Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Delivery of the second twin.

OBJECTIVE: To determine the likelihood of cesarean for the second twin after vaginal delivery of the first and the risk of vaginal delivery. METHOD: A retrospective analysis of twin deliveries was performed on 10,365 live born twin pairs (20,730 births), using birth certificate data from the State of Illinois from 1997 through 2000. RESULT: The incidence of cesarean for the second twin after vaginal delivery of the first was 10.1%. The greatest incidence of failed vaginal delivery of the second twin was in the vertex/non-vertex group. Five-minute Apgar scores <4 were significantly more frequent in vaginally delivered twins <2000 g compared to those delivered via cesarean (p<0.001). CONCLUSION: Twin presentation type is predictive of the likelihood of a failed vaginal delivery of the second twin. Cesarean appears to significantly reduce the incidence of Apgars <4 for neonates <2000 g.

First-trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique.

OBJECTIVE: To describe the process of training for measuring nuchal translucency at five clinical centers in North America and to evaluate methods of quality assurance and feedback. DESIGN: Throughout a period of 18 months, the performance of sonographers in measuring fetal nuchal translucency was monitored using qualitative and quantitative methods of review. After 12 months, different approaches (written and personal feedback) were used to inform sonographers of technical aspects that needed to or could be improved. RESULTS: On initial qualitative review, discrepancies in judgment from different reviewers coincided with suboptimal magnification, failure to visualize the amniotic membrane and/or use of cross-shaped calipers. At subsequent global review, 13 (29%) images of nuchal translucency measurements were considered unacceptable. Quantitative assessment revealed that, during the first part of the study, the means from four sonographers were significantly smaller and the mean from the fifth sonographer was significantly larger than expected on the basis of findings from The Fetal Medicine Foundation (P < 0.0001). Following feedback, sonographers who underestimated nuchal translucency and who received a written report only did not change measurements overall (P = 0.9759). In contrast, those who received additional intervention showed a marked difference (P < 0.0001). CONCLUSIONS: Global qualitative review of images from one sonographer may be preferable to assessment of individual aspects of images. Results from global qualitative review correspond well with findings from quantitative analysis, indicating that the latter can be applied for ongoing audit. Observation of divergent results should prompt extensive personal feedback, rather than a written report, to prevent sonographers from settling in their own, inappropriate technique.

How to predict recurrent shoulder dystocia.

OBJECTIVE: Our aim was to determine the rate and risk factors for recurrent shoulder dystocia. STUDY DESIGN: A retrospective analysis of patients diagnosed with shoulder dystocia was performed by searching a computerized database from January 1, 1993, to June 30, 1999 for the following information: (1) vaginal deliveries, either spontaneous or operative, (2) shoulder dystocia, (3) birth weight, (4) duration of second stage of labor, (5) parity, and (6) gestational diabetes. Statistical analyses included chi(2) and t test. RESULTS: There were 39,681 vaginal deliveries with 602 (1.5%) complicated by shoulder dystocia. Sixty-six patients underwent a subsequent vaginal delivery, and 11 (16.7%) experienced another shoulder dystocia. The odds ratio for a recurrent shoulder dystocia was 10.98 (P <.000001). Nine of the 11 patients with recurrent shoulder dystocia compared with 28 of 55 without a recurrence were nulliparous women in their index pregnancy (P <.001). The mean fetal weights were 3885 g in the recurrent dystocia group and 3702 g in the group without recurrence (P <.03). Gestational age, operative delivery, and gestational diabetes were similar in the two groups. CONCLUSION: Factors that appear to increase the recurrence risk of shoulder dystocia include fetal weight and maternal parity. Prior shoulder dystocia is the single greatest predictive factor.

Crown-rump lengths in missed miscarriages and trisomy 21.

OBJECTIVES: To compare crown-rump lengths with karyotypes of missed miscarried fetuses and to determine a relationship between crown-rump length and trisomy 21. STUDY DESIGN: Chorionic villus sampling was performed on 129 consecutive missed miscarriages between 10 and 12 weeks by last menstrual period in patients >or= 35 years of age. Crown-rump length was correlated with the karyotype. Statistical analysis was performed using Student's t-test. RESULTS: Twenty-one of 129 missed miscarriages involved fetuses affected by trisomy 21. The crown-rump length was < 22 mm in 77% of missed miscarriages. Using a crown-rump length of >or= 22 mm for the prediction of trisomy 21 had a sensitivity of 86%, specificity of 89%, positive predictive value of 60% and negative predictive value of 97%. At 10-12 weeks, the crown-rump lengths of missed miscarried fetuses with trisomy 21 was significantly larger (P or= 35 years of age, with a missed miscarriage, in whom pregnancies reached >or= 10 weeks from the last menstrual period, a fetal crown-rump length of >or= 22 mm has a high probability that the etiology of the loss will be secondary to trisomy 21.

