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Context: Heel prick is one among the common painful procedures in neonates. We performed a systematic review and network metaanalysis (NMA) to compare the efficacy of different interventions for analgesia during heel prick in neonates. Evidence acquisition: Medline, Cochrane, Embase and CINAHL databases were searched from inception until February 2023. Randomized and quasi-randomized trials that evaluated different pharmacological and non-pharmacological interventions for analgesia during heel prick for neonates were included. Data from the included trials were extracted in duplicate. A NMA with a frequentist random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. We adhered to the PRISMA-NMA guidelines. Results: One-hundred-and-three trials comparing 51 different analgesic measures were included. Among the 38 interventions, for pain "during" heel prick, non-nutritive suckling (NNS) plus sucrose [SMD Ȓ3.15 (Ȓ2.62, Ȓ3.69)], followed by breastfeeding, glucose, expressed breast milk (EBM), sucrose, NNS and touch massage, had a high certainty of evidence (CoE) to reduce pain scores when compared to no intervention. Among the 23 interventions for pain at 30 seconds after heel-prick, moderate CoE was noted for facilitated tucking plus NNS plus music, glucose, NNS plus sucrose, sucrose plus swaddling, mother holding, EBM, sucrose and NNS. Conclusions: Oral sucrose 2 minutes before combined with NNS during the procedure, was the best intervention for reducing pain during heel prick. It also effectively reduced pain scores 30 seconds and 1 minute after the procedure. Other interventions with moderate to high CoE for a significant reduction in pain during and at 30 seconds after heel prick are oral sucrose, oral glucose, EBM and NNS. All these are low-cost and feasible interventions for most of the settings. [ABSTRACT FROM AUTHOR]

Vitamin D deficiency in infants is widely prevalent. Most paediatric professional associations recommend routine vitamin D prophylaxis for infants. However, the optimal dose and duration of supplementation are still debated. We aimed to compare the efficacy and safety of different vitamin D supplementation regimens in term and late preterm neonates. For this systematic review and network meta-analysis, we searched MEDLINE, the Cochrane Central Register of Controlled Trials and Embase. Randomised and quasi-randomised clinical trials that evaluated any enteral vitamin D supplementation regimen initiated within 6 weeks of life were included. Two researchers independently extracted data on study characteristics and outcomes and assessed quality of included studies. A network meta-analysis with a Bayesian random-effects model was used for data synthesis. Certainty of evidence (CoE) was assessed using GRADE. Primary outcomes were mean serum vitamin D concentrations and the proportion of infants with vitamin D insufficiency (VDI). We included twenty-nine trials that evaluated fourteen different regimens of vitamin D supplementation. While all dosage regimens of ≥400 IU/d increased the mean 25(OH)D levels compared with no treatment, supplementation of ≤250 IU/d and 1400 IU/week did not. The CoE varied from very low to high. Low CoE indicated that 1600 IU/d, compared with lower dosages, reduced the proportion of infants with VDI. However, our results indicated that any dosage of ≥800 IU/d increased the risk of hypervitaminosis D and hypercalcaemia. Data on major clinical outcomes were sparse. Vitamin D supplementation of 400–600 IU/d may be the most effective and safest in infants. [ABSTRACT FROM AUTHOR]

Byline: Srivijayalakshmi. Ravichandran, Balakrishnan. Rajaiah, Rajendran. Karupanan, Thangaraj. Abiramalatha, Kannan. Gunasekaran, Shriram. Varadharajan, Srinivas. Ramakrishnan Most neonatal seizures are acute-provoked, and the common etiologies are hypoxic-ischemic encephalopathy (HIE), stroke, central [...]

Neonatal strokes constitute a major cause of pediatric mortality and morbidity. Neuroimaging helps in its diagnosis as well as prognostication. However, advanced imaging, including magnetic resonance imaging (MRI), carries multiple challenges. Limited data exists in the literature on imaging-based predictors of neurological outcomes in neonatal stroke in the Indian population. In this study, we reviewed our available data on neonatal stroke patients between 2015 and 2020 for clinico-radiological patterns. During this period, 17 neonatal strokes were admitted and the majority were term births with a slight male preponderance. Seizures and encephalopathy were the most common presentation. Multiple maternal risk factors such as gestational diabetes, meconium-stained liquor, APLA syndrome, fever, deranged coagulation profile, oligohydramnios, cord prolapse, and non-progressive labor were seen. Cardiac abnormalities were seen in only less than half of these patients with the most common finding being atrial septal defects (ASD). Transcranial ultrasound was performed in eight neonates and the pick-up rate of ultrasound was poor. MR imaging showed large infarcts in 11 patients. The MCA territory was most commonly involved. Interestingly, five neonates had venous thrombosis with three showing it in addition to arterial thrombosis. Associated ictal, as well as Wallerian changes, were noted in 10. Although large territorial infarcts were the most common pattern, non-contrast MR angiography did not show major vessel occlusion in these cases. Outcomes were fairly good and only three patients had a residual motor deficit at 1 year. No recurrence of stroke was seen in any of the neonates. [ABSTRACT FROM AUTHOR]

