Correction to: Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis.

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Oral propranolol in prevention of severe retinopathy of prematurity: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the efficacy of oral beta blockage treatment in primary (before established) and secondary (in threshold stages) prevention of severe retinopathy of prematurity (ROP) in premature infants born ≤32 weeks gestational age. STUDY DESIGN: Following the PRISMA guidelines, published literature was systematically assessed up to April 27, 2018. Trials and observational studies, in which beta blockage was used to prevent severe ROP (defined as stage ≥3, or requiring treatment) were included. Meta-analyses including random effects models were conducted to determine the overall effect of oral beta blockage on prevention of ROP. RESULTS: Six studies (five clinical trials and one observational study) including 461 infants met inclusion criteria using propranolol. The pooled relative risk (RR) of severe ROP in the primary and secondary prophylaxis groups were 0.65 (95% CI 0.43-0.98, NNT = 7) and 0.48 (95% CI 0.35-0.65, NNT = 6) in RCTs, respectively. The RR of severe ROP in one observational study was 0.21 (95% CI 0.08-0.55) with a NNT of 3. There were low heterogeneity and publication bias. Side effects occurred in 8.4% of participants on propranolol. CONCLUSIONS: Systematic assessment of studies showed that prophylactic oral propranolol appeared to be effective in preventing severe ROP in premature infants ≤32 weeks gestational age. Additional well powered, multinational, randomized control trials reporting on long-term outcomes are needed.

Effect of oropharyngeal colostrum therapy in the prevention of necrotising enterocolitis among very low birthweight neonates: A meta-analysis of randomised controlled trials.

BACKGROUND: Necrotising enterocolitis (NEC) is one of the most common life-threatening emergencies of the gastrointestinal tract in preterm neonates. The present study aimed to determine the efficacy of oropharyngeal colostrum with respect to reducing NEC in preterm neonates. METHODS: A literature search was conducted for various randomised control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE and ongoing clinical trials. Randomised or quasi-randomised trials comparing oropharyngeal colostrum versus placebo in neonates (birthweight ≤ 1500 g or gestational age ≤ 32 weeks) were included in the review. The methodological quality of each trial was independently reviewed by the authors. For categorical and continuous variables, typical estimates for relative risk and typical estimates for weighted mean difference were calculated, respectively. A random effect model was assumed for meta-analysis. RESULTS: In total, four eligible trials were included in the review. Oropharyngeal colostrum therapy was not associated with a statistically significant reduction in the incidence of NEC stage ≥2 [typical relative risk (RR) = 0.64; 95% confidence interval (CI) = 0.27-1.49], mortality from any cause (typical RR = 0.86; 95% CI = 0.15-4.80) and time to reach full feed [typical weighted mean difference (WMD) = -3.26; 95% CI = -8.87 to 2.35]. Duration of hospital stay was significantly less in the control group (typical WMD = 9.77; 95% CI = 3.96-15.59). CONCLUSIONS: The current evidence is insufficient for recommending oropharyngeal colostrum as a routine clinical practice in the prevention of NEC. We emphasise the need for large randomised controlled trials with an adequate sample size and validated clinical outcomes in preterm neonates.

Neonatal Cerebral Air Embolism.

BACKGROUND: Vascular air embolism (VAE) is rare but potentially lethal condition, and survival is rarely reported in newborn. CHARACTERISTICS: A preterm (27+1 weeks) neonate on Continuous positive airway pressure developed sudden cardiac asystole on day 3 of life and required 30 minutes of cardiopulmonary resuscitation. OBSERVATION: Infant had air embolism in liver and brain. He survived but developed cystic encephalomalcia requiring extensive neuro-rehabilitation. MESSAGE: Air embolism should be considered as differential diagnosis of sudden unexplained cardiac deterioration in well neonate.

Oral paracetamol in treatment of closure of patent ductus arteriosus in preterm neonates.

We herewith report a case series of six premature neonates with hemodynamically significant paten ductus successfully treated with oral paracetamol. This is a first case series describing the use of oral paracetamol treatment patent ductus in preterm neonates from India. Further prospective randomized-controlled trials are needed to evaluate the efficacy and safety of oral paracetamol in the treatment of patent ductus in preterm neonates.

