The normal fetus of an acardiac twin pregnancy: Perinatal management based on echocardiographic and sonographic evaluation

Experience with three prenatally diagnosed pregnancies complicated by an acardiac twin reveals that ultrasonography and echocardiography are helpful in detecting early signs of in-utero congestive heart failure in the normal twin. The use of Doppler blood flow analysis to determine direction of blood flow, post-mortem placental and fetal angiography, and umbilical cord blood gas determination provided proof that retrograde arterial perfusion occurs in the acardiac fetus. In a fourth pregnancy, an experimental approach to occlude the acardiac twin's umbilical cord was attempted, but was unsuccessful.     

Acardiac anomaly: current issues in prenatal assessment and treatment

Acardiac anomaly is a rare condition affecting monochorionic multiple pregnancies. We review this condition with emphasis on its prenatal diagnostic features and treatment options. Due to the parasitic hemodynamic dependence of the acardiac twin on the pump twin, it is important to monitor the pump twin for signs of decompensation and, if indicated, intervene by interrupting vascular supply to the acardiac twin. The goal of treatment is to maximize the pump-twin's chance of survival. To assist with the decision of when to treat, we suggest a new classification system based on prognostic factors, specifically the size and growth of the acardiac twin and the cardiovascular condition of the pump twin. When the acardiac twin is small and no signs of cardiovascular impairment in the pump twin are present, we suggest serial ultrasound surveillance to detect any worsening of the condition. In cases with a large acardiac twin or rapid growth of the acardiac mass, we recommend prompt intervention. Once treatment is indicated, the intrafetal approach to interrupt the vascular supply to the acardiac twin appears to be superior to cord occlusion techniques as it is simpler, safer and more effective. The first line of treatment, if available, should be ultrasound-guided laser coagulation or radiofrequency ablation of the intrafetal vessels. Copyright © 2005 John Wiley & Sons, Ltd.     

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.     

A misdiagnosis of X-linked adrenoleucodystrophy in cultured chorionic villus cells by the measurement of very long chain fatty acids

A case is reported of a male fetus at risk of X-linked adrenoleucodystrophy who showed a normal cultured chorionic villus cell very long chain fatty acid (VLCFA) profile but at birth exhibited grossly abnormal plasma and cultured fibroblast VLCFAs. Maternal contamination or a sample mix-up was excluded by chromosome analysis and analysis of polymorphic markers. This is the second report of a fetus affected with this disorder who showed normal cultured chorionic villus cell VLCFAs. It highlights the importance of a proper audit of all prenatal diagnoses to evaluate method reliability.     

Mid–trimester hyperechogenic bowel in a fetus of Japanese origin carrying a new mutation of CFTR gene (L548Q)

We present a case of a fetus with hyperechogenic bowel, in which the L548Q mutation was detected in the mother of Japanese origin and the ΔF508 mutation in the father of Caucasian origin. The fetus proved to be compound heterozygous. Research into cystic fibrosis transmembrane conductance regulator (CFTR) mutations in this case was triggered by the fact that the fetus had a characteristic hyperechogenic bowel image with normal karyotype and no indications of intrauterine infections. Hyperechogenic bowel is highly indicative of a CFTR gene mutation. The incidence of cystic fibrosis (CF) in fetuses with mid-trimester hyperechogenic bowel is 5%, but once the most frequent mutations have been accounted for, rarer mutations must be investigated. Copyright © 2006 John Wiley & Sons, Ltd.     

Cystic hygroma simulating an encephalocele

An ultrasound examination at 17 weeks gestation on a woman with a family history of spina bifida suggested that the fetus had a closed encephalocele. Amniotic fluid alphafetoprotein, rapidly adhering cells and acetylcholinesterase gel electrophoresis were normal. The pregnancy was terminated and the fetus was found to have a large cystic hygroma. It is suggested that in counselling parents of an infant or fetus with a cystic hygroma and with a normal chromosome constitution, ultrasound examination in future pregnancies is advisable, because of the possibility of autosomal recessive inheritance.     

