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).

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.

Predictors of length of hospital stay among preterm infants admitted to neonatal intensive care unit: Data from a multicentre collaborative network from India (INNC: Indian National Neonatal Collaborative).

AIM: Prediction of length of stay (LOS) among preterm neonates is important for counselling of parents and for assessing neonatal intensive care unit (NICU) census and economic burden. The aim of this study is to evaluate perinatal and postnatal factors that influence LOS in preterm infants (25-33 weeks of gestation) admitted to participating NICUs of Indian National Neonatal Collaborative (INNC). METHODS: From the INNC database, the data which were prospectively entered using uniformed pre-defined criteria were analysed. RESULTS: A total of 3095 infants were included from 12 centres. Every week decrease in gestation increased LOS by 9 days. The median LOS for infants with gestational age of 25, 26, 27, 28, 29, 30, 31, 32 and 33 weeks were 86, 70, 62, 52, 40, 30, 23, 16 and 10 days, respectively. On multivariate analysis, abnormal antenatal umbilical artery doppler, severe small for gestational age (SGA), requirement of resuscitation, respiratory distress syndrome (RDS), seizures, sepsis, necrotising enterocolitis (NEC), major malformations and bronchopulmonary dysplasia (BPD) increased LOS by 5.4 (3.5-7.4), 21.6 (19-23.9), 4.7 (3.3-6.1), 3 (1.7-4.3), 15.2 (8.5-22.1), 11.2 (9.1-13.2), 9.8 (5.2-14.4), 8.8 (4.4-13.3) and 5.6 (0.5-10.7) days, respectively. CONCLUSIONS: Apart from lower gestation and birth weight, abnormal antenatal umbilical artery doppler, severe SGA, resuscitation need, major malformations, RDS, seizures, sepsis, NEC and BPD influenced LOS in preterm infants. In comparison with other networks or data from developed countries, LOS in our network was comparatively less for similar gestational age infants.

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).

Red Cell Distribution Width (RDW): Normative Data in Indian Neonates.

Red cell distribution width (RDW) is altered because of prematurity and fetal growth restriction (FGR). We conducted a prospective observational study to determine normal RDW values in Indian neonates (N=964) with significant FGR. Mean RDW values in preterm neonates were higher than term neonates (P<0.0004). The RDW values in Indian neonates (with significant FGR) were higher than their western counterparts (P<0.0001). The mean RDW values for different gestational ages in Indian neonates are higher than those observed in other studies. This could be attributable to the FGR component among Indian neonates.

Effect of Expressed Breast Milk versus Swaddling versus Oral Sucrose Administration on Pain Associated with Suctioning in Preterm Neonates on Assisted Ventilation: A Randomized Controlled Trial.

OBJECTIVE: The objective of our study was to assess the pain associated with suctioning in preterm neonates on assisted ventilation and comparing the use of expressed breast milk (EBM), sucrose, and swaddling to alleviate pain. METHODS: Study design: A randomized controlled clinical trial. INCLUSION CRITERIA: Preterm neonates on assisted ventilation. EXCLUSION CRITERIA: Major congenital anomalies and severe encephalopathy. STUDY DURATION AND SITE: 6 months in level III neonatal Intensive Care Unit. In the first phase, we used premature infant pain profile (PIPP) score to assess pain associated with suctioning in preterm neonates on assisted ventilation. In the second phase, the effect of EBM, swaddling, and sucrose on pain relief during suctioning in neonates on assisted ventilation was assessed. RESULTS: There was a significant increase in pain associated with suctioning in preterm neonates on assisted ventilation (preprocedure PIPP score 7.90 ± 2.50; procedural PIPP score 13.63 ± 2.57; P < 0.05). The postintervention mean procedural PIPP score was not significantly different between the EBM, swaddling, and sucrose groups (P = 0.24). CONCLUSIONS: Suctioning is painful for preterm neonates on assisted ventilation. There was no difference between EBM, swaddling, and sucrose in relieving pain associated with suctioning.

Comparison of Neonatal Pain, Agitation, and Sedation Scale with Premature Infant Pain Profile for the Assessment of Acute Prolonged Pain in Neonates on Assisted Ventilation: A Prospective Observational Study.

