Late surfactant administration after 48 hours of age in preterm neonates with respiratory insufficiency: a systematic review and meta-analysis.

OBJECTIVE: To systematically review and meta-analyse the effect of late surfactant administration versus placebo in reducing the incidence of death or bronchopulmonary dysplasia (BPD) in preterm infants. DESIGN: PubMed, EMBASE, CINAHL and Cochrane CENTRAL were searched until 30 May 2023, for randomised controlled trials (RCTs) comparing administration of surfactant after 48 hours of age versus placebo in preterm ventilator-dependent neonates. The primary outcome was incidence of death or BPD at 36 weeks' postmenstrual age (PMA). Secondary outcomes included incidence of BPD at 36 weeks PMA, pre-discharge mortality, use of postnatal steroids, post-discharge respiratory support, treatment with steroids or hospitalisation prior to 1-year corrected age. RESULTS: Pooled analyses of four RCTs (N=850) showed no statistically significant difference between groups in the incidence of death or BPD at 36 weeks' PMA (relative risk (RR) 0.99; 95% CI 0.90 to 1.10; Grades of Recommendation, Assessment, Development and Evaluation (GRADE): moderate). Late surfactant administration significantly decreased the need for post-discharge respiratory support prior to 1-year corrected age (two RCTs; N=522; RR 0.72; 95% CI 0.59 to 0.89; GRADE: low). Other secondary outcomes did not differ significantly between the groups. CONCLUSIONS: Administration of late surfactant does not improve the rates of death or BPD at 36 weeks when administered to preterm infants with prolonged respiratory insufficiency. Additional adequately powered trials are needed to establish the efficacy of late surfactant therapy in preterm infants. PROSPERO REGISTRATION NUMBER: CRD42023432463.

Surfactant delivery via thin catheter in preterm infants: A systematic review and meta-analysis.

OBJECTIVE: Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants <29 weeks' gestation and the neurodevelopmental outcomes remain unclear. Thus, our objective was to systematically review and meta-analyze the efficacy and safety of STC compared to intubation for surfactant or nasal continuous positive airway pressure (nCPAP) in preterm infants with RDS. METHODS: Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE. RESULTS: Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate). CONCLUSIONS: Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation.

Mucous fistula refeeding in neonates: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Mucous fistula refeeding (MFR) aims to maximise bowel function when an ostomy is active after abdominal surgery, by introducing the proximal ostomy effluent into the distal mucous fistula to maintain intestinal physiology. The aim of the study was to assess the effectiveness and complications of MFR in neonates following abdominal surgery. DESIGN, SETTING AND INTERVENTIONS: Systematic review and meta-analysis of randomised controlled trials and observational studies. PubMed, Embase, Cochrane and CINAHL were searched until June 2022 for studies including neonates with ostomy receiving MFR compared with neonates with ostomy without MFR. OUTCOMES: The primary outcome was duration of parenteral nutrition. Secondary outcomes were time to full enteral feeds, rates of cholestasis, peak total serum bilirubin, sepsis, time to reanastomosis and length of hospital stay. RESULTS: A total of 16 observational studies were included (n=623). Compared with comparator group, neonates who received MFR had fewer days of parenteral nutrition (mean difference 37.17 days, 95% CI -63.91 to -10.4, n=244, 5 studies, GRADE: low). In addition, neonates who received MFR had lower rates of cholestasis, shorter time to reach full feeds and shorter hospital stay. CONCLUSION: Low certainty of evidence suggests that MFR is associated with shorter duration of parenteral nutrition in neonates following abdominal surgery and stoma creation. Results of ongoing and future randomised trials may help to corroborate these findings.

Placental Transfusion Strategies in Preterm Infants in Low- and Middle-Income Countries: A Systematic Review and Network Meta-Analysis.

