Changes in Lung Function among Infants Born Extremely Preterm over a 20-year Period in the Post-surfactant era: A Retrospective Study.

Lung function was assessed at 8 years in 308 infants born extremely preterm between 1994 and 2013. Although lung function remained unchanged those infants born at 22 through 25 weeks, those who were born at 26 to 27 weeks showed a significant improvement over the past two decades.

Continuous oxygen saturation and risk of retinopathy of prematurity in a Japanese cohort.

BACKGROUND/AIMS: We assessed the associations between retinopathy of prematurity (ROP) and continuous measurements of oxygen saturation (SpO2), and developed a risk prediction model for severe ROP using birth data and SpO2 data. METHODS: This retrospective study included infants who were born before 30 weeks of gestation between August 2009 and January 2019 and who were screened for ROP at a single hospital in Japan. We extracted data on birth weight (BW), birth length, gestational age (GA) and minute-by-minute SpO2 during the first 20 days from the medical records. We defined four SpO2 variables using sequential measurements. Multivariate logistic regression was used to develop a model that combined birth data and SpO2 data to predict treatment-requiring ROP (TR-ROP). The model's performance was evaluated using the area under the receiver operating characteristic curve (AUC). RESULTS: Among 350 infants, 83 (23.7%) required ROP treatment. The SpO2 variables in infants with TR-ROP differed significantly from those with non-TR-ROP. The average SpO2 and high SpO2 showed strong associations with GA (r=0.73 and r=0.70, respectively). The model incorporating birth data and the four SpO2 variables demonstrated good discriminative ability (AUC=0.83), but it did not outperform the model incorporating BW and GA (AUC=0.82). CONCLUSION: Data obtained by continuous SpO2 monitoring demonstrated valuable associations with severe ROP, as well as with GA. Differences in the distribution of average SpO2 and high SpO2 between infants with TR-ROP and non-TR-ROP could be used to establish efficient cut-off values for risk determination.

Erythropoietin and retinopathy of prematurity: a retrospective cohort study in Japan, 2008-2018.

BACKGROUND: Erythropoietin has an angiogenic effect on the retina and might increase the risk of retinopathy of prematurity (ROP). METHODS: This retrospective cohort study included infants born at 22 to 27 weeks' gestation between 2008 and 2018 who were admitted to neonatal intensive care units (NICUs). We compared mortality and morbidities between infants who received erythropoietin and those who did not. RESULTS: Among 18,955 livebirth infants, this study included 16,031 infants, among which 14,373 infants received erythropoietin. The risk of ROP requiring treatment was significantly higher in the erythropoietin group than in the control group (33% vs. 26%; aOR 1.50 [95% CI 1.28-1.76]). On the other hand, the erythropoietin group had lower risks of death and necrotizing enterocolitis. CONCLUSIONS: This study with a large sample size found that erythropoietin use was associated with increased risk of ROP requiring treatment, while being associated with reductions in deaths and NEC.

Postneonatal mortality of severely small for gestational age extremely low birth weight infants.

BACKGROUND: Infants born with weights below the 10th percentile of the expected birth weight for gestational age, defined as small for gestational age (SGA), have an increased risk of neonatal mortality and prematurity-related complications. However, the relationship between SGA and postneonatal (28 days to <1 year) mortality among extremely low birth weight infants (ELBWIs) remains uncertain. Hence, this study aimed to investigate the association between birth weight percentiles and postneonatal mortality in ELBWIs. METHODS: A cohort of ELBWIs with a gestational age greater than 23 weeks who were admitted to Osaka Women's and Children's Hospital between 2008 and 2019 were considered eligible. Infants with major congenital anomalies, those large for their gestational age, or those who died within 28 days of birth were excluded. Baseline characteristics and outcomes of the three groups of ELBWIs-severe SGA (sSGA; birth weight, <3rd percentile), moderate SGA (mSGA; birth weight, 3rd to <10th percentile), and appropriate for gestational age (AGA; birth weight, 10th to <90th percentile)-were compared. Logistic regression analysis was used to identify perinatal factors associated with postneonatal mortality in sSGA infants. RESULTS: sSGA ELBWIs demonstrated higher incidence of meconium obstruction (25% vs. 8.3% vs. 7.6%, P < 0.001), cholestasis (21% vs. 4.2% vs. 9.7%, P < 0.003), and postneonatal mortality (7.3% vs. 0% vs. 0.7%, P < 0.004) than mSGA and AGA ELBWIs. In the logistic regression analysis, cholestasis (odds ratio, 30.1; 95% confidence interval, 2.98-304) and sepsis (odds ratio, 13.5; 95% confidence interval, 1.06-173) were significantly related to postneonatal mortality among ELBWIs with sSGA. The leading cause of postneonatal mortality in sSGA ELBWIs was liver failure (55.5%). CONCLUSION: sSGA ELBWIs exhibited a higher rate of postneonatal mortality compared to mSGA and AGA ELBWIs. Therefore, strategies aimed at preventing liver dysfunction in severely cholestatic ELBWIs with sSGA are necessary.

