Search

The baby boy was born to a 27-year-old primigravida mother at 33 weeks’ gestation with a birth weight of 1800 g. Parents were non-consanguineous. The mother conceived spontaneously and did not undergo any antenatal sonography. The baby was delivered vaginally. He cried immediately after birth, and

Despite decades of research, there is inadequate evidence on the etiological factors of brain injury in preterm infants.To study the perinatal risk factors for preterm brain injury and to assess their strength of association.In this retrospective cohort study, we included infants born at32 weeks' gestation and had either magnetic resonance imaging (MRI) or cranial ultrasound (CUS) performed at term equivalent age. Significant brain injury was diagnosed based on Kidokoro global brain injury score was ≥4 in MRI or cystic periventricular leukomalacia in CUS.Among the 698 infants, 48 had significant brain injury and 650 were taken as controls. In multiple logistic regression, intraventricular hemorrhage (IVH) grade 3-4 [adjusted odds ratio, 92.892 (19.495-442.619)], culture-positive sepsis [4.162 (1.729-10.021)], prolonged ventilation [3.688 (1.087-12.510)], and small for gestational age (SGA) [2.645 (1.181-5.924] were associated with greater risk of preterm brain injury.Severe IVH, culture-positive sepsis, prolonged ventilation and SGA were significant risk factors for preterm brain injury with severe IVH being the most significant contributing factor.

OBJECTIVE To assess the effect of different frequencies of ventilator circuit changes in neonates and children through a systematic review and meta-analysis. INTERVENTIONS (1) "No routine change of ventilator circuit (unless visibly soiled)" versus "routine change at any fixed interval"; (2) routine change of circuit at "less frequent" versus "more frequent" intervals. OUTCOMES Primary outcomes were VAP rate (number of VAP episodes per 1000 ventilator-days) and all-cause mortality before discharge. METHODS MEDLINE, CENTRAL, EMBASE, and CINAHL were systematically searched from inception till November 3, 2020. Two authors assessed trial eligibility and risk of bias, and independently extracted data. Data were synthesized using fixed effects model. GRADE was used to assess certainty of evidence (CoE). RESULTS We identified six studies enrolling 768 participants evaluating circuit changes at two fixed intervals. Meta-analysis of studies on circuit changes "once in less than 7 days" versus "once weekly" showed no difference in VAP rate (risk ratio: 0.83 [0.38-1.81]; one randomized controlled trial (RCT) and 0.94 [0.49-1.81]; two before-after studies) or mortality before discharge (0.67 [0.34-1.3]; one RCT and 1.01 [0.63-1.64]; two before-after studies). CoE was very low. Less frequent circuit changes reduced health-care costs. No study evaluating "circuit changes only when visibly soiled" versus "circuit changes at a fixed interval" was identified. CONCLUSION There is no evidence to suggest that ventilator circuits can be safely left unchanged until visibly soiled in neonates and children. Extending circuit changes interval to "once weekly" may not increase VAP rate (CoE-very low) and reduces healthcare costs.

OBJECTIVE: To evaluate the diagnostic accuracy and utility of bedside ultrasound (US) by neonatology residents to confirm position of umbilical venous catheter (UVC), umbilical arterial catheter (UAC), and peripherally inserted central catheter (PICC). METHODS: In this prospective study, we included neonates who required UVC, UAC or PICC insertion. Two neonatology residents performed all bedside US examinations after a short period of training. Plain radiograph was taken as gold standard. Time taken for confirmation of catheter position by US and radiograph was recorded. RESULTS: We recruited 71 neonates for UVC and UAC, and 40 neonates for PICC. Sensitivity and specificity of US in identifying a malpositioned catheter was good for UVC (94% and 66.7% respectively) and UAC (86.7% and 94.5%). Agreement between radiograph and US was good for UVC [0.718 (0.512, 0.861); p

OBJECTIVE To assess the utility of autologous umbilical cord blood (UCB) for red cell concentrate (RCC) transfusion in preterm infants. METHODS We recruited preterm infants born at ≤30 weeks' gestation or have an estimated fetal weight

BACKGROUND AND OBJECTIVES Hypoglycemia occurs in 5% to 15% of neonates in the first few days. A significant proportion requires admission for intravenous fluids. Dextrose gel may reduce admissions and mother-infant separation. We aimed to study the utility of dextrose gel in reducing the need for intravenous fluids. METHODS This stratified randomized control trial included at-risk infants with asymptomatic hypoglycemia. Study populations were stratified into 3 categories: small for gestational age (SGA) and intrauterine growth-restriction (IUGR), infants of diabetic mothers (IDM) and large for gestational age (LGA), and late preterm (LPT) neonates. Intervention group received dextrose gel followed by breastfeeding, and the control group (CG) received only breastfeeding. RESULTS Among 629 at-risk infants, 291 (46%) developed asymptomatic hypoglycemia; 147 (50.4%) in the dextrose gel group (DGG) and 144 (49.6%) in CG. There were 97, 98, and 96 infants in SGA/IUGR, IDM/LGA, and LPT categories, respectively. Treatment failure in the DGG was 17 (11.5%) compared to 58 (40.2%) in CG, with a risk ratio of 0.28 (95% confidence interval [CI]: 0.17–0.46; P < .001). Treatment failure was significantly less in DGG in all 3 categories: SGA/IUGR, IDM/LGA, and LPT with a risk ratio of 0.29 (95% CI:0.13-0.67), 0.31 (95% CI:0.14–0.66) and 0.24 (95% CI:0.09–0.66), respectively. CONCLUSIONS Dextrose gel reduces the need for intravenous fluids in at-risk neonates with asymptomatic hypoglycemia in the first 48 hours of life.

