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).

Providing Positive End-Expiratory Pressure during Neonatal Resuscitation: A Meta-analysis.

Our objective was to conduct a systematic review and meta-analysis evaluating the effects of administering positive end-expiratory pressure (PEEP) during neonatal resuscitation at birth. Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Clinicaltrials.gov databases were systematically searched from inception to 15 December 2020. Randomized controlled trials and cohort studies were held eligible. Studies were included if they compared the administration of PEEP using either a T-piece resuscitator or a self-inflating bag with a PEEP valve versus resuscitation via a self-inflating bag without a PEEP valve. Data were extracted by two reviewers independently. The credibility of evidence was appraised with the Grading of Recommendations, Assessment, Development, and Evaluations approach. Random-effects models were fitted to provide pooled estimates of risk ratio (RR) and 95% confidence intervals (CIs). Overall, 10 studies were included, comprising 4,268 neonates. This included five randomized controlled trials, one quasi-randomized trial, and four cohort studies. The administration of PEEP was associated with significantly lower rates of mortality till discharge (odds ratio [OR]: 0.60, 95% CI: 0.49-0.74, moderate quality of evidence). The association was significant in preterm (OR: 0.57, 95% CI: 0.46-0.69) but not in term (OR: 1.03, 95% CI: 0.52-2.02) neonates. Low-to-moderate quality evidence suggests that providing PEEP during neonatal resuscitation is associated with lower rates of mortality in preterm neonates. Evidence regarding term neonates is limited and inconclusive. Future research is needed to determine the optimal device and shed more light on the long-term effects of PEEP administration during neonatal resuscitation. This study is registered with PROSPERO with registration number: CRD42020219956. KEY POINTS: · PEEP administration during neonatal resuscitation in the delivery room reduces mortality in preterm.. · Evidence regarding term neonates is limited and inconclusive.. · Future research is needed to determine the optimal device..

Human Milk Calorie Guide: A Novel Color-Based Tool to Estimate the Calorie Content of Human Milk for Preterm Infants.

Fixed-dose fortification of human milk (HM) is insufficient to meet the nutrient requirements of preterm infants. Commercial human milk analyzers (HMA) to individually fortify HM are unavailable in most centers. We describe the development and validation of a bedside color-based tool called the 'human milk calorie guide'(HMCG) for differentiating low-calorie HM using commercial HMA as the gold standard. Mothers of preterm babies (birth weight ≤ 1500 g or gestation ≤ 34 weeks) were enrolled. The final color tool had nine color shades arranged as three rows of three shades each (rows A, B, and C). We hypothesized that calorie values for HM samples would increase with increasing 'yellowness' predictably from row A to C. One hundred thirty-one mother's own milk (MOM) and 136 donor human milk (DHM) samples (total n = 267) were color matched and analyzed for macronutrients. The HMCG tool performed best in DHM samples for predicting lower calories (<55 kcal/dL) (AUC 0.87 for category A DHM) with modest accuracy for >70 kcal/dL (AUC 0.77 for category C DHM). For MOM, its diagnostic performance was poor. The tool showed good inter-rater reliability (Krippendorff's alpha = 0.80). The HMCG was reliable in predicting lower calorie ranges for DHM and has the potential for improving donor HM fortification practices.

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.

Urinary beta-2 microglobulin as an early predictive biomarker of acute kidney injury in neonates with perinatal asphyxia.

To evaluate the role of urinary beta-2 microglobulin (B2mG) as an early predictive biomarker of acute kidney injury (AKI) in neonates with perinatal asphyxia. In this prospective cohort study, 80 term infants with perinatal asphyxia were included. The neonates were divided into AKI and no-AKI groups. Urinary B2mG levels were measured at 24 h of life. The diagnostic efficacy of the biomarker was determined using receiver operating characteristic (ROC) curves. Compared to infants without AKI, infants with AKI had higher levels of urinary B2mG (mean 6.8 versus 2.6 mg/L, p < 0.001). Area under the receiver operating characteristic curve (ROC curve) was 0.944. The balanced sensitivity/specificity trade-off was found at a cut-off value of 3.8 mg/L (81% sensitive and 81.6% specific).Conclusion Urinary B2mG can be useful to predict AKI early in term neonates with perinatal asphyxia. What is Known: • AKI is seen in 20-40% of neonates with asphyxia. • AKI affects the treatment plan and the prognosis of such neonates. What is New: • Urinary biomarkers are the easiest way to diagnose AKI in asphyxiated neonates. • Beta 2 microglobulin is the cheapest and readily available one such urinary biomarker with good sensitivity and specificity.

