Stellan Håkansson

Objective: To investigate international variation in gestational age (GA) specific severe intraventricular hemorrhage (IVH) rates, among infants of <30 weeks’ GA from the neonatal networks of 11 high-income countries/region. Methods: Retrospective cohort study of outcomes of grade 3/4 IVH rates and composite of g3/4 IVH or death in GA groups of 22-23, 24-25, 26-27 and 28-29 weeks infants admitted to networks of Australia and New Zealand, Canada, Finland, Israel, Italy (Tuscany), Japan, Spain, Sweden, Switzerland and the UK. Their risk adjusted trends across 3 epochs (2007-11, 2012-15 and 2016-19) were also evaluated. Results: Outcomes of 165,329 infants (median GA 27 weeks, birthweight 950g) were analyzed. Overall, the lowest grade 3/4 IVH rate was observed in Japan (6.4%) and the highest in Israel (16.1%). The overall gestation-specific rate of IVH grade 3/4 were 25.8%, 18.6%, 9.0% and 3.8% and composite outcome of grade 3/4 IVH/death rates 52.2%, 33.6%, 15.6% and 6.7% for the 22-23, 24-25, 26-27, and 28-29 weeks’ GA groups respectively. These Inter-network variations were greater at lower GA. In epoch comparisons, almost all networks showed significant decreases in GA specific composite outcome rates, particularly in the 26-27 week’ GA group. Japan and Canada demonstrated significant decreases in each GA group while Spain demonstrated significant decreases in each GA group except for 22-23 weeks’ gestation. Conclusions: Rates of grade 3/4 IVH and composite outcome rates varied internationally and have decreased over time. Identification of the driving factors behind variations may allow for opportunities for practice review and improvement.

Studies on pain in preterm infants have usually been confined to observations of painful procedures, and information from extremely preterm infants is limited. Using registry data from a Swedish nationwide cohort, this study explored the epidemiology of pain in very preterm infants, its causes, assessments, and treatment strategies. We included liveborn infants <32 weeks' gestational age (GA) discharged between January 2020 and June 2024. Proportions of infants exposed to potentially painful procedures, experiencing pain, assessed with pain scales, and receiving pharmacological treatment were calculated by each postnatal day. Among 3686 infants (mean birthweight 1176 g, GA 28.2 weeks), 11.6% had a painful condition and 84.1% were exposed to at least 1 potentially painful procedure. In total, 74.6% experienced pain, corresponding to 28,137/185,008 (15.2%) days of neonatal care. For every 2-week increase in GA, significantly lower proportions of infants experienced pain. In infants <28 weeks of GA, proportions with reported pain were approximately half the rate of painful procedures, while in infants born at 28 to 31 weeks, reported pain closely matched exposure to painful procedures. Pain scales were used in 75.0% of the infants. Pharmacological pain treatment was administered to 81.7% of infants, primarily topically or orally. Among infants with pain, proportions treated intravenously were larger at higher GAs. Despite effective analgesia/anesthesia, many very preterm infants experience pain. Visualizing pain epidemiology, procedures, conditions, and treatment by postnatal and gestational age may guide clinical management and generate research hypotheses to reduce short- and long-term adverse effects.

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis. Methods: We performed a retrospective population-based cohort study. Infants born at 24–28 weeks’ gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007–11, 2012–15, and 2016–19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network. Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5–18 days compared to infants with no late-onset sepsis. Conclusions: One in 5 neonates of 24–28 weeks’ gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay.

Introduction: Our objective was to evaluate the temporal trend of systemic postnatal steroid (PNS) receipt in infants of 24–28 weeks’ gestational age, identify characteristics associated with PNS receipt, and correlate PNS receipt with the incidence of bronchopulmonary dysplasia (BPD) and BPD/death from an international cohort included in the iNeo network. Methods: We conducted a retrospective study using data from 2010 to 2018 from seven international networks participating in iNeo (Canada, Finland, Israel, Japan, Spain, Sweden, and Switzerland). Neonates of 24 and 28 weeks’ gestational age who survived 7 days and who received PNS were included. We assessed temporal trend of rates of systemic PNS receipt and BPD/death. Results: A total of 47,401 neonates were included. The mean (SD) gestational age was 26.4 (1.3) weeks and birth weight was 915 (238) g. The PNS receipt rate was 21% (12–28% across networks) and increased over the years (18% in 2010 to 26% in 2018; p < 0.01). The BPD rate was 39% (28–44% across networks) and remained unchanged over the years (35.2% in 2010 to 35.0% in 2018). Lower gestation, male sex, small for gestational age status, and presence of persistent ductus arteriosus (PDA) were associated with higher rates of PNS receipt, BPD, and BPD/death. Conclusion: The use of PNS in extremely preterm neonates increased, but there was no correlation between increased use and the BPD rate. Research is needed to determine the optimal timing, dose, and indication for PNS use in preterm neonates.