Validation of the PELOD score for multiple organ dysfunction in children.

We conducted a prospective study to identify the children having multiple organ dysfunction at admission using the PELOD score, and its impact on the mortality in a pediatric intensive care unit of a tertiary care hospital in north India over a 13 month period. Data were collected in a predesigned collection sheet and the PELOD score was calculated. 209 patients were admitted. In 37.2% primary indication of admission was severe sepsis/ septic shock. Ninety-one percentage of children admitted had multiple organ dysfunction. The area under the curve for predicting death using PELOD score equation was 0.80.

Multiple versus single lumen umbilical venous catheters for newborn infants.

BACKGROUND: Multiple lumen umbilical venous catheters (ML-UVCs) instead of single lumen UVCs (SL-UVCs) may decrease the need for additional venous lines. Although it seems self-evident that ML-UVCs would reduce the need of additional venous lines, the rates of associated complications might be different. OBJECTIVES: To compare the effectiveness and the safety of ML-UVCs versus SL-UVCs in terms of need of additional vascular access, rates of complications, morbidity and mortality in newborn infants. SEARCH STRATEGY: Randomized and quasi-randomized trials were identified by searching the MEDLINE (1966 - February 2005), EMBASE (1980- February 2005), CINAHL (1982 - February 2005), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2004) and Science Direct (subject area: medicine, journal and abstract database; 1967 to February 2005). Literature search also included a manual search of the abstracts of scientific meetings published in Pediatric Research (1990-2004). Additional citations were sought using references in articles retrieved from searches. Subject experts were contacted to identify the unpublished and ongoing studies. SELECTION CRITERIA: Randomized and quasi-randomized controlled clinical trials comparing safety and efficacy of multiple versus single lumen umbilical venous catheter in neonates (both term and preterm) who were in need of umbilical venous catheter insertion for vascular access in first four weeks of life. DATA COLLECTION AND ANALYSIS: Each review author performed data extraction independently and differences were resolved by discussion. The following outcomes were determined: total number of additional peripheral intravenous lines per baby in first week and first four weeks of life, total number of additional percutaneously and surgically placed central venous lines per baby in first four weeks of life, and other safety and efficacy measures. The treatment effect estimators used were RR, RD, and WMD when appropriate along with their 95% CI. If RD was statistically significant, then number needed to treat (NNT) or number needed to harm (NNH) was calculated. MAIN RESULTS: Three studies qualified for inclusion in this review (Khilnani 1991; Loisel 1996; Soupre 1998). There was a decrease in the ML-UVCs group in the number of additional PIVs used in the first week of life [WMD -1.42, (95% CI -1.74, -1.10), p<0.00001, number of infants (n) = 99]. There was no significant effect on the number of additional PIVs used in the first four weeks of life [MD -2.30, (95% CI -6.65, 2.05), n=36]. There was an increase in catheter malfunction in the ML-UVCs group [typical RR 3.69 (95% CI 0.99, 13.81), p=0.05; RD 0.15 (95% CI 0.03, 0.27), p=0.01; NNH was 7, 95% CI 4, 33; n=99]. The following outcomes were not significantly different in the two groups: clinical sepsis, catheter related blood stream infection, catheter-associated thrombosis, complications related to catheter malposition in heart and great vessels, NEC and early neonatal mortality. AUTHORS' CONCLUSIONS: The use of ML-UVCs in comparison to SL-UVCs in neonates is associated with decrease in the usage of PIVs in first week of life, but an increase in catheter malfunctions. As the quality of included randomized studies is poor and the estimates of clinically important complications are imprecise, no firm recommendations can be made regarding the choice of UVC. Adequately powered, properly randomized and properly blinded controlled trials are needed that address the effectiveness and safety of ML-UVCs (double and triple lumen) in comparison to SL-UVCs. These studies should also address the impact of type of catheter material.

Carnitine supplementation for preterm infants with recurrent apnea.

