Effect of Minimization of Early Blood Sampling Losses Among Extremely Premature Neonates: A Randomized Clinical Trial.

OBJECTIVE: To evaluate the effect of blood sampling stewardship on transfusion requirements among infants born extremely preterm. STUDY DESIGN: In this single-center, randomized controlled trial (RCT), infants born at <28 weeks of gestation and birth weight of <1000 g were randomized at 24 hours of age to two different blood sampling approaches: restricted sampling (RS) vs conventional sampling (CS). The stewardship intervention in the RS group included targeted reduction in blood sampling volume and frequency and point of care testing methods in the first 6 weeks after birth. Both groups received early recombinant erythropoietin from day three of age. Primary outcome was the rate of early red blood cell (RBC) transfusions in the first six postnatal weeks. RESULTS: A total of 102 infants (mean gestational age: 26 weeks; birth weight: 756 g) were enrolled. Fidelity to the sampling protocol was achieved in 95% of the infants. Sampling losses in the first 6 weeks were significantly lower in the RS group (16.8 ml/kg vs 23.6 ml/kg, P < .001). The RS group had a significantly lower rate of early postnatal RBC transfusions (41% vs 73%, RR: 0.56 [0.39-0.81], P = .001). The hazard of needing a transfusion during neonatal intensive care unit (NICU) stay was reduced by 55% by RS. Mortality and neonatal morbidities were similar between the two groups. CONCLUSION: Minimization of blood sampling losses by approximately one-third in the first 6 weeks after birth leads to substantial reduction in the early red blood cell transfusion rate in infants born extremely preterm and weighing <1000 g at birth. TRIAL REGISTRATION: http://www.ctri.nic.in (CTRI/2020/01/022  964).

Meta-analysis of Cerebrospinal Fluid Cell Count and Biochemistry to Diagnose Meningitis in Infants Aged < 90 Days.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, protein, and glucose (cytochemistry) are performed to aid in the diagnosis of meningitis in young infants. However, studies have reported varying diagnostic accuracies. We assessed the diagnostic accuracy of CSF cytochemistry in infants below 90 days and determined the certainty of evidence. STUDY DESIGN: We searched PubMed, Embase, Cochrane Library, Ovid, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Scopus databases in August 2021. We included studies that evaluated the diagnostic accuracy of CSF cytochemistry compared with CSF culture, Gram stain, or polymerase chain reaction in neonates and young infants <90 days with suspected meningitis. We pooled data using the hierarchical summary receiver operator characteristic (ROC) model. RESULTS: Of the 10,720 unique records, 16 studies were eligible for meta-analysis, with a cumulative sample size of 31,695 (15 studies) for WBC, 12,936 (11 studies) for protein, and 1,120 (4 studies) for glucose. The median (Q1, Q3) specificities of WBC, protein, and glucose were 87 (82, 91), 89 (81, 94), and 91% (76, 99), respectively. The pooled sensitivities (95% confidence interval [CI]) at median specificity of WBC count, protein, and glucose were 90 (88, 92), 92 (89, 94), and 71% (54, 85), respectively. The area (95% CI) under ROC curves were 0.89 (0.87, 0.90), 0.87 (0.85, 0.88), and 0.81 (0.74, 0.88) for WBC, protein, and glucose, respectively. There was an unclear/high risk of bias and applicability concern in most studies. Overall certainty of the evidence was moderate. A bivariate model-based analysis to estimate the diagnostic accuracy at specific thresholds could not be conducted due to a paucity of data. CONCLUSION: CSF WBC and protein have good diagnostic accuracy for the diagnosis of meningitis in infants below 90 days of age. CSF glucose has good specificity but poor sensitivity. However, we could not identify enough studies to define an optimal threshold for the positivity of these tests. KEY POINTS: · Median specificity of CSF leucocyte count, protein and glucose are similar in young infants.. · At median specificity, CSF leukocyte count and protein are more sensitive than glucose.. · Owing to inadequate data, bivariate modelling to suggest optimal diagnostic thresholds is not possible..