Introduction: A detailed understanding of respiratory support patterns in preterm infants is lacking. The aim was to explore and visualize this practice in Sweden. Methods: Preterm infants with gestational ages of 22–31 weeks, admitted to neonatal units reporting daily to the Swedish Neonatal Quality Register and discharged alive in November 2015–April 2022, were included in this descriptive cohort study. Proportions receiving mechanical ventilation, noninvasive support, or supplemental oxygen were calculated and graphically displayed for each gestational week and postnatal day (range 0–97) up to hospital discharge or 36 weeks of postmenstrual age. Results: Respiratory support in 148,515 days of care (3,368 infants; 54% males; median [interquartile range] birthweight = 1,215 [900–1,525] g) was evaluated. Trajectories showed distinct nonlinear patterns for each category of respiratory support, but differences in respiratory support over the gestational age range were linear: the proportion of infants on mechanical ventilation decreased by −11.7 to −7.3% (variability in estimates related to the postnatal day chosen for regression analysis) for each week higher gestational age (r = −0.99 to −0.87, p ≤ 0.001). The corresponding proportions of infants with supplemental oxygen decreased by −12.4% to −4.5% for each week higher gestational age (r = −0.98 to −0.94, p < 0.001). At 36 weeks of postmenstrual age, dependencies on mechanical ventilation, noninvasive support, and supplemental oxygen varied from 3%, 84%, and 94% at 22 weeks to 0%, 3%, and 5% at 31 weeks of gestational age, respectively. Conclusions: Respiratory support patterns in very preterm infants follow nonlinear, gestational age-specific postnatal trajectories in a dose-response-related fashion.

Introduction: Understanding factors that associate with neonatal death may lead to strategies or interventions that can aid clinicians and inform families. Objective: The aim of the study was to develop an early prediction model of neonatal death in extremely low gestational age (ELGA, <28 weeks) neonates. Methods: A predictive cohort study of ELGA neonates was derived from the Swedish Neonatal Quality Register between the years 2011 to May 2021. The goal was to use readily available clinical variables, collected within the first hour of birth, to predict in-hospital death. Data were split into a train cohort (80%) to build the model and tested in 20% of randomly selected neonates. Model performance was assessed via area under the receiver operating characteristic curve (AUC) and compared to validated mortality prediction models and an external cohort of neonates. Results: Among 3,752 live-born extremely preterm infants (46% girls), in-hospital mortality was 18% (n = 685). The median gestational age and birth weight were 25.0 weeks (interquartile range [IQR] 24.0, 27.0) and 780 g (IQR 620, 940), respectively. The proposed model consisted of three variables: birth weight (grams), Apgar score at 5 min of age, and gestational age (weeks). The BAG model had an AUC of 76.9% with a 95% confidence interval (CI) (72.6%, 81.3%), while birth weight and gestational age had an AUC of 73.1% (95% CI: 68.4%,77.9%) and 71.3% (66.3%, 76.2%). In the validation cohort, the BAG model had an AUC of 68.9%. Conclusion: The BAG model is a new mortality prediction model in ELGA neonates that was developed using readily available information.

Introduction: The availability of and variability in healthcare professionals in neonatal units in different countries has not been well characterized. Our objective was to identify variations in the healthcare professionals for preterm neonates in 10 national or regional neonatal networks participating in the International Network for Evaluating Outcomes (iNeo) of neonates. Method: Online, pre-piloted questionnaires about the availability of healthcare professionals were sent to the directors of 390 tertiary neonatal units in 10 international networks: Australia/New Zealand, Canada, Finland, Illinois, Israel, Japan, Spain, Sweden, Switzerland, and Tuscany. Results: Overall, 325 of 390 units (83%) responded. About half of the units (48%; 156/325) cared for 11–30 neonates/day and had team-based (43%; 138/325) care models. Neonatologists were present 24 h a day in 59% of the units (191/325), junior doctors in 60% (194/325), and nurse practitioners in 36% (116/325). A nurse-to-patient ratio of 1:1 for infants who are unstable and require complex care was used in 52% of the units (170/325), whereas a ratio of 1:1 or 1:2 for neonates requiring multisystem support was available in 59% (192/325) of the units. Availability of a respiratory therapist (15%, 49/325), pharmacist (40%, 130/325), dietitian (34%, 112/325), social worker (81%, 263/325), lactation consultant (45%, 146/325), parent buddy (6%, 19/325), or parents’ resource personnel (11%, 34/325) were widely variable between units. Conclusions: We identified variability in the availability and organization of the healthcare professionals between and within countries for the care of extremely preterm neonates. Further research is needed to associate healthcare workers’ availability and outcomes.

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.

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.