Respiratory distress is a prominent clinical feature in newborns with early-onset GBS disease. A previous study suggested it might be caused by pulmonary hypertension induced by a GBS infection. Pulmonary hypertension reflects an increase in pulmonary vascular resistance, impairing exchange of oxygen and carbon dioxide. It was found repeatedly that infusion of live or heat-killed GBS into sheep promptly induces pulmonary hypertension, with little or no effect on systemic pressure. The hypertension is mediated by an increase in thromboxane A2. [unreadable] [unreadable] Curtis and associates recently purified and identified phospholipids (cardiolipin and phosphatidylglycerol) from the GBS cell wall as pulmonary hypertensive compounds. Infusion of GBS phospholipids into baby lambs caused pulmonary hypertension. They hypothesized that patients infected with GBS may acquire a dose of bacterial phospholipids capable of causing pulmonary hypertension and respiratory distress. Other scientists demonstrated that exposure of Streptococcus mutans to penicillin induces an immediate release of phospholipids from bacteria; cardiolipin and phosphatidylglycerol constitute more than one half of S. mutans phospholipids. Newborns infected with GBS or whose mothers carry GBS are usually treated with penicillin or its derivatives. Thus, antibiotic treatment may cause an increase in production and excretion of phospholipids.[unreadable] [unreadable] We used clinical and epidemiologic data collected in the NICHD multi center GBS study to examine a possible association between GBS colonization, penicillin treatment and pulmonary hypertention in neonates. This was a prospective study conducted from 1995 to 1999 in which 1674 of 17,690 newborns cultured at 4 sited were found to be colonized with GBS. Our analyses included 1610 colonized newborns of >=32 weeks gestation without early-onset disease. Clinical features were compared between 1003 lightly colonized (GBS positive at <2 sites) and 607 heavily colonized (positive at 3 or 4 sites) newborns. The rates of respiratory distress were compared between colonized newborns of penicillin-treated mothers and those of untreated mothers. [unreadable] [unreadable] Of the 1610 colonized newborns, 8.8% had signs of respiratory distress within 48 hours after birth (cases) as compared to 2-3% in the general newborn population. Oxygen supplementation was used in 60% of the cases, mechanical ventilation was required in 5% and persistent pulmonary hypertension was diagnosed in 2%. Compared with light colonization, heavy colonization increased the rate of respiratory distress 1.73 fold (95% CI, 1.26-2.38), a discharge diagnosis of respiratory disorder 2.02 fold (95% CI, 1.16-3.52). Penicillin use during labor was associated with a 2.62 fold (95% CI, 1.79-3.83) increase in respiratory distress in the colonized newborns. [unreadable] [unreadable] Experimental data have shown the effect of penicillin on the release of phospholipids from S. mutans. Extrapolating these data to clinical observations in human newborns would require an assay to measure bacterial phospholipids in biologic specimens of GBS colonized newborns. An assay to measure serum bacterial phospholipids is being developed in collaboration with Dr. Alfred Yergey. A prospective study aiming at relating the serum bacterial phospholipids level to the occurrence of respiratory distress in newborns of GBS colonized mothers is expected to begin this year.