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.

Prevalence of symptomatic tracheal morbidities after fetoscopic endoluminal tracheal occlusion: a systematic review and meta-analysis.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) has been shown to improve survival of infants with congenital diaphragmatic hernia (CDH). However, there are concerns that FETO may lead to tracheomegaly, tracheomalacia and related complications. METHODS: A systematic review was conducted to estimate the prevalence of symptomatic tracheal complications in infants who underwent FETO for CDH. Presence of one or more of the following was considered as tracheal complication: tracheomalacia, stenosis, laceration or tracheomegaly with symptoms such as stridor, effort-induced barking cough, recurrent chest infections or the need for tracheostomy, tracheal suturing, or stenting. Isolated tracheomegaly on imaging or routine bronchoscopy without clinical symptoms was not considered as tracheal morbidity. Statistical analysis was performed using the metaprop command on Stata V.16.0. RESULTS: A total of 10 studies (449 infants) were included (6 retrospective cohort, 2 prospective cohort and 2 randomised controlled trials). There were 228 infants who survived to discharge. Prevalence rates of tracheal complications in infants born alive were 6% (95% CI 2% to 12%) and 12% (95% CI 4% to 22%) in those who survived to discharge. The spectrum of severity ranged from relatively mild symptoms such as effort-induced barking cough to the need for tracheostomy/tracheal stenting. CONCLUSION: A significant proportion of FETO survivors have symptomatic tracheal morbidities of varying severity. Units that are planning to adopt FETO for managing CDH should consider ongoing surveillance of survivors to enable early identification of upper airway issues. Inventing FETO devices that minimise tracheal injury is needed.

Mortality and neurodevelopmental outcomes of infants with spontaneous intestinal perforation: a systematic review and meta-analysis.

BACKGROUND: There is limited information about the mortality and neurodevelopmental outcomes of very preterm infants (<32 weeks) with spontaneous intestinal perforation (SIP). OBJECTIVE: To explore the association between SIP and neurodevelopmental outcomes and mortality in very preterm infants. DATA SOURCES: Medline, EMBASE, Cochrane Library, EMCARE and MedNar. STUDY SELECTION: Databases were searched until September 2021. Studies comparing outcomes of 'SIP' versus 'no SIP or necrotising enterocolitis (NEC)' were included. DATA EXTRACTION: Neurodevelopmental outcomes at ≥1 year corrected age were extracted as the main outcome measure. Data were pooled separately for adjusted and unadjusted ORs using the random-effects model. The evidence level was assessed using the GRADE (Grading of Recommendations, Assessments, Development and Evaluations) framework. RESULTS: Eighteen cohort studies (13 606 infants) were included. Meta-analysis of unadjusted ORs showed that SIP was significantly associated with increased odds of mortality, cerebral palsy, composite outcome of death or disability, visual impairment and hearing impairment. However, pooling of adjusted ORs (aOR) found significant associations only for mortality (aOR (95% CI) 2.27 (2.07 to 2.49); I2: 0%; four studies (n=10 695)), severe disability (aOR (95% CI) 2.06 (1.38 to 3.08); I2: 0%; two studies (n=321)) and composite outcome of 'death or disability' (aOR (95% CI) 2.18 (1.55 to 3.06); I2: 0%; two studies (n=321)). The level of evidence was 'low' or 'very low'. LIMITATIONS: Lack of information on aORs from many studies. CONCLUSIONS: SIP in very preterm infants is associated with higher odds of mortality, severe disability, and death or disability.

Local nitroglycerin to facilitate peripheral arterial cannulation in children: systematic review and meta-analysis.

