Publications by authors named "Sanjay Patole"

135 Publications

The Use of Postnatal Weight Gain Algorithms to Predict Severe or Type 1 Retinopathy of Prematurity: A Systematic Review and Meta-analysis.

JAMA Netw Open 2021 Nov 1;4(11):e2135879. Epub 2021 Nov 1.

Department of Ophthalmology, Perth Children's Hospital, Perth, Australia.

Importance: The currently recommended method for screening for retinopathy of prematurity (ROP) is binocular indirect ophthalmoscopy, which requires frequent eye examinations entailing a heavy clinical workload. Weight gain-based algorithms have the potential to minimize the need for binocular indirect ophthalmoscopy and have been evaluated in different setups with variable results to predict type 1 or severe ROP.

Objective: To synthesize evidence regarding the ability of postnatal weight gain-based algorithms to predict type 1 or severe ROP.

Data Sources: PubMed, MEDLINE, Embase, and the Cochrane Library databases were searched to identify studies published between January 2000 and August 2021.

Study Selection: Prospective and retrospective studies evaluating the ability of these algorithms to predict type 1 or severe ROP were included.

Data Extraction And Synthesis: Two reviewers independently extracted data. This meta-analysis was performed according to the Cochrane guidelines and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines.

Main Outcomes And Measures: Ability of algorithms to predict type 1 or sever ROP was measured using statistical indices (pooled sensitivity, specificity, and summary area under the receiver operating characteristic curves, as well as pooled negative likelihood ratios and positive likelihood ratios and diagnostic odds ratios).

Results: A total of 61 studies (>37 000 infants) were included in the meta-analysis. The pooled estimates for sensitivity and specificity, respectively, were 0.89 (95% CI, 0.85-0.92) and 0.57 (95% CI, 0.51-0.63) for WINROP (Weight, IGF-1 [insulinlike growth factor 1], Neonatal, ROP), 1.00 (95% CI, 0.88-1.00) and 0.60 (95% CI, 0.15-0.93) for G-ROP (Postnatal Growth and ROP), 0.95 (95% CI, 0.71-0.99) and 0.52 (95% CI, 0.36-0.68) for CHOP ROP (Children's Hospital of Philadelphia ROP), 0.99 (95% CI, 0.73-1.00) and 0.49 (95% CI, 0.03-0.74) for ROPScore, 0.98 (95% CI, 0.94-0.99) and 0.35 (95% CI, 0.22-0.51) for CO-ROP (Colorado ROP). The original PINT (Premature Infants in Need of Transfusion) ROP study reported a sensitivity of 0.98 (95% CI, 0.91-0.99) and a specificity of 0.36 (95% CI, 0.30-0.42). The pooled negative likelihood ratios were 0.19 (95% CI, 0.13-0.27) for WINROP, 0.0 (95% CI, 0.00-0.32) for G-ROP, 0.10 (95% CI, 0.02-0.53) for CHOP ROP, 0.03 (95% CI, 0.00-0.77) for ROPScore, and 0.07 (95% CI, 0.03-0.16) for CO-ROP. The pooled positive likelihood ratios were 2.1 (95% CI, 1.8-2.4) for WINROP, 2.5 (95% CI, 0.7-9.1) for G-ROP, 2.0 (95% CI, 1.5-2.6) for CHOP ROP, 1.9 (95% CI, 1.1-3.3) for ROPScore, and 1.5 (95% CI, 1.2-1.9) for CO-ROP.

Conclusions And Relevance: This study suggests that weight gain-based algorithms have adequate sensitivity and negative likelihood ratios to provide reasonable certainty in ruling out type 1 ROP or severe ROP. Given the implications of missing even a single case of severe ROP, algorithms with very high sensitivity (close to 100%) and low negative likelihood ratios (close to zero) need to be chosen to safely reduce the number of unnecessary examinations in infants at lower risk of severe ROP.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.35879DOI Listing
November 2021

Vitamin A supplementation in very-preterm or very-low-birth-weight infants to prevent morbidity and mortality: a systematic review and meta-analysis of randomized trials.

Am J Clin Nutr 2021 Sep 28. Epub 2021 Sep 28.

Neonatal Clinical Care Unit, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.

Background: A previous systematic review showed that intramuscular vitamin A supplementation reduced the risk of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants. However, more recent studies have questioned this finding.

Objectives: Our objective was to synthesize current evidence on vitamin A supplementation in very-preterm (<32 wk gestational age) or VLBW infants and investigate the factors that may modify its efficacy.

Methods: A systematic review was conducted using the Cochrane systematic review methodology. We included randomized controlled trials investigating vitamin A supplementation for reducing morbidity and mortality in very-preterm or VLBW infants. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) recommendations. Prespecified subgroup analyses assessed factors that may modify the effects of vitamin A supplementation.

Results: We included 17 studies (n = 2471) in the qualitative and 15 studies (n = 2248) in the quantitative synthesis. Moderate-certainty evidence suggested a beneficial effect of vitamin A for decreasing the risk of BPD at 36 wk postmenstrual age (RR: 0.83; 95% CI: 0.74, 0.93; numbers needed to treat for an additional beneficial outcome: 16; 95% CI: 9, 53; 9 studies, n = 1752; P = 0.002). Subgroup analysis suggested that the beneficial effect was limited to infants with baseline vitamin A intake <1500 IU · kg-1 · d-1. Both enteral and parenteral routes were effective. Vitamin A supplementation did not have adverse effects and did not alter mortality before discharge (12 studies, n = 1917) or neurodevelopmental outcomes at 18-22 mo (1 study, n = 538).

Conclusions: The benefit of vitamin A supplementation for reducing BPD is likely to be limited to infants with baseline vitamin A intake <1500 IU · kg-1 · d-1 and is not affected by the route of administration.
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http://dx.doi.org/10.1093/ajcn/nqab294DOI Listing
September 2021

Effect of Enteral Vitamin A on Fecal Calprotectin in Extremely Preterm Infants: A Nested Prospective Observational Study.

Neonatology 2021 Sep 10:1-7. Epub 2021 Sep 10.

Neonatal Clinical Care Unit, King Edward Memorial and Perth Children's Hospitals, Perth, Washington, Australia.

Background: Vitamin A has anti-inflammatory and immune-modulating properties. We aimed to assess whether enteral water-soluble vitamin A supplementation in extremely preterm infants decreases fecal calprotectin, a marker of intestinal inflammation.

