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.     

Isolating fetal nucleated red blood cells from maternal blood: The baylor experience—1995

In our previous work we have isolated fetal cells from maternal blood and used fluorescent in situ hybridization (FISH) for chromosome-specific probes to detect aneuploidy. Current efforts in the Baylor College of Medicine programme are focusing on obtaining consistency in flow-sorting methodology and on determining sensitivity and specificity. To this end, systematic evaluation of five glycophorin A (gly A) antibodies all produced agglutination, leading us to abandon the use of gly A antibodies for positive selection of fetal cells. Conversely, we have found LDS-751 to be useful for nuclear selection. CD45 negative selection can best be accomplished by the use of flasks coated with goat antibodies against mouse antibodies. Positive selection by flow sorting for either CD71⁺ cells or gamma-globin-positive cells seems to be successful. Using these two approaches, we have recently detected male (fetal) cells in pregnancies in which the fetus was 46, XY in 10 of 18 and in 12 of 14 cases, respectively.     

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.     

Isolating fetal cells in maternal circulation for prenatal diagnosis

Fetal cells unequivocally exist in and can be isolated from maternal blood. Erythroblasts, trophoblasts, granulocytes and lymphocytes have all been isolated by various density gradient and flow sorting techniques. Chromosomal abnormalities detected on isolated fetal cells include trisomy 21, trisomy 18, Klinefelter syndrome (47,XXY) and 47,XYY. Polymerase chain reaction (PCR) technology has enabled the detection of fetal sex, Mendelian disorders (e.g. β-globin mutations), HLA polymorphisms, and fetal Rhesus (D) blood type. The fetal cell type that has generated the most success is the nucleated erythrocyte; however, trophoblasts, lymphocytes and granulocytes are also considered to be present in maternal blood. Fetal cells circulate in maternal blood during the first and second trimesters, and their detection is probably not affected by Rh or ABO maternal-fetal incompatibilities. Emphasis is now directed toward determining the most practical and efficacious manner for this technique to be applied to prenatal genetic diagnosis. Only upon completion of clinical evaluations could it be considered appropriate to offer this technology as an alternative to conventional invasive and non-invasive methods of prenatal cytogenetic diagnosis.     

Immediate and unexplained fetal death during mid-trimester amniocentesis

Immediate and unexplained fetal death during mid-trimester amniocentesis for prenatal diagnosis was found to be an uncommon though real phenomenon. A survey of programmes in the United States detected 5 cases from 7524 at 4 centres. Postmortem examination was not helpful and a neurogenic mechanism is postulated. Awareness of this phenomenon and routine pre- and post-amniocentesis ultrasound monitoring may clarify the actual prevalence and etiology.     

Parental reaction and adaptability to the prenatal diagnosis of fetal defect or genetic disease leading to pregnancy interruption

The objective of the study was to evaluate the psychological reaction of two groups of parents to a pregnancy termination after they had undergone a prenatal diagnostic procedure. The analysis involved interviews with a study group of 76 patients who were at risk of giving birth to a child with a genetic disease or defect and a comparison group of 124 who had a pregnancy termination after a major anomaly had been detected by routine ultrasound and who were not at known risk for a genetic disease. Only patients in the study group had received counselling before the prenatal diagnosis and were aware that the fetus could be affected. The overall reaction of the comparison group was one of shock, denial of fetal abnormality, and guilt over ‘abandoning the fetus’. A feeling of guilt was expressed by patients in the comparison group (73 per cent versus 29 per cent) in the period immediately following the interruption. One-third of patients in both groups felt obliged to undergo a therapeutic abortion. More patients in the study group than in the comparison group expressed the need to see a psychiatrist at the time of the study (19 per cent versus 7 per cent) and viewed future pregnancies as a replacement for the lost pregnancy (63 per cent versus 19 per cent). The recommendations of the study focus on information sessions to personnel, nursing support, analgesia during the expulsion period, an atmosphere of respect that should be present at the time that the fetus is viewed, the anticipation of mourning, and the long-term follow-up of the couple to ensure that counselling for future pregnancies and psychological support are provided when needed.     

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.     

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.     

Normal fetal growth in women with antiphospholipid syndrome treated with high-dose intravenous immunoglobulin (IVIG)

Antiphospholid antibodies are associated with fetal distress and fetal death. Although different therapeutic regimens have been used, the incidence of fetal growth retardation varies between 30 and 60 per cent of reported cases. We report the evolution of fetal growth in patients with antiphospholipid antibody syndrome treated with high-dose intravenous immunoglobulins (IVIG). Fourteen patients with a history of recurrent spontaneous abortion and immunological diagnosis of antiphospholipid syndrome were followed longitudinally. Intravenous immunoglobulin at a dose of 0.5 g/kg body weight for two consecutive days was started from the fifth week of pregnancy and repeated every 4 weeks until the 33rd week of gestation. Fetal biometry was evaluated longitudinally from the appearance of the gestational sac at 4 weekly intervals. In the period between 26 and 34 weeks, the frequency of evaluation was increased to every 14 days. Data obtained were compared with a control group of 70 fetuses with uneventful pregnancies matched for gestational age. Neonatal weight is shown in relation to the centiles for the normal population. One patient out of 14 (7.1 per cent) developed gestational hypertension and abruptio placentae. No other pregnancy complications were seen. No proteinuria was found. The mean maternal age was 31.2±3.8 years. Median birth weight was 3433 g±287. The median centile of the birth weight was 65.3±18.6. Mean gestational age at delivery was 1.3 weeks. No fetal or neonatal growth retardation was seen. No significant differences were found in the biometrical parameters investigated in the various gestational ages vs. the control group (Student's t-test not significant); a significant increase in head circumference (P< 0.001) and abdominal circumference (P< 0.05) was found at 36–37 weeks gestational age in the IVIG-treated fetuses. The presence of antiphospholipid antibodies is considered detrimental for pregnancy outcome because of their negative effects on placental vascular perfusion and fetal transfer of metabolites. The use of IVIG seems to avoid or inhibit the reduced availability of nutrients for the fetal anabolic functions, as the expected reduction in fetal growth was not seen in our series.     

Amniotic fluid analysis in a fetus with laryngeal atresia

Complete laryngeal atresia is a rare congenital malformation that is known to cause hypertrophy of the fetal lung in utero. A fetus with laryngeal atresia was found to have markedly immature amniotic fluid lung maturity studies at term. Inappropriately low amniotic fluid lung maturity studies may be an important clue to the diagnosis of this condition.