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Over the last few decades, several articles have examined the feasibility of attempting primary reduction and closure of gastroschisis without general anesthesia (GA). We aimed to systematically evaluate the impact of forgoing routine intubation and GA during primary bedside reduction and closure of gastroschisis.The primary outcome was closure success. Secondary outcomes were mortality, time to enteral feeding, and length of hospital stay.12 studies were included: 5 comparative studies totalling 192 patients and 7 descriptive case studies totalling 56 patients. Primary closure success was statistically equivalent between the two groups, but trended toward improved success with GA/intubation (RR = 0.86, CI 0.70-1.03, p = 0.08). Mortality was equivalent between groups (RR = 1.26, CI 0.26-6.08, p = 0.65). With respect to time to enteral feeds and length of hospital stay, outcomes were either equivalent between the two groups or favored the group that underwent primary closure without intubation and GA.There are few comparative studies examining the impact of performing primary bedside closure of gastroschisis without GA. A meta-analysis of the available data found no statistically significant difference when forgoing intubation and GA. Foregoing GA also did not negatively impact time to enteral feeds, length of hospital stay, or mortality.

Background The impact of the permissive hypotension approach in clinically well infants on regional cerebral oxygen saturation (rScO(2)) and autoregulatory capacity (CAR) remains unknown. Methods Prospective cohort study of blinded rScO(2) measurements within a randomized controlled trial of management of hypotension (HIP trial) in extremely preterm infants. rScO(2), mean arterial blood pressure, duration of cerebral hypoxia, and transfer function (TF) gain inversely proportional to CAR, were compared between hypotensive infants randomized to receive dopamine or placebo and between hypotensive and non-hypotensive infants, and related to early intraventricular hemorrhage or death. Results In 89 potentially eligible HIP trial patients with rScO(2) measurements, the duration of cerebral hypoxia was significantly higher in 36 hypotensive compared to 53 non-hypotensive infants. In 29/36 hypotensive infants (mean GA 25 weeks, 69% males) receiving the study drug, no significant difference in rScO(2) was observed after dopamine (n = 13) compared to placebo (n = 16). Duration of cerebral hypoxia was associated with early intraventricular hemorrhage or death. Calculated TF gain (n = 49/89) was significantly higher reflecting decreased CAR in 16 hypotensive compared to 33 non-hypotensive infants. Conclusions Dopamine had no effect on rScO(2) compared to placebo in hypotensive infants. Hypotension and cerebral hypoxia are associated with early intraventricular hemorrhage or death. Impact Treatment of hypotension with dopamine in extremely preterm infants increases mean arterial blood pressure, but does not improve cerebral oxygenation. Hypotensive extremely preterm infants have increased duration of cerebral hypoxia and reduced cerebral autoregulatory capacity compared to non-hypotensive infants. Duration of cerebral hypoxia and hypotension are associated with early intraventricular hemorrhage or death in extremely preterm infants. Since systematic treatment of hypotension may not be associated with better outcomes, the diagnosis of cerebral hypoxia in hypotensive extremely preterm infants might guide treatment.

ObjectivesExtremely preterm babies have a significant risk of neurodevelopmental impairment (NDI). There has been little investigation regarding the impact of prematurity on families. The objective of this study was to explore parental perspectives regarding the impact of prematurity on themselves/their family.MethodsOver 1 year, parents of children born ResultsAmong parents (n=248, 98% participation rate), most (74%) reported that their child’s prematurity had both positive and negative impacts on their life or their family’s life, while 18% reported only positive impacts and 8% only negative impacts. These proportions were not correlated with GA, brain injury, nor level of NDI. The positive impacts reported included: an improved outlook on life, such as gratitude and perspective (48%), stronger family relationships (31%) and the gift of the child (28%). The negative themes were stress and fear (42%), loss of equilibrium due to medical fragility (35%) and concerns about developmental outcomes including the child’s future (18%).ConclusionParents report both positive and negative impacts after an extremely preterm birth, independent of disability. These balanced perspectives should be included in neonatal research, clinical care and provider education.

To explore decisional regret of parents of extremely preterm babies and analyze neonatal, pediatric and parental factors associated with regret.Parents of infants born29 weeks' gestational age, aged between 18-months and 7-years, attending neonatal follow-up were enrolled. Hospital records were reviewed to examine morbidities and conversations with parents about levels of care. Parents were asked the following question: "Knowing what you know now, is there anything you would have done differently?" Mixed methods were used to analyze responses.248 parents (98% participation) answered and 54% reported they did not have regret. Of those who reported regret (n=113), three themes were most frequently invoked: 35% experienced guilt, thinking they were responsible for the preterm birth; 28% experienced regret about self-care decisions; 20% regretted decisions related to their parental role, generally wishing they knew sooner how to get involved. None reported regret about life-and-death decisions made at birth or in the NICU. Impairment at follow-up, gestational age, and decisions about levels/reorientation of care, were not associated with regret. More mothers reported feeling guilt about the preterm birth (compared with fathers); parents of children with severe lesions on head ultrasounds were less likely to report regret.Approximately half of the parents of extremely preterm infants had regrets regarding their NICU stay. Causes of regret and guilt should be addressed and minimized.

