Effectiveness of Alberta Family Integrated Care on infant length of stay in level II neonatal intensive care units: a cluster randomized controlled trial.

BACKGROUND: Parents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits. METHODS: In this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge. RESULTS: We enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups. CONCLUSIONS: Alberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.

Respiratory outcomes of late preterm infants of mothers with early and late onset preeclampsia.

OBJECTIVE: To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants. STUDY DESIGN: Cohort study of late preterm infants admitted to a tertiary care NICU from January 2014-July 2015. Outcomes of late preterm infants of EOPE mothers were compared with the next late preterm infant of a LOPE mother and the next two late preterm infants of normotensive non-PE mothers. Primary outcome comprised use of continuous positive airway pressure, mechanical ventilation and/or surfactant in the 24 h after birth. RESULTS: Compared to normotensives (n = 131), adjusted odds ratio (AORs) of the primary outcome was higher in the EOPE (n = 64) and LOPE (n = 65) groups but reached statistical significance only in the EOPE group, AORs 12.9, 95% CI 3.5-37 and 2.7, 95% CI 0.95-8.1, respectively. CONCLUSIONS: Compared to late preterm infants of normotensive and LOPE mothers, infants of mothers with EOPE have significantly higher respiratory morbidity.

Evolution of empiric vancomycin dosing in a neonatal population.

BACKGROUND: In 2014, we assessed the effectiveness of our neonatal vancomycin empirical dosing regimen (15-45 mg/kg/day) which led to development of a revised regimen (20-60 mg/kg/day). OBJECTIVE: To validate the revised empirical vancomycin dosage regimen in achieving target troughs. METHODS: The primary outcome of this multicenter retrospective before-and-after cohort study was the proportion of neonates in the present cohort achieving trough levels below, at or above target (<10, 10-20 and >20 mg/L). Secondary outcomes included difference between cohorts (historical and present) in mean troughs and proportion of patients achieving target levels. RESULTS: Out of 118 participants, 63 (53.39%) achieved target troughs, 44 (37.29%) had below target troughs and 11 (9.32%) reached above target levels. Mean trough levels and proportion of patients achieving target levels were higher in the present versus historical cohort (p < 0.01 for all comparisons). CONCLUSIONS: The revised empiric dosing regimen was more effective in achieving target serum trough concentrations.

Effectiveness of Injectable Ibuprofen Salts and Indomethacin to Treat Patent Ductus Arteriosus in Preterm Infants: Observational Cohort Study.

BACKGROUND: There is no injectable ibuprofen product marketed to treat patent ductus arteriosus (PDA) in newborns in Canada. The authors' institution has used ibuprofen arginine in the past. In the absence of published evidence supporting use of this salt form of ibuprofen for neonatal PDA, a retrospective analysis was undertaken. OBJECTIVE: To compare the effectiveness and adverse effects of ibuprofen arginine, ibuprofen tromethamine, and indomethacin in the treatment of PDA. METHODS: This retrospective observational cohort study, for patients admitted between 2009 and 2015, included preterm infants with symptomatic PDA who received at least one dose of injectable indomethacin, ibuprofen tromethamine, or ibuprofen arginine. Three effectiveness end points were analyzed: closure after one course of treatment, repeat medical treatment, and surgical ligation. The secondary end points included acute kidney injury, necrotizing enterocolitis, chronic lung disease, and time to full enteral feeding. RESULTS: A total of 179 infants were included. There were no differences among groups in terms of closure after one course of treatment (37/54 [69%] with indomethacin, 42/70 [60%] with ibuprofen tromethamine, and 28/55 [51%] with ibuprofen arginine; p = 0.21) or surgical ligation (10/54 [19%] with indomethacin, 13/70 [19%] with ibuprofen tromethamine, and 12/55 [22%] with ibuprofen arginine; p = 0.88). However, there was a difference regarding use of a repeat course of treatment, ibuprofen arginine having the highest rate (8/54 [15%] with indomethacin, 18/70 [26%] with ibuprofen tromethamine, and 20/55 [36%] with ibuprofen arginine; p = 0.04). After adjustment for gestational age, the association between ibuprofen arginine and increased use of a repeat course of treatment remained significant. The groups did not differ with respect to adverse effects. CONCLUSION: These results highlight the potential for differences in effectiveness among various salt forms of injectable ibuprofen and indomethacin. Because of the small sample size and retrospective methodology, confirmation of the present results through a larger prospective study is needed.

