Oxygen saturation centiles in healthy preterm neonates in the first 10 min of life: a prospective observational study.

Current oxygen saturation targets in delivery room given by Neonatal Resuscitation Program (NRP) are essentially derived from term neonates. This prospective observational study was conducted in a level-III neonatal unit in preterm neonates (< 37 weeks) who did not receive resuscitation or supplemental oxygen to create centile charts for pre-ductal oxygen saturations using robust statistical modelling methods. Pre-ductal oxygen saturations (SPO2) were recorded from birth till 10 min of age using current generation Masimo pulse oximeters. Centile charts were created by generalized additive models. The change in oxygen saturations over time across subjects was modelled as a Bayesian linear regression mixed-effects model after including 'a priori' covariates. Oxygen saturation data was analysed in 180 subjects with mean gestation of 34 ± 2 weeks. Mean (SD) time to first SPO2 was 167 ± 77 s. The median time to SPO2 of > 90% was 310 s (IQR: 235-400). Time to > 90% SPO2 was shorter in (a) 34-36 weeks compared to < 34 weeks (290 vs 340; p = 0.03) and (b) vaginally delivered compared to caesarean-section born neonates (300 vs 360; p = 0.2).    Conclusions: Oxygen saturations in first 10 min of age in healthy preterm neonates are significantly higher than the targets proposed by the NRP-2020. Larger preterm neonates and those born through vaginal route attained a preductal saturation of > 90% sooner. What is Known: • Pulse oximetry is the standard for oxygen saturation monitoring during immediate postnatal period. • Healthy term neonates take many minutes after birth to reach a pre-ductal saturation of >90%. But, postnatal oxygen saturation trend data in healthy preterm neonates are scarce. What is New: • Provides centile charts for oxygen saturations till 10 minutes of age using current generation Masimo pulse oximeters in a large cohort of healthy preterm neonates using robust statistical modelling methods. • Identifies covariates that significantly modifies the saturation trends using a Bayesian mixed models' regression.

To feed or not to feed during therapeutic hypothermia in asphyxiated neonates: a systematic review and meta-analysis.

The practice of withholding feed during therapeutic hypothermia (TH) in neonates with hypoxemic ischemic encephalopathy (HIE) is based on conventions rather than evidence. Recent studies suggest that enteral feeding might be safe during TH. We systematically compared the benefits and harms of enteral feeding in infants undergoing TH for HIE. We searched electronic databases and trial registries (MEDLINE, CINAHL, Embase, Web of Science, and CENTRAL) until December 15, 2022, for studies comparing enteral feeding and non-feeding strategies. We performed a random-effects meta-analysis using RevMan 5.4 software. The primary outcome was the incidence of stage II/III necrotizing enterocolitis (NEC). Other outcomes included the incidence of any stage NEC, mortality, sepsis, feed intolerance, time to full enteral feeds, and hospital stay. Six studies ((two randomized controlled trials (RCTs) and four nonrandomized studies of intervention (NRSIs)) enrolling 3693 participants were included. The overall incidence of stage II/III NEC was very low (0.6%). There was no significant difference in the incidence of stage II/III NEC in RCTs (2 trials, 192 participants; RR, 1.20; 95% CI: 0.53 to 2.71, I2, 0%) and NRSIs (3 studies, no events in either group). In the NRSIs, infants in the enteral feeding group had significantly lower sepsis rates (four studies, 3500 participants, RR, 0.59; 95% CI: 0.51 to 0.67, I2-0%) and lower all-cause mortality (three studies, 3465 participants, RR: 0.43; 95% CI: 0.33 to 0.57, I2-0%) than the infants in the "no feeding" group. However, no significant difference in mortality was observed in RCTs (RR: 0.70; 95% CI: 0.28 to 1.74, I2-0%). Infants in the enteral feeding group achieved full enteral feeding earlier, had higher breastfeeding rates at discharge, received parenteral nutrition for a shorter duration, and had shorter hospital stays than the control group.  Conclusion: In late preterm and term infants with HIE, enteral feeding appears safe and feasible during the cooling phase of TH. However, there is insufficient evidence to guide the timing of initiation, volume, and feed advancement. What is Known: • Many neonatal units withhold enteral feeding during therapeutic hypothermia, fearing an increased risk of complications (feed intolerance and necrotizing enterocolitis). • The overall risk of necrotizing enterocolitis in late-preterm and term infants is extremely low (< 1%). What is New: • Enteral feeding during therapeutic hypothermia is safe and does not increase the risk of necrotizing enterocolitis, hypoglycemia, or feed intolerance. It may reduce the incidence of sepsis and all-cause mortality until discharge.

