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In situations where the immediate safety of children or others is at risk, residential workers are authorized to use specific measures intended as last resort, namely restraint and seclusion (R&S). This study sought to identify and detail the reasons invoked by residential workers when justifying their decision to restrain or seclude a child. Researchers reviewed and coded 628 anonymized official R&S reports written by residential workers from two different residential treatment centers over the 14 months between September 2015 and May 2017. Researchers used qualitative thematic analysis to analyze official reports. Researchers found nine reasons invoked by residential workers that they regrouped into four themes as follows: workers justified their use of R&S based on their own perceptions of 1) the danger associated with children’s affects and behaviors; 2) their obligation to yield to external constraints; 3) the benefits associated with R&S for children, and 4) the demands imposed by their professional culture. Researchers found that the reasons invoked in official reports by residential workers to justify their decisions are not always consistent with R&S as being methods of last resort. Specifically, residential workers appear to be missing the training and organizational resources needed to use alternative forms of intervention.

Objective: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants

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

IntroductionPatent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants.Methods and analysisA multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3–7 days.Intravenous indomethacin (0.1–0.3 mg/kg intravenous every 12–24 hours for a total of three doses).OutcomesThe primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment.Sites and sample sizeThe study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years.AnalysisTo examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student’s t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach.Ethics and disseminationThe study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres.Trial registration numberNCT04347720.

Primary Subject area Neonatal-Perinatal Medicine Background Mechanical ventilation is frequently used in preterm infants for various indications, but is associated with multiple complications, including bronchopulmonary dysplasia and poorer neurodevelopmental outcomes. Noninvasive high-frequency oscillatory ventilation (nHFOV) is a noninvasive ventilation (NIV) strategy used to avoid mechanical ventilation and associated complications. However, its effectiveness remains controversial, and its safety has not been established. Objectives The objectives were to evaluate the effectiveness of nHFOV to prevent intubations and support adequate ventilation in preterm infants, and to assess its safety profile. Design/Methods This was a retrospective crossover case study including 24 infants and 30 nHFOV instances between May 2018 and June 2020. Infants were included if they were placed on nHFOV for at least one hour; each nHFOV trial contributed as one instance. Data was collected from health records. Effectiveness outcomes were: successful transition to another NIV mode without requiring intubation, and variations in CO2, FiO2, and number of spells. Safety outcomes were: apparition of intraventricular hemorrhage (IVH), gastrointestinal complications, nasal cutaneous trauma, and comfort as assessed with the Neonatal Pain, Agitation and Sedation Scale (N-PASS). Descriptive statistics were used for baseline characteristics. Nonparametric and semiparametric tests were used to compare outcomes pre- and during nHFOV. Results Baseline characteristics are presented in Table 1. At initiation of nHFOV, mean chronological age and weight were 24 days (95% CI: 20 – 28) and 1119 grams (95% CI: 1038 – 1200) respectively. The most frequent indication for nHFOV was spells (56.7%), and the mean duration of nHFOV instances was 3.9 days (95% CI: 2.7 – 5.1) (Table 1). In 18 (60%) cases, infants transitioned successfully to another NIV mode without requiring intubation. Levels of CO2 and number of spells were significantly lower during nHFOV than pre-nHFOV. There was no significant difference in FiO2 pre-nHFOV and during nHFOV. No apparition or progression of IVH was observed following the use of nHFOV. There was no significant difference in N-PASS, nasal trauma, and gastrointestinal complications pre-nHFOV and during nHFOV (Table 2). Conclusion This study suggests that nHFOV is an effective ventilation method to avoid intubation and to decrease spells in preterm infants, without increasing complications.

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited.This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally.This retrospective cohort study included inborn, nonanomalous infants, born at29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment.Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88).Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

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

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very 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.

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 examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN).This was a population-based cohort study of infants born at33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding.Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12).Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge.

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.

Background One of the controversies in the management of twin gestations relates to mode of delivery, especially when the second twin is in a nonvertex presentation (Vertex/nonVertex pairs) and birth is imminent at extremely low gestation. Objective We hypothesized that, for Vertex/nonVertex twins born before 28 weeks’ gestation, cesarean delivery would be associated with a lower risk of adverse neonatal outcomes than trial of vaginal delivery. Our aim was to test this hypothesis by comparing the neonatal outcomes of Vertex/nonVertex twins born before 28 weeks’ gestation by mode of delivery using a large national cohort. Study Design This work is a retrospective cohort study of all twin infants born at 240/7 to 276/7 weeks’ gestation and admitted to level III neonatal intensive care units participating in the Canadian Neonatal Network (2010–2017). Exposure is defined a trial of vaginal delivery for Vertex/nonVertex twins. Nonexposed (control) groups are defined as cases where both twins were delivered by cesarean delivery, either in vertex or nonvertex presentation (control group 1) or owing to the nonvertex presentation of the first twin (control group 2). Outcome measures are defined as a composite of neonatal death, severe neurologic injury, or birth trauma. Results A total of 1082 twin infants (541 twin pairs) met the inclusion criteria: 220 Vertex/nonVertex pairs, of which 112 had a trial of vaginal delivery (study group) and 108 had cesarean delivery for both twins (control group 1); 170 pairs with the first twin in nonvertex presentation, all of which were born by cesarean delivery (control group 2); and 151 pairs with both twins in vertex presentation (vertex or nonvertex). In the study group, the rate of urgent cesarean delivery for the second twin was 30%. The rate of the primary outcome in the study group was 42%, which was not significantly different compared with control group 1 (37%; adjusted relative risk, 0.93; 95% confidence interval, 0.71–1.22) or control group 2 (34%; adjusted relative risk, 1.20; 95% confidence interval, 0.92–1.58). The findings remained similar when outcomes were analyzed separately for the first and second twins. Conclusion For preterm Vertex/nonVertex twins born at

