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Background and Objective: The effects of neonatal hypoglycemia on the developing brain are well known, resulting in poor neurological outcomes. We aimed to perform an updated meta-analysis on neonatal hypoglycemia, the severity of hypoglycemia, and the associated neurodevelopmental outcomes from infancy to adulthood., Methods: A systematic literature search was conducted from inception until March 2024, using the PubMed, CINAHL, Embase, and the CENTRAL databases. Randomized/quasi-randomized trials and observational studies that evaluated at least one of the pre-specified outcomes were included. A random-effects model meta-analysis was performed to yield the pooled OR and its 95% CI for each outcome due to the expected heterogeneity in the studies. The study findings were reported as per the PRISMA guidelines. Neurodevelopmental impairment (NDI), cognitive impairment, and visual-motor or visual impairment were the primary outcomes., Results: A total of 17 studies (19 publications) were included in the final analysis. NDI, as defined by authors, was significantly higher in early- (OR = 1.16; 95% CI = 1.11-1.43) and mid-childhood (OR = 3.67; 95%CI = 1.07-12.2) in infants with neonatal hypoglycemia. 'Any cognitive impairment' was significantly more common in infants with neonatal hypoglycemia (OR = 2.12; 95%CI = 1.79-2.52). Visual-motor impairment (OR = 3.33; 95%CI = 1.14-9.72) and executive dysfunction (OR = 1.99; 95%CI = 1.36-2.91) were also more common in the hypoglycemic group. No difference in the incidence of epilepsy, motor impairment, emotional-behavioral problems, or hearing impairment were noted. Certainty of evidence was adjudged as 'low' to 'very low' for most outcomes. The severity of hypoglycemia was studied at different intervals, with NDI more common with a blood glucose interval between 20 and 34 mg/dL (1.1-1.9 mmol/L)., Conclusions: Low-quality evidence from large observational studies finds a significant association with hypoglycemia in the early neonatal period and long-term neurodevelopmental problems. Additional studies with long enough follow-up are paramount to determine the cut-off concentration and to quantify the impact beyond the infancy period.

Surfactant therapy in preterm and term born infants has been a huge success story. In the meantime, we have very detailed answers to the five essential questions of each medical therapy: which infant should be treated, when, with which drug, in/at what dose, and via which route of administration. The answers to these questions depend on the gestational age of the infant. We have focused on preterm infants <28 weeks of gestation as they are the most vulnerable and may have the maximum benefit of appropriate treatment. Therefore, we performed a sub-group analysis for data available from the published trials in infants less than 28 weeks who received less/minimal invasive surfactant administration/therapy [LISA/MIST] versus intubation-surfactant-extubation (INSURE). The need for mechanical ventilation (MV) was significantly reduced by 28 % (RR:0.72, 95%CI:0.64-0.80, n = 548 infants) after LISA/MIST. The incidence of bronchopulmonary dysplasia (BPD) was significantly decreased by 30 % (RR:0.70, 95%CI:0.66-0.75, n = 6528 infants) after LISA/MIST. No difference in mortality was noted between the two groups. In the current review, we discuss the applicability of guidelines to individual patient groups like the infants <28 weeks and emphasize the individual assessment of published data by the treating physician., (Copyright © 2024. Published by Elsevier Ltd.)