CONTEXTE: Il n'y a pas sur le marché de produit injectable à base d'ibuprofène pour traiter la persistance du canal artériel (PCA) chez le nouveau-né au Canada. L'ibuprofène arginine a été utilisé auparavant dans l'établissement de santé des auteurs. En l'absence de données publiées appuyant l'utilisation de ce médicament sous forme de ce sel pour traiter la PCA chez le nouveau-né, une analyse rétrospective a été réalisée. OBJECTIF: Comparer l'efficacité et les effets indésirables de l'ibuprofène arginine, de l'ibuprofène trométhamine et de l'indométhacine dans le traitement de la PCA. MÉTHODES: Cette étude de cohorte observationnelle rétrospective, au sujet de patients hospitalisés entre 2009 et 2015, incluait des nourrissons prématurés atteints d'une PCA symptomatique ayant reçu par injection au moins une dose d'indométhacine, d'ibuprofène trométhamine ou d'ibuprofène arginine. Trois paramètres d'évaluation de l'efficacité ont été analysés : la fermeture après un seul traitement, la répétition du traitement médical et la ligature chirurgicale. Les paramètres d'évaluation secondaires étaient les cas d'insuffisance rénale aiguë, d'entérocolite nécrosante et de maladie pulmonaire chronique ainsi que le temps pour atteindre l'alimentation entérale complète. RÉSULTATS: Au total, 179 nourrissons ont été admis à l'étude. Aucune différence n'a été relevée entre les groupes en ce qui touche à la fermeture après un seul traitement (37/54 [69 %] pour l'indométhacine, 42/70 [60 %] pour l'ibuprofène trométhamine et 28/55 [51 %] pour l'ibuprofène arginine; p = 0,21) ou à la ligature chirurgicale (10/54 [19 %] pour l'indométhacine, 13/70 [19 %] pour l'ibuprofène trométhamine et 12/55 [22 %] pour l'ibuprofène arginine; p = 0,88). Cependant, une différence a été observée pour ce qui est de la répétition du traitement et l'ibuprofène arginine a obtenu le taux le plus élevé (8/54 [15 %] pour l'indométhacine, 18/70 [26 %] pour l'ibuprofène trométhamine et 20/55 [36 %] pour l'ibuprofène arginine; p = 0,04). Après ajustement pour l'âge gestationnel, l'association entre l'utilisation de l'ibuprofène arginine et une augmentation du recours à un second traitement demeurait significative. Il n'y avait pas de différence entre les groupes en ce qui touche aux effets indésirables. CONCLUSION: Ces résultats soulignent la possible différence d'efficacité parmi les divers sels d'ibuprofène injectable et l'indométhacine. Cependant, en raison de la petite taille de l'échantillon et de l'emploi d'une méthodologie rétrospective, une étude prospective plus importante doit être menée pour confirmer les résultats de la présente étude.

Use and timing of surfactant administration: impact on neonatal outcomes in extremely low gestational age infants born in Canadian Neonatal Intensive Care Units.

BACKGROUND: Use, timing and doses of surfactant in preterm infants are variable in practice in modern NICUs. OBJECTIVE: The objective of this study is to explore the association between use and timing of surfactant administration and common neonatal adverse outcomes in preterm infants with gestational age (GA) < 28 weeks. MATERIAL AND METHODS: Neonates admitted to a participating Canadian Neonatal Network NICU between 2013 and 2015 were studied. Infants were divided into three groups based on surfactant administration: none, early (within 30 min of life), and late surfactant (>30 min). The primary outcome was a composite of ≥2 predefined outcomes: bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and severe neurological injury (intraventricular hemorrhage or intraventricular hemorrhage (IVH) grade III/IV ± periventricular leukomalacia). RESULTS: Of 2512 eligible neonates, 430 were in the early, and 1228 were in the late surfactant group. There was no difference in the primary outcome (p = .88). There was a slightly lower risk of late onset sepsis [25% versus 29%, adjusted odds ratio (aOR): 0.8; 95% CI: 0.6-0.9] and ROP (12.4 versus 15%, aOR: 0.7; 95% CI: 0.5-0.9) in the early surfactant group. CONCLUSIONS: In preterm neonates, early administration of surfactant within 30 min of life was not associated with an increased risk of the primary composite outcome, but did have decreased rates of late onset sepsis and ROP.

