Trial of Selective Early Treatment of Patent Ductus Arteriosus with Ibuprofen.

BACKGROUND: The cyclooxygenase inhibitor ibuprofen may be used to treat patent ductus arteriosus (PDA) in preterm infants. Whether selective early treatment of large PDAs with ibuprofen would improve short-term outcomes is not known. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled trial evaluating early treatment (≤72 hours after birth) with ibuprofen for a large PDA (diameter of ≥1.5 mm with pulsatile flow) in extremely preterm infants (born between 23 weeks 0 days' and 28 weeks 6 days' gestation). The primary outcome was a composite of death or moderate or severe bronchopulmonary dysplasia evaluated at 36 weeks of postmenstrual age. RESULTS: A total of 326 infants were assigned to receive ibuprofen and 327 to receive placebo; 324 and 322, respectively, had data available for outcome analyses. A primary-outcome event occurred in 220 of 318 infants (69.2%) in the ibuprofen group and 202 of 318 infants (63.5%) in the placebo group (adjusted risk ratio, 1.09; 95% confidence interval [CI], 0.98 to 1.20; P = 0.10). A total of 44 of 323 infants (13.6%) in the ibuprofen group and 33 of 321 infants (10.3%) in the placebo group died (adjusted risk ratio, 1.32; 95% CI, 0.92 to 1.90). Among the infants who survived to 36 weeks of postmenstrual age, moderate or severe bronchopulmonary dysplasia occurred in 176 of 274 (64.2%) in the ibuprofen group and 169 of 285 (59.3%) in the placebo group (adjusted risk ratio, 1.09; 95% CI, 0.96 to 1.23). Two unforeseeable serious adverse events occurred that were possibly related to ibuprofen. CONCLUSIONS: The risk of death or moderate or severe bronchopulmonary dysplasia at 36 weeks of postmenstrual age was not significantly lower among infants who received early treatment with ibuprofen than among those who received placebo. (Funded by the National Institute for Health Research Health Technology Assessment Programme; Baby-OSCAR ISRCTN Registry number, ISRCTN84264977.).

Successful transition for adolescent survivors of CHD: the Cambridge cardiac transition pathway.

PURPOSE: National standards to ensure effective transition and smooth transfer of adolescents from paediatric to adult services are available but data on successful transition in CHD are limited. The aim of this study is to assess the effectiveness of our transition pathway. METHODS: Adolescents with CHD, aged 15-19 years, who attended the joint cardiac transition clinic between 2009 and 2018 were identified from the Patient Administration Systems. Patient attendance at their first adult CHD service appointment at Royal Papworth Hospital was recorded. RESULTS: 179 adolescents were seen in the joint cardiac transition clinic in the 9-year study period. The median age of the patients when seen was 16 (range 15-19) years. 145 patients were initially planned for transfer to the Royal Papworth Hospital adult CHD service. Three patients were subsequently excluded and the success of the transfer of care in 142 patients were analysed. 112 (78%) attended their first follow-up in the adult CHD clinic as planned, 28 (20%) attended after reminders were sent out with 5/28 requiring multiple reminders, and only 2 (1.4%) failed to attend. Overall, transfer of care was achieved in 140 (98.6%) patients. CONCLUSION: A dedicated joint cardiac transition clinic involving multi-professional medical and nursing teams from paediatric and adult cardiology services appears to achieve high engagement rates with the adult services. This approach allows a 'face' to be put on a named clinician delivering the adult service and should be encouraged.

Managing CHD in Tertiary NICU in Collaboration with a Cardiothoracic Center.

