Interrupted versus uninterrupted anticoagulation therapy for catheter ablation in adults with arrhythmias.

BACKGROUND: The management of anticoagulation therapy around the time of catheter ablation (CA) procedure for adults with arrhythmia is critical and yet is variable in clinical practice. The ideal approach for safe and effective perioperative management should balance the risk of bleeding during uninterrupted anticoagulation while minimising the risk of thromboembolic events with interrupted therapy. OBJECTIVES: To compare the efficacy and harms of interrupted versus uninterrupted anticoagulation therapy for catheter ablation (CA) in adults with arrhythmias. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and SCI-Expanded on the Web of Science for randomised controlled trials on 5 January 2021. We also searched three registers on 29 May 2021 to identify ongoing or unpublished trials. We performed backward and forward searches on reference lists of included trials and other systematic reviews and contacted experts in the field. We applied no restrictions on language or publication status. SELECTION CRITERIA: We included randomised controlled trials comparing uninterrupted anticoagulation with any modality of interruption with or without heparin bridging for CA in adults aged 18 years or older with arrhythmia. DATA COLLECTION AND ANALYSIS: Two review authors conducted independent screening, data extraction, and assessment of risk of bias. A third review author resolved disagreements. We extracted data on study population, interruption strategy, ablation procedure, thromboembolic events (stroke or systemic embolism), major and minor bleeding, asymptomatic thromboembolic events, cardiovascular and all-cause mortality, quality of life (QoL), length of hospital stay, cost, and source of funding. We used GRADE to assess the certainty of the evidence.  MAIN RESULTS: We identified 12 studies (4714 participants) that compared uninterrupted periprocedural anticoagulation with interrupted anticoagulation. Studies performed an interruption strategy by either a complete interruption (one study) or by a minimal interruption (11 studies), of which a single-dose skipped strategy was used (nine studies) or two-dose skipped strategy (two studies), with or without heparin bridging. Studies included participants with a mean age of 65 years or greater, with only two studies conducted in relatively younger individuals (mean age less than 60 years). Paroxysmal atrial fibrillation (AF) was the primary type of AF in all studies, and seven studies included other types of AF (persistent and long-standing persistent). Most participants had CHADS2 or CHADS2-VASc demonstrating a low-moderate risk of stroke, with almost all participants having normal or mildly reduced renal function. Ablation source using radiofrequency energy was the most common (seven studies). Ten studies (2835 participants) were conducted in East Asian countries (Japan, China, and South Korea), while the remaining two studies were conducted in the USA. Eight studies were conducted in a single centre. Postablation follow-up was variable among studies at less than 30 days (three studies), 30 days (six studies), and more than 30 days postablation (three studies). Overall, the meta-analysis showed high uncertainty of the effect between the interrupted strategy compared to uninterrupted strategy on the primary outcomes of thromboembolic events (risk ratio (RR) 1.76, 95% confidence interval (CI) 0.33 to 9.46; I2 = 59%; 6 studies, 3468 participants; very low-certainty evidence). However, subgroup analysis showed that uninterrupted vitamin A antagonist (VKA) is associated with a lower risk of thromboembolic events without increasing the risk of bleeding. There is also uncertainty on the outcome of major bleeding events (RR 1.10, 95% CI 0.59 to 2.05; I2 = 6%; 10 studies, 4584 participants; low-certainty evidence). The uncertainty was also evident for the secondary outcomes of minor bleeding (RR 1.01, 95% CI 0.46 to 2.22; I2 = 87%; 9 studies, 3843 participants; very low-certainty evidence), all-cause mortality (RR 0.34, 95% CI 0.01 to 8.21; 442 participants; low-certainty evidence) and asymptomatic thromboembolic events (RR 1.45, 95% CI 0.85 to 2.47; I2 = 56%; 6 studies, 1268 participants; very low-certainty evidence). There was a lower risk of the composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality) in the interrupted compared to uninterrupted arm (RR 0.23, 95% CI 0.07 to 0.81; 1 study, 442 participants; low-certainty evidence). In general, the low event rates, different comparator anticoagulants, and use of different ablation procedures may be the cause of imprecision and heterogeneity observed. AUTHORS' CONCLUSIONS: This meta-analysis showed that the evidence is uncertain to inform the decision to either interrupt or continue anticoagulation therapy around CA procedure in adults with arrhythmia on outcomes of thromboembolic events, major and minor bleeding, all-cause mortality, asymptomatic thromboembolic events, and a composite endpoint of thromboembolic events (stroke, systemic embolism, major bleeding, and all-cause mortality).  Most studies in the review adopted a minimal interruption strategy which has the advantage of reducing the risk of bleeding while maintaining a lower level of anticoagulation to prevent periprocedural thromboembolism, hence low event rates on the primary outcomes of thromboembolism and bleeding. The one study that adopted a complete interruption of VKA showed that uninterrupted VKA reduces the risk of thromboembolism without increasing the risk of bleeding. Hence, future trials with larger samples, tailored to a more generalisable population and using homogeneous periprocedural anticoagulant therapy and ablation source are required to address the safety and efficacy of the optimal management of anticoagulant therapy prior to ablation.

