Early Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome

Barton, Michelle; Shen, Alex; O’Brien, Karel; Robinson, Joan; Davies, H. Dele; Simpson, Kate; Asztalos, Elizabeth; Langley, Joanne M.; Saux, Nicole Le; Sauve, Reginald S.; Synnes, Anne; Tan, Ben; Repentigny, Louis de; Rubin, Earl; Hui, Christy Y.; Kovács, Lajos; Yau, Yvonne; Richardson, Susan E.

doi:10.1093/cid/cix001

Cited by 22 publications

(39 citation statements)

References 29 publications

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“…Therefore, prevention of neonatal sepsis in infants born very preterm (<32 weeks' gestation) is clearly desirable as this would contribute to reducing mortality and morbidity (22,59). There is ample evidence indicating that neonatal sepsis can lead to long-term disability, including cerebral palsy, cognitive deficit, delayed mental and psychomotor, vision and hearing impairment (1,8,26,30,31,37). Periventricular white matter damage (PWMD) is a distinctive pathological feature of brain injury in septic neonates (38,63).…”

Section: Introductionmentioning

confidence: 99%

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Huang

Zhang

Lin³

et al. 2019

Brain Pathology

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Neuroinflammation is thought to play a pivotal role in the pathogenesis of periventricular white matter (PWM) damage (PWMD) induced by neonatal sepsis. Because the complement cascade is implicated in inflammatory response, this study was carried out to determine whether C3a is involved in PWMD, and, if so, whether it would induce axonal hypomyelination. Furthermore, we explored if C3a would act through its C3a receptor (C3aR) and thence inhibit maturation of oligodendrocyte precursor cells (OPCs) via the WNT/β-catenin signal pathway. Sprague Dawley (SD) rats aged 1 day were intraperitoneally injected with lipopolysaccharide (LPS) (1 mg/ kg). C3a was upregulated in activated microglia and astrocytes in the PWM up to 7 days after LPS injection. Concomitantly, enhanced C3aR expression was observed in NG2 + oligodendrocytes (OLs). Myelin proteins including CNPase, PLP, MBP and MAG were significantly reduced in the PWM of 28-day septic rats. The number of PLP + and MBP + cells was markedly decreased. By electron microscopy, myelin sheath thickness was thinner and the average g-ratios were higher. This was coupled with an increase in number of NG2 + cells and decreased number of CC1 + cells. Olig1, Olig2 and SOX10 protein expression was significantly reduced in the PWM after LPS injection. Very strikingly, C3aRa administration for the first 7 days could reverse the above-mentioned pathological alterations in the PWM of septic rats. When incubated with C3a, expression of MBP, CNPase, PLP, MAG, Olig1, Olig2, SOX10 and CC1 in primary cultured OPCs was significantly downregulated as opposed to increased NG2. Moreover, WNT/β-catenin signaling pathway was found to be implicated in inhibition of OPCs maturation and differentiation induced by C3a in vitro. As a corollary, it is speculated that C3a in the PWM of septic rats is closely associated with the disorder of OPCs differentiation and maturation through WNT/β-catenin signaling pathway, which would contribute ultimately to axonal hypomyelination. Huang et al C3a induces hypomyelination in the septic brain

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Section: Introductionmentioning

confidence: 99%

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Huang

Zhang

Lin³

et al. 2019

Brain Pathology

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“…Neonatal candidemia during the first week of life is less common and less well described than the later onset of this group of infections. According to Barton et al [33], risk factors for candidemia among neonates had not been studied before their research, in early onset disease (EOD, ≤7 days) or compared to late onset disease (LOD, >7 days). After a 2-year study, the authors concluded that risk factors such as birthweight <750 g, gestation <25 weeks, chorioamnionitis and vaginal delivery were strongly associated with EOD.…”

Section: Neonatal Candida Infectionsmentioning

confidence: 99%

“…Dissemination and cardiovascular involvement are common, and affected infants often die. Empiric treatment should be considered in these risk situations [33,34].…”

