Comparing very low birth weight versus very low gestation cohort methods for outcome analysis of high risk preterm infants.

BACKGROUND: Compared to very low gestational age (<32 weeks, VLGA) cohorts, very low birth weight (<1500 g; VLBW) cohorts are more prone to selection bias toward small-for-gestational age (SGA) infants, which may impact upon the validity of data for benchmarking purposes. METHOD: Data from all VLGA or VLBW infants admitted in the 3 Networks between 2008 and 2011 were used. Two-thirds of each network cohort was randomly selected to develop prediction models for mortality and composite adverse outcome (CAO: mortality or cerebral injuries, chronic lung disease, severe retinopathy or necrotizing enterocolitis) and the remaining for internal validation. Areas under the ROC curves (AUC) of the models were compared. RESULTS: VLBW cohort (24,335 infants) had twice more SGA infants (20.4% vs. 9.3%) than the VLGA cohort (29,180 infants) and had a higher rate of CAO (36.5% vs. 32.6%). The two models had equal prediction power for mortality and CAO (AUC 0.83), and similarly for all other cross-cohort validations (AUC 0.81-0.85). Neither model performed well for the extremes of birth weight for gestation (<1500 g and ≥32 weeks, AUC 0.50-0.65; ≥1500 g and <32 weeks, AUC 0.60-0.62). CONCLUSION: There was no difference in prediction power for adverse outcome between cohorting VLGA or VLBW despite substantial bias in SGA population. Either cohorting practises are suitable for international benchmarking.

Scoping review shows wide variation in the definitions of bronchopulmonary dysplasia in preterm infants and calls for a consensus.

The use of different definitions for bronchopulmonary dysplasia (BPD) has been an ongoing challenge. We searched papers published in English from 2010 and 2015 reporting BPD as an outcome, together with studies that compared BPD definitions between 1978 and 2015. We found that the incidence of BPD ranged from 6% to 57%, depending on the definition chosen, and that studies that investigated correlations with long-term pulmonary and/or neurosensory outcomes reported moderate-to-low predictive values regardless of the BPD criteria. CONCLUSION: A comprehensive and evidence-based definition for BPD needs to be developed for benchmarking and prognostic use.

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.

Country-Specific vs. Common Birthweight-for-Gestational Age References to Identify Small for Gestational Age Infants Born at 24-28 weeks: An International Study.

BACKGROUND: Controversy exists as to whether birthweight-for-gestational age references used to classify infants as small for gestational age (SGA) should be country specific or based on an international (common) standard. We examined whether different birthweight-for-gestational age references affected the association of SGA with adverse outcomes among very preterm neonates. METHODS: Singleton infants (n = 23 788) of 24(0) -28(6) weeks' gestational age in nine high-resource countries were classified as SGA (<10th centile) using common and country-specific references based on birthweight and estimated fetal weight (EFW). For each reference, the adjusted relative risk (aRR) for the association of SGA with composite outcome of mortality or major morbidity was estimated. RESULTS: The percentage of infants classified as SGA differed slightly for common compared with country specific for birthweight references [9.9% (95% CI 9.5, 10.2) vs. 11.1% (95% CI 10.7, 11.5)] and for EFW references [28.6% (95% CI 28.0, 29.2) vs. 24.6% (95% CI 24.1, 25.2)]. The association of SGA with the composite outcome was similar when using common or country-specific references for the total sample for birthweight [aRRs 1.47 (95% CI 1.43, 1.51) and 1.48 (95% CI 1.44, 1.53) respectively] and for EFW references [aRRs 1.35 (95% CI 1.31, 1.38) and 1.39 (95% CI 1.35, 1.43) respectively]. CONCLUSION: Small for gestational age is associated with higher mortality and morbidity in infants born <29 weeks' gestational age. Although common and country-specific birthweight/EFW references identified slightly different proportions of SGA infants, the risk of the composite outcome was comparable.

The International Network for Evaluating Outcomes of very low birth weight, very preterm neonates (iNeo): a protocol for collaborative comparisons of international health services for quality improvement in neonatal care.

