Abstract
Background
Pregnancy-associated listeriosis caused by foodborne infections poses a significant threat to maternal and neonatal health, with a high mortality rates. There is limited data on epidemiology of pregnancy-associated listeriosis in southeastern China (Xiamen), and we will report it in this study.
Methods
A retrospective analysis was conducted on confirmed cases of pregnancy-associated listeriosis in Xiamen from 2015 to 2023. Patient data was extracted from the hospital’s electronic medical records. Data analysis and epidemiological investigations were performed based on demographic information, onset time, clinical and laboratory characteristics. Antibacterial susceptibility testing was conducted on isolated Listeria monocytogenes (LM) strains using the broth microdilution method.
Results
In Xiamen, pregnancy-associated listeriosis incidence over 9 years was 7.15/100,000 (9/125,816) deliveries, with sporadic cases. Predominant symptoms among pregnant women included fever (88.9%), abdominal pain (66.7%), decreased fetal movement (66.7%), fetal tachycardia (66.7%), and flu-like symptoms (55.6%). Elevated neutrophil percentages (NE%), C-reactive protein (CRP), and procalcitonin (PCT) were observed in all pregnant women. Placental pathology consistently showed acute chorioamnionitis and micro-abscesses. Although all pregnant women recovered, out of 10 offspring, only 5 survived birth, and merely 3 were eventually cured, resulting in a feto-neonatal mortality rate of 70.0% (7/10). All LM strains showed susceptibility to ampicillin, penicillin, meropenem, erythromycin, and trimethoprim-sulfamethoxazole (SXT).
Conclusions
Although pregnancy-associated listeriosis is rare in Xiamen, it can have catastrophic effects on fetuses. Its atypical clinical features require timely testing in cases of inflammation and infection signs, stressing the significance of prevention awareness and prompt medical intervention.
Keywords: Pregnancy, Listeria monocytogenes, Foodborne infectious disease, Neonate
Introduction
Listeria monocytogenes (LM) is an intracellular aerobic or facultative anaerobic Gram-positive bacterium. Due to its psychrophilic nature, LM can survive and grow at different pH values, temperatures, and high salt concentrations. The pathogen is almost ubiquitous in nature and can be isolated from soil, water sources, fruits, vegetables, dairy products, raw meat, ready-to-eat foods, and even frozen foods. Consequently, LM is often transmitted to humans through the consumption of contaminated food. Pregnant women are particularly susceptible to LM infection, with incidence rates 12–20 times higher than those of the general population Pregnant women infected with LM often exhibit flu-like symptoms, such as fever, headache, diarrhea, muscle pain, or other digestive-related symptoms [1, 2]. However, the consequences can be severe, potentially resulting in premature birth, miscarriage, sepsis, central nervous system (CNS) involvement, and even death, with a mortality rate of up to 57.1% [3]. In Europe, the incidence of LM infection ranges from 0.1 to 11.3 per million people, with approximately 20% of cases affecting perinatal pregnant women or newborns [4]. However, to the best of our knowledge, there have been no reports on the study of LM infection among pregnant women in Xiamen, a city situated in southeastern China with a current permanent population exceeding 5 million [5]. This study aims to investigate the occurrence of pregnancy-associated listeriosis at a tertiary maternal and child health hospital (Women and Children’s Hospital, School of Medicine, Xiamen University, China) with 700 beds in southeastern China from 2015 to 2023. It will analyze the clinical and laboratory characteristics of mothers and infants after infection and conduct antibacterial susceptibility testing on isolated strains to provide research data supporting clinical diagnosis and treatment.
Methods
This study was conducted in compliance with the 2013 revised Helsinki Declaration and received review and approval from the Ethics Committee of Xiamen Maternal and Child Health Hospital (KY-2023-074-H01).
