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Objective: To evaluate the changes in the associations of antenatal corticosteroids (ACS) with neonatal mortality and severe neurological injury over time (2003–17). Design: National, population‐representative, retrospective cohort study. Setting: Level III neonatal intensive care units participating in the Canadian Neonatal Network. Population: All infants born at 230/7–336/7 weeks of gestation (n = 43 456). Methods: We estimated the associations between exposure to ACS and neonatal outcomes by year of birth. Year of birth was considered both continuously and categorically as three consecutive epochs. Main outcome measure: Neonatal mortality and severe neurological injury. Results: The absolute rates of neonatal mortality and severe neurological injury decreased during the study period in both the ACS and No ACS groups. For infants born at 230/7–306/7 weeks of gestation, ACS was associated with similar reductions in neonatal mortality across the three epochs (9.0% versus 18.1%, adjusted relative risk [aRR] 0.54, 95% CI 0.47–0.61 in 2003–09; 7.6% versus 19.6%, aRR 0.51, 95% CI 0.44–0.59 in 2010–13; and 7.3% versus 14.5%, aRR 0.56, 95% CI 0.46–0.68 in 2014–17) and in severe neurological injury (13.2% versus 25.8%, aRR 0.57, 95% CI 0.50–0.64 in 2003–09; 7.4% versus 17.4%, aRR 0.53, 95% CI 0.43–0.66 in 2010–14; and 7.2% versus 14.8%, aRR 0.59, 95% CI 0.48–0.74 in 2014–17). Conclusion: Despite the ongoing improvements in neonatal care of preterm infants, as reflected by the gradual decrease in the absolute rates of neonatal mortality and severe neurological injury, the association of ACS treatment with neonatal mortality and severe neurological injury among extremely preterm infants born at 23–30 weeks of gestation has remained stable throughout the study period of 15 years. Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care. Despite the gradual decrease in the rates of neonatal mortality and severe neurological injury, antenatal corticosteroids remain an important intervention in the current era of neonatal care. [ABSTRACT FROM AUTHOR]

Background: Excessive antimicrobial exposure is associated with an increase in neonatal mortality, morbidities and adverse neurodevelopment. Canadian Neonatal Network has been promoting judicious antimicrobial use through the Evidence-based Practice for Improving Quality processes. Our objective was to evaluate the antimicrobial consumption among neonates in tertiary neonatal intensive care units (NICU) in Canada in the recent decade., Methods: This is a retrospective cohort study including data from very preterm infants (born at <33 weeks gestational age) admitted to all NICUs in Canada between January 1, 2013, and December 31, 2022. Nationwide antimicrobial utilization rate (AUR) benchmarking started in 2016, and quality improvement initiatives were continued in the subsequent years to promote judicious use of antimicrobials across the network. AUR is defined as the number of days with ≥1 antimicrobial divided by the total patient days (PD). Culture-proven sepsis refers to a neonate with positive culture of pathogens in blood and/or cerebrospinal fluid. The outcomes were evaluated during pre- (2013-2017) and post-intervention periods (2018-2022). Interrupted time-series analysis was used, and comparison of AUR calculated per each 3-month time block and the slope changes were conducted across the pre- and post-intervention periods regarding total patients and subgroups., Findings: A total of 41,253 infants were included, with 22,644 (55%) being male. The AUR was significantly lower among infants from the post- vs. those from the pre-intervention periods (152 vs. 184, p < 0.0001). Among 35,670 infants without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2, AUR was significantly lower in the post-intervention group vs. the pre-intervention group (110 vs. 136, p < 0.0001). Interrupted time-series showed significant reduction in AUR during both pre- and post-intervention periods among all infants with and without culture proven sepsis or necrotizing enterocolitis ≥ Stage 2 (all p < 0.0001), as well as those born at <29 weeks gestational age., Interpretation: A comprehensive, network-wide quality improvement initiatives led to a significant and sustained reduction in antimicrobial use among preterm infants born at <33 weeks gestational age with and without culture-proven sepsis or necrotizing enterocolitis ≥ Stage 2., Funding: This study was supported by the Canadian Institutes of Health Research Project Grant 2019 (201903PJT-420294-CA2-CAAA-245530), matched funding from the British Columbia Women's Health Foundation and start-up funding from the Women and Children's Health Research Institute, University of Alberta. The coordinating center in Toronto is funded by the Canadian Institutes of Health Research grant for the Canadian Preterm Birth Network (PBN 150642)., Competing Interests: The funding agency has no role in the study design, analysis or interpretation of data, or preparation of this manuscript. None of the authors have been paid to write this article by a pharmaceutical company or other agency., (© 2024 The Authors.)

