PDA management strategies and pulmonary hypertension in extreme preterm infants with bronchopulmonary dysplasia.

BACKGROUND: Premature infants are at risk for developing pulmonary hypertension (PH) in the context of bronchopulmonary dysplasia (BPD). Studies suggest a potential link between prolonged patent ductus arteriosus (PDA) exposure and BPD-PH, though management strategies remain controversial. METHODS: Retrospective echocardiographic evaluation of newborns <29 weeks gestational age with BPD at two distinct centers. Primary objective was to evaluate the relationship between center-specific PDA management strategies (interventional or conservative) and the prevalence of BPD-PH. BPD was defined as oxygen or respiratory support at 36 weeks post-menstrual age (PMA). The presence of PH was defined as either an estimated sPAP of ≥40 mmHg or sEI ≥1.3. Center A has a conservative PDA policy. Center B has a targeted interventional policy. RESULTS: PH rates were similar between sites (21% vs 17%), while rates of PDA treatment was different (7% vs 81). Adjusted models did not demonstrate an association for center or PDA treatment exposure for PH and EI, although infants from Center A had echocardiography evidence of higher systolic eccentricity index (EI; 1.12 ± 0.19 vs 1.06 ± 0.15, p = 0.04). Markers of RV function (TAPSE and RV-FAC) were similar between groups. CONCLUSION: In preterm infants <29 weeks with BPD, conservative PDA treatment policy was not associated with higher rate of pulmonary hypertension diagnosis. IMPACT: The association between PDA-management approaches and the occurrence of BPD-associated pulmonary vascular disease in premature infants has sparsely been described. We found that a conservative policy, regarding the PDA, was not associated with an increase in pulmonary hypertension diagnosis. We identified that, in patients with BPD, echocardiographic metrics of LV performance were lower.

CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

Vasopressin in newborns with refractory acute pulmonary hypertension.

BACKGROUND: Acute pulmonary hypertension (aPH) in newborns can be life threatening and challenging to manage. In newborns with refractory aPH, there is currently limited therapeutic agents. METHODS: Retrospective single-center cohort study in newborns less than one month old who were treated with vasopressin for a minimum of one hour in the context of refractory aPH in the neonatal and pediatric intensive care units of a tertiary university center between 2016 and 2022. The objective was to evaluate the efficacy and safety of vasopressin in newborns as an adjuvant treatment for refractory aPH. RESULTS: Twenty-five patients met inclusion criteria. In patients who received vasopressin, oxygenation index improved from 28.4 to 14.4 (p = 0.004) after twelve hours of continuous infusion. Oxygen requirements (FiO2) decreased from 0.91 to 0.50 (p = 0.004) and mean arterial pressure increased from 41 to 51 mmHg (p = 0.001). In our cohort, 68% of patients presented an episode of hyponatremia (serum sodium <130 mmol/L). CONCLUSIONS: The use of vasopressin may be associated with improvement in oxygenation and hemodynamic status of neonatal patients with aPH refractory to initial therapy. Further prospective studies are needed to establish the safety profile of vasopressin in newborns, particularly in preterm infants. IMPACT: Vasopressin may be an effective cardiotropic agent to improve oxygenation and hemodynamic status in newborns with acute pulmonary hypertension. Careful monitoring of serum sodium levels are warranted in newborns who are receiving vasopressin infusion. This provides additional evidence for the consideration of vasopressin in newborns with acute pulmonary hypertension refractory to inhaled nitric oxide.

Variability in antimicrobial use among infants born at <33 weeks gestational age.

Excessive antimicrobial use is associated with adverse neonatal outcomes. In our cohort of 27,163 infants born at <33 weeks gestational age, the first week after birth accounted for the highest rates of antimicrobial use, and variability across sites persisted after adjustment for patient characteristics correlated with illness severity.

Association of Weight Changes by Three Days after Birth and Mortality and/or Severe Neurological Injury in Preterm Infants < 29 Weeks Gestational Age: A Multicenter Cohort Study.