This retrospective study included 9 pregnant women and their newborns who were admitted to Xiamen Maternal and Child Health Hospital from 2015 to 2023. They were diagnosed with pregnancy-associated listeriosis during pregnancy or within the first 4 weeks postpartum through microbial culture of sterile sites such as whole blood, amniotic fluid, placental swab, cerebrospinal fluid, tracheal sputum, or neonatal gastric fluid [6]. Newborn cases were categorized as early-onset (diagnosed within 7 days of birth) and late-onset (diagnosed between 7 and 28 days of birth). If LM is detected in blood culture, it is considered that the patient has sepsis. Similarly, if LM is identified in cerebrospinal fluid culture, it is considered that the patient has a central nervous system infection [3]. To conduct a comprehensive statistical analysis, retrieve demographic information, clinical manifestations, laboratory test results, complications, and outcomes from electronic medical records of patients.
The term “stillbirth” refers to fetal death that occurs between 24 and 41 weeks of pregnancy, while fetal loss before 24 weeks is referred to as inevitable miscarriage [3]. Furthermore, we calculated the overall feto-neonatal mortality rate of pregnancy-associated listeriosis, which includes miscarriage, stillbirth, and newborn deaths.
Blood cultures were performed using Bactec blood culture bottles (Becton Dickinson, USA). Amniotic fluid, cervical secretions, placental swabs, and neonatal gastric fluid were cultured on blood agar plates, while tracheal sputum and cerebrospinal fluid were cultured on a combination of blood and chocolate agar plates. The suspicious bacterial isolates were cultured and isolated using traditional blood agar plate laying methods. The isolated colonies were then automatically confirmed using the Phoenix 100 ID/AST system (Becton Dickinson, USA) for biochemical identification. Additionally, CAMP testing and catalase testing were performed on the isolated colonies. The isolated bacterial strains were tested for antimicrobial susceptibility using a manual broth microdilution method with commercial reagent kits (Corynebacterium ID/AST test kit, Zhuhai DL Biotech. Co., LTD), following the manufacturer’s instructions. The tested antibiotics included ampicillin, penicillin, meropenem, erythromycin, trimethoprim-sulfamethoxazole (SXT), levofloxacin, vancomycin, tetracycline, rifampicin, gentamicin, ceftriaxone, cefotaxime, and cefepime. Antimicrobial susceptibility was determined based on the clinical breakpoints and recommendations of the European Committee on Antimicrobial Susceptibility Testing (EUCAST) [7].
Statistical analysis was conducted using SPSS 22.0 (IBM, Armonk, NY, USA). Descriptive statistics were employed to summarize the data in this study where data was presented as mean ± standard deviation (M ± SD), median, minimum, and maximum values. Categorical data was reported in numerical form as percentages.
Results
From 2015 to 2023, a total of 125,816 pregnant women gave birth at our hospital, all residing in Xiamen and its surrounding areas. Among them, 9 cases of pregnancy-associated listeriosis were identified, with an incidence rate of 7.15/100,000, consisting of 8 singleton pregnancies and 1 twin pregnancy. Patient outcomes exhibited considerable variation, notably, a fetal mortality rate of 70%, involving 4 instances of intrauterine death (including the twin pregnancy), 2 post-delivery neonatal deaths, and successful treatment of 3 neonates after birth. Detailed information regarding these cases and their attributes can be found in Table 1.
Table 1.
