Antiseptic solutions for skin preparation during central catheter insertion in neonates.

BACKGROUND: Central venous catheters (CVC) are associated with potentially dangerous complications such as thromboses, pericardial effusions, extravasation, and infections in neonates. Indwelling catheters are amongst the main risk factors for nosocomial infections. The use of skin antiseptics during the preparation for central catheter insertion may prevent catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI). However, it is still not clear which antiseptic solution is the best to prevent infection with minimal side effects. OBJECTIVES: To systematically evaluate the safety and efficacy of different antiseptic solutions in preventing CRBSI and other related outcomes in neonates with CVC. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and trial registries up to 22 April 2022. We checked reference lists of included trials and systematic reviews that related to the intervention or population examined in this Cochrane Review.  SELECTION CRITERIA: Randomised controlled trials (RCTs) or cluster-RCTs were eligible for inclusion in this review if they were performed in the neonatal intensive care unit (NICU), and were comparing any antiseptic solution (single or in combination) against any other type of antiseptic solution or no antiseptic solution or placebo in preparation for central catheter insertion. We excluded cross-over trials and quasi-RCTs. DATA COLLECTION AND ANALYSIS: We used the standard methods from Cochrane Neonatal. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included three trials that had two different comparisons: 2% chlorhexidine in 70% isopropyl alcohol (CHG-IPA) versus 10% povidone-iodine (PI) (two trials); and CHG-IPA versus 2% chlorhexidine in aqueous solution (CHG-A) (one trial). A total of 466 neonates from level III NICUs were evaluated. All included trials were at high risk of bias. The certainty of the evidence for the primary and some important secondary outcomes ranged from very low to moderate. There were no included trials that compared antiseptic skin solutions with no antiseptic solution or placebo. CHG-IPA versus 10% PI Compared to PI, CHG-IPA may result in little to no difference in CRBSI (risk ratio (RR) 1.32, 95% confidence interval (CI) 0.53 to 3.25; risk difference (RD) 0.01, 95% CI -0.03 to 0.06; 352 infants, 2 trials, low-certainty evidence) and all-cause mortality (RR 0.88, 95% CI 0.46 to 1.68; RD -0.01, 95% CI -0.08 to 0.06; 304 infants, 1 trial, low-certainty evidence). The evidence is very uncertain about the effect of CHG-IPA on CLABSI (RR 1.00, 95% CI 0.07 to 15.08; RD 0.00, 95% CI -0.11 to 0.11; 48 infants, 1 trial; very low-certainty evidence) and chemical burns (RR 1.04, 95% CI 0.24 to 4.48; RD 0.00, 95% CI -0.03 to 0.03; 352 infants, 2 trials, very low-certainty evidence), compared to PI. Based on a single trial, infants receiving CHG-IPA appeared less likely to develop thyroid dysfunction compared to PI (RR 0.05, 95% CI 0.00 to 0.85; RD -0.06, 95% CI -0.10 to -0.02; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 10 to 50; 304 infants). Neither of the two included trials assessed the outcome of premature central line removal or the proportion of infants or catheters with exit-site infection. CHG-IPA versus CHG-A The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI when applied on the skin of neonates prior to central line insertion (RR 0.80, 95% CI 0.34 to 1.87; RD -0.05, 95% CI -0.22 to 0.13; 106 infants, 1 trial, low-certainty evidence) and CLABSI (RR 1.14, 95% CI 0.34 to 3.84; RD 0.02, 95% CI -0.12 to 0.15; 106 infants, 1 trial, low-certainty evidence), compared to CHG-A. Compared to CHG-A, CHG-IPA probably results in little to no difference in premature catheter removal (RR 0.91, 95% CI 0.26 to 3.19; RD -0.01, 95% CI -0.15 to 0.13; 106 infants, 1 trial, moderate-certainty evidence) and chemical burns (RR 0.98, 95% CI 0.47 to 2.03; RD -0.01, 95% CI -0.20 to 0.18; 114 infants, 1 trial, moderate-certainty evidence). No trial assessed the outcome of all-cause mortality and the proportion of infants or catheters with exit-site infection. AUTHORS' CONCLUSIONS: Based on current evidence, compared to PI, CHG-IPA may result in little to no difference in CRBSI and mortality. The evidence is very uncertain about the effect of CHG-IPA on CLABSI and chemical burns. One trial showed a statistically significant increase in thyroid dysfunction with the use of PI compared to CHG-IPA. The evidence suggests CHG-IPA may result in little to no difference in the rate of proven CRBSI and CLABSI when applied on the skin of neonates prior to central line insertion. Compared to CHG-A, CHG-IPA probably results in little to no difference in chemical burns and premature catheter removal. Further trials that compare different antiseptic solutions are required, especially in low- and middle-income countries, before stronger conclusions can be made.

