Rapid aneuploidy screening with fluorescence in-situ hybridisation: is it a sufficiently robust stand-alone test for prenatal diagnosis?

OBJECTIVES: To assess the clinical utility of fluorescence in-situ hybridisation with chromosomes 13, 18, 21, X and Y as a stand-alone test in detecting chromosomal abnormalities, and the types of chromosomal abnormalities missed. DESIGN: Retrospective analysis. SETTING: A restructured Government hospital in Singapore and an academic hospital in the United States. PARTICIPANTS: Cytogenetic data of prenatal specimens and results of fluorescence in-situ hybridisation of 5883 patients performed between January 2000 and August 2007 were reviewed. RESULTS: Fluorescence in-situ hybridisation detected 558 (9.5%) patients with chromosomal abnormalities. Abnormal ultrasounds (70%) and maternal serum screens (21%) were the most indicative of chromosomal abnormalities. When comparing fluorescence in-situ hybridisation data with karyotype results for the five chromosomes of interest, the sensitivity and specificity were 99.3% and 99.9%, respectively. When comparing fluorescence in-situ hybridisation data with karyotype results for all chromosomes, the sensitivity decreased to 86.8%, whereas the specificity remained at 99.9%. Of 643 cases with karyotype abnormalities, 85 were fluorescence in-situ hybridisation-negative (false negative rate, 13.2%), which included structural rearrangements, chromosome mosaicism, and other trisomies. Despite abnormal ultrasound indications, fluorescence in-situ hybridisation missed 32 cases which included structural rearrangements, mosaicisms, and other trisomies. CONCLUSION: This study does not support fluorescence in-situ hybridisation as a stand-alone test. Institutions supporting fluorescence in-situ hybridisation as a stand-alone test must seriously consider the risks of a missed diagnosis.

The course of pregnancy in a patient with nail-patella syndrome.

INTRODUCTION: The nail-patella syndrome is a rare autosomal dominant condition with high penetrance. Pregnancy in such a patient is rare and we believe this to be the first report of a live birth occurring in a patient with nail-patella syndrome. CLINICAL PICTURE: A 25-year-old patient presented in her first pregnancy with nephrotic syndrome associated with characteristic bone abnormalities and nail dysplasia and was later diagnosed to have nail-patella syndrome. In her second pregnancy, the course of her pregnancy was complicated by further deterioration of renal function with superimposed pre-eclampsia resulting in early delivery at 28 weeks. CONCLUSION: Such pregnancies should be regarded as high risk and managed jointly with the renal physician in a tertiary care centre to ensure an optimal outcome to the mother and baby.

Gestational diabetes mellitus: a call for systematic tracing.

INTRODUCTION: Women with history of gestational diabetes mellitus (GDM) have up to 50% lifetime risk of developing frank diabetes mellitus (DM). They are an ideal group of patients to implement early interventional measures to halt the progression to diabetes. The success of any early intervention programme would depend largely on postpartum follow-up. We set out to study the response rate to postpartum oral glucose tolerance test (OGTT) and to profile the non-responders on 105 women who attended our Gestational Diabetes Joint Clinic (GDJC). MATERIALS AND METHODS: We divided these women into 3 groups according to their response to postpartum OGTT and compared their weights, glycaemic parameters and other clinical characteristics during gestation. Group A comprised non-responders or those who did not turn up for postpartum OGTT; group B comprised responders with a normal postpartum OGTT; and group C comprised responders with an abnormal postpartum OGTT defined as 2-hour plasma glucose equal or more than 7.8 mmol/L. RESULTS: The non-respondent rate to postpartum diabetes screening was 37.1%. The non-responders were found to be significantly heavier, with more severe hyperglycaemia during their pregnancy (in terms of glycosylated haemoglobin and results of antepartum OGTT) and had bigger babies compared to the responders with normal postpartum OGTT. Their features instead resembled those who had failed their postpartum OGTT. CONCLUSION: The group of non-responders was probably at similar risk of developing glucose intolerance postpartum as those who were tested abnormal. A more effective call and recall system and education programme is, therefore, needed to ensure postpartum attendance of all patients with GDM.

Pregnancy after renal transplantation: experience in Singapore General Hospital.

