Outcome after preterm delivery of infants antenatally diagnosed with congenital heart disease.

OBJECTIVE: To determine outcome of delivery before 36 weeks gestation in babies diagnosed antenatally with serious congenital heart disease (CHD). STUDY DESIGN: A retrospective database review at 2 tertiary care fetal cardiology centers. Details of neonatal course and outcome were obtained for those antenatally diagnosed with serious CHD who were live born before 36 weeks gestation. RESULTS: Between January 1998 and December 2002, 9918 women were referred for fetal echocardiography. Serious CHD was diagnosed in 1191 fetuses (12%), of which 46 (4%) delivered prematurely. Median gestation was 33 (range 24-35) weeks, and median birth weight 1.56 (0.50-3.59) kg. Extracardiac/karyotypic anomalies occurred in 23 (50%). Twenty-six babies (57%) underwent neonatal surgery: 16 a cardiac procedure, 5 a general surgical procedure, and 5 both. Eight died during or after operation (31%). Two babies underwent interventional heart catheterization; both died. The overall mortality rate was 72%. Extracardiac/karyotypic anomalies increased the relative risk of death by a factor of 1.36. Mean hospital stay for those surviving to initial discharge was 46 (2-137) days. CONCLUSIONS: There is a very high morbidity and mortality rate in this group, particularly for those with extracardiac/karyotypic anomalies. This should be reflected in decisions over elective preterm delivery and when counseling parents.

Dynamics of FSH-induced follicular growth in subfertile women: relationship with age, insulin resistance, oocyte yield and anti-Mullerian hormone.

BACKGROUND: During excess FSH treatment, different categories of follicles can be discerned: those responding and appearing to grow immediately (FolsS8) and those appearing subsequently during the follicular phase (Fols/d). These follicular categories were explored in cycles of assisted reproduction in the context of follicular biology, including primordial follicle pool (PFP) depletion, age, insulin resistance and potential markers. METHODS: Follicular cohorts were examined in 365 conventional ART cycles and related to patient insulin sensitivity, plasma FSH and anti-Mullerian hormone (AMH). RESULTS: Age had no influence upon the FolsS8 category but was associated with a significant (P < 0.005) decline in the Fols/d. In contrast, insulin-resistant polycystic ovary syndrome (IR-PCOS) showed a significant (P = 0.005) increase in FolsS8. Circulating AMH correlated strongly with oocyte yield and Fols/d. CONCLUSION: Age showed little impact on the initial follicular cohort, but a significant impact upon the secondary cohort, while insulin resistance appeared to promote the former category alone. The disturbance to follicular dynamics and AMH in IR-PCOS reflected a larger stockpile of FSH-sensitive follicles. Circulating AMH appears to represent all categories of antral follicles observed.

Echocardiographic assessment of conjoined twins.

OBJECTIVE: To determine the accuracy of prenatal and postnatal echocardiography in delineating the degree of cardiac fusion, intracardiac anatomy (ICA), and ventricular function of 23 sets of conjoined twins with thoracic level fusion presenting to a single centre over a 20 year period. METHODS: 13 thoracopagus, 5 thoraco-omphalopagus, and 5 parapagus pairs presenting to the authors' institution between 1985 and 2004 inclusive were assessed. Echocardiographic data were analysed together with operative intervention and outcome. Twins were classified according to the degree of cardiac fusion: separate hearts and pericardium (group A, n = 5), separate hearts and common pericardium (group B, n = 7), fused atria and separate ventricles (group C, n = 2), and fused atria and ventricles (group D, n = 9). RESULTS: The degree of cardiac fusion was correctly diagnosed in all but one set. ICA was correctly diagnosed in all cases, although the antenatal diagnosis was revised postnatally in three cases. Abnormal ICA was found in one twin only in two group A pairs, one group B pair, and both group C pairs. All group D twins had abnormal anatomy. Ventricular function was good in all twins scanned prenatally, and postnatally function correlated well with clinical condition. Thirteen sets of twins in groups A-C were surgically separated; 16 of 26 survived. None from groups C or D survived. CONCLUSIONS: Prenatal and postnatal echocardiography accurately delineates cardiac fusion, ICA, and ventricular function in the majority of twins with thoracic level fusion. It is integral in assessing feasibility of separation. The outcome in twins with fused hearts remains dismal.

