Postnatal acetaminophen exposure and neurodevelopmental outcomes at 18-21 months corrected gestational age in preterm infants <29 weeks gestation: a retrospective cohort study.

BACKGROUND: Studies have reported prenatal acetaminophen exposure is associated with abnormal neurodevelopment. There is limited and conflicting data on neurodevelopmental outcomes following postnatal acetaminophen exposure. Our objective was to investigate the neurodevelopmental outcomes of preterm infants < 29 weeks gestation postnatally exposed to acetaminophen. METHODS: Retrospective cohort study of infants born between 2008 and 2017 at a tertiary care perinatal center. Exclusion criteria included chromosomal disorders, major congenital abnormalities, and congenital infections. The primary outcome was a composite score of <85 on the cognitive, language, or motor components of the Bayley Scales of Infant and Toddler Development, 3rd edition, assessed at 18 to 21 months corrected gestational age. Multivariate logistic regression was used to assess confounders. RESULTS: Of the 945 infants included in the study, 120 were in the acetaminophen group. There was no difference in any of Bayley-III cognitive, language or motor composite scores of < 85 between the two groups for postnatal acetaminophen exposure, adjusted odds ratios (aORs) 1.03, 95% CI 0.60-1.78, or days of acetaminophen use, aORs 1.10, 95% CI 0.93-1.29. CONCLUSIONS: There was no difference in neurodevelopmental outcome between the acetaminophen exposed and non-exposed groups. Our results need validation in larger cohorts. IMPACT: Animal research and cohort studies have suggested that prenatal acetaminophen exposure may be associated with an elevated risk of neurobehavioral abnormalities. However, there is limited and conflicting research on the impact of postnatal acetaminophen on neurodevelopment. The results of this study suggest that postnatal acetaminophen does not negatively impact neurodevelopment at 18 to 21 months in preterm infants born at <29 weeks gestational age. While these results need validation in larger and more longitudinal studies, this study provides reassurance for the use of postnatal acetaminophen in extremely preterm infants.

Rates and Determinants of Home Nasogastric Tube Feeding in Infants Born Very Preterm.

OBJECTIVE: To examine rates and determinants of home nasogastric (NG)-tube feeding at hospital discharge in a cohort of very preterm infants within the Canadian Neonatal Network (CNN). STUDY DESIGN: This was a population-based cohort study of infants born <33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2010, and December 31, 2018. We excluded infants who had major congenital anomalies, required gastrostomy-tube, or were discharged to non-CNN facilities. Multivariable logistic regression analysis was used to identify independent determinants of home NG-tube feeding at hospital discharge. RESULTS: Among the 13 232 infants born very preterm during the study period, 333 (2.5%) were discharged home to receive NG-tube feeding. Rates of home NG-tube feeding varied across Canadian NICUs, from 0% to 12%. Determinants of home NG-tube feeding were gestational age (aOR 0.94 per each gestational week increase, 95% CI 0.88-0.99); duration of mechanical ventilation (aOR 1.02 per each day increase, 95% CI 1.01-1.02); high illness severity at birth (aOR 1.32, 95% CI 1.01-1.74); small for gestational age (aOR 2.06, 95% CI 1.52-2.78); male sex (aOR 0.61, 95% CI 0.49-0.77); severe brain injury (aOR 1.60, 95% CI 1.10-2.32); and bronchopulmonary dysplasia (aOR 2.22, 95% CI 1.67-2.94). CONCLUSIONS: Rates of home NG-tube feeding varied widely between Canadian NICUs. Higher gestational age and male sex reduced the odds of discharge home to receive NG-tube feeding; and in contrast small for gestational age, severe brain injury, prolonged duration on mechanical ventilation and bronchopulmonary dysplasia increased the odds.

Neonatal outcomes of twins <29 weeks gestation of mothers with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. METHODS: Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. RESULTS: Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. CONCLUSION: Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. IMPACT: Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

Impact of Lockdown Measures during COVID-19 Pandemic on Pregnancy and Preterm Birth.