Bronchopulmonary dysplasia (BPD) has multifactorial etiology and long-term adverse consequences. An umbrella review enables the evaluation of multiple proposed interventions for the prevention of BPD.To summarize and assess the certainty of evidence of interventions proposed to decrease the risk of BPD from published systematic reviews.MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and Web of Science were searched from inception until November 9, 2020.Meta-analyses of randomized clinical trials comparing interventions in preterm neonates that included BPD as an outcome.Data extraction was performed in duplicate. Quality of systematic reviews was evaluated using Assessment of Multiple Systematic Reviews version 2, and certainty of evidence was assessed using Grading of Recommendation, Assessment, Development, and Evaluation.(1) BPD or mortality at 36 weeks' postmenstrual age (PMA) and (2) BPD at 36 weeks' PMA.A total of 154 systematic reviews evaluating 251 comparisons were included, of which 110 (71.4%) were high-quality systematic reviews. High certainty of evidence from high-quality systematic reviews indicated that delivery room continuous positive airway pressure compared with intubation with or without routine surfactant (relative risk [RR], 0.80 [95% CI, 0.68-0.94]), early selective surfactant compared with delayed selective surfactant (RR, 0.83 [95% CI, 0.75-0.91]), early inhaled corticosteroids (RR, 0.86 [95% CI, 0.75-0.99]), early systemic hydrocortisone (RR, 0.90 [95% CI, 0.82-0.99]), avoiding endotracheal tube placement with delivery room continuous positive airway pressure and use of less invasive surfactant administration (RR, 0.90 [95% CI, 0.82-0.99]), and volume-targeted compared with pressure-limited ventilation (RR, 0.73 [95% CI, 0.59-0.89]) were associated with decreased risk of BPD or mortality at 36 weeks' PMA. Moderate to high certainty of evidence showed that inhaled nitric oxide, lower saturation targets (85%-89%), and vitamin A supplementation are associated with decreased risk of BPD at 36 weeks' PMA but not the competing outcome of BPD or mortality, indicating they may be associated with increased mortality.A multipronged approach of delivery room continuous positive airway pressure, early selective surfactant administration with less invasive surfactant administration, early hydrocortisone prophylaxis in high-risk neonates, inhaled corticosteroids, and volume-targeted ventilation for preterm neonates requiring invasive ventilation may decrease the combined risk of BPD or mortality at 36 weeks' PMA.

Periventricular leukomalacia (PVL) is a result of various antenatal, intrapartum, or postnatal insults to the developing brain and is an important harbinger of cerebral palsy in preterm neonates. There is no proven therapy for PVL. This calls for appraisal of targeted therapies that have been investigated in animal models to evaluate their relevance in a clinical research context. This systematic review identifies interventions that were evaluated in preclinical studies for neuroprotective efficacy against PVL. We identified 142 studies evaluating various interventions in PVL animal models (search method is detailed in section 2). Interventions that have yielded significant results in preclinical research, and that have been evaluated in a limited number of clinical trials include stem cells, erythropoietin, and melatonin. Many other therapeutic modalities evaluated in preclinical studies have been identified, but more data on their neuroprotective potential in PVL must be garnered before they can be considered for clinical trials. Because most of the tested interventions had only a partial efficacy, a combination of interventions that could be synergistic should be investigated in future preclinical studies. Furthermore, since the nature and pattern of perinatal insults to preterm brain predisposing it to PVL are substantially variable, individualized approaches for the choice of appropriate neuroprotective interventions tailored to different subgroups of preterm neonates should be explored.

Importance Prevention of hypothermia in the delivery room is a cost-effective, high-impact intervention to reduce neonatal mortality, especially in preterm neonates. Several interventions for preventing hypothermia in the delivery room exist, of which the most beneficial is currently unknown. Objective To identify the delivery room thermal care intervention that can best reduce neonatal hypothermia and improve clinical outcomes for preterm neonates born at 36 weeks' gestation or less. Data sources MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and CINAHL databases were searched from inception to November 5, 2020. Study selection Randomized and quasi-randomized clinical trials of thermal care interventions in the delivery room for preterm neonates were included. Peer-reviewed abstracts and studies published in non-English language were also included. Data extraction and synthesis Data from the included trials were extracted in duplicate using a structured proforma. A network meta-analysis with bayesian random-effects model was used for data synthesis. Main outcomes and measures Primary outcomes were core body temperature and incidence of moderate to severe hypothermia on admission or within the first 2 hours of life. Secondary outcomes were incidence of hyperthermia, major brain injury, and mortality before discharge. The 9 thermal interventions evaluated were (1) plastic bag or plastic wrap covering the torso and limbs with the head uncovered or covered with a cloth cap; (2) plastic cap covering the head; (3) skin-to-skin contact; (4) thermal mattress; (5) plastic bag or plastic wrap with a plastic cap; (6) plastic bag or plastic wrap along with use of a thermal mattress; (7) plastic bag or plastic wrap along with heated humidified gas for resuscitation or for initiating respiratory support in the delivery room; (8) plastic bag or plastic wrap along with an incubator for transporting from the delivery room; and (9) routine care, including drying and covering the body with warm blankets, with or without a cloth cap. Results Of the 6154 titles and abstracts screened, 34 studies that enrolled 3688 neonates were analyzed. Compared with routine care alone, plastic bag or wrap with a thermal mattress (mean difference [MD], 0.98 °C; 95% credible interval [CrI], 0.60-1.36 °C), plastic cap (MD, 0.83 °C; 95% CrI, 0.28-1.38 °C), plastic bag or wrap with heated humidified respiratory gas (MD, 0.76 °C; 95% CrI, 0.38-1.15 °C), plastic bag or wrap with a plastic cap (MD, 0.62 °C; 95% CrI, 0.37-0.88 °C), thermal mattress (MD, 0.62 °C; 95% CrI, 0.33-0.93 °C), and plastic bag or wrap (MD, 0.56 °C; 95% CrI, 0.44-0.69 °C) were associated with greater core body temperature. Certainty of evidence was moderate for 5 interventions and low for plastic bag or wrap with a thermal mattress. When compared with routine care alone, a plastic bag or wrap with heated humidified respiratory gas was associated with less risk of major brain injury (risk ratio, 0.23; 95% CrI, 0.03-0.67; moderate certainty of evidence) and a plastic bag or wrap with a plastic cap was associated with decreased risk of mortality (risk ratio, 0.19; 95% CrI, 0.02-0.66; low certainty of evidence). Conclusions and relevance Results of this study indicate that most thermal care interventions in the delivery room for preterm neonates were associated with improved core body temperature (with moderate certainty of evidence). Specifically, use of a plastic bag or wrap with a plastic cap or with heated humidified gas was associated with lower risk of major brain injury and mortality (with low to moderate certainty of evidence).

