Publications by authors named "Karen Simmer"

144 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

Longitudinal Follow-up of Preterm Breastfeeding to 12 Weeks Corrected Gestational Age.

Adv Neonatal Care 2021 Nov 2. Epub 2021 Nov 2.

School of Molecular Sciences, Faculty of Science, The University of Western Australia, Crawley, Australia (Dr Perrella and Prof Geddes); Neonatology Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Australia (Ms Nancarrow and Prof Simmer); Mathematics and Statistics, Murdoch University, Murdoch, Australia (Dr Rea); School of Population and Global Health, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Australia (Dr Murray); and Centre for Neonatal Research and Education, School of Paediatrics and Child Health, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, Australia (Prof Simmer).

Background: Preterm infants have shorter breastfeeding duration than that of term infants. Details of postdischarge feeding methods and difficulties are needed to inform the care of preterm breastfeeding dyads.

Purpose: To describe postdischarge breastfeeding characteristics of mother-preterm infant dyads up to 12 weeks corrected gestational age (CGA).

Methods: A prospective observational study of preterm dyads (birth 24-33 weeks' gestation) that fed their mother's own milk (MOM) at discharge from a neonatal unit in Perth, Western Australia. Feeding method and frequency, breastfeeding duration, difficulties, and nipple shield use were recorded at 2, 6, and 12 weeks CGA.

Results: Data were obtained for 49 mothers (singleton infant n = 39, twins n = 10). At 12 weeks CGA, 59% fed any MOM with 47% exclusively fed MOM and 31% fully breastfed. Nipple shield use reduced from 42% at 2 weeks CGA to 11% at 12 weeks CGA. Compared with mothers who exclusively fed MOM at discharge (n = 41) those who fed both MOM and infant formula (n = 8) were more likely to wean before 12 weeks CGA (P < .001). Weaning occurred before 2 weeks CGA in 12/19 (63%), with low milk supply the most frequently cited reason.

Implications For Practice: Most mothers with a full milk supply at discharge successfully transition to predominant breastfeeding. Frequent milk removal needs to be prioritized throughout the preterm infant's hospital stay.

Implications For Research: Examination of facilitators and barriers to early and continued frequent milk removal across the postpartum period is required to identify strategies to optimize lactation after preterm birth.
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http://dx.doi.org/10.1097/ANC.0000000000000925DOI 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

Postnatal weight gain in very preterm infants: are we aiming too high?

Lancet Child Adolesc Health 2021 10 25;5(10):683-685. Epub 2021 Aug 25.

Neonatal Directorate, King Edward Memorial and Perth Children's Hospitals, Perth, WA 6009, Australia; School of Medicine, University of Western Australia, Perth, WA, Australia. Electronic address:

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http://dx.doi.org/10.1016/S2352-4642(21)00247-9DOI Listing
October 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

Plasma secretory phospholipase A2 as an early marker for late-onset sepsis in preterm infants-a pilot study.

Acta Paediatr 2021 Nov 26;110(11):3011-3013. Epub 2021 Jun 26.

Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, WA, Australia.

Preterm infants are particularly susceptible to bacterial late-onset sepsis (LOS). Diagnosis by blood culture and inflammatory markers have sub-optimal sensitivity and specificity and prolonged reporting times. There is an urgent need for more rapid, accurate adjunctive diagnostics in LOS to improve management and minimise antibiotic exposure. We measured the diagnostic performance of secretory phospholipase A2 type IIA (sPLA2-IIA) in very preterm infants (<30 weeks gestational age) with suspected LOS. Plasma sPLA2-IIA levels were elevated in infants with LOS (n = 28) compared to those without LOS (n = 21; median 30,970 vs. 2534 pg/ml, p < 0.0001). The mean area under the curve was 0.884 (95% CI: 0.771, 0.977) with a sensitivity of 0.907 (95% CI: 0.667, 1.00) and specificity of 0.804 (95% CI: 0.600, 1.00). The positive and negative predictive values were 0.833 (95% CI: 0.664, 0.927) and 0.842 (95% CI: 0.624, 0.945), respectively. This pilot study suggests that sPLA2-IIA may have clinical utility for the early diagnosis of LOS in very preterm infants, potentially informing clinical management and antibiotic stewardship.
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http://dx.doi.org/10.1111/apa.15969DOI Listing
November 2021

Protocol for assessing if behavioural functioning of infants born <29 weeks' gestation is improved by omega-3 long-chain polyunsaturated fatty acids: follow-up of a randomised controlled trial.