Introduction: Optimal oxygen saturation targets remain unknown for extremely preterm infants., Methods: Cohort analysis of eligible preterm infants born &lt;29 weeks' gestation admitted between 2011 and 2018 to centers submitting data to the Canadian Neonatal Network (CNN) database. Site questionnaires to determine saturation targets, alarm settings, and date of change, allowed assignation of centers to intermediate (88-93%) or high (90-95%) saturation targets. A 6-month washout period was applied to sites which switched targets during the study period. Our primary outcome was survival free of major morbidity. Secondary outcomes were death, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), treated retinopathy of prematurity, and evidence of brain injury during admission. Generalized estimating equations were applied to compensate for demographic differences and site practices., Results: There were 2,739 infants in the high (mean gestational age [GA] 26 ± 1.6 weeks) and 6,813 infants in the intermediate (mean GA 26.2 ± 1.6 weeks) saturation target group. Survival without morbidity was higher in the intermediate target group (adjusted odds ratio [aOR] 1.59; 95% CI: 1.04, 2.45). There was no difference in mortality between groups (aOR 0.81; 95% CI: 0.59, 1.11), in NEC, treated retinopathy, or brain injury. On subgroup analysis, restricting data to sites which switched targets during the study, intermediate saturation targets were associated with lower rates of BPD (aOR 0.45; 95% CI: 0.28, 0.72)., Conclusion: For neonates &lt;29 weeks' gestation, intermediate saturation target was associated with higher odds of survival without major morbidity compared to higher oxygen saturation target., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: One of the controversies regarding the management of twin gestations relates to the mode of delivery. Currently, counseling regarding the mode of delivery and the chance of successful vaginal twin delivery is based on the average risk for intrapartum cesarean delivery in the general population of twin pregnancies. Decision support tools that provide an individualized risk for intrapartum cesarean delivery based on the unique characteristics of each patient can improve counseling and decision-making regarding the choice of mode of delivery in twin pregnancies., Objective: This study aimed to develop and validate a prediction model to determine the risk for intrapartum cesarean delivery in twin pregnancies., Study Design: In this secondary analysis of the Twin Birth Study, a multicenter randomized controlled trial, we considered the subgroup of individuals who underwent a trial of vaginal delivery. Candidate predictors included maternal age, parity, previous cesarean delivery, conception method, chorionicity, diabetes and hypertension in pregnancy, gestational age at birth, the onset of labor, presentation of the second twin, sonographic fetal weight estimation, and fetal sex. The co-primary outcomes were overall intrapartum cesarean delivery and cesarean delivery of the second twin. Multivariable logistic regression models were used to estimate the probability of the study outcomes. Model performance was evaluated using measures of discrimination (the area under the receiver operating characteristic curve), calibration, and predictive accuracy. Internal validation was performed using the bootstrap resampling technique., Results: A total of 1221 individuals met the study criteria. The rate of overall intrapartum cesarean delivery and cesarean delivery for the second twin was 25.4% and 5.7%, respectively. The most contributory predictor variables were nulliparity, term birth (≥37 weeks), a noncephalic presentation of the second twin, previous cesarean delivery, and labor induction. The models for overall intrapartum cesarean delivery and cesarean delivery of the second twin had good overall discriminatory accuracy (area under the receiver operating characteristic curve, 0.720; 95% confidence interval, 0.688-0.752 and 0.736; 95% confidence interval, 0.669-0.803, respectively) and calibration (as illustrated by the calibration plot and Brier scores of 0.168; 95% confidence interval, 0.156-0.180 and 0.051; 95% confidence interval, 0.040-0.061, respectively). The models achieved good specificity (66.7% and 81.6%, respectively), high negative predictive value (86.0% and 96.9%, respectively), and moderate sensitivity (68.1% and 57.1%, respectively)., Conclusion: The prediction models developed in this study may assist care providers in counseling individuals regarding the optimal timing and mode of delivery in twin pregnancies by providing individualized estimates of the risk for intrapartum cesarean delivery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Antenatal detection of accelerated fetal growth and macrosomia in pregnancies complicated by diabetes mellitus is important for patient counseling and management. Sonographic fetal weight estimation is the most commonly used tool to predict birthweight and macrosomia. However, the predictive accuracy of sonographic fetal weight estimation for these outcomes is limited. In addition, an up-to-date sonographic fetal weight estimation is often unavailable before birth. This may result in a failure to identify macrosomia, especially in pregnancies complicated by diabetes mellitus where care providers might underestimate fetal growth rate. Therefore, there is a need for better tools to detect and alert care providers to the potential risk of accelerated fetal growth and macrosomia., Objective: This study aimed to develop and validate prediction models for birthweight and macrosomia in pregnancies complicated by diabetes mellitus., Study Design: This was a completed retrospective cohort study of all patients with a singleton live birth at ≥36 weeks of gestation complicated by preexisting or gestational diabetes mellitus observed at a single tertiary center between January 2011 and May 2022. Candidate predictors included maternal age, parity, type of diabetes mellitus, information from the most recent sonographic fetal weight estimation (including estimated fetal weight, abdominal circumference z score, head circumference-to-abdomen circumference z score ratio, and amniotic fluid), fetal sex, and the interval between ultrasound examination and birth. The study outcomes were macrosomia (defined as birthweights >4000 and >4500 g), large for gestational age (defined as a birthweight >90th percentile for gestational age), and birthweight (in grams). Multivariable logistic regression models were used to estimate the probability of dichotomous outcomes, and multivariable linear regression models were used to estimate birthweight. Model discrimination and predictive accuracy were calculated. Internal validation was performed using the bootstrap resampling technique., Results: A total of 2465 patients met the study criteria. Most patients had gestational diabetes mellitus (90%), 6% of patients had type 2 diabetes mellitus, and 4% of patients had type 1 diabetes mellitus. The overall proportions of infants with birthweights >4000 g, >4500 g, and >90th percentile for gestational age were 8%, 1%, and 12%, respectively. The most contributory predictor variables were estimated fetal weight, abdominal circumference z score, ultrasound examination to birth interval, and type of diabetes mellitus. The models for the 3 dichotomous outcomes had high discriminative accuracy (area under the curve receiver operating characteristic curve, 0.929-0.979), which was higher than that achieved with estimated fetal weight alone (area under the curve receiver operating characteristic curve, 0.880-0.931). The predictive accuracy of the models had high sensitivity (87%-100%), specificity (84%-92%), and negative predictive values (84%-92%). The predictive accuracy of the model for birthweight had low systematic and random errors (0.6% and 7.5%, respectively), which were considerably smaller than the corresponding errors achieved with estimated fetal weight alone (-5.9% and 10.8%, respectively). The proportions of estimates within 5%, 10%, and 15% of the actual birthweight were high (52.3%, 82.9%, and 94.9%, respectively)., Conclusion: The prediction models developed in the current study were associated with greater predictive accuracy for macrosomia, large for gestational age, and birthweight than the current standard of care that includes estimated fetal weight alone. These models may assist care providers in counseling patients regarding the optimal timing and mode of delivery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: In the case of prelabor rupture of membranes at term, the risk for neonatal and maternal infectious morbidity increases progressively with time from prelabor rupture of membranes. Although most studies identified a benefit associated with early induction within the first 24 hours following term prelabor rupture of membranes, there is currently no precise data regarding how early should induction be scheduled., Objective: This study aimed to identify the optimal timing of labor induction among women with term prelabor rupture of membranes by comparing the maternal and neonatal outcomes associated with labor induction with those of expectant management at any given 1-hour interval following prelabor rupture of membranes., Study Design: This was a secondary analysis of data from the TERMPROM trial, an international, multicenter, randomized clinical trial on immediate delivery vs expectant management of women with prelaor rupture of membranes at term (≥37+0/7 weeks' gestation). We considered all participants as a single cohort of women with term prelabor rupture of membranes, irrespective of the original randomized study group allocation. For each given 1-hour time interval within the first 36 hours following prelabor rupture of membranes, we compared the outcomes of subjects for whom labor induction was initiated during this interval with those of subjects managed expectantly at the same time interval. The primary neonatal outcome was a composite of neonatal infection and admission to the neonatal intensive care unit. The primary maternal outcomes included maternal infection (clinical chorioamnionitis or postpartum fever) and cesarean delivery., Results: Of the 4742 subjects who met the study criteria, 2622 underwent labor induction, and 2120 experienced a spontaneous onset of labor. The rates of the neonatal composite outcome, neonatal admission to intensive care unit, and maternal infection increased progressively with time after prelabor rupture of membranes. The risk for these outcomes was lower among women who underwent induction when compared with those managed expectantly within the first 15 to 20 hours after prelabor rupture of membranes without affecting the risk for cesarean delivery. In addition, women who underwent labor induction within the first 30 to 36 hours had a shorter prelabor rupture of membranes to delivery time and a shorter total maternal hospital stay when compared with those managed expectantly at the same time interval. Among women managed expectantly, less than two-thirds (64%; 1365/2120) experienced a spontaneous onset of labor within the first 24 hours following prelabor rupture of membranes., Conclusion: These findings suggest that immediate labor induction seems to be the optimal management strategy to minimize neonatal and maternal morbidity in the setting of prelabor rupture of membranes at term gestations. In cases for which immediate induction is not feasible, labor induction remains the preferred option over expectant management if performed within the first 15 to 20 hours after prelabor rupture of membranes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

