Prevalence of hearing impairment in neonatal encephalopathy due to hypoxia-ischemia: a systematic review and meta-analysis.

BACKGROUND: This systematic review was undertaken to estimate the overall prevalence of hearing impairment in survivors of neonatal HIE. METHODS: PubMed, EMBASE, CINAHL, EMCARE and Cochrane databases, mednar (gray literature) were searched till January 2023. Randomized controlled trials and observational studies were included. The main outcome was estimation of overall prevalence of hearing impairment in survivors of HIE. RESULTS: A total of 71studies (5821 infants assessed for hearing impairment) were included of which 56 were from high income countries (HIC) and 15 from low- or middle-income countries (LMIC). Overall prevalence rate of hearing impairment in cooled infants was 5% (95% CI: 3-6%, n = 4868) and 3% (95% CI: 1-6%, n = 953) in non-cooled HIE infants. The prevalence rate in cooled HIE infants in LMICs was 7% (95% CI: 2-15%) and in HICs was 4% (95% CI: 3-5%). The prevalence rate in non-cooled HIE infants in LMICs was 8% (95% CI: 2-17%) and HICs was 2% (95% CI: 0-4%). CONCLUSIONS: These results would be useful for counseling parents, and in acting as benchmark when comparing institutional data, and while monitoring future RCTs testing new interventions in HIE. There is a need for more data from LMICs and standardization of reporting hearing impairment. IMPACT: The overall prevalence rate of hearing impairment in cooled infants with HIE was 5% (95% CI: 3-6%) and 3% (95% CI: 1-6%) in the non-cooled infants. The prevalence rate in cooled HIE infants in LMICs was 7% (95% CI: 2-15%) and in HICs was 4% (95% CI: 3-5%). The prevalence rate in non-cooled HIE infants in LMICs was 8% (95% CI: 2-17%) and HICs was 2% (95% CI: 0-4%). These results would be useful for counseling parents, and in acting as benchmark when comparing institutional data, and while monitoring future RCTs testing new interventions in HIE.

Outcomes of Neonates with Hypoxic-Ischemic Encephalopathy Treated with Magnesium Sulfate: A Systematic Review with Meta-analysis.

OBJECTIVE: To assess magnesium sulfate (MgSO4) as a neuroprotective agent in hypoxic-ischemic encephalopathy. STUDY DESIGN: For this systematic review, PubMed, EMBASE, the Cochrane Library, EMCARE, and MedNar were searched in November 2022 for randomized controlled trials (RCTs). Meta-analysis was conducted using Stata 16.0 and RevMan 5.3. RESULTS: Twenty RCTs with a total sample size of 1485 were included, of which 16 were from settings where therapeutic hypothermia (TH) was not offered. Regarding MgSO4 in settings where TH was not offered, only 1 study evaluated composite outcome of death or disability at ≥18 months and reported such poor outcome in 8 of 14 control infants and 4 of 8 in the MgSO4 group. MgSO4 was not associated with mortality (RR, 0.86; 95% CI, 0.72-1.03; 13 RCTs) or hypotension (RR, 1.02; 95% CI, 0.88-1.18; 5 RCTs). Thirteen studies reported that MgSO4 improved in-hospital outcomes, such as reduced seizure burden and improved neurological status at discharge. MgSO4 reduced the risk of poor suck feeds (RR, 0.52; 95% CI, 0.40-0.68; 6RCTs) and abnormal electroencephalogram (RR, 0.64; 95% CI, 0.45-0.93; 5 RCTs). Certainty of evidence was moderate for mortality and low or very low for other outcomes. For studies with MgSO4 as an adjunct to TH, none reported on death or neurodevelopmental disability at ≥18 months. MgSO4 was not associated with mortality (RR, 0.65; 95% CI, 0.34-1.27; 3 RCTs) or hypotension (RR, 1.0; 95% CI, 0.71-1.40; 3 RCTs). CONCLUSIONS: Evidence around long-term outcomes of MgSO4 when used with or without TH was scant. MgSO4 therapy may improve in-hospital neurological outcomes without affecting mortality in settings where TH is not offered. Well-designed RCTs for neuroprotection are needed, especially in low-resource settings. TRIAL REGISTRATION: "Open Science Forum" (https://doi.org/10.17605/OSF.IO/FRM4D).

Bifidobacterium infantis as a probiotic in preterm infants: a systematic review and meta-analysis.

