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PubMed1995

Hepatic biotransformation capacity in low-birth-weight infants as measured with the [15N]methacetin urine test: influences of gestational age, postnatal age, and intrauterine growth retardation.

The influences of the gestational age (range: 28-36 weeks) and the postnatal age (range: 6-100 days) on the biotransformation capacity of the liver were studied in 51 preterm appropriate-for-gestational-age infants and in 20 preterm small-for-gestational-age infants using the [15N]methacetin urine test. Methacetin is a test drug assessing a two-step pathway of biotransformation including monooxygenation and conjugation. After oral administration of 3 mg [15N]methacetin/kg body-weight, the cumulative 15N excretion in urine during the consecutive 9 h was measured and used as a marker of microsomal biotransformation capacity. In preterm appropriate-for-gestational-age infants, the biotransformation capacity increases with gestational age as well as with postnatal age, but the strongest correlation could be found between cumulative [15N] excretion and postmenstrual age. Intrauterine growth retardation results in lower biotransformation capacity (26.3 +/- 11.3 vs. 36.1 +/- 9.6% [15N] excretion, expressed as percentage of intake) and disturbed postnatal development of this hepatic function. The data indicate that normal intrauterine development is a prerequisite for normal postnatal development of the biotransformation capacity, which might have consequences for the metabolism and efficacy of certain drugs in small-for-gestational-age infants.

Acetamides↗

PubMed1997

Effects of long-term maternal intravenous magnesium sulfate therapy on neonatal calcium metabolism and bone mineral content.

A prospective study was designed to determine whether calcium homeostasis and bone mineral content were affected adversely in preterm infants born to mothers receiving long-term antenatal therapy with magnesium sulfate. Preterm infants born to mothers receiving long-term antenatal therapy with magnesium sulfate and requiring prolonged bed rest for preterm labor were compared with infants of mothers not receiving magnesium sulfate but in whom prolonged bed rest was also required. Serum magnesium, calcium, phosphorus, osteocalcin, and parathyroid hormone were measured in infants at 0, 24, 48, and 72 h after delivery. Bone mineral content of the distal radius was measured 1 week postnatally and at term-equivalent postmenstrual age. Maternal serum mineral status indices obtained near delivery and bone indices were compared with those of their infants. The clinical characteristics and morbidities of the infants were similar between groups. We observed significantly greater serum concentrations of magnesium, phosphorus, and osteocalcin during the 72 h after delivery and a lower serum calcium concentration which normalized by 72 h in preterm infants whose mothers were treated with magnesium sulfate compared with infants whose mothers did not receive magnesium sulfate. Both groups, however, had similar radius bone mineral content measurements and anthropometric indices after delivery. These data suggest that although preterm infants born to mothers treated with magnesium sulfate have delayed clearance of magnesium and phosphorus, they have a normalization of serum calcium by 72 h after delivery and no significant differences in bone mineral content after delivery compared with infants whose mothers do not receive magnesium sulfate.

Adult↗

PubMed2002

Urine bombesin-like peptide elevation precedes clinical evidence of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of very low birth weight infants, associated with oxygen therapy, barotrauma, and/or infections. Improved medical care has led to a paradoxically increased incidence of BPD due to greater infant survival. Early prediction of BPD has proven challenging. Increased pulmonary neuroendocrine cells containing bombesin-like peptide immunoreactivity occur in infants with BPD. We hypothesized that elevated urine bombesin-like peptide levels precede BPD. One hundred thirty-two infants, 28-weeks gestation or less, were studied. Urine bombesin-like peptide levels, determined by radioimmunoassay, were normalized for creatinine. BPD was defined as oxygen dependence at 36 weeks postmenstrual age. A first urine bombesin-like peptide level greater than 20,000 pg/mg creatinine (12,500 fmol/mg) between postnatal days 1-4 occurred among 54% of the infants who later developed BPD (p < or = 0.001), versus 10% among non-BPD infants (specificity 90%). Multivariable logistic regression analyses revealed that elevated urine bombesin-like peptide levels are associated with BPD (odds ratio 9.9, 95% confidence interval: 3.4, 29) (p < or = 0.001) after adjusting for all confounding factors. Thus, elevated bombesin-like peptide levels in these infants at 1-4 days after birth are associated with a 10-fold increased risk of developing BPD. Utilizing urine bombesin-like peptide for screening might permit early therapeutic interventions to reduce disease progression and could provide a target for new preventive therapies.