Prenatal determination of dihydropteridine reductase in a normal fetus at risk for malignant hyperphenylalaninemia

Assay of dihydropteridine reductase in amniotic cells from a fetus at risk for malignant hyperphenylalaninemia is described. A normal result was obtained, this was confirmed after delivery. On two-dimensional polyacrylamide gel electrophoresis the enzyme from amniotic cells showed the same mobility as the mature liver reductase.     

Prenatal ultrasound diagnosis of congenital heart disease associated with intrauterine growth retardation. A report of 2 cases

Two fetuses with extreme growth retardation (IUGR) of 31 and 34 weeks gestation were studied using a combination of two dimensional echocardiography (2DE), pulse wave Doppler (PWD) and differential measurement of the instantaneous vessel diameter techniques. The first fetus was diagnosed as having univentricular heart or possible double outlet right ventricle (DORV). Descending aorta blood flow was reduced as was indexing for weight. The second fetus was diagnosed as having univentricular heart with periodic bigeminal and trigeminal rhythm. Descending aorta blood flow was measured on two occasions and was reduced both times. Indexing for weight was within normal limits the first time and showed gross reduction on the second occasion prior to fetal demise. Fetal death occurred in both cases at 34 weeks gestation. Cardiovascular evaluation in fetuses with IUGR is useful as the detection of severe congenital cardiac abnormalities may substantially alter the management of these pregnancies, in particular caesarean section may be avoided when the prognosis for the fetus is considered hopeless.     

Non-ketotic hyperglycinaemia: Glycine/serine ratio in amniotic fluid–an unreliable method for prenatal diagnosis

We describe a prenatal diagnosis of a fetus at risk for non-ketotic hyperglycinaemia based on the glycine/serine ratio in amniotic fluid at 16 weeks of gestation. Although the glycine level and the glycine/serine ratio in amniotic fluid were within the normal range, the fetus was affected and therefore a false-negative prediction was made. The reliability of this method is questioned.     

Marker chromosomes in A series of 10000 prenatal diagnoses. Cytogenetic and follow-up studies

In a series of 10 000 prenatal diagnoses 15 marker chromosomes were detected in our centre. Six of these were familial whilst nine had originated de novo. They were analysed with various staining methods. DA-DAPI staining was positive in nine out of 12 pregnancies. Six pregnancies were continued. Five normal children were born, one ended in intrauterine fetal death of a normal fetus at 37 weeks. Nine pregnancies were terminated, showing six normal fetuses, one familial cat-eye syndrome, one fetus with Down syndrome caused by additional trisomy 21 and one fetus with cystic kidneys resp. It is concluded that it seems safe to continue the pregnancy in cases of a familial marker, identical to that of one parent, whilst a de novo DA-DAPI positive marker seems to present a low risk for fetal anomalies.     

The possibility of prenatal diagnosis by gene dosage: Confirmation of duplication 10q24→qter from Got-l activity in fetal erythrocytes

The activity of four enzymes, including GOT-1, has been investigated in the erythrocytes of a 10q→24qter trisomic fetus. Analyses have been performed on a feto-maternal blood mixture sampled by fetoscopy and on red cells obtained by cardiac puncture, following therapeutic abortion. The demonstration of a 40 percent increase of GOT-1 activity, as compared to normal fetuses of similar gestational age, suggests that gene dosage studies may be a useful confirmatory technique in prenatal diagnosis of unbalanced chromosomal aberrations. Practical application of a similar diagnostic approach is conditioned by (1) precise characterization of fetal chromosome imbalance; (2) confirmed assignment of the gene locus coding for the gene product under investigation; (3) evidence of a linear proportionality between gene dose and concentration of the gene product in patients with the same chromosome imbalance detected in the fetus; (4) knowledge of the range of normal variation at different weeks of gestation of the enzyme activity to be tested in the fetus; (5) safety of fetal sampling procedure.     

