Vascular aging and cardiac maladaptation in growth-restricted preterm infants.

OBJECTIVE: To assess arterial morphology and mechanics in preterm infants with fetal growth restriction (FGR) compared with those appropriate for gestational age (AGA) in the early neonatal period. STUDY DESIGN: This observational study involved 20 preterm FGR infants (28 to 32 weeks) of gestational age (GA) and birth weight (BW) <10th centile and 20 preterm AGA infants. Vascular ultrasound was performed to measure aortic properties. RESULTS: GA and BW of FGR and AGA infants were 29.8±1.3 vs 30±0.9 weeks (P=0.78) and 923.4±168 vs 1403±237 g (P<0.001), respectively. At 10.5±1.3 (s.d.) days after birth, blood pressure (systolic 51±3 vs 46±4 mm Hg, P<0.001) and maximum aorta intima-media thickness (621±76 vs 479±54 µm; P<0.001) were significantly higher in FGR infants. Arterial wall stiffness and peripheral resistance were also increased in the FGR infants (2.36±0.24 vs 2.14±0.24, P=0.008 and 22.2±5 vs 13.7±2.3 mm Hg min ml-1, P<0.001), respectively. Significant correlations between vascular mechanics and cardiac function were observed (resistance vs E/E', r=0.7 and Tei index, r=0.79). CONCLUSION: Maladaptive arterial-ventricular coupling was noted. Early detection may aid in early therapeutic strategies such as afterload reduction.

ABO incompatible renal transplantation following lung transplantation.

We present management strategies utilised for the first case of an urgent live-donor ABO incompatible B blood group renal transplant, in a patient with a prior A blood group lung transplant for cystic fibrosis. Three years on, renal function is excellent and stable, whilst lung function has improved.

Systemic arterial stiffness in infants with bronchopulmonary dysplasia: potential cause of systemic hypertension.

OBJECTIVE: Systemic hypertension is common among preterm infants with severe bronchopulmonary dysplasia (BPD); the exact cause is unknown. The objective of this preliminary hypothesis generating study was to examine systemic arterial structure and vasomotor function in a cohort of preterm infants with severe BPD, using a cohort of preterm infants without BPD and a cohort of term infants for comparison. STUDY DESIGN: After obtaining informed consent, we measured aortic wall thickness and vasomotor function by ultrasonography in 20 infants with severe BPD, 7 infants with no BPD, and compared them with 20 healthy term infants. RESULTS: Maximum aortic thickness was significantly higher in infants with BPD (827±163 µm) compared to those with no BPD (674±22 µm) and term infants (657±67 µm) (unadjusted P<0.0001). The input impedance was similarly elevated in the infants with BPD (574±127 dynes s( )cm(-5)) compared to those with no BPD (325±24 dynes s cm(-)(5)) or term infants (328±113 dynes s cm(-)(5)) (unadjusted P<0.0001). Stiffness index was significantly higher in the infants with BPD (3.4±0.6) compared to those with no BPD (2.6±0.3) or term infants (2.3±0.4) (unadjusted P<0.0001). Systemic vascular resistance was also significantly elevated in the infants with BPD. The results remained significant even after adjusting for gestational age and birth weight. Measures of vasomotor function significantly correlated with blood pressure. CONCLUSION: The aortic wall thickness and vasomotor function are significantly altered in preterm infants with severe BPD. These findings may explain the higher incidence of systemic hypertension in this population.

Outcomes of simultaneous heart-kidney and lung-kidney transplantations: the Australian and New Zealand experience.

