Key messages
– The studies included in this review suggest that molecular tests (based on a molecule that carries the genetic instructions used in growth, development, functioning and reproduction from bacteria) may be very helpful additional tests in detecting blood infection (sepsis) in babies because they provide rapid results.
– Using molecular tests may help us stop using antibiotics in babies without a blood infection quicker because the results are faster than blood cultures (a test that checks for bacteria or other germs in the blood). However, further research is needed to prove this.
Why is improving the diagnosis of sepsis in babies important?
The current method of detecting infection (illness caused by germs) in newborn babies is to obtain blood or other body fluids (or both) and culture (grow) the bacteria (germs) in a laboratory. However, culture methods may miss some infections and take a long time to produce results (48 to 72 hours). We have new molecular tests for detecting infections. Molecular tests are rapid and may be more accurate in detecting infections compared to traditional culture methods.
What is a molecular test?
A molecular test is based on detecting DNA (a molecule that carries the genetic instructions used in growth, development, functioning and reproduction) from bacteria and other organisms that cause infections.
What did we want to find out?
We wanted to find out whether molecular tests detect infection better than the standard culture methods in newborn babies.
What did we do?
We searched for studies that investigated the accuracy of molecular tests for detecting infections in newborn babies. We compared and summarized the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 74 studies that compared the molecular methods to culture methods. We could only use the data from 68 studies, which included 14,309 babies.
The results of these studies suggest that the molecular methods may have moderate accuracy in detecting infections in newborn infants. Molecular tests may be very helpful additional tests in diagnosing blood infections because they provide rapid results.
Although there were some issues with selection of newborn babies for this review, overall, the methods used by the studies were adequate.
What are the limitations of the evidence?
The included studies made the diagnosis of infection using conventional blood culture (this is called the reference standard). It is unclear if this detects all newborn infants with infections correctly. We included studies over a long period (1997 to 2022) and the methods used may have changed, which could explain why the results were different between studies. It is possible that studies with poor accuracy were not published.
How up to date is this evidence?
The evidence is up to date to August 2023.
Study funding sources
None of the studies received funding.
Molecular assays have the advantage of producing rapid results and have moderate diagnostic accuracy. Molecular assays may prevent overuse of antibiotics in neonates with suspected sepsis. The efficacy and cost-effectiveness of these molecular assays should be evaluated using randomized trials comparing molecular assays as an add-on test versus conventional methods without the add-on test in neonates with suspected sepsis.
Microbial cultures for diagnosis of neonatal sepsis have low sensitivity and reporting delay. Advances in molecular microbiology have fostered new molecular assays that are rapid and may improve neonatal outcomes.
To assess the diagnostic accuracy of various molecular methods for the diagnosis of culture-positive bacterial and fungal sepsis in neonates and to explore heterogeneity among studies by analyzing subgroups classified by gestational age and type of sepsis onset and compare molecular tests with one another.
We searched CENTRAL, MEDLINE, Embase and trial registries in August 2023. We checked reference lists of included studies and systematic reviews where subject matter related to the intervention or population examined in this review.
We included studies that were prospective or retrospective, cohort or cross-sectional design, which evaluated molecular assays (index test) in neonates with suspected sepsis in comparison with microbial cultures (reference standard).
Two review authors independently screened studies, extracted data and assessed the methodological quality of the studies. We performed meta-analyses using the bivariate model and entered data into Review Manager.
Seventy-four studies were eligible for inclusion, of which 68 studies provided data for meta-analysis. The total number of participants was 14,309 (1328 infants who were culture-positive and 12,981 infants who were culture-negative) from 68 studies that were included in the meta-analysis. The summary estimate of sensitivity was 0.91 (95% confidence interval (CI) 0.85 to 0.95) and of specificity was 0.88 (95% CI 0.83 to 0.92) (low-certainty evidence). We explored heterogeneity by subgroup analyses of type of test, gestational age, type of sepsis onset and prevalence of sepsis. We found insufficient explanations for the heterogeneity (low- to very low-certainty evidence). Sensitivity analyses including studies that analyzed blood samples, using good methodology and those that did not use multiple samples from the same participant revealed similar results (low-certainty evidence).