Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019.

BackgroundNeonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.AimThe aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.MethodsIn 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.ResultsIn Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.ConclusionsIn this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.

Factors associated with the increased incidence of necrotising enterocolitis in extremely preterm infants in Sweden between two population-based national cohorts (2004-2007 vs 2014-2016).

OBJECTIVE: To investigate potential risk factors behind the increased incidence of necrotising enterocolitis (NEC) in Swedish extremely preterm infants. DESIGN: Registry data from two population-based national cohorts were studied. NEC diagnoses (Bell stage ≥II) were validated against hospital records. PATIENTS: All liveborn infants <27 weeks of gestation 2004-2007 (n=704) and 2014-2016 (n=895) in Sweden. MAIN OUTCOME MEASURES: NEC incidence. RESULTS: The validation process resulted in a 28% reduction of NEC cases but still confirmed a higher NEC incidence in the later epoch compared with the earlier (73/895 (8.2%) vs 27/704 (3.8%), p=0.001), while the composite of NEC or death was lower (244/895 (27.3%) vs 229/704 (32.5%), p=0.022). In a multivariable Cox regression model, censored for mortality, there was no significant difference in early NEC (0-7 days of life) between epochs (HR=0.9 (95% CI 0.5 to 1.9), p=0.9), but being born in the later epoch remained an independent risk factor for late NEC (>7 days) (HR=2.7 (95% CI 1.5 to 5.0), p=0.001). In propensity score analysis, a significant epoch difference in NEC incidence (12% vs 2.8%, p<0.001) was observed only in the tertile of infants at highest risk of NEC, where the 28-day mortality was lower in the later epoch (35% vs 50%, p=0.001). More NEC cases were diagnosed with intramural gas in the later epoch (33/73 (45.2%) vs 6/26 (23.1%), p=0.047). CONCLUSIONS: The increase in NEC incidence between epochs was limited to cases occurring after 7 days of life and was partly explained by increased survival in the most extremely preterm infants. Misclassification of NEC is common.

One-year survival and outcomes of infants born at 22 and 23 weeks of gestation in Sweden 2004-2007, 2014-2016 and 2017-2019.

OBJECTIVE: To explore associations between perinatal activity and survival in infants born at 22 and 23 weeks of gestation in Sweden. DESIGN/SETTING: Data on all births at 22 and 23 weeks' gestational age (GA) were prospectively collected in 2004-2007 (T1) or obtained from national registers in 2014-2016 (T2) and 2017-2019 (T3). Infants were assigned perinatal activity scores based on 3 key obstetric and 4 neonatal interventions. MAIN OUTCOME: One-year survival and survival without major neonatal morbidities (MNM): intraventricular haemorrhage grade 3-4, cystic periventricular leucomalacia, surgical necrotising enterocolitis, retinopathy of prematurity stage 3-5 or severe bronchopulmonary dysplasia. The association of GA-specific perinatal activity score and 1-year survival was also determined. RESULTS: 977 infants (567 live births and 410 stillbirths) were included: 323 born in T1, 347 in T2 and 307 in T3. Among live-born infants, survival at 22 weeks was 5/49 (10%) in T1 and rose significantly to 29/74 (39%) in T2 and 31/80 (39%) in T3. Survival was not significantly different between epochs at 23 weeks (53%, 61% and 67%). Among survivors, the proportions without MNM in T1, T2 and T3 were 20%, 17% and 19% for 22 weeks and 17%, 25% and 25% for 23 weeks' infants (p>0.05 for all comparisons). Each 5-point increment in GA-specific perinatal activity score increased the odds for survival in first 12 hours of life (adjusted OR (aOR) 1.4; 95% CI 1.3 to 1.6) in addition to 1-year survival (aOR 1.2; 95% CI 1.1 to 1.3), and among live-born infants it was associated with increased survival without MNM (aOR 1.3; 95% CI 1.1 to 1.4). CONCLUSION: Increased perinatal activity was associated with reduced mortality and increased chances of survival without MNM in infants born at 22 and 23 weeks of GA.

Trends, Characteristic, and Outcomes of Preterm Infants Who Received Postnatal Corticosteroid: A Cohort Study from 7 High-Income Countries.

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.

Preterm birth in the Nordic countries-Capacity, management and outcome in neonatal care.

