Sonographic markers of fetal aneuploidy--a review.

The most effective sonographic marker of trisomy 21 and other chromosomal defects is increased nuchal translucency (NT) thickness at 11-14 weeks. Extensive studies over the last decade have examined the methodology of measuring NT, the development of the necessary algorithms for calculating the individual patient risk for trisomy 21 by NT in combination with maternal age and with various maternal serum biochemical markers, and the performance of this test. Another promising marker for trisomy 21, both in the first and second trimesters, is absence of the fetal nasal bone.

Monozygotic twins discordant for body stalk anomaly.

We report on two cases of monozygotic twins discordant for body stalk anomaly, diagnosed prenatally in a multicenter ultrasound screening study at 10-14 weeks of gestation. Ultrasound showed a large abdominal wall defect with most of the abdominal contents and almost half of the body in the celomic cavity, in association with severe kyphoscoliosis and a very short umbilical cord. Both pregnancies were managed expectantly and delivered by Cesarean section.

Screening for fetal abnormalities in multiple pregnancies.

Multiple gestations account for 1-2% of all pregnancies but contribute disproportionately to the incidence of both perinatal loss and fetal structural abnormalities. Ultrasound examination provides essential information about screening for, and the management of, such defects, including accurate determination of chorionicity, assessment of risk, invasive testing and selective termination if appropriate.

Cardiac gene expression of GATA-4 transcription factor in human trisomy 21 fetuses with increased nuchal translucency.

This study examines GATA-4 gene expression in cardiac tissue from fetuses with trisomy 21 presenting with increased nuchal translucency thickness at 10-14 weeks of gestation. mRNA was extracted from cardiac tissue after termination of pregnancy at 10-18 weeks of gestation in ten trisomy 21 fetuses and 29 normal controls. Northern and slot blots were performed and densitometric analysis of slot blots was used to determine the steady-state levels of expression of GATA-4.

Collagen type VI gene expression in the skin of trisomy 21 fetuses.

Objective: To determine whether the mechanism for the retention of interstitial fluid in trisomy 21 fetuses presenting with nuchal translucency at 10-14 weeks' gestation is an alteration in the composition of collagen type VI, which is normally a triple helix formed of three single chains, alpha1, alpha2, and alpha3. The genes responsible for the alpha1 and alpha2 chains, COL6A1 and COL6A2, are located on chromosome 21 and therefore may be overexpressed in trisomy 21, whereas COL6A3 is located in chromosome 2.

Methods: Skin tissue was obtained after termination of pregnancy at 11-16 weeks' gestation in five fetuses with trisomy 21 and five normal controls.

Maternal serum alpha-fetoprotein in fetal neural tube and abdominal wall defects at 10 to 14 weeks of gestation.

Maternal serum alpha-fetoprotein concentration was determined in nine pregnancies with fetal anencephaly, seven with exomphalos containing liver, two with spina bifida and 100 normal controls at 10 to 14 weeks of gestation. The median alpha-fetoprotein in the group with fetal anencephaly and exomphalos was significantly higher than in normal fetuses but the sensitivity of this test is likely to be only about 30% for a false positive rate of 5%.

Lethal congenital arthrogryposis presents with increased nuchal translucency at 10-14 weeks of gestation.

This study examines the ultrasonographic features of congenital lethal arthrogryposis. In 27 cases of arthrogryposis diagnosed in the second and third trimesters there was severe bilateral talipes, fixed flexion deformities of the wrists and elbows and either fixed flexion or extension of the knees. In seven (26%) of the cases there was nuchal edema.

Abnormalities of the heart and great arteries in first trimester chromosomally abnormal fetuses.

Pathological examination of the heart and great arteries was performed in 112 chromosomally abnormal fetuses after surgical termination of pregnancy at 11-16 weeks of gestation. The chromosomal abnormalities were diagnosed by chorion villus sampling which was carried out because screening of the pregnancies by a combination of maternal age and fetal nuchal translucency thickness at 10-14 weeks of gestation identified them as being at increased risk. The group consisted of 60 fetuses with trisomy 21, 29 with trisomy 18, 17 with trisomy 13 and 6 with Ullrich-Turner syndrome.

