Early-onset Neonatal Infection Clinical Trial
Official title:
Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines; Impact on Antibiotic Use in Newborns With Suspected Early-onset Neonatal Infection (EONI)
Neonatal bacterial infection remains a serious pathology in industrialized countries despite
the use of prophylaxis measures for group B streptococcus (GBS) (peri-partum antibiotic in
women with GBS colonization), which was implemented in the United States in 1996 and in
France in 2001 and has led to a dramatic decrease in the incidence of neonatal bacterial
infections. However, early onset neonatal infection (EONI), which is defined as an infection
occurring during the first 6 days after birth (as opposed to late onset neonatal infections
(LONI) occurring between days 7-89), is still one of the leading causes of neonatal morbidity
and mortality. Physicians consider EONI a significant diagnostic and therapeutic emergency
due to the potential for sudden onset and rapid evolution of sepsis in newborns with immature
immune systems. Currently, in France, detection of EONI is based on national consensus
guidelines published in 2002 (ANAES recommendations). There are broad indications to provide
empirical antibiotic treatment pending diagnostic confirmation through different
complementary exams. To ensure that every infected newborn is diagnosed, biological
assessments are often repeated and result in the use of invasive and painful procedures,
anemia and financial concerns. Moreover, in cases of abnormal biological results, many
newborns are subjected to intravenous (IV) antibiotic treatments requiring hospitalization
and separation from their mother. However recent studies have shown that antibiotics can have
a potentially deleterious effect on the neonatal digestive microbiota and result in the
appearance of antibiotic-resistant bacteria, with possible long-term consequences on the
health of the child.
Procalcitonin (PCT) is a calcitonin prohormone secreted from the parenchymal tissues. This
marker of inflammation has been shown to be a valuable diagnostic marker for bacterial
infection in adults and in children. It also seems to be a reliable marker for neonatal
bacterial infection, which would make it useful in the detection of EONI. Because
physiological levels of PCT vary during the first days of life, possibly due to postnatal
intestinal bacterial colonization, levels of this marker are difficult to interpret in the
early neonatal period. However, in a study of 2151 newborns with suspected EONI, Nicolas
Joram et al. found that PCT obtained from the umbilical blood cord, prior to newborn
intestinal colonization, bypasses this postnatal physiological peak of PCT and effectively
constitutes a discriminant marker to distinguish between infected and healthy infants using a
cutoff value of 0.6 ng/ml.
Subsequent to this pilot study, several studies on PCT in umbilical blood cord confirmed its
good diagnostic performance for EONI, particularly when included in a diagnostic algorithm.
This marker could contribute to a better estimation of EONI risk in order to limit the use of
unnecessary complementary exams and prescription of antibiotics and their associated short-
and long-term side effects in healthy newborns.
Therefore, in this study, the investigators propose to test the diagnostic value of a
PCT-based algorithm in newborns suspected of having EONI. The investigators hypothesize that
this algorithm is as efficient as those currently used (ANAES), but will limit coinciding
biological exams and exposure to antibiotics during the neonatal period.
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