Extended-interval Dosing of Gentamicin in Premature Neonates Born at <32 Weeks' Gestation and >7 Days of age.

PURPOSE: Extended-interval dosing (EID) regimens of gentamicin have been validated for treating confirmed or suspected early- and late-onset sepsis in preterm infants in the first week of life. Despite the marked changes in volume of distribution and renal clearance in preterm infants after the first few days of life, few studies have validated EID regimens of gentamicin in this population. The objective of the study was to evaluate an EID regimen of gentamicin in infants born at <32 weeks' gestational age and aged >7 days. METHODS: This observational study of an EID regimen was conducted in 39 infants. Dosing interval was based on the serum drug concentration at 22 hours after the administration of the first dose of 5 mg/kg. Gentamicin peak (5-12 µg/mL) and trough (<2 µg/mL) levels were compared to those in a historical control group of 39 infants who received traditional-interval dosing (TID) of 2.5 mg/kg of gentamicin with dosing intervals of 8, 12, or 24 hours. FINDINGS: There were no differences in birthweight, gestational age at birth, postmenstrual age, weight at the start of gentamicin administration, postnatal age, small for gestational age status, antenatal corticosteroid use, or postnatal indomethacin exposure between the 2 groups. In the EID group, dosing intervals were 24 hours in 30 infants, 36 hours in 6 infants, and 48 hours in 3 infants. Compared with the TID group (n = 39), the EID group had a significantly higher peak level (median, 9.0 vs 4.7 µg/mL) and a significantly lower trough level (median, 0.7 vs 1.1 µg/mL) (both, P < 0.001). On regression analysis, the postmenstrual age was correlated significantly with trough levels in the EID group. There was no adverse effect on renal function in either group. On follow-up, 1 infant in the EID group and 2 infants in the TID group had evidence of sensorineural hearing loss. IMPLICATIONS: In infants born at <32 weeks' gestation and >7 days of age, an EID gentamicin regimen, with a dosing interval based on a single concentration measurement at 22 hours after the administration of the first dose, achieved therapeutic peak and trough levels and performed significantly better than did a TID regimen in reaching target peak and trough levels. Larger-scale trials are needed for assessing the clinical efficacy (treatment failure/success) of these regimens.

Performance of a dosage individualization table for extended interval gentamicin in neonates beyond the first week of life.

OBJECTIVE: To assess the performance of a gentamicin dosing table for the individualization of extended-interval dosing (EID) in a neonatal population >7 days old. METHODS: A prospective observational study was carried out on gentamicin concentrations achieved using a dosing table in neonates >7 days old. Neonates were given 5 mg/kg IV gentamicin; then a table using 22 h post-first dose gentamicin concentrations was used to individualize dosing intervals. Pre- and post-serum gentamicin concentrations were measured and used to calculate the true peak and trough concentrations achieved. RESULTS: Use of the table resulted in dosing intervals that provided appropriate peak (mean 9.8 ± 1.8 mg/L) and trough (mean 0.6 ± 0.3 mg/L) concentrations in all neonates (n = 38). All trough concentrations were <2 mg/L, 83% were <1 mg/L. The majority of peak concentrations were in the usual target range (87%, 5-12 mg/L), with a few being in a higher, although likely safe range (13%, 12.1-15.7 mg/L). CONCLUSIONS: Use of this dosing table to individualize extended-interval gentamicin dosages in neonates >7 days old resulted in appropriate peak and trough concentrations in all neonates studied. This allows appropriate extended-interval aminoglycoside dosages in neonates early in treatment.