Biomarkers↗

PubMed1987

Airway responsiveness to methacholine during the natural menstrual cycle and the effect of oral contraceptives.

Exacerbations of symptoms have been reported in some women with asthma just prior to and during menstruation. We examined changes in airway responsiveness to methacholine during 2 consecutive menstrual cycles in 17 well-controlled asthmatics with a wide range of airway responsiveness. In 10 women with regular natural cycles, measurements were made 1 wk before and 1 wk after the start of menstruation to coincide with the highest and lowest progesterone levels. The mean concentration of methacholine to cause a fall in FEV1 of 20% (PC20) premenstruation was 1.49 mg/ml, which was not significantly different from the mean postmenstruation PC20 of 1.34 mg/ml (p = 0.45). Although there were only 10 subjects, the power was 96%, indicating little likelihood of any difference between the 2 phases. In 7 women taking oral contraceptives, the mean PC20, measured within 1 wk of completing a 21-day course, was 1.19 mg/ml, which was not different from the mean PC20 of 0.97 mg/ml measured after the start of menstruation but before restarting medication (p = 0.17). The power was 98%. In both groups, there was no difference in FEV1 or medication use during the cycle, but symptoms were worse during menstruation. The results suggest that the fluctuations in serum progesterone levels that occur during natural menstrual cycles are insufficient to alter airway responsiveness in an unselected sample of asthmatic women. They also demonstrate that changes in symptoms occur during the cycle both in women with natural cycles and those using contraceptives and that these changes are not related to serum progesterone levels or airway responsiveness.

Adult↗

PubMed2005

Growth of pulmonary microvasculature in ventilated preterm infants.

RATIONALE: Density-based morphometric studies have demonstrated decreased capillary density in infants with bronchopulmonary dysplasia (BPD) and in BPD-like animal models, leading to the prevailing view that microvascular development is disrupted in BPD. OBJECTIVE: To perform a comprehensive analysis of the early and late effects of ventilation on pulmonary microvascular growth in preterm infants. METHODS: Postmortem lung samples were collected from ventilated preterm infants who died between 23 and 29 wk ("short-term ventilated") or between 36 and 39 wk ("long-term ventilated") corrected postmenstrual age. Results were compared with age-matched infants or stillborn infants ("early" and "late" control subjects). Microvascular growth was studied by anti-platelet endothelial cell adhesion molecule (PECAM)-1 immunohistochemistry, quantitative stereology, analysis of endothelial cell proliferation, and Western blot analysis of pulmonary PECAM-1 protein levels. MEASUREMENTS: Measurements were made of capillary density, volume of air-exchanging parenchyma, volume of microvascular endothelial cells, Ki67 labeling index of endothelial cells, and PECAM-1/actin protein levels. MAIN RESULTS: Lungs of long-term ventilated infants showed a significant (more than twofold) increase in volume of air-exchanging parenchyma and a 60% increase in total pulmonary microvascular endothelial volume compared with late control subjects, associated with 60% higher pulmonary PECAM-1 protein levels. The marked expansion of the pulmonary microvasculature in ventilated lungs was, at least partly, attributable to brisk endothelial cell proliferation. The microvasculature of ventilated lungs appeared immature, retaining a saccular architectural pattern. CONCLUSIONS: The pulmonary microvasculature of ventilated preterm infants displayed marked angiogenesis, nearly proportionate to the growth of the air-exchanging lung parenchyma. These results challenge the paradigm of microvascular growth arrest as a major pathogenic factor in BPD.

Blotting, Western↗

PubMed2003

Ocular growth and refractive error development in premature infants without retinopathy of prematurity.

