Results
Characteristics of the study population.
The flow chart of the study is shown in Supplementary material, Figure
S1. Overall, 1,223 pregnant women visited our hospital from the first
trimester of pregnancy to 31 weeks of gestation and were eligible for
the study. A total of 898 pregnant women agreed to participate and were
enrolled in the study. Their clinical characteristics are shown in
supplementary material (Table S1). 55 of all pregnant women (6.1%) were
colonized with MRSA according to nasal or vaginal swabs (Figure S1). 46
pregnant women (5.1%) had MRSA colonization only from the nasal swab,
and nine (1.0%) had MRSA colonization from the vaginal swab (Figure
S1). We categorized the 55 MRSA-positive pregnant women as the M-group,
and the remaining 843 uninfected pregnant women as the non-M group.
These women were followed prospectively, and there was no loss to
follow-up.
All mothers had live births, and there were no perinatal deaths during
the study period. These 898 mothers, including seven with twin
pregnancies, delivered 905 neonates. One twin pregnancy was included in
the M-group, which resulted in 56 neonates in the M-group. Six twin
pregnancies were included in the non-M group, which resulted in 849
neonates. We monitored the clinical course of all neonates throughout
the study period.
Risk factors for maternal MRSA colonization
We first examined the differences in maternal backgrounds between the
M-group and the non-M group (Table 1A). Among the maternal background
information, the percentages of multiparous mothers and mothers who
worked as healthcare providers were significantly higher in the M-group
compared to the non-M group. In the M-group, 67.3% (37/55) were
multiparous, and 29.1% (16/55) were healthcare providers. Only 48.4%
(408/843) were multiparous, and 13.8% (116/843) were healthcare
providers in the non-M group (OR: 2.09, 95%CI: 1.23 to 3.01 and OR:
2.57, 95%CI: 1.39 to 4.75, respectively). The frequency of a parity of
two or more was also significantly higher in the M-group compared to the
non-M group (15/55: 27.3% vs. 119/843: 14.1%, OR: 2.28, 95%CI: 1.22
to 4.26). Although not significant, the proportion of mothers who used
antibiotics during pregnancy tended to be higher in the M-group than the
non-M group (5/55: 9.1% vs. 32/843: 3.8%, OR: 2.53, 95%CI: 0.95 to
6.79).
We performed multivariable logistic regression analysis to determine
whether multiparity, occupation (healthcare provider), and history of
antibiotic use during pregnancy were independently associated with
maternal MRSA colonization. We found that multiparity and occupation
(healthcare provider) were independent risk factors for MRSA
colonization (OR: 2.35, 95% CI; 1.25-4.42 and OR: 2.58, 95% CI;
1.39-4.79, respectively, Table 1B).
We analyzed the association between maternal background and MRSA
colonization in the vagina. We compared the maternal backgrounds of
vaginal MRSA-positive patients (VM group, n=9) and vaginal MRSA-negative
patients (non-VM group, n=889). The results are shown in Table 1A. The
multiparity rate was significantly higher in the VM group compared to
the non-VM group (9/9: 100% vs. 436/889: 49.0%, OR: 19.74, 95%CI:
1.15 to 340.4). The proportion of women with a parity of two or more was
also significantly higher in the VM group compared to the non-VM group
(6/9: 66.6% vs. 128/889: 14.4%, OR: 11.89, 95%CI: 2.94 to 48.16).
There was no significant difference in the proportion of patients who
worked as healthcare providers (VM group; 0/9: 0% vs. non-VM group;
132/889: 14.8%, OR: 0.30, 95%CI: 0.017 to 5.20, Table 1A).
These analyses showed that being multiparous and a healthcare provider
were independent risk factors for maternal MRSA colonization.
Multiparity, particularly a parity of two or more, was obviously a
significant risk factor for vaginal and maternal MRSA colonization.
Vertical transmission of MRSA to neonates at delivery
Of the 905 neonates delivered in the present study, MRSA was detected in
the umbilical stump or nasal cavity at the time of delivery in eight
neonates (0.8%) (Table 2A). We assessed the primary outcome of this
study, the vertical transmission of MRSA to neonates during delivery and
analyzed this outcome in mother-neonate pairs.