AIM: Organisation of care, perinatal and neonatal management of very preterm infants in the Nordic regions were hypothesised to vary significantly. The aim of this observational study was to test this hypothesis. METHODS: Information on preterm infants in the 21 greater healthcare regions of Denmark, Finland, Iceland, Norway and Sweden was gathered from national registers in 2021. Preterm birth rates, case-mix, perinatal interventions, neonatal morbidity and survival to hospital discharge in very (<32 weeks) and extremely preterm infants (<28 weeks of gestational age) were compared. RESULTS: Out of 287 642 infants born alive, 16 567 (5.8%) were preterm, 2389 (0.83%) very preterm and 800 (0.28%) were extremely preterm. In very preterm infants, exposure to antenatal corticosteroids varied from 85% to 98%, live births occurring at regional centres from 48% to 100%, surfactant treatment from 28% to 69% and use of mechanical ventilation varied from 13% to 77% (p < 0.05 for all comparisons). Significant regional variations within and between countries were also seen in capacity in neonatal care, case-mix and number of admissions, whereas there were no statistically significant differences in survival or major neonatal morbidities. CONCLUSION: Management of very preterm infants exhibited significant regional variations in the Nordic countries.

Patterns of Respiratory Support by Gestational Age in Very Preterm Infants.

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.

Infants Born to Mothers Who Were SARS-CoV-2 Positive during Pregnancy and Admitted to Neonatal Intensive Care Unit.

INTRODUCTION: Our objective was to compare neonatal outcomes and resource use of neonates born to mothers with SARS-CoV-2 positivity during pregnancy with neonates born to mothers without SARS-CoV-2 positivity. METHODS: We conducted a two-country cohort study of neonates admitted between January 1, 2020, and September 15, 2021, to tertiary neonatal intensive care unit (NICU) in Canada and Sweden. Neonates from mothers who were SARS-CoV-2 positive during pregnancy were compared with three randomly selected NICU neonates of mothers who were not test-positive, matched on gestational age, sex, and birth weight (±0.25 SD). Subgroup analyses were conducted for neonates born <33 weeks' gestation and mothers who were SARS-CoV-2 positive ≤10 days prior to birth. Primary outcome was duration of respiratory support. Secondary outcomes were in-hospital mortality, neonatal morbidity, late-onset sepsis, receipt of breast milk at discharge, and length of stay. RESULTS: There were 163 exposed and 468 matched neonates in Canada, and 303 exposed and 903 matched neonates in Sweden. There was no statistically significant difference in invasive or noninvasive respiratory support durations, mortality, respiratory and other neonatal morbidities, or resource utilizations between two groups in both countries in entire cohort and in subgroup analyses. Receipt of breast milk at discharge was lower in the Canadian neonates of mothers who were SARS-CoV-2 positive ≤10 days before birth (risk ratio 0.68, 95% CI: 0.57-0.82). CONCLUSION: Maternal SARS-CoV-2 positivity was not associated with increased durations of respiratory support, morbidities, mortality, or length of hospital stay in Canada and Sweden among neonates admitted to tertiary NICU.

Development and Validation of a Mortality Prediction Model in Extremely Low Gestational Age Neonates.

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.

Perinatal risk factors for mortality in very preterm infants-A nationwide, population-based discriminant analysis.

AIM: To assess the strength of associations between interrelated perinatal risk factors and mortality in very preterm infants. METHODS: Information on all live-born infants delivered in Sweden at 22-31 weeks of gestational age (GA) from 2011 to 2019 was gathered from the Swedish Neonatal Quality Register, excluding infants with major malformations or not resuscitated because of anticipated poor prognosis. Twenty-seven perinatal risk factors available at birth were exposures and in-hospital mortality outcome. Orthogonal partial least squares discriminant analysis was applied to assess proximity between individual risk factors and mortality, and receiver operating characteristic (ROC) curves were used to estimate discriminant ability. RESULTS: In total, 638 of 8,396 (7.6%) infants died. Thirteen risk factors discriminated reduced mortality; the most important were higher Apgar scores at 5 and 10 min, GA and birthweight. Restricting the analysis to preterm infants <28 weeks' GA (n = 2939, 16.9% mortality) added antenatal corticosteroid therapy as significantly associated with lower mortality. The area under the ROC curve (the C-statistic) using all risk factors was 0.86, as determined after both internal and external validation. CONCLUSION: Apgar scores, gestational age and birthweight show stronger associations with mortality in very preterm infants than several other perinatal risk factors available at birth.

International Variation in the Management of Patent Ductus Arteriosus and Its Association with Infant Outcomes: A Survey and Linked Cohort Study.