Early erythropoietin for preventing necrotizing enterocolitis in preterm neonates - an updated meta-analysis.

Previous systematic reviews suggest reduction in necrotizing enterocolitis (NEC) among preterm infants supplemented with erythropoietin (EPO). We aimed to update our 2018 systematic review in this field considering the evidence accumulated over the last 3 years. Randomized controlled trials (RCTs) reporting the effect of early EPO supplementation vs placebo/no EPO supplementation on any stage NEC in preterm infants were included. Fixed effect model was used for meta-analysis. Trial sequential analysis (TSA) was conducted to verify the effects of EPO on NEC after accounting for repeated significance testing. A total of 22 RCTs (n = 5359) were included, of which six were new (n = 2541 additional preterm infants) in comparison to our previous systematic review. EPO significantly decreased the risk of any stage NEC (232/2669 (8.7%) vs 313/2690 (11.6%); RR: 0·76; TSA adjusted 95% CI (0·64, 0·90); p = 0·0008, number needed to treat (NNT) = 34). The risk of definite NEC (≥ Stage II) was also significantly reduced by EPO administration (105/2219 (4.7%) vs 141/2246 (6.3%); RR: 0.77; 95% CI (0.61, 0.98); p = 0.03, NNT: 62). However, the results for definite NEC were no longer significant on sensitivity analyses that included (a) only double-blind RCTs and (b) only prospectively registered trials. The quality of evidence was deemed moderate-to-low for the reported outcomes. CONCLUSION: There is moderate to low-quality evidence that early prophylactic EPO reduces any stage and ≥ Stage II NEC in preterm neonates. Prospectively registered, adequately powered, double-blind RCTs are required to confirm these findings. WHAT IS KNOWN: • Experimental studies have shown that erythropoietin (EPO) has gastrointestinal trophic effects. • Systematic reviews have shown that early treatment with EPO may decrease the risk of gut injury in preterm or low birth weight infants. WHAT IS NEW: • Early EPO supplementation significantly reduced the incidence of any stage NEC and definite NEC in preterm infants < 34 weeks of gestation. • EPO had no significant effect on definite NEC in the analyses that included only double-blinded and prospectively registered RCTs. How might it impact clinical practice in the foreseeable future? • Early prophylactic EPO can be recommended for NEC prevention if its benefits are consistently demonstrated in adequately powered randomized trials with a low risk of bias.

Probiotic sepsis in preterm neonates-a systematic review.

Sepsis due to the administered probiotic strain/s is a barrier against adoption of prophylactic probiotic supplementation in preterm infants to reduce the risk of necrotising enterocolitis (NEC ≥ Stage II), all-cause mortality, late-onset sepsis, and feeding intolerance. We aimed to conduct a systematic review for reports of probiotic sepsis in preterm infants (gestation < 37 weeks). Databases including PubMed, Embase, Emcare, Cochrane Central library, and Google Scholar were searched in August 2021 and updated in Jan 2022. Probiotic sepsis was defined as positive blood/CSF culture isolating administered probiotic strain with symptoms suggestive of infection. Data collection included birth weight, gestation, comorbidities (e.g. gut surgery, NEC), presence of central venous catheters, treatment, and outcome. Literature search revealed 1569 studies. A total of 16 reports [randomised control trial (RCT): none; non-RCT: 1; case series: 8; case report: 7] involving 32 preterm infants with probiotic sepsis were included after exclusions for various reasons. Majority of the cases were born < 32 weeks' gestation. Bifidobacterium (N = 19) was the most commonly isolated organism followed by Lactobacillus (N = 10), and Saccharomyces (N = 3). A total of 25/32 cases were confirmed to be due to the administered probiotic strain on full genomic analysis. Two studies reported one neonatal death each. Twelve neonates had comorbidities. Majority were treated with antibiotics (29/32) whereas others (3/32) required antifungal treatment. CONCLUSION: Probiotics sepsis is relatively an uncommon event in preterm infants. Majority of the cases recovered after antibiotic or antifungal treatment. The importance of optimal surveillance and treatment of probiotic sepsis and research towards alternatives to probiotics (e.g. postbiotics) is emphasised. WHAT IS KNOWN: • Probiotics have been shown to reduce necrotising enterocolitis, late-onset sepsis, all-cause mortality, and time to reach full enteral feeds in preterm infants. • Despite the evidence, use of probiotics is not universal due to concerns regarding probiotic-associated sepsis in preterm infants. WHAT IS NEW: • This comprehensive systematic review showed that probiotic sepsis is a relatively rare phenomenon in preterm infants. • All except one case where the diagnosis was uncertain recovered after antimicrobial therapy.

