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ObjectiveTo evaluate annual trends in the administration and duration of respiratory support among preterm infants.DesignRetrospective cohort study.SettingTertiary neonatal intensive care units in the Canadian Neonatal Network.Patients8881 extremely preterm infants born from 2010 to 2017 treated with endotracheal and/or non-invasive positive pressure support (PPS).Main outcome measuresCompeting risks methods were used to investigate the outcomes of mortality and time to first successful extubation, definitive extubation, weaning off PPS, and weaning PPS and/or low-flow oxygen, according to gestational age (GA). Cox proportional hazards and regression models were fitted to evaluate the trend in duration of respiratory support, survival and surfactant treatment over the study period.ResultsThe percentages of infants who died or were weaned from respiratory support were presented graphically over time by GA. Advancing GA was associated with ordinally earlier weaning from respiratory support. Year over year, infants born at 23 weeks were initially and definitively weaned from endotracheal and all PPS earlier (HR 1.06, 95% CI 1.01 to 1.11, for all outcomes), while survival simultaneously increased (OR 1.11, 95% CI 1.03 to 1.18). Infants born at 26 and 27 weeks remained on non-invasive PPS longer (HR 0.97, 95% CI 0.95 to 0.98 and HR 0.97, 95% CI 0.95 to 0.99, respectively). Early surfactant treatment declined among infants born at 24–27 weeks GA.ConclusionsInfants at the borderline of viability have experienced improved survival and earlier weaning from all forms of PPS, while those born at 26 and 27 weeks are spending more time on PPS in recent years. GA-based estimates of the duration of respiratory support and survival may assist in counselling, benchmarking, quality improvement and resource planning.

Umbilical cord arterial and venous blood gas values reflect the acid-base balance status of a newborn at birth. Derangement in these values has been linked to poor neonatal outcomes in term and late preterm neonates; however, the utility of these values in preterm neonates of29 weeks' gestation is unclear.This study aimed to determine the associations of umbilical cord arterial and venous blood gas values with neonatal mortality and severe neurologic injury in extremely preterm neonates and to identify the cutoff values associated with 2.5-fold increases or decreases in the posttest probabilities of outcomes.This was a retrospective cohort study of neonates who were born at 23+0 to 28+6 weeks' gestation between January 1, 2018 and December 31, 2019, and who were admitted to neonatal units in Canada.Various cut-offs of umbilical cord blood gas values and lactate values were studied.The main outcomes were mortality before discharge from the neonatal unit and severe neurologic injury defined as grade 3 or 4 periventricular or intraventricular hemorrhage or periventricular leukomalacia. The outcome rates were calculated for various cutoff values of umbilical cord blood gas parameters and were adjusted for birthweight, gestational age, sex, and multiple births. Likelihood ratios were calculated to derive posttest probabilities.A total of 1040 and 1217 neonates had analyzable umbilical cord arterial and venous blood gas values, respectively. In the cohort, the mean (standard deviation) gestational age was 26.5 (1.5) weeks, the mean birthweight was 936 (215) g, the prevalence of mortality was 10% (105/1040), and the prevalence of severe neurologic injury was 9% (92/1016). An umbilical cord arterial pH of ≤7.1 and base excess of ≤-12 mmol/L were associated with2.5-fold higher posttest probability of mortality, and an umbilical cord arterial or venous lactate value of3 was associated with a 2.5-fold lower posttest probability of mortality. An umbilical cord arterial lactate value of3 was associated with a lower posttest probability of severe neurological injury.In preterm neonates of29 weeks' gestation, low umbilical cord arterial pH and high umbilical cord arterial base excess values were associated with a clinically important increase in the posttest probability of mortality, whereas low umbilical cord arterial or venous lactate values were associated with a decrease in the posttest probability of mortality.

Objective: To evaluate the association of a combined exposure to antenatal steroids and prophylactic indomethacin with the outcome of spontaneous intestinal perforation (SIP) among neonates born at 7 days before birth) exposures. The co-exposure was prophylactic indomethacin. The primary outcome was SIP. Multivariable logistic regression analysis was used to calculate aORs. Results: Among 4720 eligible infants, 4121 (87%) received antenatal steroids and 1045 (22.1%) received prophylactic indomethacin. Among infants exposed to antenatal steroids, those who received prophylactic indomethacin had higher odds of SIP (aOR 1.61, 95% CI 1.14-2.28) compared with no prophylactic indomethacin. Subgroup analyses revealed recent antenatal steroids exposure with prophylactic indomethacin had higher odds of SIP (aOR 1.67, 95% CI 1.15-2.43), but latent antenatal steroids exposure with prophylactic indomethacin did not (aOR 1.24, 95% CI 0.48-3.21), compared with the respective groups with no prophylactic indomethacin. Among those not exposed to antenatal steroids, mortality was lower among those who received prophylactic indomethacin (aOR 0.45, 95% CI 0.28-0.73) compared with no prophylactic indomethacin. Conclusions: In preterm neonates of

Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown.Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infantslt;29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers.Of the 2414 eligible twin infantslt;29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes.Preterm twin infantslt;29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality.Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

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.