AIM: This study aimed to compare Neonatal Pain, Agitation, and Sedation Scale (N-PASS) with Premature Infant Pain Profile (PIPP) for the assessment of acute prolonged pain in ventilated neonates. METHODS: This study was conducted in two phases. In phase 1 of the study, we assessed whether neonates on assisted ventilation experienced acute prolonged pain. In phase 2, the aim was to compare N-PASS with PIPP for the assessment of acute prolonged pain in neonates on assisted ventilation.. DESIGN: This is a prospective observational study. STUDY SETTING AND DURATION: This study was conducted at a tertiary care neonatal intensive care unit for 6 months. INCLUSION CRITERIA: Neonates on assisted ventilation for >48 h were selected for this study. EXCLUSION CRITERIA: Neonates with lethal congenital anomalies and severe encephalopathy were excluded from the study. N-PASS and PIPP tools were used to assess acute prolonged pain in ventilated neonates. Taking PIPP as gold standard and N-PASS as a new test, the correlation coefficient was calculated. The sensitivity, specificity, positive predictive value, and negative predictive value were also computed. The time taken to administer the tools was also computed. RESULTS: The average PIPP score for ventilated neonates was 8.33. The correlation coefficient of N-PASS when compared to PIPP was 0.62. The average time taken to apply the N-PASS scale was 4.42 min as compared to 8.20 min for PIPP scale. In term neonates, the sensitivity, specificity, positive predictive value, and negative predictive value of N-PASS were 75%, 100%, 100%, and 60%, respectively. The corresponding values in preterm neonates were lesser. CONCLUSIONS: The study proves that neonates on assisted ventilation experience acute prolonged pain. N-PASS is clinically reliable and valid to assess acute prolonged pain in ventilated term neonates. The N-PASS is quicker than PIPP in assessing acute prolonged pain in ventilated neonates. FUTURE DIRECTIONS: The modified N-PASS tool (including the gestational age) should be developed.

Effects of timing of cord clamping on neonatal hemoglobin and bilirubin levels in preterm and term infants-A prospective observational cohort study.

BACKGROUND: Delayed cord clamping (DCC) is a proven beneficial intervention, but the suggested timings of DCC vary from 30 to 300 seconds after birth or until cord pulsation stops. This study aimed to find the optimum timing of DCC to maximize the benefits such as an increase in hemoglobin, and hematocrit without increasing the risks of polycythemia and hyperbilirubinemia. METHODS: We conducted a single-center prospective observational cohort study. All singleton neonates with gestational age ≥ 28 weeks born at the center in the 17 months of the study period from November 2020 to March 2022 were enrolled. Participants were divided into four groups based on DCC time: group A: <60 sec, group B: 60-119 sec, group C: 120-180 sec, and group D: >180 sec. The primary outcome was the levels of hemoglobin, hematocrit, and bilirubin at 48 hours of life. RESULTS: Four hundred and eight neonates were enrolled. They were divided into four groups based on the timing of DCC (group A: n = 52, group B: n = 137, group C: n = 155, group D: n = 64). With an increase in the duration of DCC, there was an increase in the level of hemoglobin and hematocrit without an increase in the risk of polycythemia or neonatal hyperbilirubinemia. The benefits were best in group C (120-180 sec) and group D (>180 sec). CONCLUSIONS: DCC of ≥ 120 seconds appears to be optimal where hemoglobin and hematocrit are highest without an increase in the risk of neonatal hyperbilirubinemia. The risk of adverse effects like polycythemia or neonatal hyperbilirubinemia requiring phototherapy did not increase even after extending the time of cord clamping to >180 seconds.

Feasibility of exclusive enteral feeds from birth in VLBW infants >1200 g--an RCT.

AIM: To evaluate the feasibility of initiation of exclusive enteral feeds on first day of life in very low birthweight infants >1200 g. METHODS: Haemodynamically stable infants with birthweights 1200-1500 g irrespective of gestational age were randomized into two groups. STUDY GROUP: Enteral feeds 80 mL/kg/day started within 1 h of birth and increased by 20 mL/kg/day to 180 mL/kg/day. No intravenous fluids given. CONTROL GROUP: Intravenous fluids 50 mL/kg/day started along with enteral feeds 30 mL/kg/day within 1 h of birth and increased by 20 mL/kg/day to 180 mL/kg/day. The outcome measures were - primary: time to regain birthweight and secondary: duration of hospital stay, incidence of necrotizing enterocolitis and sepsis. RESULTS: Twenty three babies randomized in each group. Infants in study group regained birthweight earlier [mean 5.52 days, SD ± 2.94] compared to those in control group [mean 12.7 days, SD ± 2.25] (p < 0.0001). Duration of hospital stay was lower in study group [mean 15.04 days, SD ± 5.26] compared to those in control group [mean 28.04 days, SD ± 6.76] (p < 0.0001). No necrotizing enterocolitis detected. CONCLUSION: It is feasible to initiate exclusive enteral feeds from first day of life in stable infants with birthweight between 1200 and 1500 g without any parenteral fluid support. It leads to twice as faster regaining of birthweight and halves duration of hospital stay.