BMJ Open 2021 05 5;11(5):e044740. Epub 2021 May 5.

Discipline of Paediatrics, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, South Australia, Australia.

Introduction: During the last trimester of pregnancy, the fetal brain undergoes a rapid growth spurt and accumulates essential nutrients including docosahexaenoic acid (DHA). This takes place ex-utero for infants born <29 weeks' gestation, without the in-utero provisions of DHA. Infants born <29 weeks' are more likely to experience behavioural and emotional difficulties than their term-born counterparts. It has been hypothesised that supplementing preterm infants with dietary DHA may alleviate insufficiency and subsequently prevent or minimise behavioural problems. This protocol describes a follow-up of infants born <29 weeks gestation who were enrolled in a randomised controlled trial (RCT) of DHA supplementation. We aim to determine whether DHA supplementation improves the behaviour, and general health of these infants.

Methods And Analysis: Infants born <29 weeks' gestation were enrolled in a multicentre blinded RCT of enteral DHA supplementation. Infants were randomised to receive an enteral emulsion that provided 60 mg/kg/day of DHA or a control emulsion commenced within the first 3 days of enteral feeding, until 36 weeks' postmenstrual age or discharge home, whichever occurred first. Families of surviving children (excluding those who withdrew from the study) from the Australian sites (up to 955) will be invited to complete a survey. The survey will include questions regarding child behavioural and emotional functioning, executive functioning, respiratory health and general health. We hypothesise that the DHA intervention will have a benefit on the primary outcome, parent-rated behaviour and emotional status as measured using the Total Difficulties score of the Strengths and Difficulties Questionnaire. Detecting a 2-point difference between groups (small effect size of 0.25 SD) with 90% power will require follow-up of 676 participants.

Ethics And Dissemination: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/16/WCHN/184). Results will be disseminated in peer-reviewed publications and conference presentations.

Trial Registration Number: ACTRN12612000503820.
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http://dx.doi.org/10.1136/bmjopen-2020-044740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103387PMC
May 2021

Protocol for assessing whether cognition of preterm infants <29 weeks' gestation can be improved by an intervention with the omega-3 long-chain polyunsaturated fatty acid docosahexaenoic acid (DHA): a follow-up of a randomised controlled trial.

BMJ Open 2021 02 5;11(2):e041597. Epub 2021 Feb 5.

Women and Kids, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Introduction: Docosahexaenoic acid (DHA) is an omega-3 (n-3) fatty acid that accumulates into neural tissue during the last trimester of pregnancy, as the fetal brain is undergoing a growth spurt. Infants born <29 weeks' gestation are deprived the normal in utero supply of DHA during this period of rapid brain development. Insufficient dietary DHA postnatally may contribute to the cognitive impairments common among this population. This follow-up of the N-3 fatty acids for improvement in respiratory outcomes (N3RO) randomised controlled trial aims to determine if enteral DHA supplementation in infants born <29 weeks' gestation during the first months of life improves cognitive development at 5 years of age corrected for prematurity.