Characteristics of 9 maternal and 10 neonatal cases of pregnancy-associated listeriosis
| Group | Maternal | Neonatal |
|---|---|---|
| Total, n | 9 | 10 |
| Median age (min, max), y | 30 (24, 36) | |
| Median gestation at Delivery (min, max), wk | 31.1 (13.6, 39.1) | |
| Clinical manifestations, n(%) | ||
| Fever | 8 (88.9) | |
| Gastrointestinal symptoms | 2 (22.2) | |
| Flu-like symptoms | 5 (55.6) | |
| Abdominal pain | 6 (66.7) | |
| Decreased fetal movement | 6 (66.7) | |
| Fetal tachycardia | 6 (66.7) | |
| Vaginal bleeding | 3 (33.3) | |
| Abdominal tightness | 2 (22.2) | |
| Abnormal vaginal discharge | 2 (22.2) | |
| Laboratory findings | ||
| WBC, median (min, max), 109/L | 17.3 (6.5, 31.4) | 16.6 (4.5, 19.5)a |
| NE%, median (min, max) | 82.5 (58.6, 92.9) | 68.7 (42.1, 72.8)a |
| M%, median (min, max) | 6.9 (4.0, 7.5) | 5.0 (2.9, 12.7)a |
| CRP, median (min, max), mg/mL | 64.2 (15.2, 132.3) | 93.2 (64.0, 263.1)a |
| PCT, median (min, max), (ng/mL) | 0.16 (0.09, 0.41) | 2.98 (0.25, 69.05)a |
| ALT, median (min, max), U/L | 15 (8, 31) | 53 (9, 100)a |
| AST, median (min, max), U/L | 18 (16, 31) | 90 (63, 658)a |
| Hospital stays, median (min, max), d | 7 (5,19) | 10 (3, 46)a |
| Weight, median (min, max), g | 1688 (1450, 2960)a | |
| Mortality, n(%) | 0 (0%) | 7 (70.0%) |
aOnly 5 live births were counted
Abbreviations: min minimum, max maximum, WBC white blood cell count, NE% neutrophil percentage, M% monocytes percentage, CRP C-reactive protein, PCT procalcitonin, ALT glutamic-pyruvic transaminase, AST glutamic oxaloacetic transaminase
According to seasonal statistics, among the nine cases of pregnancy-associated listeriosis, there were 4 cases (44.44%) in spring and summer respectively, and one case in winter (11.11%) (Fig. 1A). Annual data analysis revealed a sporadic pattern of listeriosis cases without evidence of concentrated outbreaks (Fig. 1B).
Fig. 1.
Incidence and seasonal variation of pregnancy-associated listeriosis cases from 2015 to 2023. A seasonal distribution and incidence of perinatal listeriosis cases. B annual distribution and incidence of perinatal listeriosis cases
Clinical characteristics and outcomes of maternal listeriosis cases
Nine cases of pregnancy-associated listeriosis were reported, with a median age of 30 years and a median gestational age of 31.1 weeks (range: 13.6–39.1 weeks). All patients were discharged after successful recovery. Two cases (22.2%) occurred during the second trimester of pregnancy (between 14 and 27 weeks), while seven cases (77.8%) occurred during the third trimester of pregnancy (between 28 and 41 weeks). Among the clinical manifestations, 8 cases (88.9%) experienced prenatal fever (38℃-40℃), 5 cases (55.6%) had flu-like symptoms lasting from 1 to 5 days, and only 2 cases (22.2%) experienced gastrointestinal discomfort. Pregnancy-associated listeriosis also presented various obstetric symptoms, including decreased fetal movement, fetal tachycardia, abdominal pain, abdominal tightness, vaginal bleeding, abnormal vaginal secretions, and others. Premature birth resulting from intrauterine LM infection may explain these symptoms. Additionally, pregnant women commonly experience complications such as anaemia, umbilical cord entanglement, cord torsion, and breech presentation (see Table 2 for details). Notably, four women had upper respiratory tract infections, possibly linked to the LM infection. All patients received antibiotic treatment, with 4 cases (44.4%) receiving a single cephalosporin antibiotic. Ultimately, among the 9 cases of pregnancy-associated listeriosis, 4 resulted in preterm birth, 2 ended in inevitable miscarriage, 2 had intrauterine fetal death, and only 1 had a full-term delivery.
Table 2.