Objective: To determine the rates and perinatal factors associated with initiation and early discontinuation of breastfeeding among very preterm neonates., Methods: This was a retrospective cohort study of very preterm infants (<29 weeks gestation) admitted to 2 regional Level III neonatal intensive care units (NICUs) from January 1, 2015, to December 31, 2019. A national neonatal database was used to evaluate initiation and continuation rates of breastfeeding and associated perinatal factors. Stored nutrition profiles and delivery record books were used to determine feeding volumes associated with continuation of breastfeeding to hospital discharge for a subgroup of infants at a single site. Descriptive and inferential statistics were used to present the results between groups, and logistic regression modeling was used to calculate crude and adjusted odds ratios (OR) and 95% CI., Results: Of 391 eligible neonates, 84% initiated breastfeeding but only 38% continued to discharge. Interestingly, frequency of breastfeeding initiation (P < 0.001) and continuation (P < 0.001) declined over the study period. After adjustment for confounders, younger maternal age, earlier gestational age, cigarette smoking, and multiparity were significantly associated with early discontinuation of breastfeeding prior to hospital discharge. Early discontinuation of breastfeeding was also related to lower volumes of breastmilk by day 7 of life (P = 0.004)., Conclusion: Very preterm neonates are at high risk for non-initiation and early discontinuation of breastfeeding. The early postnatal period represents a critical time to establish breastmilk volumes, and the identification of key perinatal risk factors allows for early and targeted breastfeeding support., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine the association between probiotic use and antimicrobial utilization., Study Design: We retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days., Result: Of 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97])., Conclusion: Probiotic use was associated with a significant reduction in AUR among VLBW infants., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To compare 2% aqueous chlorhexidine gluconate (AQC) vs. 2% chlorhexidine gluconate in 70% isopropyl alcohol (ALC) for pre-venipuncture skin antisepsis in very-low-birth-weight neonates (VLBW, birth-weight <1500 grams)., Study Design: Double-blind, non-inferiority trial randomized 199 VLBW neonates, age 2-28 days, to receive pre-venipuncture skin preparation using single application of swabstick impregnated with AQC (n = 99) or ALC (n = 100). Skin clearance rate (percentage post-cleansing skin swabs with <15 bacterial colony forming units) with a 10% non-inferiority margin for AQC was primary outcome. Absolute and relative CFU reduction and adverse skin reactions were compared., Results: AQC's clearance was non-inferior to ALC (91% vs. 88%; 95% CI -6.6%, +12.4%). Median (interquartile range) absolute [61 (16, 110) vs. 63 (18, 100); p = 0.65] and relative [100% (97%, 100%) vs. 100% (99.7%, 100%); p = 0.20] CFU reductions were similar. Neither group experienced any adverse reactions., Conclusion: AQC may provide non-inferior skin disinfection to ALC in VLBW neonates., Clinical Trial Registration: ClinicalTrials.gov NCT01270776., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objectives: To identify the predictors of successful first trial off nasal continuous positive airway pressure (nCPAP)., Methods: A retrospective cohort study of infants ≤29 weeks' gestation who required nCPAP for >24 h was conducted. Logistic regression was used to detect predictors for successful trial off nCPAP. Statistical analysis was performed using the SAS software., Results: A total of 727 infants were included in the analysis. Infants who were successful in their first trial off nCPAP (n = 313) were of higher gestational age (GA) and birth weight (BW), as well as a higher proportion of female infants, compared with those who were not successful (p < 0.01). When stratified by GA, a negative correlation was noted between GA and postmenstrual age at successful trial off nCPAP or high flow nasal cannula (HFNC) (r = 0.45, p < 0.01). Logistic regression analysis showed that GA (odds ratio [OR] 1.13, 95% confidence interval [CI] [1.03-1.24], p = 0.01) and percentage of time spent with an oxygen saturation over 89% in the 24 h preceding the trial off nCPAP (OR 1.08, 95% CI [1.05-1.11], p = 0.00) were independent predictors for successful trial off nCPAP., Conclusion: Successful trial off nCPAP or HFNC in preterm infants is significantly associated with higher GA, BW, female gender, and the specific oxygen saturation histogram in the preceding 24-h period., (© 2022 Wiley Periodicals LLC.)