BACKGROUND: Apnea of prematurity is a common problem in preterm infants in the neonatal intensive care setting (NICU), often delaying their discharge home or transfer to a step down unit. Premature infants are at increased risk of carnitine deficiency. Carnitine supplementation has been used for both prevention and treatment of apnea. OBJECTIVES: To determine whether treatment with carnitine will reduce the frequency of apnea, the duration of ventilation and the duration of hospital stay in preterm infants with recurrent apnea. SEARCH STRATEGY: Computerised searches were carried out by two reviewers independently. Searches were made of MEDLINE (1966 to May 2004), EMBASE (1980 to May 2004), CINAHL (1982-2004 June 2004,1st week), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), abstracts of annual meetings of the Society for Pediatric Research (1995-2004), and contacts were made with the subject experts. SELECTION CRITERIA: Only randomized or quasi-randomized treatment trials of preterm infants with a diagnosis of recurrent apnea of prematurity were considered. Trials were included if they involved treatment with carnitine compared to placebo or no treatment, and measured at least one of the following outcomes: failure of resolution of apneas, the duration of ventilation and the duration of hospital stay. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the papers for inclusion criteria and quality. Corresponding authors were contacted for further information where needed. MAIN RESULTS: No eligible trials were identified. REVIEWERS' CONCLUSIONS: Despite the plausible rationale for the treatment of apnea of prematurity with carnitine, there are insufficient data to support its use for this indication. Further studies are needed to determine the role of this treatment in clinical practice.

Correlation between clinical diagnoses at the time of death and autopsy findings in critically sick neonates at a regional neonatal intensive care unit in India.

This study was carried out to examine the correlation between clinical diagnoses at the time of death and autopsy findings in newborn babies who died in the regional Neonatal Intensive Care Unit (NICU) of King Edward VII Memorial Hospital affiliated to Bombay University. A consecutive sample of 240 newborns that died during the study period constituted the study cohort. Of these 240 (172 born in the hospital and 68 born outside) newborns who died during the study period, 197 (82.1 per cent) had autopsies performed. The mean Rushton's score for all the autopsies was 307+/-25.8 (range 300-400). There were 24 cases (12.2 per cent) where autopsy revealed a major finding (class I) that, if known prior to death, would have altered clinical management and could have resulted in cure or prolonged survival. In 53 patients (26.9 per cent) the autopsy revealed a major finding (class II) that, if known prior to death, would not have altered clinical management because specific therapy was unavailable or the patient had received appropriate therapy. It is concluded that a good quality autopsy continues to yield valuable and unsuspected information in a substantial number of newborn deaths.

Congenital splenic cyst: a case report and review of the literature.

There are very few cases of antenatally diagnosed congenital splenic cyst described in literature. The present case of congenital splenic cyst was first suspected on ultrasound examination at 20 weeks of gestation and followed subsequently. Its exact location in the spleen was found on postnatal ultrasound examination. The aetiology, differential diagnosis, complications and management strategies of this lesion are also discussed.

Survival after an acute pericardial tamponade as a result of percutaneously inserted central venous catheter in a preterm neonate.

Percutaneously inserted central venous catheters (PICC) are used in premature infants to deliver intravenous fluids, total parenteral nutrition (TPN) and medications. This article reports a case in which the baby developed pericardial tamponade within 3 hours of starting TPN through a PICC. This was successfully treated with percutaneous subxiphoid pericardiocentesis. Pericardial tamponade should be suspected in any infant with a PICC line in place, and who suddenly develops shock like symptoms, non-attributable to usual causes.

"Porcine bronchus" diagnosed in neonatal period.

"Porcine bronchus" is a right upper lobe bronchus arising directly from the trachea. This is an infrequent congenital abnormality and it usually represents the displaced origin of a normal bronchus. We herewith report a case of a child who was diagnosed to have tracheal bronchus in neonatal period and followed subsequently until 13 months of age.

FADD-deficient T cells exhibit a disaccord in regulation of the cell cycle machinery.

