Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants

doi:10.1016/j.ajog.2009.03.006

American Journal of Obstetrics and Gynecology

Volume 201, Issue 1, July 2009, Pages 38.e1-38.e6

Presented at the Joint Meeting of the Pediatric Academic Societies and the Asian Society for Pediatric Research, Honolulu, HI, May 2-6, 2008.

https://doi.org/10.1016/j.ajog.2009.03.006 Get rights and content

Objective

The purpose of this study was to determine the incidence, causative pathogens, and risk factors for early onset sepsis (EOS) among very-low-birthweight (VLBW) infants.

Study Design

This was a population based observational study. Data were prospectively collected by the Israel Neonatal Network between 1995 and 2005. Multivariable analyses identified independent risk factors for EOS.

Results

EOS developed in 383 of 15,839 infants (2.42%). Fifty-five percent of pathogens isolated were gram-negative bacteria. Lack of prenatal care (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.32-2.86), delivery room resuscitation (OR, 2.49; 95% CI, 1.91-3.24), membrane rupture > 24 hours without amnionitis (OR, 2.10; 95% CI, 1.53-2.88), amnionitis with membrane rupture < 24 hours (OR, 4.28; 95% CI, 2.97-6.16), and amnionitis with membrane rupture ≥ 24 hours (OR, 8.15; 95% CI, 5.98-11.10) were associated with EOS, but not antenatal steroids or gestational age.

Conclusion

EOS was caused mainly by gram-negative bacteria. Prolonged rupture of membranes and amnionitis have an additive effect on EOS with an above 8-fold excess risk when both were present.

Section snippets

Materials and Methods

This population-based observational study was performed on data obtained from the Israel National VLBW Infant Database (Appendix). This study was approved by the Human Research Committee of the Sheba Medical Center.

Results

The study cohort comprised 15839 infants of whom 383 (2.42%) had EOS. In infants with EOS, 404 pathogens were isolated, 9 of which were considered contaminants, leaving 395 pathogens available for analysis (Table 1). Three hundred eighty-three infants were diagnosed with EOS (in 12 infants 2 different pathogens were isolated). Gram-negative bacteria were the most common pathogens with E coli responsible for 26.8% of the episodes of EOS. Only 9.4% of all episodes of EOS were caused by GBS.

The

Comment

The incidence of EOS was 2.4% in a near-complete national Israeli cohort of VLBW infants. Episodes of EOS were caused predominantly by gram-negative organisms. EOS was independently associated with lack of antenatal care, delivery room resuscitation, PROM and amnionitis, and was not associated with antenatal steroid use, premature contractions, or GA.

The most common organisms causing EOS were gram-negative bacteria, similar to reports by the NICHD network.1, 2 GBS was isolated in less than 10%

References (22)

B.J. Stoll et al.
Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network
J Pediatr
(1996)
L. Gluck et al.
Septicemia of the newborn
Pediatr Clin North Am
(1966)
R.L. Goldenberg et al.
The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants
Am J Obstet Gynecol
(2008)
B.J. Stoll et al.
Infections in VLBW infants: studies from the NICHD Neonatal Research Network
Semin Perinatol
(2003)
B.J. Stoll et al.
Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants
N Engl J Med
(2002)
B.J. Stoll et al.
Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002 2003
Pediatr Infect Dis J
(2005)
J.O. Klein
Bacterial sepsis and meningitis
A. Ronnestad et al.
Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants
Pediatrics
(2005)
S.Y. Salem et al.
Risk factors for early neonatal sepsis
Arch Gynecol Obstet
(2006)
I.R. Makhoul et al.
Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey
Pediatrics
(2002)

