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Novel liquid crystal (LC) materials of ester derivatives were synthesized and studied with a view to understanding and establishing the effects of molecular structure on LC properties. The novel molecules consist of two phenyl rings bonded through –COO– central group and a laterally substituted methoxy group with –OCnH2n+1as well as –COOCH3terminal end groups, and yielded 12 homologous members of an ester series. The C1to C3members are nonmesomorphic, the C4to C12members are enantiotropic nematic only, and the C14to C16members are enantiotropically smectogenic in addition to nematogenic. Transition temperatures and the textures of LC state were observed through an optical polarizing microscope (POM) equipped with a heating stage. The textures of nematic phase are threaded or Schlieren, and that of smectic phase are focal conic of the type A or C. Transition curves of a phase diagram behave in normal manner with the exhibition of an odd-even effect (only N-I). Analytical and spectral data support the molecular structures of the novel ester derivatives. The LC properties of the present series are compared with structurally similar other known series. The average thermal stability of the series is 93°C for smectic and 120.88°C for nematic and the mesogenic phase length ranges between 2°C and 46°C. [ABSTRACT FROM AUTHOR]

Eight binary systems consisting of mesomorphs and nonmesomorphs (A1 or A2, + B1, B2, … B7, B8) were studied with a view to determine the latent transition temperature (LTT) for the nonmesomorphic component (B) of a binary system by an extrapolation method. Encouraging results supporting earlier views and LTT values were obtained for seven binary systems. Instead of reporting a single value of LTT, the range of temperature or two or three values are reported herewith depending upon the possible paths of extrapolation. LTT reported earlier for nonmesomorphs lie within the range of temperature determined presently. Though the “group slope value” differs from the earlier reported value, the group efficiency order remains the same. Thus, the present investigation raises the credibility of an extrapolation method to determine LTT and group efficiency order for nematic mesophase. Component A1 and A2 are nematogenic, namely, p-(p′-n-propyloxy benzoyloxy) anisole (A1) (90.0 to 116.0) and p-(p′-n-butyloxy benzoyloxy) anisole (A2) (116.0 to 105.5). B1 to B8 are Schiff's bases. Transition and melting temperatures are observed through hot stage polarizing microscope for binary mixtures and pure components. [ABSTRACT FROM PUBLISHER]

Introduction: The safest oxygen levels needed for preterm infant respiratory support at birth are uncertain. We aimed to compare the outcomes of infants up to 28 6 weeks gestation who had respiratory care initiated at birth with fractional inspired oxygen (FiO 2 ) 0.3 or 0.6, which was adjusted to meet specific oxygen saturations (SpO 2 )., Methods: This randomised controlled phase III trial was stratified by (1) site, (2) gestation and (3) multiplicity. Infants between 23+0 to 28+6 weeks gestation were randomised to initial respiratory support with FiO 2 0.3 or 0.6, adjusted to meet common SpO 2 targets for the first 10 min., Primary Outcome: Survival to 36 weeks gestation without documented brain injury., Assessments: FiO 2 , SpO 2 and heart rate were recorded each minute from delivery for 10 min. Assessments were obtained at baseline, 36 weeks, discharge and at 2 years corrected gestation, along with a parent questionnaire., Statistical Analysis Plan: Assuming 32% of infants would die or survive with brain injury by 36 weeks, 735 infants per arm (1470 total) were needed to detect a risk difference of 8% (25% relative risk reduction), with 10% non-adherence to protocol, 85% β and 5% α., Ethics: Approved by the John Hunter Human Research Ethics Committee (2019/ETH/3837) for waiver of consent for all Australian sites for randomised allocation and primary outcome., Conclusion: Recruitment started in 2018 and was achieved on 30 September 2024. The Data and Safety Committee review found no major safety concerns at 50% recruitment., Trial Registration Number: ACTRN 12618000879268., Competing Interests: Competing interests: JLO received honoraria from Mallinkrodt Inc for travel, research and presentations. No other has any known conflict of interest., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Importance: Children born at less than 29 weeks' gestation are at risk of behavioral difficulties. This may be due in part to the lack of transplacental supply of docosahexaenoic acid (DHA), a key fatty acid with structural and functional roles in the brain., Objective: To determine