Umeå University's logo

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.

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 97377 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.

Aim: The definition of necrotising enterocolitis (NEC) is based on clinical and radiological signs that can be difficult to interpret. The aim of the present study was to validate the incidence of NEC in the Extremely Preterm Infants in Sweden Study (EXPRESS)

Methods: The EXPRESS study consisted of all 707 infants born before 27 + 0 gestational weeks during the years 2004–2007 in Sweden. Of these infants, 38 were recorded as having NEC of Bell stage II or higher. Hospital records were obtained for these infants. Furthermore, to identify missed cases, all infants with a sudden reduction of enteral nutrition, in the EXPRESS study were identified (n = 71). Hospital records for these infants were obtained. Thus, 108 hospital records were obtained and scored independently by two neonatologists for NEC.

Results: Of 38 NEC cases in the EXPRESS study, 26 were classified as NEC after validation. Four cases not recorded in the EXPRESS study were found. The incidence of NEC decreased from 6.3% to 4.3%.

Conclusion: Validation of the incidence of NEC revealed over- and underestimation of NEC in the EXPRESS study despite carefully collected data. Similar problems may occur in other national data sets or quality registers.

Background:  Transfusion practices are highly variable between hospitals and previous studies have suggested that blood transfusions may increase the risk of necrotizing enterocolitis (NEC).

Aim: To explore the association between blood transfusions and incidence of NEC in extremely preterm infants.

Methods: We used data from a Swedish population-based study including extremely preterm infants (<27 weeks) born between 2004–2007, (n = 602). All data on blood transfusions and haemoglobin (Hb) concentrations up to 28 days of age was collected for survivors. We performed a nested case-control study where two controls were chosen for each case of NEC (n = 21).

Results: During the first 28 days of life, infants received a median (25th-75th percentile) of 6 (3–9) blood transfusions resulting in 75 (44–120) ml/kg of blood. Predictors for receiving a higher volume of blood transfusions were days on respiratory support (R = 0.345, p < 0.001), hospital (R = 0.339, p < 0.001), low birth weight (R = -0.236, p < 0.001) and total steroid dose (R = 0.209, p < 0.001). Hb was not a significant predictor.

Overall NEC incidence was 5.8%. There was no significant difference between NEC cases and controls in number of blood transfusions (p = 0.420), volume of blood transfused from birth to NEC diagnosis (p = 0.274), or during the 48 h preceding NEC diagnosis (p = 0.459).

Conclusions: Blood transfusions were given liberally in Sweden compared to other studied populations. Morbidity related variables, especially those related to respiratory illness, were significant predictors of blood transfusion. NEC incidence was comparable with other populations but no significant association was found between blood transfusions and NEC among these extremely preterm infants.