BACKGROUND: Neonates and children admitted to intensive care units require peripheral arterial cannulation to monitor their blood pressures and for blood sampling, but many times it is unsuccessful. OBJECTIVE: To conduct a systematic review and meta-analysis to evaluate the efficacy and safety of local nitroglycerin (NTG) to facilitate peripheral artery cannulation in neonates and children. REVIEW METHODS: PubMed, EMBASE, CINAHL, Emcare and Cochrane library were searched till August 2021. Grey literature was searched through Mednar. Data were extracted by two reviewers independently using a prespecified form and the risk of bias was assessed. Meta-analysis was conducted using a random-effects model. The I2 statistic was used to quantify statistical heterogeneity. Certainty of evidence was assessed using the criteria of inconsistency, imprecision, indirectness, publication bias and size of effect as per the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) guidelines. RESULTS: Two randomised controlled trials (RCTs) were included in this meta-analysis (n=153). One was conducted in children 2-8 years of age and the other was in children <2 years. Both trials found increased success rates with the use of local NTG. Pooling of the two studies found that the first-attempt success rate was significantly higher in the NTG group (risk difference: 0.44, 95% CI 0.05 to 0.83; I2=89%). Overall procedure time was significantly lower in the NTG group (mean difference: -100.28 s, 95% CI -136.74 to -63.82; I2=0%). No major complications secondary to the use of NTG were noted. The GRADE of evidence was very low. CONCLUSION: Local NTG may be useful in facilitating peripheral arterial cannulation in children. Adequately powered RCTs are needed to confirm these findings.

Outcomes of very preterm infants with neonatal hyperglycaemia: a systematic review and meta-analysis.

OBJECTIVE: To explore the association between hyperglycaemia and adverse outcomes in very preterm infants. DESIGN: Systematic review and meta-analysis. Data were pooled separately for adjusted and unadjusted odds ratios (ORs) using random-effects model. Subgroup analysis was conducted based on study design (cohort and case control). MAIN OUTCOME MEASURES: Association between hyperglycaemia in preterm neonates (<32 weeks or <1500 g) and mortality and morbidities. FINDINGS: Forty-six studies (30 cohort and 16 case control) with data from 34 527 infants were included. Meta-analysis of unadjusted ORs from cohort studies found hyperglycaemia to be significantly associated with mortality, any-grade intraventricular haemorrhage (IVH), severe IVH, any-stage retinopathy of prematurity (ROP), severe ROP, sepsis, chronic lung disease and disability. However, pooling of adjusted ORs found significant associations only for mortality (adjusted OR (CI): 2.37 (1.40 to 4.01); I2: 36%; 6 studies), 'Any grade IVH' (adjusted OR (CI): 2.60 (1.09 to 6.20); I2: 0%; 2 studies) and 'Any stage ROP' (adjusted OR (CI): 3.70 (1.55 to 8.84); I2: 0%; 2 studies). Meta-regression analysis found glucose levels >10 mmol/L to be associated with increased odds of mortality compared with <10 mmol/L. Pooled analysis from case-control studies were similar to cohort studies for most outcomes but limited by small sample size. Longer duration of hyperglycaemia was associated with adverse outcomes. GRADE of evidence was 'Low' or 'Very low'. CONCLUSION: Hyperglycaemia in very preterm infants is associated with higher odds of mortality, any-grade IVH and any-stage ROP. A limitation was lack of availability of adjusted ORs from many of the included studies. PROSPERO REGISTRATION NUMBER: CRD42020193016.

Comparison of the efficacy and safety of cuffed versus uncuffed endotracheal tubes for infants in the intensive care setting: a pilot, unblinded RCT.

OBJECTIVE: To study effectiveness and safety of cuffed versus uncuffed endotracheal tubes (ETTs) in small infants in the intensive care unit (ICU). DESIGN: Pilot RCT. SETTING: Neonatal and paediatric ICUs of children's hospital in Western Australia. PARTICIPANTS: Seventy-six infants ≥35 weeks gestation and infants <3 months of age, ≥3 kg. INTERVENTIONS: Patients randomly assigned to Microcuff cuffed or Portex uncuffed ETT. MAIN OUTCOMES MEASURES: Primary outcome was achievement of optimal ETT leak in target range (10%-20%). Secondary outcomes included: reintubations, ventilatory parameters, ventilatory complications, postextubation complications and long-term follow-up. RESULTS: Success rate (achievement of mean leak in the range 10%-20%) was 13/42 (30.9%) in the cuffed ETT group and 6/34 (17.6%) in uncuffed ETT group (OR=2.09; 95% CI (0.71 to 6.08); p=0.28). Mean percentage time within target leak range in cuffed ETT group 28% (IQR: 9-42) versus 15% (IQR: 0-28) in uncuffed ETT group (p=0.01). There were less reintubations to optimise size in cuffed ETT group 0/40 versus 10/36 (p<0.001). No differences were found in gaseous exchange, ventilator parameters or postextubation complications. There were fewer episodes of atelectasis in cuffed ETT group 0/42 versus 4/34 (p=0.03). No patient had been diagnosed with subglottic stenosis at long-term follow-up. CONCLUSIONS: There was no difference in the primary outcome, though percentage time spent in optimal leak range was significantly higher in cuffed ETT group. Cuffed ETTs reduced reintubations to optimise ETT size and episodes of atelectasis. Cuffed ETTs may be a feasible alternative to uncuffed ETTs in this group of patients. TRIAL REGISTRATION NUMBER: ACTRN12615000081516.