Risk factor analyses for intraventricular hemorrhage in preterm infants: A retrospective cohort study.

BACKGROUND: Very-low-birthweight (VLBW) infants can experience severe intraventricular hemorrhage (IVH) that can lead to life-long disability by impairing neurodevelopment. The aim of this study was to identify the risk and protective factors for severe IVH in VLBW infants. METHODS: A retrospective, cross-sectional review of VLBW infants born at 22-28 weeks' gestation between January 2003 and December 2012 and listed in the Database of Neonatal Research Network in Japan was performed using a statistical model incorporating an odds ratio (OR) and medical center variation as a center variance ratio (CVR). A two-dimensional analysis using a combination of OR and the CVR described evolving measures of a clinical trial (for OR > 1) and standardization (for CVR > 1) concerning a factor of interest. RESULTS: The noteworthy significant protective factors were antenatal steroids (ANS) with and without premature rupture of membrane (OR: 0.43, CVR: 1.08, and OR: 0.68, CVR: 1.14, respectively) and the number of neonatal beds (OR: 0.94, CVR: 0.99) and staff nurses per neonatal bed (OR: 0.89, CVR: 0.99). CONCLUSIONS: Active promotion of ANS administration and consolidation of perinatal medical centers can mitigate the development of severe IVH in VLBW infants.

Burden of Treatments for Respiratory Complications in Extremely Premature Infants: Interviews with Caregivers.

Introduction: Extremely premature (EP) infants (<28 weeks gestational age) with respiratory conditions after discharge from the neonatal intensive care unit (NICU) impose a significant burden on caregivers. This study explored caregiver burden post-NICU discharge and perceptions of meaningful change in infant chronic respiratory morbidity. Methods: Adult primary caregivers of EP infants 3-14 months corrected age were recruited through patient advocacy organizations or hospital centers in the USA, Northern Ireland, Germany, and Japan and interviewed by phone. Interviews explored caregiver experiences with infants with respiratory conditions, associated treatment burden, and meaningful change in infant respiratory morbidity as measured by treatment use. Qualitative analysis of interview data was performed using MAXQDA software. Sociodemographic data were summarized using descriptive statistics. Results: Forty-five caregivers (95.6% female) of EP infants were interviewed. Respiratory morbidities post-NICU discharge included coughing (78%), breathing difficulties (76%), wheezing (58%), and bronchopulmonary dysplasia/chronic lung disease of prematurity (56%). Respiratory medications were required by 87% of infants, 80% used home respiratory technology support (e.g., supplemental oxygen), 38% were re-hospitalized, and 33% had emergency department visits. Caregivers considered visits to the emergency department to be the most burdensome treatment requirement they experienced, and reduction in the number of emergency department visits was considered the most meaningful change in treatment use. Conclusion: These findings underscore the significant burden faced by caregivers of EP infants with respiratory morbidities. Development of treatments for respiratory complications should take into consideration the concerns and preferences of caregivers in order to provide a meaningful benefit.

The Association between Early Gram-Negative Bacteria in Tracheal Aspirate Cultures and Severe Bronchopulmonary Dysplasia among Extremely Preterm Infants Requiring Prolonged Ventilation.