OBJECTIVE: The objective of this study is to assess the effect of the lockdown measures during the coronavirus disease 2019 (COVID-19) pandemic on pregnancy outcomes of women who were not affected by severe acute respiratory syndrome coronavirus 2 infection. STUDY DESIGN: We used data from the perinatal health program and neonatal databases to conduct a cohort analysis of pregnancy outcomes during the COVID-19 lockdown in the Calgary region, Canada. Rates of preterm birth were compared between the lockdown period (March 16 to June 15, 2020) and the corresponding pre-COVID period of 2015 to 2019. We also compared maternal and neonatal characteristics of preterm infants admitted to neonatal intensive care units (NICUs) in Calgary between the two periods. FINDINGS: A total of 4,357 and 24,160 live births occurred in the lockdown and corresponding pre-COVID period, respectively. There were 366 (84.0 per 1,000 live births) and 2,240 (92.7 per 1,000 live births) preterm births in the lockdown and corresponding pre-COVID period, respectively (p = 0.07). Rates of very preterm and very-low-birth-weight births were lower in the lockdown period compared with the corresponding pre-COVID period (11.0 vs. 15.6 and 9.0 vs. 14.4 per 1,000 live births, p = 0.02 and p = 0.005, respectively). There was no difference in spontaneous stillbirth between the two periods (3.7 vs. 4.1 per 1,000 live birth, p = 0.71). During the lockdown period, the likelihood of multiple births was lower (risk ratio [RR] 0.73, 95% confidence interval [CI]: 0.60-0.88), while gestational hypertension and clinical chorioamnionitis increased (RR 1.24, 95%CI: 1.10-1.40; RR 1.33, 95%CI 1.10-1.61, respectively). CONCLUSION: Observed rates of very preterm and very-low-birth-weight births decreased during the COVID-19 lockdown. Pregnant women who delivered during the lockdown period were diagnosed with gestational hypertension and chorioamnionitis more frequently than mothers in the corresponding pre-COVID period. KEY POINTS: · Lockdown measures to reduce COVID-19 transmission were associated with a lower rate of preterm birth.. · Mental and physical wellbeing of pregnant women were significantly affected by the lockdown measures.. · A comprehensive public health plan to relieve psychosocial stress during pregnancy is required..

High Early Parenteral Lipid in Very Preterm Infants: A Randomized-Controlled Trial.

OBJECTIVE: To determine whether high early parenteral soybean oil lipid intake in very low birth weight (VLBW) infants in the first week after birth decreases the proportion of weight loss and subsequently the incidence of extrauterine growth restriction (EUGR). STUDY DESIGN: This was a randomized controlled trial of appropriate for gestational- ge VLBW infants. Lipid intake in the control group started at 0.5-1 g/kg per day and increased daily by 0.5-1 g/kg per day till reaching 3 g/kg per day. The intervention group was started on 2 g/kg per day that increased to 3 g/kg per day the following day. RESULTS: Of the 176 infants assessed for eligibility, 83 were included in the trial. Infants in the intervention group were started on lipid sooner (13.8 ± 7.8 vs 17.5 ± 7.8 hour; P = .03) and had higher cumulative lipid intake in the first 7 days of age (13.5 ± 4.2 vs 10.9 ± 3.5 g/kg per day; P = .03). Infants in the intervention group had a lower percentage of weight loss (10.4 vs 12.7%; P = .02). The mean triglyceride level was higher in the intervention group (1.91 ± 0.79 vs 1.49 ± 0.54 mmol/L; P = .01), however, hypertriglyceridemia was similar between the 2 groups. The incidence of EUGR was lower in the intervention group (38.6% vs 67.6%; P = .01). Head circumference z score was higher in the intervention group (-1.09 ± 0.96 vs -1.59 ± 0.98; P = .04). CONCLUSIONS: In VLBW infants, provision of a high early dose of parenteral lipid in the first week of age results in less weight loss and lower incidence of EUGR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03594474.

Neonatal coning secondary to hypoxic ischaemic encephalopathy: A case study and literature review.

INTRODUCTION: Brain herniation is an extremely rare complication of hypoxic ischaemic encephalopathy (HIE) in the neonatal period with only a single report described. We report a 2-day-old term infant with severe HIE, who developed diffuse brain oedema and herniation. CASE PRESENTATION AND DESCRIPTION: A term female infant delivered by vacuum, required therapeutic hypothermia for severe encephalopathy. At 36 hours of age, a marked change in neurological status was noted with signs of brainstem involvement. A head Computed Tomography Scan showed uncal and tonsillar herniation. CONCLUSION: Vigilance in monitoring neonatal neurological status during therapeutic hypothermia is imperative for early brain herniation detection.

