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\begin{document}

\title{Growing Threat of Extended-Spectrum \selectlanguage{greek}β-\selectlanguage{english}Lactamase-Producing
Enterobacteriaceae Colonization in High-Risk Pregnancies: a
retrospective cohort study\selectlanguage{english}}



\author[1]{Yun-Sun Choi}%
\author[1]{Yejin Kim}%
\author[1]{Hye Jung  Cho}%
\author[1]{Ji-Hee  Sung}%
\author[2]{Suk-Joo  Choi}%
\author[1]{Soo-young Oh}%
\author[1]{Yae-Jean  Kim}%
\author[1]{Cheong-Rae Roh}%
\affil[1]{Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul}%
\affil[2]{Samsung Medical Center, Sungkyunkwan University School of Medicine}%


\vspace{-1em}



  
  \date{May 27, 2024}


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\selectlanguage{english}
\begin{abstract}
Objective To investigate the epidemiological changes in
extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamase-producing Enterobacteriaceae (ESBL-E)
vaginal colonization in high-risk pregnant women and identify
independent risk factors. Further, the differences in perinatal outcomes
according to maternal ESBL-E vaginal colonization were analyzed. Design
Retrospective cohort study. Setting Republic of Korea Population 1,460
women admitted to our high-risk pregnancy unit between 14+0 and 35+6
gestational weeks. Methods The study period was divided into periods 1
(January 2010 to July 2015) and 2 (August 2015 to December 2020). The
main outcomes were analyzed according to each period and ESBL-E vaginal
colonization. Main Outcome Measures ESBL-E vaginal colonization rate,
risk factors for ESBL-E vaginal colonization, and perinatal outcomes.
Results The ESBL-E vaginal colonization rate was higher in period 2,
which was attributed to a significantly higher proportion of
ESBL-producing Escherichia coli. Cerclage (odds ratio {[}OR{]}: 3.248;
95\% confidence interval {[}CI{]}: 1.744--6.049) and prior antibiotic
treatment (OR: 3.044; 95\% CI: 1.713--5.410) were found as independent
risk factors for ESBL-E vaginal colonization. Earlier gestational age at
delivery, and higher proven early-onset neonatal sepsis (EONS) rate were
observed in the ESBL-E-positive group. Conclusions The ESBL-E vaginal
colonization rate in high-risk pregnant patients has increased over the
past decade, and the independent risk factors for colonization are
cerclage and prior antibiotic treatment. Additionally, maternal ESBL-E
vaginal colonization is associated with higher proven EONS rates.
Funding This study received no funding. Keywords Extended-spectrum
\selectlanguage{greek}β-\selectlanguage{english}lactamase, Enterobacteriaceae, vaginal colonization, antibiotics use,
cerclage, neonatal sepsis%
\end{abstract}%



\sloppy


\selectlanguage{greek}\textbf{Growing Threat of Extended-Spectrum
β-Lactamase-Producing\emph{Enterobacteriaceae} Colonization in High-Risk
Pregnancies: a retrospective cohort study}\selectlanguage{english}

11The names are listed in order of contribution to the paper.

Yun-sun Choi,\textsuperscript{a} Yejin Kim,\textsuperscript{a} Hye Jung
Cho,\textsuperscript{a} Ji-Hee Sung,\textsuperscript{a} Suk-Joo
Choi,\textsuperscript{a} Soo-young Oh,\textsuperscript{a}Yae-Jean
Kim,\textsuperscript{b} Cheong-Rae Roh\textsuperscript{a}

\textsuperscript{a}Department of Obstetrics and Gynecology, Samsung
Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

\textsuperscript{b}Department of Pediatrics, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Korea

\textbf{Running title:} ESBL-E vaginal colonization in high-risk
pregnancies

\textbf{Correspondence to} Soo-young Oh

Department of Obstetrics and Gynecology, Samsung Medical Center,
Sungkyunkwan University School of Medicine, Seoul, Korea

81 Irwon-ro, Gangnam-gu, Seoul 06351 Korea

E-mail: ohsymd@skku.edu.

\textbf{Abstract}

\textbf{Objective}

To investigate the epidemiological changes in extended-spectrum
\selectlanguage{greek}β-\selectlanguage{english}lactamase-producing \emph{Enterobacteriaceae} (ESBL-E) vaginal
colonization in high-risk pregnant women and identify independent risk
factors. Further, the differences in perinatal outcomes according to
maternal ESBL-E vaginal colonization were analyzed.

\textbf{Design}

Retrospective cohort study.