BACKGROUND: Bifidobacterium infantis has special abilities to utilise human milk oligosaccharides. Hence we hypothesised that probiotic supplements containing B. infantis may confer greater benefits to preterm infants than probiotic supplements without B. infantis. METHODS: A systematic review with meta-analysis was conducted according to standard guidelines. We selected RCTs evaluating probiotics compared to placebo or no treatment in preterm and/or low birth weight infants. Probiotic effects on Necrotizing Enterocolitis (NEC), Late Onset Sepsis (LOS) and Mortality were analysed separately for RCTs in which the supplemented probiotic product contained B. infantis and those that did not contain B. infantis. RESULTS: 67 RCTs were included (n = 14,606), of which 16 used probiotics containing B. infantis (Subgroup A) and 51 RCTs did not (Subgroup B) Meta-analysis of all RCTs indicated that probiotics reduced the risk of NEC, LOS, and mortality. The subgroup meta-analysis demonstrated greater reduction in the incidence of NEC in subgroup A than subgroup B [(relative risk in subgroup A: 0.38; 95% CI, 0.27-0.55) versus (0.67; 95% CI, 0.55-0.81) in subgroup B; p value for subgroup difference: 0.01]. CONCLUSIONS: These results provide indirect evidence that probiotic supplements that include B. infantis may be more beneficial for preterm infants. Well-designed RCTs are necessary to confirm these findings. IMPACT: Evidence is emerging that beneficial effects of probiotics are species and strain specific. This systematic review analyses if B. infantis supplementation provides an advantage to preterm infants. This is the first systematic review evaluating the effects of probiotics containing B. infantis in preterm infants. The results of this systematic review provides indirect evidence that probiotics that include B. infantis may be more beneficial for preterm infants. These results will help in guiding future research and clinical practice for using B. infantis as a probiotic in preterm infants.

Probiotic supplementation for neonates with congenital gastrointestinal surgical conditions: guidelines for future research.

Our pilot RCT found that probiotic supplementation with the three-strain bifidobacterial product (B. breve M-16V, B. longum subsp. infantis M-63 and B. longum subsp. longum BB536) attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions (CGISC). In this article, we have provided guidelines for designing future multicentre RCTs based on the experience gained from our pilot RCT. The recommendations include advice about sample size, potential confounders, outcomes of interest, probiotic strain selection, storage, dose, duration and microbial quality assurance, collection of stool samples, storage and analysis and reporting. Following these guidelines will increase the validity of future RCTs in this area and hence confidence in their results. IMPACT: Probiotic supplementation attenuates gut dysbiosis, increases stool short-chain fatty acid (SCFA) levels and improves the growth of head circumference in neonates with congenital gastrointestinal surgical conditions. The current review provides evidence-based guidelines to conduct adequately powered RCTs in this field.

Performance of smartphone application to accurately quantify hyperbilirubinemia in neonates: a systematic review with meta-analysis.

Neonatal jaundice is a common clinical condition that can progress to severe hyperbilirubinemia if identification and intervention are delayed. In this study, we aimed to analyze the current evidence on the accurate performance of smartphone applications to quantify bilirubin levels. PubMed, Embase, Emcare, MEDLINE, the Cochrane Library, and Google Scholar were searched from inception until July 2022. Grey literature was searched on "OpenGrey" and "MedNar" databases. We included prospective and retrospective cohort studies that recruited infants with a gestation of ≥ 35 weeks and reported paired total serum bilirubin (TSB) and smartphone app-based bilirubin (ABB) levels. We conducted the review using the guidelines of the Cochrane Collaboration Diagnostic Test Accuracy Working Group and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-diagnostic test accuracy (PRISMA-DTA) statement. The data were pooled using the random effects model. The outcome of interest was agreement between ABB and TSB measurements, provided as correlation coefficient, mean difference, and standard deviation. Certainty of evidence (COE) was assessed based on GRADE guidelines. Fourteen studies were included in the meta-analysis. The number of infants in individual studies ranged between 35 and 530. The pooled correlation coefficient (r) between ABB and TSB was 0.77 (95% CI 0.69 to 0.83; p < 0.01). Reported sensitivities for predicting a TSB of 250 µmol/L in individual studies ranged between 75 and 100% and specificities ranged from 61 to 100%. Similarly, a sensitivity of 83 to 100% and a specificity of 19.5 to 76% were reported for predicting a TSB of 205 µmol/L. Overall COE was considered moderate.    Conclusion: Smartphone app-based bilirubin estimation showed a reasonable correlation to TSB levels. Well-designed studies are required to determine its utility as a screening tool for various TSB cut-off levels. What is Known: • Neonatal jaundice is a common clinical condition. Timely screening and intervention are necessary to prevent neurological morbidities • Transcutaneous bilirubinometer is a widely used non-invasive screening device but is mostly available in hospital settings and has cost limitations. Researchers have recently explored the utility of smartphone applications to estimate bilirubin levels in neonates. What is New: • This is the first systematic review and meta-analysis conducted to assess the performance of smartphone applications to detect neonatal hyperbilirubinemia. • Bilirubin estimates of newborn infants obtained through smartphone applications had a reasonable correlation with serum bilirubin levels.