Efficacy and Safety of Two Different Flow Rates of Nasal High-Flow Therapy in Preterm Neonates ≥28 Weeks of Gestation: A Randomized Controlled Trial.

OBJECTIVE: The study aimed to compare the efficacy and safety of two different nasal high-flow rates for primary respiratory support in preterm neonates STUDY DESIGN: In this single-center, double-blinded randomized controlled trial, preterm neonates ≥28 weeks of gestation with respiratory distress from birth were randomized to treatment with either increased nasal flow therapy (8-10 L/min) or standard nasal flow therapy (5-7 L/min). The primary outcome of nasal high-flow therapy failure was a composite outcome defined as the need for higher respiratory support (continuous positive airway pressure [CPAP] or mechanical ventilation) or surfactant therapy. RESULTS: A total of 212 neonates were enrolled. Nasal high-flow failure rate in the increased flow group was similar to the standard flow group (22 vs. 29%, relative risk = 0.81 [95% confidence interval: 0.57-1.15]). However, nasal flow rate escalation was significantly more common in the standard flow group (64 vs. 43%, p = 0.004). None of the infants in the increased flow group developed air leak syndromes. CONCLUSION: Higher nasal flow rate (8-10 L/min) when compared with lower nasal flow rate of 5 to 7 L/min did not reduce the need for higher respiratory support (CPAP/mechanical ventilation) or surfactant therapy in moderately and late preterm neonates. However, initial flow rates of 5 L/min were not optimal for most preterm infants receiving primary nasal flow therapy. KEY POINTS: · Use of high nasal flows (8-10 L/min) did not reduce the need for higher respiratory support in moderately and late preterm infants.. · Nasal flow rate of 5 L/min was not optimal for most preterms with respiratory distress from birth.. · Careful patient selection and optimized flow settings could enhance nasal flow success in neonates..

Effects of blood sampling stewardship and erythropoietin administration in extremely low birth weight infants-a quality improvement non-controlled before-and-after retrospective study.

The majority of extremely low birth weight (ELBW) neonates receive red blood cell (RBC) transfusions; at least 50% receive multiple transfusions. Anemia care bundles could be the most effective approach to reduce transfusion rates. We conducted a quality improvement non-controlled before-and-after retrospective study involving 345 ELBW infants admitted over a 5-year period in two consecutive epochs before and after implementation of an anemia care bundle in January 2017. Bundle components included (a) prophylactic subcutaneous erythropoietin twice each week (600 IU/kg/week) from day 7 through 8 weeks of age and (b) blood sampling stewardship in the first five postnatal weeks. Early postnatal blood sampling losses were significantly reduced following the implementation of the care bundle (21.2 ml/kg vs 25 ml/kg, P < 0.001). We found a 50% reduction in the rate of multiple RBC transfusions (adjusted RR 0.45, 95% CI: 0.34-0.59) and a reduced odds of necrotizing enterocolitis (NEC) (4% vs 10%, adjusted OR 0.38 (95% CI: 0.15-0.78)) among infants that received the anemia care bundle (n = 182 infants). The overall transfusion rate, number and volume of transfusions, and multiple donor exposures were also significantly reduced.Conclusion: The combination of extended subcutaneous erythropoietin administration and reduced early postnatal blood sampling was associated with a significant reduction in the rate of multiple erythrocyte transfusions and NEC in ELBW neonates. What is known: • The majority of extremely low birth weight neonates continue to require blood transfusions despite advances in standardized transfusion practices; at least 50% require multiple transfusions. • Anemia care bundles, employing a combination of anemia prevention strategies, can effectively reduce the RBC transfusion rates in ELBW infants. What is new: • A combination of extended subcutaneous erythropoietin supplementation and blood sampling stewardship practices reduced the rate of multiple RBC transfusions in ELBW neonates by 50%. • Implementation of the anemia care bundle was associated with a significant reduction in the rates of necrotizing enterocolitis.

