Infection plays a larger role than lack of oxygen in premature infants with brain injury

Johns Hopkins researchers have dispelled the widespread belief among obstetricians that, in premature infants, brain injury results from a lack of oxygen, also called hypoxia, when, in fact, infection plays a larger role.

Periventricular leukomalacia is characterized by the death of the white matter of the brain due to softening of the brain tissue. It can affect fetuses or newborns; premature babies are at the greatest risk of the disorder.

"Infection plays a much larger role than lack of oxygen in brain injury among premature infants," said high-risk obstetrician Ernest Graham, M.D., an assistant professor at The Johns Hopkins University School of Medicine, and lead author of the study, presented at the 24th annual meeting of the Society for Maternal-Fetal Medicine and set for publication in the American Journal of Obstetrics and Gynecology online Oct. 25.

"To reduce the risk of brain injury in the premature neonate, physicians may have to pay more attention to infections that occur around the time of birth."

The injury to the premature brain white matter, known as periventricular leukomalacia (PVL), is a condition in which small, cyst-like regions of brain tissue die. PVL is the most common form of brain injury in premature infants and results in cerebral palsy in 60 percent to 100 percent of those who live to adulthood. It can only be identified by ultrasound, MRI scan or CT scan of the infant's brain.

As part of their analysis, the researchers reviewed the records of 150 cases of white matter injury in premature infants born at Hopkins from 1994 to 2001. Rates of PVL were assessed by ultrasound recordings taken at three different times after birth. Using control cases without brain injury and matched by length of pregnancy, the researchers studied several factors believed to play a role in causing brain injury, including multiple births, lack of oxygen, and the presence of infections.

Overall, the researchers confirmed previous research that showed in women who had had twins or triplets, subsequent infants were at higher risk for the subsequent development of brain injury.

However, to their surprise, the researchers found a very small portion of cases with brain injury also had metabolic acidosis, a sign that oxygen was lacking. Indeed, the rates of severe metabolic acidosis were statistically the same among the cases with PVL and the in the control cases without brain injury, ranging from 3 percent to 6 percent, respectively.

The most striking results came from bacterial cultures of samples from the premature infants' cerebrospinal fluid, blood and trachea. Researchers found a two- to four fold increase in the rates of PVL among those premature infants with an infection, tested positive by culture samples. The rates of injury were independent of the type of infection - more than a dozen different kinds of bacteria were found.