Follicular diameters in conception cycles with and without multiple pregnancy after stimulated ovulation induction.

BACKGROUND: Controlled ovulation induction and intrauterine insemination (OI-IUI) is associated with multiple pregnancies, which are a cause of much concern. No reliable datasets have shown clear criteria for predicting multiple pregnancy. The aim of this study was to eliminate a number of variables by examining only conception cycles to determine ultrasound criteria posing risks of multiple pregnancy. METHODS: 112 OI-IUI conception cycles (multiple pregnancy rate 19.6%) were analysed retrospectively to identify factors that may be used to evaluate multiple pregnancy risk. Analyses of ultrasound data on the day of hCG administration allowed study of the role of primary, secondary and tertiary follicle diameters (FD). RESULTS: There were no multiple pregnancies in cases where there was a single FD > or = 14 mm, and no higher-order pregnancies where the tertiary follicle measured <14 mm. Follicles with an FD of 15 mm showed an 8% attributable implantation rate. CONCLUSIONS: Revision of the criteria for administration of the ovulatory dose of hCG should include the concept that follicles of 15 mm diameter may yield a pregnancy. We suggest that rigorous application of such criteria (critical FD of 16 mm combined with secondary FD evidence) will not reduce the programme pregnancy rate, but will reduce the incidence of multiple conceptions.

Concordance for hypoplastic left heart syndrome in a monochorionic twin pregnancy.

The risk of structural heart disease is significantly higher in twin pregnancies than in singleton pregnancies, but the concordance rate has been found to be relatively low, even in monochorionic pregnancies. This is the first report of a monochorionic twin pregnancy concordant for hypoplastic left heart syndrome (HLHS), the diagnosis having been made by fetal echocardiography at 15 weeks' gestation. The findings were confirmed at necropsy at 17 weeks' gestation, following termination of pregnancy. Both twins had mitral and aortic atresia, with severely hypoplastic aortic arches. This report adds weight to there being a genetic component to the cause of HLHS in some cases and illustrates how the findings from early fetal echocardiography with postmortem follow up can help to extend the understanding of the aetiology of this condition.

Traumatic disruption of the ascending aorta in a child after heart transplant.

We report a traumatic disruption of the ascending aorta in an 8-year-old boy who had undergone orthotopic cardiac transplant at 6.5 years of age for congenital heart block and dilated cardiomyopathy. At presentation his aortic injury was not immediately recognized, but persistence in identifying and confirming a suspicious aortic rupture was lifesaving.

Suppression of LH during ovarian stimulation: effects differ in cycles stimulated with purified urinary FSH and recombinant FSH.

There has been much debate about the role of luteinizing hormone (LH) during follicle stimulating hormone (FSH)-treated ovarian stimulation for assisted reproduction, where the endogenous LH is suppressed using a gonadotrophin-releasing hormone analogue. The requirement for LH in oestradiol biosynthesis is established, but other effects of 'insufficiency' are less clear, and little attention has been paid to the specific origin of the FSH used. The aim of this study was to examine the roles of profoundly suppressed circulating LH concentrations in cycles of ovarian stimulation for IVF, which were affected in two large separate cohorts of patients undergoing assisted reproduction. They were stimulated by either purified urinary FSH (MHP) or recombinant human FSH (rFSH). Within each dataset, outcomes were examined with respect to the circulating concentrations of LH in the mid-follicular phase, as plasma samples were stored prospectively, and assayed retrospectively. Patients with profoundly suppressed LH showed much reduced oestradiol concentrations at mid-follicular phase and at human chorionic gonadotrophin administration in cycles treated with either MHP or rFSH. However, gross ovarian response, as became evident by FSH dose demands, duration of stimulation, and also oocyte and embryo yields and embryo cryopreservation were influenced only in cycles treated with MHP. Furthermore, no effect upon pregnancy survival was observed. Thus, it is concluded that there is a demand for additional exogenous LH treatment only in cycles treated with purified urinary FSH where the LH is profoundly suppressed.

