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, d
uring the following 8 months all haemoglobin tests included simultaneo
us measurements of methb on an OSM 3 hemoximeter (Radiometer): 8% (n =
33) of 415 neonates were found to be methb positive (defined as great
er than or equal to 6% methb). Mean methb was 19% (range 6.5-45.5%). M
aximum 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 w
eeks of gestation and 60% with a birth weight <1000 g were methb posit
ive. Also, there was a negative correlation between the size of the me
thb positive concentration and gestational age (r = -0.38,p = 0.02). M
easurements of C-reactive protein and leucocytes, NADH reductase, pH,
Cl, nitrate and nitrite were carried out in methb positive patients. T
he tests were repeated 1 week after cessation of methb. The only signi
ficant difference was an increase in NADH reductase at the second meas
urement. Likewise, a wide range of clinical parameters were registered
and they occurred with a higher frequency among the methb positive pa
tients when compared with a methb negative control group matched with
regard to gestational age and the closest possible birth weight. The m
ean birth weight of methb positive patients was 1170 g and that of neg
ative controls 1380 g (p < 0.006). Epidemiological data and interventi
on studies indicated that para-chloraniline was the direct cause of th
e epidemic. The substance was derived from 0.02% chlorhexidine being i
nadvertently added to the humidifying fluid of the new incubators. Tre
atment of severe methb in premature neonates with 0.3-1.0 mg methylene
blue/kg body weight proved efficient. In conclusion, premature neonat
es developed severe methb when exposed to even small amounts of para-c
hloraniline. Immaturity, severe illness, the time exposed to para-chlo
raniline and low concentrations of NADH reductase probably played a pa
rt while other well known factors such as increased nitrite and nitrat
e concentrations, acidosis and hyperchloraemia did not seem to be sign
ificant.