Increasingly non-cardiac tertiary neonatal intensive care units (NCTNs) manage newborns with CHD prior to planned transfer to specialist cardiac surgical centres (SCSC). It improves patient flow in SCSCs, enables families to be nearer home, and improves psychological well-being Parker et al. (Evaluating models of care closer to home for children and young people who are ill: a systematic review, 2011). This practice has gradually increased as the number of SCSCs has decreased. This study examines the effectiveness of this expanding practice. The management provided, length of stay in the NCTN and outcomes are described for one UK NCTN situated at a significant distance from its SCSC. A retrospective observational study of cardiac-related admissions to a NCTN between January 2010 and December 2019 was conducted. 190 neonates were identified: 41 had critical CHD; 64 had major CHD. The cohort includes babies with a wide range of cardiac conditions and additional complexities. 23.7% (n = 45) required transfer to a specialist center after a period of stabilization and growth ranging from several hours to 132 days. 68% (n = 130) were discharged home or repatriated to a local NICU. Of the remaining 15 babies, 13 were transferred to other specialties including the hospice. Two died on NICU. The mortality was consistent with the medical complexity of the group Best and Rankin (J Am Heart Assoc 5:e002846, 2016), Laas et al. (BMC Pediatr 17:124, 2017). 8.9% (n = 17) died before age 2. Nine babies had care redirected due to an inoperable cardiac condition or life-limiting comorbidities. Our study demonstrates a complex neonatal cohort with CHD can be managed effectively in a NCTN, supporting the current model of care. The NCTN studied was well supported by pediatricians with expertise in cardiology alongside visiting pediatric cardiologists.

Ductal ligation timing and neonatal outcomes: a 12-year bicentric comparison.

Patent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications.

Study protocol: baby-OSCAR trial: Outcome after Selective early treatment for Closure of patent ductus ARteriosus in preterm babies, a multicentre, masked, randomised placebo-controlled parallel group trial.

BACKGROUND: The question of whether to treat patent ductus arteriosus (PDA) early or wait until symptoms appear remains high on the research agenda for neonatal medicine. Around 7000 extremely preterm babies under 29 weeks' gestation are born in the UK every year. In 40% of cases the PDA will fail to close spontaneously, even by 4 months of age. Untreated PDA can be associated with several serious and life-threatening short and long-term complications. Reliable data to support clinical decisions about PDA treatment are needed to prevent serious complications in high risk babies, while minimising undue exposure of infants. With the availability of routine bedside echocardiography, babies with a large PDA can be diagnosed before they become symptomatic. METHODS: This is a multicentre, masked, randomised, placebo-controlled parallel group trial to determine if early-targeted treatment of a large PDA with parenteral ibuprofen in extremely preterm babies (23+ 0-28+ 6 weeks' gestation) improves short and long-term health and economic outcomes. With parental informed consent, extremely preterm babies (born between 23+ 0-28+ 6 weeks' gestation) admitted to tertiary neonatal units are screened using echocardiography. Babies with a large PDA on echocardiography, defined by diameter of at least 1.5 mm and unrestricted pulsatile PDA flow pattern, are randomly allocated to either ibuprofen or placebo within 72 h of birth. The primary endpoint is the composite outcome of death by 36 weeks' postmenstrual age or moderate or severe bronchopulmonary dysplasia (BPD) at 36 weeks postmenstrual age. DISCUSSION: Prophylactic pharmacological treatment of all preterm babies unnecessarily exposes them to potentially serious side effects of drug treatment, when their PDA may have closed spontaneously. However, delaying treatment until babies become symptomatic could result in loss of treatment benefit as irreversible damage may have already been done. Targeted, early pharmacological treatment of PDA in asymptomatic babies has the potential to overcome the disadvantages of both prophylactic (overtreatment) and symptomatic approaches (potentially too late). This could result in improvements in the clinically important short-term clinical (mortality and moderate or severe BPD at 36 weeks' postmenstrual age) and long-term health outcomes (moderate or severe neurodevelopment disability and respiratory morbidity) measured at 2 years corrected age. TRIAL REGISTRATION: ISRCTN84264977 . Date assigned: 15/09/2010.

Changes in hemodynamics, cerebral oxygenation and cerebrovascular reactivity during the early transitional circulation in preterm infants.

BACKGROUND: Changes in systemic and cerebral hemodynamics in preterm infants during early transitional circulation are complex and may differ between infants with or without intraventricular hemorrhage (IVH). METHOD: In total, 43 infants born at median (range) 25 + 5 (23 + 3-31) had continuous near-infrared spectroscopy (NIRS) monitoring of tissue oxygenation index (TOI) and cerebrovascular reactivity within the first 48 h of life. Measurements of left and right cardiac outputs (LVO, RVO) and patent ductus arteriosus (PDA) were collected at 6, 12, 24, and 48 h of life. RESULTS: LVO increased within the first 48 h in the IVH (P = 0.007) and no-IVH (P < 0.001) groups. The pattern of change in LVO and RVO was not different between these two groups. TOI was lower in the IVH (P < 0.001) group. A positive correlation between TOI and LVO (P = 0.003) and a negative correlation between the tissue oxygen reactivity index (TOx) and LVO (P = 0.04) were observed at 24 h of life in the IVH group. PDA diameter was not different between IVH groups at any time interval. CONCLUSION: Cerebral oxygenation was lower and cerebrovascular reactivity was passive to systemic blood flow at 24 h in infants who developed an IVH.