Effect of Maternal Docosahexaenoic Acid Supplementation on Bronchopulmonary Dysplasia-Free Survival in Breastfed Preterm Infants: A Randomized Clinical Trial.

Importance: Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective: To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia-free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants: Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions: There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks' postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures: The primary outcome was bronchopulmonary dysplasia-free survival in infants at 36 weeks' postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results: Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, -5.0% [95% CI, -11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04], P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, -3.9% [95% CI, -6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13], P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73], P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance: Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia-free survival at 36 weeks' postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration: ClinicalTrials.gov Identifier: NCT02371460.

Outcomes of singleton small for gestational age preterm infants exposed to maternal hypertension: a retrospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of small for gestational age (SGA). Preterm SGA infants have higher rates of adverse outcomes than appropriate for gestational age infants. However, the outcomes are not well established in the setting of HDP. METHODS: Retrospective population-based study using the Canadian Neonatal Network database from January 1, 2010 to December 31, 2016 of SGA infants <33 weeks gestation. Using multivariable models, we determined the adjusted odds ratios (AORs) with 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, and patent ductus arteriosus (PDA) in infants of HDP mothers and compared them to infants of non-HDP mothers. RESULTS: Of the 2081 eligible SGA infants, 1317 (63%) were born to HDP mothers and had lower odds of mortality (AOR 0.57, 95% CI 0.39-0.83) and BPD (AOR 0.69, 95% CI 0.53-0.90). Sub-group analysis demonstrated decreased mortality in 26-28 and 29-32 weeks gestation groups, decreased BPD in 29-32 weeks gestation group, and decreased PDA in <26 weeks gestation group. CONCLUSION: Preterm SGA infants of HDP mothers have lower odds of mortality and BPD compared to infants of non-HDP mothers.

Dexmedetomidine Use in a Tertiary Care NICU: A Descriptive Study.

BACKGROUND: Continuous infusions of dexmedetomidine are increasingly used for sedation in critically ill pediatric patients. Emerging data suggest potential benefits when used for sedation in neonates, including reduced sedative requirements and earlier enteral feeds. OBJECTIVE: To describe the use, adverse effects, and signs of withdrawal in a cohort of neonates receiving dexmedetomidine, the majority of whom were receiving concomitant opioids. METHODS: This was a retrospective, descriptive review of 38 neonates receiving dexmedetomidine in a medical surgical neonatal intensive care unit, including data on duration of use, dose, adverse effects, weaning, and signs of withdrawal. RESULTS: Dexmedetomidine was used for a median of 183 hours, at a median maximum dose of 0.5 µg/kg/h. Premature infants were started on dexmedetomidine at a later chronological age than term infants (41 vs 9 days, P = 0.004). Of 18 patients receiving an opioid infusion at the time of dexmedetomidine initiation, 67% had a dose reduction in opioids by 24 hours. The majority (89%) of neonates had at least 1 potentially related adverse effect during the dexmedetomidine infusion, though no discontinuations were needed as a result. In all, 80% of patients had their dexmedetomidine gradually weaned off, and 71% had at least 1 sign of withdrawal. CONCLUSIONS AND RELEVANCE: In this cohort, dexmedetomidine was often used in a postsurgical setting, with concomitant opioids, over prolonged periods. These factors appear to affect and likely confound the rates of adverse effects and withdrawal signs from dexmedetomidine. Clinicians considering the use of dexmedetomidine in a similar population can draw guidance from our data.

The Impact of Prenatal Diagnosis of Selected Central Nervous System Anomalies for Prenatal Counselling Based on Significant Pregnancy Morbidity and Neonatal Outcomes.

