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.

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.

Constitutive androstane receptor (CAR) encoded by the nuclear receptor subfamily 1, group I, member 3 (NR1I3) gene regulates the elimination of bilirubin through activating the components of the bilirubin clearance pathway. Hence, NR1I3 genetic variants may affect bilirubin metabolism and result in neonatal hyperbilirubinemia. Thus far, research which investigates the association between NR1I3 variants and neonatal hyperbilirubinemia has not been undertaken in any population. The present study aimed to evaluate the influence of MPJ6_1I3008 (rs10157822), IVS8+116T>G (rs4073054) and 540A>G (rs2307424) on neonatal hyperbilirubinemia development in the Malay population. Buccal swabs were collected from 232 hyperbilirubinemia and 277 control term newborns with gestational age ≥ 37 weeks and birth weight ≥ 2500 g. The NR1I3 variants were genotyped by using high resolution melting (HRM) assays and verified by DNA sequencing. Gender, mode of delivery and birth weight did not differ between hyperbilirubinemia and control groups. The genotypic and allelic frequencies of MPJ6_1I3008, IVS8+116T>G and 540A>G were not significantly different between the groups. However, stratification by gender revealed a significant inverse association between homozygous variant genotype of MPJ6_1I3008 and risk of neonatal hyperbilirubinemia in the females (OR, 0.44; 95% CI, 0.20–0.95; p = 0.034). This study demonstrates that the homozygous variant genotype of MPJ6_1I3008 was associated with a significant reduced risk of neonatal hyperbilirubinemia in the females.