OBJECTIVE: The study aimed to evaluate the association between bronchopulmonary dysplasia (BPD) development at 36 weeks' postmenstrual age (PMA) and Gram-negative bacteria in tracheal aspirate cultures among extremely preterm infants. STUDY DESIGN: This study has a retrospective cohort. Patients were 155 infants aged less than or equal to 26 gestational weeks who were admitted to the neonatal intensive care unit of Osaka Women's and Children's Hospital from 2009 to 2018. Primary outcome was respiratory outcomes expressed as BPD development.Multivariable logistic regression analysis was used to identify neonatal and bacterial factors associated with BPD. RESULTS: After adjusting for gestational age, birth weight, sex, chorioamnionitis, Gram-positive cocci (GPC) and Gram-negative rods (GNRs) in tracheal aspirate cultures within 28 days after birth, GNRs were significantly associated with BPD development (odds ratio [OR]: 3.88, 95% confidence interval [CI]: 1.68-8.94). In contrast, GPCs were not associated with BPD development (OR: 0.47, 95% CI: 0.05-1.61). CONCLUSION: Gram-negative bacteria in tracheal cultures within 28 days of birth are associated with BPD development in infants aged less than or equal to 26 gestational weeks. KEY POINTS: · BPD is a factor for morbidity in extremely preterm infants.. · Respiratory infection is an adverse outcome of BPD.. · GNRs in tracheal cultures soon after birth disturb BPD development.. · GPC was not associated with BPD development..

Inhaled Nitric Oxide Therapy in the Post-Acute Phase in Extremely Preterm Infants: A Japanese Cohort Study.

OBJECTIVE: To determine the trends in inhaled nitric oxide (iNO) utilization in the late phase of hospitalization in a large Japanese cohort of extremely preterm infants and evaluate its benefit on long-term outcomes. STUDY DESIGN: This was a retrospective multicenter cohort study of 15 977 extremely preterm infants born at <28 weeks of gestational age between 2003 and 2016, in the Neonatal Research Network, Japan. Demographic characteristics, morbidity, and mortality were compared between extremely preterm infants with and without post-acute iNO therapy. Multivariable logistic analysis was performed to determine factors associated with post-acute iNO and its impact on neurodevelopmental outcomes at 3 years of age. RESULTS: Post-acute iNO utilization rates increased from 0.3% in 2009 to 1.9% in 2016, even under strict insurance coverage rules starting in 2009. Gestational age (1-week increment; aOR 0.82, 95% CI 0.76-0.88), small for gestational age (1.47, 1.08-1.99), histologic chorioamnionitis (1.50, 1.21-1.86), 5-minute Apgar score <4 (1.51, 1.10-2.07), air leak (1.92, 1.30-2.83), and bubbly/cystic appearance on chest X-Ray (1.68, 1.37-2.06) were associated with post-acute iNO. Post-acute iNO was not associated with neurodevelopmental outcomes at 3 years of age. CONCLUSIONS: The increasing post-acute iNO utilization rate among extremely preterm infants has been concurrent with improved survival rates of extremely preterm infants in Japan. Infants treated with post-acute iNO had more severe disease and complications than the comparison group, but there were no differences in neurodevelopmental outcome at 3 years. This suggests post-acute iNO may benefit extremely preterm infants.

Intrauterine Ureaplasma is associated with small airway obstruction in extremely preterm infants.

