Table 2. Identified bacterial infection and histopathological changes in preterm birth.
| Author, Year | Reported pathogenic microorganism | Diagnostic method | No. PTB (%) | Infection | Histopathological abnormalities | Triad of histopathology, infection and PTB |
|---|---|---|---|---|---|---|
| Cox, 2016 [30] | Mycoplasma, Ureaplasma (parvum, urealyticum), GBS, Gardnerella | RT-PCR (placental tissue) | 57/57 (100%) | U. parvum was detected in 11 (19.3%), G. vaginalis in 10 (17.5%), GBS in 9 (15.8%), and U. urealyticum in 2 (3.5%) placental samples. However, M. hominis and M. genitalium were not detected. | Histological chorioamnionitis was found in 24/57 (42.1%) preterm placentas and 26/57 (45.6%) preterm placentas had at least one bacterial infection. | Only U. parvum was significantly associated with histological chorioamnionitis in preterm placentas (OR 5.0; 95%CI 1.2–21.5, P = 0.002). |
| U. urealyticum and GBS were more common in second trimester, and G. vaginalis was more detected in third trimester samples. | U. urealyticum and GBS in 2nd trimester placental sample and G. vaginalis in 3rd trimester were not associated with histological chorioamnionitis. | |||||
| Dammann, 2003 [31] | U. urealyticum M.hominis | Culture (placental swab) | 464/464 (100%) | U. urealyticum and M. hominis were detected in 139/464 (30%) and 27/464 (6%) of placentas, respectively. Both microorganisms were positive in 21/464 (4.5%) placental samples. | Fetal vasculitis was associated with U. urealyticum (53%, P ≤0.001) and M. hominis (14%, P ≤0.001) compared to those without fetal vasculitis. | In multivariate analysis (adjusted by gestational age, duration of membrane rupture), U. urealyticum culture positive placenta was associated with increased risk of fetal vasculitis (aOR 3.4; 95%CI 2.1–5.7) compared to U. urealyticum culture negative placenta: risk increased with a short duration of membrane rupture and with a gestational age >28 weeks. |
| Hecht, 2008 [35] | Actinomyces spp, Prevotella spp, Corynebacterium spp, E.coli, Lactobacillus spp, staphylococcus spp, GBS, group D streptococcus, Alpha hemolytic streptococcus, anaerobic streptococcus, G. vaginalis, Mycoplasma spp, U. urealyticum | Culture (placental tissue) | 835/835 (100%) | 41% of cultured preterm placentas were positive; E. coli and Mycoplasma spp were most common microorganisms. | The microorganisms associated with high grade/stage inflammation of chorionic plate and fetal vasculitis were Actinomyces spp, Prevotella spp, Corynebacterium spp, E. coli, Lactobacillus spp, staphylococcus spp, GBS, group D streptococcus, Alpha hemolytic streptococcus, anaerobic streptococcus, G. vaginalis, Mycoplasma spp, U. urealyticum. | In preterm birth delivered by Caesarean section, high grade/stage inflammation of the chorionic plate (OR 4.6; 95%CI 3.2–6.7), chorionic vasculitis (OR 3.9; 95%CI 2.6–5.8) and umbilical cord vasculitis (OR 3.4; 95%CI 2.2–5.4) were more associated with bacterial infection compared to placentas without inflammation. |
| Hillier, 1988 [37] | U. urealyticum, M. hominis, G. vaginalis, Mobiluncus spp, Peptostreptococcus spp, Bateroides spp, streptococci, Lactobaccilli | Culture (placental swab and vaginal swab) Gram stain | 38/74 (51%) | The most common microorganisms found in preterm placentas were U. urealyticum 18/38 (47%) and G. vaginalis 10/38 (26%). | Bacterial vaginosis was also associated with histological chorioamnionitis (OR 2.6, 95%CI 1.0–6.6). | After controlling for demographic and obstetric variables, preterm birth was related to bacterial infections of placentas (OR 3.8; 95% CI 1.5–9.9) and with histological chorioamnionitis (OR 5.0; 95%CI 1.6–15.3). Any microorganisms recovered from the placentas (OR 7.2; 95%CI 2.7–19.5) and U. urealyticum with or without other organisms (OR 9.8; 95%CI 3.5–19.5) were significantly associated with histological chorioamnionitis, regardless of gestational age. Preterm birth did not alter the result. |