Persistent pulmonary hypertension of the newborn (PPHN) is a common neonatal condition in newborns admitted to the neonatal intensive care units (NICUs). PPHN has still a high mortality and morbidity. Inhaled nitric oxide (iNO) is the first line vasodilator therapy for PPHN in high income countries. In low-to-middle income countries (LMICs), availability of iNO remains scarce and expensive. The purpose of this scoping review was to evaluate the current existing literature for milrinone therapy in PPHN and to identify the knowledge gaps in milrinone use in infants with PPHN. The available evidence for milrinone remains limited both as monotherapy and as an adjuvant to iNO. The studies were heterogeneous, conducted in different settings, with different populations and more importantly the endpoints of these trials were short-term outcomes such as changes in oxygenation and blood pressure. Large prospective studies investigating long-term outcomes, mortality, and the need for Extracorporeal membrane oxygenation (ECMO) are warranted. Randomized controlled trials with milrinone as monotherapy are needed in LMICs where iNO availability remains limited. IMPACT: Milrinone has a potential role in the management of PPHN both as an adjuvant to iNO as well as a monotherapy. This scoping review identified the problems existing in the published literature on milrinone and the barriers to generalization of these results. Multi-centre randomized controlled trials on milrinone, especially involving centers from low- and middle-income countries are needed, where it can be evaluated as first-line pulmonary vasodilator therapy., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

This meta-analysis assessed short-term outcomes after using human milk-derived fortifiers (HMFs) compared with bovine milk fortifiers (BMFs) in preterm infants fed an exclusive human milk (HM) diet, either mother's own milk (MOM) or donor human milk (DHM). We searched PubMed, Embase, Google Scholar, CENTRAL and CINHAL between January 2015 and August 2023 for studies reporting outcomes in infants with ≤28 weeks gestation and/or birthweight ≤ 1500 g on an exclusive human milk diet fortified with HMF versus BMF. The primary outcomes were death and NEC (stage ≥ 2). Four studies with a total of 681 infants were included. Mortality was significantly lower in infants fed with an HM-HMFs diet (four studies, 681 infants; RR = 0.50, 95% CI = 0.26-0.94; p = 0.03; I 2 = 0%), NEC was similar between the two groups (four studies, 681 infants; RR = 0.48, 95% CI = 0.20-1.17; p = 0.11; I 2 = 39%). BPD was higher in the HM-BMFs group (four studies, 663 infants; RR = 0.83, 95% CI = 0.69-1.000; p = 0.05, I 2 = 0%), although not statistically significant. No differences were found for sepsis (RR = 0.97, 95% CI = 0.66-1.42; p = 0.96; I 2 = 26%) or combined ROP (four studies, 671 infants; RR = 0.64, 95% CI = 0.53-1.07; p = 0.28; I 2 = 69%). An HM-HMFs diet could possibly be associated with decreased mortality with no association with NEC, BPD, sepsis, or ROP. This meta-analysis was limited by the small number of studies included. However, the results should not be refuted for this reason as they provide an impetus for subsequent clinical trials to assess the observed associations.

Objectives: To test whether Kangaroo mother care (KMC) aids in transfer of favourable skin microbiome from mother to infant by comparing the microbiome composition before and after KMC., Methods: A prospective cohort pilot study was conducted in a Level III neonatal intensive care unit (NICU) in South India, recruiting 30 preterm infants with gestation <32 wk from October 2020 through December 2020. Neonatal skin involving the area in contact with the mother during KMC i.e., axilla, chest and abdomen was swabbed at the end of first week of life, prior to initiation of KMC. The 2nd swab involving the same areas was taken following KMC for 7 d for at least 6 h a day. The swabs were analysed using Next Generation Sequencing (NGS) - 16sRNA and abundance of organisms isolated were mapped. Statistical analyses using t-test and PERMANOVA were performed to compare phyla and genera of bacterial abundance pre-KMC and post-KMC., Results: KMC at phyla level increased the relative abundance of Firmicutes (p=0.52) and significantly decreased Proteobacteria (p=0.02). At species level, KMC decreased pathogenic bacterial count of Escherichia (p=0.05), while counts of S. hemolyticus (p=0.01) and S. hominis (p=.002) significantly increased post KMC., Conclusions: KMC has a potential role in altering the neonatal skin microbiota towards a more favourable microenvironment. The clinical significance of these novel findings needs to be validated with larger studies., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) or nasal prongs. Current literature indicates that either of these are associated with similar outcomes., Summary: Nonetheless, FM remains the most utilized and the best choice. However, most available FM sizes are too large for extremely preterm infants, which leads to mask leak and ineffective PPV. Challenges to providing effective PPV include poor respiratory drive, complaint chest wall, weak thoracic muscle, delayed liquid clearance, and surfactant deficiency in preterm infants. Mask leak, airway obstruction, poor technique, and inappropriate size are correctable causes of ineffective PPV. Visual assessment of chest rise is often used to assess the efficacy of PPV. However, its accuracy is debatable. Though end tidal CO2 may adjudge the effectiveness of PPV, clinical studies are limited. The compliance of a preterm lung is highly dynamic. The inflating pressure set on T-piece is constant throughout the resuscitation, but the lung volume and dynamics changes with every breath. This leads to huge fluctuations of tidal volume delivery and can trigger inflammatory cascade in preterm infants leading to brain and lung injury. Respiratory function monitoring in the delivery room has potential for guiding and optimizing delivery room resuscitation. This is, however, limited by high costs, complex information that is difficult to interpret during resuscitation, and absence of clinical trials., Key Messages: This review summarizes the existing literature on PPV in preterm infants, the various aspects related to it such as the pathophysiology, interfaces, devices utilized to deliver it, appropriate technique, emerging technologies, and future directions., (© 2024 S. Karger AG, Basel.)

