Lung ultrasound for prediction of surfactant requirement in Indian preterm neonates: a diagnostic accuracy study.

Surfactant replacement for respiratory distress syndrome (RDS) is currently guided by oxygen (FiO2) requirement in preterm neonates. Lung ultrasound (LUS) has emerged as an important predictive tool; however, there is a paucity of evidence from developing countries. The objective of this study was to determine the diagnostic accuracy of the LUS score in comparison to standard criteria based on FiO2 requirement for prediction of surfactant requirement. In this prospective study, preterm neonates of < 34 weeks' gestation with RDS were included within 2 h of life. Surfactant was administered if the FiO2 requirement exceeded 30%. Baseline characteristics, respiratory parameters, and LUS clips were recorded soon after birth and compared between the surfactant and non-surfactant groups. LUS scoring was later performed by masked assessors which was not used in the management of neonates. Among 82 neonates (mean gestation 30.6 weeks and weight 1375 g) included in the study, 33 (40.2%) received surfactant. The surfactant group had a higher Silverman score, required higher FiO2 and mean airway pressure, and needed invasive ventilation more frequently. The mean (± SD) LUS score was significantly higher in the surfactant (9.4 ± 3.2) compared to the non-surfactant group (5.1 ± 2.1). The diagnostic accuracy of LUS scoring was determined by ROC curve analysis (AUC (95% CI): 0.83 (0.74-0.92), p < 0.01). A cutoff score of ≥ 8 for LUS was considered optimal for the prediction of surfactant requirement (sensitivity and specificity (95% CI) of 70% (51-84) and 80% (66-90), respectively).    Conclusion: Lung ultrasound is a valid diagnostic tool for the prediction of surfactant requirements in resource-limited settings. What is Known: • Lung ultrasound has a good diagnostic accuracy in predicting the need for surfactant administration in preterm neonates in developed countries, but its role in developing countries is unclear. What is New: • Lung ultrasound proved to be a valid diagnostic tool in predicting surfactant replacement therapy in resource-limited settings. • The diagnostic performance of lung ultrasound was better in neonates on non-invasive ventilation, compared to invasive ventilation.

Transitional Hemodynamics in Neonates Born Through Meconium-Stained Amniotic Fluid: A Prospective Observational Study.

Neonates born through meconium-stained amniotic fluid (MSAF) are at increased risk of altered cardiopulmonary transition at birth. There is a paucity of literature evaluating the transitional hemodynamics in these neonates. We aimed to evaluate transitional hemodynamics via echocardiography in neonates born through MSAF, compared to healthy neonates. The primary objective was to assess pulmonary vascular resistance using left pulmonary artery-velocity time integral (LPA-VTI). The secondary objectives were to assess other pulmonary vascular parameters and myocardial function. We enrolled 35 MSAF-born and 35 healthy neonates. Echocardiography was performed at 24 and 48 h of life by a pediatric cardiologist. Echocardiographic parameters were compared between MSAF-born and healthy neonates, and between MSAF-born neonates who developed meconium aspiration syndrome (MAS) and who did not (non-MAS). Among 35 MSAF-born neonates, 14 (40%) were non-vigorous, 18 (51%) required admission to neonatal intensive care unit, 8 (23%) developed MAS, 3 (9%) pulmonary hypertension and 1 (3%) air leak. On echocardiography, LPA-VTI (cm; mean ± SD) was significantly decreased at 24 and 48 h in MSAF-born neonates (14.38 ± 2.48; 15.55 ± 2.48), compared to healthy neonates (16.60 ± 2.14; 17.66 ± 2.71), respectively. Further, LPA-VTI was significantly reduced at 24 and 48 h among MAS (11.81 ± 3.0; 12.43 ± 2.5), compared to non-MAS neonates (15.15 ± 1.72; 16.48 ± 1.55), respectively. Other pulmonary vascular and myocardial function parameters were comparable between the two groups. Pulmonary adaptation was significantly delayed in neonates with MSAF, which was more pronounced in MAS neonates. Further studies should explore the utility of these parameters for early prediction of cardiorespiratory morbidities in this population.

