Investigators identify proteins that may indicate fetus at risk for UTI-induced prematurity

Investigators in The Research Institute at Nationwide Children's Hospital have developed a mouse model in which a mother's urinary tract infection negatively affects the offspring, an occurrence anecdotally observed in humans. Using this first-of-its-kind model, they have identified proteins in the blood that may indicate whether such an infection might stunt fetal growth. Study findings have been published in the March 21, 2012, edition of PLoS ONE.

Nearly 50 percent of all women are affected by urinary tract infections (UTIs). Although most UTIs rarely cause complications in the general population, UTIs during pregnancy can impact the developing fetus, raising the risk for prematurity, low birth weight and possibly childhood asthma. In fact, all pregnant women are routinely screened for UTIs during the first trimester and repeatedly for high-risk patients.

Mouse models have been helpful in understanding the immunological changes that occur during pregnancy when a mother develops an infection within the uterus. Yet, no animal model exists to show how side-effects of a localized infection outside of the uterus, such as bladder inflammation from a urinary tract infection, impact a developing fetus.

"Observations that an infection isolated to the urinary tract is associated with adverse perinatal outcomes have been anecdotal," said Sheryl S. Justice, PhD, principal investigator in the Center for Microbial Pathogenesis at The Research Institute at Nationwide Children's Hospital and lead study author. "The effects that bladder inflammation and other infection symptoms have on pregnancy have not been fully characterized in humans. Currently, there are no reliable biomarkers to indicate whether urinary tract infected pregnant women's babies are at risk for poor outcomes." Dr. Justice is also a faculty member at The Ohio State University College of Medicine.

To examine such a scenario, Dr. Justice and fellow investigators at Nationwide Children's developed a mouse model of urinary tract infection in pregnant mice. Due to the short gestational length of the mouse, they were unable to observe premature delivery under experimental conditions. However, the offspring of mothers that experienced experimental UTI displayed up to 80 percent decrease in fetal weight when compared to non-infected mothers.

Blood draws showed significant differences in pro-inflammatory proteins between infected mothers and non-infected mothers days before delivery. "The inflammatory response in the uterus was more severe than in the kidney, suggesting that the tissue of the placenta may be more susceptible to changes in immune status than other nearby organs," said Dr. Justice.

The lowest offspring weight correlated with the highest serum levels of the inflammatory protein IL-6. "Our findings strongly suggest that serum levels of IL-6 may be linked to poor growth of the baby within the womb," said Dr. Justice. "We are now positioned to investigate these proteins as potential biomarkers that may have predictive value to identify a fetus at risk for UTI-induced prematurity."