After detection of a few clinical cases of methaemoglobinaemia (methb) in our NICU, a prospective clinical study was undertaken to determine the extent of the problem and to identify the causes. Consequently, during the following 8 months all haemoglobin tests included simultaneous measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n= 33) of 415 neonates were found to be methb positive (denned as ≥6% methb). Mean methb was 19% (range 6.5–45.5%). Maximum methb concentrations were found on day 4–31 postpartum (mean 12 days) and the number of days with a positive methb sample ranged from 1 to 18 days (mean 6 days). About 40% of the neonates born at 25–30 weeks of gestation and 60%) with a birth weight < 1000 g were methb positive. Also, there was a negative correlation between the size of the methb positive concentration and gestational age (r=– 0.38,p= 0.02). Measurements of C–reactive protein and leucocytes, NADH reductase, pH, CI, nitrate and nitrite were carried out in methb positive patients. The tests were repeated 1 week after cessation of methb. The only significant difference was an increase in NADH reductase at the second measurement. Likewise, a wide range of clinical parameters were registered and they occurred with a higher frequency among the methb positive patients when compared with a methb negative control group matched with regard to gestational age and the closest possible birth weight. The mean birth weight of methb positive patients was 1170g and that of negative controls 1380g (p < 0.006). Epidemiological data and intervention studies indicated that para–chloraniline was the direct cause of the epidemic. The substance was derived from 0.02% chlorhexidine being inadvertently added to the humidifying fluid of the new incubators. Treatment of severe methb in premature neonates with 0.3–1.0mg methylene blue/kg body weight proved efficient. In conclusion, premature neonates developed severe methb when exposed to even small amounts of para–chloraniline. Immaturity, severe illness, the time exposed to para–chloraniline and low concentrations of NADH reductase probably played a part while other well known factors such as increased nitrite and nitrate concentrations, acidosis and hyperchloraemia did not seem to be significant.
