Variations in Neonatal Length of Stay of Babies Born Extremely Preterm: An International Comparison Between iNeo Networks.

OBJECTIVE: To compare length of stay (LOS) in neonatal care for babies born extremely preterm admitted to networks participating in the International Network for Evaluating Outcomes of Neonates (iNeo). STUDY DESIGN: Data were extracted for babies admitted from 2014 to 2016 and born at 24 to 28 weeks of gestational age (n = 28 204). Median LOS was calculated for each network for babies who survived and those who died while in neonatal care. A linear regression model was used to investigate differences in LOS between networks after adjusting for gestational age, birth weight z score, sex, and multiplicity. A sensitivity analysis was conducted for babies who were discharged home directly. RESULTS: Observed median LOS for babies who survived was longest in Japan (107 days); this result persisted after adjustment (20.7 days more than reference, 95% CI 19.3-22.1). Finland had the shortest adjusted LOS (-4.8 days less than reference, 95% CI -7.3 to -2.3). For each week's increase in gestational age at birth, LOS decreased by 12.1 days (95% CI -12.3 to -11.9). Multiplicity and male sex predicted mean increases in LOS of 2.6 (95% CI 2.0-3.2) and 2.1 (95% CI 1.6-2.6) days, respectively. CONCLUSIONS: We identified between-network differences in LOS of up to 3 weeks for babies born extremely preterm. Some of these may be partly explained by differences in mortality, but unexplained variations also may be related to differences in clinical care practices and healthcare systems between countries.

Family Rooms in Neonatal Intensive Care Units and Neonatal Outcomes: An International Survey and Linked Cohort Study.

OBJECTIVES: To evaluate the proportion of neonatal intensive care units with facilities supporting parental presence in their infants' rooms throughout the 24-hour day (ie, infant-parent rooms) in high-income countries and to analyze the association of this with outcomes of extremely preterm infants. STUDY DESIGN: In this survey and linked cohort study, we analyzed unit design and facilities for parents in 10 neonatal networks of 11 countries. We compared the composite outcome of mortality or major morbidity, length of stay, and individual morbidities between neonates admitted to units with and without infant-parent rooms by linking survey responses to patient data from 2015 for neonates of less than 29 weeks of gestation. RESULTS: Of 331 units, 13.3% (44/331) provided infant-parent rooms. Patient-level data were available for 4662 infants admitted to 159 units in 7 networks; 28% of the infants were cared for in units with infant-parent rooms. Neonates from units with infant-parent rooms had lower odds of mortality or major morbidity (aOR, 0.76; 95% CI, 0.64-0.89), including lower odds of sepsis and bronchopulmonary dysplasia, than those from units without infant-parent rooms. The adjusted mean length of stay was 3.4 days shorter (95%, CI -4.7 to -3.1) in the units with infant-parent rooms. CONCLUSIONS: The majority of units in high-income countries lack facilities to support parents' presence in their infants' rooms 24 hours per day. The availability vs absence of infant-parent rooms was associated with lower odds of composite outcome of mortality or major morbidity and a shorter length of stay.

Cardiovascular Outcomes in Young Adulthood in a Population-Based Very Low Birth Weight Cohort.

OBJECTIVES: To assess differences in left heart structure and function, and endothelial function in a national cohort of very low birth weight (VLBW) young adults and term-born controls. STUDY DESIGN: The New Zealand VLBW study is a prospective, population-based, longitudinal cohort study which included all infants born <1500 g in 1986. The VLBW cohort (n = 229; 71% of survivors) and term-born controls (n = 100), were assessed at age 26-30 years. Measures of left heart structure and function were evaluated by echocardiography, vascular function was assessed using blood pressure, reactive hyperemia index, and arterioventricular coupling by calculating left ventricular (LV) and arterial elastance. RESULTS: Compared with controls, those born VLBW had smaller LVs, even when indexed for body surface area (mean LV mass, 89.7 ± 19.3 g/m2 vs 95.0 ± 22.3 g/m2 [P = .03]; LV end-diastolic volume, 58.3 ± 10.9 mL/m2 vs 62.4 ± 12.4 mL/m2 [P = .002]; and LV end-systolic volume, 20.8 ± 4.9 mL/m2 vs 22.6 ± 5.8 mL/m2 [P = .004]). VLBW participants had lower stroke volume (median, 37.2 mL/m2 [IQR, 33-42 mL/m2] vs median, 40.1 mL/m2 [IQR, 34-45 mL/m2]; P = .0059) and cardiac output (mean, 4.8 ± 1.2 L/min vs 5.1 ± 1.4 L/min; P = .03), but there was no difference in ejection fraction. The VLBW group had higher LV elastance (3.37 ± 0.88 mm Hg/mL vs 2.86 ± 0.75 mm Hg/mL; P < .0001) and arterial elastance (1.84 ± 0.4 vs 1.6 ± 0.4; P < .0001) and lower reactive hyperemia index (0.605 ± 0.28 vs 0.688 ± 0.31; P = .041). These measures were influenced by birth weight and sex, but we found limited associations with other perinatal factors. CONCLUSIONS: Being born preterm and VLBW is associated with differences in cardiovascular structure and function in adulthood. This population may be more vulnerable to cardiovascular pathology as they age. TRIAL REGISTRATION: Australian Clinical Trials Registry ACTRN12612000995875.

