Noninvasive Respiratory Support or Intubation during Stabilization after Birth and Neonatal and Neurodevelopmental Outcomes in Infants Born Preterm at 23-25 Weeks of Gestation.

OBJECTIVE: To examine the association between noninvasive respiratory support (NRS) or tracheal intubation (TI) during stabilization in infants born at 23-25 weeks of gestation and severe brain injury (sBI) or death, and significant neurodevelopmental impairment (sNDI). STUDY DESIGN: A retrospective cohort study of infants born at 23°/7-256/7 weeks of gestation in Canada. We compared infants successfully managed with NRS or TI during 30 minutes after birth. The primary outcomes were sBI or death before discharge, and sNDI among survivors with follow-up data at 18-24 months corrected age. The associations between exposures and outcomes were assessed using logistic regression models, and propensity score-matched analyses. RESULTS: The mean (SD) of gestational age and birth weight were 24.6 (0.6), 24.3 (0.7) weeks [P < .01], and 757 (173), 705 (130) grams [P < .01] in the NRS, and tracheal intubation (TI) groups, respectively, and 77% of infants in the NRS group were intubated by 7 days of age. sBI or death occurred in 25% (283/1118), and 36% (722/2012) of infants in the NRS and TI groups, respectively (aOR and 95% CI 0.74 [0.60, 0.91]). Among survivors with follow-up data, sNDI occurred in 17% (96/551), and 23% (218/937) of infants in the NRS and TI groups, respectively (aOR [95% CI] 0.77 [0.60, 0.99]). In the propensity score-matched analyses (NRS vs TI), results were consistent for sBI or death (OR [95% CI] 0.72 [0.60, 0.86]), but not for sNDI (OR [95% CI] 0.78 [0.58, 1.05]). CONCLUSIONS: Infants born at 23-25 weeks who were successfully managed with NRS, compared with TI, in the first 30 minutes after birth had lower odds of sBI or death before discharge, but had no significant differences in neurodevelopmental outcomes among survivors.

Variations in Site-Specific Costs for Infants Born Extremely Preterm in Canadian Neonatal Intensive Care Units.

OBJECTIVE: To quantify site-specific costs and their association with survival without major morbidity (SWMM) in Canada for neonates <28 weeks of gestation admitted to large tertiary neonatal intensive care units. METHODS: We conducted a retrospective analysis of infants born at <28 weeks of gestation and admitted to Canadian Neonatal Network sites from 2010 through 2021. Sites that cared for at least 50 eligible infants by gestational age in weeks over the study period were included. Using a validated costing algorithm that assessed physician, nursing, respiratory therapy, diagnostic imaging, transfusions, procedural, medication, and certain indirect costs, we calculated site and resource-specific costs in 2017 Canadian dollars (CAD) and evaluated their relationship with SWMM. RESULTS: Seven sites with 8180 (range 841-1605) eligible neonates with a mean (SD) gestation of 25.4 [1.3] weeks were included. Survival to discharge or transfer was 85.3% with a mean (SD) length of stay of 75 (46) days. The mean (SD) total and daily costs per neonate varied between $94 992 ($60 283) and $174 438 ($130 501) CAD and $1833 ($916) to $2307 ($1281) CAD, respectively. Between sites, there was no relationship between costs and SWMM. CONCLUSIONS: There was marked variation in costs and SWMM between sites in Canada with universal health care. The lack of concordance between both outcomes and costs among sites may provide possibilities for outcomes improvement and cost containment.

Continuous Positive Airway Pressure versus Nasal Intermittent Positive Pressure Ventilation in Preterm Neonates: What if Mean Airway Pressures Were Equivalent?

