Epidemiological characteristics of pregnancy-associated listeriosis cases
During the study period, 14 cases of pregnancy-associated listeriosis were identified. 12 cases were inborn neonates, the rest (B2 and B3) were outborn neonates. The incidence of pregnancy-associated listeriosis in our hospital was 16.69/100,000 (14/83,875) births during our study period. They were occurred in all seasons, and a half were occurred in summer (50.0%, 7/14).
Characteristics of maternal cases
The characteristics of the 14 maternal listeriosis cases of pregnancy-associated listeriosis were summarized in table 1. Among them, 13 (M1-11, 13, 14) were singleton pregnancies and 1 (M12) was a twin pregnancy. Positive L. monocytogenes cultures from blood, amniotic fluid or placental tissue samples were found in eight (57.1%, 8/14) mothers.
Table 1. Characteristics of maternal listeriosis cases
No.
|
Gestation
|
Clinical presentation
|
Culture sites
|
MSAF
|
WBC (109/L)
|
CRP (mg/L)
|
Mode of delivery
|
Antibiotic(s)
Before Delivery
|
Admission-delivery interval(hour/s)
|
Concomitant
disease
|
Maternal outcome
|
Neonatal/fetal outcome
|
Blood
|
Amniotic fluid
|
Placental tissue
|
M1
|
38
|
None
|
/
|
/
|
/
|
No
|
8.5
|
4.7
|
Cesarean section
|
Cefuroxime
|
24
|
Pelvic adhesions
|
Recovered
|
Survived
|
M2
|
32
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Vaginal delivery
|
NA
|
NA
|
NA
|
NA
|
Death, neonatal listeriosis
|
M3
|
26
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Vaginal delivery
|
NA
|
NA
|
NA
|
NA
|
Death, neonatal listeriosis
|
M4
|
30
|
Fever Tmax 38.2℃, Abd pain, vaginal bleeding
|
/
|
/
|
/
|
Yes
|
19.0
|
25
|
Vaginal delivery
|
Cefuroxime
|
22.5
|
GDM, HSP
|
Recovered
|
Survived, neonatal listeriosis
|
M5
|
29
|
Abd pain, vaginal bleeding, RFM
|
/
|
/
|
/
|
Yes
|
13.9
|
54.4
|
Vaginal delivery
|
No
|
4
|
Chorioamnionitis
|
Recovered
|
Survived, neonatal listeriosis
|
M6
|
34
|
RFM
|
/
|
/
|
/
|
Yes
|
17.3
|
30
|
Cesarean section
|
Azithromycin
|
3.5
|
Thrombophilia, chorioamnionitis
|
Recovered
|
Survived, neonatal listeriosis
|
M7
|
30
|
Abd pain, vaginal bleeding
|
/
|
(+)
|
(+)
|
Yes
|
27.6
|
56.8
|
Cesarean section
|
Piperacillin and sulbactam
|
10
|
URI, HBV carrier, Ovarian teratoma
|
Recovered
|
Survived, neonatal listeriosis
|
M8
|
30
|
Fever Tmax 39.7℃
|
(+)
|
(+)
|
(+)
|
Yes
|
17.0
|
52.9
|
Cesarean section
|
Ceftriaxone
|
1
|
GBS colonization, chorioamnionitis, sepsis, moderate anemia, Gallbladder polyps
|
Recovered
|
Survived, neonatal listeriosis
|
M9
|
37
|
Abd pain
|
(+)
|
/
|
/
|
No
|
7.1
|
64
|
Cesarean section
|
Cefuroxime
|
1
|
Chorioamnionitis, sepsis
|
Recovered
|
Survived, neonatal listeriosis
|
M10
|
28
|
Abd pain, ROM, flu-like symptoms
|
/
|
(+)
|
(+)
|
Yes
|
24.8
|
62.8
|
Cesarean section
|
Ceftriaxone
|
1.5
|
Chorioamnionitis,
|
Recovered
|
Death, neonatal listeriosis
|
M11
|
32
|
Abd pain, ROM
|
/
|
(+)
|
/
|
No
|
23.6
|
35
|
Cesarean section
|
Piperacillin and sulbactam+ Metronidazole
|
5.5
|
No
|
Recovered
|
Survived
|
M12
|
36
|
Fever Tmax 38.4℃
|
/
|
(-)
|
(+)
|
No
|
24.0
|
85.2
|
Cesarean section
|
Cefotaxime
|
4
|
Chorioamnionitis, hyperthyroidism, polycystic ovarian syndrome
|
Recovered
|
Survived
|
M13
|
18
|
Fever Tmax 38℃, Abd pain, ROM, vaginal bleeding
|
(-)
|
(+)
|
/
|
No
|
17.2
|
96.9
|
Inevitable miscarriage
|
Piperacillin and sulbactam
|
17.5
|
Chorioamnionitis, Mild anemia
|
Recovered
|
Intrauterine fetal death
|
M14
|
35
|
Fever Tmax 38℃, Abd pain
|
(-)
|
(+)
|
(+)
|
Yes
|
23.1
|
36.3
|
Cesarean section
|
Ceftriaxone
|
3.5
|
Bilateral mesosalpinx cyst
|
Recovered
|
Survived
|
MSAF meconium-stained amniotic fluid, WBC white blood cell, CRP C-reactive protein, NA not available, Tmax maximal temperature, Abd pain abdominal pain, GDM gestational diabetes mellitus, HSP hereditary spastic paraplegia, RFM reduced fetal movements, URI upper respiratory infection, HBV hepatitis B virus, GBS Group B streptococcus, ROM rupture of membranes.