INTRODUCTION: Placental transfusion strategies in preterm newborns have not been evaluated in low- and middle-income countries (LMICs). The objective of this systematic review was to compare placental transfusion strategies in preterm newborns in LMICs, including delayed cord clamping (DCC) for various time intervals, DCC until cord pulsations stop, umbilical cord milking, and immediate cord clamping (ICC). METHODS: Medline, Embase, CINAHL, and CENTRAL were searched from inception. Observational studies and randomized controlled trials (RCTs) were included. Two authors independently extracted data for Bayesian random-effects network meta-analysis (NMA) if more than 3 interventions reported an outcome or a pairwise meta-analysis was utilized. RESULTS: Among newborns <34 weeks of gestation, NMA of 9 RCTs could not rule out benefit or harm for survival from DCC 30-60 s compared to ICC: relative risk (RR) (95% credible interval) 0.96 (0.78-1.12), moderate certainty, or any included strategy compared to each other (low to very low certainty). Among late preterm newborns, DCC 120 s might be associated with improved survival: RR (95% confidence interval) 1.11 (1.01-1.22), very low certainty. We could not detect differences in the risk of intraventricular hemorrhage grade > II and bronchopulmonary dysplasia for any included intervention (low to very low certainty). DCC 60 s and 120 s might improve the hematocrit level among all preterm newborns (very low certainty), and DCC 45 s may decrease the risk of receipt of inotropes among newborns <34 weeks of gestation (low certainty). CONCLUSIONS: In LMICs, DCC for 60 s and 120 s might improve hematocrit level in preterm newborns, and DCC for 45 s may decrease the risk of receipt of inotropes in newborns <34 weeks, with no conclusive effect on survival.

Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants.

BACKGROUND: The different management strategies for patent ductus arteriosus (PDA) in preterm infants are expectant management, surgery, or medical treatment with non-selective cyclo-oxygenase inhibitors. Randomized controlled trials (RCTs) have suggested that paracetamol may be an effective and safe agent for the closure of a PDA. OBJECTIVES: To determine the efficacy and safety of paracetamol as monotherapy or as part of combination therapy via any route of administration, compared with placebo, no intervention, or another prostaglandin inhibitor, for prophylaxis or treatment of an echocardiographically-diagnosed PDA in preterm or low birth weight infants. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and three trials registers on 13 October 2021, and one other database on 1 March 2022. We also checked references and contacted study authors to identify additional studies. SELECTION CRITERIA: We included RCTs and quasi-RCTs in which paracetamol (single-agent or combination therapy) was compared to no intervention, placebo, or other agents used for closure of PDA, irrespective of dose, duration, and mode of administration in preterm infants. Two independent authors reviewed the search results and made a final selection of potentially eligible articles through discussion. DATA COLLECTION AND ANALYSIS: We performed data collection and analyses in accordance with the methods of Cochrane Neonatal. We used the GRADE approach to assess the certainty of evidence for the following outcomes: failure of ductal closure after the first course of treatment; all-cause mortality during initial hospital stay; and necrotizing enterocolitis (NEC). MAIN RESULTS: For this update, we included 27 studies enrolling 2278 infants. We considered the overall risk of bias in the 27 studies to vary from low to unclear. We identified 24 ongoing studies. Paracetamol versus ibuprofen  There was probably little to no difference between paracetamol and ibuprofen for failure of ductal closure after the first course (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.88 to 1.18; 18 studies, 1535 infants; moderate-certainty evidence). There was likely little to no difference between paracetamol and ibuprofen for all-cause mortality during hospital stay (RR 1.09, 95% CI 0.80 to 1.48; 8 studies, 734 infants; moderate-certainty evidence), and for NEC (RR 1.30, 95% CI 0.87 to 1.94; 10 studies, 1015 infants; moderate-certainty evidence). Paracetamol versus indomethacin There was little to no difference between paracetamol and indomethacin for failure of ductal closure after the first course (RR 1.02, 95% CI 0.78 to 1.33; 4 studies, 380 infants; low-certainty evidence). There was little to no difference between paracetamol and indomethacin for all-cause mortality during hospital stay (RR 0.86, 95% CI 0.39 to 1.92; 2 studies, 114 infants; low-certainty evidence). The rate of NEC may be lower in the paracetamol group (3.7%) versus the indomethacin group(9.2%) (RR 0.42, 95% CI 0.19 to 0.96; 4 studies, 384 infants; low-certainty evidence).  Prophylactic paracetamol versus placebo/no intervention Prophylactic paracetamol (17%) compared to placebo/no intervention (61%) may reduce failure of ductal closure after one course (RR 0.27, 95% CI 0.18 to 0.42; 3 studies, 240 infants; low-certainty evidence). There was little to no difference between prophylactic paracetamol and placebo/no intervention for all-cause mortality during hospital stay (RR 0.59, 95% CI 0.24 to 1.44; 3 studies, 240 infants; low-certainty evidence). No studies reported on NEC.  Early paracetamol treatment versus placebo/no intervention Early paracetamol treatment (28%) compared to placebo/no intervention (79%) may reduce failure of ductal closure after one course when used before 14 days' postnatal age (RR 0.35, 95% CI 0.23 to 0.53; 2 studies, 127 infants; low-certainty evidence). No studies reported on all-cause mortality during hospital stay or NEC.  Late paracetamol treatment versus placebo/no intervention  There was little to no difference between late paracetamol and placebo for failure of ductal closure after one course of treatment when used at or after 14 days' postnatal age (RR 0.85, 95% CI 0.72 to 1.01; 1 study, 55 infants; low-certainty evidence) or NEC (RR 1.04, 95% CI 0.07 to 15.76; 1 study, 55 infants; low-certainty evidence). No data were reported for all-cause mortality during hospital stay.  Paracetamol combined with ibuprofen versus ibuprofen combined with placebo or no intervention There was little to no difference between paracetamol plus ibuprofen compared to ibuprofen plus placebo or no intervention for failure of ductal closure after the first course (RR 0.77, 95% CI 0.43 to 1.36; 2 studies, 111 infants; low-certainty evidence). There was little to no difference between paracetamol plus ibuprofen compared to ibuprofen plus placebo or no intervention for NEC (RR 0.33, 95% CI 0.01 to 7.45; 1 study, 24 infants; low-certainty evidence). No data were reported for all-cause mortality during hospital stay.  AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that there is probably little or no difference in effectiveness between paracetamol and ibuprofen; low-certainty evidence suggests that there is probably little or no difference in effectiveness between paracetamol and indomethacin; low-certainty evidence suggests that prophylactic paracetamol may be more effective than placebo/no intervention; low-certainty evidence suggests that early paracetamol treatment may be more effective than placebo/no intervention; low-certainty evidence suggests that there is probably little or no difference between late paracetamol treatment and placebo, and probably little or no difference in effectiveness between the combination of paracetamol plus ibuprofen versus ibuprofen alone for the closure of PDA after the first course of treatment. The majority of neonates included in these studies were of moderate preterm gestation. Thus, establishing the efficacy and safety of paracetamol for PDA treatment in extremely low birth weight (ELBW: birth weight < 1000 grams) and extremely low gestational age neonates (ELGANs < 28 weeks' gestation) requires further studies.