Oxandrolone for growth hormone-treated girls aged up to 18 years with Turner syndrome.

BACKGROUND: The final adult height of untreated girls aged up to 18 years with Turner syndrome (TS) is approximately 20 cm shorter compared with healthy females. Treatment with growth hormone (GH) increases the adult height of people with TS. The effects of adding the androgen, oxandrolone, in addition to GH are unclear. Therefore, we conducted this systematic review to investigate the benefits and harms of oxandrolone as an adjuvant therapy for people with TS treated with GH. OBJECTIVES: To assess the effects of oxandrolone on growth hormone-treated girls aged up to 18 years with Turner syndrome. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was October 2018. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) that enrolled girls aged up to 18 years with TS who were treated with GH and oxandrolone compared with GH only treatment. DATA COLLECTION AND ANALYSIS: Three review authors independently screened titles and abstracts for relevance, selected trials, extracted data and assessed risk of bias. We resolved disagreements by consensus, or by consultation with a fourth review author. We assessed trials for overall certainty of the evidence using the GRADE instrument. MAIN RESULTS: We included six trials with 498 participants with TS, 267 participants were randomised to oxandrolone plus GH treatment and 231 participants were randomised to GH only treatment. The individual trial sample size ranged between 22 and 133 participants. The included trials were conducted in 65 different paediatric endocrinology healthcare facilities including clinics, centres, hospitals and academia in the USA and Europe. The duration of interventions ranged between 3 and 7.6 years. The mean age of participants at start of therapy ranged from 9 to 12 years. Overall, we judged only one trial at low risk of bias in all domains and another trial at high risk of bias in most domains. We downgraded the level of evidence mainly because of imprecision (low number of trials, low number of participants or both). Comparing oxandrolone plus GH with GH only for final adult height showed a mean difference (MD) of 2.7 cm in favour of oxandrolone plus GH treatment (95% confidence interval (CI) 1.3 to 4.1; P < 0.001; 5 trials, 270 participants; moderate-quality evidence). The 95% prediction interval ranged between 0.3 cm and 5.1 cm. For adverse events, we based our main analysis on reliable date from two trials with overall low risk of bias. There was no evidence of a difference between oxandrolone plus GH and GH for adverse events (RR 1.81, 95% CI 0.83 to 3.96; P = 0.14; 2 trials, 170 participants; low-quality evidence). Six out of 86 (18.6%) participants receiving oxandrolone plus GH compared with 8/84 (9.5%) participants receiving GH only reported adverse events, mainly signs of virilisation (e.g. deepening of the voice). One trial each investigated the effects of treatments on speech (voice frequency; 88 participants), cognition (51 participants) and psychological status (106 participants). The overall results for these comparisons were inconclusive (very low-quality evidence). No trial reported on health-related quality of life or all-cause mortality. AUTHORS' CONCLUSIONS: Addition of oxandrolone to the GH therapy led to a modest increase in the final adult height of girls aged up to 18 years with TS. Adverse effects identified included virilising effects such as deepening of the voice, but reporting was inadequate in some trials.

Glycerin laxatives for prevention or treatment of feeding intolerance in very low birth weight infants.