PURPOSE: This investigation studied the factors involved in the development of refractive error (RE) in premature infants unaffected by retinopathy of prematurity (ROP). METHODS: Premature infants enrolled in the national ROP screening program were recruited and examined at 32, 36, 40, 44, and 52 weeks' postmenstrual age. At each examination, axial length (AXL), anterior chamber depth (ACD), and lens thickness (LT) were measured on the A-scan biometer. Corneal curvature (CC) was recorded with a video-ophthalmophakometer, and refractive state was determined with routine cycloplegic refraction. Multilevel modeling techniques were used to determine the relationships between all the variables throughout the study period, as well as individual growth rates. RESULTS: Sixty-eight premature infants were included. AXL and ACD showed linear patterns of growth, whereas LT changed little over the study period. CC showed a quadratic growth pattern, and unlike the previous variables, correlated well with refractive state. Premature infants were myopes at the start of the study, with refraction becoming emmetropic as they neared full term and then hypermetropic toward the end of the study. CONCLUSIONS: Most of the components of refractive status showed linear patterns of growth during this early phase of ocular development. CC displayed a more complex pattern of growth, which correlated well with refractive state. Compared with full-term infants examined around term, this group has shorter AXLs, shallower anterior chambers, and more highly curved corneas. In addition, less of the expected hypermetropia developed in the premature group, which seems mainly due to the differences in ACD and corneal curvature.

Anterior Chamber↗

PubMed2006

Optic disk size and optic disk-to-fovea distance in preterm and full-term infants.

PURPOSE: Few studies have assessed optic disk and retinal morphology in infants. Here the optic disk and optic disk-to-fovea distance were measured in preterm and full-term infants in vivo. METHODS: Optic disk (OD) dimensions and the center-to-center distance between the OD and the macula were measured using digital imaging in infants undergoing routine ophthalmic examinations. Postmenstrual age of the mother at the time of examination ranged from 32 to 50 weeks. From each image, the OD-to-fovea distance (ODF) and the OD height (ODH) and OD width (ODW) were measured. RESULTS: In 51 retinal images from 51 infants, mean +/- SD values obtained were 4.4 +/- 0.4 mm (ODF), 1.41 +/- 0.1 9 mm (ODH), and 1.05 +/- 0.13 mm (ODW). These dimensions did not change significantly over the age range studied. The mean value for the ratio between ODF and mean OD diameter (ODF/DD) was 3.76. CONCLUSIONS: Results of this in vivo study suggest that though the optic nerve head diameter increases by more than 50%, only limited growth occurs at the highly organized area of the posterior pole from birth to adulthood. This study discusses the finding of a large-angle kappa in infants and the use of a disk macula/disk diameter ratio in the diagnosis of optic nerve hypoplasia.

Birth Weight↗

PubMed2006

Premenstrual symptoms and perimenopausal depression.

OBJECTIVE: The role of ovarian steroids in both premenstrual dysphoria and perimenopausal depression has led to the suggestion that these conditions represent expressions of the same underlying disorder. Premenstrual mood symptoms were evaluated in women with perimenopause-related depression. METHOD: Self-reports and daily symptom ratings during one menstrual cycle were examined in 70 depressed perimenopausal women attending a menopause clinic and 35 nondepressed perimenopausal women. RESULTS: Twenty-six percent of the depressed and 9% of the nondepressed women reported premenstrual symptoms. Thirty-one percent of the depressed and 20% of the nondepressed women met criteria for significant menses-related symptom cyclicity (at least a 30% increase in the average ratings of at least two of four measured negative mood symptoms in the premenstrual versus the postmenstrual week); 5 of these depressed women and none of the comparison subjects described premenstrual symptoms on self-reports. Finally, 21% of the depressed and 3% of the nondepressed women met criteria for premenstrual dysphoria (symptom cyclicity and at least moderate severity, with symptoms exceeding a minimum luteal symptom severity threshold of 2.5). CONCLUSIONS: A higher-than-expected rate of menses-related symptom cyclicity and premenstrual dysphoria was observed in perimenopausal depressed women. However, neither menses-related symptom cyclicity nor premenstrual dysphoria was an invariant accompaniment of perimenopausal depression. Additionally, the rate of premenstrual dysphoria was not predicted by initial self-reports.

Adult↗

PubMed1999

Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian women.