OBJECTIVE: To assess whether treating patients with a presymptomatic patent ductus arteriosus (PDA), based on early routine echocardiography, performed regardless of clinical signs, improved outcomes. STUDY DESIGN: This multicenter, survey-linked retrospective cohort study used an institutional-level questionnaire and individual patient-level data and included infants of <29 weeks of gestation born in 2014-2016 and admitted to tertiary neonatal intensive care units (NICUs) of 9 population-based national or regional neonatal networks. Infants in NICUs receiving treatment of presymptomatic PDA identified by routine echocardiography and those not were compared for the primary composite outcome (early death [≤7 days after birth] or severe intraventricular hemorrhage) and secondary outcomes (any in-hospital mortality and major morbidities). RESULTS: The unit survey (response rates of 86%) revealed a wide variation among networks in the treatment of presymptomatic PDA (7%-86%). Among 246 NICUs with 17 936 infants (mean gestational age of 26 weeks), 126 NICUs (51%) with 7785 infants treated presymptomatic PDA. The primary outcome of early death or severe intraventricular hemorrhage was not significantly different between the NICUs treating presymptomatic PDA and those who did not (17% vs 21%; aOR 1.00, 95% CI 0.85-1.18). The NICUs treating presymptomatic PDA had greater odds of retinopathy of prematurity treatment (13% vs 7%; aOR 1.47, 95% CI 1.01-2.12); however, it was not significant in a sensitivity analysis excluding Japanese data. CONCLUSIONS: Treating presymptomatic PDA detected by routine echocardiography was commonplace but associated with no significant benefits. Well-designed trials are needed to assess the efficacy and safety of early targeted PDA treatment.

Five-minute Apgar score and outcomes in neonates of 24-28 weeks' gestation.

OBJECTIVES: To assess associations between 5 min Apgar score and mortality and severe neurological injury (SNI) and to report test characteristics in preterm neonates. DESIGN, SETTING AND PATIENTS: Retrospective cohort study of neonates 240 to 286 weeks' gestation born between 2007 and 2016 and admitted to neonatal units in 11 high-income countries. EXPOSURE: 5 min Apgar score. MAIN OUTCOME MEASURES: In-hospital mortality and SNI defined as grade 3 or 4 periventricular/intraventricular haemorrhage or periventricular leukomalacia. Outcome rates were calculated for each Apgar score and compared after adjustment. The diagnostic characteristics and ORs for each value from 0 versus 1-10 to 0-9 versus 10, with 1-point increments were calculated. RESULTS: Among 92 412 included neonates, as 5 min Apgar score increased from 0 to 10, mortality decreased from 60% to 8%. However, no clear increasing or decreasing pattern was identified for SNI. There was an increase in sensitivity and decrease in specificity for both mortality and SNI associated with increasing scores. The Apgar score alone had an area under the curve of 0.64 for predicting mortality, which increased to 0.73 with the addition of gestational age. CONCLUSIONS: In neonates of 24-28 weeks' gestation admitted to neonatal units, higher 5 min Apgar score was associated with lower mortality in a graded manner, while the association with SNI remained relatively constant at all scores. Among survivors, low Apgar scores did not predict SNI.

Association of Adherence to Surfactant Best Practice Uses With Clinical Outcomes Among Neonates in Sweden.

Importance: While surfactant therapy for respiratory distress syndrome (RDS) in preterm infants has been evaluated in clinical trials, less is known about how surfactant is used outside such a framework. Objective: To evaluate registered use, off-label use, and omissions of surfactant treatment by gestational age (GA) and associations with outcomes, mainly among very preterm infants (GA <32 weeks). Design, Setting, and Participants: This population-based cohort study used registry data for 97 377 infants born in Sweden between 2009 and 2018. Infants did not have malformations and were admitted for neonatal care. Data analysis was conducted from June 2019 to June 2020. Exposures: Timing and number of surfactant administrations, off-label use, and omission of use. Registered use was defined by drug label (1-3 administrations for RDS). Omissions were defined as surfactant not administered despite mechanical ventilation for RDS. Main Outcome and Measures: In-hospital survival, pneumothorax, intraventricular hemorrhage grade 3 to 4, duration of mechanical ventilation, use of postnatal systemic corticosteroids for lung disease, treatment with supplemental oxygen at 28 days' postnatal age and at 36 weeks' postmenstrual age. Odds ratios (ORs) were calculated and adjusted for any prenatal corticosteroid treatment, cesarean delivery, GA, infant sex, Apgar score at 10 minutes, and birth weight z score of less than -2. Results: In total, 7980 surfactant administrations were given to 5209 infants (2233 [42.9%] girls; 2976 [57.1%] boys): 629 (12.1%) born at full term, 691 (13.3%) at 32 to 36 weeks' GA, 1544 (29.6%) at 28 to 31 weeks' GA, and 2345 (45.0%) at less than 28 weeks' GA. Overall, 977 infants (18.8%) received off-label use. In 1364 of 3508 infants (38.9%) with GA of 22 to 31 weeks, the first administration of surfactant was given more than 2 hours after birth, and this was associated with higher odds of pneumothorax (adjusted OR [aOR], 2.59; 95% CI, 1.76-3.83), intraventricular hemorrhage grades 3 to 4 (aOR, 1.71; 95% CI, 1.23-2.39), receipt of postnatal corticosteroids (aOR, 1.57; 95% CI, 1.22-2.03), and longer duration of assisted ventilation (aOR, 1.34; 95% CI, 1.04-1.72) but also higher survival (aOR, 1.45; 95% CI, 1.10-1.91) than among infants treated within 2 hours of birth. In 146 infants (2.8%), the recommended maximum of 3 surfactant administrations was exceeded but without associated improvements in outcome. Omission of surfactant treatment occurred in 203 of 3551 infants (5.7%) who were receiving mechanical ventilation and was associated with lower survival (aOR, 0.49; 95% CI, 0.30-0.82). In full-term infants, 336 (53.4%) of those receiving surfactant had a diagnosis of meconium aspiration syndrome. Surfactant for meconium aspiration was not associated with improved neonatal outcomes. Conclusions and Relevance: In this study, adherence to best practices and labels for surfactant use in newborn infants varied, with important clinical implications for neonatal outcomes.