Diffuse excessive high signal intensity on term equivalent MRI does not predict disability: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether diffuse excessive high signal intensity (DEHSI) on term equivalent age MRI (TEA-MRI) predicts disability in preterm infants. DESIGN: This is a systematic review and meta-analysis. Medline, EMBASE, Cochrane Library, EMCARE, Google Scholar and MedNar databases were searched in July 2019. Studies comparing developmental outcomes of isolated DEHSI on TEA-MRI versus normal TEA-MRI were included. Two reviewers independently extracted data and assessed the risk of bias. Meta-analysis was undertaken where data were available in a format suitable for pooling. MAIN OUTCOME MEASURES: Neurodevelopmental outcomes ≥1 year of corrected age based on validated tools. RESULTS: A total of 15 studies (n=1832) were included, of which data from 9 studies were available for meta-analysis. The pooled estimate (n=7) for sensitivity of DEHSI in predicting cognitive/mental disability was 0.58 (95% CI 0.34 to 0.79) and for specificity was 0.46 (95% CI 0.20 to 0.74). The summary area under the receiver operating characteristics (ROC) curve was low at 0.54 (CI 0.50 to 0.58). A pooled diagnostic OR (DOR) of 1 indicated that DEHSI does not discriminate preterm infants with and without mental disability. The pooled estimate (n=8) for sensitivity of DEHSI in predicting cerebral palsy (CP) was 0.57 (95% CI 0.37 to 0.75) and for specificity was 0.41 (95% CI 0.24 to 0.62). The summary area under the ROC curve was low at 0.51 (CI 0.46 to 0.55). A pooled DOR of 1 indicated that DEHSI does not discriminate between preterm infants with and without CP. CONCLUSIONS: DEHSI on TEA-MRI did not predict future development of cognitive/mental disabilities or CP. PROSPERO REGISTRATION NUMBER: CRD42019130576.

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.

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.

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.

Inter-rater reliability of amplitude-integrated EEG for the detection of neonatal seizures.

BACKGROUND: Amplitude-integrated electroencephalogram (aEEG) is being used increasingly for seizure detection in neonates. However, data regarding inter-rater reliability among neonatologists for the use of aEEG for the detection of neonatal seizures is lacking. METHODS: Term and late-preterm infants at risk of seizures were monitored simultaneously with 24-h video-electroencephalography (vEEG) and aEEG. vEEG was interpreted by an experienced neurologist. Five neonatologists with experience in aEEG interpretation from four different neonatal units interpreted aEEG recordings independently. The Brennan and Prediger kappa coefficient and Intra-class Correlation Coefficients (ICC) were used to assess inter-rater reliability between the neonatologists. RESULTS: Thirty-five infants at risk of seizure with gestational age at birth 35-42 weeks were recruited for the study after informed parental consent. vEEG detected seizures in seven infants with a total of 169 individual seizure episodes. Neonatologists detected seizures in 10 to 15 infants on aEEG. The sensitivities for the detection of individual seizures by neonatologists ranged from 18% to 38%. The inter-rater reliability for detection of: individual seizure was "fair" (kappa = 0.37; 95% CI: 0.32-0.42), infant with seizure was "moderate" (kappa = 0.60; 95% CI: 0.44-0.75), duration of individual seizure (ICC: 0.22; 95% CI: 0.18-0.28) and total duration of seizures in an infant (ICC: 0.46; 95% CI: 0.30-0.63) was "poor". The neonatologists missed 77-90% of the duration of seizures. CONCLUSION: The inter-rater reliability of aEEG for the detection of neonatal seizures was suboptimal. Even when interpreted by experienced and trained clinicians, seizure detection with aEEG has limitations and can miss large number and duration of seizures.