BACKGROUND & OBJECTIVES: Prenatal screening and diagnostic imaging advances have led to an increased detection of CNS anomalies, including ventriculomegaly/congenital hydrocephalus (HCP), Dandy-Walker malformation (DWM), and myelomeningocele (MMC). Data on pregnancy outcomes and the impact of prenatal diagnosis on neonatal outcomes is limited. Our study aimed to provide data on obstetric and neonatal outcomes following prenatal diagnosis of one of three CNS anomalies. METHODS: A retrospective search of two databases in Alberta, Canada and NICU chart review of cases between 2001 and 2011was completed. Primary outcomes for each group were pregnancy outcome (live birth, stillbirth, and termination) and detection rate. Secondary outcomes were live and total birth prevalence, mode of delivery, GA at delivery, and length of NICU stay for inborn versus outborn patients. RESULTS: Prenatal detection rates were 91.6% (HCP), 83.4% (DWM), and 92.9 % (MMC). Termination rates were 30.2% (DWM), 34.2% (HCP), and 48.5% (MMC). Median GA (weeks, range) at diagnosis were 22 (17-38), 20 (12-37), and 20.5 (18-34) for HCP, DWM, and MMC, respectively. Rate of Caesarean section for fetal indication was 50.0%, 44.4%, and 42.9% for HCP, DWM, and MMC, respectively. Median NICU length of stay was longer for outborn patients than inborn patients and were as follows: (range) 33.0 (21-38) versus 8.5 (1-49) d (HCP), and 29 (29-57) versus 14 (2-75) d (DWM). CONCLUSION: This study provides termination rates, obstetric interventions, and NICU length of stay for prenatally-identified CNS anomalies. Collectively, this study assists prenatal counselling women with a fetus affected by a described CNS anomaly.

Elective transfers of preterm neonates to regional centres on non-invasive respiratory support is cost effective and increases tertiary care bed capacity.

AIM: Managing capacity at regional facilities caring for sick neonates is increasingly challenging. This study estimated the clinical and economic impact of the elective transfer of stable infants requiring nasal continuous positive airway pressure (NCPAP) from level three to level two neonatal intensive care units (NICUs) within an established clinical network of five NICUs. METHODS: We retrospectively analysed the records of 99 stable infants transferred on NCPAP between two level three NICUs and three level two NICUs in Calgary, Canada, between June 2014 and May 2016. RESULTS: The median gestational age and weight at birth were 28 weeks and 955 g, and the median corrected gestational age and weight at transfer were 33 weeks and 1597 g, respectively. This resulted in cost savings of $2.65 million Canadian dollars during the two-year study period, and 848 level three NICU days were freed up for potentially sick neonates. There were no adverse events associated with the transfers. CONCLUSION: The elective transfer of stable neonates on NCPAP from level three to level two NICUs within an established clinical network led to substantial cost savings, was safe and increased the bed capacity at the two level three NICUs.

Comparison of the Fagerström Test for Cigarette Dependence and the Heaviness of Smoking Index in the Second and Third Trimester of Pregnancy.

INTRODUCTION: Smoking cessation at any stage of pregnancy can benefit the mother and fetus. Cigarette dependence is a significant factor in women who continue to smoke during pregnancy and accurate assessment of cigarette dependence can be helpful in planning smoking cessation programs. The objective of our study was to investigate the validity of the Fagerstrom Test for Cigarette Dependence (FTCD) and Heaviness of Smoking Index (HSI) as measures of cigarette dependence in the second and third trimesters of pregnancy by comparing them to serum cotinine levels. METHODS: Prospective cohort study of 167 women in their second and third trimester of pregnancy who self-reported cigarette smoking. They were administered the FTCD questionnaire and blood was drawn for cotinine measurements using a direct enzyme linked immunoassay. Linear regression was used to adjust for maternal age, body mass index, gestation, and parity to investigate the association between cotinine levels and the two scores. RESULTS: Both the FTCD and HSI correlated significantly with serum cotinine levels (Spearman coefficient 0.42 and 0.37, respectively, p < .001). The correlation coefficients of both scores were higher in primigravidas (n = 51) compared to multigravidas, but the difference was statistically nonsignificant. Using multiple linear regression, both scores were significantly related to serum cotinine levels. For each unit increase in the FTCD and HSI, the serum cotinine level increased by 21.4 ng/mL (95% confidence interval 10.1-32.7, p <0.001) and 37 ng/mL (95% confidence interval 18.6-55.4, p < 0.001), respectively. CONCLUSIONS: Both the FTCD and HSI can be used to assess cigarette dependence in the second and third trimester of pregnancy. IMPLICATIONS: There is lack of data on the validity of the FTCD and the HSI as markers of cigarette dependence during the second and third trimester of pregnancy. Our study suggests that both the FTCD and HSI perform well in assessing cigarette dependence in the second and third trimester of pregnancy and can be used to plan smoking cessation programs.

