Air pollution and postpartum depression: the interplay with prenatal stress

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Just, Ivan. Gutierrez-Avila, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8523355/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Postpartum depression (PPD) is a global health issue that can lead to high levels of maternal morbidity. We previously found that ambient air pollution (PM 2.5 ) during pregnancy is associated with PPD. However, the modifying role of psychosocial stress on this relationship is unclear. Methods We measured pregnancy stress in the PROGRESS cohort (n = 475 mothers) using negative life events (NLE) and perceived stress score (PSS). We assessed the modifying role of NLE and PSS on the association between prenatal PM 2.5 exposure and PPD at 6 months. Daily residence level PM 2.5 estimates generated from a spatiotemporal model was averaged over pregnancy. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS ≥ 13) and categorized as chronic depression (EPDS ≥ 13 during pregnancy and at 6 months), new-onset PPD (EPDS < 13 during pregnancy and EPDS ≥ 13 at 6 months), or prevalent PPD (EPDS ≥ 13 at 6 months, regardless of EPDS score during pregnancy). Modified Poisson regression evaluated the association between PM 2.5 and PPD, stratified by NLE and PSS scores, dichotomized around the median (low/high). We repeated the analyses with other proposed EPDS cut-offs for Mexico (EPDS ≥ 10 and ≥ 12). Results Each 5-µg/m³ increase in average pregnancy PM 2.5 exposure was associated with 129% higher risk of prevalent PPD among mothers with low PSS (RR: 2.29, 95% CI: 1.17–4.47). The risk of new-onset PPD at 6 months per 5-µg/m³ increase in PM 2.5 during pregnancy quadrupled among mothers with low PSS (RR: 4.58, 95% CI: 1.83–11.49) and high NLE (RR: 4.71, 95% CI: 1.72–12.92) scores. Similar findings were observed with an EPDS ≥ 10 or EPDS ≥ 12 cut-off. Conclusion The risk of PPD from PM 2.5 exposure was enhanced in mothers with low PSS or high NLE scores, especially new-onset PPD, regardless of the EPDS threshold used. These findings suggest that well-characterized stress phenotyping during pregnancy may help identify which women are at-risk for depression. Air pollution postpartum depression prenatal stress Figures Figure 1 Figure 2 Figure 3 Introduction Stress is a biological and physiological response to challenges and threats ( 1 ). Although stress is a normal part of life, its intensity and frequency can heighten during pregnancy due to physiological and psychological changes ( 2 , 3 ) and worries related to pregnancy and parenting (i.e., labor and delivery, financial constraints) ( 4 ). Thus, stress can act as an exposure capable of triggering biological response including neuroendocrine and immune changes ( 5 ). During pregnancy, the maternal endocrine, nervous, and immune systems undergo adjustments to support fetal development and maternal health ( 6 ). However, prenatal stress can disrupt these processes through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis ( 6 ), increase corticotropin-releasing hormone (CRH) ( 6 , 7 ) and inflammatory cytokines ( 6 , 8 ), resulting in downstream health effects in the mother ( 6 , 9 , 10 ). Prenatal stress is associated with various maternal health outcomes ( 9 , 10 ), including postpartum depression (PPD) ( 6 , 11 , 12 ). Findings from a recent systematic review and meta-analysis with 17 cohort studies showed a 82% increase in PPD in women exposed to a prenatal stressful life event ( 13 ). Further, studies suggest the role of HPA axis dysregulation including dysfunction in synaptic transmission and the neurotransmitter system in the mechanism that links stress to PPD ( 14 – 17 ). While emerging studies point to additional environmental exposures that can impact the same HPA axis and neuroendocrine pathways to exacerbate or antagonize these associations, most studies have only looked at stress as a single exposure ( 13 , 18 – 20 ). Ambient air pollution (PM 2.5 ) is an exposure positively associated with PPD, ( 21 ) which may act on similar mechanisms as stress ( 22 , 23 ). There was a 56% increase in PPD risk among mothers with higher PM 2.5 exposure during the second trimester of pregnancy ( 22 ), similar to a study conducted by our team which found a 59% increased risk of PPD per 5-µg/m3 increase in average PM 2.5 exposure during pregnancy ( 24 ). However, findings from a recent meta-analysis of 12 European birth cohorts found no association between PM 2.5 and PPD. While variability in PM 2.5 and PPD assessment methods between the cohorts, heterogeneity across the cohorts, and bias from complete case analysis likely influenced the analysis ( 25 ), null findings in the meta-analysis may also suggest additional confounders. Because both prenatal stress and PM 2.5 are individually associated with PPD, pregnant women may be particularly more vulnerable to their combined effects, as these stressors may interact through shared biological pathways to exacerbate the risk of PPD. However, while a study in mice suggests that maternal stress exposure during late gestation heightens offspring susceptibility—particularly in males—to the harmful effects of prenatal air pollutant exposure on neurocognitive disorders in adulthood ( 26 ), research that examined the interplay of prenatal stress on the association between PM 2.5 and the risk of PPD in humans remains limited. Further, while the Edinburgh Postnatal Depression Scale (EPDS) is a commonly used screening tool for identifying probable PPD, the use of varying cut-off scores such as 7/8 ( 27 ), 9/10 ( 28 ), 11/12 ( 27 ), ≥ 12 ( 29 , 30 ), and ≥ 14 ( 31 ) in Mexico, can complicate cross-study comparisons and interpretations. For example, our team previously used an EPDS threshold of 13 or more ( 24 , 32 ) in analyses from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort as a conservative threshold to reduce the probability of false positives within the context of a population-based cohort allowing for the identification of cases with more marked symptomatology. In this study, we assessed the role of prenatal stress—negative life events (NLE) and perceived stress on the association between PM 2.5 and PPD using data from a prospective cohort of Mexican mothers. Understanding their potential joint effects is critical for identifying vulnerable women and informing preventive screening strategies. We primarily used an EPDS cut-off score of ≥ 13, consistent with the threshold commonly applied in previous PROGRESS studies and assessed the robustness of our findings using two of the proposed cut-offs (≥ 10 and ≥ 12) for screening probable PPD in Mexico. Methods Study population Healthy pregnant women who received prenatal care through the Mexican Social Security Institute (Instituto Mexicano del Seguro Social – IMSS) between 2007 and 2011 were recruited in the PROGRESS study ( 24 ). Participants were included in the study if they met the following criteria: less than 20 weeks of gestation, singleton pregnancy, at least 18 years old, completed primary education, intended to remain in Mexico City for the next three years, had telephone access, no history of heart or kidney disease, did not consume alcohol daily, reported no drug addiction, and were not taking steroids or anti-epileptic medications. This study included 475 participants with complete data on PPD at 6 months postpartum, prenatal stress, pregnancy PM 2.5 , and all covariates. The sample size in this study is smaller than that of the original cohort study on PM 2.5 PPD (509 participants) ( 24 ) due to missing data on perceived stress for approximately 7% of the participants. Outcomes The Spanish version of the EPDS, validated in Mexico ( 29 , 31 ), was used to collect data on mother’s depressive symptoms during the second or third trimester of pregnancy and at 6 months postpartum. EPDS is a widely used screening tool to identify and monitor postpartum depressive symptoms in mothers ( 33 – 35 ). The EPDS is a 10-item self-report questionnaire that assesses how the participants felt over the past seven days ( 36 ). These items include: “I have laughed and been able to see the funny side of things,” “I have looked forward with enjoyment to things,” “I have blamed myself unnecessarily when things went wrong,” “I have been anxious or worried for no good reason,” “I have felt scared or panicky for no very good reason,” “Things have been getting on top of me,” “I have been so unhappy that I have had difficulty sleeping,” “I have felt sad or miserable,” “I have been so unhappy that I have been crying,” and “The thought of harming myself has occurred to me.” Participant’s responses are scored on a 4-point Likert scale, from zero (0) to three based on the seriousness of the symptom. A score of zero (0) indicates that the