Objectives: To study whether early-onset neonatal sepsis is associated with a prenatal immune response with elevated umbilical plasma levels of inflammatory mediators, and to study whether mediator levels may be helpful in identifying infected neonates. Setting: Nested case-control study. Methods: Cord blood was sampled from 7,073 consecutively delivered neonates. After review of the medical records, neonates suspected to suffer from infection were classified as infected (n = 52) or noninfected but sick controls (n = 33). We also included a group of healthy controls (n = 99). Umbilical plasma levels of tumour necrosis factor-α (TNFα), interleukin (IL)-1β, IL-6, IL-8, soluble TNF receptors (p55 and p75), IL-1 receptor antagonist (IL-1RA) and C-reactive protein were measured by immunoassays. Results: Infected neonates had higher levels of TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA than healthy controls (all p < 0.01). Among preterm infants (GA <37 weeks), those with infection (n = 11) had higher levels of IL-1β, IL-6, IL-8, p55 and p75 than noninfected sick controls (n = 13) (all p < 0.05), but among term infants, the infected did not differ from the noninfected sick controls. Receiver operator characteristic plots showed that IL-1β, IL-6 and IL-8 identified preterm infected neonates accurately. Conclusions: Early-onset neonatal sepsis is associated with a prenatal immune response with increased TNFα, IL-1β, IL-6, IL-8, p55, p75 and IL-1RA levels in umbilical plasma. Among neonates who present symptoms suggestive of infection, cytokine levels may be helpful in identifying preterm, but not term infected individuals.

Atopic disease, including atopic dermatitis (AD), is associated with a T-helper 2 (Th2)-dependent immune response. The cytokine receptor CD30 appears to be preferentially expressed on, and its soluble form (sCD30) released by, Th2 cells. Therefore, sCD30 may be a potential marker for atopic disorders. The aim of this study was to test the hypothesis that the sCD30 level in cord blood could be used to predict the development of atopy or AD in early childhood. In a case-control study, levels of sCD30, as well as soluble low-affinity immunoglobulin E (IgE) receptor (sCD23), interleukin-4 (IL-4) and IgE, were measured in cord blood in 35 children who subsequently developed allergic sensitization and AD before the age of three, and the results were compared to those of 35 matched children without a history of atopy. There was no difference in cord blood levels of sCD30 between controls (32.5 U/ml; 19.7-80.1) and children with subsequent atopy and AD (32.2 U/ml; 22-75.9) (median; quartiles). The concentration of sCD30 showed no relation to the levels of total IgE, sCD23 or IL-4. Levels of sCD23 were similar in children with subsequent atopy (60.2 U/ml; 44.5-76.8) and controls (55.2 U/ml; 38.3-72.5), whereas IL-4 was detectable in 10 of the atopic children and in only two of the controls (p <0.05). In conclusion, cord blood levels of sCD30 or sCD23 do not seem to be related to the subsequent development of atopy or AD at the age of three.

LETTERSsevere stomatitis, and the drug was discontinued for 14 days. Naproxen, which had been given concomitantly with MTX, was reduced to 375 mglday. When MTX was reinstituted at lower weekly doses (5 mg or 7.5 mg), stomatitis recurred; however, the RA continued to respond very well to the drug. He received a total of 52.5 mg of MTX before it was again discontinued.Because he experienced severe stomatitis with 5-mg doses of injectable MTX, it was considered that oral MTX would likewise produce stomatitis. However, this change in the mode of drug administration was tried, along with the addition of leucovorin to the treatment regimen. A regimen of 5 mg of oral MTX taken at 8 AM once a week, followed by 5 mg of leucovorin 14-16 hours later, was begun. He had no stomatitis with that regimen, and the MTX dosage was later increased to 7.5 mg/week, without adverse effects. He has been on this regimen for the last 10 months and has had approximately 95% improvement, as judged by both his self-reported symptoms and his physical examination results. Hematologic and biochemical studies have not indicated any adverse effects.This case illustrates that an intolerable side effect from MTX, severe stomatitis, can be abrogated by leucovorin, allowing the patient to continue taking MTX. Because this patient noticed rapid (somewhat early) symptomatic improvement with only a few, low doses of MTX, an interesting question arises as to the correlation, if any, with his early development of severe stomatitis.