Temperature probe placement in very preterm infants during delivery room stabilization: an open-label randomized trial.

BACKGROUND: Variation in practice exists for temperature probe positioning during stabilization of very preterm infants (<32 weeks gestation). We explored the influence of temperature probe sites on thermoregulation. METHODS: An open-label, stratified, balanced, parallel, randomized trial was conducted. Inborn infants were randomly assigned temperature probe to the axilla or to the upper back. The primary outcome was normothermia (local range: 36.8-37.3 °C and World Health Organization (WHO) range: 36.5-37.5 °C) at admission to the neonatal intensive care unit. RESULTS: Between 1 November 2018 and 4 July 2022, 178 infants were randomly assigned to one of the two sites (n = 89 each), 175 included in the final analysis. Normothermia (local range) was achieved for 39/87 infants (44.8%) assigned to the upper back compared to 28/88 infants (31.8%) assigned to the axilla [risk difference:13%; 95% CI -1.3-27.3]. Normothermia (WHO range) was achieved for 78/87 infants (89.7%) assigned to the upper back compared to 70/88 infants (79.6%) assigned to the axilla [risk difference:10.1%; 95% CI -0.5-20.7]. No infant recorded temperatures >38 °C or developed skin injury. CONCLUSIONS: In very preterm infants, upper back site was equally effective as the axilla in maintaining normothermia, with no increase in adverse events. CLINICAL TRIAL REGISTRATION: The study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000293965). IMPACT: Substantial variation in practice exists for the site of securing a temperature probe during delivery room stabilization of very preterm infants and the influence of temperature probe site on thermoregulation remains unknown. In this study, upper back site was equally effective as the axilla in maintaining normothermia, with no increase in adverse events. Clinicians could adopt upper back site for maintaining normothermia. This study may contribute data to future international participant data prospective meta analysis of randomized controlled trials worldwide on temperature probe positioning in very preterm infants, increasing translation of research findings to optimize thermoregulation and clinical outcomes.

Role of a radiopaque agent and surveillance radiographs for peripherally inserted central catheters in newborn infants.

BACKGROUND: Controversy exists regarding the use of a radiopaque agent to identify peripherally inserted central catheter (PICC) tip positions in newborn infants and of serial radiography to monitor PICC tip migration. OBJECTIVE: To investigate the roles of (1) the injection of a radiopaque agent to identify PICC tip position and (2) the performance of weekly radiography to monitor PICC migration. MATERIALS AND METHODS: This retrospective single-centre cohort study included newborn infants who received a PICC between 1 January 2016 and 31 December 2020. A radiopaque agent was injected to identify PICC tip position and radiographs were performed weekly to detect PICC migration. RESULTS: We identified 676 PICC episodes in 601 infants. A radiopaque agent was used for 590 of these episodes. There was no difference in the proportion of central PICC tip positions based on radiopaque agent use status (490/590, 83% for the radiopaque agent used group versus 73/85, 85.8% for the radiopaque agent not used group, P=0.51). Irrespective of the site of PICC insertion, outward migration was observed for most centrally placed PICCs over their entire in situ duration. Inward migration was identified in 23 out of 643 PICC episodes (3.6%) only on radiographs obtained on or before day 7. Based on serial radiographs, the odds for PICC tips remaining in a central position were lower the longer the PICC remained in situ (adjusted odds ratio-OR 0.93; 95% confidence interval 0.92-0.95). There was no difference in PICC migration between side and limb of insertion. CONCLUSION: PICC tips can be identified without injection of a radiopaque agent. Serial radiographs identified PICC migration over the in situ duration. This study has implications for reducing exposure to a radiopaque agent and ongoing migration surveillance practices.

An Audit to Evaluate Vancomycin Therapeutic Drug Monitoring in a Neonatal Intensive Care Unit.