BACKGROUND: Birth asphyxia in term neonates remains a serious condition that causes significant mortality and long-term neurodevelopmental sequelae despite hypothermia treatment. The objective of this study was to review therapeutic hypothermia practices in a large population of neonates with hypoxic-ischemic encephalopathy (HIE) across Canada and to identify determinants of adverse outcome. METHODS: Our retrospective observational cohort study examined neonates≥36 weeks, admitted to the Canadian Neonatal Network NICUs between 2010 and 2014, diagnosed with HIE, and treated with hypothermia. Adverse outcome was defined as death and/or brain injury. Maternal, birth, and postnatal characteristics were compared between neonates with adverse outcome and those without. The association between the variables which were significantly different (p

Background Coagulase-negative staphylococci (CoNS) frequently causes late-onset sepsis in preterm infants. Vancomycin is the first-line therapy, but the emergence of reduced vancomycin-susceptibility strains has resulted in linezolid use, of which long-term safety in preterm infants is unknown. Objective Evaluate the association between linezolid exposure and neurodevelopmental impairment (NDI) or death at 18-21 months of corrected age, in preterm infants with CoNS sepsis. Methods Multicentric retrospective cohort study comparing long-term outcomes of preterm infants exposed to linezolid versus other antistaphylococcal antimicrobials. We included infants ≤28 weeks' gestational age (GA), with CoNS sepsis, admitted between January 2011 and June 2015 in 3 level-3 Canadian NICUs. Primary outcome was a composite of death or significant NDI (sNDI) at 18-21 months of corrected age. Secondary outcomes included NDI and individual components of the primary outcome. We assessed the relationship between linezolid exposure and outcomes using a multivariable logistic regression. Results Of 274 infants included, 67 (24.4%) were exposed to linezolid. Median GA was 26 weeks and clinical characteristics were similar between groups. There was no difference in composite outcome of death or sNDI among the infants of both groups, but significantly more death by 18-21 months in the linezolid group (29.9% vs. 17.6%; P = 0.01). Conclusions Linezolid exposure was not associated with composite outcome of death or sNDI at 18-21 months. The association between linezolid and death may be due to indication bias. Further studies are warranted.

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

Background: Trisomy 13 and trisomy 18 are common life-limiting conditions associated with major disabilities. Many parents have described conflictual relationships with clinicians, but positive and adverse experiences of families with healthcare providers have not been well described. Aim: (1) To investigate parental experiences with clinicians and (2) to provide practical recommendations and behaviors clinicians could emulate to avoid conflict. Design: Participants were asked to describe their best and worse experiences, as well as supportive clinicians they met. The results were analyzed using mixed methods. Setting/participants: Parents of children with trisomy 13 and 18 who were part of online social support networks. A total of 503 invitations were sent, and 332 parents completed the questionnaire about 272 children. Results: The majority of parents (72%) had met a supportive clinician. When describing clinicians who changed their lives, the overarching theme, present in 88% of answers, was trust. Parents trusted clinicians when they felt he or she cared and valued their child, their family, and made them feel like good parents (69%), had appropriate knowledge (66%), and supported them and gave them realistic hope (42%). Many (42%) parents did not want to make—or be part of—life-and-death decisions. Parents gave specific examples of supportive behaviors that can be adopted by clinicians. Parents also described adverse experiences, generally leading to conflicts and lack of trust. Conclusion: Realistic and compassionate support of parents living with children with trisomy 13 and 18 is possible. Adversarial interactions that lead to distrust and conflicts can be avoided. Many supportive behaviors that inspire trust can be emulated.

To determine whether deferred cord clamping (DCC) compared with early cord clamping (ECC) was associated with reduction in death and/or severe neurologic injury among twins born at30 weeks of gestation.We performed a retrospective cohort study including all liveborn twins of30 weeks admitted to a tertiary-level neonatal intensive care unit (NICU) in Canada between 2015 and 2018 using the Canadian Neonatal/Preterm Birth Network database. We compared DCC ≥30 seconds vs ECC30 seconds. Our primary outcome was a composite of death and/or severe neurologic injury (severe intraventricular hemorrhage grade III/IV and/or periventricular leukomalacia). Secondary outcomes included neonatal morbidity and health care utilization outcomes. We calculated aORs and β coefficients for categorical and continuous variables, along with 95% CI. Models were fitted with generalized estimated equations accounting for twin correlation.We included 1597 twins (DCC, 624 [39.1%]; ECC, 973 [60.9%]). Death/severe neurologic injury occurred in 17.8% (n = 111) of twins who received DCC and in 21.7% (n = 211) of those who received ECC. The rate of death/severe neurologic injury did not differ significantly between the DCC and ECC groups (aOR 1.07; 95% CI, 0.78-1.47). DCC was associated with reduced blood transfusions (adjusted β coefficient, -0.49; 95% CI, -0.86 to -0.12) and NICU length of stay (adjusted β coefficient, -4.17; 95% CI, -8.15 to -0.19).The primary composite outcome of death and/or severe neurologic injury did not differ between twins born at30 weeks of gestation who received DCC and those who received ECC, but DCC was associated with some benefits.

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

Many observational studies have shown that infants with blood pressures (BPs) that are in the lower range for their gestational age tend to have increased complications such as an increased rate of significant intraventricular hemorrhage and adverse long-term outcome. This relationship does not prove causation nor should it create an indication for treatment. However, many continue to intervene with medication for low BP on the assumption that an increase in BP will result in improved outcome. Only adequately powered prospective randomized controlled trials can answer the question of whether individual treatments of low BP are beneficial.