participant is the most favorable condition (i.e., unlikely to have a clinically significant depressive symptom), while a score of three suggests the least favorable condition (i.e., likely to have a clinically significant depressive symptom). The total score, ranging from zero (0) to 30 is calculated by summing the scores of all 10 items. We applied the commonly used threshold in PROGRESS publications (EPDS ≥ 13: Yes/No) to identify women with probable PPD, a clinically relevant cut-off used in other settings to identify women at risk for major depression ( 36 , 37 ). Because lower cut-offs have been proposed for screening women with probable PDD in Mexico ( 27 – 31 ), we compared our findings with other cut-off values of EPDS ≥ 10 and EPDS ≥ 12. These cut-off values refer to the most updated thresholds proposed for screening for major depressive symptoms in adult women in Mexico ( 28 , 30 ). This strategy allowed us to assess whether the observed associations between PM 2.5 and PPD are consistent, and not sensitive to a specific threshold. We assessed prevalent PPD, chronic PPD, and new-onset PPD at 6 months using the three cut-off values. Chronic PPD included mothers with an EPDS ≥ 13 during pregnancy and at 6 months postpartum. New-onset PPD included mothers with an EPDS < 13 during pregnancy but EPDS ≥ 13 at 6 months postpartum ( 24 ). Prevalent PPD refers to any mother with an EPDS ≥ 13 at 6 months postpartum, regardless of EPDS score during pregnancy ( 24 ). Thus, prevalent depression included mothers with both chronic PPD, and new-onset PPD. Similar definitions were applied when considering the EPDS ≥ 10 and EPDS ≥ 12 cut-offs. Prenatal PM 2.5 exposure during pregnancy Daily PM 2.5 exposure for each participant’s residence was assessed during pregnancy using a validated spatiotemporal model ( 38 ). The model integrated data from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite-derived Aerosol Optical Depth (AOD) at a 1×1 km spatial resolution with ground-based PM 2.5 measurements, meteorological data (including temperature, relative humidity, wind speed, and planetary boundary layer height), and land use regression variables (such as roadway density). Mixed-effects modeling, which incorporated spatial and temporal predictors alongside day-specific random effects, was employed to capture temporal variability in the relationship between PM 2.5 and AOD. The model incorporated a seasonal smoothing function for latitude and longitude, along with a time-varying average, to integrate local monitoring data on days when AOD measurements were unavailable. The model exhibited strong predictive accuracy, with an R² of 0.724 from cross-validation, and has undergone external validation in prior studies ( 39 , 40 ). Daily exposure estimates were assigned to participants based on GPS coordinates of their residential locations, collected by study personnel. Gestational age was determined using maternal reports of the last menstrual period and standardized physical examinations. The average PM 2.5 exposure during pregnancy was calculated using the average PM 2.5 measurements from each trimester (1–13 weeks for the first trimester, 14–27 weeks for the second, and 28 weeks to delivery for the third). We convert PM 2.5 exposure to a 5-unit change during pregnancy to simplify the interpretation of its effects on the outcomes. More details on the model's development and validation are available elsewhere ( 38 ). Prenatal stress during pregnancy. NLE was measured using the Crisis in Family Systems-Revised (CRISYS) survey, previously validated in Spanish ( 41 ) CRISYS is a flexible, multidimensional, and standardized tool developed to quantify contemporary sources of life stress ( 42 ). It measures life events across 11 domains: financial, legal, career, relationship, home safety, neighborhood safety, medical issues (self and others), home, prejudice, and authority ( 42 ). Participants in their third trimester of pregnancy( 43 ) indicated whether they experienced specific life events in the past six months as positive, negative or neutral. Therefore, the NLE captures stress during the pregnancy period. The NLE domain score is calculated by summing the number of domains that have one or more negative events. NLE score ranges from 0 to 11, with higher score indicating greater stress ( 42 ). Perceived stress score (PSS) during the third trimester of pregnancy was measured using the validated Spanish version of the 4-item Perceived Stress Scale (PSS-4) ( 44 , 45 ). Participants rated their perceived stress level in a 5-point Likert scale, ranging from zero (0) to 4 ( 46 ). The PSS score is calculated by summing the scores of individual items, with a higher score indicating greater perceived stress ( 44 ). Covariates Maternal age (in years), maternal level of education (less than high school, high school, more than high school), socioeconomic status (SES), body mass index (BMI) pre-pregnancy, maternal exposure to smoke inside the home (yes/no), prenatal stress, and gestational age at birth (in weeks) were used as covariates in this study. SES in PROGRESS is calculated based on the Mexican Association of Market and Public Opinion Research Agencies (Spanish acronym AMAI) ( 47 ). We used maternal exposure to second-hand smoke inside the home instead of self-reported smoking during pregnancy, as only one mother reported smoking during pregnancy. Statistical analysis We performed descriptive analysis for all the variables included in this study. We assessed the association between mean PM 2.5 during pregnancy and the outcomes using modified Poisson regression with robust error variance, allowing us to calculate the relative risk for the current study sample size ( 24 ). To evaluate departures from multiplicativity, we tested for interactions by including a product term between the average PM 2.5 and prenatal stress (NLE and PSS levels) dichotomized around the median ( 48 , 49 ). We then stratified the model by low and high stress levels. The analyses were adjusted for maternal age, maternal education, maternal exposure to smoke inside the home, and gestational age at birth. Statistical significance was determined at a p-value of less than 0.05. All the analyses were conducted using R, version 4.4.1 (2024-06-14 ucrt). Results Table 1 summarizes the characteristics of the study population. On average, maternal age during pregnancy was 27.7 (SD: 5.5). PM 2.5 exposure during pregnancy was 22.9 µg/m 3 (IQR: 20.3–24.5). Maternal education ranged from 23.4% among mothers with more than a high school education to 41.1% among those with less than a high school education. Approximately 11% of mothers belonged to a high socioeconomic status, while 51.4% were classified as low socioeconomic status. The median NLE and PSS scores during pregnancy were 3 (IQR: 2–5) and 5 (IQR: 3–7), respectively. At 6 months postpartum, median EPDS score was 5 (IQR: 2–10). Over 18% of mothers had prevalent PPD, 9.7% had chronic PPD, and 8.6% had new-onset PPD, using a cut-off of EPDS ≥ 13. However, considering an EPDS ≥ 10, 30.3% of mothers identified with prevalent depression, 20.8% with chronic PPD, and 9.5% with new-onset PPD (Table 1). Table 1 Characteristics of the study population (N = 475). Variables Description N (%) Maternal age (years) during pregnancy 27.7 (SD: 5.5) Maternal exposure to smoke inside home during pregnancy Yes 145 (30.5) No 330 (69.5) Maternal education during pregnancy High school 111 (23.4) Socioeconomic status during pregnancy Low 244 (51.4) Medium 180 (37.9) High 51 (10.7) Average PM2.5 in pregnancy 22.9 (IQR: 20.3–24.5) Mother's body mass index pre-pregnancy 26.9 (SD: 4.1) NLE during pregnancy 3 (IQR:2–5) Perceived stress during pregnancy 5 (IQR: 3–7) Gestational age at birth (weeks) 39 (IQR: 38–39) EPDS at 6 months postpartum 5 (IQR: 2–10) EPDS ≥ 10 prevalent PPD Yes 144 (30.3) No 331 (69.7) EPDS ≥ 10 chronic PPD Yes 99 (20.80) No 376 (79.20) EPDS < 10 new-onset PPD Yes 45 (9.47) No 430 (90.53) EPDS ≥ 12 prevalent PPD Yes 98 (20.63) No 377 (79.37) EPDS ≥ 12 chronic PPD Yes 55 (11.60) No 420 (88.40) EPDS < 12 new-onset PPD Yes 43 (9.05) No 432 (90.95) EPDS ≥ 13 prevalent PPD Yes 86 (18.1) No 389 (81.9) EPDS ≥ 13 chronic PPD Yes 46 (9.70) No 429 (90.30) EPDS < 13 new-onset PPD Yes 41 (8.6) No 434 (91.4) Footnotes: EPDS: Edinburgh Postnatal Depression Scale, NLE: Negative life events, SD: Standard deviation, IQR: Interquartile range, prevalent PPD: all participants with EPDS equal to or above the cut-off at 6 months, regardless of EPDS score during pregnancy; chronic depression: EPDS equal to or above cut-off during pregnancy and at 6 months postpartum; new-onset PPD: EPDS equal to or above cut-off at 6 months postpartum, but below the cut-off during pregnancy We assessed the association between PPD and average PM 2.5 exposure during