Benefits of simulation based training for neonatal resuscitation education: a systematic review.

BACKGROUND: Simulation-based training (SBT) is being more frequently recommended for neonatal resuscitation education (NRE). It is important to assess if SBT improves clinical outcomes as neonatal resuscitation aims to improve survival without long-term neurodevelopmental impairment. We aimed to assess the evidence supporting benefits of SBT in NRE. METHOD: A systematic review was conducted using the Cochrane methodology. PubMed, Embase, PsycInfo and Cochrane databases were searched. Related abstracts were scanned and full texts of the potentially relevant articles were studied. Randomised controlled trials (RCT) and quasi-experimental studies with controls (non-RCT) assessing SBT for NRE were eligible for inclusion in the review. RESULTS: Four small studies [three RCT (n=126) and one non-RCT (n=60)] evaluated SBT for NRE. Participants included medical students (one RCT and one non-RCT), residents (one RCT) and nursing staff (one RCT). Outcomes included performance in a simulation scenario, theoretical knowledge, and confidence in leading a resuscitation scenario. One RCT favoured simulation [improved resuscitation score (p=0.016), 2.31 more number of critical actions (p=0.017) and decreased time to achieve resuscitation steps (p=<0.001)]. The remaining two RCTs and the non-RCT did not find any difference between SBT and alternate methods of instruction. None of the four studies reported clinical outcomes. CONCLUSIONS: Evidence regarding benefits of SBT for NRE is limited. There are no data on clinical outcomes following SBT for NRE. Large RCTs assessing clinically important outcomes are required before SBT can be recommended widely for NRE.

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

BACKGROUND: The n-3 and n-6 fatty acids linolenic acid and linoleic acid are precursors of the n-3 and n-6 long chain fatty acids (LCPUFA). Infant formula has historically only contained the precursor fatty acids. Controversy exists over whether LCPUFA are also essential nutrients in infancy. Over the last few years, some manufacturers have added LCPUFA to formulae and marketed them as providing an advantage for the development of term infants. OBJECTIVES: To assess whether supplementation of formula with LCPUFA is safe and of benefit to term infants. SEARCH STRATEGY: Eligible studies were identified by searching MEDLINE (March 2007), EMBASE 1980 - 2007, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007) and CINAHL (December 1982 - March 2007). Abstracts of the Society for Pediatric Research were hand searched from 1980 to 2006 inclusive. Reference lists of published narrative and systematic reviews were also reviewed. No language restrictions were applied. SELECTION CRITERIA: All randomised and quasi randomised trials comparing LCPUFA supplemented formula milk vs. non-supplemented formula milk and with clinical endpoints were reviewed. DATA COLLECTION AND ANALYSIS: Methodological quality of eligible studies was assessed according to allocation concealment, blinding of intervention, blinding of outcome assessment and completeness of follow up. Data were sought regarding effects on visual acuity, neurodevelopmental outcomes and physical growth. When appropriate, meta-analysis was conducted to provide a pooled estimate of effect. Continuous data were analysed using weighted mean difference (WMD). There were no categorical outcomes in this review. MAIN RESULTS: Twenty randomised studies were identified. Fourteen were included (n = 1719) and six excluded. Eleven included studies were of good quality. The main outcomes assessed were visual acuity, neurodevelopmental and physical growth. Visual acuity was measured at various stages throughout the first three years of life by nine studies. Visual evoked potential was used to assess visual acuity in five studies. The remaining four used Teller visual acuity cards. The results were inconsistent. Three studies reported beneficial effect of LCPUFA supplementation on visual acuity while the remaining six did not. Neurodevelopmental outcome was measured at different ages throughout the first two years by eleven studies. Bayley scales of infant development (BSID) was used in eight studies. Only one showed beneficial effect of LCPUFA supplementation on BSID scales. Pooled meta-analysis of the data also did not show any statistically significant benefit of LCPUFA supplementation on either mental or psychomotor developmental index of BSID. One study reported better novelty preference measured by Fagan Infant test at nine months in supplemented infants compared with controls. Another study reported better problem solving at 10 months with supplementation. One study used Brunet and Lezine developmental test to assess the developmental quotient and did not find beneficial effects of LCPUFA supplementation. Physical growth was measured at various ages throughout first three years of life by twelve studies. Some studies reported the actual measurements while some reported the rate of growth over a time period. Some studies z scores. Irrespective of the type of LCPUFA supplementation, duration of supplementation and method of assessment, none of the individual studies found beneficial or harmful effects of LCPUFA supplementation. Meta-analysis of relevant studies also did not show any effect of LCPUFA supplementation on growth of term infants. AUTHORS' CONCLUSIONS: The results of most of the well conducted RCTS have not shown beneficial effects of LCPUFA supplementation of formula milk on the physical, visual and neurodevelopmental outcomes of infants born at term. Only one group of researchers have shown some beneficial effects on VEP acuity. Two groups of researchers have shown some beneficial effect on mental development. Routine supplementation of milk formula with LCPUFA to improve the physical, neurodevelopmental or visual outcomes of infants born at term can not be recommended based on the current evidence. Further research is needed to see if the beneficial effects demonstrated by Dallas 2005 trial of Birch et al can be replicated in different settings.