ObjectiveTo determine whether restricting the use of inotrope after diagnosis of low blood pressure (BP) in the first 72 hours of life affects survival without significant brain injury at 36 weeks of postmenstrual age (PMA) in infants born before 28 weeks of gestation.DesignDouble-blind, placebo-controlled randomised trial. Caregivers were masked to group assignment.Setting10 sites across Europe and Canada.ParticipantsInfants born before 28 weeks of gestation were eligible if they had an invasive mean BP less than their gestational age that persisted for ≥15 min in the first 72 hours of life and a cerebral ultrasound free of significant (≥ grade 3) intraventricular haemorrhage.InterventionParticipants were randomly assigned to saline bolus followed by either a dopamine infusion (standard management) or placebo (5% dextrose) infusion (restrictive management).Primary outcomeSurvival to 36 weeks of PMA without severe brain injury.ResultsThe trial terminated early due to significant enrolment issues (7.7% of planned recruitment). 58 infants were enrolled between February 2015 and September 2017. The two groups were well matched for baseline variables. In the standard group, 18/29 (62%) achieved the primary outcome compared with 20/29 (69%) in the restrictive group (p=0.58). Additional treatments for low BP were used less frequently in the standard arm (11/29 (38%) vs 19/29 (66%), p=0.038).ConclusionThough this study lacked power, we did not detect major differences in clinical outcomes between standard or restrictive approach to treatment. These results will inform future studies in this area.Trial registration numberNCT01482559, EudraCT 2010-023988-17.

With improvements in perinatal care, even the most immature babies can now survive, the majority of survivors having good long-term outcomes. At the very limits of what modern perinatal care is able to achieve, for the smallest babies, there are ongoing debates and passionate disagreements about institution of intensive care. To help clinicians make decisions about life-sustaining interventions, many national academic societies have developed policy statements. Guidelines usually describe a risk-based approach for interventions in the ‘peri-viable’ period by dividing preterm infants into three categories: ‘beneficial’, where intervention is generally recommended, ‘grey zone’ where interventions follow the decision of parents and ‘futile’, where comfort care is recommended.1 Unfortunately, many policies divide infants into these categories using gestational age (GA) alone: based on imprecise estimates of completed 7-day periods of gestation. However, prognosis depends on many variables, and several academic societies now propose also using other factors to make important decisions. The new framework from the British Association of Perinatal Medicine (BAPM) takes a welcome, and slightly different approach, describing a process for arriving at decisions, rather than offering rigid recommendations. The previous BAPM framework was more directive, strongly suggesting comfort care at 23 weeks gestation, up until 23 weeks and 6 days, but active intensive care for most infants born at 24 weeks1. During the same period, the French policy statement had similar GA cut-offs to make life-and-death decisions,1 but in the French statement babies born at …

BACKGROUND AND OBJECTIVES: Clinicians are urged to optimize communication with families, generally without empirical practical recommendations. The objective of this study was to identify core behaviors associated with good communication during and after an unsuccessful resuscitation, including parental perspectives. METHODS: Clinicians from different backgrounds participated in a standardized, videotaped, simulated neonatal resuscitation in the presence of parent actors. The infant remained pulseless; participants communicated with the parent actors before, during, and after discontinuing resuscitation. Twenty-one evaluators with varying expertise (including 6 bereaved parents) viewed the videos. They were asked to score clinician-parent communication and identify the top communicators. In open-ended questions, they were asked to describe 3 aspects that were well done and 3 that were not. Answers to open-ended questions were coded for easily reproducible behaviors. All the videos were then independently reviewed to evaluate whether these behaviors were present. RESULTS: Thirty-one participants’ videos were examined by 21 evaluators (651 evaluations). Parents and actors agreed with clinicians 81% of the time about what constituted optimal communication. Good communicators were more likely to introduce themselves, use the infant's name, acknowledge parental presence, prepare the parents (for the resuscitation, then death), stop resuscitation without asking parents, clearly mention death, provide or enable proximity (clinician-parent, infant-parent, clinician-infant, mother-father), sit down, decrease guilt, permit silence, and have knowledge about procedures after death. Consistently, clinicians who displayed such behaviors had evaluations >9 out of 10 and were all ranked top 10 communicators. CONCLUSIONS: During a neonatal end-of-life scenario, many simple behaviors, identified by parents and providers, can optimize clinician-parent communication.