Methods And Analysis: N3RO was a randomised controlled trial of enteral DHA supplementation (60 mg/kg/day) or a control emulsion (without DHA) in 1273 infants born <29 weeks' gestation to determine the effect on bronchopulmonary dysplasia (BPD). We showed that DHA supplementation did not reduce the risk of BPD and may have increased the risk.In this follow-up at 5 years' corrected age, a predefined subset (n=655) of children from five Australian sites will be invited to attend a cognitive assessment with a psychologist. Children will be administered the Wechsler Preschool and Primary Scale of Intelligence (fourth edition) and a measure of inhibitory control (fruit stroop), while height, weight and head circumference will be measured.The primary outcome is full-scale IQ. To ensure 90% power, a minimum of 592 children are needed to detect a four-point difference in IQ between the groups.Research personnel and families remain blinded to group assignment.

Ethics And Dissemination: The Women's and Children Health Network Human Research Ethics Committee reviewed and approved the study (HREC/17/WCHN/187). Caregivers will give informed consent prior to taking part in this follow-up study. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.

Trial Registration Number: ACTRN12612000503820.
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http://dx.doi.org/10.1136/bmjopen-2020-041597DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925903PMC
February 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

Estimates of Preterm Infants' Breastfeeding Transfer Volumes Are Not Reliably Accurate.

Adv Neonatal Care 2020 Oct;20(5):E93-E99

School of Molecular Sciences, Faculty of Science (Dr Perrella and Prof Geddes), School of Mathematics and Statistics, Faculty of Engineering and Mathematical Sciences (Dr Rea), School of Population and Global Health, Faculty of Health and Medical Sciences (Dr Murray), and Centre for Neonatal Research and Education, School of Paediatrics and Child Health, Faculty of Health and Medical Sciences (Prof Simmer), The University of Western Australia, Crawley, Western Australia; and Neonatology Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia (Ms Nancarrow and Prof Simmer).

Background: Adequate human milk nutrition is critical for infant growth and neurodevelopment; however, low milk transfer volumes are common when establishing preterm breastfeeding. Despite clinical assessments of milk transfer volumes at the breast being inaccurate, measurement of feed volume via test weighing is rarely carried out either routinely or in cases where infant weight gain is inadequate.

Purpose: To assess the accuracy of the Preterm Breastfeeding Assessment Tool (PBAT) in determining transfer volumes and examine factors associated with PBAT accuracy.

Methods: Pre/postfeed weights were performed using electronic scales and PBAT scores recorded for 1186 breastfeeds in 60 preterm infants born less than 33/40 and 33 to 39/40 postmenstrual age. Measured milk intake volumes were converted to percent prescribed feed volume and compared with PBAT estimates of milk transfer.

Results: The PBAT is accurate in identifying when no milk is transferred at the breast but not in estimating transfer of half or the full prescribed volume (accuracy 26% and 47%, respectively). Wide ranges of transfer volumes (11-75 mL) were observed within and between infants, and for 20% of breastfeeds, no milk was transferred. Preterm Breastfeeding Assessment Tool accuracy decreased with each 1-week increase in birth gestation (odds ratio = 0.82; 95% confidence interval, 0.71-0.94; P = .004).

Implications For Practice: When establishing breastfeeding, test weighing facilitates adequate nutrition by guiding appropriate complementary feeding. For mothers breastfeeding several times per day in preparation for discharge home, test weighing may offer a useful tool for developing maternal confidence in assessing milk transfer. Preterm Breastfeeding Assessment Tool is inaccurate in assessing preterm infants' milk transfer volumes when breastfeeding.

Implications For Research: While studies have typically focused on medically stable infants, test weighing offers a useful tool to examine breastfeeding efficacy and inform nutritional management of preterm infants with complications such as chronic lung and cardiac disease.
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http://dx.doi.org/10.1097/ANC.0000000000000721DOI Listing
October 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

Validation of WINROP (online prediction model) to identify severe retinopathy of prematurity (ROP) in an Australian preterm population: a retrospective study.

Eye (Lond) 2021 May 17;35(5):1334-1339. Epub 2020 Jul 17.