BACKGROUND: Therapeutic drug monitoring (TDM) is routinely used for optimization of vancomycin therapy, because of exposure-related efficacy and toxicity, in addition to significant variability in pharmacokinetics, which leads to unpredictable drug exposure. OBJECTIVE: The aim of this study was to evaluate target attainment and TDM of vancomycin in neonates. METHODS: The authors conducted a retrospective study and collected data from medical records of all neonates who received vancomycin therapy in the neonatal intensive care unit between January 2019 and December 2019. The primary outcome was the proportion of vancomycin courses that reached target trough concentrations of 10-20 mg/L based on appropriate TDM samples collection. Secondary outcomes included proportion of courses with appropriate dose and dose frequency, and proportion of patients who achieved target concentrations after the first dose adjustment. RESULTS: In total, 69 patients were included, with 129 vancomycin courses. The median initial vancomycin trough concentration was 12 (range: 4-36) mg/L. The target trough concentration was achieved in 75% of courses after the initial dose with appropriate TDM, and 84% of courses after TDM-guided dose adjustments. Patients were dosed appropriately in 121/129 courses and TDM was performed correctly according to protocol in 51/93 courses. A dose adjustment was performed in 18/29 courses, to increase target attainment. CONCLUSIONS: This study showed that there is a need for an increase in dose to improve target attainment. There is also a need to explore more effective TDM strategies to increase the proportion of neonatal patients attaining vancomycin target trough concentrations.

Improvement in thermoregulation outcomes following the implementation of a thermoregulation bundle for preterm infants.

AIM: Hypothermia is associated with increased morbidity and mortality in preterm infants. A local audit revealed 60% preterm infants ≤32 weeks gestation and/or very low birth weight (VLBW) infants (<1500 g) had an abnormal body temperature at admission. This study compares thermoregulatory outcomes before and after the implementation of a thermoregulation bundle in the birthing environment. METHODS: This retrospective cohort study reviewed thermoregulatory data for all inborn preterm (≤32 weeks) and/or VLBW infants for a period of 30 months before (Group 1: 1st January 2013 to 30 June 2015) and after changes to thermoregulation practice (Group 2: 1st July 2015 to 31 December 2017). The key practice changes included: improved anticipation and staff preparedness, wrapping infant in a polyethylene sheet, using a polyethylene lined bonnet, using servo-control mode at birth and during transport. RESULTS: There were 282 and 286 infants in group 1 and group 2 respectively, with similar baseline characteristics. A clinically and statistically significant improvement was observed in the proportion of infants with normothermia (33% in group 1 to 60% in group 2, P < 0.0001) including the sub-group of extremely preterm (<28 weeks gestation) infants (38 to 60%, P = 0.0083). A higher mean admission temperature was observed for group 2 (36.10°C ± 0.78 in group 1 vs 36.52°C ± 0.61 in group 2, P < 0.0001). Moderate hypothermia was reduced by two-thirds in group 2 (41-12%, P = <0.0001). CONCLUSIONS: The introduction of a thermoregulation bundle improved admission temperature, improved the proportion of normothermia and reduced moderate hypothermia in preterm infants.

Reducing antibiotic use in asymptomatic term infants exposed to maternal chorioamnionitis: Predictive role of sepsis risk calculator.

AIM: The sepsis risk calculator (SRC) has been shown to reduce empirical antibiotic usage in neonates at risk of early-onset sepsis without increasing adverse clinical outcomes. However, its use for categorising and improving identification of at-risk neonates exposed to chorioamnionitis in the local population has not been reported. This study compares the management guided by the SRC to our unit's clinical practice of administering empirical antibiotics to all term neonates (born ≥37 weeks gestation), symptomatic and asymptomatic, who were exposed to chorioamnionitis, and evaluates the performance of the SRC in managing asymptomatic term neonates exposed to chorioamnionitis. METHODS: This single-centre retrospective study identified 178 eligible term neonates exposed to chorioamnionitis over a 17-month study period. Relevant demographic and clinical information on the mother-infant dyad was collected. The SRC was executed retrospectively in the study cohort. Descriptive statistics were used for reporting the findings. RESULTS: The mean gestational age was 39 (standard deviation, SD 1) weeks, and the mean birth weight was 3472 (SD 482) g. Of the 178 neonates, 136 (76%) were asymptomatic and received empirical antibiotic therapy for 2 days (mean). Based on management recommendations from the SRC, empirical antibiotic therapy could have been avoided in 98% of asymptomatic neonates; 88% could have been managed by observation alone, avoiding mother-infant separation. No neonate died or had a positive blood culture result. CONCLUSIONS: The SRC could reduce antibiotic exposure in asymptomatic neonates exposed to chorioamnionitis. It could assist clinicians to categorise risk in neonates exposed to chorioamnionitis.