BACKGROUND: Feeding intolerance is a common clinical problem among preterm infants. It may be an early sign of necrotising enterocolitis, sepsis or other serious gastrointestinal conditions, or it may result from gut immaturity with delayed passage of meconium. Glycerin laxatives stimulate passage of meconium by acting as an osmotic dehydrating agent and increasing osmotic pressure in the gut; they stimulate rectal contraction, potentially reducing the incidence of feeding intolerance. OBJECTIVES: To assess the effectiveness and safety of glycerin laxatives (enemas/suppositories) for prevention or treatment of feeding intolerance in very low birth weight (VLBW) infants. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 4), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL). We restricted our search to all randomised controlled trials and applied no language restrictions. We searched the references of identified studies and reviews on this topic and handsearched for additional articles. We searched the database maintained by the US National Institutes of Health (www.clinicaltrials.gov) and European trial registries to identify ongoing trials. SELECTION CRITERIA: We considered only randomised or quasi-randomised controlled trials that enrolled preterm infants < 32 weeks' gestational age (GA) and/or < 1500 g birth weight. We included trials if they administered glycerin laxatives and measured at least one prespecified clinical outcome. DATA COLLECTION AND ANALYSIS: We used standard methods of The Cochrane Collaboration and its Neonatal Group to assess methodological quality of trials, to collect data and to perform analyses. MAIN RESULTS: We identified three trials that evaluated use of prophylactic glycerin laxatives in preterm infants. We identified no trials that evaluated therapeutic use of glycerin laxatives for feeding intolerance. Our review showed that prophylactic administration of glycerin laxatives did not reduce the time required to achieve full enteral feeds and did not influence secondary outcomes, including duration of hospital stay, mortality and weight at discharge. Prophylactic administration of glycerin laxatives resulted in failure of fewer infants to pass stool over the first 48 hours. Included trials reported no adverse events. AUTHORS' CONCLUSIONS: Our review of available evidence for glycerin laxatives does not support the routine use of prophylactic glycerin laxatives in clinical practice. Additional studies are needed to confirm or refute the effectiveness and safety of glycerin laxatives for prevention or treatment of feeding intolerance in VLBW infants.

A prospective study of maternal preference for indomethacin prophylaxis versus symptomatic treatment of a patent ductus arteriosus in preterm infants.

BACKGROUND: The management of a patent ductus arteriosus in preterm infants continues to be debated among neonatologists due to the absence of concrete evidence that precisely weighs the long term outcomes of active, early intervention against a conservative approach. In the majority of institutions, parents are encouraged to play an active role in the complex, decision -making processes with regard to the care of their infants. The objective of this study is to elicit maternal preferences for indomethacin prophylaxis versus treatment of a patent ductus arteriosus (PDA) in extremely low birth weight (ELBW) infants, utilizing a decision aid instrument (DAI). METHODS: Healthy and high risk pregnant women at 23-28 weeks gestation, and mothers of admitted ELBW infants were enrolled. A computer based, validated DAI was utilized during interviews. The DAI first provides information about prematurity and concurrent morbidities with comprehensive facts of the pros and cons about prophylactic versus treatment options. It subsequently coaches participants how to select values and preferences based on their decisions. A 17-item questionnaire assessed and valued each short and long term morbidity of extreme prematurity and preferred choice for PDA management. RESULTS: Two hundred ninety nine subjects were enrolled; 75% were healthy women at 23-28 weeks gestation, 19% were high risk and 6% recently delivered an ELBW infant. Eighty-two percent preferred a prophylactic indomethacin strategy versus symptomatic treatment for the management of PDA. Across a spectrum of potential morbidities, the occurrence of severe intraventricular hemorrhage was viewed by mothers as the most un-wanted outcome irrespective of the two proposed options. CONCLUSIONS: In contrast to neonatal practitioners, mothers who used this particular DAI strongly endorsed prophylactic indomethacin versus a treatment intervention for the management of PDA in preterm infants.

Probiotics for prevention of necrotizing enterocolitis in preterm infants.

BACKGROUND: Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. OBJECTIVES: To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. SEARCH METHODS: For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). SELECTION CRITERIA: Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. DATA COLLECTION AND ANALYSIS: Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. MAIN RESULTS: Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized.

Intranasal ipratropium bromide for the common cold.

