Associations of PM_2.5 and its components with term preterm rupture of membranes: a retrospective study

Introduction

Premature rupture of membranes (PROM) refers to the breaking of foetal membranes before labour begins, with no sign of labour present after one hour (Committee on Practice Bulletins-Obstetrics, 2018). PROM can be divided into preterm and term PROM (TPROMs). Preterm PROM typically occurs before 37 weeks of gestation, and TPROM are defined as the rupture of membranes that occurs from 37 weeks of gestation to the start of labour (Endale et al., 2016). Approximately 8% of pregnant women at term experience PROM (American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics, 2016). The incidence of PROM in the United States is 5% (Getahun et al., 2007); in Nepal, it is 8% (Prasad Dwa, Bhandari & Bajracharya, 2023); and in China, the incidence of PROM is 18.72% (Zhuang et al., 2020). Despite the widespread concern about preterm PROMs, TPROMs are also a pregnancy complication that should not be ignored, and their occurrence can lead to adverse outcomes such as perinatal death, increased rates of caesarean section, early-onset neonatal pneumonia, and neonatal sepsis (Herbst & Kallen, 2007; Middleton et al., 2017; Namli Kalem et al., 2017; Zhuang et al., 2022).

Although the causes of PROM remain unclear, several factors have been implicated, including age, previous preterm birth, smoking, polyhydramnios, urinary and sexually transmitted infections, previous PROM, caesarean section and cervical incompetence (ACOG Committee on Practice Bulletins-Obstetrics, 2007; Kaye, 2001; Kilpatrick et al., 2006; Puji Astuti, Ariyani & Mahayati, 2022). Exposure to fine particulate matter (PM_2.5) increases the risk of PROM, according to the findings of recent investigations into the relationship between air pollutants and PROM (Dadvand et al., 2014; Han et al., 2020; Ren et al., 2024; Zhang et al., 2021). A retrospective study conducted in Anhui, China, involving 4,276 participants reported that for each 10 µg/m³ increase in PM_2.5 exposure, the risk of PROM increased by 48% (95% confidence interval (CI) [1.16–1.89]) (Yang et al., 2024). A retrospective cohort study conducted in southern California revealed that mothers exposed to higher levels of PM_2.5 during pregnancy had an increased risk of PROM associated with heatwaves (Jiao et al., 2023b). A meta-analysis by Liang et al. (2024) indicated that PM_2.5 exposure during mid-pregnancy and short-term maternal exposure to PM_2.5 are associated with an increased risk of PROM. Therefore, PM_2.5 exposure during pregnancy is closely associated with PROM.

The aim of this study was to analyse data from pregnant women delivering at the Maternal and Children Health Care Hospital of Huadu in Guangzhou from 2018–2022, with a focus on the associations between exposure to PM_2.5 and its components and TPROM during pregnancy.

Methods

Subjects

This retrospective study involved pregnant women who delivered at the Maternal and Children Health Care Hospital of Huadu in Guangzhou from November 2018 to December 2022. Data were collected using the hospital’s electronic medical record management system. Relevant information, including age, occupation, ethnicity, blood type, delivery date, and clinical diagnosis, was obtained by reviewing the electronic medical records. Diagnoses were classified according to the ICD-10 codes. The exclusion criteria for the study participants were as follows: (1) residing outside Guangzhou; (2) in vitro fertilisation; (3) pregnancy of twins; (4) diabetes before pregnancy; (5) hypertension before pregnancy; and (6) insufficient data (Fig. 1). The study focused on subjects diagnosed with PROM (ICD-10 codes O42.000, O42.000 × 001, O42.100, O42.100 × 011, O42.200, O42.900), designated the disease group, with the other subjects forming the control group. This study received approval from the Ethics Committee of the Maternal and Children’s Health Care Hospital of Huadu (approval no. 2024-001). The committee waived the requirement for informed consent because anonymised data were used. This study complied with the ethical principles outlined in the 1975 Declaration of Helsinki.

Results

Discussion

In a retrospective study, we investigated the associations of exposure to PM_2.5 and its components during pregnancy with TPROM. We found that exposure to PM_2.5, ${\mathrm{SO}}_4^{2-}$, ${\mathrm{NO}}_3^{-}$, ${\mathrm{NH}}_4^{+}$, and BC was significantly associated with an increased risk of TPROM. However, when we conducted subgroup analyses by age, ethnicity, occupation, blood type, parity, adverse reproductive history, and uterine scarring, we did not observe any significant interactions between exposure to PM_2.5 and its components and TPROM. The findings suggest that exposure to air pollution during pregnancy increases the risk of TPROM irrespective of individual characteristics.

