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.     

Prenatal diagnosis of congenital cytomegalovirus infection in 189 pregnancies with known outcome

An Erratum has been published for this article in Prenatal Diagnosis 21(7) 2001, 605. Prenatal diagnosis (PD) of fetal cytomegalovirus (CMV) infection was performed in 242 pregnancies, with known outcome in 189 cases. In 141/189 pregnancies, PD was carried out on account of suspicious maternal CMV serology up to gestational week (WG) 23, and in 48 cases on account of abnormal ultrasonic findings detected between WG 18 and 39. Chorionic villus samples (n=6), amniotic fluid (AF, n=176) and/or fetal blood specimens (n=80) were investigated for detection of virus by cell culture, shell vial assay, PCR and/or CMV-specific IgM antibodies. Of 189 fetuses correctly evaluated by CMV detection either in fetal tissue following therapeutic abortion/stillbirth (n=24) or in urine of neonates within the first 2 weeks of life (n=33), 57 were congenitally infected. In women with proven or suspected primary infection, the intrauterine transmission rates were 20.6% (7/34) and 24.4% (10/41), respectively. Of the congenitally infected live-born infants, 57.6% (19/33) had symptoms of varying degree. The overall sensitivity of PD in the serologic and ultrasound risk groups was 89.5% (51/57). A sensitivity of 100% was achieved by combining detection of CMV-DNA and CMV-specific IgM in fetal blood or by combined testing of AF and fetal blood for CMV-DNA or IgM antibodies. There was no instance of intrauterine death following the invasive procedure. The predictive value of PD for fetal infection was 95.7% (132/138) for negative results and 100% (51/51) for positive results. Correct results for congenital CMV infection by testing AF samples can be expected with samples obtained after WG 21 and after a time interval of at least 6 weeks between first diagnosis of maternal infection and PD. In case of negative findings in AF or fetal blood and the absence of ultrasound abnormalities at WG 22–23, fetal infection and neonatal disease could be excluded with high confidence. Positive findings for CMV infection in AF and/or fetal blood in combination with CMV suspicious ultrasound abnormalities predicted a high risk of cytomegalic inclusion disease (CID). Furthermore, detection of specific IgM antibodies in fetal blood was significantly correlated with severe outcome for the fetus or the newborn (p=0.0224). However, normal ultrasound of infected fetuses at WG 22–23 can neither completely exclude an abnormal ultrasound at a later WG and the birth of a severely damaged child nor the birth of neonates which are afflicted by single manifestations at birth or later and of the kind which are not detectable by currently available ultrasonographic techniques. Copyright © 2001 John Wiley & Sons, Ltd.     

Hydrops fetalis and neonatal death from human parvovirus B19: an unusual complication

A case of prenatally diagnosed human parvovirus B19 (HPVB19) infection is reported. The neonate died after intrauterine therapy and premature delivery. The fetus was diagnosed with oedema, cardiomegaly, poor myocardial contractility and a pericardial effusion at 24/40 weeks' gestation. Ultrasound using colour flow Doppler showed a midcerebral artery peak systolic velocity (MCA PSV) raised at 45 cm/s, suggesting fetal anaemia. This was confirmed on fetal blood sampling, but recovery was suggested with a reticulocyte count of 16.8%. The fetal karyotype was normal, 46,XY. Fetal IgM was positive for Parvovirus. A week later, severe fetal anaemia was suspected and intrauterine transfusion carried out. Altogether three transfusions were given. At 31/40 weeks, the mother presented to her local hospital with suspected preterm labour, a caesarean section was carried out because of fetal compromise on cardiotocography. The baby was in poor condition at birth and resuscitation was stopped at 45 min of age. The post-mortem examination confirmed the hydrops and proved persistent Parvovirus infection, cardiac involvement and severe liver fibrosis. HPVB19 generally follows a benign course with intrauterine therapy; however, in this case, the fetus died despite successful transfusions. The reasons for this are discussed. Copyright © 2005 John Wiley & Sons, Ltd.     

