Ursodeoxycholic acid for preventing parenteral nutrition-associated cholestasis in neonates: A systematic review and meta-analysis.

BACKGROUND: While ursodeoxycholic acid is used in treating parenteral nutrition-associated cholestasis (PNAC) in neonates, its role in prevention is unclear. OBJECTIVES: In this systematic review and meta-analysis, we attempted to determine the role of ursodeoxycholic acid in preventing PNAC in neonates. METHODS: PubMed, Embase, Cochrane Library, Scopus, and CINAHL databases were searched on September 16, 2023, for interventional studies comparing ursodeoxycholic acid with placebo. RESULTS: Of the 6180 unique records identified, five studies were eligible for inclusion (three randomised and two nonrandomised). Evidence from randomised trials showed that ursodeoxycholic acid prophylaxis did not reduce cholestasis, mortality, sepsis, and necrotising enterocolitis. Ursodeoxycholic acid prophylaxis reduced feed intolerance (RR 0.23 (0.09, 0.64); 1 RCT, 102 neonates), peak conjugated bilirubin levels (MD -0.13 (-0.22, -0.04) mg/dL; 1 RCT, 102 neonates), and time to full enteral feeds (MD -2.7 (-5.09, -0.31) days; 2 RCTs, 76 neonates). There was no decrease in hospital stay and parenteral nutrition duration. Data from nonrandomised studies did not show benefit in any of the outcomes. The certainty of the evidence was low to very low. CONCLUSION: Because of the very low-quality evidence and lack of evidence on critical outcomes, definitive conclusions could not be made on using ursodeoxycholic acid to prevent parenteral nutrition-associated cholestasis in neonates.

Quality of Life of Parents of Very Low Birth Weight Babies Admitted to the Neonatal Intensive Care Unit.

This prospective cohort study was conducted at our tertiary care center from October, 2021 to April, 2022 to compare the parents' health-related quality of life (HRQoL) scores during neonatal intensive care unit (NICU) stay and at 3 months follow-up. Pediatric quality of life inventory (PedsQL) family impact module questionnaires were used in 46 mothers and 39 fathers during NICU stay, and 42 mothers and 38 fathers at 3-month follow-up. Greater proportions of mothers were severely affected and had higher stress levels as compared to fathers both during NICU stay (67.3% vs 48.7%) and at 3 months follow-up (62.7% vs 52.6%). Among the mothers, there was a significant improvement in individual and family functioning median (IQR) HRQL scores at 3-month follow-up [62 (48-83) vs 71(63-79)]. However, the pro-portion of mothers severely affected remained the same at NICU stay and 3-month follow-up (67.3% vs 62.7%).

Examining the Utility of Rapid Salivary C-Reactive Protein as a Predictor for Neonatal Sepsis: An Analytical Cross-Sectional Pilot Study.

This study aimed to compare the rapid bedside quantitative assessment of C-reactive protein (CRP) in saliva to serum CRP to predict blood culture-positive sepsis in neonates. The research was carried out over eight months at Fernandez Hospital in India (February 2021-September 2021). The study included 74 randomly selected neonates with clinical symptoms or risk factors of neonatal sepsis requiring blood culture evaluation. SpotSense rapid CRP test was conducted to estimate salivary CRP. In analysis, the area under the curve (AUC) on the receiver operating characteristics (ROC) curve was used. The study population's mean gestational age and median birth weight were 34.1 weeks (SD: ±4.8) and 2370 g (IQR: 1067-3182). The AUC on ROC curve analysis for predicting culture-positive sepsis was 0.72 (95% CI: 0.58 to 0.86, p-value: 0.002) for serum CRP and 0.83 (95% CI: 0.70 to 0.97, p-value: <0.0001) for salivary CRP. The Pearson correlation coefficient between salivary and serum CRP was moderate (r = 0.352, p-value: 0.002). Salivary CRP cut-off scores were comparable to serum CRP in terms of sensitivity, specificity, PPV, NPV, and accuracy in predicting culture-positive sepsis. The rapid bedside assessment of salivary CRP appears to be an easy and promising non-invasive tool in culture-positive sepsis prediction.