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

Introduction: Retinopathy of prematurity (ROP) is the most common disease leading to blindness in extreme preterm infants. Current screening guidelines recommend frequent eye examinations. There is a dearth of trained ophthalmologists for these frequent screening procedures. The ANZNN neonatal network report (2013) found that only 6.4% of all screened infants had severe ROP and less than half received treatment. WINROP (online prediction model, Sweden) uses the postnatal weight gain (surrogate marker for low insulin-like growth factor IGF-1 and poor retinal vascular growth) to identify ROP requiring treatment and aims to reduce the number of examinations. Our objective was to validate the WINROP model in an Australian cohort of preterm infants.

Methods: Birth weight, gestational age, and weekly weight measurements were retrieved retrospectively along with the final ROP outcomes and plotted on the online WINROP software.

Results: The sensitivity, specificity, positive predictive value, and negative predictive value of WINROP were 85.7%, 59.0%, 6.98%, and 99.1% respectively for a cohort of 221 preterm infants (Median birth weight, 1040 g; Gestational age, 27.9 weeks). WINROP alarm was signaled in 42.6% of all infants. WINROP did not signal an alarm in one infant who needed treatment. This infant had intra ventricular hemorrhage grade 3-4 and temporary ventricular dilatation.

Conclusions: This is the first Australian study validating WINROP model. Our findings suggest that it lacked sensitivity to be used alone. However, adjusting the algorithm for the Australian population may improve the efficacy and reduce the number of examinations when used along with the current screening guidelines.
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http://dx.doi.org/10.1038/s41433-020-1094-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182793PMC
May 2021

Early Use of Antibiotics Is Associated with a Lower Incidence of Necrotizing Enterocolitis in Preterm, Very Low Birth Weight Infants: The NEOMUNE-NeoNutriNet Cohort Study.

J Pediatr 2020 12 14;227:128-134.e2. Epub 2020 Jun 14.

Department of Neonatology, Shenzhen Bao'an Maternal and Child Health Hospital, Shenzhen, China.

Objective: To determine whether commencement of antibiotics within 3 postnatal days in preterm, very low birth weight (VLBW; ≤1500 g) infants is associated with the development of necrotizing enterocolitis (NEC).

Study Design: Preplanned statistical analyses were done to study the association between early antibiotic treatment and later NEC development, using the NEOMUNE-NeoNutriNet cohort of VLBW infants from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2831). NEC incidence was compared between infants who received early antibiotics and those who did not, with statistical adjustments for NICU, gestational age, birth weight, sex, delivery mode, antenatal steroid use, Apgar score, and type and initiation of enteral nutrition.

Results: The incidence of NEC was 9.0% in the group of infants who did not receive early antibiotics (n = 269), compared with 3.9% in those who did receive early antibiotics (n = 2562). The incidence remained lower in the early antibiotic group after stepwise statistical adjustments for NICU (OR, 0.57; 95% CI, 0.35-0.94, P < .05) and other potential confounders (OR, 0.25; 95% CI, 0.12-0.47; P < .0001).

Conclusions: In this large international cohort of preterm VLBW infants, a small proportion of infants did not receive antibiotics just after birth, and these infants had a higher incidence of NEC. It is important to better understand the role of such variables as time, type, and duration of antibiotic treatment on NEC incidence, immune development, gut colonization, and antibiotic resistance in the NICU.
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http://dx.doi.org/10.1016/j.jpeds.2020.06.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686259PMC
December 2020

Plasma cytokine profiles in very preterm infants with late-onset sepsis.

PLoS One 2020 14;15(5):e0232933. Epub 2020 May 14.

Centre for Neonatal Research and Education and Division of Paediatrics, Medical School, University of Western Australia, Perth, Western Australia, Australia.

Introduction: Deficiencies in innate immune responses may contribute to the increased susceptibility to infection in preterm infants. In vivo cytokine profiles in response to sepsis in very preterm infants are not fully understood.

Aims: To characterise plasma pro- and anti-inflammatory cytokine concentrations and pre-defined ratios in very preterm infants with late-onset sepsis (LOS).