BACKGROUND: The long-term follow-up of lung function (LF) in extremely preterm (EP) infants with bronchopulmonary dysplasia (BPD) has shown a worldwide increase in small airway obstructions (SAO). OBJECTIVES: We investigated the relationships between intrauterine Ureplasma infection in EP infants and bubbly/cystic lung, BPD, and SAO at school age. METHODS: Placental pathology, placental Ureaplasma DNA (pU-DNA), and cord blood immunoglobulin M (IgM) (C-IgM) were investigated in 360 EP infants born from 1981 to 2004. Maternal amniotic inflammatory response (M-AIR) scores and hemosiderin deposition (HD) were estimated in the chorioamnion. The study subjects were divided into groups based on their M-AIR scores. Their LF at school age was compared with those of 33 healthy siblings. FINDINGS: pU-DNA and C-IgM were significantly related to SAO at school age (p < 0.012). M-AIR score 3 and pU-DNA >1000 units had an odds ratio (OR) of 35 (95% confidence interval: 10-172) and 18 (5.6-67) for bubbly/cystic lung, and 11 (3.1 - 43) and 31 (4.5-349) for severe BPD, and 5.3 (2.1-11) and 12 (2.4-74) for SAO, respectively. The ORs of surfactant treatment, BPD grade III, O2 at 40 weeks, HD, and C-IgM >30 mg/dl for SAO were 0.21 (0.075-0.58), 5.3 (2.1-15), 2.5 (1.4-4.6), 3.6 (1.5-9.1) and 2.5 (1.0-5.2). 84% (90/107) SAO infants showed no or mild BPD in infancy, and 61% of infants had no severe CAM. CONCLUSION: Our long-term cohort study of LF in EP infants revealed that intrauterine Ureaplasma was associated with bubbly/cystic lung, severe BPD, and SAO at school age.

Feasibility of portable capnometer for mechanically ventilated preterm infants in the delivery room.

This study aimed to determine whether a specific portable capnometer (EMMA™) can facilitate the maintenance of an appropriate partial pressure of arterial carbon dioxide (PaCO2) in intubated preterm infants in the delivery room. This study included preterm infants with a gestational age of 26 + 0 to 31 + 6 weeks who required intubation in the delivery room. We prospectively identified 40 infants who underwent the EMMA™ monitoring intervention group and 43 infants who did not undergo monitoring (historical control group). PaCO2 was evaluated either at admission in the neonatal intensive care unit or at 2 h after birth. The proportion of infants with an appropriate PaCO2 (35-60 mmHg) was greater in the intervention group than in the control group (80% vs. 42%; p = 0.001). There were no significant differences in the rate of accidental extubation (5.0% vs. 7.0%, p = 1.00) or in the proportion of infants with an appropriate PaCO2 among infants whose birth weight was < 1000 g (54% vs. 40%, p = 0.49). However, among infants whose birth weight was ≥ 1000 g, the PaCO2 tended to be more appropriate in the intervention group than in the control group (93% vs. 44%; p < 0.001).Conclusion: The EMMA™ facilitated the maintenance of an appropriate PaCO2 for mechanically ventilated preterm infants, especially infants with birth weight ≥1000 g, in the delivery room. What is Known: • An inappropriate partial pressure of arterial carbon dioxide has been associated with intraventricular hemorrhage in preterm infants. • There is a need to appropriately control the partial pressure of arterial carbon dioxide in preterm infants. What is New: • This is the first report regarding the feasibility of a portable capnometer, the EMMA™, in the delivery room. • The EMMA™ may be considered a feasible monitoring device in the delivery room for intubated preterm infants, especially infants with birth weight ≥1000 g.

A Retrospective Cohort Study on Mortality and Neurodevelopmental Outcomes of Preterm Very Low Birth Weight Infants Born to Mothers with Hypertensive Disorders of Pregnancy.

OBJECTIVE: We examined the effects of maternal hypertensive disorders of pregnancy (HDP) on the mortality and neurodevelopmental outcomes in preterm very low birth weight (VLBW) infants (BW ≤1,500 g) based on their intrauterine growth status and gestational age (GA). STUDY DESIGN: We included singleton VLBW infants born at <32 weeks' gestation registered in the Neonatal Research Network Japan database. The composite outcomes including death, cerebral palsy (CP), and developmental delay (DD) at 3 years of age were retrospectively compared among three groups: appropriate for GA (AGA) infants of mothers with and without HDP (H-AGA and N-AGA) and small for GA (SGA) infants of mothers with HDP (H-SGA). The adjusted odds ratios (AOR) and 95% confidence intervals (CI) stratified by the groups of every two gestational weeks were calculated after adjusting for the center, year of birth, sex, maternal age, maternal diabetes, antenatal steroid use, clinical chorioamnionitis, premature rupture of membranes, non-life-threatening congenital anomalies, and GA. RESULTS: Of 19,323 eligible infants, outcomes were evaluated in 10,192 infants: 683 were H-AGA, 1,719 were H-SGA, and 7,790 were N-AGA. Between H-AGA and N-AGA, no significant difference was observed in the risk for death, CP, or DD in any GA groups. H-AGA had a lower risk for death, CP, or DD than H-SGA in the 24 to 25 weeks group (AOR: 0.434, 95% CI: 0.202-0.930). The odds for death, CP, or DD of H-SGA against N-AGA were found to be higher in the 24 to 25 weeks (AOR: 2.558, 95% CI: 1.558-3.272) and 26 to 27 weeks (AOR: 1.898, 95% CI: 1.427-2.526) groups, but lower in the 30 to 31 weeks group (AOR: 0.518, 95% CI: 0.335-0.800). CONCLUSION: There was a lack of follow-up data; however, the outcomes of liveborn preterm VLBW infants of mothers with HDP depended on their intrauterine growth status and GA at birth. KEY POINTS: · The effects of HDP on preterm low birth weight infants need to be further examined.. · The outcomes were not different between AGA infants with and without maternal HDP.. · The outcomes of SGA infants with maternal HDP were dependent on their GA..