Methods: This was a prospective observational study nested in a randomized, double-blind, placebo-controlled clinical trial investigating enteral vitamin A (5,000 IU/day) for reducing the severity of bronchopulmonary dysplasia (BPD) in extremely preterm infants. Fecal calprotectin levels were measured using enzyme-linked immunosorbent assay after 28 days of Vitamin A or placebo supplementation.

Results: Fecal calprotectin was measured in 66 infants (Vitamin A: 33, Placebo: 33). The mean (standard deviation) gestational age (25.5 [1.55] vs. 25.8 [1.48]; p = 0.341) (week), birth weight (810 [200] vs. 877 [251]; p = 0.240) (gram), and factors influencing fecal calprotectin levels were comparable between the vitamin A versus placebo group infants. All infants were exclusively fed with mother's or donor's human breast milk if mother's milk was unavailable using a standardized feeding regimen and received prophylactic probiotic supplementation. Fecal calprotectin levels (median; 25th-75th centiles) (micrograms/gram of feces) were not significantly different between vitamin A (152; 97-212) and placebo groups (179; 91-313) (p = 0.195). Two infants in the vitamin A group developed definite necrotizing enterocolitis compared to none in the placebo group. Incidence of BPD at 36 weeks postmenstrual age was similar between the groups (vitamin A: 18/33, placebo: 13/33, p = 0.218).

Conclusion: Enteral supplementation with water-soluble vitamin A did not affect fecal calprotectin levels in extremely preterm infants. Studies with a larger sample size are required to confirm the findings.
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http://dx.doi.org/10.1159/000518680DOI Listing
September 2021

Correction to: Association of gastric residual volumes with necrotising enterocolitis in extremely preterm infants-a case-control study.

Eur J Pediatr 2021 Aug 17. Epub 2021 Aug 17.

Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia.

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http://dx.doi.org/10.1007/s00431-021-04230-9DOI Listing
August 2021

Use of parenteral nutrition in term and late preterm infants: an Australian and New Zealand survey.

Br J Nutr 2021 Aug 11:1-8. Epub 2021 Aug 11.

The University of Western Australia, Medical School, Perth, WA, Australia.

There is limited information regarding the use of parenteral nutrition (PN) in term and late preterm infants. We conducted a survey to study the current clinical practices within Australia and New Zealand (ANZ). A fifteen-question online survey was distributed to 232 neonatologists and fifty-five paediatric intensivists across ANZ between September and November 2019. At least one neonatologist from twenty-seven out of thirty tertiary neonatal intensive care units responded (90 %). Responses were received from sixty-nine neonatologists (30 %) and seven paediatric intensivists (13 %). The overall response rate was 26 % (76/287). Thirty-three percent (25/76) commenced PN within 24 h of admission, 27 % (20/75) between 24 and 48 h, 24 % (18/75) between 48 and 72 h, 9 % (7/75) between 72 and 96 h and 4 % (3/75) between 96 h and 7 days. None of the respondents commenced PN after 7 d of admission. Sixty-one percent (46/75) aimed for 1·5-3 g/kg per d of parenteral amino acids, whereas 27 % (20/75) aimed for 2-3 g/kg per d. Renal failure (59 %; 38/64) and high plasma urea (44 %; 28/64) were the major indications for withholding/decreasing the amino acid intake. Eighty-three percent (63/76) aimed for a dose of 2·5g-3·5 g/kg per d of parenteral lipids; about 9 % (7/76) targeted a dose of 1-2·5 g/kg per d and 4 % (3/76) for > 3·5 g/kg per d. Thirty-two percent (24/74) reported that they would withhold/decrease the dose of parenteral lipids in infants with sepsis. The variations in clinicians' practices with respect to the use of PN in term and late preterm infants highlight the need for high-quality research in this population.
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http://dx.doi.org/10.1017/S0007114521003020DOI Listing
August 2021

Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis.

Arch Dis Child Fetal Neonatal Ed 2021 Jul 30. Epub 2021 Jul 30.

Neonatology, King Edward Memorial Hospital for Women, Subiaco, Western Australia, Australia.

Objective: To explore the association between hyperglycaemia and adverse outcomes in very preterm infants.

Design: Systematic review and meta-analysis. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. Subgroup analysis was conducted based on study design (cohort and case control).

Main Outcome Measures: Association between hyperglycaemia in preterm neonates (<32 weeks or <1500 g) and mortality and morbidities.

Findings: Forty-six studies (30 cohort and 16 case control) with data from 34 527 infants were included. Meta-analysis of unadjusted ORs from cohort studies found hyperglycaemia to be significantly associated with mortality, any-grade intraventricular haemorrhage (IVH), severe IVH, any-stage retinopathy of prematurity (ROP), severe ROP, sepsis, chronic lung disease and disability. However, pooling of adjusted ORs found significant associations only for mortality (adjusted OR (CI): 2.37 (1.40 to 4.01); I: 36%; 6 studies), 'Any grade IVH' (adjusted OR (CI): 2.60 (1.09 to 6.20); I: 0%; 2 studies) and 'Any stage ROP' (adjusted OR (CI): 3.70 (1.55 to 8.84); I: 0%; 2 studies). Meta-regression analysis found glucose levels >10 mmol/L to be associated with increased odds of mortality compared with <10 mmol/L. Pooled analysis from case-control studies were similar to cohort studies for most outcomes but limited by small sample size. Longer duration of hyperglycaemia was associated with adverse outcomes. GRADE of evidence was 'Low' or 'Very low'.

Conclusion: Hyperglycaemia in very preterm infants is associated with higher odds of mortality, any-grade IVH and any-stage ROP. A limitation was lack of availability of adjusted ORs from many of the included studies.

Prospero Registration Number: CRD42020193016.
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http://dx.doi.org/10.1136/archdischild-2020-321449DOI Listing
July 2021

Association of gastric residual volumes with necrotising enterocolitis in extremely preterm infants-a case-control study.

Eur J Pediatr 2021 Jul 17. Epub 2021 Jul 17.

Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, WA, Australia.