Methods: In this observational study, peripheral blood samples were collected at the time of evaluation for suspected LOS from 31 preterm infants (<30 weeks gestational age). Plasma cytokine concentrations were determined by 12-plex immunoassay.

Results: IL-10, IFN-γ, IL-12p70, IP-10, IL-6 and CCL2 were elevated in the majority infants with LOS (n = 12) compared to those without LOS (n = 19). There was no difference in TNF-α, IL-1β, IL-17AF, IL-8 and IL-15 concentrations between groups. IL-10/TNF-α ratios were increased, while CCL2/IL-10 and IL-12p70/IL-10 ratios were decreased in infants with LOS compared to those without.

Conclusion: Very preterm infants have a marked innate inflammatory response at the time of LOS. The increase in IL-10/TNF-α ratio may indicate early immune hypo-responsiveness. Longitudinal studies with a larger number of participants are required to understand immune responses and clinical outcomes following LOS in preterm infants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232933PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7224469PMC
August 2020

Do infants of breast-feeding mothers benefit from additional long-chain PUFA from fish oil? A 6-year follow-up.

Br J Nutr 2020 10 21;124(7):701-708. Epub 2020 Apr 21.

School of Paediatrics and Child Health, Faculty of Health and Medical Science, The University of Western Australia, Crawley, WA6009, Australia.

Fish-oil supplements are marketed as enhancing intelligence and cognitive performance. However, empirical data concerning the utility of these products in healthy term infants are mixed, particularly with respect to lasting effects into childhood. We evaluated whether fish-oil supplementation during infancy leads to better neurocognitive/behavioural development at 6 years. We conducted a double-blind randomised controlled trial of supplementation with n-3 long-chain PUFA in 420 healthy term infants. Infants received either fish oil (containing at least 250 mg DHA and at least 60 mg EPA) or placebo (olive oil) daily from birth to 6 months of age. Neurodevelopmental follow-up was conducted at a mean age of 6 years (sd 7 months), whereby 335 children were assessed for language, executive functioning, global intelligence quotient and behaviour. No significant differences were observed between the groups for the main neurocognitive outcomes. However in parent-report questionnaire, fish-oil supplementation was associated with negative externalising (P = 0·035, d = 0·24) and oppositional/defiant behaviour (P = 0·006, d = 0·31), particularly in boys (P = 0·01, d = 0·45; P = 0·004, d = 0·40). Our results provide evidence that fish-oil supplementation to predominantly breast-fed infants confers no significant cognitive or behavioural benefit to children at 6 years.
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http://dx.doi.org/10.1017/S000711452000135XDOI 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

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

BMC Pediatr 2020 02 8;20(1):59. Epub 2020 Feb 8.

Paediatric Intensivist, Sydney Children's Hospital, Sydney, Australia.

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.
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http://dx.doi.org/10.1186/s12887-020-1958-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007668PMC
February 2020

Impaired Cytokine Responses to Live Staphylococcus epidermidis in Preterm Infants Precede Gram-positive, Late-onset Sepsis.

Clin Infect Dis 2021 01;72(2):271-278

Murdoch Children's Research Institute, Royal Children's Hospital, Victoria, Australia.

Background: Late-onset sepsis (LOS) with Staphylococcus epidermidis is common in preterm infants, but the immunological mechanisms underlying heightened susceptibility are poorly understood. Our aim is to characterize the ontogeny of cytokine responses to live S. epidermidis in preterm infants with and without subsequent Gram-positive LOS.

Methods: We conducted a prospective, observational cohort study of preterm infants (<30 weeks gestational age [GA]) with blood sampling on Days 1, 7, 14, 21, and 28 of life. Cytokine responses in peripheral whole blood stimulated with live S. epidermidis were analyzed by 11-plex immunoassay.