Congenital disorders of glycosylation (CDG) are a rapidly expanding group of inborn errors of metabolism with around 100 types described so far. Because of the limited number of reported cases in each type except PMM2-CDG, the complete clinical picture of other types is not known. RFT1-CDG is a rare type, with ten cases reported in the literature. Our patient presented as a floppy neonate with severe respiratory insufficiency and ventilator dependence in the newborn period. He had fetal growth restriction, facial dysmorphism, high arched palate, bilateral cryptorchidism, hypoplastic pons and cerebellum and probable hearing impairment. He succumbed to the illness on day 24 of life. There was a similar history of two previous sibling deaths in the early neonatal period due to respiratory insufficiency and history of multiple neonatal and infant deaths in the extended family. Transferrin iso-electric focusing was normal. Clinical exome sequencing revealed a novel homozygous missense mutation (c.1018 G > A) in RFT1 gene [NM_052859; c.1018G > A; p.G340S; ENST00000296292] and the parents were heterozygous for the same (ClinVar SVC000778540). The pathogenic variants so far reported are all missense variants affecting the luminal loops; whereas the variant in our case is in the trans-membrane helical domain. A strong family history of neonatal deaths and similar presentations in the previous 2 siblings suggests the homogenous phenotype of this mutation. Severe respiratory insuffiency and ventilator dependence shows the lethality of the disease phenotype and incompatibility with survival beyond the neonatal period.

BackgroundThere are no evidence-based recommendations for surfactant use in late preterm (LPT) and term infants with respiratory distress syndrome (RDS).ObjectiveTo investigate the safety and efficacy of surfactant in LPT and term infants with RDS.MethodsSystematic review, meta-analysis and evidence grading.InterventionsSurfactant therapy versus standard of care.Main outcome measuresMortality and requirement for invasive mechanical ventilation (IMV).ResultsOf the 7970 titles and abstracts screened, 17 studies (16 observational studies and 1 randomised controlled trial (RCT)) were included. Of the LPT and term neonates with RDS, 46% (95% CI 40% to 51%) were treated with surfactant. We found moderate certainty of evidence (CoE) from observational studies evaluating infants supported with non-invasive respiratory support (NRS) or IMV that surfactant use may be associated with a decreased risk of mortality (OR 0.45, 95% CI 0.32 to 0.64). Very low CoE from observational trials in which surfactant was administered at FiO2 >0.30–0.40 to infants on Continuous Positive Airway Pressure (CPAP) indicated that surfactant did not decrease the risk of IMV (OR 1.20, 95% CI 0.40 to 3.56). Very low to low CoE from the RCT and observational trials showed that surfactant use was associated with a significant decrease in risk of air leak, persistent pulmonary hypertension of the newborn (PPHN), duration of IMV, NRS and hospital stay.ConclusionsCurrent evidence base on surfactant therapy in LPT and term infants with RDS indicates a potentially decreased risk of mortality, air leak, PPHN and duration of respiratory support. In view of the low to very low CoE and widely varying thresholds for deciding on surfactant replacement in the included studies, further trials are needed.

Background To evaluate digital tracheal intubation (DTI) when compared to laryngoscope-assisted TI; finger palpation of endotracheal tube (ETT) tip position when compared to any standard method. Design A systematic review of Medline, Embase, CENTRAL, and CINAHL with synthesis of data using meta-analysis was performed. Main outcome measure The proportion of successful TI and correct ETT tip positioning were the main outcome measures. Results Five studies (one observational study and four RCTs) enrolling 310 neonates were included. 94% (81%-98%) of the DTI were successful on the first attempt (certainty of evidence [CoE]: low). The proportion of successful intubation on the first attempt was higher with DTI when compared to laryngoscope-assisted TI (RR 95% CI: 1.81 [1.18; 2.76]) (CoE: very low). Time to successful TI with DTI was 7.4 (95% CI: 6.3, 8.5) s (CoE: low). Time to successful TI was significantly shorter with DTI when compared to laryngoscope assisted TI (MD [95% CI]: -4.9 [-7.3, -2.4] s) (CoE: very low). There was a trend towards a higher proportion of correct ETT tip positions with finger palpation when compared to weight-based formulae alone (RR 95% CI: 1.12 [0.96; 1.31]) (CoE: very low). Conclusions DTI and finger palpation to ascertain ETT tip position in neonates are promising strategies. Future studies with emphasis on their learning trajectory and generalizability are needed.

Aim The International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support forms the basis for guidelines developed by regional councils such as the American Heart Association (AHA) and the European Resuscitation Council (ERC). We aimed to determine if the updated guidelines are congruent, identify the source of variation, and score their quality. Methods We compared the approach to developing recommendations, final recommendations, and cited evidence in the AHA 2020 and ERC 2021 neonatal resuscitation guidelines. Two investigators scored guideline quality using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Results Differences in the recommendations were found between AHA 2020 and ERC 2021 neonatal resuscitation guidelines. The councils gave differing recommendations for practices that had sparse evidence and made recommendations based on expert consensus or observational studies. AGREE II assessment revealed that AHA scored better for the domain ‘rigour of development’, but ERC had a higher score for ‘stakeholder involvement’. Both AHA and ERC scored relatively less for ‘applicability’. Conclusion AHA and ERC guidelines are predominantly based on the ILCOR CoSTR. Differences in recommendations between the two were largely related to the evidence gathering process for questions not reviewed by ILCOR, paucity of evidence for some recommendations based on existing regional practices and supported by expert opinion, and different interpretation or application of same evidence. Overall, both guidelines scored well on the AGREE II assessment, but each had domains that could be improved in future editions.