General Movement Assessment in Babies Born Preterm: Motor Optimality Score-Revised (MOS-R), Trajectory, and Neurodevelopmental Outcomes at 1 Year.

Objective: To assess the association between the General Movement Assessment (GMA) findings, including Motor Optimality Scores-Revised (MOS-R) at 16 weeks, and neuromotor outcome assessed by the Amiel-Tison Neurological Assessment at 9 months of corrected age and the Developmental Assessment Scales for Indian Infants (DASII) at 1 year of corrected age in preterm ≤32 weeks. Study design: Serial GMA videos of infants born preterm ≤32 weeks were recorded on day 7, 35 weeks of postmenstrual age, 40 weeks of postmenstrual age, and 16 weeks of corrected age. The association between GMA findings, including MOS-R scores and GM trajectory between 35 to 40 weeks and the Amiel-Tison Neurological Assessment and DASII scores, was assessed by Spearman correlation, Fisher exact tests, and ordinal regression. Results: Moderate correlations were observed between MOS-R and the DASII motor DQ (Spearman r = 0.70, P < .001) and between MOS-R and DASII Mental DQ (r = 0.65, P < .001). The GMA trajectory at 35-40 weeks was associated with DASII motor DQ (Fisher exact, P = .002), and also with the Amiel-Tison Neurological Assessment at 9 months of corrected age (P < .01 by the Fisher exact test). On analysis by performing ordinal regression of predictive values of the general movements (GM) at 7 days of age, GM at 35 weeks, GM at 40 weeks, GM at 16 weeks, and MOS-R at 16 weeks, MOS-R alone was a statistically significant predictor of motor DQ at 1 year of age (OR -0.59; 95% CI -0.97 to -0.22; Wald statistics, P < .02). Conclusions: Consistent with findings in high-income countries, GMA including MOS-R scores performed in Indian infants born preterm during the neonatal period and early infancy is associated with neurodevelopmental outcomes in the first year of life. GMA can help initiate focused early intervention in low- and middle-income settings, where resources may be limited.

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.

Short-term Outcome and Predictors of Survival Among Neonates with Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative.

BACKGROUND: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. OBJECTIVE: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. SETTING: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. OUTCOME: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. RESULTS: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. CONCLUSION: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds of survival.

Predictors and ocular outcomes of rescue treatment in preterm infants with treated retinopathy of prematurity-a retrospective study.

AIM: To determine predictors of rescue treatment among infants treated for retinopathy of prematurity and to evaluate their ocular outcomes at 18-24 months of corrected age. METHODS: This is a single centre retrospective study of infants who received treatment for type 1 ROP, using laser photocoagulation or anti VEGF agents. Multivariable logistic regression was used to generate a prediction model for rescue treatment of ROP. The primary outcome was an abnormal refractive outcome by 24 months of corrected age, among infants primarily treated with laser therapy. RESULTS: Two hundred and eight infants (including 416 eyes) who received single (n = 151) or rescue (multiple) treatments (n = 57) were included. Ninety three percent of the infants were primarily treated with laser photocoagulation. Lower gestational age, small for gestational age, early packed red blood cell transfusion (within 2 weeks of postnatal age), and presence of Zone 1 retinopathy predicted the need for rescue treatment in treated infants [area under the receiver operating characteristic curve: 0.81 (0.73-0.89)]. The incidence of abnormal refractive outcome, assessed in a total of 174 infants, was found to be significantly higher in the rescue treatment group (67% versus 21%, adjusted odds ratio: 7.56 (3.3-17.2), P < 0.001). Myopia, very high myopia and use of spectacles was significantly higher in the rescue treatment group (P < 0.001 for each). CONCLUSIONS: Rescue treatment for ROP was associated with an increased incidence of refractive errors and requirement of spectacles by 2 years of age. Larger prospective multicentre studies are required to confirm the findings from our study.