OBJECTIVE: This study aimed to determine the range of weight loss, at 3 days postnatal age, associated with the lowest risk of mortality/short-term morbidity in preterm infants <29 weeks gestational age (GA). STUDY DESIGN: This multicenter retrospective cohort study employed data from the Canadian Neonatal Network database. The primary outcome was a composite of mortality and/or severe neurological injury. Multivariable quadratic and linear regression models which adjusted for potential confounders were built. RESULTS: A total of 9275 preterm infants (median GA 26, IQR 25, 28 weeks) were included. The optimal weight change range at day three, after adjustment for potential confounders for the primary outcomes, was -15 to -8.9%. CONCLUSIONS: There is a 'U'-shaped relationship between weight change from birth to day three and mortality and/or severe neurological injury. Interventional studies, which target weight loss within the range found in this study and evaluate the impact on neonatal outcomes, are needed to corroborate our findings.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Neurodevelopmental outcomes of singleton large for gestational age infants <29 weeks' gestation: a retrospective cohort study.

OBJECTIVE: To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants <29 weeks' gestation at 18-24 months of corrected age. STUDY DESIGN: Retrospective cohort study using the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases. Primary outcome was a composite of death or significant neurodevelopmental impairment (NDI), defined as severe cerebral palsy, Bayley III cognitive, language and motor scores of <70, need for hearing aids or cochlear implant and bilateral visual impairment. Univariate and multivariable logistic analyses were applied for outcomes. RESULTS: The study cohort comprised 170 LGA and 1738 AGA infants. There was no difference in significant NDI or individual components of the Bayley III between LGA and AGA groups. LGA was associated with the increased risk of death by follow-up, 44/170 (25.9%) vs. 320/1738 (18.4%) (aOR: 1.60 95% CI: 1.00-2.54). CONCLUSIONS: Risk of NDI was similar between LGA and AGA infants.

The Use of Restraint and Seclusion in Residential Treatment Care for Youth: A Systematic Review of Related Factors and Interventions.

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

Sex-based differences in apnoea of prematurity: A retrospective cohort study.

NEW FINDINGS: What is the central question of the study? Is there a sex-based difference in the incidence of apnoea of prematurity and the success or failure of caffeine therapy in preterm infants? What is the main finding and its importance? Our data show that females received fewer days of caffeine treatment than males. This was most noticeable in infants born between 260/7 and 276/7  weeks of gestational age. These results highlight the importance of considering sex in clinical and basic research investigating the pathophysiology of apnoea of prematurity. ABSTRACT: This retrospective cohort study assessed whether sex influences the occurrence of apnoea of prematurity (AOP) in preterm infants. The analysis included a cohort of 24,387 preterm infants born between the gestational ages (GA) of 240/7 and 336/7  weeks that were admitted to tertiary neonatal care units participating in the Canadian Neonatal Network from January 2011 to December 2015. Of those, 13,983 (57%) were diagnosed with AOP. More females were diagnosed with AOP than males, but the difference in the male/female ratio was marginal (P = 0.058). The majority (89%) of infants diagnosed with AOP received caffeine (89% of males; 89% of females). By using the discontinuation of caffeine therapy as a proxy for the resolution of significant AOP, data analysis showed that females born before 336/7 weeks of GA stopped caffeine treatment earlier than males whether the caffeine was discontinued before 34 or 37 weeks of GA. Consequently, females had fewer days of caffeine therapy than males, especially infants born between 260/7 and 276/7  weeks (P < 0.004), 280/7 and 296/7  weeks (P < 0.03), and 320/7 and 336/7  weeks of GA (P < 0.04). Similar trends were observed when the corrected GA at discontinuation of caffeine was used. Given that AOP is indicative of an immature respiratory system, our data suggest that the maturation of the respiratory system might occur more rapidly in females than males. We conclude that sex needs to be considered in future studies on AOP.

Hemolytic disease of the newborn caused by anti-Wright (anti-Wra): case report and review of literature.

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