Date Published: March 20, 2019
Publisher: Public Library of Science
Author(s): Alberto Berardi, Caterina Spada, Maria Letizia Bacchi Reggiani, Roberta Creti, Lorenza Baroni, Maria Grazia Capretti, Matilde Ciccia, Valentina Fiorini, Lucia Gambini, Giancarlo Gargano, Irene Papa, Giancarlo Piccinini, Vittoria Rizzo, Fabrizio Sandri, Laura Lucaccioni, Umberto Simeoni.
International guidelines lack a substantial consensus regarding management of asymptomatic full-term and late preterm neonates at risk for early-onset disease (EOS). Large cohorts of newborns are suitable to increase the understanding of the safety and efficacy of a given strategy.
This is a prospective, area-based, cohort study involving regional birth facilities of Emilia-Romagna (Italy). We compared cases of EOS (at or above 35 weeks’ gestation) registered in 2003–2009 (baseline period: 266,646 LBs) and in 2010–2016, after introduction of a new strategy (serial physical examinations, SPEs) for managing asymptomatic neonates at risk for EOS (intervention period: 265,508 LBs).
There were 108 cases of EOS (baseline period, n = 60; intervention period, n = 48). Twenty-two (20.4%) remained asymptomatic through the first 72 hours of life, whereas 86 (79.6%) developed symptoms, in most cases (52/86, 60.5%) at birth or within 6 hours. The median age at presentation was significantly earlier in the intrapartum antibiotic prophylaxis (IAP)-exposed than in the IAP-unexposed neonates (0 hours, IQR 0.0000–0.0000 vs 6 hours, IQR 0.0000–15.0000, p<0.001). High number of neonates (n = 531) asymptomatic at birth, exposed to intrapartum fever, should be treated empirically for each newborn who subsequently develops sepsis. IAP exposed neonates increased (12% vs 33%, p = 0.01), age at presentation decreased (median 6 vs 1 hours, p = 0.01), whereas meningitis, mechanical ventilation and mortality did not change in baseline vs intervention period. After implementing the SPEs, no cases had adverse outcomes due to the strategy, and no cases developed severe disease after 6 hours of life. Infants with EOS exposed to IAP developed symptoms at birth in almost all cases, and those who appeared well at birth had a very low chance of having EOS. The risk of EOS in neonates (asymptomatic at birth) exposed to intrapartum fever was low. Although definite conclusions on causation are lacking, our data support SPEs of asymptomatic newborns at risk for EOS. SPEs seems a safe and effective alternative to laboratory screening and empirical antibiotic therapy.
Group B Streptococcus (GBS) is a leading cause of neonatal sepsis in high-income countries. GBS early-onset sepsis (EOS) results from mother-to-infant transmission at delivery. Most neonates with EOS are symptomatic at birth, but some may present with subtle and nonspecific symptoms or may initially appear well. Among asymptomatic neonates, clinicians must identify those with bacteraemia and significant risks for progression to EOS. Previous studies have identified maternal risk factors (RFs) for EOS, and guidelines have suggested algorithms for managing asymptomatic neonates with RFs. However, the majority of information for risk assessment was derived from data obtained before the widespread use of intrapartum antibiotic prophylaxis (IAP) for EOS prevention. Recent data have reduced the validity of the risk-based approach, which results in prolonged hospitalization and unnecessary antibiotic use for a large number of well-appearing infants.[4,5] The Centers for Disease Control and Prevention (CDC) guidelines recommend a full diagnostic evaluation and antibiotic therapy if a patient shows signs of sepsis, a limited evaluation and antibiotic therapy in cases of chorioamnionitis, and a limited evaluation and observation in cases of preterm birth or prolonged membrane rupture. Two recent European guidelines recommend observation without further testing for all asymptomatic neonates with RFs,[6,7] although neither guideline provides any data to support their recommendations. However, neonatal management is controversial, especially among chorioamnionitis-exposed newborns.[1,8–10] Because EOS has become rare due to widespread use of IAPs and because chorioamnionitis is also uncommon (0.5–10% of deliveries), large cohorts of newborns are better suited to providing information regarding the safety and efficacy of a given strategy.
This study shows the clinical impact of a 14-year screening-based policy[12,13] for EOS prevention in an Italian cohort and the results of a strategy for managing asymptomatic neonates at risk. A significant proportion of newborns with EOS were at low risk for sepsis. Most cases were unexposed to IAP because they were born to pregnant women who tested negative for GBS colonization or were not tested as they were not at risk. High rates of neonates with EOS born to GBS-negative mothers have been reported in areas where the screening-based strategy and IAP reached high coverage,[15,16] which is one of the main drawbacks of this strategy. However, the rates of false-negative screening cultures had a borderline decrease over time.