Clinical characteristics and outcomes of 9 pregnancy-associated listeriosis cases
| No. | Age (years) | Gertation (wk) | Culture sites | Obstetrical manifestations | Initial antibiotic | Switch antibiotic | Complications and outcomes | Hospital stays (d) | WBC, 109/L | NE% | M% | CRP, mg/mL | PCT, ng/mL | ALT, U/L | AST, U/L |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A | 27 | 13.6 | placental swab; cervical secretions | slight vaginal bleeding for 4d, abdominal pain. Tmax: 40℃ | CXM 4d | AMP + GEN 7d; AMP 3d |
inevitable miscarriage; intrauterine infection; moderate anemia; upper respiratory tract infection recovered |
19 | 15.7 | 79% | 6.90% | 116.5 | 0.41 | 8 | 17 |
| B | 30 | 15.7 | placental swab | abdominal pain, abdominal tightness, feeling of bloating in the lower abdomen, slight vaginal bleeding, fetal tachycardia. Tmax: 38.8℃ | CTX + MTR 3d | TZP 3d |
inevitable miscarriage; intrauterine infection recovered |
10 | 6.53 | 82.50% | 4.60% | 26.64 | 0.19 | 31 | 17 |
| C | 28 | 38.3 | placental swab; blood; amniotic fluid | abdominal tightness, decreased fetal movement, increased vaginal discharge and foul odor, fetal tachycardia. Tmax: 38.1℃ | TZP + MTR + MFX 2d | AMP 4d |
stillbirth; intrauterine infection; bacteremia; gestational diabetes mellitus; umbilical cord torsi; mild anemia; recovered |
6 | 31.35 | 90.50% | 4.00% | 132.26 | 0.19 | 18 | 18 |
| D | 30 | 31.1 | placental swab | flu like symptoms for 1d, decreased fetal movement, slight vaginal bleeding, fetal tachycardia. Tmax: 38.4℃ | TZP + MTR + MFX 8d | - |
stillbirth; intrauterine infection; nuchal cord; breech presentation; mild anemia; upper respiratory tract infection recovered |
8 | 24.3 | 84.60% | 7.40% | 111.3 | 0.09 | 13 | 18 |
| E | 36 | 31.1 | placental swab | flu like symptoms for 5d, decreased fetal movement, irregular abdominal pain. Tmax: 39.1℃ | CTX 2d | AMP 1d; AMX 2d |
premature delivery; intrauterine infection; mild anemia; GBS infection in the reproductive tract; upper respiratory tract infection recovered |
5 | 20.1 | 87.80% | 4.90% | 64.18 | 0.16 | 18 | 16 |
| F | 35 | 29.6 | placental swab; cervical secretions | flu like symptoms for 2d, abdominal pain, pale brown vaginal discharge, decreased fetal movement, fetal tachycardia. Tmax:39.1℃ | CTX 2d | AMP 4d |
premature delivery; intrauterine infection; nuchal cord; fetal distress; mild anemia; advanced maternal age; recovered |
7 | 16.11 | 75.10% | 5.20% | 58.2 | 0.22 | 15 | 18 |
| G | 30 | 39.1 | placental swab | abnormal fetal position. Tmax: 36.5℃ | CTX + MTR 2d | CLI + MTR 4d |
C-section; intrauterine infection; fetal distress; mild anemia; breech presentation; recovered |
7 | 11.1 | 58.60% | 7.50% | 15.2 | 0.15 | 14 | 23 |
| H | 28 | 34.9 | placental swab | flu like symptoms for 3d, abdominal pain, decreased fetal movement, fetal tachycardia. Tmax: 38.0℃ | CTX + MTR + MFX 2d | AMP + GEN 5d |
premature delivery; intrauterine infection; fetal distress; umbilical cord torsi; mild anemia; breech presentation; recovered |
10 | 17.3 | 70.80% | 7.50% | 95.5 | 0.13 | 25 | 31 |
| I | 24 | 32.6 | placental swab | flu like symptoms for 1d, abdominal pain, decreased fetal movement, fetal tachycardia. Tmax: 39.8℃ | CTX 2d | TZP + MTR + MFX 3d |
premature delivery; intrauterine infection; umbilical cord torsi; mild anemia; fetal distress; thyroid nodule; upper respiratory tract infection recovered |
6 | 24.37 | 92.90% | 7.50% | 62.25 | 0.1 | 14 | 19 |
Abbreviations: CXM cefuroxime, TZP piperacillin/ tazobactam, GEN gentamicin, AMP ampicillin, CLI clindamycin, AMX amoxicillin, MFX moxifloxacin, MTR metronidazole, CTX cefotaxime
All 9 affected individuals had LM identified in placental swabs, with 2 cases also exhibiting LM in cervical secretions. One case presented LM in both blood and amniotic fluid cultures. Substantial increases in neutrophil percentage (NE%), C-reactive protein (CRP), and procalcitonin (PCT) levels were observed across all patients (Table 2). Histopathological examination of the placenta consistently showed signs of acute chorioamnionitis (Grade II-III) and micro-abscess formation (Fig. 2). The median hospital stay for these cases was 7 days, ranging from 5 to 19 days. Their hospitalization duration is not significantly different. Postpartum recovery was complete for all patients, with no sequelae reported during a six-month follow-up period. Remarkably, one patient identified LM in a placental swab culture during the third trimester (39.1 weeks) without exhibiting any symptoms, and her newborn remained uninfected.
