First-trimester prenatal diagnosis of a familial subtelomeric translocation.

A new fluorescent in situ hybridization (FISH) technique utilizes a complete set of telomeric probes to screen for deletions or rearrangements within the subtelomeric regions of all chromosomes on a single slide. Such cryptic chromosome rearrangements would otherwise remain undetected by standard cytogenetic analysis. In this case report, we describe the first-trimester prenatal diagnosis of an unbalanced rearrangement in a family where such a cryptic subtelomeric rearrangement is segregating. Interestingly the fetus was also noted to have an increased nuchal translucency at the time first-trimester chorionic villus sampling was performed and a FISH diagnosis made. The result was subsequently confirmed on fetal material obtained after elective termination of the pregnancy. We believe this to be the first report in the literature (as by Medline, December 1999) of a first-trimester prenatal diagnosis using such subtelomeric probes where confirmation by conventional cytogenetic analysis was not possible.

The resolution of fetal hydrops using combined maternal digoxin and dexamethasone therapy in a case of isolated complete heart block at 30 weeks gestation.

The development of hydrops fetalis in cases of isolated complete heart block is associated with a very poor prognosis. Various pharmacological strategies have been proposed, involving both direct fetal access and transplacental therapy, with inconsistent results in small numbers of subjects. The optimal antenatal management will remain uncertain until multicentre controlled trials are organised. We report the complete resolution of fetal hydrops at 30 weeks of gestation using combination of maternal digoxin and dexamethasone therapy, despite persistence of the complete heart block. A Caesarean section was performed at 37 weeks of gestation due to evidence of fetal intrauterine growth restriction. The baby girl is now 8 months of age and remains well, with a heart rate of 45-50 beats per minute on no medication and without pacing.

Outcome after prenatal diagnosis of hypoplastic left-heart syndrome: a case series.

BACKGROUND: Traditionally, after prenatal diagnosis of hypoplastic left-heart syndrome (HLHS) couples have been offered termination of pregnancy or comfort care. Success of postnatal surgical options such as the Norwood procedure have been associated with survival of up to 60%. Whether survival is affected by the congenital anomaly being identified prenatally or postnatally remains uncertain. METHODS: We reviewed all cases of prenatally diagnosed HLHS referred to the Fetal Medicine Unit at Birmingham Women's Hospital over 6 years between 1994 and 1999. FINDINGS: 87 cases of HLHS were referred at a median gestational age (95% CI) of 23 (19-37) weeks. Of these, 53 (61%) chose prenatal karyotyping. The overall frequency of abnormal karyotype was found in seven of 59 cases (12%) and associated structural anomalies in 18 of 87 (21%). After counselling, 38 of 87 couples (44%) chose termination of pregnancy. Of the remaining 49 fetuses, 11 (23%) were not considered for postnatal surgery because of parental choice and they died after compassionate care. Of the 36 babies who had surgery postnatally, 12 survived (33%). We recorded a survival rate of 38% for the stage-1 Norwood procedure in the prenatally diagnosed HLHS in our centre. These data suggest that at the point of prenatal detection, the overall survival rate for fetuses with HLHS is 25% (if terminated pregnancies are excluded). INTERPRETATION: Fetal echocardiography allows early diagnosis of HLHS and gives clinicians the opportunity to triage this group dependent on prenatal findings, including karyotyping and the exclusion of other structural anomalies. These prospective data provide up-to-date information on the basis of which parents can make decisions.

The maternal cerebral circulation in pre-eclampsia: investigations using Laplace transform analysis of Doppler waveforms.

OBJECTIVE: To compare the maternal cerebral circulation in pre-eclampsia and normal pregnancy using an alternative method of Doppler waveform analysis called the Laplace transform analysis, which provides haemodynamic data additional to standard Doppler indices. DESIGN: A prospective cross-sectional study. SETTING: Department of Obstetrics and Gynaecology, Nottingham University Hospital. SAMPLE: The study involved 17 women in the third trimester of a normal pregnancy, 11 with pregnancy-induced hypertension and 26 with pre-eclampsia. METHODS: Doppler recordings were obtained from the internal and external carotid and middle cerebral arteries, with the measurements in hypertensive women being carried out before any treatment was given. The waveforms were then subjected to Laplace transform analysis which provides information on vessel wall stiffness and upstream and downstream flow conditions. MAIN OUTCOME MEASURES: The determination of the Laplace transform analysis parameters, including alpha, the natural frequency of oscillation and real pole, and pulsatility index. RESULTS: Laplace transform analysis demonstrated a significant increase in vessel wall stiffness in all the arteries in hypertensive pregnancies, but this was more marked in pre-eclampsia. The data were also consistent with, but do not prove, increased downstream resistance in the middle cerebral artery in women with pre-eclampsia but not in those with pregnancy-induced hypertension. CONCLUSIONS: The Laplace transform analysis of Doppler waveforms yields important physiological information concerning the cerebral circulation in pre-eclampsia, not detected using conventional Doppler indices. The results suggest that both pre-eclampsia and pregnancy-induced hypertension are associated with increased cerebral arterial wall stiffness and that, in addition, there may be cerebral vasoconstriction in pre-eclampsia.