Effect of Early Parent Participation Program on Physiological Stability in Preterm Infants: A Randomized Controlled Trial.

OBJECTIVE: This research aimed to study the impact of early parent participation program (EPPP) for preterm infants in neonatal intensive care unit (NICU) on physiological instability, breastmilk feeding rates, and discharge timing. STUDY DESIGN: Families of 147 infants born between 28 and 33 weeks' gestation were randomized at birth to EPPP group or conventional care (CC). Families in the EPPP group were trained soon after admission by using a structured education program and encouraged to spend more time with their baby. Soon after enrolment (day of life 1 to 2), they would sequentially participate in daily NICU care processes such as orogastric tube feeding, nesting, oil massages, diaper changes, and daily weight checks. Families in the CC group would undergo the same after their infant was off parenteral nutrition and respiratory support. Proportion of infants having physiological instability (significant apnea, feeding intolerance, or needing investigation for sepsis) in two groups was compared. RESULTS: There was a significant reduction in the proportion of infants with physiological instability (feeding intolerance) in the EPPP group (relative risk = 0.70 [0.52-0.94], p = 0.016). Infants in EPPP group had a trend toward higher breastmilk feeding rates at discharge (66 vs. 51%, p = 0.076). CONCLUSION: Very early parent participation was feasible in the NICU and led to decrease in physiological instability in preterm infants. KEY POINTS: · Family-integrated care is beneficial; however, it is often started later in the NICU course.. · This trial showed that very early involvement of family in NICU care processes is feasible and safe.. · Structured parent participation started very early improves physiological stability in preterm infants (mainly tolerance to feeds)..

Corrected fortification approach improves the protein and energy content of preterm human milk compared with standard fixed-dose fortification.

OBJECTIVE: To evaluate whether a pragmatic corrected fortification (CF) model achieves recommended target protein and calorie content of human milk (HM) for preterm infants when compared with standard fixed-dose fortification (SF). DESIGN: In this prospective non-interventional study, we enrolled mothers of infants with birth weight ≤1500 g fed exclusive HM. Infants with chromosomal or intestinal disorders were excluded. A total of 405 HM samples from 29 mothers and 45 donor milk samples were analysed for macronutrient content using a real-time HM analyser. A stepwise CF model was derived based on published data on HM calorie and protein content corrected for lactation stage and milk type. We applied both models to the measured protein and calorie content for all HM samples and compared the proportion of samples achieving target nutrient requirement in each group. RESULTS: Target protein and calorie content of feed was achieved in 68% of HM samples with CF, compared with 5% samples with SF model (p<0.0001). For mother's own milk, none of the samples met the target macronutrient range with SF fortification during later lactation periods (≥week 5). With SF, over 40% of infants had poor growth (decline in weight z-score ≥0.8 SD) by 8 weeks. The final feed osmolality was acceptable for all fortification steps of the CF model. CONCLUSION: The proposed CF model significantly improved the final protein and calorie content of HM with acceptable osmolality. It provides a proactive option to improve nutrient intake in premature infants.

Perinatal COVID-19: review of current evidence and practical approach towards prevention and management.