Prenatal diagnosis of 46,XX male fetuses.

Ultrasonography can accurately determine phenotypic sex differences from those of the genetic sex. Two cases were identified; they were the result of a translocation of the SRY gene from the Y chromosome to the X chromosome during meiosis. An ultrasonographic difference may represent an otherwise unsuspected genetic abnormality.

Sex difference in crown-rump length in first-trimester twins.

OBJECTIVE: To determine if there is a difference in the crown-rump length (CRL) between male and female fetuses in the first trimester. STUDY DESIGN: CRL was determined in 77 normal twin pairs at the time of chorionic villus sampling. The sex of each fetus was assigned based upon the results of the sampling. RESULTS: A small difference was found between the CRL of males as compared to females, but this was not statistically significant. However, if there was a difference in size between the twin pairs, the odds were 1.5:1 that the larger would be male. CONCLUSION: There is no clinically significant difference in size between male and female fetuses in the first trimester of pregnancy.

Association of parvovirus infection with isolated fetal effusions.

The association of parvovirus B19 infection and hydrops fetalis is well known. However, the association of parvovirus and fetal pleural or pericardial effusions has not been reported. We present five cases of isolated pleural or pericardial effusion with documented maternal parvovirus infection in four of these pregnancies. In the absence of structural or karyotypic abnormalities, spontaneous resolution of the effusion portends for a successful pregnancy outcome.

Management of a triplet gestation complicated by uterus didelphys.

BACKGROUND: Assisted reproductive technologies are making it possible for women to conceive when it was otherwise impossible. One of the side effects is multiple gestations. This may be especially disadvantageous when it occurs within an anomalous uterus. PATIENT AND METHODS: A 36-year-old women with the help of gamete intrafallopean transfer conceived triplets in a uterus didelphys. This pregnancy was further complicated by anencephaly of one of the triplets. The patient was managed by a combination of chorionic villi sampling and selective reduction that ended with the successful delivery of a term infant. CONCLUSION: Pregnancy reduction can be safely performed in a twin pregnancy on one side of a uterus didelphys. More reports will be required to determine whether this is the most optimal choice.

Arteriovenous malformation of the uterus associated with a missed abortion.

Arteriovenous malformation of the uterus is a rare uterine abnormality. This entity is generally associated with the presence of molar disease, choriocarcinoma and uterine surgery, but may be congenitally acquired. The presence of an arteriovenous malformation generally leads to unexplained profuse uterine bleeding. The diagnosis of this entity has traditionally been made by arteriography, and the treatment is usually hysterectomy. We present a patient with an arteriovenous malformation of the uterus whose prior delivery was by Cesarean section. The patient experienced episodes of heavy vaginal bleeding in the first month following the procedure of suction curettage for a first-trimester pregnancy loss. Chorionic villus sampling performed prior to the procedure showed a chromosomally normal fetus. The diagnosis of an arteriovenous malformation was made by color Doppler velocimetry and confirmed with arteriography. The patient desired to maintain her fertility. Interventional radiological techniques were successfully utilized to obliterate the arteriovenous malformation with the use of polyvinyl alcohol particles (250 micro m) and gelfoam. Discussion includes the presenting signs and symptoms along with the method of both diagnosis and conservative management.

Decreasing risk of pregnancy loss following chorionic villus sampling. Elimination of transabdominal chorionic villus sampling during the ninth week of pregnancy.

Chorionic villus sampling (CVS) is a method of obtaining fetal cells in the first trimester of pregnancy for genetic analysis. The transcervical (TC) approach was the first technique to be widely used. In the National Institute of Child Health and Human Development collaborative study the absolute loss rate following CVS (the total number of spontaneous abortions and neonatal deaths following CVS) was 4%. More recently the transabdominal (TA) approach has been introduced. This study compares the loss rates for the two approaches at various gestational ages for three 6-month periods following the addition of the TA approach with each other and with the loss rates prior to the introduction of TA CVS. We found that the percentage of pregnancy losses following TA CVS during the ninth week of gestation (63-69 days) was consistently higher than for TC CVS performed at the same gestational age. The loss rate for TC CVS has steadily decreased since the introduction of TA CVS after remaining the same for the two years prior to the introduction of the TA approach. After minimizing the number of TA CVS performed during the ninth week of gestation, the overall loss rate during the most recent 6-month period has been reduced to 0.94%. We conclude that the lowest loss rate following CVS can be obtained if both the TA and TC methods are available, and that the number of TA procedures performed during the ninth week of gestation is minimized.