We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.Medline, CENTRAL, Embase, and CINAHL were searched. Cohort and case-control studies and randomised randomized controlled trials were included. Data extraction was performed in duplicate. A random random-effects meta-analysis was utilizedused. CoE was evaluated as per Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines.One hundred eighty-six studies evaluating 95 risk factors for PVL were included. Of the 2,509,507 neonates assessed, 16,569 were diagnosed with PVL. Intraventricular hemorrhage [adjusted odds ratio: 3.22 (2.52-4.12)] had moderate CoE for its association with PVL. Other factors such as hypocarbia, chorioamnionitis, PPROM48 hour, multifetal pregnancy reduction, antenatal indomethacin, lack of antenatal steroids, perinatal asphyxia, ventilation, shock/hypotension, patent ductus arteriosus requiring surgical ligation, late-onset circulatory collapse, sepsis, necrotizing enterocolitis, and neonatal surgery showed significant association with PVL after adjustment for confounders (CoE: very low to low). Amongst the risk factors associated with mother placental fetal (MPF) triad, there was paucity of literature related to genetic predisposition and defective placentation. Sensitivity analysis revealed that the strength of association between invasive ventilation and PVL decreased over time (P 0.01), suggesting progress in ventilation strategies. Limited studies had evaluated diffuse PVL.Despite decades of research, our findings indicate that the CoE is low to very low for most of the commonly attributed risk factors of PVL. Future studies should evaluate genetic predisposition and defective placentation in the MPF triad contributing to PVL. Studies evaluating exclusively diffuse PVL are warranted.

We report a neonate who developed external iliac artery thrombosis after insertion of femoral venous catheter, without an apparent arterial puncture during the procedure. The baby developed acute limb ischaemia. As there was no improvement despite heparin infusion for 24 hours, thrombectomy was done. Following surgery, the limb perfusion improved gradually in 1 week. However, pulses did not reappear even after antithrombotic therapy for 3 months. There was residual Doppler abnormality in the form of severe narrowing at the origin of superficial femoral artery with reduced flow velocity in superficial femoral, popliteal and tibial arteries. The baby was kept under regular follow-up, with a plan for clinical assessment and Doppler every 6 months and to perform a vascular reconstructive surgery if he develops any clinical feature of chronic limb ischaemia. The baby is now 1 year of age. He is walking normally and there is no limb length discrepancy.

Clinical profile of extreme preterm neonates and more so, of microprimies with birth weight 800 g is not studied till now. Our article elaborates the profile of 5 microprimies with C.auris sepsis and review of literature. The mean gestational age and birth weight were 26 weeks ± 5 days and 709 ± 64 g respectively. Mortality was 80%. The organism was susceptible to micafungin, voriconazole but was resistant to fluconazole and amphotericin. Among the 5 babies, one had organ involvement in the form of cardiac vegetation. Early identification and optimal choice of drug are crucial for better survival in C.auris sepsis.

BACKGROUND: Human milk is the best enteral nutrition for preterm infants. However, human milk, given at standard recommended volumes, is not adequate to meet the protein, energy, and other nutrient requirements of preterm or low birth weight infants. One strategy that may be used to address the potential nutrient deficits is to give a higher volume of enteral feeds. High volume feeds may improve nutrient accretion and growth, and in turn may improve neurodevelopmental outcomes. However, there are concerns that high volume feeds may cause feed intolerance, necrotising enterocolitis, or complications related to fluid overload such as patent ductus arteriosus and chronic lung disease. This is an update of a review published in 2017. OBJECTIVES: To assess the effect on growth and safety of high versus standard volume enteral feeds in preterm or low birth weight infants. In infants who were fed fortified human milk or preterm formula, high and standard volume feeds were defined as > 180 mL/kg/day and ≤ 180 mL/kg/day, respectively. In infants who were fed unfortified human milk or term formula, high and standard volume feeds were defined as > 200 mL/kg/day and ≤ 200 mL/kg/day, respectively. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search Cochrane Central Register of Controlled Trials (CENTRAL; 2020 Issue 6) in the Cochrane Library; Ovid MEDLINE (1946 to June 2020); Embase (1974 to June 2020); and CINAHL (inception to June 2020); Maternity & Infant Care Database (MIDIRS) (1971 to April 2020); as well as previous reviews, and trial registries. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared high versus standard volume enteral feeds for preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) and risk difference for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. The primary outcomes were weight gain, linear and head growth during hospital stay, and extrauterine growth restriction at discharge. MAIN RESULTS: We included two new RCTs (283 infants) in this update. In total, we included three trials (347 infants) in this updated review. High versus standard volume feeds with fortified human milk or preterm formula Two trials (283 infants) met the inclusion criteria for this comparison. Both were of good methodological quality, except for lack of masking. Both trials were performed in infants born at < 32 weeks' gestation. Meta‐analysis of data from both trials showed high volume feeds probably improves weight gain during hospital stay (MD 2.58 g/kg/day, 95% CI 1.41 to 3.76; participants = 271; moderate‐certainty evidence). High volume feeds may have little or no effect on linear growth (MD 0.05 cm/week, 95% CI ‐0.02 to 0.13; participants = 271; low‐certainty evidence), head growth (MD 0.02 cm/week, 95% CI ‐0.04 to 0.09; participants = 271; low‐certainty evidence), and extrauterine growth restriction at discharge (RR 0.71, 95% CI 0.50 to 1.02; participants = 271; low‐certainty evidence). We are uncertain of the effect of high volume feeds with fortified human milk or preterm formula on the risk of necrotising enterocolitis (RR 0.74, 95% CI 0.12 to 4.51; participants = 283; very‐low certainty evidence). High versus standard volume feeds with unfortified human milk or term formula One trial with 64 very low birth weight infants met the inclusion criteria for this comparison. This trial was unmasked but otherwise of good methodological quality. High volume feeds probably improves weight gain during hospital stay (MD 6.2 g/kg/day, 95% CI 2.71 to 9.69; participants = 61; moderate‐certainty evidence). The trial did not provide data on linear and head growth, and extrauterine growth restriction at discharge. We are uncertain as to the effect of high volume feeds with unfortified human milk or term formula on the risk of necrotising enterocolitis (RR 1.03, 95% CI 0.07 to 15.78; participants = 61; very low‐certainty evidence). AUTHORS' CONCLUSIONS: High volume feeds (≥ 180 mL/kg/day of fortified human milk or preterm formula, or ≥ 200 mL/kg/day of unfortified human milk or term formula) probably improves weight gain during hospital stay. The available data is inadequate to draw conclusions on the effect of high volume feeds on other growth and clinical outcomes. A large RCT is needed to provide data of sufficient quality and precision to inform policy and practice.