Physical activity programs for promoting bone mineralization and growth in preterm infants.

BACKGROUND: Lack of physical stimulation may contribute to metabolic bone disease of preterm infants resulting in poor bone mineralization and growth. Physical activity programs in the presence of adequate nutrition might help to promote bone mineralization and growth. OBJECTIVES: The primary objective of this review was to assess whether physical activity programs in preterm infants improve bone mineralization and growth and reduce the risk of fractures. SEARCH STRATEGY: Following the standard search strategy of the Cochrane Neonatal Review Group, a search was conducted in September 2006 including PubMed, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2006), cross-references and handsearching of abstracts of the Society for Pediatric Research and the International Journal of Sports Medicine. No language restrictions were applied. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing physical activity programs (extension and flexion, range-of-motion exercises for several minutes a day several days per week for at least two weeks) to no organized physical activity programs in preterm infants. Eligible studies included those that provided physical activity for the experimental group, with or without massage and/or tactile stimulation for both experimental and control groups, as well as information on at least one outcome of interest. DATA COLLECTION AND ANALYSIS: Two review authors independently performed searches and extracted data. All three review authors were involved in selection and assessment of quality of studies. The statistical methods included relative risk (RR), risk difference (RD) and number needed to treat (NNT) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, reported with 95% confidence intervals (CI). Heterogeneity was estimated by the I(2) statistic. A fixed effect model was used to pool data for meta-analyses. MAIN RESULTS: Six trials enrolling 169 preterm infants (gestational age 26 to 34 weeks) were included in this review. All were small (N = 20 - 49) single center studies evaluating daily physical activity for 3.5 to 4 weeks during initial hospitalization. The methodological quality and reporting of all trials was poor. None of them stated the methods of concealment of patient allocation, the method of randomization or attempted blinding of the intervention. Only two trials attempted blinding of outcome assessors for outcomes relevant to this review. Two trials (N = 55) demonstrated moderate short-term benefits of physical activity on bone mineralization at completion of the physical activity program. Data was not pooled for meta-analyses due to methodological differences. The only trial (N = 20) assessing long-term effects on bone mineralization showed no effect of physical activity administered during initial hospitalization on bone mineralization at 12 months corrected age. Meta-analysis from three trials (N = 78) demonstrated an effect of physical activity on daily weight gain (WMD 2.77 g/kg/d, 95% CI 1.62, 3.92). Data from two trials (N = 58) showed no effect on linear growth (WMD -0.04 cm/week, 95% CI -0.19, 0.11) or head growth (WMD -0.03 cm/week, 95% CI -0.14, 0.09) during the study period. The I(2) statistic suggested heterogeneity on the analysis of linear growth (p = 0.006, I(2) = 86.9%). None of the trials assessed fractures or other outcomes relevant to this review. Data was insufficient for subgroup analyses based on birth weight and calcium/phosphorus intake. AUTHORS' CONCLUSIONS: There is weak evidence from six small randomized trials of poor methodological and reporting quality that physical activity programs might promote moderate short-term weight gain and bone mineralization in preterm infants. The clinical importance of these findings is questionable given the small effect size and low baseline risk of poor bone mineralization and growth in study participants. Data is inadequate to assess harm or long term effects. Current evidence does not justify the standard use of physical activity programs in preterm infants. Further evaluation of this intervention in well designed trials incorporating extremely low birth weight infants who are at high risk of osteopenia is required. Future trials should report on adverse events and long term outcomes including fractures, growth, bone mineralization, skeletal deformities and neurodevelopmental impairment. These trials should address the possibility that nutritional intake (calories, protein, calcium, phosphorus) might modify the effects of physical activity.