BACKGROUND: The International Network for Evaluating Outcomes in Neonates (iNeo) is a collaboration of population-based national neonatal networks including Australia and New Zealand, Canada, Israel, Japan, Spain, Sweden, Switzerland, and the UK. The aim of iNeo is to provide a platform for comparative evaluation of outcomes of very preterm and very low birth weight neonates at the national, site, and individual level to generate evidence for improvement of outcomes in these infants. METHODS/DESIGN: Individual-level data from each iNeo network will be used for comparative analysis of neonatal outcomes between networks. Variations in outcomes will be identified and disseminated to generate hypotheses regarding factors impacting outcome variation. Detailed information on physical and environmental factors, human and resource factors, and processes of care will be collected from network sites, and tested for association with neonatal outcomes. Subsequently, changes in identified practices that may influence the variations in outcomes will be implemented and evaluated using quality improvement methods. DISCUSSION: The evidence obtained using the iNeo platform will enable clinical teams from member networks to identify, implement, and evaluate practice and service provision changes aimed at improving the care and outcomes of very low birth weight and very preterm infants within their respective countries. The knowledge generated will be available worldwide with a likely global impact.

EXPRESS study shows significant regional differences in 1-year outcome of extremely preterm infants in Sweden.

AIM: The aim of this study was to investigate differences in mortality up to 1 year of age in extremely preterm infants (before 27 weeks) born in seven Swedish healthcare regions. METHODS: National prospective observational study of consecutively born, extremely preterm infants in Sweden 2004-2007. Mortality was compared between regions. Crude and adjusted odds ratios and 95% CI were calculated. RESULTS: Among 844 foetuses alive at mother's admission for delivery, regional differences were identified in perinatal mortality for the total group (22-26 weeks) and in the stillbirth and perinatal and 365-day mortality rates for the subgroup born at 22-24 weeks. Among 707 infants born alive, regional differences were found both in mortality before 12 h and in the 365-day mortality rate for the subgroup (22-24 weeks) and for the total group (22-26 weeks). The mortality rates were consistently lower in two healthcare regions. There were no differences in the 365-day mortality rate for infants alive at 12 h or for infants born at 25 weeks. Neonatal morbidity rates among survivors were not higher in regions with better survival rates. Perinatal practices varied between regions. CONCLUSION: Mortality rates in extremely preterm infants varied considerably between Swedish healthcare regions in the first year after birth, particularly between the most immature infants.

Early skin-to-skin care in extremely preterm infants: thermal balance and care environment.

OBJECTIVE: To evaluate infant thermal balance and the physical environment in extremely preterm infants during skin-to-skin care (SSC). STUDY DESIGN: Measurements were performed in 26 extremely preterm infants (gestational age 22-26 weeks; postnatal age, 2-9 days) during pretest (in incubator), test (during SSC), and posttest (in incubator) periods. Infants' skin temperature and body temperature, ambient temperature, and relative humidity were measured. Evaporimetry was used to determine transepidermal water loss, and insensible water loss through the skin was calculated. RESULTS: The infants maintained a normal body temperature during SSC. Transfer to and from SSC was associated with a drop in skin temperature, which increased during SSC. Ambient humidity and temperature were lower during SSC than during incubator care. Insensible water loss through the skin was higher during SSC. CONCLUSION: SSC can be safely used in extremely preterm infants. SSC can be initiated during the first week of life and is feasible in infants requiring neonatal intensive care, including ventilator treatment. During SSC, the conduction of heat from parent to infant is sufficiently high to compensate for the increase in evaporative and convective heat loss. The increased water loss through the skin during SSC is small and should not affect the infant's fluid balance.

Respiratory Management of Extremely Preterm Infants: An International Survey.