Necrotising enterocolitis (NEC) is a potentially serious illness with significant mortality and morbidity in preterm infants. Previous studies have reported association of volume and colour (bile and blood stained) of gastric residuals (GR) with NEC. We aimed to study this association in our cohort of extremely preterm (EP) infants. In a case-control study using retrospective data (January 2006-December 2011), EP (gestation < 28 weeks) infants with confirmed NEC ≥ stage II (cases) were compared with infants without NEC (controls) matched for birth weight (BW) and gestational age (GA). Forty cases of NEC ≥ stage II diagnosed at a median (IQR) age of 16.5 days (10.3-23) were compared with 40 controls matched for gestation (± 3 days) and birth weight (± 680 g). Median maximum GR volume (GRV) from birth to the day of occurrence of NEC was significantly higher in cases vs. controls (5.9 vs.3.7 ml; p < 0.001). Increased maximum GRV was associated with NEC ≥ Stage II in adjusted analysis (aOR 1.36, 95%CI 1.06-1.75, p = 0.017). There was no significant difference in GRV between cases and controls throughout the clinical course, including 72, 48 and 24 h before the onset of NEC. However, green (65.0% vs. 27.5%, p = 0.001) and haemorrhagic GRs (45.0% vs. 27.5%, p = 0.092) were higher 24 h before the diagnosis of NEC.Conclusion: GRV was not associated with NEC ≥ stage II. However, green and haemorrhagic GRs were significantly higher 24 h before the diagnosis of the illness. Adequately powered prospective studies are needed to confirm the significance of our findings. What is Known: •It is unclear whether large volume, dark-coloured and blood-stained GRs are associated with NEC. •The value of routine monitoring of gastric residuals in preterm infants is currently being questioned. What is New: •Volume of gastric residuals was not associated with significant NEC. •Green and haemorrhagic GRs were significantly higher 24 hours before diagnosis of NEC.
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http://dx.doi.org/10.1007/s00431-021-04193-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285712PMC
July 2021

Current Status of Probiotics for Preterm Infants.

Indian J Pediatr 2021 07 20;88(7):703-708. Epub 2021 Apr 20.

Neonatal Directorate, King Edward Memorial Hospital for Women, 374 Bagot Road, Subiaco, Western Australia, 6008.

Probiotics have been shown to reduce the risk of all-cause mortality, necrotizing enterocolitis (NEC ≥ stage II), late onset sepsis (LOS), and feeding intolerance in preterm infants. Considering the substantial health burden imposed by these conditions, the importance of probiotics in preterm infants cannot be overemphasized. Based on the data from experimental studies, and systematic reviews of randomized controlled trials (RCTs) and non-RCTs, the uptake of this intervention in neonatal medicine has been increasing over the last few years. However, many are still hesitating to adopt this intervention for various reasons, including concerns about probiotic sepsis, product quality, and lack of clarity on optimal strain/s or their combinations. Some question the validity of meta-analyses of studies involving different probiotic strains or their combinations because probiotics effects are considered to be strain-specific. Some of the early concerns about probiotics in preterm infants have been shown to be unjustified. However, the resistance to probiotics continues in many neonatal units around the world. The future of probiotics for preterm infants depends on continued efforts to develop high-quality probiotic products using stringent quality control, improving access to such products, and robust head-to-head comparisons to know the optimal strains or their combinations. Monitoring for adverse effects such as probiotic sepsis and development of antibiotic resistance is crucial. The authors review the current status of probiotics in preterm infants and discuss the scope for further research in this field.
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http://dx.doi.org/10.1007/s12098-021-03736-2DOI Listing
July 2021

Antenatal corticosteroids for impending late preterm (34-36+6 weeks) deliveries-A systematic review and meta-analysis of RCTs.

PLoS One 2021 22;16(3):e0248774. Epub 2021 Mar 22.

School of Medicine, University of Western Australia, Perth, Western Australia.

Background: Administration of antenatal corticosteroids (ANC) for impending preterm delivery beyond 34 weeks of gestation continues to be a controversial issue despite various guidelines for obstetricians and gynaecologists.

Objective: To compare outcomes following exposure to ANC for infants born between 34-36+6 weeks' gestation.

Methods: A systematic review of randomised controlled trials (RCT) reporting neonatal outcomes after ANC exposure between 34-36+6 weeks' gestation using Cochrane methodology. Databases including PubMed, Embase, Emcare, Cochrane Central library and Google Scholar were searched in May 2020. Primary outcomes: (1) Need for respiratory support (Mechanical ventilation, CPAP, high flow) or oxygen (2) Hypoglycemia. Secondary outcomes included respiratory distress syndrome (RDS), transient tachypnoea of newborn (TTN), need for neonatal resuscitation at birth [only in the delivery room immediately after birth (not in neonatal intensive care unit (NICU)], admission to NICU, mortality and developmental follow up. Level of evidence (LOE) was summarised by GRADE guidelines.

Main Results: Seven RCTs (N = 4144) with low to high risk of bias were included. Only one RCT was from high income countries, Meta-analysis (random-effects model) showed (1) reduced need for respiratory support [5 RCTs (N = 3844); RR = 0.68 (0.47-0.98), p = 0.04; I2 = 55%; LOE: Moderate] and (2) higher risk of neonatal hypoglycaemia [4 RCTs (N = 3604); RR = 1.61(1.38-1.87), p<0.00001; I2 = 0%; LOE: High] after ANC exposure. Neonates exposed to ANC had reduced need for resuscitation at birth. The incidence of RDS, TTN and surfactant therapy did not differ significantly. None of the included studies reported long-term developmental follow up.

Conclusions: Moderate quality evidence indicates that ANC exposure reduced need for respiratory support, and increased the risk of hypoglycaemia in late preterm neonates. Large definitive trials with adequate follow up for neurodevelopmental outcomes are required to assess benefits and risks of ANC in this population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984612PMC
October 2021

Effect of early kangaroo mother care on time to full feeds in preterm infants - A prospective cohort study.

Early Hum Dev 2021 03 22;154:105312. Epub 2021 Jan 22.

Neonatal Directorate, KEM Hospital for Women, Perth 6009, Australia; School of Medicine, University of Western Australia, Perth 6009, Australia. Electronic address:

Background: Kangaroo mother care (KMC) is known to reduce neonatal mortality and morbidity. In preterm neonates, KMC is usually initiated only after stabilization.

Aims: We aimed to assess if early initiation of KMC starting within the first week of life is safe, and reduces the time to full feeds (TFF) in preterm neonates.

Study Design: Prospective cohort study.

