Our results highlight that CT infection is associated with an increased risk of PTB, LBW, and ICU admission. The adverse feto-maternal outcome was meaningfully high for CT-positive cases, with an OR of 3.5 and 3.72 for PTB and BV, respectively. BV appears to act as an effect modifier for PTB and may amplify the risk for adverse pregnancy outcomes among positive CT cases, even when appropriate therapy was introduced, which suggests a synergistic effect of BV with PTB.
Low socioeconomic status is significantly higher among CT-positive cases; those patients often have poor access to preventive and therapeutic healthcare services. Moreover, those areas are often crowded, and a lack of hygiene contributes to increased infection vulnerability [22]. Notably, both BV and CT were linked to increased PTB risk, and low socioeconomic status showed a similar impact, highlighting the combined influence of social and infectious factors on pregnancy outcome.
The role of CT in PTB was controversial in the literature. The majority of studies reported an association between CT and higher PTB risk. Kanninen et al.‘s meta-analysis discussed higher positive CT cases among affected pregnant vs. healthy controls with an OR of 7.74; 95%CI (2.6–22.7). In accordance with our results, the OR was 3.52, and the 95%CI was 1.04–11.8. Their analysis showed an overall 9% of CT among PTB cases compared to 3–7% in the current study [23].
He et al..‘s meta-analysis supported the association between CT and PTB with an OR of 1.57 and 95% CI of 1.11–2.22. Their analysis linked CT with low birth weight and small for gestational age with an OR and 95% CI of 2.2 (1.14–4.27); 1.93 (1.09–1.30), respectively. Our study results aligned with theirs, with an OR of 3.52 and a 95% CI (1.04–11.86) for low birth weight [24].
Another meta-analysis reported that CT was associated with increased PTB, with an OR of 1.27 (95% CI, 1.05–1.54), and with low birth weight, with an OR of 1.34 (95% CI, 1.21–1.48) [25].
A Dutch cross-sectional study found no association between STDs, including CT, and low birth weight. However, they confirmed a significant association with mothers’ educational status (OR = 7.81), smoking (OR = 2.9), and racial background (OR = 4.4), highlighting these factors’ influence on neonatal outcomes. The current study showed a significant impact of socioeconomic status (OR = 3.10), but it contradicts their report with respect to low-birth-weight incidence, with an OR of 3.5 in positive CT cases [26].
Andrews et al. recruited pregnant women of different gestational ages in the second trimester and showed no association of CT infection with PTB. Additionally, they showed no reduction in PTB risk upon treating positive cases with antibiotics [27].
A large population-based study examined 101,558 pregnant found that after treating positive CT cases during pregnancy, they did not exhibit an increased risk of PTB nor low birth weight after adjustment for age, smoking status, and other bacterial infections. They emphasized that the risk for untreated cases requires further examination and investigation [28].
Gravett et al. looked into the impact of CT infection with concurrent BV on the feto-maternal outcome. They reported an independent association between CT and PTB (OR = 4.3), premature rupture of membranes (OR = 2.4), and low birth weight (OR = 2.7). Conversely, BV-positive cases had an increased risk of PTB labor before 37 weeks (OR = 2), premature rupture of membranes, PROM(OR = 2), and amniotic fluid infection (OR = 2.7) [6].
In line with the above results, Martius et al.‘s study confirmed a positive association of CT and BV with PTB, with an OR of 3.9 and 2.3, respectively [14]. Our cohort results aligned with these, with increased PTB risk among CT positive cases with OR = 2.48, and suggest a synergistic association between BV and PTB.
Shipitsyna et al. study discussed an association between BV and the risk of STD, including CT. They discussed an age-independent association between BV and CT with an OR of 2.9 and suggested this link as a cause for study bias [8]. Their results signify the critical role of vaginal microbiota composition in STD prevention and the importance of promoting protective lactobacilli as part of screening and intervention programs. Adopting such approaches may support improved reproductive performance and reduce STD transmission [15,16,17].
Abou Chakra et al. study investigated the association of BV with STD among pregnant and nonpregnant cases; they confirmed a higher risk of STD of mono- and multi-organism, including CT among positive BV cases, underscoring the protective role of a healthy vaginal microbiota. This aligns with our results that showed significantly more frequent BV infections among positive CT; P = 0.006 [18].
