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Pitfalls in the Diagnosis of Meningitis in Neonates and Young Infants: the Role of Lumbar Puncture

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Pitfalls in the Diagnosis of Meningitis in Neonates and Young Infants: the Role of Lumbar Puncture The Journal of Maternal-Fetal & Neonatal Medicine ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20 Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture Luca Bedetti, Lucia Marrozzini, Alessandro Baraldi, Elisabetta Spezia, Lorenzo Iughetti, Laura Lucaccioni & Alberto Berardi To cite this article: Luca Bedetti, Lucia Marrozzini, Alessandro Baraldi, Elisabetta Spezia, Lorenzo Iughetti, Laura Lucaccioni & Alberto Berardi (2018): Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture, The Journal of Maternal-Fetal & Neonatal Medicine, DOI: 10.1080/14767058.2018.1481031 To link to this article: https://doi.org/10.1080/14767058.2018.1481031 Accepted author version posted online: 23 May 2018. Submit your article to this journal View related articles View Crossmark data Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Pitfalls in the diagnosis of meningitis in neonates and young infants: the role of lumbar puncture Luca Bedetti, MDa; Lucia Marrozzini, MDa; Alessandro Baraldi, MDa; Elisabetta Spezia, MDa; Lorenzo Iughetti, MDa,b; Laura Lucaccioni, MDc; Alberto Berardi MDc; Affiliations: a Scuola di Specializzazione in Pediatria, Università di Modena e Reggio Emilia, Modena, Italy b Unità Operativa di Pediatria, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Azienda Ospedaliero-Universitaria Policlinico, Modena; Italy c Unità Operativa di Terapia Intensiva Neonatale, Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell’Adulto, Azienda Ospedaliero-Universitaria Policlinico, Modena; Italy Correspondence to:Luca Bedetti, Scuola di Specializzazione in Pediatria, Università di Modena e Reggio Emilia, Modena, Italy, Via del Pozzo, 71 - 41124 Modena (MO), Italy Phone: +39 347 3667447. e-mail: [email protected] Keywords: meningitis, infections, neonate, young infant, paediatric practice Running head: Contributors AllLu mauthorsbar pu madencture substantive in neonates intellectual and young icontributionsnfants to the published study and approved the final manuscript as submitted. Funding None declared Competing interests None declared JUST ACCEPTED Abstract Meningitis occurs frequently in neonates and can lead to a number of acute, severe complications and long-termdisabilities. An early diagnosis of neonatal meningitis is essential to reduce mortality and to improve outcomes. Initial clinical signs of meningitis are often subtle and frequently overlap with those of sepsis, and current haematologic tests do not distinguish sepsis from meningitis. Thus, lumbar puncture remains the gold standard for the diagnosis of meningitis in infants, and this procedure is recommended in clinical guidelines. Nevertheless, in clinical practice, lumbar puncture is frequently deferred or omitted due to concerns regarding hypothetical adverse events or limited experience of the performer. Future studies should assess whether a combination of clinical findings and select haematological tests at disease onset can identify those neonates with the highest risk of meningitis who should undergo lumbar puncture. Furthermore, clinicians should be convinced that the actual benefits of an early diagnosis of meningitis far outweigh the hypothetical risks associated with lumbar puncture. JUST ACCEPTED INTRODUCTION Neonates and young infants (0-90 days) are the most susceptible to infections; sepsis and meningitis occur more frequently during the first month of life than during later periods1. Sepsis can be classified as early onset sepsis (EOS), presenting from birth to day 3 and reflecting vertical transmission, or as late onset sepsis (LOS), from day 4 to 89, mostly reflecting horizontal transmission2. The main mechanism of meningitis development is primary bacteraemia with secondary spread to the central nervous system; for this reason, meningitis frequently overlaps with sepsis in neonates. Incidence rates of neonatal meningitis are lower in high-income countries than in low-income countries (0.3 vs 0.8-6.1/1000 live births),3 partly due to the decline in early onset meningitis because of widespread intrapartum antibiotic prophylaxis for preventing group B streptococcus EOS4,5. Nevertheless, group B streptococcus remains a leading cause of both sepsis and meningitis in high-income countries2,6. Neonatal meningitis can cause a number of acute, severe complications (seizure, stroke, intracerebral thrombosis, haemorrhage and brain abscess)7 and long- termdisabilities(neurodevelopmental or sensory neural impairment)8. An early diagnosis of neonatal meningitis is essential for correct