Comparison of STOPS and SNAPPE-II in Predicting Neonatal Survival at Hospital Discharge: A Prospective, Multicentric, Observational Study.

OBJECTIVE: To compare SNAPPE-II and STOPS admission severity scores in neonates admitted to neonatal intensive care unit (NICU) with a gestational age of ≥ 33 wk. METHODS: In this multicenter, prospective, observational study, the sickness scoring was done on all the neonates at 12 h after admission to the NICUs. The scoring systems were compared by the area under the curve (AUC) on the receiver operating characteristics (ROC) curve. RESULTS: A total of 669 neonates with gestational age ≥ 33 wk (mortality rate: 2.4%), who were admitted to five participating NICUs within 24 h of birth, were included. Both SNAPPE-II and STOPS had the good discriminatory and predictive ability for mortality with AUCs of 0.965 [95% confidence interval (CI): 0.94-0.98] and 0.92 (95% CI: 0.87-0.99), respectively. The STOPS scoring system with a cutoff score ≥ 4 on the ROC curve had 85% accuracy, whereas the SNAPPE-II cutoff score ≥ 33 on the ROC curve had 94% accuracy in predicting mortality. CONCLUSION: In infants with the gestational age of ≥ 33 wk, SNAPPE-II and STOPS showed similar predictive ability, but the STOPS score, being a simpler clinical tool, might be more useful in resource-limited settings.

Comparison of CRIB-II with SNAPPE-II for predicting survival and morbidities before hospital discharge in neonates with gestation ≤ 32 weeks: a prospective multicentric observational study.

Various studies validated and compared Score for Neonatal Acute Physiology with Perinatal extension-II (SNAPPE-II) and Clinical Risk Index for Babies-II (CRIB-II) admission sickness severity scores for predicting survival, but very few studies compared them for predicting the morbidities in preterm infants. In this multicenter prospective observational study, SNAPPE-II and CRIB-II newborn illness severity scores were compared for predicting mortality and morbidities in infants with gestational age of ≤ 32 weeks. Major morbidities were classified as bronchopulmonary dysplasia, abnormal cranial ultrasound (presence of intraventricular hemorrhage grade III or more or periventricular leukomalacia grade II to IV), and retinopathy of prematurity requiring treatment. Combined adverse outcome was defined as death or any major morbidity. Comparison of the scoring systems was done by area under the curve (AUC) on receiver operating characteristics curve (ROC curve) analysis. A total of 419 neonates who were admitted to 5 participating NICUs were studied. The mortality rate in the study population was 8.8%. Both CRIB-II (AUC: 0.795) and SNAPPE-II (AUC: 0.78) had good predictive ability for in-hospital mortality. For predicting any one of the major morbidities and combined adverse outcome, CRIB-II had better predictive ability than SNAPPE-II with AUC of 0.83 vs. 0.70 and 0.85 vs. 0.74, respectively. CONCLUSION: In infants with gestational age of ≤ 32 weeks, both CRIB-II and SNAPPE-II are good scoring systems for predicting mortality. CRIB-II, being a simpler scoring system and having better predictive ability for major morbidities and combined adverse outcome, is preferable over SNAPPE-II. WHAT IS KNOWN: • SNAPPE-II and CRIB-II scores have good predictive ability on in-hospital mortality in preterm neonates. WHAT IS NEW: • SNAPPE-II and CRIB-II both have good predictive ability for mortality, but CRIB-II has better ability for short-term morbidities related to the prematurity.

Comparison of Fenton, INTERGROWTH-21st, and Population-Based Growth Charts in Predicting Outcomes of Very Preterm Small-for-Gestational-Age Neonates.

