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.     

Isolated choroid plexus cysts—the need for routine offer of karyotyping

The management of isolated fetal choroid plexus cysts remains controversial. We have prospectively studied 15 565 pregnancies at two large obstetric units for the presence of choroid plexus cysts. In all cases where cysts were present at 19 weeks' gestation or greater, and were multiple, bilateral or solitary and greater than 5 mm maximum diameter, women were offered amniocentesis or placental biopsy, irrespective of the presence or absence of other abnormalities. Choroid plexus cysts were present in 152 (0·98 per cent) of cases. Four cases (2·6 per cent) of autosomal trisomy (three of trisomy 18, one of trisomy 21) were detected on prenatal karyotyping. In all cases, choroid plexus cysts were the only detectable prenatal anomaly. This study and a review of other large studies do not support the view that isolated choroid plexus cysts are a benign variant, the risk of trisomy being 1 in 82. Until further evidence is available, we recommend that cases of isolated fetal choroid plexus cysts at 19 weeks' gestation or greater should be offered prenatal karyotyping.     

Presentation of ventriculomegaly at 11–14 weeks of gestation: An analysis of longitudinal data

Objectives

The aim of this study was to examine the value of the sonographic measurements of the choroid plexus and the lateral ventricles at 11–14 gestational weeks in fetuses that had the diagnosis of second-trimester ventriculomegaly (VM) as a clinical reference.

Methods

The standard axial plane used for biparietal diameter measurement from 2D stored images in the first trimester was used to calculate the ratio between the choroid plexus and lateral ventricle diameter (PDVDR), the choroid plexus and lateral ventricle length (PLVLR) and the choroid plexus and lateral ventricle area (PAVAR) in 100 normal and 15 fetuses diagnosed with second-trimester VM.

Results

In fetuses with VM, the measurements of PDVDR, PLVLR and PAVAR were all significantly smaller compared to normal fetuses (p = < 0.001, <0.001, <0.01). Four out of seven cases with mild VM had measurements below the 5th percentile (57%). 75% of cases with moderate or severe VM had at least one measurement below the 5th percentile.

Conclusions

Since the axial plane of the fetal head is obtained in all first-trimester routine screenings, the measurements of PDVDR, PLVLR and PAVAR could easily be integrated into routine examinations for an early detection of VM.     

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.     

46,XY/47,XY,+ 17p+ mosaicism in amniocytes associated with fetal abnormalities despite normal fetal blood karyotype

46,XY/47,XY, + 17p + mosaicism was found in two primary amniotic fluid cultures (AFCs). Fetal blood karyotype was normal, but ultrasonography revealed Dandy-Walker malformation and bilateral choroid plexus cysts. Following termination of pregnancy, fetal examination revealed post-axial polydactyly and neuroblastoma-in-situ affecting both adrenals in addition to the cerebellar abnormalities. Mosaicism for the aberrant cell line was confirmed in all fetal tissues sampled and in the placenta.     

Fetal choroid plexus cysts and trisomy 18: Assessment of risk based on ultrasound findings and maternal age

This paper examines the association between fetal choroid plexus cysts (CPCs) and trisomy 18 and proposes a method by which risks can be derived taking into account both sonographic findings and maternal age. Data from our centre on the sonographic findings of 58 fetuses with trisomy 18 and 387 fetuses with CPCs as well as data from published series were used. It was calculated that the prevalence of CPCs in the general population is approximately 1 per cent and at mid-gestation the incidence of CPCs in fetuses with trisomy 18 is approximately 50 per cent. In the 387 fetuses with CPCs, the incidence of trisomy 18 increased with maternal age and the likelihood ratio for trisomy 18 increased with the number of additional abnormalities, from 0·03 for those with isolated CPCs to 0·4 if there was one additional abnormality and 20·5 if there were two or more additional abnormalities. It was concluded that if the cysts are apparently isolated, the risk for trisomy 18 is only marginally increased and maternal age should be the main factor in deciding whether or not to offer fetal karyotyping. If one additional abnormality is found, the maternal age-related risk is increased, so that even for a 20-year-old the risk for trisomy 18 is at least as high as the risk for trisomy 21 in a 35-year-old. In this respect, it may be considered desirable to offer such patients the option of karyotyping.     