Two cases were infected with L. monocytogenes in the second trimester pregnancy (between 14 and 27 weeks), and others were infected in the trimester pregnancy (between 28 and 41 weeks). Their median gestational age at the time of infection was 31 weeks (range: 18-38 weeks). Among the 14 maternal patients, 12 had premature deliveries, 1 experienced intrauterine fetal death and 1 had term delivery.
One of the 14 maternal patients experienced inevitable miscarriage, 4 had nature labor, and caesarean sections were performed in 9 cases, 8 due to fetal distress or intrauterine infection, 1 due to scarred uterus. Among the 12 mothers who delivered in this hospital, 41.7% (5/12) had prenatal fever at admission, only one patient (1/12, 8.3%) had flu-like symptoms before delivery. No patient with gastrointestinal symptoms before delivery has been observed, and only one patient had diarrhea after delivery. Various obstetrical symptoms were observed, including abdominal pain (8/12, 66.7%), vaginal bleeding (4/12, 33.3%), rupture of membranes (9/12, 75.0%), and reduced fetal movement (2/12, 16.7%).
83.3% (10/12) maternal listeriosis patients had leukocytosis, and 91.7% (11/12) had elevated CRP levels. 58.3% (7/12) maternal cases had meconium-stained amniotic fluid (MSAF), and 58.3% (7/12) had chorioamnionitis. 91.7% (11/12) mothers were treated with pre-delivery antibiotics, but none received antepartum first-line empirical treatment (ampicillin or in combination with gentamicin). All of them eventually recovered after delivery shortly with no sequelae. However, the perinatal data of two maternal patients who delivered outside this hospital were unacquirable for analysis.
Characteristics of the neonatal cases
The characteristics of neonatal listeriosis cases were summarized in table 2. There were 11 culture-confirmed cases and 3 probable cases.
Table 2. Characteristics of neonatal cases
No.
|
Sex
|
GA
(wk)
|
BW (g)
|
Apgara
|
Clinical presentation
|
Culture sites
|
Intuba-
tion
|
WBC (109/L)
|
PLT (109/L)
|
Empirical antibiotic treatment
|
Complications
|
Outcome
|
Blood
|
Gastric fluid
|
Others
|
B1
|
F
|
38
|
3760
|
9-10
|
Fever Tmax 38.1℃
|
(+)
|
/
|
/
|
No
|
8
|
171
|
Amoxicillin and
Clavulanate Potassium
|
Septicemia, patent foramen ovale
|
A
|
B2
|
F
|
32
|
1650
|
5-8
|
RD, apnea, cyanosis, petechiae
|
(+)
|
/
|
Catheter (+)
|
No
|
9.6
|
220
|
Azlocillin
|
Abnormal liver function, pneumonia, septicemia, preterm birth, low birth weight
|
D
|
B3
|
F
|
26
|
1000
|
4-4
|
RD, apnea, petechiae, rash, cyanosis
|
(+)
|
/
|
/
|
Yes
|
6.3
|
103
|
Penicillin
|
Pneumonia, extremely premature infant, very low birth weight
|
D
|
B4
|
M
|
30
|
1650
|
5-7
|
RD, apnea, cyanosis
|
(+)
|
(+)
|
Eye secretions (+)
|
Yes
|
3.0
|
100
|
Penicillin + Meropenem
|
Septicemia, purulent meningitis, pneumonia, congenital heart disease, neonatal anaemia, BIPI, neonatal intracranial hemorrhage, premature infant, low birth weight
|
A
|
B5
|
F
|
29
|
1350
|
7-8
|
RD, apnea, hypoglycemia, cyanosis, DOIC 5min
|
(+)
|
(+)
|
Sputum (+)
|
Yes
|
18.4
|
111
|
Cefotiam+ Penicillin
