Extremely low birth weight newborns (ELBW; <1,000g) frequently require central venous catheters for total parenteral nutrition and drug administration. To determine the frequency of catheter-related complications we reviewed the medical records of 100 PIC catheters placed in 89 ELBW patients born between 1/29/93 and 10/30/95. Fifty-seven percent of PIC catheters were removed for complications including: sepsis (85% [49/57]), mechanical problems (5% [3/57]), thrombosis (5% [3/57]), malposition(2%[1/57]) and leakage (2% [1/57]). Because of this, patients were divided into two groups: sepsis vs no-sepsis to compare putative risk factors. Sepsis was defined as a clinical deterioration comprising new apnea, desaturation, feeding intolerance, lethargy, temperature instability, etc and ≥7 days antibiotic treatment. Catheter-related sepsis was defined by a positive blood culture when no other source could be identified. Septic patients had a similar birth weight (745g ± 17 [median 757] vs 792g ± 20[median 802]; p-ns) but a lower weight at PICC line insertion (688g ± 15 [median 686] vs 836g ± 40 [median 758]; p <0.002) and a lower gestational age (25 wk ± 0.2 vs 27 wk ± 0.4; p <0.03). In fact, 10% (4/42) of the non-septic group were <26 wk as compared to 32%(15/47) of the septic neonates (p<0.02). Septic neonates also had a statistically significant difference in the time from insertion-to removal of catheter for infection (18 ± 1d [median 15] vs 14 ± 1d [median 12]; p<0.03). The cumulative risk of sepsis was found to be 3 per 100 PICC line days vs 0.9 infections per 100 non-PICC line days (p<0.002). The average length of stay was 105 hospital days per septic patient vs 80 hospital days per non-septic patient. Total PICC line days in septic neonates was 17%(882/5157) as compared to 22% (714/3296) in the non-septic group (p-ns). There was no difference between septic and non-septic groups with regard to the person who placed the PIC catheter (fellow, nurse practitioner, resident) or in their CBC, RDS, IVH or other common clinical variables. We speculate that(1) the higher infection rate might reflect the functional immaturity of the immune system that predisposes neonates who are more premature to an increased risk of PICC line-related infection and (2) prophylactic measures used to augment immune function of extremely low birth weight neonates may further reduce the incidence of sepsis in this population.