Martina A. Steurer

Survival rates of extremely preterm infants (gestational age < 26 weeks) in Switzerland: impact of the Swiss guidelines for the care of infants born at the limit of viability

Background: Because ethical decision making in the care of extremely preterm infants varies widely across Europe, the Swiss Society of Neonatology decided to publish its own guidelines on the care of infants born at the limit of viability in 2002. Objective: To examine the potential impact of the guidelines on survival rates, short-term complication rates and centre-to-centre outcome differences of extremely preterm infants (22–25 completed weeks). Design: Population-based, retrospective cohort study. Setting: All nine level III neonatal intensive care units (NICU) and affiliated paediatric hospitals in Switzerland. Patients: 516 extremely preterm infants born alive between 1 January 2000 and 31 December 2004. Main outcome measures: Delivery room and NICU mortality rates, survival to hospital discharge and incidence of short-term complications in survivors were assessed. To study the impact of the guidelines, two cohorts from two different time periods were compared (years 2000/2001, n = 220; years 2003/2004, n = 204) whereas patients born in the year of the publication (2002, n = 92) were excluded. For centre-to-centre comparisons, the entire population (n = 516) was analysed. Results: There was a significant increase in survival rates of extremely preterm infants from 31% to 40% (RR 1.24, 95% CI 1.02, 1.50) after the publication of the Swiss guidelines. This improvement was largely explained by significantly improved survival from 42% to 60% (p = 0.01) among infants born at 25 completed weeks because of decreased NICU mortality. Improved survival was not associated with statistically significant changes in the incidence of short-term complications. Despite national guidelines, considerable centre-to-centre outcome differences have persisted. Conclusions: The publication of the Swiss guidelines was followed by significantly improved survival of extremely preterm infants but had no impact on centre-to-centre differences.

Late pharmacologic conditioning with volatile anesthetics after cardiac surgery

IntroductionThe aim of this randomized controlled trial was to investigate whether volatile anesthetics used for postoperative sedation have any beneficial effects on myocardial injury in cardiac surgery patients after on-pump valve replacement.MethodsAnesthesia was performed with propofol. After arrival in the intensive care unit (ICU), 117 patients were randomized to be sedated for at least 4 hours with either propofol or sevoflurane. Sevoflurane was administered by using the anesthetic-conserving device. Troponin T, creatine kinase, creatine kinase from heart muscle tissue, myoglobin, and oxygenation index were determined on arrival at the ICU, 4 hours after sedation, and in the morning of the first postoperative day (POD1). Primary end points were cardiac injury markers on POD1. As secondary end points oxygenation, postoperative pulmonary complications, and ICU and hospital stay were documented.ResultsFifty-six patients were analyzed in the propofol arm, and 46 patients in the sevoflurane arm. Treatment groups were comparable with regard to patient demographics and intraoperative characteristics. Concentration of troponin T as the most sensitive marker for myocardial injury at POD1 was significantly lower in the sevoflurane group compared with the propofol group (unadjusted difference, -0.4; 95% CI, -0.7 to -0.1; P < 0.01; adjusted difference, -0.2; 95% CI, -0.4 to -0.02; P = 0.03, respectively).ConclusionsThe data presented in this investigation indicate that late postconditioning with the volatile anesthetic sevoflurane might mediate cardiac protection, even with a late, brief, and low-dose application.Trial registrationClinicalTrials.gov: NCT00924222.

Trends and centre-to-centre variability in survival rates of very preterm infants (<32 weeks) over a 10-year-period in Switzerland.

Background The publication of Swiss guidelines for the care of infants at the limit of viability (22–25 completed weeks) was followed by increased survival rates in the more mature infants (25 completed weeks). At the same time, considerable centre-to-centre (CTC) differences were noted. Objectives To examine the trend of survival rates of borderline viable infants over a 10-year-period and to further explore CTC differences. Design Population-based, retrospective cohort study. Setting All nine level III neonatal intensive care units (NICUs) and affiliated paediatric hospitals in Switzerland. Patients 6532 preterm infants with a gestational age (GA) <32 weeks born alive between 1 January 2000 and 31 December 2009. Main outcome measures Trends of GA-specific delivery room and NICU mortality rates and survival rates to hospital discharge were assessed. For CTC comparisons, centre-specific risk-adjusted ORs for survival were calculated in three GA groups: A: 23 0/7 to 25 6/7 weeks (n=976), B: 26 0/7 to 28 6/7 weeks (n=1943) and C: 29 0/7 to 31 6/7 weeks (n=3399). Results Survival rates of infants with a GA of 25 completed weeks which had improved from 42% in 2000/2001 to 60% in 2003/2004 remained unchanged at 63% over the next 5 years (2005–2009). Statistically significant CTC differences have persisted and are not restricted to borderline viable infants. Conclusions In Switzerland, survival rates of infants born at the limit of viability have remained unchanged over the second half of the current decade. Risk-adjusted CTC outcome variability cannot be explained by differences in baseline demographics or centre case loads.