pregnancy for EPDS ≥ 10, EPDS ≥ 12, and EPDS ≥ 13) (Fig. 1). The risk of prevalent PPD and new-onset PPD (EPDS ≥ 13) increased by 49% (RR: 1.49, 95%CI: 1.02–2.19) (Fig. 1a), and 167% (RR: 2.67, 95%CI: 1.37–5.21) (Fig. 1c), respectively, per 5-µg/m 3 increase in average PM 2.5 during pregnancy, similar to analyses performed in the larger cohort of 509 women (24). Likewise, there was a positive association between the average PM 2.5 exposure during pregnancy and the risk of new-onset PPD using an EPDS ≥ 10 (RR: 2.12, 95%CI: 1.28–3.54) and an EPDS ≥ 12 (RR: 2.07, 95%CI: 1.10–3.91) (Fig. 1c), respectively. No association was found between the average PM 2.5 and chronic PPD for all cut-offs (Fig. 1b). We then investigated how prenatal stress modified the relationship between PM 2.5 and prevalent PPD. Perceived stress modified the association between PM 2.5 exposure and prevalent PPD, but not NLE (Fig. 2). Each 5-µg/m³ increase in pregnancy PM 2.5 exposure was associated with 129% increased risk of prevalent PPD (EPDS ≥ 13) in mothers with low PSS (RR: 2.29, 95%CI: 1.17–4.47) (Fig. 2f). Similarly, there was an increased risk of prevalent PPD per 5-µg/m 3 increase in average PM 2.5 among mothers with low PSS stratum using an EPDS ≥ 10 or EPDS ≥ 12 (RR: 1.68, 95%CI: 1.04–2.77; RR: 2.57, 95%CI: 1.35–4.90, respectively) (Fig. 2b and 2d). The analyses between chronic PPD and average PM 2.5 exposure during pregnancy according to NLE and PSS stratums did not yield any significant association (Supplementary Fig. 1a-1f). However, the effect of PM 2.5 on chronic PPD appeared to be in the positive direction among mothers with low PSS across the different EPDS threshold (Supplementary Fig. 1b, 1d, and 1f), consistent with the above findings for prevalent PPD. The associations between PM 2.5 exposure and new-onset PPD according to NLE and PSS stratum were assessed (Fig. 3). Each 5-µg/m³ increase in average PM 2.5 during pregnancy was associated with a 371% increase in the risk of new-onset PPD (EPDS ≥ 13) in mothers with high NLE (RR: 4.71, 95%CI: 1.72–12.92) (Fig. 3e) and a 358% increase among those with a low PSS scores (RR: 4.58, 95%CI: 1.83–11.49) (Fig. 3f). Similar findings were observed using an EPDS ≥ 12 in mothers with high NLE (RR: 4.66, 95%CI: 1.80–12.10) Fig. 3c) and among those with low PSS (RR: 2.67, 95%CI: 1.27–5.64) (Fig. 3d). Increased risk of new-onset PPD per 5-µg/m³ increase in average PM 2.5 was also observed among mothers with high NLE (RR: 3.34, 95%CI: 1.36–8.21) (Fig. 3a), and with high PSS (RR: 4.77, 95%CI: 1.04–21.81) using an EPDS ≥ 10, although the association was borderline among those with a low PSS (RR: 1.83, 95%CI: 0.99–3.40) (Fig. 3b). Finally, we assessed whether the association between average PM 2.5 level during pregnancy and depression depended on stress (Supplementary Table 1). Indeed, a statistically significant interaction was observed between the average PM 2.5 level and PSS on new-onset PPD (p = 0.035) using an EPDS ≥ 13 as well as between average PM 2.5 level and NLE on new-onset PPD o using an EPDS ≥ 12 (P = 0.005). A similar finding was observed between average PM 2.5 level and PSS on prevalent PPD using an EPDS ≥ 12 (Supplementary Table 1). Discussion This study assessed the modifying role of prenatal psychosocial stress on the association between prenatal PM 2.5 exposure and postpartum depression in Mexico, using three EPDS cut-offs (≥ 13, ≥ 12, and ≥ 10). We observed that PM 2.5 exposure during pregnancy was consistently associated with increased risk of new-onset PPD across all thresholds. Among mothers with a low PSS, the effect of PM 2.5 on prevalent PPD was stronger independently of the EPDS threshold used. Similar findings were observed for new-onset PPD among mothers with a high NLE and a low PSS across all the three EPDS cut-offs. These findings indicate that PM 2.5 exposure during pregnancy is a consistent environmental risk factor for PPD, independently of the EPDS threshold used. Whether using a lower threshold (EPDS ≥ 10) to capture milder symptoms or a higher cut-off to identify cases with more marked symptomatology, the association between PM 2.5 and new-onset PPD remained consistent. More importantly, the findings indicate that prenatal stress, particularly high exposure to NLE and low PSS may heighten the effect of ambient air pollution on new-onset PPD at 6 months postpartum, regardless of the cut-off used. However, we observed no statistically significant association between depression that began during pregnancy and persisted to six months postpartum (i.e., chronic PPD), suggesting that PM 2.5 may not play a significant role in the continuation of pre-existing depressive symptoms. The fact that PM 2.5 was positively associated with prevalent PPD which included both new and old cases of probable depression suggests that PM 2.5 may contribute more to the incidence of new cases or exacerbate existing symptoms enough to meet the minimal EPDS threshold, which was evident when considering new-onset PPD, which includes only new cases of PPD at 6 months postpartum. The amplified effect of PM 2.5 on prevalent depression, particularly on new-onset PPD in mothers with a low PSS highlights the increase vulnerability of these mothers to the mental health effects of PM 2.5 . In this population, mothers with low perceived stress might not have established coping mechanisms, and therefore, be more overwhelmed by environmental stressors such as air pollution. Similarly, these mothers may live in environments with greater environmental hazards due to socioeconomics challenges and lack social support networks making them even more vulnerable to the effect of PM 2.5 . As shown in previous studies, exposure to higher levels of PM 2.5 may elicit a more pronounced biological stress response in these mothers, which may lead to over-activation of the HPA axis ( 50 – 52 ), elevated cortisol ( 52 , 53 ), and release of pro-inflammatory cytokines like 1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor-α( 17 , 52 , 53 ), with subsequent downstream consequences on maternal mental health. Given that perceived stress is subjective, mothers with low PSS can still face significant stressors like PM 2.5 and other postpartum life challenges that make them more susceptible to the risk of these outcomes, if effective coping mechanisms or social support is lacking ( 54 , 55 ). In this study, the NLE captured events that occurred in the past six months, while the PSS focused on stress that occurred in the last month during the third trimester of pregnancy. Although the NLE and PSS capture different dimensions of stress, it is possible that stressful events throughout the gestational period align more closely to the detrimental effect of PM 2.5 on new-onset PPD at six months postpartum, compared to perceived stress. The stronger effect of PM 2.5 on the risk of new-onset PPD in mothers with high NLE scores across all three threshold suggests that prolonged exposure to stressors like NLE may increase their susceptibility to air pollution, increasing the risk of new-onset PPD at 6 months. However, we observed that the effect of PM 2.5 on prevalent PPD at 6 months remained similar across different levels of NLE scores indicating that NLE do not act as an effect modifier in this relationship. The difference in the effect of PM 2.5 on prevalent PPD and new-onset PPD across NLE scores suggests that the combination of air pollution and NLE has a stronger influence on the later postpartum onset of depression rather than on depression that is persistence from pregnancy to 6 months postpartum. Overall, our findings highlight the interplay between environmental and psychosocial stressors, emphasizing pregnancy as a heightened period of susceptibility for postpartum mental health outcomes. This also highlights the need to account for air pollution and the need for well-characterized prenatal stressors when assessing the risk to postpartum maternal mental health outcomes. While past analyses established the independent link between both prenatal stress ( 6 , 13 – 15 )and PM 2.5 (21, 22) with PPD, there is a lack of studies assessing the role of prenatal stress on the association between prenatal PM 2.5 exposure and the risk of PPD. Given that both increased PM 2.5 and prenatal stress independently place significant psychological strain on individuals ( 18 ), primarily by activating the HPA axis and triggering an inflammatory response, such disruption in the presence of the combined effect of prenatal stress and PM 2.5 may overwhelm stress regulation mechanisms, exacerbating the risk of PPD particularly new-onset PPD at 6 months as we see here. Our study has strengths and limitations. To our knowledge, this is the first study to examine whether the association between PM 2.5 and the risk of PPD differs according to prenatal