\textbf{Setting}

Republic of Korea

\textbf{Population}

1,460 women admitted to our high-risk pregnancy unit between
14\textsuperscript{+0} and 35\textsuperscript{+6} gestational weeks.

\textbf{Methods}

The study period was divided into periods 1 (January 2010 to July 2015)
and 2 (August 2015 to December 2020). The main outcomes were analyzed
according to each period and ESBL-E vaginal colonization.

\textbf{Main Outcome Measures}

ESBL-E vaginal colonization rate, risk factors for ESBL-E vaginal
colonization, and perinatal outcomes.

\textbf{Results}

The ESBL-E vaginal colonization rate was higher in period 2, which was
attributed to a significantly higher proportion of
ESBL-producing\emph{Escherichia coli} . Cerclage (odds ratio {[}OR{]}:
3.248; 95\% confidence interval {[}CI{]}: 1.744--6.049) and prior
antibiotic treatment (OR: 3.044; 95\% CI: 1.713--5.410) were found as
independent risk factors for ESBL-E vaginal colonization. Earlier
gestational age at delivery, and higher proven early-onset neonatal
sepsis (EONS) rate were observed in the ESBL-E-positive group.

\textbf{Conclusions}

The ESBL-E vaginal colonization rate in high-risk pregnant patients has
increased over the past decade, and the independent risk factors for
colonization are cerclage and prior antibiotic treatment. Additionally,
maternal ESBL-E vaginal colonization is associated with higher proven
EONS rates.

\textbf{Funding}

This study received no funding.

\textbf{Keywords}

Extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamase, \emph{Enterobacteriaceae} , vaginal
colonization, antibiotics use, cerclage, neonatal sepsis

\textbf{Introduction}

Extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamases (ESBLs) are a heterogeneous group of
enzymes produced by certain bacteria that inactivate \selectlanguage{greek}β-\selectlanguage{english}lactam
antibiotics via hydrolysis. They are most often found
in\emph{Enterobacteriaceae} , especially \emph{Escherichia coli}
and\emph{Klebsiella pneumoniae} . Because of antimicrobial resistance,
diagnosing and treating ESBL-producing bacterial species are important
challenges.\textsuperscript{1,2}

The prevalence of ESBL-producing \emph{Enterobacteriaceae} (ESBL-E)
infection is not exactly known; however, the reported prevalence has
increased globally in recent years,\textsuperscript{3-5} while the
estimated prevalence in Asia is approximately 4.8\% to
12.0\%.\textsuperscript{2,6-8} Furthermore, the rates of ESBL-E
infection in maternity wards and outpatient clinics are also increasing.
Therefore, these issues related to ESBL-E infection are becoming more
crucial among obstetricians.\textsuperscript{9}

Following the report of maternal ESBL-E vaginal colonization as a
precursor of mother-to-child transmission, the importance of vaginal
colonization was recently noted.\textsuperscript{10} According to a
recent systematic review, neonatal ESBL-E infection in neonatal
intensive care units is associated with significant morbidity and
mortality, with a mortality rate as high as
31\%.\textsuperscript{11}Meanwhile, the risk factors for ESBL-E
infection in the general population include prior antibiotic treatment,
increased illness severity, indwelling catheter use, and intensive care
unit admission.\textsuperscript{12,13} However, the specific risk
factors for ESBL-E vaginal colonization during pregnancy have not been
studied, and the potential clinical implications are still
unclear.\textsuperscript{14}

With this background, we aimed to evaluate the changes in the rate of
ESBL-E vaginal colonization in high-risk pregnancies over the study
period and identify the risk factors for ESBL-E vaginal colonization
during pregnancy. Further, we analyzed the perinatal outcomes of
ESBL-E-positive patients.

\textbf{Methods}

\textbf{Study population}

This retrospective cohort study included consecutive pregnant women who
were admitted to the high-risk pregnancy unit of our institution between
14\textsuperscript{+0/7} and 35\textsuperscript{+6/7} weeks of gestation
and delivered a baby at our hospital. The indications for admission were
preterm premature rupture of membrane (pPROM), preterm labor (PTL),
incompetent internal os of the cervix (IIOC), and short cervical length
(CL) (defined as a CL of \textless{}25 mm on transvaginal ultrasound).
The study period was from January 2010 to December 2020 and was
arbitrarily divided into period 1 (January 2010 to July 2015) and period
2 (August 2015 to December 2020) to evaluate changes in the association
of ESBL-E vaginal colonization over the time periods. The study was
approved by our institutional review board (no. 2020-08-006). The
requirement for written informed consent was waived owing to the
retrospective design of our study. Prior to analysis, all patient
records were anonymized.

