fetal anomalies and intrauterine growth retardation in three and polyhydramnios in one. Of those cases associated with fetal anomalies, one woman underwent amniocentesis at 21 weeks revealing trisomy 18. The other two declined prenatal karyotyping; neonatal karyotyping revealed trisomy 13 in one and trisomy 18 in the other. Although an enlarged fetal gall bladder can be a normal variant in the second and third trimesters, the prenatal detection of cholecystomegaly should prompt a search for associated anomalies and other markers of aneuploidy. If found, prenatal karyotyping should be considered.     

Early prenatal detection of diastrophic dysplasia

Diastrophic dysplasia, an autosomal recessive disorder, results in severe short-limbed dwarfism, progressive spinal and joint problems, and secondary psychosocial disability. The results of treatments are unsatisfactory. Four pregnant mothers at risk for an affected fetus were studied with an ultrasound scanner at 16 and 19 weeks of gestation. Each mother had a previous child with diastrophic dysplasia. The biparietal distance and the length of the long bones of the extremities were normal in three fetuses, whereas in one fetus there was a 30 per cent shortening of all long bones. The biparietal distance corresponded with the gestational age in all fetuses. In one fetus, diastrophic dysplasia was confirmed by fetoscopy and fetal radiograph at 19 weeks of gestation after the parents had decided to terminate the pregnancy. The skeletal radiograph and autopsy findings of the fetus verified the diagnosis. All other mothers were followed with repeated ultrasound examinations, and they delivered healthy babies. The retrospective follow-up of the four previous pregnancies and of the present one with affected fetuses disclosed that two mothers had had vaginal bleeding, two lymphedema, one abdominal pains, and one mother had had polyhydramnios. These complications were, however, mild and transient, and they could not be regarded as specific for pregnancies with affected fetuses.     

Misdiagnosis of omphalocele associated with Edwards syndrome and congenital heart disease

We present a case in which an apparent omphalocele, diagnosed at 30 weeks gestation ultrasound, led to identification of fetal trisomy 18 and congenital heart disease. At delivery, the fetus had the features of trisomy 18 and congenital heart disease but the omphalocele was absent. We suggest that the appearances seen are easily confused with a small omphalocele and could potentially result in unnecessary further investigations being performed.     

Maternal urinary β-core fragment of hCG/creatinine ratios and fetal chromosomal abnormalities in the second trimester of pregnancy

Our aim was to evaluate the potential value of the ratio of the maternal urinary beta-core fragment of human chorionic gonadotropin (βC-hCG) to creatinine (Cr) in discriminating between normal pregnancies and pregnancies associated with fetal chromosomal abnormalities. We hypothesized that pregnancies with fetal chromosomal abnormalities had abnormal quantities of βC-hCG in the urine. The aims of the present study were to investigate retrospectively whether maternal urinary ratios of βC-hCG/Cr are abnormal in women carrying fetuses with chromosome aberrations and to determine normative median values and a reference range for βC-hCG/Cr between 14 and 19 weeks' gestation. Maternal urinary βC-hCG and Cr concentrations were measured in 150 healthy women from 14 to 19 weeks and compared with ten cases of fetal chromosomal abnormalities matched for gestational age. The preliminary cut-off points corresponded to 0·29 multiple of the normal median (MOM) and 2·83 MOM, which were equivalent to the tenth and 90th centiles of the normal range. Of ten cases of fetal chromosomal abnormalities, one out of one (100 per cent) case with trisomy 18 and three of four (75 per cent) cases of variant 9 chromosome had low βC-hCG/Cr (≤0·29 MOM). One of five (20 per cent) cases with Down syndrome had elevated βC-hCG/Cr (≤2·83 MOM). Urinary βC-hCG/Cr ratios obtained in the second trimester may be useful for improved detection efficiency of Down syndrome, trisomy 18, and inversion of chromosome 9. Second-trimester maternal urinary βC-hCG/Cr should be investigated further as a potential marker for fetal chromosome anomalies.     