Role of perfusion index and plethysmography variability index for predicting outcomes in neonatal sepsis.

AIM: (i) To compare perfusion index (PI) and plethysmography variability index (PVI) between neonates with proven or probable sepsis versus no-sepsis, (ii) to examine an association of PI and PVI with in-hospital mortality. METHODS: We enrolled neonates with clinically presumed sepsis. Culture-proven or probable sepsis were categorised as 'cases' and no-sepsis as 'controls'. PI and PVI were recorded hourly for 120 h and averaged in 20-time epochs (0-6 h to 115-120 h). RESULTS: We analysed 148 neonates with sepsis (proven sepsis = 77, probable sepsis = 71) and 126 with no-sepsis. Neonates with proven/probable sepsis and no-sepsis had comparable PI and PVI values. Among 148 neonates with sepsis, 43 (29%) died. Non-survivors had significantly lower PI values than survivors (mean difference 0.21 [95% CI 0.14-0.29], p-value <0.001). PI had a significant but modest discriminative ability to identify non-survivors. However, PI did not independently predict mortality. CONCLUSION: Neonates with proven/probable sepsis and no-sepsis had comparable PI and PVI values in the first 120 h of sepsis. PI but not PVI values were significantly lower in non-survivors than survivors. PI did not independently predict in-hospital mortality. Due to modest discriminative ability, PI should be interpreted along with other vital signs to take clinical decisions.

Room air versus 100% oxygen for delivery room resuscitation of preterm neonates in low resource settings: A randomised, blinded, controlled trial.

AIM: International Liaison Committee on Resuscitation (ILCOR-2020) report recommend starting delivery room resuscitation of all preterm neonates of <35 weeks' gestation with 21-30% oxygen. However, the correct initial oxygen concentration for resuscitation of preterm neonates in delivery room is inconclusive. In this blinded, randomised, controlled trial, we compared room air with 100% oxygen for oxidative stress and clinical outcomes in delivery room resuscitation of preterm neonates. METHODS: Preterm neonates 28-33 weeks' gestation requiring positive pressure ventilation at birth were randomly allocated to room air or 100% oxygen. Investigators, outcome assessors and data analysts were blinded. Rescue 100% oxygen was used whenever trial gas failed (need for positive pressure ventilation >60 s or chest compression). PRIMARY OUTCOME: Plasma 8-isoprostane levels at 4 h of age. SECONDARY OUTCOMES: mortality by discharge, bronchopulmonary dysplasia, retinopathy of prematurity and neurological status at 40 weeks post-menstrual age. All subjects were followed till discharge. Intention to treat analysis was carried out. RESULTS: A total of 124 neonates were randomised to room air (n = 59) or 100% oxygen (n = 65). Isoprostane level at 4 h was similar in both the groups (median (interquartile range): 280 (180-430) vs. 250 (173-360) pg/mL, P = 0.47). No difference was observed in mortality and other clinical outcomes. Room air group had higher treatment failures (27 (46%) vs. 16 (25%); relative risk (RR) 1.9 (1.1-3.1)) and took longer time to establish regular respiration (230 ± 231 vs. 182 ± 261, mean difference = 48 (40, 136) seconds). CONCLUSIONS: In preterm neonates 28-33 weeks' gestation requiring resuscitation in the delivery room, room air (21%) is not the correct concentration to initiate resuscitation. Larger controlled trials involving multiple centres in low- and middle-income countries are immediately required for a conclusive answer.

Clinical characteristics & outcome of SARS-CoV-2 infected neonates presenting to paediatric emergency.