BACKGROUND: The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. OBJECTIVES: To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects (for example, dry mucous membranes, epistaxis and systemic anticholinergic effects) were reported as a secondary outcome. SEARCH METHODS: In this updated review we searched CENTRAL 2013, Issue 3, MEDLINE (1950 to March week 4, 2013), MEDLINE in-process and other non-indexed citations (8 April 2013), EMBASE (1974 to April 2013), AMED (1985 to April 2013), Biosis (1974 to February 2011) and LILACS (1985 to April 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. MAIN RESULTS: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. The overall risk of bias in the included studies was moderate. AUTHORS' CONCLUSIONS: For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well tolerated and self limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.

Probiotics for infantile colic: a systematic review.

BACKGROUND: Infantile colic is a common paediatric condition which causes significant parental distress. Increased intestinal coliform colonization in addition to alteration in Lactobacillus abundance and distribution may play an important role in its pathogenesis. The objectives of this systematic review are to evaluate the efficacy of probiotic supplementation in the reduction of crying time and successful treatment of infantile colic. METHODS: Literature searches were conducted of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Only randomized controlled trials enrolling term, healthy infants with colic were included. A meta-analysis of included trials was performed utilizing the Cochrane Collaboration methodology. RESULTS: Three trials that enrolled 220 breastfed infants met inclusion criteria, of which 209 infants were available for analysis. Two of the studies were assessed as good quality. Lactobacillus reuteri (strains-American Type Culture Collection Strain 55730 and DSM 17 938) was the only species utilized in the therapeutic intervention. Two of the trials were industry funded. Probiotic supplementation compared to simethicone or placebo significantly and progressively shortened crying times to 7 days reaching a plateau at three weeks post initiation of therapy [mean difference -56.03 minutes; 95% CI (-59.92, -52.15)]. Similarly, probiotics compared to placebo significantly increased the treatment success of infantile colic with a relative risk (RR) of 0.06; 95% CI (0.01, 0.25) and a number needed to treat of 2. CONCLUSIONS: Although L. reuteri may be effective as a treatment strategy for crying in exclusively breastfed infants with colic, the evidence supporting probiotic use for the treatment of infant colic or crying in formula-fed infants remains unresolved. Results from larger rigorously designed studies will help draw more definitive conclusions.

Fluid restriction and prophylactic indomethacin versus prophylactic indomethacin alone for prevention of morbidity and mortality in extremely low birth weight infants.

BACKGROUND: Although survival of extremely low birth weight (ELBW) infants has dramatically improved over the last decades, the rate of bronchopulmonary dysplasia (BPD) has not changed. The use of indomethacin prophylaxis in ELBW infants results in improved short-term outcomes with no effect on long-term outcomes. The addition of fluid restriction to the indomethacin prophylaxis policy could result in a reduction of BPD and improve long-term survival without neurosensory impairment at eighteen months corrected age. OBJECTIVES: To determine the effect of a policy of fluid restriction compared with a policy of no fluid restriction on morbidity and mortality in ELBW infants receiving indomethacin prophylaxis. SEARCH STRATEGY: We used the standard search strategy for the Cochrane Neonatal Review Group (CNRG). This included searches of the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2010, Issue 1), MEDLINE (1966 to December 2010), and EMBASE (1980 to December 2010). Additional searches included conference proceedings, references in articles and unpublished data. SELECTION CRITERIA: We planned to include all randomized or quasi-randomized trials that compared fluid restriction and indomethacin prophylaxis versus indomethacin prophylaxis alone in ELBW infants. DATA COLLECTION AND ANALYSIS: If we had identified any eligible studies, we would have assessed the methodological quality of the trials using the standard methods of the CNRG. We planned to use Review Manager 5 software for statistical analysis. MAIN RESULTS: We did not identify any eligible trials. AUTHORS' CONCLUSIONS: We found no randomized controlled trials to investigate the possible interaction between fluid restriction and indomethacin prophylaxis versus indomethacin prophylaxis alone in ELBW infants. A well-designed randomized trial is needed to address this question.

Intranasal ipratropium bromide for the common cold.