Effect of Umbilical Cord Blood Sampling versus Admission Blood Sampling on Requirement of Blood Transfusion in Extremely Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of blood sampling from the placental end of the umbilical cord compared with initial blood sampling from neonates, on the need for first packed red blood cell transfusion in extremely preterm infants. We hypothesized that cord blood sampling could delay the time to first blood transfusion. STUDY DESIGN: In this single-center, assessor blind, randomized controlled trial, we included extremely low birth weight neonates <28 weeks of gestational age at birth. Five milliliter of blood for initial laboratory investigations was collected either from the placental end of the umbilical cord (study group) or from the neonate upon neonatal intensive care unit admission (control group). Both groups received similar anemia prevention strategies. The primary outcome was the time (in days) to the first packed red blood cell transfusion, and was compared using survival analysis. RESULTS: Eighty neonates were enrolled. The time to first transfusion was significantly delayed in the cord sampling group (30 vs 14 days, hazard ratio: 0.44, [95% CI 0.27-0.72], P < .001). Fewer neonates in the cord sampling group were transfused in the first 28 days of life (30% vs 75%, P < .001). Overall transfusion requirements and other clinical outcomes were similar in the groups. CONCLUSIONS: Initial blood sampling from placental end of umbilical cord, when combined with anemia prevention strategies, significantly prolonged the time to first transfusion and reduced the need for early transfusions among extremely premature neonates. TRIAL REGISTRATION: Ctri.nic.in/ (CTRI/2017/04/008320).

Placental Findings in Singleton Stillbirths: A Case-control Study.

Aims: This prospective observational study compared placental lesions of stillbirth cases and live birth controls, and aimed to determine the cause of stillbirth. Methods: The study enrolled 85 stillbirths and 85 live births at the time of delivery. Results: There was significantly increased incidence of placental abruption (p = 0.005) and gestational diabetes (p = 0.032) in mothers with stillbirths. Histopathological examination of placenta was significantly abnormal in stillbirths compared with live births (p = 0.004). Delayed villous maturation was significantly more in stillbirths (38.82 vs. 16.47%; p = 0.002). Acute (30.59 vs. 16.47%; p = 0.04) and chronic diffuse villitis (16.47 vs. 4.7%; p = 0.02), chorionic plate acute vasculitis (28.235 vs. 14.11%; p = 0.04) were significantly more in stillbirths. Foetal vascular thrombi in the chorionic plate (30.58 vs. 14.12%; p = 0.02) and avascular villi (24.7 vs. 8.23%; p = 0.006) were significantly more in stillbirths. Conclusion: These abnormal placental patterns could provide information about the etiopathogenisis in stillbirths of unknown aetiology.

Postoperative Stridor following Repair of Tracheoesophageal Fistula: A Case Report.

We report a case of prolonged post-operative stridor in a full-term neonate who was operated for tracheoesophageal fistula. Initial evaluation including an endoscopy and contrast-enhanced computed tomography scan was normal. Repeat endoscopic evaluation under anesthesia revealed tight aryepiglottic folds. Aryepiglottic split was performed and stridor improved dramatically. Tight aryepiglottic folds should be kept in differential diagnosis in a case of postoperative stridor in an infant.

Probiotic supplementation in children with cystic fibrosis-a systematic review.

