Prenatal diagnosis of congenital human cytomegalovirus infection

Fifteen fetuses at risk of congenital human cytomegalovirus (HCMV) infection underwent prenatal diagnosis at 16–30 weeks' gestation by a combination of amniocentesis and fetal blood sampling. HCMV was isolated from the amniotic fluid in six patients, but HCMV-specific IgM was detected in only three of them. Two of the nine neonates, who were delivered following a negative prenatal diagnosis, had congenital HCMV infection diagnosed by virus isolation in the urine. The interval from infection to prenatal testing was 3 and 4 weeks in the two false-negative cases and ⩾ 7 weeks in the true-positive cases. Although timely testing for HCMV infection allows the option of termination of pregnancy, it may be flawed by false-negative results.     

Sonographic diagnosis of fetal congenital cataracts

Five fetuses with congenital cataracts diagnosed in utero by ultrasound are reported. The fetuses, who were between 14 and 27 weeks' gestation, also had other severe malformations. The sonographic features of the cataracts are presented.     

Transvaginal sonography—detection of findings suggestive of fetal chromosomal anomalies in the first and early second trimesters

Over a 4-year period, 14 dyskaryotic fetuses were diagnosed by amniocentesis, performed after early detection of malformations using transvaginal sonography (TVS). These 14 dyskaryotic fetuses were detected out of 4878 sonographic screenings performed by TVS between 9 and 16 weeks' gestation. Twenty-eight per cent of the referrals were at high risk and 72 per cent were at low risk for fetal malformations. Two hundred and twenty-nine fetuses (4.7 per cent) of the screened population had 265 anomalies, 39 per cent of them being transient. In 7 of the 14 dyskaryotic fetuses (50 per cent), the sonographically detected anomalies were transient, being undetected by follow-up sonographic screenings at later gestational ages (⩾18 weeks). Postponing the first sonographic scan aimed at malformation detection to a later gestational age may lead to transient anomalies and their associated dyskaryosis being missed.     

Prenatal Diagnosis of congenital disorder of glycosylation type Ia (CDG-Ia) by cordocentesis and transferrin isoelectric focussing of serum of a 27-week fetus with non-immune hydrops

Blood was obtained by cordocentesis from a fetus with non-immune hydrops demonstrated by ultrasound scanning at 27 weeks' gestation. Abnormalities of serum transferrin isoelectric focussing (IEF) were identified, characteristic of a congenital disorder of glycosylation type I (CDG-Ia). A diagnosis of CDG-Ia was confirmed by enzyme analysis of cultured amniocytes. This is the first report of CDG-Ia diagnosed by serum analysis in a fetus. Previous reports have warned that diagnostic abnormalities do not appear in serum until several weeks after birth. The sensitivity of cordocentesis transferrin IEF is unknown but is less than 100% effective because cases have been diagnosed postnatally after normal prenatal or neonatal studies. Enzyme analysis or mutation analysis is required for diagnosis of congenital disorder of glycosylation (CDGs) regardless of whether a diagnostic transferrin pattern is identified prenatally. The analysis of a small sample of serum, from cordocentesis, performed to check for fetal anemia, simplified the investigation, diagnosis, and genetic counselling of a case of non-immune hydrops detected at 27 weeks' gestation. This might be a useful test for other cases in these circumstances, as fetal blood is usually collected to check for anemia. Copyright © 2006 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.     

Novel mutation and prenatal sonographic findings of glutaric aciduria (type I) in two Taiwanese families

Glutaric aciduria type I (GA I) is an autosomal recessively inherited inborn error with a defect of the enzyme glutaryl-CoA dehydrogenase (GCDH), which has never been diagnosed prenatally in Taiwanese patients. We present the prenatal sonographic findings and mutational analysis data of three children in two Taiwanese families. One patient from each family was diagnosed postnatally due to macrocephaly and neurological deterioration at 4 months and 10 months, respectively. The third child, sister of the first patient, was diagnosed prenatally at 11 weeks' gestation through chorionic villus sampling (CVS). Molecular analysis revealed that the fetus and child in Family 1 were homozygous for a common mutation, IVS10 -2A>C, which has not been reported in the Caucasian population. The patient in Family 2 was a compound heterozygote for IVS10 -2A>C and a novel mutation 749T>C (L238P). After genetic counseling, the couple decided to continue the second pregnancy. However, dilatation of quadrigeminal cistern (QC) and suspicious macrocephaly were noted at 30 weeks. Progressive dilatation of the QC associated with macrocephaly, fronto-temporal atrophy and wide space of perisylvian fissure were found in the follow-up scans. The affected girl was delivered at 37 weeks' gestation by cesarean section. Postnatal magnetic resonance imaging (MRI) studies confirmed the prenatal sonographic findings. With prenatal sonographic findings and mutational analysis presented in the present cases, the feasibility of prenatal diagnosis of GA I in high-risk pregnancy can not be overlooked. Copyright © 2002 John Wiley & Sons, Ltd.     