BACKGROUND: Heart or lung transplantation alone in individuals with significant pre-existing renal impairment results in high mortality and morbidity. Simultaneous heart-kidney (SHK) or simultaneous lung-kidney (SLK) transplantation may be considered in patients with dual organ failure not suitable for single organ transplantation. AIM: We aimed to outline the Australian and New Zealand experience of SHK and SLK transplantations, focussing on patient characteristics and survival. METHODS: We analysed all SHK and SLK transplants performed in four centres across Australia and New Zealand between 1990 and 2014. RESULTS: Over the study period, 35 SHK and 3 SLK transplants were performed across 4 transplant centres. Mean age at transplantation for SHK transplants was 45 years, and for SLK transplant was 27 years. The most common aetiology of renal failure was glomerulonephritis. Most SHK transplant patients (77%) required renal replacement therapy prior to transplantation, with only one of the three patients undergoing SLK transplant, dialysis dependent. One-year survival for the cohort was 79%, which is lower than reported for single organ transplantation. However, 5- and 10-year survivals of 76% and 68%, respectively, were comparable. Isolated renal graft loss was seen in five patients, with only one patient successfully re-transplanted and the rest commencing dialysis. CONCLUSION: The Australian and New Zealand experience of SHK and SLK includes 38 patients with a high 1-year mortality, but excellent 5- and 10-year survivals. Based on this, it seems reasonable to continue to offer combined organ transplantation to select patients with dual organ failure.

Why babies - what Australian mothers say.

Earlier studies, mostly overseas, have explored the reasoning and thought processes underlying women's desires to conceive. A retrospective qualitative study was conducted to explore the motivations and anxieties of an Australian sample of women proceeding to a pregnancy and to explore their decision-making process. Twenty women over 18 years old who had one or more successful pregnancies and were recruited from a tertiary centre and private clinics, completed a questionnaire and a semi-structured interview. Thematic analysis was applied to the data. Multiple factors motivated women to proceed to a pregnancy and including influences arising from society or existing personal relationships, goals and desired experiences for parenthood and innate drives and reproductive related issues. The motivations of an urban Australian sample to proceed to a pregnancy differed little from studies elsewhere. This knowledge may assist in dealing with the concerns that underlie any pregnancy allowing for better obstetric management.

Why babies - What Australian mothers say.

Earlier studies, mostly overseas, have explored the reasoning and thought processes underlying women's desires to conceive. A retrospective qualitative study was conducted to explore the motivations and anxieties of an Australian sample of women proceeding to a pregnancy and to explore their decision-making process. Twenty women over 18 years old who had one or more successful pregnancies and were recruited from a tertiary centre and private clinics, completed a questionnaire and a semi-structured interview. Thematic analysis was applied to the data. Multiple factors motivated women to proceed to a pregnancy and including influences arising from society or existing personal relationships, goals and desired experiences for parenthood and innate drives and reproductive related issues. The motivations of an urban Australian sample to proceed to a pregnancy differed little from studies elsewhere. This knowledge may assist in dealing with the concerns that underlie any pregnancy allowing for better obstetric management.

Parental experiences of their infant's hospitalization for cardiac surgery.

BACKGROUND: Parents are increasingly recognized as important partners in children's health care. Despite their involvement in care, parental experiences of their child's hospitalization have received little research attention. In this study we explored parents' perceptions of what they found difficult, what they would like to be different and what they found to be helpful during their infant's hospitalization and surgery for the treatment of congenital heart disease. METHODS: Structured interviews were conducted with 154 parents (91 mothers, 63 fathers) whose infant underwent cardiac surgery (at <3 months of age) 1 month post discharge from hospital. Thematic and frequency analyses were performed. RESULTS: Parents reported a range of difficulties from dealing with their baby's unfolding illness, surgery and recovery to the structural and systemic issues associated with the broader context of their experiences. In an effort to be near their baby, parents struggled to obtain the necessities for daily living at the hospital and negotiate transitions between their hospital and home lives throughout the admission. Domains parents identified for change included the availability of facilities and resources and the quantity and quality of information and emotional support. Parents reported relationships with hospital staff as the most common source of support during this challenging time. CONCLUSIONS: Opportunities to improve parents' experiences when their infant is in hospital exist at an organizational level as well as at the clinical level. The significance of parents' relationship with hospital staff indicates the potential for each professional to impact on families' experiences on a daily basis. The range of challenges indicates the scope and need for allied health services.

Rightward convexity of the great vessel arising from the anterior ventricle: a novel fetal marker for transposition of the great arteries.