Introduction: To evaluate the effect of antenatal magnesium sulfate (MgSO 4 ) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants., Methods: Data sources: A systematic literature search was conducted in November 2022. PubMed, CINAHL Plus with Full Text (EBSCOhost), Embase (Elsevier), and CENTRAL (Ovid) were searched. There were 6695 references. After deduplication, 4332 remained. Ninety-nine full-text articles were assessed and forty four articles were included in the final analysis., Study Eligibility Criteria: Randomized or quasi-randomized clinical trials and observational studies that evaluated at least one of the pre-specified outcomes were included. Preterm infants whose mothers were given antenatal MgSO 4 were included and whose mothers did not receive antenatal MgSO 4 were the comparators. The main outcomes and measures were: Necrotizing enterocolitis (NEC) (stage ≥ 2), surgical NEC, spontaneous intestinal perforation (SIP), feeding intolerance, time to reach full feeds, and GI-associated mortality., Study Appraisal and Synthesis Methods: A random-effects model meta-analysis was performed to yield pooled OR and its 95% CI for each outcome due to expected heterogeneity in the studies. The analysis for each predefined outcome was performed separately for adjusted and unadjusted comparisons. All included studies were assessed for methodological quality. The risk of bias was assessed using elements of the Cochrane Collaboration's tool 2.0 and the Newcastle-Ottawa Scale for randomized controlled trials (RCTs) and non-randomized studies (NRS), respectively. The study findings were reported as per PRISMA guidelines., Results: A total of thirty-eight NRS and six RCTs involving 51,466 preterm infants were included in the final analysis. There were no increased odds of stage ≥2 NEC, (NRS : n = 45,524, OR: 0.95; 95% CI: 0.84-1.08, I 2 - 5% & RCT's: n = 5205 OR: 1.00; 95% CI: 0.89-1.12, I 2 - 0%), SIP (n = 34,186, OR: 1.22, 95% CI: 0.94-1.58, I 2 -30%), feeding intolerance (n = 414, OR: 1.06, 95% CI: 0.64-1.76, I 2 -12%) in infants exposed to antenatal MgSO 4 . On the contrary, the incidence of surgical NEC was significantly lower in MgSO 4 exposure infants (n = 29,506 OR:0.74; 95% CI: 0.62-0.90, ARR: 0.47%). Studies assessing the effect on GI-related mortality were limited to make any conceivable conclusion. The certainty of evidence (CoE) for all outcomes was adjudged as 'very low' as per GRADE., Conclusion: Antenatal magnesium sulfate did not increase the incidence of gastrointestinal-related morbidities or mortality in preterm infants. With the current evidence concerns, regarding the adverse effects of MgSO 4 administration leading to NEC/SIP or GI-related mortality in preterm infants should not be a hurdle in its routine use in antenatal mothers., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Limited evidence shows minimal enteral nutrition (MEN) during therapeutic hypothermia (TH) in neonates to be feasible and have benefits of shorter time to full-feeds. This study aimed to assess the feasibility of MEN during TH. MEN was initiated after 12 h if there were no altered aspirates, abdominal distension, and inotrope requirement. The authors retrospectively analyzed the records from May 2017 to April 2022. The number of episodes of feed intolerance and the length of hospital stay were the key outcomes. A total of 99 neonates were fed during cooling. MEN could be initiated at a median duration (IQR) of 24 (24-30) h. There were 9 (9%) neonates with feed intolerance during TH. None had necrotizing enterocolitis. Ninety-two (93%) neonates were discharged, with a median hospital stay (IQR) of 9 d (6-15). Hence, MEN during TH is feasible and provides a rationale for future controlled trials., (© 2023. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Retinopathy of prematurity (ROP) and abnormal brain development share similar risk factors and mechanisms. There has been contrasting evidence on the association of ROP with adverse neurodevelopmental outcomes., Objective: We analysed the association between ROP at levels of severity and treatment with all neurodevelopmental outcomes until adolescence., Data Source: We followed PRISMA guidelines and searched Medline and Embase between 1 August 1990 and 31 March 2022., Study Selection and Participants: Randomised or quasi-randomised clinical trials and observational studies on preterm infants (<37 weeks) with ROP [type 1 or severe ROP, type 2 or milder ROP, laser or anti-vascular endothelial growth factor (VEGF) treated] were included., Data Extraction and Synthesis: We included studies on ROP and any neurocognitive or neuropsychiatric outcomes., Outcomes: The primary outcomes were as follows: cognitive composite scores evaluated between the ages of 18 and 48 months by the Bayley Scales of Infant and Toddler Development (BSID) or equivalent; neurodevelopmental impairment (NDI; moderate to severe NDI or severe NDI), cerebral palsy, cognitive impairment; and neuropsychiatric or behavioural problems. The secondary outcomes were as follows: motor and language composite scores evaluated between the ages of 18 and 48 months by BSID or equivalent; motor/language impairment; and moderate/severe NDI as defined by the authors., Results: In preterm infants, "any ROP" was associated with an increased risk of cognitive impairment or intellectual disability [ n  = 83,506; odds ratio (OR): 2.56; 95% CI: 1.40-4.69; p  = 0.002], cerebral palsy ( n  = 3,706; OR: 2.26; 95% CI: 1.72-2.96; p  < 0.001), behavioural problems ( n  = 81,439; OR: 2.45; 95% CI: 1.03-5.83; p  = 0.04), or NDI as defined by authors ( n  = 1,930; OR: 3.83; 95% CI: 1.61-9.12; p  = 0.002). Type 1 or severe ROP increased the risk of cerebral palsy (OR: 2.19; 95% CI: 1.23-3.88; p  = 0.07), cognitive impairment or intellectual disability ( n  = 5,167; OR: 3.56; 95% CI: 2.6-4.86; p  < 0.001), and behavioural problems ( n  = 5,500; OR: 2.76; 95% CI: 2.11-3.60; p  < 0.001) more than type 2 ROP at 18-24 months. Infants treated with anti-VEGF had higher odds of moderate cognitive impairment than the laser surgery group if adjusted data (gestational age, sex severe intraventricular haemorrhage, bronchopulmonary dysplasia, sepsis, surgical necrotising enterocolitis, and maternal education) were analysed [adjusted OR (aOR): 1.93; 95% CI: 1.23-3.03; p  = 0.04], but not for cerebral palsy (aOR: 1.29; 95% CI: 0.65-2.56; p  = 0.45). All outcomes were adjudged with a "very low" certainty of evidence., Conclusion and Relevance: Infants with "any ROP" had higher risks of cognitive impairment or intellectual disability, cerebral palsy, and behavioural problems. Anti-VEGF treatment increased the risk of moderate cognitive impairment. These results support the association of ROP and anti-VEGF treatment with adverse neurodevelopmental outcomes., Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022326009., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Diggikar, Gurumoorthy, Trif, Mudura, Nagesh, Galis, Vinekar and Kramer.)