Heterogeneity in fetal akinesia deformation sequence (FADS): autopsy confirmation in three 20–21-week fetuses

Fetal akinesia deformation sequence (FADS) is a rare condition characterized by intrauterine growth retardation (IUGR), congenital limb contractures, pulmonary hypoplasia, hydramnios and craniofacial abnormalities. The present report comprises an autopsy study of three fetuses to illustrate the variable clinical manifestations and neuropathological findings. Fetus 1 had arthrogryposis and no movement on fetal ultrasound examination. Aborted at 21 weeks, the fetus showed micrognathia, bilateral joint contracture with pterygia at the elbow and axilla. Growth retardation and pulmonary hypoplasia were not major features. Neuropathologic examination revealed anterior horn cell loss and lateral corticospinal tract degeneration in spinal cord, with marked muscular atrophy. Fetus 2, 20 weeks' gestation, had fetal akinesia, nuchal thickening, left pleural effusion, and Dandy-Walker malformation on ultrasound examination. Autopsy showed low-set ears, ocular hypertelorism, cleft palate, flexion contractures with pterygia over axilla, elbow and groin, pulmonary hypoplasia, Dandy-Walker malformation, unremarkable spinal cord and skeletal muscle. Fetus 3, 21 weeks' gestation, was aborted for fetal akinesia, neck and limb webbing and severe arthrogryposis. At autopsy, similar facial abnormalities, contracture and pterygia in neck and multiple major joints were found. Borderline pulmonary hypoplasia and severe lumbar scoliosis were also present. The brain, spinal cord and muscle were unremarkable. In these three fetuses, the prenatal ultrasound and autopsy findings were characteristic of FADS. Neurogenic spinal muscular atrophy was the basis of fetal akinesia in Case 1. Dandy-Walker malformation was present in Case 2, but the pathogenetic mechanism of fetal akinesia was not clear as spinal cord and muscle histology appeared normal. The etiology of akinesia was undetermined in Case 3; no extrinsic or intrinsic cause was identified. Copyright © 2002 John Wiley & Sons, Ltd.     

Fetal toxoplasmosis and negative amniocentesis: necessity of an ultrasound follow-up

Prenatal diagnosis of congenital toxoplasmosis relies on the PCR test on amniotic fluid and ultrasound follow-up of the fetus. We report two cases of toxoplasma infection during the first trimester of gestation with a discrepant diagnosis of fetal infection. PCR performed more than four weeks after the estimated date of contamination was negative. Ultrasound follow-up was normal up to the third trimester when major hydrocephalus was detected, leading to pregnancy termination. In both cases, post-mortem examination revealed a diffuse infection with severe brain lesions. These observations confirm the necessity to continue a monthly ultrasound follow-up, even if amniocentesis is negative, in case of fetal toxoplasma infection in pregnancy. Copyright © 2003 John Wiley & Sons, Ltd.     

The MRI spectrum of congenital cytomegalovirus infection

Human cytomegalovirus (CMV) is an ubiquitous pathogen, with a high worldwide seroprevalence. When acquired in the prenatal period, congenital CMV (cCMV) is a major cause of neurodevelopmental sequelae and hearing loss. cCMV remains an underdiagnosed condition, with no systematic screening implemented in pregnancy or in the postnatal period. Therefore, imaging takes a prominent role in prenatal diagnosis of cCMV. With the prospect of new viable therapies, accurate and timely diagnosis becomes paramount, as well as identification of fetuses at risk for neurodevelopmental sequelae. Fetal magnetic resonance imaging (MRI) provides a complementary method to ultrasound (US) in fetal brain and body imaging. Anterior temporal lobe lesions are the most specific finding, and MRI is superior to US in their detection. Other findings such as ventriculomegaly, cortical malformations and calcifications, as well as hepatosplenomegaly, liver signal changes and abnormal effusions are unspecific. However, when seen in combination these should raise the suspicion of fetal infection, highlighting the need for a full fetal assessment. Still, some fetuses deemed normal on prenatal imaging are symptomatic at birth or develop delayed cCMV-associated symptoms, leaving room for improvement of diagnostic tools. Advanced MR sequences may help in this field and in determining prognosis, but further studies are needed.     