Prenatal diagnosis and outcome in sacrococcygeal teratomas: a review of cases between 1992 and 1998.

A review of sacrococcygeal teratomas diagnosed in the antenatal period in the West Midlands region over a six year interval is reported. The aim of the study was to assess the contribution of ultrasound scanning to the management of cases and to determine the outcome of prenatally diagnosed sacrococcygeal teratomas. A retrospective review of 10 cases was performed to obtain pregnancy details, ultrasound scan data and outcome information. Two fetuses were electively aborted. Perinatal mortality was 62.5% in the remaining cases with all stillbirths and neonatal deaths occurring in babies delivered preterm (at or before 34 weeks' gestation). Marked increase in tumour size (mainly vascular/solid) was observed in five of the fetuses, which was often associated with local compression effects and the development of hydrops. Eight out of 10 cases were delivered vaginally, one following aspiration of the large cystic tumour. Three of the four neonates surviving to surgery underwent successful resection of their benign tumours. As well as guiding prognosis, serial ultrasound scans may also allow the mode of delivery to be planned more effectively. The importance of a multidisciplinary team approach to these difficult cases is emphasized.

Twin-twin transfusion syndrome.

Twin-twin transfusion syndrome is a complication of monochorionic twin pregnancies associated with extremely high perinatal morbidity and mortality. This article describes the ultrasound features associated with this condition and possible pathophysiological mechanisms. Management options are outlined, including recent development such as laser ablation of placental vascular communications.

The effect of the menstrual cycle on human cerebral blood flow: studies using Doppler ultrasound.

OBJECTIVE: Previous studies have demonstrated hemodynamic changes at different phases in the menstrual cycle, but the cerebral circulation has not been investigated. Our aim was to study carotid and cerebral blood flow during the menstrual cycle using Doppler ultrasound. Two different techniques of Doppler waveform analysis were used: standard Doppler indices and Laplace transform analysis (LTA), which may provide additional hemodynamic information. DESIGN: This was a prospective study of healthy volunteers who were providing pre-conception data for a subsequent longitudinal study set in the Department of Obstetrics and Gynaecology, Nottingham University Hospital. Nineteen women were studied in the mid-follicular and mid-luteal phases of 27 ovulatory menstrual cycles. Doppler recordings were obtained from the internal and external carotid and middle cerebral arteries. The standard Doppler indices (systolic/diastolic ratio, pulsatility index and resistance index) and LTA parameters were calculated. RESULTS: The standard Doppler indices were all significantly higher in the luteal compared to the follicular phase in the right middle cerebral artery (p < 0.05). However, no changes were seen in the standard indices in the carotid arteries or in any of the LTA parameters in any artery. Using the LTA, vessel wall stiffness was greater and absolute velocity of flow lower in the middle cerebral compared to the carotid arteries. CONCLUSIONS: Increased ventilation and a subsequent lowering of alveolar CO2 pressure secondary to a raised progesterone level in the mid-luteal phase could account for the observed changes within the middle cerebral artery. Under the conditions of this study the LTA appears less sensitive at detecting alterations in downstream resistance compared to the standard Doppler indices.

A case of recurrent congenital fetal anomalies associated with a familial subtelomeric translocation.

The potential of a new fluorescent in situ hybridization technique is discussed, which uses a complete set of telomeric probes to reveal cryptic chromosome rearrangements that remain undetected by standard cytogenetic analysis. We report the obstetric history of a patient who had a termination of pregnancy at 20 weeks for a fetus with multiple congenital anomalies but a normal male karyotype using conventional G-banding analysis on a mid-trimester placental biopsy. In a subsequent pregnancy, a diaphragmatic hernia and intra-uterine growth restriction were detected at 34 weeks' gestation and a fetal blood sample showed a normal female karotype. However, her child was born with dysmorphic features and additional severe abnormalities including microcephaly, anophthalmos and left fixed talipes. The child has shown marked developmental delay. In view of a strong family history of congenital abnormalities and recurrent miscarriage suggestive of a familial translocation, a fluorescent in situ hybridization technique using specific telomeric probes was performed on blood from the affected child and her parents. An unbalanced subtelomeric translocation was detected involving the long arms of chromosomes 2 and 7 in the child and a balanced translocation was detected in her father. Accurate genetic counselling and the opportunity for early prenatal diagnosis can now be offered to this family.