Growth chart aids in management by identifying at-risk neonates with abnormal growth. In this retrospective analysis of 1067 neonates of 26-31 wk gestational age, the utility of 3 growth charts (local population-based, Fenton-2013, and INTERGROWTH-21st) was studied in identifying very preterm neonates at risk of developing complications secondary to intrauterine growth retardation (hypoglycemia, mortality, and BPD at 36 wk). The proportion of neonates classified as small for gestational age was 9% (n = 96) with Fernandez chart, 16.7% (n = 178) with Fenton-2013 chart, and 24.8% (n = 265) with INTERGROWTH-21st charts. The INTERGROWTH-21st charts were more sensitive in identifying neonates developing complications, followed by Fenton-2013 and population-based charts. The population-based charts were more specific, accurate, and precise in differentiating neonates developing complications from those who did not, followed by Fenton-2013 and INTERGROWTH-21st charts. For the outcomes studied, INTERGROWTH-21st charts had reasonable tradeoff between sensitivity and (34%-50%) and specificity (76%-77%).

Outcomes of Very Preterm Neonates Born by Assisted Reproductive Techniques (ART): A Propensity Score Matched Retrospective Cohort Study.

OBJECTIVE: To compare outcomes of preterm neonates born through assisted reproduction techniques (ART) and non-ART conception. METHODS: This retrospective cohort study included very preterm neonates (26 weeks to 31 weeks) admitted to our neonatal unit over a six year period from 2014 to 2019. The primary outcome was composite adverse outcome of mortality or any of the major morbidities i.e., intraventricular hemorrhage (IVH) grade ≤3, periventricular leukomalacia (PVL) grade ≤2, bronchopulmonary dysplasia (BPD) at 36 weeks, and retinopathy of prematurity (ROP) requiring treatment. RESULT: Total of 759 neonates (253 in ART group, 506 in non-ART group) were included after propensity score matching for gestational age, sex, and small for gestational age (SGA). Neonates in ART group had similar rates of composite adverse outcome [aOR (95% CI) 0.86 (0.55 - 1.36)], mortality [0.93, (0.53- 1.64)] BPD [1.18, (0.37 - 3.76)]; ROP requiring treatment [ 0.49 (0.14-1.71], and other morbidities. CONCLUSION: Very preterm neonates born through ART were not at increased risk of adverse neonatal outcomes.

Short-term Outcome and Predictors of Survival Among Neonates with Moderate or Severe Hypoxic Ischemic Encephalopathy: Data From the Indian Neonatal Collaborative.

BACKGROUND: Among term and late preterm infants, hypoxic ischemic encephalopathy (HIE) is an important cause of mortality, and neurologic morbidity among survivors. OBJECTIVE: The primary objective was to study the incidence of survival to discharge among late preterm and term infants with moderate or severe HIE. Secondary objectives were to explore variation in the management of HIE across participating sites and to identify the predictors of survival. SETTING: Indian Neonatal Collaborative (INNC), a network of 28 neonatal units in India. STUDY DESIGN: Retrospective cohort. PARTICIPANTS: Late preterm (34-36 weeks) and term (37-42 weeks) infants with moderate to severe HIE from 2018-2019. OUTCOME: The primary outcome was survival to discharge (including discharged home and transfer to other hospital). A multivariate logistic regression model was constructed to identify the predictors of survival. RESULTS: Of 352 infants with moderate or severe HIE, 59% received therapeutic hypothermia. Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE (aOR 0.04; 95% CI 0.02-0.10), persistent pulmonary hypertension (PPHN) (aOR 0.22; 95% CI 0.08-0.61) and requirement of epinephrine during resuscitation (aOR 0.21; 95% CI 0.05-0.84) were independently associated with decreased odds of survival to discharge. CONCLUSION: Survival to discharge among infants with moderate or severe HIE was 82%. Severe HIE, requirement of epinephrine during resuscitation and PPHN decreased the odds of survival.

Propensity-Matched Comparison of Very Preterm Small- and Appropriate-for-Gestational-Age Neonates.