Background: Data on the optimal gestational weight gain in twin pregnancies are limited. As a result, the Institute of Medicine currently provides only provisional recommendations on gestational weight gain in this population., Objective: This study aimed to identify the optimal range of gestational weight gain in twin pregnancies and to estimate the association between inappropriate gestational weight gain and adverse pregnancy outcomes., Study Design: This was a retrospective cohort study of all women with twin pregnancies that were followed up in a single, tertiary center between 2000 and 2014. We used 2 approaches to identify the optimal range of gestational weight gain: a statistical approach (the interquartile range of gestational weight gain in low-risk pregnancies with normal outcomes) and an outcome-based approach (by identifying thresholds of gestational weight gain below or above which the rate of adverse outcomes increases). The primary outcome was preterm birth. Associations of gestational weight gain below or above the normal range with the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence intervals. These associations were stratified by prepregnancy body mass index group., Results: A total of 1274 women with twin pregnancies met the study criteria: 43 were classified as underweight, 777 were normal weight, 278 were overweight, and 176 were obese. Our estimates of the optimal gestational weight gain range were similar to those recommended by the Institute of Medicine except for the obese category, in which our optimal gestational weight gain range at 37 weeks (9.3-16.3 kg) was lower than in the provisional Institute of Medicine recommendations (11.3-19.1 kg). Nearly half of our cohort experienced inappropriate gestational weight gain: 30% (n=381) gained weight below and 17% (n=216) gained weight above current Institute of Medicine recommendations. In the normal weight group, gestational weight gain below recommendations was associated with an increased risk of preterm birth and birthweight at the <10th centile and with a reduction in the risk of hypertensive disorders, whereas gestational weight gain above recommendations was associated with an increased risk of hypertensive disorders and a reduction in the risk of birthweight at the <10th centile. Associations were less consistent in the overweight and obese groups., Conclusion: These findings identify gestational weight gain as a potentially modifiable risk factor for preterm birth and other pregnancy complications in twin gestations. Further prospective studies are needed to determine whether interventions aimed at optimizing gestational weight gain can improve the outcomes of these high-risk pregnancies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Gestational diabetes mellitus is associated with accelerated fetal growth in singleton pregnancies but may affect twin pregnancies differently because of the slower growth of twin fetuses during the third trimester of pregnancy and their greater predisposition to fetal growth restriction., Objective: This study aimed to evaluate the association of gestational diabetes mellitus with longitudinal fetal growth in twin pregnancies and to compare this association with that observed in singleton pregnancies., Study Design: This was a retrospective cohort study of all women with a singleton or twin pregnancy who were followed up at a single tertiary referral center between January 2011 and April 2020. Data on estimated fetal weight and individual fetal biometric indices were extracted from ultrasound examinations of eligible women. Generalized linear models were used to model and compare the change in fetal weight and individual biometric indices as a function of gestational age between women with and without gestational diabetes mellitus in twin pregnancies and between women with and without gestational diabetes mellitus in singleton pregnancies. The primary outcome was estimated fetal weight as a function of gestational age. The secondary outcomes were longitudinal growth of individual fetal biometric indices and the rate of small for gestational age and large for gestational age at birth., Results: A total of 26,651 women (94,437 ultrasound examinations) were included in the analysis: 1881 with a twin pregnancy and 24,770 with a singleton pregnancy. The rate of gestational diabetes mellitus in the twin and singleton groups was 9.6% (n=180) and 7.6% (n=1893), respectively. The estimated fetal weight in singleton pregnancies with gestational diabetes mellitus was significantly higher than that in pregnancies without gestational diabetes mellitus (P<.001) starting at approximately 30 weeks of gestation. The differences remained similar after adjusting for maternal age, chronic hypertension, nulliparity, and neonatal sex (P<.001). In twin pregnancies, fetal growth was similar between pregnancies with and without gestational diabetes mellitus (P=.105 and P=.483 for unadjusted and adjusted models, respectively). The findings were similar to the association of gestational diabetes mellitus with the risk of large for gestational fetuses and the growth of each biometric index. When stratified by type of gestational diabetes mellitus treatment, twin pregnancies with gestational diabetes mellitus was associated with accelerated fetal growth only in the subgroup of women with medically treated gestational diabetes mellitus (P<.001), which represented 12% (n=21) of the twin pregnancy group with gestational diabetes mellitus., Conclusion: In contrast to singleton pregnancies, twin pregnancies with gestational diabetes mellitus is less likely to be associated with accelerated fetal growth. This finding has raised the question of whether the diagnostic criteria for gestational diabetes mellitus and the blood glucose targets in women diagnosed with gestational diabetes mellitus should be individualized for twin pregnancies., (Copyright © 2021. Published by Elsevier Inc.)

Background: Intertwin size discordance is an independent risk factor for adverse neonatal outcomes in twin pregnancies. However, size discordance at a given point in gestation fails to take into consideration information, such as the timing of onset and the rate of progression of discordance, that may be of prognostic value., Objective: In this study, we aimed to identify distinct patterns of discordant fetal growth in twin pregnancies and to determine whether these patterns are predictive of adverse pregnancy outcomes., Study Design: This was a retrospective cohort study of women with twin pregnancies in a single tertiary referral center between January 2011 and April 2020, who had at least 3 ultrasound examinations during pregnancy that included assessment of fetal biometry. Size discordance was calculated at each ultrasound examination, and pregnancies were classified into 1 of 4 predetermined patterns based on the timing of onset and the progression of discordance: pattern 1, no significant discordance group (referent); pattern 2, early (<24 weeks' gestation) progressive discordance group; pattern 3, early discordance with plateau group; or pattern 4, late (≥24 weeks' gestation) discordance group. The associations of discordance pattern (using pattern 1 as referent) with preterm birth, preeclampsia, size discordance at birth, and birthweight<10th percentile were expressed as adjusted relative risk with 95% confidence intervals and were compared with those observed for a single measurement of size discordance at 32 weeks' gestation., Results: Of 2075 women with a twin gestation who were identified during the study period, 1059 met the study criteria. Of the 1059 women, 599 (57%) were classified as no significant discordance (pattern 1), 23 (2%) as early progressive discordance (pattern 2), 160 (15%) as early discordance with plateau (pattern 3), and 277 (26%) as late discordance (pattern 4). The associations of discordance pattern with preterm birth at <34 weeks' gestation and preeclampsia were strongest for pattern 2 (rates of 43% [adjusted relative risk, 3.43; 95% confidence interval, 2.10-5.62] and 17% [adjusted relative risk, 5.81; 95% confidence interval, 2.31-14.60], respectively), intermediate for pattern 3 (rates of 23% [adjusted relative risk, 1.82; 95% confidence interval, 1.28-2.59] and 6% [adjusted relative risk, 2.08; 95% confidence interval, 1.01-4.43], respectively), and weakest for pattern 4 (rates of 12% [adjusted relative risk, 0.96; 95% confidence interval, 0.65-1.42] and 4% [adjusted relative risk, 1.41; 0.68-2.92], respectively). In contrast, a single measurement of size discordance at 32 weeks' gestation showed no association with preeclampsia and only a weak association with preterm birth at <34 weeks' gestation., Conclusion: We identified 4 distinct discordance growth patterns among twins that demonstrated a dose-response relationship with adverse outcomes and seemed to be more informative than a single measurement of size discordance., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Shock index and continuous non-invasive haemoglobin monitoring (SpHb) have both been proposed for the timely recognition of postpartum haemorrhage (PPH). We sought to determine, in parallel, the association of each of shock index and SpHb with blood loss after vaginal delivery., Methods: Sixty-six women were recruited to this prospective observational study. Shock index and SpHb were recorded postpartum for 120 min. The association between each of shock index and SpHb with quantitative blood loss (QBL) at 30, 60 and 120 min postpartum was determined using linear mixed models. Area-under-the-receiver-operator-characteristic (AUROC) curves were constructed to evaluate the diagnostic ability of shock index and SpHb to detect PPH (defined as QBL ≥1000 mL)., Results: Shock index trend was associated with QBL over the first 30 min (r=0.37, P=0.002), but not over 60 or 120 min. There was an association of SpHb trend with QBL over the first 30 min (P=0.06), but not over 60 min (r=-0.32, P=0.009) or 120 min (r=-0.26, P=0.03). Maximum shock index within 60 min correlated with QBL (r=0.54, P <0.001) and was a predictor of PPH (P=0.0012, AUROC 0.796). Maximum change in SpHb within 60 min negatively correlated with QBL (r=-0.4, P <0.001) and was a predictor of PPH (P=0.048, AUROC 0.761)., Conclusions: The trend of shock index and its peak values are associated with blood loss after vaginal delivery and are early indicators of PPH. Negative trend of SpHb is a late sign of PPH and has a weaker association with blood loss than shock index., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objectives: To identify characteristics and outcomes of infants who received multiple doses of surfactant vs those who received one dose or none., Study Design: In this retrospective study, we included neonates of 22-28 weeks' gestation admitted to NICUs in the Canadian Neonatal Network. Patients were divided into three groups: no surfactant, single dose, and multiple doses. The primary outcome was a composite of mortality or any of the major morbidities, including severe neurological injury, bronchopulmonary dysplasia, or ≥stage 3 retinopathy of prematurity., Results: Of 8024 eligible neonates, 2461 (31%) did not receive surfactant, 3545 (44%) received one dose, and 2018 (25%) received >1 dose. Receiving one or more doses of surfactant was associated with significantly higher adjusted odds of mortality or major morbidities in a dose-dependent manner., Conclusions: Receiving one or more doses of surfactant was associated with adverse neonatal outcomes. Receipt of more than one dose may reflect underlying severe lung immaturity.

