Kamran Yusuf

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.

Coagulase-negative staphylococcus sepsis in preterm infants and long-term neurodevelopmental outcome

Objective:The objective of this study was to examine the impact of Coagulase-negative staphylococcus (CoNS) sepsis in preterm infants on the neurodevelopmental outcomes at 30 to 42 months corrected age (CA).Study Design:This is a retrospective cohort study. All preterm infants born at <29 weeks gestational age between 1995 and 2008 and had a neurodevelopmetnal assessment at 30 to 42 months CA were eligible. The neurodevelopmetnal outcomes of infants exposed to CoNS sepsis were compared with infants unexposed to any type of neonatal sepsis.Result:A total of 105 eligible infants who were exposed to CoNS sepsis were compared with 227 infants with no neonatal sepsis. In univariate analysis, infants with CoNS sepsis were more likely to have total major disability (odds ratio (OR)=1.9; 95% CI: 1.07 to 3.38) and cognitive delay (OR=2.53; 1.26 to 5.14).There was no significant difference in the incidence of cerebral palsy, blindness and deafness between the two groups. After correcting for potential confounders, CoNS sepsis was associated with increased risk of cognitive delay (adjusted odds ratio (aOR)= 2.23; 95% CI 1.01 to 4.9), but not with the total major disability (aOR=1.14; 95% CI: 0.55 to 2.34).Conclusion:Our study suggests that CoNS sepsis in preterm infants might be associated with increased risk for cognitive delay at 36 months CA.

Neonatal Hypercalcemia Secondary to Subcutaneous Fat Necrosis Successfully Treated with Pamidronate: A Case Series and Literature Review

Subcutaneous fat necrosis (SCFN) is a noninfectious panniculitis that occurs in term infants who experience significant distress in the 1st weeks of life, including hypoxic ischemic encephalopathy (HIE). Since the introduction of therapeutic hypothermia for HIE, there have been a few published case reports of SCFN, following this modality of treatment. Although, most cases of SCFN resolve spontaneously, SCFN may be associated with hypercalcemia, which may sometimes reach dangerous levels. Approaches used for the management of this potentially life-threatening condition, include hyperhydration, calciuric diuretics, corticosteroids, and in more resistant cases pamidronate, a bisphosphonate. We report our experience on the use of pamidronate in two cases of severe hypercalcemia associated with SCFN following therapeutic hypothermia for HIE. We believe that with increasing use of therapeutic hypothermia for HIE, clinicians are likely to encounter this condition more frequently.

Bilateral cataracts associated with glucose-6-phosphate dehydrogenase deficiency

Glucose-6-phosphate dehydrogenase (G6PD) has an essential role in the defense against cellular oxidative injury. In neonates, the most common manifestation of G6PD deficiency is jaundice and hemolysis due to factors causing oxidative stress. Less known are the ocular associations described with G6PD deficiency, including cataracts. Oxidative injury is involved in the pathogenesis of almost all forms of cataracts, causing the lens proteins to undergo modifications, denaturation and form insoluble aggregates resulting in cataracts. Although cataracts in adult males have been reported in several studies, there are few reports of cataracts in infants with G6PD deficiency. We describe a preterm male neonate with G6PD deficiency who developed bilateral cataracts following an episode of neonatal sepsis and severe hemolysis necessitating an exchange blood transfusion.

Intraventricular Hemorrhage and Multiple Intracranial Cysts Associated with Congenital Cytomegalovirus Infection

ABSTRACT Intraventricular hemorrhage with congenital cytomegalovirus (CMV) infection is rare and has been reported only in extremely premature infants or in association with thrombocytopenia. We report the first case of a full-term male infant with congenital CMV infection and intraventricular hemorrhage with a normal platelet count and coagulation profile. The infant also had a left subependymal cyst and bilateral occipital cysts without any other manifestations of CMV infection.

The mystery of persistent pulmonary hypertension: an idiopathic infantile arterial calcification

BackgroundIdiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disorder, characterized by wide spread calcifications in arterial walls, leading to vaso-occlusive ischaemia of multiple organs. Mortality is high, and there is no definitive treatment.Case presentationA male neonate, 36+5 weeks gestation, 2.81 kg, was admitted to NICU for respiratory distress. At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary oedema. An echocardiogram (ECHO) indicated moderate persistent pulmonary hypertension (PPHN) of unclear etiology. A diagnosis of Idiopathic infantile arterial calcification was made and a trial of Editronate therapy was given without success.ConclusionIIAC is a rare disorder, it should be considered whenever a neonate presents with unexplainable cardiac failure, PPHN, echogenic vessels on X-ray/ultrasound and, or concentric hypertrophic ventricles on ECHO. Serial antenatal ultrasound findings of echogenic cardiac foci should raise the suspicion of IIAC. Further studies to determine the long term effects of Editronate on vascular calcifications, disease outcome, and other treatment options are needed.