The Key Aspects of Neonatal and Infant Neurological Examination: The Ballard Score, the Infant's Head with Hydrocephalus and Assessment in a Clinical Setting.

The physical examination of the newborn is essential in diagnosing neurological or neurosurgical conditions in the newborn. This article focuses on three clinical assessments of newborns and infants that are especially important if neurological problems are suspected: The Ballard score, the examination of the head in a baby with (suspected) hydrocephalus, and the neurological and developmental evaluation of an infant in an ambulatory setting. A textual description and a link to a video describe each assessment.

Short versus long feeding interval for bolus feedings in very preterm infants.

BACKGROUND: There is presently no certainty about the ideal feeding intervals for preterm infants. Shorter feeding intervals of, for example, two hours, have the theoretical advantage of allowing smaller volumes of milk. This may have the potential to reduce the incidence and severity of gastro-oesophageal reflux. Longer feeding intervals have the theoretical advantage of allowing more gastric emptying between two feeds. This potentially provides periods of rest (and thus less hyperaemia) for an immature digestive tract. OBJECTIVES: To determine the safety of shorter feeding intervals (two hours or shorter) versus longer feeding intervals (three hours or more) and to compare the effects in terms of days taken to regain birth weight and to achieve full feeding. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to run comprehensive searches in CENTRAL (2020, Issue 6) and Ovid MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions, and CINAHL on 25 June 2020. We searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. SELECTION CRITERIA: We included RCTs and quasi-RCTs comparing short (e.g. one or two hours) versus long (e.g. three or four hours) feeding intervals in preterm infants of any birth weight, all or most of whom were less than 32 weeks' gestation. Infants could be of any postnatal age at trial entry, but eligible infants should not have received feeds before study entry, with the exception of minimal enteral feeding. We included studies of nasogastric or orogastric bolus feeding, breast milk or formula, in which the feeding interval is the intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were days taken to achieve full enteral feeding and days to regain birth weight. Our other outcomes were duration of hospital stay, episodes of necrotising enterocolitis (NEC) and growth during hospital stay (weight, length and head circumference). MAIN RESULTS: We included four RCTs, involving 417 infants in the review. One study involving 350 infants is awaiting classification. All studies compared two-hourly versus three-hourly feeding interval. The risk of bias of the included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies were included in meta-analysis for the number of days taken to achieve full enteral feeding (351 participants). The mean days to achieve full feeds was between eight and 11 days. There was little or no difference in days taken to achieve full enteral feeding between two-hourly and three-hourly feeding, but this finding was of low certainty (mean difference (MD) ‒0.62, 95% confidence interval (CI) ‒1.60 to 0.36). There was low-certainty evidence that the days taken to regain birth weight may be slightly longer in infants receiving two-hourly feeding than in those receiving three-hourly feeding (MD 1.15, 95% CI 0.11 to 2.20; 3 studies, 350 participants). We are uncertain whether shorter feeding intervals have any effect on any of our secondary outcomes including the duration of hospital stay (MD ‒3.36, 95% CI ‒9.18 to 2.46; 2 studies, 207 participants; very low-certainty evidence) and the risk of NEC (typical risk ratio 1.07, 95% CI 0.54 to 2.11; 4 studies, 417 participants; low-certainty evidence). No study reported growth during hospital stay. AUTHORS' CONCLUSIONS: The low-certainty evidence we found in this review suggests that there may be no clinically important differences between two- and three-hourly feeding intervals. There is insufficient information about potential feeding complications and in particular NEC. No studies have looked at the effect of other feeding intervals and there is no long-term data on neurodevelopment or growth.

Primum Non Nocere.