Respiratory support for preterm neonates in modern neonatal intensive care units is predominantly with the use of noninvasive interfaces. Continuous positive airway pressure (CPAP) and nasal intermittent positive pressure ventilation (NIPPV) are the prototypical and most commonly utilized forms of noninvasive respiratory support, and each has unique gas flow characteristics. In meta-analyses of clinical trials till date, NIPPV has been shown to likely reduce respiratory failure and need for intubation compared to CPAP. However, a significant limitation of the included studies has been the higher mean airway pressures used during NIPPV. Thus, it is unclear to what extent any benefits seen with NIPPV are due to the cyclic pressure application versus the higher mean airway pressures. In this review, we elaborate on these limitations and summarize the available evidence comparing NIPPV and CPAP at equivalent mean airway pressures. Finally, we call for further studies comparing noninvasive respiratory support modes at equal mean airway pressures. KEY POINTS: · Most current literature on CPAP vs. NIPPV in preterm neonates is confounded by use of higher mean airway pressures during NIPPV.. · In this review, we summarize existing evidence on CPAP vs. NIPPV at equivalent mean airway pressures.. · We call for future research on noninvasive support modes to account for mean airway pressures..

The Impact of Infant Sex on Multiple Courses versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. STUDY DESIGN: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth trial, which randomly allocated pregnant people to multiple courses versus a single course of ACS. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotizing enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. An interaction between exposure to ACS and infant sex was assessed for significance and multivariable regression analyses were conducted with adjustment for predefined covariates, when feasible. RESULTS: Data on 2,300 infants were analyzed. The interaction term between treatment status (multiple courses vs. a single course of ACS) and infant sex was not significant for the primary outcome (p = 0.86), nor for any of the secondary outcomes (p > 0.05). CONCLUSION: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex-specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention. KEY POINTS: · We explored the impact of infant sex on perinatal outcomes after multiple versus a single course of ACS.. · Infant sex was not a significant effect modifier of ACS exposure and perinatal outcomes.. · Animal literature indicates that sex-specific differences after ACS exposure may emerge over time.. · Further investigation of long-term sex-specific outcomes is warranted..

Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: • Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: • This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

Nasal Intermittent Positive Pressure Ventilation versus Continuous Positive Airway Pressure and Apnea of Prematurity: A Systematic Review and Meta-Analysis.

OBJECTIVE: The study aimed to systematically review and analyze the impact of nasal intermittent positive pressure ventilation (NIPPV) versus continuous positive airway pressure (CPAP) on apnea of prematurity (AOP) in preterm neonates. STUDY DESIGN: In this systematic review and meta-analysis, experimental studies enrolling preterm infants comparing NIPPV (synchronized, nonsynchronized, and bi-level) and CPAP (all types) were searched in multiple databases and screened for the assessment of AOP. Primary outcome was AOP frequency per hour (as defined by authors of included studies). RESULTS: Out of 4,980 articles identified, 18 studies were included with eight studies contributing to the primary outcome. All studies had a high risk of bias, with significant heterogeneity in definition and measurement of AOP. There was no difference in AOPs per hour between NIPPV versus CPAP (weighted mean difference = -0.19; 95% confidence interval [CI]: -0.76 to 0.37; eight studies, 456 patients). However, in a post hoc analysis evaluating the presence of any AOP (over varying time periods), the pooled odds ratio (OR) was lower with NIPPV (OR: 0.46; 95% CI: 0.32-0.67; 10 studies, 872 patients). CONCLUSION: NIPPV was not associated with decrease in AOP frequency, although demonstrated lower odds of developing any AOP. However, definite recommendations cannot be made based on the quality of the published evidence. KEY POINTS: · AOP is a common clinical complication related to preterm birth.. · NIPPV is often used to mitigate AOP and complications.. · Relative impact of NIPPV and CPAP on AOP remains unclear..