Results: Of 129 infants (mean GA, 26.2 weeks; mean birth weight, 887g), 23 (17.8%) had confirmed LOS with Gram-positive organisms and 15 (11.6%) had clinical sepsis, with median onsets at 13 and 15 days, respectively. Blood cytokine responses to an in vitro S. epidermidis challenge were similar between infected and uninfected infants on Day 1, but diverged thereafter. Infants with subsequent LOS displayed broadly reduced S. epidermidis-induced responses from Day 7 onwards, compared to those who did not develop LOS. This pattern was observed with chemokines (interleukin [IL]-8, monocyte chemotactic protein-1, and macrophage inflammatory protein-1α), pro-inflammatory cytokines (IL-1, IL-6, and tumor necrosis factor-α) and the regulatory cytokine IL-10.

Conclusions: Cytokine responses to a live S. epidermidis challenge are impaired in infants with LOS and precede the onset of clinical illness. Quantifying pathogen-specific cytokine responses at Day 7 may identify those high-risk preterm infants at the greatest risk of LOS, and prospective replication is warranted.
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http://dx.doi.org/10.1093/cid/ciaa063DOI Listing
January 2021

and Polymorphisms Modulate Fatty Acid Metabolism and Dietary Impact on Health.

Annu Rev Nutr 2019 08;39:21-44

Dr. von Hauner Children's Hospital, University of Munich Medical Center, Ludwig-Maximilians-Universität München, 80337 Munich, Germany; email:

Variants in the gene cluster modify the activity of polyunsaturated fatty acid (PUFA) desaturation and the lipid composition in human blood and tissue. variants have been associated with plasma lipid concentrations, risk of cardiovascular diseases, overweight, eczema, pregnancy outcomes, and cognitive function. Studies on variations in the genecluster provided some of the first examples for marked gene-diet interactions in modulating complex phenotypes, such as eczema, asthma, and cognition. Genotype distribution differs markedly among ethnicities, apparently reflecting an evolutionary advantage of genotypes enabling active long-chain PUFA synthesis when the introduction of agriculture provided diets rich in linoleic acid but with little arachidonic and eicosapentaenoic acids. Discovering differential effects of PUFA supply that depend on variation of genotypes could open new opportunities for developing precision nutrition strategies based either on an individual's genotype or on genotype distributions in specific populations.
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http://dx.doi.org/10.1146/annurev-nutr-082018-124250DOI Listing
August 2019

Short-term rate of milk synthesis and expression interval of preterm mothers.

Arch Dis Child Fetal Neonatal Ed 2020 May 11;105(3):266-269. Epub 2019 Jul 11.

Department of Molecular Sciences, The University of Western Australia, Crawley, Western Australia, Australia.

Aim: To determine the impact of the pumping regimes of women with preterm infants on the daily milk production, and on the short-term rate of milk synthesis during early lactation to support evidence-based recommendations for optimising milk production.

Methods: Mothers of preterm infants (n=25) recorded start time, finish time and expression volumes from every breast expression on days 10, 15-20 postpartum.

Results: Expressing more often than five times per day did not result in a significant increase in daily milk production. Milk volume per expression per breast increased for intervals between expressions of between 2and6 hours then reached a plateau when the interval between expression was 7 hours or longer. The short-term rate of milk synthesis decreased as the interval between expressions increased until about 7.5 hours at which point it begun to increase (p value associated with interval between expressions^2<0.001).

Conclusion: The strong inverse association between the short-term rate of milk synthesis and the interval between expressions for intervals up to 7 hours suggest that the maximum interval between expressions should be 7 hours. Data suggest that, on average, the mothers should express at least five times a day to maximise daily milk production. Considering inter-individual variation, determination of an individual mother's maximum interval between expressions that does not compromise the short-term rate of milk synthesis will help to optimise daily milk production while minimising the demands on the mother's time.
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http://dx.doi.org/10.1136/archdischild-2018-316551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363781PMC
May 2020

Docosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: follow-up of a randomized controlled trial.

Am J Clin Nutr 2019 06;109(6):1600-1610

Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia.