OBJECTIVES: Traditionally transposition of the great arteries (TGA) is suggested by bifurcation of the great vessel arising from the posterior ventricle and the parallel course of the great vessels as they leave the heart. These findings may be difficult to demonstrate, requiring additional fetal echocardiographic features to indicate TGA. In this study, we investigated a new marker of TGA, namely rightward convexity of the great vessel arising from the anterior ventricle. METHODS: We reviewed fetal studies from 2006 to 2010 in which an antenatal diagnosis of TGA was confirmed postnatally. We specifically viewed images obtained by scanning the great vessel arising from the anterior ventricle cranially to the superior mediastinum at the level of the three vessels and trachea view and compared them with similar views in normal hearts. RESULTS: In 21 cases of confirmed TGA, the great vessel arising from the anterior ventricle (aorta) coursing cranially demonstrated an abnormal convexity to the right. This was in contrast to convexity to the left or lack of convexity of the great vessel (pulmonary artery) arising from the anterior ventricle in fetuses with a normal heart. In two fetuses rightward vessel convexity from the anterior ventricle was the clue on the initial scan suggesting TGA, which was subsequently confirmed. In addition, only two vessels, the superior vena cava and aorta, were demonstrated in fetuses with TGA, the pulmonary artery and ductus arteriosus lying below (caudal to) the transverse arch. CONCLUSIONS: Noting the rightward convexity of the great vessel arising from the anterior ventricle may aid in the prenatal diagnosis of TGA. Furthermore, the relative simplicity of this sign may make it valuable in fetal screening for this cardiac defect.

Fetal cardiac catheterization using a percutaneous transhepatic access technique: preliminary experience in a lamb model.

OBJECTIVES: Human fetal cardiac intervention has hitherto typically involved a percutaneous transventricular approach. In fetal lambs, a transhepatic approach to access the fetal intra-abdominal veins after exteriorization of the uterus by laparotomy has been described. We aimed to develop a percutaneous transhepatic technique for catheterization of the fetal heart at mid-gestation that avoids maternal laparotomy. METHODS: In 10 fetal lambs (90-97 days' gestation), access to the fetal venous system was attempted by percutaneous puncture with a 5-F sheath into the umbilical vein (n = 1) or a 16-gauge IV-catheter into the hepatic vein (n = 9). This was followed by cardiac catheterization using a 1.8-2.6-F tapered coronary catheter. Euthanasia and postmortem examination were performed immediately postprocedure in two cases, or after normal term delivery in the remaining cases that survived the procedure. RESULTS: In one case fetal position precluded procedural attempts, and in another, the fetus, accessed by a 5-F sheath, died from umbilical hemorrhage. In eight cases, access to the fetal hepatic vein was achieved. In seven of these cases, the access catheter was advanced into the inferior vena cava, followed by catheterization of the right atrium (all cases) and four cardiac chambers (three cases). One fetus died during cardiac catheterization owing to right ventricle perforation, and the other seven fetuses were alive at the end of the procedure (87.5% survival). Immediate postmortem after euthanasia in two of the fetuses that survived the procedure detected intraperitoneal bleeding (4 mL and 20 mL), while postnatal postmortem examination following uneventful delivery at term in the remaining five fetuses revealed no vascular or cardiac trauma. CONCLUSIONS: Ultrasound-guided percutaneous transhepatic cardiac catheterization is feasible in mid-gestational fetal sheep. This technique has the potential for translation into human fetal cardiac and circulatory interventions.

Medical and ethical considerations in twin pregnancies discordant for serious cardiac disease.