Ahmadi et al. study was unable to link PTB with vaginal bacteria in a case-control study. They discussed reduced incidents of STDs and emphasized the role of screening and prevention in breaking the chain of STDs and improving reproductive health within the community [29]. Their findings contrast with ours, where BV was associated with increased PTB risk in what appears to be a synergistic relation.
The inconsistency in CT’s role in PTB remains a point of debate. Some attributed this uncertainty to the quality of examined studies. Olson-Chen et al. meta-analysis noted that the association between PTB and BV was diminished when the analysis was restricted to high-quality studies assessed using the Newcastle-Ottawa Scale [25]. In addition, many studies were constrained by significant heterogeneity and reliance on less accurate diagnostic methods for Chlamydia, which underscores the importance of adopting more robust and standardized methodologies in future works [30]. The overall incidence of CT in the current study was 23%, while the incidence of BV was 42% among CT-positive cases vs. 19.48% among CT-negative cases. Gravett et al.‘s study reported 9% and 19% of CT and BV, respectively [6], while others reported 9% and 17.25% for CT and BV cases, respectively [7]. 4vIn Europe, the CT incident rate was 9%, and for BV, it is below 20%, reflecting an apparent increase in incidents compared to the 90 s of the last century [18, 31, 32].
This higher prevalence of BV infection among CT-positive cases may reflect a disrupted vaginal ecosystem triggered by CT. The latter may create condition that favors anaerobic bacteria overgrowth associated with BV, which may contribute to the onset of PTB [33, 34].
Several potential mechanisms were suggested for how vaginal bacteria trigger PTB. The presence of infection will trigger an inflammatory response at the site. A chronic inflammatory status will occur with inflammatory mediators such as interleukins and cytokines release, which have been associated with heightened adverse pregnancy outcomes, including abortion and PTB [35, 36].
The pregnancy by itself is characterized by unique immunological tolerance. In the presence of a chronic inflammatory status, this tolerance may be disturbed, potentially increasing the risk of pregnancy loss [37]. Lastly, direct infection of endometrial cells by CT hinders normal placental function, potentially leading to pregnancy loss [38].
Unfortunately, our country lacks a screening program for CT; in light of the observed associations with adverse outcomes discussed in this study, we believe that there are points of strength in our results.
First, the sample taken was representative of the community and excluded many confounders to test the impact of CT on PTB risk. Second, the association between BV and STD was reported in a handful of studies with statistically significant odds ratios supporting the potential role of promoting a healthy vaginal environment to reduce the risk of acquiring STD [8, 16,17,18].
Incorporation of CT screening into routine antenatal care may aid in risk stratification and could support the development of more tailored interventions and therapeutic approaches [39].
Third, the significant association of BV with increased PTB risk observed in the current cohort emphasizes the need for targeted treatment strategies, particularly in cases of concurrent CT infection [40, 41]. Fourth, the insight gained from these results can inform public health strategy, especially in areas of low access to high-quality health services and a high CT prevalence [42].
We must acknowledge the study’s limitations. Despite the high diagnostic accuracy of PCR-based methods, their implementation in low-resource settings may be limited by cost constraints, the need for specialized equipment, and a lack of technical expertise. These factors may hinder the widespread application, underscoring the need for more accessible diagnostic alternatives [43].
A notable limitation of this study is the low explanatory power of the logistic regression model, as reflected in the low Nagelkerke value (R² = 0.072). This implies that while CT and BV are associated with PTB risk, other unmeasured variables may contribute significantly to its onset. Future studies should consider incorporating additional confounding factors, such as maternal nutritional status, smoking habits, number of sexual partners, and HIV status [26] to improve the model’s robustness to capture the PTB ‘s multifactorial nature. A wide 95% CI suggests that the sampling power should be increased to improve the precision of the effect estimate. The exclusion of other microorganisms, such as viruses and protozoa, represents a potential source of residual confounding. Incorporating amniotic fluid and placental sample in future works may add a more comprehensive understanding of microbial contributions to PTB [44].