An increasing number of studies indicate that exposure to respirable particulate matter, especially PM_2.5, is closely related to oxidative stress responses (Ambroz et al., 2016; Moller & Loft, 2010; Orellano et al., 2020; Saffari et al., 2014). Long-term exposure to PM_2.5 can inhibit nitric oxide (NO)-dependent microvascular dilation and impair mitochondrial oxidative capacity (Della Guardia & Wang, 2023). Because mitochondria are prone to accumulate oxidative DNA modifications in oxidative environments (Muftuoglu, Mori & De Souza-Pinto, 2014), this may affect the function and integrity of foetal membranes, potentially leading to PROM. A study conducted in Taiyuan, China, revealed a significant association between oxidative stress and exposure to PM_2.5 and its components (Li et al., 2023). Kumari et al. (2023) reported in a case-control study that the mtDNA copy number was significantly greater in patients with early membrane rupture than in controls. In addition, Menon et al. (2012) conducted a study in the United States on telomere length in foetal leukocytes associated with preterm-PROM compared with intact membranes in preterm and term births. They reported that telomere length was significantly shorter in preterm-PROM cases than in age-matched preterm controls. Therefore, exposure to PM_2.5 during pregnancy may contribute to PROM.

The incidence of TPROM in this study was 19.66%, which is consistent with the 19.55% incidence rate reported in Shanghai (Li et al., 2021). This similarity may be attributed to both cities being economically developed metropolitan areas with similar healthcare conditions, socioeconomic levels, and environmental factors. Additionally, although the study periods differed, their time spans were relatively close, and similarities in public health policies and living environments may also have contributed to the similarity of the results. Previous studies of the relationship between PM_2.5 and the risk of PROM have yielded inconsistent results. A retrospective study conducted in the United States revealed that the risk of PROM increased in the days or hours before delivery (Wallace et al., 2016). In a cohort study in Wuhan, China, involving 4,364 pregnant women, there was a positive association between PM_2.5 exposure and PROM. For each 10 µg/m³ increase in PM_2.5 exposure, the risk of PROM increased by 14% (95% CI [1.02–1.26]), 9% (95% CI [1.00–1.18]), and 13% (95% CI [1.03–1.24]) in the first, second, and third trimesters, respectively (Wang et al., 2019). However, a time series study by Li et al. (2021) in Shanghai, China, involving 100,200 pregnant women revealed that PM_2.5 exposure did not increase the risk of PROM. Similarly, a longitudinal study conducted in New York, USA, with 130,070 participants reported no association between PM_2.5 levels and preterm PROM (Pereira et al., 2016). Additionally, a study in Spain on the relationship between air pollution and preterm PROM indicated that increasing PM_2.5 exposure by one quartile did not increase the risk of preterm PROM (OR: 1.04, 95% CI [0.76–1.43]) (Dadvand et al., 2014). The results of this study differ from those of previous investigations. In this study, exposure to PM_2.5 during the second and third trimesters of pregnancy increased the risk of TPROM. The differences in the results may be due to several factors. First, differences in geographical regions and environmental conditions between studies could lead to differences in the composition and concentration of PM_2.5, which could affect the risk of PROM. Second, differences in study methods and designs, such as sample size, exposure assessment methods and analytical techniques, could affect the accuracy of the results. For example, time series analysis was used in a study conducted in Shanghai, logistic regression models were used in Wuhan, and Cox proportional hazards models were used in this study. Finally, differences in the lifestyle, health status and genetic background of pregnant women may lead to different responses to PM_2.5 exposure.