Background: Docosahexaenoic acid (DHA, 22:6n-3) supplementation in the prenatal period is associated with a reduction in the incidence of some symptoms of allergic disease. Infants born preterm are at increased risk of allergic disease, but it is unknown if DHA supplementation reduces the risk of childhood allergies.

Objectives: The aim of this study was to determine if supplementation of infants born at <33 wk gestation with high-DHA compared with standard-DHA enteral feeds decreases the incidence and severity of parent-reported allergic disease symptoms at a corrected age (CA) of 7 y.

Methods: This study was a follow-up of an Australian multicenter randomized controlled trial. Infants were given high-DHA (∼1% total fatty acids) or standard-DHA (∼0.3% total fatty acids) enteral feeds from 2-4 d of postnatal age until 40 wk postmenstrual age. Parent-reported incidence of respiratory allergic disease symptoms including wheeze and rhinitis at 7 y CA were the main outcomes. Other outcomes included the incidence of eczema symptoms; severity of any symptoms; and the incidence of wheeze, rhinitis, rhinoconjunctivitis, and eczema from birth to 7 y CA.

Results: Data were available for 569 of 657 (87%) children originally randomized. Symptoms of wheeze or rhinitis at 7 y CA did not differ between high- and standard-DHA groups [wheeze: RR: 1.10; 95% CI: 0.73, 1.65; P = 0.66; rhinitis: RR: 1.09; 95% CI: 0.81, 1.46; P = 0.59]. There was no difference in other allergic disease symptoms at 7 y CA or in the severity of symptoms. Parent-reported symptoms of wheeze, rhinitis, rhinoconjunctivitis, or eczema from birth to 7 y CA did not differ between the groups.

Conclusions: High-dose DHA supplementation of infants born at <33 wk gestation did not alter allergic disease symptoms or severity at 7 y CA, or from birth to 7 y CA compared with standard-dose DHA. This trial was registered with the Australian New Zealand Clinical Trials Registry as ANZCTR 12606000327583 (http://www.anzctr.org.au).
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http://dx.doi.org/10.1093/ajcn/nqz010DOI Listing
June 2019

A clinical audit of the growth of preterm infants fed predominantly pasteurised donor human milk those fed mother's own milk in the neonatal intensive care unit.

Br J Nutr 2019 May 5;121(9):1018-1025. Epub 2019 Apr 5.

Medical School, University of Western Australia, Crawley, WA6009, Australia.

Preterm infants whose mothers are unable to produce sufficient breast milk are increasingly being supplemented with pasteurised donor human milk (PDHM) instead of commercial preterm infant formula. Concerns have been raised that this practice can result in reduced growth. This retrospective clinical audit collected data from the medical records of a cohort of preterm infants (≤30 weeks gestational age) receiving either ≥28 d of PDHM (n 53) or ≥28 d of their mother's own milk (MOM, n 43) with standard fortification supplied to both groups during admission. Weight growth velocity was assessed from regained birth weight to 34+1 weeks' postmenstrual age (PMA); and weight, length and head circumference were compared at discharge and 12 months (corrected age). At 34+1 weeks' PMA, the weight growth velocity (g/kg per d) was significantly lower in the PDHM group (15·4 g/kg per d, 95 % CI 14·6, 16·1) compared with the MOM group (16·9 g/kg per d, 95 % CI 16·1, 17·7, P=0·007). However, the increase was still within clinically acceptable limits (>15 g/kg per d) and no significant difference was observed in the weight between the two groups. There was no significant difference in weight between the groups at discharge or at the 12-month corrected gestational age review. Although we demonstrated a significant reduction in the weight growth velocity of preterm infants receiving PDHM at 34 weeks' PMA, this difference is not present at discharge, suggesting that the growth deficit is reduced by supplementation before discharge.
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http://dx.doi.org/10.1017/S0007114519000357DOI Listing
May 2019

Effect of vacuum-release teat versus standard teat use on feeding milestones and breastfeeding outcomes in very preterm infants: A randomized controlled trial.