UNLABELLED: Probiotics may benefit in cystic fibrosis (CF) as gut dysbiosis is associated with gastrointestinal symptoms and exacerbation of respiratory symptoms in CF. We conducted a systematic review of randomized controlled trials (RCTs) and non-RCTs of probiotic supplementation in children with CF, using the Cochrane methodology, preferred reporting items for systematic reviews (PRISMA) statement, and meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Primary outcomes were pulmonary exacerbations, duration of hospitalization and antibiotics, and all-cause mortality. Secondary outcomes included gastrointestinal symptoms, markers of gut inflammation, and intestinal microbial balance. A total of nine studies (RCTs, 6, non-RCTs, 3; N = 275) with some methodological weaknesses were included in the review. The pooled estimate showed significant reduction in the rate of pulmonary exacerbation (fixed effects model, two parallel group RCTs and one cross-over trial: relative risk (RR) 0.25, (95 % confidence interval (95 % CI) 0.15,0.41); p < 0.00001; level of evidence: low) and decrease in fecal calprotectin (FCLP) levels (fixed effect model, three RCTs: mean difference (MD) -16.71, 95 % CI -27.30,-6.13); p = 0.002; level of evidence: low) after probiotic supplementation. Probiotic supplementation significantly improved gastrointestinal symptoms (one RCT, one non-RCT) and gut microbial balance (decreased Proteobacteria, increased Firmicutes, and Bacteroides in one RCT, one non-RCT). CONCLUSION: Limited low-quality evidence exists on the effects of probiotics in children with CF. Well-designed adequately powered RCTs assessing clinically meaningful outcomes are required to study this important issue. WHAT IS KNOWN: • Gut dysbiosis is frequent in children with cystic fibrosis due to frequent exposure to pathogens and antibiotics. • Probiotics decrease gut dysbiosis and improve gut maturity and function. What is New: • This comprehensive systematic review shows that current evidence on the safety and efficacy of probiotics in children with cystic fibrosis is limited and of low quality. • Well-designed and adequately powered trials assessing clinically important outcomes are required considering the health burden of cystic fibrosis and the potential benefits of probiotics.

Developmental outcomes in cerebrospinal fluid proven enteroviral meningitis in neonates > 32 weeks of gestation.

AIM: The aim of this study is to assess the short-term and long-term (1 year) outcomes of cerebrospinal fluid (CSF) confirmed enteroviral meningitis in neonates > 32 weeks of gestation. METHODS: A retrospective audit of neonates admitted between 1 July 2002 to 30 June 2012. RESULTS: Thirty-three neonates were diagnosed with enteroviral meningitis based on a positive CSF enteroviral PCR. Physical growth and neurodevelopmental outcomes at 1 year corrected for prematurity were available for 24 infants. All infants were alive at 1 year. The median weight, length and head circumference at 1 year were in the 72nd, 62nd and 78th centile and were comparable with the birth parameters. The mean general quotient (GQ) was 98.5 (SD 7.1) and was not significantly different from the population mean of 100.2 (P = 0.27). None of the infants had a GQ > 2SD below the population mean. Neurological recovery was complete in the 24 neonates assessed except one, who developed cerebral palsy, epilepsy and progressive hydrocephalus requiring ventriculoperitoneal shunt at 1 year. CONCLUSION: Neonatal enteroviral meningitis was associated with optimal growth and neurodevelopment in the majority of the infants at 1 year corrected for prematurity. Longer term studies are needed to better define developmental outcomes.

Comparison of parent or caregiver-completed development screening tools with Bayley Scales of Infant Development: a systematic review and meta-analysis.