stress levels. We used an EPDS ≥ 13 considered as a conservative threshold to identify postpartum women at risk for major depressive symptoms ( 33 , 36 ), and compared our findings with two other proposed thresholds (EPDS ≥ 10, EPDS ≥ 12) for screening PPD in Mexico to determine robustness of the associations. Data used in this study came from a well-defined longitudinal cohort study, with substantial sample size, and high spatial resolution of PM 2.5 exposure data that covers the whole pregnancy period. The study showed that prenatal stress particularly low PSS and high NLE exacerbated the effect of prenatal PM 2.5 exposure on PPD, especially new-onset PPD. However, our findings must be interpreted as an increased risk for PPD as the EPDS is a screening tool used to assess possible depression, instead of clinical depression per se. Furthermore, considering that the NLE scale and the PSS used in this study represent different periods of exposure during pregnancy, the results of our study must be interpreted accordingly. It is necessary to measure perceived stress throughout all trimesters of pregnancy for comparative purposes and to identify critical periods of vulnerability during pregnancy. Conclusion and recommendation Prenatal low perceived stress and high negative life events exacerbate the effect of prenatal PM 2.5 exposure on the risk of PPD, particularly new-onset PPD, across EPDS thresholds of ≥ 10 to ≥ 13. This highlights the robustness of our findings and the complex interplay between environmental and psychosocial factors, particularly among mothers facing psychosocial challenges. More longitudinal study is needed particularly using perceived stress collected across all trimesters of pregnancy to understand the interplay between environmental exposures and prenatal stress on PPD. Abbreviations AOD: Aerosol Optical Depth BMI: Body mass index (BMI) CRH: Corticotropin-releasing hormone CRISYS: Crisis in Family Systems-Revised EPDS: Edinburgh Postnatal Depression Scale HPA: Hypothalamic-pituitary-adrenal IMSS: Instituto Mexicano del Seguro Social MODIS: Moderate Resolution Imaging Spectroradiometer NLE: Negative life events PM2.5: Ambient air pollution PPD: Postpartum depression PROGRESS: Programming Research in Obesity, Growth, Environment, and Social Stressors PSS: Perceived stress score SES: Socioeconomic status Declarations Ethics approval and consent to participate: Each participant signed a written informed consent before participating in the study. Approval was obtained from the institutional review boards at the Harvard School of Public Health, Icahn School of Medicine at Mount Sinai, the National Institute of Perinatology, and the Mexican National Institute of Public Health. Consent for publication : Not applicable Clinical trial number : Not applicable Availability of data and materials: The data that support the findings of this study are available from the corresponding authors upon reasonable request. Competing interests: The authors declare no competing interests. Funding and Acknowledgements: This study was funded by the National Institutes of Health/National Institute of Environmental Health Sciences [R01 ES036725, R01 ES014930, R01 ES013744, P30 ES023515, R00 ES027496, R01 ES031117, and UL1TR004419] and the National Institute of Public Health/Ministry of Health of Mexico. We are grateful to the ABC (American British Cowdray Medical Center) in Mexico for providing research facilities. Authors’ contributions: Conceptualization: LP, MN, EC, CHC. Data curation and verification: IK, ACJ, IG-A. Funding acquisition: ROW, MT-J, LP. Methodology development: CHC, MN. Formal analysis: GJ. Supervision: LP. Original draft: GJ and LP. Writing-review and editing: All authors. Approval of final version: All authors. References Russell G, Lightman S. The human stress response. Nat reviews Endocrinol. 2019;15(9):525–34. Ritter C, Hobfoll SE, Lavin J, Cameron RP, Hulsizer MR. Stress, psychosocial resources, and depressive symptomatology during pregnancy in low-income, inner-city women. Health Psychol. 2000;19(6):576. Lobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA. Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol. 2008;27(5):604. Taylor K, Compton S, Kolenic G. Financial Hardship Among Pregnant and Postpartum Women in the United States, 2013 to 2018. JAMA Network Open. 2021; 4 (10): e2132103. 2021. Alotiby A. Immunology of stress: a review article. J Clin Med. 2024;13(21):6394. Coussons-Read ME. Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstetric Med. 2013;6(2):52–7. Rich-Edwards J, Mohllajee A, Kleinman K, Hacker M, Majzoub J, Wright R, et al. Elevated midpregnancy corticotropin-releasing hormone is associated with prenatal, but not postpartum, maternal depression. J Clin Endocrinol Metabolism. 2008;93(5):1946–51. Kendall-Tackett K. A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health. Int Breastfeed J. 2007;2:1–14. Schneider S, Freerksen N, Maul H, Roehrig S, Fischer B, Hoeft B. Risk groups and maternal-neonatal complications of preeclampsia–current results from the national. German Perinat Qual Registry. 2011. Sargent IL, Borzychowski AM, Redman CW. Immunoregulation in normal pregnancy and pre-eclampsia: an overview. Reprod Biomed Online. 2006;13(5):680–6. Li P, Wang H, Feng J, Chen G, Zhou Z, Gou X et al. Association between perceived stress and prenatal depressive symptoms: moderating effect of social support. J Multidisciplinary Healthc. 2021:3195–204. Gokoel AR, Abdoel Wahid F, Zijlmans WC, Shankar A, Hindori-Mohangoo AD, Covert HH, et al. Influence of perceived stress on prenatal depression in Surinamese women enrolled in the CCREOH study. Reproductive health. 2021;18:1–10. Ding X, Liang M, Wang H, Song Q, Guo X, Su W, et al. Prenatal stressful life events increase the prevalence of postpartum depression: Evidence from prospective cohort studies. J Psychiatr Res. 2023;160:263–71. Zoubovsky SP, Williams MT, Hoseus S, Tumukuntala S, Riesenberg A, Schulkin J, et al. Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment. Translational psychiatry. 2022;12(1):22. Weinstock M. Prenatal stressors in rodents: Effects on behavior. Neurobiol stress. 2017;6:3–13. Marchisella F, Creutzberg KC, Begni V, Sanson A, Wearick-Silva LE, Tractenberg SG, et al. Exposure to prenatal stress is associated with an excitatory/inhibitory imbalance in rat prefrontal cortex and amygdala and an increased risk for emotional dysregulation. Front Cell Dev Biology. 2021;9:653384. Payne JL, Maguire J. Pathophysiological mechanisms implicated in postpartum depression. Front Neuroendocr. 2019;52:165–80. Qobadi M, Collier C, Zhang L. The effect of stressful life events on postpartum depression: Findings from the 2009–2011 Mississippi pregnancy risk assessment monitoring system. Matern Child Health J. 2016;20:164–72. Leonard KS, Evans MB, Kjerulff KH, Downs DS. Postpartum perceived stress explains the association between perceived social support and depressive symptoms. Women's Health Issues. 2020;30(4):231–9. Dias JM, Kelty EC, Nicklas JM, Doucette JT, Levkoff SE, Seely EW. Perceived Stress and Early Postpartum Depressive Symptoms in Women with Recent GDM: Implications for Postpartum Lifestyle Programs. Matern Child Health J. 2025:1–7. Sheffield PE, Speranza R, Chiu Y-HM, Hsu H-HL, Curtin PC, Renzetti S, et al. Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning. PLoS ONE. 2018;13(4):e0195267. Bastain TM, Chavez T, Habre R, Hernandez-Castro I, Grubbs B, Toledo-Corral CM, et al. Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort. Environ Health. 2021;20:1–12. Sun Y, Headon KS, Jiao A, Slezak JM, Avila CC, Chiu VY, et al. Association of Antepartum and Postpartum Air Pollution Exposure With Postpartum Depression in Southern California. JAMA Netw Open. 2023;6(10):e2338315–e. Niedzwiecki MM, Rosa MJ, Solano-González M, Kloog I, Just AC, Martínez-Medina S, et al. Particulate air pollution exposure during pregnancy and postpartum depression symptoms in women in Mexico City. Environ Int. 2020;134:105325. Cadman T, Strandberg-Larsen K, Calas L, Christiansen M, Culpin I, Dadvand P, et al. Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts. Environ Int. 2024;185:108453. Bolton JL, Huff NC, Smith SH, Mason SN, Foster WM, Auten RL, et al. Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice. Environ Health Perspect. 2013;121(9):1075–82. Alvarado-Esquivel C, Sifuentes-Alvarez A, Salas-Martinez C, Martínez-García S. Validation of the Edinburgh Postpartum Depression Scale in a population of puerperal women in Mexico. Clin Pract Epidemiol Mental Health. 2006;2:1–5. Alvarado-Esquivel C, Sifuentes-Alvarez A, Salas-Martinez C. Validation of the Edinburgh postpartum depression scale in a population of adult pregnant women in Mexico. J Clin Med Res. 2014;6(5):374. Ortega L, Lartigue T, Figueroa ME. Prevalencia de depresión, a través de la Escala de Depresión Perinatal de Edinburgh (EPDS), en una muestra de mujeres mexicanas embarazadas. Perinatología y Reproducción Humana. 