Background In Canada alone, almost 3000 VLBW infants are born and treated annually with almost 1200 going onto death or survival with severe brain injury, chronic lung disorders, aggressive retinopathy of prematurity, late-onset sepsis, or significant necrotizing enterocolitis. Lactoferrin is an antimicrobial, antioxidant, anti-inflammatory iron-carrying, bifidogenic glycoprotein found in all vertebrates and in mammalian milk, leukocytes and exocrine secretions. Lactoferrin aids in creating an environment for growth of beneficial bacteria in the gut, thus reducing colonization with pathogenic bacteria. It is hypothesized that oral bovine lactoferrin (bLF), through its antimicrobial, antioxidant and anti-inflammatory properties, will reduce the rate of mortality or major morbidity in very low birth weight preterm infants. Method Lactoferrin Infant Feeding Trial_Canada (LIFT_Canada) is a multi-centre, double-masked, randomized controlled trial with the aim to enroll 500 infants whose data will be combined with the data of the 1542 infants enrolled from Lactoferrin Infant Feeding Trial_Australia/New Zealand (LIFT_ANZ) in a pooled intention-to-treat analysis. Eligible infants will be randomized and allocated to one of two treatment groups: 1) a daily dose of 200 mg/kg bLF in breast/donor human milk or formula milk until 34 weeks corrected gestation or for a minimum of 2 weeks, whichever is longer, or until discharge home or transfer, if earlier; 2) no bLF with daily feeds. The primary outcome will be determined at 36 weeks corrected gestation for the presence of neonatal morbidity and at discharge for survival and treated retinopathy of prematurity. The duration of the trial is expected to be 36 months. Discussion Currently, there continues to be no clear answer related to the benefit of bLF in reducing mortality or any or all of the significant neonatal morbidities in very low birth weight infants. LIFT_Canada is designed with the hope that the pooled results from Australia, New Zealand, and Canada may help to clarify the situation. Trial registration Clinical Trials.Gov, Identifier: NCT03367013, Registered December 8, 2017.

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.

Extremely preterm infants are at higher risk of pulmonary (PH) and intraventricular (IVH) haemorrhage during the transitioning physiology due to immature cardiovascular system. Monitoring of haemodynamics can detect early abnormal circulation that may lead to these complications. We described time-frequency relationships between near infrared spectroscopy (NIRS) cerebral regional haemoglobin oxygen saturation (CrSO2) and preductal peripheral perfusion index (PI), capillary oxygen saturation (SpO2) and heart rate (HR) in extremely preterm infants in the first 72 h of life. Patients were sub-grouped in infants with PH and/or IVH (N H = 8) and healthy controls (N C = 11). Data were decomposed in wavelets allowing the analysis of localized variations of power. This approach allowed to quantify the percentage of time of significant cross-correlation, semblance, gain (transfer function) and coherence between signals. Ultra-low frequencies (CrSO2 and oximetry (PI, SpO2 and HR) as well as in-phase semblance and gain between CrSO2 and HR were significantly lower while anti-phase semblance between CrSO2 and HR was significantly higher in PH-IVH infants compared to controls. These differences may reflect haemodynamic instability associated with cerebrovascular autoregulation and hemorrhagic complications observed during the transitioning physiology.

The 2015 neonatal resuscitation guidelines added ECG to assess an infant’s heart rate when determining the need for resuscitation at birth. However, a recent case report raised concerns about this technique in the delivery room. We report four cases of pulseless electrical activity during neonatal cardiopulmonary resuscitation in levels II–III neonatal intensive care units in Canada (Edmonton [n=3] and Winnipeg [n=1]).Healthcare providers should be aware that pulseless electrical activity can occur in newborn infants during cardiopulmonary resuscitation. We propose an adapted neonatal resuscitation algorithm to include pulseless electrical activity. Furthermore, in compromised newborns, heart rate should be assessed using a combination of methods/techniques to ensure accurate heart rate assessment. When ECG displays a heart rate but the infant is unresponsive, pulseless electrical activity should be suspected and chest compression should be started.

Medium- and long-term outcomes have been collected and described among survivors of neonatal intensive care units for decades, for a number of purposes: (1) quality control within units, (2) comparisons of outcomes between NICUs, (3) clinical trials (whether an intervention improves outcomes), (4) end-of-life decision-making, (5) to better understand the effects of neonatal conditions and/or interventions on organs and/or long-term health, and finally (6) to better prepare parents for the future. However, the outcomes evaluated have been selected by investigators, based on feasibility, availability, cost, stability, and on what investigators consider to be important. Many of the routinely measured outcomes have major limitations: they may not correlate well with long-term difficulties, they may artificially divide continuous outcomes into dichotomous ones, and may have no clear relationship with quality of life and functioning of children and their families. Several investigations, such as routine term cerebral resonance imaging for preterm infants, have also not yet been shown to improve the outcome of children nor their families. In this article, the most common variables used in neonatology as well as some variables which are rarely measured but may be of equal importance for families are presented. The manner in which these outcomes are communicated to families will be examined, as well as recommendations to optimize communication with parents.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a disease entity that describes a physiology in which there is persistence of increased pulmonary arterial pressure. PPHN is characterised by failure to adapt to a functional postnatal circulation with a fall in pulmonary vascular resistance. PPHN is responsible for impairment in oxygenation and significant neonatal mortality and morbidity. Prostanoids and their analogues may be useful therapeutic interventions due to their pulmonary vasodilatory and immunomodulatory effects. OBJECTIVES: Primary objective • To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and the need for extracorporeal membrane oxygenation (ECMO) among neonates with PH Secondary objective • To determine the efficacy and safety of prostanoids and their analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) and improving neurodevelopmental outcomes among neonates with PH Comparisons • Prostanoids and their analogues at any dosage or duration used to treat PPHN versus ‘standard treatment without these agents’, placebo, or inhaled nitric oxide (iNO) therapy • Prostanoids and their analogues at any dosage or duration used to treat refractory PPHN as an ‘add‐on’ therapy to iNO versus iNO alone SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 9), MEDLINE via PubMed (1966 to 16 September 2018), Embase (1980 to 16 September 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 16 September 2018). We also searched clinical trials databases, conference proceedings of the Pediatric Academic Societies (1990 to 16 September 2018), and the reference lists of retrieved articles for randomized controlled trials and quasi‐randomized trials. We contacted authors who have published in this field as discerned from the reference lists of identified clinical trials and review authors' personal files. SELECTION CRITERIA: Randomized and quasi‐randomized controlled trials evaluating prostanoids or their analogues (at any dose, route of administration, or duration) used in neonates at any gestational age less than 28 days' postnatal age for confirmed or suspected PPHN. DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal to conduct a systematic review and to assess the methodological quality of included studies (neonatal.cochrane.org/en/index.html). Three review authors independently assessed the titles and abstracts of studies identified by the search strategy and obtained full‐text versions for assessment if necessary. We designed forms for trial inclusion or exclusion and for data extraction. We planned to use the GRADE approach to assess the quality of evidence. MAIN RESULTS: We did not identify any eligible neonatal trials evaluating prostanoids or their analogues as sole agents in the treatment of PPHN. AUTHORS' CONCLUSIONS: Implications for practice Currently, no evidence shows the use of prostanoids or their analogues as pulmonary vasodilators and sole therapeutic agents for the treatment of PPHN in neonates (age 28 days or less). Implications for research The safety and efficacy of different preparations and doses and routes of administration of prostacyclins and their analogues in neonates must be established. Well‐designed, adequately powered, randomized, multi‐center trials are needed to address the efficacy and safety of prostanoids and their analogues in the treatment of PPHN. These trials should evaluate long‐term neurodevelopmental and pulmonary outcomes, in addition to short‐term outcomes.