Prenatal diagnosis of tuberous sclerosis with intracerebral signs at 14 weeks' gestation.

We report the ultrasound detection of cranial abnormalities at 14 weeks' gestation in a fetus subsequently confirmed as having tuberous sclerosis using DNA linkage analysis within the affected family. The presence of asymmetrical ventricular enlargement persisted antenatally. Magnetic resonance imaging at 26 weeks indicated the possibility of poor gyral formation consistent with a neuronal migration disorder. Cardiac rhabdomyomata were not visualized on ultrasound scan until 30 weeks' gestation. Postnatal cranial ultrasound confirmed the significant neuropathology which was manifested by severe developmental delay and intractable fits in the child. The potential benefits of earlier diagnosis of tuberous sclerosis by cranial imaging are discussed, although in this patient the routine booking scan resulted in a path of prenatal diagnosis being undertaken which had originally been declined. A mechanism is proposed to explain the variable expression of tuberous sclerosis within this family based on altered TSC2 activity affecting neuronal migration.

A longitudinal study of maternal bloodflow in normal pregnancy and the puerperium: analysis of Doppler waveforms using Laplace transform techniques.

OBJECTIVE: To describe changes in the maternal cerebral circulation and the external iliac arteries throughout pregnancy and the puerperium using the Laplace transform analysis of Doppler waveforms. DESIGN: A prospective longitudinal study. SETTING: Department of Obstetrics and Gynaecology, Nottingham University Hospital. SAMPLE: A cohort of 17 healthy women studied every four weeks from early pregnancy until term and up to three months postpartum. Pre-conception data were available for 10 subjects. METHODS: Doppler signals were recorded from the internal carotid, middle cerebral and external iliac arteries. The waveforms were analysed using two different techniques: standard indices (systolic:diastolic ratio, pulsatility and resistance indices) and Laplace transform analysis, an alternative method of waveform shape analysis which may provide additional haemodynamic information. RESULTS: Vessel wall tone decreased at an early stage in pregnancy in the cerebral circulation and in the external iliac artery, but this rose again following delivery. The Laplace transform analysis techniques suggest dramatic eight-fold increases in downstream resistance within the external iliac artery in the second half of pregnancy. An increase in downstream resistance to flow also occurred in the internal carotid artery whereas more stable conditions were noted in the middle cerebral artery. CONCLUSIONS: Having a preliminary idea of the normal ranges for the Laplace transform analysis variables during pregnancy in a variety of maternal vessels, haemodynamic changes in pregnancies complicated by conditions, such as pre-eclampsia, can now be studied.

A longitudinal study of umbilical artery Doppler waveforms in normal pregnancy: analysis using Laplace transform techniques.

OBJECTIVE: To analyse umbilical artery Doppler waveforms using the Laplace transform analysis technique, an alternative method of waveform shape analysis, and to determine the normal ranges for the variables of this technique throughout normal pregnancy. DESIGN: A prospective longitudinal study. SETTING: Department of Obstetrics and Gynaecology, Nottingham University Hospital. SAMPLE: A cohort of 17 healthy women investigated every four weeks from the end of the first trimester until term. METHODS: Umbilical artery Doppler signals were recorded and analysed using the Laplace transform analysis technique. The median and interquartile ranges for each variable were determined and serial changes during pregnancy described. RESULTS: Vessel wall tone decreases in the umbilical artery at the beginning of the second trimester. Alpha, the variable related to upstream flow conditions, also decreases at this stage of pregnancy but values are then comparatively stable from 24 weeks of gestation until term. A fall in downstream resistance within the fetoplacental circulation during pregnancy is detected using the C-coefficient. Real pole appears to be of no value in the assessment of downstream resistance to flow in the fetus. CONCLUSIONS: The normal ranges for the Laplace transform analysis variables have been established for the umbilical artery longitudinally through normal pregnancy. Changes in fetal blood flow during complicated pregnancy can now be investigated using this technique.