Umbilical cord milking in preterm infants: a systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis of the efficacy and safety of umbilical cord milking in preterm infants. DESIGN: Randomised controlled trials comparing umbilical cord milking with delayed cord clamping/immediate cord clamping in preterm infants were identified by searching databases, clinical trial registries and reference list of relevant studies in November 2019. Fixed effects model was used to pool the data on various clinically relevant outcomes. MAIN OUTCOME MEASURES: Mortality and morbidities in preterm neonates. RESULTS: Nineteen studies (2014 preterm infants) were included. Five studies (n=922) compared cord milking with delayed cord clamping, whereas 14 studies (n=1092) compared milking with immediate cord clamping. Cord milking, as opposed to delayed cord clamping, significantly increased the risk of intraventricular haemorrhage (grade III or more) (risk ratio (RR): 1.95 (95% CI 1.01 to 3.76), p=0.05). When compared with immediate cord clamping, cord milking reduced the need for packed RBC transfusions (RR:0.56 (95% CI 0.43 to 0.73), p<0.001). There was limited information on long-term neurodevelopmental outcomes. The grade of evidence was moderate or low for the various outcomes analysed. CONCLUSION: Umbilical cord milking, when compared with delayed cord clamping, significantly increased the risk of severe intraventricular haemorrhage in preterm infants, especially at lower gestational ages. Cord milking, when compared with immediate cord clamping, reduced the need for packed RBC transfusions but did not improve clinical outcomes. Hence, cord milking cannot be considered as placental transfusion strategy in preterm infants based on the currently available evidence.

Probiotic research in neonates with congenital gastrointestinal surgical conditions - Now is the time.

Neonates with congenital gastrointestinal surgical conditions (CGISC) receive parenteral nutrition, get exposed to multiple courses of antibiotics, undergo invasive procedures, and are nursed in intensive care units. They do not receive early enteral feeding and have limited opportunities for skin to skin contact with their mothers. Many of these infants receive gastric acid suppression therapies. All these factors increase the risk of gut dysbiosis in these infants. Gut dysbiosis is known to be associated with increased risk of infections and other morbidities in ICU patients. Experimental studies have shown that probiotics inhibit gut colonization with pathogenic bacteria, enhance gut barrier function, facilitate colonization with healthy commensals, protect from enteropathogenic infection through production of acetate, reduce antimicrobial resistance, enhance innate immunity, and increase the maturation of the enteric nervous system and promote gut peristalsis. Through these mechanisms, probiotics have the potential to decrease the risk of sepsis and inflammation, improve feed tolerance and minimise cholestasis in neonates with CGISC. Among preterm non-surgical infants, evidence from more than 35 RCTs and multiple observational studies have shown probiotics to be safe and beneficial. A RCT in neonates (N=24) with gastroschisis found that probiotic supplementation partially attenuated gut dysbiosis. Two ongoing RCTs (total N=168) in neonates with gastrointestinal surgical conditions are expected to provide feasibility data to enable the conduct of large RCTs. Rigorous quality assurance of the probiotic product, ongoing microbial surveillance and clinical vigilance are warranted while conducting such RCTs.

Prevalence of Autism Spectrum Disorder in Preterm Infants: A Meta-analysis.

CONTEXT: Evidence is emerging that preterm infants are at risk for autism spectrum disorder (ASD). OBJECTIVES: To conduct a systematic review and meta-analysis to estimate the prevalence of ASD in preterm infants. DATA SOURCES: Medline (via PubMed and Ovid), Embase, PsycINFO, and relevant conference proceedings were searched in May 2017. STUDY SELECTION: Original studies in which researchers report on the prevalence of ASD using diagnostic tests in children born preterm were included. Studies in which researchers used only ASD screening tools were excluded. DATA EXTRACTION: Relevant data were extracted independently by 3 authors. RESULTS: Researchers in a total of 18 studies (3366 preterm infants) used ASD diagnostic tools. The median gestation, birth weight, and age at assessment were 28.0 weeks (range: 25.1-31.3 weeks), 1055 g (range: 719-1565 g), and 5.7 years (range: 1.5-21 years), respectively. Meta-analysis revealed that the overall prevalence rate for ASD was 7% (95% confidence interval: 4% to 9%). The funnel plot and Egger's test revealed that there was probably no evidence of publication bias. LIMITATIONS: The limitations were significant heterogeneity and a lack of studies from middle- and low-income countries. CONCLUSIONS: The prevalence of ASD is significantly high in the preterm population. Adequate resources are needed to improve the outcomes of these children.