Asymptomatic full-term infants born to women with chorioamnionitis may not need routine antibiotics.

AIM: While infants with early-onset sepsis require antibiotics, there is little evidence to support their routine use in asymptomatic infants exposed to maternal chorioamnionitis. We aimed to ascertain the incidence of culture-proven sepsis in full-term infants exposed to chorioamnionitis and to determine whether asymptomatic infants need routine antibiotic treatment. METHODS: This study was retrospective. Included were all full-term infants admitted to our neonatal intensive care unit between 1 January 2017 and 31 May 2018 who were given intravenous antibiotics for maternal chorioamnionitis. After identifying eligible infants, relevant maternal and infant data were collected from our medical records and the Neonatal Intensive Care Units Database. RESULTS: We selected 167 term infants from 7736 deliveries. The incidence of chorioamnionitis was 21 per 1000 deliveries. The mean gestational age was 39 weeks (range 37-41), and 57% infants were male. Asymptomatic infants (76%) received intravenous antibiotics for an average of 2 days compared to 4 days in the symptomatic group (24%), p < 0.001. No infant died or developed culture-positive sepsis. CONCLUSION: The risk of early-onset sepsis in well-appearing term infants of mothers with chorioamnionitis is low. Further studies are mandatory to determine whether asymptomatic infants of mothers with clinical chorioamnionitis need antibiotic treatment.

The expanding LARS2 phenotypic spectrum: HLASA, Perrault syndrome with leukodystrophy, and mitochondrial myopathy.

LARS2 variants are associated with Perrault syndrome, characterized by premature ovarian failure and hearing loss, and with an infantile lethal multisystem disorder: Hydrops, lactic acidosis, sideroblastic anemia (HLASA) in one individual. Recently we reported LARS2 deafness with (ovario) leukodystrophy. Here we describe five patients with a range of phenotypes, in whom we identified biallelic LARS2 variants: three patients with a HLASA-like phenotype, an individual with Perrault syndrome whose affected siblings also had leukodystrophy, and an individual with a reversible mitochondrial myopathy, lactic acidosis, and developmental delay. Three HLASA cases from two unrelated families were identified. All were males with genital anomalies. Two survived multisystem disease in the neonatal period; both have developmental delay and hearing loss. A 55-year old male with deafness has not displayed neurological symptoms while his female siblings with Perrault syndrome developed leukodystrophy and died in their 30s. Analysis of muscle from a child with a reversible myopathy showed reduced LARS2 and mitochondrial complex I levels, and an unusual form of degeneration. Analysis of recombinant LARS2 variant proteins showed they had reduced aminoacylation efficiency, with HLASA-associated variants having the most severe effect. A broad phenotypic spectrum should be considered in association with LARS2 variants.

Standardised neonatal parenteral nutrition formulations - Australasian neonatal parenteral nutrition consensus update 2017.

BACKGROUND: The first consensus standardised neonatal parenteral nutrition formulations were implemented in many neonatal units in Australia in 2012. The current update involving 49 units from Australia, New Zealand, Singapore, Malaysia and India was conducted between September 2015 and December 2017 with the aim to review and update the 2012 formulations and guidelines. METHODS: A systematic review of available evidence for each parenteral nutrient was undertaken and new standardised formulations and guidelines were developed. RESULTS: Five existing preterm Amino acid-Dextrose formulations have been modified and two new concentrated Amino acid-Dextrose formulations added to optimise amino acid and nutrient intake according to gestation. Organic phosphate has replaced inorganic phosphate allowing for an increase in calcium and phosphate content, and acetate reduced. Lipid emulsions are unchanged, with both SMOFlipid (Fresenius Kabi, Australia) and ClinOleic (Baxter Healthcare, Australia) preparations included. The physicochemical compatibility and stability of all formulations have been tested and confirmed. Guidelines to standardise the parenteral nutrition clinical practice across facilities have also been developed. CONCLUSIONS: The 2017 PN formulations and guidelines developed by the 2017 Neonatal Parenteral Nutrition Consensus Group offer concise and practical instructions to clinicians on how to implement current and up-to-date evidence based PN to the NICU population.

Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants.