\textbf{Vaginal culture examinations}

Since 2010, our institution has introduced a practice protocol in which
upper vaginal culture is routinely performed for high-risk patients
diagnosed with pPROM, PTL, IIOC, and short CL. Vaginal culture samples
were collected under sterile technique using a sterile swab and a
sterile non-lubricated speculum and transported to the laboratory for
analysis using a suitable transportation medium. The samples were
Gram-stained and cultured according to the standard laboratory
procedures of our institution. They were directly inoculated on a blood
agar plate, MacConkey agar plate, and Thayer--Martin agar plate and
incubated at 35\selectlanguage{ngerman}°C for up to 72 h in a 5\% CO\textsubscript{2} incubator.
Antimicrobial susceptibility testing, including that for ESBL-E
activity, was performed using the VITEK 2 system (bioMérieux, Hazelwood,
MO). Cefepime,~cefotaxime, ceftazidime, cefepime/clavulanic acid,
cefotaxime/clavulanic acid, and ceftazidime/clavulanic acid were
included~in the ESBL-E testing using the VITEK 2 system. There was no
significant change in the diagnostic method for ESBL-E during the study
period.

\textbf{Clinical characteristics of the study population}

We collected data on maternal characteristics, including age, parity,
pre-pregnancy body mass index, history of preterm birth (PTB),
plurality, infertility treatment (intrauterine insemination and \emph{in
vitro} fertilization {[}IVF{]}) of index pregnancy, gestational age at
admission, diagnosis at admission (pPROM, IIOC, PTL, or short CL), and
use of antibiotics before admission. Prior antibiotic treatment was
defined as the use of antibiotics within 4 weeks prior to the vaginal
culture test. Perinatal outcomes included gestational age at delivery,
mode of delivery, abortion, stillbirth, histologic chorioamnionitis,
sex, birth weight, Apgar score, neonatal mortality, neonatal intensive
care unit admission rate, and neonatal sepsis. Abortion included all
fetal loss in utero occurring before 20 weeks of gestation, while
stillbirth included fetal loss occurring beyond 20 weeks of gestation
with 5-min Apgar scores of 0. According to the protocol used by Redline
et al.,\textsuperscript{15} histologic chorioamnionitis was reviewed by
a single pathologist (JSK) as previously
defined.\textsuperscript{16}Early-onset neonatal sepsis (EONS) was
defined as neonatal sepsis within the first 3 days of life, including
infection by any kind of organism. Suspected sepsis was diagnosed
clinically by pediatricians, while proven sepsis was diagnosed when
microorganisms were isolated from the blood or cerebrospinal fluid of
neonates.

\textbf{Statistical analysis}

Statistical analysis was performed using Pearson's chi-square test and
Fisher's exact test for categorical data and the Wilcoxon rank sum test
for continuous data. Neonatal outcomes were analyzed using the
generalized estimating equation method, considering twins and triplets
born to the same mother. A multiple logistic regression analysis was
performed to identify the independent risk factors for ESBL-E vaginal
colonization. The adjustment factors were selected backward for
variables with \emph{P} -values of \textless{}0.05 in the univariate
analysis, and a multivariate analysis was performed after confirmation
that these adjustment factors had no collinearity in the covariate
analysis. Statistical significance was set at \emph{P} -values of
\textless{}0.05. Statistical analysis was performed using SAS version
9.4 (SAS Institute, Cary, NC) and R version 4.0.4 (Vienna, Austria;
http://www.R-project.org/).

\textbf{Results}

\textbf{Clinical characteristics of the study population according to
the study period}

During the study period, a total of 1,460 women were eligible for this
study. Table 1 summarizes the comparison of maternal ESBL-E vaginal
colonization according to the study period. The overall maternal ESBL-E
vaginal colonization rate was significantly higher in period 2 than in
period 1 (6.2\% vs 2.4\%, \emph{P} \textless{} 0.001). Notably, the
positivity rate for \emph{E. coli} colonization (14.3\% vs
6.3\%,\emph{P} \textless{} 0.001) and the rate of ESBL-E-positive
\emph{E. coli} colonization were significantly higher in period 2 than
in period 1 (5.3\% vs 1.7\%, \emph{P} \textless{} 0.001). However, there
was no significant difference in the rates of \emph{K. pneumoniae}
colonization and ESBL-E-positive \emph{K. pneumoniae} colonization
between periods 1 and 2.

