Diagnosis, management and long term cardiovascular outcomes of phenotypic profiles in pulmonary hypertension associated with congenital diaphragmatic hernia.

Congenital diaphragmatic hernia (CDH) is a developmental defect of the diaphragm resulting in herniation of viscera into the chest. This condition is characterized by pulmonary hypoplasia, pulmonary hypertension (PH) and cardiac ventricular dysfunction. PH is a key component of the pathophysiology of CDH in neonates and contributes to morbidity and mortality. Traditionally, PH associated with CDH (CDH-PH) is thought to be secondary to increased pulmonary arterial resistance and vasoreactivity resulting from pulmonary hypoplasia. Additionally, there is increasing recognition of associated left ventricular hypoplasia, dysfunction and elevated end diastolic pressure resulting in pulmonary venous hypertension in infants with CDH. Thus, hemodynamic management of these infants is complex and cautious use of pulmonary vasodilators such as inhaled nitric oxide (iNO) is warranted. We aim to provide an overview of different phenotypic profiles of CDH associated PH and potential management options based on current evidence and pathophysiology.

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

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

Diagnostic utility of lung ultrasound in predicting the need for surfactant therapy in preterm neonates with respiratory distress.

Background: Lung ultrasound is an accurate and early predictor for surfactant replacement therapy in respiratory distress syndrome (RDS) as compared to clinical parameters and chest x-ray. However, lung pathologies for respiratory distress at birth have overlapping symptomatology and low middle-income countries have a higher incidence of congenital pneumonia, in addition to RDS, making the immediate diagnosis difficult. Thus, there is a need for assessing a cutoff for lung ultrasound scores in the given setting. Objectives: The primary objective was to determine the diagnostic accuracy of the lung ultrasound score (LUS) in predicting the need for surfactant therapy in preterm neonates with respiratory distress. Secondary objectives were to correlate LUS with corresponding oxygen saturation to the fraction of inspired oxygen ratio (SpO2/FiO2), arterial/Alveolar oxygen pressure ratio (a/A), and chest x-ray (CXR) findings. Methodology: A prospective observational study was carried out at a tertiary-level neonatal intensive care unit in India in 2022 enrolling 100 neonates <34 weeks gestational age with respiratory distress at birth. After initial stabilization of the neonate, LUS was performed and baseline parameters were noted. Surfactant was administered as per the 2019 European Consensus guidelines and LUS was repeated after 6 h of therapy. Results: The mean gestation of enrolled neonates was 31.06 ± 2.12 weeks and the mean birthweight was 1,412 ± 391 g. Approximately 58% were diagnosed with RDS and 30% had congenital pneumonia. Surfactant was administered to 40% of neonates. The cutoff LUS for surfactant therapy was 7 [area under the curve (AUC) 0.977; 95% CI, 0.947-1; P < 0.001; with sensitivity 92.5%, specificity 96.67%, PPV 94.87%, and NPV 95.08%] and the cutoff LUS for the second dose of surfactant was 10 (AUC 0.964; 95% CI, 0.913-1; P < 0.001). The score decreased by 3.24 (2.44-4.05) after 6 h of the first dose and correlated significantly with SpO2/FiO2 ratio (-0.750), a/A ratio (-0.650), and CXR findings (0.801). Conclusion: The study predicted an optimal LUS cutoff of 7 and 10 for the need for the first dose of surfactant and re-treatment, respectively, in neonates <34 weeks gestational age with respiratory distress.

Randomised controlled trial to compare the effect of PIOMI (structured) and routine oromotor (unstructured) stimulation in improving readiness for oral feeding in preterm neonates.