BACKGROUND: The safest ranges of oxygen saturation in preterm infants have been the subject of debate. METHODS: In two trials, conducted in Australia and the United Kingdom, infants born before 28 weeks' gestation were randomly assigned to either a lower (85 to 89%) or a higher (91 to 95%) oxygen-saturation range. During enrollment, the oximeters were revised to correct a calibration-algorithm artifact. The primary outcome was death or disability at a corrected gestational age of 2 years; this outcome was evaluated among infants whose oxygen saturation was measured with any study oximeter in the Australian trial and those whose oxygen saturation was measured with a revised oximeter in the U.K. trial. RESULTS: After 1135 infants in Australia and 973 infants in the United Kingdom had been enrolled in the trial, an interim analysis showed increased mortality at a corrected gestational age of 36 weeks, and enrollment was stopped. Death or disability in the Australian trial (with all oximeters included) occurred in 247 of 549 infants (45.0%) in the lower-target group versus 217 of 545 infants (39.8%) in the higher-target group (adjusted relative risk, 1.12; 95% confidence interval [CI], 0.98 to 1.27; P=0.10); death or disability in the U.K. trial (with only revised oximeters included) occurred in 185 of 366 infants (50.5%) in the lower-target group versus 164 of 357 infants (45.9%) in the higher-target group (adjusted relative risk, 1.10; 95% CI, 0.97 to 1.24; P=0.15). In post hoc combined, unadjusted analyses that included all oximeters, death or disability occurred in 492 of 1022 infants (48.1%) in the lower-target group versus 437 of 1013 infants (43.1%) in the higher-target group (relative risk, 1.11; 95% CI, 1.01 to 1.23; P=0.02), and death occurred in 222 of 1045 infants (21.2%) in the lower-target group versus 185 of 1045 infants (17.7%) in the higher-target group (relative risk, 1.20; 95% CI, 1.01 to 1.43; P=0.04). In the group in which revised oximeters were used, death or disability occurred in 287 of 580 infants (49.5%) in the lower-target group versus 248 of 563 infants (44.0%) in the higher-target group (relative risk, 1.12; 95% CI, 0.99 to 1.27; P=0.07), and death occurred in 144 of 587 infants (24.5%) versus 99 of 586 infants (16.9%) (relative risk, 1.45; 95% CI, 1.16 to 1.82; P=0.001). CONCLUSIONS: Use of an oxygen-saturation target range of 85 to 89% versus 91 to 95% resulted in nonsignificantly higher rates of death or disability at 2 years in each trial but in significantly increased risks of this combined outcome and of death alone in post hoc combined analyses. (Funded by the Australian National Health and Medical Research Council and others; BOOST-II Current Controlled Trials number, ISRCTN00842661, and Australian New Zealand Clinical Trials Registry number, ACTRN12605000055606.).

Unilateral vocal cord paralysis after surgical closure of a patent ductus arteriosus in extremely preterm infants.

AIM: Left vocal cord paralysis (LVCP) is variably reported post ligation of patent ductus arteriosus (PDA). Our objective was to determine the incidence of LVCP and identify predictive factors and associated morbidities in preterm infants post PDA ligation. METHODS: This is a retrospective cohort study of infants less than 29 weeks gestational age from 2006 to 2014 who underwent PDA ligation. Infants with laryngeal symptoms underwent flexible fibreoptic nasopharyngolaryngoscopy to evaluate vocal cord function. We compared short- and long-term morbidities among infants with and without symptomatic LVCP. RESULTS: A total of 35 infants underwent PDA ligation in the study period, of which 11 infants (31%) developed symptomatic LVCP. Dysphonia was the presenting symptom in all neonates with LVCP and stridor was present in 46% (5/11) of them. The median (interquartile range) gestation (25 weeks (24-27) vs. 25 weeks (23-28)), birthweight (810 g (550-1180) vs. 825 g (550-1220)) and age at surgery (19 days (9-27) vs. 20 (5-69)) were similar in infants with and without LVCP, respectively. Infants with LVCP took significantly longer to reach suck feeds (128 vs. 90 days, P = <0.001), stayed longer in hospital (119 vs. 95 days, P = 0.01) and were more likely to go home on oxygen (73 vs. 27%; P = 0.024). Neurodevelopmental outcomes were similar in the two groups. CONCLUSIONS: LVCP was noted in 31% of infants post PDA ligation and was associated with prolonged hospital stay, a longer time to reach suck feeds and a need for home oxygen. No predictive factors for development of LVCP were identified.