Table 2 compares the maternal baseline characteristics according to the
study period. The maternal age, primiparity, pre-pregnancy body mass
index, IVF-embryo transfer pregnancy rate, and short CL rate were
significantly higher in period 2 than in period 1. In particular, the
prior antibiotic treatment rate within 4 weeks was significantly higher
in period 2 than in period 1 (18.5\% vs 13.9\%, \emph{P} = 0.018). We
additionally checked the indications for antibiotic use among the women
with prior antibiotic treatment (\emph{n} = 238). Suspected diagnosis or
confirmed diagnosis of pPROM (\emph{n} = 160) was most often indicated,
followed by PTL, prophylactic antibiotic use before or after cerclage,
IIOC, and fever, as shown in Table 2. No significant difference was
observed for any indication between the two periods.

\textbf{Clinical characteristics of the study population according to
maternal ESBL-E vaginal colonization}

We also compared the maternal baseline characteristics according to
ESBL-E vaginal colonization (Table 3). During the study period, 64
patients (4.4\%) were confirmed to be positive for ESBL-E based on the
vaginal culture findings. As shown in Table 3, the rates of IVF-embryo
transfer pregnancy, IIOC, and cerclage before admission were
significantly higher in the ESBL-E-positive group. In addition, the rate
of antibiotic treatment before vaginal culture was significantly higher
in the ESBL-E-positive group than in the ESBL-E-negative group (43.8\%
vs 15.0\%, \emph{P} \textless{} 0.001). The gestational age at admission
was significantly lower in the ESBL-E-positive group than in the
ESBL-E-negative group. We compared the duration of antibiotic use in 238
patients who used antibiotics before vaginal culture according to ESBL-E
vaginal colonization. The median duration of antibiotic treatment was
significantly longer in the ESBL-E-positive group than in the
ESBL-E-negative group (7.0\% vs 4.0\%, \emph{P} = 0.015).

\textbf{Independent risk factors for maternal ESBL-E vaginal
colonization}

We identified the independent risk factors for the increase in ESBL-E
vaginal colonization through a multivariate analysis (Table 4). The
analysis showed that cerclage (odds ratio {[}95\% confidence
interval{]}: 3.248 {[}1.744--6.049{]}) and prior antibiotic treatment
(odds ratio {[}95\% confidence interval{]}: 3.044 {[}1.713--5.410{]})
remained as significant risk factors for positive ESBL-E vaginal
colonization.

\textbf{Perinatal outcomes according to maternal ESBL-E vaginal
colonization}

Finally, we compared the perinatal outcomes according to ESBL-E vaginal
colonization in 1,460 mothers and 1,616 live-born neonates. As shown in
Table 5, the gestational age at admission and delivery was significantly
earlier, and the rates of abortion and histologic chorioamnionitis were
significantly higher in the ESBL-E-positive group than in the
ESBL-E-negative group. The overall rate of EONS (7.6\% vs 2.5\%,\emph{P}
= 0.040) and the rate of proven EONS were significantly higher in the
ESBL-E-positive group than in the ESBL-E-negative group (6.0\% vs 1.1\%,
\emph{P} = 0.002).

\textbf{Discussion}

\textbf{Main Findings}

Our study clearly showed a significant increase in the rate of ESBL-E
vaginal colonization, especially ESBL-producing \emph{E. coli} , in
high-risk pregnancies over the past decade. We also demonstrated that
prior antibiotic treatment and cerclage were the independent risk
factors for ESBL-E vaginal colonization after adjusting for confounding
variables. In addition, maternal ESBL-E vaginal colonization was
associated with earlier gestational age at admission and delivery and
higher rate of EONS, especially in cases of proven sepsis.

\textbf{Strengths and Limitations}

Our study has some limitations. First, since we analyzed the
relationship between the results of vaginal culture at admission and
neonatal outcomes, our analysis did not consider antibiotic treatment
during hospitalization, which may affect the neonatal outcomes. Second,
although cerclage was identified as a risk factor for ESBL-E vaginal
colonization, the causality is uncertain. In fact, a previous study has
demonstrated that the proportion of \emph{Lactobacillus spp.} was
reduced, while that of abnormal vaginal flora increased before rescue
cerclage.\textsuperscript{28} Considering this result, the possibility
that ESBL-E vaginal colonization had already occurred before the
operation could not be excluded because information on vaginal culture
before cerclage was not available in this study population.