Children placed in residential treatment centers (RTCs) typically present challenging behavior including aggression. In this context, restraint and seclusion (R&S) are seen as “last resort” strategies for educators to manage youth aggression. The use of R&S is controversial, as they can lead to psychological and physical consequences for both the client and the care provider and have yet to be empirically validated as therapeutic. The objectives of this systematic review are to identify the factors related to R&S use in RTCs for youth and to review the interventions aiming to reduce the use of R&S. The identification of these factors is the first step to gaining a better understanding of the decision-making process leading to the use of R&S and ultimately to reducing the use of these strategies to a minimum. Thus, the present systematic review was conducted by searching PubMed, CINAHL, ERIC, and PsycNET for articles published between 2002 and 2017. Key words used were synonyms of R&S, youth, and RTCs. Thirty-one studies met the inclusion criteria: must report on factors affecting the use of R&S in RTCs, must be conducted in RTCs for youth under the age of 21, and must report on original and empirical data. Factors related to the characteristics of the client, the care provider, and the environment, as well as to the implementation of programs for the reduction of R&S, were found to influence the use of R&S in RTCs. A conceptual model is presented. The implementation of programs to reduce R&S use is discussed.

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 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 assess associations between neonatal intensive care unit (NICU)-level patent ductus arteriosus (PDA) treatment rates (pharmacologic or surgical) and neonatal outcomes.This cohort study included infants born at 24-28 weeks of gestation and birth weight1500 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.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.Both low and high PDA treatment rates were associated with death or severe neurologic injury, whereas a moderate approach was associated with optimal outcomes.

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.

NEW FINDINGS What is the central question of the study? Is there a sex-based difference in the incidence of apnoea of prematurity and the success or failure of caffeine therapy in preterm infants? What is the main finding and its importance? Our data show that females received fewer days of caffeine treatment than males. This was most noticeable in infants born between 260/7 and 276/7 weeks of gestational age. These results highlight the importance of considering sex in clinical and basic research investigating the pathophysiology of apnoea of prematurity. ABSTRACT This retrospective cohort study assessed whether sex influences the occurrence of apnoea of prematurity (AOP) in preterm infants. The analysis included a cohort of 24,387 preterm infants born between the gestational ages (GA) of 240/7 and 336/7 weeks that were admitted to tertiary neonatal care units participating in the Canadian Neonatal Network from January 2011 to December 2015. Of those, 13,983 (57%) were diagnosed with AOP. More females were diagnosed with AOP than males, but the difference in the male/female ratio was marginal (P = 0.058). The majority (89%) of infants diagnosed with AOP received caffeine (89% of males; 89% of females). By using the discontinuation of caffeine therapy as a proxy for the resolution of significant AOP, data analysis showed that females born before 336/7 weeks of GA stopped caffeine treatment earlier than males whether the caffeine was discontinued before 34 or 37 weeks of GA. Consequently, females had fewer days of caffeine therapy than males, especially infants born between 260/7 and 276/7 weeks (P

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.

Objective To assess the impact of variations in the definition of severe neurodevelopmental impairment (NDI) on the incidence of severe NDI and the association with risk factors using the Canadian Neonatal Follow-Up Network cohort. Study design Literature review of severe NDI definitions and application of these definitions were performed in this database cohort study. Infants born at 23-28 completed weeks of gestation between 2009 and 2011 (n = 2187) admitted to a Canadian Neonatal Network neonatal intensive care unit and assessed at 21 months' corrected age were included. The incidence of severe NDI, aORs, and 95% CIs were calculated to express the relationship between risk factors and severe NDI using the definitions with the highest and the lowest incidence rates of severe NDI. Results The incidence of severe NDI ranged from 3.5% to 14.9% (highest vs lowest rate ratio 4.29; 95% CI 3.37-5.47). The associations between risk factors and severe NDI varied depending on the definition used. Maternal ethnicity, employment status, antenatal corticosteroid treatment, and gestational age were not associated consistently with severe NDI. Although maternal substance use, sex, score of neonatal acute physiology >20, late-onset sepsis, bronchopulmonary dysplasia, and brain injury were consistently associated with severe NDI irrespective of definition, the strength of the associations varied. Conclusions The definition of severe NDI significantly influences the incidence and the associations between risk factors and severe NDI. A standardized definition would facilitate site comparisons and scientific communication.