Is it feasible to identify preterm infants with respiratory distress syndrome for early extubation to continuous positive airway pressure post-surfactant treatment during retrieval?

AIM: Preterm infants with respiratory distress syndrome (RDS) requiring surfactant treatment are often retrieved mechanically ventilated to the receiving hospital. INSURE (INtubate, SURfactant, Extubate) technique is not routinely performed by Newborn and Pediatric Emergency Transport Services NSW (NETS) during retrieval. This study aims to evaluate the likelihood of using INSURE technique during retrieval. We attempted to study the clinical characteristics of preterm infants with RDS who were favourably extubated (FE) shortly after admission to the receiving hospital. METHODS: Retrospective study of preterm infants, gestational age (GA) > 28 weeks with RDS requiring retrieval by NETS. RESULTS: Two hundred twenty-three infants, median GA of 33 weeks (range 29-36), median birthweight 2200 g (1000-4080) were examined. A percentage of 49.7 received CPAP, and 50.3% required MV. Eighteen (16%) infants were FE (<6 h) at receiving hospital. FiO2 on stabilisation (FiO2 (st)) by NETS correlated with FiO2 on admission to receiving hospital (r = 0.863). A percentage of 81 of ventilated infants received premedications including morphine. No significant differences were noted for GA, stabilisation ventilator settings, surfactant dose (mean 155 mg/kg) and mode of transport between FE and non-FE groups. FiO2 (st) post-surfactant treatment was significantly lower in FE compared with non-FE group (mean 0.28 vs. 0.41 respectively). The area under the curve from receiver operating characteristic based on FiO2 (st) was 0.646 (P = 0.050), the sensitivity and specificity of FiO2 (st) cut-off points (between 0.25 and 0.30) was low. CONCLUSION: FiO2 on stabilisation post-surfactant treatment has a weak predictive value and may not be adequate to be used as sole criteria to extubate to CPAP prior to transport. FiO2 at stabilisation should be included as an eligibility criteria for a randomised trial of INSURE during retrieval, but other clinical assessments are needed.

Review of respiratory management of extremely premature neonates during transport.

INTRODUCTION: The objective was to evaluate the respiratory management of neonates of 23 to 26 weeks' gestation transported after birth outside a tertiary center. Another objective was to collect data regarding survival, intraventricular hemorrhage (IVH), and chronic lung disease. METHODS: This was a retrospective study of transports from a statewide dedicated neonatal and pediatric transport service over a 3-year period. Data were collected from the local databases. Neonates with and without transcutaneous carbon dioxide (TcCO2) monitoring were compared. Outcomes were compared with the inborn group from the same period. RESULTS: A total of 43 mechanically ventilated neonates were included. Significant hypocarbia and/or hypercarbia were seen in 49%. Hyperoxia was noted in 46.5%. Despite the moderate correlation between PCO2 and TcCO2 readings, no clinical benefit was seen with TcCO2 monitoring. Survival was 65.1%. Rates of IVH were 60% for any IVH and 27.5% for severe IVH. IVH was more common in the study cohort. CONCLUSIONS: Neonates born at 23 to 26 weeks' gestation outside tertiary centers have high rates of mortality and morbidity. The avoidance of hypocarbia, hypercarbia, and hyperoxia is challenging in the transport environment. Transcutaneous monitoring is an imperfect tool for following PCO2 levels.

Bayesian Vancomycin Model Selection for Therapeutic Drug Monitoring in Neonates.

BACKGROUND AND OBJECTIVE: Pharmacokinetic models can inform drug dosing of vancomycin in neonates to optimize therapy. However, the model selected needs to describe the intended population to provide appropriate dose recommendations. Our study aims to identify the population pharmacokinetic (PopPK) model(s) with the best performance to predict vancomycin exposure in neonates in our hospital. METHODS: Relevant published PopPK models for vancomycin in neonates were selected based on demographics and vancomycin dosing strategy. The predictive performance of the models was evaluated in Tucuxi using a local cohort of 69 neonates. Mean absolute error (MAE), relative bias (rBias) and relative root mean square error (rRMSE) were used to quantify the accuracy and precision of the predictive performance of each model for three different approaches: a priori, a posteriori, and Bayesian forecasting for the next course of therapy based on the previous course predictions. A PopPK model was considered clinically acceptable if rBias was between ± 20 and 95% confidence intervals included zero. RESULTS: A total of 25 PopPK models were identified and nine were considered suitable for further evaluation. The model of De Cock et al. 2014 was the only clinically acceptable model based on a priori [MAE 0.35 mg/L, rBias 0.8 % (95% confidence interval (CI) - 7.5, 9.1%), and rRMSE 8.9%], a posteriori [MAE 0.037 mg/L, rBias - 0.23% (95% CI - 1.3, 0.88%), and rRMSE 6.02%] and Bayesian forecasting for the next courses [MAE 0.89 mg/L, rBias 5.45% (95% CI - 8.2, 19.1%), and rRMSE 38.3%) approaches. CONCLUSIONS: The De Cock model was selected based on a comprehensive approach of model selection to individualize vancomycin dosing in our neonates.

