Safely reduce newborn antibiotic exposure with the early-onset sepsis calculator: a cluster randomized study

Newborns are at risk for early-onset sepsis (EOS). A (suspected) EOS is defined
as a (suspected) infection that develops within 72 hours after birth. The
incidence of confirmed EOS is 0.5-2.0 per 1000 live births. For the
Netherlands, this translates to approximately 85-340 EOS cases yearly. However,
approximately 5% of late preterm and term newborns are given antibiotics in
compliance with current Dutch guideline, which is equivalent to 8,500 newborns
per year. An alternative is the CE certified EOS calculator application, an
algorithm that divides newborns into risk groups with concrete treatment advice
(antibiotics, extra observation, normal care), which calculates an individual
risk of EOS for each newborn using 5 maternal risk factors combined with the
newborn*s clinical condition after birth. This study aims to investigate
whether the use of the EOS calculator safely reduces antibiotic exposure in
newborns with suspected EOS compared to the current Dutch guideline.

The primary objective of this study is to investigate whether the use of the
EOS calculator safely reduces antibiotic exposure in newborns with suspected
EOS in the first 24 hours after birth compared to the current Dutch guidelines.

Secondary objectives of the study are:
1. To investigate if the use of the EOS calculator decreases the total duration
of antibiotic therapy in newborns with suspected EOS.
2. To investigate if the use of the EOS calculator decreases the percentage of
antibiotic therapy started for suspected and, or proven EOS between 24 hours
and 7 days after birth.
3. To study the impact of (suspected) EOS on parents/guardians.

This is prospective, cluster-randomized trial. We aim to include 1830 newborns
from 10 hospitals in the Netherlands during an 18-month period.
Cluster-randomization happens at the hospital level. A cluster is finished when
a total of 183 participants are included into the cluster.

This study will have negligible risks and minimal burden.

Burden
- Newborns who receive antibiotic therapy: An intravenous cannula will be
inserted for antibiotic treatment and blood sampling. A second blood sample by
venipuncture will be collected after 24 hours. This is part of standard medical
treatment.
- Newborns who do not receive antibiotic therapy: No blood samples taken.
Clinical observation for at least 24 hours. This is part of standard medical
treatment.
- All newborns: One short questionnaire will be sent to the parents/guardians
to fulfill on day 14. The questionnaire will take about 10-15 minutes to
complete.

Risks:
The risks associated with participation are very low because newborns will be
closely observed when no antibiotics will be prescribed.

Benefits
- More specific risk analysis.
- Not all subjects will benefit personally from study participation. When no
antibiotics will be prescribed: no separation of mother and child, no painful
procedures, and a shorter hospital stay (including fewer costs), and no
unnecessary exposure to antibiotics.

Group relatedness
This study can only be performed with this specific group of patients, as it
will provide age-specific and risk factor-specific data that cannot be obtained
otherwise.