whether meeting the neonatal DHA requirement through supplementation is associated with improved behavioral functioning of children born at less than 29 weeks' gestation., Design, Setting and Participants: This was a follow-up of children from 10 Australian participating centers in a multi-center, blinded, parallel group randomized clinical trial of infants born at less than 29 weeks' gestation conducted from June 2012 and September 2015, excluding those with additional fatty acid supplementation or major congenital or chromosomal abnormalities. Follow-up took place from August 2018 to May 2021. Parents of surviving children who had not withdrawn from the original trial were invited to complete questionnaires when the child turned 5 years' corrected age., Interventions: Infants were randomized to receive daily enteral emulsions providing 60 mg/kg/d of DHA or a soy-oil emulsion (with no DHA) from within the first 3 days of enteral feeding until 36 weeks' postmenstrual age or discharge home, whichever occurred first., Main Outcomes and Measures: The primary outcome of this follow-up was parent-rated behavior and emotional functioning as indicated by the Total Difficulties score of the Strengths and Difficulties Questionnaire. Parents also completed questionnaires about their child's behavioral manifestations of executive functioning, as well as a range of health outcomes to assess potential longer-term side effects of DHA intervention., Results: Primary outcome data were available for 731 children (76% of 958 surviving eligible children; 361 in the intervention group and 370 in the control group). Of these 731, 452 (47%) were female, and the mean (SD) corrected age at follow-up was 5.4 (0.5) years. Following imputation for missing data, the mean Total Difficulties score was the same in both groups (intervention group, n = 465; mean [SD], 11.8 [6.3]; control group, n = 493; mean [SD], 11.8 [6.0]; mean difference adjusted for sex, gestational age stratum, and hospital, 0.01; 95% CI, -0.87 to 0.89; P = .98). There was no evidence for differences between the groups in any secondary outcomes of behavior, executive functioning, or health., Conclusions and Relevance: In this follow-up of a randomized clinical trial, enteral DHA supplementation at the equivalent of the estimated in utero dose for infants born at less than 29 weeks' gestation did not improve behavioral functioning at age 5 years. There were no indications of adverse effects with DHA supplementation., Trial Registration: Australian New Zealand Clinical Trial Registry: ACTRN12612000503820.

Introduction: Many extremely preterm newborns develop anaemia requiring a transfusion, with most receiving three to five transfusions during their admission. While transfusions save lives, the potential for transfusion-related adverse outcomes is an area of growing concern. Transfusion is an independent predictor of death and is associated with increased morbidity, length of hospital stay, risk of infection and immune modulation. The underlying mechanisms include adverse pro-inflammatory and immunosuppressive responses. Evidence supports an association between transfusion of washed red cells and fewer post-transfusion complications potentially through removal of chemokines, lipids, microaggregates and other biological response modifiers. However, the clinical and cost-effectiveness of washed cells have not been determined., Methods and Analysis: This is a multicentre, randomised, double-blinded trial of washed versus unwashed red cells. Infants <28 weeks' gestation requiring a transfusion will be enrolled. Transfusion approaches will be standardised within each study centre and will occur as soon as possible with a recommended fixed transfusion volume of 15 mL/kg whenever the haemoglobin is equal to or falls below a predefined restrictive threshold, or when clinically indicated. The primary outcome is a composite of mortality and/or major morbidity to first discharge home, defined as one or more of the following: physiologically defined bronchopulmonary dysplasia; unilateral or bilateral retinopathy of prematurity grade >2, and; necrotising enterocolitis stage ≥2. To detect a 10% absolute reduction in the composite outcome from 69% with unwashed red blood cell (RBCs) to 59% with washed RBCs with 90% power, requires a sample size of 1124 infants (562 per group). Analyses will be performed on an intention-to-treat basis with a prespecified statistical analysis plan. A cost-effectiveness analysis will also be undertaken., Ethics and Dissemination: Ethics approval has been obtained from the Women's and Children's Health Network Human Research Ethics Committee (HREC/12/WCHN/55). The study findings will be disseminated through