To compare mortality and neurodevelopmental outcomes of outborn and inborn preterm infants born at29 weeks of gestation admitted to Canadian neonatal intensive care units (NICUs).Data were obtained from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases for infants born at29 weeks of gestation admitted to NICUs from April 2009 to September 2011. Rates of death, severe neurodevelopmental impairment (NDI), and overall NDI were compared between outborn and inborn infants at 18-21 months of age, corrected for prematurity.Of 2951 eligible infants, 473 (16%) were outborn. Mean birth weight (940 ± 278 g vs 897 + 237 g), rates of treatment with antenatal steroids (53.9% vs 92.9%), birth weight small for gestational age (5.3% vs 9.4%), and maternal college education (43.7% vs 53.9%) differed between outborn and inborn infants, respectively (all P values.01). The median Score for Neonatal Acute Physiology-II (P = .01) and Apgar score at 5 minutes (P .01) were higher in inborn infants. Severe brain injury was more common among outborn infants (25.3% vs 14.7%, P .01). Outborn infants had higher odds of death or severe NDI (aOR 1.7, 95% CI 1.3-2.2), death or overall NDI (aOR 1.6, 95% CI 1.2-2.2), death (aOR 2.1, 95% CI 1.5-3.0), and cerebral palsy (aOR 1.9, 95% CI 1.1-3.3).The composite outcomes of death or neurodevelopmental impairment were significantly higher in outborn compared with inborn infants admitted to Canadian NICUs. Adverse outcomes were mainly attributed to increased mortality and cerebral palsy in outborn neonates.

Background Data regarding the effects of antenatal corticosteroids in twin pregnancies are limited because of the insufficient number of women with twins enrolled in randomized controlled trials on antenatal corticosteroids. Furthermore, the interpretation of available data is limited by the fact that the interval from the administration of antenatal corticosteroids to delivery is greater than 7 days in a large proportion of twins, a factor that has been shown to affect the efficacy of antenatal corticosteroids and has not been controlled for in previous studies. Objective The objective of the study was to compare neonatal mortality and morbidity in preterm twins receiving a complete course of antenatal corticosteroids 1–7 days before birth to those who did not receive antenatal corticosteroids and to compare these outcome effects with those observed in singletons. Study Design We performed a retrospective cohort study using data collected on singleton and twin neonates born between 24 0/7 and 33 6/7 weeks' gestational age and were admitted to tertiary neonatal units in Canada between 2010 and 2014. A comparison of neonatal outcomes between twin neonates who received a complete course of antenatal corticosteroids 1–7 days before birth (n = 1758) and those who did not receive antenatal corticosteroids (n = 758) and between singleton neonates who received a complete course of antenatal corticosteroids 1–7 days before birth (n = 4638) and those did not receive antenatal corticosteroids (n = 2312) was conducted after adjusting for gestational age, sex, hypertension, outborn status, small for gestational age, parity, and cesarean birth. Adjusted odds ratios and 95% confidence intervals for various neonatal outcomes were calculated. Results Administration of a complete course of antenatal corticosteroids within 1–7 days before birth in both twins and singletons was associated with similar reduced odds of neonatal death (for twins adjusted odds ratio 0.42 [95% confidence interval, 0.24–0.76] and for singletons adjusted odds ratios, 0.38 [95% confidence interval, 0.28–0.50]; P = .7 for comparison of twins vs singletons), mechanical ventilation (for twins adjusted odds ratio, 0.47 [95% confidence interval, 0.35–0.63] and for singletons adjusted odds ratio, 0.47 [95% confidence interval, 0.41–0.55]; P = .9), respiratory distress syndrome (for twins adjusted odds ratio, 0.53 [95% confidence interval, 0.40–0.69], and for singletons adjusted odds ratio, 0.54 [95% confidence interval, 0.47–0.62]; P = .9) and severe neurological injury (for twins adjusted odds ratio, 0.50 [95% confidence interval, 0.30–0.83] and for singletons adjusted odds ratio, 0.45 [95% confidence interval, 0.34–0.59]; P = .7). Administration of a complete course of antenatal corticosteroids was not associated with a reduced odds of bronchopulmonary dysplasia, severe retinopathy of prematurity, or necrotizing enterocolitis in both twins and singletons. Conclusion Administration of a complete course of antenatal corticosteroids 1–7 days before birth in twin pregnancies is associated with a clinically significant decrease in neonatal mortality, short-term respiratory morbidity, and severe neurological injury that is similar in magnitude to that observed among singletons.

Antibodies to red cell antigens that are found at low frequency in the general population are rare causes of hemolytic disease of the newborn. To understand how to detect these cases, we provide a basic review of routine antenatal maternal antibody testing and report a case of a neonate with severe HDN caused by anti-Wright (anti-Wra), successfully managed with transfusion, phototherapy, and high-dose intravenous immunoglobulin.When hemolysis in a newborn is suspected in the absence of major blood group incompatibility or commonly detected maternal red cell antibodies, a direct antiglobulin test should be performed. A positive DAT should alert the clinician to the presence of maternal antibodies against low-incidence antigens. Antibodies to the Wraantigen are one such rare cause of HDN.