Systemic postnatal corticosteroid use for the prevention of bronchopulmonary dysplasia and its relationship to early neurodevelopment in extremely preterm infants.

BACKGROUND: Systemic postnatal corticosteroid use in extremely preterm infants poses a risk of adverse neurodevelopmental outcomes. This study explores their use beyond seven days of age with early neurodevelopmental assessments during the fidgety period (9-20 weeks postterm age). METHODS: This retrospective single-center cohort study included inborn extremely preterm infants from 1 January 2014 to 31 December 2018. Outborn infants, those with congenital or genetic abnormalities, and those who received postnatal corticosteroids for nonrespiratory reasons were excluded. The cohort was dichotomized based on the status of corticosteroid receipt. Early neurodevelopmental outcomes were reported using Prechtl's General Movements Assessment. RESULTS: Of the 282 infants, 67 (23.75%) received corticosteroids. Of these, 34 (50.75%) received them for dependency on invasive ventilation (intermittent positive-pressure ventilation), and the remainder received them for dependency on non-invasive ventilation continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BiPAP). Abnormal or absent fidgety movements were observed in 13% of infants (7/54) who received corticosteroids compared to 2% of infants (3/146) who did not. An increased odds for an abnormal general movements assessment from corticosteroid use after adjusting for gestational age [adjusted odds ratio (aOR) = 5.5, 95% confidence interval (CI) = 1.14-26.56] was observed. The motor optimality scores differed between the two groups [corticosteroid group: 25.5 (23-26) versus no-corticosteroid group: 26 (24-28); z = - 2.02]. A motor optimality score < 20 was observed in 14.8% of infants (8/54) in the corticosteroid group compared to 2% of infants (3/146) in the noncorticosteroid group. This difference was significant after adjustment for gestational age (aOR 5.96, 95% CI 1.28-27.74). CONCLUSIONS: Abnormal early neurodevelopment was observed in infants who received systemic postnatal corticosteroids. The relationship between these findings and other factors influencing early neurodevelopment needs further exploration.

Dosing of vancomycin and target attainment in neonates: a systematic review.

INTRODUCTION: Neonatal infections caused by Gram-positive bacteria are commonly treated with vancomycin. However, there is a lack of agreement on the optimal vancomycin dosing regimen and corresponding vancomycin exposure to correlate with efficacy and toxicity. OBJECTIVES: This review aimed to evaluate dosing of vancomycin in neonates, therapeutic target attainment and clinical toxicity and efficacy outcomes. METHODS: Two electronic databases - Embase and PubMed (Medline) - were systematically searched between 1995-2020. Studies that reported dosing regimens, drug concentrations, toxicity, and efficacy of vancomycin in neonates were eligible for inclusion. Descriptive analysis and a narrative synthesis were performed. RESULTS: The systematic review protocol was registered with the PROSPERO International Prospective Register of Systematic reviews in 2020 (registration number: CRD42020219568). Twenty-four studies were included for final analysis. Overall, the data from the included studies showed a great degree of heterogeneity. Therapeutic drug monitoring practices were different between institutions. Although most studies used trough concentration with a target range of 10-20 mg/L, target attainment was different across the studies. The probability of target attainment was < 80% in all tested dosing algorithms. Few studies reported on vancomycin efficacy and toxicity. CONCLUSION: This is a comprehensive overview of dosing strategies of vancomycin in neonates. There was inadequate evidence to propose an optimal therapeutic regimen in the newborn population, based on the data obtained, due to the heterogeneity in the design and objectives of the included studies. Consistent and homogeneous comparative randomised clinical trials are needed to identify a dosing regimen with a probability of target attainment of > 90% without toxicity.