BACKGROUND: The common cold is one of the most common illnesses in humans and constitutes an economic burden both in terms of productivity and expenditure for treatment. There is no proven cure for the common cold and symptomatic relief is the mainstay of treatment. The use of intranasal ipratropium bromide (IB) has been addressed in several studies and might prove an effective treatment for the common cold. OBJECTIVES: To determine the effect of IB versus placebo or no treatment on severity of rhinorrhoea and nasal congestion in children and adults with the common cold. Subjective overall improvement was another primary outcome and side effects were reported as a secondary outcome. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 1) which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to January week 4, 2011), MEDLINE in-process and other non-indexed citations (February 2011), EMBASE (1974 to February 2011), AMED (1985 to February 2011), Biosis (1974 to February 2011) and LILACS (1985 to February 2011). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing IB to placebo or no treatment in children and adults with the common cold. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We used a standardised form to extract relevant data and we contacted trial authors for additional information. MAIN RESULTS: Seven trials with a total of 2144 participants were included. Four studies (1959 participants) addressed subjective change in severity of rhinorrhoea. All studies were consistent in reporting statistically significant changes in favour of IB. Nasal congestion was reported in four studies and was found to have no significant change between the two groups. Two studies found a positive response in the IB group for the global assessment of overall improvement. Side effects were more frequent in the IB group, odds ratio (OR) 2.09 (95% confidence interval (CI) 1.40 to 3.11). Commonly encountered side effects included nasal dryness, blood tinged mucus and epistaxis. AUTHORS' CONCLUSIONS: For people with the common cold, the existing evidence, which has some limitations, suggests that IB is likely to be effective in ameliorating rhinorrhoea. IB had no effect on nasal congestion and its use was associated with more side effects compared to placebo or no treatment although these appeared to be well-tolerated and self-limiting. There is a need for larger, high-quality trials to determine the effectiveness of IB in relieving common cold symptoms.

Probiotics for prevention of necrotizing enterocolitis in preterm infants.

BACKGROUND: Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and associated morbidity. OBJECTIVES: To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC and/or sepsis in preterm infants. SEARCH STRATEGY: For this update, searches were made of MEDLINE (1966 to October 2010), EMBASE (1980 to October 2010), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2010), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2010). SELECTION CRITERIA: Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age and/or < 2500 g birth weight were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials, data collection and analysis. MAIN RESULTS: Sixteen eligible trials randomizing 2842 infants were included. Included trials were highly variable with regard to enrollment criteria (i.e. birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. Data regarding extremely low birth weight infants (ELBW) could not be extrapolated. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical RR 0.35, 95% CI 0.24 to 0.52) and mortality (typical RR 0.40, 95% CI 0.27 to 0.60). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.90, 95% CI 0.76 to 1.07). The included trials reported no systemic infection with the probiotics supplemental organism. The statistical test of heterogeneity for NEC, mortality and sepsis was insignificant. AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence supports a change in practice. More studies are needed to assess efficacy in ELBW infants and assess the most effective formulation and dose to be utilized.

A decision aid for considering indomethacin prophylaxis vs. symptomatic treatment of PDA for extreme low birth weight infants.

BACKGROUND: Decision Aids (DA) are well established in various fields of medicine. It can improve the quality of decision-making and reduce decisional conflict. In neonatal care, and due to scientific equipoise, neonatologists caring for extreme low birth weight (ELBW) infants are in need to elicit parents' preferences with regard to the use of indomethacin therapy in ELBW infants. We aimed to develop a DA that elicits parents' preferences with regard to indomethacin therapy in ELBW infants. METHODS: We developed a DA for the use of the indomethacin therapy in ELBW infants according to the Ottawa Decision Support Framework. The development process involved parents, neonatologists, DA developers and decision making experts. A pilot testing with healthy volunteers was conducted through an evaluation questionnaire, a knowledge scale, and a validated decisional conflict scale. RESULTS: The DA is a computer-based interactive tool. In the first part, the DA provides information about patent ductus arteriosus (PDA) as a disease, the different treatment options, and the benefits and downsides of using indomethacin therapy in preterm infants. In the second part, it coaches the parent in the decision making process through clarifying values and preferences. Volunteers rated 10 out of 13 items of the DA positively and showed significant improvement on both the knowledge scale (p = 0.008) and the decisional conflict scale (p = 0.008). CONCLUSION: We have developed a computer based DA to assess parental preferences with regard to indomethacin therapy in preterm infants. Future research will involve measurement of parental preferences to guide and augment the clinical decisions in current neonatal practice.

Probiotics for prevention of necrotizing enterocolitis in preterm infants.