2001;15(1):11–20. Macías-Cortés EdC, Lima-Gómez V, Asbun-Bojalil J. Exactitud diagnóstica de la Escala de Depresión Posnatal de Edimburgo: consecuencias del tamizaje en mujeres mexicanas. Gac Med Mex. 2020;156(3):202–8. Oquendo M, Lartigue T, González-Pacheco I, Méndez S. Validez y seguridad de la Escala de Depresión Perinatal de Edinburgh como prueba de tamiz para detectar depresión perinatal. Perinatología y Reproducción Humana. 2008;22(3):195–202. McRae N, Bello G, Svensson K, Solano-González M, Wright RJ, Niedzwiecki MM, et al. Blood manganese levels during pregnancy and postpartum depression: A cohort study among women in Mexico. Neurotoxicology. 2020;76:183–90. Sit DK, Wisner KL. Identification of postpartum depression. Clin Obstet Gynecol. 2009;52(3):456–68. Fellmeth G, Opondo C, Henderson J, Redshaw M, Mcneill J, Lynn F, et al. Identifying postnatal depression: Comparison of a self-reported depression item with Edinburgh Postnatal Depression Scale scores at three months postpartum. J Affect Disord. 2019;251:8–14. Flom JD, Chiu Y-HM, Tamayo-Ortiz M, Schnaas L, Curtin PC, Wright RJ, et al. Subconstructs of the Edinburgh Postpartum Depression Scale in a postpartum sample in Mexico City. J Affect Disord. 2018;238:142–6. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J psychiatry. 1987;150(6):782–6. Sit D, Rothschild AJ, Wisner KL. A review of postpartum psychosis. J women's health. 2006;15(4):352–68. Just AC, Wright RO, Schwartz J, Coull BA, Baccarelli AA, Tellez-Rojo MM, et al. Using high-resolution satellite aerosol optical depth to estimate daily PM2. 5 geographical distribution in Mexico City. Environ Sci Technol. 2015;49(14):8576–84. Huang Y, Zhang T, Zhu Z, Gong W, Xia X. PM2. 5 concentration estimation with 1-km resolution at high coverage over urban agglomerations in China using the BPNN-KED approach and potential application. Atmos Res. 2021;258:105628. Zhang W, Zheng F, Zhang W, Yang X. Estimating Ground-Level Hourly PM 2.5 Concentrations Over North China Plain with Deep Neural Networks. J Indian Soc Remote Sens. 2021;49:1839–52. Berry CA, Quinn KA, Portillo N, Shalowitz MU. Reliability and validity of the Spanish version of the Crisis in Family Systems–Revised. Psychol Rep. 2006;98(1):123–32. Shalowitz MU, Berry CA, Rasinski KA, Dannhausen-Brun CA. A new measure of contemporary life stress: development, validation, and reliability of the CRISYS. Health Serv Res. 1998;33(5 Pt 1):1381. y Ortiz MT, Téllez-Rojo MM, Trejo-Valdivia B, Schnaas L, Osorio-Valencia E, Coull B, et al. Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment. Environ Int. 2017;98:191–7. Vallejo MA, Vallejo-Slocker L, Fernández-Abascal EG, Mañanes G. Determining factors for stress perception assessed with the Perceived Stress Scale (PSS-4) in Spanish and other European samples. Front Psychol. 2018;9:37. Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983:385–96. Campbell RK, Tamayo-Ortiz M, Cantoral A, Schnaas L, Osorio-Valencia E, Wright RJ, et al. Maternal prenatal psychosocial stress and prepregnancy BMI associations with fetal iron status. Curr Developments Nutr. 2020;4(2):nzaa018. López Romo H. AMAI advances: Distribution of socioeconomic levels in urban Mexico. Mexican Association of Marketing Research and Public Opinion Agencies: Mexico City, Mexico, 2006. Social Investigations Institute, SC [Online]. Available at: http//www.amai.org 2006. Rosa MJ, Just AC, Kloog I, Pantic I, Schnaas L, Lee A, et al. Prenatal particulate matter exposure and wheeze in Mexican children: effect modification by prenatal psychosocial stress. Ann Allergy Asthma Immunol. 2017;119(3):232–7. e1. Islam T, Urman R, Gauderman WJ, Milam J, Lurmann F, Shankardass K, et al. Parental stress increases the detrimental effect of traffic exposure on children's lung function. Am J Respir Crit Care Med. 2011;184(7):822–7. Ahlers NE, Weiss SJ. Exposure to particulate matter, prenatal depressive symptoms and HPA axis dysregulation. Heliyon. 2021;7(6). Thomson EM, Filiatreault A, Guénette J. Stress hormones as potential mediators of air pollutant effects on the brain: rapid induction of glucocorticoid-responsive genes. Environ Res. 2019;178:108717. Wu S, Yin Y, Du L. Blood–brain barrier dysfunction in the pathogenesis of major depressive disorder. Cell Mol Neurobiol. 2022;42(8):2571–91. Jia Z, Wei Y, Li X, Yang L, Liu H, Guo C, et al. Exposure to ambient air particles increases the risk of mental disorder: findings from a natural experiment in Beijing. Int J Environ Res Public Health. 2018;15(1):160. Acoba EF. Social support and mental health: the mediating role of perceived stress. Front Psychol. 2024;15:1330720. Rivera Rivera NY, McGuinn L, Osorio-Valencia E, Martinez-Medina S, Schnaas L, Wright RJ, et al. Changes in depressive symptoms, stress and social support in Mexican women during the COVID-19 pandemic. Int J Environ Res Public Health. 2021;18(16):8775. Additional Declarations No competing interests reported. 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Just","email":"","orcid":"","institution":"Brown University School of Public Health","correspondingAuthor":false,"prefix":"","firstName":"Allan","middleName":"C.","lastName":"Just","suffix":""},{"id":583150308,"identity":"7b499eaa-ce9b-47af-a5ed-d1c9e8c1284c","order_by":4,"name":"Ivan. 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Wright","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"O.","lastName":"Wright","suffix":""},{"id":583150313,"identity":"5bc33e87-ed05-43b4-85a7-c0007f4953bf","order_by":8,"name":"Carmen Hernandez-Chavez","email":"","orcid":"","institution":"National Institute of Perinatology","correspondingAuthor":false,"prefix":"","firstName":"Carmen","middleName":"","lastName":"Hernandez-Chavez","suffix":""},{"id":583150314,"identity":"b12ade43-5b03-4ab4-83ec-56266b1895e9","order_by":9,"name":"Gabriela Gil Martínez","email":"","orcid":"","institution":"National Institute of Perinatology","correspondingAuthor":false,"prefix":"","firstName":"Gabriela","middleName":"Gil","lastName":"Martínez","suffix":""},{"id":583150315,"identity":"f22be2d2-6683-412c-a947-ab48f5fc3d4f","order_by":10,"name":"Rosalind J. Wright","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Rosalind","middleName":"J.","lastName":"Wright","suffix":""},{"id":583150316,"identity":"1fd4f914-1980-4ea2-9bc4-551530c3a74a","order_by":11,"name":"Veerle Bergink","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Veerle","middleName":"","lastName":"Bergink","suffix":""},{"id":583150317,"identity":"e119e176-65e6-4e30-b78d-e628cc16dbed","order_by":12,"name":"Lauren M. Petrick","email":"","orcid":"","institution":"Icahn School of Medicine at Mount Sinai","correspondingAuthor":false,"prefix":"","firstName":"Lauren","middleName":"M.","lastName":"Petrick","suffix":""}],"badges":[],"createdAt":"2026-01-05 16:23:18","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8523355/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8523355/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101753802,"identity":"e10b11cd-5da9-4ce3-81e7-54aac2444a74","added_by":"auto","created_at":"2026-02-03 10:40:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":325087,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between the average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) exposure during pregnancy and postpartum depression (prevalent, new-onset, and chronic depression).\u003c/p\u003e\n\u003cp\u003eFootnotes: Analyses were adjusted for maternal age, maternal education, socioeconomic status, body mass index, maternal exposure to smoke inside the home, and gestational age at birth. EPDS: Edinburgh Postnatal Depression Scale, PPD: Postpartum depression; a) Association between prevalent depression (both old and new cases of depression) and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e); b) Association between chronic PPD (mothers that had depression during pregnancy and continued to be depressed at 6 months postpartum) and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e); c) Association between new-onset PPD at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e).\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8523355/v1/991ba693bc9a111f0e21e16a.png"},{"id":101663749,"identity":"a32d5cff-c3c3-4f2a-bb6e-e8186716c63b","added_by":"auto","created_at":"2026-02-02 11:18:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":390740,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between prevalent depression and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) exposure during pregnancy according to negative life events and perceived stress scores stratum.