Trends in Outcomes for Neonates Born Very Preterm and Very Low Birth Weight in 11 High-Income Countries.

OBJECTIVE: To evaluate outcome trends of neonates born very preterm in 11 high-income countries participating in the International Network for Evaluating Outcomes of neonates. STUDY DESIGN: In a retrospective cohort study, we included 154 233 neonates admitted to 529 neonatal units between January 1, 2007, and December 31, 2015, at 240/7 to 316/7 weeks of gestational age and birth weight <1500 g. Composite outcomes were in-hospital mortality or any of severe neurologic injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia (BPD); and same composite outcome excluding BPD. Secondary outcomes were mortality and individual morbidities. For each country, annual outcome trends and adjusted relative risks comparing epoch 2 (2012-2015) to epoch 1 (2007-2011) were analyzed. RESULTS: For composite outcome including BPD, the trend decreased in Canada and Israel but increased in Australia and New Zealand, Japan, Spain, Sweden, and the United Kingdom. For composite outcome excluding BPD, the trend decreased in all countries except Spain, Sweden, Tuscany, and the United Kingdom. The risk of composite outcome was lower in epoch 2 than epoch 1 in Canada (adjusted relative risks 0.78; 95% CI 0.74-0.82) only. The risk of composite outcome excluding BPD was significantly lower in epoch 2 compared with epoch 1 in Australia and New Zealand, Canada, Finland, Japan, and Switzerland. Mortality rates reduced in most countries in epoch 2. BPD rates increased significantly in all countries except Canada, Israel, Finland, and Tuscany. CONCLUSIONS: In most countries, mortality decreased whereas BPD increased for neonates born very preterm.

Metabolic Syndrome in Very Low Birth Weight Young Adults and Controls: The New Zealand 1986 VLBW Study.

OBJECTIVE: To assess the physical well-being and components of the metabolic syndrome in a national cohort of very low birth weight (VLBW) young adults and same age controls. STUDY DESIGN: The New Zealand VLBW Study cohort prospectively included all infants with birth weight <1500 g born in 1986, with 338 (82%) surviving to discharge home. Height and weight were measured at age 7-8 years. The VLBW cohort (n = 229; 71% alive) and term-born controls (n = 100) aged 27-29 years were clinically assessed in a single center over 2 days, including assessment for components of the metabolic syndrome. RESULTS: Compared with controls, both male and female VLBW adults were significantly shorter (P < .001), but only females were lighter (P < .001) and had lower mean body mass index (P = .044), fat mass, and body fat percentage. Males, but not females, had significantly higher systolic blood pressure (P = .028), but there were no significant differences in other components of the metabolic syndrome. There was no difference in the prevalence of the metabolic syndrome in VLBW adults compared with controls (males, 22.2% vs 11.1%; P = .15: females, 12.8% vs 13.1%; P = .95). Examining the VLBW cohort with logistic regression, male sex, gestational age <28 weeks, Maori/Pacific Island ethnicity, and body mass index >90th percentile at age 7-8 years were significant predictors for the metabolic syndrome at age 27-29 years, with ORs of 2-4. CONCLUSIONS: Systolic blood pressure in males was the only component of the metabolic syndrome that was significantly elevated in VLBW adults compared with controls. Extreme prematurity (<28 weeks) and body mass index >90th percentile at age 7-8 years were significant predictors of the metabolic syndrome at age 27-29 years. TRIAL REGISTRATION: Registered at the Australian Clinical Trials Registry: ACTRN12612000995875.

Neonatal Outcomes of Very Low Birth Weight and Very Preterm Neonates: An International Comparison.