| Hillier, 1991 [36] | Genital mycoplasma (U. Urealyticum, M. hominis), Facultative bacteria (GBS, E.coli, G. vaginalis, Streptococci, Enterococcus, Lactobacillus), Anaerobic bacteria (Peptostreptococcus, Fusobacterium, Bacteroides, Actinomyces, Mobiluncus), Yeast (C. Albicans) | Culture (placental swab) | 112/268 (42%) | Microorganisms were detected 36/112 (32%) and 29/156 (19%) placentas in cases (≤ 34 weeks’ gestation) and controls (>34 weeks’ gestation), respectively. Two or more bacteria were identified from 17 (15%) of 112 placentas in the case group (≤ 34 weeks’ gestation) and 12 (8%) of 156 placentas in the control group (>34 weeks’ gestation) (P = 0.05). | Placental histological chorioamnionitis was detected in 66/112 (59%) of cases and 35/156 (22%) of controls. | Histological chorioamnionitis and bacterial infection (U. urealyticum not included) were strongly associated in cases after controlling for cofounding variables e.g. mode of delivery, duration of membrane rupture and bacterial vaginosis (OR 7; 95%CI 3.0–16.4). U. urealyticum, E. coli, Bacteriodes were significantly associated with histological chorioamnionitis (P<0.05). GBS but not Peptostreptococcus was also associated with both preterm delivery and histological chorioamnionitis. |
| Honma, 2007 [38] | U. urealyticum | Culture (placental swab) | 105/105 (100%) | U. urealyticum was positive in 17 placentas (25.8%) of non-chronic lung disease (N-CLD), and 15 placentas (38.5%) of chronic lung disease group. | 39/105 (37%) preterm placentas (<32 weeks’ gestation) had histological chorioamnionitis. | In multivariate analysis, histologic chorioamnionitis was associated with premature rupture of membrane (OR 10.19; 95%CI: 3.10–33.56), placental colonization of U. urealyticum (OR 6.73, 95%CI: 1.89–23.91), neonatal colonization of other microorganisms (OR 7.33, 95%CI: 1.22–44.13). |
| Other microorganisms detected in 12 placentas (18.2%) with or without U. urealyticum were coagulase-negative Staphylococcus (CoNS), Enterococcus, Candida, α-Streptococcus, Enterobacter, Bacillus and Mycoplasma hominis. | 21/39 (54%) placentas with histological chorioamnionitis had colonisation of U. urealyticum (OR 6.73, 95% CI:1.89–23.91). | |||||
| Ingrid, 2011 [39] | Chlamydia trachomatis | PCR (placental tissue) | 304/304 (100%) | C. trachomatis was harbored in 76/304 (25%) preterm placentas (≤32 weeks’ gestation). | Histological evidence of placental inflammation was found in 123/304 (40%) preterm placentas: 64/123 (52%) had inflammation of maternal and fetal placental tissue, 50/123 (41%) had only maternal tissue inflammation and 4/123 (3%) had inflammation of fetal placental tissue. Other abnormal placental findings such as peripheral funisitis, acute villitis, acute intervillositis with intervillous abscesses were detected in 5/123 (4%) placentas. | C. trachomatis infection was more associated with placental histological inflammation: 41/76 (54%) placentas with C. trachomatis versus 82/228 (36%) preterm placentas without C. trachomatis infection (OR 2.1; 95%CI 1.2–3.5). |
| Kwak, 2014 [41] | U. urealyticum, M. hominis | Culture (vaginal swab) | 179/179 (100%) | 112/179 (62%) of vaginal fluid cultures were positive for genital mycoplasma (99 cases were only positive for U. urealyticum and 13 were positive for both U. urealyticum and M. hominis). But no samples were positive for M. hominis. | 50/179 (28%) of preterm placentas had histological chorioamnionitis. However, 36/112 (32%) of U. urealyticum positive cases had histological chorioamnionitis, which was statistically significant (P<0.05). | Patients with culture positive for both U. urealyticum and M. hominis 13/112 (12%) had a significantly higher proportion of preterm birth (100% (13/13) vs 73% (73/99), P<0.001) and histological chorioamnionitis (62% (8/13) vs 29% (29/99), P = 0.019) than patients only positive for U. urealyticum. |