Efficacy and safety of short- vs. standard-course antibiotics for culture-negative neonatal sepsis: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis of evidence from randomized controlled trials (RCTs) comparing a short course of antibiotics (2-4 days), to a standard course (5-7 days), for the treatment of culture-negative neonatal sepsis. METHODS: Relevant databases were searched for RCTs comparing short- vs. standard-course of antibiotics for culture-negative sepsis. The primary outcomes were mortality and treatment failure, defined as the reappearance of clinical signs suggestive of sepsis within 7 days of stoppage of antibiotics. Secondary outcomes included neurological impairment, duration of hospital stay, need for oxygen, respiratory support and double-volume exchange transfusion (DVET). RESULTS: Seven RCTs were included in the review with 729 neonates >30 weeks gestational age at birth. No mortality occurred in either of the groups (2 studies; 276 neonates). Treatment failure rates were similar in the short- and standard-course antibiotic groups [7 studies; 729 neonates; risk ratio (RR) = 1.01; 95% confidence interval (CI), 0.55 to 1.86; very low certainty]. The short course of antibiotics resulted in a shorter hospital stay [3 studies; 293 neonates; mean difference (MD), -2.46 days; 95% CI, -3.16 to -1.75]. There was no difference in the need for oxygen supplementation (2 studies; 258 neonates; RR, 1.40; 95% CI, 0.40 to 4.91), any respiratory support (2 studies; 258 neonates; RR, 1.04; 95% CI, 0.92 to 1.17) or DVET (2 studies; 258 neonates; RR, 1.29; 95% CI, 0.56 to 2.95). CONCLUSION: Very-low certainty evidence suggests that a short antibiotic course, compared to a standard course, does not affect treatment failure rates in culture-negative neonatal sepsis. There is a need for well-designed RCTs powered enough to assess critical outcomes such as mortality and neurological sequelae to generate stronger evidence and inform guidelines. PROSPERO REGISTRATION NUMBER: CRD42023437199.

Prolonged antibiotic usage has been associated with increased mortality and morbidity in neonates. The standard practice in culture-negative neonatal sepsis has been to administer antibiotics for 5­7 days, based on expert consensus. In this systematic review, a short course of antibiotics (2­4 days), in comparison to a standard course (5­7 days), did not affect the treatment failure rates in culture-negative neonatal sepsis. However, the certainty of evidence was too low to make robust conclusions. There is a need for well-designed large trials to generate stronger evidence and inform guidelines.

Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

T-Piece resuscitator versus self-inflating bag for delivery room resuscitation in preterm neonates: a randomized controlled trial.

The establishment of adequate ventilation is the cornerstone of neonatal resuscitation in the delivery room (DR). This parallel-group, accessor-blinded randomized controlled trial compared the changes in peripheral oxygen saturation (SpO2), heart rate (HR), and cerebral regional oxygen saturation (crSO2) with the use of a T-piece resuscitator (TPR) versus self-inflating bag (SIB) as a mode of providing positive pressure ventilation (PPV) during DR resuscitation in preterm neonates. Seventy-two preterm neonates were randomly allocated to receive PPV with TPR (n = 36) or SIB (n = 36). The primary outcome was SpO2 (%) at 5 min. The secondary outcomes included the time to achieve a SpO2 ≥ 80% and > 85%, HR > 100/min, fractional-inspired oxygen (FiO2) requirement, minute-specific SpO2, HR and FiO2 trends for the first 5 min of life, need for DR-intubation, crSO2, need and duration of respiratory support, and other in-hospital morbidities. Mean SpO2 at 5 min was 74.5 ± 17.8% and 69.4 ± 22.4%, in TPR and SIB groups, respectively [Mean difference, 95% Confidence Interval 5.08 (-4.41, 14.58); p = 0.289]. No difference was observed in the time to achieve a SpO2 ≥ 80% and > 85%, HR > 100/min, the requirement of FiO2, DR-intubation, and the need and duration of respiratory support. There was no significant difference in the minute-specific SpO2, HR, and FiO2 requirements for the first 5 min. CrSO2 (%) at one hour was lower by 5% in the TPR group compared to SIB; p = 0.03. Other complications were comparable. CONCLUSIONS: TPR and SIB resulted in comparable SpO2 at 5 min along with similar minute-specific SpO2, HR, and FiO2 trends. CLINICAL TRIAL REGISTRATION: Clinical trial registry of India, Registration no: CTRI/2021/10/037384, Registered prospectively on: 20/10/2021, https://ctri.icmr.org.in/ . WHAT IS KNOWN: • Compared to self-inflating bags (SIB), T-piece resuscitators (TPR) provide more consistent inflation pressure and tidal volume as shown in animal and bench studies. • There is no strong recommendation for one device over the other in view of low certainty evidence. WHAT IS NEW: • TPR and SIB resulted in comparable peripheral oxygen saturation (SpO2) at 5 min along with similar minute-specific SpO2, heart rate, and fractional-inspired oxygen requirement trends. • Short-term complications and mortality rates were comparable with both devices.