Prenatal diagnosis of osteogenesis imperfecta type III

Ultrasonographic and radiographic evaluation of a fetus at risk for osteogenesis imperfecta (O.I) type III was performed. Real-time ultrasound measurements at 15 weeks gestation were interpreted as normal, but at 20 and 22 weeks of gestation revealed marked shortening of the long bones and deformity of the femurs. The findings were confirmed by fetal radiography at 22 weeks gestation. Radiographic and histologic changes characteristic of O.I. were observed in the aborted fetus. Thus the antenatal manifestations of O.I. type III maybe severe enough to make prenatal diagnosis possible in the second trimester for families at risk for recurrence of this disorder.     

Evaluation of inorganic pyrophosphate in amniotic fluid as a mode of prenatal diagnosis of osteogenesis imperfecta

Using a modified procedure by Solomons and Styner (1969), an evaluation of inorganic pyrophosphate (PPi) was performed on the amniotic fluid of two fetuses at risk for osteogenesis imperfecta (OI) at 14½ weeks gestation. The parents of both cases had a previous child with OI, Type II. The normal control group at 14–16 weeks gestation had PPi values ranging from 22.0–59.2 ug/100 ml, with a mean of 38.6±9.51 ug/100 ml. In each at-risk fetus, the amniotic fluid PPi value was within normal range. The first baby was born phenotypically normal at term. Intrauterine radiographic and fetal sonograms were done on the second fetus at approximately 19 weeks gestation. Both showed evidence of OI, Type II. The pregnancy was terminated at 21 weeks. Radiologic studies of the aborted fetus were consistent with OI, Type II. Our results indicate that the evaluation of PPi levels in amniotic fluid is not the method of choice for prenatal diagnosis of IO.     

Pitfalls in the prenatal diagnosis of peroxisomal β-oxidation defects by chorionic villus sampling

Variability in the level of expression of very long chain fatty acids (VLCFAs) is documented in cultured chorionic villus (CV) cells derived from two fetuses, one at risk for an unusual peroxisomal fatty acid β-oxidation defect, and the other at risk for the X-linked form of adrenoleucodystrophy (ALD). Cells from early subcultures of chorionic cells from both cases gave normal values for VLCFA ratios. The results for the fetus at risk for the β-oxidation defect were interpreted to indicate that the fetus was not affected; however, at birth, the infant was clinically and biochemically affected. In the case of the fetus at risk for X-linked ALD, although VLCFAs were normal in subculture 1, the levels of these fatty acids increased dramatically in subculture 3, suggesting an abnormal fetus. Termination of the pregnancy and subsequent biochemical and morphological follow-up confirmed that the fetus was indeed affected by ALD.     

Prenatal diagnosis of familial ring 21 chromosome

Ring chromosome 21 is a rare chromosome anomaly often associated with mental retardation and dysmorphic features. Less commonly, the ring chromosome can be familial and associated with a normal phenotype. Phenotypically normal female carriers, however, are at increased risk of having children with Down syndrome, mosaic monosomy 21, and variable duplication or deletion of chromosome 21. Because of the relative mitotic and meiotic instability of ring chromosomes, abnormal cytogenetic findings encountered during prenatal diagnosis may not reflect the true genetic status of the fetus. This is a report of a phenotypically normal female carrier of a familial ring 21 chromosome. Prenatal diagnosis on her twin pregnancy revealed a mosaic 46,XX,r(21)(p13;q22) (77 per cent)/45,XX, – 21 in one fetus and a normal male karyotype in the second. The pregnancy was carried to term. Both infants are completely normal, with a non-mosaic ring 21 karyotype from the lymphocytes of one twin. The diagnostic uncertainty and problematic genetic counselling related to fetal cytogenetic abnormalities are the subjects of this report.     

Cystic hygroma: Prenatal diagnosis and genetic counselling

Six cases of cystic hygromas detected during second trimester ultrasound examination are reported: 4 fetuses (67 per cent) had a 45, X karyotype, 1 fetus had trisomy 18, 1 fetus had a normal karyotype (46,XX) and at autopsy multiple anomalies were observed. In the latter case the family history suggested an autosomal recessive pattern of inheritance. In order to reach a definite diagnosis and give proper genetic counselling when a fetus is found to have cystic hygroma, a fetal karyotype as well as a family and reproductive history should be obtained.     