Congenital tuberculosis in an extremely preterm infant conceived after in vitro fertilization: case report.

BACKGROUND: Congenital tuberculosis is a rare manifestation of tuberculosis. The diagnosis is often delayed, especially in preterm neonates because of the non-specific clinical presentation and the lack of awareness of maternal disease prior to pregnancy. CASE PRESENTATION: We report a case of congenital tuberculosis in an infant born at 24 weeks of gestation to a mother who presented with uncontrolled seizures during preterm labor. Maternal diagnosis was initially made by placental pathology, and later confirmed by isolation of Mycobacterium tuberculosis in urine, gastric aspirates and sputum. Full screening was performed on the newborn infant, and both mother and infant were successfully treated for tuberculosis with a four drug regimen. CONCLUSION: Pregnancy can exacerbate latent tuberculosis and women originating from endemic areas are especially susceptible. The best way to prevent congenital tuberculosis is to have a high index of suspicion and identify and treat tuberculosis in pregnant women.

Preeclampsia and the Risk of Bronchopulmonary Dysplasia in Preterm Infants Less Than 32 Weeks' Gestation.

Objective Angiogenesis is essential for normal lung development. The objective of our study was to test the hypothesis that preeclampsia, an antiangiogenic state, is a risk factor for bronchopulmonary dysplasia (BPD). Design Prospective cohort study of infants less than 32 weeks' gestation born to mothers with preeclampsia between January 2007 and June 2010 at a single tertiary care center. Their BPD outcome was compared with infants born to the next two normotensive mothers with a ± 1 week gestational age difference. BPD was defined as oxygen dependency at 36 weeks' postmenstrual age. Multivariable binary regression was used to estimate the risk ratio (RR) of BPD with preeclampsia exposure and adjust for confounders. Results Of 102 infants in the preeclampsia group, 23 (23%) developed BPD and of the 217 infants in the normotensive group, 56 (26%) developed BPD. On multivariable binary regression modeling, preeclampsia was not a risk factor for development of BPD (RR: 0.5, 95% confidence interval [CI]: 0.20-1.20). Surfactant use, Score for Neonatal Acute Physiology Perinatal Extension-II score, sepsis, blood transfusion, and intrauterine growth restriction (IUGR) were significant risk factors for BPD. Conclusion In our cohort, preeclampsia was not a significant risk factor for BPD. IUGR infants of preeclamptic and normotensive mothers were at higher risk for BPD.

Assessment of initial vancomycin dosing in neonates.

BACKGROUND: Vancomycin is recommended for optimal treatment of late-onset sepsis caused by coagulase-negative Staphylococcus in neonates. OBJECTIVES: To assess the performance of an empirical vancomycin dosing regimen in achieving target trough levels, and to revise this regimen if needed. METHODS: Data regarding doses and levels were collected and pharmacokinetic parameters were calculated, where possible, for neonates receiving vancomcyin in a neonatal intensive care unit. The primary measure was the percentage of neonates with initial prevancomycin levels of <10 mg/L, 10 mg/L to 20 mg/L and >20 mg/L. Secondary measures included the percentage of neonates with extrapolated trough levels in these ranges, total daily doses that achieved target levels (10 mg/L to 20 mg/L) and total daily doses/dosing intervals that were pharmacokinetically predicted to achieve trough levels of 15 mg/L. RESULTS: Of 153 infants started on the empirical regimen (15 mg/kg/day to 45 mg/kg/day, depending on postnatal age and weight), 34.2% initially achieved target trough levels (mean 8.7 mg/L). Analysis of actual doses and pharmacokinetically predicted doses required to reach target levels suggested increasing the empirical dosing for all neonatal age groups. The revised regimen used in the present study (20 mg/kg/day to 40 mg/kg/day, depending on postmenstrual age and postnatal age) was predicted to result in 72% of infants achieving initial target trough levels (mean 15.4 mg/L). CONCLUSIONS: A revised empirical vancomycin dosage regimen for neonates was required based on poor achievement of target trough levels (10 mg/L to 20 mg/L) using the previous regimen. The modified regimen is predicted to reach target trough levels more often and increase the mean initial trough levels achieved. This regimen requires clinical validation in an independent cohort in the future.