Subjects: Preterm neonates (Gestation ≤ 34 weeks, Birth weight ≤ 1250 g). This was studied in two epochs, (epoch 1) which was before early KMC vs. epoch 2 which was after implementation of early KMC even if they needed respiratory support, with umbilical/central lines in situ.

Outcome: The primary outcome of the study was time to establish full feeds (TFF) of 150 ml/kg/day.

Results: The neonatal demographic characteristics were comparable between epoch 1 and epoch 2 except for lower gestational age, higher surfactant, and any respiratory support in epoch 2. On univariate analysis, early KMC significantly reduced TFF (12.5 vs. 9 days, P < 0.001). Feed intolerance, duration of parenteral nutrition were significantly reduced, and discharge weight Z score improved significantly in epoch 2. On multivariate regression analysis early KMC, exclusive mother's own milk feeding and blood culture-positive late-onset sepsis were important predictors of TFF. Early KMC was safe and well-tolerated.

Conclusion: Early KMC was safe and associated with reduced TFF and other nutritional benefits in moderately ill preterm neonates.
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http://dx.doi.org/10.1016/j.earlhumdev.2021.105312DOI Listing
March 2021

Prophylactic Probiotic Supplementation for Preterm Neonates-A Systematic Review and Meta-Analysis of Nonrandomized Studies.

Adv Nutr 2021 07;12(4):1411-1423

Neonatal Directorate, King Edward Memorial Hospital, Perth, Western Australia.

Systematic review and meta-analyses of randomized controlled trials (RCTs) show that probiotics reduce the risk of necrotizing enterocolitis (NEC ≥ Stage II), late onset sepsis (LOS), all-cause mortality, and feeding intolerance in preterm neonates. Data from observational studies is important to confirm probiotic effects in clinical practice. We aimed to compare outcomes before and after implementing routine probiotic supplementation (RPS) in preterm neonates (<37 weeks of gestation) by performing a systematic review of non-RCTs using Cochrane methodology. Databases including PubMed, The Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Cochrane Central library, and Google Scholar were searched in May 2020. A meta-analysis was performed using a random effects model. Categorical measure of effect size was expressed as OR and 95% CI. Statistical heterogeneity was assessed by the chi-squared test, I2 statistic. The level of evidence (LOE) was summarized using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) guidelines. Primary outcomes were NEC ≥ Stage II, LOS, and all-cause mortality. Secondary outcomes included probiotic sepsis. Thirty good-quality non-RCTs (n = 77,018) from 18 countries were included. The meta-analysis showed RPS was associated with significantly reduced: 1) NEC ≥ Stage II (30 studies, n = 77,018; OR: 0.60; 95% CI: 0.50, 0.73; P <0.00001, I2: 65%; LOE: Moderate), 2) LOS: (21 studies, n = 65,858; OR: 0.85; 95% CI: 0.74, 0.97; P = 0.02, I2: 74%; LOE: Low), and 3) all-cause mortality (27 non-RCTs, n = 70,977; OR: 0.77; 95% CI: 0.68, 0.88; P = 0.0001, I2: 49%; LOE: Low). Subgroups: 1) extremely low birth weight (ELBW: birth weight <1000 g) neonates: RPS was associated with significantly reduced NEC ≥ Stage II (4.5% compared with 7.9%). However, there was no difference in LOS and mortality. 2) Multistrain RPS was more effective than single strain. One study reported 3 nonfatal cases of probiotic sepsis. In summary, moderate- to low-quality evidence indicates that RPS was associated with significantly reduced NEC ≥ Stage II, LOS, and all-cause mortality in neonates <37 weeks of gestation and NEC ≥ Stage II in ELBW neonates.
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http://dx.doi.org/10.1093/advances/nmaa164DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321836PMC
July 2021

Effect of shift work on fatigue and sleep in neonatal registrars.

PLoS One 2021 14;16(1):e0245428. Epub 2021 Jan 14.

Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Western Australia, Australia.

Objective: We aimed to study fatigue and sleep in registrars working 12-hour rotating shifts in our tertiary neonatal intensive unit.

Methods And Participants: This study involved neonatal registrar's working day (08:00-21:00) and night (20:30-08:30) shifts. Participants maintained a sleep diary, answered a self-reported sleepiness questionnaire assessing subjective sleepiness, and performed a 10-minute psychomotor vigilance task (PVT) at the start and end of each shift. Primary outcomes: (1) Fatigue at the (i) "start vs end" of day and night shifts, (ii) end of the "day vs night" shifts, and (iii) end of "first vs last shift" in block of day and night shifts. (2) Duration and quality of sleep before the "day vs night" shifts. Mean reaction time (RTM), relative coefficient of variation (RTCV), and lapses (reaction time > 500ms) were used as measures of fatigue on PVT. Secondary outcome: Subjective sleepiness (self-reported sleepiness questionnaire) at the 'start vs end" of day and night shifts.

Results: Fifteen registrars completed the study. Acuity was comparable for all shifts. (1) Psychomotor responses were impaired at the end vs start of day shifts [RTM (p = 0.014), lapses (p = 0.001)], end vs start of night shifts [RTM (p = 0.007), RTCV (p = 0.003), lapses (p<0.001)] and end of night vs day shifts [RTM (p = 0.007), RTCV (p = 0.046), lapses (p = 0.001)]. Only lapses were significantly increased at the end of the last (p = 0.013) vs first shift (p = 0.009) in a block of day and night shifts. (2) Duration of sleep before the night (p = 0.019) and consecutive night shifts was decreased significantly (p = 0.034). Subjective sleepiness worsened after day (p = 0.014) and night shifts (p<0.001).

Conclusion: Fatigue worsened after the 12-hour day and night shifts with a greater change after night shifts. Lapses increased after block of day and night shifts. Sleep was decreased before night shifts. Our findings need to be confirmed in larger studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245428PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808639PMC
June 2021

Enteral Vitamin A for Reducing Severity of Bronchopulmonary Dysplasia: A Randomized Trial.

Pediatrics 2021 01 18;147(1). Epub 2020 Dec 18.

Centre for Child Health Research, Medical School, The University of Western Australia and Telethon Kids Institute, Perth, Western Australia, Australia.

Background And Objectives: Evidence suggests that intramuscular vitamin A reduces the risk of bronchopulmonary dysplasia (BPD) in preterm infants. Our objective was to compare enteral water-soluble vitamin A with placebo supplementation to reduce the severity of BPD in extremely preterm infants.