| Namba, 2010 [44] | Ureaplasma spp | Culture (placental swab) PCR (placental tissue) | 151/151 (100%) | 63/151 (42%) of preterm placentas (<32 weeks’ gestation) harboured Ureaplasma spp compared to 10/41 (24%) term placentas (P<0.05). | Histological chorioamnionitis was more common in preterm placentas of Ureaplasma spp positive (52/63, 83%) compared to placentas without infection (29/63, 46%), P<0.001. Histological chorioamnionitis with funisitis was also significantly associated with Ureaplasma positive preterm placentas than negative group (46% vs 7%, P<0.001). | In multivariate analysis, the association between Ureaplasma spp positivity in preterm placentas and histological chorioamnionitis was significant (OR 8.6; 95%CI 3.72–19.89). |
| Patel, 2018 [46] | GBS | Culture (vaginal and rectal swab) | 181/181 (100%) | GBS was positive in 55/181 (29.4%) of preterm cases. | The rate of histological chorioamnionitis was not significantly different between GBS negative and positive groups (81/126 (64.2%) vs 38/55 (69%), P = 0.62). Histologic chorioamnionitis was associated with earlier gestational age (29.2 versus 31.3 weeks, P < .0001) at birth. Earlier gestational age (<30 weeks) was associated with histological chorioamnionitis (P<0.001). | This single-centered, retrospective cohort study demonstrated that genital GBS colonization does not appear to be associated with an increased rate of Histologic chorioamnionitis in patients with PPROM <34 weeks of gestation. |
| Pettker, 2007 [47] | U. urealyticum, Bacteriodes, Gram(+) anaerobes, E.coli, Group B Streptococcus, Peptostreptococcus spp, Streptococcus Pneumoniae | Culture (amniocentesis microbial culture, placental tissue biopsy, placental swab) | 183/183 (100%) | Of 29/56 amniotic culture positive preterm samples, the most common micro-organism was U. urealyticum (12/29,31.5%). | Amniotic fluid culture negative with preterm birth was more associated with histological chorioamnionitis and funisitis than term pregnancy control group (P<0.001). | “Positive amniotic fluid cultures with preterm birth had higher severities (median grades) of funisitis and acute histologic chorioamnionitis compared with those with negative amniotic cultures and term pregnancy controls group (P<0.05)”. |
| Queiros da Mota, 2013 [48] | Bacteria species including gram positive and negative | Culture (placental swab) | 202/376 (53.7%) | 73/376 (19.4%) placentas were bacterial culture positive; 38/73 (52%) were preterm placentas. 193 microorganisms were detected in 152 positive cultures and gram positive cocci was the most common. | 101/376 (26.9%) placentas had histological chorioamnionitis; 43/101 (42%) of term and 53/101 (52%) of preterm placentas. The rate of positive cultures was higher in placentas with histological chorioamnionitis compared to those without (27% vs 16%, P = 0.01). | Preterm deliveries (extremely, plus very, plus moderate, plus late preterm) in which the proportion of histologic chorioamnionitis with positive and negative cultures was 25% (14/56) and 75% (42/56) respectively. |
| Sweeney 2016 [49] | U. parvum, U. urealyticum, GBS, Bacteroides, E. coli, G. vaginalis, Bifidobacterium spp, Propionibacterium spp | Culture (placental swab) 16s rRNA PCR (placental tissue) | 535/535 (100%) | Microorganisms were identified in 57/535 (10.6%) placentas. A total of 61 microorganisms were isolated from these placentas and U. parvum (36/61, 59%) was the most prevalent. | Placentas infected by microorganisms were more likely to have histological chorioamnionitis than noninfected placentas (31/47, 54.4% vs 90/427, 18.8%; P <0.001), irrespective of gestational age and ethnicity (P = 0.528). | Histological chorioamnionitis was significantly associated with moderate/late preterm birth in the presence of Ureaplasma spp (P<0.001). |
Abbreviations: AC, amniocentesis; C. albican, candida albican; C. trachomatis, Chlamydia trachomatis; E.coli, Escherichia coli; GBS, group B streptococcus; G. vaginalis, Gardnerella vaginalis; M. hominis, Mycoplasma hominis; M. genitalium, Mycoplasma genitalium; spp, species; U. urealyticum, Ureaplasma urealyticum; U. parvum, Ureaplasma parvum.