Outcomes of very preterm infants with hyperglycaemia treated with insulin: A systematic review and meta-analysis.

AIM: To study the outcomes of very preterm infants with hyperglycaemia treated with Insulin. METHODS: This is a systematic review of randomised controlled trials (RCTs) and observational studies. PubMed, Medline, EMBASE, Cochrane Library, EMCARE and MedNar databases were searched in May 2022. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. MAIN OUTCOME MEASURES: Mortality and morbidities (e.g. Necrotising enterocolitis [NEC], retinopathy of prematurity [ROP]) in very preterm (<32 weeks) or very low birth weight infants (<1500 g) after treatment of hyperglycaemia with insulin. RESULTS: Sixteen studies with data from 5482 infants were included. Meta-analysis of unadjusted ORs from cohort studies showed that insulin treatment was significantly associated with increased mortality [OR 2.98 CI (1.03 to 8.58)], severe ROP [OR 2.23 CI (1.34 to 3.72)] and NEC [OR 2.19 CI (1.11 to 4)]. However, pooling of adjusted ORs did not show significant associations for any outcomes. The only included RCT found better weight gain in the insulin group, but no effect on mortality or morbidities. Certainty of evidence was 'Low' or 'Very low'. CONCLUSION: Very low certainty evidence suggests that Insulin therapy may not improve outcomes of very preterm infants with hyperglycaemia.

Probiotic supplementation in neonates and long-term gut colonisation: A systematic review of randomised controlled trials.

BACKGROUND: Probiotic supplementation in the neonatal period results in improved gut colonisation with probiotic bacteria in the short term. There is limited information on the long-term sustainability of this colonisation. AIMS: To evaluate whether oral probiotic supplementation in the neonatal period results in sustained gut colonisation with probiotic bacteria at or beyond 6 months after its cessation. METHODS: A systematic review of neonatal probiotic randomised controlled trials (RCTs) that reported on the stool microbiota during post-discharge follow-up was carried out using guidelines of the Cochrane neonatal group. RESULTS: Four RCTs (n = 605 infants) were included in the review. The studies were heterogeneous in case selection, choice of probiotics, duration of supplementation, timing and the method of stool microbial analysis. Three RCTs (n = 471) showed the presence of intestinal probiotic bacteria at 6-12 months. The overall certainty of evidence was very low in view of small sample size, heterogeneity and identification only to the genus/species level. CONCLUSION: Low certainty of evidence suggests that probiotic supplementation in the neonatal period may result in sustained gut colonisation 6-12 months post-cessation, but not at 24 months. Adequately powered, well-designed RCTs with strain-specific assays are needed in this area.

Probiotic supplementation in neonates with congenital gastrointestinal surgical conditions: a pilot randomised controlled trial.

OBJECTIVE: To evaluate whether probiotic supplementation attenuates gut-dysbiosis in neonates with congenital gastrointestinal surgical conditions (CGISC). METHODS: Sixty-one neonates (≥35 weeks gestation) with CGISC were randomised to receive daily supplementation with a triple-strain bifidobacterial probiotic (n = 30) or placebo (n = 31) until discharge. Stool microbiota was analysed using 16S ribosomal RNA gene sequencing on samples collected before (T1), 1 week (T2), and 2 weeks (T3) after supplementation and before discharge (T4). The primary outcome was the sum of the relative abundance of potentially pathogenic families of Clostridiaceae, Enterobacteriaceae, Enterococcaceae, Pseudomonaceae, Staphylococcaeae, Streptococcaceae, and Yersiniaceae at T3. RESULTS: The median gestational age [38 weeks (IQR: 37.1-38.9)] was similar in both groups. The probiotic group had lower rates of caesarean deliveries (40% versus 70%, p = 0.02). The relative abundance of potentially pathogenic families was lower in the probiotic group compared to placebo at T3 [(median: 50.4 (IQR: 26.6-67.6) versus 67.1 (IQR: 50.9-96.2); p = 0.04). Relative abundance of Bifidobacteriaceae was higher in the probiotic group at T3 [(median: 39.8 (IQR: 24.9-52.1) versus 0.03 (IQR 0.02-2.1); p < 0.001). Stratified analysis continued to show a higher abundance of Bifidobacteriaceae in the probiotic group, irrespective of the mode of delivery. CONCLUSIONS: Probiotic supplementation attenuated gut dysbiosis in neonates with CGISC. TRIAL REGISTRATION: http://www.anzctr.org.au (ACTRN12617001401347). IMPACT: Probiotic supplementation attenuates gut dysbiosis and improves stool short-chain fatty acid levels in neonates with congenital gastrointestinal surgical conditions. This is the second pilot RCT of probiotic supplementation in neonates with congenital gastrointestinal conditions. These findings will pave the way for conducting multicentre RCTs in this area.