To the best of our knowledge, this is the first study to identify
changes in the prevalence and risk factors of ESBL-E vaginal
colonization in high-risk pregnancies. Our study is also meaningful in
that we included a relatively large number of patients who underwent
vaginal culture according to the protocol of our institution. In
addition, the need for further studies on the treatment of ESBL-E
colonization and pregnancy outcomes was identified in this study. For
example, there are only a few randomized controlled trials on ESBL-E
infection treatment, and there are many controversies on whether
antibiotic treatment for ESBL-E infection is effective or on which
treatment methods are effective.\textsuperscript{45,46}

\textbf{Interpretation}

New \selectlanguage{greek}β-\selectlanguage{english}lactamases have emerged rapidly with the development of new
\selectlanguage{greek}β-\selectlanguage{english}lactam antibiotics over the past 20 years, and the prevalence of
ESBL-producing bacteria is increasing
worldwide.\textsuperscript{1,3-5}The prevalence of community-acquired
ESBL-E infections among hospitalized patients has also increased in
Korea.\textsuperscript{17}In our study, the rate of maternal ESBL-E
vaginal colonization increased to 6.2\% in the recent period. In a
Norwegian study, the prevalence of ESBL-E rectal colonization was 2.9\%
among pregnant women at 36 weeks of gestation.\textsuperscript{18} In
another study conducted in Sri Lanka, the pre-delivery ESBL-E lower
vaginal colonization rate was 1.6\%.\textsuperscript{19}

Our data are in line with previously reported findings that prior use of
antibiotics, particularly fluoroquinolone and cephalosporin, is a risk
factor for ESBL-E infection in hospitalized
patients.\textsuperscript{1,2} It is well recognized that an increase in
the rate of ESBL-E infection is associated with the widespread use of
antibiotics.\textsuperscript{1,2,20-22} In our study, the multivariate
analysis confirmed that prior antibiotic treatment and cerclage were the
independent risk factors for ESBL-E vaginal colonization in high-risk
pregnant patients. In fact, previous studies have suggested that
antibiotic administration during pregnancy may alter the vaginal
microbiological ecology.\textsuperscript{23,24} For example,
less\emph{Lactobacillus} species colonization than expected was reported
in pregnant women using antibiotics, and an increased vaginal
colonization rate by \emph{E. coli} was reported after antibiotic use
during pregnancy.\textsuperscript{24} Similar to the general population,
prolonged antibiotic use in pregnant women is also a known risk factor
for ESBL-producing bacterial infection.\textsuperscript{12,13}Similarly,
our study also showed that the duration of antibiotic administration was
significantly longer in the ESBL-E-positive group. Clinically, the
proper use of antibiotics during pregnancy is very important for the
health of both the mother and fetus.\textsuperscript{25} Considering our
study results, antibiotic treatment during pregnancy could be a risk
factor for ESBL-E vaginal colonization infection and thus should be used
only when needed. Therefore, our study also indirectly supports the
limited exposure to antibiotics during pregnancy with narrow-spectrum
antibiotics, if possible.

Cerclage is an effective treatment option for preventing PTB in women
with cervical incompetency.\textsuperscript{26,27} In several studies,
dilated cervix and short CL were associated with a paucity
of\emph{Lactobacillus} species in the vagina.\textsuperscript{28,29} A
reduced abundance of normal vaginal flora could make it vulnerable to
colonization by abnormal vaginal flora. Previous studies have suggested
that cerclage increases the risk of maternal infection requiring medical
intervention and puerperal pyrexia\textsuperscript{27,30}; the
possibility of vaginal dysbiosis owing to the effects of suture
materials has also been suggested.\textsuperscript{31} Our study found
that cerclage was associated with the risk of ESBL-E vaginal
colonization. However, it is unclear whether cerclage is the cause or
result of ESBL-E vaginal colonization. Similarly, one study confirmed
that when postoperative vaginal culture was performed in patients
undergoing cerclage, more than 75\% of the samples were positive
for\emph{E. coli.} \textsuperscript{32} Based on the results of these
studies, it is necessary to consider the risks and benefits when
deciding whether to perform cerclage.

Abnormal vaginal colonization by \emph{E. coli} or \emph{K.
pneumoniae}during pregnancy is clinically important with respect to
neonatal infection and PTB.\textsuperscript{33-36} Especially, ESBL-E is
very important because it has been reported to be the major cause of
neonatal infection, which increases neonatal mortality owing to
limitations in therapeutic options.\textsuperscript{10,37,38} In light
of this importance, it is considerably regrettable that there are only a
few studies on the screening or treatment of ESBL-E colonization in
pregnant women.

