Impact of villitis of unknown etiology and adverse acute neonatal outcomes in Eastern Ontario.

INTRODUCTION: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes. METHODS: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference. RESULTS: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis. DISCUSSION: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management.

Elevated Sound Levels in the Neonatal Intensive Care Unit: What Is Causing the Problem?

BACKGROUND: Premature and sick neonates may require weeks of hospitalization in a noisy neonatal intensive care unit (NICU) environment with sound levels that may reach 120 decibels. The American Academy of Pediatrics recommends a maximum sound level of 45 decibels. PURPOSE: To measure sound levels in a level III NICU and to describe contributing environmental factors. METHODS: Descriptive quantitative study. Sound levels were measured using a portable sound meter in an open-bay level III NICU. Contributing environmental factors were recorded and analyzed. RESULTS: Mean sound levels for day, evening, and night shifts were 83.5, 83, and 80.9 decibels, respectively. Each period of time exceeded the recommended guidelines 90% of the time and was almost double the American Academy of Pediatrics' recommendation. Multiple linear regression findings demonstrated significant factors associated with elevated sound levels including number of neonates, number of people, number of alarms, acuity level, and shift type. Observational data explain 14.5% of elevated sound levels. IMPLICATIONS FOR PRACTICE: An understanding of baseline sound levels and contributing environmental factors is the first step in developing strategies to mitigate excessive noise in the NICU. IMPLICATIONS FOR RESEARCH: Research should focus on effective and sustainable ways to reduce sound levels in the NICU, including inside the isolette, in order to provide an environment that is conducive to optimal growth and neurodevelopment for preterm and sick infants.

The Association of Placental Abruption and Pediatric Neurological Outcome: A Systematic Review and Meta-Analysis.

Placental histopathology provides insights, or "snapshots", into relevant antenatal factors that could elevate the risk of perinatal brain injury. We present a systematic review and meta-analysis comparing frequencies of adverse neurological outcomes in infants born to women with placental abruption versus without abruption. Records were sourced from MEDLINE, Embase, and the CENTRAL Trials Registry from 1946 to December 2019. Studies followed the PRISMA guidelines and compared frequencies of neurodevelopmental morbidities in infants born to pregnant women with placental abruption (exposure) versus women without placental abruption (comparator). The primary endpoint was cerebral palsy. Periventricular and intraventricular (both severe and any grades of IVH) and any histopathological neuronal damage were the secondary endpoints. Study methodologic quality was assessed by the Ottawa-Newcastle scale. Estimated odds ratios (OR) and hazards ratio (HR) were derived according to study design. Data were meta-analyzed using a random effects model expressed as pooled effect sizes and 95% confidence intervals. We included eight observational studies in the review, including 1245 infants born to women with placental abruption. Results of the random effects meta-analysis show that the odds of infants born to pregnant women with placental abruption who experience cerebral palsy is higher than in infants born to pregnant women without placental abruption (OR 5.71 95% CI (1.17, 27.91); I2 = 84.0%). There is no statistical difference in the odds of infants born to pregnant women with placental abruption who experience severe IVH (grade 3+) (OR 1.20 95% CI (0.46, 3.11); I2 = 35.8%) and any grade of IVH (OR 1.20 95% CI (0.62, 2.32); I2 = 32.3%) vs. women without placental abruption. There is no statistically significant difference in the odds of infants born to pregnant women with placental abruption who experience PVL vs. pregnant women without placental abruption (OR 6.51 95% CI (0.94, 45.16); I2 = 0.0%). Despite our meta-analysis suggesting increased odds of cerebral palsy in infants born to pregnant women with placental abruption versus without abruption, this finding should be interpreted cautiously, given high heterogeneity and overall poor quality of the included studies.

Extremely low gestational age infants: Developing a multidisciplinary care bundle.

BACKGROUND: Clinical experience in managing extremely low gestational age infants, particularly those born <24 weeks' gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born <26 weeks' gestation, with special considerations for infants of <24 weeks, to harmonize and improve quality of care. METHODS: We created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology. RESULTS: A care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants <26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%). CONCLUSION: It will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.

Neonatal necrotizing enterocolitis: a case series examining clinical diagnosis with discrepant versus concordant autopsy results.

OBJECTIVE: The objective of this study is to determine whether rapidity of death in necrotizing enterocolitis (NEC) increased odds of discordance between clinical and pathological diagnosis. STUDY DESIGN: Retrospective case-series study including preterm infants admitted to the NICU. RESULTS: Twenty-two infants met the selection criteria. Gross pathologic evidence of NEC was present in 1/6 cases (17%) where demise occurred <12 h after onset of symptoms, 3/5 cases (60%) within 12-24 h, and 8/11 cases (73%) in >24 h. Histological evidence of necrosis was present in 4/6 (67%) cases when death occurred <12 h, 4/5 (80%) in 12-24 h, and 9/11 (82%) in >24 h. The percentage with gross pathologic evidence showed a monotonic trend (P = 0.031), while the trend was less clear for histologic findings (P = 0.496). CONCLUSION: Pathologic features of cell death may not have had sufficient time to develop. This study could reassure both healthcare providers and families when pathologic and clinical diagnoses are not consistent.

Therapeutic strategies, including a high surgical ligation rate, for patent ductus arteriosus closure in extremely premature infants in a North American centre.