BACKGROUND: Necrotizing enterocolitis (NEC) and nosocomial sepsis are associated with increased morbidity and mortality in preterm infants. Through prevention of bacterial migration across the mucosa, competitive exclusion of pathogenic bacteria, and enhancing the immune responses of the host, prophylactic enteral probiotics (live microbial supplements) may play a role in reducing NEC and the associated morbidity. OBJECTIVES: To compare the efficacy and safety of prophylactic enteral probiotics administration versus placebo or no treatment in the prevention of severe NEC or sepsis, or both, in preterm infants. SEARCH METHODS: For this update, searches were made of MEDLINE (1966 to October 2013), EMBASE (1980 to October 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (2013, Issue 10), and abstracts of annual meetings of the Society for Pediatric Research (1995 to 2013). SELECTION CRITERIA: Only randomized or quasi-randomized controlled trials that enrolled preterm infants < 37 weeks gestational age or < 2500 g birth weight, or both, were considered. Trials were included if they involved enteral administration of any live microbial supplement (probiotics) and measured at least one prespecified clinical outcome. DATA COLLECTION AND ANALYSIS: Standard methods of The Cochrane Collaboration and its Neonatal Group were used to assess the methodologic quality of the trials and for data collection and analysis. MAIN RESULTS: Twenty-four eligible trials were included. Included trials were highly variable with regard to enrolment criteria (that is birth weight and gestational age), baseline risk of NEC in the control groups, timing, dose, formulation of the probiotics, and feeding regimens. In a meta-analysis of trial data, enteral probiotics supplementation significantly reduced the incidence of severe NEC (stage II or more) (typical relative risk (RR) 0.43, 95% confidence interval (CI) 0.33 to 0.56; 20 studies, 5529 infants) and mortality (typical RR 0.65, 95% CI 0.52 to 0.81; 17 studies, 5112 infants). There was no evidence of significant reduction of nosocomial sepsis (typical RR 0.91, 95% CI 0.80 to 1.03; 19 studies, 5338 infants). The included trials reported no systemic infection with the supplemental probiotics organism. Probiotics preparations containing either lactobacillus alone or in combination with bifidobacterium were found to be effective. AUTHORS' CONCLUSIONS: Enteral supplementation of probiotics prevents severe NEC and all cause mortality in preterm infants. Our updated review of available evidence strongly supports a change in practice. Head to head comparative studies are required to assess the most effective preparations, timing, and length of therapy to be utilized. PLAIN LANGUAGE SUMMARY: Probiotics for prevention of necrotizing enterocolitis in preterm infants Necrotizing enterocolitis (NEC) is a serious disease that affects the bowel of premature infants in the first few weeks of life. Although the cause of NEC is not entirely known, milk feeding and bacterial growth play a role. Probiotics (dietary supplements containing potentially beneficial bacteria or yeast) have been used to prevent NEC. Our review of studies found that the use of probiotics reduces the occurrence of NEC and death in premature infants born weighing less than 1500 grams. There is insufficient data with regard to the benefits and potential adverse effects in the most at risk infants weighing less than 1000 grams at birth.

Use of topical petroleum jelly for prevention of sepsis in very low-birthweight infants: a prospective, randomised controlled trial.

BACKGROUND: Emollient therapy is used frequently to prevent nosocomial infection in the management of preterm infants, despite a lack of adequate evidence of its efficacy. OBJECTIVE: To assess the efficacy of prophylactic whole-body application of pure preservative-free topical petroleum jelly on the incidence of nosocomial sepsis in very low-birthweight (VLBW) infants. STUDY DESIGN: A prospective, randomised controlled trial of the application of topical petroleum jelly was conducted. Infants weighing <1250 g at birth and with a gestational age of ≤32 weeks were included. The intervention group received twice-daily topical therapy of 2 g/kg pure, preservative-free topical petroleum jelly until the completion of 34 weeks of gestation. The control group received no topical petroleum jelly treatment. The primary outcome was the incidence of late-onset sepsis during hospitalisation. Other data collected included the pattern of temperature control, weight changes, fluid requirements, serum bilirubin level, electrolyte imbalance and skin condition. RESULTS: Thirty-five infants in the intervention group and 39 in the control group were recruited. Birthweight, gestational age, gender and perinatal variables were comparable in the two groups. There was a trend towards an increased incidence of culture-proven nosocomial sepsis in the intervention group - 19 episodes (54%) in the intervention group vs 16 (41%) in the control group, and an increased rate of NEC - 20% in the intervention group vs 8% in the control group. The intervention group had better skin condition throughout their stay and the incubator ambient temperature was lower in the intervention group in the 1st week of life. The fluid balance of the infants in the intervention group was better, as reflected by their mean (SD) shorter time to regain birthweight [12 (5) vs 14 (6) days], and there were fewer episodes of hypernatraemia in the 1st week of life, although none of these reached statistical significance. However, there was a significantly lower mean (SD) level of maximum hyperbilirubinaemia [157 (40) vs 182 (46) mmol/L, P = 0·02) in the intervention group. CONCLUSION: Although prophylactic topical application of pure, preservative-free petroleum jelly brought substantial improvement of skin condition and temperature control, it was associated with a trend towards an increased rate of nosocomial sepsis.