Simpson—Golabi—Behmel syndrome: Disproportionate fetal overgrowth and elevated maternal serum alpha-fetoprotein

Simpson—Golabi—Behmel (SGB) syndrome is an X-linked condition with pre- and postnatal overgrowth, characteristic facies, and visceral and skeletal anomalies. We report an affected male who presented at 16 weeks' gestation with elevated maternal serum α-fetoprotein (MSAFP). Fetal measurements at 20 and 31 weeks' gestation were disproportionate, with marked macrosomia but a low head to abdominal circumference ratio and normal femur length. Fetal overgrowth with elevated MSAFP may prove to be useful markers for the prenatal diagnosis of SGB syndrome.     

Prenatal diagnosis of congenital cytomegalovirus infection: False-negative amniocentesis at 20 weeks' gestation

Cytomegalovirus (CMV) is the most common cause of congenital infection. Recent studies show amniocentesis to be a 100 per cent sensitive and 100 per cent specific predictor of congenital infection, and recommend that it be offered in the at-risk pregnancy. However, these publications have focused on pregnancies at or beyond 22 weeks' gestation. Here, we report a case of maternal CMV hepatitis at 7–8 weeks' gestation, in which culture and polymerase chain reaction testing for CMV in amniotic fluid at 20 weeks' gestation were negative, but the infant had a positive CMV urine culture shortly after delivery. Implications for the prenatal diagnosis of CMV infection are discussed.     

Early second trimester prenatal diagnosis of Neu-Laxova syndrome

Neu-Laxova is a rare, uniformly lethal, autosomal recessive condition with characteristic limb posturing, facial dysmorphic features, and central nervous system abnormalities. Forty-two cases of Neu-Laxova syndrome have been reported, with only four of these diagnosed prenatally. Three of the four cases were diagnosed at or after 32 weeks' gestation. The fourth case was diagnosed at 22 weeks' gestation in a patient who was followed with serial ultrasound studies due to having a prior affected child. At 19 weeks' gestation, we present the earliest reported prenatal diagnosis of Neu-Laxova syndrome in a primigravida with a non-informative family history. Copyright © 2002 John Wiley & Sons, Ltd.     

Ultrasonographic method for detection of haemoglobin Bart's hydrops fetalis in the second trimester of pregnancy

In nine pregnant women at risk for fetal alpha-thalassaemia, the two affected fetuses were diagnosed by ultrasonography at 18–20 weeks' gestation. In countries with limited resources, ultrasonography provides a cost-effective method of prenatal screening for this condition.     

Cystic hygroma and congenital diaphragmatic hernia: Early prenatal sonographic evaluation of Fryns' syndrome

We report a case of cystic hygroma and diffuse lymphangiectasia detected by sonogram at 12 weeks' gestation. Fetal karyotype was normal. At 20 weeks' gestation, herniation of the bowel into the chest was noted. At delivery, the infant was diagnosed as having Fryns' syndrome. This is the first reported case of Fryns' syndrome presenting with cystic hygroma.     

Cardiac and extra-cardiac anomalies as indicators for trisomies 13 and 18: A prenatal ultrasound study

The purpose of the present study was to establish sonographic markers for prenatal diagnosis of trisomies 13 and 18. Retrospective analysis of sonographic morphology was therefore carried out in seven fetuses with trisomy 13, and 16 fetuses with trisomy 18. Gestational age ranged between 17 and 39 weeks (median 28 weeks). Polyhydramnios and symmetrical growth retardation were present in 14 of 23 fetuses. A cardiac anomaly was diagnosed in all 23 fetuses, the majority representing a ventricular septal defect (n = 8) or double outlet right ventricle (n = 8). Extra-cardiac anomalies were characterized by a high incidence of limb deformities (polydactyly, clenched hands, club feet; n = 15) and omphalocele (n = 7). We conclude that the combined appearance of cardiac and extra-cardiac anomalies should prompt fetal karyotyping. Cardiac anomalies in combination with fetal limb deformities and omphalocele are suspicious for trisomies 13 and 18.     

Prenatal exclusion of Hurler's disease by leucocyte α-L-iduronidase assay

Hurler's disease was excluded in a fetus at 23 weeks' gestation by demonstrating normal iduronidase activity in fetal leucocytes following failure of amniotic cell culture after amnic-centesis at 16 and 19 weeks' gestation. The diagnosis was confirmed in the neonate.     

Short-rib polydactyly syndrome (SRPS) type III diagnosed during routine prenatal ultrasonographic screening. A case report

The prenatal diagnosis of skeletal dysplasias is often initiated by the finding of a shortened extremity during a routine sonographic examination. Second-trimester diagnosis of these anomalies allows the couple to consider the option of terminating a pregnancy when a lethal anomaly is detected. A 21-year-old Bedouin woman underwent routine ultrasonographic screening at 20 weeks' gestation. Severe micromelia, a narrow thorax with shortened ribs, and postaxial polydactyly were detected. The patient delivered a male dwarf at 20 weeks' gestation following prostaglandin induction of labour for a diagnosis of short-rib polydactyly syndrome type III. The prenatal ultrasonographic diagnosis of short-rib polydactyly syndrome type III was made at 20 weeks' gestation, allowing termination of the pregnancy. A proper sonographic approach to skeletal dysplasias allows both early detection and differentiation between lethal and non-lethal anomalies.     