Prenatal diagnosis of a fetus with androgen insensitivity syndrome (AIS)

Objective The aim of this study is to describe a fetus with androgen insensitivity syndrome diagnosed at mid-second trimester. Case and Methods Nuchal translucency was measured thick and double test was found higher. The patient referred to our center at 16^th weeks of gestation. Fetal ultrasound examination and amniocentesis was performed. Results The nuchal translucency (NT) of fetus in present pregnancy was measured approximately 10 mm at 13 weeks and Down syndrome risk was calculated 1 in 10 by double test. On ultrasound examination; thick nuchal fold (NF) and short fetal limbs were found, and the fetus was seen a female and amniocentesis was performed. Three weeks later the fetal karyotype was reported normal as 46,XY. Thereupon the fetus reexamined for 2D and 4D ultrasound, and confirmed previous findings. The fetus was terminated at 19^th weeks and seen a female phenotype. The fetal gonads removed in abdomen and testicles confirmed histopatologically. Conclusion In generally, diagnosis of AIS is most made postnatally. This is the second case in English literature, which diagnosed mid-second trimester. In this situation, the fetus with thick NT/NF and short limbs may be AIS, therefore appearance of fetal sex on ultrasound should be compared with genetic sex Copyright © 2007 John Wiley & Sons, Ltd.     

Prenatal diagnosis and management of fetal ovarian cysts

Congenital ovarian cysts are a pathological condition which can be diagnosed in utero by ultrasound. We report 14 consecutive diagnoses of fetal ovarian cysts, obtained in the second and third trimesters of pregnancy. Congenital ovarian cysts have almost invariably a good prognosis, and no change in the standard obstetrical management is required. However, the evolution of the disease in utero is extremely variable. The cyst may increase in size, decrease or even disappear, or undergo complications such as torsion and rupture, which may carry some risks to the fetus. When a fetal ovarian cyst is detected, serial ultrasound examinations should be performed. If one of the above complications is suspected, the option of prompt caesarean section should be considered.     

The fetal circulation

Accumulating data on the human fetal circulation shows the similarity to the experimental animal physiology, but with important differences. The human fetus seems to circulate less blood through the placenta, shunt less through the ductus venosus and foramen ovale, but direct more blood through the lungs than the fetal sheep. However, there are substantial individual variations and the pattern changes with gestational age. The normalised umbilical blood flow decreases with gestational age, and, at 28 to 32 weeks, a new level of development seems to be reached. At this stage, the shunting through the ductus venosus and the foramen ovale reaches a minimum, and the flow through the lungs a maximum. The ductus venosus and foramen ovale are functionally closely related and represent an important distributional unit for the venous return. The left portal branch represents a venous watershed, and, similarly, the isthmus aorta an arterial watershed. Thus, the fetal central circulation is a very flexible and adaptive circulatory system. The responses to increased afterload, hypoxaemia and acidaemia in the human fetus are equivalent to those found in animal studies: increased ductus venosus and foramen ovale shunting, increased impedance in the lungs, reduced impedance in the brain, increasingly reversed flow in the aortic isthmus and a more prominent coronary blood flow. Copyright © 2004 John Wiley & Sons, Ltd.     

Amniotic band syndrome causing fetal head deformity

Amniotic band syndrome is a rare cause of fetal head deformity. We report a case in which antenatal ultrasound in the first half of pregnancy indicated the presence of a fetal cranial deformity, reported as either anencephaly or encephalocele. At assessment autopsy, disruption of the fetal skull was associated with amniotic band formation. Appropriate genetic counselling can be offered to such patients only when detailed pathological examination of the aborted fetus is made. The recurrence rate of amniotic band syndrome does not warrant amniocentesis in a subsequent pregnancy.     

Prenatal diagnosis and prenatal imaging features of fetal monosomy 1p36

Deletion of the distal end of the short arm of chromosome 1 (1p36) is thought to be a common terminal chromosomal deletion. However, few cases prospectively diagnosed prenatally have been reported. In this case, prenatal ultrasound at 21 weeks of gestation noted the fetus to have mild ventriculomegaly (Vhanterior = 11 mm and Vhposterior = 12 mm) and increased nuchal edema (6 mm). Maternal serum α-fetoprotein was normal unlike in a majority of previously described cases. The prenatal ultrasound features were further clarified with fetal MRI. Chromosome analysis following amniocentesis demonstrated a 1p36 deletion, which was confirmed by fluorescence in situ hybridization (FISH). The syndrome associated with 1p36 deletion is well described in infants and is characterized by typical facial features (prominent forehead, straight eyebrows. deep-set eyes, flat nasal bridge and a pointed chin). Other associated features are neurodevelopmental delay, seizures, cardiomyopathy and neurosensory hearing impairment. This case supplements our knowledge of the prenatal features of 1p36. Identification of this deletion by direct chromosomal analysis can be technically difficult and vigilance is required to improve diagnosis. FISH analysis is an important diagnostic adjunct where the diagnosis is suspected following classical G-banding techniques. However, in this chromosomal anomaly there remain few characteristic prenatal signs that are readily diagnosed with prenatal imaging. Copyright © 2007 John Wiley & Sons, Ltd.     