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

Recommendations for umbilical cord management in intrauterine growth-restricted (IUGR) neonates are lacking. The present randomized controlled trial compared hemodynamic effects of umbilical cord milking (UCM) with delayed cord clamping (DCC) in IUGR neonates > 28 weeks of gestation, not requiring resuscitation. One hundred seventy IUGR neonates were randomly allocated to intact UCM (4 times squeezing of 20 cm intact cord; n = 85) or DCC (cord clamping after 60 s; n = 85) immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24 ± 2 h. Secondary outcomes assessed were anterior cerebral artery (ACA) and superior mesenteric artery (SMA) blood flow indices, right ventricular output (RVO), regional cerebral oxygen saturation (CrSO2) and venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), incidences of in-hospital complications, need and duration of respiratory support, and hospital stay. SVC flow was significantly higher in UCM compared to DCC (111.95 ± 33.54 and 99.49 ± 31.96 mL/kg/min, in UCM and DCC groups, respectively; p < 0.05). RVO and ACA/SMA blood flow indices were comparable whereas CrSO2 was significantly higher in UCM group. Incidences of polycythemia and jaundice requiring phototherapy were similar despite significantly higher venous hematocrit and peak TSB in UCM group. The need for non-invasive respiratory support was significantly higher in UCM group though the need and duration of mechanical ventilation and other outcomes were comparable. CONCLUSIONS:  UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/03/031864). WHAT IS KNOWN: • Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). • An association between UCM and intraventricular hemorrhage in preterm neonates < 28 weeks of gestation is still being investigated. WHAT IS NEW: • Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. • UCM also increases the need for non-invasive respiratory support compared to DCC.

'Lip-to-Tip' study: comparison of three methods to determine optimal insertion length of endotracheal tube in neonates.

The aim of this prospective observational study was to compare the incidence of endotracheal tube (ETT) malposition using weight-based (Tochen), gestation-based (Kempley), and nasotragal length (NTL) methods in deceased neonates and fresh stillbirths. We enrolled deceased neonates and fresh stillbirths within 2 ± 1 h of death or delivery, respectively; without hydrops, tracheostomy or major congenital anomalies affecting face, neck, or thorax. Each enrolled subject was intubated orotracheally, with lip-to-tip distance determined by three methods in random succession. Chest X-ray was acquired after each insertion. The primary outcome was proportion of malpositioned ETTs on chest X-ray (defined as ETT tip not lying between upper border of T1 and lower border of T2 vertebrae), assessed by two experts masked to the methods used. The proportion of malpositioned tubes was not significantly different with any of the three methods: (weight 27/50 (54%), gestation 35/50 (70%), and NTL 35/50 (70%), p value 0.055). The malpositioned tubes were too far in (87/150; 58%) than too far out (10/150; 6.7%).Conclusions: None of the currently recommended methods accurately predicts optimal ETT length in neonates. There is an urgent need for newer bedside modalities for estimating ETT position in neonates. What is known? • NRP guidelines recommend gestation-based and nasotragal length (NTL) methods to estimate initial ETT depth in neonates. Weight-based (Tochen) method is still widely used in neonatal units for ETT depth estimation. Evidence till date has not proven superiority of one method over the other. What is new? • All three methods for ETT depth estimation (Tochen, gestation-based, and NTL) resulted in high rates of ETT malposition in neonates. Formulae, devised from this study based on linear regression models, did not perform well for estimation of optimal ETT position.

Infantile Tremor Syndrome and Subdural Hemorrhage in an Infant with Cystic Fibrosis.

Cystic fibrosis (CF), an autosomal recessive disease with multi-system involvement, may present with bleeding in infancy owing to vitamin K malabsorption. Infantile tremor syndrome (ITS) is an obscure condition associated with vitamin B12 and other micronutrient deficiencies, described predominantly in Indian subcontinent. We describe an infant presenting with ITS and chronic subdural hemorrhage. He was subsequently diagnosed to have CF. The ITS and subdural hemorrhage is rarely reported in children with CF. In the background of increasing recognition of CF in Indian children, this case demonstrates a new association of this disease.

Effect of Splint Application on the Functional Duration of Peripheral Intravenous Cannulation in Neonates: A Systematic Review and Meta-analysis.