Evaluation of myocardial perfusion using positron emission tomography in infants following a neonatal arterial switch operation.

This study was performed to examine the use of positron emission tomography (PET) as a method of evaluating myocardial perfusion after the arterial switch operation for correction of transposition of the great arteries. Eleven asymptomatic patients (median age 2.3 years, range 1.3-4.3 years) post successful neonatal arterial switch repair for transposition underwent cardiac PET scanning using N(13) ammonia before and after dipyridamole infusion. Reconstructed data from static scans were analyzed for regional perfusion defects before and after pharmacological stress. Simultaneous assessment of coronary flow before and after stress was performed using a Patlak graphical analysis of data from dynamic scans. Results obtained from PET scanning were correlated with patterns of coronary artery anatomy, electrocardiogram (ECG) recordings, and echocardiographic evaluation. PET scanning demonstrated normal distribution of myocardial perfusion before and after stress in all but one patient, who was found to have a discrete inferior transmural perfusion defect. The defect was well correlated with perioperative ECG changes and a complicated postoperative course. Myocardial blood flow before dipyridamole (0.690 ml/min/g) was similar to reported adult rest values. There was a small but significant (p < 0.002) increase in myocardial blood flow after dipyridamole stress with a mean coronary flow reserve of 1.19 (+/-0.103). Echocardiographic evaluation failed to demonstrate significant wall motion abnormalities in any of the patients. Cardiac PET scanning is a reliable noninvasive method for evaluation of myocardial perfusion in small children. In this study, the incidence of myocardial perfusion defects after the arterial switch operation is lower than previously reported. The data obtained concerning coronary flow and coronary flow reserve after the arterial switch need to be interpreted with caution because normal data in children are not available.

Structured sedation programme for magnetic resonance imaging examination in children.

One thousand, eight hundred and fifty-seven patients underwent magnetic resonance imaging following the establishment of a structured sedation programme. Forty-eight of these patients came from the intensive care unit with a secure airway and were therefore excluded from any further analysis. Oral sedation was to be given to children aged 5 years and below. For children >/= 6 years old, oral sedation could be given only if their level of co-operation was judged to be inadequate by the referring physician. Oral sedation consisted of chloral hydrate 90 mg x kg-1 (maximum 2.0 g) orally with or without rectal paraldehyde 0.3 ml x kg-1. All magnetic resonance imaging requests for children who failed oral sedation as well as those referred for general anaesthesia from the outset were reviewed by a consultant anaesthetist who then allocated patients to undergo the procedure with either general anaesthesia or intravenous sedation. Scans requiring intravenous sedation or general anaesthesia were performed in the presence of a consultant anaesthetist. Intravenous sedation consisted of either a propofol 0.5 mg x kg-1 bolus followed by an infusion (maximum 3 mg x kg-1 x h-1) or midazolam 0.2-0.5 mg x kg-1 boluses. General anaesthesia was given using spontaneous ventilation with a mixture of 66% nitrous oxide in oxygen and isoflurane following either inhalation (sevoflurane) or intravenous (propofol) induction. One thousand and thirty-nine (57.4%) of the scans were done without sedation whereas 93 scans were performed during the consultant anaesthetist supervised sessions. Oral sedation failed in 50 out of 727 patients (6.9%). Eighty-seven per cent of children aged 5 years and below needed sedation compared with 4.5% of those aged over 10 years. Two patients who had only received chloral hydrate developed significant respiratory depression. This structured sedation programme has provided a safe, effective and efficient use of limited resources.