HISTORIQUE: La vancomycine est recommandée pour le traitement optimal du sepsis à apparition tardive causé par le staphylocoque à coagulase négative chez les nouveau-nés. OBJECTIFS: Évaluer le rendement d'une posologie empirique de vancomycine pour obtenir les concentrations minimales ciblées et réviser cette posologie, au besoin. MÉTHODOLOGIE: Les chercheurs ont colligé les données relatives aux doses et aux concentrations et calculé les paramètres pharmacocinétiques, dans la mesure du possible, chez les nouveau-nés d'une unité de soins intensifs néonatals qui recevaient de la vancomycine. La mesure primaire était le pourcentage de nouveau-nés dont les concentrations étaient inférieures à 10 mg/L, se situaient entre 10 mg/L et 20 mg/L et étaient supérieures à 20 mg/L avant l'administration de vancomycine. Les mesures secondaires incluaient le pourcentage de nouveau-nés dont les concentrations minimales extrapolées se situaient dans ces plages, dont les doses quotidiennes totales atteignaient les concentrations ciblées (10 mg/L à 20 mg/L) et dont le ratio entre les doses quotidiennes totales et l'intervalle entre les doses devait, sur le plan pharmacocinétique, atteindre des concentrations minimales de 15 mg/L. RÉSULTATS: Des 153 nourrissons à qui on avait d'abord administré la posologie empirique (15 mg/kg/jour à 45 mg/kg/jour, selon leur âge postnatal et leur poids), 34,2 % ont obtenu les concentrations minimales initiales ciblées (moyenne de 8,7 mg/L). D'après l'analyse des doses réelles et des doses prédites sur le plan pharmacocinétique pour atteindre les concentrations minimales ciblées, il semblait nécessaire d'accroître la posologie empirique dans tous les groupes d'âge néonatal. Cette analyse prédisait que la posologie révisée utilisée dans la présente étude (20 mg/kg/jour à 40 mg/kg/jour selon l'âge postmenstruel et l'âge postnatal) permettrait à 72 % des nourrissons d'obtenir les concentrations minimales initiales ciblées (moyenne de 15,4 mg/L). CONCLUSIONS: Il a fallu réviser la posologie empirique de vancomycine chez les nouveau-nés parce qu'ils n'atteignaient pas les concentrations minimales ciblées (10 mg/L à 20 mg/L) au moyen des posologies antérieures. Il est prévu que la posologie modifiée atteindra plus souvent les concentrations minimales ciblées et accroîtra la concentration minimale initiale ciblée moyenne obtenue. Cette posologie devra être validée sur le plan clinique auprès d'une cohorte indépendante.

Assessment of initial vancomycin dosing in neonates.

BACKGROUND: Vancomycin is recommended for optimal treatment of late-onset sepsis caused by coagulase-negative Staphylococcus in neonates. OBJECTIVES: To assess the performance of an empirical vancomycin dosing regimen in achieving target trough levels, and to revise this regimen if needed. METHODS: Data regarding doses and levels were collected and pharmacokinetic parameters were calculated, where possible, for neonates receiving vancomcyin in a neonatal intensive care unit. The primary measure was the percentage of neonates with initial prevancomycin levels of <10 mg/L, 10 mg/L to 20 mg/L and >20 mg/L. Secondary measures included the percentage of neonates with extrapolated trough levels in these ranges, total daily doses that achieved target levels (10 mg/L to 20 mg/L) and total daily doses/dosing intervals that were pharmacokinetically predicted to achieve trough levels of 15 mg/L. RESULTS: Of 153 infants started on the empirical regimen (15 mg/kg/day to 45 mg/kg/day, depending on postnatal age and weight), 34.2% initially achieved target trough levels (mean 8.7 mg/L). Analysis of actual doses and pharmacokinetically predicted doses required to reach target levels suggested increasing the empirical dosing for all neonatal age groups. The revised regimen used in the present study (20 mg/kg/day to 40 mg/kg/day, depending on postmenstrual age and postnatal age) was predicted to result in 72% of infants achieving initial target trough levels (mean 15.4 mg/L). CONCLUSIONS: A revised empirical vancomycin dosage regimen for neonates was required based on poor achievement of target trough levels (10 mg/L to 20 mg/L) using the previous regimen. The modified regimen is predicted to reach target trough levels more often and increase the mean initial trough levels achieved. This regimen requires clinical validation in an independent cohort in the future.