BACKGROUND: There are significant international variations in chronic lung disease rates among very preterm infants yet there is little data on international variations in respiratory strategies. OBJECTIVE: To evaluate practice variations in the respiratory management of extremely preterm infants born at < 29 weeks' gestational age (GA) among 10 neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of Neonates collaboration. METHODS: A web-based survey was sent to the representatives of 390 neonatal intensive care units from Australia/New Zealand, Canada, Finland, Illinois (USA), Israel, Japan, Spain, Sweden, Switzerland, and Tuscany (Italy). Responses were based on practices in 2015. RESULTS: Overall, 321 of the 390 units responded (82%). The majority of units within networks (40-92%) mechanically ventilate infants born at 23-24 weeks' GA on continuous positive airway pressure (CPAP) with 30-39% oxygen in respiratory distress within 48 h after birth, but the proportion of units that offer mechanical ventilation for infants born at 25-26 weeks' GA at similar settings varied significantly (20-85% of units within networks). The most common respiratory strategy for infants born at 27-28 weeks' GA on CPAP with 30-39% oxygen with respiratory distress within 48 h after birth used by units also varied significantly among networks: mechanical ventilation (0-60%), CPAP (3-82%), intubation and surfactant administration with immediate extubation (0-75%), and less invasive surfactant administration (0-68%). CONCLUSIONS: There are marked variations but also similarities in respiratory management of extremely preterm infants between networks. Further collaboration and exploration is needed to better understand the association of these variations in practice with pulmonary outcomes.

Variations in Oxygen Saturation Targeting, and Retinopathy of Prematurity Screening and Treatment Criteria in Neonatal Intensive Care Units: An International Survey.

BACKGROUND: Rates of retinopathy of prematurity (ROP) and ROP treatment vary between neonatal intensive care units (NICUs). Neonatal care practices, including oxygen saturation (SpO2) targets and criteria for the screening and treatment of ROP, are potential contributing factors to the variations. OBJECTIVES: To survey variations in SpO2 targets in 2015 (and whether there had been recent changes) and criteria for ROP screening and treatment across the networks of the International Network for Evaluating Outcomes in Neonates (iNeo). METHODS: Online prepiloted questionnaires on treatment practices for preterm infants were sent to the directors of 390 NICUs in 10 collaborating iNeo networks. Nine questions were asked and the results were summarized and compared. RESULTS: Overall, 329/390 (84%) NICUs responded, and a majority (60%) recently made changes in upper and lower SpO2 target limits, with the median set higher than previously by 2-3% in 8 of 10 networks. After the changes, fewer NICUs (15 vs. 28%) set an upper SpO2 target limit > 95% and fewer (3 vs. 5%) a lower limit < 85%. There were variations in ROP screening criteria, and only in the Swedish network did all NICUs follow a single guideline. The initial retinal examination was carried out by an ophthalmologist in all but 6 NICUs, and retinal photography was used in 20% but most commonly as an adjunct to indirect ophthalmoscopy. CONCLUSIONS: There is considerable variation in SpO2 targets and ROP screening and treatment criteria, both within networks and between countries.

Survival in Very Preterm Infants: An International Comparison of 10 National Neonatal Networks.

OBJECTIVES: To compare survival rates and age at death among very preterm infants in 10 national and regional neonatal networks. METHODS: A cohort study of very preterm infants, born between 24 and 29 weeks' gestation and weighing <1500 g, admitted to participating neonatal units between 2007 and 2013 in the International Network for Evaluating Outcomes of Neonates. Survival was compared by using standardized ratios (SRs) comparing survival in each network to the survival estimate of the whole population. RESULTS: Network populations differed with respect to rates of cesarean birth, exposure to antenatal steroids and birth in nontertiary hospitals. Network SRs for survival were highest in Japan (SR: 1.10; 99% confidence interval: 1.08-1.13) and lowest in Spain (SR: 0.88; 99% confidence interval: 0.85-0.90). The overall survival differed from 78% to 93% among networks, the difference being highest at 24 weeks' gestation (range 35%-84%). Survival rates increased and differences between networks diminished with increasing gestational age (GA) (range 92%-98% at 29 weeks' gestation); yet, relative differences in survival followed a similar pattern at all GAs. The median age at death varied from 4 days to 13 days across networks. CONCLUSIONS: The network ranking of survival rates for very preterm infants remained largely unchanged as GA increased; however, survival rates showed marked variations at lower GAs. The median age at death also varied among networks. These findings warrant further assessment of the representativeness of the study populations, organization of perinatal services, national guidelines, philosophy of care at extreme GAs, and resources used for decision-making.