peer-reviewed articles and conferences., Trial Registration Number: ACTRN12613000237785 Australian New Zealand Clinical Trials Registry., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To investigate the relationship between preterm birth and hospital/out-of-hospital care and costs over the first 5 years of life., Study Design: Birth data from a population-based cohort of 631 532 infants born between 2007 and 2013 were linked probabilistically with data on hospitalizations, primary and secondary care, and the use of medications. We analyzed the distribution of health care use and public health care costs for infants who survived at least 5 years, comparing the outcomes of extremely preterm (<28 weeks of gestation), very preterm (28-32 weeks), moderate to late preterm (32-37 weeks), and term infants (at least 37 weeks). A linear regression model was used to investigate the effect of preterm birth on these outcomes, controlling for important confounders including pregnancy and birth complications, neonatal morbidity, survival, and maternal socioeconomic characteristics., Results: Preterm birth has a statistically significant and economically relevant effect on health care use and costs in the first 5 years of life. Compared with a term infant, preterm infants born at 32-36 weeks, 28-32 weeks, and <28 weeks of gestation had, respectively, an average of 7.0 (SE 0.06), 41.6 (0.18), and 68.7 (0.35) more hospital days; 3.1 (0.04), 11.0 (0.13), and 13.2 (0.25) more outpatient specialist physician visits; and 1.2-fold (<0.01), 6.8-fold (0.01), and 10.9-fold (0.02) higher 5-year public health care costs. Preterm infants also had statistically significantly higher levels of general practitioner visits and use of medications., Conclusions: Higher levels of accessible care are needed for preterm infants across health care settings and over sustained periods. As our understanding of the impact of preterm birth on long-term clinical outcomes continues to improve, clinicians and policymakers should develop an accurate recognition of these needs to enable appropriate resource allocation toward research priorities and early intervention strategies., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: High-dose omega-3 docosahexaenoic acid (DHA) supplementation of children born at less than 29 weeks' gestation has been shown to improve IQ despite increasing the risk of bronchopulmonary dysplasia (BPD). Given that BPD is associated with poorer cognitive outcomes, it is unclear whether the increased risk of BPD with DHA supplementation is associated with decreased benefit to IQ., Objective: To investigate whether the increased risk of BPD with DHA supplementation was associated with diminished IQ benefit., Design, Setting, and Participants: This cohort study used data collected from a multicenter, blinded, randomized controlled trial of DHA supplementation in children born at less than 29 weeks' gestation. Participants were recruited from 2012 to 2015 and followed up until 5 years' corrected age. Data were analyzed from November 2022 to February 2023., Interventions: Enteral DHA emulsion (60 mg/kg/d, to match the estimated in-utero requirement) or a control emulsion from the first 3 days of enteral feeds until 36 weeks' postmenstrual age or discharge home., Main Outcomes and Measures: Physiological BPD was assessed at 36 weeks' postmenstrual age. IQ was assessed at 5 years' corrected age using the Wechsler Preschool and Primary Scale of Intelligence, 4th Edition; children from the 5 highest-recruiting Australian hospitals were assessed. The total effect of DHA supplementation on IQ was divided into direct and indirect effects using mediation analysis, with BPD as the presumed mediating variable., Results: Among 656 surviving children from hospitals involved in IQ follow-up (mean [SD] gestational age at birth, 26.8 [1.4] weeks; 346 males [52.7%]), there were 323 children with DHA supplementation and 333 children in the control group. Mean IQ was 3.45 points (95% CI, 0.38 to 6.53 points) higher in the DHA group than the control group, despite an increase in the risk of BPD (160 children [49.7%] vs 143 children [42.8%] with BPD). The indirect effect of DHA on IQ via BPD was not statistically significant (-0.17 points; 95% CI, -0.62 to 0.13 points), with most of the effect of DHA on IQ occurring independently of BPD (direct effect = 3.62 points; 95% CI, 0.55 to 6.81 points)., Conclusions and Relevance: This study found that associations of DHA with BPD and IQ were largely independent. This finding suggests that if clinicians supplement children born preterm with high-dose DHA, any resulting increase in BPD risk would not be associated with meaningful reductions in the IQ benefit.