Objective: To provide comprehensive, contemporary information on the actuarial survival of infants born at 22-25 weeks of gestation in Canada., Study Design: In a retrospective cohort study, we included data from preterm infants of 22-25 weeks of gestation admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 2010 and 2017. Infants with major congenital anomalies were excluded. We calculated gestational age using in vitro fertilization date, antenatal ultrasound dating, last menstrual period, obstetrical estimate, or neonatal estimate (in that order). Infants were followed until either discharge or death. Each day of gestational age was considered a category except for births at 22 weeks, where the first 4 days were grouped into one category and the last 3 days were grouped into another category. For each day of life, an actuarial survival rate was obtained by calculating how many infants survived to discharge out of those who had survived up to that day., Results: Of 4335 included infants, 85, 679, 1504, and 2067 were born at 22, 23, 24, and 25 weeks of gestation, respectively. Survival increased from 32% at 22 weeks to 83% at 25 4-6/7  weeks. Graphs of actuarial survival developed for the first 6 weeks after birth in male and female children indicated a steep increase in survival during the first 7-10 days postnatally., Conclusions: Survival increased steadily with postnatal survival and was dependent on gestational age in days and sex of the child., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To assess the rate, location, risk factors, management, and outcomes of neonatal thrombosis (NT)., Design: A retrospective study investigating infants admitted to NICUs in Canadian Neonatal Network between January 2014 and December 2016 and diagnosed with NT. Each infant with NT was matched with an infant without NT., Results: Of 39,971 infants, 587 (1.5%) were diagnosed with NT: 440 (75%) venous, 112 (19%) arterial, 29 (5%) both. NT rate was 1.4% in full-term and 1.7% in preterm infants. Venous thrombi occurred most commonly in the portal vein and arterial thrombi in the cerebral artery. Conservative management and low molecular weight heparin were the most common treatment modalities. Hospital stay was longer (p < 0.001) in the NT patients, but mortality was similar., Conclusions: NT was diagnosed in ~15/1000 NICU admissions and most commonly in the portal vein and cerebral arteries. Management varied based on the type and location of thrombi. Large multicenter trials are needed to address the best management strategies.

Objective: To examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks' gestation., Design: A retrospective cohort study., Setting: Data collected by the Canadian Neonatal Network., Patients: Neonates born at <29 weeks' gestation between January 2007 and December 2016., Main Outcome Measures: We examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities., Results: Our study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25-28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was -0.043 (95% CI -0.071 to -0.015) and for girls was -0.012 (95% CI -0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes., Conclusion: The difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care., Study Design: We conducted a retrospective cohort study of neonates ≥35 weeks' gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities., Results: Of 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22-0.52) compared with standard care group., Conclusion: Despite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.

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 < 0.05) between the two groups and adverse outcome were further tested, while adjusting for gestational age, birth weight, gender, and initial severity of encephalopathy., Results: A total of 2187 neonates were admitted for HIE; 52% were treated with hypothermia and 40% developed adverse outcome. Initial severity of encephalopathy (moderate, p = 0.006; severe, p < 0.0001), hypotension treated with inotropes (p = 0.001), and renal failure (p = 0.007) were significantly associated with an increased risk of death and/or brain injury., Conclusions: In asphyxiated neonates treated with hypothermia, not only their initial severity of encephalopathy on admission, but also their cardiac and renal complications during the first days after birth were significantly associated with risk of death and/or brain injury. Careful monitoring and cautious management of these complications is warranted.

Background: The current resuscitation guidelines for neonates recommend considering stopping resuscitation efforts if the heart rate remains undetectable after 10 min of adequate resuscitation. However, this recommendation does not take into account the gestational age (GA) of the neonates. We determined the outcomes of neonates with a 10-min Apgar score of zero (Apgar 10  = 0) with respect to their GA., Methods: In a retrospective matched cohort study, we studied neonates admitted to the Canadian Neonatal Network NICUs between 2010 and 2016 with an Apgar 10  = 0. The neonates were divided into 3 subgroups according to their GA: (1) ≥36 weeks', (2) 32 0/7 -35 6/7 weeks', and (3) <32 weeks'. Each neonate with Apgar 10  = 0 was matched 1:1 with neonates of same GA and sex but Apgar 10  = 1-2 and Apgar 10  = 3-5. Survival and brain injury were compared between matched groups., Results: 177 neonates had Apgar 10  = 0. Survival to discharge was significantly different between GA groups [≥36 weeks' 61% vs. 32 0/7 -35 6/7 weeks' 58% vs. <32 weeks' 35%, p = 0.04]. Survival to discharge was similar to their matched cohort with Apgar 10  = 1-2 for neonates born at ≥36 weeks' (61% vs. 66%) and between 32 0/7 to 35 6/7 weeks' (58% vs. 54%), but significantly different for neonates <32 weeks (35% vs. 61%, p = 0.04)., Conclusion: Neonates with Apgar 10  = 0 had different outcomes depending on their GA. Less than half of neonates born at <32 weeks GA survived; however, a majority of neonates born at 32 0/7 -35 6/7 weeks' and ≥36 weeks' GA survived at similar rates than their matched neonates with Apgar 10  = 1-2., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To determine if the reported reduction in hospital-acquired infections is due to reduced central line-associated blood stream infections (CLABSI) or non-CLABSIs., Study Design: 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 neonates <33 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., Results: 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., Conclusion: 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., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Meningitis is a serious disease that occurs more commonly in the neonatal period than in any other age group. Recent data from large national cohorts are needed to determine if the epidemiology of neonatal meningitis (NM) has changed., Aim: To assess the rates, causative organisms, risk factors, temporal trends and short-term outcomes of NM in Canadian Neonatal Intensive Care Units (NICUs)., Methods: A retrospective review of newborn infants admitted to NICUs participating in the Canadian Neonatal Network between January 2010 and December 2016. Patients with meningitis were reviewed. Outcomes of patients with meningitis were compared with 1:2 matched (for gestation, sex and birth weight) neonates without meningitis., Results: Rates of NM ranged between 2.2 and 3.5/1000 NICU admissions during the 7-year study period with the majority of patients (87%) having late-onset meningitis (at >3 days after birth). The most common bacterial organism for both early- and late-onset meningitis was Escherichia coli followed by group B streptococci. Only 31% [95% confidence interval (CI): 24.06-38.63) of neonates with meningitis had simultaneous bacteremia. NM was associated with increased seizures [odds ratio (OR): 8.63; 95% CI: 4.73-15.7], retinopathy of prematurity (OR: 3.23; 95% CI: 1.30-8.02), bronchopulmonary dysplasia (OR: 1.93; 95% CI: 1.11-3.35), days of mechanical ventilation (OR: 1.03; 95% CI: 1.02-1.04) and length of hospital stay (OR: 1.02; 95% CI: 1.01-1.02), but not with mortality before discharge (OR: 1.29; 95% CI: 0.74-2.23)., Conclusions: The rate of NM remains largely unchanged in Canadian NICUs. NM was associated with increased major morbidities and longer hospital stay but not with mortality before discharge.