BACKGROUND: Overuse of antibiotics can facilitate antibiotic resistance and is associated with adverse neonatal outcomes. We studied the association between duration of antibiotic therapy and short-term outcomes of very low birth weight (VLBW) ( METHODS: We included VLBW infants admitted to NICUs in the Canadian Neonatal Network between 2010–2016 who were exposed to antibiotics but did not have culture-proven sepsis in the first week. Antibiotic exposure was calculated as the number of days an infant received antibiotics in the first week of life. Composite primary outcome was defined as mortality or any major morbidity (severe neurologic injury, retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, or hospital-acquired infection). RESULTS: Of the 14 207 included infants, 21% (n = 2950), 38% (n = 5401), and 41% (n = 5856) received 0, 1 to 3, and 4 to 7 days of antibiotics, respectively. Antibiotic exposure for 4 to 7 days was associated with higher odds of the composite outcome (adjusted odds ratio 1.24; 95% confidence interval [CI] 1.09–1.41). Each additional day of antibiotic use was associated with 4.7% (95% CI 2.6%–6.8%) increased odds of composite outcome and 7.3% (95% CI 3.3%–11.4%) increased odds in VLBW infants at low risk of early-onset sepsis (born via cesarean delivery, without labor and without chorioamnionitis). CONCLUSIONS: Prolonged empirical antibiotic exposure within the first week after birth in VLBW infants is associated with increased odds of the composite outcome. This practice is a potential target for antimicrobial stewardship.

Trisomy 13 and 18 are life-limiting conditions for which a palliative approach is frequently recommended. The objective of this study was to examine parental goals/decisions, the length of life of their child and factors associated with survival. Parents of children who lived with trisomy 13 or 18 that were part of English-speaking social networks were invited to participate in a questionnaire study. Participants answered questions about their hopes/goals, decisions regarding neonatal interventions, and the duration of their children's lives. The participants were 332 parents who answered questions about their 272 children (87% response rate based on site visits; 67% on invitations sent). When parents were asked about their hope after the diagnosis, the main themes invoked by parents were the following: meet their child alive (80% of parents with a prenatal diagnosis), spend some time as a family (72%), bring their child home (52%), and give their child a good life (66%). Parents wanted to give them a chance, but also reported their fears were medical complexity, pain and/or life in the hospital (61%). Healthcare providers recommended comfort care at birth to all parents. Life-sustaining interventions “as for any other child” was chosen as a plan of care by 25% of parents. Of the 216 children with full trisomy, 69% were discharged home after birth and 40% lived >1 y. The presence of a prenatal diagnosis was the strongest independent factor negatively associated with longevity: 36% of children with a prenatal diagnosis lived

Background: Substantial health care resources are expended on standardised formal neonatal resuscitation training (SFNRT) programmes, but their effectiveness has not been proven. Objectives: To determine whether SFNRT programmes reduce neonatal mortality and morbidity, improve acquisition and retention of knowledge and skills, or change teamwork and resuscitation behaviour. Methods: We searched CENTRAL, MEDLINE, PREMEDLINE, EMBASE, CINAHL, Web of Science and the Oxford Database of Perinatal Trials, ongoing trials and conference proceedings in April 2015, and included randomised or quasi-randomised trials that reported at least one of our specified outcomes. Results: SFNRT in low- and middle-income countries decreased early neonatal mortality [risk ratio (RR) 0.85 (95% CI 0.75-0.96)]; the number needed to treat for benefit [227 (95% CI 122-1,667; 3 studies, 66,162 participants, moderate-quality evidence)], and 28-day mortality [RR 0.55 (95% CI 0.33-0.91); 1 study, 3,355 participants, low-quality evidence]. Decreasing trends were noted for late neonatal mortality [RR 0.47 (95% CI 0.20-1.11)] and perinatal mortality [RR 0.94 (95% CI 0.87-1.00)], but there were no differences in fresh stillbirths [RR 1.05 (95% CI 0.93-1.20)]. Teamwork training with simulation increased the frequency of teamwork behaviour [mean difference (MD) 2.41 (95% CI 1.72-3.11)] and decreased resuscitation duration [MD -149.54 (95% CI -214.73 to -84.34); low-quality evidence, 2 studies, 130 participants]. Conclusions: SFNRT in low- and middle-income countries reduces early neonatal mortality, but its effects on birth asphyxia and neurodevelopmental outcomes remain uncertain. Follow-up studies suggest normal neurodevelopment in resuscitation survivors.