Objective: To determine whether the use of non-invasive respiratory support, such as continuous positive airway pressure and nasal high flow, to treat term infants in Australian and New Zealand tertiary neonatal intensive care units (NICUs) has changed over time, and if so, whether there are parallel changes in short-term respiratory morbidities., Design: Retrospective database review of patient-level data from the Australian and New Zealand Neonatal Network (ANZNN) from 2010 to 2018. Denominator data on the number of term inborn livebirths in each facility was only available as annual totals., Patients and Setting: Term, inborn infants cared for in NICUs within the ANZNN., Main Outcome Measures: The primary outcome was the annual change in hospital-specific rates of non-invasive respiratory support per 1000 inborn livebirths, expressed as a percentage change. Secondary outcomes were the change in rates of mechanical ventilation, pneumothorax requiring drainage, exogenous surfactant treatment and death before hospital discharge., Results: A total of 14 656 term infants from 21 NICUs were included from 2010 to 2018, of whom 12 719 received non-invasive respiratory support. Non-invasive respiratory support use increased on average by 8.7% per year (95% CI: 7.9% to 9.4% per year); the number of term infants receiving non-invasive respiratory support almost doubled from 980 in 2010 (10.8/1000 livebirths) to 1913 in 2018 (20.8/1000). There was no change over time in rate of mechanical ventilation or death. The rate of pneumothorax requiring drainage increased over time, as did surfactant treatment., Conclusions: Non-invasive respiratory support use to treat term infants cared for in NICUs within the ANZNN is increasing over time. Clinicians should be diligent in selecting infants most likely to benefit from treatment with non-invasive respiratory support in this relatively low-risk population of term newborn infants. Analysis of patient-level data by individual NICUs is recommended to control for potential confounding due to changes in population over time., Competing Interests: Competing interests: BJM, LSO, CTR and PGD and their research activities are supported by Medical Research Future Fund (MRFF, Australia) or National Health and Medical Research Council (NHMRC, Australia) fellowships and grants., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Docosahexaenoic acid (DHA) is a component of neural tissue. Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks' gestation do not receive the normal supply of DHA. The effect of this deficiency on subsequent cognitive development is not well understood., Methods: We assessed general intelligence at 5 years in children who had been enrolled in a trial of neonatal DHA supplementation to prevent bronchopulmonary dysplasia. In the previous trial, infants born before 29 weeks' gestation had been randomly assigned in a 1:1 ratio to receive an enteral emulsion that provided 60 mg of DHA per kilogram of body weight per day or a control emulsion from the first 3 days of enteral feeds until 36 weeks of postmenstrual age or discharge home, whichever occurred first. Children from 5 of the 13 centers in the original trial were invited to undergo assessment with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) at 5 years of corrected age. The primary outcome was the full-scale intelligence quotient (FSIQ) score. Secondary outcomes included the components of WPPSI., Results: A total of 1273 infants underwent randomization in the original trial; of the 656 surviving children who had undergone randomization at the centers included in this follow-up study, 480 (73%) had an FSIQ score available - 241 in the DHA group and 239 in the control group. After imputation of missing data, the mean (±SD) FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group (adjusted difference, 3.45; 95% confidence interval, 0.38 to 6.53; P = 0.03). The results for secondary outcomes generally did not support that obtained for the primary outcome. Adverse events were similar in the two groups., Conclusions: In infants born before 29 weeks' gestation who had been enrolled in a trial to assess the effect of DHA supplementation on bronchopulmonary dysplasia, the use of an enteral DHA emulsion until 36 weeks of postmenstrual age was associated with modestly higher FSIQ scores at 5 years of age than control feeding. (Funded by the Australian National Health and Medical Research Council and Nu-Mega Ingredients; N3RO Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820.)., (Copyright © 2022 Massachusetts Medical Society.)