Effects of the insulin sensitizing drug metformin on ovarian function, follicular growth and ovulation rate in obese women with oligomenorrhoea.

Hyperinsulinaemic insulin resistance is commonly associated with hyperandrogenaemia, and menstrual dysfunction. The aim of this study was to examine the effects of the insulin sensitizing drug, metformin, on ovarian function, follicular growth, and ovulation rate in obese women with oligomenorrhoea. Twenty obese subjects with oligomenorrhoea [polycystic ovarian syndrome; (PCOS)] were observed longitudinally for 3 weeks prior to and for 8 weeks during treatment with metformin (850 mg twice per day). Fifteen patients completed the study. The frequency of ovulation was significantly higher during treatment than before treatment (P = 0.003). A significant decline in both testosterone and luteinizing hormone concentrations was recorded within 1 week of commencing treatment. Patients with elevated pretreatment testosterone concentrations showed the most marked increase in ovulation rate (P < 0.005), and significant reductions in circulating testosterone from 1.02 to 0.54 ng/ml (P < 0.005) after only 1 week of treatment. However, the sub-group with raised fasting insulin showed less marked changes, and the sub-group with normal testosterone concentrations showed no effect of treatment. Metformin had a rapid effect upon the abnormal ovarian function in hyperandrogenic women with PCOS, correcting the disordered ovarian steroid metabolism and ovulation rate; however, there appeared to be no effect in cases where the circulating androgen concentration was normal.

The effect of oral selenium supplementation on human sperm motility.

OBJECTIVES: To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility. PATIENTS AND METHODS: Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months. A further semen sample was collected at the end of the trial. Plasma selenium status was determined at the beginning and end of the trial period, as was total sperm density and motility. RESULTS: Plasma selenium concentrations were significantly (P < 0.001) higher in both selenium-treated groups than in controls. No significant effect of treatment on sperm density was recorded. Sperm motility increased in both selenium-treated groups, in contrast to a slight decline in the placebo group, but the difference was not significant. However, as the provision of additional vitamins had no effect on any variable measured it was considered justified to combine the two selenium-treated groups and compare them with the placebo treatment. On this basis, selenium treatment significantly (P < 0.002) increased plasma selenium concentrations and sperm motility (P = 0.023) but sperm density was again unaffected. Five men (11%) achieved paternity in the treatment group, in contrast to none in the placebo group. CONCLUSION: This trial confirms the result of an earlier study, that selenium supplementation in subfertile men with low selenium status can improve sperm motility and the chance of successful conception. However, not all patients responded; 56% showed a positive response to treatment. The low selenium status of patients not supplemented again highlights the inadequate provision of this essential element in the Scottish diet.

Effect of profound suppression of luteinizing hormone during treatment with gonadotrophin-releasing hormone analogue and purified follicle stimulating hormone upon development of cryopreserved embryos.

In response to previously published evidence from monkeys, this study examined the influence of the degree of luteinizing hormone (LH) suppression during the follicular phase of the stimulation cycle, upon cryopreserved embryo survival and development. The LH concentration of the mid-follicular phase was assessed in 250 in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone analogue (GnRHa) and either purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG), and was related to the performance of cryopreserved embryos in 351 subsequent embryo transfer cycles. Rates of embryo survival, embryo development rates, implantation rates, and pregnancy rates were examined with respect to the LH concentration recorded in the mid-follicular phase. In contrast to experimental evidence from other primates, there was no significant influence of the follicular phase LH concentration upon any of the parameters examined.

Palmoplantar keratoderma associated with congenital heart disease.

We report the case of a 14-month-old boy suffering from total anomalous pulmonary venous connection (TAPVC) associated with congenital diffuse palmoplantar keratoderma (PPK). An association between TAPVC and PPK has not been described previously, but PPK has been reported in association with a variety of cardiac abnormalities. Given the low frequency of both conditions, a genetic link seems likely. It is therefore advisable for dermatologists to check for heart abnormalities in children with congenital PPK.