Methods: We conducted a double-blind randomized controlled trial in infants <28 weeks' gestation who were to receive either enteral water-soluble vitamin A (5000 IU per day) or a placebo. Supplementation was started within 24 hours of introduction of feeds and continued until 34 weeks' postmenstrual age (PMA). The primary outcome was the severity of BPD, assessed by using the right shift of the pulse oximeter saturation versus the inspired oxygen pressure curve.

Results: A total of 188 infants were randomly assigned. The mean ± SD birth weight (852 ± 201 vs 852 ± 211 g) and gestation (25.8 ± 1.49 vs 26.0 ± 1.39 weeks) were comparable between the vitamin A and placebo groups. There was no difference in the right shift (median [25th-75th percentiles]) of the pulse oximeter saturation versus inspired oxygen pressure curve (in kilopascals) between the vitamin A (11.1 [9.5-13.7]) and placebo groups (10.7 [9.5-13.1]) ( = .73). Enteral vitamin A did not affect diagnosis of BPD or other clinical outcomes. Plasma retinol levels were significantly higher in the vitamin A group versus the placebo group on day 28 and at 34 weeks' PMA.

Conclusions: Enteral water-soluble vitamin A supplementation improves plasma retinol levels in extremely preterm infants but does not reduce the severity of BPD.
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http://dx.doi.org/10.1542/peds.2020-009985DOI Listing
January 2021

Stability of the Initial Diagnosis of Autism Spectrum Disorder by DSM-5 in Children: A Short-Term Follow-Up Study.

J Trop Pediatr 2021 01;67(1)

Neonatal Directorate, KEM Hospital for Women, Perth, Western Australia.

Background: Assessing the stability of the diagnosis of autism spectrum disorder (ASD) in children is important. Only few such studies have been reported from India. We aimed to assess the stability after 18-30 months, of an initial diagnosis of ASD based on DSM-5, in children ≤ 5 years of age using Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2).

Methods: A total of 125 children with ASD diagnosed by DSM-5 at ≤ 5 years of age were followed up at 18-30 months using ADOS-2, which is considered as the 'gold-standard' observational assessment for diagnosing ASD and hence suitable for confirming the stability of the diagnosis.

Results: Similar to previous studies from developed countries, the stability of ASD diagnosis was 80%. There was no significant correlation between gender, socioeconomic status and the stability of the final diagnosis. All the children continued to have some developmental difficulties mainly in the domain of language, attention or social communication.

Conclusion: Our results suggest that DSM-5 can be used for the initial diagnosis ASD to initiate early intervention for children with this condition in resource-limited set-ups. Adequately powered prospective studies with long-term follow-up are needed to confirm our findings.
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http://dx.doi.org/10.1093/tropej/fmaa104DOI Listing
January 2021

A survey on criteria for intubation in moderate to late preterm infants with respiratory distress.

Pediatr Pulmonol 2020 11 17;55(11):2970-2982. Epub 2020 Sep 17.

Neonatal Directorate, King Edward Memorial Hospital and Perth Children's Hospital, Subiaco, Western Australia, Australia.

Background: Majority of preterm infants do well with continuous positive airway pressure (CPAP) as the sole respiratory management; but some require endotracheal intubation and surfactant administration. While intubation is needed predominantly in extremely preterm infants (<28 weeks); some of the more mature preterm infants also require it. Currently, there are no clear guidelines regarding indications for endotracheal intubation in such infants.

Aims: To understand the current practice regarding "criteria for intubation" in moderate to late preterm infants with respiratory distress.

Methods: A survey of neonatologists in Australia New Zealand Neonatal Network (ANZNN) was conducted between April and June 2019.

Results: At least one neonatologist each from 29 of the 30 tertiary ANZNN Neonatal Intensive Care Units (NICUs) responded to the survey. In total, 118/200 (59%) neonatologists responded. The most common criteria for intubation were CPAP = 8 cmH O (61%), pH < 7.2 (55%), pCO  > 70 mmHg (48%), FiO  > 40% (40%), chest retractions (48%), more than two episodes of apnea requiring intervention (54%), and chest X-ray (CXR) showing moderate-severe hyaline membrane disease (HMD, 49%).

Conclusion: While there were variations in practice, nearly 50% of the neonatologists shared a common threshold with regards to the CPAP level, FiO , blood gas parameters, and clinical and radiological findings. The results of this survey will help in designing future randomized controlled trials (RCTs) on this subject.
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http://dx.doi.org/10.1002/ppul.25054DOI Listing
November 2020

Lactoferrin Expression Is Not Associated with Late-Onset Sepsis in Very Preterm Infants.

Neonatology 2020 28;117(5):606-611. Epub 2020 Aug 28.

Wesfarmers' Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Washington, Australia.

Background: Preterm infants are at a high risk of developing late-onset sepsis (LOS). Lactoferrin is one of the most abundant endogenous antimicrobial proteins expressed in breast milk, stools, and blood, and a candidate for preventive intervention. Large clinical trials have recently investigated whether enteral supplementation with bovine lactoferrin reduces LOS.

Aim: To characterize lactoferrin levels in preterm infants with and without LOS during the first month of life.

Methods: Very preterm and term infants were recruited and serial biosamples collected during the first month of life. Lactoferrin levels were determined by immunoassay in cord blood and peripheral blood on days 1, 7, 14, 21, and 28; in the stools on days 1 and 28; and in the mother's breast milk on days 7 and 21. Furthermore, we assessed the capacity of the peripheral blood to release lactoferrin in response to an in vitro challenge with live Staphylococcus epidermidis, lipopolysaccharide, and fibroblast-stimulating lipopeptide 1.

Results: Plasma lactoferrin levels were higher in cord blood and day 1 peripheral blood and declined during the first month of life. Plasma lactoferrin levels were similar in term infants and in preterm infants with (n = 32) and without LOS (n = 53). S. epidermidis-induced lactoferrin levels were lower following the sepsis episode.

Conclusions: Endogenous lactoferrin expression in preterm infants does not appear to affect their risk of developing LOS. These findings are in line with the lack of benefit recently observed in large trials of enteral supplementation with bovine lactoferrin to prevent LOS.
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http://dx.doi.org/10.1159/000509404DOI Listing
August 2021

Composition of Coloured Gastric Residuals in Extremely Preterm Infants-A Nested Prospective Observational Study.