BACKGROUND: Uncertainty exists about the optimal point at which multi‐component fortifier should be added to human milk for promoting growth in preterm infants. The most common practice is to start fortification when the infant’s daily enteral feed volume reaches 100 mL/kg body weight. Another approach is to commence fortification earlier, in some cases as early as the first enteral feed. Early fortification of human milk could increase nutrient intake and growth rates but may increase the risk of feed intolerance and necrotising enterocolitis (NEC). OBJECTIVES: To assess effects on growth and safety of early fortification of human milk versus late fortification in preterm infants To assess whether effects vary based upon gestational age (≤ 27 weeks; 28 to 31 weeks; ≥ 32 weeks), birth weight (< 1000 g; 1000 to 1499 g; ≥ 1500 g), small or appropriate for gestational age, or type of fortifier (bovine milk‐based human milk fortifier (HMF); human milk‐based HMF; formula powder) SEARCH METHODS: We used the standard strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 8); OVID MEDLINE (R) and Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Daily and Versions (R) (1946 to 15 August 2019); MEDLINE via PubMed (1 August 2018 to 15 August 2019) for the previous year; and the Cumulative Index to Nursing and Allied Health Literatue (CINAHL) (1981 to 15 August 2019). We searched clinical trials databases and reference lists of included studies. SELECTION CRITERIA: We included randomised controlled trials that compared early versus late fortification of human milk in preterm infants. We defined early fortification as fortification started at < 100 mL/kg/d enteral feed volume or < 7 days postnatal age, and late fortification as fortification started at ≥ 100 mL/kg/d feeds or ≥ 7 days postnatal age. DATA COLLECTION AND ANALYSIS: Both review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials, and we reported risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, with respective 95% confidence intervals (CIs). We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: We included two trials with a total of 237 infants. All participants were very low birth weight infants (birth weight < 1500 g). Early fortification was started at 20 mL/kg/d enteral feeds in one study and 40 mL/kg/d in the other study. Late fortification was started at 100 mL/kg/d feeds in both studies. One study used bovine milk‐based fortifier, and the other used human milk‐based fortifier. Meta‐analysis showed that early fortification may have little or no effect on growth outcomes including time to regain birth weight (MD ‐0.06 days, 95% CI ‐1.32 to 1.20 days), linear growth (MD 0.10 cm/week, 95% CI ‐0.03 to 0.22 cm/week), or head growth (MD ‐0.01 cm/week, 95% CI ‐0.07 to 0.06 cm/week) during the initial hospitalisation period. Early fortification may have little or no effect on the risk of NEC (MD ‐0.01, 95% CI ‐0.07 to 0.06). The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). Early fortification may have little or no effect on incidence of surgical NEC, time to reach full enteral feeds, extrauterine growth restriction at discharge, proportion of infants with feed interruption episodes, duration of total parenteral nutrition (TPN), duration of central venous line usage, or incidence of invasive infection, all‐cause mortality, and duration of hospital stay. The certainty of evidence was low for these outcomes due to risk of bias (lack of blinding) and imprecision (small sample size). We did not have data for other outcomes such as subsequent weight gain after birth weight is regained, parenteral nutrition‐associated liver disease, postdischarge growth, and neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: Available evidence is insufficient to support or refute early fortification of human milk in preterm infants. Further large trials would be needed to provide data of sufficient quality and precision to inform policy and practice.

To assess the efficacy of adding plastic bag or portable thermal nest (PTN) to standard care in preventing hypothermia soon after birth in 1500–2499 g infants. Infants were randomized into standard thermal care alone, plastic bag with standard care or PTN with standard care. Axillary temperature was measured at admission and every 30 min till euthermia. All babies were followed-up till day 7. We recruited 300 infants: plastic bag (101), PTN (99) and standard care group (100). Admission temperature was 36.4 °C (0.52) in plastic bag group, 36.3 °C (0.50) in PTN and 36.1 °C (0.59) in standard care group (p

