Predisposing Factors In Fetal And Neonatal Infection

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Despite its presence in 25% of all pregnant women, isolation of Candida from the placenta is rare (12,13). Baley reported an incidence of less than 1% (14). In the presence of chorioamnionitis, fetal infection can occur and presents as congenital cutaneous candidiasis (CCC). Risk factors for congenital infection include early preterm birth, the presence of a foreign body such as an intrauterine device or cervical sutures, and possibly diagnostic amniocentesis (6,12). Factors that do not appear to play a role in congenital candidiasis are maternal age, prolonged rupture of membranes, diabetes, urinary tract infection, parity, and antibiotic, tocolytic, or corticosteroid therapy (15). The role of congenital candidiasis in precipitating preterm labor or premature rupture of membranes remains unknown and warrants further investigation (16,17).

There are many factors that may make the neonate more susceptible to fungal infections. These include an immature immune system, low birth weight, prematurity, congenital immunodeficiency, indwelling vascular and urinary catheters, prolonged broad-spectrum antibiotic use, intralipid and parenteral nutrition, and early fungal colonization of the GI tract. At the end of the 20th century, the incidence of candidemia and its relationship to colonization has been studied.

The overall incidence of neonatal candidemia is 7.7% in low birth weight colonized infants (5). The incidence of candidemia in the low birth weight infants has increased over the last 20 years. In one study, the rate of candidemia in 1407 infants weighing less than 1000 g increased from 10.4 cases per 1000 admissions in 1981-1985 to 98.9 per 1000 in 1991-1995 (1). The mean age of onset of candidemia ranged from 15 to 173 days of age, with mean ages of 43-47 days in some studies (1,2). The incidence of candidemia was 0.2% (7/3033) in infants with birth weights above 2500 g admitted to the neonatal intensive care nursery (18). This risk is much lower than that for low birth weight infants. The most frequent underlying condition in these term infants was a major congenital malformation, which occurred in half of the infants with fungal sepsis.

Colonization has been shown to be a significant risk factor for mucocutaneous and invasive candidiasis. In one study, one third of the colonized infants developed muco-cutaneous candidiasis, and 7.7% developed systemic fungal disease (5). In another study of 383 low birth weight infants, the overall incidence of invasive disease was 4.5%, and for mucocutaneous candidiasis, it was 7.8%. Invasive disease developed in 32% of the infants with mucocutaneous candidiasis compared to 2% without (19).

The largest prospective multicenter cohort study was conducted in six level-III neonatal intensive care nurseries in diverse geographical areas from 1993 to 1995 to determine the incidence and associated risk factors for candidemia in 2847 infants (20). The overall risk for candidemia was lower than previous reports (1.2%). The significant risk factors identified included preterm, low 5-minute Apgar score, disseminated intra-vascular coagulation, prior use of intralipid, parenteral nutrition, central venous catheters, H2 blockers, intubation, or length of stay for more than 7 days. Although GI tract colonization was not identified as an independent risk factor, almost half of the patients who developed candidemia had preceding colonization. In fact, enteral feeds may be protective and prevent or decrease GI colonization.

Some studies have looked at other factors, such as the nursery environment (5). There was no evidence of environmental contamination found in chest tubes, ventilators, water reservoirs, breast milk, umbilical or central line catheters, or isolette walls documented, but it probably does occur. Vaginal delivery (compared to cesarean section) did not seem to be a risk factor. The only statistically significant factor was a grade 3 or 4 intraventricular hemorrhage (for infants delivered vaginally) (5). These infants tended to be sicker.

A univariate analysis of factors associated with colonization in a study of 116 low birth weight infants showed no significant difference between colonized and noncolonized infants. These factors included birth weight, gestational age, duration of nursery stay, vaginal delivery, steroid administration, or duration of intubation. Infants with colonization had a significantly longer duration of antimicrobial therapy, parenteral nutrition, and intralipid infusions. The duration of use of intravascular catheters approached significance (3).

Because of the increasing occurrence of C. parapsilosis, the risk of invasive disease associated with colonization of the GI tract in newborns was investigated (9). Of 82 colonized, low birth weight infants, 6% developed C. parapsilosis septicemia. There was an association with umbilical artery catheters and absence of enteral feeds. In that particular nursery, enteral feeds were not given if an umbilical artery catheter was in place.

Colonization of the urinary tract and respiratory tract may be risk factors for invasive candidiasis in the newborn. In one study, almost 15% of the infants with urinary tract colonization developed invasive disease (5). There is evidence to suggest that endotracheal colonization, especially in the first week of life, is a marker for invasive disease in low birth weight infants. These infants were 10 times more likely to develop invasive disease. It is unclear whether the trachea is a portal of entry or is a marker of high fungal burden (8).

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