Does patent ductus arteriosus affect feed tolerance in preterm neonates?

Patent ductus arteriosus (PDA), especially PDA with sepsis, has been reported as a risk factor for feed intolerance in preterm neonates. In this study, the start to full feeds interval was found to be longest in preterm neonates (

Renal impairment associated with indomethacin treatment for patent ductus arteriosus in extremely preterm neonates--is postnatal age at start of treatment important?

OBJECTIVE: To study serum creatinine (SCr) levels following indomethacin for patent ductus arteriosus (PDA) closure in extremely preterm neonates in relation to postnatal age at the start of treatment. METHODS: This was a retrospective (January 2000-December 2002) analysis of data on preterm neonates (gestation <29 weeks) who received indomethacin for PDA. Pre-existing renal malformation and/or impairment and high serum levels of nephrotoxic drugs were criteria for exclusion. RESULTS: Indomethacin was commenced at postnatal age <7 days and >or=7 days in 60 (group 1) and 30 (group 2) neonates, respectively. The median (Q1, Q3) gestational age and birth weight for group 1 and group 2 neonates were 25 (23, 27) vs. 25 (24, 26) weeks and 740 (620, 909) vs. 780 (663, 966) grams, respectively. Postnatal age <7 days at start of indomethacin was associated with higher baseline (0.083 (0.074, 0.090) vs. 0.073 (0.054, 0.083) mmol/L, p=0.001) and peak SCr levels (0.099 (0.089,0.109) vs. 0.090 (0.064, 0.104) mmol/L, p=0.015). Logistic regression analysis controlling for gestational age and baseline SCr level indicated that postnatal age >or=7 days was a risk factor for elevated SCr after indomethacin (OR=13.4, 95% CI: 3.8-46.6, p < 0.001). CONCLUSION: Postnatal age >or=7 days at the start of indomethacin is a predictor of a significant rise in SCr in extremely preterm neonates.

Does carboxymethylcellulose have a role in reducing time to full enteral feeds in preterm neonates?

The efficacy of prophylactic carboxymethylcellulose (CMC) in reducing the time to reach full enteral feeds (FEFs) in neonates <32 weeks' gestation was studied in a clinical trial. When ready for feeds, enrolled neonates were allocated to either CMC (dose: CMC content of 12 mg oral erythromycin ethyl succinate syrup, 6 hourly) or placebo till either maximum 10 days treatment or FEF (150 ml/kg/day) was reached. A standardised regimen guided enteral feeding. Demographic characteristics of enrolled neonates (CMC, placebo: n = 35) were comparable. Median (interquartile range) gestational age and birth weight were 29 (28, 30) vs. 29 (27, 31) weeks and 1090 (905, 1390) vs. 1236 g (928, 1565) for the CMC and placebo groups, respectively. Median (interquartile range) time to reach FEF was 5 (4, 6) vs. 5 (3, 8) days for CMC and placebo group, respectively (p = 0.5). No CMC-related adverse effects occurred. Prophylactic CMC did not have a significant role in reducing time to reach FEF.

Is surgical ligation of patent ductus arteriosus necessary? The Western Australian experience of conservative management.

BACKGROUND: Surgical ligation of patent ductus arteriosus (PDA) is widely practised in preterm infants despite no clear evidence that this improves outcomes. Geographical isolation meant that ductal ligation was not an option in King Edward Memorial Hospital until recently. OBJECTIVE: A retrospective data analysis to test the hypothesis that outcomes of infants with persistent PDA were no worse than those of infants with no significant duct or a duct that closed after medical treatment. PATIENTS AND METHODS: A total of 252 infants (gestation < or =28 weeks) born between 1 January 2000 and 30 June 2002 were divided into three groups: group 1, no significant PDA (n = 154); group 2, significant PDA which closed after medical treatment (n = 65); group 3, significant PDA remaining patent after medical treatment (n = 33). A significant PDA was defined by a left atrium to aortic root ratio of >1.4 or a ductal diameter >1.5 mm with a left to right shunt. RESULTS: Twenty four (10%) infants died at median (interquartile range) 15.5 (9-35) days. After adjustment for gestational age, relative to group 1, the infants from group 3 were at a 4.02 times increased risk of death (95% confidence interval 1.12 to 14.51). There was no significant difference between groups in the incidence of chronic lung disease, chronic lung disease or death, necrotising enterocolitis, intraventricular haemorrhage, duration of oxygen, or hospital stay. CONCLUSION: Mortality was higher in infants with a persistent PDA, but other morbidities were not significantly different. A randomised trial is needed to determine whether surgical ligation will reduce mortality in such infants.