Timing of Systemic Steroids and Neurodevelopmental Outcomes in Infants < 29 Weeks Gestation

Objective: To determine the association between postnatal age (PNA) at first administration of systemic postnatal steroids (sPNS) for bronchopulmonary dysplasia (BPD) and mortality or significant neurodevelopmental impairment (sNDI) at 18−24 months corrected age (CA) in infants < 29 weeks' gestation. Methods: Data from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases were used to conduct this retrospective cohort study. Infants exposed to sPNS for BPD after the 1st week of age were included and categorized into 8 groups based on the postnatal week of the exposure. The primary outcome was a composite of mortality or sNDI. A multivariable logistic regression model adjusting for potential confounders was used to determine the association between the sPNS and ND outcomes. Results: Of the 10,448 eligible infants, follow-up data were available for 6200 (59.3%) infants. The proportion of infants at first sPNS administration was: 8%, 17.5%, 23.1%, 18.7%, 12.6%, 8.3%, 5.8%, and 6% in the 2nd, 3rd, 4th, 5th, 6th, 7th, 8−9th, and ≥10th week of PNA respectively. No significant association between the timing of sPNS administration and the composite outcome of mortality or sNDI was observed. The odds of sNDI and Bayley-III motor composite < 70 increased by 1.5% (95% CI 0.4, 2.9%) and 2.6% (95% CI 0.9, 4.4%), respectively, with each one-week delay in the age of initiation of sPNS. Conclusions: No significant association was observed between the composite outcome of mortality or sNDI and PNA of sPNS. Among survivors, each week's delay in initiation of sPNS may increase the odds of sNDI and motor delay.

Is late treatment with acetaminophen safe and effective in avoiding surgical ligation among extremely preterm neonates with persistent patent ductus arteriosus?