Toward Optimal High Continuous Positive Airway Pressure as Postextubation Support in Preterm Neonates: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to evaluate whether the initial pressure level on high continuous positive airway pressure (CPAP; ≥9 cm H2O), in relation to preextubation mean airway pressure (Paw), influences short-term clinical outcomes in preterm neonates. STUDY DESIGN: In this retrospective cohort study, preterm neonates <29 weeks' gestational age (GA) extubated from mean Paw ≥9 cm H2O and to high CPAP (≥9 cm H2O) were classified into "higher level CPAP" (2-3 cm H2O higher than preextubation Paw) and "equivalent CPAP" (-1 to +1 cm H2O in relation to preextubation Paw). Only the first eligible extubation per infant was analyzed. The primary outcome was failure within ≤7 days of extubation, defined as any one or more of (1) need for reintubation, (2) escalation to an alternate noninvasive respiratory support mode, or (3) use of CPAP >preextubation Paw + 3 cm H2O. Secondary outcomes included individual components of the primary outcome, along with other clinical and safety outcomes. RESULTS: Over a 10-year period (Jan 2011-Dec 2020), 175 infants were extubated from mean Paw >9 cm H2O to high CPAP pressures. Twenty-seven patients (median GA = 24.7, [interquartile range (IQR)]: (24.0-26.4) weeks and chronological age = 31, IQR: [21-40] days) were classified into the "higher level CPAP" group while 148 infants (median GA = 25.4, IQR: [24.6-26.6] weeks and chronological age = 26, IQR: [10-39] days) comprised the "equivalent CPAP" group. There was no difference in the primary outcome (44 vs. 51%; p = 0.51), including postadjustment for confounders (adjusted OR [aOR] = 0.47 [95% confidence interval (CI): 0.17-1.29; p = 0.14]). However, reintubation risk within 7 days was lower with higher level CPAP (7 vs. 37%; p < 0.01), including postadjustment (aOR = 0.07; 95% CI: 0.02-0.35; p < 0.01). CONCLUSION: In this cohort, use of initial distending CPAP pressures 2 to 3 cm H2O higher than preextubation Paw did not alter the primary outcome of failure but did lower the risk of reintubation. The latter is an interesting hypothesis-generating finding that requires further confirmation. KEY POINTS: · Use of high CPAP pressures (≥9 cm H2O) is gradually increasing in the care of preterm neonates.. · This study compares higher level versus equivalent CPAP in relation to preextubation Paw.. · The findings demonstrate no difference in failure as defined with use of higher level CPAP pressures..

Comparison of High CPAP versus NIPPV in Preterm Neonates: A Retrospective Cohort Study.

OBJECTIVE: The aim of this study was to compare outcomes following receipt of high continuous positive airway pressure (CPAP) versus nasal intermittent positive pressure ventilation (NIPPV) in extremely preterm neonates. STUDY DESIGN: We retrospectively compared outcomes of preterm neonates (22-28 weeks' gestation) following their first episode of either high CPAP (≥ 9 cm H2O) or NIPPV. Primary outcome was failure of high CPAP or NIPPV within 7 days, as determined by either need for intubation or use of an alternate noninvasive mode. RESULTS: During the 3-year study period, 53 infants received high CPAP, while 119 patients received NIPPV. There were no differences in the primary outcome (adjusted odds ratio 1.21; 95% confidence interval 0.49-3.01). The use of alternate mode of noninvasive support was higher with the use of high CPAP but no other outcome differences were noted. CONCLUSION: Based on this cohort, there was no difference in incidence of failure between high CPAP and NIPPV, although infants receiving high CPAP were more likely to require an alternate mode of noninvasive support. KEY POINTS: · Use of high CPAP pressures (defined as ≥9 cm H2O) is gradually increasing during care of preterm neonates.. · Limited data exists regarding its efficacy and safety.. · This study compares high CPAP with NIPPV, and demonstrates comparable short-term clinical outcomes..

Costs of Neonatal Intensive Care for Canadian Infants with Preterm Birth.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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 of <29 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. CONCLUSIONS: 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.

Necrotizing enterocolitis and mortality after transfusion of ABO non-identical blood.