The urinary ratio of 6-beta-hydroxycortisol/cortisol has been used as a noninvasive probe for human cytochrome P450 3A4 isoforms (CYP3A4). Ethnic-related differences in the ratio have not been evaluated. The aim of this study was to determine if there are differences in the ratio between Asian and Caucasian women over a menstrual cycle. First-morning urine samples were collected every other day starting from the second day of menstruation for a complete menstrual cycle from 15 Asians and 16 Caucasian women who were 18 to 40 years old, healthy, nonsmoking, and alcohol and drug free, including oral contraceptives. Urine concentrations of 6-beta-hydroxycortisol and cortisol were measured by high-pressure liquid chromatography (HPLC). For statistical analysis, three phases of the menstrual cycle were evaluated: menstruation (days 1-4), follicular or postmenstruation (days 6-10), and the luteal phase (days 21-24) based on the average menstrual cycle (28 days). Statistical analysis was performed by an independent sample t-test using the Bonferroni correction for repeated measures. Large intersubject and intrasubject variations of the 6-beta-hydroxycortisol/cortisol ratios were observed during the menstrual cycles in both ethnic groups. Asian women had a statistically significant lower ratio than Caucasian women did for all three phases of the menstrual cycle: 2.2 +/- 1.1 versus 5.1 +/- 3.5, 2.1 +/- 1.1 versus 6.0 +/- 4.9, and 2.8 +/- 1.6 versus 5.6 +/- 3.0 for the menstruation, follicular, and luteal phases, respectively. The two- to threefold lower 6-beta-hydroxycortisol/cortisol ratios in Asian women suggest that Asian women may have a lower CYP3A activity compared with Caucasian women. Differences in ethnicity may mask potential gender-related effects if ethnic background is not evaluated as a contributing factor.

Adolescent↗

PubMed2005

Memory function in women with premenstrual complaints and the effect of serotonergic stimulation by acute administration of an alpha-lactalbumin protein.

Serotonergic hypofunction may underlie at least part of the symptoms that are experienced by women with premenstrual complaints, including memory deficits. In the current study we investigated changes in memory functions in the premenstrual phase compared to the early postmenstrual phase in 16 women with premenstrual complaints. In addition, the effect of an acute serotonergic stimulation by administration of an alpha-lactalbumin protein on premenstrual memory performance was assessed using a double-blind placebo-controlled crossover design. It was found that both short-term and long-term memory for words (30-word learning task) and abstract figures (abstract visual learning task) were mildly impaired in the premenstrual phase. Administration of alpha-lactalbumin during the premenstrual phase could only partially attenuate the memory performance decrements that are seen in the premenstrual phase. Specifically, alphalactalbumin improved long-term memory for abstract figures, but not for words. There were no effects of menstrual phase or alpha-lactalbumin on planning functions (computerized Tower of London). The data suggest that serotonergic hypofunction may play a role in premenstrual memory decline, but serotonergic mechanisms cannot fully account for observed cognitive changes in the premenstrual phase.

Adolescent↗

PubMed2006

Joint distribution approaches to simultaneously quantifying benefit and risk.

BACKGROUND: The benefit-risk ratio has been proposed to measure the tradeoff between benefits and risks of two therapies for a single binary measure of efficacy and a single adverse event. The ratio is calculated from the difference in risk and difference in benefit between therapies. Small sample sizes or expected differences in benefit or risk can lead to no solution or problematic solutions for confidence intervals. METHODS: Alternatively, using the joint distribution of benefit and risk, confidence regions for the differences in risk and benefit can be constructed in the benefit-risk plane. The information in the joint distribution can be summarized by choosing regions of interest in this plane. Using Bayesian methodology provides a very flexible framework for summarizing information in the joint distribution. RESULTS: Data from a National Institute of Child Health & Human Development trial of hydrocortisone illustrate the construction of confidence regions and regions of interest in the benefit-risk plane, where benefit is survival without supplemental oxygen at 36 weeks postmenstrual age, and risk is gastrointestinal perforation. For the subgroup of infants exposed to chorioamnionitis the confidence interval based on the benefit-risk ratio is wide (Benefit-risk ratio: 1.52; 90% confidence interval: 0.23 to 5.25). Choosing regions of appreciable risk and acceptable risk in the benefit-risk plane confirms the uncertainty seen in the wide confidence interval for the benefit-risk ratio--there is a greater than 50% chance of falling into the region of acceptable risk--while visually allowing the uncertainty in risk and benefit to be shown separately. Applying Bayesian methodology, an incremental net health benefit analysis shows there is a 72% chance of having a positive incremental net benefit if hydrocortisone is used in place of placebo if one is willing to incur at most one gastrointestinal perforation for each additional infant that survives without supplemental oxygen. CONCLUSION: If the benefit-risk ratio is presented, the joint distribution of benefit and risk also should be shown. These regions avoid the ambiguity associated with collapsing benefit and risk to a single dimension. Bayesian methods allow even greater flexibility in simultaneously quantifying benefit and risk.