Background: Oral motor stimulation interventions improve oral feeding readiness and earlier full oral feeding in preterm neonates. However, using a structured method may improve the transition time to full oral feeds and feeding efficiency with respect to weight gain and exclusive breastfeeding when compared to an unstructured intervention. Objective: To compare the effect of Premature Infant Oral Motor Intervention (PIOMI) and routine oromotor stimulation (OMS) on oral feeding readiness. Methods: Randomised controlled trial conducted in a neonatal intensive care unit between June-December 2022. Preterm neonates, 29+0-33+6 weeks corrected gestational age, were studied. The intervention group received PIOMI and the control group received OMS. Primary outcome: time to oral feeding readiness by Premature Oral Feeding Readiness Assessment Scale (POFRAS) score ≥30. Secondary outcomes: time to full oral feeds, duration of hospitalisation, weight gain, and exclusive breastfeeding rates. Results: A total of 84 neonates were included and were randomised 42 each in PIOMI and OMS groups. The mean chronological age and time to oral feeding readiness were lower by 4.6 and 2.7 days, respectively, for PIOMI. The transition time to full oral feeds was 2 days lower for PIOMI and the duration of hospitalisation was 8 days lower. The average weight gain was 4.9 g/kg/day more and the exclusive breastfeeding rates at 1 month and 3 months post-discharge were higher by 24.5% and 27%, respectively, for the PIOMI group. The subgroup analysis of study outcomes based on sex and weight for gestational age showed significant weight gain on oral feeds in neonates receiving PIOMI. Similarly, the subgroup analysis based on gestational age favoured the PIOMI group with significantly earlier transition time and weight gain on oral feeds for the neonates >28 weeks of gestational age. The odds of achieving oral feeding readiness by 30 days [OR 1.558 (0.548-4.426)], full oral feeds by 45 days [OR 1.275 (0.449-3.620)], and exclusive breastfeeding at 1 month [OR 6.364 (1.262-32.079)] and 3 months [3.889 (1.186-12.749)] after discharge were higher with PIOMI. Conclusion: PIOMI is a more effective oromotor stimulation method for earlier and improved oral feeding in preterm neonates. Clinical trial registration: https://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=70054&EncHid=34792.72281&modid=1&compid=19','70054det', identifier, CTRI/2022/06/043048.

Investigating short-stay admission to a neonatal intensive care unit as a risk factor for reduced breast feeding at discharge in infants ≥36 weeks' gestation: a retrospective cohort study.

OBJECTIVE: This study aims to determine the effect of infant-mother separation following a short-stay (≤72 hours) admission to a Level 5 neonatal unit versus no admission on infant-feeding outcomes at hospital discharge. DESIGN: Retrospective cohort study. SETTING: An Australian Level 5 neonatal unit within a tertiary referral hospital. PARTICIPANTS: Mothers and their infants born between 1 January 2018 and 31 December 2020 had a short-stay admission to the neonatal unit or no admission. All participants met admission criteria to the postnatal ward and were discharged home at ≤72 hours (n=12 540). Postnatal ward admission criteria included ≥36 weeks' gestation and birth weight ≥2.2 kg. MAIN OUTCOME MEASURES: Infant feeding at discharge from hospital. Multivariate logistic regression analysis was conducted, adjusting for confounders associated with known breastfeeding issues. These included age, ethnicity, parity, obesity, socioeconomic score, hypertensive disorders of pregnancy, diabetes, infant gestation and birthweight centile, caesarean section birth, postpartum haemorrhage and skin-to-skin contact. RESULTS: Of the 12 540 live births meeting inclusion criteria, 1000 (8%) infants were admitted to the neonatal unit. The primary reasons for admission were suspicion of sepsis (24%), maternal diabetes (19%) and jaundice (16%). We found a reduction in full breast feeding at hospital discharge in cases of a short admission to the neonatal unit compared with no admission (aOR 0.40; 95% CI 0.34 to 0.47; p<0.001). We identified that women of different ethnicities had differing levels of risk for formula supplementation at hospital discharge. The ethnic grouping least likely to be fully breast feeding at discharge was Southeast Asian women (aOR 0.47; 95% CI 0.39 to 0.57; p<0.001). CONCLUSIONS: Identifying mother-infant dyads at risk of non-exclusive breast feeding at hospital discharge will help target resources for practice improvement.

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

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

Lactoferrin for the postoperative management of term neonates after gastrointestinal surgery.