Background: The current treatment approach in patent ductus arteriosus suggests the identification of high-risk infants that may benefit the most from treatment. Small for gestational age infants are a high-risk population in which the treatment approach to the patent ductus arteriosus and outcomes have not been described., Aim: To compare the patent ductus arteriosus treatment approach and outcomes in small for gestational age and appropriate for gestational age infants., Study Design: Retrospective analysis of infants born between January 1, 2011 and December 31, 2015 at <33 weeks' GA and admitted to neonatal intensive care units (NICU) part of the Canadian Neonatal Network., Results: 595 of 2507 small for gestational age infants (23.7%) and 4714 of 20,002 appropriate for gestational age infants (23.6%) had a patent ductus arteriosus. The patent ductus arteriosus treatment approach (conservative, medical, surgical) was similar in both groups. Small for gestational age infants with and without a patent ductus arteriosus had increased risk of the composite outcome of death or bronchopulmonary dysplasia (aOR 3.40; 95% CI 2.73, 4.24; and aOR 2.72; 95% CI 2.24, 3.31) respectively., Conclusions: Patent ductus arteriosus management did not differ between small for gestational age and appropriate for gestational age infants. Small for gestational age infants had increased risk of death or bronchopulmonary dysplasia regardless of their patent ductus arteriosus status., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Percutaneous endoscopic gastrostomy (PEG) is considered the route of choice for long-term enteral nutrition. In this study, we evaluated the short term outcomes of PEG and aimed to identify the risk factors for in-hospital mortality as well as adverse events such as aspiration pneumonia., Methods: Three hundred and twenty-four patients who received PEG for enteral nutrition between January 2007 and December 2011 were included in this study. Data regarding baseline characteristics, preoperative biomarkers and clinical outcomes were collected and analyzed., Results: The average patient age was 82.3±10.9 (SD) years old. 149 patients (46%) were men and 199 patients (61%) had stroke as a comorbidity. Postoperatively, feeding-related aspiration pneumonia was observed in 72 patients (22%), diarrhea in 40 patients (12%) and peristomal infection in 34 patients (11%). The average postoperative length of stay was 34.6 days. 51 patients (16%) died before discharge, 22 (6.8%) of them within 30 days after PEG. Two deaths (0.6%) were considered procedure-related (bleeding). Multivariate analysis revealed the male gender, lower serum albumin levels and higher blood urea nitrogen (BUN) levels as significant prognostic factors for in-hospital mortality. Higher C-reactive protein levels and BUN levels were found to be independently associated with the occurrence of postoperative aspiration pneumonia., Conclusions: Our experience reconfirmed PEG as a minimally invasive and safe procedure for long-term enteral nutrition in patients with impaired oral intake. However, significant prognostic factors should be taken into account during the preoperative evaluation of patients. Deferral of procedure or specialized postoperative care may be indicated in high risk patients.

: media-1vid110.1542/5984244681001PEDS-VA&#95;2018-2286 Video Abstract 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) (<1500 g) infants without culture-proven sepsis., 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., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: Pasteurized donor milk is the recommended supplement for preterm infants when mother's milk volumes are insufficient. Compared with mother's milk, the macronutrient content of donor milk is thought to be lower due to pasteurization and additional container changes during processing. Given that poor growth is concerning for preterm infants, it is important to understand how processing and feeding methods influence the nutrition composition of donor milk feeds. The research aim of this study was to determine the effects of pasteurization and feeding method on the macronutrient and energy composition of donor milk. Ten donor milk pools were pasteurized, prepared according to neonatal practices, and infused through nasogastric tubes to simulate 4 feeding methods: bolus, 30 minutes, 60 minutes, and continuous feeding over 4 hours. Macronutrient concentrations were assessed after pasteurization, preparation, and each feeding method using a mid-infrared human milk analyzer., Results: There were no significant decreases in macronutrient content after pasteurization or bolus feeding. However, energy and fat losses increased with slower infusion rates. After continuous feeding for 4 hours, energy and fat concentrations decreased by a mean of 17.3 (15.8-18.8) kcal/dL and 2.08 (1.90-2.25) g/dL (P < .0001), respectively., Conclusions: Pasteurization did not significantly reduce donor milk macronutrient and energy content; however, feeding method significantly impacted the final delivery of energy and fat., (© 2018 American Society for Parenteral and Enteral Nutrition.)

Salicylate-induced acute respiratory syndrome (ARDS) is a well-known entity occurring in 35% of salicylate-intoxicated patient. Careful history taking, physical examination, arterial blood gas analysis, and measurement of serum salicylate concentration will lead to early recognition to initiate appropriate treatment.

Recurrent aspiration pneumonia can impede the continuation of enteral nutrition. Semi-solid feeds have been demonstrated to reduce the incidence of aspiration pneumonia but are difficult to administer via the nasogastric tube. A novel semi-solidifying enteral formula may be used instead to avoid the occurrence of severe gastroesophageal reflux.