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., Competing Interests: Competing interests: Study product for the original trial was donated by Clover Corporation Limited (Melbourne, Australia). MM and RAG report holding a patent relating to methods and compositions for promoting the neurological development for preterm infants (2009201540), owned by the South Australian Health and Medical Research Institute and licensed to Clover Corporation Limited. MM is supported by an Australian NHMRC Senior Research Fellowship ID: 1061704 and CTC is supported by a NHMRC Translating Research into Practice (TRIP) Fellowship ID 1132596. TS is supported by a NHMRC Emerging Leadership Investigator Grant ID: 1173576. KPB is supported by a Women’s and Children’s Hospital MS McLeod Postdoctoral Fellowship. PGD is supported by an Australian NHMRC Practitioner Fellowship ID: 1157782. JC is supported by a MRFF Career Development Fellowship ID: 1354. Honoraria have been paid to JFG’s institution to support conference travel by Fonterra. MM and RAG report serving on the board for Trajan Nutrition. No other authors reported any financial disclosures. The contents of the published material are solely the responsibility of the authors and do not reflect the views of the NHMRC., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Competing interests: Study product for the original trial was donated by Clover (Melbourne, Australia). MM and RAG report holding a patent relating to methods and compositions for promoting the neurological development for preterm infants (2009201540), owned by the South Australian Health and Medical Research Institute and licensed to Clover Corporation Limited. MM is supported by an Australian NHMRC Senior Research Fellowship ID: 1061704 and CC is supported by an NHMRC Translating Research into Practice (TRIP) Fellowship ID 1132596. TS is supported by an NHMRC Emerging Leadership Investigator Grant ID: 1173576. KPB is supported by a Women’s and Children’s Hospital MS McLeod Postdoctoral Fellowship. PGD is supported by an Australian NHMRC Practitioner Fellowship ID: 1157782. JC is supported by an MRFF Career Development Fellowship ID: 1141354. Honoraria have been paid to Dr JFG’s institution to support conference travel by Fonterra. MM and RAG report serving on the board for Trajan Nutrition. No other authors reported any financial disclosures., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Very low birthweight or preterm infants are at increased risk of adverse outcomes including sepsis, necrotising enterocolitis, and death. We assessed whether supplementing the enteral diet of very low-birthweight infants with lactoferrin, an antimicrobial protein, reduces all-cause mortality or major morbidity., Methods: We did a multicentre, double-blind, pragmatic, randomised superiority trial in 14 Australian and two New Zealand neonatal intensive care units. Infants born weighing less than 1500 g and aged less than 8 days, were eligible and randomly assigned (1:1) using minimising web-based randomisation to receive once daily 200 mg/kg pasteurised bovine lactoferrin supplements or no lactoferrin supplement added to breast or formula milk until 34 weeks' post-menstrual age (or for 2 weeks, if longer), or until discharge from the study hospital if that occurred first. Designated nurses preparing the daily feeds were not masked to group assignment, but other nurses, doctors, parents, caregivers, and investigators were unaware. The primary outcome was survival to hospital discharge or major morbidity (defined as brain injury, necrotising enterocolitis, late-onset sepsis at 36 weeks' post-menstrual age, or retinopathy treated before discharge) assessed in the intention-to-treat population. Safety analyses were by treatment received. We also did a prespecified, PRISMA-compliant meta-analysis, which included this study and other relevant randomised controlled trials, to estimate more precisely the effects of lactoferrin supplementation on late-onset sepsis, necrotising enterocolitis, and survival. