Original article Correlation between the serum level of endotoxin and periventricular leukomalacia in preterm infants Akihisa Okumura a, c, * , Fumio Hayakawa b , Toru Kato c , Kuniyoshi Kuno c , Kazuyoshi Watanabe a a Department of Pediatrics, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya,Aichi 466-8550, Japan b Department of Pediatrics, Okazaki Municipal Hospital, Okazaki, Japan c Department of Pediatrics, Anjo Kosei Hospital, Anjo, Japan Received 20 October 1998; received in revised form 2 April 1999; accepted 6 April 1999 Abstract The objective of our study was to determine the relation between the serum level of endotoxin at birth and the development of periventricular leukomalacia (PVL) in preterm infants. We studied 68 preterm infants whose gestational ages ranged between 27 and 33 weeks, and birthweights between 1000 and 2000 g. The serum endotoxin level was measured in the blood immediately after birth by means of a conventional chromogenic Limulus test. Serum endotoxin was taken as present when it was .5 pg/ml (indicated by ENDO(1)). Premature rupture of membranes (PROM), the mode of delivery, EEG ®ndings and the development of PVL were investigated. Six infants were diagnosed as having cystic PVL on ultrasonography. Endotoxin was detected in 28 infants. PROM was observed in 18 ENDO(1) infants and 16 ENDO(2) infants (P  0:085). Caesarean section was performed in nine ENDO(1) infants and 14 ENDO(2) infants (P  0:29). PVL was observed in two ENDO(1) infants and four ENDO(2) infants (P . 0:99). EEG abnormalities were recognized in ®ve ENDO(1) infants and six ENDO(2) infants (P . 0:99). Between ENDO(1) infants and ENDO(2) infants, no signi®cant difference was observed in any of the four parameters. These results may indicate that endotoxin itself does not directly cause PVL. q 1999 Elsevier Science B.V. All rights reserved. Keywords: Periventricular leukomalacia; Endotoxin; Premature rupture of membranes Periventricular leukomalacia (PVL) is a major cause of neurological sequelae in preterm infants. Despite intensive investigations, the pathogenesis of PVL is not fully under- stood. Recently, the importance of chemically mediated brain injury was emphasized. Some authors reported that premature rupture of membranes increases the risk of PVL [1,2]. In animal experiments, the administration of endo- toxin produced periventricular white matter lesions similar to those in PVL. However, the relation between the serum level of endotoxin and the neurological outcome was not clari®ed. The aim of this study was to determine the relation between endotoxemia at birth and the development of PVL in preterm infants. 1. Patients and methods Between October 1992 and April 1994, 69 preterm infants, whose gestational ages ranged between 27 and 33 weeks and birthweights between 1000 and 2000 g, were admitted to Anjo Kosei Hospital. The serum endotoxin level was measured in the blood immediately after birth in all of them. We excluded one infant with a lumbar menin- gocele and hydrocephalus from the analysis because the neurodevelopmental outcome was strongly affected by the malformation itself. Blood cultures were routinely performed using the same blood samples. Informed consent was obtained from all the parents of the infants. The average gestational age was 31:5 ^ 11:6 weeks (range 27±33 weeks) and the average birthweight was 1641 ^ 253 g (range 1008± 1995 g). Premature rupture of membranes (PROM, de®ned as rupture from more than 24 h before delivery) and the mode of delivery were investigated in the medical records of the mothers. Cranial ultrasonography was performed at least twice within the ®rst week of life, and thereafter one to three times a week. Coronal and sagittal sections of the anterior fontanelle were examined. PVL was diagnosed when multiple cystic formations of more than 3 mm in diameter were observed. Electroencephalography (EEG) was performed in all of the cases within 72 h. EEG was Brain & Development 21 (1999) 378±381 0387-7604/99/$ - see front matter q 1999 Elsevier Science B.V. All rights reserved. PII: S0387-7604(99)00036-4 * Corresponding author. Tel.: 181-52-744-2309; fax: 181-52-744- 2974,.