Association of Maternal SARS-CoV-2 Infection in Pregnancy With Neonatal Outcomes.

Importance: The outcomes of newborn infants of women testing positive for SARS-CoV-2 in pregnancy is unclear. Objective: To evaluate neonatal outcomes in relation to maternal SARS-CoV-2 test positivity in pregnancy. Design, Setting, and Participants: Nationwide, prospective cohort study based on linkage of the Swedish Pregnancy Register, the Neonatal Quality Register, and the Register for Communicable Diseases. Ninety-two percent of all live births in Sweden between March 11, 2020, and January 31, 2021, were investigated for neonatal outcomes by March 8, 2021. Infants with malformations were excluded. Infants of women who tested positive for SARS-CoV-2 were matched, directly and using propensity scores, on maternal characteristics with up to 4 comparator infants. Exposures: Maternal test positivity for SARS-CoV-2 in pregnancy. Main Outcomes and Measures: In-hospital mortality; neonatal resuscitation; admission for neonatal care; respiratory, circulatory, neurologic, infectious, gastrointestinal, metabolic, and hematologic disorders and their treatments; length of hospital stay; breastfeeding; and infant test positivity for SARS-CoV-2. Results: Of 88 159 infants (49.0% girls), 2323 (1.6%) were delivered by mothers who tested positive for SARS-CoV-2. The mean gestational age of infants of SARS-CoV-2-positive mothers was 39.2 (SD, 2.2) weeks vs 39.6 (SD, 1.8) weeks for comparator infants, and the proportions of preterm infants (gestational age <37 weeks) were 205/2323 (8.8%) among infants of SARS-CoV-2-positive mothers and 4719/85 836 (5.5%) among comparator infants. After matching on maternal characteristics, maternal SARS-CoV-2 test positivity was significantly associated with admission for neonatal care (11.7% vs 8.4%; odds ratio [OR], 1.47; 95% CI, 1.26-1.70) and with neonatal morbidities such as respiratory distress syndrome (1.2% vs 0.5%; OR, 2.40; 95% CI, 1.50-3.84), any neonatal respiratory disorder (2.8% vs 2.0%; OR, 1.42; 95% CI, 1.07-1.90), and hyperbilirubinemia (3.6% vs 2.5%; OR, 1.47; 95% CI, 1.13-1.90). Mortality (0.30% vs 0.12%; OR, 2.55; 95% CI, 0.99-6.57), breastfeeding rates at discharge (94.4% vs 95.1%; OR, 0.84; 95% CI, 0.67-1.05), and length of stay in neonatal care (median, 6 days in both groups; difference, 0 days; 95% CI, -2 to 7 days) did not differ significantly between the groups. Twenty-one infants (0.90%) of SARS-CoV-2-positive mothers tested positive for SARS-CoV-2 in the neonatal period; 12 did not have neonatal morbidity, 9 had diagnoses with unclear relation to SARS-CoV-2, and none had congenital pneumonia. Conclusions and Relevance: In a nationwide cohort of infants in Sweden, maternal SARS-CoV-2 infection in pregnancy was significantly associated with small increases in some neonatal morbidities. Given the small numbers of events for many of the outcomes and the large number of statistical comparisons, the findings should be interpreted as exploratory.