Objective: To examine the association between the duration of antibiotic exposure and development of stage 2 or 3 necrotizing enterocolitis (NEC) in very preterm neonates., Study Design: A retrospective case-control study was conducted from Canadian Neonatal Network data for preterm neonates born before 29 weeks' gestation and admitted 2010 through 2013. Efforts were made to match each NEC case to two controls for gestational age, birth weight (±100 g) and sex., Results: A total of 224 cases and 447 controls were identified. The incidence of antenatal steroid administration, the number of days nil-per-os and the number of antibiotic days prior to onset of NEC were significantly different in neonates with NEC. A multiple regression analysis revealed that the duration of antibiotic use was higher among NEC cases compared to controls (P<0.01). Empiric antibiotic treatment of 5 or more days was associated with significantly increased odds of NEC as compared with antibiotic exposure of 0 to 4 days (adjusted odds ratio: 2.02; 95% CI 1.55, 3.13)., Conclusion: Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks' gestation was associated with an increased risk of NEC.

[This corrects the article DOI: 10.1155/2018/8439791.].

Background: Unpasteurized human donor milk typically contains a variety of bacteria. The impact of neonatal intensive care unit (NICU) admission of the donor's infant and duration of lactation on bacterial contamination of human milk is unknown. Research aim: This study aimed (a) to describe the frequency/concentration of skin commensal bacteria and pathogens in unpasteurized human donor milk and (b) to assess the impact of NICU admission and (c) the duration of milk expression on bacterial colonization of donated milk., Methods: The authors conducted a retrospective cohort study of human milk donated to the Rogers Hixon Ontario Human Milk Bank from January 2013 to June 2014. Milk samples from each donor were cultured every 2 weeks., Results: The study included 198 donor mothers, of whom 63 had infants admitted to the NICU. Of 1,289 cultures obtained, 1,031 (80%) had detectable bacterial growth and 363 (28%) yielded bacterial growth in excess of 10 7 cfu/L, a local threshold for allowable bacteria prior to pasteurization. The mean (standard deviation) donation period per donor was 13.0 (7.5) weeks. Milk from mothers with NICU exposure had significantly higher concentrations of commensals, but not pathogens, at every time period compared with other mothers. For every 1-month increase in donation from all donors, the odds ratio of presence of any commensal in milk increased by 1.13 (95% confidence interval [1.03, 1.23]) and any pathogen by 1.31 (95% confidence interval [1.20, 1.43])., Conclusion: Commensal bacteria were more abundant in donor milk expressed from mothers exposed to neonatal intensive care. Bacterial contamination increased over the milk donation period.

Objective: To evaluate the safety of fentanyl in non-intubated infants undergoing peripherally inserted central catheter (PICC) placement., Methods: A retrospective chart review of PICC placements over a 3 years' period. We compared the 12h periods before and after fentanyl for clinically significant cardiorespiratory events (spells)., Results: Of the 998 neonates screened, 258 were eligible. The mean standard deviation gestational age was 34.1 (4.3) weeks and the median (inter-quartile range) postnatal age was 4 (7, 11) days. The mean (standard deviation) fentanyl dose was 0.6 (0.2) µg/kg. Respiratory depression occurred only in two infants (prevalence rate = 0.78%, 95% CI (0, 1.85)). No cases of hypotension or chest wall rigidity occurred. There was no evidence of an increase in the number of infants with spells or in the number of spells per infant (p = 0.34 and p = 0.06, respectively)., Conclusion: Fentanyl appears to be associated with only a small risk of respiratory depression in non-intubated infants.

When elderly patients are prescribed many different medications, the risk for developing serious adverse events should be kept in mind. One of these adverse events is agranulocytosis, which, although rare, can be life-threatening if left untreated. The majority of agranulocytosis cases are caused by drugs, including antibiotics. Here, we report a case of severe agranulocytosis in a 96-year-old woman following antibiotic therapy which was successfully managed using recombinant human granulocyte colony-stimulating factor (rhG-CSF) and the appropriate choice of antibiotics to treat her concomitant infection.

Objective: Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term., Methods: We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed., Results: We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65)., Conclusion: Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

Background: Percutaneous transesophageal gastro-tubing (PTEG) is a minimally invasive technique to access the gut via an esophagostomy. However, this procedure is not well known and the literature available is still fairly limited. This observational study was conducted to evaluate our experience using this method as an alternative long-term tube feeding procedure when gastrostomy is not suitable., Methods: A total of 15 patients (10 males and 5 females) who underwent PTEG at our institution from 2012 to 2016 were observed and analyzed in this study., Results: The average age was 80.1 (71-93) years. Underlying conditions that required PTEG were previous gastric resection in 11 patients, left diaphragm disorder in 2 patients, interposing transverse colon between the abdominal wall and anterior gastric wall in 1 patient, and severe gastrostomy site leakage in 1 patient. Tube placement was successful in all patients by approaching the left side of the neck, using a 15 Fr size tube. The mean postoperative length of stay was 22 (8-48) days. Postoperative adverse events included accidental tube dislodgement in three patients, tracheoesophageal fistula in one patient, inferior thyroid artery injury in one patient and thyroid gland mispuncture in one patient. There was no procedure-related mortality nor mortality at 30 days. Eight patients were discharged with some oral intake., Conclusions: PTEG is feasible in patients requiring long-term tube feeding for whom gastrostomy is unsuitable. It is an effective long-term tube feeding procedure and should be offered as a more comfortable alternative to nasogastric tubing., Competing Interests: Conflict of interest statement: The authors declare that there is no conflict of interest.

Venomous snake bites can be life threatening, occasionally requiring intensive care. For Mamushi bites, conservative treatment may be possible in mild cases but for severe cases or in cases where symptoms do not improve, a horse-derived antivenom is indicated.

Dysphagia can be caused by many different underlying conditions. The assessment and management of dysphagia depend on each individual patient, often requiring a multidisciplinary approach. Structural cause of dysphagia can be dealt with using endoscopic interventions before the patient's general status deteriorates.

Classical lymphadenopathies, such as Virchow's node (left supraclavicular lymph node metastasis) and Irish node (left axillary lymph node metastasis), are important findings that may indicate the presence of gastric cancer and other gastrointestinal malignancies.

Percutaneous endoscopic gastrostomy (PEG) is the method of choice in patients requiring long-term enteral tube feeding. In patients with intrathecal baclofen infusion therapy (IBT) pump implantation, infection via the skin and soft tissue may be an issue of concern. The introducer technique for gastrostomy tube insertion may be useful in reducing the risk of peristomal infection. Although the presence of a PEG tube has been reported as a risk factor for implantation site infection (for newly inserted IBT pumps), whether existing IBT pumps are at risk for infection during or after the placement of a PEG tube is not clear. We report a case where PEG was successfully performed using the introducer technique on a patient with an IBT pump implant.