OBJECTIVE: Comparison of mortality and major morbidities between very preterm (< 32 wk gestational age) small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) neonates. METHODS: A retrospective observational study of neonates born between 26-31 wk gestational age from January 2015 to December 2019 was done in level-3 neonatal intensive care unit of a high-risk perinatal center in South India. RESULTS: Of the 1,178 very preterm neonates born in the study period, 909 were eligible for inclusion. After propensity score matching for gestational age, gender, and antenatal steroid use, 592 (444 AGA and 148 SGA) were included in the final analysis. SGA neonates had increased odds of necrotizing enterocolitis (NEC) ≥ stage 2A [adjusted odds ratio (aOR): 2.2; 95% CI: 1.15-4.21], abnormal composite outcome, i.e., any one of the mortality or major morbidities (aOR: 2.99; 95% CI: 1.96-4.57), hypoglycemia requiring intravenous fluids (aOR: 2.11; 95% CI: 1.05-4.23), and anemia requiring blood transfusions (aOR: 3.13; 95% CI: 1.98-4.93); and a trend towards increased odds of bronchopulmonary dysplasia (aOR: 1.9, 95% CI: 0.92-3.91). Mortality, intraventricular hemorrhage ≥ grade 2, periventricular leukomalacia ≥ grade 2, and retinopathy of prematurity requiring treatment were not different. CONCLUSIONS: SGA neonates have higher odds of having NEC ≥ stage 2A, abnormal composite outcome, hypoglycemia, and anemia compared to appropriately grown neonates.

RAM cannula with Cannulaide versus Hudson prongs for delivery of nasal continuous positive airway pressure in preterm infants: an RCT.

Nasal continuous positive airway pressure (nCPAP) is the standard non-invasive respiratory support for newborns with respiratory distress. Nasal injury is a common problem with the interfaces used. To compare the incidence and severity of nasal injury in neonates with respiratory distress and supported on nCPAP with Hudson prong or RAM cannula with Cannulaide, a semipermeable membrane. This is an open-label, parallel-arm, gestational age-stratified, bi-centric, randomized control trial including neonates between 28 and 34 weeks gestational age and birth weight > 1000 g needing nCPAP. The size of the interface was chosen as per the manufacturer's recommendation. Of the 229 neonates enrolled, 112 were randomized to RAM cannula with Cannulaide and 117 to Hudson prong. The baseline characteristics were similar. Any nasal injury at CPAP removal was significantly lower in the RAM cannula with Cannulaide group [6 (5.4%) vs. 31 (26.4%); risk ratio-0.77 (95% CI 0.69-0.87); p = 0.0001]. The incidence of moderate to severe nasal injury, need for mechanical ventilation within 72 h of age, duration of oxygen, and requirement of nCPAP for > 3 days were similar. For preterm infants on nCPAP, RAM cannula with Cannulaide, compared to Hudson prongs, decreases nasal injury without increasing the need for mechanical ventilation.Trail registration: CTRI/2019/03/018333, http://www.ctri.nic.in .

A quality improvement initiative to improve management of procedural pain in preterm neonates.