Cuffed endotracheal tubes in infants less than 3 kg: A retrospective cohort study.

BACKGROUND: Cuffed endotracheal tubes are being increasingly used in infants; however, current evidence in the literature mostly includes infants ≥ 3-kg weight. AIMS: The aim of this observational study was to compare the short-term outcomes with the use of Microcuff® cuffed vs uncuffed endotracheal tubes in neonates < 3 kg. METHODS: We performed a retrospective cohort study in a single-centre, tertiary children's hospital neonatal intensive care unit. The study included all infants < 3 kg receiving Microcuff® cuffed endotracheal tubes over the period January 2015 to January 2016. Controls were all infants 2000-2999 g receiving an uncuffed endotracheal tube over the period September 2015 to January 2016. RESULTS: Twenty-three patients < 3 kg were intubated with cuffed endotracheal tubes. All were inserted in the operating room. Of 23 patients, 14 (60.9%) patients had the cuff inflated in the operating room and none subsequently in the neonatal intensive care unit. The group receiving cuffed endotracheal tubes was compared with 23 patients with uncuffed endotracheal tubes. There was no difference in weight (median 2620 g vs 2590 g, diff in median = 10, 95% CI -120, 130) or duration of intubation (median 27 vs 44 hours, diff in median = 17, 95% CI -5, 46). However, there was a significant difference in gestational age (median 37 vs 35 weeks, diff in median = -1, 95% CI -2, 0) and age at intubation (median 6 vs 0 days, diff in median = -4, 95% CI -10, -1). There were no significant differences in the rates of: change of endotracheal tube to find correct size (0/23 vs 4/23, P = .109, OR = 0.13, 95% CI 0.01, 1.41); median ventilator leak reading (0% [IQR 0%-12%] vs 0% [IQR 0%-5.5%], P = .201, diff in median = 0, 95% CI -5.5, 0); unplanned extubations (0/23 vs 2/23; atelectasis (4/23 vs 0/23; endotracheal tube blockage (0/23 vs 0/23; pneumonia (0/23 vs 0/23; or postextubation stridor (1/23 vs 2/23). CONCLUSION: This retrospective study with a small sample size found that Microcuff® cuffed endotracheal tubes may be safe in neonates < 3 kg. Well-designed randomized controlled trials are needed to address this issue definitively.

Severe acquired subglottic stenosis in neonatal intensive care graduates: a case-control study.

OBJECTIVE: To analyse current incidence and risk factors associated with severe acquired subglottic stenosis (SASGS) requiring surgical intervention in neonates. DESIGN: Retrospective case-control study. SETTING: Sole tertiary children's hospital. PARTICIPANTS: Patients who underwent surgical intervention for SASGS from January 2006 to December 2014. For each neonatal intensive care unit (NICU) graduate with acquired SASGS, two controls were selected (matched for gestation and year of birth). MAIN OUTCOMES AND MEASURES: Incidences were calculated and cases and controls compared using conditional logistic regression analysis to identify risk factors for SASGS. RESULTS: Thirty-seven NICU graduates required surgical intervention for SASGS of whom 35 were <30-week gestation at birth. The incidence of SASGS in surviving children who had required ventilation in the neonatal period was 27/2913 (0.93%). Incidence was higher in infants <28-week gestation (24/623=3.8%) compared with infants ≥28-week gestation (3/2290=0.13%; p=0.0001). On univariate analysis, risk factors for SASGS were: higher number of intubations (4 vs 2; p<0.001); longer duration ventilation (16 vs 9.5 days; p<0.001); unplanned extubation (45.7% vs 20.0%; p=0.007); traumatic intubation (34.3% vs 7.1%; p=0.003) and oversized endotracheal tubes (ETTs) (74.3% vs 42.9%; p=0.001). On multivariate analysis, risk factors for SASGS were: Sherman ratio >0.1 (adjusted OR (aOR) 6.40; 95% CI 1.65 to 24.77); more than five previous intubations (aOR 3.74; 95% CI 1.15 to 12.19); traumatic intubation (aOR 3.37; 95% CI 1.01 to 11.26). CONCLUSIONS: SASGS is a serious consequence of intubation for mechanical ventilation in NICU graduates, especially in preterm infants. Minimising trauma during intubations, avoiding recurrent extubation/reintubations and using appropriate sized ETTs may help prevent this serious complication.