First-trimester alpha-fetoprotein screening for Down syndrome

Screening for Down syndrome and other chromosomal aneuploidies by biochemical parameters in maternal serum is well established for the second trimester. With screening as late as 16 weeks of gestation, the option of chorionic villus sampling (CVS) unfortunately is lost. In our study population, the maternal serum alpha-fetoprotein (MSAFP) concentration was determined in 2471 women in the first trimester immediately prior to CVS. Although in this sample MSAFP tended to be lower in Down syndrome (DS) pregnancies than in pregnancies with a chromosomally normal fetus, at this early gestational age neither a fixed cut-off level of 0·5 multiples of the normal median (MOM) nor one of 0·6 MOM was suitable for identifying pregnancies at higher risk for DS. This also applied to trisomy 18, although on average MSAFP in trisomy 18 pregnancies was lower than in normal and DS pregnancies.     

The effect of fetal gender on second-trimester maternal serum inhibin-A concentration

Second-trimester serum inhibin-A is increasingly used as a fourth marker in addition to the triple test to screen for Down syndrome. We investigated whether fetal gender had an effect on serum inhibin-A concentration. A retrospective analysis was done on 316 normal pregnancies and 48 Down syndrome pregnancies in which maternal serum inhibin-A assays were performed between 15 and 20 weeks of gestation and in which the fetal sex was known. The median inhibin-A MoM (95% CI) for normal pregnancies in the presence of a male fetus was 0.93 (range 0.88–1.03). This was significantly lower than that in the presence of a female fetus (median MoM=1.04). The gender difference was not observed in the Down syndrome pregnancies. The increased inhibin-A concentration would lead to a 2.3-fold higher false-positive rate in the presence of a female fetus (10.6% vs 4.6%; p<0.05, Chi-square test). Because of the small number of cases studied, the results need to be substantiated by a larger series. If the gender effect is confirmed, adjustment for fetal sex may be necessary when inhibin-A is used as a screening marker. Copyright © 2001 John Wiley & Sons, Ltd.     

Pericentric inversion of chromosome 19: prenatal diagnosis and genetic counselling

During prenatal diagnosis for advanced maternal age, a pericentric inversion of a chromosome 19 was detected in a male fetus. The inversion was familial, transmitted to the fetus by the phenotypically normal mother. The pregnancy resulted in a term birth of a phenotypically normal male infant. Inversion 19 appears to be a rare abnormality with only seven families reported thus far including ours. Infants with duplication deficiencies for chromosome 19 have not been reported in these families. This may suggest an apparent suppression of crossing over and recombination within the inverted segment of chromosome 19 during meiosis.     

Genetic basis of lethal junctional epidermolysis bullosa in an affected fetus: Implications for prenatal diagnosis in one family

Fetal skin biopsy at 20 weeks' gestation in a woman at risk for a child with the lethal skin-blistering disorder junctional epidermolysis bullosa (Herlitz) confirmed an affected fetus. Genomic DNA from the aborted fetus was examined for mutations in laminin 5, a macromolecule involved in adhesion at the dermal-epidermal junction, and a candidate protein in this condition. Polymerase chain reaction (PCR) amplification of exon 10 and parts of the flanking introns of the gene encoding the β3 chain of laminin 5 (LAMB3) and subsequent analysis by agarose gel electrophoresis showed a more slowly migrating band in the affected fetus compared with the normal control. Nucleotide sequencing of the abnormal PCR product revealed a homozygous 77 bp duplication within the exon, resulting in a premature termination codon 250 bp downstream from the 3′ end of the duplication. Maternal DNA was heterozygous for the mutant and wild-type alleles. These findings illustrate the genetic basis of the skin disease in this case and also offer the prospects of a simple, rapid, and reliable first-trimester DNA-based prenatal, or even preimplantation, diagnostic test for future pregnancies in this family.