| Abstract |
Introduction: Candidiasis refers to infection with fungi of the genus Candida. The
most common and more virulent is C. albicans, responsible for 40-80% of neonatal
candidiasis cases. Neonatal Candida colonization may happen, as neonates acquire
Candida species vertically through the vagina during labour, or horizontally from the
hospital environment. Τhere is an increased rate of vaginal Candida colonisation of
pregnant women during pregnancy. Colonized neonates are asymptomatic. However,
colonisation could be the first step on the development of candidiasis, in case of
imbalance on host’s bacterial flora or immature immune status of the neonate.
Usually, candidiasis present as localized mucocutaneous candidiasis, either on neonate’s
genital area as diaper rash, or on neonate’s oral mucosa as oral thrush. Rarely,
Candida may cause candidemia and invasive candidiasis, invading vital organs, as
heart, central nervous system, kidneys, liver, eyes and others. Congenital candidiasis
may affect some neonates. Invasive (systemic) candidiasis is a serious condition
associated with high morbidity and mortality. Invasive candidiasis is a major problem,
especially for premature and low birth weight neonates, admitted to the neonatal
intensive care unit (NICU), and causing high mortality (25 to 35%). It is estimated
that 15% of these neonates are colonised from their mother, where as the rest of them
(85%) are acquiring the fungus from the environment of the NICU, during their
nursery. Despite the fact, that it is common belief the major role of vertical
transmission on neonatal Candida colonization, there is a deficit on verification.
Objective: The objective of the present study is to explore the percentage of neonatal
Candida colonisation, with or without symptoms of neonatal candidiasis and its
correlation with the vaginal Candida colonization of their mothers, with or without
symptoms of vulvovaginal candidiasis.
Material: The collection of the samples was made at random order, from 347
pregnant women and their neonates, who were born at Obstetrics Department of the
University General Hospital and Venizeleion General Hospital in Heraklion, Crete,
during the period February 2005 until April 2009. Vaginal samples were collected
from pregnant women, within 48 hours before delivery, who at the time of sampling
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were expected to give birth by vaginal route. Pregnant women who finally gave birth
by caesarean section were still included in the study. Neonatal samples were obtained
from oral and rectal mucosa, within 72 hours after delivery. Concurrently, demographic
and clinical data, involving mothers and neonates, were reported.
Methods: A sterile fibre-tipped swab was used to collect the samples. The mother’s
and neonate’s specimens were inoculated onto Sabouraud dextrose agar plates
(Becton Dickinson Microbiology Systems, Cockeysville, MD, USA), and incubated
for 72 hours at 36°C under aerobic conditions. Results were categorized semiquantitavely.
Yeast isolates were identified to species level using the API 20CAUX
system (BioMérieux, Marcy, L’Etoile, France). Antifungal susceptibility testing
against amphotericin B, 5-fluorocytosine, fluconazole, ketoconazole, itraconazole,
voriconazole, was performed by the E-test as recommended by the manufacturer
(BioMérieux). Furthermore, antifungal susceptibility testing against echinocandins:
caspofungin, anidulafungin and micafungin, was performed only for the Candida
strains isolated from mother-neonate pairs. Genetic relatedness of C.albicans isolates
from mother-infant pairs was investigated by pulsed-field gel electrophoresis (PFGE)
method.
Results: Overall, 82 mothers and 16 neonates were colonized by Candida species.
Among pregnant women, the predominant species was C. albicans (n=68) followed
by C.glabrata(n=11). No significant differences were observed regarding colonization
rates or C.albicans predominance among mothers in the vaginal delivery or caesarean
section groups. During pregnancy, 26.8% (22/82) colonized pregnant women experienced
vulvovaginal candidiasis, while only 17% (14/82) referred antifungal therapy.
Among neonates the only species isolated was C.albicans, mostly from rectal mucosa
(87.5%). All colonized neonates were born to colonized mothers. Most of the
colonized neonates were born to mothers colonized by C.albicans, which developed
significant amount of Candida on culture of vaginal samples. In every pair motherneonate,
was isolated the same Candida species (C.albicans), having the same
antifungal susceptibility. All C.albicans isolates were susceptible to amphotericin B
and the echinocandins. Candida genotyping revealed identical strains in all
investigated neonate-mother pairs. All of the 16 mother’s strains were different
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between them. Only one neonate developed oral thrush, on the 10th day of life, while
no neonate had invasive candidiasis.
Conclusions: Vaginal Candida colonization of pregnant women was 23.6%, in
accordance with increased reported rates, during pregnancy, compared to general
population. The most common species was C.albicans (82%). Our study showed that
sexual intercourse, tobacco use and vulvovaginal candidiasis during pregnancy are
risk factors for maternal vaginal Candida colonization. Almost all colonized neonates
were born by vaginal delivery (15/16) from colonized mothers, indicating vaginal
delivery as perinatal risk factor for infant colonization. The significance of vaginal
delivery was not proven, as statistical analysis was limited by small number of
samples.In every mother-neonate pair was identified identical pulsotype of C.albicans
between mother and neonate. It was found that the single factor that contributed to
infant’s colonization was the colonization of the mother. All of the non colonized
neonates were born from non colonized mothers. Also, it was confirmed the susceptibility
of C.albicans, in vitro, against amphotericin B and echinocandins. Limitations
of this study included the absence of investigating the horizontal transmission of the
yeast from other sources. Furthermore, it was not explored the full process of neonatal
colonization on the next days of neonatal life, unless there was a case of candidiasis
with clinical symptoms.Nevertheless, our findings strongly suggest that early neonatal
colonization of healthy, full term neonates by C.albicans, occurs through vertical
transmission during or immediately after birth. Based on the fact that neonatal
colonization is considered risk factor for neonatal candidiasis, a screening control
should be performed for detection of the vaginal Candida colonization of pregnant
women in high risk for preterm labour, in order to eliminate it early, during pregnancy
and to avoid the vertical transmission of the yeast to the neonate.
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