OBJECTIVE: To document the rate of surgical ligation of a patent ductus arteriosus (PDA) in extremely premature infants who had received more than one course of indomethacin. Outcomes were compared among three subgroups (ligation, further indomethacin and no further treatment) of infants who received at least one course of indomethacin, and between two subgroups (one course of indomethacin and more than one course) among infants who underwent ligation. STUDY DESIGN: A retrospective chart review of all 23 weeks+0 days to 26 weeks+6 days' gestational age infants with a PDA born between 1994 and 2005 was performed. Secondary outcomes were compared among the subgroups. RESULTS: The final study population consisted of 196 extremely premature infants with a PDA. The rate of surgical ligation in the 88 infants who received more than one course of indomethacin was 64%. The ligation subgroup, in comparison with the no further treatment subgroup, spent a greater median time on mechanical ventilation (39 versus 29 days, P<0.001) and in hospital (115 versus 92 days P=0.002), while trending toward lower mortality (18% versus 40%, P=0.07). The PDA closed following the first course of indomethacin in only 20% of infants. CONCLUSIONS: A majority of extremely premature infants receiving more than one course of indomethacin underwent surgical ligation. Repeated indomethacin courses were generally well tolerated, but were mostly unsuccessful. Ligation appears to have potential risks and benefits. A randomized trial should be performed after studies define a hemodynamically significant PDA that will result in morbidity and/or mortality unless treated.

OBJECTIF: Étayer le taux de ligatures chirurgicales de persistances du canal artériel (PCA) chez des grands prématurés qui avaient reçu plus d'une série de traitement à l'indométhacine. Les chercheurs ont comparé les issues entre les trois sous-groupes (ligature, nouvelle série de traitement à l'indométhacine et aucun traitement supplémentaire) et les nourrissons qui avaient reçu au moins une série de traitement à l'indométhacine, ainsi qu'entre deux sous-groupes (une série de traitement à l'indométhacine et plus d'une dose) et les nourrissons qui avaient eu une ligature. MÉTHODOLOGIE: Les chercheurs ont procédé à l'analyse rétrospective des dossiers de tous les nourrissons de 23+0 à 26+6 semaines d'âge gestationnel ayant une PCA, qui étaient nés entre 1994 et 2005. Ils ont comparé les issues secondaires entre les sous-groupes. RÉSULTATS: La population finale à l'étude se composait de 196grands prématurés ayant une PCA. Le taux de ligatures chirurgicales chez les 88 nourrissons qui avaient reçu plus d'une série de traitement à l'indométhacine s'élevait à 64 %. Le sous-groupe ligaturé, par rapport au sous-groupe n'ayant pas reçu de traitement supplémentaire, présentait une durée médiane plus élevée sous ventilation mécanique (39 jours par rapport à 29, P<0,001) et d'hospitalisation (115 jours par rapport à 92, P=0,002), tout en manifestant une tendance vers une mortalité moins élevée (18 % par rapport à 40 %, P=0,07). La PCA s'est fermée après la première dose d'indométhacine chez seulement 20% des nourrissons. CONCLUSIONS: La majorité des grands prématurés qui avaient reçu plus d'une série de traitement à l'indométhacine ont subi une ligature chirurgicale. Les nouvelles séries de traitement à l'indométhacine étaient généralement bien tolérées, mais la plupart étaient sans effet sur la PCA. La ligature semble s'associer à des risques et bienfaits potentiels. Il faudrait procéder à un essai aléatoire après que des études auront défini une PCA significative sur le plan hémodynamique qui s'associe à une morbidité ou une mortalité à moins d'être traitée.

Cloxacillin versus vancomycin for presumed late-onset sepsis in the Neonatal Intensive Care Unit and the impact upon outcome of coagulase negative staphylococcal bacteremia: a retrospective cohort study.

BACKGROUND: Coagulase negative staphylococcus (CONS) is the main cause of late-onset sepsis in Neonatal Intensive Care Units (NICU). Although CONS rarely causes fulminant sepsis, vancomycin is frequently used as empiric therapy. Indiscriminate use of vancomycin has been linked to the emergence of vancomycin resistant organisms. The objective of this study was to compare duration of CONS sepsis and mortality before and after implementation of a policy of selective vancomycin use and compare use of vancomycin between the 2 time periods. METHODS: A retrospective study was conducted of infants > or =4 days old, experiencing signs of sepsis with a first positive blood culture for CONS, during two 12-month periods. Late-onset sepsis was treated empirically with vancomycin and gentamicin during period 1, and cloxacillin and gentamicin during period 2. The confidence interval method was used to assess non-inferiority of the outcomes between the two study groups. RESULTS: There were 45 episodes of CONS sepsis during period 1 and 37 during period 2. Duration of sepsis was similar between periods (hazard ratio of 1.00, 95%CI: 0.64, 1.57). One death during period 2 was possibly related to CONS sepsis versus none in period 1. Vancomycin was used in 97.8% of episodes in period 1 versus 81.1% of episodes in period 2. CONCLUSION: Although we failed to show non-inferiority of duration of sepsis in the cloxacillin and gentamicin group compared to the vancomycin and gentamicin group, duration of sepsis was clinically similar. Restricting vancomycin for confirmed cases of CONS sepsis resistant to oxacillin appears effective and safe, and significantly reduces vancomycin use in the NICU.