Abnormal immunological development in fetuses with trisomy 18

Flow cytometry was used to enumerate the lymphocyte subpopulations in fetal blood obtained by cordocentesis from eight trisomy 18 fetuses at 20–36 weeks' gestation. Compared with values in chromosomally normal fetuses, in trisomy 18 the mean T- and natural killer (NK) cell counts were significantly lower (t= − 7·63, P<0·001 and t= − 3·58, P<0·01, respectively); the mean B-cell count was not significantly different (t= − 1·32). These findings demonstrate that in trisomy 18 there is abnormal intrauterine development of the immune system.     

Ultrasound evaluation of pregnancies at risk for homozygous α-thalassaemia-1

Twenty-six pregnant Chinese women who were at risk of giving birth to a fetus affected with homozygous α-thalassaemia-1 were examined serially by ultrasound. Six of these 26 pregnancies were affected. In one third of the affected pregnancies progressive fetal ascites appeared before 24 weeks gestation and these pregnancies were terminated. In the remaining two thirds abnormal estimated fetal weight-placental volume (EFW-PV) ratio and fetal growth retardation as evidenced by a falling biparietal diameter (BPD), femur length (FL) but a normal abdominal circumference (AC) was apparent by 28 weeks gestation. Increased transverse cardiac (TC) diameter was another consistent finding but appeared late. All these features appeared before the onset of fetal ascites. A normal EFW-PV ratio and fetal growth until 28 weeks gestation was a reassuring sign of normality. Abnormal EFW-PV ratio was the earliest sign to appear in affected pregnancies and a normal ratio until 28 weeks gestation had a 100 per cent predictive value.     

The effect of fetal gender on nuchal translucency at 10–14 weeks of gestation

Recent data have suggested that fetal nuchal translucency (NT) is affected by fetal gender. We investigated the size of this effect in 12 189 unselected pregnancies with known normal outcomes that had undergone NT measurements between 10 and 14 weeks of gestation. NT increased with gestation and was converted to multiples of the median (MoM) for the gestational day. The median NT MoM (95% CI) for female fetuses was 0.98 (0.97–0.99). This was significantly lower than that of the male fetuses (1.03; range1.02–1.04) (p<0.0005; Wilcoxon rank-sum test). The gender difference was not observed at 10 weeks but was observed from 11 weeks onwards. There is no obvious explanation for the above findings. Copyright © 2001 John Wiley & Sons, Ltd.     

Sonographically determined anomalies and outcome in 170 chromosomally abnormal fetuses

Structural pathology and outcome were studied in 170 chromosomally abnormal fetuses. Numerical chromosomal abnormalities were established in 158 (93 per cent) cases, of which 110 (71 per cent) represented trisomies, 30 (18 per cent) Turner syndrome, and 18 (11 per cent) triploidy. Structural chromosomal abnormalities were diagnosed in 12 (7 per cent) cases. Gestational age at referral was significantly shorter for pregnancies with Turner syndrome than for the other chromosomal abnormalities. Referral before 20 weeks of gestation was mainly based on fetal structural pathology alone (92 per cent); after 20 weeks, patients were referred because of structural pathology combined with small for gestational age, oligohydramnios, or polyhydramnios. Referral as a result of suspected multiple organ pathology occurred in 73.5 per cent of pregnancies. An abnormal amniotic fluid volume was present in 59/170 (34.5 per cent) chromosomally affected pregnancies, i.e., oligohydramnios in 31 and polyhydramnios in 28 cases. Birth weight was below the tenth percentile in over half of the chromosomally abnormal fetuses, except for Turnersyndrome. Fetal outcome was poor, with a survival rate at 1 month of 30 per cent for trisomies which was mainly determined by trisomy 21 (14/18=77.5 per cent).     

Screening for trisomy 21 in twin pregnancies in the first trimester: does chorionicity impact on maternal serum free β-hCG or PAPP-A levels?