Prenatal detection of rubella-specific IgM in fetal sera

Serum specimens were obtained by fetoscopy at 19–25 weeks' gestation from four fetuses whose mothers had had confirmed rubella earlier in pregnancy. They were tested for rubellaspecific IgM by antibody capture radioimmunoassay. No specific IgM was detected in one fetus and a healthy infant was delivered at term. Specific IgM was detected in the other three fetuses. In one case the level was low (1 unit) and this pregnancy went to term resulting in a neonate with clinical and laboratory evidence of congenital rubella infection. The remaining two fetuses had 2.8 and 2.4 units of specific IgM and the pregnancies were terminated. Blood obtained from these two fetuses after abortion showed levels of 5.4 and 2.9 units respectively. No specific IgM was detected in sera from eleven other fetuses aborted because of maternal rubella but five of these cases were terminated before 19 weeks and in five the interval between rash and abortion was three weeks or less. The results show that the human fetus can produce detectable specific IgM antibody by 19–20 weeks' gestation after exposure to rubella sevella several weeks earlier. However, a larger study is required to define the reliablity of fetoscopic blood sampling for the diagnosis of intrauterine infection.     

Trisomy 16 fetus surviving into the second trimester

A 27-year-old gravida 4, para 3 was found to have anhydramnios at 14 weeks' gestation following a size/date discrepancy noted at her routine prenatal visit. A detailed ultrasound revealed multiple fetal anomalies including congenital heart defect, chest hypoplasia, and bilateral dysplastic kidneys. Karyotype revealed trisomy 16 in 15/15 cells from a tissue specimen obtained from the fetal cord insertion site following elective pregnancy termination.     

Ultrasonography in pregnancy and fetal abnormalities: Screening or diagnostic test? IPIMC 1986–1990 register data

The aim of the present study was to assess the sensitivity of ultrasound diagnosis used as a screening test in detecting major congenital anomalies in the prenatal period in a large nation-based multicentre setting. Data from the IPIMC register were collected in the period 1986–1990. One hundred and thirty-five hospitals, located in 17 out of the 20 regions in Italy, participated in the register. Study cases were 3479 infants with major congenital anomalies diagnosed at birth or in the first week of life. Subjects with chromosomal anomalies or multiple defects were excluded. The sensitivity of ultrasound prenatal diagnosis was 49.5 per cent for central nervous system anomalies, 3.8 per cent for congenital heart diseases, 17.1 per cent for gastrointestinal tract defects, 46.6 per cent for abdominal wall defects, 74.8 per cent for urinary tract anomalies, and 22.9 per cent for skeletal abnormalities. The detection rate for diaphragmatic hernia was 24.2 per cent. Overall, only 18 per cent of the defects diagnosed in utero were detected before 24 weeks' gestation. The sensitivity of prenatal diagnosis was 30.1 and 19.0 per cent in the northern, central, and southern regions, respectively. In light of its low sensitivity, ultrasonography as a screening test in the general population should be abandoned, although some improvement in its performance should be expected following adequate training of the ultrasound staff and the use of good technical equipment.     

Short communication the natural history of fetal cytomegalovirus infection as assessed by serial ultrasound and fetal blood sampling: A case report

A patient in whom intrauterine fetal cytomegalovirus (CMV) infection was diagnosed at approximately 25 weeks' gestation is presented. The fetus was evaluated by serial fetal blood samplings and ultrasound examinations. The fetus manifested evidence of severe thrombocytopenia and hepatic inflammation, with recovery over a period of approximately 8 weeks. The initial sonographic findings of marked fetal ascites and cardiomegaly gradually resolved; ventriculomegaly developed during the third trimester. At delivery, the baby was morphologically normal with the exception of mild ventriculomegaly. Cord blood was negative for CMV IgM but urine was culture-positive for CMV. At age 3, the child has a severe but stable unilateral hearing deficit and is otherwise developmentally normal. This case demonstrates the utility of serial ultrasound and fetal blood sampling in the prenatal diagnosis and management of fetal CMV infection.     

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: The diagnostic role of prenatal ultrasonography

Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alpha- fetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed.     

Prenatal diagnosis of the Klippel-Trenaunay-Weber syndrome

The Klippel-Trenaunay-Weber syndrome is a complex developmental disorder of the vascular and skeletal systems. While many features of the syndrome are congenital, it has not been diagnosed often before birth. This paper describes a case of Klippel-Trenaunay-Weber syndrome diagnosed at 19 weeks' gestation on the basis of sonographic findings and family history. The clinical variability of the syndrome is emphasized and the importance of family history in differential diagnosis is stressed.