Mortality among infants born with orofacial clefts in a single cleft network.

OBJECTIVE: To determine mortality rate and cause of death in infants born with orofacial clefts. METHODS: Retrospective case note review of all children with orofacial clefts within the East of England Cleft Network who have died. RESULTS: Between 2002 and 2010, of 638 children born with orofacial clefts, 23 died at a median age of 5 months (range, 1 day to 4 years). The overall mortality rate was 36 per 1000 cleft births. A total of 21 deaths were in the isolated cleft palate group, with a calculated death rate of 68.1 per 1000. One child each from the cleft lip and the cleft lip and palate groups died. Of the children who died, 21 (91%) had other structural abnormalities. Of these children, 19 (83%) died before their first birthday. The causes of death were mainly due to associated congenital anomalies (61%) and infection (17%). CONCLUSIONS: Children born with cleft palate have a 15-fold increase in mortality compared with the regional East of England infant mortality rate and at least a 10-fold increase when compared with other clefts. Pediatricians should be involved in the care of these complicated patients.

A randomized study to validate a midspinal canal depth nomogram in neonates.

Improving the accuracy of lumbar puncture (LP) in neonates should reduce the incidence of hemorrhagic contamination of cerebrospinal fluid (CSF) samples. We have previously demonstrated a linear correlation between neonatal weight and midspinal canal depth (MSCD), generating a nomogram and simple formula to allow MSCD estimation. In this study, we attempted to validate the nomogram by improving the quality of the CSF samples obtained. We consecutively randomized 99 infants in whom LP was clinically warranted to receive either a standard, "blind" ( N = 48) or "measured" ( N = 51) procedure. If allocated to the measured technique, the operator marked the LP needle with a Steri-Strip (TM) at the predicted depth of insertion (i.e., MSCD) derived from the weight-based nomogram. CSF samples were classified as clear (<500 red blood cells [rbc]/mL), mildly bloodstained (500 to 10,000 rbc/mL), heavily bloodstained (>10,000 rbc/mL or clotted), or failed procedures. Clear and mildly bloodstained LPs were "successful." Heavily bloodstained or failed procedures were considered "unsuccessful." We also recorded the number of attempts required to obtain a CSF sample. The overall success rate (

Retrospective study of neonatal ligation during 2002 in the United Kingdom of persistently patent arterial ducts.

Our aim was to ascertain the number of neonatal ligations of the patent arterial duct performed in the United Kingdom in 2002, and to determine the survival of the neonates after 30 days. A postal questionnaire was sent to the lead paediatician in every hospital in the United Kingdom possessing a special care or neonatal intensive care unit, requesting information on the number of babies referred for ligation of a persistently patent arterial duct. A separate questionnaire was sent to the paediatric cardiothoracic centres for information on babies who underwent the procedure. Cross-referencing the responses identified neonates who were not reported in the separate questionnaires. Additional information was requested from the central cardiac audit database. The overall response rate was 74%, with 172 forms returned of 234 distributed. From the combined responses, we ascertained that ligation has been performed in 244, with survival at 30 days of 94%. There were problems in identifying some babies because of the incomplete nature of the information received from both referring hospitals and specialist cardiothoracic centres. We would recommend a joint prospective study is conducted by paediatricians and paediatric cardiologists to determine the short and long term outcomes in this population known to be at high risk.

Review of resuscitation training amongst consultants and middle grade paediatricians.