The prenatal diagnosis of transient cysts of the fetal choroid plexus

Ultrasound scanning during the second trimester of pregnancy revealed cysts of the choroid plexus in the posterior horn of the lateral ventricle in five cases. All disappeared spontaneously between 20 and 23 weeks and normal infants were subsequently delivered.     

Prenatal ultrasonic findings in congenital chloride diarrhoea

In 3 fetuses affected by congenital chloride diarrhoea there were characteristic prenatal ultrasonic findings. In all cases the fetal abdominal cavity was filled with distended loops of fetal intestine, the fetal stomach was of normal size and polyhydramnios was present. The prenatal ultrasonic findings in this metabolic inherited disease are identical to those caused by mechanical obstruction of the distal fetal intestine. Whenever these findings are encountered prenatally, the possibility of chloride diarrhoea should be considered, because therapy with electrolytes is needed rather than the surgical intervention required in mechanical intestinal obstruction.     

Fetal ear measurements in the prenatal detection of trisomy 21

Although prominent fetal nuchal folds, short long bones, echogenic bowel, and renal pelviectasis have been shown to be associated with trisomy 21, none has acceptable diagnostic efficacy. Diminished fetal ear lengths measured by ultrasound have recently been reported as yet another potential morphological marker for the prenatal detection of trisomy 21. To investigate this further, we measured ear lengths and widths of normal (n = 107) and trisomy 21 (n = 25) second-trimester formalin-preserved fetuses. The normal ear growth characteristics are described and compared with those of trisomy 21 fetuses. The normal fetal ear shape, not unlike that of the neonates, manifested a marked variation. When the ear lengths and widths were regressed against gestational age, the slopes of the regression lines for the two groups were found to be different (P < 0·001). However, despite the statistically significant difference between the ear sizes of normal and trisomy 21 fetuses, the wide range of normal variation seen at each gestational age means that the fetal ear measurements are not diagnostically helpful.     

Karyotype abnormalities in fetuses diagnosed as abnormal on ultrasound before 20 weeks' gestational age

This study examined rates of karyotype abnormalities in fetuses diagnosed by ultrasound as abnormal before 20 weeks' gestational age and which prompted a follow-up amniocentesis or chorionic villus sampling. Those diagnosed before 20 weeks were compared with those diagnosed at or after 20 weeks. A retrospective study identified ultrasonographically abnormal fetuses in whom karyotyping had been undertaken, 306 fetuses before 20 weeks' gestational age and 241 after. Isolated malformations before 20 weeks had, on average, an 18 per cent risk of karyotype abnormality, compared with 20 per cent later. Specific rates were calculated; for example, heart abnormality was associated with karyotype abnormality in 7 per cent of cases before 20 weeks and in 14 per cent later. Multiple malformations and karyotype abnormalities were found together in 28 per cent of fetuses prior to 20 weeks and in 33 per cent of the older fetuses. Specific associations included nuchal oedema and trisomy 21 in 21 per cent of fetuses before 20 weeks. No karyotype abnormalities were found in fetuses diagnosed with choroid plexus cysts. An overview of trisomies in Victoria, in 1991, showed that 50 per cent of trisomy 18, 42 per cent of trisomy 13, and 9·5 per cent of trisomy 21 cases were identified by ultrasound in women less than 37 years of age. Another 28·6 per cent of trisomy 21 fetuses were detected in women of advanced maternal age who underwent amniocentesis or chorionic villus sampling, making a total of 38·1 per cent of trisomy 21 that were detected prenatally. The importance of early karyotyping specifically relates to the ongoing management of the pregnancy if the chromosomes are normal, and facilitates decision-making regarding termination of pregnancy if the chromosomes are abnormal.     