The clinical spectrum of the perinatal COVID-19 and prospective data on neonatal outcomes remains largely unexplored. Most of the existing literature is in the form of case series or single-centre experience. In this review, we aim to summarize available literature on the clinical spectrum of COVID-19 in neonates and mothers and suggest a practical approach towards management of clinical scenarios. This review explores the clinical characteristics and outcomes of COVID-19 in neonates born to mothers who were detected with the virus during the pregnancy. We conducted a comprehensive search of PubMed, Google Scholar and Cochrane Database of Systematic Review between November 2019 and June 2020 and screened articles related to perinatal COVID-19. This review included 786 mothers, among which 64% (504) were delivered by caesarian section. There were 3 still births and 107 (14%) were delivered preterm. Out of 793 neonates born, 629 neonates (79%) were tested after birth. The commonest symptom in neonates was respiratory distress. Respiratory support was needed in 60 neonates (7.6%), with 14 babies needing mechanical ventilation (1.8%), 25 needing non-invasive ventilation and 21 needing nasal oxygen. Only 35 of the 629 tested neonates (5.5%) were positive for COVID-19. Of the 35 positive neonates, 14 (40%) were symptomatic. The COVID-19 seems to have favourable neonatal outcomes. Majority of neonates are asymptomatic. Respiratory distress is the most common manifestation. What is known: •COVID-19 affects all ages. •Neonatal disease is usually mild. What is new: •Vertical transmission is a possible route of infection in neonates. •Breast milk and skin-to-skin contact are safe in COVID-19-infected mothers if performed with appropriate use of precautions such as hand and breast hygiene and masking.

Does probiotic bacteremia in premature infants impact clinically relevant outcomes? A case report and updated review of literature.

Prophylactic use of probiotics decreases the incidence of necrotizing enterocolitis (NEC) in premature infants. However, there are ongoing concerns related to the routine use of probiotics including inconsistent literature regarding optimal dose and strain, lack of regulatory standards in production and reports regarding potential side effects. There is limited data regarding the incidence of probiotic bacteremia and its impact on relevant clinical outcomes in the premature population. We report the first case of Bifidobacterium longum bacteremia in our center since the routine introduction of probiotics. The neonate had NEC with perforation on day of life 7, which likely led to translocation of the probiotic strain to the blood stream. The neonate did not have any hemodynamic instability and the repeat blood culture was negative after starting antibiotic therapy. We also conducted a literature review and found 13 other cases of probiotic bacteremia in premature or very low birth weight neonates. Although the incidence of probiotic bacteremia is low, it can impact several clinical outcomes including prolonged exposure to antibiotics, removal of central lines and additional laboratory testing such as lumbar puncture. There has been no mortality attributable to probiotic bacteremia and there is no data regarding long term neurodevelopmental outcomes.

Pathogenesis and Management of Indirect Hyperbilirubinemia in Preterm Neonates Less Than 35 Weeks: Moving Toward a Standardized Approach.

Premature infants have a higher incidence of indirect hyperbilirubinemia than term infants. Management of neonatal indirect hyperbilirubinemia in late preterm and term neonates has been well addressed by recognized, consensus-based guidelines. However, the extension of these guidelines to the preterm population has been an area of uncertainty because of limited evidence. This leads to variation in clinical practice and lack of recognition of the spectrum of bilirubin-induced neurologic dysfunction (BIND) in this population. Preterm infants are metabolically immature and at higher risk for BIND at lower bilirubin levels than their term counterparts. Early use of phototherapy to eliminate BIND and minimize the need for exchange transfusion is the goal of treatment in premature neonates. Although considered relatively safe, phototherapy does have side effects, and some NICUs tend to overuse phototherapy. In this review, we describe the epidemiology and pathophysiology of BIND in preterm neonates, and discuss our approach to standardized management of indirect hyperbilirubinemia in the vulnerable preterm population. The proposed treatment charts suggest early use of phototherapy in preterm neonates with the aim of reducing exposure to high irradiance levels, minimizing the need for exchange transfusions, and preventing BIND. The charts are pragmatic and have additional curves for stopping phototherapy and escalating its intensity. Having a standardized approach would support future research and quality improvement initiatives that examine dose and duration of phototherapy exposure with relation to outcomes.

Infant of diabetic mother: what one needs to know?

The global incidence of diabetes mellitus, including diabetes in pregnant women, is on the rise. Diabetes mellitus in a pregnant woman jeopardizes not only maternal health but can also have significant implications on the child to be born. Therefore, timely diagnosis and strict glycemic control are of utmost importance in achieving a safe outcome for both the mother and fetus. The treating physician should be aware of the complications that can arise due to poor glycemic control during pregnancy. The objective of this article is to discuss the key concerns in a neonate born to diabetic mother, the underlying pathogenesis, and the screening schedule during pregnancy.

Leucocyte adhesion defect presenting as fulminant sepsis in a new born.