Impact of standardised feeding regimens on incidence of neonatal necrotising enterocolitis: a systematic review and meta-analysis of observational studies.

BACKGROUND: A significant and prolonged decline in the incidence of necrotising enterocolitis (NEC), nearing virtual elimination in some centres, has been observed consistently since implementation of a standardised feeding regimen. AIM: To systematically review the observational studies reporting incidence of NEC in preterm, low birth weight (LBW) neonates "before" and "after" implementation of a standardised feeding regimen. METHODS: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2002), Medline, Embase, Cinahl, and proceedings of the Pediatric Academic Societies (published in Pediatric Research from 1980) were searched in July and again in October 2003. The reference lists of identified observational studies, and personal files, were searched. No language restriction was applied. Key words were: standardised, enteral, feeding, neonates, necrotising enterocolitis. Authors were contacted for clarification of data. RESULTS: Six eligible studies (1978-2003) were identified. A significant heterogeneity was noted between the studies indicating the variations in the population characteristics and feeding practices over a period of 25 years. Meta-analysis of the six studies using a random effects model revealed a pooled risk ratio of 0.13 (95% confidence interval 0.03 to 0.50)-that is, introduction of a standardised feeding regimen reduced the incidence of NEC by 87%. CONCLUSION: Standardised feeding regimens may provide the single most important global tool to prevent/minimise NEC in preterm neonates. Randomised controlled trials are needed.

Neonatal necrotizing enterocolitis following intrauterine transfusions: is there an association?

The case of a neonate with necrotizing enterocolitis (NEC) following intrauterine transfusions (IUTs) for Rhesus hemolytic disease (RHD) prompted us to undertake a retrospective study (1995-2002) to determine whether there is an association between IUT and NEC. Maternal and neonatal demographics, and details concerning IUT and definite (> or =Stage II) NEC, were collected. Chi2 tests of association were performed. In our population 281/38,200 (0.73%) pregnancies were complicated by RHD. Fetal anemia necessitated IUT in 25/281 pregnancies. Definite NEC occurred in 59/11,814 (very low birth weight=1874) neonatal admissions. Except for the index case, no other neonate developed NEC following IUT. No significant association was found between IUT and NEC.

Phosphodiesterase inhibitors for persistent pulmonary hypertension of the newborn: a review.

Persistent pulmonary hypertension of the newborn (PPHN) is a complex syndrome with multiple causes, with an incidence of 0.43-6.8/1,000 live births and a mortality of 10-20%. Survivors have high morbidity in the forms of neurodevelopmental and audiological impairment, cognitive delays, hearing loss, and a high rate of rehospitalization. The optimal approach to the management of PPHN remains controversial. Inhaled nitric oxide (iNO) is currently regarded as the gold standard therapy, but with as many as 30% of cases failing to respond, has not proven to be the single magic bullet. Given the complex pathophysiology of the disease, any such magic bullet is unlikely. A number of recent studies have suggested a role for specific phosphodiesterase (PDE) inhibitors in the management of PPHN. Sildenafil, a specific PDE5 inhibitor, appears the most promising of such agents. We aim to review the current status and limitations of iNO and the potential of PDE inhibitors in the management of PPHN. The reasons why caution is warranted before specific PDE5 inhibitors like sildenafil are labelled as potential magic bullets for PPHN will be discussed. The need for randomized-controlled trials to determine the safety, efficacy, and long-term outcome following treatment with sildenafil in PPHN is emphasized.

Gastric pneumatosis in neonates: revisited.

Pneumatosis intestinalis, found commonly in neonatal necrotising enterocolitis (NEC), can occur in any part of the gastrointestinal tract, from the oesophagus to the rectum. Gastric pneumatosis, defined as air within the wall of the stomach, however, is an extremely rare sign during infancy and is usually secondary to gastric outlet obstruction. The clinical course and outcome of a neonate with gastric pneumatosis associated with NEC is reported along with a brief review of the literature. The findings illustrate that gastric pneumatosis can be the presenting feature of fulminant NEC and may indicate widespread, severe gastrointestinal insult.