HISTORIQUE: La vancomycine est recommandée pour le traitement optimal du sepsis à apparition tardive causé par le staphylocoque à coagulase négative chez les nouveau-nés. OBJECTIFS: Évaluer le rendement d'une posologie empirique de vancomycine pour obtenir les concentrations minimales ciblées et réviser cette posologie, au besoin. MÉTHODOLOGIE: Les chercheurs ont colligé les données relatives aux doses et aux concentrations et calculé les paramètres pharmacocinétiques, dans la mesure du possible, chez les nouveau-nés d'une unité de soins intensifs néonatals qui recevaient de la vancomycine. La mesure primaire était le pourcentage de nouveau-nés dont les concentrations étaient inférieures à 10 mg/L, se situaient entre 10 mg/L et 20 mg/L et étaient supérieures à 20 mg/L avant l'administration de vancomycine. Les mesures secondaires incluaient le pourcentage de nouveau-nés dont les concentrations minimales extrapolées se situaient dans ces plages, dont les doses quotidiennes totales atteignaient les concentrations ciblées (10 mg/L à 20 mg/L) et dont le ratio entre les doses quotidiennes totales et l'intervalle entre les doses devait, sur le plan pharmacocinétique, atteindre des concentrations minimales de 15 mg/L. RÉSULTATS: Des 153 nourrissons à qui on avait d'abord administré la posologie empirique (15 mg/kg/jour à 45 mg/kg/jour, selon leur âge postnatal et leur poids), 34,2 % ont obtenu les concentrations minimales initiales ciblées (moyenne de 8,7 mg/L). D'après l'analyse des doses réelles et des doses prédites sur le plan pharmacocinétique pour atteindre les concentrations minimales ciblées, il semblait nécessaire d'accroître la posologie empirique dans tous les groupes d'âge néonatal. Cette analyse prédisait que la posologie révisée utilisée dans la présente étude (20 mg/kg/jour à 40 mg/kg/jour selon l'âge postmenstruel et l'âge postnatal) permettrait à 72 % des nourrissons d'obtenir les concentrations minimales initiales ciblées (moyenne de 15,4 mg/L). CONCLUSIONS: Il a fallu réviser la posologie empirique de vancomycine chez les nouveau-nés parce qu'ils n'atteignaient pas les concentrations minimales ciblées (10 mg/L à 20 mg/L) au moyen des posologies antérieures. Il est prévu que la posologie modifiée atteindra plus souvent les concentrations minimales ciblées et accroîtra la concentration minimale initiale ciblée moyenne obtenue. Cette posologie devra être validée sur le plan clinique auprès d'une cohorte indépendante.

Clinical Outcomes of Cardiogenic Shock due to Spontaneous Coronary Artery Dissection versus Cardiogenic Shock due to Coronary Artery Disease.

Spontaneous coronary artery dissection (SCAD) can be treated conservatively. However, some SCAD patients can develop cardiogenic shock (CS). We evaluated the outcomes of SCAD-related CS using data from a national population-based cohort study from January 1, 2016, to December 30, 2019. In our study of 32,640 patients with SCAD, about 10.6% of patients presented with cardiogenic shock. We found that SCAD patients with cardiogenic shock had higher mortality as well as greater complications including use of mechanical circulatory devices, arrythmias, respiratory support, and acute heart failure compared to those without cardiogenic shock. When comparing cardiogenic shock due to SCAD with that due to coronary artery disease (CAD), we found that while mortality rates were similar, those with cardiogenic shock due to SCAD were associated with higher risk of use of mechanical circulatory support, major bleeding, blood transfusion and respiratory failure.