Fig. 2.
Pathologic examination of placental tissue from patient I: acute chorioamnionitis and micro-abscess formation (hematoxylin and eosin stained, ×400 magnification)
Clinical characteristics and outcomes of listeriosis infections in offspring
The clinical features and outcomes of 10 offspring were detailed in Table 3. There were three inevitable miscarriages and two stillbirths occurred, and five live births were delivered with a median weight of 1688 g (range 1450–2960 g). Four out of five live births were diagnosed with early-onset LM infection (1 cases of gastric fluid + tracheal sputum; 3 cases of blood + gastric fluid + tracheal sputum), of which three had sepsis. The remaining newborn was fortunately not infected. Initially, all live births received advanced antibiotics, such as TZP or MEM. Unfortunately, two live births passed away on the 3rd and 4th days after birth, leaving only three newborns cured. The hospital stays lasted 10, 33, and 46 days, respectively. No late-onset LM infection was observed in newborns. All live births showed an increase in CRP, PCT, glutamic-pyruvic transaminase (ALT), and glutamic oxaloacetic transaminase (AST), with 4 cases (80%) showing an increase in white blood cell count.
Table 3.
Clinical characteristics and outcomes among the 10 neonates in the 9 pregnancy-associated listeriosis cases
| No. | Birth weight(g) | Culture sites | Apgar score | Initial antibiotic | Switch antibiotic | Complications | Outcomes | Hospital stays (d) | WBC, 109/L | NE% | M% | CRP, mg/mL | PCT, ng/mL | ALT, U/L | AST, U/L |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A.1/A.2 | -/- | - | - | - | - | inevitable miscarriage/inevitable miscarriage | death/death | - | - | - | - | - | - | - | - |
| B | - | - | - | - | - | inevitable miscarriage | death | - | - | - | - | - | - | - | - |
| C | 1690 | - | - | - | - | stillbirth | induced labor | - | - | - | - | - | - | - | - |
| D | 1660 | - | - | - | - | stillbirth | induced labor | - | - | - | - | - | - | - | - |
| E | 1688 | gastric juice; endotracheal sputum | 6 | TZP 1d | MEM + AMP 3d | preterm birth; infant listeriosis; neonatal pulmonary hyaline membrane disease; pneumonia; neonatal ABO hemolysis; myocardial damage; low birth weight. | deceased day 5 | 3 | 19.5 | 42.10% | 5.00% | 76.54 | 0.25 | 53 | 90 |
| F | 1450 | blood; gastric juice; endotracheal sputum | 6 | MEM + AMP 4d | No | preterm birth; infant listeriosis; neonatal intracranial hemorrhage; neonatal respiratory distress syndrome; neonatal respiratory failure; disseminated intravascular coagulation; neonatal septic shock; neonatal multiple organ failure; neonatal pneumonia; neonatal anemia (severe); neonatal pulmonary hypertension; high risk infants (low Apgar score); extremely low birth weight | deceased day 5 | 4 | 13.89 | 45.30% | 5.00% | 118.03 | 69.05 | 90.9 | 658 |
| G | 2960 | No | 10 | MEM 5d | TZP 5d | caesarean; neonatal pneumonia; neonatal hypoglycemia | survived | 10 | 18.06 | 72.8 | 12.70% | 93.2 | 8.74 | 9 | 63 |
| H | 1970 | blood; gastric juice; endotracheal sputum | 5 | CTX + MTR + MFX 2d | AMP + GEM 5d | preterm birth; infant listeriosis; neonatal purulent meningitis; neonatal meconium aspiration pneumonia; neonatal mild asphyxia; neonatal mixed acidosis; neonatal anemia (moderate); neonatal hypoalbuminemia; low birth weight | survived | 33 | 16.58 | 68.70% | 11.70% | 263.06 | 0.26 | 26 | 94 |
| I | 1602 | blood; gastric juice; endotracheal sputum | 5 | TZP + MEM 3d | AMP + MEM 28d | preterm birth; infant listeriosis; neonatal pulmonary hyaline membrane disease; pneumonia; neonatal hypoglycemia; neonatal purulent meningitis; neonatal myocardial damage; growth retardation; bronchopulmonary dysplasia; neonatal anemia (moderate); neonatal hypoalbuminemia; high risk infants (low Apgar score); low birth weight | survived | 46 | 4.53 | 68.80% | 2.90% | 63.97 | 2.98 | 100 | 85 |
Abbreviations: MEM meropenem