Persistent Pulmonary Hypertension of the Newborn in Late Preterm and Term Infants in California

BACKGROUND AND OBJECTIVES: There are limited epidemiologic data on persistent pulmonary hypertension of the newborn (PPHN). We sought to describe the incidence and 1-year mortality of PPHN by its underlying cause, and to identify risk factors for PPHN in a contemporary population-based dataset. METHODS: The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharges, readmissions, and birth and death certificates from 1 year before to 1 year after birth. We searched the database (2007–2011) for cases of PPHN (identified by International Classification of Diseases, Ninth Revision codes), including infants ≥34 weeks’ gestational age without congenital heart disease. Multivariate Poisson regression was used to identify risk factors associated with PPHN; results are presented as risk ratios, 95% confidence intervals. RESULTS: Incidence of PPHN was 0.18% (3277 cases/1 781 156 live births). Infection was the most common cause (30.0%). One-year mortality was 7.6%; infants with congenital anomalies of the respiratory tract had the highest mortality (32.0%). Risk factors independently associated with PPHN included gestational age <37 weeks, black race, large and small for gestational age, maternal preexisting and gestational diabetes, obesity, and advanced age. Female sex, Hispanic ethnicity, and multiple gestation were protective against PPHN. CONCLUSIONS: This risk factor profile will aid clinicians identifying infants at increased risk for PPHN, as they are at greater risk for rapid clinical deterioration.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age

This study quantified the impact of perinatal predictors and medical centre on the outcome of very low‐gestational‐age neonates (VLGANs) born at <32 completed weeks in Switzerland.

B-type natriuretic peptide: prognostic marker in congenital diaphragmatic hernia

Background:B-type natriuretic peptide (BNP) has not been evaluated in newborns with congenital diaphragmatic hernia (CDH). We hypothesized that BNP and severity of pulmonary hypertension (PH) would predict clinical outcome in these infants.Methods:We measured BNP levels and assessed severity of PH by echocardiography at 1 d and 1 wk of life. Outcome was classified by status at 56 d (or prior discharge): Good (n = 13) if alive on room air and Poor (n = 14) if expired or receiving respiratory support. We estimated area under the curve (AUC) and 95% confidence interval (CI).Results:BNP levels were higher at 1 d in newborns with Poor outcome (median 220 pg/ml vs. 55 pg/ml, P < 0.01). At 1 wk, there was no significant difference in BNP level (median 547 pg/ml vs. 364 pg/ml, P = 0.70, for Poor and Good outcomes). At 1 d, BNP level predicted outcome (AUC = 0.91, 95% CI = 0.77–1.0), but this relationship dissipated by 1 wk (AUC = 0.55, 95% CI = 0.31–0.79). Severity of PH did not predict outcome at 1 d (AUC = 0.51, 95% CI = 0.27–0.74), but prediction improved at 1 wk (AUC = 0.80, 95% CI = 0.61–0.99).Conclusion:BNP is a strong predictor of clinical outcome in newborns with CDH at 1 d of life.

Outcome of extremely low gestational age newborns (ELGANs) following a pro-active treatment approach: a Swiss single centre experience over 10 years.

QUESTIONS UNDER STUDY To determine the impact of a pro-active treatment approach on outcome of extremely low gestational age neonates (ELGANs; gestational age [GA] <28 weeks) born at the perinatal centre of Lucerne, Switzerland. METHODS We assessed rates of survival, severe neonatal morbidity and neuro-developmental impairment (NDI) of all ELGANs born alive and treated at our centre between 2000 and 2009. The results were compared with published data from contemporary national and international cohorts. RESULTS Over the 10-year study period, a total of 216 ELGANs were born alive at the perinatal centre of Lucerne. The survival rate was 74% for all live-born infants, and 81% for those admitted to the neonatal intensive care unit. Among the 160 survivors, 25% sustained at least one major neonatal morbidity; severe brain injury (i.e., periventricular/intraventricular haemorrhage grade 3 or 4 and/or cystic periventricular leukomalacia) affected 10%; moderate or severe bronchopulmonary dysplasia 16%; retinopathy of prematurity ≥ stage 3 1%; and necrotising enterocolitis 2%. Neuro-developmental outcome data at 18 to 24 months was available for 92% of all survivors: 88% had no or mild NDI, whereas moderate and severe NDI were present in 10% and 2%, respectively. CONCLUSION When compared with published national or international data, our pro-active treatment approach to ELGANs was associated with higher or equal survival rates without increasing rates of severe neonatal morbidity or neuro-developmental impairment at the age of 18 to 24 months.