Background & objectives: Data on neonatal COVID-19 are limited to the immediate postnatal period, with a primary focus on vertical transmission in inborn infants. This study was aimed to assess the characteristics and outcome of COVID-19 in outborn neonates. Methods: All neonates admitted to the paediatric emergency from August 1 to December 31, 2020, were included in the study. SARS-CoV-2 reverse transcription- (RT)-PCR test was done on oro/nasopharyngeal specimens obtained at admission. The clinical characteristics and outcomes of SARS-CoV-2 positive and negative neonates were compared and the diagnostic accuracy of a selective testing policy was assessed. Results: A total of 1225 neonates were admitted during the study period, of whom SARS-CoV-2 RT-PCR was performed in 969. The RT-PCR test was positive in 17 (1.8%). Mean (standard deviation) gestation and birth weight of SARS-CoV-2-infected neonates were 35.5 (3.2) wk and 2274 (695) g, respectively. Most neonates (11/17) with confirmed COVID-19 reported in the first two weeks of life. Respiratory distress (14/17) was the predominant manifestation. Five (5/17, 29.4%) SARS-CoV-2 infected neonates died. Neonates with COVID-19 were at a higher risk for all-cause mortality [odds ratio (OR): 3.1; 95% confidence interval (CI): 1.1-8.9, P=0.03]; however, mortality did not differ after adjusting for lethal malformation (OR: 2.4; 95% CI: 0.7-8.7). Sensitivity, specificity, accuracy, positive and negative likelihood ratios (95% CI) of selective testing policy for SARS-CoV-2 infection at admission was 52.9 (28.5-76.1), 83.3 (80.7-85.6), 82.8 (80.3-85.1), 3.17 (1.98-5.07), and 0.56 (0.34-0.93) per cent, respectively. Interpretation & conclusions: SARS-CoV-2 positivity rate among the outborn neonates reporting to the paediatric emergency and tested for COVID-19 was observed to be low. The selective testing policy had poor diagnostic accuracy in distinguishing COVID-19 from non-COVID illness.

Relationship between Decrease in Urine Output following Treatment with Prostaglandin Inhibitors and PDA Closure.

OBJECTIVE: Prostaglandin inhibitors are used for the treatment of patent ductus arteriosus (PDA) and they often transiently decrease the urine output (UO) due to prostaglandin inhibition in the renal vasculature. We hypothesized that preterm infants whose renal vasculature shows greater sensitivity to prostaglandin inhibitors are likely to have ductal tissue with greater sensitivity to the same. Our objective was to determine whether the decrease in UO following treatment of PDA with a prostaglandin inhibitor is associated with a higher probability of PDA closure. STUDY DESIGN: In a prospective, proof-of-concept, cohort study, we enrolled 40 preterm neonates with hemodynamically significant PDA (hsPDA), being treated with a prostaglandin inhibitor. The key predictor, UO, was measured at baseline and daily until 72 hours. We repeated echocardiography daily until PDA closure or the end of treatment. The key outcome was PDA closure. We compared "PDA-closed" (n = 28) and "PDA-open" (n = 12) groups for change in UO from baseline. RESULTS: The median (Q1, Q3) percent decrease in UO (figures rounded off to integers) was greater in the "PDA-closed" versus "PDA-open" group: from baseline to 0 to 24 hours [-45% (-55%, +0.04%) vs. -15% (-28%, +49%)]; baseline to 24 to 48 hours [-41% (-53%, +14%) vs. -3% (-25%, +62%), p = 0.03] and baseline to 48 to 72 hours [-33% (-49%, +32%) vs. +21% (-7%, +98%), p = 0.02]. Decrease in UO preceded PDA closure. The "PDA-closed" group had significantly greater weight loss, despite a greater decrease in UO. A decrease in UO of 27 and 17% by 24 to 48 hours and 48 to 72 hours, respectively, best predicted PDA closure. CONCLUSION: A decrease in UO after treating hsPDA with a prostaglandin inhibitor is associated with successful closure of PDA. KEY POINTS: · Prostaglandin inhibition causes both decrease in urine output and PDA closure following medical treatment. · The association between drug-induced decrease in urine output and PDA closure has been inadequately studied.. · Decrease in urine output after treatment with prostaglandin inhibitors increases the chances of PDA closure..

Is Lumbar Puncture Avoidable in Low-Risk Neonates with Suspected Sepsis?