Few studies have investigated the relationships between PM_2.5 components and PROM, particularly TPROM. Han et al. (2020) conducted a study in Nanjing on 1,715 pregnant women and reported that exposure to black carbon and organic matter increased the risk of PROM and shortened the gestational age. A previous study conducted in Spain on the relationship between air pollution and PROM indicated that for each interquartile range (IQR) increase in PM_2.5 absorbance, the risk of PROM increased by 47% (95% CI [1.08–2.00]) (Dadvand et al., 2014). PM_2.5 absorbance is considered a measure of black carbon (Durant et al., 2014). A large retrospective study conducted in the United States on prenatal exposure to air pollutants and PROM revealed that exposure to sulphates, nitrates, ammonium, and organic matter increased the risk of spontaneous PROM (Jiao et al., 2023a). A case-crossover study conducted in Shijiazhuang, China, on mixtures of PM_2.5 components and TPROM revealed that exposure to ${\mathrm{SO}}_4^{2-}$, ${\mathrm{NO}}_3^{-}$, ${\mathrm{NH}}_4^{+}$, and OM was significantly associated with an increased risk of TPROM (Ren et al., 2024). The results of these works differ slightly from those of this study, in which prenatal exposure to ${\mathrm{SO}}_4^{2-}$, ${\mathrm{NO}}_3^{-}$, ${\mathrm{NH}}_4^{+}$, and BC was significantly associated with an increased risk of TPROM. Inconsistencies in results may stem from multiple factors. First, the precision of exposure assessment may be affected by the use of different assessment methods, such as monitoring station data and satellite remote-sensing data, thereby influencing the estimation of the relationship between exposure and health. Second, the biological activities of the components of PM_2.5 differ, and their direct effects on membranes and indirect effects on maternal physiology can vary depending on region and environmental conditions. Third, discrepancies in the level of control over confounding factors in studies also contribute to the variations in results. Therefore, pregnant women should therefore minimise outdoor activities during peak pollution periods and may use air purifiers to reduce indoor PM_2.5 levels. If outdoor activities in highly polluted areas are necessary, masks and other personal protective equipment should be worn to reduce the risk of inhaling harmful particulate matter. In addition, government policies can achieve long-term improvements in air quality through a range of measures, including increasing urban green spaces; strictly enforcing vehicle emission standards; restricting highly polluting industrial activities; and promoting the use of clean energy. These integrated strategies not only help improve environmental quality in general but also effectively reduce the risk of PROM in pregnant women.

This study has several strengths. First, there was a significant association between prenatal PM_2.5 exposure and preterm labour, particularly in the second and third trimesters, which improves our understanding of the effects of environmental pollution on maternal health. Second, this study considered the effects of PM_2.5 components on preterm rupture of membranes, providing insight into the roles of ${\mathrm{SO}}_4^{2^{-}}$, ${\mathrm{NO}}_3^{-}$, ${\mathrm{NH}}_4^{+}$ and black carbon in the risk of preterm rupture of membranes. Finally, the data support further investigations into the effects of PM_2.5 on the PROM and are consistent with findings from other cities, providing robust evidence for use by air pollution control policy-makers. However, the study has several limitations. First, the exposure assessment was based on the average exposure level at the home address, without accounting for individual exposure variations at different locations, such as daily activity spaces and workplaces. Therefore, the values may not accurately reflect the true exposure levels of individuals and could lead to biased results. Second, the analysis did not include certain health behaviours and lifestyle factors, such as smoking or cocaine use during pregnancy, as covariates, which increase the risk of PROM (Myles et al., 1998). Other factors, such as diet, exercise, and weight management, could also influence the results (Faucett et al., 2016; Lin et al., 2024; Woods Jr, Plessinger & Miller, 2001). Although age and last menstrual period were used as matching criteria to reduce confounding effects from age and gestational age, differences in gestational age might have biased the results. Finally, there are limitations regarding sample representativeness; the participants were primarily from Guangzhou, which may restrict the generalisability and applicability of the findings. The regional and socioeconomic backgrounds of the participants may not be broadly representative, affecting the applicability of the results. Further research should incorporate participants from other regions and with other backgrounds to validate and generalise the findings.

Conclusions

This retrospective study, which was conducted in Guangzhou, China, investigated the associations between maternal exposure to PM_2.5 and its components and TPROM. The results revealed that exposure to PM_2.5 and its components (${\mathrm{SO}}_4^{2-}$, ${\mathrm{NO}}_3^{-}$, ${\mathrm{NH}}_4^{+}$, and BC) significantly increased the risk of TPROM, adding new evidence to the literature and deepening our understanding of the underlying mechanisms of this adverse pregnancy outcome. Given the regional differences in air pollution levels and composition, further studies in other areas are needed to validate these findings and to explore potential regional differences.

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