International variations and trends in the treatment for retinopathy of prematurity.

OBJECTIVE: To compare the rates of retinopathy of prematurity (ROP) and treatment of ROP by laser or intravitreal anti-vascular endothelial growth factor among preterm neonates from high-income countries participating in the International Network for Evaluating Outcomes (iNeo) of neonates. METHODS: A retrospective cohort study was conducted on extremely preterm infants weighing <1500 g at 240 to 276 weeks' gestation who were admitted to neonatal units in Australia/New Zealand, Canada, Finland, Israel, Japan, Spain, Sweden, Switzerland, Tuscany (Italy) and the UK between 2007 and 2013. Pairwise comparisons of ROP treatment in survivors between countries were evaluated by Poisson and multivariable logistic regression analyses after adjustment for confounders. A composite outcome of death or ROP treatment was compared between countries using logistic regression and standardised ratios. RESULTS: Of 48 087 infants included in the analysis, 81.8% survived to 32 weeks postmenstrual age, and 95% of survivors were screened for ROP. Rates of any ROP ranged from 25.2% to 91.0% in Switzerland and Japan, respectively, among those examined. The overall rate of those receiving treatment was 24.9%, which varied from 4.3% to 30.4%. Adjusted risk ratios for ROP treatment were lower for Switzerland in all pairwise comparisons, whereas Japan displayed significantly higher ratios. Comparisons of the composite outcome between countries revealed similar, but less marked differences. CONCLUSIONS: Rates of any ROP and ROP treatment varied significantly between iNeo members, while an overall decline in ROP treatment was observed during the study period. It is unclear whether these variations represent differences in care practices, diagnosis and/or treatment thresholds.

Neonatal Morbidity After Maternal Use of Antidepressant Drugs During Pregnancy.

OBJECTIVES: To estimate the rate of admissions to NICUs, as well as infants' morbidity and neonatal interventions, after exposure to antidepressant drugs in utero. METHODS: Data on pregnancies, deliveries, prescription drug use, and health status of the newborn infants were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We included 741 040 singletons, born between July 1, 2006, and December 31, 2012. Of the infants, 17 736 (2.4%) had mothers who used selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Infants exposed to an SSRI were compared with nonexposed infants, and infants exposed during late pregnancy were compared with those exposed during early pregnancy only. The results were analyzed with logistic regression analysis. RESULTS: After maternal use of an SSRI, 13.7% of the infants were admitted to the NICU compared with 8.2% in the population (adjusted odds ratio: 1.5 [95% confidence interval: 1.4-1.5]). The admission rate to the NICU after treatment during late pregnancy was 16.5% compared with 10.8% after treatment during early pregnancy only (adjusted odds ratio: 1.6 [95% confidence interval: 1.5-1.8]). Respiratory and central nervous system disorders and hypoglycemia were more common after maternal use of an SSRI. Infants exposed to SSRIs in late pregnancy compared with early pregnancy had a higher risk of persistent pulmonary hypertension (number needed to harm: 285). CONCLUSIONS: Maternal use of antidepressants during pregnancy was associated with increased neonatal morbidity and a higher rate of admissions to the NICU. The absolute risk for severe disease was low, however.

Intensity of perinatal care for extremely preterm infants: outcomes at 2.5 years.

OBJECTIVE: To examine the association between intensity of perinatal care and outcome at 2.5 years' corrected age (CA) in extremely preterm (EPT) infants (<27 weeks) born in Sweden during 2004-2007. METHODS: A national prospective study in 844 fetuses who were alive at the mother's admission for delivery: 707 were live born, 137 were stillborn. Infants were assigned a perinatal activity score on the basis of the intensity of care (rates of key perinatal interventions) in the infant's region of birth. Scores were calculated separately for each gestational week (gestational age [GA]-specific scores) and for the aggregated cohort (aggregated activity scores). Primary outcomes were 1-year mortality and death or neurodevelopmental disability (NDI) at 2.5 years' CA in fetuses who were alive at the mother's admission. RESULTS: Each 5-point increment in GA-specific activity score reduced the stillbirth risk (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.83-0.97) and the 1-year mortality risk (aOR: 0.84; 95% CI: 0.78-0.91) in the primary population and the 1-year mortality risk in live-born infants (aOR: 0.86; 95% CI: 0.79-0.93). In health care regions with higher aggregated activity scores, the risk of death or NDI at 2.5 years' CA was reduced in the primary population (aOR: 0.69; 95% CI: 0.50-0.96) and in live-born infants (aOR: 0.68; 95% CI: 0.48-0.95). Risk reductions were confined to the 22- to 24-week group. There was no difference in NDI risk between survivors at 2.5 years' CA. CONCLUSIONS: Proactive perinatal care decreased mortality without increasing the risk of NDI at 2.5 years' CA in EPT infants. A proactive approach based on optimistic expectations of a favorable outcome is justified.