Aim To examine nutritional and growth outcomes in very preterm infants with a birthweight (BW) of ≤1300 g before and after the introduction of enhanced enteral and parenteral nutrition protocols. Methods A comparison of two historical cohorts. Results There were 153 infants in cohort 1 and 118 in cohort 2. A total of 19% were growth restricted at birth in both cohorts. Feeds advanced more quickly in cohort 2, with decreased duration of central lines and TPN; breastmilk fortification occurred sooner. Calorie and protein intakes were increased during all of the first 14 days of life. Adverse clinical outcomes were unchanged, including NEC. The proportion of infants discharged

Staying abreast of the neonatal literature is an important task. Being aware of new information and knowing how to evaluate its reliability remain essential to be able to provide the most appropriate, evidence-based, therapy to our patients. This article discusses methods for being informed of, and critically reviewing, published research in order to fulfill these tasks without being overwhelmed by the number or complexity of publications.

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 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.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: Primary objective To determine the efficacy and safety of PGI(2) and its analogues (iloprost, treprostinil, and beraprost) in decreasing mortality and need for ECMO in neonates with PH. Secondary objectives To determine the efficacy and safety of PGI(2) and its analogues (iloprost, treprostinil, and beraprost) in decreasing neonatal morbidity (necrotizing enterocolitis (NEC), chronic lung disease (CLD), retinopathy of prematurity (ROP), neurodevelopmental outcomes, intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), length of hospital stay, and duration of mechanical ventilation) in neonates with PH.

BackgroundThe 2015 neonatal resuscitation guidelines added ECG as a recommended method of assessment of an infant’s heart rate (HR) when determining the need for resuscitation at birth. However, a recent case report raised concerns about this technique in the delivery room.ObjectivesTo compare accuracy of ECG with auscultation to assess asystole in asphyxiated piglets.MethodsNeonatal piglets had the right common carotid artery exposed and enclosed with a real-time ultrasonic flow probe and HR was continuously measured and recorded using ECG. This set-up allowed simultaneous monitoring of HR via ECG and carotid blood flow (CBF). The piglets were exposed to 30 min normocapnic alveolar hypoxia followed by asphyxia until asystole, achieved by disconnecting the ventilator and clamping the endotracheal tube. Asystole was defined as zero carotid blood flow and was compared with ECG traces and auscultation for heart sounds using a neonatal/infant stethoscope.ResultsOverall, 54 piglets were studied with a median (IQR) duration of asphyxia of 325 (200-491) s. In 14 (26%) piglets, CBF, ECG and auscultation identified asystole. In 23 (43%) piglets, we observed no CBF and no audible heart sounds, while ECG displayed an HR ranging from 15 to 80/min. Sixteen (30%) piglets remained bradycardic (defined as HR of ConclusionClinicians should be aware of the potential inaccuracy of ECG assessment during asphyxia in newborn infants and should rather rely on assessment using a combination of auscultation, palpation, pulse oximetry and ECG.

BACKGROUND Assessment of hemodynamics during the transitional period in preterm infants is challenging. OBJECTIVES We aimed to describe the relationship between cerebral regional tissue oxygenation saturation (CrSO2), preductal perfusion index (PI), echocardiographic and clinical parameters in extremely preterm infants in their first 72 hours of life. DESIGN/METHODS This single center prospective observational study was conducted in the level 3 neonatal intensive care unit of Sainte-Justine Hospital between July 2015 and May 2016. Twenty newborns born at RESULTS Median gestational age and birth weight were 25.0 weeks (24–26) and 750 g (655–920) respectively. Table 1 describes the measures over the 72 hours of the study period. CrSO2 and preductal PI were weakly correlated with mean blood pressure, PaCO2, lactates and haemoglobin. Fifteen patients had at least one episode of low left and/or right ventricular output (RVO) measured and showed strong correlation between CrSO2 and superior vena cava (SVC) flow at H6 (r=0.74) and H24 (r=0.86) and between PI and RVO at H6 (r=0.68) and H24 (r=0.92). Five patients had low SVC flowat H6 and showed strong correlation between PI and RVO (r=0.98). CONCLUSION CrSO2 and preductal PI were weakly correlated with clinical parameters in the preterm infants. However, CrSO2 and PI showed stronger correlation with RVO and SVC flow during low cardiac output states.

Objective The aim was to compare survival of patients with septic shock receiving or not hydrocortisone (HC) and to analyze the hemodynamic response to HC. Study Design It is a retrospective study of 62 premature neonates with septic shock (confirmed bacteremia) and/or necrotizing enterocolitis (NEC) stage 2 and above receiving inotropes with or without HC. We analyzed survival and hemodynamic response to HC. Results Thirty-nine (63%) premature neonates received HC and were compared with 23 (37%) who only received inotropes. Vasoactive index score (VAI) decreased and blood pressure, urine output, and oxygen requirements improved significantly following HC. Despite receiving more inotropes (VAI of 33 [20–53] vs 10 [8–20], p Conclusion HC was used in infants with increased inotropic support. HC during septic shock was associated with similar survival from episode, but with decreased survival at 1-year postmenstrual age.

