G. Barkai

DOWN'S SYNDROME SCREENING MARKER LEVELS FOLLOWING ASSISTED REPRODUCTION

Maternal serum α‐fetoprotein (AFP), human chorionic gonadotrophin (hCG), and unconjugated oestriol (uE3) levels were examined in 1632 women who had ovulation induction and 327 who had in vitro fertilization. There was a highly statistically significant increase in hCG and reduction in uE3 among those with ovulation induction. The median levels were respectively 1·09 and 0·92 multiples of the normal gestation‐specific median (MOM) based on a total of 34 582 women. Ovulation induction appeared to have no material effect on the median AFP level but this masked a significant increase when treatment was with Clomiphene (1·05 MOM) and a significant decrease when Pergonal was used (0·93 MOM). There was a highly statistically significant reduction in uE3 among women having in vitro fertilization with a median level of 0·92 MOM. Those fertilized with a donor egg (21) had significantly higher AFP and uE3 levels than when their own egg was used. Our results were confounded by differences in gravidity, but formally allowing for this factor did not materially change the findings. None of the observed effects is great enough to warrant routine adjustment of marker levels to allow for them. Moreover, women with positive Downs syndrome screening results can be reassured that this is unlikely to be due to them having had assisted reproduction.

Detection of numerical chromosome aberrations by comparative genomic hybridization.

At least 50 per cent of all first‐trimester spontaneous abortions are cytogenetically abnormal, including trisomy, monosomy X, triploidy, tetraploidy and structural chromosome anomalies. Traditionally, the detection of aneuploidy in fetal tissues is performed by tissue sampling, cell culturing, metaphase spread preparation, and conventional banding analyses. This is a tedious, laborious and time‐consuming process, prone to errors due to external contamination, culture failure and selective growth of maternal cells. In the present study, we applied the CGH technique in the detection of numerical chromosome abnormalities in 50 placentae of spontaneously aborted fetuses. CGH detected six different types of trisomy (trisomy 8, 15, 16, 18, 22 and 21), one double trisomy (involving chromosomes 14 and 21), and one monosomy X. Overall, nine samples (18 per cent) harboured numerical chromosome aberrations. Aneuploidy was detected in eight samples by CGH and in six samples by conventional cytogenetic analysis. In only one case, CGH failed to detect a mosaic for trisomy revealed by conventional cytogenetic analysis.

Intravenous pethidine and nalbuphine during labor : a prospective double-blind comparative study

The perfect analgesic regimen is constantly sought, no matter how labor is conducted. The quest for an effective drug that will afford maximum relaxation and pain relief with minimum interruption of any natural homeostatic mechanism is a foremost subject in present obstetric analgesics research. Synthetic alternatives are being offered, promising perfect compatibility with the clinicians demands. Nalbuphine, a semisynthetic narcotic agonist-antagonist analgesic of the penanthren series, is supposed not to be liable to cause respiratory depression and is expected to have fewer side effects. A double-blind, randomised prospective study of 137 patients who received 10 mg nalbuphine or 50 mg pethidine i.v. during the active phase of labor in term was carried out. Maternal cardiovascular variables, pain intensity, progress of labor and fetal heart rate during labor were related to side effect and neonatal outcome (1- and 5-min Apgar scores and umbilical venous pH). Neither regimen showed an advantage over the other. Data analysis points to a possible transient depressive effect induced by nalbuphine on the fetal or neonatal central nervous system.

Use of interphase fluorescence in situ hybridization in third trimester fetuses with anomalies and growth retardation

In the last few years, attention has been focused on the use of interphase fluorescence in situ hybridization (FISH) for prenatal diagnosis with chromosome-specific DNA probes in the second trimester. This technique is accurate, rapid, and detects the most common aneuploidies. We present a preliminary study using FISH technique on uncultured amniotic cells derived from 30 fetuses with ultrasonographic evidence of intrauterine growth retardation (IUGR) in the third trimester. Fifteen fetuses were males and 15 were females. Seven fetuses (23.3%) had abnormal chromosomal constitution: five (18.6%) had trisomy 21, one (2.35%) had trisomy 18, and one (2.35%) showed a mosaic trisomy 18. No abnormalities were detected in the other 23 fetuses. Amniocentesis combined with FISH appears to be a safe, rapid, and accurate alternative to blood sampling in the third trimester, reducing the clinical and emotional stress of the time required to complete chromosome analysis by routine cytogenetics.