Use of parenteral nutrition in term and late preterm infants: an Australian and New Zealand survey.

There is limited information regarding the use of parenteral nutrition (PN) in term and late preterm infants. We conducted a survey to study the current clinical practices within Australia and New Zealand (ANZ). A fifteen-question online survey was distributed to 232 neonatologists and fifty-five paediatric intensivists across ANZ between September and November 2019. At least one neonatologist from twenty-seven out of thirty tertiary neonatal intensive care units responded (90 %). Responses were received from sixty-nine neonatologists (30 %) and seven paediatric intensivists (13 %). The overall response rate was 26 % (76/287). Thirty-three percent (25/76) commenced PN within 24 h of admission, 27 % (20/75) between 24 and 48 h, 24 % (18/75) between 48 and 72 h, 9 % (7/75) between 72 and 96 h and 4 % (3/75) between 96 h and 7 days. None of the respondents commenced PN after 7 d of admission. Sixty-one percent (46/75) aimed for 1·5-3 g/kg per d of parenteral amino acids, whereas 27 % (20/75) aimed for 2-3 g/kg per d. Renal failure (59 %; 38/64) and high plasma urea (44 %; 28/64) were the major indications for withholding/decreasing the amino acid intake. Eighty-three percent (63/76) aimed for a dose of 2·5g-3·5 g/kg per d of parenteral lipids; about 9 % (7/76) targeted a dose of 1-2·5 g/kg per d and 4 % (3/76) for > 3·5 g/kg per d. Thirty-two percent (24/74) reported that they would withhold/decrease the dose of parenteral lipids in infants with sepsis. The variations in clinicians' practices with respect to the use of PN in term and late preterm infants highlight the need for high-quality research in this population.

Does abnormal Doppler on cranial ultrasound predict disability in infants with hypoxic-ischaemic encephalopathy? A systematic review.

AIM: To evaluate whether abnormal resistive index or cerebral blood flow velocity (CBFV) on cranial ultrasound predicts disability (≥1 year) in infants with hypoxic-ischaemic encephalopathy (HIE). METHOD: This was a systematic review and meta-analysis of studies comparing developmental outcomes of infants with HIE with normal versus abnormal resistive index or CBFV. RESULTS: Twenty-six studies were included (pre-therapeutic hypothermia era, 20; therapeutic hypothermia era, six). Data from 15 studies (pre-therapeutic hypothermia, 10; therapeutic hypothermia, five) were available for meta-analysis. Pooled sensitivity and specificity, summary area under the receiver operating characteristic curve, and diagnostic odds ratio of resistive index or CBFV for predicting 'death or severe disability' were as follows. Pre-therapeutic hypothermia era: 0.83 (95% confidence interval [CI] 0.45-0.97) and 0.92 (95% CI 0.74-0.98), 0.94 (95% CI 0.92-0.96), 54 (95% CI 7-391). Therapeutic hypothermia era (measurements before therapeutic hypothermia): 0.62 (95% CI 0.41-0.80) and 0.96 (95% CI 0.88-0.99), 0.93 (95% CI 0.89-0.94), 23 (95% CI 6-91). Therapeutic hypothermia era (measurements during/after therapeutic hypothermia): 0.51 (95% CI 0.24-0.78) and 0.83 (95% CI 0.73-0.90), 0.81 (95% CI 0.78-0.85), 5 (95% CI 2-13). Overall Grading of Recommendations Assessment, Development and Evaluation (GRADE) rating of evidence was 'low' or 'very low'. INTERPRETATION: Low-level evidence suggests that abnormal resistive index or CBFV can predict death or disability with high sensitivity and specificity in infants with HIE who are not cooled. The specificity of these tests was high when performed before starting cooling in infants who received therapeutic hypothermia. WHAT THIS PAPER ADDS: Cerebral doppler ultrasound may be useful in predicting death or disability in infants with hypoxic-ischaemic encephalopathy who are not cooled. Cerebral doppler ultrasound may also be useful in infants who are cooled, if done before starting cooling. Cerebral doppler ultrasound may not be useful when performed during or after completing cooling.