Luteinizing hormone increases estradiol secretion but has no effect on progesterone concentrations in the late follicular phase of in vitro fertilization cycles in women treated with gonadotropin-releasing hormone agonist and follicle-stimulating hormone.

OBJECTIVE: To determine whether the late follicular phase increase in circulating P concentrations during controlled ovarian stimulation with GnRH-a and FSH can be influenced by addition of LH to the stimulating gonadotropin during the final 2 days. DESIGN: Randomization of patients to receive either FSH alone or FSH with LH (hMG) for the final 2 days before hCG, after follicular phase stimulation with purified FSH. SETTING: A.C.S. Unit at the Royal Infirmary, Glasgow, U.K. PATIENT(S): Patients were unselected and were undergoing IVF. INTERVENTION(S): Patients received stimulation with purified FSH (300 IU/d) until a follicle of 15 mm was observed; the regimen was then changed to either 225 IU of FSH or 225 IU of hMG. MAIN OUTCOME MEASURE(S): Estradiol and P in the peripheral circulation. RESULT(S): Significant increases in E2 concentration were observed, but there were no changes in the circulating progesterone. CONCLUSION(S): The late follicular phase increase in P is unrelated to any luteinizing process attributable to effects in the circulation or sensitization of follicular cells to LH.

The predictive value of the sperm-cervical mucus interaction test on the outcome of in vitro fertilization and ovulation induction combined with intrauterine insemination.

We investigated the effect of the sperm-cervical mucus penetration tests (SPT) on the fertilization rate (FR) and pregnancy rate (PR) in patients treated with either in vitro fertilization (IVF) or ovulation induction combined with intrauterine insemination (OI + IUI). Infertile couples where the women had normal ovarian function and a normal pelvis at laparoscopy and her partner had normal seminology who had failed at least 2 SPTs were treated with either IVF or OI + IUI. These patients were compared with similar couples in whom SPTs were satisfactory (SPT/ve). Group A (SPT+ve) consisted of 46 patients who underwent 78 treatment cycles of IVF and Group B (SPT-ve) comprised 31 patients who underwent 35 IVF cycles. Group C (SPT/ve) consisted of 39 patients who underwent 84 treatment cycles with OI + IUI, and Group D (SPT-ve) consisted of 15 patients who underwent 37 cycles with the same treatment. In patients treated with IVF, the FR and PR per embryo transfer were 77.0% and 20.0% respectively in Group A, and 64.0% and 22.6% respectively in Group B. The difference in FRs was statistically significant (p > 0.001) but there was no difference in the PRs. In patients treated with OI + IUI, the PR per cycle were 22.0% in Group C and 16.2% in Group D. These results indicate that SPT failure was associated with a lower FR in IVF but this did not affect the PRs. Similarly there was no difference in PRs following OI + IUI.

Outcome of intermittent tachyarrhythmias in the fetus.

Persistent fetal tachycardias are known to have an adverse effect on fetal outcome. The outcomes of intermittent fetal tachyarrhythmias over a 12-year period at a tertiary fetal cardiology center were studied. Main outcome criteria included control of arrhythmia and death during the prenatal or postnatal period. A total of 28 fetuses had an intermittent tachyarrhythmia: 4 had intermittent atrial flutter and 24 had supraventricular tachycardia. At the time of presentation 14 fetuses were hydropic, and in 5 of the 14 an arrhythmia had not been noted prior to referral. Of the 28 fetuses, 23 were treated by drug administration to the mother. Control of arrhythmia was achieved in 10 of 11 (91%) nonhydropic fetuses and 8 of 12 (67%) hydropic fetuses, with resolution of hydrops in four cases. In the overall group there was one intrauterine death, two neonatal deaths, and one infant death, all of which occurred in the hydropic group. The arrhythmia recurred postnatally in 11 of 23 (48%) fetuses. We conclude that intermittent tachyarrhythmias may have a deleterious effect on the fetus with a significant risk of death pre- or postnatally. The fetus with nonimmune hydrops should be evaluated for a cardiac cause. Maternal antiarrhythmic therapy is indicated for intermittent fetal tachyarrhythmias. There is a high risk of recurrence of the arrhythmia during infancy, particularly if hydrops was documented during the prenatal period or if Wolff-Parkinson-White syndrome is diagnosed. Fetal echocardiography is a useful tool for diagnosis and for monitoring the progress of the fetus.