Cardiotocographic and sonographic findings in two cases of antenatally diagnosed intrauterine fetal brain death

Intrauterine fetal brain death is a rare cause of a fixed fetal heart rate pattern. Seven cases have been previously reported in the literature, but only two of them were diagnosed prenatally and all the newborns died soon after delivery. Two additional cases of antepartum diagnosis of intrauterine fetal brain death, managed expectantly, are reported. We had the unique opportunity to document progressive sonographic cerebral changes during the follow-up period, following the neurological event, while the fetus continued life and growth in utero. The cardiographic and sonographic findings suggesting intrauterine fetal brain death were a prolonged fixed fetal heart rate, even following a vibroacoustic and contraction stress test; an atonic fetus without breathing and body movement; and the appearance of hydramnios and the development of ventriculomegaly.     

Prenatal diagnosis of Hunter syndrome using fetal plasma

The X-linked Hunter syndrome or mucopolysaccharidosis II was diagnosed in a male fetus by demonstrating a severe deficiency of iduronate 2-sulphate sulphatase activity in fetal plasma obtained by umbilical fetal blood sampling at 23 weeks of pregnancy. The diagnosis was confirmed after termination of pregnancy.     

Mild fetal cerebral ventriculomegaly as a prenatal sonographic marker for Kartagener syndrome

Primary ciliary dyskinesia (PCD), also referred to as immotile-cilia syndrome or Kartagener syndrome, is a group of genetic disorders caused by defective cilia leading to chronic sinupulmonary infection, situs inversus and reduced fertility. Some PCD patients also have cerebral ventriculomegaly or hydrocephalus. We report here two fetuses and one newborn with mild cerebral ventriculomegaly and a suspected and/or confirmed diagnosis of PCD. These cases demonstrate that mild fetal cerebral ventriculomegaly can be a prenatal sonographic marker of PCD, certainly in fetuses with situs inversus or a history of a previous sib with PCD. Copyright © 2003 John Wiley & Sons, Ltd.     

Trisomy 12 mosaicism in amniocytes and dysmorphic child despite normal chromosomes in fetal blood sample

Trisomy 12 mosaicism (44 per cent) was detected prenatally in cultured amniocytes. A cordocentesis was performed to confirm the result. Only normal cells were found in the fetal blood sample. The fetus was estimated to be at a low risk of having a chromosomal abnormality and the pregnancy continued. Eight days after birth, a congenital heart defect was detected in the child. Several dysmorphic features were also evident. Further karyotyping of different tissues revealed normal blood and urinary cells but trisomic cells in the placenta (100 per cent) and in skin fibroblasts (25 per cent). The child died at 5 weeks of age. In this case, the fetal blood sample failed to reveal the real chromosome constitution of the fetus.     

Prenatal interventions for fetal lung lesions

The widespread availability of high resolution ultrasound equipment and almost universal routine anatomy scanning in all pregnant women in the developed world has lead to increased detection of abnormalities in the fetal thorax. Already in the 1980s, large pleural effusions and significant macrocystic lesions in the fetus were easily detected on ultrasound. However, smaller lung tumours were often missed. Nowadays, fetal medicine centres receive many referrals for evaluation of fetal lung lesions, of which the most common are congenital cystic adenomatoid malformation and bronchopulmonary sequestration. Almost invariably, both the parents and the referring physicians experience anxiety after detection of large lung masses in the fetus. However, the vast majority of the currently detected fetal lung lesions have an excellent prognosis without the need for prenatal intervention. In the small group of fetuses in which the prognosis is poor, almost exclusively those with concomitant fetal hydrops and cardiac failure, several options for fetal therapy exist, often with a more than 50% survival rate. Indications, techniques, complications and outcomes of these interventions will be described in this review. Copyright © 2011 John Wiley & Sons, Ltd.     