OBJETIVO: Avaliar se o índice de resistência anormal ou a velocidade do fluxo sanguíneo cerebral (VFSC) na ultrassonografia craniana prediz incapacidade (≥1 ano) em bebês com encefalopatia hipóxico-isquêmica (EHI). MÉTODO: Esta foi uma revisão sistemática e meta-análise de estudos comparando os resultados do desenvolvimento de bebês com EHI com índice de resistência normal versus anormal ou VFSC. RESULTADOS: Vinte e seis estudos foram incluídos (hipotermia pré-terapêutica, 20; hipotermia terapêutica, 6). Dados de 15 estudos (hipotermia pré-terapêutica, 10; hipotermia terapêutica, 5) estavam disponíveis para meta-análise. Sensibilidade e especificidade agrupadas, área de resumo sob a curva característica de operação do receptor e razão de chances de diagnóstico do índice resistivo ou VFSC para prever "morte ou incapacidade grave" foram os seguintes. (1) Hipotermia pré-terapêutica: 0,83 (intervalo de confiança de 95% [IC] 0,45-0,97) e 0,92 (IC 95% 0,74-0,98), 0,94 (IC 95% 0,92-0,96),54 (IC 95% 7-391). (2) Hipotermia terapêutica (medições antes da hipotermia terapêutica): 0,62 (IC 95% 0,41-0,80) e 0,96 (IC 95% 0,88-0,99), 0,93 (IC 95% 0,89-0,94), 23 (IC 95% 6-91). (3) Hipotermia terapêutica (medidas durante/após a hipotermia terapêutica): 0,51 (IC 95% 0,24-0,78) e 0,83 (IC 95% 0,73-0,90), 0,81 (IC 95% 0,78-0,85),5 (IC 95% 2 -13). A classificação geral das evidências de Avaliação, Desenvolvimento e Avaliação de Recomendações (GRADE) foi 'baixa' ou 'muito baixa'. INTERPRETAÇÃO: Evidências de baixo nível sugerem que anormalidades índice resistivo ou VFSC pode prever morte ou incapacidade com alta sensibilidade e especificidade em bebês com EHI que não são resfriados. A especificidade desses testes foi alta quando realizados antes do início do resfriamento em bebês que receberam hipotermia terapêutica.

Early erythropoietin for preventing necrotizing enterocolitis in preterm neonates - an updated meta-analysis.

Previous systematic reviews suggest reduction in necrotizing enterocolitis (NEC) among preterm infants supplemented with erythropoietin (EPO). We aimed to update our 2018 systematic review in this field considering the evidence accumulated over the last 3 years. Randomized controlled trials (RCTs) reporting the effect of early EPO supplementation vs placebo/no EPO supplementation on any stage NEC in preterm infants were included. Fixed effect model was used for meta-analysis. Trial sequential analysis (TSA) was conducted to verify the effects of EPO on NEC after accounting for repeated significance testing. A total of 22 RCTs (n = 5359) were included, of which six were new (n = 2541 additional preterm infants) in comparison to our previous systematic review. EPO significantly decreased the risk of any stage NEC (232/2669 (8.7%) vs 313/2690 (11.6%); RR: 0·76; TSA adjusted 95% CI (0·64, 0·90); p = 0·0008, number needed to treat (NNT) = 34). The risk of definite NEC (≥ Stage II) was also significantly reduced by EPO administration (105/2219 (4.7%) vs 141/2246 (6.3%); RR: 0.77; 95% CI (0.61, 0.98); p = 0.03, NNT: 62). However, the results for definite NEC were no longer significant on sensitivity analyses that included (a) only double-blind RCTs and (b) only prospectively registered trials. The quality of evidence was deemed moderate-to-low for the reported outcomes. CONCLUSION: There is moderate to low-quality evidence that early prophylactic EPO reduces any stage and ≥ Stage II NEC in preterm neonates. Prospectively registered, adequately powered, double-blind RCTs are required to confirm these findings. WHAT IS KNOWN: • Experimental studies have shown that erythropoietin (EPO) has gastrointestinal trophic effects. • Systematic reviews have shown that early treatment with EPO may decrease the risk of gut injury in preterm or low birth weight infants. WHAT IS NEW: • Early EPO supplementation significantly reduced the incidence of any stage NEC and definite NEC in preterm infants < 34 weeks of gestation. • EPO had no significant effect on definite NEC in the analyses that included only double-blinded and prospectively registered RCTs. How might it impact clinical practice in the foreseeable future? • Early prophylactic EPO can be recommended for NEC prevention if its benefits are consistently demonstrated in adequately powered randomized trials with a low risk of bias.

Early versus late parenteral nutrition in term and late preterm infants: study protocol for a randomised controlled trial.