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.

Impact of oxygen concentration on time to resolution of spontaneous pneumothorax in term infants: a population based cohort study.

BACKGROUND: Little evidence exists regarding the optimal concentration of oxygen to use in the treatment of term neonates with spontaneous pneumothorax (SP). The practice of using high oxygen concentrations to promote "nitrogen washout" still exists at many centers. The aim of this study was to identify the time to clinical resolution of SP in term neonates treated with high oxygen concentrations (HO: FiO2 ≥ 60%), moderate oxygen concentrations (MO: FiO2 < 60%) or room air (RA: FiO2 = 21%). METHODS: A population based cohort study that included all term neonates with radiologically confirmed spontaneous pneumothorax admitted to all neonatal intensive care units in Calgary, Alberta, Canada, within 72 hours of birth between 2006 and 2010. Newborns with congenital and chromosomal anomalies, meconium aspiration, respiratory distress syndrome, and transient tachypnea of newborn, pneumonia, tension pneumothorax requiring thoracocentesis or chest tube drainage or mechanical ventilation before the diagnosis of pneumothorax were excluded. The primary outcome was time to clinical resolution (hours) of SP. A Cox proportional hazards model was developed to assess differences in time to resolution of SP between treatment groups. RESULTS: Neonates were classified into three groups based on the treatment received: HO (n = 27), MO (n = 35) and RA (n = 30). There was no significant difference in time to resolution of SP between the three groups, median (range 25th-75th percentile) for HO = 12 hr (8-27), MO = 12 hr (5-24) and RA = 11 hr (4-24) (p = 0.50). A significant difference in time to resolution of SP was also not observed after adjusting for inhaled oxygen concentration [MO (a HR = 1.13, 95% CI 0.54-2.37); RA (a HR = 1.19, 95% CI 0.69-2.05)], gender (a HR = 0.87, 95% CI 0.53-1.43) and ACoRN respiratory score (a HR = 0.7, 95% CI 0.41-1.34). CONCLUSIONS: Supplemental oxygen use or nitrogen washout was not associated with faster resolution of SP. Infants treated with room air remained stable and did not require supplemental oxygen at any point of their admission.

Carboxyhemoglobin levels in umbilical cord blood of women with pre-eclampsia and intrauterine growth restriction.

OBJECTIVE: Pre-eclampsia (PE) and intrauterine growth restriction (IUGR) are associated with abnormal placentation. Heme oxygenase (HO) and carbon monoxide (CO) are involved in normal placental development and function and vasomotor control in the placenta. The objective of our study was to measure CO levels, as assessed by carboxyhemoglobin (COHb) levels in the umbilical cord arterial blood of women with PE, normotensive IUGR (<10th percentile for birth weight), and normotensive pregnancies with appropriate-for-gestational age (AGA) infants. DESIGN AND METHODS: We prospectively analyzed COHb levels in the umbilical arterial blood of women with PE, normotensive IUGR, and normotensive AGA pregnancies. Exclusion criteria included cigarette smoke exposure, hemolytic disorders, a positive direct anti-globulin test, chronic hypertension, fever, and any significant medical illness. COHb levels were measured using the ABL 725 blood gas analyzer. RESULTS: There were 41 women in the normotensive AGA group, 42 in the PE group, and 36 in the normotensive IUGR group. Maternal age, mode of delivery, gravidity, parity, and gender of the infants were similar in the three groups. Gestational age and birth weight were significantly higher in the normotensive AGA group compared with the other two groups. COHb levels were significantly lower in the PE group compared with the normotensive AGA group (0.38±0.06% vs. 0.77±0.11%, P<0.05). COHb levels, although lower in the normotensive IUGR group compared with the normotensive AGA group, did not reach statistical significance. CONCLUSION: Our data suggests the HO-CO system may have a role in the pathogenesis of PE. We also, for the first time, provide information on umbilical arterial COHb levels in normotensive IUGR pregnancies.

Extended interval dosing of gentamicin in premature neonates ≤ 28-week gestation.

