Prenatal diagnosis of recurrent Larsen syndrome: Further definition of a lethal variant

Larsen syndrome is characterized by multiple congenital joint dislocations and flattened facies. Some cases have been familial, with both autosomal dominant and recessive patterns of inheritance. Reports of a form of Larsen syndrome, lethal in the neonatal period, are reviewed. We present a family in which recurrence of the syndrome was diagnosed prenatally, but a lethal outcome again resulted despite preparation for anticipated perinatal complications. Because of the wide clinical variation and the lack of a known metabolic defect, delineation between the various forms of Larsen syndrome is difficult. While the lethal variant appears to be a combination of the Larsen phenotype and pulmonary hypoplasia, other features noted in the lethal cases, such as abnormal palmar creases and laryngotracheomalacia, are also seen in patients with Larsen syndrome who survive.     

Fetal blood sampling and cytogenetic abnormalities

From September 1984 to April 1991, we performed cytogenetic analysis on fetal blood samples from 214 second-and third-trimester pregnancies. One hundred and thirty-four cases were referred to consider the possibility of chromosomal mosaicism following amniocyte studies. The confirmation rate of mosaicism is at 0 per cent (0/9), 1·4 per cent (1/70), and 40 per cent (22/55) for cases of level I, level II, and level III mosaicism, respectively. Four out of 17 cases were positive for the diagnosis of fragile X syndrome. Of 63 cases with abnormal ultrasound findings, blood disorders, or other genetically related clinical conditions, 11 were found to have a chromosome abnormality. Fetal blood sampling is a valuable adjunct to other methods in the prenatal diagnosis of chromosomal mosaicism or pseudomosaicism. It is also useful when rapid cytogenetic diagnosis is desired because of malformations detected in pregnancies at a late gestational age.     

Ecological Survey of Coastal I Water Adjacent to Nuclear Power I Plants in Taiwan

A total of six nuclear reactors installed in three power plants, two along the northern and one along the southern coasts of Taiwan, started their operations one after another since October 1977. Owing to the large quantities of cooling water intake into and discharge from the plants, some environmental factors such as water temperature, chlorine, environmental radioactivity and nearshore currents may be significantly changed. Variations of these abiotic environmental factors may influence the biological activities in the ecosystem, particularly doing some kinds of damage to marine biological resources. Therefore, the possible environmental impact upon the biological systems including the fishery resources along the northern and southern coasts of Taiwan should be studied before and during the plant operation.

We have started the long-term programmes of biological, chemical and hydro-graphical surveys of the nuclear power plant sites on both northern (since July 1974) and southern (since July 1979) coasts of Taiwan. the survey items include ocean currents, physical and chemical properties of sea water, primary productivity, specific compositions and interspecific relationships among phyto- and zooplankton, algae, invertebrates, corals, and fishes; and radionuclides in water and biological specimens, and fishery statistics. in general, except for a few events, the operations of the six units of nuclear power plants have not produced detectable effects on the marine ecosystem. Radio activity levels and radionuclides in water and the biological specimens remained the same as background levels throughout the survey period. However, the events of coral bleaching and fish body anomalies caused by thermal discharges were observed respectively along the outlets of third and second Nuclear Power Plants. the purposes of this paper are to report and evaluate these two events during the operations of nuclear power plants in Taiwan.     

Fetal chromosome analysis: Screening for chromosome disease?

The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocenteses performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25–34 years of age, in whom all heritable diseases were excluded (group Q. The risk of unbalanced chromosome abnormality in group A (women with elevated risk) is significantly higher than in group B + C (women without elevated risk) (relative risk 2–4). Women with a known familial translocation and women 40 years or more have a relative risk of 5–7 of having an unbalanced chromosome abnormality compared with women without elevated risk. Spontaneous abortion rate and prematurity rate did not differ from rates expected without amniocentesis. It is concluded that current indications may be characterized as a mixture of evident high risk factors and factors with only a minor influence on risk. Indications for amniocentesis should therefore be reconsidered. Because it must be considered impractical and ethically wrong to limit amniocentesis to the two mentioned real high risk groups, and illogical to continue the present policy, which is not based on clearcut evidence, the possibility of offering amniocentesis to all who want it, is discussed. Screening for chromosome disease in all pregnancies is not without problems, but may be reasonable in some localities.     

Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities

The alpha subunit of human chorionic gonadotropin (alpha-hCG), human chorionic gonadotropin (hCG) and alpha fetoprotein (AFP) were measured in the serum of 25 women with chromosomally abnormal fetuses between 18 and 25 weeks of gestation and in 74 normal pregnancies. AFP levels less than 0.5 multiples of the median (MoM) or greater than 2.5 MoM were observed in 24 per cent of the abnormal pregnancies and in 6.76 per cent of the normal pregnancies. A low concentration of hCG (< 0.25 MoM) was observed in 8 per cent of abnormals and in 2.7 per cent of normals while an elevated concentration of hCG (>2.5 MoM) was observed in 56 per cent of abnormals and in 1.35 per cent of normals. Elevated hCG-alpha (>2.5 MoM) was observed in 28 per cent of abnormals and in none of the normals. Determination of elevated levels of hCG-alpha or hCG resulted in detection of 68 per cent of pregnancies with chromosomally abnormal fetuses with a false positive rate of 1.35 per cent. Determination of both elevated and depressed gonadotropin levels resulted in detection of 76 per cent of abnormal pregnancies with a false positive rate of 4.05 per cent. Measurement of hCG and hCG-alpha in maternal serum samples can be used as a screening procedure for detecting pregnancies at risk for fetal chromosome abnormalities.     

Incidence of fetal chromosome abnormalities in 2264 low-risk women

Among a population of 6305 pregnant women, aged 25 to 34 years and estimated to be at no increased risk of genetic disease in the fetus, 4606 women participated in a randomized controlled trial of genetic amniocentesis between 1980 and 1984. In the study group having amniocentesis (2264 women), 23 fetal chromosome abnormalities (1.0 per cent) were found: eight autosomal aneuploidies, seven sex chromosome aneuploidies, seven balanced structural rearrangements and one case of a marker some. The structural rearrangements and the marker chromosome were all shown to be inherited. The study group seemed representative for the whole population of younger women at low genetic risk. Therefore, a 1.0 per cent total rate of fetal chromosome abnormalities, consisting of one-third autosomal aneuploidies, one-third sex chromosome aneuploidies and one-third structural rearrangements, may be expected in the second trimester in younger low-risk women. In the same period of time, 562 women in the same age group were offered amniocentesis because of an estimated increased risk of fetal genetic disease. The total rate of fetal chromosome abnormality in this ‘high-risk’ group was 0.9 per cent and thus no different from the rate in the low-risk group.     

Does chorionic villus sampling compromise fetal umbilical blood flow?

A possible association of limb reduction defects with chorionic villus sampling (CVS) may be related to compromised umbilical blood flow from the trauma of the procedure. We hypothesized that because CVS may disrupt or compromise umbilical blood flow to the fetus, either by vasoconstriction, bradycardia, or emboli, we would detect these changes using Doppler velocimetry. A cohort of 21 consecutive consenting patients undergoing first-trimester elective CVS for prenatal diagnosis were entered into a prospective longitudinal study. Colour flow Doppler velocimetry was performed on fetal umbilical arterial blood flow immediately before and after CVS to measure the pulsatility index, fetal heart rate, per cent flow time, and maximum flow velocity. Measurements were obtained from three consecutive cardiac cycles in three different umbilical segments and averaged. Potentially confounding variables also recorded included gestational age, method of CVS, number of passes, number of aspirations, placental location, tissue sample size, and operator. Umbilical velocimetry values before and after CVS were compared using the paired t-test and showed no statistically significant differences. No differences were found when data were analysed by gestational age, sample size, method, number of aspirations, placental location, or operator. We were unable to detect any significant change in fetal umbilical arterial blood flow velocimetry or heart rate after performing CVS. Umbilical blood flow does not appear to be routinely compromised by CVS.     

First-trimester maternal serum alphafetoprotein and chorionic gonadotropin in aneuploid pregnancies

First-trimester maternal serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels were measured in samples from 29 women with cytogenetically abnormal pregnancies and 145 women with cytogenetically normal pregnancies matched for gestational age, race, and sample storage time. All patients had a risk of fetal aneuploidy greater than or equal to that of a mother 35 years of age. AFP was significantly lower in samples from pregnancies affected with trisomy 21 (0.67 MoM;p <0.05), while HCG values were no different from those of matched controls. Trisomies 13 and 18 could not be distinguished from matched controls by AFP. However, levels of HCG were significantly lower in such pregnancy samples, with median values of 0.65 MoM in trisomy 13 and 0.32 MoM in trisomy 18 (p<0.05). Variations in AFP and HCG levels suggest that expressed differences between autosomal aneuploidies include differences in fetal and placenta! protein production in the first trimester.