OBJECTIVE To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants

Infants with restricted growth for age are frequently exposed to insufficient placental circulation and are more likely to develop postnatal complications. Delayed cord clamping at birth for these infants requires further exploration.This study aimed to compare the short-term neonatal outcomes of delayed cord clamping with that of early cord clamping in small for gestational age preterm infants and to explore whether the effects of delayed cord clamping in small for gestational age preterm infants are different from that in non-small for gestational age preterm infants.We conducted a national retrospective cohort study, including infants born at33 weeks' gestation and admitted to the Canadian Neonatal Network units between January 2015 and December 2017. Small for gestational age infants (birthweight of10th percentile for gestational age and sex) who received delayed cord clamping ≥30 seconds were compared with those who received early cord clamping. In addition, non-small for gestational age infants who received delayed cord clamping were compared with those who received early cord clamping. The main study outcomes included composite outcome of mortality or major morbidity, neonatal morbidity rate, mortality rate, peak serum bilirubin, and number of blood transfusions. Multivariable logistic and linear regression models with a generalized estimation equation approach were used to account for the clustering of infants within centers.Overall, 9722 infants met the inclusion criteria. Of those infants, 1027 (10.6%) were small for gestational age. The median (interquartile range) gestational age was 31 weeks (range, 28-32 weeks). After adjusting for potential confounders, delayed cord clamping in small for gestational age infants was associated with a reduction in the composite outcome of mortality or major morbidity (adjusted odds ratio, 0.60; 95% confidence interval, 0.42-0.86) compared with early cord clamping. There was no difference between the 2 groups in peak serum bilirubin. Many associated benefits of delayed cord clamping in small for gestational age infants were similar to those in non-small for gestational age infants.Delayed cord clamping in small for gestational age preterm infants was associated with decreased odds of mortality or major morbidity. Many of the benefits of delayed cord clamping in the small for gestational age preterm infants were similar to those identified in the non-small for gestational age preterm infants.

To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses.We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates.We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada.NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.

Background The current resuscitation guidelines for neonates recommend considering stopping resuscitation efforts if the heart rate remains undetectable after 10 min of adequate resuscitation. However, this recommendation does not take into account the gestational age (GA) of the neonates. We determined the outcomes of neonates with a 10-min Apgar score of zero (Apgar10 = 0) with respect to their GA. Methods In a retrospective matched cohort study, we studied neonates admitted to the Canadian Neonatal Network NICUs between 2010 and 2016 with an Apgar10 = 0. The neonates were divided into 3 subgroups according to their GA: (1) ≥36 weeks’, (2) 320/7–356/7 weeks’, and (3) Results 177 neonates had Apgar10 = 0. Survival to discharge was significantly different between GA groups [≥36 weeks’ 61% vs. 320/7–356/7 weeks’ 58% vs. Conclusion Neonates with Apgar10 = 0 had different outcomes depending on their GA. Less than half of neonates born at

Objective To evaluate the impact of prophylactic indomethacin on early death ( Study design This was a multicenter, retrospective cohort study of neonates (n = 12 515) born at 236/7 weeks of gestational age, admitted to neonatal intensive care units participating in the Canadian Neonatal Network who received prophylactic indomethacin started within the first 12 hours after birth. Univariate and multivariate analysis compared the composite outcomes of early death or severe neurologic injury and early death or spontaneous intestinal perforation. Results Of 12 515 eligible neonates, 1435 (11.5%) were exposed to prophylactic indomethacin; recipients were of lower gestational age and birth weight and had greater severity of illness (Score of Neonatal Acute Physiology with Perinatal Extension) on admission compared with nonrecipients. After we adjusted for confounders, prophylactic indomethacin was associated with reduced odds of early death or severe neurologic injury and early death or spontaneous intestinal perforation in neonates born at 23-24 weeks of gestational age. However, prophylactic indomethacin was associated with increased odds of early mortality or spontaneous intestinal perforation for neonates born at 26-28 weeks of gestational age. Conclusions Prophylactic indomethacin use was associated with benefit in neonates born at 23-24 weeks of gestational age, but with harm at 26-28 weeks of gestational age. Given the observation of significantly improved survival, a randomized controlled trial is needed to investigate the effect of prophylactic indomethacin in babies born at 23-25 weeks of gestational age.

Objective To provide comprehensive, contemporary information on the actuarial survival of infants born at 22-25 weeks of gestation in Canada. Study design In a retrospective cohort study, we included data from preterm infants of 22-25 weeks of gestation admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 2010 and 2017. Infants with major congenital anomalies were excluded. We calculated gestational age using in vitro fertilization date, antenatal ultrasound dating, last menstrual period, obstetrical estimate, or neonatal estimate (in that order). Infants were followed until either discharge or death. Each day of gestational age was considered a category except for births at 22 weeks, where the first 4 days were grouped into one category and the last 3 days were grouped into another category. For each day of life, an actuarial survival rate was obtained by calculating how many infants survived to discharge out of those who had survived up to that day. Results Of 4335 included infants, 85, 679, 1504, and 2067 were born at 22, 23, 24, and 25 weeks of gestation, respectively. Survival increased from 32% at 22 weeks to 83% at 254−6/7 weeks. Graphs of actuarial survival developed for the first 6 weeks after birth in male and female children indicated a steep increase in survival during the first 7-10 days postnatally. Conclusions Survival increased steadily with postnatal survival and was dependent on gestational age in days and sex of the child.