Section: Neonatal Candida Infectionsmentioning

confidence: 99%

Fungal Infections in Neonatal Intensive Care

Neves¹,

Parahym²,

daSilva³

et al. 2018

Selected Topics in Neonatal Care

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Neonates represent a unique and highly vulnerable patient population. Advances in medical technology have improved the survival and quality of life of newborns, particularly those with extreme prematurity or with congenital defects. Furthermore, immunologic immaturity and altered cutaneous barriers play some role in the vulnerability of neonates to nosocomial infections. In this context, the incidence of invasive fungal infections has increased significantly worldwide, representing an important infective complication in patients hospitalized in intensive care units. Invasive fungal infections in Neonatal Intensive Care Unit (NICUs) show high mortality; being species of Candida, the most isolates etiologic agents. The better prognosis of the patient is associated with the early diagnosis and fast treatment. However, guidelines to facilitate the optimal therapy choice for the treatment of neonatal fungal disease do not exist. The current antifungal agents that are available to treat fungemia among newborns and children are based on clinical trials in adults, since there are few comparative studies of antifungal agents in infants. The most commonly used drugs for the treatment of invasive fungal infections in neonates are classified in four different classes: polyene, azoles, analogs of pyrimidines and echinocandins.

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“…Despite the high incidence of vulvovaginal candidiasis during pregnancy (13–20%) [ 1 , 2 ], Candida species rarely cause chorioamnionitis. A recent neonatal study demonstrated that chorioamnionitis is an important risk factor of invasive early-onset candidiasis in extremely low-birth-weight infants, which leads to high mortality (71%) and neurodevelopmental impairment rates (86%) [ 3 ]; thus, the establishment of antenatal management is crucial. Since the first case of chorioamnionitis caused by Candida albicans that resulted in preterm birth and neonatal death was reported in 1958 [ 4 ], many case reports and short case series have been published.…”

Section: Introductionmentioning

confidence: 99%

CandidaChorioamnionitis Leads to Preterm Birth and Adverse Fetal-Neonatal Outcome

Maki

Fujisaki

Sato

et al. 2017

Infectious Diseases in Obstetrics and Gynecology

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Candida chorioamnionitis is rare but can lead to neonatal infection, high mortality, and neurodevelopmental impairment. We aimed to investigate maternal clinical features and perinatal outcomes and discuss future management strategies. We reviewed the medical records of women with Candida chorioamnionitis at our hospital over a 10-year period (n = 9) and previous published case reports and case series. The most prevalent Candida species was C. albicans (71.3% of the all cases). The most prevalent predisposing condition was preterm premature rupture of membranes (31/123, 25.2%), followed by pregnancy with a retained intrauterine contraceptive device (26/123, 21.1%) and pregnancy after in vitro fertilization (25/123, 20.3%). Preterm labor was the most common symptom (52/123, 42.3%), and only 13% of cases involved fever. Of the infants, 27% of the singletons and 23.8% of the twins were born before 22 gestational weeks, while 60% of the singletons and 76.2% of the twins were born at 22–36 weeks. The median birth weight of the babies born after 22 weeks was 1230 g. The mortality rates of the singletons and twins born after 22 weeks of gestation in the year 2000 or later were 28.6% and 52.4%, respectively. Antenatal treatment for Candida chorioamnionitis has not been established.

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Early Onset Invasive Candidiasis in Extremely Low Birth Weight Infants: Perinatal Acquisition Predicts Poor Outcome

Cited by 22 publications

References 29 publications

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Complement C3a induces axonal hypomyelination in the periventricular white matter through activation of WNT/β‐catenin signal pathway in septic neonatal rats experimentally induced by lipopolysaccharide

Fungal Infections in Neonatal Intensive Care

CandidaChorioamnionitis Leads to Preterm Birth and Adverse Fetal-Neonatal Outcome

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