Anti-Inflammatory Agents↗

PubMed1991

Development of the transdermal potential of human skin.

The development of the transdermal electrical potential (TDP) with postnatal age was studied in neonates born at gestational ages of 25 to 42 wk. The TDP of neonates born at less than 28 wk gestational age was of similar magnitude over the whole skin surface when measured in the first 5 d of life (mean value -5.4 mV; skin surface negative with respect to s.c. tissues). The TDP increased progressively with increasing gestational and postnatal age. The rate of increase of the TDP with postmenstrual age was not accelerated in neonates born prematurely. TDP values of infants born at term were lower than those of adults, but the sites of high and low TDP were similar in both term infants and adults.

Adult↗

PubMed1994

Compartmental analysis of calcium metabolism in very-low-birth-weight infants.

The calcium metabolism of 13 very-low-birth-weight infants fed a high-calcium diet was evaluated by means of stable isotope kinetic and balance studies. The studies used orally and i.v. administered stable isotopes, and the kinetic data were evaluated with the aid of a sequential, three-compartment model. The infants (postmenstrual age 33 +/- 1 wk, weight 1.34 +/- 0.03 kg) had higher bone calcium deposition rates (160 +/- 7 mg.kg-1.d-1 or 4.00 +/- 0.18 mmol.kg-1.d-1) than those previously reported for either older children or adults. Furthermore, when analyzed as a function of net calcium absorption, bone calcium deposition rates increased markedly and significantly as net calcium absorption increased (r = 0.70, p < 0.01), whereas in older individuals, bone calcium deposition is a relatively invariant function of absorption. A relatively smaller response of bone calcium removal to calcium absorption was found for the very-low-birth-weight infants in this study (r = -0.39, p = 0.18), whereas in adults, bone calcium removal constitutes the major regulatory response. It is suggested that the calcium kinetic results in the very-low-birth-weight infants reflect the high rate of bone growth typical of the third trimester of gestation.

Adult↗

PubMed1995

Sucrose reduces pain reaction to heel lancing in preterm infants: a placebo-controlled, randomized and masked study.

In term infants sucrose given by mouth has been reported to reduce duration of crying after a heel prick. This study was designed primarily to investigate the effect of sucrose administered orally immediately before heel lancing on the nociceptive reaction in preterm infants as assessed by change in heart rate and duration of crying. A secondary objective was to document changes in cerebral blood volume during acute pain. We used a randomized, masked, placebo-controlled, crossover trial in a neonatal intermediate care unit in a level 3 perinatal center. The patients studied were 16 preterm infants; birth weight, 900-1900 g; gestational wk, 27-34; corrected postmenstrual age at time of investigation, 33-36 wk. Each infant was assessed twice receiving 2 mL of sucrose 50% or 2 mL of distilled water in random order immediately before heel lance. Heart rate, thoracic movements, and transcutaneous blood gases were monitored continuously. Crying during the procedure was documented by a video-camera. A change in cerebral blood volume was assessed by near-infrared spectroscopy. We found the heart increased by a mean of 35 beats/min (bpm) after sucrose and 51 bpm after placebo (median difference 16 bpm, interquartile range 1-30 bpm, p = 0.005). Infants cried 67% of time after sucrose and 88% after placebo (median difference 10%, interquartile range 3-33%, p = 0.002). Cerebral blood volume decreased in 5 of 14 infants after sucrose and in 6 of 14 infants after placebo (difference not significant).

Administration, Oral↗

PubMed1996

Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin.