BACKGROUND: Despite the wide use of parenteral nutrition (PN) in neonatal intensive care units (NICU), there is limited evidence regarding the optimal time to commence PN in term and late preterm infants. The recommendations from the recently published ESPGHAN/ESPEN/ESPR/CPEN and NICE guidelines are substantially different in this area, and surveys have reported variations in clinical practice. The aim of this randomised controlled trial (RCT) is to evaluate the benefits and risks of early versus late PN in term and late preterm infants. METHODS/DESIGN: This study is a single-centre, non-blinded RCT in the NICU of Perth Children's Hospital, Western Australia.A total of 60 infants born ≥34 weeks of gestation who have a high likelihood of intolerance to enteral nutrition (EN) for at least 3-5 days will be randomised to early (day 1 or day 2 of admission) or late commencement (day 6 of admission) of PN after informed parental consent. In both groups, EN will be commenced as early as clinically feasible. Primary outcomes are plasma phenylalanine and plasma F2-isoprostane levels on Day 4 and Day 8 of admission. Secondary outcomes are total and individual plasma amino acid profiles, plasma and red blood cell fatty acid profiles, in-hospital all-cause mortality, hospital-acquired infections, length of hospital/NICU stay, z scores and changes in z scores at discharge for weight, height and head circumference, time to full EN, duration of respiratory (mechanical, non-invasive) support, duration of inotropic support, the incidence of hyper and hypoglycaemia, incidence of metabolic acidosis, liver function, blood urea nitrogen, and C-reactive protein (CRP). DISCUSSION: This RCT will examine the effects of early versus late PN in term and late preterm infants by comparing key biochemical and clinical outcomes and has the potential to identify underlying pathways for beneficial or harmful effects related to the timing of commencement of PN in such infants. TRIAL REGISTRATION: ANZCTR; ACTRN12620000324910 (3rd March 2020).

Early or delayed parenteral nutrition for infants: what evidence is available?

PURPOSE OF REVIEW: To review the current evidence evaluating early versus delayed commencement of parenteral nutrition in infants. RECENT FINDINGS: Recent studies in very premature infants (<32 weeks gestation) have shown that early commencement of parenteral nutrition immediately after birth improves physical growth. However, there are concerns that early use of very high dose of amino-acids (>3.5 g/kg/day immediately after birth) may cause metabolic acidosis, elevated blood urea, slower head growth and refeeding-hypophosphatemia syndrome. A recent multicentre randomized controlled trial found that commencement of parenteral nutrition within 24-h of admission increases the risk of infections and prolongs the duration of ventilation and ICU stay in full-term neonates, older infants and children. The study also found that delaying to day 8 of admission increased the risk of hypoglycaemia. SUMMARY: Benefits of commencing parenteral nutrition on the first day of life appear to outweigh risks in very premature infants; however, it is prudent to avoid early very high doses of amino acids (>3.5 g/kg/day) in the first few days of life. In moderate to late preterm infants, if enteral feeds are not tolerated by 72 h, it is reasonable to commence parenteral nutrition. In full-term and older infants, it is preferable to avoid parenteral nutrition within 24 h of admission and consider delaying by further few days. Diligent monitoring of blood glucose, serum phosphate and other parameters is essential while on parenteral nutrition.

Time to regain birth weight - a marker to predict the severity of retinopathy of prematurity?

BACKGROUND: Poor weight gain in the first few weeks of life has been studied as a predictor of retinopathy of prematurity (ROP). Our aim was to assess whether time taken to regain birthweight (BW) be used as an additional marker to identify infants with type 1 ROP. METHODS: In this retrospective study, preterm infants (< 27 weeks gestational age at birth) born during the period from 1/1/2010-31/12/2015 at a tertiary neonatal intensive care unit in Australia were included. Twenty-seven preterm infants with Type 1 ROP were identified. Controls (No ROP or ROP other than type 1) were matched with cases on gestational age at birth and BW (1:4 ratio). Data were collected from the database and medical records. RESULTS: The median (IQR) gestational age for Type 1 ROP and control groups were 24 (24-26) and 25 (24-26) weeks respectively and median (IQR) BW for Type 1 ROP and control groups were 675 (635-810) and 773 (666-884) grams respectively. Preterm infants with Type 1 ROP were more likely to be small for gestational age (SGA) (18.5% vs 3.7%, p = 0.015) and had increased weeks on oxygen therapy (median 11.9 vs 9.1, p = 0.028). Time to regain BW was longer in preterm infants with type 1 ROP than controls but did not reach statistical significance (median 9 vs 7 days, OR 1.08, 95% CI 1.00-1.17, p = 0.059) adjusted for SGA and duration of oxygen therapy. The area under the curve from the time to regain BW model with adjustment for SGA and duration of oxygen therapy was 0.73 (95% CI 0.62-0.83). CONCLUSION: We hypothesize that time to regain BW has potential to aid prediction of Type 1 ROP and this warrants further investigation in a larger prospective study.

Trans-anastomotic tube feeding in the management of congenital duodenal obstruction: a systematic review and meta-analysis.