therapy and to reduce mortality and complications. Lumbar puncture (LP) is currently the best way to confirm the diagnosis3. However, the indications for LP vary across studies1,9. Clinicians are sometimes reluctant to perform an LP, potentially because of concerns regarding the potential risks of adverse events during the procedure (i.e., hypoxia or bradycJUSTardia) or further comp licACCEPTEDations (see below). However, these potential risks, even if they are real, have not been precisely defined in large prospective studies, particularly with regard to neonates of younger gestational age. Perhaps because of these uncertainties, the rate of performing an LP seems to vary across gestational ages, and rates of LP are lower in neonates of younger gestational age10,11. WHEN TO SUSPECT MENINGITIS IN INFANTS WITH SEPSIS Clinical signs The diagnosis of meningitis remains challenging because the initial signs are often subtle and overlap with those of sepsis. The suspicion of meningitis is greater in the presence of seizures, irritability, fever, bulging fontanel, abnormal consciousness, hypotonia and tremors12. Signs of meningitis may also vary according to birth weight. Crebs and Costa13 compared clinical signs in 34 neonates with birth weights <2500 g and in 53 neonates with birth weights >2500 g and found that apnoea (20.6%), jaundice (17.6%) and abdominal distension (23.5%) were predominant in neonates <2500 g, whereas irritability (45.3%), seizures (41.5%) and bulging fontanel (30.2%) were the most frequent clinical findings in neonates >2500 g. Laboratory tests Attempts have been made to identify blood indicators to rule out meningitis in sick infants. However, none of the currently available tests are sufficiently accurate to exclude bacterial meningitis without performing an LP. C-reactive protein (CRP). A retrospective cohort study including 97 new-borns with culture- negative EOS14 evaluatedthe immature-to-total neutrophil (I/T) ratio, CRP at 12 and 24 hours, and LP. CRP >40 mg/L and an I/T ratio >0.3 had poor sensitivity (70-73% and 18-70%, respectively) and specificity (28-45% and 63-76%, respectively) for confirming meningitis. The authors concluded that these are not valid screening tests for diagnosing meningitis in patients with culture- negative EOS. JUST ACCEPTED Procalcitonin (PCT). ThePCT assay is currently an excellent laboratory test for diagnosing serious bacterial infections in young infants. The diagnostic value of PCT >0.3 ng/ml (specificity 78%, sensitivity 90%) is greater than that of CRP >20 mg/L (specificity 75%, sensitivity 75%)15. Unfortunately, no studies have compared PCT levels in septic neonates with and without meningitis. White blood cell (WBC) count. Total WBC count has little value in the diagnosis of neonatal meningitis16. Bonsu17 demonstrated that no WBC count intervals or cut-off points are sufficiently accurate to guide the decision to perform an LP; otherwise, there is a risk of missing a substantial proportion of meningitis cases. Martinez18 found that in young infants with fever without a source, haematological tests (leukocyte count, absolute neutrophil count, CRP and/or PCT levels) were performed in 92% of 21- to 90-day-old infants who appeared well, whereas 19% of these infants underwent an LP. LP was more likely to be performed in infants with abnormal blood tests than in infants with entirely normal blood tests (29% vs 14%). However, no infants had confirmed bacterial meningitis, suggesting that the decision to perform an LP should not be based on laboratory test results only. Blood culture (BC). In daily practice, someone performs an LP on the basis of BC results. By studying 90 cases of EOS, Berardi10 found that an LP was performed in only 32% of neonates; furthermore, LP was performed even less often among new-borns with birth weights <1500 g (13% of cases).Stoll19 retrospectively evaluated >9000 very low birth weight (VLBW) neonates with suspected late onset meningitis and found that LP was more likely to be performed in infants with a positive BC than in those with a sterile BC (66% vs 34%). Notably, meningitis was more likely in neonates with a positive BC than in those with a sterile BC (7.2% vs 1.5%, p<.001), but ~1/3 of those with meningitis had a sterile BC. False negative BC results are frequent (due to insufficient blood samples), whereas meningitis may occur in some (up to ~50%) neonates with a sterile BC16,20. Therefore, if an LP is performed on the basis of BC results, cases of meningitis can be missed, and the diagnosis is delayed until the BC results are available21. Because antibiotics are frequently given at disease presentation, these drugs could inhibit the growth of pathogens in cerebral spinal fluid (CSF) culture. Meningitis and CSF parameters.
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