Antibacterial susceptibility testing
The isolated LM strains underwent antimicrobial susceptibility testing, and the results were presented in Table 4 (the antimicrobial susceptibility phenotypes of the strains isolated from newborns and mothers are completely consistent and thus not listed separately). As per the EUCAST clinical breakpoints, the LM strains we isolated exhibited susceptibility to ampicillin, penicillin, meropenem, erythromycin, and SXT, with lower MIC values observed for other antibiotics lacking clinical breakpoints (e.g., levofloxacin, vancomycin, tetracycline, rifampicin, and gentamicin).
Table 4.
The antibacterial susceptibility testing of 9 invasive LM isolates collected from pregnancy-associated listeriosis cases
| Patient ID | AMPa | PENa | MEMa | ERYa | SXTa | LEV | VA | TET | RIF | GEN | CRO | CTX | FEP |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A | 0.25 | 0.5 | ≤ 0.12 | 0.25 | ≤ 0.06 | 2 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| B | 0.25 | 0.5 | ≤ 0.12 | 0.25 | ≤ 0.06 | 1 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| C | 0.25 | 0.25 | ≤ 0.12 | 0.25 | ≤ 0.06 | 2 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| D | 0.25 | 0.25 | ≤ 0.12 | 0.25 | ≤ 0.06 | 2 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| E | 0.25 | 0.25 | ≤ 0.12 | 0.25 | ≤ 0.06 | 1 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| F | 0.25 | 0.25 | ≤ 0.12 | 0.25 | ≤ 0.06 | 1 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| G | 0.25 | 0.25 | ≤ 0.12 | 0.25 | ≤ 0.06 | 1 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| H | 0.25 | 0.5 | ≤ 0.12 | 0.25 | ≤ 0.06 | 2 | 1 | 1 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
| I | 0.25 | 0.5 | ≤ 0.12 | 0.25 | ≤ 0.06 | 2 | 1 | ≤ 0.5 | ≤ 0.06 | ≤ 1 | > 4 | > 4 | > 4 |
|
MIC breakpoints (S≤/R>) |
1/1 | 1/1 | 0.25/0.25 | 1/1 | 0.06/0.06 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A |
Abbreviations: AMP ampicillin, PEN penicillin, SXT trimethoprim-sulfamethoxazole (trimethoprim-sulfamethoxazole in the ratio 1:19. Breakpoints are expressed as the trimethoprim concentration.), CLI clindamycin, ERY erythromycin, TET tetracycline, DOX doxycycline, VA vancomycin, FEP cefepime, CRO ceftriaxone, CTX cefotaxime, RIP rifampicin, GEN gentamicin, DAP daptomycin, CIP ciprofloxacin, LEV levofloxacin, MEM meropenem, IPM imipenem, LNZ linezolid. Concentration unit: µg/mL, NA no available
aInterpretation according to the EUCAST clinical breakpoint value for LM
Discussion
The motivation behind this article stems from our desire to enhance awareness and strategies for the prevention and eradication of LM infection during the perinatal period. This issue, although critical, remains insufficiently acknowledged as a public health concern, endangering the well-being of pregnant individuals and newborns. Notably, the prevalence of LM infection exhibits significant variation globally, with higher incidence rates observed in certain developing regions and an uptrend in developed nations [8]. As a major coastal city in the southeast of China, Xiamen belongs to the subtropical marine monsoon season, the incidence of pregnancy-associated listeriosis is 7.15/100,000 deliveries, lower than Ningbo (an eastern city) and Xi’an (a northwestern city) in China, but higher than Beijing (a northern city) [3, 9, 10], also higher than some European countries [8, 11, 12]. The differences in economic and health levels, climate, and dietary habits of local residents in different regions may be the reasons for the varying infection rates. The humid and hot climate in Xiamen, residents’ preference for cold dishes, and high population density may lead to a higher infection rate. Furthermore, numerous studies have documented the contamination of seafood with LMs, which could potentially contribute to the higher incidence of listeriosis patients in coastal regions [5, 13, 14]. Pregnancy-associated