\u003c/p\u003e\n\u003cp\u003eFootnotes: Analyses were adjusted for maternal age, maternal education, socioeconomic status, body mass index, maternal exposure to smoke inside the home, and gestational age at birth. NLE: Negative life events, PSS: Perceived stress scale score. EPDS: Edinburgh Postnatal Depression Scale, PPD: Postpartum depression; Association between prevalent PPD at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) according to NLE stratum for a) EPDS≥10, c) EPDS≥12, and e) EPDS≥13. Association between prevalent PPD at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) according to PSS stratum for b) EPDS≥10, d) EPDS≥12, and f) EPDS≥13\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8523355/v1/a30ca66b6f29e36fa2c54d95.png"},{"id":101753182,"identity":"c706ba45-1234-4842-8ab5-17532b9b9966","added_by":"auto","created_at":"2026-02-03 10:39:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":126042,"visible":true,"origin":"","legend":"\u003cp\u003eAssociation between postpartum depression onset at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) exposure during pregnancy according to negative life events and perceived stress scores stratum.\u003c/p\u003e\n\u003cp\u003eFootnotes: Analyses were adjusted for maternal age, maternal education, socioeconomic status, body mass index, maternal exposure to smoke inside the home, and gestational age at birth. NLE: Negative life events, PSS: Perceived stress scale score. EPDS: Edinburgh Postnatal Depression Scale, PPD: Postpartum depression; Association between new-onset PPD at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) according to NLE stratum for a) EPDS≥10, c) EPDS≥12, and e) EPDS≥13. Association between new-onset PPD at 6 months postpartum and average particulate air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) according to PSS stratum for b) EPDS≥10, d) EPDS≥12, and f) EPDS≥13.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8523355/v1/a7e1c2460ed9a5d8fb60a991.png"},{"id":101755691,"identity":"c0a1400d-6df3-4fbd-88f6-4b16592495b2","added_by":"auto","created_at":"2026-02-03 10:53:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1516240,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8523355/v1/b157570a-a940-4a47-b417-6c27848058f3.pdf"},{"id":101663750,"identity":"e58dc13e-f11d-4722-b21a-b346a4451cdc","added_by":"auto","created_at":"2026-02-02 11:18:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":141833,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarymaterials.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8523355/v1/7b90ff3f7b9b008224ebfa5c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Air pollution and postpartum depression: the interplay with prenatal stress","fulltext":[{"header":"Introduction","content":"\u003cp\u003eStress is a biological and physiological response to challenges and threats (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Although stress is a normal part of life, its intensity and frequency can heighten during pregnancy due to physiological and psychological changes (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) and worries related to pregnancy and parenting (i.e., labor and delivery, financial constraints) (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Thus, stress can act as an exposure capable of triggering biological response including neuroendocrine and immune changes (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). During pregnancy, the maternal endocrine, nervous, and immune systems undergo adjustments to support fetal development and maternal health (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, prenatal stress can disrupt these processes through dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e), increase corticotropin-releasing hormone (CRH) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e) and inflammatory cytokines (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e), resulting in downstream health effects in the mother (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePrenatal stress is associated with various maternal health outcomes (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e), including postpartum depression (PPD) (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Findings from a recent systematic review and meta-analysis with 17 cohort studies showed a 82% increase in PPD in women exposed to a prenatal stressful life event (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Further, studies suggest the role of HPA axis dysregulation including dysfunction in synaptic transmission and the neurotransmitter system in the mechanism that links stress to PPD (\u003cspan additionalcitationids=\"CR15 CR16\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e–\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). While emerging studies point to additional environmental exposures that can impact the same HPA axis and neuroendocrine pathways to exacerbate or antagonize these associations, most studies have only looked at stress as a single exposure (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e–\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAmbient air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) is an exposure positively associated with PPD, (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) which may act on similar mechanisms as stress (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). There was a 56% increase in PPD risk among mothers with higher PM\u003csub\u003e2.5\u003c/sub\u003e exposure during the second trimester of pregnancy (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e), similar to a study conducted by our team which found a 59% increased risk of PPD per 5-µg/m3 increase in average PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). However, findings from a recent meta-analysis of 12 European birth cohorts found no association between PM\u003csub\u003e2.5\u003c/sub\u003e and PPD. While variability in PM\u003csub\u003e2.5\u003c/sub\u003e and PPD assessment methods between the cohorts, heterogeneity across the cohorts, and bias from complete case analysis likely influenced the analysis (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e), null findings in the meta-analysis may also suggest additional confounders.\u003c/p\u003e \u003cp\u003eBecause both prenatal stress and PM\u003csub\u003e2.5\u003c/sub\u003e are individually associated with PPD, pregnant women may be particularly more vulnerable to their combined effects, as these stressors may interact through shared biological pathways to exacerbate the risk of PPD. However, while a study in mice suggests that maternal stress exposure during late gestation heightens offspring susceptibility—particularly in males—to the harmful effects of prenatal air pollutant exposure on neurocognitive disorders in adulthood (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e), research that examined the interplay of prenatal stress on the association between PM\u003csub\u003e2.5\u003c/sub\u003e and the risk of PPD in humans remains limited. Further, while the Edinburgh Postnatal Depression Scale (EPDS) is a commonly used screening tool for identifying probable PPD, the use of varying cut-off scores such as 7/8 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), 9/10 (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e), 11/12 (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e), ≥ 12 (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e), and ≥ 14 (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e) in Mexico, can complicate cross-study comparisons and interpretations. For example, our team previously used an EPDS threshold of 13 or more (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) in analyses from the Programming Research in Obesity, Growth, Environment, and Social Stressors (PROGRESS) cohort as a conservative threshold to reduce the probability of false positives within the context of a population-based cohort allowing for the identification of cases with more marked symptomatology.\u003c/p\u003e \u003cp\u003eIn this study, we assessed the role of prenatal stress—negative life events (NLE) and perceived stress on the association between PM\u003csub\u003e2.5\u003c/sub\u003e and PPD using data from a prospective cohort of Mexican mothers. Understanding their potential joint effects is critical for identifying vulnerable women and informing preventive screening strategies. We primarily used an EPDS cut-off score of ≥ 13, consistent with the threshold commonly applied in previous PROGRESS studies and assessed the robustness of our findings using two of the proposed cut-offs (≥ 10 and ≥ 12) for screening probable PPD in Mexico.