The organisms known to cause EONS are generally colonized in the
maternal genito-urinary tract.\textsuperscript{39} Among them,
maternal\emph{E. coli} vaginal colonization has been widely studied as
an independent risk factor for neonatal \emph{E.
coli}sepsis.\textsuperscript{40,41} In addition, a previous study has
shown that EONS with \emph{E. coli} was associated with worse perinatal
outcomes compared with EONS with group B\emph{Streptococcus.}
\textsuperscript{42} For this reason, neonatal\emph{E. coli} sepsis,
especially ESBL-E sepsis, which is difficult to treat, is emerging as an
important condition. A recent study on ESBL-E infection during pregnancy
identified that maternal ESBL-E colonization is an important risk factor
for vertical transmission. The authors explained that the rate of
ESBL-E-positive postnatal swabs was significantly higher in neonates
born to mothers who were positive for ESBL-E colonization at
delivery.\textsuperscript{43} Among the total neonatal sepsis cases in
the ESBL-E-positive group in our study, ESBL-E was identified in five
cases. Consequently, the mother-to-neonate transmission rate of ESBL-E
infection was estimated to be 7.6\% (5/66). According to a Sri Lankan
study, the mother-to-neonate transmission rate of
\emph{Enterobacteriaceae} was 6.9\%, of which ESBL producers had a
transmission rate of 0.6\%.\textsuperscript{19} Another study reported a
mother-to-neonate ESBL-E transmission rate of
34.3\%.\textsuperscript{44} Our study also confirmed that the rate of
proven EONS was significantly higher in the ESBL-E-colonized mothers.
This finding supports the results of previous studies and highlights the
importance of evaluating the need for screening and treatment for ESBL-E
colonization in high-risk pregnancies.

\textbf{CONCLUSION}

To date, upper vaginal culture is not routinely recommended even in
high-risk pregnancies\textsuperscript{47,48}; nevertheless, screening
for high-risk pregnancies may be justified if there is evidence that
treatment of ESBL-E vaginal colonization improves neonatal outcomes.
Therefore, we suggest the need for further studies on screening and
treatment of ESBL-E vaginal colonization to improve the perinatal
outcomes against the increasing threat of ESBL-E colonization during
pregnancy. In conclusion, our findings indicate that judicious use of
antibiotics and prudent cerclage are needed.

\textbf{DISCLOSURE OF INTEREST}

The authors have no conflict of interest to disclose.

\textbf{CONTRIBUTION TO AUTHORSHIP}

YC wrote the manuscript and researched data. YK researched data. HC
researched data. JS researched data and reviewed/edited the manuscript.
SC reviewed/edited the manuscript. SO contributed to the discussion and
reviewed/edited the manuscript. YK reviewed/edited the manuscript. CR
reviewed/edited the manuscript.

\textbf{ETHICS APPROVAL}

The study protocol was approved by our institutional review board (no.
2020-08-006) and followed the principles of Declaration of Helsinki. The
requirement for written informed consent was waived owing to the
retrospective design of our study.



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\textbf{31} Kindinger LM, MacIntyre DA, Lee YS, Marchesi JR, Smith A,
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\textbf{32} Kessler I, Shoham Z, Lancet M, Blickstein I, Yemini M,
Miskin A, et al. Complications associated with genital colonization in
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\textbf{36} Saez-Lopez E, Guiral E, Fernandez-Orth D, Villanueva S,
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\textbf{37} Hyle EP, Lipworth AD, Zaoutis TE, Nachamkin I, Fishman NO,
Bilker WB, et al. Risk factors for increasing multidrug resistance among
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\textbf{38} Koizumi A, Maruyama K, Ohki Y, Nakayama A, Yamada Y,
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health: state of the art. \emph{Res Microbiol} 2017;168:892-901.

\textbf{40} Kim JY, Sung JH, Chang KH, Choi SJ, Oh SY, Roh CR, et al.
Abnormal vaginal colonization by gram-negative bacteria is significantly
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\textbf{41} Tameliene R, Barcaite E, Stoniene D, Buinauskiene J,
Markuniene E, Kudreviciene A, et al. Escherichia coli colonization in
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\textbf{42} Mayor-Lynn K, Gonzalez-Quintero VH, O'Sullivan MJ, Hartstein
AI, Roger S, Tamayo M. Comparison of early-onset neonatal sepsis caused
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\textbf{43} Foessleitner P, Gasser J, Kiss H, Flunt A, Presterl E,
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\textbf{44} Danino D, Melamed R, Sterer B, Porat N, Hazan G, Gushanski
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\textbf{45} Seo YB, Lee J, Kim YK, Lee SS, Lee JA, Kim HY, et al.
Randomized controlled trial of piperacillin-tazobactam, cefepime and
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Probiotics for intestinal decolonization of ESBL-producing
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\textbf{48} Nygren P, Fu R, Freeman M, Bougatsos C, Klebanoff M, Guise
JM, et al. Evidence on the benefits and harms of screening and treating
pregnant women who are asymptomatic for bacterial vaginosis: an update
review for the U.S. Preventive Services Task Force. \emph{Ann Intern
Med} 2008;148:220-33.