AIM: To evaluate an extended interval dosing (EID) regimen of gentamicin in neonates ≤28-week gestation. METHODS: In 2008, an EID regimen for gentamicin was introduced for all neonates admitted to the NICU in Calgary. The dosing interval was based on a 22 h level after the first dose of 5mg/kg. We conducted an observational study in 33 infants ≤28-week gestation on the EID regimen from the first day of life and compared gentamicin peak and trough levels with a historical control of 34 infants who received gentamicin in a dose of 2.5 mg/kg every 24 h (TID, traditional interval dosing). RESULTS: In the EID group, based on the 22 h level, dosing interval was 36 h in 20 neonates and 48 h in 13 neonates. All neonates, except one, achieved therapeutic peak and trough levels. Compared to the TID group, the EID group had higher peak levels (median 9.8 µg/mL vs. 4.6 µg/mL, p < 0.001) with no difference in trough levels. With target peak levels of 5-12 µg/mL and trough levels of <2 µg/mL, a higher proportion of neonates in the TID group would need dose adjustment. CONCLUSION: In neonates ≤ 28-week gestation, an EID regimen from day one of life, using a single level 22 h after the first dose for dosing interval, achieves therapeutic peak and trough levels and more optimum peak levels as compared to a TID regimen.

Validation of a dosage individualization table for extended-interval gentamicin in neonates.

BACKGROUND: Extended-interval aminoglycoside dosing is increasingly used in neonates; however, guidance on how to monitor concentrations and adjust dosages accordingly is limited. OBJECTIVE: To prospectively validate the use of a 22-hour gentamicin concentration dosing table for the individualization of extended-interval dosing in the neonatal population by examining the peak and trough concentrations achieved through its use. METHODS: A prospective observational study was carried out on gentamicin concentrations achieved using a 22-hour post-first-dose gentamicin concentration dosing table for determining dosing intervals in neonates. Neonates (N = 104) in the first week of life, gestational age 23 weeks to full term, in level II and III neonatal intensive care units were included. Neonates were given gentamicin 5 mg/kg intravenously; a table using 22-hour post-first-dose gentamicin concentrations was then used to individualize dosing intervals. Pre- and post-serum gentamicin concentrations on the dosing interval indicated were measured with the second or third doses and used to calculate the peak and trough concentrations achieved. RESULTS: Use of the 22-hour post-first-dose gentamicin concentration dosing table resulted in dosing intervals that provided appropriate peak (mean 10.55 mg/L) and trough (mean 0.75 mg/L) concentrations (with second or third doses) in all neonates. All patients had trough concentrations less than 2 mg/L, and 73% had a trough concentration less than 1 mg/L. No peak concentrations were less than 5 mg/L, 82% of patients had a peak concentration from 5 to 12 mg/L, and the remaining 18% had concentrations from 12.1 to 16 mg/L. Peak and trough concentrations were similar across all gestational ages. CONCLUSIONS: Use of a 22-hour post-first-dose gentamicin concentration dosing table to individualize extended-interval gentamicin dosages in neonates resulted in appropriate peak and trough concentrations in all neonates studied. Use of this table will result in appropriate extended-interval aminoglycoside dosages in neonates early in treatment, using a single serum concentration.

Neonatal withdrawal syndrome due to maternal codeine use.

Neonatal withdrawal from maternal drugs and medications is not uncommon. Codeine-containing analgesic preparations given to pregnant mothers for headache have been identified as a cause of neonatal withdrawal syndrome. The present case highlights the importance of obtaining a detailed maternal drug history including prescription and nonprescription drugs, and highlights the need for prenatal counselling for women who are taking narcotic-containing analgesics.

Il n'est pas rare de sevrer un nouveau-né des drogues et médicaments qu'a consommés la mère. Il est établi que les préparations analgésiques qui contiennent de la codéine et qui sont données aux femmes enceintes pour soulager les maux de tête représentent une cause de syndrome de sevrage néonatal. Le présent cas fait ressortir l'importance d'obtenir les antécédents détaillés de la mère quant à ses médicaments, qu'ils soient sur ordonnance ou en vente libre, ainsi que la nécessité de donner des conseils prénatals aux femmes qui prennent des analgésiques contenant des narcotiques.