Objective: To assess whether laryngeal mask airway (LMA) as compared with face mask (FM) or endotracheal intubation (ETT) is more effective in delivering positive pressure ventilation (PPV) during neonatal resuscitation in low-and-middle income countries (LMICs)., Study Design: We followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and searched Medline (PubMed interphase), Cumulative Index of Nursing and Allied Health Literature, Embase and Cochrane Registry between January 1990 and April 2022 for the studies that examined the effect of LMA in delivering PPV compared with the FM or ETT in infants during neonatal resuscitation. We included the studies conducted in LMIC only. We assessed the quality of all the included studies using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) recommendations., Results: Our search resulted in eight randomised studies Six studies compared LMA with FM and three studies compared LMA with ETT. When used as the primary device for providing PPV, the LMA as compared with FM resulted in a significant lower failure rate (relative risk (RR) 0.23, 95% CI 0.13 to 0.43) with moderate certainty of evidence (CoE) and lesser need for intubation (RR 0.21, 95% CI 0.07 to 0.58) with low CoE. There was no difference in the incidence of encephalopathy, neonatal admission, need for advanced resuscitations or death. No differences were observed between LMA and ETT. Studies comparing LMA to ETT were limited for any conceivable conclusion., Conclusion: LMA is more effective than FM in delivering PPV with less failure rates and reduced need for intubation during neonatal resuscitation in term infants and in LMIC without any difference in the incidence of encephalopathy or death. Studies comparing LMA to ETT are scarce with important methodological limitations., Prospero Registration Number: CRD42021283478., Competing Interests: Competing interests: DT is a member of the ILCOR Neonatal Task Force and a member of the European Resuscitation Council Neonatal Life Support Task Force. SL is a member of the American Academy of Pediatrics – Neonatal Resuscitation Program Steering Committee. The views expressed in this manuscript are individual opinions of the authors and do not reflect the official position of ILCOR or AAP., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Studies from high-income countries indicates that infants born preterm are at increased risk of respiratory infections; however in the low and middle-income countries (LMICs) data are limited. Our aim was to systematically review the studies evaluating the risk of respiratory infections in preterm children born in LMICs., Methods: We searched Medline, PubMed, Cumulative Index of Nursing and Allied Health Literature, Embase, and Psych-INFO databases for studies reporting respiratory outcomes in children born preterm in LMICs. Two authors extracted the data and evaluated the risk of bias with appropriate assessment methods independently., Results: Twelve observational studies evaluating 5969 children were included in the review. The risk of lower respiratory tract infection varied from 5% to 73.9%. Similarly, respiratory syncytial virus (RSV) infection risk ranged from 4.4% to 22.7%. The unadjusted relative risk for any respiratory tract infection or lower respiratory tract infection was significantly higher in the children born preterm than in children born at term (1.52 [95% confidence interval 1.25-1.85]). We also noted wide-ranging risk of respiratory infections requiring in-hospital or emergency care (range: 0.5%-27.7%) and hospital stay in children born preterm (range: 6-14.3 days)., Conclusions: Preterm-born children in LMICs are at risk of increased respiratory infections compared to term-born children; however, the baseline risk is variable, although substantial; This highlights the need for preventive strategies, including RSV immunoprophylaxis., (© 2022 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background and Objective: With improved survival in neonates with meconium aspiration syndrome (MAS), the focus is currently on mitigating the morbidities. The objective of this study was to predict factors determining prolonged hospital stay in neonates with MAS., Materials and Methods: It was a retrospective cohort from five centers of south India between 2018 and 2020. Neonates ≥35 weeks of gestation admitted to neonatal intensive care unit with the diagnosis of MAS and requiring oxygen beyond 24 h of life were included in the study. The morbidities in the neonates with stay ≤7 days (short stay) were compared with >7 days (prolonged stay). Logistic regression by the backward stepwise method was used for predictive score creation., Results: Out of 347 neonates with MAS discharged home, 103 (29%) had a short stay and 244 (71%) had prolonged stay. The primary support beyond O 2 (continuous positive airway pressure/mechanical ventilation) (42% vs. 83%, p < 0.001), fractional inspired oxygen (FiO 2 ) at 1 h >30% (45% vs. 87%, p < 0.001), hypoxic ischemic encephalopathy (HIE) stage 2 or 3 (1% vs. 27%, p < 0.001), moderate-severe persistent pulmonary artery hypertension (PPHN) (3% vs. 31%, p < 0.001) were independent factors associated with prolonged stay on logistic regression. A prediction model was devised using weighted scores of these four associated morbidities. The clinical score thus developed had 83% sensitivity, 68% specificity for the prediction of prolonged stay (area under curve: 82%, 95% confidence interval [78-87], p < 0.001)., Conclusion: More than two-thirds of neonates with MAS had prolonged stay. The primary support beyond oxygen, FiO 2 requirement >30%, Moderate to severe PPHN, HIE stage 2 or 3 were predictive of prolonged stay in neonates with MAS., (© 2022 Wiley Periodicals LLC.)