Pregnancy outcomes in women with gestational diabetes mellitus by models of care: a retrospective cohort study.

OBJECTIVE: To compare birth outcomes of women with gestational diabetes mellitus (GDM) with background obstetric population, stratified by models of care. DESIGN: Retrospective cohort study. SETTING: A tertiary referral centre in Sydney, Australia. PARTICIPANTS: All births 1 January 2018 to 30 November 2020. Births <24 weeks, multiple gestations and women with pre-existing diabetes were excluded. METHODS: Data were obtained from electronic medical records. Women were classified according to GDM status and last clinic attended prior to delivery. Model of care included attendance at dedicated GDM obstetric clinics, and routine antenatal care. MAIN OUTCOME MEASURES: Hypertensive disorders of pregnancy (HDP), pre-term birth (PTB), induction of labour (IOL), operative delivery, small for gestational age (SGA), large for gestational age, postpartum haemorrhage, obstetric anal sphincter injury (OASIS), neonatal hypoglycaemia, neonatal hypothermia, neonatal respiratory distress, neonatal intensive care unit (NICU) admission. RESULTS: The GDM rate was 16.3%, with 34.0% of women managed in dedicated GDM clinics. Women with GDM had higher rates of several adverse outcomes. Only women with GDM attending non-dedicated clinics had increased odds of HDP (adjusted OR (adj OR) 1.6, 95% CI 1.2 to 2.0), PTB (adj OR 1.7, 95% CI 1.4 to 2.0), OASIS (adj OR 1.4, 95% CI 1.0 to 2.0), similar odds of induction (adj OR 1.0, 95% CI 0.9 to 1.1) compared with non-GDM women. There were increased odds of NICU admission (adj OR 1.5, 95% CI 1.3 to 1.8) similar to women attending high-risk GDM clinics. CONCLUSIONS: Women with GDM receiving care in lower risk clinics had similar or higher rates of adverse outcomes. Pathways of care need to be similar in all women with GDM.

Clinical Outcomes of Single vs. Two-Strain Probiotic Prophylaxis for Prevention of Necrotizing Enterocolitis in Preterm Infants.

Background: The administration of live microbiota (probiotic) via enteral route to preterm infants facilitates intestinal colonization with beneficial bacteria, resulting in competitive inhibition of the growth of pathogenic bacteria preventing gut microbiome dysbiosis. This dysbiosis is linked to the pathogenesis of necrotizing enterocolitis (NEC), an acquired multi-factorial intestinal disease characterized by microbial invasion of the gut mucosa, particularly affecting preterm infants. Probiotic prophylaxis reduces NEC; however, variations in strain-specific probiotic effects, differences in administration protocols, and synergistic interactions with the use of combination strains have all led to challenges in selecting the optimal probiotic for clinical use. Aim: To compare any differences in NEC rates, feeding outcomes, co-morbidities in preterm infants receiving single or two-strain probiotics over a 4-year period. The two-strain probiotic prophylaxis was sequentially switched over after 2 years to the single strain probiotic within this 4-year study period, in similar cohort of preterm infants. Methods: During two consecutive equal 2-year epochs, preterm infants (<32 weeks and or with birth weight <1,500 g) receiving two-strain (Lactobacillus acidophilus and Bifidobacterium bifidum) and single strain (Bifidobacterium breve M-16 V,) probiotic prophylaxis for prevention of NEC were included in this retrospective, observational study. The primary outcome included rates of NEC; secondary outcomes included prematurity related co-morbidities and feeding outcomes. Time to reach full enteral feeds was identified as the first day of introducing milk feeds at 150 ml/kg/day. Results: There were 180 preterm infants in the two-strain, 196 in the single strain group from the two equal consecutive 2-year epochs. There were no differences in the NEC rates, feeding outcomes, all-cause morbidities except for differences in rates of retinopathy of prematurity. Conclusion: In our intensive-care setting, clinical outcomes of single vs. two-strain probiotic prophylaxis for prevention of NEC were similar. Although our study demonstrates single strain probiotic may be equally effective than two-strain in the prevention of NEC, small sample size and low baseline incidence of NEC in our unit were not sufficiently powered to compare single vs. two-strain probiotic prophylaxis in preventing NEC. Further clustered randomized controlled trials are required to study the effects of single vs. multi-strain probiotic products for NEC prevention in preterm infants.