The coronavirus disease 2019 (COVID-19) pandemic is severe and has not shown any signs of warning up to today. Biotech companies around the world have raced to come up with an acceptable vaccine and recently two mRNA vaccines have received emergency usage authorisation from regulatory bodies in several countries. mRNA vaccines, which consist of a new and revolutionary technology have not been previously tested widely on humans. Medium- and long-term safety data are not available. While many experts seem to support the start of a mass vaccination campaign, others feel there are too many unknowns to embark on a mass vaccination campaign. Concerns include uncertainties about the long-term effects of foreign mRNA on human cellular physiology and the possibility of vaccine-enhanced disease severity, which may not be unlikely with the current disease presentation of COVID-19.

Use of reflective materials during phototherapy for newborn infants with unconjugated hyperbilirubinaemia.

BACKGROUND: Phototherapy is a well-established effective therapy for treating babies with significant neonatal jaundice. Studies have shown that increasing light intensity will increase its efficiency. A potentially inexpensive and easy way of increasing the intensity of light on the body of the infant may be to hang reflective materials from the sides of phototherapy units. OBJECTIVES: To assess the effects of reflective materials in combination with phototherapy compared with phototherapy alone for unconjugated hyperbilirubinaemia in neonates. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 11), in the Cochrane Library; Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions(R); and the Cumulative Index of Nursing and Allied Health Literature (CINAHL), on 1 November 2019. We also searched clinical trials databases and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: We included randomised and quasi-randomised controlled trials if the participants, who were term or preterm infants, received phototherapy with curtains made of reflective materials of any type in the treatment arm, and if those in the comparison arm received similar phototherapy without curtains or other intensified phototherapy, such as a double bank of lights. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS: Of 15 studies identified, we included 12 (1288 babies) in the review - 11 comparing phototherapy with reflective materials and phototherapy alone, and one comparing a single phototherapy light bank with reflective materials with double phototherapy. All reflective materials consisted of curtains on three or four sides of the cot and were made of white plastic (five studies), white linen (two studies), or aluminium (three studies); materials were not specified in two studies. Only 11 studies (10 comparing reflective materials versus none and one comparing reflective curtains and a single bank of lights with a double (above and below) phototherapy unit) provided sufficient data to be included in the meta-analysis. Two excluded studies used the reflective materials in a way that did not meet our inclusion criteria, and we excluded one study because it compared four different phototherapy interventions not including reflective materials. The risk of bias of included studies was generally low, but all studies had high risk of performance bias due to lack of blinding of the intervention. Three studies (281 participants) reported a decline in serum bilirubin (SB) (µmol/L) at four to eight hours (mean difference (MD) -14.61, 95% confidence interval (CI) -19.80 to -9.42; I² = 57%; moderate-certainty evidence). Nine studies (893 participants) reported a decline in SB over 24 hours and showed a faster decline in SB in the intervention group, but heterogeneity (I² = 97%) was too substantial to permit a meaningful estimate of the actual effect size (very low-certainty evidence). Subgroup analysis by type of reflective material used did not explain the heterogeneity. Exchange transfusion was reported by two studies; both reported none in either group. Four studies (466 participants) reported the mean duration of phototherapy, and in each of these studies, it was reduced in the intervention group but there was substantial heterogeneity (I² = 88%), precluding meaningful meta-analysis of data. The only two studies that reported the mean duration of hospital stay in hours showed a meaningful reduction (MD -41.08, 95% CI -45.92 to -36.25; I² = 0; moderate-certainty evidence). No studies reported costs of the intervention, parental or medical staff satisfaction, breastfeeding outcomes, or neurodevelopmental follow-up. The only study that compared use of curtains with double phototherapy reported similar results for both groups. Studies that monitored adverse events did not report increased adverse events related to the use of curtains, including acute life-threatening events, but other rarer side effects could not be excluded. AUTHORS' CONCLUSIONS: Moderate-certainty evidence shows that the use of reflective curtains during phototherapy may result in greater decline in SB. Very low-certainty evidence suggests that the duration of phototherapy is reduced, and moderate-certainty evidence shows that the duration of hospital stay is also reduced. Available evidence does not show any increase in adverse events, but further studies are needed.

