Toxic additives in medication for preterm infants.

BACKGROUND: Little is known about exposure of preterm infants to excipients during routine clinical care. OBJECTIVE: To document excipient exposure in vulnerable preterm babies in a single centre, taking into account chronic lung disease (CLD) as a marker of illness severity. DESIGN: Excipient exposure after treatment with eight oral liquid medications was determined by retrospectively analysing the drug charts of infants admitted to a neonatal unit. SETTING: The Leicester Neonatal Service. PARTICIPANTS: 38 infants born between June 2005 and July 2006 who were less than 30 weeks' gestation and 1500 g in weight at birth and managed in Leicester to discharge. RESULTS: The 38 infants represented 53% of the eligible target group; 7/38 infants had CLD. During their in-patient stay, infants were exposed to over 20 excipients including ethanol and propylene glycol, chemicals associated with neurotoxicity. Infants with CLD were exposed to higher concentrations of these toxins. Infants were also exposed to high concentrations of sorbitol, with some infants being exposed to concentrations in excess of recommended guidelines for maximum exposure in adults. CONCLUSIONS: Preterm infants are commonly exposed to excipients, some of which are potentially toxic. Strategies aimed at reducing excipient load in preterm infants are urgently required.

The role of neutrophil apoptosis in the resolution of acute lung injury in newborn infants.

BACKGROUND: The persistent airway neutrophilia observed in chronic lung disease of prematurity (CLD) may reflect inappropriate suppression of neutrophil apoptosis. METHODS: 134 bronchoalveolar lavage (BAL) samples were obtained from 32 infants requiring mechanical ventilation for respiratory distress syndrome (RDS): 13 infants (median gestation 26 weeks, range 23 to 28) subsequently developed CLD (CLD group), and 19 infants (gestation 31 weeks, range 25 to 39) recovered fully (RDS group). A further 73 BAL samples were obtained from 20 infants (median age 2 days, range 1 to 402) receiving extracorporeal membrane oxygenation (ECMO) for severe respiratory failure. RESULTS: Neutrophil apoptosis was increased in the RDS group (mean (SEM) neutrophil apoptosis on day 7 BAL: RDS 17.0 (8.6)% v CLD 0.7 (0.2)% (p<0.05)). BAL fluid obtained from RDS but not CLD patients was proapoptotic to neutrophils (apoptosis ratio BAL fluid/saline control: day 1, RDS 9.8 (5.5) v CLD 1.2 (0.1) (p<0.05); day 2, RDS 4.32 (2.8) v CLD 0.5 (0.4) (p<0.05)). There were similar findings in the ECMO group: survivors had proapoptotic BAL fluid compared with non-survivors (apoptosis ratio day 1, survivors 7.9 (2.1) v non-survivors 2.1 (0.7) (p<0.05)). CONCLUSIONS: Inappropriate suppression of neutrophil apoptosis may be associated with a poor outcome in newborn infants with respiratory failure.

Fibroblast mitogenic activity of lung lavage fluid from infants with chronic lung disease of prematurity.

BACKGROUND: Lung fibrosis is thought to be important in chronic lung disease of prematurity (CLD). METHODS: Fibroblast proliferative activity was assessed in 207 bronchoalveolar lavage fluid (BALF) samples from 43 infants. Sixteen developed CLD (birth weight 765 g (630-1230), gestation 26.5 weeks (23-29)), 18 developed respiratory distress syndrome (RDS) (birth weight 1415 g (430-4160), gestation 31 weeks (23-39)), and nine control infants (birth weight 2110 g (900-3720), gestation 32 weeks (26-41)) received mechanical ventilation for non-pulmonary reasons. RESULTS: The fibroblast proliferative activity relative to 10% fetal calf serum was 64-75% in infants with CLD, 55-86% in the RDS group, and 42-68% in control infants during the first 5 weeks of life. Only at day 3 was there a difference between the groups (CLD 72% v control 42%, p < 0.01; RDS 63% v control 42%, p < 0.05). With the use of neutralising antibodies, platelet derived growth factor BB (PDGF-BB) and epidermal growth factor were undetectable, and insulin-like growth factor I (IGF-I) accounted for 14% (p < 0.05) and 11% (p < 0.005) of BALF mitogenic activity from the RDS and CLD groups respectively. CONCLUSIONS: The mitogenic activity of BALF was similar in the three groups studied and was only partially accounted for by IGF-I. Growth factors other than PDGF-BB and IGF-I contribute significantly to this process.

Epidermal growth factor in the lungs of infants developing chronic lung disease.

Growth factors important to lung growth and fibrosis have been poorly studied in chronic lung disease (CLD) of prematurity. Epidermal growth factor (EGF) promotes epithelial cell maturation, and vascular endothelial growth factor (VEGF) is important in angiogenesis. The concentration of these growth factors was determined in 111 bronchoalveolar lavage fluid (BALF) samples from 35 ventilated infants: 13 developed CLD (median gestation 27 weeks, birthweight 820 g), 16 developed and recovered from respiratory distress syndrome (RDS) (31 weeks, 1,415 g) and six control infants (33 weeks, 2,075 g) were ventilated for nonpulmonary reasons. At birth, EGF in BALF from the CLD and RDS infants was lower than in the control infants (control versus CLD, 7.3 versus 0.0 pg x mL(-1), p<0.01; control versus RDS, 7.3 versus 5.0, p=0.08). EGF increased in all groups with a more rapid increase in control infants. A close relationship was noted between BALF EGF and gestational age (R=0.73). VEGF was undetectable at birth but increased at a similar rate in all three groups and did not correlate with gestation. In conclusion, these data suggest that epidermal growth factor is closely correlated to gestation and that it may predispose preterm infants to develop chronic lung disease.

Concentration of nitric oxide products in bronchoalveolar fluid obtained from infants who develop chronic lung disease of prematurity.

AIMS: To determine if nitric oxide (NO) products (nitrate and nitrite) are increased in bronchoalveolar lavage (BAL) fluid obtained from infants who develop chronic lung disease of prematurity (CLD). METHODS: One hundred and thirty six serial bronchoalveolar lavages were performed on 37 ventilated infants (12 with CLD, 18 with respiratory distress syndrome (RDS), and seven control infants) who did not receive inhaled NO. RESULTS: During the first week of life nitrate concentration was between 25-31 micromol/l in all three groups. Thereafter, the concentration of BAL fluid nitrate decreased to 14 micromol/l and 5.5 micromol/l, respectively in the RDS and control groups by 14 days of age. In contrast, nitrate in the CLD infants remained constant until 28 days of age (31.3 micromol/l at day 14; p<0.05). In all BAL fluid samples the mean concentration of nitrite was <1.2 micromol/l throughout the first 28 days with no significant differences noted among the three groups. CONCLUSION: The similar concentration of BAL fluid nitrate in all groups during the first week of life suggest that NO may be important in the adaptation of the pulmonary circulation after birth. However, persistence of nitrate in the BAL fluid of infants with CLD during the second week may reflect pulmonary maladaptation, or, more likely, persisting pulmonary inflammation.

The pathology of clubbing: vascular changes in the nail bed.

In this study post-mortem angiograms were prepared from both normal and clubbed hands and attempts were made to estimate the size of the vascular bed in the terminal parts of each finger. Representative cases were also examined histologically. There were no differences between the groups. The increase in blood flow in clubbing is the result of vasodilatation rather than hyperplasia of vessels in the nail bed.