Extended-interval gentamicin administration in neonates: an over-simplified approach

We read with interest the paper by El-Chaar et al on a simplified approach to extended interval dosing (EID) of gentamicin in neonates. We are pleased to see others recognize the benefits of using EID in neonates and approaching it in such a practical way. Our present practice is to adjust dosing intervals in neonates on EID using a single level drawn at 22 h post dose; we have validated this method in neonates less than and greater than 7 days of age and have found it a very effective and practical method. Our first concern with the authors’ approach is the very broad gestational age groupings. Maturation of nephrons occurs between 34 to 36 weeks, and the rate at which neonatal renal function increases ex utero is inversely related to the gestational age at birth. Because of this, the broad gestational age categories used in this study may not accurately account for these differences in renal function. For the authors’ dosing recommendation to be extended to infants of all gestational ages (GA), a much more detailed examination using smaller GA subgroups is required. The authors’ own data showing a higher rate of Cmin values 42 mg l − 1 in Group 1 supports this. In addition, the authors do not consider postnatal age in their suggested dosing scheme. Renal function changes rapidly over the first few weeks of life, and a lack of consideration of this in dosing aminoglycosides most certainly will render any dosing scheme inaccurate. There is a wide range of postnatal ages in the study groups (particularly in Group 1) and this most certainly will have created variability in the pharmacokinetic parameters of the study subjects. While the low rate of elevated Cmin values42 mg l 1 is reassuring, the authors may be missing a group of individuals in whom trough levels are undetectable for a prolonged period of time and may benefit from q24h dosing. For these reasons, we feel that the study results do not clarify the question of dosing for a 24-week GA infant in the first week of life compared with an ex 28-week infant with a corrected gestational age of 32 weeks or compared with a term infant on day 1 of life. The elevated mean AUC values and low percentage of target AUC values suggests that the values achieved in these groups may require closer examination for trends related to corrected gestational age and/or postnatal age. Dosage modifications in 24% of Group 1 study arm patients and 40% of Group 2 study arm patients raised further concern for adopting this proposed ‘simplified approach’ to EID gentamicin. It was good to see the positive safety outcomes reported by the authors, and we share the frustration when trying to determine clinical efficacy in this population.

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.

Neonatal outcomes of extremely preterm infants exposed to maternal hypertension and cigarette smoking

Objective:To study the outcomes of extremely preterm infants of hypertensive mothers who smoke.Study design:This retrospective cohort study included infants born between 2003 and 2012 at <29 weeks’ gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network. Infants were divided into four mutually exclusive groups. Infants of hypertensive mothers who smoked; infants of hypertensive, non-smoking mothers; infants of normotensive mothers who smoked; and infants of normotensive, non-smoking mothers. Using infants of normotensive, non-smoking mothers as the reference group, neonatal outcomes were compared between the groups. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate regression analysis.Results:Of the 12,307 eligible infants, 172 had hypertensive mothers who smoked, 1689 had hypertensive non-smoking mothers, 1535 had normotensive mothers who smoked, and 8911 had normotensive non-smoking mothers. Compared to infants of normotensive non-smoking mothers, infants of hypertensive mothers, regardless of smoking status, had higher odds of developing bronchopulmonary dysplasia (AORs of smokers 1.62; 95% CI 1.12–2.35 and of non-smokers 1.43; 95% CI 1.24–1.64). There was no difference in the odds of mortality and retinopathy of prematurity stage ≥3 between the groups. Infants of hypertensive, non-smoking mothers had decreased odds of intraventricular hemorrhage >grade 2 and higher odds of necrotizing enterocolitis. There was decreased odds of hypertension if the mother was a smoker (AOR 0.71; 95% CI 0.59–0.85).Conclusion:Maternal hypertension is associated with increased rates of bronchopulmonary dysplasia, irrespective of smoking status.

Evolution of empiric vancomycin dosing in a neonatal population

BackgroundIn 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).ObjectiveTo validate the revised empirical vancomycin dosage regimen in achieving target troughs.MethodsThe 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.ResultsOut 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).ConclusionsThe revised empiric dosing regimen was more effective in achieving target serum trough concentrations.