Haemodynamic assessment during the transitional period in preterm infants is challenging. We aimed to describe the relationships between cerebral regional tissue oxygen saturation (CrSO2), perfusion index (PI), echocardiographic, and clinical parameters in extremely preterm infants in their first 72 h of life. Twenty newborns born at

Aim This study evaluated the clinical and haemodynamic effects of norepinephrine infusion in preterm infants. Methods The effects of norepinephrine therapy for refractory hypotension were evaluated in preterm infants between April 2009 and April 2011 at the neonatal intensive care unit of Sainte-Justine Hospital, Montreal, Quebec. Changes in haemodynamics and clinical parameters were analysed eight hours before and eight hours after the start of norepinephrine infusion, and eight hours after its cessation. Results During the study, 30 preterm infants at a mean gestational age of 26.5 ± 2.6 weeks (median: 25.7, 23.4-34) and birthweight of 903 ± 437 g (median 827, 450-2550) received norepinephrine infusion for neonatal septic shock. After eight hours of treatment, mean blood pressure, urine output and FiO2 significantly improved. Eight hours after cessation of norepinephrine infusion, the number of patients treated with other inotropes decreased significantly, 24 patients (80%) had normal mean blood pressure and 27 patients (90%) had normal urine output. Conclusion Norepinephrine therapy could be considered to improve blood pressure and urine output during neonatal septic shock in preterm infants. Further studies are needed to prove the efficacy and safety of norepinephrine infusion in neonates.

OBJECTIVES Assess impact of neonatal simulation and simulated death on trainees' stress and performance. DESIGN A parallel-group randomized trial (November 2011 to April 2012). SETTING Sainte-Justine University Hospital, Montreal, Canada. SUBJECTS Sixty-two pediatric trainees eligible, 59 consented, and 42 completed the study. INTERVENTIONS Trainees performed two simulations where a term neonate was born pulseless. They were randomized to start with either survival (manikin responded to appropriate resuscitation) or death scenario (manikin remained pulseless despite resuscitation). MEASUREMENTS AND MAIN RESULTS Performance was assessed using the Neonatal Resuscitation Program megacode score sheet by two reviewers. Subjective stress was assessed with a questionnaire. Three salivary cortisol (objective stress) values were compared: at baseline (T0: during lecture), presimulation (T1), and postsimulation (T2: after first scenario). Performance scores were similar in both groups in the first (83% vs 82%; p = 0.85) and second scenarios (82% vs 79 %; p = 0.87). Salivary cortisol levels at T0 (0.10 vs 0.10; p = 0.54), T1 (0.15 vs 0.11; p = 0.35), and T2 (0.23 vs 0.17; p = 0.23) did not differ between groups. Perceived stress level was six out of 10 in survival group versus seven out of 10 in death group (p = 0.19). Salivary cortisol increased significantly from T0 to T1 (p < 0.01). T2 cortisol levels were significantly higher than T1 (p< 0.001), yet this increase was not scenario dependent (p = 0.41) nor associated with performance on either scenario. Subscores for bag mask ventilation were lower than subscores for advanced resuscitation skills. CONCLUSIONS Neonatal simulations cause significant anticipatory and participatory stress. Despite this, trainees' performance score in simulation was over 80%. Simulated death did not impact performance, magnitude of rise in salivary cortisol level, and perceived stress level. Trainees performed better at advanced resuscitation skills (which are rarely needed) compared with basic skills routinely performed in practice.

The majority of neonatal deaths occur after a decision to limit life-sustaining interventions (LSIs).1 Decisions on when to withhold/withdraw LSIs in fragile neonates are among the most difficult decisions in paediatric practice. Two rigorous investigations shed some light on this topic. Durrmeyer et al 2 systematically described the management of 73 delivery room deaths in the EPIPAGE-2 cohort. The vast majority of neonates had LSI withheld, at a median gestational age of 24 weeks. Pain was usually assessed: 50% of infants received comfort medication, the administration of which was not associated with the evaluation of pain but rather with the presence of gasping. Satisfaction of healthcare providers was strongly associated with the occurrence of parent-child contact, which frequently occurred. Aladangady et al 3 describe the short-term outcome of LSI-limitation discussions with parents in a prospective multicentre trial in the UK (the WILST study). Half of the parents did not agree with providers and opted to continue LSI. When this occurred, it was not rare for the neonates to survive. When parents and providers agreed that LSI should be limited, neonates rarely survived. When examining these issues, three important questions should be considered: 1. When should limitations of LSI be considered? 2. How can we optimise communication with parents?4 3. How should we care for dying neonates and their families? Fragile neonates can be grouped into three decision-making ‘zones’: (1) ‘Beneficial’, where LSIs are indicated because of good outcomes; …