BACKGROUND: Neonates who have undergone gastrointestinal surgery are particularly susceptible to infectious complications in the postoperative period. This may be due in part to disruption of the integrity of the gut and its altered intestinal microflora. Lactoferrin is a whey protein found in milk and is an important innate mammalian defence mechanism. Lactoferrin has been reported to have antimicrobial and anti-inflammatory properties. It has also been reported to help establish a healthy gut microflora and aid in the intestinal immune system. Lactoferrin supplementation has been reported to decrease sepsis in preterm infants. There may be a role for lactoferrin to reduce the incidence of sepsis, thus reducing morbidity and mortality and improving enteral feeding in postoperative term neonates. OBJECTIVES: The primary objective of this review was to evaluate the efficacy of administering lactoferrin on the incidence of sepsis and mortality in term neonates after gastrointestinal surgery. The secondary objective was to assess the impact of administering lactoferrin on time to full enteral feeds, the intestinal microflora, duration of hospital stay, and mortality before discharge in the same population. SEARCH METHODS: The Cochrane Neonatal Information Specialist searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase Ovid, CINAHL, the WHO ICTRP and ClinicalTrials.gov trials registries. The date of the last search was February 2023. There were no restrictions to language, publication year or publication type. We checked references of potentially relevant studies and systematic reviews. SELECTION CRITERIA: We planned to include randomised controlled trials that studied infants born at 37 or more weeks of gestation who had one or more episodes of gastrointestinal surgery within 28 days of birth, and compared administration of lactoferrin with a placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We planned to use the GRADE approach to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified no published randomised controlled studies that assessed the efficacy of lactoferrin for the postoperative management of term neonates following gastrointestinal surgery. AUTHORS' CONCLUSIONS: There is currently no evidence available from randomised controlled trials to show whether lactoferrin is effective or ineffective for the postoperative management of term neonates after gastrointestinal surgery. There is a need for randomised controlled trials to be performed to assess the role of lactoferrin in this setting.

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

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

Thyroid function in infants born to women with hypothyroidism: An observational study at an Australian tertiary perinatal centre.

OBJECTIVE: Concerns have been raised regarding thyroid dysfunction in infants born to women with hypothyroidism including those with autoimmune hypothyroidism. This concern has led to the practice of thyroid function testing in the early neonatal period. We evaluated the practice of performing a routine thyroid function test around 2 weeks of age in all healthy full-term infants (≥37 weeks gestation) born to women with hypothyroidism to identify thyroid dysfunction. DESIGN, PATIENTS, AND MEASUREMENTS: This retrospective, observational single centre study included full-term infants born to women with hypothyroidism, including non-Graves' autoimmune hypothyroidism, over a 3-year period. Preterm infants and those born to women with Graves' disease or thyroidectomy were excluded. RESULTS: Of the 790 mother-infant dyads, 780 infants (99%) had normal thyroid function. Only 10 infants (1%) had thyroid stimulating hormone (TSH) levels > 10mIU/L at 2 weeks of age (range 10.25-106.37 mU/L). Of these, follow-up thyroid function normalized in nine infants within 2 weeks. A routine newborn screening test identified congenital hypothyroidism in one infant. No infant born to women with known presence of anti-thyroid antibodies had TSH levels > 10 mIU/L. Thyroid function was normal for most infants where maternal anti-thyroid antibodies were not known (125/133, 94%). CONCLUSIONS: Infants born to women with hypothyroidism (including autoimmune hypothyroidism) had normal thyroid function in the early neonatal period. A small proportion of infants may develop TSH levels > 10 mU/L that normalizes by 4 weeks of age. The practice of routine thyroid function testing for this cohort in addition to newborn screening test offers no additional benefit.

Thermoregulation and golden hour practices in extremely preterm infants: an international survey.

