B. A. Darlow

High iron status in very low birth weight infants is associated with an increased risk of retinopathy of prematurity

OBJECTIVE To explore the hypothesis that excessive iron loads may increase the formation of free radicals and the development of retinopathy of prematurity in preterm infants, we carried out a prospective observational study of the association between transfusion volume, iron status, and retinopathy.

Elevated protein carbonyls and lipid peroxidation products correlating with myeloperoxidase in tracheal aspirates from premature infants.

The purpose of this study is to determine whether the oxidative injury markers, protein carbonyls and malondialdehyde (MDA), are elevated in tracheal aspirates from very low birth weight (<1500 g) infants; to determine whether levels correlate with myeloperoxidase as a marker of neutrophil inflammation; and to assess whether high levels are associated with poor respiratory outcome. Tracheal aspirates (144 samples) were collected from 86 infants <1500 g at times of routine suctioning. Aspirates (82 samples) from 54 infants ≥1500 g who required intubation for a variety of diagnoses were analyzed for comparison. Analyses were performed for protein carbonyls by ELISA, total malondialdehyde by HPLC, and myeloperoxidase activity. Respiratory outcome was assessed as oxygen requirement at 28-d or 36-wk postmenstrual age, and as the number of days of oxygen requirement. Protein carbonyls were significantly higher in infants <1500 g than larger infants, and were highest close to birth. MDA concentrations were also higher in the earlier samples. There was a strong positive correlation between protein carbonyls and myeloperoxidase, suggesting a link between protein oxidation and neutrophil activation. A similar but weaker correlation was seen for MDA. Carbonyls in samples taken after steroid administration were less than for controls with a similar age distribution. We did not see significant associations between oxidant marker levels and development of chronic lung disease. Our findings of higher amounts of protein and lipid oxidation products in tracheal aspirates with high myeloperoxidase activity, taken together with other studies showing a link between neutrophil accumulation and chronic lung disease, suggest a possible contribution by neutrophil-derived reactive oxygen species to the injury.

Limiting light-induced lipid peroxidation and vitamin loss in infant parenteral nutrition by adding multivitamin preparations to Intralipid

Parenteral lipids are susceptible to light‐induced peroxidation, particularly under phototherapy. Ascorbic acid is protective. The aim of this study was to investigate whether dark delivery tubing and/or coadministration of multivitamin preparations could prevent peroxidation of Intralipid without undue vitamin loss. In experiments carried out on the benchtop, lipid peroxidation occurred in ambient light and was more extensive under phototherapy. Dark tubing decreased peroxide formation, but only by about 65%. In simulated clinical conditions in which solutions were pumped through standard clear or dark minibore plastic tubing, Intralipid accumulated lipid peroxides as measured by the FOX assay (280 μM) or as triglyceride hydroperoxides (52 μM). Multivitamin preparations (MVIP or Soluvit/Vitlipid) inhibited peroxide formation almost completely, and were fully protective when used with dark tubing. There was loss of riboflavin (65% from Soluvit and 35% from MVIP) in clear tubing but this was decreased to 18% and 11%, respectively, in dark tubing. Ascorbate loss was 20% (MVIP) and 50% (Soluvit) and only slightly less in dark tubing. Ascorbate loss was also seen in the absence of Intralipid and is due to riboflavin‐induced photo‐oxidation.

Late-onset infections of infants in neonatal units

Objective: To examine regional variations in the incidence of late‐onset neonatal infections in Australian and New Zealand neonatal units.

Protein Carbonyls and Lipid Peroxidation Products as Oxidation Markers in Preterm Infant Plasma: Associations with Chronic Lung Disease and Retinopathy and Effects of Selenium Supplementation

The purpose of this study was to determine whether protein carbonyls and the lipid peroxidation product malondialdehyde (MDA) are elevated in plasma from very low birth weight (<1500 g) infants, whether they are affected by selenium supplementation, and whether they are associated with poor respiratory outcome or retinopathy. The study group comprised 173 infants enrolled in a randomized controlled trial of selenium supplementation. Plasma samples, collected before randomization, at 7 and 28 d after birth, and at 36 wk postmenstrual age, were analyzed for protein carbonyls and total MDA. Respiratory outcome was assessed as oxygen requirement at 28 d of age or 36 wk postmenstrual age and as number of days on oxygen. Protein carbonyl concentrations in very low birth weight infants were significantly higher than for adults but lower than for cord blood from term infants. Median values decreased significantly by 28 d, and there was no relationship with birth weight. MDA concentrations in very low birth weight infants overlapped the ranges for healthy adults and cord blood from term infants. They correlated positively with birth weight at 28 d but not at other times. Supplementation almost doubled plasma selenium concentrations, but carbonyls and MDA did not differ between the supplemented and unsupplemented groups. There were no significant differences in oxidant marker levels in infants who did or did not develop chronic lung disease or retinopathy. Protein carbonyls and MDA measurements in plasma do not show evidence of systemic oxidative stress in <1500-g infants and are not affected by selenium supplementation. Oxidative injury at sites such as the lung may be important in prematurity, but markers from such sites must be measured to relate to outcome and antioxidant supplementation.