Creating experiences from active treatment towards extremely preterm infants born at less than 25 weeks in Japan.

Treatment for extremely preterm infants born at less than 25 weeks of gestation in Japan was initiated mainly due to the amendment of the Maternal Health Act lowering the upper limit of abortion from 24 weeks to 22 weeks in 1990. Five years after the amendment, the Japanese national government started a nationwide project to improve the perinatal care system. Once selected perinatal centers reported improvements in survival rates, more centers have adopted aggressive treatments. They have accumulated their knowledge by experiencing the treatment of infants with a limit of viability. As a result, more than 50% of infants born even at 22 weeks of gestation can survive to discharge currently. This progress has resulted from the accumulation of experience at each perinatal center rather than the results from clinical trials. Furthermore, these experiences have been standardized to some extent through sharing information.

Outcomes of outborn very-low-birth-weight infants in Japan.

BACKGROUND: Outcomes of prenatal covariate-adjusted outborn very-low-birth-weight infants (VLBWIs) (≤1500 g) remain uncertain. OBJECTIVE: To compare morbidity and mortality between outborn and inborn VLBWIs. DESIGN: Observational cohort study using inverse-probability-of-treatment weighting. SETTING: Neonatal Research Network of Japan. PATIENTS: Singleton VLBWIs with no major anomalies admitted to a neonatal intensive care unit from 2012 to 2016. METHODS: Inverse-probability-of-treatment weighting with propensity scores was used to reduce imbalances in prenatal covariates (gestational age (GA), birth weight, small for GA, sex, maternal age, premature rupture of membranes, chorioamnionitis, preeclampsia, maternal diabetes mellitus, antenatal steroids and caesarean section). The primary outcome was severe intraventricular haemorrhage (IVH). The secondary outcomes were outcomes at resuscitation, other neonatal morbidities and mortality. RESULTS: The full cohort comprised 15 842 VLBWIs (668 outborns). The median (IQR) GA and birth weight were 28.9 (26.4-31.0) weeks and 1128 (862-1351) g for outborns and 28.7 (26.3-30.9) weeks and 1042 (758-1295) g for inborns. Outborn VLBWIs had a higher incidence of severe IVH (8.2% vs 4.1%; OR, 3.45; 95% CI 1.16 to 10.3) and pulmonary haemorrhage (3.7% vs 2.8%; OR, 5.21; 95% CI 1.41 to 19.2). There were no significant differences in Apgar scores, oxygen rates at delivery, intubation ratio at delivery, persistent pulmonary hypertension of the newborn, IVH of any grade, periventricular leukomalacia, chronic lung disease, oxygen at discharge, patent ductus arteriosus, retinopathy of prematurity, necrotising enterocolitis, sepsis or mortality. CONCLUSION: Outborn delivery of VLBWIs was associated with an increased risk of severe IVH.

Availability of portable capnometers in children with tracheostomy.

