Prenatal Diagnosis Center Research Articles

Audit of prenatal diagnosis for haemoglobin disorders in the United Kingdom: the first 20 years

Objectives: To audit services for prenatal diagnosis for haemoglobin disorders in the United Kingdom.Design: Comparison of the annual number of cases recorded in a United Kingdom register of prenatal diagnoses...

Umbilical artery Doppler velocimetry in fetuses with a single umbilical artery

Doppler waveform analysis of the umbilical artery is an important tool for the evaluation of high-risk pregnancies. Yet, available data are based on normal values from three-vessel umbilical cords. Our purpose was to evaluate the value of umbilical artery Doppler velocimetry in fetuses with a single umbilical artery. One hundred thirteen consecutive singleton fetuses with a single umbilical artery between 16 and 40 weeks' gestational age were studied prospectively at a tertiary referral center for prenatal diagnosis and therapy. Complete follow-up was obtained from 103 cases. The systolic-diastolic ratio in the umbilical artery was abnormal in 31 fetuses (30%) and normal in 72 fetuses (70%). Fetuses with abnormal Doppler waveform analysis in the umbilical artery were significantly more likely to be growth restricted (55 compared with 15%), to have complex malformations (58 compared with 1%) or an abnormal karyotype (29 compared with 0%), or not to survive the fetal/perinatal period (42 compared with 0%) than those with normal Doppler waveform analysis. Fetuses with a single umbilical artery and abnormal umbilical Doppler velocimetry had a significantly increased risk of adverse fetal and neonatal outcome compared with those with a single umbilical artery but normal Doppler studies.

First-trimester growth restriction and fetal aneuploidy: The effect of type of aneuploidy and gestational age

OBJECTIVE: Our purpose was to determine the effect of type of aneuploidy and gestational age on first-trimester fetal growth. STUDY DESIGN: Crown-rump length measurement was obtained in pregnancies undergoing chorionic villus sampling in three large prenatal diagnosis centers. One hundred forty-four aneuploid fetuses, from 9 to 13 weeks' gestation, were compared with 440 matched control fetuses for evidence of crown-rump length shortening. Shortening was defined by the observed/expected crown-rump length. Expected values of crown-rump length based on last menstrual period were obtained from regression equations generated from a separate normal group. Threshold values for aneuploidy screening were determined on the basis of receiver-operator characteristic curves. RESULTS: There was significant crown-rump length shortening in trisomy 18 compared with normal fetuses, with observed/expected values ≤0.80 (odds ratio 13.78, 95% confidence interval 5.64 to 33.88, p <0.000001); for trisomy 13 the observed/expected crown-rump length was ≤0.90 (odds ratio 3.64, 95% confidence interval 1.08 to 12.96, p <0.03). There was no significant shortening of crown-rump length in Down syndrome, with observed/expected values ≤0.92 (odds ratio 0.86, 95% confidence interval 0.50 to 1.47, p = 0.6). With shortened crown-rump length (observed/expected value <0.86) the risk of any aneuploidy is increased (odds ratio 2.52, 95% confidence interval 1.6 to 3.96, p <0.0001). When the first-trimester crown-rump length was shortened by ≥14 mm, the aneuploidy risk was high (odds ratio 9.04, 95% confidence interval 3.26 to 28.67, p <0.00001). CONCLUSION: In the first trimester fetuses with trisomy 18 and 13 appear to be growth restricted, in contrast to fetuses with trisomy 21. In at-risk pregnancies crown-length that is shorter than expected significantly increase the odds that aneuploidy is present. (Am J Obstet Gynecol 1997;176:976-80.)

Improved ultrasound detection of fetal anomalies in a state designated prenatal diagnosis center

Improved ultrasound detection of fetal anomalies in a state designated prenatal diagnosis center

The influence of the experience of the investigator on the rate of sonographic diagnosis of fetal malformations in Vienna.

The quality of prenatal ultrasound may be influenced by different factors. In this study, the influence of the experience of the investigator on the quality of routine ultrasound screening during pregnancy was evaluated. We related the detection rate of fetal malformations in routine ultrasound screening in the region of Vienna to the experience level of the examiner. All 323 cases of fetal malformations registered by the obstetrical departments of Vienna or registered by the Vienna perinatal mortality statistics of 1990 and 1991 were evaluated. For analysis we used the medical charts or the patient-held antenatal records ("Mutter-Kind-Pass'). Obstetricians in private offices (level I) detected 22 per cent, the examiner in the hospital (level I-II) 40 per cent, and the examiner in the centre for prenatal diagnosis and therapy (level III) 90 per cent of all fetal malformations. The detection rate before the 24th week of gestation was significantly different (25 per cent vs. 34 per cent vs. 58 per cent). Our results suggest that an important factor for the quality of prenatal ultrasound investigation is the education of the sonographers. Furthermore, each pregnant woman should undergo ultrasound screening once in a level II or III centre before 24 weeks or before fetal viability.