In a study of 180 twin pregnancies I have examined the distribution of maternal serum free β-human chorionic gonadotrophin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A), in addition to fetal nuchal translucency thickness (NT), in twins classified as monochorionic or dichorionic, based on ultrasound appearance at 10–14 weeks of gestation. In 45 monochorionic and 135 dichorionic twin pregnancies the median MoM free β-hCG was not significantly different (1.00 vs 1.01), whilst that for PAPP-A was lower (0.89 vs 1.01) but again with no statistical significance. Previous reports of an increased fetal NT in monochorionic twins pregnancies could not be confirmed (1.03 vs 1.00). It is concluded that the existing pseudo risk twin correction algorithm is appropriate for both monochorionic and dichorionic twins in providing accurate first trimester risks for trisomy 21. Copyright © 2001 John Wiley & Sons, Ltd.     

Human chorionic gonadotropin levels in pregnancies with aneuploid fetuses

Maternal serum human chorionic gonadotropin (hCG) and the free alpha-hCG subunit were evaluated in 249 women from 9 to 11 weeks gestation who subsequently underwent chorionic villus sampling for determination of fetal karyotype and in 20 women of 18 or more weeks gestation who were ascertained to have an aneuploid fetus by genetic amniocentesis. Seven of the first-trimester pregnancies were determined to be aneuploid and six had hCG levels in the normal range (one triploid pregnancy had elevated hCG levels) whereas 12 of the 20 secondtrimester cases had abnormal hCG levels and an additional three had elevated levels of alpha-hCG. This study confirms the previous report of abnormal maternal serum hCG levels in women with an aneuploid fetus at ≥ 18 weeks gestation and demonstrates that hCG evaluation is not useful at 9–11 weeks gestation for selecting pregnancies at risk for fetal aneuploidy.     

First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18

Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free β-human chorionic gonadotrophin (β-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10–13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (p<0.0001) than in the control group (1.00 MoM). In the trisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free β-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free β-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free β-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free β-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free β-hCG. Copyright © 2001 John Wiley & Sons, Ltd.     

Increased nuchal translucency as a prenatal manifestation of congenital adrenal hyperplasia

We present two cases of pregnant women with a previous history of congenital adrenal hyperplasia. In both cases the only abnormal feature in the initial pregnancy had been increased nuchal translucency at 10–14 weeks of gestation. The fetal karyotype was normal and a diagnosis of congenital adrenal hyperplasia was made after delivery. In their current pregnancies, both fetuses also had increased nuchal translucency and normal fetal karyotype. Diagnosis of 21-hydroxylase deficiency was made prenatally by DNA analysis. These findings in four affected fetuses suggest that congenital adrenal hyperplasia should be added to the list of genetic anomalies associated with an increase in nuchal translucency. Copyright © 2001 John Wiley & Sons, Ltd.     

The development of the fetal eye: In utero ultrasonographic measurements of the vitreous and lens

Our objective was to establish nomograms for fetal eye measurements from 12 weeks' gestation by using transvaginal and transabdominal high-resolution ultrasound techniques. A prospective cross-sectional study was performed on 450 normal singleton pregnancies between 12 and 37 weeks' gestation. Vitreous and lens circumferences were measured by transvaginal ultrasonography until 17 weeks, and by abdominal ultrasound between 18 and 37 weeks' gestation. Regression analyses were used to create nomograms, and several transformations were done to obtain linearity. Eye measurements of 12 fetuses at risk for ocular disturbances were plotted on the constructed nomograms. Linear relationships were fitted between vitreous (r²=0.79) and lens (r²=0.88) circumferences and gestational age. In addition, there was a significant correlation between these measurements and the biparietal diameter. Data of the fetuses at risk showed that disturbances in ocular growth were associated mainly with abnormal cerebral development. These normative data may be helpful in the prenatal diagnosis of suspected congenital syndromes that include, among their manifestations, ocular growth disturbances such as microphthalmos and anophthalmos.