OBJECTIVE: Prenatal ultrasound has led to the early diagnosis of major anomalies. However, the ready availability of this technology has led to increasing challenges for physicians counseling affected parents, which is all the more difficult in a twin pregnancy with only one affected fetus. This paper reviews the medical and ethical considerations in twin pregnancies discordant for a serious cardiac condition. STUDY DESIGN: Six recent twin pregnancies discordant for a serious cardiac condition and their outcomes are presented. Options considered in the management of the pregnancy were to continue or terminate the pregnancy, selectively terminate the affected twin or to decide whether to treat the affected twin once delivered. An approach to decision making in such situations has been formulated after critical analysis of the factors involved. RESULTS: Four of the six pregnancies were monochorionic twins. Two sets of parents decided to terminate the pregnancy. In the four that continued, two opted for the affected twin to be appropriately managed once delivered. A further two considered selective termination but opted to continue the pregnancy because of the risk of premature labor and/or cerebral hypoxia following such intervention. They sought a commitment, however, that they be given the option whether to treat the affected twin following delivery. Eventually both elected to have their babies treated, one of whom died in the postoperative period. DISCUSSION: Medical considerations included the risks of continuation of the pregnancy for the mother and her twins, the safety of termination (total or selective), and the risks to the unaffected fetus. Ethical issues revolved around concepts of autonomy, beneficence and justice from the standpoint of the family and the twins. The gestation and the viability of the twins played an important role in decision making and approaches, taking into account the local legal and other considerations. CONCLUSION: Attention is drawn to the complexities of the issues involved in twin pregnancies complicated by a serious cardiac condition in one of the twins. Optimal counseling requires sound clinical knowledge about the medical risks to the mother and her twins, and a clear understanding of the key ethical considerations. Such an approach will assist parents in their very difficult decision making.

Prenatal cardiac ultrasound finding in congenital disorder of glycosylation type 1a.

We present the antenatal cardiac findings in an infant in whom a postnatal diagnosis of congenital disorder of glycosylation type Ia (CDG-Ia) was confirmed. The antenatal findings at 34 weeks' gestation included biventricular cardiac hypertrophy with pericardial effusion, multiple skeletal anomalies and cerebral ventricular dilatation. A severe CDG-Ia multisystem clinical phenotype evolved in the postnatal period, with the infant succumbing at 3.5 weeks of age secondary to a large pericardial effusion with tamponade. A literature review suggests that this is the first case of cardiac manifestations of CDG-Ia observed antenatally. We would also like to suggest that CDG-Ia should be considered and if possible prenatal diagnosis performed in cases with hypertrophic cardiomyopathy, and/or pericardial effusion.

Fetal cardiac diagnosis and its influence on the pregnancy and newborn--a tertiary centre experience.

OBJECTIVES: To evaluate the impact of an abnormal fetal cardiac scan on the management of the pregnancy and the outcome of the newborn. METHODS: We reviewed all pregnancies that were referred to the Fetal Cardiac Unit for assessment to determine if the finding of a cardiac abnormality influenced the pregnancy and fetus, timing and mode of delivery, the treatment and outcome of the newborn. Diagnoses were confirmed by echocardiography following the baby's delivery. RESULTS: Between January 2005 and July 2006, there were 251 detailed fetal cardiac scans carried out on at risk pregnancies or those with suspected abnormal scans in 127 fetuses. Seven of the 92 mothers with abnormal fetal cardiac scans opted for termination. Two were successfully treated during the pregnancy for hydrops fetalis arising from a tachyarrhythmia. One was induced early because of deterioration of fetal well-being and increasing cardiac size. Twenty-six infants required a prostaglandin infusion prior to surgery. Two required intensive care for associated malformations. There were 24 survivors following complex surgery, and 2 deaths. Two infants with severe tricuspid valve incompetence from a dysplastic valve died, one associated with a septicaemia and the other where surgery was delayed because of prematurity and low birth weight. There was no maternal morbidity or mortality. CONCLUSIONS: Early detection of fetal cardiac malformation allows for careful counselling of the parents, ongoing antenatal review with a planned site and timing of delivery, and anticipatory postnatal care for optimum outcomes. The importance of careful screening is emphasized to allow for referral of mothers with potentially abnormal scans to an appropriate tertiary centre for confirmation and management.

Dysregulated growth factor gene expression is associated with tubulointerstitial apoptosis and renal dysfunction.