General Movement assessment and neurodevelopmental trajectory in extremely preterm infants with hypothyroxinaemia of prematurity (THOP).

BACKGROUND: Transient hypothyroxinaemia of prematurity (THOP) has been associated with neurodevelopmental deficits with a paucity of literature leading to variable practice. AIM: Evaluation of the relationship between free T4 (fT4) levels at 2 weeks after birth and early markers of neurodevelopmental outcome. STUDY DESIGN: A retrospective study of prospectively collected data from infants born <29 weeks' gestation, admitted to NICU between January 2012 and December 2014. The primary outcomes were the relationship between fT4 levels at 2 weeks, Prechtl General Movement Assessment (GMA) at 36 weeks and 3 months postterm age, and Bayley Scales of Infant Development (BSID-III) at 2 years postterm age. Secondary outcomes were survival free of disability and other neonatal morbidities. RESULTS: Of 122 infants, 101 infants had normal fT4 levels (No-THOP) and 21 had fT4 levels >1SD below the mean (THOP group). There was increased frequency of abnormal GMA in the No-THOP group compared with the THOP group at 36 weeks (abnormal writhing GMs: 43% vs 21%, p = 0.15) and 3 months corrected age (absent fidgety GMs: 7.6% vs 0%, p = 0.36), though not statistically significant. The neurodevelopmental outcome was worse in the No-THOP group compared with the THOP group with significantly lower mean cognitive and motor scores at 2 year of corrected age (90 ±â€¯13.8 vs 100 ±â€¯8.3, p = 0.01 and 91 ±â€¯15.2 vs 100 ±â€¯13.2, p = 0.04 respectively). CONCLUSIONS: This is the first report describing General Movements (GMs) in preterm infants with THOP. We found worse neurodevelopmental outcome in No-THOP infants reflected by significantly worse cognitive and motor outcomes at 2 years corrected age.

Vein of Galen aneurysmal malformation: Pit-falls in the diagnosis.

Vein of Galen aneurysmal malformation (VGAM) is a rare congenital vascular malformation. We report a case of VGAM being associated with presence of bilateral hydrocephalus, gross cardiomegaly and is unique in two ways. Firstly, clinical presentation was associated with a large discrete cystic swelling along right side of the neck, which has not previously been reported. Secondly, this was a missed diagnosis of VGAM due to omission of colour Doppler study while performing diagnostic fetal cranial ultrasound just prior to delivery, following referral for assessment on a previously identified abnormality.

Epidemiology of necrotizing enterocolitis--Part I: Changing regional trends in extremely preterm infants over 14 years.

OBJECTIVES: Advances in perinatal care include exogenous surfactant, unequivocal acceptance of antenatal steroids and in utero and ex utero transfers to tertiary centres. Increased survival of extremely premature infants may change the incidence and outcome of necrotizing enterocolitis (NEC). Our aim was to examine the trends in the incidence of NEC, surgery and mortality in infants of 24-28 weeks gestation in a retrospective regional review of three epochs over a span of 14 years. METHODS: Radiologically or surgically proven NEC cases were determined from the New South Wales Neonatal Intensive Care Unit Study database. Three epochs were examined. A total of 360 infants were admitted in 1986-87 (Epoch 1), 622 in 1992-93 (Epoch 2) and 673 in 1998-99 (Epoch 3). RESULTS: There was an increase in neonatal intensive care unit admissions and a decrease in early and overall mortality of these very premature infants across the epochs. None of the early deaths was due to NEC. The incidence of NEC decreased in post day 5 survivors: 33 cases in Epoch 1 (12%), 60 cases in Epoch 2 (12%) and 34 cases in Epoch 3 (6%, P < 0.001). There was no change in surgical intervention (45%, 57% and 41%, respectively) or mortality due to NEC (37%, 27% and 32%). The reduced incidence of NEC was not singularly influenced by antenatal steroids, exogenous surfactant or outborn delivery. In a multivariate analysis, only later epoch of birth was independently associated with reduced NEC risk. CONCLUSIONS: With improved care and survival of extremely premature infants, the incidence of NEC has decreased, but it remains a disease of high mortality and morbidity.