Randomised controlled trial: Shoulder-umbilicus length versus body weight measurement for optimal endotracheal tube depth estimation in ventilated infants.

AIM: The optimal placement of the endotracheal tube (ETT) in ventilated infants is essential, but birthweight may be not the best parameter to predict it. The aim of this study was a direct comparison of shoulder-umbilical length (experimental group) versus birthweight (control group) as predictor of optimal ETT placement in Malaysian ventilated infants. METHODS: All infants requiring ventilation in the neonatal intensive care unit of a tertiary hospital in Malaysia during the 4-month study period were eligible to enter this randomised controlled trial. All participants were randomised into two groups: experimental and control group. The main outcome measure was malposition of the ETT (requiring adjustment), as seen on the chest X-ray performed within 1 h after intubation. Tube placement was assessed by two neonatologists, blinded to the allocation. RESULTS: One hundred and ten infants were randomised, 55 in each group. The ETT was malpositioned in 13 of 55 infants (23%) for the experimental group and 22 of 55 infants (40%) in the control group (P = 0.06). CONCLUSION: In the experimental group, fewer infants showed a need for tube adjustment than in the control group. While a larger study may be necessary to show statistical significance, the difference shown in this study may be large enough to be of clinical significance.

Human albumin infusion for treating oedema in people with nephrotic syndrome.

BACKGROUND: Oedema is a common clinical symptom in people with nephrotic syndrome and human albumin has been widely used in the treatment of oedema by increasing vascular volume and this inducing diuresis. It may be used with or without diuretics such as furosemide. However, the quantitative contribution of human albumin in treating oedema is not fully understood. If human albumin were found to be effective and safe in the treatment of oedema, it could help clinicians to develop therapeutic strategies to improve the management of diuretic resistance associated with nephrotic syndrome. OBJECTIVES: This review aimed to examine the benefits and harms of human albumin infusion for treating oedema associated with nephrotic syndrome. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 23 June 2019 through contact with the Information Specialists using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of human albumin infusion compared with placebo or no intervention, human albumin with diuretics compared with diuretic alone, human albumin compared with diuretics and other treatments, clinical outcomes, death, quality of life, kidney function and adverse effects in people with nephrotic syndrome. We excluded cross-over studies but data for the first period was to be included if available. DATA COLLECTION AND ANALYSIS: Standard methods of the Cochrane Collaboration were used. Two authors independently assessed eligibility, risk of bias, study quality and extracted data. We calculated mean difference (MD) for continuous data with 95% confidence intervals (CI). We assessed the certainty of the evidence using GRADE. MAIN RESULTS: One study met our inclusion criteria (26 children with minimal change nephrotic syndrome) and 11 were excluded (nine cross-over studies, one where albumin was not used for nephrotic syndrome and one where authors did not state whether the children had oedema). Risk of bias for the included study was unclear for selection bias, high for performance and detection bias, low for attrition bias, and high for selective reporting. The included study compared albumin plus furosemide with an equal volume of dextrose. Of our prespecified outcomes, the authors reported clinical improvement as weight change, serum sodium and adverse outcomes (blood pressure). The authors reported a greater weight loss in the albumin treated group initially but no difference overall at 10 days. However, the data in the text and the figures were inconsistent so we could not confirm the authors statements (very low certainty evidence). It is uncertain whether albumin infusion improves serum sodium when compared with an equal volume of dextrose (MD 2.00 mEq/L, 95% CI -0.09 to 4.09), systolic blood pressure (MD 2.00 mmHg, 95% CI -3.52 to 7.52) or diastolic blood pressure (MD 2.00 mmHg, 95%CI -4.29 to 8.29). Death, quality of life, and kidney function were not reported. AUTHORS' CONCLUSIONS: We identified only one small study that was relevant to our review, therefore we are unable to draw any conclusions regarding the use of human albumin with or without diuretics in nephrotic syndrome. More RCTs are needed.

Placebo Controlled Trials: Interests of Subjects versus Interests of Drug Regulators.