Context Morbidity and mortality amongst extremely low birth weight (ELBW) and extremely low gestational age neonates (ELGANs) in developing nations has not been well studied. Objectives Evaluate survival until discharge, short- and long-term morbidities of ELBW and ELGANs in LMICs. Data sources CENTRAL, EMBASE, MEDLINE and Web of Science. Study selection Prospective and retrospective observational studies were included. Data extraction and synthesis Four authors extracted data independently. Random-effects meta-analysis of proportions was used to synthesize data, modified QUIPS scale to evaluate quality of studies and GRADE approach to ascertain the certainty of evidence (CoE). Results 192 studies enrolling 22,278 ELBW and 18,338 ELGANs were included. Survival was 34% (95% CI: 31% - 37%) (CoE–low) for ELBW and 39% (34% - 44%) (CoE—moderate) for ELGANs. For ELBW neonates, the survival for low-income (LI), lower middle-income (LMI) and upper middle income (UMI) countries was 18% (11% - 28%), 28% (21% - 35%) and 39% (36% - 42%), respectively. For ELGANs, it was 13% (8% - 20%) for LI, 28% (21% - 36%) for LMI and 48% (42% - 53%) for UMI countries. There was no difference in survival between two epochs: 2000–2009 and 2010–2020. Except for necrotising enterocolitis [ELBW and ELGANs—8% (7% - 10%)] and periventricular leukomalacia [ELBW—7% (4% - 11%); ELGANs—6% (5%-7%)], rates of all other morbidities were higher compared to developed nations. Rates of neurodevelopmental impairment was 17% (7% - 34%) in ELBW neonates and 29% (23% - 37%) in ELGANs. Limitations CoE was very low to low for all secondary outcomes. Conclusions Mortality and morbidity amongst ELBW and ELGANs is still a significant burden in LMICs. CoE was very low to low for all the secondary outcomes, emphasizing the need for high quality prospective cohort studies. Trial registration PROSPERO (CRD42020222873).

Background Troponin-T is a commonly used cardiac biomarker, which could be useful in perinatal asphyxia. We aimed to analyze troponin-T concentrations in asphyxiated neonates and to correlate the concentrations with clinical outcomes. Methods Data were collected from electronic medical records of neonates diagnosed with perinatal asphyxia over a period of four years. Results There were 63 neonates with moderate to severe encephalopathy, in whom serial troponin-T concentrations had been done on days 1, 3, and 7. 53 (84%) asphyxiated infants had troponin-T concentration >100 pg/ml at 2-4 h of life.The difference in troponin-T concentrations between moderate and severe encephalopathy was not statistically significant (173 vs. 263 pg/ml, p value 0.40). The difference in the concentrations at 72 hours between cooled and non-cooled neonates was not significant (48.5 vs. 62.5 pg/ml, p value 0.22). Troponin-T concentration was significantly higher in babies with hypotensive shock and hepatic injury, but not acute kidney injury. There was no significant correlation between troponin-T and the extent of resuscitation needed.Troponin-T concentration on day 1 of life was significantly higher in babies who died than who survived (407 vs. 168 pg/ml, p value 0.03). ROC curve for troponin-T to predict mortality had an area under the curve (AUC) of 0.803; the best cut-off value (190 pg/ml) had 82% sensitivity and 80% specificity. Conclusion There was no significant difference in troponin-T concentrations between cooled and non-cooled neonates. Troponin-T concentration had a good predictive accuracy for mortality before discharge.

BACKGROUND We present the diagnostic dilemma of a neonate with two umbilical soft tissue masses. Case report: The baby had an umbilical mass herniating through the umbilical cord, and another mass hanging from the umbilical mass by a string of tissue. Both masses were amorphous solid soft tissues and the hanging mass had hair on the surface. Clinical diagnosis was umbilical cord teratoma. However, histopathological examination of the masses showed that tissues representing various organs were arranged in cephalocaudal order as in a fetus, revealing that it was a parasitic twin. The hanging mass was probably the cephalic part and the umbilical mass was malformed torso and limbs. Conclusion: This parasitic omphalopagus heteropagus parasitic twin presented as two amorphous masses without externally identifiable anatomic structure, The parasitic twin of omphalopagus heteropagus may have unusual presentations. Histopathological examination was essential to diagnose whether it is a twin or a tumor.

Neonatal encephalopathy manifests with altered sensorium, tone abnormalities, and often with abnormal movements and seizures. The causes are heterogeneous and many. We report a late preterm neonate who presented with depressed sensorium, cranial nerve abnormalities, mixed hypertonia and hypotonia, and respiratory failure. Neuroimaging and electrophysiological studies were normal. She had neutropenia and elevated lactates in blood. Her dried blood spot analysis by tandem MS/MS showed normal acylcarnitine and amino acid profile. Plasma and cerebro spinal fluid (CSF) amino acid quantification were inconclusive, CSF folate was normal. Urine organic acid analysis showed elevated lactate. Semi-quantitative analysis of urine showed borderline elevation of 3-methylglutaconic acid. Diagnosis of 3-methylglutaconic aciduria (3MGA) type VIII was suggested by whole-exome sequencing, which revealed a homozygous, likely pathogenic, missense mutation in Exon 2 of HTRA2 gene (chr2.74757898A>C). Her parents were found to be carriers of the same mutation. This underscores the importance of genetic studies in the evaluation of neonatal neuro-metabolic disorders. We report the first case of 3MGA type VIII from our region with a review of already reported 11 cases.