BACKGROUND: Are thermoregulation and golden hour practices in extremely preterm (EP) infants comparable across the world? This study aims to describe these practices for EP infants based on the neonatal intensive care unit's (NICUs) geographic region, country's income status and the lowest gestational age (GA) of infants resuscitated. METHODS: The Director of each NICU was requested to complete the e-questionnaire between February 2019 and August 2021. RESULTS: We received 848 responses, from all geographic regions and resource settings. Variations in most thermoregulation and golden hour practices were observed. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission, and having local protocols were the most consistent practices (>75%). The odds for the following practices differed in NICUs resuscitating infants from 22 to 23 weeks GA compared to those resuscitating from 24 to 25 weeks: respiratory support during resuscitation and transport, use of polyethylene plastic wrap and servo-control mode, commencing ambient humidity >80% and presence of local protocols. CONCLUSION: Evidence-based practices on thermoregulation and golden hour stabilisation differed based on the unit's region, country's income status and the lowest GA of infants resuscitated. Future efforts should address reducing variation in practice and aligning practices with international guidelines. IMPACT: A wide variation in thermoregulation and golden hour practices exists depending on the income status, geographic region and lowest gestation age of infants resuscitated. Using a polyethylene plastic wrap, commencing humidity within 60 min of admission and having local protocols were the most consistent practices. This study provides a comprehensive description of thermoregulation and golden hour practices to allow a global comparison in the delivery of best evidence-based practice. The findings of this survey highlight a need for reducing variation in practice and aligning practices with international guidelines for a comparable health care delivery.

Global variation in skin injures and skincare practices in extremely preterm infants.

BACKGROUND: Globally, are skincare practices and skin injuries in extremely preterm infants comparable? This study describes skin injuries, variation in skincare practices and investigates any association between them. METHODS: A web-based survey was conducted between February 2019 and August 2021. Quantifying skin injuries and describing skincare practices in extremely preterm infants were the main outcomes. The association between skin injuries and skincare practices was established using binary multivariable logistic regression adjusted for regions. RESULTS: Responses from 848 neonatal intensive care units, representing all geographic regions and income status groups were received. Diaper dermatitis (331/840, 39%) and medical adhesive-related skin injuries (319/838, 38%) were the most common injuries. Following a local skincare guideline reduced skin injuries [medical adhesive-related injuries: adjusted odds ratios (aOR) = 0.63, 95% confidence interval (CI) = 0.45-0.88; perineal injuries: aOR = 0.66, 95% CI = 0.45-0.96; local skin infections: OR = 0.41, 95% CI = 0.26-0.65; chemical burns: OR = 0.46, 95% CI = 0.26-0.83; thermal burns: OR = 0.51, 95% CI = 0.27-0.96]. Performing skin assessments at least every four hours reduced skin injuries (abrasion: aOR = 0.48, 95% CI = 0.33-0.67; pressure: aOR = 0.51, 95% CI = 0.34-0.78; diaper dermatitis: aOR = 0.71, 95% CI = 0.51-0.99; perineal: aOR = 0.52, 95% CI = 0.36-0.75). Regional and resource settings-based variations in skin injuries and skincare practices were observed. CONCLUSIONS: Skin injuries were common in extremely preterm infants. Consistency in practice and improved surveillance appears to reduce the occurrence of these injuries. Better evidence regarding optimal practices is needed to reduce skin injuries and minimize practice variations.

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

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

Effect of Tunnel Drilling Portal on Femoral Tunnel Entry Aperture's Location in Arthroscopic Anterior Cruciate Ligament Reconstruction.

Introduction Transportal techniques for femoral tunnel drilling have the advantage of anatomical anterior cruciate ligament reconstruction, which was earlier difficult to achieve through transtibial femoral tunnels. However, the medial arthroscopic portal used for femoral tunnel drilling in single-bundle anterior cruciate ligament reconstruction (ACLR) has not been uniformly placed in different studies. Therefore, we performed a computed tomography-based analysis to compare the femoral tunnel entry aperture of the ACLR cases that used the standard AM portal and those using a far medial portal for femoral tunnel drilling. Methods We retrospectively reviewed computed tomography images of patients who underwent isolated single-bundle ACLR in our institute with either standard anteromedial portal or the far medial portal used for the femoral tunnel drilling. The femoral tunnel aperture's depth and height, measured using the quadrant method, were compared between the two portal methods. Results A total of forty-two case records were reviewed, sixteen belonging to standard anteromedial portal technique and twenty-six belonging to far medial portal technique. The tunnels created through the far AM portal were significantly shallower (more anterior) and inferior than the standard AM portal-created femoral tunnels. Conclusion The choice of drilling portals can influence transportal femoral tunnel drilling. A tendency towards anterior and inferior positioning of the femoral tunnel entry aperture has been observed when a far medial arthroscopic portal is used for femoral tunnel drilling. Therefore, care must be taken to ensure that the drilling guide pin position does not change when the reamer is passed over it.