Subcutaneous fat necrosis as a complication of therapeutic hypothermia in a term neonate.

Subcutaneous fat necrosis of the newborn (SCFN) is a benign self-limited disorder commonly associated with hypothermia and perinatal asphyxia. SCFN secondary to therapeutic whole body hypothermia has rarely been reported. With increasing use of cooling for moderate to severe hypoxic ischemic encephalopathy (HIE), clinicians should recognize this potential complication.

Ionized calcium levels in umbilical cord blood of women with preeclampsia and normotensive pregnancies.

Calcium is essential for normal fetal growth and development. During intrauterine life, the fetus is entirely dependent on the mother and a normally functioning placenta for calcium accretion. Preeclampsia is associated with abnormal calcium metabolism and placental dysfunction. The objective of our study was to investigate ionized calcium levels in the umbilical cord arterial blood of women with preeclampsia and normotensive pregnancies. There were 24 women in the preeclampsia group and 25 in the normotensive group. There was no difference in the cord pH and fetal growth restriction between the two groups. Ionized calcium levels were significantly lower in the preeclampsia group (p < 0.001). Our results emphasize the need for further studies on the calcium status of infants born to mothers with preeclampsia.

Role of hemocoagulase in pulmonary hemorrhage in preterm infants: a systematic review.

Pulmonary hemorrhage (PH) in neonates is associated with significant morbidity and mortality. Hemocoagulase is an established hemostatic agent and may be beneficial in neonates with severe PH.This systematic review was performed to investigate the clinical efficacy and safety of hemocoagulase therapy in preterm infants with Pulmonary hemorrhage (PH). The search strategy of the Cochrane Neonatal Review Group was used to determine outcomes following PH in neonates. The primary outcomes were mortality, duration of PH and length of mechanical ventilation. Other morbidities included: Respiratory Distress Syndrome, sepsis, intraventricular hemorrhage, necrotizing enterocolitis and bronchopulmonary dysplasia. The Cochrane Library, MEDLINE, EMBASE and CINAHL and bibliographies of identified trials were searched. The standard methods of the Cochrane Neonatal Review Group and van Tulder's guidelines were followed independently by the authors to assess study quality, enter data and report outcomes. Typical treatment effects were calculated using fixed confidence intervals (CI). Heterogeneity tests were performed. Two 'randomized' controlled studies related to the role of hemocoagulase in neonates were identified: One for treatment of PH and the other for prevention of PH. All preterm infants' of gestational age ≤ 32 weeks and birth weight ≤ 1500 g with PH were included in the study. A total of 48 and 72 preterm infants were enrolled and randomized into two groups in trial 1 and trial 2 respectively. Mortality risk was significantly lower in the treatment group (RR 0.52; 95%CI 0.31, 0.89, p < 0.02) when hemocoagulase was used as therapy compared to prophylactic use in neonates (RR 0.52; 95%CI 0.26, 1.07, p = 0.07). Duration of PH and mean duration of ventilation were shorter in both treatment and prophylactic groups. Use of hemocoagulase appeared to be effective in preventing PH in premature infants and reduced mortality. However, the potential risks of use of hemocoagulase including adverse effects and the effectiveness of hemocoagulase still remain uncertain due to the lack of good quality large randomized controlled studies. This needs further evaluation, before routine use can be recommended.

Non-Rotavirus infection causing apnea in a neonate.

Apnea in a premature infant is not always due to immaturity and caffeine is not always the answer. We report a case of apnea in a preterm infant who presented at two weeks of life with increase in frequency of apnea that did not respond to caffeine. Family history was significant for diarrhea in a sibling. Stool PCR was positive for Norovirus Genogroup II. Enteric isolation was instituted and the apnea resolved spontaneously with conservative management. Re-emergence of apnea or persistent apnea necessitates further investigation to elucidate the etiology.

Severe congenital chylothorax treated with octreotide.

We report a neonate with severe congenital chylothorax. Subcutaneous octreotide was added to the standard treatment regime. The chylothorax resolved with no observed side effects.