The correlation of elevated levels of an index of lipid peroxidation (MDA‐TBA) with adverse outcome in the very low birthweight infant

The objective of this study was to examine the relationship between malondialdehyde‐thiobarbituric acid (MDA‐TBA) levels, as a measure of lipid peroxidation, in very low birthweight (VLBW) infants and outcome measures. A prospective observational longitudinal study was carried out in two level III neonatal units in the South Island of New Zealand measuring MDA‐TBA levels in 61 VLBW infants in 1993. MDA‐TBA levels were measured in (i) maternal plasma within 48 h of parturition, (ii) cord plasma, and (iii) infants’plasma at 2, 7, 14 and 28 days of age, and correlated with antenatal and postnatal factors. Elevated levels of plasma MDA‐TBA at 7 days were associated with adverse respiratory and ophthalmological outcome in the VLBW infants. Elevated MDA‐TBA levels were measured at sample times close to the time of death in the infants who died. These results substantiate previously reported preliminary observations and support the hypothesis that oxidative injury, particularly within the first 7 days of life, is associated with the development of the long‐term complications of the pre‐term infant. MDA‐TBA levels appear to be a useful measure to continue to explore the role of free radical mediated disease in the VLBW infant.

Prospective study of New Zealand very low birthweight infants: Outcome at 7–8 years

To determine the survival and sensorineural outcome at 7–8 years in very low birthweight (VLBW) infants born in New Zealand in 1986.

Endotracheal suctioning of the neonate: Comparison of two methods as a source of mucus material for research

Endotracheal suctioning in the neonatal intensive care setting is a routine procedure performed to maintain patency of the airway in ventilated infants. Harvested material can also be a source of mucus for research into neonatal respiratory disorders. We aimed to investigate whether the composition of material obtained by our clinically preferred technique of dry shallow suctioning differed significantly from that obtained with saline lavage and deep suctioning. Eleven pairs of dry and saline lavage aspiration samples were compared for neutrophil enzyme myeloperoxidase, total and active α1‐antitrypsin, α1‐antitrypsin complexed with elastase, and secretory leukoprotease inhibitor. Even though individual values of each analyte, expressed per gram of albumin, varied over at least a fivefold range, there was no difference between mean values of dry and lavage samples for any of the constituents. We conclude that the yield of material for research obtained by dry shallow suctioning is adequate and the quality at least as satisfactory as that provided by saline lavage. Pediatr. Pulmonol. 1997; 23:217–221

Chronic lung disease in very low birthweight infants: A prospective population-based study

Abstract A prospective population‐based study of chronic lung disease among all very low birthweight infants (birthweight 500–1499 g) born in New Zealand in 1986 is reported. Of 413 of these infants admitted to neonatal units, 355 (86%) survived to 28 days. An additional 50 infants were recorded as liveborn but died in the labour ward or other place of birth. Both observed survival and survival adjusted for birthweight, gestation and gender were significantly (P<0.05) better in larger centres. Oxygen requirement was assessed at 28 days of age, 36 weeks equivalent gestation and 84 days of age, when 38.6,23.1 and 13.8% of infants, respectively, were being treated with oxygen. To examine the joint effects of predictor variables on oxygen requirement at each age, the data were analysed using multiple logistic regression methods. At 28 days, lower birthweight, shorter gestation, respiratory distress syndrome (all P<0.0001), and gender and hospital principally caring for the infant (both P<0.05) were significantly associated with treatment with oxygen. In comparison with other studies, New Zealand appears to have a relatively high rate of chronic lung disease. We speculate that a contributing factor may be the small size of some regional neonatal units.

Selenium status of New Zealand infants fed either a selenium supplemented or a standard formula

Objective: New Zealand soils are deficient in the essential micronutrient, selenium. New Zealand infants have low selenium levels at birth and experience a further decline if fed cows milk based formula. This study examined the selenium status of infants fed with a new commercially available selenium supplemented formula.