BACKGROUND: The application of splints is one of the most used methods to prolong the life span of peripheral intravenous cannulation (PIVC). OBJECTIVE: To assess the effect of splint application on the functional duration of PIVC in neonates. METHODS: This systematic review and meta-analysis identified, appraised, and synthesized available evidence from randomized and quasi-randomized controlled trials (RCT) related to the effects of splint application compared to no splinting on the functional duration of PIVC and its associated complications in term and preterm neonates. Data were pooled using RevMan 5.4. The quality of evidence for predefined outcomes was analyzed by GRADE. RESULTS: Available evidence (5 RCTs, 826 neonates) showed a significantly lesser functional duration of PIVC in the splint group compared to no-splint [Mean Difference (MD) 95% Confidence Interval (CI) -3.07 (-5.63, -0.51); Low Certainty of Evidence (CoE)]. On gestation-based subgroup analysis, PIVC duration remained significantly lesser in the splint group in preterm neonates [MD (95% CI), -5.09 (-9.53, -0.65), 2 studies, n = 220; Low CoE], whereas it was comparable in the term neonates [MD (95% CI), 3.92 (-4.27, 12.10), 2 studies, n = 89; Very low CoE]. The overall complications were comparable between the groups [Risk Ratio (95% CI), 1.02 (1.00, 1.05), 5 studies, n = 826; Very low CoE]. CONCLUSION: Based on the very low to low CoE found in this systematic review, it is not possible to recommend or refute splint application in neonates. Further well-designed RCTs are needed.

Assessment of Patient Satisfaction and Treatment Outcomes in Digital Smile Design vs. Conventional Smile Design: A Randomized Controlled Trial.

Background: The esthetics of a smile holds significant importance in an individual's self-esteem and overall quality of life. In the realm of cosmetic dentistry, smile design has traditionally relied on conventional methods, but recent advances in technology have introduced digital smile design (DSD) as a promising alternative. Materials and Methods: In this randomized controlled trial, 150 adult patients seeking smile enhancement procedures were enrolled and randomly assigned to one of two groups: the DSD group or the conventional smile design group. The DSD group underwent smile design using digital technology, including intraoral scans, computer-aided design, and 3D simulations. Meanwhile, the conventional smile design group received smile design through traditional methods, involving manual impressions, stone models, and manual wax-ups. Patient satisfaction was measured using a visual analog scale (VAS) ranging from 0 to 100 immediately after the procedure, while treatment outcomes were assessed three months post-procedure by dental professionals using a standardized assessment scale. Results: In terms of patient satisfaction, the DSD group demonstrated a mean score of 85.4 (SD ± 6.2), while the conventional smile design group had a mean score of 79.8 (SD ± 7.1). This suggests that patients in the DSD group reported higher levels of satisfaction with their smile enhancements. Regarding treatment outcomes, 92% of patients in the DSD group exhibited excellent restoration fit, occlusion, and esthetics, whereas 78% of patients in the conventional smile design group achieved the same level of excellence. These findings collectively indicate that digital smile design (DSD) may yield superior patient satisfaction and improved treatment outcomes when compared to conventional smile design methods, particularly with regard to esthetic results and overall patient contentment. Conclusion: In conclusion, the results of this randomized controlled trial emphasize the potential advantages of integrating digital technology into smile design procedures.

Investigating the Long-Term Success and Complication Rates of Zirconia Dental Implants: A Prospective Clinical Study.

This study addresses the durability and complications of zirconia dental implants through a prospective clinical investigation. Zirconia implants are increasingly utilized in dental implantation, and a comprehensive understanding of their long-term performance is essential. Background: Zirconia dental implants have gained attention due to their biocompatibility and aesthetics. However, research on their extended success and complication rates is limited. Materials and Methods: A prospective clinical study involved the placement of 30 zirconia dental implants in patients requiring tooth replacement. The implants were followed up for five years. Success was defined as the implant remaining stable and functional. Complications, including peri-implant mucositis and peri-implantitis, were monitored. Statistical analysis included descriptive statistics, Chi-square test, and P-values were set at P < 0.05. Results: The long-term success rate of zirconia dental implants was found to be 93.3%. Among the 30 implants, only 2 exhibited failure. The most common complication was peri-implant mucositis, occurring in 16.7% of implants. Notably, the incidence of peri-implantitis was limited, observed in 6.7% of implants. Statistical analysis showed significant associations between implant failure and smoking (P = 0.021). Conclusion: Zirconia dental implants demonstrated a high long-term success rate of 93.3% over five years. Peri-implant mucositis was the predominant complication, with a relatively low occurrence of peri-implantitis. The findings underscore the potential of zirconia implants for reliable dental implantation. Addressing modifiable risk factors, such as smoking, could further enhance implant success. Continued research is recommended to validate and expand upon these outcomes.