Total parenteral nutrition-associated cholestasis and risk factors in preterm infants.

BACKGROUND/AIM: Development of hepatic dysfunction is a well-recognized complication of total parenteral nutrition in preterm infants. Previous studies reported the incidence of total parenteral nutrition-associated cholestasis and described possible contributing factors to its pathogenesis, but little is done trying to determine its possible predictive risk factors. The aims of this study was to determine the incidence of total parenteral nutrition-associated cholestasis and to develop a possible predictive model for its occurrence. PATIENTS AND METHODS: A review of medical records of all very low birth weight infants admitted to neonatal intensive care unit at King Khalid University Hospital, Riyadh, Saudi Arabia, between January 2001 and December 2003 was carried out. The infants were divided into two groups: Cholestasis and noncholestasis, based on direct serum bilirubin level >34 µmol/L. A multivariate logistic regression analysis was performed to calculate the statistical significance of risk factors. Receiver-operating characteristic curve was used to determine the optimal cutoff points for the significant risk factors and to calculate their sensitivity and specificity. The level of significance was set at P ≤ 0.05. RESULTS: A total of 307 patients were included in the analysis. The incidence of cholestasis in the whole population was 24.1% (74 patients). Infants with cholestasis had a lower birth weight, 735.4 ± 166.4 g vs. 1185.0 ± 205.6 g for noncholestasis group (P < 0.001), whereas the mean gestational age for the two groups was 25.4 ± 2.1 week and 28.9 ± 2.1 week, respectively (P < 0.001). The significant risk factors for the development of cholestasis were birth weight (P = 0.006) with an odds ratio of 0.99 [95% confidence interval (CI), 0.98, 0.99]; sensitivity of 92%, specificity of 87%; and total parenteral nutrition duration (P < 0.001) with an odds ratio of 1.18 (95% CI, 1.10, 1.27); sensitivity of 96%, specificity of 89%. CONCLUSIONS: A lower birth weight and longer duration of total parenteral nutrition were strong predictive risk factors for the development of cholestasis in preterm infants.

Prevalence of vitamin D deficiency in Saudi newborns at a tertiary care center.

OBJECTIVE: To evaluate vitamin D levels in Saudi newborns utilizing umbilical cord samples, and to benchmark the results with international figures. METHODS: This cross-sectional study was carried out at King Khalid University Hospital, Riyadh, Saudi Arabia between November 2013 and March 2013. Vitamin D levels were assessed in the umbilical cord of healthy term neonates born above 2.5 kg from healthy pregnant mothers. Gestational age (GA), birth weight, gender, levels of sun exposure, and consumption of vitamin D rich food data were collected. Our primary outcome was the percentage of newborns with vitamin D deficiency (vitamin D level below 25 nmol/l). Association of vitamin D deficiency with sun exposure and consumption of vitamin D rich food was tested using a Chi-squared test. RESULTS: Umbilical samples of 200 newborns were obtained. The average birth weight was 3.2 kg. Deficient vitamin D levels were detected in 59% of the sample. Almost 90% of included newborns had vitamin D levels below 50 nmol/l. We found no association of vitamin D deficiency status to level of sun exposure or to consumption of vitamin D rich food. CONCLUSION: Vitamin D deficiency is very common in Saudi newborns at hospital, and is consistent with regional data. Efforts to assess and treat vitamin D deficiency during pregnancy and provide adequate supplementation to newborns are necessary to rectify such a public health concern.