OBJECTIVE: To compare rates of a composite outcome of mortality or major morbidity in very-preterm/very low birth weight infants between 8 members of the International Network for Evaluating Outcomes. STUDY DESIGN: We included 58 004 infants born weighing <1500 g at 24(0)-31(6) weeks' gestation from databases in Australia/New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the United Kingdom. We compared a composite outcome (mortality or any of grade ≥3 peri-intraventricular hemorrhage, periventricular echodensity/echolucency, bronchopulmonary dysplasia, or treated retinopathy of prematurity) between each country and all others by using standardized ratios and pairwise using logistic regression analyses. RESULTS: Despite differences in population coverage, included neonates were similar at baseline. Composite outcome rates varied from 26% to 42%. The overall mortality rate before discharge was 10% (range: 5% [Japan]-17% [Spain]). The standardized ratio (99% CIs) estimates for the composite outcome were significantly greater for Spain 1.09 (1.04-1.14) and the United Kingdom 1.16 (1.11-1.21), lower for Australia/New Zealand 0.93 (0.89-0.97), Japan 0.89 (0.86-0.93), Sweden 0.81 (0.73-0.90), and Switzerland 0.77 (0.69-0.87), and nonsignificant for Canada 1.04 (0.99-1.09) and Israel 1.00 (0.93-1.07). The adjusted odds of the composite outcome varied significantly in pairwise comparisons. CONCLUSIONS: We identified marked variations in neonatal outcomes between countries. Further collaboration and exploration is needed to reduce variations in population coverage, data collection, and case definitions. The goal would be to identify care practices and health care organizational factors, which has the potential to improve neonatal outcomes.

Educating neonatal nurses in Brazil: a before-and-after study with interrupted time series analysis.

BACKGROUND: Preterm birth contributes significantly to infant mortality and morbidity, including blindness from retinopathy of prematurity (ROP). Access to intensive neonatal care is expanding in many countries, but care is not always optimal, one factor being that nursing is often by inadequately trained nurse assistants. OBJECTIVE: The aim of this study was to evaluate whether an educational package for nurses improves a range of outcomes including survival rates and severe ROP in 5 neonatal units in Rio de Janeiro, Brazil. METHODS: The study design included an uncontrolled before-and-after study in 5 units, with interrupted time series analysis. Participatory approaches were used to develop a self-administered educational package for control of pain, oxygenation, infection, nutrition, and temperature and to improve supportive care ('POINTS of Care'). Educational materials and DVD clips were developed and training skills of nurse tutors were enhanced. There were two 1-year periods of data collection before and after a 3-month period of self-administration of the education package. RESULTS: Overall, 74% of 401 nurses and nurse assistants were trained. A total of 679 and 563 infants were included in the pre- and post-training periods, respectively. Despite improvement in knowledge and nursing practices, such as the delivery and monitoring of oxygen, there was no change in survival (pre-training 80%, post-training 78.2%), severe ROP (1.6 vs. 2.8%), sepsis (11.3 vs. 12.3 cases per 1,000 infant days) or other outcomes. Outcomes worsened over the pre-intervention period but the change to an improvement after the intervention was not statistically significant. During the study period many trained staff left the units, but few were replaced. CONCLUSIONS: Future studies need to focus on barriers to implementation, team building, leadership and governance, as well as the acquisition of knowledge and skills.

Randomized controlled trial of oxygen saturation targets in very preterm infants: two year outcomes.

OBJECTIVE: To assess whether an oxygen saturation (Spo2) target of 85%-89% compared with 91%-95% reduced the incidence of the composite outcome of death or major disability at 2 years of age in infants born at <28 weeks' gestation. STUDY DESIGN: A total 340 infants were randomized to a lower or higher target from <24 hours of age until 36 weeks' gestational age. Blinding was achieved by targeting a displayed Spo2 of 88%-92% using a saturation monitor offset by ±3% within the range 85%-95%. True saturations were displayed outside this range. Follow-up at 2 years' corrected age was by pediatric examination and formal neurodevelopmental assessment. Major disability was gross motor disability, cognitive or language delay, severe hearing loss, or blindness. RESULTS: The primary outcome was known for 335 infants with 33 using surrogate language information. Targeting a lower compared with a higher Spo2 target range had no significant effect on the rate of death or major disability at 2 years' corrected age (65/167 [38.9%] vs 76/168 [45.2%]; relative risk 1.15, 95% CI 0.90-1.47) or any secondary outcomes. Death occurred in 25 (14.7%) and 27 (15.9%) of those randomized to the lower and higher target, respectively, and blindness in 0% and 0.7%. CONCLUSIONS: Although there was no benefit or harm from targeting a lower compared with a higher saturation in this trial, further information will become available from the prospectively planned meta-analysis of this and 4 other trials comprising a total of nearly 5000 infants.