BACKGROUND: Parent/caregiver-completed developmental testing (PCDT) is integral to developmental care in children; however, there is limited information on its accuracy. In this systematic review, we compared the diagnostic accuracy of PCDT with concurrently administered Bayley Scales of Infant Development for detection of developmental delay (DD) in children below 4 years of age. METHODS: We searched databases PubMed, Embase, CINAHL, PsycINFO and Google Scholar until November 2023. Bivariate and multiple thresholds summary receiver operating characteristics were used to obtain the summary sensitivity and specificity with 95% CIs. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for risk of bias assessment. RESULTS: A total of 38 studies (31 in the meta-analysis) were included. Ages and Stages Questionnaire (ASQ) and Parent Report of Children's Abilities-Revised (PARCA-R) were the most commonly evaluated PCDTs. ASQ score >2 SD below the mean had an overall sensitivity of 0.72 (0.6, 0.82) and 0.63 (0.50, 0.75) at a median specificity of 0.89 (0.82, 0.94) and 0.81 (0.76, 0.86) for diagnosing moderate to severe DD and severe DD, respectively. PARCA- R had an overall sensitivity of 0.69 (0.51, 0.83) at median specificity of 0.75 (0.64, 0.83) for predicting severe DD. Participant selection bias and partial verification bias were found in over 50% of the studies. The certainty of evidence was low for the studied outcomes. CONCLUSIONS: The most commonly studied parental tools, ASQ and PARCA-R, have moderate to low sensitivity and moderate specificity for detecting DD in young children. High risk of bias and heterogeneity in the available data can potentially impact the interpretation of our results. PROSPERO REGISTRATION NUMBER: CRD42021268629.

Lactobacillus rhamnosus GG as a probiotic for preterm infants: a strain specific systematic review and meta-analysis.

Lactobacillus rhamnosus GG (LGG) is a widely used and extensively researched probiotic. Probiotic effects are considered to be strain specific. We aimed to comprehensively assess the strain-specific effects of LGG in preterm infants. A systematic review of RCTs and non-RCTs to evaluate the effect of LGG in preterm infants. We followed the Cochrane methodology, and preferred reporting items for systematic reviews (PRISMA) statement for conducting and reporting this review. We searched the Cochrane central register of controlled trials, PubMed, EMBASE and CINAHL databases till December 2023. The review was registered in PROSPERO 2022 CRD42022324933. Meta-analysis of data from RCTs that used LGG as the sole probiotic showed significantly lower risk of NEC ≥Stage II [5 RCTs, n = 851, RR:0.50 (95% CI: 0.26, 0.93), P = 0.03] in the LGG group. There was no significant difference in the risk of LOS [7 RCTs, n = 1037, RR:1.08 (95% CI 0.84, 1.39), P = 0.55], mortality [3 RCTs, n = 207, RR: 0.99 (95% CI: 0.42, 2.33), P = 0.99], time to reach full feeds [2 RCTs, n = 19, SMD = 0.11 days (95% CI: -0.22, 0.45), P = 0.51] and duration of hospital stay [3 RCTs, n = 293, SMD: -0.14 days (95% CI: -0.37 to 0.09), P = 0.23]. Meta-analysis of data from non-RCTs showed no significant effect of LGG on NEC, LOS, and mortality. RCTs showed beneficial effects of LGG when used as the sole probiotic in reducing the risk of NEC, whereas observational studies did not. Strain-specific systematic review of LGG provides important data for guiding research and clinical practice.

Low dose paracetamol for management of patent ductus arteriosus in very preterm infants: a randomised non-inferiority trial.