Preterm infants fed formulas with docosahexaenoic acid (DHA, 22:6n-3) during the interval equivalent to the last intrauterine trimester and beyond have higher circulating DHA and transiently higher visual acuity compared with infants fed formulas containing linolenic acid. In term infants several nonrandomized studies of infants receiving DHA from human milk suggest a relationship between DHA status and acuity, but the evidence for a cause-and-effect relationship is mixed. In the present study, term infants were randomly assigned to a standard term formula (n = 20) or the same formula with egg yolk lecithin to provide DHA (0.1%) and arachidonic acid (AA, 20:4n-6, 0.43%) (n = 19) at levels reported in milk of American women. A third group of infants was breast fed for > or = 3 mo (n = 19). Grating visual acuity (Teller Acuity Card procedure) and plasma and red blood cell (RBC) phosphatidylcholine (PC) and phosphatidylethanolamine (PE) DHA and AA were determined at corrected ages of 2, 4, 6, 9 (acuity only), and 12 mo past term = 40 wk postmenstrual age (PMA). At 2 mo breast-fed infants and infants fed the supplemented formula had higher grating acuity than term infants fed standard formula. As in preterm infants, the increase was transient. Plasma PC DHA and AA and RBC PE AA increased by 2 mo in supplemented infants, but RBC PE DHA in supplemented infants was not higher than in controls until 4 mo and beyond. Despite normal intrauterine accumulation of DHA and AA, infants fed formula with 2% linolenic acid and 0.1% DHA had better 2-mo visual acuity than infants fed formula with 2% linolenic acid.

Arachidonic Acid↗

PubMed2000

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 > or = 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.

Bronchoalveolar Lavage Fluid↗

PubMed2000

Plasma concentrations of the carboxyterminal propeptide of type I procollagen (PICP) in preterm neonates from birth to term.

Carboxyterminal propeptide of type I procollagen (PICP), a marker of bone formation, has not yet been studied in preterm infants. In this study, PICP concentrations were measured longitudinally for 12 wk after birth using the ELISA technique in 43 preterm infants with a gestational age (GA) ranging from 24-29 wk and in 35 preterm infants with a GA ranging from 30-34 wk. PICP values in these preterm infants were higher than in children and adults. In cord plasma of preterm infants there was a significant gender difference, with higher PICP concentrations in male infants. A characteristic longitudinal pattern with an initial decrease during the first 3 postnatal days followed by a rapid increase from d 7 to d 28 was seen in both groups. Regarding the individual gestational ages, all preterm infants attained maximum PICP concentrations around 36 wk postmenstrual age. Multiple regression analysis revealed cord plasma PICP concentrations were significantly associated with GA, birth weight, sex, and IGF-I. A significant correlation between PICP concentrations and GA was seen at wk 1-4 and between PICP concentrations and protein intake at wk 1. Body weight and energy intake were shown to exert a significant effect on the PICP concentrations at 2 wk. The collected data in preterm infants may serve further studies evaluating PICP as a marker for bone formation and growth in very low birth weight premature infants.

Adult↗

PubMed2003

3-Chlorotyrosine as a marker of protein damage by myeloperoxidase in tracheal aspirates from preterm infants: association with adverse respiratory outcome.

Oxidative injury is implicated in the development of chronic lung disease in preterm infants with respiratory distress. However, direct evidence of a causal role is limited and the source of reactive oxidants has not been identified. We have previously shown that protein carbonyl levels in tracheal aspirates correlate positively with myeloperoxidase, suggesting that neutrophil oxidants could be the source of this protein injury. We have extended these observations by measuring 3-chlorotyrosine, a specific biomarker of the neutrophil oxidant, hypochlorous acid, in tracheal aspirate proteins (144 samples) from 69 infants with birth weight <1500 g. 3-Chlorotyrosine levels were higher in these infants than in larger infants without respiratory distress (median 83 compared with 13 micromol/mol tyrosine). They correlated strongly with myeloperoxidase activity (correlation coefficient 0.75, p < 0.0001) and to a lesser extent with protein carbonyls. 3-Chlorotyrosine levels (at 1 wk after birth) correlated negatively with birth weight or gestational age. They were significantly higher in infants who developed chronic lung disease (oxygen requirement at 36 wk postmenstrual age) than in those who did not (median 88 and 49 micromol/mol tyrosine, respectively) and correlated with days of supplemental oxygen. 3-Chlorotyrosine was also significantly higher in infants who had lung infection or were Ureaplasma urealyticum positive. Our results are the first evidence that chlorinated proteins are produced in the lungs of premature infants and that they are higher in infection. The higher 3-chlorotyrosine levels in infants who develop chronic lung disease suggest that neutrophil oxidants contribute to the pathology of this disease.

Biomarkers↗