Nutrients 2020 08 26;12(9). Epub 2020 Aug 26.

Neonatal Directorate, King Edward Memorial Hospital, Perth 6008, Western Australia, Australia.

Green gastric residuals (GR) are often considered as a sign of feed intolerance and discarded in preterm infants. Probiotics are known to enhance feed tolerance in preterm infants. To assess the composition (primary outcome) and volume of discarded green GRs, and feeding outcomes in extremely preterm (EP) infants in a probiotic trial, composition of pale and dark green GRs in the first two weeks of life from EP infants (<28 weeks) in a randomized controlled trial (RCT: SiMPro) of single vs. three-strain probiotics was assessed. Feeding outcomes included time to full feeds (TFF: 150 mL/kg/day) and duration of parenteral nutrition (PN). EP infants given placebo in our previous probiotic RCT served as the reference group. Analysis involved linear regression modelling with clustered standard errors for repeated measurements. GRs of 74/103 from 39 SiMPro infants (18: single-strain, 21: three-strain) were analyzed. Bile acid content was higher but statistically insignificant (825.79 vs. 338.1 µmol/L; = 0.12) in dark vs. pale green GRs. Mean (95% confidence interval) fat, nitrogen, and carbohydrate loss in GRs over the study period was 0.02 g (0.01-0.03), 0.011 g (0.009-0.013), and 0.05 g (0.04-0.06), respectively. Overall, SiMPro infants had shorter median TFF (10 vs. 14 days, = 0.02) and duration of PN (10 vs. 16 days, = 0.022) compared with control group infants. Z scores for growth parameters at discharge were comparable. Discarding dark green GRs meant higher loss of bile acids during early enteral nutrition in EP infants. Probiotic supplementation was associated with reduced TFF and duration of PN.
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http://dx.doi.org/10.3390/nu12092585DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551671PMC
August 2020

Early neurodevelopmental outcomes of congenital gastrointestinal surgical conditions: a single-centre retrospective study.

BMJ Paediatr Open 2020 11;4(1):e000736. Epub 2020 Aug 11.

Neonatal Directorate, Perth Children's Hospital and King Edward Memorial Hospital for Women, Perth, Western Australia, Australia.

Background: Evidence is emerging that surgery in the neonatal period is associated with increased risk of suboptimal neurodevelopmental outcomes (SNDO). The aim of this study was to describe neurodevelopmental outcomes (at 1 year) of neonatal surgery for congenital gastrointestinal surgical conditions (CGSC) and to explore risk factors.

Methods: Retrospective study (2005-2014) of infants born ≥34 weeks gestation with CGSC and admitted to the surgical neonatal intensive care unit of Perth Children's Hospital, Western Australia. Clinical details and 1-year developmental outcomes based on Griffiths Mental Developmental Assessment Scales were collated from the database and by reviewing the medical records of study infants. SNDO was defined as one or more of the following: a general quotient less than 88 (ie, >1 SD below mean), cerebral palsy, blindness or sensorineural deafness. Univariable and multivariable logistic regression analyses were carried out to explore risk factors for SNDO. A total of 413 infants were included, of which 13 died. Median gestation was 37.6 weeks (IQR: 36.4-39.1). Information on developmental outcomes was available from 262 out of 400 survivors. A total of 43/262 (16.4%) had SNDO. On univariable analysis, lower z scores for birth weight, prolonged duration of antibiotics, increased episodes of general anaesthesia and prolonged duration of hospital stay were associated with SNDO. On multivariable analysis, lower z scores for birth weight and prolonged hospital stay were associated with increased risk of SNDO.

Conclusions: Late preterm and term infants undergoing neonatal surgery for CGSC may be at risk for SNDO. Studies with longer duration of follow-up are needed to further evaluate the role of potentially modifiable risk factors on their neurodevelopmental outcomes.
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http://dx.doi.org/10.1136/bmjpo-2020-000736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422631PMC
August 2020

Comparison of wide field imaging by nurses with indirect ophthalmoscopy by ophthalmologists for retinopathy of prematurity: a diagnostic accuracy study.

BMJ Open 2020 08 5;10(8):e036483. Epub 2020 Aug 5.

Department of Neonatology, King Edward Memorial Hospital for Women, Perth, Western Australia, Australia.

Objectives: Retinopathy of prematurity (ROP) is a vasoproliferative disease of the preterm retina with the potential to cause irreversible blindness. Timely screening and treatment of ROP are critical. Neonatal nurses trained in wide field digital retinal photography (WFDRP) for screening may provide a safe and effective strategy to reduce the burden of ophthalmologists in performing binocular indirect ophthalmoscopy (BIO). The objective of the study was to determine the diagnostic accuracy of WFDRP in the diagnosis of referral warranting ROP (RWROP).

Design: Prospective diagnostic accuracy study.

Setting: A tertiary neonatal intensive care unit in Perth, Western Australia.

Participants: Preterm infants who fulfilled the Australian ROP screening criteria (gestational age (GA) <31 weeks, birth weight (BW) <1250 g).

Intervention: Sets of 5-6 images per eye (index test) were obtained within 24-48 hours prior to or after the BIO (reference standard), and uploaded onto a secured server. A wide field digital camera (RetCam, Natus, Pleasanton, California, USA) was used for imaging. A paediatric ophthalmologist performed the BIO. The ophthalmologists performing BIO versus reporting the images were masked to each other's findings.

Primary Outcome: The area under the receiver operating characteristic (ROC) curve was used as a measure of accuracy of WFDRP to diagnose RWROP.

Results: A total of 85 infants (mean BW; 973.43 g, mean GA; 29 weeks) underwent a median of two sessions of WFDRP. There were 188 episodes of screening with an average of five images per eye. WFDRP identified RWROP in 7.4% (14/188 sessions) of examinations. In one infant, BIO showed bilateral plus disease and WFDRP did not pick up the plus disease. WFDRP image interpretation had a sensitivity of 80%, specificity of 94.5% for the detection of RWROP. The 'area under the ROC curve' was 88% when adjusted for covariates.

Conclusions: WFDRP by neonatal nurses was feasible and effective for diagnosing RWROP in our set up.

Trial Registration Number: ACTRN12616001386426.
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http://dx.doi.org/10.1136/bmjopen-2019-036483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409991PMC
August 2020

Diffuse excessive high signal intensity on term equivalent MRI does not predict disability: a systematic review and meta-analysis.