A risk-benefit assessment of corticosteroids in the management of croup.

Croup is an acute clinical syndrome of childhood characterised by a barking cough, hoarse voice, stridor and a variable degree of respiratory distress. A meta-analysis and subsequent controlled trials clearly demonstrate that corticosteroids are efficacious in the management of croup, with their benefits conclusively outweighing their risks. In mild to moderate cases of croup either systemic or nebulised corticosteroids decrease symptoms and need for hospitalisation. Most reports use IM dexamethasone 0.6 mg/kg, although it is likely that dexamethasone 0.15 mg/kg has a similar effect. In controlled studies nebulised budesonide 2 mg is superior to placebo, and appears to have equivalent efficacy to oral dexamethasone. The risk of a single or short course of systemic corticosteroids are minimal, the only potential significant adverse effect being increased risk of severe varicella infection. Short courses of nebulised budesonide have no major adverse effects, and thus are likely to cause fewer adverse effects than systemic corticosteroids, although this is as yet unproven. On the body of data published to date, either oral dexamethasone 0.15 mg/kg or nebulised budesonide 2 mg are effective for mild to moderate croup. In severe croup requiring intubation, oral prednisolone 1 mg/kg every 12 hours decreases the duration of intubation and the need for re intubation. Unless there are clear contraindications, corticosteroids are the treatment of choice in mild, moderate and severe croup.

Isomerism of the atrial appendages associated with 22q11 deletion in a fetus.

There is a strong association between prenatally diagnosed structural heart disease and fetal chromosomal abnormalities. Isomerism of the atrial appendages is an exception to this because the fetal karyotype is usually normal in this condition. A case of atrial isomerism diagnosed antenatally with a normal female karyotype but with a microdeletion of chromosome 22q11 is reported.

Purified urinary follicle stimulating hormone induces different hormone profiles compared with menotrophins, dependent upon the route of administration and endogenous luteinizing hormone activity.

The effects of treatment of patients with gonadotrophin-releasing hormone analogue (GnRHa) combined with purified follicle stimulating hormone (FSH) for in-vitro fertilization (IVF) were investigated in detail to determine the influences of different administration routes and the degree of suppression of luteinizing hormone (LH). Responses to exogenous gonadotrophins were studied in infertile women (n = 60) with normal menstrual rhythm whose endogenous gonadotrophin activity was suppressed using a GnRHa in a long protocol. They were randomized to receive i.m. administration of human menopausal gonadotrophins (HMGim, Pergonal) or purified follicle stimulating hormone (FSH, Metrodin High Purity) administered either i.m. (MHPim) or s.c. (MHPsc). Responses were assessed by measuring plasma FSH, LH, oestradiol, testosterone and progesterone. After stimulation day 4, the MHPsc group showed significantly higher circulating concentrations of FSH than either the MHPim or HMGim group. However, the HMG group showed significantly higher oestradiol concentrations after stimulation day 5 than either MHP group. The differences in circulating oestradiol concentrations in the MHP-treated patients appeared to be strongly influenced by the mean circulating concentrations of LH in the follicular phase. The patients who showed mean follicular phase LH concentrations of < 1 IU/l showed longer follicular phases, lower circulating oestradiol and testosterone concentrations and also lower follicular fluid concentrations of oestradiol and testosterone, indicating a reduction in the normal follicular metabolism of progesterone to androgens and oestrogens under these conditions. This group of patients also showed longer follicular phases, which may have consequences for future clinical management.