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Management of clinical chorioamnionitis: an evidence-based approach
2020, American Journal of Obstetrics and Gynecology
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This syndrome is a well-known risk factor for adverse maternal outcomes such as postpartum hemorrhage secondary to uterine atony,8,9 uterine rupture,5 unplanned hysterectomy,7 blood transfusion,5–8 postoperative wound infection,6,10 endometritis,6,11 pelvic abscess,8 septic pelvic thrombophlebitis,8,12 sepsis,13–15 and intensive care unit admission.5–7 Neonates born to mothers diagnosed as having clinical chorioamnionitis are at a higher risk of low Apgar scores at 5 minutes,7,8,16 neonatal seizures,7,8,16,17 neonatal sepsis,8,16–22 bronchopulmonary dysplasia,23,24 intraventricular hemorrhage (IVH),18,25,26 periventricular leukomalacia,24,26–28 use of mechanical ventilation,7,17 admission to the neonatal intensive care unit (NICU),17 neonatal death,2,7,20 and long-term infectious morbidity29 than neonates born to women without this syndrome. Evidence regarding the association between clinical chorioamnionitis and the risk of cerebral palsy and long-term adverse neurodevelopmental outcomes is conflicting: some studies reported a positive association,20,30–35 whereas others did not.36–40
This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.
The correct blood volume for paediatric blood cultures: a conundrum?
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The prevalence of BSI-causing pathogens very much depends on the patient's age, underlying diseases and current therapy [6], as well as on the socioeconomic environment. The most common pathogens identified in BSI in infants younger than 1 month are Escherichia coli, group B Streptococcus, Listeria monocytogenes and Staphylococcus aureus [2,7,8]. Above that age the predominant pathogens are Staphylococcus aureus, Streptococcus pneumoniae, Neisseria meningitidis and E. coli [6].
Bloodstream infections (BSIs) are a major cause of morbidity and mortality in paediatric patients. For fast and accurate diagnosis, blood culture (BC) is the reference standard. However, the procedure for blood sampling in paediatric patients, particularly the optimal blood volume, is the subject of controversy stemming from a lack of knowledge of the bacterial load and because of several obstacles such as low intravascular volume and the risk of causing anaemia.
The aim of this narrative review is to summarize current knowledge on blood sampling in paediatric patients for BC purposes, in particular blood volume and number and type of BC bottles needed for reasonable future guidelines/recommendations.
A comprehensive literature search of PubMed, including all publications in English, was performed in June 2019 using the search terms ‘blood culture’, ‘blood volume’, ‘bloodstream infection’, ‘diagnostic’, ‘paediatric’ and/or ‘sepsis’.
The amount of inoculated blood determines the sensitivity, specificity and time to positivity of a BC, and low-level bacteraemia (≤10 cfu/mL) in paediatric patients is presumed to be more common than reported. Current approaches for ‘adequate’ blood volume for paediatric BC are mainly weight- or age-dependent. Of these recommendations, the scheme devised by Gaur and colleagues seems most appropriate and calls for a sample of 1–1.5 mL for children weighing <11 kg and 7.5 mL for a patient weight of 11–17 kg to be drawn into one BC bottle. Inclusion of a more detailed grading in the weight range 4–14 kg, as published by Gonsalves and colleagues, might be useful.
This review could be important for future guidelines on paediatric BC collection and thus could contribute to improving patient management and lowering the economic and global health burden associated with BSI. Furthermore, upcoming molecular-based approaches with low sample volumes might be an interesting alternative.
Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore
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Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations
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View all citing articles on Scopus

: The Israel National VLBW infant database is partially funded by the Israel Center for Disease Control and the Israel Ministry of Health.

: Cite this article as: Klinger G, Levy I, Sirota L, et al. Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants. Am J Obstet Gynecol 2009;201:38.e1-6.

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American Journal of Obstetrics and Gynecology

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

References (22)

Early-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network

J Pediatr

Septicemia of the newborn

Pediatr Clin North Am

The Alabama Preterm Birth Study: umbilical cord blood Ureaplasma urealyticum and Mycoplasma hominis cultures in very preterm newborn infants

Am J Obstet Gynecol

Infections in VLBW infants: studies from the NICHD Neonatal Research Network

Semin Perinatol

Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants

N Engl J Med

Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002 2003

Pediatr Infect Dis J

Bacterial sepsis and meningitis

Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants

Pediatrics

Risk factors for early neonatal sepsis

Arch Gynecol Obstet

Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey

Pediatrics

Cited by (95)

Management of clinical chorioamnionitis: an evidence-based approach

The correct blood volume for paediatric blood cultures: a conundrum?

Strain-resolved metagenomic analysis of the gut as a reservoir for bloodstream infection pathogens among premature infants in Singapore

Late-Onset Sepsis in Very Low Birth Weight Infants

Association of delivery risk phenotype with early-onset sepsis in preterm infants

Phage Targeting Neonatal Meningitis E. coli K1 In Vitro in the Intestinal Microbiota of Pregnant Donors and Impact on Bacterial Populations

ResearchObstetricsEpidemiology and risk factors for early onset sepsis among very-low-birthweight infants

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

J Pediatr

Pediatr Clin North Am

Am J Obstet Gynecol

Semin Perinatol

Changes in pathogens causing early-onset sepsis in very-low-birth-weight infants

N Engl J Med

Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002 2003

Pediatr Infect Dis J

Bacterial sepsis and meningitis

Septicemia in the first week of life in a Norwegian national cohort of extremely premature infants

Pediatrics

Risk factors for early neonatal sepsis

Arch Gynecol Obstet

Epidemiological, clinical, and microbiological characteristics of late-onset sepsis among very low birth weight infants in Israel: a national survey

Pediatrics

Research
Obstetrics
Epidemiology and risk factors for early onset sepsis among very-low-birthweight infants