The use of placebo-controlled trials in situations where established therapies are available is considered ethically problematic since the patients randomised to the placebo group are deprived of the beneficial treatment. The pharmaceutical industry and drug regulators seem to argue that placebo-controlled trials with extensive precautions and control measures in place should still be allowed since they provide necessary scientific evidence for the efficacy and safety of new drugs. On the other hand, the scientific value and usefulness for clinical decision-making may be much higher if the new drug is compared directly to existing therapies. As such, it may still be unethical to impose the burden and risk of placebo-controlled trials on patients even if extensive precautions are taken. A few exceptions do exist. The use of placebo-controlled trials in situations where an established, effective and safe therapy exists remains largely controversial.

Informed Consent Template and Guidelines on the Ethical Practice in Human Genetics and Human Genomic Research; Initiatives of the Universiti Sains Malaysia.

Malaysia is advancing and nearly on pace with the international scientific community in human genetics and human genomics research. However, this research poses unique challenges. Although Malaysia already regulates medical genetic services, these regulations are insufficient for coping with the ethical issues emerging from recent genomic technologies. The Universiti Sains Malaysia recently created in-house guidelines and an informed consent template for genetic and genomic research. This article presents these guidelines and the informed consent template and discusses the justification and the background of the initiative. We also propose recommendations pertaining to local social studies and regulatory arrangements.

Randomised controlled trial of single phototherapy with reflecting curtains versus double phototherapy in term newborns with hyperbilirubinaemia.

AIM: The use of reflecting curtains with single phototherapy has not yet been directly compared with double phototherapy (DP). The objective of this study is to compare the efficacy of single phototherapy with reflecting curtains (SPRC) and DP in treating neonatal jaundice. METHODS: This randomised controlled trial involved 160 term newborns with severe neonatal jaundice in the first 2 weeks of life. The subjects were randomised in two groups: the intervention group receiving SPRC (n = 80) and a control group receiving DP (n = 80). Because of post-hoc exclusions, 78 subjects resulted in each group, respectively. The primary outcome was mean decrease in total serum bilirubin (TSB) levels after 4 h of phototherapy. The secondary outcomes were mean decrease in TSB levels after 10 h of phototherapy and duration of phototherapy. RESULTS: The mean decrease in TSB after 4 h of phototherapy in the intervention group was similar for the intervention and the control groups (23.46 ± 27.03 vs. 22.43 ± 27.38 µmol/L; P = 0.81). Also, after 10 h, it was similar in both groups (56.06 ± 31.36 vs. 58.17 ± 31.71 µmol/L, respectively; P = 0.67). Cox proportional hazards regression analysis indicated that there was no statistically significant difference in duration of phototherapy in both intervention (SPRC) and control (DP) (x2 change 0.393, P = 0.531; hazard ratio 1.060; 95% confidence interval 0.883-1.273). There were no significant adverse events noted. CONCLUSIONS: This study suggested that single phototherapy with reflecting curtain is as effective as DP in the treatment of neonatal hyperbilirubinaemia requiring intensive phototherapy.

Non-attendance to the paediatric clinics in a Malaysian tertiary hospital: a sizeable problem and identification of an efficacious intervention.

AIM: To determine the rate, causes and risk factors of non-attendance to the paediatric clinic in a tertiary hospital in Malaysia and to determine the efficacy of one telephone call to confirm a new appointment. METHODS: For all non-attending patients, during a 2-month period, a pro forma was filled up based on patients' records. During a phone call, additional questions were asked, and a new appointment was offered. RESULTS: Of 1563 patients who had an appointment, 497 (31.8%) were non-attendees. Weather conditions, the sub-specialty and timing (morning or afternoon) had a significant effect on non-attendance. Forgetfulness was the main cause. Only 160 patients could be successfully contacted. Among the contactable patients, 55 already had an appointment, and 10 had reasons not to get a new appointment. Of the 95 remaining patients, 73 (76.8%) attended the new appointment. CONCLUSION: The non-attendance rate was high. One telephone call had a reasonable efficacy for the contactable patients, but because a high number of patients were not contactable, overall effectiveness was poor.

The Role of Heme Oxygenase-1 Promoter Polymorphisms in Perinatal Disease.