Routine testing of umbilical cord blood after normal delivery should be discontinued.

On many newborns in Sweden routine samples of blood are taken from the umbilical cord after birth to measure the acid-base balance. These tests were introduced with the aim to objectively measure the well-being and stress levels of the newborn. The information was to be used as a measurement of quality of care, for research and as a tool to help guide decisions around the care-needs of the newborn. After 10 years of routine analysis it has become clear that the results of these tests have limited clinical value and that they are a poor measurement of quality of care.

Ambient humidity influences the rate of skin barrier maturation in extremely preterm infants.

OBJECTIVES: To test the hypothesis that the level of relative humidity (RH) in which preterm infants are nursed might influence their postnatal skin maturation. STUDY DESIGN: In 22 preterm infants (GA 23-27 weeks), transepidermal water loss (TEWL) was determined at postnatal ages (PNA) of 0, 3, 7, 14, and 28 days. At a PNA of 7 days, the infants were randomized to care at either 50% or 75% RH. RESULTS: TEWL decreased at a slower rate in infants nursed at the higher RH. At a PNA of 28 days, TEWL was about twice as high in infants nursed at 75% RH (22 +/- 2 g/m2 h) than in those nursed at 50% RH (13 +/- 1 g/m2 h; P < .001). CONCLUSIONS: The results indicate that the level of RH influences skin barrier development, with more rapid barrier formation in infants nursed at a lower RH. The findings have an impact on strategies for promoting skin barrier integrity in extremely preterm infants.

Earlier Apgar score increase in severely depressed term infants cared for in Swedish level III units with 40% oxygen versus 100% oxygen resuscitation strategies: a population-based register study.

OBJECTIVES: The aim of this study was to evaluate whether a resuscitation strategy based on administration of 40% oxygen influences mortality rates and rates of improvement in 5-minute Apgar scores, compared with a strategy based on 100% oxygen administration. METHODS: A population-based study evaluated data from 4 Swedish perinatal level III centers during the period of 1998 to 2003. During this period, the centers used either of 2 resuscitation strategies (initial oxygen administration of 40% or 100%). Live-born, singleton, term infants with 1-minute Apgar scores of <4, with a birth weight appropriate for gestational age, and without major malformations were included in the study (n = 1223). RESULTS: Infants born in hospitals using a 40% oxygen strategy had a more rapid Apgar score increase than did infants born in hospitals using a 100% oxygen strategy; however, no difference remained at 10 minutes. The mean Apgar score increased from 2.01 at 1 minute to 6.74 at 5 minutes in the 2 hospitals initiating resuscitation with 40% oxygen, compared with 2.01 to 6.38 in the 2 hospitals using 100% oxygen, with a mean difference in Apgar score increases of 0.36. At 5 minutes, 44.3% of infants born in the hospitals using 100% oxygen had an Apgar score of <7, compared with 34.0% of infants at the hospitals using 40% oxygen. At 10 minutes, the mean Apgar scores were 8.16 at the hospitals using 40% oxygen and 8.07 at the hospitals using 100% oxygen. There were no significant differences in rates of neonatal death, hypoxic ischemic encephalopathy, or seizures in relation to the 2 oxygen strategies. CONCLUSION: Severely depressed term infants born in hospitals initiating resuscitation with 40% oxygen had earlier Apgar score recovery than did infants born in hospitals using a 100% oxygen strategy.