listeriosis is sporadic, mainly concentrated in spring and summer, consistent with previous studies [9, 15]. The mortality rate of offspring with pregnancy-associated listeriosis in this study was 70.0%, higher than the 32.7%~57.1% reported in two recent systematic reviews in China [5, 16]. This could be attributed to the fact that our hospital is the sole tertiary maternity and pediatric facility in the region, catering to a significant number of critically ill pregnant women and newborns [10]. Infections contracted during the first trimester present the gravest outcomes, with a mortality rate of 100%, whereas third-trimester infections show a reduced mortality rate of 57.1%. The most severe pregnancy complication linked to listeriosis is intrauterine infection, leading to premature birth. Other complications are consistent with typical pregnancy issues. The outcomes for pregnant women were largely positive, aligning with findings from other studies [3, 5, 12, 17].
Listeriosis is primarily contracted through the consumption of foods contaminated with LM, a bacterium capable of surviving under various conditions, including refrigeration. It can be transmitted to humans through ingestion of contaminated food, such as improperly heated meat, unpasteurized dairy products, raw or improperly cleaned vegetables and fruits [18]. Currently, China does not have dietary guidelines for preventing LM infection. Therefore, strengthening education on food safety awareness among pregnant women can promote prevention [3]. It is essential to adhere to good hygiene practices, such as properly cooking or implementing suitable disinfection methods, for dairy products, meat, vegetables, and other food items. Nevertheless, while it is desirable for pregnant women to avoid consuming food that might be contaminated with LM, it is important to acknowledge that a well-balanced diet is linked to improved pregnancy outcomes [19]. Pregnant women are more susceptible and more severe after infection due to changes in their immune system during pregnancy, which may be attributed to pregnancy induced maternal T-cell suppression, as well as LM and their various virulence factors to facilitate entry into host cells and escape intracellular degradation by the host immune system [1, 17, 20, 21]. The placenta plays an essential role in protecting the fetus from external stimuli. However, once bacteria invade the villous space, the placenta may become a lesion that leads to repeated maternal infections [20]. In healthy individuals, LM infection is usually limited to mild gastrointestinal symptoms. Pregnant patients infected with LM exhibit symptoms ranging from mild respiratory symptoms to mild gastrointestinal symptoms, resembling influenza or even being asymptomatic [17]. In this study, the primary symptom in pregnant women was fever, with temperatures ranging from 38 °C to 40 °C, accompanied by early signs of premature birth such as abdominal pain, reduced fetal movement, and fetal tachycardia. The laboratory test results showed elevated levels of NE%, CRT, and PCT in all pregnant women and most newborns, indicating their potential use in diagnosing intrauterine infections. Nevertheless, these symptoms and laboratory findings do not possess distinctive characteristics. Therefore, the diagnosis of LM infection mainly relies on nucleic acid testing or microbial culture [17]. In our study, LM was cultured from placental swabs of all mothers and gastric juice from 80% of live births, highlighting the importance of microbial culture in diagnosing listeriosis through maternal placental swabs and neonatal gastric juice. In addition, histopathological evaluation of the placenta also plays an important role [1, 17]. For example, in our study, all placental histopathological examinations showed varying degrees of acute chorioamnionitis (Grade II-III) and micro-abscess formation in patients.