BACKGROUND: Feed intolerance is a common problem in neonates with congenital duodenal obstruction (CDO). Some surgeons insert trans-anastomotic tubes (TAT) to facilitate feed tolerance. We conducted a systematic review to evaluate the efficacy and safety of TATs in CDO. METHODS: Medline, EmBase, CINAHL, and Cochrane Library were searched till July 2020. Risk of bias was assessed using ROBINS-I tool. Meta-analysis was conducted using Random Effects Model. RESULTS: No randomized controlled trials addressing the question were identified. In the 6 included observational studies, 96 infants underwent intraoperative TAT placement and 117 did not. Four studies reported benefits of TAT such as early attainment of full feeds and decreased need for parenteral nutrition. Two studies reported better outcomes in the no-TAT group. Accidental removal of TAT without clinical harm was reported in three studies [5/37 (14%), 4/17 (23%), and 2/4 (50%)]. Overall meta-analysis found no differences between the groups on any outcome. However, sensitivity analysis after excluding two studies with high risk of bias found that TAT tubes are associated with shorter duration of PN and shorter time to full enteral feeds. GRADE of evidence was very low for all outcomes. CONCLUSIONS: Evidence is limited regarding the efficacy and safety of intraoperative TAT placement in neonates with CDO. Well-designed RCTs are needed to address the issue definitively.

Gut microbiota in neonates with congenital gastrointestinal surgical conditions: a prospective study.

BACKGROUND: There is limited information on gut microbiota of neonates with congenital gastrointestinal surgical conditions (CGISCs) available. METHODS: This study compared stool microbiota and short-chain fatty acids (SCFAs) of 37 term infants with CGISCs with 36 term healthy infants (HIs). Two stool samples were collected from each infant: as soon as possible after birth (week 1) and 10-14 days of life (week 2). RESULTS: Bacterial richness and alpha diversity were comparable between CGISCs and HIs at week 1 and week 2 (all p > 0.05). Beta diversity analysis revealed that at week 1, CGISCs had similar community structures to HIs (p = 0.415). However, by week 2, community structures of CGISCs were significantly different from HIs (p = 0.003). At week 1, there were no significant differences in the relative abundances of genera Bifidobacterium and Bacteroides between CGISCs and HIs. At week 2, the relative abundance of Bifidobacterium was significantly lower in CGISCs (mean percentage 7.21 ± 13.49 vs. 28.96 ± 19.6; p = 0.002). Bacteroides were also less abundant in the CGISC group (mean percentage 0.12 ± 0.49 vs. 6.59 ± 8.62; p = 0.039). Relative abundance of genera Pseudomonas and Escherichia-Shigella were higher in CGISCs. At week 2, stool concentrations of all SCFAs were lower in CGISCs (all p < 0.001). CONCLUSIONS: During hospitalization, neonates with CGISCs develop gut dysbiosis and deficiency of SCFAs. IMPACT: During hospitalisation, neonates with congenital gastrointestinal surgical conditions develop gut dysbiosis with deficiency of Bifidobacteria and Bacteroides and increased abundance of Escherichia-Shigella and Pseudomonas. They also have low levels of short chain fatty acids in their stools compared to healthy infants. This is the first study evaluating the gut microbiota using 16S ribosomal RNA sequencing methods and stool short chain fatty acids in neonates with congenital gastrointestinal surgical conditions and comparing them to healthy infants. The findings of this study will pave the way for randomised trials of bifidobacterial supplementation in neonates with congenital gastrointestinal surgical conditions.

Early versus late parenteral nutrition for critically ill term and late preterm infants.

