Babies in the neonatal intensive care unit (NICU) are highly vulnerable to infection. This can lead to neonatal sepsis, in which the body induces an extreme response that can be life-threatening. Clinicians most commonly diagnose neonatal sepsis through a positive blood culture — but obtaining an adequate volume of blood can be difficult from tiny infants.
Clinicians divide neonatal sepsis into two categories. Late-onset sepsis entails infections that arise at least 72 hours after birth and are most often caused by an immature immune system and environmental exposures in the NICU. In these instances, the American Academy of Pediatrics (AAP) recommends that clinicians obtain two separate site blood cultures to rule out false positives caused by other contaminants that aren’t associated with sepsis.
Early-onset sepsis, on the other hand, occurs within the first 72 hours of life and is usually caused by an infection that occurred right before or during the birthing process. While there are AAP recommendations for diagnosing early-onset sepsis, there is little research on the benefit of two separate site blood cultures from babies who may have the condition. Now, a study published in the Journal of Perinatology on February 26 has found that the practice of taking two blood cultures for early-onset sepsis does not improve diagnostic accuracy. Instead, the method by which the blood culture was obtained and the volume of the blood sample are what matters.
“It’s not about how many blood cultures you take, but more about how you obtain the blood and the volume you obtain in a single culture,” says Noa Fleiss, MD, assistant professor of pediatrics at Yale School of Medicine and the study’s first author.
How is early-onset sepsis diagnosed in the NICU?
Early-onset sepsis, especially in full-term babies, is very rare. It occurs in fewer than 0.5 out of every 1,000 live births. Even in premature infants, the condition is relatively rare, impacting around 13.5 per 1,000 births. As a result, obtaining a large enough cohort to study early-onset sepsis is difficult.
It’s not about how many blood cultures you take, but more about how you obtain the blood and the volume you obtain in a single culture.
Noa Fleiss, MD
There are several ways to collect blood samples from infants. Clinicians may obtain blood through a venipuncture, in which they use a sterile needle to puncture an artery or vein. “In little babies, you can imagine the veins and arteries are very small, and it’s very hard to obtain enough blood volume,” says Fleiss. As a result, this method may require multiple sticks in order to collect enough blood for testing.
Another way to collect blood is to sterilely place a specialized catheter such as an umbilical venous or arterial catheter in the baby’s umbilical cord. “This catheter allows us to give the infants nutrition, but it’s also very easy to extract blood through that catheter and obtain an adequate volume of blood,” says Fleiss.
Multiple blood cultures do not improve diagnosis
Yale New Haven Hospital’s NICU has a database of all early- and late-onset neonatal sepsis cases from 2013 to 2021. For their latest study, Fleiss and her team explored factors that may aid clinicians in their diagnosis of the condition. First, they compared whether the infant received one or two blood cultures. They also compared whether the sample was obtained by a venipuncture or umbilical catheter. “We wanted to determine if we needed multiple blood samples from different sites on the baby in order to detect an organism that causes sepsis,” says Fleiss. “Or, if we obtained blood through a central umbilical catheter, would that make a difference in getting a positive result?”
The team found that obtaining two blood cultures did not improve diagnostic utility. Of the 2,259 infants studied, approximately two-thirds had received two blood cultures and the rest received one. The study found no significant difference between test accuracy rates.
On the other hand, the researchers found that the accuracy of using an umbilical catheter to diagnose early-onset sepsis was significantly greater than from using a venipuncture. They believe this is because it is easier to obtain an adequate amount of blood through this process.
More data needed to inform best practices
This finding has implications beyond diagnostic utility, Fleiss says. Taking multiple venipunctures introduces more pain and likelihood of contamination to the infant. “Sometimes getting more than one culture is necessary to get the amount of blood that we need,” she says. “But more often than not, a second venipuncture is just another painful procedure that doesn’t provide much more yield than one culture would have.”
In future studies, Fleiss’s team is focusing more closely on the diagnostic value of blood volume. They are measuring and recording the volume of blood obtained from infants with neonatal sepsis to provide further evidence that an adequate amount of blood is truly the most important factor for diagnosing early-onset sepsis. “We need more blood volume data to make concrete recommendations for diagnosis,” says Fleiss. “Once we have more data, we will be able to start making practice changes in our own NICU.”