Arch Dis Child Fetal Neonatal Ed 2021 Jan 25;106(1):9-16. Epub 2020 May 25.

Neonatal Intensive Care Unit, King Edward Memorial Hospital for Women Perth, Subiaco, Western Australia, Australia.

Objective: To evaluate whether diffuse excessive high signal intensity (DEHSI) on term equivalent age MRI (TEA-MRI) predicts disability in preterm infants.

Design: This is a systematic review and meta-analysis. Medline, EMBASE, Cochrane Library, EMCARE, Google Scholar and MedNar databases were searched in July 2019. Studies comparing developmental outcomes of isolated DEHSI on TEA-MRI versus normal TEA-MRI were included. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was undertaken where data were available in a format suitable for pooling.

Main Outcome Measures: Neurodevelopmental outcomes ≥1 year of corrected age based on validated tools.

Results: A total of 15 studies (n=1832) were included, of which data from 9 studies were available for meta-analysis. The pooled estimate (n=7) for sensitivity of DEHSI in predicting cognitive/mental disability was 0.58 (95% CI 0.34 to 0.79) and for specificity was 0.46 (95% CI 0.20 to 0.74). The summary area under the receiver operating characteristics (ROC) curve was low at 0.54 (CI 0.50 to 0.58). A pooled diagnostic OR (DOR) of 1 indicated that DEHSI does not discriminate preterm infants with and without mental disability. The pooled estimate (n=8) for sensitivity of DEHSI in predicting cerebral palsy (CP) was 0.57 (95% CI 0.37 to 0.75) and for specificity was 0.41 (95% CI 0.24 to 0.62). The summary area under the ROC curve was low at 0.51 (CI 0.46 to 0.55). A pooled DOR of 1 indicated that DEHSI does not discriminate between preterm infants with and without CP.

Conclusions: DEHSI on TEA-MRI did not predict future development of cognitive/mental disabilities or CP.

Prospero Registration Number: CRD42019130576.
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http://dx.doi.org/10.1136/archdischild-2019-318207DOI Listing
January 2021

Letter to the Editor.

J Paediatr Child Health 2020 04;56(4):658

Department of Neonatal Paediatrics, King Edward Memorial Hospital for Women, Perth, Western Australia, Australia.

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http://dx.doi.org/10.1111/jpc.14843DOI Listing
April 2020

Human Milk-Derived Fortifiers Compared with Bovine Milk-Derived Fortifiers in Preterm Infants: A Systematic Review and Meta-Analysis.

Adv Nutr 2020 09;11(5):1325-1333

School of Medicine, University of Western Australia, Perth, Western Australia, Australia.

This systematic review assessed outcomes after using human milk-derived fortifier (HMF) compared with bovine milk-derived fortifier (BMF) in preterm infants. Six randomized controlled trials (RCTs) were included. Meta-analysis using a random-effects model showed the following results: 1) lower risk of necrotizing enterocolitis (NEC; ≥Stage II) (RR: 0.38; 95% CI: 0.15, 0.95; P = 0.04, I2 = 9%; n = 334, 4 RCTs) and surgical NEC (RR: 0.13; 95% CI: 0.02, 0.67; P = 0.02, I2 = 0%; n = 209, 3 RCTs) in the HMF group; 2) no significant difference in mortality (RR: 0.40; 95% CI: 0.14, 1.15; P = 0.09, I2 = 0%; n = 334, 4 RCTs); 3) lower weight gain in the HMF group [mean difference (MD) = -1.08 g · kg-1 · d-1; 95% CI: -1.96, -0.21 g · kg-1 · d-1; P = 0.02, I2 = 0%; n = 241, 4 RCTs]; 4) no differences for length (MD = -0.11 cm/wk; 95% CI: -0.26, 0.04 cm/wk; P = 0.14, I2 = 68%) and head circumference (MD = -0.02 cm/wk; 95% CI: -0.08, 0.05 cm/wk; P = 0.59, I2 = 23%); and 5) no significant difference in late-onset sepsis (RR: 0.96; 95% CI: 0.56, 1.67; P = 0.90, I2 = 63%; n = 334, 4 RCTs). The beneficial effects of HMF for NEC were no longer significant in sensitivity analyses after excluding studies with high risk of bias. Quality of evidence as per Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis was low to very low, and hence the confidence in these results is low. In summary, fortification of milk in preterm infants with HMF compared with BMF decreased the risk of NEC but was associated with lower weight gain. Given the low quality of evidence, adequately powered and well-designed RCTs without the influence of industry are required in this field.
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http://dx.doi.org/10.1093/advances/nmaa039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490161PMC
September 2020

Probiotics for Preterm Infants in India - Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Indian J Pediatr 2020 Oct 17;87(10):817-825. Epub 2020 Mar 17.

School of Medicine, University of Western Australia, Perth, Western Australia, Australia.

The objective of the present study is to review current evidence from randomized controlled trials (RCTs) of probiotics for preterm infants in India. A systematic review of RCTs of probiotics for preterm infants in India was conducted using Cochrane methodology and PRISMA guidelines. Fixed effects model was used for meta-analysis. Nine RCTs (n = 1514) were included. Meta-analysis showed reduced risk of necrotizing enterocolitis (NEC) ≥ Stage II {Risk ratio (RR): 036 [95% confidence interval (CI): 0.20, 0.66], p = 0.0009, (9 RCTs)}, late onset sepsis [RR: 0.56 (95% CI: 0.45, 0.71), p < 0.00001, (7 RCTs)] and mortality [RR: 0.62 (95% CI: 0.41, 0.95, p = 0.03 (8 RCTs)] in the probiotic group. Probiotics also reduced the time to full feeds [Mean difference (MD): -4.09 d (95% CI: -4.52, -3.65), p < 0.00001, 5 RCTs] and duration of hospital stay [Fixed effects model (FEM): MD: -2.00 d (95% CI: -2.46, -1.53), p < 0.00001, 6 RCTs]. Current evidence from RCTs supports probiotic supplementation for optimizing outcomes of preterm infants in India.
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http://dx.doi.org/10.1007/s12098-020-03223-0DOI Listing
October 2020

Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study.

Pediatr Res 2020 12 16;88(6):878-886. Epub 2020 Mar 16.

Centre for Marine Science and Innovation at the University of New South Wales (UNSW), Sydney, NSW, Australia.

Background: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available.

