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.

Feasibility of Minimal Enteral Nutrition During Therapeutic Hypothermia for Perinatal Asphyxia: A Five-Year Multicenter Experience from South India.

Limited evidence shows minimal enteral nutrition (MEN) during therapeutic hypothermia (TH) in neonates to be feasible and have benefits of shorter time to full-feeds. This study aimed to assess the feasibility of MEN during TH. MEN was initiated after 12 h if there were no altered aspirates, abdominal distension, and inotrope requirement. The authors retrospectively analyzed the records from May 2017 to April 2022. The number of episodes of feed intolerance and the length of hospital stay were the key outcomes. A total of 99 neonates were fed during cooling. MEN could be initiated at a median duration (IQR) of 24 (24-30) h. There were 9 (9%) neonates with feed intolerance during TH. None had necrotizing enterocolitis. Ninety-two (93%) neonates were discharged, with a median hospital stay (IQR) of 9 d (6-15). Hence, MEN during TH is feasible and provides a rationale for future controlled trials.

Effect of Enteral Long-Chain Polyunsaturated Fatty Acids on Retinopathy of Prematurity: A Systematic Review and Meta-Analysis.

BACKGROUND: Long-chain polyunsaturated fatty acids (LCPUFA) are critical for the maturation of the brain and retina. Retinopathy of prematurity (ROP) is a preventable cause of blindness in preterm infants. LCPUFA have anti-inflammatory, antioxidant, and antiangiogenesis effects. Supplementation of enteral LCPUFA might mitigate the incidence of ROP in these infants. Available limited randomized studies showed promising results. We aimed to assess the effect of enteral supplementation of LCPUFA on ROP in preterm infants. METHODS: We followed PRISMA guidelines and searched MEDLINE, Cumulative Index of Nursing and Allied Health Literature, Embase, and Cochrane Registry from 1990 to 2021 for the studies that examined the effects of enteral LCPUFA and ROP in preterm infants. We included the studies that satisfied the predefined inclusion criteria. RevMan 5.3 software derived the forest plot of pooled relative risk. We assessed the quality of all the included studies using GRADE recommendations. RESULTS: Nine studies were eligible for the meta-analysis involving 2,482 infants. Of the nine RCTs, six studies provided LCPUFA (DHA/AA) as a separate intervention in different concentrations, and three studies provided formula milk enriched with LCPUFA. In addition, five studies recruited infants below 32 weeks of gestational age. Supplementation of LCPUFA did not reduce the incidence of severe ROP (RR 0.71, 95% CI: 0.50-1.01, 5 studies, 1,822 infants) with very low CoE or any ROP (RR 0.95, 95% CI: 0.73-1.12, 6 studies, 1,177 infants) with very low CoE or ROP requiring treatment (RR 0.92, 95% CI: 0.62-1.38, 4 studies, 1,395 infants) with very low CoE. Regarding safety outcomes, enteral LCPUFA did not increase the risk of necrotizing enterocolitis or mortality. DISCUSSION/CONCLUSION: Supplementation of enteral LCPUFA to preterm infants did not reduce ROP incidence; however, there was a trend toward benefit in mitigating severe form of ROP. More well-designed, large, randomized controlled studies are warranted.

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.

Neonatal Total Parenteral Nutrition: Clinical Implications From Recent NICE Guidelines.

Postnatal growth failure and its impact on the long term outcomes in preterm neonates is a long-standing problem. Optimal and aggressive nutrition strategies are required to ameliorate these concerns. Total parenteral nutrition (TPN) is widely practiced in management of preterm neonates. Recently published National Institute for Health and Care Excellence (NICE) guidelines provide recommendations for best practices for parenteral nutrition in neonates. However, healthcare associated sepsis, expertise as well as infrastructure of TPN, monitoring facilities and cost remain major constraints for widespread use of TPN in resource limited settings. Current update is aimed to summarize NICE and European society for Clinical Nutrition and Metabolism (ESPEN) guidelines to inform best practice for TPN for neonatologists in India.