Aborting a malformed fetus: a debatable issue in saudi arabia.

Congenital anomalies contribute a significant proportion of infant morbidity and mortality, as well as fetal mortality. They are generally grouped into three major categories: structural/metabolic, congenital infections, and other conditions. The most prevalent conditions include congenital heart defects, orofacial clefts, Down syndrome, and neural tube defects. Several prenatal diagnostic procedures have been introduced, both cytogenetic (such as chorion biopsy, amniocentesis and funiculocentesis) and biophysical (ultrasound 2-D, 3-D and 4-D, ultrasonography with Doppler, etc.). Insufficient data are currently available from Saudi Arabia on the epidemiology of the lethal congenital abnormalities which should be a priority due to high rate of consanguineous marriages among first cousins and their association with congenital anomalies. In terms of consanguinity and birth defects, a significant positive association has been consistently demonstrated between consanguinity and morbidity, and congenital defects with a complex etiology appear to be both more prevalent in consanguineous families and have a greater likelihood of recurrence. A debate regarding aborting a malformed fetus still exists among the senior Islamic scholars in many of the Islamic countries. The progressive interpretations of Islam have resulted in laws allowing for early abortion on request in two countries; six others permit abortion on health grounds and three more also allow abortion in cases of rape or fetal impairment. In Saudi Arabia, efforts to legalize abortion in certain circumstances have been recently discussed among Senior Religious Scholars and specialized physicians to permit abortions in certain circumstances. In this mini-review we discuss the current debate regarding aborting a malformed fetus in Saudi Arabia with a focus on the Islamic perspective.

Premedication for neonatal intubation: Current practice in Saudi Arabia.

BACKGROUND: Despite strong evidence of the benefits of rapid sequence intubation in neonates, it is still infrequently utilized in neonatal intensive care units (NICU), contributing to avoidable pain and secondary procedure-related physiological disturbances. OBJECTIVES: The primary objective of this cross-sectional survey was to assess the practice of premedication and regimens commonly used before elective endotracheal intubation in NICUs in Saudi Arabia. The secondary aim was to explore neonatal physicians' attitudes regarding this intervention in institutions across Saudi Arabia. METHODS: A web-based, structured questionnaire was distributed by the Department of Pediatrics, Umm Al Qura University, Mecca, to neonatal physicians and consultants of 10 NICUs across the country by E-mail. Responses were tabulated and descriptive statistics were conducted on the variables extracted. RESULTS: 85% responded to the survey. Although 70% believed it was essential to routinely use premedication for all elective intubations, only 41% implemented this strategy. 60% cited fear of potential side effects for avoiding premedication and 40% indicated that the procedure could be executed more rapidly without drug therapy. Treatment regimens varied widely among respondents. CONCLUSION: Rates of premedication use prior to non-emergent neonatal intubation are suboptimal. Flawed information and lack of unified unit policies hampered effective implementation. Evidence-based guidelines may influence country-wide adoption of this practice.

Neonatal short-term outcomes of gestational diabetes mellitus in saudi mothers: a retrospective cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) affects up to 10% of all pregnancies and results in significant maternal and neonatal morbidities. OBJECTIVES: Our main objective was to investigate retrospectively the rate of neonatal intensive care unit (NICU) admissions and significant neonatal complications in pregnant mothers with gestational diabetes. MATERIALS AND METHODS: A retrospective cohort study was conducted. The medical records of King Khalid University Hospital (KKUH) were reviewed from January till December 2007. All pregnant women with GDM along with their offsprings were included and matched with healthy pregnant women. The primary outcome was the rate of NICU admission, hypoglycemia, birth weight and length of hospital stay. RESULTS: A total of 766 mothers (419 GDM mothers and 347 controls) with their term babies were included. Infants born to GDM mothers had significantly higher risk of NICU admissions [OR 2.7 (95% CI 1.5, 4.9), P value 0.0004], longer hospital stay and higher rates of hypoglycemia. Newborns of GDM mothers had higher rates of perinatal distress and macrosomia; however, the difference did not reach statistical significance. CONCLUSION: GDM remains a significant morbidity to newborns resulting in increased intensive care admission, prolongation of hospital stay and higher rates of neonatal hypoglycemia. More efforts to assure early recognition and strict sugar control during pregnancy are still needed.