AIMS: To review the resuscitation training of senior and middle grade paediatricians. METHODS: A questionnaire was sent to all paediatricians above the level of senior house officer in the Eastern Region of the UK to determine: (1) completion of basic life support (BLS) training in the previous year; (2) previous attendance at a paediatric/neonatal advanced life support course; (3) resuscitation provider accreditation; (4) instructor status. RESULTS: Replies were received from 153 out of 160 paediatricians. During the study period 48% 95% CI (36% and 60%) of general hospital consultants (GC), 40% (21% and 61%) of community consultants (CC), 75% (59% and 87%) of specialist registrars (SpRs) and 53% (28% and 77%) of non-consultant grade doctors (T/SG) had received BLS training. 86% (76% and 93%) GC, 24% (9% and 45%) CC, 100% (91% and 100%) SpRs and 82% (57% and 96%) of T/SG had previously attended an advanced life support (ALS) course. Accredited provider skills were maintained by 54% (41% and 65%) GC, 12% (3% and 31%) CC, 83% (67% and 93%) SpRs and 53% (28% and 77%) of T/SG. Only 28% GC, 4% CC, 20% SpRs and 6% T/SG were instructors on any of the advanced courses. CONCLUSIONS: Most paediatricians have attended an ALS courses at some point during their training. Consultants are poor at maintaining/re-certifying their advanced resuscitation skills. Few paediatric consultants and residents instruct on ALS courses.

Outcome following patent ductus arteriosus ligation in premature infants: a retrospective cohort analysis.

BACKGROUND: The patent ductus arteriosus (PDA) is an important problem in premature infants. Surgical PDA ligation is usually only be considered when medical treatment has either failed or was contraindicated. The aims of our study were to determine the mortality and morbidity following patent ductus arteriosus ligation in premature infants, and whether prostaglandin synthetase inhibitor (PSI) use prior to ligation affects outcome. METHODS: A retrospective case note review study to determine the outcome of premature infants undergoing patent ductus arteriosus ligation in one tertiary neonatal intensive care unit and two paediatric cardiothoracic centres. RESULTS: We had follow-up data on 87 infants. Cumulative mortality rates at 7 days, 30 days and at hospital discharge were 2%, 8% and 20% respectively. The incidence of chronic lung disease, intraventricular haemorrhage, necrotising enterocolitis and retinopathy of prematurity were 77%, 39%, 26% and 28% respectively. There was no difference in mortality, incidence of chronic lung disease or duration of oxygen dependence between those who had and those who had not received a PSI prior to surgical ligation. In those who had received 2 or more courses of PSI prior to surgical ligation, there was a trend to increase in the duration of oxygen therapy and chronic lung disease, but no difference in mortality. CONCLUSION: This study shows that patent ductus arteriosus ligation is a relatively safe procedure (30 day survival 92%) but there is substantial late mortality and a high incidence of morbidity in the survivors. 2 or more courses of PSI prior to surgical ligation trends to increased oxygen dependence and chronic lung disease. This high risk population requires careful follow-up. A definitive prospective cohort study is lacking.

ASSESSING THE IMPACT OF A NEWLY INTRODUCED ELECTRONIC PRESCRIBING SYSTEM ACROSS A PAEDIATRIC DEPARTMENT - LESSONS LEARNED.

AIM: Prescribing audits have shown that the Women's and Children's Directorate reported higher number of prescription errors on the paediatric and neonatal wards compared to other areas in the Trust. Over the last three years a multidisciplinary prescribing team (PT), which included senior clinicians, pharmacists and trainees introduced a number of initiatives to improve the quality of prescribing. Strategies included structured departmental inductions, setting up of designated prescribing areas and reviewing errors with the prescriber. Year on year there were fewer prescribing errors.1 With the introduction of a new electronic prescribing system in October 2014 prescribing error rates were expected to decrease further, eradicating omissions around allergy recording, ward location and drug names. The aim of this abstract is to highlight the impact of the new system and describe lessons learned. METHOD: In the summer of 2014, all inpatient drug charts across the department were reviewed on three non-consecutive days over a period of three weeks. Prescribing errors were identified by the ward pharmacist. Errors were grouped according to type and further analyzed by the PT. Errors deemed to have no clinical significance were excluded. Error rates were compared to the previous audits performed with identical methodology. Following the introduction of the electronic prescribing system, the ward pharmacists continued to review prescription charts on daily basis and generate regular error reports to notify the staff of new challenges. RESULTS: There were 174 (14%) errors out of 1225 prescriptions on 181 drug charts. The most commonly made mistakes included drug name errors, strength of preparation, allergies and ward documentation, prescriber's signature omissions, and antibiotic review and end dates. The introduction of an electronic system has eliminated drug name, strength of preparation, allergy recording and ward errors. However, serious challenges have been identified: entering of an incorrect weight resulted in all drug dosages being inaccurate; the timing of drug levels for Vancomycin and Gentamicin and the administration of subsequent doses have been problematic. Communication difficulties between all staff groups has led to dosage omission, duplicate administration and confusion around start and stop dates. The ability to prescribe away from the bedside and indeed the ward has compounded some of these problems. CONCLUSION: The implementation of a new electronic system has reduced prescribing errors but has also resulted in new challenges, some with significant patient safety implications. The lessons learned and good practice introduced following previous audits of "traditional paper based" prescribing are equally important with electronic prescribing. Communication between staff groups is crucial. It is likely that the full benefits of the system will be realized a year after its introduction. On-going audit is required to assess the impact and safety of the electronic prescribing and lessons learned.