Inter-center variability in neonatal outcomes of preterm infants: A longitudinal evaluation of 298 neonatal units in 11 countries.

Collaboration and cooperation of clinicians and neonatal units at regional, national, and international levels are key features of many networks or systems that aim to improve neonatal outcomes. Network performance is typically assessed by comparing individual, unit-level outcomes. In this paper, we provide insight into another dimension, i.e., inter-center outcome variation in 10 national/regional neonatal collaborations from 11 high-income countries. We illustrate the use of coefficients of variation for evaluation of mortality and a composite outcome of mortality, severe neurological injury, treated retinopathy of prematurity, and bronchopulmonary dysplasia, as a measure of inter-center variation. These inter-center variation estimates could help to identify areas of opportunities and challenges for each country/region; they also provide "macro"-level evaluations that can be useful for clinicians, administrators, managers and policy makers.

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.

Neonatal outcomes of extremely preterm twins by sex pairing: an international cohort study.

OBJECTIVE: Infant boys have worse outcomes than girls. In twins, the 'male disadvantage' has been reported to extend to female co-twins via a 'masculinising' effect. We studied the association between sex pairing and neonatal outcomes in extremely preterm twins. DESIGN: Retrospective cohort study SETTING: Eleven countries participating in the International Network for Evaluating Outcomes of Neonates. PATIENTS: Liveborn twins admitted at 23-29 weeks' gestation in 2007-2015. MAIN OUTCOME MEASURES: We examined in-hospital mortality, grades 3/4 intraventricular haemorrhage or cystic periventricular leukomalacia (IVH/PVL), bronchopulmonary dysplasia (BPD), retinopathy of prematurity requiring treatment and a composite outcome (mortality or any of the outcomes above). RESULTS: Among 20 924 twins, 38% were from male-male pairs, 32% were from female-female pairs and 30% were sex discordant. We had no information on chorionicity. Girls with a male co-twin had lower odds of mortality, IVH/PVL and the composite outcome than girl-girl pairs (reference group): adjusted OR (aOR) (95% CI) 0.79 (0.68 to 0.92), 0.83 (0.72 to 0.96) and 0.88 (0.79 to 0.98), respectively. Boys with a female co-twin also had lower odds of mortality: aOR 0.86 (0.74 to 0.99). Boys from male-male pairs had highest odds of BPD and composite outcome: aOR 1.38 (1.24 to 1.52) and 1.27 (1.16 to 1.39), respectively. CONCLUSIONS: Sex-related disparities in outcomes exist in extremely preterm twins, with girls having lower risks than boys and opposite-sex pairs having lower risks than same-sex pairs. Our results may help clinicians in assessing risk in this large segment of extremely preterm infants.

Prolonged Tracheal Intubation and the Association Between Patent Ductus Arteriosus and Bronchopulmonary Dysplasia: A Secondary Analysis of the PDA-TOLERATE trial.

In the PDA-TOLERATE trial, persistent (even for several weeks) moderate to large patent ductus arteriosus (PDA) was not associated with an increased risk of BPD when the infant required <10 days of intubation. However, in infants requiring intubation for ≥10 days, prolonged PDA exposure (≥11 days) was associated with an increased risk of moderate/severe BPD.

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.

Neonatal Intensive Care Unit-Level Patent Ductus Arteriosus Treatment Rates and Outcomes in Infants Born Extremely Preterm.

OBJECTIVES: To assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes. STUDY DESIGN: This cohort study included infants born at 24-28 weeks of gestation and birth weight <1500 g in 2007-2015 in NICUs caring for ≥100 eligible infants in 6 countries. The ratio of observed/expected (O/E) PDA treatment rates was derived for each NICU by estimating the expected rate using a logistic regression model adjusted for potential confounders and network. The primary composite outcome was death or severe neurologic injury (grades III-IV intraventricular hemorrhage or periventricular leukomalacia). The associations between the NICU-level O/E PDA treatment ratio and neonatal outcomes were assessed using linear regression analyses including a quadratic effect (a square term) of the O/E PDA treatment ratio. RESULTS: From 139 NICUs, 39 096 infants were included. The overall PDA treatment rate was 45% in the cohort (13%-77% by NICU) and the O/E PDA treatment ratio ranged from 0.30 to 2.14. The relationship between the O/E PDA treatment ratio and primary composite outcome was U-shaped, with the nadir at a ratio of 1.13 and a significant quadratic effect (P<.001). U-shaped relationships were also identified with death, severe neurologic injury, and necrotizing enterocolitis. CONCLUSIONS: Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.