|
Pneumonia, septicemia, purulent meningitis, neonatal aneamia, BPD, hypoglycemia, premature infant, very low birth weight, apnea neonatorum
|
A
|
B6
|
M
|
34
|
2250
|
1-6
|
RD, apnea, lethargy, DOIC 5min
|
(+)
|
(+)
|
/
|
Yes
|
9.2
|
177
|
Penicillin+ Ceftazidime
|
Sepsis, Pneumonia, PDA, preterm birth, low birth weight
|
A
|
B7
|
F
|
30
|
1400
|
6-9
|
RD, apnea, DOIC 1min
|
(+)
|
(+)
|
/
|
Yes
|
12.3
|
186
|
Penicillin + Meropenem
|
Pneumonia, septicemia, purulent meningitis, aneamia, ROP, preterm birth, low birth weight
|
A
|
B8
|
M
|
30
|
1900
|
5-7
|
RD, apnea, cyanosis, DOIC 5min
|
(+)
|
(+)
|
/
|
Yes
|
9.3
|
35
|
Vancomycin+ Meropenem
|
Sepsis, shock, respiratory failure, cardiac insufficiency, AKI, capillary leak syndrome, purulent meningitis, intracranial hemorrhage, seizure, patent ductus arteriosus, coagulation disorders, thrombocytopenia, aneamia, low birth weight, preterm birth, pneumorrhagia, hypoproteinemia, pneumonia, hypernatremia
|
A
|
B9
|
F
|
37
|
2700
|
9-10
|
Lethargy, rash
|
(+)
|
/
|
/
|
Yes
|
1.5
|
115
|
Penicillin+ Ceftazidime
|
Sepsis, septic shock, respiratory failure, pneumonia, acidosis, coagulation disorders, thrombocytopenia, hypoproteinemia, seizure, hypocalcemia, purulent meningitis, acute renal injury
|
A
|
B10
|
M
|
28
|
1250
|
8-9
|
RD
|
(-)
|
(+)
|
/
|
Yes
|
13.5
|
140
|
Penicillin + Meropenem
|
Respiratory failure, pneumonia, septicemia, very low birth weight, preterm birth, patent ductus arteriosus, hypoproteinemia, aneamia, congenital hypothyroidism
|
D
|
B11
|
F
|
32
|
1600
|
9-10
|
RD
|
(-)
|
/
|
/
|
No
|
19.6
|
350
|
Azlocillin
|
Pneumonia, preterm birth, low birth weight
|
A
|
B12.1
|
F
|
36
|
2550
|
9-10
|
RD, lethargy
|
(-)
|
/
|
/
|
No
|
19.6
|
236
|
Ceftazidime
|
Pneumonia, preterm birth
|
A
|
B12.2
|
M
|
36
|
2250
|
9-10
|
RD, lethargy, petechiae
|
(-)
|
/
|
/
|
No
|
16.2
|
223
|
Ceftazidime
|
Pneumonia, preterm birth, low birth weight
|
A
|
B13
|
M
|
35
|
2570
|
9-10
|
Cyanosis
|
(-)
|
(+)
|
/
|
No
|
17.5
|
230
|
Penicillin+ Ceftazidime
|
Pneumonia,preterm birth, septicemia, neonatal hypocalcemia, neonatal anemia, neonatal hypokalemia, ASD
|
A
|
a Apgar score at 1st min - 5th min,
GA gestational age, BW birth weight, PLT platelet, A alive, RD respiratory distress, D dead, BIPI brain injure in premature infants, DOIC delay of initial crying, BPD bronchopulmonary dysplasia, PDA patent ductus arteriosus, ROP retinopathy of prematurity, AKI acute kidney injur, ASD atrial septal defect
Culture-confirmed neonatal listeriosis cases
In the 11 culture-confirmed cases, blood and newborn gastric fluid were the sensitive samples for microbiological diagnosis (positive in 9 [81.8%] of 11 blood samples and 7 [100.0%] of 7 gastric fluid samples), 9 (81.8%) were inborn neonates and 2 (18.2%) were outborn neonates, 6 (54.5%) were female and 5 (45.5%) were male. Most of them were preterm infants (9/11, 81.8%), with a median gestational age (GA) of 30 weeks (range: 26-38 weeks) and a median birth weight (BW) of 1650g (range: 1000-3760g), 8 (72.7%) weighed <2500g and 4 (36.4%) weighed <1500g.
