New Protocol for Febrile Neonate Management
Condition: Newborn; Infection; Newborn Sepsis
MeSH terms: Infections
Study type: Observational

Summary: 
      The objective of present study was to evaluate clinical and laboratory characteristics of
      febrile neonate and describe the incidence of SBI in febrile neonates. Secondarly
      investigators aimed to test usefulness of major protocols and new protocol in evaluating only
      febrile neonate.
    

Detailed description: 
      This was a prospective observational cohort study, conducted between January 2011 and
      December 2015 (5 years) at Sisli Hamidiye Etfal Hospital, a tertiary care
      university-affiliated medical center in Istanbul. Written informed consent was obtained from
      the parents of all infants enrolled in the study before inclusion. The study protocol was
      approved by the local ethic committee.

      Study population All neonates who were admitted to the neonatal intensive care unit with a
      rectal temperature of ≥38°C (documented at the time of medical evaluation) were eligible for
      the participation in this study. The exclusion criteria were gestational age less than 35
      weeks, who refused to participate in the study, chromosome abnormality (e.g., trisomy 21,
      18), the presence of a chronic disease, congenital malformations (cyanotic heart disease,
      meningomyelocele), admission to pediatric surgery, started on antibiotics before admission,
      and incomplete records. A complete history was obtained from the parents of infants, and a
      specialist in neonatology carried out a physical examination for localizing the source of the
      fever in all infants.

      Data collection The data obtained for all infants included: demographic information (age at
      admission, gender, and birth weight), general assessment (well or sick-appearing), medical
      history, physical examination findings, laboratory test results, and final diagnosis.
      Laboratory investigations including complete blood count, CRP level, blood chemistry and
      culture, urine sample analysis and culture (obtained by bladder catheterization), and
      cerebrospinal fluid sample analysis and culture, were carried out. In the presence of
      respiratory symptoms or signs, chest radiography was performed. Lumbar puncture was performed
      according to the ward's policy, which is required for every infant if neurologic findings are
      positive or without the focus on fever. Stool specimens were obtained when a history of
      diarrhea was noted and sent for white blood cell analysis and bacterial culture. Other tests
      were conducted as necessary. Skin, soft tissue, and ear infections were diagnosed by physical
      examination.

      Definition of SBI An episode of SBI was defined as (A) the growth of a known pathogenic
      bacteria in one or more of cultures (bacteremia, meningitis, osteomyelitis, suppurative
      arthritis, urinary tract infection, bacterial enteritis, and pneumonia), (B) any disease
      commonly associated with bacterial pathogens including pneumonia, acute otitis media,
      suppurative arthritis, osteomyelitis, and soft-tissue infections (cellulitis, abscess,
      mastitis, and omphalitis). Pneumonia was defined as a new discrete infiltration on the chest
      film, which was confirmed by an attending pediatric radiologist with the presence of typical
      clinical signs and symptoms.

      All specimens for culture were evaluated by standard microbiological methods. No specimens
      were processed for viral cultures. The blood culture isolates were considered pathogenic if
      the organism was known to cause disease in healthy infants. UTI (urinary tract infection) was
      defined as the isolation of >104 CFU/mL of urine of a single pathogen by catheterization. A
      positive urine analysis was defined by a positive test for leucocyte esterase or nitrite by
      the dipstick method or leukocyte ≥10 cells/mm3 in uncentrifuged urine. Methods of viral agent
      evaluation: in infants with viral respiratory symptoms and complaints (a runny nose,
      sneezing, coughing), the presence of RSV-Ag (rapid immunochromatographic test produced by
      Prima lab SA, Switzerland), and influenza-Ag (Immunoassay test produced by Dalian Rongbang
      Medical Healthy Devices, Spain) were assessed from nasopharyngeal secretions. The body weight
      of the subjects was taken on admission and weight loss was assessed according to the birth
      weight. The proportion of weight loss more than twelve percent of birth weight was considered
      as dehydration.

      All patients were hospitalized and prophylactic antibiotic therapy was started and continued
      for at least 72 hours (cases diagnosed only with dehydration did not receive antibiotics).

      Newly proposed protocol (Sisli Etfal) includes:

      (1) Unremarkable medical history (no perinatal antibiotics, no underlying disease, not
      hospitalized longer than the mother), (2) Good appearance, (3) No focal physical signs of
      infection, (4) CRP level < 1 mg/dl, (5) WBC 5000-15000 counts/mm3 and band/neutrophil ratio
      (I/T) <0.2, (6) A normal urine analysis.

      The infants with all these criteria were considered to have a low risk for SBI. All infants
      were classified at low-risk by the criteria of Rochester, Boston, Philadelphia and Sisli
      Etfal protocols. The criteria of four protocols are presented in Table 1.

      Statistical analysis The data were analyzed by using SPSS version 15.0 (SPSS, Chicago, IL,
      USA). Categorical variables are reported as percentages, and normally distributed data are
      expressed as mean±SD. Statistical comparisons between two groups performed with Student's
      t-test for normally distributed data, Mann-Whitney U test for non-normally distributed data,
      and chi-square test for all numerical and categorical values. The positive predictive value
      (PPV) for SBI of at least one abnormal criteria and the NPV for SBI of the low-risk criteria,
      in combination, were calculated by the standard statistical formula. All patients were
      evaluated according to the Boston, Philadelphia, Rochester and Sisli Etfal protocols, and the
      results were compared for sensitivity, specificity, NPV, PPV, and accuracy values. For
      predicting SBI, the serum levels of CRP and WBC count were subjected to receiver operating
      characteristics (ROC) curve analysis. The results were considered to be significant if
      analysis yielded p<0.05.
    

Intervention name(s): C reactive protein
Intervention type(s): Diagnostic Test
Intervention description(s): Addition of C-reactive protein test for management strategies to follow-up febrile neonates in outpatient.
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        newborn babies admitted to hospital with fever