A possible prenatal evaluation of renal function by amino acid analysis on fetal urine

Intrauterine treatment of 4 fetuses with urethral obstruction was attempted in the third trimester of pregnancy. The fetuses displayed varying sonographic findings including pyelectasis, caliectasis, hydroureter, bladder dilatation, ascites, hydrops, missing kidneys and oligohydramnios. Ultrasonically guided aspiration from the dilated structures was carried out to relieve pressure on the kidney parenchyme and to collect fluid samples for diagnostic purposes. Amino acid concentrations in the fetal urine showed a pattern similar to plasma in 2 fetuses, a pattern almost like urine in 1 fetus and an intermediate pattern in the 4th fetus. Only the fetus with normal amino acid concentrations in the urine survived: the other 3 died in uremia shortly after birth. In 3 cases cells from the aspirated urine were cultured and used for chromosome analysis. The cell cultures grew fast and karyotyping was possible within 1 week. In 2 fetuses an intrauterine catheter was inserted to drain the kidney permanently into the amniotic cavity. In the first case the catheter was displaced to the fetal abdomen after some days of successful drainage. In the second case the catheter tore the placenta, and the child had to be delivered immediately.     

The early prenatal sonographic diagnosis of renal agenesis: Techniques and possible pitfalls

Out of 13 252 cases in which fetal bilateral echogenic kidneys were detected by transvaginal sonography between 12 and 18 weeks' gestation, there were nine fetuses where oval hypoechogenic masses were detected in the renal bed. In five fetuses where hypoechogenic masses in the renal bed were sonographically visualized, postabortal examination was compatible with renal agenesis and the hypoechogenic masses proved to be enlarged adrenals. In three additional cases, unilateral renal agenesis was accompanied by unilateral enlarged adrenals, radiologically confirmed postnatally. In one case, a false-positive sonographic diagnosis of Potter syndrome was made because of bilateral hypoechogenic masses in the renal bed. Postabortal examination detected hypoplastic kidneys, but of normal histology, in a dyskaryotic fetus with trisomy 22. In four cases of renal agenesis, the amniotic fluid was of normal volume until the 17th week. In two of the five cases of Potter syndrome, a cystic structure, compatible with the urinary bladder, was detected in the pelvis at 14 weeks. The diagnostic criteria for renal agenesis in the early fetus differ from those used in the second half of gestation.     

Prenatal diagnosis of anhidrotic ectodermal dysplasia

This paper reports on successful prenatal diagnosis of X-linked anhidrotic ectodermal dysplasia (AED) by means of light and electron microscopy on fetal skin biopsies obtained under fetoscopy. In the present family two brothers of the proband were severely affected with the full symptomatology of AED, the pregnant female and her mother revealed minor symptoms with patches of skin lacking vellus hair. Control of lesional skin of the affected family members by electron microscopy revealed no ultrastructural abnormalities. However, all biopsies lacked skin appendages including hair follicles, sebaceous glands, and sweat glands. The lack of pilosebaceous follicles can be used as a diagnostic criterion since these structures are fully developed in normal fetuses of 20 weeks whereas the development of sweat glands does not start before week 20 to 24 of fetal life. Skin biopsies were taken from various regions of the fetus at risk via fetoscopy in week 20 and processed for light and electron microscopy. All samples revealed complete absence of all skin appendages in contrast to a total of 61 non-AED fetuses. Thus positive prenatal diagnosis of AED was made and the pregnancy was terminated. Control investigations after abortion confirmed the diagnosis.     

Blood chemistry of human fetuses in the second and third trimesters

Six biochemical parameters and four enzyme activities were determined from the serum of 76 healthy and 56 pathological human fetuses between the 20th and 38th week of pregnancy. In the normal fetuses studied within that period, creatinine, immunoglobulin M, lactate dehydrogenase, and gamma-glutamyltransferase increased; haemoglobin F and glucose progressively decreased; and alkaline phosphatase was at a peak around the 26th week; cholesterol and triglycerides were always low. The same parameters were also measured in some of the pathological fetuses and compared with their normal counterparts.     