\u003c/p\u003e "},{"header":"Methods","content":"\u003cp\u003eStudy population\u003c/p\u003e\u003cp\u003eHealthy pregnant women who received prenatal care through the Mexican Social Security Institute (Instituto Mexicano del Seguro Social – IMSS) between 2007 and 2011 were recruited in the PROGRESS study (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Participants were included in the study if they met the following criteria: less than 20 weeks of gestation, singleton pregnancy, at least 18 years old, completed primary education, intended to remain in Mexico City for the next three years, had telephone access, no history of heart or kidney disease, did not consume alcohol daily, reported no drug addiction, and were not taking steroids or anti-epileptic medications. This study included 475 participants with complete data on PPD at 6 months postpartum, prenatal stress, pregnancy PM\u003csub\u003e2.5\u003c/sub\u003e, and all covariates. The sample size in this study is smaller than that of the original cohort study on PM\u003csub\u003e2.5\u003c/sub\u003e PPD (509 participants) (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e) due to missing data on perceived stress for approximately 7% of the participants.\u003c/p\u003e\u003cp\u003eOutcomes\u003c/p\u003e\u003cp\u003eThe Spanish version of the EPDS, validated in Mexico (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), was used to collect data on mother’s depressive symptoms during the second or third trimester of pregnancy and at 6 months postpartum. EPDS is a widely used screening tool to identify and monitor postpartum depressive symptoms in mothers (\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e–\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e). The EPDS is a 10-item self-report questionnaire that assesses how the participants felt over the past seven days (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e). These items include: “I have laughed and been able to see the funny side of things,” “I have looked forward with enjoyment to things,” “I have blamed myself unnecessarily when things went wrong,” “I have been anxious or worried for no good reason,” “I have felt scared or panicky for no very good reason,” “Things have been getting on top of me,” “I have been so unhappy that I have had difficulty sleeping,” “I have felt sad or miserable,” “I have been so unhappy that I have been crying,” and “The thought of harming myself has occurred to me.” Participant’s responses are scored on a 4-point Likert scale, from zero (0) to three based on the seriousness of the symptom. A score of zero (0) indicates that the participant is the most favorable condition (i.e., unlikely to have a clinically significant depressive symptom), while a score of three suggests the least favorable condition (i.e., likely to have a clinically significant depressive symptom). The total score, ranging from zero (0) to 30 is calculated by summing the scores of all 10 items.\u003c/p\u003e\u003cp\u003eWe applied the commonly used threshold in PROGRESS publications (EPDS ≥ 13: Yes/No) to identify women with probable PPD, a clinically relevant cut-off used in other settings to identify women at risk for major depression (\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e, \u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e). Because lower cut-offs have been proposed for screening women with probable PDD in Mexico (\u003cspan additionalcitationids=\"CR28 CR29 CR30\" citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e–\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e), we compared our findings with other cut-off values of EPDS ≥ 10 and EPDS ≥ 12. These cut-off values refer to the most updated thresholds proposed for screening for major depressive symptoms in adult women in Mexico (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e). This strategy allowed us to assess whether the observed associations between PM\u003csub\u003e2.5\u003c/sub\u003e and PPD are consistent, and not sensitive to a specific threshold.\u003c/p\u003e\u003cp\u003eWe assessed prevalent PPD, chronic PPD, and new-onset PPD at 6 months using the three cut-off values. Chronic PPD included mothers with an EPDS ≥ 13 during pregnancy and at 6 months postpartum. New-onset PPD included mothers with an EPDS \u0026lt; 13 during pregnancy but EPDS ≥ 13 at 6 months postpartum (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Prevalent PPD refers to any mother with an EPDS ≥ 13 at 6 months postpartum, regardless of EPDS score during pregnancy (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Thus, prevalent depression included mothers with both chronic PPD, and new-onset PPD. Similar definitions were applied when considering the EPDS ≥ 10 and EPDS ≥ 12 cut-offs.\u003c/p\u003e\u003cp\u003ePrenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy\u003c/p\u003e\u003cp\u003eDaily PM\u003csub\u003e2.5\u003c/sub\u003e exposure for each participant’s residence was assessed during pregnancy using a validated spatiotemporal model (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e). The model integrated data from Moderate Resolution Imaging Spectroradiometer (MODIS) satellite-derived Aerosol Optical Depth (AOD) at a 1×1 km spatial resolution with ground-based PM\u003csub\u003e2.5\u003c/sub\u003e measurements, meteorological data (including temperature, relative humidity, wind speed, and planetary boundary layer height), and land use regression variables (such as roadway density). Mixed-effects modeling, which incorporated spatial and temporal predictors alongside day-specific random effects, was employed to capture temporal variability in the relationship between PM\u003csub\u003e2.5\u003c/sub\u003e and AOD. The model incorporated a seasonal smoothing function for latitude and longitude, along with a time-varying average, to integrate local monitoring data on days when AOD measurements were unavailable. The model exhibited strong predictive accuracy, with an R² of 0.724 from cross-validation, and has undergone external validation in prior studies (\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e, \u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e). Daily exposure estimates were assigned to participants based on GPS coordinates of their residential locations, collected by study personnel. Gestational age was determined using maternal reports of the last menstrual period and standardized physical examinations. The average PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy was calculated using the average PM\u003csub\u003e2.5\u003c/sub\u003e measurements from each trimester (1–13 weeks for the first trimester, 14–27 weeks for the second, and 28 weeks to delivery for the third). We convert PM\u003csub\u003e2.5\u003c/sub\u003e exposure to a 5-unit change during pregnancy to simplify the interpretation of its effects on the outcomes. More details on the model's development and validation are available elsewhere (\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePrenatal stress during pregnancy.\u003c/p\u003e\u003cp\u003eNLE was measured using the Crisis in Family Systems-Revised (CRISYS) survey, previously validated in Spanish (\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e) CRISYS is a flexible, multidimensional, and standardized tool developed to quantify contemporary sources of life stress (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). It measures life events across 11 domains: financial, legal, career, relationship, home safety, neighborhood safety, medical issues (self and others), home, prejudice, and authority (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Participants in their third trimester of pregnancy(\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e) indicated whether they experienced specific life events in the past six months as positive, negative or neutral. Therefore, the NLE captures stress during the pregnancy period. The NLE domain score is calculated by summing the number of domains that have one or more negative events. NLE score ranges from 0 to 11, with higher score indicating greater stress (\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e). Perceived stress score (PSS) during the third trimester of pregnancy was measured using the validated Spanish version of the 4-item Perceived Stress Scale (PSS-4) (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e, \u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e). Participants rated their perceived stress level in a 5-point Likert scale, ranging from zero (0) to 4 (\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e). The PSS score is calculated by summing the scores of individual items, with a higher score indicating greater perceived stress (\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eCovariates\u003c/p\u003e\u003cp\u003eMaternal age (in years), maternal level of education (less than high school, high school, more than high school), socioeconomic status (SES), body mass index (BMI) pre-pregnancy, maternal exposure to smoke inside the home (yes/no), prenatal stress, and gestational age at birth (in weeks) were used as covariates in this study. SES in PROGRESS is calculated based on the Mexican Association of Market and Public Opinion Research Agencies (Spanish acronym AMAI) (\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e). We used maternal exposure to second-hand smoke inside the home instead of self-reported smoking during pregnancy, as only one mother reported smoking during pregnancy.