\textbf{Table 1.} Comparison of maternal ESBL-E vaginal colonization
according to the study period\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Total (\emph{n} = 1,460)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Period 1} \textbf{January 2010 to July 2015 (\emph{n} =
704)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Period 2} \textbf{August 2015 to July 2020 (\emph{n} =
756)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\emph{P}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Positive for ESBL-E (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.4 (17/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.2 (47/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{Escherichia coli} (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.3 (44/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
14.3 (108/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
ESBL-positive \emph{Escherichia coli} (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.7 (12/704)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
5.3 (40/756)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\emph{Klebsiella pneumonia} (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.3 (16/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
3.3 (25/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.232*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
ESBL-positive \emph{Klebsiella pneumonia} (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.7 (5/704)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
1.1 (8/756)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.479*\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Pearson's chi-square test.

Data are presented as numbers (percentages).

ESBL-E, extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamase-producing

\emph{Enterobacteriaceae}

\textbf{Table 2.} Maternal baseline characteristics according to the
study period\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Total (\emph{n} = 1,376)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Period 1} \textbf{January 2010 to July 2015 (\emph{n} =
704)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Period 2} \textbf{August 2015 to July 2020 (\emph{n} =
756)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\emph{P}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Maternal age (yr)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
32 (30--35)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
33 (31--36)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Primiparity (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
41.5 (292/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
51.2 (387/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Body mass index (kg/m\textsuperscript{2}) before pregnancy\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20.7 (19.3--22.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
21.3 (19.5--24.2)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
History of preterm delivery (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.5 (81/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.39 (71/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.186**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Multifetal pregnancy\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Twin (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18.6 (131/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18.7 (141/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.983**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Triplet (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.4 (10/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.1 (16/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.315**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Pregnancy by \emph{in vitro} fertilization-embryo transfer (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
15.8 (111/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
20.2 (153/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Pregnancy by intrauterine insemination (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.3 (16/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.3 (17/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.972**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Gestational age at admission (wk)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
28.2 (24.6--32.4)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
29.3 (24.1--33.1)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.097*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Diagnosis at admission\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Preterm premature rupture of membrane (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
39.6 (279/704)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
40.0 (302/756)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.902**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
Incompetent internal os of the cervix (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
16.6 (117/704)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
18.7 (141/756)\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
0.309**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cerclage (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.0 (63/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.2 (85/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.147**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Preterm labor (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
41.3 (291/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
35.7 (270/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.027**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Short cervical length (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.6 (18/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
8.5 (64/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Prior antibiotic treatment (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
13.9 (98/704)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
18.5 (140/756)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.018**\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Wilcoxon rank-sum test, **Pearson's chi-square test.

Data are presented as nos. (percentages) and medians (interquartile
ranges).

\textbf{Table 3.} Maternal baseline characteristics according to
maternal ESBL-E vaginal colonization\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Total (\emph{n} = 1,460)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Negative for ESBL-E} \textbf{(\emph{n} = 1,396)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Negative for ESBL-E} \textbf{(\emph{n} = 1,396)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\textbf{Positive for ESBL-E (\emph{n} = 64)}\strut
\end{minipage} & \begin{minipage}[b]{0.19\columnwidth}\raggedright\strut
\emph{P}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Maternal age (yr)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
33 (30--36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
33 (30--36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
34 (32--36)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.078*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Primiparity (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
46.7 (652/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
46.7 (652/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
42.2 (27/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.479**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Body mass index (kg/m\textsuperscript{2}) before pregnancy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21.0 (19.4--23.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21.0 (19.4--23.4)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21.5 (19.1--25.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.425*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
History of preterm delivery (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10.0 (140/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
10.0 (140/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
18.8 (12/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.026**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Multifetal pregnancy\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Twin (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
18.5 (258/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
18.5 (258/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
21.9 (14/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.495**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Triplet (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
1.7 (24/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.1 (2/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.1 (2/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.406***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Pregnancy by \emph{in vitro} fertilization-embryo transfer (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
17.6 (245/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29.7 (19/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29.7 (19/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.014**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Pregnancy by intrauterine insemination (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
2.2 (31/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.1 (2/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
3.1 (2/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.634***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Gestational age at admission (wk)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29.00 (24.6--32.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24.3 (20.9--26.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24.3 (20.9--26.9)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Diagnosis at admission\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Preterm premature rupture of membrane (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
39.8 (556/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
39.1 (25/64)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
39.1 (25/64)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
0.903**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
Incompetent internal os of the cervix (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
16.8 (235/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
35.94 (23/64)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
35.94 (23/64)\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
\textless{}0.001**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Cerclage (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
9.2 (129/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29.7 (19/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
29.7 (19/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Preterm labor (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
38.9 (543/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28.1 (18/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28.1 (18/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.083**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Short cervical length (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
5.6 (78/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.3 (4/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
6.3 (4/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.822***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Prior antibiotic treatment (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15.0 (210/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
43.8 (28/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
43.8 (28/64)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\textless{}0.001**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
Duration of prior antibiotic treatment (d)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
4.0 (2.0--8.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7.0 (5.0--12.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
7.0 (5.0--12.0)\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
0.015*\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Wilcoxon rank-sum test, **Pearson's chi-square test, ***Fisher's exact
test.