BACKGROUND: Recently conducted randomised controlled trials (RCTs) suggest that late commencement of parenteral nutrition (PN) may have clinical benefits in critically ill adults and children. However, there is currently limited evidence regarding the optimal timing of commencement of PN in critically ill term and late preterm infants. OBJECTIVES: To evaluate the benefits and safety of early versus late PN in critically ill term and late preterm infants. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (5 April 2019), MEDLINE Ovid (1966 to 5 April 2019), Embase Ovid (1980 to 5 April 2019), EMCare (1995 to 5 April 2019) and MEDLINE via PubMed (1966 to 5 April 2019). We searched for ongoing or recently completed clinical trials, and also searched the grey literature and reference lists of relevant publications. SELECTION CRITERIA: We included RCTs comparing early versus late initiation of PN in term and late preterm infants. We defined early PN as commencing within 72 hours of admission, and late PN as commencing after 72 hours of admission. Infants born at 37 weeks' gestation or more were defined as term, and infants born between 34 and 36+6 weeks' gestation were defined as late preterm. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, extracted the data and assessed the risk of bias. Treatment effects were expressed using risk ratio (RR) and risk difference (RD) for dichotomous outcomes and mean difference (MD) for continuous data. The quality of the evidence was assessed using the GRADE approach. MAIN RESULTS: Two RCTs were eligible for inclusion. Data were only available from a subgroup (including 209 term infants) from one RCT in children (aged from birth to 17 years) conducted in Belgium, the Netherlands and Canada. In that RCT, children with medium to high risk of malnutrition were included if a stay of 24 hours or more in the paediatric intensive care unit (PICU) was expected. Early PN and late PN were defined as initiation of PN within 24 hours and after day 7 of admission to PICU, respectively. The risk of bias for the study was considered to be low for five domains and high for two domains. The subgroup of term infants that received late PN had significantly lower risk of in-hospital all-cause mortality (RR 0.35, 95% confidence interval (CI) 0.14 to 0.87; RD -0.10, 95% CI -0.18 to -0.02; number needed to treat for an additional beneficial outcome (NNTB) = 10; 1 trial, 209 participants) and neonatal mortality (death from any cause in the first 28 days since birth) (RR 0.29, 95% CI 0.10 to 0.88; RD -0.09, 95% CI -0.16 to -0.01; NNTB = 11; 1 trial, 209 participants). There were no significant differences in rates of healthcare-associated blood stream infections, growth parameters and duration of hospital stay between the two groups. Neurodevelopmental outcomes were not reported. The quality of evidence was considered to be low for all outcomes, due to imprecision (owing to the small sample size and wide confidence intervals) and high risk of bias in the included studies. AUTHORS' CONCLUSIONS: Whilst late commencement of PN in term and late preterm infants may have some benefits, the quality of the evidence was low and hence our confidence in the results is limited. Adequately powered RCTs, which evaluate short-term as well as long-term neurodevelopmental outcomes, are needed.

Topical application of coconut oil to the skin of preterm infants: a systematic review.

Preterm infants are at risk of increased trans-epidermal water loss and infections due to epidermal immaturity. The emollient and anti-infective properties of coconut oil make it a potentially beneficial topical agent for this population. We aimed to systematically review randomised trials assessing the effects of topical coconut oil in preterm infants. Medline, EMBASE, Cochrane Central Register of Controlled Trials and CINAHL were searched. Seven trials (n = 727 infants) were included. The majority of trials included relatively mature infants (gestation > 32 weeks, birth weight > 1200 g). The duration of intervention (5-31 days) and outcomes of interest varied among included studies. Meta-analysis using random effects model found significantly lower incidence of hospital-acquired blood stream infections (HABSI) in the coconut oil group (11/164 vs 32/166; relative risk 0.35, 95% confidence interval 0.18, 0.67, p = 0.001; I2 = 0%, two RCTs). Overall, infants in the coconut oil group had decreased water loss, decreased infection rates, better growth and skin condition. There were no significant adverse effects associated with coconut oil application. The overall quality of evidence was considered moderate for the outcome of HABSI and low for the outcome of physical growth based on GRADE guidelines.Conclusion: Topical coconut oil application to the skin may be beneficial in preterm infants, but the quality of evidence is low to moderate. Adequately powered randomised controlled trials, especially in very preterm (< 32 weeks) and extremely preterm (< 28 weeks) infants, are needed. What is Known: • Coconut oil has been used traditionally for topical application in terms of infants in Asian countries What is New: • This systematic review found that topical application of coconut oil may reduce the risk of infection and improve weight gain and skin condition in preterm infants. However, the quality of evidence was considered to be moderate to low based on GRADE guidelines.

Effects of probiotics on experimental necrotizing enterocolitis: a systematic review and meta-analysis.

BackgroundMeta-analyses of randomized controlled trials (RCTs) suggest that probiotics decrease the risk of necrotizing enterocolitis (NEC) in preterm infants. Many animal RCTs have evaluated probiotics for preventing NEC. We systematically reviewed the literature on this topic.MethodsThe protocol for systematic review of animal intervention studies (SYRCLE) was followed. Medline, Embase, ISI Web of Science, e-abstracts from the Pediatric Academic Society meetings, and other neonatal conferences were searched in December 2015 and August 2016. RCTs comparing probiotics vs. placebo/no probiotic were included.ResultsA total of 29 RCTs were included (Rats: 16, Mice: 7, Piglets: 3, Quail: 2, Rabbit: 1; N~2,310), with 21 reporting on histopathologically confirmed NEC; remaining 8 assessed only pathways of probiotic benefits. Twenty of the 21 RCTs showed that probiotics significantly reduced NEC. Pooling of data was possible for 16/21 RCTs. Meta-analysis using random-effects model showed that probiotics significantly decreased the risk of NEC (203/641 (31.7%) vs. 344/571 (60.2%); relative risk: 0.51; 95% confidence interval (CI): 0.42-0.62; P<0.00001; I2=44%; number needed to treat: 4; 95% CI: 2.9, 4.3).ConclusionProbiotics significantly reduced NEC via beneficial effects on immunity, inflammation, tissue injury, gut barrier, and intestinal dysbiosis.