The objective of this study was to determine changes in neutrophil volume conductivity scatter (VCS) parameters and their distribution widths (DW) in neonatal sepsis and to estimate their optimal cutoff levels using receiver operating characteristic (ROC) curves.In a cohort of neonates evaluated for sepsis, blood counts and blood culture were performed initially, with repeat counts and C-reactive protein (CRP) done after 24 to 48 h. Neutrophil VCS parameters from both the initial and repeat blood counts were analyzed. Babies were classified as having blood culture-positive sepsis, probable sepsis (clinical course consistent with sepsis and CRP-positive, but culture-negative) and no sepsis (clinical course not compatible with sepsis, culture- and CRP-negative).A total of 600 babies were included: 240 (40%) babies in the sepsis group and 360 (60%) babies in the control group. All the neutrophil VCS parameters and their DWs (except for low angle light scatter in the repeat counts) were significantly different between the two groups, with an area under curve in the ROC curve of0.6 for most parameters. The five most significant VCS parameters (mean neutrophil volume (MNV), median angle light scatter (MALS), lower median angle light scatter (LMALS), MNV-DW and ALL-DW) had around 65 to 75% sensitivity and specificity. A combination of leukopenia, thrombocytopenia, MNV and LMALS had a likelihood ratio (LR)+ of 15.3 and LR- of 0.17. With a pre-test probability of 40%, post-test probability increased to 91% for a positive test and decreased to 10% for a negative test. A prospective validation study was performed recruiting an additional 60 babies, which showed similar results, assuring that the cutoffs were robust.Neutrophil VCS parameters cannot be considered as stand-alone tests to diagnose or rule out neonatal sepsis, but can be used in combination with other hematological screening tests to improve the diagnostic accuracy of the neonatal sepsis screen.

ObjectiveAdequate data on fentanyl pharmacokinetics in neonates are lacking. The study was performed to compare serum concentrations and clinical outcome between continuous infusion (CI) and intermittent bolus (IB) doses of fentanyl for analgesia and sedation in neonates.MethodsIn this open-label randomised controlled trial, neonates requiring 24–48 hours of mechanical ventilation and fentanyl administration were recruited. In CI regimen, 1 mcg/kg loading dose was followed by 1 mcg/kg/hour infusion. In IB regimen, 1mcg/kg/dose was administered every 4 hours.Maximum six blood samples were collected in 48 hours from each baby at prespecified time points for estimating serum fentanyl concentration. Secondary outcomes were pain scores (Neonatal Infant Pain Scale and Neonatal Pain, Agitation and Sedation Scale for acute and ongoing pain, respectively) and incidence of adverse effects of fentanyl.Results100 neonates were recruited, 53 in CI and 47 in IB group. In CI regimen, median (IQR) serum fentanyl concentration was 0.42 (0.35, 0.46) to 0.61 (0.47, 0.89) ng/mL throughout the infusion period. In IB regimen, median (IQR) peak concentration ranged from 2.21 (1.82, 3.55) to 3.61 (2.91, 4.51) ng/mL and trough concentration 0.41 (0.33, 0.48) to 0.97 (0.56, 1.25) ng/mL for various doses.Median (IQR) peak concentration (Cmax, 3.06 (1.09, 4.50) vs 0.78 (0.49, 1.73) ng/mL; p0–24, 19.6 (10.4, 33.5) vs 13.2 (10.8, 22.6) µg·hour/L; p=0.12) was higher (though not statistically significant) in IB than CI regimen. Pain scores and adverse effects were comparable between the two regimens.ConclusionCI regimen of fentanyl produces steady serum concentrations, whereas IB regimen produces wide fluctuations in serum concentration with high-peak concentrations. A serum fentanyl concentration of 0.4–0.6 ng/mL produces adequate analgesia and sedation in neonates.Trial registration numberCTRI/2014/11/005190.

BACKGROUND: Routine monitoring of gastric residuals in preterm infants on gavage feeds is a common practice in many neonatal intensive care units and is used to guide the initiation and advancement of feeds. No guidelines or consensus is available on whether to re‐feed or discard the aspirated gastric residuals. Although re‐feeding gastric residuals may replace partially digested milk, gastrointestinal enzymes, hormones, and trophic substances that aid in digestion and promote gastrointestinal motility and maturation, re‐feeding abnormal residuals may result in emesis, necrotising enterocolitis, or sepsis. OBJECTIVES: To assess the efficacy and safety of re‐feeding compared to discarding gastric residuals in preterm infants. The allocation should have been started in the first week of life and should have been continued at least until the baby reached full enteral feeds. The investigator could have chosen to discard the gastric residual in the re‐feeding group, if the gastric residual quality was not satisfactory. However, the criteria for discarding gastric residual should have been predefined. To conduct subgroup analysis based on gestational age (≤ 27 weeks, 28 weeks to 31 weeks, ≥ 32 weeks), birth weight (< 1000 g, 1000 g to 1499 g, ≥ 1500 g), type of milk (human milk or formula milk), quality of the gastric residual (fresh milk, curded milk, or bile‐stained gastric residual), volume of gastric residual replaced (total volume, 50% of the volume, volume of the next feed, or prespecified volume, irrespective of the volume of the aspirate, e.g. 2 mL, 3 mL), and whether the volume of gastric residual that is re‐fed is included in or excluded from the volume of the next feed (see "Subgroup analysis and investigation of heterogeneity"). SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE via PubMed (1966 to 19 February 2018), Embase (1980 to 19 February 2018), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 19 February 2018). We also searched clinical trial databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi‐randomised trials. SELECTION CRITERIA: Randomised and quasi‐randomised controlled trials that compared re‐feeding versus discarding gastric residuals in preterm infants. DATA COLLECTION AND ANALYSIS: Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported the risk ratio and risk difference for dichotomous data, and the mean difference for continuous data, with respective 95% confidence intervals. We used the GRADE approach to assess the quality of evidence. MAIN RESULTS: We found one eligible trial that included 72 preterm infants. This trial was not blinded. We are uncertain as to the effect of re‐feeding gastric residual on efficacy outcomes such as time to regain birth weight (mean difference (MD) 0.40 days, 95% confidence interval (CI) ‐2.89 to 3.69 days; very low quality evidence), time to reach enteral feeds ≥ 120 mL/kg/d (MD ‐1.30 days, 95% CI ‐2.93 to 0.33 days; very low quality evidence), number of infants with extrauterine growth restriction at discharge (risk ratio (RR) 1.29, 95% CI 0.38 to 4.34; very low quality evidence), duration of total parenteral nutrition (MD ‐0.30 days, 95% CI ‐2.07 to 1.47 days; very low quality evidence), and length of hospital stay (MD ‐1.90 days, 95% CI ‐25.27 to 21.47 days; very low quality evidence). Similarly, we are uncertain as to the effect of re‐feeding gastric residual on safety outcomes such as incidence of stage 2 or 3 necrotising enterocolitis and/or spontaneous intestinal perforation (RR 0.71, 95% CI 0.25 to 2.04; very low quality evidence), number of episodes of feed interruption lasting ≥ 12 hours (RR 0.80, 95% CI 0.42 to 1.52; very low quality evidence), or mortality before discharge (RR 0.50, 95% CI 0.14 to 1.85; low‐quality evidence). We are uncertain as to the effect of re‐feeding gastric residual in the subgroups of human milk‐fed and formula‐fed infants. We found no data on other outcomes such as linear and head growth during hospital stay, postdischarge growth, number of infants with parenteral nutrition‐associated liver disease, and neurodevelopmental outcomes. AUTHORS' CONCLUSIONS: We found only limited data from one small unblinded trial on the efficacy and safety of re‐feeding gastric residuals in preterm infants. The quality of evidence was low to very low. Hence, available evidence is insufficient to support or refute re‐feeding of gastric residuals in preterm infants. A large, randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice.