BACKGROUND: A capnometer is a noninvasive monitor that is used to assess patients' respiratory status. This study was performed to evaluate the availability of a portable capnometer in children with tracheostomy. METHODS: This retrospective study included children with tracheostomy who were treated at the Osaka Women's and Children's Hospital Osaka, Japan, from 1 September 2018 to 31 October 2019. We assessed the correlation between the partial pressure of venous carbon dioxide (PvCO2 ) and end-tidal carbon dioxide tension (EtCO2 ) using a portable capnometer (EMMA; Masimo, Irvine, CA, USA). RESULTS: Nine infants and 43 simultaneous PvCO2 -EtCO2 pairs were analyzed. The correlation coefficient of these pairs was 0.87 (95% confidence interval, 0.77-0.93; P < 0.001). The Bland-Altman plot showed that EtCO2 was on average 10.0 mmHg lower than its paired PvCO2 value (95% limits of agreement, 1.0-19.1). The difference between PvCO2 and EtCO2 was significantly greater in patients on ventilators. CONCLUSIONS: The portable capnometer evaluated in this study (EMMA) was readily available and useful for assessment of the respiratory condition in children with tracheostomy.

Postnatal physiological changes in electrical activity of the diaphragm in extremely preterm infants.

OBJECTIVES: This study aimed to describe postnatal physiological changes in maximum values of peak electrical activity of the diaphragm (Edi) in extremely preterm infants during the preterm period. WORKING HYPOTHESIS: The amplitude and frequency of neural sigh are different at each postmenstrual age in extremely preterm infants. STUDY DESIGN: A retrospective, observational study. PATIENT-SUBJECT SELECTION: Edi values were evaluated in 14 extremely preterm infants with neurally-adjusted ventilatory assist. METHODOLOGY: Data of Edi peak and Edi minimum were collected from a ventilator. Edi-sigh was defined as the Edi peak value that was more than twice as large as the median Edi peak at each postmenstrual week in each patient. The frequency of Edi-sigh, and median values of Edi-sigh, Edi peak, and Edi minimum were evaluated at each postmenstrual week. The Jonckheere-Terpstra test was used to analyze the trend between postmenstrual weeks and Edi values. RESULTS: From 26 to 35 postmenstrual weeks, the number of Edi-sighs per hour significantly increased as postmenstrual weeks increased (P < .001). Furthermore, the median values of Edi-sigh significantly increased as postmenstrual weeks increased (16.9 µV at 26 weeks to 25.4 µV at 35 weeks, P < .001). There were no significant changes in the median values of Edi peak and Edi minimum at each week. CONCLUSIONS: The amplitude and frequency of neural sigh in extremely preterm infants increase with the number of postmenstrual weeks.

Association between amount of dopamine and infections in extremely preterm infants.

This study aimed to assess the effect of dopamine on the development of infections after birth in extremely preterm infants. We retrospectively identified 258 extremely preterm infants (born at < 28 gestational weeks) between July 2009 and December 2018 in a tertiary neonatal intensive care unit (NICU). We extracted data on potential risk factors for infection, total amount of dopamine, and infection history during NICU stay for each infant. We compared the infection group with the non-infection group, and used the Cox proportional hazard regression analysis to identify risk factors for infection during NICU stay. After adjustment for all potential risk factors, factors that significantly affected development of infection were gestational age (hazard ratio [HR], 0.70; 95% confidence interval [CI] 0.55-0.89; p = 0.004) and total amount of dopamine (HR, 1.04; 95% CI 1.02-1.07; p = 0.002). The receiver operating characteristic curve of total amount of dopamine for infection suggested that total amount of dopamine greater than 7.271 mg/kg predicted infection development with 80.4% sensitivity and 41.7% specificity.Conclusion: A large amount of dopamine can increase infections in extremely preterm infants. We should avoid using a large amount of dopamine and remain aware of the potential development of infections in extremely preterm infants. What is Known: • Inotropes are often used for extremely preterm infants and dopamine is the most commonly used inotrope. • However, it is suggested that dopamine affects the immune system and related infections. What is New: • This is the first study of the association between the amount of dopamine and infection in extremely preterm infants. • We should avoid using a large amount of dopamine in extremely preterm infants.

Characterization of the Progression Pattern in Retinopathy of Prematurity Subtypes.