BACKGROUND: The relationship between ABO non-identical transfusion and the outcomes of necrotizing enterocolitis (NEC), and all-cause mortality in very-low birth weight (VLBW) neonates receiving red blood cell transfusion is unknown. STUDY DESIGN AND METHODS: A retrospective multicenter cohort study was conducted in VLBW neonates in neonatal intensive care units between 2004 and 2016. VLBW (≤1500 grams) neonates were followed until discharge or in-hospital death. The primary exposure was ABO group. Secondary exposures included platelet count, plasma transfusions, and maternal ABO group. Outcome measures were NEC (defined as Bell stage ≥ 2) and all-cause mortality. Time-dependent Cox regression models with competing risks were used to investigate factors associated with NEC and mortality. RESULTS: Thousand and sixteen neonates were included with 10.8% developing NEC (n = 110) and 14.1% mortality (n = 143). Platelet count (hazard ratio [HR] = 0.995; 95% confidence interval [CI]: 0.922-0.998) and number of plasma transfusions (HR = 2.908; 95% CI:1.265-6.682) were associated with NEC, while ABO group (non-O vs. O) was not (HR = 0.761; 95% CI: 0.393-1.471). Higher all-cause mortality occurred in neonates without NEC who were non-O compared with O (HR = 17.5; 95% CI: 1.784-171.692), but not in neonates with NEC (HR = 1.112; 95% CI: 0.142-8.841). Plasma transfusion was associated with increased mortality in both groups. DISCUSSION: ABO non-identical transfusion was not associated with NEC or mortality in neonates with NEC. It was associated with increased mortality in neonates without NEC. As many neonatal intensive care units transfuse only O group blood as routine practice, future trials are needed to investigate the association between this practice and neonatal mortality.

Nasal continuous positive airway pressure levels for the prevention of morbidity and mortality in preterm infants.

BACKGROUND: Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate gas exchange in spontaneously breathing infants. Nasal CPAP is used in the care of preterm infants around the world. Despite its common use, the appropriate pressure levels to apply during nasal CPAP use remain uncertain. OBJECTIVES: To assess the effects of 'low' (≤ 5 cm H2O) versus 'moderate-high' (> 5 cm H2O) initial nasal CPAP pressure levels in preterm infants receiving CPAP either: 1) for initial respiratory support after birth and neonatal resuscitation or 2) following mechanical ventilation and endotracheal extubation. SEARCH METHODS: We ran a comprehensive search on 6 November 2020 in the following databases: CENTRAL via CRS Web and MEDLINE via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials. SELECTION CRITERIA: We included RCTs, quasi-RCTs, cluster-RCTs and cross-over RCTs randomizing preterm infants of gestational age < 37 weeks or birth weight < 2500 grams within the first 28 days of life to different nasal CPAP levels. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal to collect and analyze data. We used the GRADE approach to assess the certainty of the evidence for the prespecified primary outcomes. MAIN RESULTS: Eleven trials met inclusion criteria of the review. Four trials were parallel-group RCTs reporting our prespecified primary or secondary outcomes. Two trials randomized 316 infants to low versus moderate-high nasal CPAP for initial respiratory support, and two trials randomized 117 infants to low versus moderate-high nasal CPAP following endotracheal extubation. The remaining seven studies were cross-over trials reporting short-term physiological outcomes. The most common potential sources of bias were absent or unclear blinding of personnel and assessors and uncertain selective reporting. Nasal CPAP for initial respiratory support after birth and neonatal resuscitation None of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months. The remaining five outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.56 to 1.85; 1 trial, 271 participants); mortality by hospital discharge (RR 1.04, 95% CI 0.51 to 2.12; 1 trial, 271 participants); BPD at 28 days of age (RR 1.10, 95% CI 0.56 to 2.17; 1 trial, 271 participants); BPD at 36 weeks' PMA (RR 0.80, 95% CI 0.25 to 2.57; 1 trial, 271 participants), and treatment failure or need for mechanical ventilation (RR 1.00, 95% CI 0.63 to 1.57; 1 trial, 271 participants). We assessed the certainty of the evidence as very low for all five outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates. Nasal CPAP following mechanical ventilation and endotracheal extubation One of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. On the basis of these data, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcome of treatment failure or need for mechanical ventilation (RR 1.52, 95% CI 0.92 to 2.50; 2 trials, 117 participants; I2 = 17%; risk difference 0.15, 95% CI -0.02 to 0.32; number needed to treat for an additional beneficial outcome 7, 95% CI -50 to 3). We assessed the certainty of the evidence as very low due to risk of bias, inconsistency across the studies, and imprecise effect estimates. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months or BPD at 28 days of age. The remaining three outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants); mortality by hospital discharge (RR 2.94, 95% CI 0.12 to 70.30; 1 trial, 93 participants), and BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants). We assessed the certainty of the evidence as very low for all three outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates.  AUTHORS' CONCLUSIONS: There are insufficient data from randomized trials to guide nasal CPAP level selection in preterm infants, whether provided as initial respiratory support or following extubation from invasive mechanical ventilation. We are uncertain as to whether low or moderate-high nasal CPAP levels improve morbidity and mortality in preterm infants. Well-designed trials evaluating this important aspect of a commonly used neonatal therapy are needed.