Methods: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10-14 days of life (week 2).

Results: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia-Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001).

Conclusions: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs.

Impact: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.
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http://dx.doi.org/10.1038/s41390-020-0824-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223116PMC
December 2020

Saliva for Assessing Vitamin A Status in Extremely Preterm Infants: A Diagnostic Study.

Neonatology 2020 28;117(3):365-368. Epub 2020 Feb 28.

The UWA Centre for Child Health Research, Telethon Kids Institute, Perth, Washington, Australia.

Background: Salivary measurement of hormones and vitamins is gaining prominence as a minimally invasive procedure with the negligible potential for harm. We aimed to assess the utility of saliva for assessing vitamin A status in extremely preterm infants.

Methods: Paired saliva and blood samples were collected at 4 weeks of age from infants born <28 weeks of gestation using a proprietary polymer swab. Plasma retinol was measured using high-performance liquid chromatography, and salivary retinol was measured using enzyme-linked immunosorbent assay.

Results: Thirty infants were recruited with a median (IQR) gestation and birth weight of 26.2 weeks (24.8-27.2) and 865 g (718-1,002), respectively. An adequate volume of saliva (>50 µL) was obtained in 68%. There was no significant correlation (Spearman's correlation coefficient = 0.16, p = 0.3) between individual plasma and salivary retinol levels. Bland-Altman analysis showed wide limits of agreement (-113 to +119%) between individual plasma and salivary retinol levels.

Conclusion: Individual vitamin A status cannot be determined reliably from saliva in extremely preterm infants using current collection materials and analysis techniques.
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http://dx.doi.org/10.1159/000506132DOI Listing
August 2021

Spinal needle size and traumatic neonatal lumbar puncture: an observational study (neo-LP).

Eur J Pediatr 2020 Jun 30;179(6):939-945. Epub 2020 Jan 30.

Neonatal Directorate, King Edward Memorial Hospital for Women, Perth, Australia.

The incidence of 'traumatic' lumbar puncture (LP; CSF red cells > 500/mm) has been reported to be 35-46% in the neonatal period. A traumatic LP incurs challenges in diagnosis and management of the underlying condition and increases the risk of complications. We aimed to assess the benefits of a smaller outer diameter, larger gauge 25G needle in reducing the incidence of traumatic LPs compared with the standard 22G LP needle. This prospective observational study compared data from two consecutive epochs. Epoch 1 (Control, April 2016-October 2016), 22G needle for LP as standard practice. Epoch 2 (Intervention, November 2016-October 2017) 25G needle used for LP. Primary outcome was the incidence of traumatic LP. Multiple logistic regression analyses were conducted adjusting for corrected gestational age (CGA) at LP, proceduralist experience and need for ventilation as an indicator of illness. There were 240 LPs during the study period involving 361 attempts (22G, n = 228; 25G, n = 133). Median gestation at birth (P = 0.617) and CGA at LP (P = 0.163) were comparable. Multivariate analysis revealed lower incidence of traumatic LP using 25G needle (P < 0.001). Incidence of obtaining a successful CSF sample was similar between groups (P = 0.944). Proceduralist experience (P = 0.189) and neonatal illness (P = 0.801) were not significant factors.Conclusion: Our results showed that traumatic LPs were ~ 50% less common with 25G vs 22G needles while retaining a comparable success rate. Dry taps were more likely among the 25G group.What is Known:• The incidence of neonatal 'traumatic' lumbar puncture (CSF red cells > 500/mm) has been reported to be 35-46%.• A traumatic lumbar puncture incurs challenges in diagnosis and management of the underlying condition and increases the risk of complications.What is New:• Multivariate analysis revealed lower incidence of traumatic lumbar puncture using 25G needle (vs 22G).• Incidence of obtaining a successful CSF sample was similar between groups.
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http://dx.doi.org/10.1007/s00431-020-03580-0DOI Listing
June 2020

Developmental Outcomes following Topical Coconut Oil in Very Preterm Infants.

Neonatology 2019 9;116(3):302-304. Epub 2019 Aug 9.

Neonatal Directorate, King Edward Memorial Hospital for Women, Subiaco, Washington, Australia.

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http://dx.doi.org/10.1159/000501655DOI Listing
June 2020

Sepsis calculator for neonatal early onset sepsis - a systematic review and meta-analysis.

J Matern Fetal Neonatal Med 2021 Jun 11;34(11):1832-1840. Epub 2019 Aug 11.

Department of Neonatal Paediatrics, King Edward Memorial Hospital, Perth, Australia.

Background: Over investigation and overuse of empirical antibiotics is a concern in management of neonatal early onset sepsis (EOS) using the Centers for Disease Control and Prevention guidelines. "Sepsis calculator" is a risk-based prediction model for managing neonates at risk of EOS.

Objective: To compare outcomes of neonatal EOS using of sepsis calculator versus conventional approach.

Methods: A systematic review of randomized controlled trials (RCT) and non-RCTs reporting on outcomes after implementation of sepsis calculator for EOS for neonates >34-week gestation was conducted using the Cochrane methodology. Databases PubMed, CINAHL, Embase, Cochrane Central library and Google Scholar were searched in May 2019. Primary outcomes were antibiotics usage and laboratory tests for managing EOS. Secondary outcomes included hospital admissions and readmissions, blood culture positive EOS and mortality. The level of evidence (LOE) was summarized using the GRADE guidelines.

Results: A total of 387 articles were retrieved after initial search. Six high quality non-RCTs fulfilled inclusion criteria. Meta-analysis (random effects model) showed that implementation of sepsis calculator was associated with reduced antibiotic usage [ = 172,385; OR = 0.22 (0.14-0.36);  < .00001; heterogeneity () = 97%, Number needed to treat (NNT): 22], laboratory tests [ = 168,432; OR = 0.14 (0.08-0.27);  < .00001;  = 99%, NNT = 8], and admissions to neonatal unit [ = 16,628; OR = 0.24 (0.11-0.51);  = .0002;  = 98%, NNT = 7]; LOE: moderate. There was no difference in mortality, culture positive EOS, and readmissions.

Conclusion: Moderate quality evidence indicates that the implementation of a sepsis calculator was associated with reduced usage of antibiotics, laboratory tests and admission to neonatal unit with no increase in mortality and readmissions.
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http://dx.doi.org/10.1080/14767058.2019.1649650DOI Listing
June 2021
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