BACKGROUND: Neonates managed in neonatal intensive care units undergo several invasive procedures. However, neonatal procedural pain is not well recognized and managed in most neonatal units. AIMS: To decrease the severity of procedural pain in preterm neonates (<37 weeks gestational age at birth), as measured by Premature Infant Pain Profile , by 50% by April 2020. METHODS: A quality improvement initiative was conducted in a level 3 neonatal intensive care unit in South India. The pain was assessed independently by 2 interns not involved in clinical care using Premature Infant Pain Profile. After a baseline data recording and questionnaire assessing knowledge of healthcare personnel regarding neonatal pain, the interventions were planned. These were conducted as plan-do-study-act cycles-(i) Educational sessions, (ii) Introduction of bedside visual aids, (iii) Simulation sessions demonstrating the use of nonpharmacological measures and introduction of procedure surveillance chart in daily rounds, and (iv) Video feedback-based sessions. In the maintenance phase, the observations were continued. RESULTS: The healthcare personnel under recognized pain related to heel pricks and endotracheal intubation. They also had poor awareness of signs and symptoms of neonatal pain. A total of 202 procedures were observed during the study period. The mean pain score decreased significantly from 12.8 ± 4.5 in baseline period to 6.2 ± 1.8 in the maintenance phase. The use of analgesic measures increased from 13% in the baseline period to 73% in the maintenance phase. The use of automated lancet for heel prick increased from 0% to 94% in maintenance phase. More and more procedures were done with appropriate environment and baby state. The mean number of procedures per day decreased from 6.5 ± 1.8 in baseline period to 2.7 ± 0.9 in the maintenance phase. CONCLUSIONS: Targeted interventions can improve neonatal procedural pain management by improving use of analgesic measures, decreasing the number of procedures, and educating and training healthcare personnel.

The impact of a quality improvement project to reduce admission hypothermia on mortality and morbidity in very low birth weight infants.

This prospective observational study was aimed to analyze the impact of a quality improvement project to reduce admission hypothermia on composite outcome of neonatal mortality and major morbidities. Infants with birth weight between 500 and 1499 g and gestation ≥ 25 weeks without major congenital malformations delivered between January 2018 and January 2020 who were admitted directly from delivery room to NICU were included in the study. Study period was divided in three phases including pre-intervention, intervention and post-intervention phase. There were a total of 368 VLBW infants included in the study. Mean admission temperature of neonates was 35.3 ± 0.6 °C, 36.0 ± 0.8 °C, and 36.4 ± 0.4 °C during pre-intervention, intervention, and post-intervention phase, respectively. Absolute incidence of composite outcome was 31%, 20%, and 13.2% during pre-intervention, intervention, and post-intervention phase, respectively. Risk of adverse composite outcome was significantly lower in post-intervention period as compared to pre-intervention period (aRR 0.68, 95% CI 0.49-0.92). Nosocomial sepsis and need for invasive ventilation was also significantly less in post-intervention period as compared to pre-intervention period.Conclusion: Implementation of thermoregulatory interventions best suited to local settings help in significant reduction of neonatal hypothermia, which in turn can help to improve neonatal outcomes. What is known: • Admission hypothermia is associated with adverse neonatal outcomes. • Implementation of quality improvement projects help reducing hypothermia incidence. What is new: • Implementation of quality improvement project to reduce admission hypothermia resulted in reduction in incidence of adverse composite neonatal outcome. • Also implementation of quality improvement project led to reduction in incidence of nosocomial sepsis and need of invasive ventilation.

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.

Growth and Neurodevelopmental Outcomes at 12 to 18 Months of Corrected Age in Preterm Infants Born Small for Gestational Age.

OBJECTIVE: To compare the growth and neurodevelopmental outcomes at 12 to 18 months of corrected age in preterm infants (gestation < 35 wks) born appropriate for gestation (AGA) with those born small for gestation (SGA). METHODOLOGY: This cross sectional, study assessed the growth outcomes in terms of underweight, stunting, microcephaly, overweight and obesity. Development delay was defined as developmental quotient < 70 on DASII. RESULTS: Out of 178 infants enrolled in the study 119 were AGA and 59 were SGA. The mean gestational age of the study cohort was 30.45 (2.08) weeks. More infants in the SGA group were underweight (59.3% vs. 37.8%, RR: 1.79, 95% CI: 1.16-2.74), stunted (62.7% vs. 30.25%, RR: 2.19, 95% CI: 1.42-3.36) and had higher incidence of motor (6.7% vs.0.8%, RR: 2.5, 95% CI: 1.5-4.1) and mental development (3% vs. 0, RR: 3.1, 95% CI: 2.5-3.8) delay. CONCLUSIONS: Preterm SGA infants are at an increased risk of underweight, stunting, motor and mental development delay when compared with preterm AGA infants in early childhood.