Objectives: To evaluate patterns of narcotic and sedative use in neonatal intensive care units (NICUs) across Canada using data collected by the Canadian Neonatal Network., Study Design: We conducted a retrospective observational cohort study of preterm neonates at <33 weeks' gestation and admitted to a participating Canadian Neonatal Network NICU. The proportion of all neonates who received sedative(s), narcotic(s), or either sedative(s), narcotic(s), or both during their NICU stay was calculated for each year. Because opioids are used for premedication before intubation, only continuous infusions of a narcotic drug were included. Variation in narcotics and sedative usage between sites in 2014 was determined using logistic regression analysis, with adjustment for gestational age, surgery, and mechanical ventilation., Results: Of 20 744 neonates, 29% of neonates received a narcotic, a sedative, or both; 23% received a narcotic and 17% a sedative. Although no clinically significant changes in drug exposure were documented during the 5-year period, there were statistically significant differences in narcotic and sedative use between sites, ranging from 3% to 41% for narcotic and 2% to 48% for sedative use (aORs 0.2-5.7 and 0.1-15, respectively, P < .05)., Conclusions: Exposure to narcotic or sedative agents is highly variable in preterm neonates across Canada despite concerns of adverse outcomes associated with these drugs. The tremendous variation in practice suggests that further research on their current usage, as well as identifying optimal practice procedures is warranted., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Competing Interests: Conflicts of Interest: None declared.

The objective of this study was to investigate the outcomes of rehabilitation (with swallowing therapy) after percutaneous endoscopic gastrostomy (PEG) in patients with neurogenic dysphagia. Forty-seven patients (29 males and 18 females) who were transferred to the rehabilitation ward of our hospital after receiving PEG tube placements during a 5-year period were enrolled in this study. Patients' demographic data, comorbidities, nutritional statuses, and laboratory biomarkers before the PEG procedure were collected. Rehabilitation (with swallowing therapy) outcomes such as changes in Functional Independence Measure (FIM) and dysphagia grade (using Fujishima's classification) were evaluated. Significant improvements in FIM scores and dysphagia grades after rehabilitation therapy were observed. Twenty-seven patients (57.4 %) were discharged with some oral intake and 10 patients (21.3%) were discharged PEG-free (defined as the PEG tube not being used or removed). Factors associated with being discharged with some oral intake were increase in FIM score (adjusted OR 1.10, 95 % CI 1.02-1.19) and higher baseline dysphagia grade (adjusted OR 1.88, 95 % CI 1.04-3.39). Factors associated with being discharged PEG-free were longer rehabilitation period (OR 1.03, 95 % CI 1.01-1.04), absence of respiratory disorders (OR 0.12, 95 % CI 0.03-0.35), and increase in FIM score (OR 1.17, 95 % CI 1.08-1.28). Changes in dysphagia grade were significantly correlated with changes in FIM score (r 2  = 0.46, p < 0.0001), indicating that improvement of FIM scores through general rehabilitation therapy may play an important role in the treatment of dysphagia.

Background and study aims: Feeding-related adverse events after percutaneous endoscopic gastrostomy (PEG) such as aspiration pneumonia may result in prolonged hospitalization and postoperative mortality. This study evaluated the efficacy of using semi-solid feeds to reduce feeding-related adverse events and improve clinical outcomes. Patients and methods: Patients who received PEG for enteral nutrition at our hospital between January 2014 and December 2015 were allocated to a postoperative feeding protocol that used either liquid feed or semi-solid feed. Baseline characteristics, postoperative feeding-related adverse events and clinical outcomes in the 2 groups were prospectively analysed and compared. Results: One hundred and seventeen PEG patients (age range: 59 - 97 years, male: 53) were enrolled with 72 patients given liquid feed and 45 patients receiving semi-solid feed. Baseline characteristics were similar in both groups. The semi-solid feed group experienced fewer incidence of feeding-related aspiration pneumonia (2.2 % vs. 22.2 %, P  < 0.005) and shorter postoperative hospital length of stay (12.7 days vs. 18.8 days, P  < 0.01). Significant differences were not observed in the frequency of peristomal infection (11.1 % vs. 12.5 %, P  = 0.82), feeding-related diarrhea (2.2 % vs. 12.5 %, P  = 0.09) and 30-day mortality rates (2.2 % vs. 8.3 %, P  = 0.25). Conclusions: Semi-solid feeding may reduce the risk of aspiration pneumonia and shorten postoperative hospital length of stay after PEG. Semi-solid feeds are safe to use and can be employed either as a first line feeding protocol or an alternative when liquid feeding is unsuccessful.

Importance: Excessive antibiotic use has been associated with altered bacterial colonization and may result in antibiotic resistance, fungemia, necrotizing enterocolitis (NEC), and mortality. Exploring the association between antibiotic exposure and neonatal outcomes other than infection-related morbidities may provide insight on the importance of rational antibiotic use, especially in the setting of culture-negative neonatal sepsis., Objective: To evaluate the trend of antibiotic use among all hospitalized very low-birth-weight (VLBW) infants across Canada and the association between antibiotic use rates (AURs) and mortality and morbidity among neonates without culture-proven sepsis or NEC., Design, Setting, and Participants: A retrospective cohort study was conducted among VLBW infants (<1500 g) admitted to level III neonatal intensive care units between January 1, 2010, and December 31, 2014, using data obtained from the Canadian Neonatal Network database., Exposure: Duration of antibiotic use during the hospitalization period., Main Outcomes and Measures: The AUR was defined as the number of days an infant was exposed to 1 or more antimicrobial agents divided by the total length of hospital stay. The composite primary outcome was defined as mortality or major morbidity, including any of the following: persistent periventricular echogenicity or echolucency on neuroimaging, chronic lung disease, and stage 3 or higher retinopathy of prematurity. Multivariable regression analysis was used to calculate adjusted odds ratios (aORs) and 95% CIs for the association between AURs and outcomes., Results: Among 13 738 eligible VLBW infants, 11 669 (84.9%) (mean [SD] gestational age, 27.7 [2.5] weeks; 47.4% female) received antibiotics during their hospital course and were included in the study. The annual AUR decreased from 0.29 in 2010 to 0.25 in 2014 (slope for the best-fit line, -0.011; 95% CI, -0.016 to -0.006; P < .01), which occurred in parallel with a reduction in the rate of late-onset sepsis from 19.0% in 2010 to 13.8% in 2014 during the same period. Of the 11 669 infants who were treated with antibiotics of varying duration during their hospital stay, 2845 were diagnosed as having sepsis-related complications. Among the remaining 8824 infants without early-onset sepsis, late-onset sepsis, or NEC, a 10% increase in the AUR was associated with an increased odds of the primary composite outcome (aOR, 1.18; 95% CI, 1.13-1.23), mortality (aOR, 2.04; 95% CI, 1.87-2.21), and stage 3 or higher retinopathy of prematurity (aOR, 1.18; 95% CI, 1.06-1.32)., Conclusions and Relevance: Antibiotic use in VLBW infants decreased between 2010 and 2014 in Canada. However, among infants without culture-proven sepsis or without NEC, higher AURs were associated with adverse neonatal outcomes.