Belal Alshaikh

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.

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.

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.

Prolonged use of antibiotics after birth is associated with increased morbidity in preterm infants with negative cultures

Abstract Background: Most preterm infants are exposed to a variable duration of antibiotic therapy after birth despite negative cultures. Data is emerging about the risks of prolonged antibiotics. We sought to assess the association between length of initial antibiotic course and neonatal outcomes in a cohort from a single large perinatal center. Methods: Retrospective cohort study of prospectively collected data on all infants with a birth weight of less than 1250 g hospitalized in our NICU in a 4 year window and who had negative blood and CSF cultures in the first 2 days of life. The primary outcome is a composite of necrotizing enterocolitis (NEC), late onset sepsis (LOS) and death evaluated using multivariable regression analysis. Results: A total of 620 infants less than 1250 g with negative cultures were eligible for study over a 4 year period. The 238 infants with more than 5 days initial antibiotic use were significantly smaller and of lower gestational age than the 382 infants who received up to 5 days of antibiotics. Their mothers had more clinical chorioamnionitis, less maternal hypertension and greater perinatal use of antibiotics. On multivariate analysis, infants who received empiric antibiotics for longer than 5 days had higher rates of neonatal morbidities after adjusting for gestational age, SNAP II, small-for-gestational age status, gender, maternal hypertension, prenatal steroid treatment, clinical chorioamnionitis, intrapartum antibiotic treatment, and multiple births. Composite outcome OR: 1.83 (1.15 to 2.92), LOS OR: 2.02 (1.20 to 3.39), bronchopulmonary dysplasia OR: 1.58 (1.04 to 2.29). Mortality and NEC were not significantly different. Conclusion: More than 5 days of antibiotic treatment in very preterm infants with negative cultures was associated with increased morbidity in our population, and that included BPD. It is of note that patterns of increased morbidity and/or mortality differ between studies. Prospective trials of clinical protocols for starting and stopping antibiotics in the very preterm infants are required.

Probiotics supplementation and length of hospital stay in neonates with gastrointestinal surgery

Highlights • Surgical stress causes disruption of the gut barrier and microbiome.• In neonates intestinal dysbiosis increases risk for feeding intolerance, prolonged use of parenteral nutrition, and post-operative infection.• Probiotics prevent bacterial overgrowth, promote gut barrier function, and modulate the local immune response.• Monitoring dynamic changes in microbiome of post-surgical infants who received probiotics and placebo will provide with important information about gut colonization.• This study will assess the effect of probiotics on length of hospital stay, duration of parenteral nutrition, and feed tolerance in post-surgical infants.

Pre-eclampsia and the risk of retinopathy of prematurity in preterm infants with birth weight <1500 g and/or <31 weeks’ gestation

Objective To evaluate the relationship between pre-eclampsia and development of retinopathy of prematurity (ROP) in infants with birth weight of <1500 g and/or gestation <31 weeks. Methods A retrospective cohort study comprising infants born to mothers with pre-eclampsia between January 2007 and June 2010 at a single tertiary care centre. Their ROP outcome was compared with infants born to the next two normotensive mothers with a ±1 week gestational age difference. Pearson χ2 test was used for categorical variables and Mann-Whitney U test was used for continuous variables. Multivariable regression was used to estimate the OR of ROP with prenatal pre-eclampsia exposure and adjust for confounders. Results Of the 97 infants in the pre-eclampsia group, 27 (27%) developed ROP and of the 185 infants in the normotensive group, 50 (27%) developed ROP. On multivariable regression modelling, pre-eclampsia was not a risk factor for the development of ROP (OR 1.4, 95% CI 0.46 to 4.1). Gestational age, intrauterine growth restriction and blood transfusion were significant risk factors for the development of ROP. Conclusions In our cohort, pre-eclampsia was not a significant risk factor for the development of ROP. Intrauterine growth restricted infants of pre-eclamptic and normotensive mothers were at higher risk of ROP.

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.