The neonatal skin microbiome consists of all the genomes and genetic products of micro-organisms harbouring the skin of babies. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. Our study was conducted to explore the neonatal skin fungal microbiome of very preterm neonates admitted to Neonatal Intensive Care Unit at a tertiary health care setting using Next Generation Sequencing of the18S rRNA gene. The most abundant genera found in 22/30 samples were Candida followed by Bipolaris & Cladosporium on the skin microbiome of these neonates. The presence of these fungi, whether just as commensals or as potential pathogens, is currently under research, owing to the risk of early exposure and incidence of infection right from birth.

The neonatal skin microbiome consists of all the genomes and genetic products of microorganisms harboring on an infant's skin. Host and the microbiota develop a harmonious environment resulting in symbiosis. Any disruption of this environment could lead to pathological disease. This study was conducted to understand the neonatal skin microbiome of very preterm neonates (under 32 weeks) admitted to the Neonatal Intensive Care Unit(NICU) at a tertiary healthcare setting before and after kangaroo mother care (KMC), using next-generation sequencing (NGS). Skin swabs were collected on two different occasions and analyzed using the NGS technique after amplification via polymerase chain reaction. The results showed relative abundance for Mycobacterium tuberculosis in 83.33% and 66.67% (p = 0.29) and Mycobacteroides abscessus in 100% and 93.33% (p = 0.30) of the very preterm neonates on the skin microbiome before and after KMC, respectively as an incidental finding. The mere presence of these bacilli as commensals or as potential pathogens is alarming due to the risk of early exposure and incidence of tuberculosis from birth. These findings, in our view, are the first findings to be established in such a setting., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aims: This structured review aimed to discuss the existing literature on therapeutic hypothermia for moderate to severe neonatal encephalopathy exclusively in low- and middle-income countries (LMICs)., Methods: Medline, Embase, CINHAL and Cochrane Registry were searched for original papers with therapeutic hypothermia (TH) for treating neonatal encephalopathy in LMIC with no language restrictions. The search identified 1413 papers from 1990 to 31 August 2021., Results: Twenty-one original papers were included after duplicates removal and full-text screening in the final review. Fourteen randomized control studies and seven non-randomized studies were discussed with various modes of cooling (servo-controlled, phase changing material, traditional methods), complications during cooling, mortality and long-term neurodevelopmental assessment. Although there is sufficient evidence in LMIC favouring cooling for the reduction in mortality and improving the neurodevelopmental outcomes, nonetheless these studies were widely heterogeneous in terms of method of cooling, tools for assessing developmental outcomes, age at assessment and variations in neuroimaging tools and reporting., Conclusion: Therapeutic hypothermia is beneficial in LMICs with low certainty of evidence in reducing mortality and improving neurodevelopmental outcomes., (© The Author(s) [2022]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Large numbers of preterm infants are born in middle-income countries and neonatal care is improving in these countries. Few studies have compared clinical outcome in preterm infants in a tertiary neonatal unit in a middle-income country with one in a high-income country., Objective: To compare the short-term outcome in preterm infants of ≤30 weeks gestation admitted to a tertiary neonatal unit in Bengaluru, India and in London, UK., Methods: This was a retrospective observational study using anonymised data from electronic patient records. Preterm infants born at ≤30 weeks gestation admitted to neonatal units in Bengaluru ( n = 294) and London ( n = 740) over a 5-year period (January 2011 to December 2015) were compared., Results: Fewer mothers in the Bengaluru centre received antenatal steroids (37% vs 73%, p < 0.001). The incidence of retinopathy of prematurity requiring treatment (12.9% vs 7.7%, NS), treated patent ductus arteriosus (32.3% vs 10.7%, NS) and blood culture-positive sepsis (32.4% vs 1.7%, p < 0.001) was higher in infants in the Indian centre. Overall survival was 83% vs 87.2% (NS) in the Bengaluru and the London cohorts, respectively. Survival of infants born at ≤28 weeks gestation was lower in Bengaluru than in London [24 weeks: 33.0% vs 79.3% (NS); 25 weeks: 50.0% vs 78.9%, p = 0.02; 26 weeks: 45.2% vs 86.5%, p < 0.01; 27 weeks: 79.3% vs 91.3% (NS); 28 weeks 82.5% vs 94.1%, p = 0.03]., Conclusion: The survival of infants ≤28 weeks gestation was significantly lower in the Bengaluru centre. Increasing the provision of antenatal corticosteroids may improve the outcome in these infants., Abbreviations: BPD: bronchopulmonary dysplasia; CPAP: continuous positive airway pressure; EPR: electronic patient records; HIC: high-income countries; HDU: high dependency unit; hsPDA: haemodynamically significant patent ductus arteriosus; IVH: intraventricular haemorrhage; ITU: Intensive Care Unit, IUGR: intrauterine growth restriction; LAMA: leaving against medical advice; LMIC: low- and middle-income countries; NICU: neonatal intensive care unit; NNFI: National Neonatal Forum of India; NS: not significant; NTS: neonatal transfer service; NNAP: National Neonatal Audit Programme; NHM: National Health Mission; NMR: neonatal mortality rate; NEC: necrotising enterocolitis; NS: not significant; PDA: patent ductus arteriosus; ROP: retinopathy of prematurity; SCBU: special care baby unit; VLBW: very low birthweight; WHO: World Health Organization.

Background: Long-chain polyunsaturated fatty acids (LCPUFA) are critical for the maturation of the brain and retina. Retinopathy of prematurity (ROP) is a preventable cause of blindness in preterm infants. LCPUFA have anti-inflammatory, antioxidant, and antiangiogenesis effects. Supplementation of enteral LCPUFA might mitigate the incidence of ROP in these infants. Available limited randomized studies showed promising results. We aimed to assess the effect of enteral supplementation of LCPUFA on ROP in preterm infants., Methods: We followed PRISMA guidelines and searched MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Embase, and Cochrane Registry from 1990 to 2021 for the studies that examined the effects of enteral LCPUFA and ROP in preterm infants. We included the studies that satisfied the predefined inclusion criteria. RevMan 5.3 software derived the forest plot of pooled relative risk. We assessed the quality of all the included studies using GRADE recommendations., Results: Nine studies were eligible for the meta-analysis involving 2,482 infants. Of the nine RCTs, six studies provided LCPUFA (DHA/AA) as a separate intervention in different concentrations, and three studies provided formula milk enriched with LCPUFA. In addition, five studies recruited infants below 32 weeks of gestational age. Supplementation of LCPUFA did not reduce the incidence of severe ROP (RR 0.71, 95% CI: 0.50-1.01, 5 studies, 1,822 infants) with very low CoE or any ROP (RR 0.95, 95% CI: 0.73-1.12, 6 studies, 1,177 infants) with very low CoE or ROP requiring treatment (RR 0.92, 95% CI: 0.62-1.38, 4 studies, 1,395 infants) with very low CoE. Regarding safety outcomes, enteral LCPUFA did not increase the risk of necrotizing enterocolitis or mortality., Discussion/conclusion: Supplementation of enteral LCPUFA to preterm infants did not reduce ROP incidence; however, there was a trend toward benefit in mitigating severe form of ROP. More well-designed, large, randomized controlled studies are warranted., (© 2022 S. Karger AG, Basel.)

Proteasome inhibitors such as PS-341 are novel agents with great potential as anticancer drugs. In early clinical studies, PS-341 was tolerated well with promising evidence of antitumor activity in diseases such as multiple myeloma. Studies also are ongoing in solid tumors, as single agent therapy and in combination with standard agents such as carboplatin. Although more research is needed to clarify the precise spectrum of antitumor activity of proteasome inhibitors, this novel approach to targeting human malignancies is highly promising.