Prenatal diagnosis and pediatric neurosurgery.

Advances in realtime ultrasound imaging and a greater availability of high-quality ultrasound equipment have resulted in an increased number of congenital abnormalities being diagnosed prenatally in the last 10-15 years. In addition, testing for maternal serum alpha-fetoprotein, beta-human chorionic gonadotropin, and serum unconjugated estriol has allowed for more sensitive screening for congenital abnormalities. In response to this, in 1989 the Prenatal Diagnosis and Treatment Center was established at our institution to coordinate the care of fetuses and newborns with congenital malformations and to provide alternatives for the parents should the fetus not be carried to term. From January 1990 through June 1993, our group diagnosed 50 singleton pregnancies with various types of central nervous system disorders by the methods outlined above. Thirty-seven fetuses were diagnosed with neural tube defects. Of these, 5 were anencephalic and 1 had an encephalocele. The remaining 31 fetuses had meningomyeloceles with associated hydrocephalus. Of these 31, 18 fetuses were terminated prior to the age of viability as a result of our counseling and 13 fetuses were brought to term. Of the remaining 13 fetuses, 8 had hydrocephalus and 5 had various other diagnoses. Three of the eight hydrocephalic fetuses were either terminated, stillborn, or died following birth. Of the other 5 fetuses with hydrocephalus, 3 had shunts placed, 1 was followed with normal head growth, and 1 had normal ventricular size at birth. Using the methods available, the accuracy of diagnosis is very high, with only 1 fetus in this series being incorrectly diagnosed. Additionally the advantages of being able to counsel the parents regarding their unborn child allows them to make informed decisions. Accurate prenatal diagnosis plays a major role in the care of the fetus and in counseling parents prenatally for pediatric neurosurgical problems.

Nuchal translucency measurement in normal fetuses

To construct a normal range for the nuchal translucency measurement in chromosomally and phenotypically normal fetuses between 9 and 14 weeks' gestation. The nuchal translucency was measured prospectively in 771 chromosomally normal fetuses of women attending our antenatal clinic or prenatal diagnosis center. The nuchal translucency measurement was expressed as the median and fifth, 25th, 75th, and 95th percentiles according to completed weeks of gestation based on ultrasound measurements. The median nuchal translucency measurement increased from 0.7 mm at 10 weeks' gestation to 1.5 mm at 13 weeks. A nuchal translucency measurement greater than 2.5 mm was found in 4.6% of the fetuses at 10 weeks' gestation; the incidence increased to 8.7% at 14 weeks. In normal fetuses, there is a physiologic variation in the nuchal translucency measurement between 9 and 14 weeks' gestation. The calculation of risk for trisomies based on this measurement should take this variation into account. The adoption of a gestational age-dependent cutoff point, based on the deviation of a given measurement from the median, may reduce the number of false-positive test results requiring invasive procedures for karyotyping.

Complications of cordocentesis in high-risk pregnancies: effects on fetal loss or preterm delivery.

Between 1990 and 1993, 166 cases underwent cordocentesis and were followed for at least the following 4 weeks in the Prenatal Diagnosis and Therapy Centre of Vienna University. The indications for the procedure were structural malformations in 46.4 per cent of the cases, other high-risk diagnosis in 48.8 per cent, and maternal age over 35 years in only 4.8 per cent. We investigated retrospectively all cases of complications resulting in fetal loss or preterm labour. Abortion, intrauterine fetal death, chorioamnionitis, and preterm delivery occurred in 0.6, 5.4, 0.6 and 9.0 per cent of these cases, respectively, adding up to a total of 26 cases (15.7 per cent). Although this rate looks relatively high, 20 of the 26 cases had already displayed signs implying a complicated prognosis. Neither maternal age, gestational age, number of attempts, nor placental location correlated with fetal loss or preterm delivery. Significantly higher rates of fetal loss or preterm delivery were observed when cordocentesis was performed in cases diagnosed as duodenal/intestinal stenosis or hydrops-ascites-hydrothorax/hygroma colli (P = 0.0488 and P = 0.0005). The frequency of complications did not decrease as the experience of the operators increased.