OBJECTIVE: To compare the efficacy of low dose-short course intravenous paracetamol with a conventional dose regimen for early targeted closure of patent ductus arteriosus (PDA). DESIGN: Single-centre, double-blinded, active controlled, randomised non-inferiority trial. SETTING: Level III neonatal intensive care unit in Western India. PATIENTS: Preterm infants <30 weeks of gestation requiring mechanical ventilation, or continuous positive airway pressure with FiO2 ≥0.35 and diagnosed with a haemodynamically significant PDA (hsPDA) at 18-24 hours of postnatal age. INTERVENTIONS: Low dose (10 mg/kg/dose 6 hourly for 72 hours) versus conventional dose (15 mg/kg/dose 6 hourly for 120 hours) intravenous paracetamol treatment. MAIN OUTCOME MEASURES: Comparison of the rates of ductal closure at completion of sixth postnatal day, using a prespecified non-inferiority margin of 20%. RESULTS: A total of 102 infants were enrolled. The median gestational age and birth weight of the included infants were 26.4 weeks and 830 g. At completion of the sixth postnatal day, closure of PDA was achieved in 92% of infants in the low dose group as compared with 94% of those in the standard dose group (risk difference: -1.6%, 95% CI: -11.6% to 8.5%, p=0.38). The rates of rescue therapies, adverse effects and other neonatal morbidities were comparable in both groups. CONCLUSION: In very preterm infants on significant respiratory support, low dose-short course intravenous paracetamol treatment was non-inferior to a conventional dosing regime of paracetamol for closure of hsPDA in the first week of postnatal age. Larger studies with narrow margins of non-inferiority are required to confirm our findings. TRIAL REGISTRATION NUMBER: CTRI/2017/10/010012.

COVID-19 Disease in Under-5 Children: Current Status and Strategies for Prevention including Vaccination.

Since the coronavirus disease (COVID-19) pandemic hit the globe in early 2020, we have steadily gained insight into its pathogenesis; thereby improving surveillance and preventive measures. In contrast to other respiratory viruses, neonates and young children infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have a milder clinical presentation, with only a small proportion needing hospitalization and intensive care support. With the emergence of novel variants and improved testing services, there has been a higher incidence of COVID-19 disease reported among children and neonates. Despite this, the proportion of young children with severe disease has not increased. Key mechanisms that protect young children from severe COVID-19 disease include the placental barrier, differential expression of angiotensin-converting enzyme 2 (ACE-2) receptors, immature immune response, and passive transfer of antibodies via placenta and human milk. Implementing mass vaccination programs has been a major milestone in reducing the global disease burden. However, considering the lower risk of severe COVID-19 illness in young children and the limited evidence about long-term vaccine safety, the risk-benefit balance in children under five years of age is more complex. In this review, we do not support or undermine vaccination of young children but outline current evidence and guidelines, and highlight controversies, knowledge gaps, and ethical issues related to COVID-19 vaccination in young children. Regulatory bodies should consider the individual and community benefits of vaccinating younger children in their local epidemiological setting while planning regional immunization policies.

Umbilical cord milking versus delayed cord clamping in term and late-preterm infants: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to compare the efficacy and safety of umbilical cord milking (UCM) versus delayed cord clamping (DCC) in term and late-preterm infants. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Clinical trial registries, and Gray literature were searched for randomized controlled trials (RCTs) comparing UCM with DCC in term and late-preterm infants for both short-term and long-term outcomes. Intact and cut UCM were compared separately with DCC using subgroup analysis. We used fixed effect model to pool the data. Random effects model was used when there was significant heterogeneity. RESULTS: Nine studies (1632 infants) were included in the systematic review. Milking was performed on intact cord (i-UCM) in five studies (n = 829) and on cut cord (c-UCM) in four studies (n = 803). Cord milking significantly improved hemoglobin level at 48-72 h of life when compared to DCC (six studies, n = 924, mean difference 0.36 g/dL; 95% CI: 0.19-0.53). In addition, hemoglobin level at six to eight weeks of age was also significantly higher in the studies comparing i-UCM with DCC (two studies, n = 550: mean difference 0.16 g/dL; 95% CI: 0.06-0.27). There was no difference between the UCM group and DCC group for any other outcome. Only one study provided information on growth and hematological parameters at one year of age. Neurodevelopmental outcomes were not reported. None of the studies included non-vigorous infants. The grade of evidence was low to very low for all the outcomes studied. CONCLUSION: UCM is comparable to DCC in improving short-term hematological outcomes in term and late-preterm vigorous infants. Trials assessing the effect of UCM on important clinical and long-term outcomes among non-vigorous mature preterm infants are urgently required.