OBJECTIVE: Performing lumbar punctures (LP) in all clinically suspected neonatal sepsis, as per current recommendations, results in many "negative" LPs. LPs are not without their own risks. With the intention of minimizing unnecessary LPs among neonates, we aimed to identify a subgroup at extremely low risk of developing possible meningitis so that an LP could be safely avoided in it. STUDY DESIGN: This was a prospective, observational, and cross-sectional study in a level III neonatal unit. We included 300 episodes, in which LP was performed for suspected sepsis. We recorded a comprehensive set of clinico-demographic variables, laboratory parameters, sickness score, organ dysfunction score, and organ localization and studied association of these factors with "definite (culture positive) or possible meningitis." "Possible" meningitis was defined with liberal criteria, intending not to miss any meningitis. A subgroup without a single factor associated with "definite or possible meningitis" was analyzed for incidence of meningitis. RESULTS: There were 121 episodes of "definite or possible meningitis" among 300 episodes of sepsis. On unadjusted analysis, apnea, irritability, high-pitched cry, seizures, neutrophilia, high C-reactive protein (CRP), score for acute neonatal physiology and perinatal extension II (SNAPPE-II), urine output, and leukomalacia were associated with "definite or possible" meningitis (p < 0.05). On multivariate analysis, no apneas, no neutrophilia, and normal CRP were independently associated with "no definite or possible meningitis." Nevertheless, the subgroup that had a combination of no apneas, no neutrophilia, and normal CRP (n = 118) had a 29% probability of "definite or possible meningitis." CONCLUSION: The lowest risk subgroup had a 29% chance of having "definite or possible" meningitis. There is no subgroup that we could identify among neonates with suspected sepsis, in which it is safe to avoid an LP. KEY POINTS: · LP are performed in all cases of late onset neonatal sepsis.. · Previous authors unsuccessfully tried to identify high-risk groups for performing LP.. · We were unable to identify an extremely low-risk group in which LP could be safely avoided..

Neuroimaging Spectrum of Severe Hypernatremia in Infants with Neurological Manifestations.

BACKGROUND: Variable neurological manifestations and imaging findings have been described in children with severe hypernatremia. We aimed to describe the spectrum of neuroimaging changes in infants with severe hypernatremia. METHODS: This retrospective study included infants with severe hypernatremia (serum sodium >160 mEq/L), abnormal neurological examination, and an abnormal magnetic resonance imaging (MRI) of the brain over a period of 2 years in a tertiary care hospital. Relevant clinical data, including the feeding practices, clinical features, complications, and biochemical and radiological parameters, were entered in a structured pro forma. MRI findings were classified as vascular (hemorrhages and cerebral sinus venous thrombosis), osmotic demyelination syndrome (pontine and extrapontine myelinolyses), and white matter changes. RESULTS: The common clinical features in the neonates were poor feeding (n = 4) and decreased urine output (n = 4); the older infants presented with gastrointestinal losses (n = 5). All cases had dehydration with encephalopathy. The patterns of radiological injury were vascular (hemorrhages, n = 5 and venous thrombosis, n = 3), osmotic demyelination (n = 8), and white matter changes (n = 7). Coagulopathy was correlated with the vascular complications (r = 0.8, p < 0.0001); the degree of dehydration was correlated with the venous thrombosis (r = 0.7, p < 0.04) and acute kidney injury (r = 0.8, p < 0.001). Neurological sequelae were seen in four cases and correlated with hypernatremia (r = 0.6, p = 0.03) and hyperosmolarity (r = 0.6, p = 0.03). CONCLUSION: Characteristic neuroimaging findings are vascular changes in the form of venous thrombosis and hemorrhages, osmotic demyelination and white matter tract injury, and/or mostly combinations of these findings. Severe hypernatremia and resulting hyperosmolarity frequently cause neurological sequelae in neonates and infants.

Effect of early withdrawal of phenobarbitone on the recurrence of neonatal seizures: An open-label randomized controlled trial.

BACKGROUND: The long-term administration of phenobarbitone in neonates may be associated with adverse neurological outcome. The timing of stopping phenobarbitone maintenance after acute seizure control in neonates is a matter of debate. OBJECTIVES: To study the effect of early withdrawal of phenobarbitone on recurrence of neonatal seizures. STUDY DESIGN: Open-label randomized controlled trial. PARTICIPANTS: Outborn neonates (≥34 weeks of gestation to <28 days of postnatal period) with seizures (n = 221) admitted to Neonatal unit in Pediatric emergency of a tertiary care hospital in north India over 1 year. INTERVENTION: After a loading dose of phenobarbitone (20 mg/kg), neonates who remained seizure free for at least 12 h were enrolled after written informed consent from parents, and randomized (computer generated block randomization) to 'phenobarbitone withdrawal group' (n = 112) where phenobarbitone maintenance was stopped and 'phenobarbitone continued group' (n = 109) where phenobarbitone maintenance was continued until discharge and further as per clinician's discretion. OUTCOMES: The primary outcome was seizure recurrence until discharge and secondary outcomes were time to reach full enteral feeds, duration of hospital stay, abnormal neurological status at discharge, and mortality in two groups. RESULTS: The baseline variables were comparable in 2 groups. The incidence of seizure recurrence was similar in the phenobarbitone withdrawal and phenobarbitone continued groups (50% vs. 37.6%, respectively, p = 0.078). Among secondary outcomes, the phenobarbitone withdrawal and continued groups had similar time to reach full enteral feeds (4.02 days vs. 4.2 days, p = 0.75), duration of hospital stay (6.3 days vs. 6.5 days, p = 0.23), abnormal neurological status at discharge (45.6% vs. 38%, p = 0.39), and mortality (11.6% vs. 8.3%, p = 0.50). CONCLUSION: Early withdrawal of phenobarbitone in neonatal seizures does not lead to a significant increase in the rate of seizure recurrence.