Molecular Study and Prenatal Diagnosis of Thalassemia in Taiwan

The carrier rates of alpha-thal 1, alpha-thal 2, and beta-thal are 4%, 1% and 1% respectively. If a couple are both the carriers of alpha-thal 1, 25% of the offspring will be affected with homozygous alpha-thal 1, which will result in Hb Bart’s hydrops fetalis and cause various maternal complications. If a couple are both the carriers of beta-thal, 25% of the offspring will be affected with beta-thal major and the patients need life-ling blood transfusion, iron chelation therapy and bone marrow transplantation. This report summarizes our results on thal study in Taiwan. With southern hybridization and various polymerase chain reaction (PCR) techniques, the molecular basis of 832 Chinese Hans with alpha-thal 1 has been characterized. 95.4% had Southeast Asian (SEA) deletion, 2.2% had Thailand (Thai) deletion, and 2.4% had Constant Spring, Quong Sze, or other mutations. 1342 blood samples from five major aboriginal groups, comprising 522 of the Ami, 246 of the Bunun, 227 of the Atayal, 214 of the Paiwan, and 133 of the Yami, were collected for thal study. In the Ami, 43 (8.2%) were alpha-thal 1 carriers (33 with Thai, 9 with SEA, and one with Phil deletion), 43 (8.2%) were alpha-thal 2 carries, one had Hb H disease, and 4 (0.8%) were beta-thal carriers (one each with nonsense 17 and -2 A-G mutation). In the Bunun, one (0.2%) had Thai deletion and 2 (0.4%) were alpha-thal 2 carriers. In the Atayal, one (0.2%) had Phil deletion. In the Paiwan, 7 (3.3%) had alpha-thal 1 (4 with SEA and 3 with Thai deletion) and one (0.5%) had alpha-thal 2. In the Yami, none had either alpha- or beta-thal. In prenatal diagnosis, 624 fetuses at risk for homozygous alpha-thal 1 or severe Hb H disease were studied. Chorionic villus sampling was mainly used to obtain fetal tissue. 170 fetuses were diagnosed as affected. For molecular characterization of beta-thal, 186 unrelated blood-transfusion dependent patients were studied. Southern hybridization, allele-specific oligonucleotide (ASO) hybridization, heteroduplex formation, amplification refractory mutation system (ARMS), artificially created restriction site (ACRS) analysis and direct DNA sequencing have been used. The four most common mutations were IVS-II 654 (C-T)(38.7%), codon 41/42 (deletion of TCTT) (36.6%), -28 (A-G) (6.9%), and nonsense 17 (A-T) (2.8%) mutations. The other mutations detected were A-gamma beta deletion, codon 1 (T-G), codon 27/28 (insertioin of C), Hb E, and codon 71/72 (insertion of A) mutations. The mutations are still unknown in 19 genes. In prenatal diagnosis, 170 fetuses at risk of beta-thal major were studied and 39 fetuses were diagnosed as affected. Three years ago, the Department of Health (DOH) of Taiwan has set up a nation-wide thal screening program. All the pregnant women are encouraged to participate. Couples both with microcytosis are referred to several centers for genotype confirmation and prenatal diagnosis if needed. DOH subsidizes NT 3000 for genotype confirmation of the couple and NT 2000 for prenatal diagnosis. The screening program seems to be running smoothly.

Early amniocentesis.

Amniocentesis before 15 weeks has been introduced in many prenatal diagnosis centres. There are, however, major anatomical differences between the appearance of fetus at 15-16 weeks, when amniocentesis has normally been performed, and in the first and early second trimester. This is mainly because of the presence of extraembryonic coelome and the relatively small amount of amniotic fluid in early pregnancy. Several small cohort studies have indicated no increased fetal loss rate with early amniocentesis. Others have suggested an increased risk of respiratory distress among the newborn. The only randomized study published, however, found a significantly increased rate of fetal losses after early amniocentesis. This incomplete study indicates the urgency of further randomized studies of early amniocentesis. A randomized study comparing early amniocentesis with transabdominal chorionic villus sampling is being undertaken at our centre in Copenhagen using a filter method that reduces the volume of fluid needed for karyotyping.

Factors Affecting Patient Satisfaction in a Prenatal Diagnosis an Treatment Population

Many investigators studying patient satisfaction have shown that the mode of medical care delivery appears to be more important to the patient than the content. Recent studies pertaining specifically to patients undergoing prenatal diagnostic testing also show an association between psychosocial and clinical history factors and patient satisfaction. The authors reviewed 535 patients in a prenatal diagnosis centre to determine which variables most significantly affect patient satisfaction; 41 variables were tested for their association with satisfaction. Of the 9 variables that were shown to be significant, patient/staff interaction was found to be most critical in predicting satisfaction. This study showed no association between psychosocial and clinical history factors and patient satisfaction.