To assess the feasibility and safety of cooling asphyxiated neonates using phase changing material based device across different neonatal intensive care units in India.Multi-centric uncontrolled clinical trial.11 level 3 neonatal units in India from November 2014 to December 2015.103 newborn infants with perinatal asphyxia, satisfying pre-defined criteria for therapeutic hypothermia.Therapeutic hypothermia was provided using phase changing material based device to a target temperature of 33.5±0.5oC, with a standard protocol. Core body temperature was monitored continuously using a rectal probe during the cooling and rewarming phase and for 12 hours after the rewarming was complete.Feasibility measure - Time taken to reach target temperature, fluctuation of the core body temperature during the cooling phase and proportion of temperature recordings outside the target range. Safety measure - adverse events during cooling.The median (IQR) of time taken to reach target temperature was 90 (45, 120) minutes. The mean (SD) deviation of temperature during cooling phase was 33.5 (0.39) ºC. Temperature readings were outside the target range in 10.8% (5.1% of the readings were33oC and 5.7% were34oC). Mean (SD) of rate of rewarming was 0.28 (0.13)oC per hour. The common adverse events were shock/ hypotension (18%), coagulopathy (21.4%), sepsis/probable sepsis (20.4%) and thrombocytopenia (10.7%). Cooling was discontinued before 72 hours in 18 (17.5%) babies due to reasons such as hemodynamic instability/refractory shock, persistent pulmonary hypertension or bleeding. 7 (6.8%) babies died during hospitalization.Using phase changing material based cooling device and a standard protocol, it was feasible and safe to provide therapeutic hypothermia to asphyxiated neonates across different neonatal units in India. Maintenance of target temperature was comparable to standard servo-controlled equipment.

Background Several low-cost methods are used in resource-limited settings to provide therapeutic hypothermia in asphyxiated neonates. There is inadequate data about their efficacy and safety. This is a retrospective study comparing two low-cost cooling methods-frozen gel packs (FGP) and phase changing material (PCM). Results There were 23 babies in FGP and 45 babies in the PCM group. Induction time was significantly shorter with FGP than PCM (45 vs. 90 minutes; p -value < 0.001). Proportion of temperature readings outside the target range was significantly higher (9.8% vs. 3.8%; p -value

Background Cytomegalovirus (CMV) enterocolitis is rare in term neonates. Case characteristics A term newborn with persistent pneumonia from birth developed enterocolitis on day 18 of life. Outcome Polymerase chain reaction (PCR) for CMV DNA was positive in urine sample. Antiviral therapy for six weeks resulted in successful treatment without any stricture formation. Message CMV enterocolitis should be considered as a differential diagnosis in atypical cases of necrotizing enterocolitis in neonates.

We report a preterm neonate who had a large cervical cystic hygroma and right chylothorax. She was operated on day-21 and a near-complete resection of cystic hygroma was done. She developed refractory hypoxemia and shock post surgery and died after 24 hours. During autopsy, the chest cavity was found to be filled with chyle. Histopathological examination showed dilated lymphatics in the pleura, hepatic capsule, serosa of stomach and intestines, peri-pancreatic regions, peri-renal capsule and peri-adrenal tissues suggestive of generalised lymphatic dysplasia. Clinical exome sequencing did not reveal any pathogenic mutation in the genes involved in primary lymphatic dysplasia, noonan syndrome or rasopathies.

We report a case of a preterm neonate born to a mother with giant placental chorioangioma. The baby had microangiopathic haemolytic anaemia, thrombocytopenia and cardiac failure at birth. In addition, she had a disseminated intravascular coagulation-like picture and had bleeding from multiple sites, which was treated with transfusion of multiple blood products. She also developed transient hypertension and required antihypertensive drugs for 3 weeks. The baby was successfully managed and discharged home, though with signs of neurosensory impairment.

Neonatal appendicitis is difficult to diagnose, and is associated with high mortality. A preterm (33 wk) neonate developed abdominal distension feeding intolerance and erythema of left inguinal region on day 4 of life. Testicular torsion was suspected but inguinal exploration revealed normal testis with feco-purulent fluid draining into processus vaginalis from peritoneal cavity. Laparotomy revealed inflamed and perforated appendix. Appendectomy and intravenous antibiotics led to a recovery. Appendicitis in a neonate can rarely present with inguinal symptoms, masquerading as testicular torsion.

Umbilical venous catheterisation (UVC) insertion is a common procedure performed in most neonatal units. We report a case of a neonate who developed pleural and pericardial effusions and ascites due to a malpositioned UVC causing diaphragmatic perforation. Timely diagnosis using bedside sonography and prompt removal of the catheter resulted in resolution of the effusions without undue complications.