Neonatal Dengue With HLH: Perks of Early Diagnosis and Management.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, aggressive syndrome. It can be primary, which involves genetic mutation with an early presentation, or secondary to infections, malignancies, etc., due to absence of immune downregulation. It is a very rare condition in newborns. Dengue is a potential virus causing HLH, but, in newborns, there are only few case reports and limited clinical literature. OBSERVATION: Herein, in this report, we highlight a case of neonatal HLH, triggered by perinatal dengue. The neonate manifested clinically within the first week of life, the earliest reported timeline so far in the literature. CONCLUSION: HLH should be excluded in neonates especially when multisystem involvement cannot be explained by sepsis alone.

Prevalence & spectrum of congenital anomalies at a tertiary care centre in north India over 20 years (1998-2017).

Background & objectives: Congenital anomalies lead to significant morbidity and mortality. Systematically published data on the prevalence and spectrum of congenital anomalies from India are scarce. This study was aimed to ascertain the prevalence, spectrum, trend, and outcome of congenital anomalies at a tertiary care centre in north India over two decades. Methods: Electronic records of all live births from January 1998 to December 2017 were retrieved, and the neonates with congenital anomaly were included in this retrospective analysis. International Statistical Classification of Diseases and Related Health Problems, tenth revision (ICD-10) was used for uniformity and international comparison. The further sub-categorization was done as per the WHO birth defects surveillance manual. The prevalence of individual as well as overall congenital anomalies was calculated. Run charts were used to analyze the trends. Results: In the two decades studied (1998-2017), there were 86850 live births, of which 1578 [1.82%, 95% confidence interval (CI): 1.73-1.91%] neonates had a major congenital anomaly. The overall prevalence of anomalies was 182 (95% CI: 173-191) per 10,000 live births. Malformation of the circulatory system was the most common (28.0%) followed by musculoskeletal (18.6%) and urinary system (14.3%). Congenital anomaly-related death rate was 6.78 per 1000 live births. No significant trend was observed in the annual prevalence, individual malformations or contribution of congenital anomalies to overall mortality over the two decades. Interpretation & conclusions: Our results showed a high prevalence of congenital anomalies which could be responsible for significant mortality, warranting the need for a national surveillance programme and birth defect services. It is important to have a national database to know the overall burden and spectrum of congenital anomalies in the country.

Microorganisms Profile and Antimicrobial Resistance Pattern in Outborn Neonates in Northern India: A Hospital-Based Observational Study.

BACKGROUND: Neonates born somewhere else (outborn) and treated in a referral centre have different microbiological profile. We report the microorganism's profile and antimicrobial resistance (AMR) in blood culture proven sepsis in outborn neonates. METHODS: Culture positive neonatal sepsis from a neonatal unit of a referral institute catering to outborn neonates was studied over an 18 months duration. Data from the hospital information system were used to analyse the culture positivity rates, the spectrum of the microorganisms isolated and AMR pattern. RESULTS: Out of 5258 admitted neonates, 3687 blood samples were sent for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Gram-positive cocci (GPC) were the most common [240 (45%)] followed by gram-negative bacilli (GNB) [233 (43.4%)] and fungi [64 (11.9%)]. Coagulase negative staphylococcus (CONS) contributed to two-thirds of GPC followed by Klebsiella [93 (17.3%)] and Acinetobacter species [52 (9.7%)]. In 403 (75%) neonates, organisms grew in the samples sent at or within 24 h of admission. The case fatality rate was significantly higher in those with culture positive sepsis. The resistance to meropenem and imipenem was documented in 57.1% and 49.7%, respectively and 48% of the GNB was multidrug resistant. CONCLUSIONS: CONS followed by Klebsiella species were the most common organisms isolated. Three-fourths of the neonates had organisms grown at or within 24 h from admission. More than half of the GNB were multidrug resistant. The case fatality rate was significantly higher in those with culture positive sepsis.