Introduction: Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). Methods: Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. Results: Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30–60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78–1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01–1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). Conclusions: In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival. [ABSTRACT FROM AUTHOR]

Background: Despite decades of research, there is inadequate evidence on the etiological factors of brain injury in preterm infants.Objective: To study the perinatal risk factors for preterm brain injury and to assess their strength of association.Methods: In this retrospective cohort study, we included infants born at <32 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.Results: 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

Aim: To study the impact of delivery room continuous positive airway pressure (DRCPAP) on outcomes of preterm neonates in low- and middle- income countries (LMICs) by comparing with interventions: oxygen supplementation, late DRCPAP, DRCPAP with sustained inflation, DRCPAP with surfactant and invasive mechanical ventilation (IMV).Methods: Medline, Embase, CENTRAL, WOS and CINAHL searched. Observational studies and randomized controlled trials (RCTs) were included. Pair-wise meta-analysis and Bayesian network meta-analysis (NMA) were utilized. Primary outcome was receipt of IMV.Results: Data from 11 of the 18 included studies (4 observational studies, 7 RCTs) enrolling 4210 preterm infants was synthesized. Moderate certainty of evidence (CoE) from NMA of RCTs comparing DRCPAP with surfactant administration versus DRCPAP alone suggested no decrease in subsequent receipt of IMV [Risk ratio (RR); 95% Credible Interval (CrI): 0.73; (0.34, 1.40)]. Very low CoE from observational studies comparing use of DRCPAP versus oxygen supplementation indicated a trend towards decreased IMV [RR; 95% Confidence Interval (CI): 0.75; (0.56-1.00)]. Although moderate CoE from NMA evaluating DRCPAP versus oxygen supplementation showed a trend towards decreased receipt of surfactant, it did not reach statistical significance [RR; 95% CrI: 0.69; (0.44, 1.06)]. Moderate CoE from NMA indicated that none of the interventions, when compared with use of supplemental oxygen alone or with each other decreased mortality or bronchopulmonary dysplasia.Limitations: CoE was very low for primary outcome.Conclusions: Present evidence is not sufficient for use of DRCPAP, but also did not show harm. Since it seems unlikely that there are marked variations in patient physiology to explain the difference in efficacy between high income countries and LMICs, we suggest future research evaluating other barriers in improving the effectiveness of DRCPAP in LMICs. [ABSTRACT FROM AUTHOR]

Background: We analyzed the certainty of evidence (CoE) for risk factors of periventricular leukomalacia (PVL) in preterm neonates, a common morbidity of prematurity.Methods: 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.Results: 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, PPROM >48 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.Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 â¤30 weeks' gestation or have an estimated fetal weight <1,200 g. We intended to perform delayed cord clamping (DCC) and to collect UCB following DCC. The quality parameters used included blood culture performed once, and biochemical and haematological parameters assessed weekly. Results: Of the 46 recruited neonates, DCC could be performed for 1 minute in 11 (23.9%) and for 30-59 seconds in 10 (21.7%) infants. The success rate of UCB collection was significantly lower in infants who underwent DCC for 1 minute (27%) compared to those who underwent DCC for 30-59 seconds (70%) or immediate cord clamping (72%) (p value 0.031). Twenty-five UCBs were stored after eliminating three that had positive culture. UCB had satisfactory quality for transfusion from day 3 (when blood culture report was available) to 14 (after which pH decreased to <6.5). Thirteen infants required 27 RCC transfusions. Autologous UCB could be used for only five (18.5%) transfusions. Conclusion: The success rate of UCB collection after DCC for 1 minute is low. Autologous UCB meets less than one-fifth of transfusion requirements. Hence, autologous UCB transfusion is not a workable option in preterm infants. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Adequate 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.Methods: In 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.Results: 100 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; p<0.001) was significantly higher and area under concentration-time curve (AUC0-24, 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.Conclusion: CI 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 Number: CTRI/2014/11/005190. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 < 0.001) and fluctuation of core body temperature was wider (standard deviation of target temperature 0.4 °C vs. 0.28 °C) in the FGP group, compared with PCM group.Conclusion: Both FGP and PCM are effective and safe, comparable with standard servo-controlled cooling equipment. PCM has the advantage of better maintenance of target temperature with less nursing input, when compared with FGP. [ABSTRACT FROM AUTHOR]

We aimed to compare continuous temperature-monitoring using Bluetooth-enabled thermometer (BET) and intermittent monitoring by digital thermometer (DT) in neonates. Continuous monitoring using BET identified 377 episodes of hypo/hyperthermias in 90 baby-days; 316 (83.8%) episodes were confirmed by DT and 61 (16.2%) were false alarms. Five episodes were missed by BET. The agreement between digital thermometer and BET was good. Continuous temperature monitoring helps in early identification of hypo/hyperthermia in neonates. [ABSTRACT FROM AUTHOR]