Proud Syndrome: A Rare Cause of Corpus Callosum Agenesis.

Agenesis of the corpus callosum (ACC) is one of the most common congenital brain anomalies with variable associations and outcomes. The incidence of ACC varies from 1.8 per 10,000 live births in normal children to as high as 600 per 10,000 in children with neurodevelopmental problems. Here, we report the case of a female neonate delivered in our institute at term gestation to a gravida 4 mother with partial ACC. The neonate was antenatally diagnosed with ACC. The mother had a previous fetus with a supratentorial cyst that was medically terminated. The neonate had a normal clinical examination, but the ultrasound of the cranium suggested ACC. Given the significant family history, a clinical exome sequencing test revealed a pathogenic frameshift mutation in the ARX gene that causes Proud syndrome. We discuss the relevant points in the diagnosis, workup, and prognosis of ACC through this case. This case highlights the importance of antenatal assessment for timely amniocentesis and a genetic diagnosis to guide the parental decision for continuation of the pregnancy, level 2 scans to detect associated anomalies, and postnatal assessment to determine the cause and prognosis of a neonate with ACC.

Neonatal Pain Response to Various Heel Prick Devices: A Randomized Controlled Trial.

BACKGROUND: Heel prick is a commonly performed painful intervention in neonates. Though different devices are available, there is a need to compare the procedural pain response elicited by them. OBJECTIVE: To compare the neonatal pain response to three different heel prick devices; automatic lancet, manual lancet, and 26-gauge (G) hypodermic needle. DESIGN: Parallel-group three-arm randomized controlled trial. PARTICIPANTS: Clinically stable neonates of gestational age >28 weeks and birth weight >800 g undergoing heel prick for estimation of random blood sugar. METHODS: One hundred and eighty neonates were randomized to automatic lancet (n=59), manual lancet (n=59), or needle (n=62) groups between March, 2021 and August, 2022. The primary outcome was the premature infant pain profile-revised (PIPP-R) score. Secondary outcomes were post-intervention cerebral regional oxygen saturation (CrSO2), changes in CrSO2 (DCrSO2), the time for CrSO2 normalization using near-infrared spectroscopy, duration of audible cry, and the number of squeezes and pricks needed. Intention-to-treat analysis was done. RESULTS: Median (IQR) of PIPP-R scores were comparable in the automatic lancet [6 (4, 7.5)], manual lancet [5.5 (3.5, 8)], and needle [6 (3-9.6)] groups; P=0.59. No difference was observed in post-intervention CrSO2, DCrSO2, and the number of pricks. However, the time required for CrSO2 normalization and the number of squeezes were significantly higher with the needle. CONCLUSION: All three devices induced similar pain responses to heel prick in neonates; though, the number of squeezes needed was higher with the needle.

Correlation of clinical pain scores with cerebral oxygenation in preterm neonates during acute painful procedures: a prospective observational study.

OBJECTIVE: The present study evaluated the correlation of Neonatal Infant Pain Scale (NIPS) and Premature Infant Pain Profile-Revised (PIPP-R), with changes in cerebral oxygenation (ΔcrSO2; measured by near-infrared spectroscopy) in preterm infants during acute painful procedures (heel lance and venepuncture). STUDY DESIGN: Prospective observational study. METHODS: Sixty-four stable preterm (28-36 weeks) neonates were videotaped. NIPS and PIPP-R scores were assessed on video-recordings by two independent assessors. The primary outcome was correlation of ΔcrSO2 with NIPS and PIPP-R scores. RESULTS: Moderate to strong correlations were observed between ΔcrSO2 and NIPS, and ΔcrSO2 and PIPP-R (r = 0.71 and 0.78 during heel lance and r = 0.66 and 0.75 during venepuncture, respectively). NIPS score was found easy to understand and perform by the bedside nurses, and took lesser time as compared to PIPP-R during both the procedures. CONCLUSION: Both pain scores, NIPS and PIPP-R, had good correlation with ΔcrSO2 during acute painful procedures.