Normal blood cell values in the early mid-trimester fetus

Samples of pure fetal blood from 116 fetuses of 15–21 weeks' gestation were obtained by direct vision fetoscopy. Ninety nine of these fetuses, presumed to be haematologically normal, were suitable for analysis. The data obtained show that the erythropoietic system is evolving rapidly in this gestational age range. The myeloid series shows no significant increase or decrease in numbers apart from eosinophils and basophils which increase significantly with gestational age whereas the platelet count remains constant. The growing application of fetoscopic blood sampling to the prenatal diagnosis and management of fetal blood disorders renders mandatory a knowledge of normal fetal blood values.     

X-linked pyruvate dehydrogenase complex deficiency due to a novel PDHA1 variant associated with structural brain abnormalities in a fetus

We report a case of pyruvate dehydrogenase E1 alpha subunit deficiency associated with a novel hemizygous PDHA1 variant presenting prenatally as multiple structural brain abnormalities in a male fetus. A healthy Finnish couple was initially referred to the Fetomaternal Medical Center because of suspected fetal choroid plexus cyst at 11 + 2 weeks of pregnancy. At 20 + 0 weeks, multiple abnormalities were observed with ultrasound including narrow thorax, slightly enlarged heart, hypoplastic cerebellum, absent cerebellar vermis and ventriculomegaly. Autopsy and genetic analyses were performed after the termination of pregnancy. The findings of macroscopic examination included cleft palate, abnormally overlapping position of fingers and toes and dysmorphic facial features. Neuropathological examination confirmed the absence of corpus callosum, cerebellar hypoplasia and ventriculomegaly. Nodular neuronal heterotopia was also observed. Trio exome sequencing revealed a novel hemizygous de novo variant c.1144C>T p.(Gln382*) in the PDHA1 gene, classified as likely pathogenic. We suggest that inherited metabolic disorders should be kept in mind as differential diagnoses in fetuses with structural brain abnormalities.     

Ultrasound movement patterns of fetuses with chromosome anomalies

Fetal movements were examined by ultrasound in 24 pregnancies in which an abnormal karyotype was detected in fetal cells and compared to ultrasound fetal movement patterns in normal pregnancies. The main features in fetuses with chromosome anomalies observed at 18–20 weeks of gestation are the persistence of global, jerky movements with twitches usually seen at 13–14 weeks of gestation in normal fetuses. This fetal motor behaviour is inconstant in trisomy 21. In trisomy 18 the hand deformities are easily detected.     

Creatine kinase estimation in pure fetal blood samples for the prenatal diagnosis of duchenne muscular dystrophy

This paper compares the results of a survey of plasma creatine kinase (CK) activity measured in fetuses at-risk for Duchenne muscular dystrophy (DMD) with a reliable control series. Only pure fetal blood samples obtained by fetoscopy at between 17–24 weeks gestational age were used. Of the at-risk group 19 male pregnancies, mostly at low risk for DMD, proceeded to term with a normal outcome; there was no significant difference between their fetal plasma CK activities and the control group. Another 21 male pregnancies were terminated. This group included the highest risk mothers and hence was expected to contain a significant proportion of affected fetuses. The fetal plasma CK activity range was overlapping but significantly higher than the control group. No grossly elevated CK value was obtained. We conclude that, on average, DMD fetuses at this gestational age have higher plasma CK activity than controls. The problems of applying this finding to the prenatal diagnosis of DMD are discussed.     

Prenatal ultrasonographic diagnosis of fetal cerebral ventriculitis associated with asymptomatic maternal cytomegalovirus infection

Cytomegalovirus is the most common cause of congenital viral infection. In utero infection is usually suspected in patients with growth-retarded fetuses or when maternal illness precipitates serological investigations. A case is presented where routine ultrasound examination at 30 weeks' gestation in an asymptomatic patient demonstrated mild fetal ventriculomegaly. Transvaginal ultrasound enabled the visualization of intraventricular adhesions and small periventricular cysts. The suspected diagnosis of in utero cytomegalovirus infection was confirmed by the presence of IgM antibodies in fetal blood and subsequently by isolation of the virus from the infant's urine. The presence of mild fetal ventriculomegaly should prompt transvaginal brain imaging.