PLoS One 2019 22;14(3):e0214091. Epub 2019 Mar 22.

Neonatology Clinical Care Unit, King Edward Memorial Hospital, Subiaco, Western Australia, Australia.

Background: Breast milk is important to infant health, yet shorter breastfeeding duration is reported for preterm infants. Both breast and bottle feeds are given in the neonatal unit, with full oral feeding often the last milestone to be achieved prior to discharge home. Unlike standard bottle teats, a vacuum release teat requires the application of negative intra-oral pressure to release milk, and so may facilitate breastfeeding in preterm infants. The objective of this study was to determine the effect of vacuum release teat use on timing of achievement of the first full oral feed and on first completion of 24 h full oral feeds. Feeding method at discharge home, 2 weeks, 6 weeks and 12 weeks corrected gestational age were also examined.

Methods: A randomized controlled trial was completed with mothers of preterm infants born 24-33 weeks gestation in the neonatal unit of a tertiary women's hospital. Infants were randomized to one of two parallel groups using a vacuum release teat or standard teat for oral feeds when the mother was not available to breastfeed. Test weights were completed for all oral feeds. It was not possible to blind participants, care givers and outcome assessors to group assignment due to the nature of the study.

Results: The groups did not differ with regard to timing of achievement of first full oral feed or 24 h of full oral feeds. Significantly more infants in the vacuum release teat group were exclusively fed breast milk at discharge from hospital and breastfed at 3 months corrected gestational age.

Conclusions: Use of a vacuum release teat when the mother is not available to breastfeed may promote preterm breastfeeding skills, resulting in higher rates of exclusivity and longer breastfeeding duration.

Trial Registration: The trial is registered with the Australian New Zealand Clinical Trials Registry ACTRN12615000245594.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214091PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430377PMC
December 2019

Histological chorioamnionitis and developmental outcomes in very preterm infants.

J Perinatol 2019 02 5;39(2):321-330. Epub 2018 Dec 5.

Division of Obstetrics and Gynaecology, University of Western Australia, Perth, WA, Australia.

Objective: To characterize the association of histological chorioamnionitis (HCA) with neurodevelopmental outcomes in children born at <30 weeks gestation.

Study Design: This retrospective cohort study included infants born 2006-2012 in whom placental histopathology, neonatal outcomes, and Bayley-III assessment at age 2 years were available. We assessed the association of HCA exposure with cognitive, language, and motor delay with logistic regression models adjusted for gestational age, sex, small for gestational age and brain injury.

Results: Of 1353 infants, 985 had histological and neonatal data available, and 708 infants had Bayley-III assessments. HCA-exposed infants were at higher risk of some neonatal adverse outcomes, and stage of HCA correlated with low Apgar score and early-onset sepsis. Exposure to HCA was not associated with neurodevelopmental outcomes in adjusted models including stage of HCA.

Conclusions: Exposure to HCA, especially higher stage, was associated with neonatal morbidity but not with adverse neurodevelopmental outcomes at 2 years of age.
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http://dx.doi.org/10.1038/s41372-018-0288-3DOI Listing
February 2019

Time to Full Enteral Feeding for Very Low-Birth-Weight Infants Varies Markedly Among Hospitals Worldwide But May Not Be Associated With Incidence of Necrotizing Enterocolitis: The NEOMUNE-NeoNutriNet Cohort Study.

JPEN J Parenter Enteral Nutr 2019 07 22;43(5):658-667. Epub 2018 Nov 22.

Department of Neonatology, Shenzhen Bao'an Maternal and Child Health Hospital, Shenzhen, China.

Background: Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes.

Method: Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates.

Results: Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8-33 days), weight gain (5.0-14.6 g/kg/day), ∆z-scores (-0.54 to -1.64), incidence of NEC (1%-13%), and mortality (1%-18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P < .001) than non-GD units, but NEC incidence and mortality were similar.

Conclusion: Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life.
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http://dx.doi.org/10.1002/jpen.1466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6531355PMC
July 2019
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