INTRODUCTION: Renal transplantation offers the best hope for those women with end-stage renal disease who wish to have children. However, pregnancy after renal transplantation is associated with increased maternal and fetal morbidity. The aim of this retrospective study was to review the outcome of pregnancy in renal transplant patients in Singapore General Hospital. MATERIALS AND METHODS: Forty-two pregnancies, occurring between December 1986 and December 2000, in 25 out of 141 renal transplant women in their reproductive age group (18 to 45 years old) were identified from our high-risk pregnancy record and retrospectively analysed. RESULTS: Thirteen (31%) pregnancies were unsuccessful; 10 abortions, 2 ectopic pregnancies and 1 stillbirth. The remaining 29(69%) successful pregnancies were complicated by maternal anaemia (65.5%), superimposed hypertension (44.8%), premature rupture of membranes (27.6%), urinary (17.2%) and lower genital tract (13.8%) infections, abnormal glucose tolerance test (13.8%), premature delivery (44.8%), low-birth-weight babies (44.8%), small-for-gestational-age babies (20.7%) and intrauterine growth restriction (20.7%). There were no documented cases of multiple pregnancies, congenital anomalies or deterioration of renal function. The outcome of pregnancy was not statistically influenced by preconception renal function and transplant-conception interval. CONCLUSIONS: Successful pregnancy is possible in women after renal transplantation. Such pregnancy is often associated with increased maternal and fetal complications and should be managed by a multidisciplinary approach in a tertiary centre. The function and survival of renal allograft was not adversely affected by pregnancy.

Outcome of pregnancy in Asian women with systemic lupus erythematosus: experience of a single perinatal centre in Singapore.

OBJECTIVE: To study maternal and fetal outcomes in women with systemic lupus erythematosus (SLE). MATERIALS AND METHODS: Retrospective study of 27 pregnancies in 18 women with SLE in a single centre. RESULTS: The mean age was 30 years and most patients were nulliparous. Twenty-six of 27 pregnancies were in disease remission at the time of booking. Renal impairment was present in 7 pregnancies (6 women), of whom 2 were in end-stage renal disease on dialysis. Gestational diabetes developed in 4 pregnancies. There were 6 cases of pre-existing hypertension and 5 with superimposed pre-eclampsia. One woman developed intrapartum eclampsia. Two women had secondary antiphospholipid syndrome (APS) and suffered late fetal losses; in addition, they also developed SLE flares in the form of autoimmune haemolytic anaemia in the postpartum period. There was no maternal mortality. There was one termination of pregnancy for severe renal disease. The median gestational age at delivery was 38 weeks (range, 24 to 40 weeks) and the mean birth weight was 3047 g; the median Apgar scores were 8 and 9 at 1 and 5 minutes of life, respectively. There were 5 cases of intrauterine growth restriction (IUGR), 4 of which occurred in women with renal impairment. There were no cases of congenital heart block or neonatal lupus. There was a late fetal loss at 24 weeks in a woman with secondary APS. There were 2 preterm deliveries (7.4%) due to intervention for IUGR. CONCLUSION: Good pregnancy outcomes can be expected in women with SLE in remission. Pre-pregnancy counselling is crucial to achieve this. All pregnancies should still be considered high risk and be managed jointly between the obstetricians, the perinatologists and the physicians. In particular, those with renal impairment are at increased risk of IUGR, superimposed pre-eclampsia and preterm births. Co-existing APS augurs a poorer prognosis for pregnancy outcome, and may present atypically as autoimmune haemolytic anaemia in the postpartum period.

Difficulties with prenatal diagnosis of the Walker-Warburg syndrome.

We describe a postnatally diagnosed case of Walker-Warburg syndrome--a form of congenital muscular dystrophy with lissencephaly and eye abnormalities. We reviewed the literature to highlight its clinico-radiological diagnostic features and discuss the difficulties encountered with prenatal diagnosis, especially in cases with no positive family history. An increased awareness of this rare but lethal condition, and a high index of suspicion during routine antenatal ultrasound, could prompt further advanced fetal ultrasonography and magnetic resonance imaging, and aid in timely prenatal diagnosis, management, and counseling.