Currently, high-dose penicillin or ampicillin is the preferred treatment for LM infection, while meropenem or SXT can be used for patients allergic to penicillin [22–24]. The general duration of antibiotic treatment is 2 weeks from the onset of the disease to delivery of the fetus, in severe cases, the application time of antibiotics can be appropriately extended [18]. Newborns born to mothers with LM should be followed up for 2–3 months after delivery [17]. Our study revealed that as cephalosporin antibiotics are the preferred empirical treatment for non-specific obstetric infections in China, 44.4% (4/9) of pregnant women initially only received treatment with cephalosporin antibiotics. However, LM is naturally resistant to cephalosporin antibiotics, which may lead to higher mortality rates in the offspring of patients with pregnancy-associated listeriosis [9]. Meanwhile, the isolated strains have shown susceptible to penicillin, ampicillin, meropenem, and erythromycin, with low MIC values for levofloxacin, vancomycin, tetracycline, gentamicin, and linezolid (Table 4). The rarity of LM infections and the limited strain exposure to antibiotics may be reasons why LM exhibits high susceptible to these antibiotics [24, 25].
Our research still has some limitations. This is a single-centre retrospective study, spanning nine years but including only nine cases. Geographical, climatic, dietary, economic, and health differences within a single region may limit the generalisability of our findings. Additionally, the small number of bacterial strains could affect the antimicrobial susceptibility results. We therefore recommend that national or regional medical centres conduct multi-centre monitoring [10].
In conclusion, while pregnancy-associated listeriosis is extremely rare in Xiamen, it is still necessary for clinical doctors to provide food safety education to pregnant women to prevent listeriosis that can lead to catastrophic fetal outcomes. We encourage a balanced diet while avoiding excessive exposure to LMs. Due to the rarity and non-specific clinical features of LM infection, early identification of pregnancy-associated listeriosis poses a challenge. When pregnant women have strong inflammation and laboratory signs, perinatal listeriosis should be suspected., samples should be actively sent for microbiological culture and placental tissue pathology testing, while considering appropriate antimicrobial therapy [1].
Acknowledgements
We express our sincere gratitude to all the personnel in the medical record department of Xiamen University Affiliated Women and Children's Hospital. We also extend our gratitude to our colleagues and expert team members. Without their invaluable contributions, this task would not have been feasible.
Authors’ contributions
Xiaochun Fu and Ling Chen conceived of and designed the study; Huiming Ye, Xiaochun Fu, Ling Chen, Jiali Cao, Xiaoli Chen, and Hanbing Yu performed the research; Xiaochun Fu, Xiaoli Chen and Ling Chen analyzed the data; and Xiaochun Fu wrote the paper. Huiming Ye and Jiali Cao contributed to the conceptualization and supervision of the study. All authors have read and approved the submitted version.
Funding
This work was supported by grants from the Fujian Provincial Natural Science Foundation of China (No. 2024J011343), the Medical and Health Guidance Project of Xiamen (No. 3502Z20209204), the Major Science and Technology Project of the Fujian Provincial Health Commission (No. 2021ZD01006, funded by the Xiamen Municipal Health Commission), and the National Natural Science Foundation of China (No. 82102379).
Data availability
The datasets generated and analyzed during this study are available with the corresponding author, on reasonable request.
Declarations
Ethics approval and consent to participate
This study adhered to the Helsinki Declaration (2013 revision) and was approved by the Ethics Committee of Xiamen Maternal and Child Health Hospital (KY-2023-074-H01). The Ethics Committee waived the requirement for informed consent for this retrospective study. All methods were conducted in accordance with relevant guidelines and regulations.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Xiaochun Fu, Ling Chen and Xiaoli Chen contributed equally to this work and share first authorship.
References
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets generated and analyzed during this study are available with the corresponding author, on reasonable request.