Background Fluid restriction is often recommended as part of the management of infants with early or established bronchopulmonary dysplasia (BPD). Objectives To determine whether fluid restriction as part of the therapeutic intervention for early or established BPD improves clinical outcomes. Search methods We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1) in the Cochrane Library (searched 16 February 2016), MEDLINE via PubMed (1966 to 16 February 2016), Embase (1980 to 16 February 2016), and CINAHL (1982 to 16 February 2016). We also searched clinical trials' databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. Selection criteria Prospective randomised clinical trials comparing two distinct fluid administration volumes in preterm infants with early or established BPD. Data collection and analysis We used the standard methods of Cochrane Neonatal. For the included trial, we extracted data and assessed the risk of bias, and used GRADE methods to assess the quality of the evidence. The outcomes considered in this review are effects on mortality or requirement for oxygen at 36 weeks' postmenstrual age (primary outcome measure), the duration of supplemental oxygen therapy, proportion of infants discharged from hospital on oxygen, duration of assisted ventilation, duration of hospitalisation, weight gain, feeding tolerance, apnoea, necrotizing enterocolitis, renal dysfunction or nephrocalcinosis, lung mechanics, and use of diuretic therapy (secondary outcome measures). Main results One trial was found, including 60 preterm infants at 28 days of age with persistent oxygen requirements. Infants were randomised to either 180 mL/kg/day of standard formula or 145 mL/kg/day of concentrated formula. This single study did not provide data regarding our primary outcome. No effects of the intervention were found on any of our secondary outcomes. The quality of the evidence from this study was graded low. Authors' conclusions There is no evidence to support the practice of fluid restriction in infants with early or established BPD.

Background Nitric oxide (NO) is a major endogenous regulator of vascular tone. Inhaled nitric oxide (iNO) gas has been investigated as treatment for persistent pulmonary hypertension of the newborn. Objectives To determine whether treatment of hypoxaemic term and near-term newborn infants with iNO improves oxygenation and reduces rate of death and use of extracorporeal membrane oxygenation (ECMO), or affects long-term neurodevelopmental outcomes. Search methods We used the standard search strategy of the Cochrane Neonatal Review Group to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 1), MEDLINE via PubMed (1966 to January 2016), Embase (1980 to January 2016) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to January 2016). We searched clinical trials databases, conference proceedings and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. We contacted the principal investigators of studies published as abstracts to ascertain the necessary information. Selection criteria Randomised studies of iNO in term and near-term infants with hypoxic respiratory failure, with clinically relevant outcomes, including death, use of ECMO and oxygenation. Data collection and analysis We analysed trial reports to assess methodological quality using the criteria of the Cochrane Neonatal Review Group. We tabulated mortality, oxygenation, short-term clinical outcomes (particularly use of ECMO) and long-term developmental outcomes. Statistics: For categorical outcomes, we calculated typical estimates for risk ratios and risk differences. For continuous variables, we calculated typical estimates for weighted mean differences. We used 95% confidence intervals and assumed a fixed-effect model for meta-analysis. Main results We found 17 eligible randomised controlled studies that included term and near-term infants with hypoxia. Ten trials compared iNO versus control (placebo or standard care without iNO) in infants with moderate or severe severity of illness scores (Ninos 1996; Roberts 1996; Wessel 1996; Davidson 1997; Ninos 1997; Mercier 1998; Christou 2000; Clark 2000; INNOVO 2007; Liu 2008). Mercier 1998 compared iNO versus control but allowed back-up treatment with iNO for infants who continued to satisfy the same criteria for severity of illness after two hours. This trial enrolled both preterm and term infants but reported most results separately for the two groups. Ninos 1997 studied only infants with congenital diaphragmatic hernia. One trial compared iNO versus high-frequency ventilation (Kinsella 1997). Six trials enrolled infants with moderate severity of illness scores (oxygenation index (OI) or alveolar-arterial oxygen difference (A-aDO2)) and randomised them to immediate iNO treatment or iNO treatment only after deterioration to more severe criteria (Barefield 1996; Day 1996; Sadiq 1998; Cornfield 1999; Konduri 2004; Gonzalez 2010). Inhaled nitric oxide appears to have improved outcomes in hypoxaemic term and near-term infants by reducing the incidence of the combined endpoint of death or use of ECMO (high-quality evidence). This reduction was due to a reduction in use of ECMO (with number needed to treat for an additional beneficial outcome (NNTB) of 5.3); mortality was not affected. Oxygenation was improved in approximately 50% of infants receiving iNO. The OI was decreased by a (weighted) mean of 15.1 within 30 to 60 minutes after the start of therapy, and partial pressure of arterial oxygen (PaO2) was increased by a mean of 53 mmHg. Whether infants had clear echocardiographic evidence of persistent pulmonary hypertension of the newborn (PPHN) did not appear to affect response to iNO. Outcomes of infants with diaphragmatic hernia were not improved; outcomes were slightly, but not significantly, worse with iNO (moderate-quality evidence). Infants who received iNO at less severe criteria did not have better clinical outcomes than those who were enrolled but received treatment only if their condition deteriorated. Fewer of the babies who received iNO early satisfied late treatment criteria, showing that earlier iNO reduced progression of the disease but did not further decrease mortality nor the need for ECMO (moderate-quality evidence). Incidence of disability, incidence of deafness and infant development scores were all similar between tested survivors who received iNO and those who did not. Authors' conclusions Inhaled nitric oxide is effective at an initial concentration of 20 ppm for term and near-term infants with hypoxic respiratory failure who do not have a diaphragmatic hernia.