Cardiac gene expression of atrial natriuretic peptide and brain natriuretic peptide in trisomic fetuses.

Objective: To investigate whether the increased nuchal translucency of trisomic fetuses is the consequence of heart failure by examining cardiac expression of atrial natriuretic peptide and brain natriuretic peptide genes.

Methods: Cardiac atrial natriuretic peptide and brain natriuretic peptide messenger RNA (mRNA) levels were measured in fetal hearts from 15 pregnancies affected by trisomy 21 or 18 at 12-16 weeks' gestation and from 30 normal controls at 10-20 weeks.

Results: In normal fetuses, mRNA levels of atrial natriuretic peptide decreased, but levels of brain natriuretic peptide did not change significantly with gestation.

Cardiac defects in 1st-trimester fetuses with trisomy 18.

In trisomy 18, echocardiographic studies of affected neonates and pathological studies of stillbirths and infants have demonstrated a high incidence of cardiac defects. Fetal trisomy 18 can now be detected at 11-14 weeks of gestation, providing the opportunity to examine the incidence of cardiac defects at this gestational age. In 19 fetuses with trisomy 18 pathological examination of heart and great vessels was carried out after termination of pregnancy at 11-14 weeks of gestation.

Increased first trimester nuchal translucency as a prenatal manifestation of Smith-Lemli-Opitz syndrome.

Routine ultrasound examination at 11 weeks of gestation in a woman with no family history of genetic disease demonstrated increased accumulation of fluid in the fetal nuchal region. In view of the association of this defect with chromosomal abnormalities, fetal karyotyping was performed by chorion villus sampling and this demonstrated a normal 46,XY karyotype. Subsequent scans showed resolution of the nuchal fluid, and at the 20-week scan the fetal genitalia appeared to be female.

Is Purkinje cell loss in Leigh's disease an excitotoxic event secondary to damage to inferior olivary nuclei?

In a series of 17 cases of Leigh's disease it has been observed that there is a close correlation between damage to the inferior olivary nuclei by vasculo-necrotic change and loss of Purkinje cells in the cerebellar cortex. It is suggested that this association may be explained on the basis of the selective loss of climbing fibres causing increased firing activity of Purkinje cells with consequent excessive entry of calcium ions. In these circumstances control of calcium ion regulation in the presence of reduced energy production, which is the basis of this metabolic disease, would be expected to put these cells' survival seriously at risk.

Aldosterone concentration in normal, growth-retarded, anemic, and hydropic fetuses.

Objective: To establish a gestational age reference range for fetal plasma aldosterone concentration and to determine whether anemia, growth retardation, or hydrops are associated with abnormal levels.

Methods: Aldosterone concentration was measured in umbilical venous blood obtained by funipuncture from pregnancies complicated by red blood cell isoimmunization (n = 17), fetal growth retardation (n = 8), and nonimmune hydrops fetalis (n = 17). Values were compared to reference ranges constructed from the study of samples obtained by funipuncture or at elective cesarean delivery from 40 essentially normal fetuses and maternal blood from 33 uncomplicated pregnancies.

Predicting the severity of rhesus alloimmunization: monocyte-mediated chemiluminescence versus maternal anti-D antibody estimation.

Anti-D haemolytic antibody concentration and chemiluminescence (CLT) opsonic index was measured in maternal blood obtained from 20 alloimmunized pregnancies at 17-28 weeks undergoing intrauterine fetal blood sampling for the estimation of fetal haemoglobin concentration. The fetal haemoglobin concentration was significantly associated with the maternal serum CLT opsonic index (r = -0.566, P < 0.

Polytherapy, monotherapy, and carbamazepine.

Despite the widespread and traditional use of polytherapy in the treatment of epilepsy, there is little evidence of its advantages over monotherapy. Among other undesirable effects, it can produce subtle cognitive and behavioral changes and sometimes even exacerbate the epilepsy. Recent studies provide evidence that in many patients seizures can be controlled by carefully monitored monotherapy: Approximately 75% of newly diagnosed, previously untreated epileptic patients will enter a 2-year remission with this form of treatment.