Sepsis is the third most common cause of neonatal mortality globally. Outborn neonates differ in their microorganisms' profile and antimicrobial resistance (AMR) pattern in comparison to inborn neonates. In this study, we report the microorganisms profile and their AMR pattern in blood culture proven sepsis in a large cohort of outborn (extramural) neonates admitted to the index institute. We have also presented the state-wise profile and have compared their AMR pattern. Out of the 5258 admitted neonates, 3687 blood samples were sent for culture for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Coagulase-negative staphylococcus (CONS) followed by Klebsiella species were the most common organisms isolated from this large cohort of outborn neonates. More than 75% of the neonates grew the organisms within 24 h from admission indicating that many of them harboured the organisms at admission. Case fatality rate was significantly higher in those neonates with culture positive sepsis in comparison to culture negative sepsis. Close to 50% of the gram-negative bacilli isolates were multidrug resistant and half of them were extensively drug resistant. A significant between-state difference in organism profile and their AMR patterns were observed.

Oral Paracetamol vs Oral Ibuprofen in Patent Ductus Arteriosus: A Randomized, Controlled, Noninferiority Trial.

OBJECTIVE: To test the hypothesis that oral paracetamol is non-inferior to oral ibuprofen in closing hemodynamically significant patent ductus arteriosus (hsPDA) with an a priori noninferiority (NI) margin of 15%. STUDY DESIGN: Multicenter, randomized, controlled, NI trial conducted in level III neonatal intensive care units. Consecutively inborn preterm neonates of <32 weeks of gestation with hsPDA were included. Those with structural heart disease, major malformations, and contraindications for enteral feeding or for administration of study drugs were excluded. Interventions included oral paracetamol in the experimental arm and oral ibuprofen in the active control arm. The primary outcome was closure of hsPDA by 24 hours from the last dose of the study drug. Secondary outcome measures included closure of hsPDA by 24 hours after the first course of the study drug, rate of reopening after the first course, and adverse events associated with the study drug. RESULTS: Out of 1250 neonates screened, 161 were randomized. Oral paracetamol was noninferior to oral ibuprofen in closure of hsPDA by both per protocol analysis (62 [95.4%] vs 63 [94%]; relative risk [RR], 1.01 [95% CI, 0.94-1.1]; risk difference [RD], 1.4 [95% CI, -6 to 9]; P = .37) and intention-to-treat analysis (63 [89%] vs 65 [89%]; RR, 0.99 [95% CI, 0.89-1.12]; RD, -0.3 [95% CI, -11 to 10]; P = .47). All adverse events were comparable in the 2 study arms. CONCLUSIONS: Oral paracetamol is noninferior to oral ibuprofen for the closure of hsPDA in preterm neonates of <32 weeks of gestation. No difference was observed in the adverse events studied.

Low vasopressin and progression of neonatal sepsis to septic shock: a prospective cohort study.

The study objective was to analyze the association between low plasma vasopressin and progression of sepsis to septic shock in neonates < 34 weeks gestation. Septic neonates of < 34 weeks gestation were consecutively enrolled; moribund neonates and those with major malformations were excluded. Subjects were monitored for progression of sepsis to septic shock over the first 7 days from enrolment. Plasma vasopressin levels and inducible nitric oxide synthase levels were measured at the onset of sepsis (T0), severe sepsis (T1), and septic shock (T2). Primary outcome was plasma vasopressin levels at the point of sepsis in those who progressed to septic shock in comparison with matched nested controls in the non-progression group. Forty-nine (47%) enrolled subjects developed severe sepsis or septic shock. Plasma vasopressin levels (pg/ml) at the onset of sepsis were significantly low in those who progressed to septic shock (median (IQR), 31 (2.5-80) versus 100 (12-156); p = 0.02). After adjusting for confounders, vasopressin levels were independently associated with progression to septic shock (adjusted OR (95% CI), 0.97 (0.96, 0.99); p = 0.01).Conclusion: Preterm septic neonates who progressed to septic shock had suppressed vasopressin levels before the onset of shock. Low vasopressin levels were independently associated with progression to septic shock.What is known:• In animal sepsis models and adult septic patients, exuberant production of nitric oxide metabolites and low vasopressin levels have been reportedly associated with progression to septic shock.• Vasopressin levels have been variably reported as low as well as elevated in children with septic shock.What is New:• Preterm neonates who progressed from sepsis to septic shock had significantly lower levels of vasopressin before the onset of shock in comparison with those who did not progress.• Low vasopressin levels independently predicted the progression from sepsis to septic shock in this population.