Chronic renal disease is characterized by declining renal function, loss of intrinsic renal cells, and their replacement with fibrotic tissue. This study investigates apoptosis and its regulation in the context of chronic renal disease. RNA was extracted from renal biopsies from patients with various forms of chronic renal disease. Expression of genes of the Bcl-2 family, death receptor pathway, and growth factors were measured by reverse-transcription real-time polymerase chain reaction. Apoptosis was detected by the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end-labeling technique. Tubulointerstitial apoptosis was positively associated with tubulointerstitial injury and renal dysfunction and increased 2.3-fold per unit (U) increase in transforming growth factor beta(1) (TGFbeta(1)) mRNA (P<0.05). Conversely, a 1 U increase in epidermal growth factor (EGF) mRNA was associated with a 47% decrease in tubulointerstitial apoptosis (P<0.05). Tubulointerstitial injury was correlated with increased TGFbeta(1) and tumour necrosis factor alpha (TNFalpha) mRNA (P<0.005) and decreased EGF mRNA (P<0.05). Additionally, for a 10 U decrease in the glomerular filtration rate there was an estimated increase of 5 and 10% in TGFbeta(1) and TNFalpha mRNA, respectively (P<0.05), whereas EGF mRNA decreased by an estimated 15% (P<0.005). Therefore dysregulation of cytokine/growth factor expression plays a central role in the progression of chronic renal disease through contribution to renal cell loss, tubulointerstitial injury, and renal dysfunction.

Parental perception of small ventricular septal defects in childhood.

OBJECTIVE: The main aim of this study was to determine the understanding and perception of parents following the diagnosis of a minor cardiac abnormality, namely a small ventricular septal defect, in the child. Other aims included discovering the reasons behind these perceptions and whether they affected the parents' management of their child and his/her cardiac problem. METHODS: Fifty-six infants and children from two tertiary centres and the private practices of the participating cardiologists were enrolled over a 5-month period. Questionnaires were prepared and distributed to all their parents. RESULTS: Complete data was obtained from 40 parents. Close to 80% of the parents perceived the small ventricular septal defect as a minor problem and most understood the nature of the defect. However, when asked about precautions for their child, only two-thirds recalled the need for antibiotic prophylaxis. Most parents experienced distress and anxiety when told initially of the diagnosis but none reportedly restricted their child's physical activity. CONCLUSIONS: Most parents have a clear understanding and perception of their child's small ventricular septal defect. There is a need for further improvement to facilitate parental understanding, especially with regard to the need for antibiotic prophylaxis.

Common pulmonary vein atresia: a diagnostic and therapeutic challenge.

Following Doppler echocardiographic evaluation, a 16 hour-old infant underwent successful surgical repair of common pulmonary vein atresia. Investigations for prolonged postoperative ventilatory assistance, including cardiac catheterization and computerized tomography, led to a clinical diagnosis of associated pulmonary lymphangiectasia. Although this has caused continuing tachypnoea, at 16 months of age, he remains otherwise well but with an uncertain prognosis.

The diagnosis of innocent murmurs in childhood.

Innocent murmurs are common in childhood. They require accurate diagnosis to avoid unnecessary anxiety and/or restrictions. With this in mind, we studied prospectively children diagnosed by a paediatric cardiologist as having innocent murmurs to review the necessity of investigations in excluding organic abnormalities. We included 63 children in the study. The majority had the so-called Still's, or musical/vibratory murmur. None had abnormal investigations, suggesting that such investigations are largely superfluous for the purpose of diagnosis in those patients with innocent murmurs seen by a paediatric cardiologist. They are often done, nonetheless, as part of the assessment and/or expectations of the parent or the referring physician.

Device closure of an atrial septal defect following successful balloon valvuloplasty in a neonate with critical pulmonary valve stenosis and persistent cyanosis.

Persistent cyanosis after successful balloon valvuloplasty for neonatal critical pulmonary valve stenosis is often related to poor right ventricular compliance and right-to-left shunting at the atrial level. A successful catheter closure of an atrial septal defect was performed with a dramatic increase in systemic oxygen saturation alleviating the need for a surgical systemic-to-pulmonary artery shunt.