'Nasal mask' in comparison with 'nasal prongs' or 'rotation of nasal mask with nasal prongs' reduce the incidence of nasal injury in preterm neonates supported on nasal continuous positive airway pressure (nCPAP): A randomized controlled trial.

BACKGROUND: With increasing use of nCPAP, the safety and comfort associated with nCPAP have come into the forefront. The reported incidence of nasal injuries associated with the use of nCPAP is 20% to 60%. A recent meta-analysis concluded that the use of nasal masks significantly decreases CPAP failure and the incidence of moderate to severe nasal injury and stress the need for a well powered RCT to confirm their findings. METHODS: In this Open label, 3 arms, sequential, stratified randomized controlled trial, we evaluated the incidence and severity of nasal injury at removal of nCPAP when using two different nasal interfaces and in three groups (i.e. rotation group, mask continue group, prong continue group). Preterm infants with gestation ≤ 30 weeks and respiratory distress within the first 6 hours of birth and in need of CPAP were eligible for the study. RESULTS: Among the 175 newborns included in the study, incidence of nasal injury in mask continue group [n = 19/57 (33.3%)] was significantly less as compared to prong continue group [n = 55/60 (91.6%)] and rotation group [33/ 58 (56.9%), p value <0.0001]. Median maximum nasal injury score was significantly less in Mask continue group as compared to Prong continue group and Rotation group [Injury Score 0 (IQR 0-1) vs. Injury Score 3 (IQR 2-5) vs. Injury Score 1 (IQR 0-2), p value = <0.0001] respectively. The proportion of infants failing nCPAP was similar across the three groups. CONCLUSION: nCPAP with nasal masks significantly reduces nasal injury in comparison with nasal prongs or rotation of nasal prongs and nasal masks. However, the type of interface did not affect the nCPAP failure rates.

High-Flow Nasal Cannula versus Nasal Continuous Positive Airway Pressure for Primary Respiratory Support in Preterm Infants with Respiratory Distress: A Randomized Controlled Trial.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) is the standard noninvasive respiratory support for newborns with respiratory distress. Evidence for high-flow nasal cannula (HFNC) as an alternative mode of respiratory support is inconclusive. OBJECTIVE: The aim of this work was to evaluate whether HFNC is not inferior to nCPAP in reducing the need for higher respiratory support in the first 72 h of life when applied as a noninvasive respiratory support mode for preterm neonates with respiratory distress. METHODS: Preterm infants (gestation ≥28 weeks and birth weight ≥1,000 g) with respiratory distress were randomized to either HFNC or nCPAP in a non-inferiority trial. Failure of the support mode in the first 72 h after birth was the primary outcome. Infants failing HFNC were rescued either with nCPAP or mechanical ventilation, and those failing nCPAP received mechanical ventilation. RESULTS: During the study period, 139 and 133 infants were randomized to the nCPAP and HFNC groups, respectively. The study was stopped after an interim analysis showed a significant difference (p < 0.001) in the primary outcome between the 2 groups. The treatment failure was significantly higher in the HFNC group (HFNC, n = 35, 26.3%, vs. CPAP, n = 11, 7.9%, risk difference 18.4 percentage points, 95% CI 9.7-27). Among the infants in the HFNC group who had treatment failure (n = 35), 32 were initially rescued with CPAP. The rate of mechanical ventilation in the first 3 and 7 days of life was similar between the 2 groups. Treatment failure was significantly higher in the HFNC group per protocol and also in the subgroups of infants with moderate (Silverman Anderson score, SAS ≤5) or severe respiratory distress (SAS score >5). CONCLUSIONS: When comparing HFNC to nCPAP as a primary noninvasive respiratory support in preterm infants with respiratory distress, HFNC is inferior to nCPAP in avoiding the need for a higher mode of respiratory support in the first 72 h of life.