Serum C-Reactive Protein Levels in Healthy Neonates in Different Gestational and Postnatal Ages.

There is paucity of normative data on serum C-reactive protein (CRP) in neonates. In Part I of study, we compared CRP in healthy neonates (from 28°/7 weeks to 416/7 weeks of gestation) between various gestational and postnatal age groups in first week. We planned recruitment of 50 participants each in 'term', 'late preterm' and 'moderate-to-very preterm' groups, equally divided in '24-95 h' and '96-168 h' postnatal age sub-groups. In Part II of study, we assayed CRP weekly in moderate-to-very preterm neonates until day 28 to evaluate its trend. Among 154 subjects, term neonates had higher CRP, with highest values among term infants aged 24-95 h. Barring postnatal age, maternal/perinatal factors did not affect CRP levels. CRP did not change significantly over 28 days in moderate-to-very preterm neonates. In conclusion, serum CRP in healthy neonates is highest among term infants aged 24-95 h and does not vary significantly in the first month of life among moderate-to-very preterm infants.

Epinephrine versus dopamine in neonatal septic shock: a double-blind randomized controlled trial.

We compared epinephrine and dopamine as a first-line vasoactive drug in 40 neonates (enrolled in two gestational age strata ≤ 306/7 and ≥ 310/7 weeks) with fluid-refractory septic shock. Epinephrine or dopamine was initiated at 0.2 or 10 µg/kg/min, respectively. If shock persisted after 15 min, epinephrine or dopamine was increased to 0.3 or 15 µg/kg/min, respectively (16-30 min), and thereafter to 0.4 or 20 µg/kg/min (31-45 min). Proportion of neonates achieving 'reversal of shock' (defined as systolic and diastolic BP > fifth centile and capillary filling time < 3 s and left ventricular output ≥ 150 mL/kg/min) by 45 min [5 (25%) vs 6 (30%), RR 0.83 (95% CI 0.30, 2.29)]; haemodynamic stability (shock reversal for ≥ 120 min without escalation of vasoactive drugs) anytime during therapy [10 (50%) vs 6 (30%), RR 1.67 (95% CI 0.75, 3.71)]; and all-cause mortality by 28 days [14 (70%) vs 16 (80%), RR 0.87 (95% CI 0.61, 1.26)] were comparable in the epinephrine and dopamine groups, respectively. On stratified analysis, we observed an interaction of gestational age strata with the group of allocation favouring epinephrine in neonates ≤ 306/7 weeks.Conclusion: Epinephrine (0.2-0.4 µg/kg/min) and dopamine (10-20 µg/kg/min) had comparable efficacy and safety in neonatal septic shock.Clinical Trial registry name and registration number: The study was registered with Clinical Trial Registry of India CTRI/2015/10/006285. What is Known: • The choice of vasoactive drugs in neonatal septic shock is empirical and dopamine is the conventional first-line vasoactive drug. • There are no randomized controlled trials comparing dopamine and epinephrine in neonatal septic shock. What is New: • In this study, epinephrine and dopamine had comparable efficacy and safety as a first-line vasoactive drug in management of neonatal septic shock. • On stratified analysis in a limited sample, epinephrine was associated with better outcomes in neonates ≤ 306/7 weeks.

Nasal injury and comfort with jet versus bubble continuous positive airway pressure delivery systems in preterm infants with respiratory distress.