Most of the 11 confirmed neonatal listeriosis cases were early onset (90.9%, 10/11) (B2-B10, B13). Among the 10 early onset cases, 8 cases (80.0%, 8/10) had respiratory distress and 7 case (70.0%, 7/10) received resuscitation at birth. The late onset one was a female who was delivered by caesarean section at GA of 38 weeks, and admitted to hospital with fever for one day at 8 days after birth.
Laboratory analysises were performed immediately on admission. Thrombocytopenia was observed in 54.5% (6/11) of culture-confirmed cases. Cerebrospinal fluid tap was performed in 81.8% (9/11) of neonates, and 4 of them were diagnosed as purulent meningitis, however, their CSF culture were all negative. Cranial imaging revealed intracranial hemorrhage in 2 neonates (B4 and B8), and one of them (B4) was diagnosed as brain injure in premature infants (BIPI).
All of the neonates with confirmed listeriosis were treated empirically, and most of them treated with Penicillin or Cephalosporin or Meropenem. Eight newborns received intubation. Three neonates (B2, B3 and B10) died, and two of them were outborn.
Probable neonatal listeriosis cases
Three newborns (B11, B12.1 and B12.2) were identified as probable neonatal listeriosis cases, including a pair of twins (B12.1 and B12.2). Both of their mothers were confirmed maternal listeriosis, but the culture results for these three neonates were negative. All of them were preterm infants, with GA of 32, 36 and 36 weeks, and BW of 1600g, 2550g and 2250g, respectively. They all had respiratory distress at birth, and were diagnosed as pneumonia subsequently, their laboratory parameters were mild abnormal. All of them were recovered soon after birth.
Risk factors for mortality in neonates with pregnancy-associated listeriosis
We compared the characteristics of the surviving neonates (n=11) with those of the non-surviving neonates (n=3), trying to identify risk factors for mortality in neonates with pregnancy-associated listeriosis (Table 3).
Fatality rates were significantly higher in outborn neonates (P=0.005). Besides, higher mortality rates were observed in neonates with lower BW (P=0.038), GA <28 weeks (P=0.056), and Apgar score (5th min) <5 (P=0.056), with marginally significant differences.
Table 3. Comparison between the survival and fatal cases of pregnancy-associated listeriosis
|
Survival
(n=11)
|
Fatality
(n=3)
|
P value
|
BW
|
|
|
|
BW (g)a
|
2250 (1600-2570)
|
1250 (1000-1650)
|
0.038
|
VLBW<1500g
|
2 (18.2%)
|
2 (66.7%)
|
0.112
|
GA
|
|
|
|
GA (weeks)a
|
34 (30-36)
|
28 (26-32)
|
0.060
|
GA < 28 weeks
|
0 (0.0%)
|
1 (33.3%)
|
0.056
|
Apgar score
|
|
|
|
Apgar score (1stmin)a
|
9 (5-9)
|
5 (4-8)
|
0.225
|
Apgar score (1st min) <5
|
1 (9.1%)
|
1 (33.3%)
|
0.305
|
Apgar score (5thmin)a
|
10 (7-10)
|
8 (4-9)
|
0.225
|
Apgar score (5th min) <5
|
0 (0.0%)
|
1 (33.3%)
|
0.056
|
Outborn (n, %)
|
0 (0.0%)
|
2 (66.7%)
|
0.005
|
Clinical Presentation
|
|
|
|
Respiratory distress
|
8 (72.7%)
|
3 (100.0%)
|
0.325
|
Apnea
|
5 (45.5%)
|
2 (66.7%)
|
0.530
|
Cyanosis
|
3 (27.3%)
|
2 (66.7%)
|
0.224
|
Laboratory parameters
|
|
|
|
WBC, 109/La
|
12.3 (8.0-18.4)
|
9.6 (6.3-13.5)
|
0.659
|
PLT, 109/La
|
177 (111-230)
|
140 (103-220)
|
0.659
|
a Median(ranges),
BW birth weight, VLBW very low birth weight, GA gestational age, WBC white blood cell, PLT platelet