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

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

Clinical outcomes and cost-effectiveness of large-scale midwifery-led, paediatrician-overseen home phototherapy and neonatal jaundice surveillance: A retrospective cohort study.

AIM: To evaluate a large midwifery-led, paediatrician-overseen home jaundice surveillance and home phototherapy (HPT) programme. METHODS: We conducted a retrospective cohort study over 2019. Included were all infants with birth gestation ≥35 weeks, discharged at 4-96 h and receiving care from midwifery-at-home (a 12-h daily, 365-days hospital-based outreach service, supported by hospital paediatricians). Phototherapy was delivered via BiliSoft blanket with treatment thresholds determined by standard nomograms. The main outcomes of interest were unplanned readmissions, and cost-effectiveness based on hospital finance department actual costs. Also examined were parental compliance, device issues and safety. RESULTS: During 2019, 4308 infants received home jaundice surveillance with 86% hospital-discharged before 72 h, 82% exclusively breastfed and 69% having overseas-born mothers. Four hundred infants received HPT, comprising 101 continuing from inpatient phototherapy (IPT), 56 rebounding after IPT, and 243 home-diagnosed as needing phototherapy and triaged to HPT. Only 1 of 400 (0.25%) HPT infants required readmission. Additionally, there were 80 home-diagnosed jaundiced infants triaged to immediate readmission for IPT. Maximal serum bilirubin was 454 µmol/L. No exchange transfusion, encephalopathy or HPT-device problems occurred. An early 2019 bilirubin analyser upgrade resulted in higher bilirubin readings and some unintended subthreshold phototherapy. Supported by midwives, most parents managed HPT with ease. HPT cost $640/day compared to $2100/day for infant IPT readmission and $1000/day for a longer birth-admission stay. Up to 2 weeks' midwifery-at-home care for the whole cohort cost $2 m less than a 2-day longer birth-admission stay. CONCLUSION: Large-scale, midwifery-led, paediatrician-overseen jaundice surveillance and HPT can achieve very low unplanned readmission rates and be cost-effective.

Role of Natural and Synthetic Flavonoids as Potential Aromatase Inhibitors in Breast Cancer: Structure-Activity Relationship Perspective.

World Health Organization categorized breast cancer as one of the leading cancer types in females worldwide, and its treatment remains challenging. Accumulated evidence suggested the role of estrogen and its metabolites in pre- and post-menopausal women. Upregulation of estrogen-dependent aromatase is significantly involved in the pathogenesis of breast cancer. Several aromatase inhibitors, such as exemestane, formestane, and letrozole, are being used clinically, owing to their estrogen suppression role. Apart from these drugs, several other molecules, such as natural and synthetic flavonoids, have been reported widely for a similar biological activity. However, some reasonable modifications are required for these structures to achieve desired efficacy and to alleviate toxicity. Designing a novel aromatase inhibitor will be possible if we can establish a rational correlation between the chemistry and biological features of the existing molecules. The benzopyranone- ring system, present in the flavonoid molecules, has been reported as a pharmacophore due to its inhibitory activity on aromatase, which helps repress breast cancer progression. This essential feature has been utilized to modify several natural flavonoids into 5 and 7 hydroxy/methoxy flavone, 4-imidazolyl/triazolyl flavone, 5,4'- diamino flavone, 7,8- benzo-4-imidazolyl flavone, α-naphthoflavone, and 2-azole/thiazolyl isoflavone derivatives. These scaffolds have been considered in this review for meticulous study in aspects of the structure-activity relationship for aromatase inhibitory activity, and it would likely pave the way for designing a potential lead candidate in the future.

Outcomes for infants with congenital diaphragmatic hernia: A single campus review with low extracorporeal membrane oxygenation utilisation.