There were seven pairs (12.7%) in which neonates were MRSA-positive at
the time of delivery in the M-group (n=55). There was only one pair
(0.12%) with a MRSA-positive neonate at the time of delivery in the
non-M group (n=843). Maternal MRSA carriers had a significantly higher
risk for having neonatal MRSA colonization at the time of delivery (OR
124; 95% CI 20.3-1393, Table 2A).
Sub-analysis compared the vertical transmission rate of MRSA in mothers
with MRSA in only the nasal cavity, mothers with MRSA in the vagina and
non-MRSA mothers (Table 2A). We found that the vertical transmission of
MRSA occurred significantly more often in mothers with MRSA in only the
nasal cavity than non-MRSA mothers (3/46, 6.38%, OR 59.2, 95% CI:
6.0-581). Vertical transmission occurred even more frequently in mothers
with MRSA in the vagina than non-MRSA mothers (4/ 9, 44.4%, OR 678.4,
95% CI, 64.0-7197). We analyzed the vertical transmission of MRSA based
on MRSA colonization in the vagina. The vertical transmission of MRSA in
the VM group was also significantly higher than the non-V-M group (V-M
group: 4/9, 44.4%, non-V-M group: 4/896, 0.45%; OR: 178, 95% CI
39.9-782, Table 2B).
We used a multivariable regression model to analyze the association
between maternal MRSA colonization and neonatal MRSA colonization by
adjusting for parity. Maternal MRSA colonization remained significantly
associated with neonatal MRSA colonization (Table 2C).
We also performed a stratified analysis to determine whether there were
certain factors that increased the frequency of MRSA transmission.
However, we did not find any factors that increased the vertical
transmission rate of MRSA. None of the neonates born via Caesarean
section (CS) had MRSA colonization, which suggests that MRSA is
transmitted directly by vaginal delivery (Supplementary material, Table
S2).
Maternal MRSA colonization was an independent risk factor for neonatal
MRSA colonization at the time of delivery in the present analysis. Even
when MRSA was detected only in the maternal nasal cavity, 6.38% of the
neonates had MRSA colonization. If the pregnant women had MRSA
colonization in the vagina, the vertical transmission rate of MRSA
increased to 44.4% at the time of delivery.
Association between maternal and neonatal adverse outcomes and MRSA
colonization
We assessed the relationship between maternal MRSA colonization and the
clinical courses of mothers and their neonates. We did not find any
significant difference in maternal adverse outcomes in maternal MRSA
colonization (Supplementary material, Table S3). However, the frequency
of SSTIs in the neonatal period was significantly higher in the neonates
of the M-group than the non-M group (M-group; 3/56, 5.4%, non-M group:
7/849, 0.82%, OR 7.47, 95% CI 2.50-22.3, Table 3).
We performed the same analysis based on MRSA colonization in the vagina
(Table 3A). We found that maternal vaginal MRSA colonization was also
significantly associated with the occurrence of SSTIs in the neonatal
period (VM group: 2/9, 22.2%, non-VM group: 8/896, 0.89%, OR:31.7 95%
CI: 5.68-177). Comparison of the frequency of SSTIs in the neonatal
period between the VM group and non-M group revealed a significantly
higher frequency in the VM group compared to the non-M group (VM group:
2/9, 22.2%, non-M group: 8/846, 0.82%, OR:34.4 95% CI: 6.04-195,
Table 3B). We also examined whether factors other than maternal MRSA
colonization were associated with SSTIs, and none of these factors had a
significant association with SSTIs (Supplementary material, Table S4).
Therefore, neonatal SSTI was significantly associated with maternal MRSA
colonization, especially via the vertical transmission of MRSA.
Table 4 shows the details of all neonatal SSTIs. MRSA was the causative
bacterium in all three cases in the M-group but only one of the seven
cases in the non-M group (p=0.033). Two of the three cases in the
M-group had symptoms on the day after birth, and only one of the seven
cases in the non-M group showed symptoms on the day after birth. We
classified all symptoms as invasive (eczema, impetigo and abscess) or
noninvasive (rash, inflammation). All three cases in the M-group and one
case in the non-M group showed invasive symptoms, and the M-group had a
significantly higher frequency of invasive symptoms (p=0.033).
Most SSTIs resolved spontaneously within a few days or resolved with
simple local disinfection procedures. However, one case of MRSA SSTI in
the M-group did not resolve with local treatment and required incision
and drainage procedures.