Nasal injuries with use of nasal continuous positive airway pressure (CPAP) range from blanching of nasal tip to septal necrosis and septal drop. This analysis was done in preterm neonates of < 34-week gestation, who received nasal CPAP as primary support as part of a randomized trial comparing Jet device with Bubble device for delivery of CPAP, both through nasal prongs of different structure, make and fixation methods. Nasal injury was assessed using a validated nasal injury score. Out of 170 neonates enrolled, 103 (61%) had nasal injuries; moderate and severe injuries were observed in 18 (11%) and 8 (5%) infants, respectively. Septum was the most common site injured. The incidence and severity of nasal injury were significantly lesser in Jet group compared to Bubble group [RR 0.6 (95% C.I. 0.5-0.8); p < 0.001]. Similarly, neonates in Jet group had lesser average [median (IQR): 3 (3,4) vs. 4 [8, 14]; p = 0.04] as well as peak N-PASS pain scores [median (IQR): 4 [8, 14] vs. 5 [13, 16]; p = 0.01] in comparison to Bubble group. However, Jet group neonates had significantly more common prong displacements. CONCLUSION: Bubble CPAP device with its nasal interface had higher and more serious incidence of nasal injuries in comparison to Jet CPAP device. What is known: • Nasal injuries are becoming increasingly common with use of nasal CPAP low gestational age, low birth weight, longer use of CPAP and longer NICU stay are risk factors for such injuries • Validated nasal injury scores have been created for assessment of nasal trauma in neonates What is new: • Bubble device with its interface had higher and more serious incidence of nasal injuries in comparison to Jet device • Even though pain assessed by N-PASS was less with Jet device, prong displacements were more frequent with its system.

Predictive Ability of Amplitude Integrated Electroencephalography for Adverse Outcomes in Neonates with Sepsis-Associated Encephalopathy: A Cohort Study.

The authors examined the prevalence of abnormal amplitude integrated electroencephalography (aEEG) patterns in neonates diagnosed with sepsis-associated encephalopathy (SAE). They recorded 36626 min of aEEG in 75 study neonates. Encephalopathy was defined by the Brighton Collaboration Neonatal Encephalopathy criteria. Neonates with primary outcome [either non-survivors or survivors with abnormal neurological examination at discharge using Amiel-Tison assessment tool, n = 58, (77%)] were compared with 17 survivors having normal neurological examination at discharge. Severely abnormal aEEG patterns (isoelectric voltage, continuous low voltage, burst suppression) collectively represented 31% of total 36626 min aEEG tracings. Neonates experiencing primary outcome had significantly higher Burdjalov scores than survivors with normal neurological exam (p value 0.01). After adjusting for gestational age, birth weight, and invasive ventilation, severely abnormal aEEG (aOR 5.8, 95% CI 1.7-19.5, p value 0.005) and Burdjalov score (aOR 0.77, 95% CI 0.63-0.95, p value 0.01) were independently associated with death or abnormal neurological examination at discharge.

Initial Oxygen Concentration for the Resuscitation of Infants Born at Less Than 32 Weeks' Gestation: A Systematic Review and Individual Participant Data Network Meta-Analysis.

Importance: Resuscitation with lower fractional inspired oxygen (FiO2) reduces mortality in term and near-term infants but the impact of this practice on very preterm infants is unclear. Objective: To evaluate the relative effectiveness of initial FiO2 on reducing mortality, severe morbidities, and oxygen saturations (SpO2) in preterm infants born at less than 32 weeks' gestation using network meta-analysis (NMA) of individual participant data (IPD). Data Sources: MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov, and WHO ICTRP from 1980 to October 10, 2023. Study Selection: Eligible studies were randomized clinical trials enrolling infants born at less than 32 weeks' gestation comparing at least 2 initial oxygen concentrations for delivery room resuscitation, defined as either low (≤0.3), intermediate (0.5-0.65), or high (≥0.90) FiO2. Data Extraction and Synthesis: Investigators from eligible studies were invited to provide IPD. Data were processed and checked for quality and integrity. One-stage contrast-based bayesian IPD-NMA was performed with noninformative priors and random effects and adjusted for key covariates. Main Outcomes and Measures: The primary outcome was all-cause mortality at hospital discharge. Secondary outcomes were morbidities of prematurity and SpO2 at 5 minutes. Results: IPD were provided for 1055 infants from 12 of the 13 eligible studies (2005-2019). Resuscitation with high (≥0.90) initial FiO2 was associated with significantly reduced mortality compared to low (≤0.3) (odds ratio [OR], 0.45; 95% credible interval [CrI], 0.23-0.86; low certainty) and intermediate (0.5-0.65) FiO2 (OR, 0.34; 95% CrI, 0.11-0.99; very low certainty). High initial FiO2 had a 97% probability of ranking first to reduce mortality. The effects on other morbidities were inconclusive. Conclusions and Relevance: High initial FiO2 (≥0.90) may be associated with reduced mortality in preterm infants born at less than 32 weeks' gestation compared to low initial FiO2 (low certainty). High initial FiO2 is possibly associated with reduced mortality compared to intermediate initial FiO2 (very low certainty) but more evidence is required.