Heme oxygenase (HO) is the rate-limiting enzyme in the heme catabolic pathway, which degrades heme into equimolar amounts of carbon monoxide, free iron, and biliverdin. Its inducible isoform, HO-1, has multiple protective functions, including immune modulation and pregnancy maintenance, showing dynamic alteration during perinatal periods. As its contribution to the development of perinatal complications is speculated, two functional polymorphisms of the HMOX1 gene, (GT)n repeat polymorphism (rs3074372) and A(-413)T single nucleotide polymorphism (SNP) (rs2071746), were studied for their association with perinatal diseases. We systematically reviewed published evidence on HMOX1 polymorphisms in perinatal diseases and clarified their possible significant contribution to neonatal jaundice development, presumably due to their direct effect of inducing HO enzymatic activity in the bilirubin-producing pathway. However, the role of these polymorphisms seems limited for other perinatal complications such as bronchopulmonary dysplasia. We speculate that this is because the antioxidant or anti-inflammatory effect is not directly mediated by HO but by its byproducts, resulting in a milder effect. For better understanding, subtyping each morbidity by the level of exposure to causative environmental factors, simultaneous analysis of both polymorphisms, and the unified definition of short and long alleles in (GT)n repeats based on transcriptional capacity should be further investigated.

Comparison of Mean Platelet Counts in Preterm Infants with and without Retinopathy of Prematurity.

Platelets are a primary source of pro- and anti-angiogenic cytokines. However, the evidence of their role in retinopathy of prematurity (ROP) is controversial. This retrospective study aimed to compare mean weekly platelet counts between infants with and without ROP over the first 6 weeks of life. A total of 93 infants matched by gestational age and birth weight were recruited (31 with ROP, 62 without ROP). Weekly mean platelet counts and other related risk factors were documented. The repeated measure analysis of variance (ANOVA) and the repeated measure analysis of covariance (ANCOVA) were used to compare mean platelet counts over time between the two groups, with and without adjusting for confounders. We found significant differences in the weekly mean platelet counts of infants with and without ROP over the first 6 weeks of life (p = 0.002). These differences disappeared after adjusting for covariates (p = 0.489). Lower mean platelet counts in ROP infants are not directly related to ROP, but rather to the presence of other risk factors for ROP, such as culture-proven sepsis, blood transfusion and bronchopulmonary dysplasia.

A Randomized Controlled Trial Comparing Two Doses of Caffeine for Apnoea in Prematurity.

Caffeine is the most commonly used methyl xanthine for the prevention of apnoea in prematurity, but the ideal dose was uncertain, until now. This study compared two doses of caffeine for the prevention of apnoea in prematurity. A clinical trial was conducted on 78 preterm infants ≤32 weeks in Neonatal Intensive Care Unit. They were randomly allocated to receive the intervention (loading 40 mg/kg/day and maintenance of 20 mg/kg/day) or the control (loading 20 mg/kg/day and maintenance of 10 mg/kg/day) dose of caffeine. The primary outcome of the study was the frequency and total days of apnoea per duration of treatment for both groups. The frequency of apnoea ranged from zero to fourteen in the intervention group and zero to twelve in the control group. There was no statistically significant difference between the groups, with a p-value of 0.839. The number of days of apnoea was also similar between both groups, with a p-value of 0.928. There was also no significant difference in adverse events between both regimens. This study did not support the use of higher doses of caffeine as a prevention for apnoea in prematurity.

A polymorphic mutation, c.-3279T>G, in the UGT1A1 promoter is a risk factor for neonatal jaundice in the Malay population.

The uridine diphosphoglucuronate-glucuronosyltransferase 1A1 (UGT1A1) gene encodes the enzyme responsible for bilirubin glucuronidation. To evaluate the contribution of UGT1A1 promoter mutations to neonatal jaundice, we determined the genotypes of c.-3279T>G, c.-3156G>A, and A(TA)7TAA in Malay infants with neonatal jaundice (patients) and in infants without neonatal jaundice (controls). In our population study, only c.-3279T>G was associated with neonatal jaundice. The genotype distributions between both groups were significantly different (p = 0.003): the frequency of homozygosity for c.-3279G was much higher in patients than those in controls. Allele frequency of c.-3279G was significantly higher in patients than those in controls (p = 0.006). We then investigated changes in transcriptional activity because of c.-3279T>G. Luciferase reporter assay in HepG2 cells demonstrated that transcriptional activity of the c.-3279G allele was significantly lower than that of the c.-3279T allele in both the absence and presence of bilirubin. Luciferase reporter assay in COS-7 cells elucidated that c.-3279T>G modified the synergistic effects of the nuclear factors associated with transcriptional machinery. In conclusion, the c.-3279T>G mutation in the UGT1A1 promoter is a genetic risk factor for neonatal jaundice.