International Guidelines 2020 for the Management of Septic Shock in Children.

The recent version of pediatric septic shock guidelines, 2020 have addressed practical issues pertaining to pediatric septic shock management, which can be applicable to resource-limited setting as well. Supportive aspects in management of septic shock such as ventilation, antibiotic stewardship, and nutrition are addressed compared to previous guidelines that concentrated more on first-hour management. The current guideline needs to be adapted to local clinical practice cautiously in the light of experience, clinical acumen and judgement.

Feed intolerance in preterm neonates with antenatal reverse end diastolic flow (REDF) in umbilical artery: a retrospective cohort study.

Background: Feed intolerance is common in growth-restricted infants with antenatal AREDF (absent or reverse end-diastolic flow) and presumed to be more severe in those with reverse end diastolic flow (REDF). Natural history of feeding in REDF is rarely reported in the literature.Aims and objectives: To determine the incidence of feed intolerance and necrotizing enterocolitis (NEC) in neonates with antenatal REDF.Design: Preterm inborn neonates with gestation <37 weeks with antenatal REDF diagnosed between January 2015 and September 2017 were included in this retrospective cohort study. The primary outcome was the proportion of neonates having feed intolerance and NEC till discharge or death or transfer to other hospitals and time to achieve full enteral feeding (150 ml/kg/day).Results: Out of total 67 born with antenatal REDF, 8 were transferred out within 48 hours, 8 records not available and 4 excluded due to major malformations. The mean (SD) gestation and birth weight of the remaining 48 neonates were 32 (2) weeks and 1096 (291) g. The median (IQR) age of initiation of feeds was 30 (24-37) hours. Feeds were advanced by median (range) 20 (10-20) ml/kg/day in which 22 babies (45%) had at least 1 episode of feed intolerance at a median (IQR) age of 79 (40-120) hours requiring nil per oral for next 48 (18-96) hours. Full feeds were reached by median age (IQR) of nine (8-12) days. Only 3 neonates (6%) had NEC stage 2 or above as per Bell's staging.Conclusions: Feed intolerance is common in neonates with REDF though the risk of NEC is not high.What is known on this subject?Neonates with antenatal AREDF are at increased risk of feed intolerance and necrotizing enterocolitis.Early introduction of enteral feeds in neonates with AREDF with appropriate monitoring is safe without increased risk of necrotizing enterocolitis.AEDF which progresses to REDF is associated with increased morbidity.What does this study add?Early enteral feeding as early as 24 hours can be initiated in REDF if there are no abdominal symptoms and signs.Feed intolerance is high in REDF cases.The risk of NEC is not higher than what is seen in AEDF cases.

Double Volume Exchange Transfusion in Severe Neonatal Sepsis.

OBJECTIVES: To study the efficacy and safety of double volume exchange transfusion (DVET) in neonates > 1000 g birth weight with severe sepsis. METHODS: Eighty-three neonates weighing >1000 g with severe sepsis were randomly assigned to DVET or standard therapy (ST) group. Primary outcome was mortality by 14 d from enrollment. RESULTS: A 21 % reduction in mortality, albeit non-significant, by 14 d from enrollment was observed in DVET group in comparison to ST group [RR: 0.79 (95 % C.I 0.45-1.3); p 0.4]. A similar trend in mortality reduction was observed with early mortality and mortality by discharge in DVET group. No difference was observed in normalization of dysfunctional organs by 14 d. Cardiovascular and hematological system benefitted the most, followed by renal dysfunction with DVET. A significant improvement in post DVET IgG, IgA, IgM, C3 and base deficit was observed. No serious adverse effects occurred following DVET. CONCLUSIONS: In neonates >1000 g with severe sepsis, DVET was associated with a trend towards decrease in mortality by 14 d from enrollment. A significant improvement in immunoglobulin and complement C3 levels and acid base status were observed following DVET. DVET is a safe procedure in severely sick and septic neonates.