Adverse perinatal outcome in patients screen-positive for neural tube defects and fetal down syndrome

An association between various abnormal mid-trimester maternal serum analyte values and adverse perinatal outcome has been reported. From an original sample of 14 857 women, we observed five women who were ‘screen-positive’ for both neural tube defects [maternal serum alpha-fetoprotein (MSAFP) ≥2·5 multiples of the median] and Down syndrome [risk ≥1/274 using MSAFP, maternal serum unconjugated oestriol (MSuE3), maternal serum human chorionic gonadotropin (MShCG), and maternal age]. The four patients who elected to undergo amniocentesis all demonstrated both normal karyotype and normal amniotic fluid AFP levels. All five cases were associated with intrauterine growth retardation (IUGR) and abnormal pregnancy outcomes. Two cases exhibiting severe IUGR on ultrasound examination were terminated at 19·1 and 21·2 weeks, respectively; the former also exhibited fetal calcifications and positive maternal serology for toxoplasmosis. In another case, fetal demise occurred at 36 weeks' gestation in a patient who had been treated for syphilis in the second trimester. Neither infection was confirmed in fetal tissue studies. Though resulting in live births, the remaining two cases required operative deliveries; emergency Caesarean sections for fetal distress were performed at 38 and 32 weeks, respectively, the latter case being associated with severe pre-eclampsia. We conclude that elevated mid-trimester MSAFP levels concurrent with maternal serum analyte values associated with increased risk for fetal Down syndrome may presage a poor perinatal outcome, particularly IUGR and possibly congenital infection.     

Noninvasive detection of fetal sex: the laboratory diagnostician's view

Toward the end of the twentieth century it was discovered that cell-free fetal DNA sequences could be detected in maternal blood plasma. Initially, Y-chromosome sequences originating from male fetuses were targeted in cell-free DNA extracted from maternal plasma in order to demonstrate proof of this concept towards the development of noninvasive prenatal diagnosis methods. Clinical application of this approach is now possible. Fetal sex can be detected through a procedure that is noninvasive with respect to the fetus. Specifically, the presence of Y-chromosome sequences in maternal blood plasma indicates that the fetus is male, whereas lack of a signal will indicate that the fetus is female. Fetal sex can be detected very early, from at least the 7th week of pregnancy (and even earlier, according to several studies), about two months before this information is available through ultrasound scanning. Although the controversial issue of fetal sexing is not new, it is expected that with the availability of an accurate noninvasive test, public interest will rise. It is therefore imperative that an authorized committee of experts in each country generates an official policy regarding application of the test. Copyright © 2006 John Wiley & Sons, Ltd.     

Trisomy 10: ultrasound features and natural history after first trimester diagnosis

We report on the ultrasound features and natural history of trisomy 10. At 12 weeks' gestation in a routine scan examination, the fetus presented with increased nuchal translucency thickness, mild skin oedema, bilateral pleural effusion, marked micrognathia, cardiomegaly, unilateral talipes and reversed A-wave in the ductus venosus blood flow. Karyotyping on chorionic villus sampling (CVS) led to the diagnosis of trisomy 10, which was confirmed by fetal blood sampling at 22 weeks' gestation. As the parents opted to continue with the pregnancy, the natural history and following ultrasound features are described. This is the third case of trisomy 10 in the literature reporting on the physical features. The most frequent ultrasound findings presented in trisomy 10 are increased nuchal translucency, micrognathia, renal agenesis, facial cleft, limbabnormalities, cardiac defects and early severe growth retardation. Copyright © 2001 John Wiley & Sons, Ltd.     

Amniotic band syndrome in second trimester associated with fetal malformations

The Possibility of severe fetal malformations, including neural tube defects, secondary to early amniotic rupture followed by formation of fibrous bands (amniotic band syndrome) is a well-known entitity. The fact that these pregnancies are usually uneventful makes prenatal diagnosis difficult, but routine determination of serum alphafetoprotein, followed by ultrasound scanning, may detect some of the malformations. We present a case, where detection of a neural tube defect led to induced second trimester abortion of a fetus severely affected by this syndrome. There appeared to be a causal relationship between maternal trauma and the amniotic rupture.