Two-hourly versus 3-hourly feeding for very low birthweight infants: a randomised controlled trial.

OBJECTIVE: To determine whether feeding with 2-hourly or 3-hourly feeding interval reduces the time to achieve full enteral feeding and to compare their outcome in very low birthweight preterm infants. DESIGN: Parallel-group randomised controlled trial with a 1:1 allocation ratio. SETTING: Two regional tertiary neonatal intensive care units. PATIENTS: 150 preterm infants less than 35 weeks gestation with birth weight between 1.0 and 1.5 kg were recruited. INTERVENTIONS: Infants were enrolled to either 2-hourly or 3-hourly interval feeding after randomisation. Blinding was not possible due to the nature of the intervention. MAIN OUTCOME MEASURES: The primary outcome was time to achieve full enteral feeding (≥100 mL/kg/day). Secondary outcomes include time to regain birth weight, episode of feeding intolerance, peak serum bilirubin levels, duration of phototherapy, episode of necrotising enterocolitis, nosocomial sepsis and gastro-oesophageal reflux. RESULTS: 72 infants were available for primary outcome analysis in each group as three were excluded due to death-three deaths in each group. The mean time to full enteral feeding was 11.3 days in the 3-hourly group and 10.2 days in the 2-hourly group (mean difference 1.1 days; 95% CI -0.4 to 2.5; p=0.14). The mean time to regain birth weight was shorter in 3-hourly group (12.9 vs 14.8 days, p=0.04). Other subgroup analyses did not reveal additional significant results. No difference in adverse events was found between the groups. CONCLUSION: 3-hourly feeding was comparable with 2-hourly feeding to achieve full enteral feeding without any evidence of increased adverse events. TRIAL REGISTRATION NUMBER: ACTRN12611000676910, pre-result.

Evaluation of mutation effects on UGT1A1 activity toward 17beta-estradiol using liquid chromatography-tandem mass spectrometry.

Mutations in the gene encoding UDP-glucuronosyltransferase 1A1 (UGT1A1) may reduce the glucuronidation of estradiol, bilirubin, etc. In the present study, we used a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to assay the activities of recombinant mutated UGT1A1 toward 17beta-estradiol (E2), by determining its glucuronide (E2G) content. Direct evidence for glucuronide formation was provided by E2G-specific ion peaks. The UGT1A1 activities of G71R (exon 1), F83L (exon 1), I322V (exon 2) and G493R (exon 5) mutants were 24, 30, 18 and 0.6% of the normal UGT1A1 activity, respectively. In conclusion, our study showed that LC/MS/MS enabled accurate evaluation of the effects of mutations on recombinant UGT1A1 activity towards E2.

Prevalence of asthma-like symptoms and assessment of lung function in schoolchildren born with low birth weight.

INTRODUCTION: This study aimed to determine the prevalence of asthma-like symptoms among schoolchildren with low birth weight (LBW), and to compare the lung function of these children with that of children with normal birth weight. METHODS: This was a comparative cross-sectional study. We recruited children aged 8-11 years from eight primary schools in Kota Bharu, Kelantan, Malaysia. The children were divided into two groups: those with LBW (< 2,500 g) and those with normal birth weight (≥ 2,500 g). Parents of the enrolled children were asked to complete a translated version of the International Study of Asthma and Allergies in Childhood questionnaire. Lung function tests, done using a MicroLoop Spirometer, were performed for the children in both groups by a single investigator who was blinded to the children's birth weight. RESULTS: The prevalence of 'ever wheezed' among the children with LBW was 12.9%. This value was significantly higher than that of the children with normal birth weight (7.8%). Forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow when 50% and 75% of the FVC had been exhaled were significantly lower among the children with LBW as compared to the children with normal birth weight. CONCLUSION: LBW is associated with an increased prevalence of asthma-like symptoms and impaired lung function indices later in life. Children born with LBW may need additional follow-up so that future respiratory problems can be detected early.