Experiences, Knowledge, and Preferences of Canadian Parents Regarding Preterm Mode of Birth.

OBJECTIVES: To describe Canadian parents' experiences with mode of birth for preterm singleton pregnancies; knowledge about maternal and infant risks of the different modes of preterm birth, particularly breech birth; and communication preferences with respect to mode of birth. METHODS: We conducted an online survey of Canadian parents who had experienced the preterm birth of a live-born infant between 2010 and 2019. Data were collected from August to September 2019. The sample size was calculated as requiring 96 participants. RESULTS: Of the 153 respondents, 152 were mothers. Respondents were approximately evenly split between those who had experienced an extremely preterm birth (<28 wk), a very preterm birth (28-31 wk), or a moderate-to-late preterm birth (32-36 wk). Most parents reported that mode of birth was discussed before the birth (61.7%, 73.3% and 77.3% for extremely, very, and moderate-to-late preterm births, respectively). The minority of parents reported being given a choice about mode of birth (20.8%, 23.0%, and 36.4% for extremely, very, and moderate-to-late preterm births, respectively). The use of written material during discussion on mode of birth was rare (2.1%, 3.3% and 6.8% for extremely, very, and moderate-to-late preterm births, respectively). Of women who had a cesarean delivery, 39.6% (36/91) were unaware of the maternal risks. Many parents expressed preference for both oral and written communication during counselling on mode of birth (62.6%). CONCLUSION: Few Canadian parents reported receiving a choice about mode of preterm birth, being aware of associated risks, or receiving written information. There is an urgent need to develop tools that provide information for parents facing preterm birth.

Classical Cesarean: What Are the Maternal and Infant Risks Compared With Low Transverse Cesarean in Preterm Birth, and Subsequent Uterine Rupture? A Systematic Review and Meta-analysis.

OBJECTIVES: Classical cesarean section may be associated with increased short- and long-term risks. The objectives of this study were to review the following systematically: first, the short-term maternal and infant risks with preterm classical compared with low transverse cesarean sections; and second, the risk of spontaneous or early-labour uterine rupture. DATA SOURCES: Medline, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from January 1980 to July 2018. STUDY SELECTION: A total of 772 studies were independently screened by two reviewers, and 91 full texts were reviewed. The review included nine studies comparing outcomes after preterm classical versus low transverse cesarean section and 15 studies addressing subsequent pregnancy outcomes. DATA SYNTHESIS: Our primary short-term outcomes were maternal death and intensive care unit (ICU) admission. For subsequent pregnancies, our primary outcome was the risk of spontaneous or early-labour uterine rupture. The data were synthesized using random effects, and odds ratios (ORs) and 95% confidence intervals (CIs) were generated. There were no significant differences between preterm classical and low transverse cesarean sections in the odds of maternal death (OR 2.38; 95% CI 0.15-38.07) or ICU admission (adjusted OR 2.38; 95% CI 0.42-13.35). A subgroup from 28 to 31 weeks gestation had increased risks of endometritis, transfusion, and ICU admission with the classical incision. The low vertical incision was associated with a lower odds of organ injury than was the low transverse incision. The incidence of uterine rupture following the classical incision without a trial of labour was 1%. CONCLUSION: Preterm classical cesarean section is not associated with significantly increased risks, but data are scarce. Subsequent uterine rupture risk when not planning a trial of labour is 1%.

Incidence, risk factors, and outcomes of pulmonary hypertension in preterm infants with bronchopulmonary dysplasia.

