Arginine supplementation in prevention of necrotizing enterocolitis in the premature infant: an updated systematic review.

BACKGROUND: Hypoxic-ischemic injury is thought to play a significant role in necrotizing enterocolitis (NEC). Nitric Oxide (NO) is the principal inhibitory neurotransmitter in the gut and is involved in regulation of mucosal blood flow and maintenance of mucosal integrity. NO is synthesized from L-arginine by NO synthases. Our primary objective was to determine the effectiveness of supplemental L-arginine versus placebo in prevention of NEC in preterm infants ≤ 34 weeks gestational age by systematic review of published randomized controlled trials (RCTs). METHODS: This review included RCTs in which L-arginine was administered as a supplement to neonates to prevent NEC. Searches were conducted in OVID MEDLINE, EMBASE, PubMed, and CINAHL from their dates of inception to July, 2014. Inclusion criteria were informed parental consent, neonates born at ≤ 34 weeks gestation, and birth weight ≤ 1500 g. Exclusion criteria included neonates with severe congenital anomalies and inborn errors of metabolism. Incidence of NEC was the primary outcome measure. Whole data were analyzed by RevMan 5.1 (Update Software, Oxford, UK). Outcome data were analyzed to determine risk ratios, number needed to treat, confidence intervals, and test for overall effect. RESULTS: Two trials including 425 neonates were eligible for this review. Of these, 235 neonates were included in the study. L-arginine had a 59% reduction in the incidence of stage II and III NEC (RR 0.41, 95% CI 0.20 to 0.85, NNT = 9) compared with placebo (P = 0.02). A similar finding was identified for all stages of NEC (60% reduction, RR 0.40, 95% CI 0.23 to 0.69, NNT = 5) (P = 0.001). At age 3 yrs, there was no significant difference between the 2 groups in terms of any neurodevelopmental disability (RR 0.65; 95% CI 0.23-1.83, P = 0.41). CONCLUSIONS: L-arginine supplementation appears to be protective in prevention of NEC in preterm infants and without any significant impact on neurodevelopmental outcomes at 36 months of corrected age. With the addition of the results of one more study to the literature, an intriguing role for L-arginine supplementation continues to gain support. However, large multi-centre RCTs are needed before this can become common practice.

Impact of oxygen concentration on time to resolution of spontaneous pneumothorax in term infants: a population based cohort study.

BACKGROUND: Little evidence exists regarding the optimal concentration of oxygen to use in the treatment of term neonates with spontaneous pneumothorax (SP). The practice of using high oxygen concentrations to promote "nitrogen washout" still exists at many centers. The aim of this study was to identify the time to clinical resolution of SP in term neonates treated with high oxygen concentrations (HO: FiO2 ≥ 60%), moderate oxygen concentrations (MO: FiO2 < 60%) or room air (RA: FiO2 = 21%). METHODS: A population based cohort study that included all term neonates with radiologically confirmed spontaneous pneumothorax admitted to all neonatal intensive care units in Calgary, Alberta, Canada, within 72 hours of birth between 2006 and 2010. Newborns with congenital and chromosomal anomalies, meconium aspiration, respiratory distress syndrome, and transient tachypnea of newborn, pneumonia, tension pneumothorax requiring thoracocentesis or chest tube drainage or mechanical ventilation before the diagnosis of pneumothorax were excluded. The primary outcome was time to clinical resolution (hours) of SP. A Cox proportional hazards model was developed to assess differences in time to resolution of SP between treatment groups. RESULTS: Neonates were classified into three groups based on the treatment received: HO (n = 27), MO (n = 35) and RA (n = 30). There was no significant difference in time to resolution of SP between the three groups, median (range 25th-75th percentile) for HO = 12 hr (8-27), MO = 12 hr (5-24) and RA = 11 hr (4-24) (p = 0.50). A significant difference in time to resolution of SP was also not observed after adjusting for inhaled oxygen concentration [MO (a HR = 1.13, 95% CI 0.54-2.37); RA (a HR = 1.19, 95% CI 0.69-2.05)], gender (a HR = 0.87, 95% CI 0.53-1.43) and ACoRN respiratory score (a HR = 0.7, 95% CI 0.41-1.34). CONCLUSIONS: Supplemental oxygen use or nitrogen washout was not associated with faster resolution of SP. Infants treated with room air remained stable and did not require supplemental oxygen at any point of their admission.

The mystery of persistent pulmonary hypertension: an idiopathic infantile arterial calcification.

BACKGROUND: Idiopathic infantile arterial calcification (IIAC) is a rare autosomal recessive disorder, characterized by wide spread calcifications in arterial walls, leading to vaso-occlusive ischaemia of multiple organs. Mortality is high, and there is no definitive treatment. CASE PRESENTATION: A male neonate, 36+5 weeks gestation, 2.81 kg, was admitted to NICU for respiratory distress. At one hour of age, he was noted to be pale, hypoperfused, with weak pulses, a hyperdynamic precordium and a grade IV/VI pansystolic murmur. The rest of his examination was normal. A chest X-ray showed massive cardiomegaly and pulmonary oedema. An echocardiogram (ECHO) indicated moderate persistent pulmonary hypertension (PPHN) of unclear etiology. A diagnosis of Idiopathic infantile arterial calcification was made and a trial of Editronate therapy was given without success. CONCLUSION: IIAC is a rare disorder, it should be considered whenever a neonate presents with unexplainable cardiac failure, PPHN, echogenic vessels on X-ray/ultrasound and, or concentric hypertrophic ventricles on ECHO. Serial antenatal ultrasound findings of echogenic cardiac foci should raise the suspicion of IIAC. Further studies to determine the long term effects of Editronate on vascular calcifications, disease outcome, and other treatment options are needed.