PURPOSE: To evaluate differences in the progression pattern among subtypes of retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. PARTICIPANTS: Premature infants screened for ROP. METHODS: Medical records of 578 premature infants who were screened at the neonatal intensive care unit from September 2009 through March 2016 were reviewed. We matched for the number of patients, gestational age at birth, and postmenstrual age at the first examination between infants with spontaneously regressed ROP and those with treated ROP. A total of 133 premature infants who were born before 27 weeks' gestation were included. MAIN OUTCOME MEASURES: The mean age at onset of any ROP and the duration from the initial examination to onset were compared between infants with regressed ROP and those with treated ROP. The mean age at treatment and the duration from onset to treatment were compared between infants with type 1 ROP and those with aggressive posterior ROP (AP-ROP). Data were analyzed for 1 randomly selected eye for each infant. RESULTS: Of 133 premature infants with any ROP, 67 regressed spontaneously, 43 demonstrated type 1 ROP, and 23 demonstrated AP-ROP. Individual trajectories of ROP progression over time showed that AP-ROP progressed through the stages in a steep linear manner in most cases. In contrast, the type 1 ROP and regressed ROP developed in a slower, stepwise manner. CONCLUSIONS: In infants with ROP, the disease trajectories across ROP stages are different based on the ROP subtype, despite postmenstrual age at onset being comparable across subtypes. Our findings could be useful for managing follow-up screening.

Effect of fluctuation of oxygenation on the development of severe retinopathy of prematurity in extremely preterm infants.

OBJECTIVE: To investigate factors associated with development of severe retinopathy of prematurity (ROP) in extremely preterm (EP) infants. STUDY DESIGN: This retrospective cohort study included 213 EP infants (22 + 0 to 27 + 6 weeks gestation) who were admitted to the neonatal intensive care unit of Osaka Women's and Children's Hospital between 2009 and 2017. Multivariable logistic regression analysis was used to identify neonatal factors associated with severe ROP requiring treatment. RESULT: After adjustments for gestational age (GA), birth weight, sex, red blood cell transfusion, average SpO2, and fluctuations of SpO2 from birth to 32 weeks postmenstrual age, fluctuations of SpO2 (odds ratio [OR]: 2.10, 95% confidence interval [CI]: 1.03-4.27), and low GA (OR: 0.95, 95% CI: 0.91-0.98) were significantly associated with severe ROP. CONCLUSIONS: Fluctuations of SpO2 from birth to 32 weeks postmenstrual age and low GA were significantly associated with development of severe ROP requiring treatment in EP infants.

The International Network for Evaluating Outcomes (iNeo) of neonates: evolution, progress and opportunities.

Neonates born very preterm (before 32 weeks' gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care.

Impact of Time to Neonatal Transport on Outcomes of Transient Tachypnea of the Newborn.

OBJECTIVE: To assess effects of neonatal transport on transient tachypnea of the newborn (TTN) in outborn term neonates. STUDY DESIGN: This retrospective cohort study included 66 term neonates diagnosed with TTN and transported to the Osaka Women's and Children's Hospital neonatal intensive care unit between January 2003 and March 2018. A multivariate logistic regression analysis identified perinatal and neonatal transport factors associated with adverse short-term outcomes defined as mechanical ventilation >48 hours, continuous positive airway pressure >72 hours, pulmonary hemorrhage, and requirement for inhaled nitric oxide, thoracentesis, or surfactant replacement therapy. RESULTS: A lower gestational age (GA) (37.7 [37.2, 38.3] vs. 39.6 [37.8, 40.3] weeks, p = 0.002), longer time to neonatal transport (10.0 [4.3, 25.5] vs. 5.5 [2.7, 9.7] hours, p = 0.01), and higher respiratory rates during transport (70 [60, 85] vs. 60 [55, 78.8] breaths/min, p = 0.04) were significantly associated with adverse short-term outcomes. After adjusting for GA, sex, cesarean section, and time to neonatal transport, GA (odds ratio [OR], 0.37; 95% confidence interval [CI], 0.24-0.87) and time to neonatal transport (OR, 1.07; 95% CI, 1.01-1.13) were significantly associated with adverse outcomes. CONCLUSION: Short-term adverse prognosis of TTN is strongly associated with a lower GA and longer time between birth and neonatal transport.