We present a term neonate with severe sepsis, presenting on day 10 of life. The neonate presented with bilateral purulent eye discharge and hepatosplenomegaly. On investigation, persistent leucocytosis was observed and thus the possibility of leucocyte adhesion defect was considered. Flow cytometry confirmed the diagnosis.

High-dose parenteral amino acid intake in very low birthweight infants: what is the current evidence?

PURPOSE OF REVIEW: There is uncertainty regarding optimal dosing for parenteral amino acids in preterm infants and wide variability exists in clinical practice. There is new data from clinical trials trying to address these concerns. We review the recent evidence on parenteral high-dose amino acid intake in very low birth weight (VLBW) neonates with a focus on relevant clinical outcomes. RECENT FINDINGS: Preterm infants often receive less protein than intended in the first week of life. Parenteral amino acid administration in doses that exceed requirements, however, leads to increased oxidation and higher blood urea concentrations. Amino acid doses greater than 3.5 g/kg/day have not shown to improve mortality, neonatal morbidities including sepsis, necrotizing enterocolitis, chronic lung disease, growth parameters or neurodevelopmental outcomes at 2 years of age. SUMMARY: Parenteral amino acid administration in VLBW infants should be initiated soon after birth at a dose of at least 1.5 g/kg/day to maintain anabolism. The maximum dose for parenteral amino acid should be between 2.5 and 3.5 g/kg/day, with adequate nonprotein calories and micronutrients to ensure efficient protein utilization and growth.

Is kangaroo mother care effective in alleviating vaccination associated pain in early infantile period? A RCT.

BACKGROUND: Childhood vaccination is a common procedure and a part of routine medical care during infancy. Although vaccination is the cornerstone for prevention of many infectious diseases, it is associated with significant pain, which is often ignored. Non pharmacological interventions such as breast feeding and kangaroo mother care (KMC) have been used to decrease this procedural pain. However there is paucity of published data on effective use of KMC in term neonates and infants beyond the neonatal age. METHOD: This randomized controlled trial included 61 infants ≤14 weeks of postnatal age, and compared KMC to swaddling during vaccination. Neonatal infant pain scale (NIPS) was used to assess the pain associated with vaccination. RESULTS: NIPS scores at 1 min and 5 min after vaccination and duration of cry were significantly less in the KMC group. CONCLUSION: KMC is effective in reducing vaccination associated pain in young infants.

Evaluation of A Concentrated Preterm Formula as a Liquid Human Milk Fortifier in Preterm Babies at Increased Risk of Feed Intolerance.

There are concerns around safety and tolerance of powder human milk fortifiers to optimize nutrition in preterm infants. The purpose of this study was to evaluate the tolerance and safety of a concentrated preterm formula (CPF) as a liquid human milk fortifier (HMF) for premature infants at increased risk of feeding intolerance. We prospectively enrolled preterm infants over an 18-month period, for whom a clinical decision had been made to add CPF to human milk due to concerns regarding tolerance of powder HMF. Data on feed tolerance, anthropometry, and serum biochemistry values were recorded. Serious adverse events, such as mortality, necrotizing enterocolitis (NEC), and sepsis, were monitored. A total of 29 babies received CPF fortified milk during the study period. The most common indication for starting CPF was previous intolerance to powder HMF. Feeding intolerance was noted in 4 infants on CPF. The growth velocity of infants was satisfactory (15.9 g/kg/day) after addition of CPF to feeds. The use of CPF as a fortifier in preterm babies considered at increased risk for feed intolerance seems well tolerated and facilitates adequate growth. Under close nutrition monitoring, this provides an additional option for human milk fortification in this challenging subgroup of preterm babies, especially in settings with limited human milk fortifier options.

Hypertension in the Neonatal Period: An Update.

There has been a growing interest among neonatologists and paediatricians regarding identification and evaluation of hypertension in the neonatal period. Despite the emergent normative data on blood pressure values in term and preterm neonates over the last two decades, there is still controversy regarding correct definition and classification of hypertension. This article will discuss the current definitions, available normative data and etiology of neonatal hypertension. There is paucity of records in terms of efficacy of antihypertensive drugs in this specific population and management is usually experience based, causing considerable heterogeneity amongst different units. This review article will also cover the evaluation, management, outcomes and follow up of neonatal hypertension with latest advances in this field.