OBJECTIVES: To determine the incidence and risk factors for pulmonary hypertension (PH) in preterm infants with moderate to severe bronchopulmonary dysplasia (BPD) and to compare short-term outcomes. METHODS: Preterm infants <32 weeks gestation born August 2013 through July 2015 with moderate to severe BPD at 36 weeks postmenstrual age were categorized into BPD-PH (exposure) and BPD-noPH (control) groups. RESULTS: Of 92 infants with BPD, 87 had echocardiographic assessment, of whom 24 (28%) had PH. On multiple logistic regression after adjustment for gestational age and sex, no significant risk factors for PH were identified based on data from this cohort. There were no differences in resource utilization or clinical outcomes including survival to discharge. CONCLUSION: Approximately one out of four patients with moderate to severe BPD were identified as having PH. No significant risk factors for PH were identified. No differences in outcomes were identified for those with and without PH.

A call for a streamlined ethics review process for multijurisdictional, child health research studies.

To be time and resource efficient in neonatal research and to answer clinically relevant questions with validity and generalizability, large numbers of infants from multiple hospitals need to be included. Multijurisdictional research in Canada is currently fraught with research ethics review process hurdles that lead to delays, administrative costs, and possibly termination of projects. We describe our experience applying for ethics review to 13 sites in 7 provinces for a project comparing two standard of care therapies for preterm born infants with respiratory distress syndrome. We welcome the current opportunity created by the Institute of Human Development Child and Youth Health and the Institute for Genetics, to collaboratively identify practical solutions that would benefit Canadian researchers, Research Ethics Boards, and children and families.

Sustained quality improvement in outcomes of preterm neonates with a gestational age less than 29 weeks: results from the Evidence-based Practice for Improving Quality Phase 3 1.

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220-286 weeks (i.e., from 22 weeks and 0 days of gestation to 28 weeks and 6 days of gestation). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and 2017 were studied. Trends in mortality and major morbidities were evaluated. The number of neonates with a GA of 220-236 weeks increased from 90 in 2013 to 139 in 2017 without a significant change in any other GA categories. In the entire cohort, the odds of composite outcome of mortality or any major morbidity (adjusted odds ratio (AOR) 0.72, 95% confidence interval (CI) 0.61-0.84) and of necrotizing enterocolitis (AOR 0.66, 95% CI 0.49-0.89) were lower in 2017 than in 2013. When calculated per year, the odds of composite outcome (AOR 0.93, 95% CI 0.89-0.97) and odds of necrotizing enterocolitis (AOR 0.89, 95% CI 0.82-0.96) decreased significantly. Among the subgroup of neonates with a GA of 260-286 weeks, the odds of composite outcome (AOR 0.63, 95% CI 0.51-0.79), necrotizing enterocolitis (AOR 0.44, 95% CI 0.26-0.73), and nosocomial infection (AOR 0.64, 95% CI 0.49-0.84) were reduced. The collaborative, multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm neonates, and the improvement was sustainable over 5 years.

What is the safest mode of delivery for extremely preterm cephalic/non-cephalic twin pairs? A systematic review and meta-analyses.

BACKGROUND: Given the controversy around mode of delivery, our objective was to assess the evidence regarding the safest mode of delivery for actively resuscitated extremely preterm cephalic/non-cephalic twin pairs before 28 weeks of gestation. METHODS: We searched Cochrane CENTRAL, MEDLINE, EMBASE and  http://clinicaltrials.gov from January 1994 to January 2017. Two reviewers independently screened titles, abstracts and full text articles, extracted data and assessed risk of bias. We included randomized controlled trials and observational studies. Our primary outcome was a composite of neonatal death (<28 days of life) and severe brain injury in survivors (intraventricular hemorrhage grade ≥ 3 or periventricular leukomalacia). We performed random-effects meta-analyses, generating odds ratios with 95% confidence intervals for the first and second twin separately, and for both twins together. We assessed the risk of bias using a modified Newcastle Ottawa Scale (NOS) for observational studies and used Grading of Recommendations Assessment, Development and Evaluation approach (GRADE). RESULTS: Our search generated 2695 articles, and after duplicate removal, we screened 2051 titles and abstracts, selecting 113 articles for full-text review. We contacted 36 authors, and ultimately, three observational studies met our inclusion criteria. In cephalic/non-cephalic twin pairs delivered by caesarean section compared to vaginal birth at 24+0-27+6 weeks the odds ratio for our composite outcome of neonatal death and severe brain injury for the cephalic first twin was 0.35 (95% CI 0.00-92.61, two studies, I2 = 76%), 1.69 for the non-cephalic second twin (95% CI 0.04-72.81, two studies, I2 = 55%) and 0.83 for both twins (95% CI 0.05-13.43, two studies, I2 = 56%). According to the modified Newcastle Ottawa Scale we assessed individual study quality as being at high risk of bias and according to GRADE the overall evidence for our primary outcomes was very low. CONCLUSION: Our systematic review on the safest mode of delivery for extremely preterm cephalic/non-cephalic twin pairs found very limited existing evidence, without significant differences in neonatal death and severe brain injury by mode of delivery.