FADD is an adapter protein that was originally isolated as a transducer of apoptotic signals for death domain-containing receptors. However, FADD-deficient mice are embryonic lethal and FADD(-/-) T cells developed from FADD(-/-) embryonic stem cells in the RAG-1(-/-) hosts lack the full potential to proliferate when stimulated through their T-cell receptor complex, suggesting that FADD protein might play a dualistic role in mediating not only cell death signaling but other non-apoptotic cellular pathways as well. Here we show that a substantial number of freshly isolated FADD(-/-) peripheral T cells are cycling but are defective in their co-stimulatory response when stimulated. Analysis of several cell cycle proteins shows normal down-regulation of p27 inhibitor but increased levels of p21, decreased levels of cyclin D2, and constitutive activation of several cyclin-dependent kinases in activated T cells. These data suggest that FADD is involved in the regulation of cell cycle machinery in T lymphocytes.

T cell-specific FADD-deficient mice: FADD is required for early T cell development.

FADD/Mort1, initially identified as a Fas-associated death-domain containing protein, functions as an adapter molecule in apoptosis initiated by Fas, tumor necrosis factor receptor-I, DR3, and TRAIL-receptors. However, FADD likely participates in additional signaling cascades. FADD-null mutations in mice are embryonic-lethal, and analysis of FADD(-)/- T cells from RAG-1(-)/- reconstituted chimeras has suggested a role for FADD in proliferation of mature T cells. Here, we report the generation of T cell-specific FADD-deficient mice via a conditional genomic rescue approach. We find that FADD-deficiency leads to inhibition of T cell development at the CD4(-)CD8(-) stage and a reduction in the number of mature T cells. The FADD mutation does not affect apoptosis or the proximal signaling events of the pre-T cell receptor; introduction of a T cell receptor transgene fails to rescue the mutant phenotype. These data suggest that FADD, through either a death-domain containing receptor or a novel receptor-independent mechanism, is required for the proliferative phase of early T cell development.

In vivo overexpression of Dad1, the defender against apoptotic death-1, enhances T cell proliferation but does not protect against apoptosis.

The Dad1 protein has been shown to play a role in prevention of apoptosis in certain cell types. Dad1 is also a subunit of the oligosaccharyltransferase enzyme complex that initiates N-linked glycosylation. It is encoded by a gene located adjacent to the TCR alpha and delta genes on mouse chromosome 14. We have investigated the role of Dad1 during T cell development and activation. We observe that endogenous Dad1 levels are modulated during T cell development to reach maximal expression in mature thymocytes. Transgenic mice that overexpress Dad1 in both the thymus and peripheral immune system have been generated. Apoptosis of thymocytes from such mice is largely unaffected, but peripheral T cells display hyperproliferation in response to stimuli. Therefore, the linkage between the TCR and Dad1 genes may have important consequences for T cell function.

A tailless fas-FADD death-effector domain chimera is sufficient to execute Fas function in T cells but not B cells of MRL-lpr/lpr mice.

The Fas receptor delivers signals crucial for lymphocyte apoptosis through its cytoplasmic death domain. Several Fas cytoplasmic-associated proteins have been reported and studied in cell lines. So far, only Fas-associated death domain protein (FADD), another death domain-containing molecule has been shown to be essential for Fas signals in vivo. FADD is thought to function by recruiting caspase-8 through its death-effector domain. To test whether FADD is sufficient to deliver Fas signals, we generated transgenic mice expressing a chimera comprised of the Fas extracellular domain and FADD death-effector domain. Expression of this protein in lymphocytes of Fas-deficient MRL-lpr/lpr mice completely diminishes their T cell but not their B cell abnormalities. These results suggest that FADD alone is sufficient for initiation of Fas signaling in primary T cells, but other pathways may operate in B cells.

Pain in neonate.

Anatomical, functional and neurochemical maturation of pain pathways is well developed in fetus and neonates. Various physiological and behavioural responses to painful stimuli in neonates substantiate their ability to feel pain. Biological effects of pain are systematically studied in human fetus and neonates. Pain expressions in the newborn not only reflect tissue damage but are a function of ongoing behavioural state. The ultimate aim should be to keep neonates free from pain and other stressful stimuli as far as possible, by advocating minimal handling protocol, giving comforts after painful procedures, local anesthesia while carrying out painful procedures like cutdown and insertion of chest tubes, and if a baby is ventilated fentanyl and/or midazalam infusion must be carried out during initial periods of ventilation.