Procalcitonin as parameter for neonatal infection

Perinatal infection is one of the most reported causes of child mortality and
morbidity worldwide. In order to treat in a fast and save way, adequate
diagnostics are major significant to clinical assessment. A range of different
parameters have been used so far. At this moment the blood culture is used as
the gold standard for establishing the presence of infection. Secondary,
C-reactive protein (CRP) also plays an important role in assessing the presence
of infection and measuring the severity of it.
Our research will investigate whether procalcitonin (PCT) is a better parameter
for determining the presence of infection. The objective of this study is to
determine if PCT is suitable for diagnosing the presence/absence of neonatal
infection in an early stage. We expect that with the knowledge acquired it is
possible to establish in an earlier stage whether it is really necessary to
start with antibiotic treatment. The importance of this is great, since
antibiotics have a long lasting and significant impact on the microbiome,
resulting in later life health complaints such as allergy and obesity.

Primary objective:
- Determine whether PCT, measured in cord blood, and the blood of the neonate,
is suitable to determine the presence or absence of neonatal infection.

Secondary objective:
- To investigate whether PCT is a suitable parameter to determine the need to
start with antibiotic treatment.
- To establish if PCT has a higher sensitivity and specificity for infection
compared to CRP.

The population will consist of neonates born in the Spaarne Gasthuis hospital
in Haarlem and the Tergooi hospital in Blaricum. Neonates <7 days old will be
included in the study.
In practice, this means inclusion will be from three groups:
1. Neonates with maternal risk factors for infection antenatally
2. Neonates without maternal risk factors antenatally but only with a clinical
suspicion for infection established by a peadiatrician.
3. Neonates without a risk factor or a suspicion for infection.

In the first group parents/guardians will be invited to participate in the
study if of one or more maternal risk factors for early-onset neonatal
infection will be present (as seen in table 2b of the NVK guideline 'prevention
and treatment of early-onset neonatal infections*). Parents/guardians will be
informed about the possibility to participate both in person and via a patient
information brochure. After permission for participation has been given,
informed consent will be requested using the consent form. In this group,
neonatal umbilical cord blood will be collected postnatally.

It is standard policy to draw blood before starting with antibiotic therapy to
determine the complete blood count with differentiation, CRP levels and for
preforming a blood culture. The moments blood is drawn from a participating
neonate for establishing CRP levels, the leftover blood material will be used
for the study. No additional blood tests will take place within the scope of
the study. According to the current guideline, one CRP-test is performed at the
first suspicion for infection and one after 24-48 hours. The PCT measurements
will be linked to this.
Ultimately, the outcomes of the PCT levels, the blood culture, CRP levels, and
the complete blood count with differentiation will be used for analysis.

In the second group, newborns of <7 days old without antenatal maternal risk
factors for infection, but with a clinical suspicion for infection, will be
selected for the study. Like the first group they will also be included in the
study starting at the moment they receive antibiotic treatment. The same
consent procedure will take place. In this group, leftover blood samples drawn
for a clinical CRP measurement will be used to do a later PCT measurement.

In the third group, newborns without risk factors, or suspicion of infection
will be included. Specific attention will be paid to the absence of maternal
risk factors for early-onset neonatal infection. In this group, neonatal
umbilical cord blood will be collected postnatally.

Blood samples from all groups are, for logistical reasons, stored and analyzed
in batches. As a result, the attending physician cannot be informed regarding
the outcome of the PCT measurement. Once PCT is measured in the blood samples,
access to the individual outcomes will be limited to the research team.

During analysis, participating newborns with a negative blood culture will
become part of the control group. Newborns with a positive blood culture will
be part of the "case group". In this cohort study 5 controls will be included
for each case.

PCT levels will be determined by the hospital laboratory of the Spaarne
Gasthuis from the (frozen) blood samples of participating patients. The interim
results of this study will have no role in the treatment strategy of the
participating patients.

In addition, clinical parameters from all participating patients, and their
mothers, will be taken from the patient file according to the parameters shown
in table 2b and 3b of the NVK guideline. Additionally data regarding, body
temperature, blood pressure, capillary refill, respiratory frequency, heart
rate, saturation, neurological state, urine output, and medical reasoning for
decisions will be collected. All data will be processed in the database in a
pseudonymized manner.

The PCT level is measured in the umbilical cord blood postnatally. No risk is
involved for both mother and child. In case of a suspicion of neonatal
infection, blood might be drawn by a paediatrician for a clinical CRP test. If
this is the case, the PCT will also be determined from the same blood sample.
No additional blood collection is therefore performed. This means that there
are no additional risks and burdens attached to this study for the newborn,
other than the blood collection already carried out.
Research data will not be shared with the patient's parents/guardian. The
treatment is not influenced by the research, unless interim analysis shows that
adjustment is desirable. The data will only be analyzed in a pseudonymised
manner and parents will be asked to provide informed consent verbally and in
writing.

There is no direct benefit for patient or parents if they cooperate with the
study. However, they will contribute to a possible improvement of the diagnosis
for neonatal infection and the consequent treatment for future patients.