Pneumatosis coli, a benign form of necrotising enterocolitis.

Necrotising enterocolitis (NEC) is the most common acquired gastrointestinal emergency in neonates. Presence of pneumatosis intestinalis is taken as evidence of definite NEC. A distinctive but rare form of NEC called "pneumatosis coli" has been described, presenting with gross blood in stools and minimal or absent local and systemic signs. Radio-graph characteristically reveal isolated colonic pneumatosis without small bowel involvement. Pneumatosis coli has a more benign course compared with definite NEC. Total parenteral nutrition, antibiotics, an appropriate duration off feeds and close observation remain the corner stones of therapy assuring a benign course.

Neonatal ascites and hyponatraemia following umbilical venous catheterization.

The complications associated with umbilical venous catheterization in neonates range from pericardial effusion, portal hypertension, and peritoneal perforation with ascites, to Wharton's jelly embolism. The case of a term neonate who developed ascites and severe hyponatraemia (serum sodium 119 mmol/L) most probably following peritoneal perforation by an umbilical venous catheter is reported. The presenting feature was convulsions associated with dilutional hyponatraemia, probably following absorption of a large quantity of ascitic fluid across the peritoneum. Conservative management was associated with gradual recovery over 24 h. The case highlights that, irrespective of the route, excessive administration of salt-free fluids can lead to dilutional hyponatraemia with adverse consequences. The present case illustrates the importance of confirming intravascular positioning of umbilical catheters by ensuring free flow of blood on aspiration, to prevent/detect inadvertent peritoneal perforation. Ideally, echocardiographic confirmation of optimal intravascular placement of such catheters is preferred as radiographic confirmation is reported to be unreliable.

Low molecular weight heparin for neonatal thrombosis.

The clinical course of a term neonate (birthweight 3.14 kg) who developed thrombosis of the left common and internal iliac veins on day 21 following recovery from Streptococcus mitis septicemia, with shock diagnosed on day 13, is reported. Subcutaneous low molecular weight heparin (LMWH) was commenced (1.5 mg/kg 12 hourly for 10 days) after 13 h of standard heparin infusion, due to difficulties in securing a peripheral venous access. The inflammation of the left leg was completely resolved by day 5 of LMWH therapy. Prothrombin time, activated prothrombin time and fibrinogen levels were within normal limits during LMWH therapy. Treatment-related side effects, such as thrombocytopenia and bleeding tendency were not noted. Doppler studies 6 weeks after discharge home on day 33 revealed complete resolution of the thrombus. Apart from septicaemia and shock, the presence of an indwelling central venous catheter and a history of untreated maternal diabetes were additional risk factors for thrombosis. Because it is as effective as standard heparin, LMWH may be a therapeutic option for thrombosis in high-risk neonates, particularly given its ease of administration by the subcutaneous route, predictable pharmacokinetics and reduced incidence of adverse effects such as bleeding complications.

Intravenous rifampicin in neonates with persistent staphylococcal bacteraemia.

UNLABELLED: Addition of intravenous rifampin is reported to be useful in prompt clearance of persistent coagulase negative staphylococcal (CONS) bacteraemia in high-risk neonates. Four neonates (mean birthweight 823 g, mean gestation 25 wk) with persistent CONS bacteraemia for > 7-10 d (mean 11) were treated with i.v. rifampicin (10 mg/kg/12 h x 10 d) while continuing vancomycin (15 mg/kg/24 h). Their age at time of infection ranged from 2 to 11 d. The mean (range) vancomycin peak and trough concentrations were 29 (25-35) and 6 (4-10) microg/ml, respectively. The blood isolates were Staphylococcus epidermidis, S. hominis, and S. haemolyticus. Addition of rifampicin was associated with prompt clearance of bacteraemia within 48 h (n = 3) and 5 d (n - 1). Rifampicin-related adverse effects such as abnormal liver function tests and thrombocytopenia did not occur. CONCLUSION: Addition of i.v. rifampicin to vancomycin may optimize the outcome of persistent CONS bacteraemia and the risk of bacterial resistance related to prolonged exposure to vancomycin.