Role of upper gastrointestinal contrast studies for suspected malrotation in neonatal population.

AIM: Upper gastrointestinal (UGI) contrast study is the preferred radiological investigation to diagnose malrotation of intestine. We aimed to review the role of UGI contrast in neonates (term and preterm) who were clinically suspected to have malrotation. METHODS: The study included a retrospective review of medical charts and radiology reports. RESULTS: A total of 164 newborn infants underwent UGI contrast study to rule out malrotation during the study period (2006-2015). Median gestational age at the time of presentation was 38 weeks (interquartile range: 35.5-39.6 weeks). Median age for clinical presentation was day 2 of life (interquartile range: 2-5 days). Out of the 164 contrast studies, 112 were normal, whereas 52 were reported to have malrotation. Of those 52 infants, 47 were confirmed to have malrotation on surgery (positive predictive value: 90). Of the 112 infants with normal UGI contrasts, nine infants underwent laparotomy for ongoing clinical symptoms out of which four infants were diagnosed to have malrotation on laparotomy. There were 22 infants born at gestational age <32 weeks, who underwent UGI contrast studies to rule out malrotation. Their clinical symptoms were similar to necrotising enterocolitis. Of 22 preterm contrast studies, six were reported to have malrotation; of these, five had surgically confirmed malrotation. No complications related to the contrast study were noted in both term and preterm infants. CONCLUSION: Current study reaffirms the role of UGI contrast study as the investigation of choice for diagnosis of malrotation, in both term and preterm infants. UGI contrast is safe and well tolerated even in preterm infants.

Long chain polyunsaturated fatty acid supplementation in infants born at term.

BACKGROUND: The long chain polyunsaturated fatty acids (LCPUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are considered essential for maturation of the developing brain, retina and other organs in newborn infants. Standard infant milk formulae are not supplemented with LCPUFA; they contain only alpha-linolenic acid and linoleic acid, from which formula-fed infants must synthesise their own DHA and AA, respectively. Over the past few years, some manufacturers have added LCPUFA to formula milk and have marketed these products as providing an advantage for the overall development of full-term infants. OBJECTIVES: To assess whether supplementation of formula milk with LCPUFA is both safe and beneficial for full-term infants, while focusing on effects on visual function, neurodevelopment and physical growth. SEARCH METHODS: Two review authors independently searched the Cochrane Central Register of Controlled Trials (CENTRAL; December 2016), MEDLINE (Ovid, 1966 to December 2016), Embase (Ovid, 1980 to December 2016), the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1980 to December 2016) and abstracts of the Pediatric Academic Societies (2000 to 2016). We applied no language restrictions. SELECTION CRITERIA: We reviewed all randomised controlled trials (RCTs) evaluating effects of LCPUFA supplemented versus non-supplemented formula milk on visual function, neurodevelopment and physical growth. We did not include trials reporting only biochemical outcomes. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently. We assessed risk of bias of included studies using the guidelines of the Cochrane Neonatal Review Group. When appropriate, we conducted meta-analysis to determine a pooled estimate of effect. MAIN RESULTS: We identified 31 RCTs and included 15 of these in the review (N = 1889).Nine studies assessed visual acuity, six of which used visual evoked potentials (VEP), two Teller cards and one both. Four studies reported beneficial effects, and the remaining five did not. Meta-analysis of three RCTs showed significant benefit for sweep VEP acuity at 12 months (log of the minimum angle of resolution (logMAR)) (mean difference (MD) -0.15, 95% confidence interval (CI) -0.17 to -0.13; I2 = 0; three trials; N = 244), but meta-analysis of three other RCTs showed no benefit for visual acuity measured with Teller cards at 12 months (cycles/degree) (MD -0.01, 95% CI -0.12 to 0.11; I2 = 0; three trials; N = 256). GRADE analysis for the outcome of visual acuity indicated that the overall quality of evidence was low.Eleven studies measured neurodevelopmental outcomes at or before two years. Nine studies used Bayley Scales of Infant Development, version II (BSID-II), and only two of these studies reported beneficial effects. Meta-analysis revealed no significant differences between LCPUFA and placebo groups in BSID Mental Developmental Index (MDI) scores at 18 months (MD 0.06, 95% CI -2.01 to 2.14; I2 = 75%; four trials; N = 661) and no significant differences in BSID Psychomotor Development Index (PDI) scores at 18 months (MD 0.69, 95% CI -0.78 to 2.16; I2 = 61%; four trials; N = 661). Results showed no significant differences between the two groups in BSID-II scores at one year and two years of age. One study reported better novelty preference measured by the Fagan Infant Test at nine months. Another study reported better problem solving at 10 months. One study used the Brunet and Lezine test to assess the developmental quotient and found no beneficial effects. Follow-up of some infants in different studies at three, six and nine years of age revealed no beneficial effects of supplementation. GRADE analysis of these outcomes indicated that the overall quality of evidence was low.Thirteen studies measured physical growth; none found beneficial or harmful effects of supplementation. Meta-analysis of five RCTs showed that the supplemented group had lower weight (z scores) at one year of age (MD -0.23, 95% CI -0.40 to -0.06; I2 = 83%; N = 521) and that the two groups showed no significant differences with respect to length and head circumference (z scores). Meta-analysis at 18 months and at two years revealed no significant differences between the two groups with respect to weight (kg), length (cm) and head circumference (cm). GRADE analysis of these outcomes indicated that the overall quality of evidence was low. AUTHORS' CONCLUSIONS: Most of the included RCTs reported no beneficial effects or harms of LCPUFA supplementation on neurodevelopmental outcomes of formula-fed full-term infants and no consistent beneficial effects on visual acuity. Routine supplementation of full-term infant milk formula with LCPUFA cannot be recommended at this time.