Tertiary centre referral of small-for-gestational age pregnancies: a 10-year retrospective analysis.

Between 1981 and 1991, 461 pregnant women between 15 and 40 weeks of gestation (mean 30 weeks) with completed follow-up were referred to our centre for prenatal diagnosis because of a small-for-gestational age (SGA) fetus or combined SGA and structural abnormality. The referral diagnosis was based either on biparietal diameter measurements or on measurement of the upper-abdominal circumference. SGA in our centre was defined as a fetal upper-abdominal circumference below the tenth centile. SGA was confirmed by ultrasound in 75 per cent of the fetuses, whilst combined SGA and fetal structural abnormality was substantiated in only 16 per cent of the fetuses. However, in our centre structural abnormality was detected in 34 fetuses who were referred because of SGA alone. Nearly half of the structurally normal SGA fetuses displayed a normal head-to-abdomen (H/A), ratio, whereas an increased H/A ratio was found in 13/15 fetuses with an abnormal karyotype. An abnormal karyotype was present in 20 fetuses, which is 7 per cent of the total SGA population. Nearly 50 per cent represented triploidy associated with oligohydramnios. SGA was confirmed by a birth weight below the tenth centile in 89 per cent, below the fifth centile in 77 per cent, and below the 2.3rd centile in 55 per cent of infants. Structural abnormality was confirmed in 65 per cent of infants, whereas in 19 per cent of infants the abnormality was missed or a misclassification was made. Perinatal mortality was 31 per cent for all SGA fetuses, 27 per cent for SGA fetuses without anomalies, and 64 per cent for SGA fetuses with structural abnormality.

The molecular basis of beta-thalassemia in Turkey.

By using oligonucleotide hybridization, restriction endonuclease analysis and direct sequencing of amplified genomic DNA, we have been able to characterize 18 different mutations in the beta-globin genes of 161 beta-thalassemia homozygotes and 107 beta-thalassemia heterozygotes from Turkey (429 beta-thalassemia chromosomes). Previous studies dealing with beta-thalassemia in Mediterranean countries have shown that, in most Mediterranean populations, only a few mutations are prevalent. In contrast, beta-thalassemia in Turkey does not seem to be associated with a few predominant mutations. The six most frequent alleles, IVS-I-110 (G----A), IVS-I-6(T----C), FSC-8 (-AA), IVS-I-1(G----A), -30(T----A) and FSC-5 (-CT), account for only 69.3% of the disease genes; indeed, all 26 mutations assayed represent 85.8% of the disease genes, confirming the considerable molecular heterogeneity of beta-thalassemia among Turks, and indicating the possible presence of rare, previously undefined, mutations in the population. Two mutations observed in this study, IVS-I-116 (T----G) and Cd44(-C), have not been reported in the Turkish population to date. Since preventive medical services, such as genetic counseling and prenatal diagnosis, are greatly improved by detailed knowledge of the molecular pathology of beta-thalassemia, we strongly believe that the presented data will facilitate the intended establishment of a prenatal diagnosis center, based on DNA analysis, in Turkey.

Nachweis des Varizellenvirus mit der DNA-Sonde im fetalen Blut und im Fruchtwasser

In our Centre for Prenatal Diagnosis, we undertook a punctuation of the umbilical cord on a pregnant woman infected with varicella, complicated by viral encephalitis, to diagnose a foetal viraemia. In cooperation with the Toma Laboratory and Clonit Ltd., who have long been working on the development of specific viral genome probes, we succeeded in proving, that the foetus had contracted varicella.

Socio‐cultural inequities in access to prenatal diagnosis: The role of insurance coverage and regulatory policies

The article presents the results of a 4-month-period survey by questionnaire among all women attending the Marseille Centre for Prenatal Diagnosis for amniocentesis. Socio-cultural status of women getting access to amniocentesis is significantly higher than in the general population of pregnant women in the same geographic area of south-eastern France. Socio-cultural status is also higher among women who have to cover costs of procedure to get access to amniocentesis than among those who benefit from it free-of-charge according to French Social Security regulations. In contrast, risk perception and attitudes toward termination of pregnancy are similar in these two groups. A total of 24.4 per cent of respondents declared that they got access to amniocentesis 'on their own initiative', the remaining 75.6 per cent declaring that they 'were following medical advice'. Multidimensional analysis shows that the women who do not benefit from free-of-charge amniocentesis, and who have a high level of education and no antecedents of fetal and perinatal deaths, are more likely to perceive themselves as 'self-referring'. The study indicates that institutional coverage may be effective in reducing socio-cultural inequities in access to prenatal diagnosis. But such a policy may conflict with the respect of women's individual autonomy in the amniocentesis decision.