AIM: To report the outcome for infants with congenital diaphragmatic hernia (CDH) and identify clinical factors affecting outcome from a tertiary perinatal surgical campus where extracorporeal membrane oxygenation (ECMO) is available however rarely utilised. METHODS: A retrospective cohort study of infants with CDH born in a co-located perinatal neonatal intensive care unit (NICU) or retrieved into and managed at a surgical NICU: 2003-2018. RESULTS: One hundred and fifty-nine infants with CDH were identified. One hundred and twenty were born in the co-located hospital and 39 retrieved from outlying hospitals. Survival of all patients with CDH was 74.8%; The survival for all isolated left CDH was 89% and the survival of post-surgery was 93%. Two patients went onto ECMO and both died. Associated major congenital anomalies were seen in 13.2%. Low birthweight (< 2500 g), 5-min Apgar <5, antenatal diagnosis, right-sided diaphragmatic hernia, herniation of the liver, associated major congenital anomalies, high oxygenation index (>25) on day 1, inotrope use, inhaled nitric oxide and need for high-frequency ventilation were associated with increased mortality on univariate analysis. Neurodevelopmental follow-up was commenced in 2013. Forty-three infants were discharged and developmental data were available for 36 at 4 months (83%) and 32 at 1 year (73%). Outcomes revealed normal motor scores and expressive language with mild delay in the receptive language at 1 year. CONCLUSION: Despite the low use of ECMO, our centre's results reveal excellent survival and neurodevelopmental outcomes consistent with or better than international data.

Solubility enhancementofcefixime trihydrate by solid dispersions using hydrotropic solubilization technique and their characterization

Abstract The aqueous solubility of cefixime trihydrate (a water insoluble drug) using different hydrotropic agents was determined and solid dispersions of cefixime trihydrate were prepared by hydrotropic solubilization technique. The drugs content were determined. The aqueous solubility of v was increased many fold in presence of sodium acetate trihydrate as hydrotropic agent. This hydrotropic agent was used to prepare solid dispersion of cefixime trihydrate. Cefixime trihydrate and sodium acetate trihydrate were accurately weighed and taken in a 200 mL beaker. Distilled water 10-15 mL was taken to dissolve hydrotropic agent using heat (48-50 °C). The drug was then added to it and magnetically stirred till whole mass get viscous. The solid dispersions of cefixime trihydrate were characterized by XRD, DSC and IR studies. DSC thermogram, XRD and Infra-Red spectra were studied. Solid dispersions, thus prepared, showed faster release of the drug as compared to pure drug and physical mixture.

Less Invasive Surfactant Administration (LISA) vs. Intubation Surfactant Extubation (InSurE) in Preterm Infants with Respiratory Distress Syndrome: A Pilot Randomized Controlled Trial.

OBJECTIVE: There has been an endeavor in recent years, to administer surfactant by minimally invasive techniques to neonates with surfactant deficiency. The objective of this study was to compare the need for intubation and mechanical ventilation after surfactant delivery, using Less Invasive Surfactant Administration (LISA) technique and Intubation SURfactant Extubation (InSurE), in preterm infants with respiratory distress syndrome (RDS). METHODS: We conducted a pilot randomized control trial (RCT) at a tertiary care center over a period of 18 months. Preterm neonates with RDS (gestational age 28-36 weeks) were randomized to receive surfactant within 6 h of birth by InSurE or LISA. The primary outcome was need for intubation and mechanical ventilation within 72 h of birth. Infants were followed until discharge for adverse events and complications. RESULTS: A total of 40 infants were analyzed (20 in each group). There was no difference in the need for intubation and mechanical ventilation within 72 h of birth between the two groups [InSurE, 6 (30%) and LISA, 6 (30%), relative risk 1.0, 95% confidence interval 0.51-1.97]. About 15% of infants in both groups had adverse events during the procedure. There was no statistically significant difference in the rates of major complications or duration of respiratory support, hospital stay and mortality. CONCLUSION: We found LISA to be feasible and equally effective as InSurE for surfactant administration in the treatment of RDS in preterm infants. Future larger RCTs are required to compare the efficacy and long-term outcomes of LISA with the standard invasive methods of surfactant administration.

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

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