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12611000247976., Findings: Between June 27, 2014, and Sept 1, 2017, we recruited 1542 infants; 771 were assigned to the intervention group and 771 to the control group. One infant who had consent withdrawn before beginning lactoferrin treatment was excluded from analysis. In-hospital death or major morbidity occurred in 162 (21%) of 770 infants in the intervention group and in 170 (22%) of 771 infants in the control group (relative risk [RR] 0·95, 95% CI 0·79-1·14; p=0·60). Three suspected unexpected serious adverse reactions occurred; two in the lactoferrin group, namely unexplained late jaundice and inspissated milk syndrome, but were not attributed to the intervention and one in the control group had fatal inspissated milk syndrome. Our meta-analysis identified 13 trials completed before Feb 18, 2020, including this Article, in 5609 preterm infants. Lactoferrin supplements significantly reduced late-onset sepsis (RR 0·79, 95% CI 0·71-0·88; p<0·0001; I 2 =58%), but not necrotising enterocolitis or all-cause mortality., Interpretation: Lactoferrin supplementation did not improve death or major morbidity in this trial, but might reduce late-onset sepsis, as found in our meta-analysis of over 5000 infants. Future collaborative studies should use products with demonstrated biological activity, be large enough to detect moderate and clinically important effects reliably, and assess greater doses of lactoferrin in infants at increased risk, such as those not exclusively receiving breastmilk or infants of extremely low birthweight., Funding: Australian National Health and Medical Research Council., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aim: The attitudes of neonatologists towards the active management of extremely premature infants in a developing country like China are uncertain., Methods: A web-based survey was sent to neonatologists from 16 provinces representing 59.6% (824.2 million) of the total population of China on October 2015 and December 2017., Results: A total of 117 and 219 responses were received in 2015 and 2017, respectively. Compared to 2015, respondents in 2017 were more likely to resuscitate infants <25 weeks of gestation (86% vs. 72%; p < 0.05), but few would resuscitate infants ≤23 weeks of gestation in either epoch (10% vs. 6%). In both epochs, parents were responsible for >50% of the costs of intensive care, but in 2017, significantly fewer clinicians would cease intensive care (75% vs. 88%; p < 0.05) and more would request for economic aid (40% vs. 20%; p < 0.05) if parents could not afford to pay. Resource availability (e.g. ventilators) was not an important factor in either initiation or continuation of intensive care (~60% in both epochs)., Conclusion: Cost is an important factor in the initiation and continuation of neonatal intensive care in a developing country like China. Such factors need to be taken into consideration when interpreting outcome data from these regions., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aim: The diagnosis of tongue-tie (or ankyloglossia) has increased more than 10-fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain., Methods: An online survey in English, Japanese, Chinese and Spanish was disseminated between May and November 2016 via 27 international professional bodies to >30 clinical professions chosen a priori to represent occupations involved in the management of neonatal ankyloglossia., Results: A total of 1721 responses came from nursing (51%), medical (40%), dental (6%) and allied health (4%) clinicians. Nurses (40%) and allied health (34%) professionals were more likely than doctors (8%) to consider ankyloglossia as important for lactation problems, as were western (83%) compared to Asian (52%) clinicians. Referrals to clinicians for ankyloglossia management originated mainly from parents (38%). Interprofessional referrals were not clearly defined. Frenectomies were most likely to be performed by surgeons (65%) and dentists (35%), who were also less likely to be involved in lactation support. Clinicians performing frenectomies were more likely to consider analgesia as important compared to those not performing frenectomies., Conclusion: The diagnosis and treatment of ankyloglossia vary considerably around the world and between professions. Efforts to standardise management are required., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: To determine rates of death or neurodevelopmental impairment (NDI) at 2 years corrected age (primary outcome) in children <32 weeks' gestation randomized to initial resuscitation with a fraction of inspired oxygen (FiO 2 ) value of 0.21 or 1.0., Study Design: Blinded assessments were conducted at 2-3 years corrected age with the Bayley Scales of Infant and Toddler Development, Third Edition or the Ages and Stages Questionnaire by intention to treat., Results: Of the 290 children enrolled, 40 could not be contacted and 10 failed to attend appointments. Among the 240 children for whom outcomes at age 2 years were available, 1 child had a lethal congenital anomaly, 1 child had consent for follow-up withdrawn, and 23 children died. The primary outcome, which was available in 238 (82%) of those randomized, occurred in 47 of the 117 (40%) children assigned to initial FiO 2 0.21 and in 38 of the 121 (31%) assigned to initial FiO 2 1.0 (OR, 1.47; 