Multicystic dysplastic kidney: Natural history of prenatally detected cases

To delineate the natural history of fetal multicystic dysplastic kidneys (MDKs), all cases that were prenatally detected in the Prenatal Diagnosis Center of the University of Virginia from September 1985 to 31 August 1988 were reviewed. All patients were followed through the Center with serial ultrasound evaluations at approximately 4-week intervals, and each liveborn infant was evaluated and followed by one of the authors (S.S.H.). Of the 14 cases detected, ten were detected in the second trimester, the earliest at 16.5 weeks' gestation. Of the nine fetuses with non-lethal disease, there were two cases in which the lesion remained unchanged during observation. Both had an initial diagnosis in the third trimester. In those cases diagnosed in the second trimester (7), all showed an initial increase in the size and number of cysts, followed by involutional changes either in utero (2) or in the neonatal period (3). Two infants had immediate surgical removal of the MDK, one because of respiratory compromise, and the other because of an uncertain diagnosis on renal scan. Abnormalities of the contralateral kidney were found in 7 of 14 fetuses. Five were lethal conditions. Associated non-renal abnormalities were common in bilateral MDK (80 per cent), but rare in unilateral MDK (11 per cent).

Prospective risk in reciprocal translocation heterozygotes at amniocentesis as determined by potential chromosome imbalance sizes. Data of the European Collaborative Prenatal Diagnosis Centres.

The Date of the European Cooperative Prenatal Diagnosis Laboratories (Boué and Gallano, 1984) of 596 prenatal (amniocyte) diagnoses of familial rcp was examined as to relationships between balanced/unbalanced result and ascertainment, carrier parent and chromosome imbalance size (percentage haploid autosome length). Each rearrangement was graphed once with actual (unbalanced result) or potential (normal or balanced result) imbalances plotted with trisomy as the ordinate and monosomy as the abscissa. The graphed data was divided into 15 regions, each of 2.0 per cent trisomy and 0.75 per cent monosomy and the rate of unbalanced pregnancies determined for each region. The highest rates of chromosomally unbalanced progeny (excluding regions with inadequate data) were found closest to the origin (i.e. associated with the smallest imbalances) and these were for ascertainment category 1 (previous rcp unbalanced child) 22.3 per cent for maternal carriers and 39 per cent for paternal carriers. Overall in pooled data for this ascertainment category (without reference to the imbalance graphs) there were for paternal carriers 28.6 per cent unbalanced pregnancies and for maternal carriers 18.1 per cent. The graphed data, therefore, revealed the higher rates associated with some of the rcp with small potential (combined duplication/deficiency) imbalances. Lesser rates were observed for ascertainment category 2 (carrier parent with a history of recurrent miscarriage) with overall percentages of imbalanced progeny ranging from 2.7 (paternal carriers) to 4.7 (maternal carriers). Again, higher rates were revealed in graphed data for small potential imbalances. All unbalanced results for this group (ascertainment category 2) plotted in the region closest to the origin with rates of 16 per cent (maternal carriers) and 9.5 per cent (paternal carriers) in this region. Remarkably in both ascertainment groups 1 and 2 there was no significant difference in the size of the imbalanced segments for unbalanced progeny. In ascertainment group 1 this was (dup/def; mean +/- S.D.): 1.09 +/- 0.77/0.47 +/- 0.45 and in ascertainment group 2: 1.09 +/- 0.80/0.66 +/- 0.71. From the graphed data which arguably denote viability relationships, a trisomy was approximately 2.7 times as likely to survive until amniocentesis as a monosomy of equivalent size. It is proposed that given further data, risk estimates could be determined for rcp heterozygotes using the present approach where empiric data (from the family history or an analysed series of similar rcp) is not available.

A collaborative study of the segregation of inherited chromosome structural rearrangements in 1356 prenatal diagnoses.

A collaborative study involving 71 European prenatal diagnosis centres has collected 1356 observations on the karyotype of fetal cells in diagnoses performed in couples in which a parent had a balanced structural rearrangement. The segregations of the inherited chromosome structural rearrangement were analysed in relation to the types of rearrangement, to the sex of the carrier parent, the methods of ascertainment of the anomaly in the family, the chromosomes involved and the potential imbalance of the anomaly. Wide differences in the incidence of unbalanced fetuses were observed in relation to these criteria, and these results can be used in counselling parents with balanced rearrangements. Distortions in segregation of normal versus balanced karyotypes were observed in some types of anomalies.