To compare mortality and neurodevelopmental outcomes of extremely low gestational age neonates who received delivery room extensive cardiopulmonary resuscitation (DR-CPR) to those who did not require DR-CPR.Preterm neonates born at29 weeks' gestational age between January 2010 and September 2011 and assessed at Canadian Neonatal Follow-Up Network centers were studied. Neonates who received DR-CPR were compared to those who did not require DR-CPR using univariate and multivariable analyses. The primary outcome was a composite of mortality or any neurodevelopmental impairment at 18 to 24 months corrected age defined as the presence of any one or more of the following: cerebral palsy; Bayley-III cognitive, language, or motor composite scores85 on any one of the components; sensorineural/mixed hearing loss or unilateral or bilateral visual impairment. Secondary outcomes were the individual components of the composite outcomes.Of the 2760 neonates born, 173 were excluded and remaining 2587 eligible neonates were included in our study. Of these 2068 had outcome data (80%) of whom 190 (9.2%) received DR-CPR. DR-CPR was independently associated with mortality or neurodevelopmental impairment (adjusted odds ratio [aOR] 1.76; 95% CI 1.21-2.55) and mortality alone (aOR1.94; 95% CI 1.33-2.83). DR-CPR was also associated with increased odds of motor impairment (aOR 2.03; 95% CI 1.28-3.23).In extremely low gestational age neonates, DR-CPR was associated with higher odds of the composite outcome of mortality or neurodevelopmental impairment, mortality alone, and lower motor scores at 18 to 24 months' corrected age.

To determine if the reported reduction in hospital-acquired infections is due to reduced central line-associated blood stream infections (CLABSI) or non-CLABSIs.A retrospective cohort study design was used to describe the change in organism pattern and incidence of hospital-acquired infections (CLABSIs and non-CLABSIs) in neonates33 weeks of gestation admitted to tertiary neonatal intensive care units in the Canadian Neonatal Network between January 1, 2010, and December 31, 2016. Hospital-acquired infection was diagnosed when a pathogenic organism was isolated from blood or cerebrospinal fluid in a neonate with suspected sepsis. CLABSI was diagnosed when a central venous catheter was present at the time or removed in the 2 days before a hospital-acquired infection diagnosis. Cochran-Armitage and Mann-Kendall trend tests and linear regression models were used for statistical analyses.Of 28 144 eligible neonates from 30 Canadian Neonatal Network neonatal intensive care units, 3306 (11.7%) developed hospital-acquired infections. There was a significant decrease in the rate of hospital-acquired infections (14.2% in 2010 and 9.2% in 2016; P .01), and the rate of both CLABSIs and non-CLABSIs (P .01) over the study period concomitant with a significant decrease in the duration of central line use (P = .01). The rates of meningitis also decreased during the study period (1.2% in 2010 and 0.9% in 2016; P .01). Infections owing to gram-positive cocci significantly decreased, but infections owing to gram-negative organisms remained unchanged.Although there was a significant decrease in CLABSIs and non-CLABSIs, hospital-acquired infections in preterm neonates remained high. Infections owing to gram-negative organisms remained unchanged and are a target for future preventative efforts.

To identify risk factors for severe neurologic injury (intraventricular hemorrhage grade 3 or greater and/or periventricular leukomalacia) diagnosed by ultrasound scan of the head among infants born at 30This was a retrospective cohort study of infants born at 30The rate of severe neurologic injury was 3.1% among infants screened (285/9221). Significant risk factors included singleton birth (aOR 1.96, 95% CI 1.35-2.85), 5-minute Apgar7 (aOR 1.81, 95% CI 1.30-2.50), mechanical ventilation on day 1 (aOR 2.65, 95% CI 1.88-3.71), and treatment with vasopressors on day 1 (aOR 3.23, 95% CI 2.19-4.75). Risk categories were low (no risk factor, 1.2%, 25/2137), moderate (singleton with no other risk factor: 1.8%, 68/3678), and high (≥1 risk factor among 5-minute Apgar7, receipt of vasopressors or mechanical ventilation on day 1: 5.6%, 192/3408). Screening moderate- to high-risk infants identified 91% (260/285) of infants with severe neurologic injury and would require screening fewer infants (1647 infants per year) than screening all infants33 weeks of gestation (2064 infants screened per year, 93% [265/285] of cases identified).Risk factor-based ultrasound scan of the head screening among infants born at 30-32 weeks of gestation could help optimize resources better than gestational age based screening.