95% CI, 0.86-2.5; P = .16). No difference in NDI was found in 215 survivors randomized to FiO 2 0.21 vs 1.0 (OR, 1.26; 95% CI, 0.70-2.28; P = .11). In post hoc exploratory analyses in the whole cohort, children with a 5-minute blood oxygen saturation (SpO 2 ) <80% were more likely to die or to have NDI (OR, 1.85; 95% CI, 1.07-3.2; P = .03)., Conclusions: Initial resuscitation of infants <32 weeks' gestation with initial FiO 2 0.21 had no significant effect on death or NDI compared with initial FiO 2 1.0. Further evaluation of optimum initial FiO 2 , including SpO 2 targeting, in a large randomized controlled trial is needed., Trial Registration: Australian and New Zealand Clinical Trials Network Registry ACTRN 12610001059055 and the National Malaysian Research Registry NMRR-07-685-957., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Studies in animals and in humans have suggested that docosahexaenoic acid (DHA), an n-3 long-chain polyunsaturated fatty acid, might reduce the risk of bronchopulmonary dysplasia, but appropriately designed trials are lacking., Methods: We randomly assigned 1273 infants born before 29 weeks of gestation (stratified according to sex, gestational age [<27 weeks or 27 to <29 weeks], and center) within 3 days after their first enteral feeding to receive either an enteral emulsion providing DHA at a dose of 60 mg per kilogram of body weight per day or a control (soy) emulsion without DHA until 36 weeks of postmenstrual age. The primary outcome was bronchopulmonary dysplasia, defined on a physiological basis (with the use of oxygen-saturation monitoring in selected infants), at 36 weeks of postmenstrual age or discharge home, whichever occurred first., Results: A total of 1205 infants survived to the primary outcome assessment. Of the 592 infants assigned to the DHA group, 291 (49.1% by multiple imputation) were classified as having physiological bronchopulmonary dysplasia, as compared with 269 (43.9%) of the 613 infants assigned to the control group (relative risk adjusted for randomization strata, 1.13; 95% confidence interval [CI], 1.02 to 1.25; P=0.02). The composite outcome of physiological bronchopulmonary dysplasia or death before 36 weeks of postmenstrual age occurred in 52.3% of the infants in the DHA group and in 46.4% of the infants in the control group (adjusted relative risk, 1.11; 95% CI, 1.00 to 1.23; P=0.045). There were no significant differences between the two groups in the rates of death or any other neonatal illnesses. Bronchopulmonary dysplasia based on a clinical definition occurred in 53.2% of the infants in the DHA group and in 49.7% of the infants in the control group (P=0.06)., Conclusions: Enteral DHA supplementation at a dose of 60 mg per kilogram per day did not result in a lower risk of physiological bronchopulmonary dysplasia than a control emulsion among preterm infants born before 29 weeks of gestation and may have resulted in a greater risk. (Funded by the Australian National Health and Medical Research Council and others; Australian New Zealand Clinical Trials Registry number, ACTRN12612000503820 .).

Background and Objectives: Lower concentrations of oxygen (O 2 ) (≤30%) are recommended for preterm resuscitation to avoid oxidative injury and cerebral ischemia. Effects on long-term outcomes are uncertain. We aimed to determine the effects of using room air (RA) or 100% O 2 on the combined risk of death and disability at 2 years in infants <32 weeks' gestation., Methods: A randomized, unmasked study designed to determine major disability and death at 2 years in infants <32 weeks' gestation after delivery room resuscitation was initiated with either RA or 100% O 2 and which were adjusted to target pulse oximetry of 65% to 95% at 5 minutes and 85% to 95% until NICU admission., Results: Of 6291 eligible patients, 292 were recruited and 287 (mean gestation: 28.9 weeks) were included in the analysis (RA: n = 144; 100% O 2 : n = 143). Recruitment ceased in June 2014, per the recommendations of the Data and Safety Monitoring Committee owing to loss of equipoise for the use of 100% O 2 . In non-prespecified analyses, infants <28 weeks who received RA resuscitation had higher hospital mortality (RA: 10 of 46 [22%]; than those given 100% O 2 : 3 of 54 [6%]; risk ratio: 3.9 [95% confidence interval: 1.1-13.4]; P = .01). Respiratory failure was the most common cause of death (n = 13)., Conclusions: Using RA to initiate resuscitation was associated with an increased risk of death in infants <28 weeks' gestation. This study was not a prespecified analysis, and it was underpowered to address this post hoc hypothesis reliably. Additional data are needed., (Copyright © 2017 by the American Academy of Pediatrics.)