Data are presented as nos. (percentages) and medians (interquartile
ranges).

ESBL-E, extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamase-producing

\emph{Enterobacteriaceae.}\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
\textbf{Variables} & \selectlanguage{greek}\textbf{β (95\% confidence interval)}\selectlanguage{english} &
\emph{P}\textbf{-value}\tabularnewline
\midrule
\endhead
Pregnancy by \emph{in vitro} fertilization-embryo transfer & 1.679
(0.917--3.076) & 0.104\tabularnewline
Cerclage before vaginal culture & 3.248 (1.744--6.049) &
\textless{}0.001\tabularnewline
Prior antibiotic treatment & 3.044 (1.713--5.410) &
\textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4.} Multivariate logistic regression analysis of the risk
factors for extended-spectrum
\selectlanguage{greek}β-\selectlanguage{english}lactamase-producing\emph{Enterobacteriaceae} colonization

\textbf{Table 5.} Comparison of the perinatal outcomes according to
maternal ESBL-E vaginal colonization\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
\begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Total (\emph{n} = 1,460)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Negative for} \textbf{ESBL-E (\emph{n} = 1,396)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\textbf{Positive for} \textbf{ESBL-E (\emph{n} = 64)}\strut
\end{minipage} & \begin{minipage}[b]{0.24\columnwidth}\raggedright\strut
\emph{P}\textbf{-value}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Gestational age at delivery (wk)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
31.0 (26.1--33.9)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
26.6 (23.0--31.8)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Cesarean section (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
51.9 (724/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
56.3 (36/64)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.492**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Abortion (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.0 (56/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.38 (6/64)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.038**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Stillbirth (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.4 (62/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.8 (5/64)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.208**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Histologic chorioamnionitis (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
46.6 (650/1,396)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
59.4 (38/64)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.045**\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Total (\emph{n} = 1,616)}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Negative for} \textbf{ESBL-E (\emph{n} = 1,550)}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\textbf{Positive for} \textbf{ESBL-E (\emph{n} = 66)}\strut
\end{minipage} & \begin{minipage}[t]{0.24\columnwidth}\raggedright\strut
\emph{P}\textbf{-value}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Sex (male) (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
56.2 (871/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
47.0 (31/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.180***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Birth weight (kg)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.64 (0.95--2.15)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.07 (0.76--1.73)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
\textless{}0.001*\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Small for gestational age (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.7 (105/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.1 (8/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.094***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1-min Apgar score of \textless{}4 (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.4 (145/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
9.1 (6/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.943***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5-min Apgar score of \textless{}7 (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
11.2 (174/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
12.1 (8/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.821***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Neonatal mortality (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
5.9 (92/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
10.6 (7/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.207***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Neonatal intensive care unit admission rate (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
86.6 (1,343/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
93.9 (62/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.098***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
EONS (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
2.5 (39/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
7.6 (5/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.040***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Proven EONS (\%)\textsuperscript{+}\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.1 (17/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.0 (4/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.002***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Suspected EONS (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.4 (22/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
1.5 (1/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.948***\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
Late-onset neonatal sepsis (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
4.1 (64/1,550)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
6.1 (4/66)\strut
\end{minipage} & \begin{minipage}[t]{0.22\columnwidth}\raggedright\strut
0.521***\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*Wilcoxon rank-sum test, **Pearson's chi-square test, ***Generalized
estimating equation

Data are presented as nos. (percentages) and medians (interquartile
ranges).

\textsuperscript{+}Among neonates with proven EONS, sepsis by ESBL-E was
not identified in the ESBL-E-negative patients but was identified in
three ESBL-E-positive patients.

ESBL-E, extended-spectrum \selectlanguage{greek}β-\selectlanguage{english}lactamase-producing\emph{Enterobacteriaceae}
; EONS, early-onset neonatal sepsis.

\selectlanguage{english}
\FloatBarrier
\end{document}