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

BACKGROUND: Animal studies and trials in older children and adults suggest that a 'one dose per day' regimen of gentamicin is superior to a 'multiple doses per day' regimen. OBJECTIVES: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates. SEARCH METHODS: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3) in the Cochrane Library (searched 8 April 2016), MEDLINE (1966 to 8 April 2016), Embase (1980 to 8 April 2016), and CINAHL (December 1982 to 8 April 2016). SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing one dose per day ('once a day') compared to multiple doses per day ('multiple doses a day') of gentamicin to newborn infants. DATA COLLECTION AND ANALYSIS: Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Eleven RCTs were included (N = 574) and 28 excluded. All except one study enrolled infants of more than 32 weeks' gestation. Limited information suggested that infants in both 'once a day' as well as 'multiple doses a day' regimens showed adequate clearance of sepsis (typical RR 1.00, 95% CI 0.84 to 1.19; typical RD 0.00, 95% CI -0.19 to 0.19; 3 trials; N = 37). 'Once a day' gentamicin regimen was associated with fewer failures to attain peak level of at least 5 µg/ml (typical RR 0.22, 95% CI 0.11 to 0.47; typical RD -0.13, 95% CI -0.19 to -0.08; number needed to treat for an additional beneficial outcome (NNTB) = 8; 9 trials; N = 422); and fewer failures to achieve trough levels of 2 µg/ml or less (typical RR 0.38, 95% CI 0.27 to 0.55; typical RD -0.22, 95% CI -0.29 to -0.15; NNTB = 4; 11 trials; N = 503). 'Once a day' gentamicin achieved higher peak levels (MD 2.58, 95% CI 2.26 to 2.89; 10 trials; N = 440) and lower trough levels (MD -0.57, 95% CI -0.69 to -0.44; 10 trials; N = 440) than 'multiple doses a day' regimen. There was no significant difference in ototoxicity between two groups (typical RR 1.69, 95% CI 0.18 to 16.25; typical RD 0.01, 95% CI -0.04 to 0.05; 5 trials; N = 214). Nephrotoxicity was not noted with either of the treatment regimens. Overall, the quality of evidence was considered to be moderate on GRADE analysis, given the small sample size and unclear/high risk of bias in some of the domains in a few of the included studies. AUTHORS' CONCLUSIONS: There is insufficient evidence from the currently available RCTs to conclude whether a 'once a day' or a 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggest that pharmacokinetic properties of a 'once a day' gentamicin regimen are superior to a 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There was no change in nephrotoxicity or auditory toxicity. Based on the assessment of pharmacokinetics, a 'once a day regimen' may be superior in treating sepsis in neonates of more than 32 weeks' gestation.