Objective: To determine Patent ductus arteriosus (PDA) closure rates for extremely preterm infants in a tertiary care centre, factors affecting response to indomethacin and outcomes of these infants relative to their PDA status., Setting: Neonatal intensive care unit in tertiary-care children's hospital., Design: Retrospective medical record review., Methods: A retrospective chart review of all infants <29 weeks gestation between 1st Jan 2003 and 30th June 2006 was carried out. Multiple courses of standard intravenous indomethacin (dose: 0.2 mg/kg 12 hourly; 3 doses) followed by a tail course (0.1 mg/kg/day; 3 doses) were used to treat PDA depending on clinical and hemodynamic status. Data on demographic characteristics, PDA status, use of indomethacin, and outcome factors such as chronic lung disease and mortality were collected., Results: A total of 166 infants were identified in the study period, of which 15 were excluded. The median gestation was 27 weeks [IQR (25, 28)] and the mean (SD) birthweight was 950 (244) grams. The remaining infants (n=151) were divided into three groups. Group1 (n=47): no or non-significant PDA, Group 2 (n=91): significant PDA closed after indomethacin treatment (= 1 course) and Group 3 (n=13): significant PDA not responding to indomethacin. The closure rate of PDA with indomethacin treatment (group 2) was 87%. A low gestational age < 26 weeks (OR 5.6, 95% CI 1.6-19.9) and female sex (OR 5.8, 95% CI 1.5-22.8) was associated with poor response to indomethacin in our study population., Conclusions: Multiple indomethacin courses using the standard dosing approach result in high PDA closure rates for infants < 29 weeks gestation.

Staphylococcus aureus can cause a spectrum of exfoliative skin conditions including staphylococcal scalded skin syndrome (SSSS) which can present as a severe and life threatening illness in extremely premature neonates. We describe a case of an extremely premature neonate with SSSS and discuss relevant pathology and issues in clinical management.

Background: Patent ductus arteriosus (PDA), a common complication in extremely preterm infants, is associated with increased mortality and morbidity. Phototherapy has been associated with PDA, and one randomized, control trial has shown that shielding of the chest may decrease the risk of PDA., Aim: To examine if chest shielding reduces the incidence and severity of PDA in extremely preterm infants., Study Design: Randomized clinical trial of infants < 29 wk gestation (stratified into two groups: < 27 wk gestation and 27-28 wk gestation)., Methods: Following written parental consent, eligible infants were randomized to receive phototherapy, with or without a chest shield. Ductal parameters were assessed by Doppler echocardiogram in all infants prior to starting phototherapy and at 48 h after initiation, or earlier if phototherapy was discontinued., Results: 54 infants were enrolled in the study. The incidence of PDA (shield 19/27 vs no shield 21/27), ductal size (1.4 vs 1.0 mm) and left atrial/aortic root (LA/Ao) ratio (1.2 vs 1.3) were similar in the two groups pre-phototherapy. There was no difference between the groups post-phototherapy in incidence (shield 12/27 vs no shield 13/27), ductal size (1.4 vs 1.5 mm) or LA/Ao ratio (1.1 vs 1.3)., Conclusion: Chest shielding did not alter the incidence or severity of PDA in our population of extremely preterm infants.

Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor alpha (TNF-alpha) has been shown to play a central role in the inflammatory cascade leading to the development of NEC. Published evidence points to a significant role of pentoxifylline in inhibition of TNF-alpha and in reducing mucosal injury and improving healing in ischemia-reperfusion experiments. Our aim was to investigate the effect of pentoxifylline on the incidence of NEC in a neonatal rat model. Newborn Sprague-Dawley rat pups originating from eight separate litters were delivered by cesarean section at 21.5 d and were formula fed from birth by orogastric gavage. The rat pups were randomized to receive either intraperitoneal pentoxifylline (15 mg/kg/dose) or placebo, given every 8 h beginning at 24 h of age, in a blinded fashion. Experimental NEC was induced by exposure to hypoxia for 60 s followed by cold stress at 4 degrees C for 10 min. The animals were euthanized at development of NEC or at 96 h and intestinal tissue was processed and examined for histologic changes of NEC. The incidence of NEC was significantly lower in the pentoxifylline group [pentoxifylline 5/38 versus placebo 15/36; p = 0.008, odds ratio (OR) = 0.21 95% confidence interval (CI) 0.07-0.67]. Among the pups developing NEC, significantly fewer rat pups treated with pentoxifylline had severe (>or=3) intestinal injury scores [pentoxifylline 1/5 versus placebo 10/15; p = 0.031, OR 0.06, 95% CI 0.01-0.79]. We conclude that intraperitoneal administration of pentoxifylline significantly reduced the incidence and severity of NEC in our experimental animal model.