Survey of noninvasive respiratory support practices in Canadian neonatal intensive care units.

AIM: To evaluate practice variation with respect to noninvasive respiratory support (NRS) use across Canadian neonatal intensive care units (NICUs). METHODS: A web-based survey was sent to all site investigators of the 30 level 3 NICUs participating in the Canadian Neonatal Network. The survey inquired about the use of five commonly described NRS modes. In addition, the presence and adherence to local guidelines were ascertained. Descriptive analyses were performed to identify variations in practice. RESULTS: In total, 28 (93%) of the 30 tertiary NICUs responded to the survey. Continuous positive airway pressure (CPAP) was employed universally (100%). High-flow nasal cannula (HFNC) was used in 89% of NICUs, biphasic CPAP in 79% and nasal intermittent positive pressure ventilation (NIPPV) in 54%, and nasal high-frequency ventilation was used in 18% of units. Only 61% of all NRS use was guided by local policies, with the lowest being for HFNC (36%). There was a wide range of settings employed and interfaces used for all NRS modes. CONCLUSION: There are significant practice variations in NRS use across Canadian NICUs. Further research is needed to evaluate the significance in relation to pulmonary outcomes to determine optimal NRS strategies.

Introduction of microsystems in a level 3 neonatal intensive care unit-an interprofessional approach.

BACKGROUND: Growth of neonatal intensive care units in number and size has raised questions towards ability to maintain continuity and quality of care. Structural organization of intensive care units is known as a key element for maintaining the quality of care of these fragile patients. The reconstruction of megaunits of intensive care to smaller care units within a single operational service might help with provision of safe and effective care. METHODS/DESIGN: The clinical team and patient distribution lay out, admission and discharge criteria and interdisciplinary round model was reorganized to follow the microstructure philosophy. A working group met weekly to formulate the implementation planning, to review the adaptation and adjustment process and to ascertain the quality of implementation following the initiation of the microsystem model. DISCUSSION: In depth examination of microsystem model of care in this study, provides systematic evaluation of this model on variable aspects of health care. The individual projects of this trial can be source of solid evidence for guidance of future decisions on optimized model of care for the critically ill newborns. TRIAL REGISTRATION: ClinicalTrial.gov, NCT02912780 . Retrospectively registered on 22 September 2016.

Use of Targeted Neonatal Echocardiography and Focused Cardiac Sonography in Tertiary Neonatal Intensive Care Units: Time to Embrace It?

Focused cardiac sonography and targeted neonatal echocardiography refer to goal-directed cardiac imaging using ultrasound, typically by noncardiologic specialists. Although the former consists of a rapid qualitative assessment of cardiac function, which is usually performed by acute care practitioners, the latter refers to detailed functional echocardiography to obtain quantitative and qualitative indexes of pulmonary and systemic hemodynamics in sick neonates and is typically performed by neonatologists. Although the use of these modalities is increasing, they still remain unavailable in most North American centers providing acute care to neonates, partly because of limited data regarding their direct impact on patient care. Here we present a series of 5 cases from a large perinatal unit in which immediate availability of relevant expertise led to important and arguably life-saving clinical interventions. In 4 of these cases, focused cardiac sonography was sufficient to make the diagnosis, whereas in 1 case, clinical integration of detailed systemic hemodynamics measured on target neonatal echocardiography was required.