Term birth after midtrimester hysterotomy and selective delivery of an acardiac twin.

OBJECTIVE: Our aim was to determine whether hysterotomy and selective removal of an acardiac twin could improve the outcome of the "pump" twin. STUDY DESIGN: A literature and case review of the outcome of the acardiac twin malformation was performed. When an acardiac malformation was diagnosed at 19 weeks' gestation the patient was monitored with weekly ultrasonographic examinations. At 23 weeks' gestation, no blood flow could be demonstrated to the acardiac twin and it was thought that the continued presence of the acardiac twin posed a risk to the "pump" twin. A midtrimester hysterotomy was performed and the acardiac twin was delivered. RESULTS: After the midtrimester hysterotomy, the pregnancy progressed to term and a healthy female infant was delivered by elective cesarean section at 37 weeks' gestation. CONCLUSION: Midtrimester hysterotomy may be a useful intervention in cases of twinning when one fetus is a threat to the health of the other.

The risk and efficacy of chorionic villus sampling in multiple gestations.

Chorionic villus sampling (CVS) in the first trimester of pregnancy provides a safe and effective method for the early prenatal diagnosis of cytogenetic abnormalities in multiple gestations. In this multicentre study involving 126 twin and 2 triplet gestations primarily at risk because of advanced maternal age, the overall success rate of obtaining an adequate villus sample from each fetus was 99.2 per cent. For women of advanced maternal age, the rate of combined losses of chromosomally normal fetuses due to spontaneous abortion, stillbirths, and neonatal deaths was 5.0 per cent, compared with a 4.0 per cent total loss rate following CVS in singleton pregnancies derived from the same population (Rhoads et al., 1989). There was a 100 per cent success rate in obtaining a cytogenetic analysis; a cytogenetic abnormality was present in five of the multiple gestations (3.9 per cent) and involved seven fetuses (2.7 per cent). There were no diagnostic errors and no cases of normal cytogenetic diagnosis followed by the birth of a cytogenetically abnormal newborn. Based on cases of XX/XY admixture, cell contamination derived either from maternal decidua or the other twin occurred in 6 of 256 samples (2.3 per cent), giving an overall estimate of the frequency of cell contamination of 4.6 per cent; these cases did not present a diagnostic problem. However, there were two cases (0.8 per cent) in which the fetal sex was incorrect, due either to complete maternal cell contamination or to the possibility that in error one twin was sampled twice.

Chorionic villi sampling: a new technique for detection of genetic abnormalities in the first trimester.

Chorionic villi sampling (CVS) was performed on 22 patients who were at risk for a variety of genetic disorders between 8.5-11 weeks of gestation to determine whether the developing fetus had a chromosomal and/or biochemical disorder. A thin Portex catheter was passed transcervically into the chorion frondosum under constant real-time ultrasound guidance, and chorionic villi were obtained by gentle suction. The villi, which have the same genotype as the fetus, were processed directly for chromosomal and/or biochemical analysis. Results were available within six to 24 hours and were confirmed by short term cell cultures within three to ten days. One fetus affected with Tay-Sachs disease and one fetus with trisomy 16 were detected. There were no instances of fetal loss or major complications. In contrast to amniocentesis, the procedure is performed early in pregnancy and results of the genetic testing are available during the first trimester, which allows a first trimester termination of pregnancy if an abnormality is detected and greatly reduces parental anxiety if the findings are normal. We believe that CVS offers an alternative to amniocentesis in the detection of genetic disorders.

Diagnostic reliability of Mi-Mark helix technique in endometrial neoplasia.

To evaluate the diagnostic reliability of the Mi-Mark helix technique in endometrial neoplasia, 138 women with abnormal uterine bleeding underwent a prospective study of Mi-Mark sampling of the uterine cavity before dilatation and curettage. Of one hundred thirty-eight patients, 42% had postmenopausal bleeding and 18% had perimenopausal bleeding. The acceptability of this procedure by patients and physicians was remarkable. All invasive endometrial carcinomas were detected by Mi-Mark cytology. The most serious limitation of this technique was its failure to detect a large number of hyperplasias without atypia. Examination of a cell block along with cytology would facilitate the histopathologic diagnosis, especially of hyperplasia. The results of this study appear to justify the use of this procedure in high-risk patients.