Capacity building of nurses providing neonatal care in Rio de Janeiro, Brazil: methods for the POINTS of care project to enhance nursing education and reduce adverse neonatal outcomes.

BACKGROUND: Increased survival of preterm infants in developing countries has often been accompanied by increased morbidity. A previous study found rates of severe retinopathy of prematurity varied widely between different neonatal units in Rio de Janeiro. Nurses have a key role in the care of high-risk infants but often do not have access to ongoing education programmes. We set out to design a quality improvement project that would provide nurses with the training and tools to decrease neonatal mortality and morbidity. The purpose of this report is to describe the methods and make the teaching package (POINTS of care--six modules addressing Pain control; optimal Oxygenation; Infection control; Nutrition interventions; Temperature control; Supportive care) available to others. METHODS/DESIGN: Six neonatal units, caring for 40% of preterm infants in Rio de Janeiro were invited to participate. In Phase 1 of the study multidisciplinary workshops were held in each neonatal unit to identify the neonatal morbidities of interest and to plan for data collection. In Phase 2 the teaching package was developed and tested. Phase 3 consisted of 12 months data collection utilizing a simple tick-sheet for recording. In Phase 4 (the Intervention) all nurses were asked to complete all six modules of the POINTS of care package, which was supplemented by practical demonstrations. Phase 5 consisted of a further 12 months data collection. In Phase 1 it was agreed to include inborn infants with birthweight ≤ 1500 g or gestational age of ≤ 34 weeks. The primary outcome was death before discharge and secondary outcomes included retinopathy of prematurity and bronchopulmonary dysplasia. Assuming 400-450 infants in both pre- and post-intervention periods the study had 80% power at p = < 0.05 to detect an increase in survival from 68% to 80%; a reduction in need for supplementary oxygen at 36 weeks post menstrual age from 11% to 5.5% and a reduction in retinopathy of prematurity requiring treatment from 7% to 2.5%. DISCUSSION: The results of the POINTS of Care intervention will be presented in a separate publication. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN83110114.

Retinopathy of prematurity in 7 neonatal units in Rio de Janeiro: screening criteria and workload implications.

OBJECTIVES: The goals were to determine optimal screening criteria for retinopathy of prematurity (ROP) in 7 neonatal units in Rio de Janeiro, Brazil, and to explore the workload implications of applying different criteria. METHODS: Infants with birth weights of < or = 2000 g or gestational age of <37 weeks were examined by 3 ophthalmologists in 7 of the largest units in Rio de Janeiro, during a 34-month period. ROP was classified by using the international classification, and laser treatment was given to infants developing type 1 ROP. RESULTS: A total of 3437 (87%) of 3953 eligible infants were examined, of whom 124 (3.6% [range: 2.1%-7.8%]) were treated. Eleven infants were treated for aggressive posterior ROP. Appropriate screening criteria for the 2 NICUs with high survival rates (ie, > or =80% among infants with birth weights of <1500 g) would be < or =1500 g or <32 weeks. For NICUs with low survival rates (ie, <80%), appropriate criteria would be < or =1500 g or < or =35 weeks. UK, US, and previous Brazilian criteria would all miss infants needing treatment. CONCLUSIONS: ROP programs in Brazil should use the wider criteria of < or =1500 g or < or =35 weeks until further evidence-based criteria become available, although this would mean a slight increase in workload across the city, compared with use of the narrower criteria in the better units. Whether survival rates can be used as a proxy to indicate screening criteria requires further investigation.

Severe holocarboxylase synthetase deficiency with incomplete biotin responsiveness resulting in antenatal insult in samoan neonates.

We describe 7 Polynesian babies with a unique severe form of holocarboxylase synthetase deficiency characterized by antenatal growth retardation, subependymal cysts, only partial response to biotin, and a poor outcome.

Markers of oxidative injury in the cerebrospinal fluid of a premature infant with meningitis and periventricular leukomalacia.

Free radicals have been hypothesized to play a key role in the evolution of periventricular leukomalacia, although direct evidence of oxidative injury in the human infant is lacking. This case report is the first to demonstrate a marked elevation in the levels of lipid and protein oxidative products in the cerebrospinal fluid during the evolution of periventricular leukomalacia in a premature infant with meningitis.