Gestational Age and Outcomes in Critical Congenital Heart Disease

Population-based cohort study to assess impact of GA on morbidity and mortality in preterm and term infants with CCHD. BACKGROUND AND OBJECTIVES: It is unknown how gestational age (GA) impacts neonatal morbidities in infants with critical congenital heart disease (CCHD). We aim to quantify GA-specific mortality and neonatal morbidity in infants with CCHD. METHODS: Cohort study using a database linking birth certificate, infant hospital discharge, readmission, and death records, including infants 22 to 42 weeks’ GA without chromosomal anomalies (2005–2012, 2 988 925 live births). The International Classification of Diseases, Ninth Revision diagnostic and procedure codes were used to define CCHD and neonatal morbidities (intraventricular hemorrhage, retinopathy, periventricular leukomalacia, chronic lung disease, necrotizing enterocolitis). Adjusted absolute risk differences (ARDs) with 95% confidence intervals (CIs) were calculated. RESULTS: We identified 6903 out of 2 968 566 (0.23%) infants with CCHD. The incidence of CCHD was highest at 29 to 31 weeks’ GA (0.9%) and lowest at 39 to 42 weeks (0.2%). Combined neonatal morbidity or mortality in infants with and without CCHD was 82.8% and 57.9% at <29 weeks and declined to 10.9% and 0.1% at 39 to 42 weeks’ GA. In infants with CCHD, being born at 34 to 36 weeks was associated with a higher risk of death or morbidity than being born at 37 to 38 weeks (adjusted ARD 9.1%, 95% CI 5.5% to 12.7%), and being born at 37 to 38 weeks was associated with a higher risk of death or morbidity than 39 to 42 weeks (adjusted ARD 3.2%, 95% CI 1.6% to 4.9%). CONCLUSIONS: Infants born with CCHD are at high risk of neonatal morbidity. Morbidity remains increased across all GA groups in comparison with infants born at 39 to 42 weeks. This substantial risk of neonatal morbidity is important to consider when caring for this patient population.

Epidemiology of Live Born Infants with Nonimmune Hydrops Fetalis—Insights from a Population-Based Dataset

OBJECTIVE To evaluate the incidence, etiology, and 1-year mortality of nonimmune hydrops fetalis (NIHF) and to identify risk factors for mortality in a contemporary population-based dataset. STUDY DESIGN The California Office of Statewide Health Planning and Development maintains a database linking maternal and infant hospital discharge, readmissions, and birth and death certificate date from 1 year before to 1 year after birth. We searched the database (2005-2012) for infants with NIHF (identified by the International Classification of Diseases, 9th Revision, Clinical Modification code). Hazard models were used to identify risk factors for mortality in infants with NIHF; results are presented as hazard ratios (HRs, 95% CI). RESULTS The incidence of NIHF was 2.5 out of 10 000 among live born infants. Neonatal mortality was 35.1% (364 out of 1037) and overall mortality was 43.2% (448 out of 1037) at 1 year of age. Gestational age (GA) was predictive of mortality with a HR of 2.4 (95% CI 1.9-3.2) for preterm compared with term infants. The GA-adjusted HR for mortality was 1.3 (95% CI 1.1-1.6) for polyhydramnios and 1.5 (95% CI 1.2-2.0) for large for gestational age infants compared with appropriate for GA infants. Aneuploid infants with critical congenital heart disease had an adjusted HR of 2.3 (95% CI 1.5-3.6) compared with euploid infants without a structural birth defect. CONCLUSIONS In this large, population-based study, prematurity, polyhydramnios, and large for gestational age were predictors of increased mortality. Mortality is highly variable among euploid and aneuploid infants with and without structural birth defects and critical congenital heart disease.

Multicenter mortality and morbidity associated with pulmonary hypertension in the pediatric intensive care unit

Despite advances in the diagnosis and management of pediatric pulmonary hypertension (PH), children with PH represent a growing inpatient population with significant morbidity and mortality. To date, no studies have described the clinical characteristics of children with PH in the pediatric intensive care unit (PICU). A retrospective multicenter cohort study of 153 centers in the Virtual PICU Systems database who submitted data between 1 January 2009 and 31 December 2015 was performed. A total of 14,880/670,098 admissions (2.2%) with a diagnosis of PH were identified. Of these, 2190 (14.7%) had primary PH and 12,690 (85.3%) had secondary PH. Mortality for PH admissions was 6.8% compared to 2.3% in those admitted without PH (odds ratio = 3.1; 95% confidence interval = 2.9–3.4). Compared to patients admitted to the PICU without PH, those with PH were younger, had longer length of stay, higher illness severity scores, were more likely to receive invasive mechanical ventilation, cardiopulmonary resuscitation, extracorporeal membrane oxygenation, and more likely to have co-diagnoses of sepsis, heart failure, and respiratory failure. In a multivariate model, factors significantly associated with mortality for children with PH included age < 6 months or > 16 years, invasive mechanical ventilation, and co-diagnoses of heart failure, sepsis, hemoptysis, disseminated intravascular coagulation, stroke, and multi-organ dysfunction syndrome. Despite therapeutic advances, the disease burden and mortality of children with PH remains significant. Further investigation of the risk factors associated with clinical deterioration and mortality in this population could improve the ability to prognosticate and inform clinical decision-making.