EFFECT OF GRAVIDITY ON MATERNAL SERUM MARKERS FOR DOWN'S SYNDROME

The effect of gravidity on maternal serum α‐fetoprotein (AFP), unconjugated oestriol (uE3), and human chorionic gonadotrophin (hCG) levels was investigated in 27 592 women being screened for Downs syndrome. There was no difference in the median AFP level in primigravid and multigravid women, but the median hCG level in multigravid women was 5·9 per cent lower than in those tested in their first pregnancy (P<0·0001) and the median uE3 level was 3·9 per cent lower (P<0·0001). Among multigravid women, there was no material difference in hCG levels according to the number of previous pregnancies or livebirths, whereas uE3 levels declined steadily with increasing numbers. Both markers declined with advancing maternal age: for hCG this was an independent effect, but for uE3 it was due to the correlation between age and gravidity. Allowing for these effects will not greatly alter the Downs syndrome screening detection and false‐positive rates.

Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies

Activity levels of total and placental alkaline phosphatase (AP) were determined in maternal serum and neutrophils of normal and Down syndrome pregnancies. The placental iso‐enzyme (PAP) was identified by its relative stability to urea and heat. Significant increase in the activity of all iso‐enzymes across gestational stages was observed in maternal sera of 28 normal pregnancies. However, in the neutrophil extracts of the same blood samples no differences were detected between trimesters. Another set of experiments was aimed at finding diagnostic differences of PAP activity in maternal neutrophils of normal and trisomy 21 affected pregnancies. No differences of heat stable AP activity were found in maternal samples of 19 normal and 19 Down syndrome affected pregnancies. Urea resistant AP proportions were also similar when measured after 40 minutes of exposure (13 samples in each group). However, a marginally significant increase was observed in the mean value of the Down syndrome affected samples, after 60 minutes of urea treatment. In view of the above results we conclude that neutrophil AP activity is not as yet a useful marker for the screening of trisomy 21 fetuses. Copyright

Fetal heart rate changes following external cephalic version under tocolysis near term

Fifty eight gravidas near‐term underwent external cephalic version using tocolytic treatment and continuous fetal monitoring by cardiotocograph and real‐time ultrasound. No unfavorable maternal or fetal effects were recorded. Fetal heart rates showed a significant decline at 10 and 30 min after the procedure with complete recovery at 1 h after external version, but no pathologic tracing was recorded. No uniform heart rate patterns due to external cephalic version could be found.

Iatrogenic Mechanical Ileus due to Over-Distended Uterus

The combination of an over-distended uterus caused by a multiple-fetus pregnancy with therapeutic bed-rest may cause mechanical ileus. Iatrogenic triggering of a pathological consequence of events is presented in purpose to highlight the simplicity of its prevention.

Neonatal alloimmune thrombocytopenia in consecutive pregnancies.

Neonatal and antenatal alloimmune thrombocytopenia is caused by the placental passage of maternal antibodies directed against platelet-specific fetal antigens. This disease is analogous to Rhesus hemolytic disease of the newborn and may be complicated by intracranial hemorrhage. Following increased awareness to the disease, it is currently no longer considered to be rare. Recent advances in the utilization of percutaneous umbilical cord blood sampling has led to a dramatic change in both prenatal and intranatal management of affected fetuses. We present a sibship with four infants, three of them found to have alloimmune thrombocytopenia. The neonatal thrombocytopenia in the subsequent births was not shown to be more severe, as could have been expected from the pathophysiologically analogous Rh hemolytic disease of the newborn. The role of prenatal determination of platelet count, intrauterine treatment with immunoglobulins and platelet transfusions, and elective cesarean section, in preventing possible hemorrhagic complications in repeated pregnancies should be reconsidered, taking into account the natural history of this rare disorder.

Amniotic Fluid α-Fetoprotein Levels and Fetal Chromosomal Abnormalities

406 midtrimester amniotic fluid samples were examined for Α-fetoprotein (AFP) levels and fetal karyotyping. 44 cases with Down syndrome, 12 with Klinefelter syndrome and 14 with other chromosomal