Diagnostic Performance Comparison Between Procalcitonin-based vs. ANAES-based Guidelines

Summary

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.

Conditions

• Early-onset Neonatal Infection

Interventions

OTHER

ANAES algorithm

care as recommended by ANAES, with ANAES algorithm

OTHER

PCT algorithm

care based on PCT algorithm

Sponsors & Collaborators

• University Hospital, Tours

  collaborator OTHER

• University Hospital, Brest

  collaborator OTHER

• Rennes University Hospital

  collaborator OTHER

• Poitiers University Hospital

  collaborator OTHER

• University Hospital, Angers

  collaborator OTHER_GOV

• University Hospital, Bordeaux

  collaborator OTHER

• Centre Hospitalier de Bretagne Sud

  collaborator OTHER

• University Hospital, Paris

  collaborator OTHER

• Créteil Hospital

  collaborator OTHER

• Nantes Polyclinic

  collaborator UNKNOWN

• Nantes University Hospital

  lead OTHER

Principal Investigators

• GRAS-LEGUEN Christele, PU-PH · Nantes University Hospital

Eligibility

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-05-03

Primary Completion

2017-01-22

Completion

2017-01-22

Countries

• France

Study Locations