Impact of infectious diseases consultation on the management of Staphylococcus aureus bacteraemia in children.

OBJECTIVES: Infectious diseases consultation (IDC) in adults with Staphylococcus aureus bacteraemia (SAB) has been shown to improve management and outcome. The aim of this study was to evaluate the impact of IDC on the management of SAB in children. STUDY DESIGN: Observational cohort study of children with SAB. SETTING: Cambridge University Hospitals National Health Service (NHS) Foundation Trust, a large acute NHS Trust in the UK. PARTICIPANTS: All children with SAB admitted to the Cambridge University Hospitals NHS Foundation Trust between 16 July 2006 and 31 December 2012. METHODS: Children with SAB between 2006 and 31 October 2009 were managed by routine clinical care (pre-IDC group) and data were collected retrospectively by case notes review. An IDC service for SAB was introduced in November 2009. All children with SAB were reviewed regularly and data were collected prospectively (IDC group) until 31 December 2012. Baseline characteristics, quality metrics and outcome were compared between the pre-IDC group and IDC group. RESULTS: There were 66 episodes of SAB in 63 children-28 patients (30 episodes) in the pre-IDC group, and 35 patients (36 episodes) in the IDC group. The median age was 3.4 years (IQR 0.2-10.7 years). Patients in the IDC group were more likely to have echocardiography performed, a removable focus of infection identified and to receive a longer course of intravenous antimicrobial therapy. There were no differences in total duration of antibiotic therapy, duration of hospital admission or outcome at 30 or 90 days following onset of SAB. CONCLUSIONS: IDC resulted in improvements in the investigation and management of SAB in children.

Outcome of infants with prenatally diagnosed congenital heart disease delivered outside specialist paediatric cardiac centres.

OBJECTIVE: To determine the outcome of neonates with a suspected antenatal diagnosis of congenital heart disease (CHD) who were delivered away from a paediatric cardiothoracic centre and were initially managed in a level 3 Neonatal Intensive Care Unit. METHODS: An 18-year ongoing study conducted in a single institution. RESULTS: Between 1992 and 2009, 143 fetuses with suspected CHD were identified, and 124 babies were delivered locally. 13 babies with a normal postnatal echocardiogram and six with isolated arrhythmias were excluded from the study. Structural CHD was confirmed in 105 infants; of these, 94 (90%) survived the neonatal period. Of the 11 neonatal deaths, only four of these infants underwent surgery; most had additional risk factors including: prematurity, very low birth weight, and genetic and other structural congenital anomalies. CONCLUSIONS: This study demonstrates that appropriately selected infants with antenatally diagnosed CHD can be safely delivered and initially managed in a non-cardiac centre during their neonatal period. Deliveries need to be carefully planned with close collaboration among neonatologists, obstetricians, paediatric cardiologists, mid-wives and parents.

The effect of antenatal corticosteroids on fetal growth, survival, and neurodevelopmental outcome in triplet pregnancies.

Triplet pregnancies have increased as a result of infertility therapy. The objectives of this study are to review the outcome of triplet pregnancies and to determine the effect of different antenatal corticosteroid treatments on fetal growth, survival, and neurodevelopmental outcome. A retrospective case note review of infant and maternal records from a single tertiary neonatal unit was performed from January 1, 1986, through December 31, 1999; 173 live births from 60 triplet pregnancies were divided into groups according to maternal antenatal corticosteroid exposure. Logistic regression model showed only gestation had a significant effect on survival. There was no adverse effect of steroid exposure on weight or head circumference at birth. Ninety percent of live births survived to discharge. Of 143 survivors, only five infants had documented neurodevelopmental problems. Survival rate in triplet pregnancy is high. In this analysis of cohort data repetitive antenatal steroids were not associated with adverse outcome.