OBJECTIVE: Evaluate the association of late treatment with acetaminophen vs. immediate surgical ligation with death or neurodevelopmental impairment (NDI) among extremely low gestational age neonates (ELGANs) with persistent patent ductus arteriosus (pPDA). STUDY DESIGN: Retrospective comparative epoch study of ELGANs with pPDA being considered for surgical ligation. ELGANs in epoch 1 (2009-2012) were referred for ligation, while infants in epoch 2 (2012-2015) were treated with oral acetaminophen and referred for ligation in the absence of improvement. The primary outcome was a composite of death/NDI at 18-24 months. RESULTS: Ninety-two ELGANs with median[IQR] GA 25.2 weeks [24.4, 26.3] had pPDA (43 in epoch 1, 49 in -epoch 2) with acetaminophen-exposed neonates receiving 7 days [7, 7] of treatment. ELGANs in epoch 2 had reduced ligation (aOR 0.30; 95%CI: [0.11, 0.87]), but there was no difference in death/NDI (aOR 1.03; 95%CI: [0.30, 3.56]). CONCLUSIONS: Late treatment with acetaminophen to avoid surgery for pPDA is associated with reduced ligation but no difference in death/NDI, supporting the safety and effectiveness of this approach.

Effectiveness and safety of nasal mask versus binasal prongs for providing continuous positive airway pressure in preterm infants-A systematic review and meta-analysis.

Continuous positive airway pressure (CPAP) delivered via binasal prongs has been the cornerstone of respiratory management in preterm infants. Though effective, the use of binasal prongs is associated with nasal trauma, and CPAP failure. To overcome these issues, nasal masks are increasingly used to deliver CPAP in preterm infants. The aim was to conduct a systematic review of randomized controlled trials (RCTs) comparing nasal mask versus binasal prongs to deliver CPAP in preterm infants. Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing, and Allied Health Literature, and E-abstracts from the Pediatric Academic Society meetings were searched in May 2017. All RCTs comparing nasal mask versus binasal prongs for delivering CPAP in preterm infants were included. Primary outcome was CPAP failure (need for mechanical ventilation within 72 h of initiating CPAP). Secondary outcomes included duration of CPAP, moderate to severe nasal trauma, any nasal trauma, pneumothorax, severe IVH, bronchopulmonary dysplasia at 36 weeks postmenstrual age, and mortality. Five RCTs with low risk of bias were included. Nasal mask significantly decreased the risk of CPAP failure (4 RCTs [N = 459]; relative risk [RR]: 0.63; 95% confidence interval [CI]: 0.45-0.88; P=.007; I2 = 0%, NNT: 9), and the incidence of moderate to severe nasal trauma (3 RCTs [N = 275], RR: 0.41; 95%CI, 0.24-0.72; P = 0.002; I2 = 74%, NNT: 6). Other outcomes did not differ significantly between the groups. Compared to binasal prongs, nasal mask may provide a safe and effective alternative by minimizing the risk of CPAP failure in preterm infants needing CPAP support.

Surfactant Replacement Therapy Beyond Respiratory Distress Syndrome in Neonates.

BACKGROUND: Surfactant replacement therapy is an established modality of treatment in preterm neonates with respiratory distress syndrome. In addition, there are various neonatal respiratory disorders which are characterized by surfactant deficiency in which surfactant therapy can be a feasible and safe option. OBJECTIVE: To collate the literature on the use of surfactant replacement therapy in neonates beyond respiratory distress syndrome and examine the evidence and newer developments. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE, and EMBASE up to June 2015; and previous reviews, including cross-references, abstracts, and conference proceedings. RESULTS: Evidence supports surfactant administration via bolus route in neonates with meconium aspiration syndrome, but additional robust evidence is required before its adoption in clinical practice. There is limited evidence to support surfactant therapy in neonates with pneumonia, pulmonary hemorrhage and bronchopulmonary dysplasia. Large multicenter randomized trials are needed to cement or refute the role of surfactant therapy in these disorders.

Neonatal aortic thrombosis as a result of congenital homocystinuria.

BACKGROUND: Arterial thrombosis, that too in aorta is rare in neonates. CASE CHARACTERISTICS: A 4-day-old presented with non-recordable BP in lower limbs. Doppler ultrasonography of abdomen revealed aortic thrombus. OBSERVATION: Serum homocysteine level was elevated (25.5 umol/L). OUTCOME: Thrombus resolved with subcutaneous LMW heparin therapy for 2 weeks. MESSAGE: Congenital classic homocystinuria can rarely cause aortic thrombosis in neonatal period.