\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eWe performed descriptive analysis for all the variables included in this study. We assessed the association between mean PM\u003csub\u003e2.5\u003c/sub\u003e during pregnancy and the outcomes using modified Poisson regression with robust error variance, allowing us to calculate the relative risk for the current study sample size (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). To evaluate departures from multiplicativity, we tested for interactions by including a product term between the average PM\u003csub\u003e2.5\u003c/sub\u003e and prenatal stress (NLE and PSS levels) dichotomized around the median (\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e, \u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e). We then stratified the model by low and high stress levels. The analyses were adjusted for maternal age, maternal education, maternal exposure to smoke inside the home, and gestational age at birth. Statistical significance was determined at a p-value of less than 0.05. All the analyses were conducted using R, version 4.4.1 (2024-06-14 ucrt).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;1 summarizes the characteristics of the study population. On average, maternal age during pregnancy was 27.7 (SD: 5.5). PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy was 22.9 µg/m\u003csup\u003e3\u003c/sup\u003e (IQR: 20.3–24.5). Maternal education ranged from 23.4% among mothers with more than a high school education to 41.1% among those with less than a high school education. Approximately 11% of mothers belonged to a high socioeconomic status, while 51.4% were classified as low socioeconomic status. The median NLE and PSS scores during pregnancy were 3 (IQR: 2–5) and 5 (IQR: 3–7), respectively. At 6 months postpartum, median EPDS score was 5 (IQR: 2–10). Over 18% of mothers had prevalent PPD, 9.7% had chronic PPD, and 8.6% had new-onset PPD, using a cut-off of EPDS ≥ 13. However, considering an EPDS ≥ 10, 30.3% of mothers identified with prevalent depression, 20.8% with chronic PPD, and 9.5% with new-onset PPD (Table\u0026nbsp;1).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eCharacteristics of the study population (N = 475).\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDescription N (%)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal age (years) during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.7 (SD: 5.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal exposure to smoke inside home during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e145 (30.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e330 (69.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal education during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;High school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e195 (41.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e169 (35.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;High school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e111 (23.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSocioeconomic status during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e244 (51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e180 (37.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e51 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAverage PM2.5 in pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.9 (IQR: 20.3–24.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMother's body mass index pre-pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26.9 (SD: 4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNLE during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (IQR:2–5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePerceived stress during pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (IQR: 3–7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGestational age at birth (weeks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (IQR: 38–39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS at 6 months postpartum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (IQR: 2–10)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 10 prevalent PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e144 (30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e331 (69.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 10 chronic PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e99 (20.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e376 (79.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS \u0026lt; 10 new-onset PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e45 (9.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e430 (90.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 12 prevalent PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e98 (20.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e377 (79.37)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 12 chronic PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55 (11.60)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e420 (88.40)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS \u0026lt; 12 new-onset PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43 (9.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e432 (90.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 13 prevalent PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e86 (18.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e389 (81.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS ≥ 13 chronic PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e46 (9.70)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e429 (90.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEPDS \u0026lt; 13 new-onset PPD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e41 (8.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e434 (91.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\"\u003eFootnotes: EPDS: Edinburgh Postnatal Depression Scale, NLE: Negative life events, SD: Standard deviation, IQR: Interquartile range, prevalent PPD: all participants with EPDS equal to or above the cut-off at 6 months, regardless of EPDS score during pregnancy; chronic depression: EPDS equal to or above cut-off during pregnancy and at 6 months postpartum; new-onset PPD: EPDS equal to or above cut-off at 6 months postpartum, but below the cut-off during pregnancy\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eWe assessed the association between PPD and average PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy for EPDS ≥ 10, EPDS ≥ 12, and EPDS ≥ 13) (Fig.\u0026nbsp;1). The risk of prevalent PPD and new-onset PPD (EPDS ≥ 13) increased by 49% (RR: 1.49, 95%CI: 1.02–2.19) (Fig.\u0026nbsp;1a), and 167% (RR: 2.67, 95%CI: 1.37–5.21) (Fig.\u0026nbsp;1c), respectively, per 5-µg/m\u003csup\u003e3\u003c/sup\u003e increase in average PM\u003csub\u003e2.5\u003c/sub\u003e during pregnancy, similar to analyses performed in the larger cohort of 509 women (24). Likewise, there was a positive association between the average PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy and the risk of new-onset PPD using an EPDS ≥ 10 (RR: 2.12, 95%CI: 1.28–3.54) and an EPDS ≥ 12 (RR: 2.07, 95%CI: 1.10–3.91) (Fig.\u0026nbsp;1c), respectively. No association was found between the average PM\u003csub\u003e2.5\u003c/sub\u003e and chronic PPD for all cut-offs (Fig.\u0026nbsp;1b).\u003c/p\u003e\n\u003cp\u003eWe then investigated how prenatal stress modified the relationship between PM\u003csub\u003e2.5\u003c/sub\u003e and prevalent PPD. Perceived stress modified the association between PM\u003csub\u003e2.5\u003c/sub\u003e exposure and prevalent PPD, but not NLE (Fig.\u0026nbsp;2). Each 5-µg/m³ increase in pregnancy PM\u003csub\u003e2.5\u003c/sub\u003e exposure was associated with 129% increased risk of prevalent PPD (EPDS ≥ 13) in mothers with low PSS (RR: 2.29, 95%CI: 1.17–4.47) (Fig.\u0026nbsp;2f). Similarly, there was an increased risk of prevalent PPD per 5-µg/m\u003csup\u003e3\u003c/sup\u003e increase in average PM\u003csub\u003e2.5\u003c/sub\u003e among mothers with low PSS stratum using an EPDS ≥ 10 or EPDS ≥ 12 (RR: 1.68, 95%CI: 1.04–2.77; RR: 2.57, 95%CI: 1.35–4.90, respectively) (Fig.\u0026nbsp;2b and 2d).\u003c/p\u003e\n\u003cp\u003eThe analyses between chronic PPD and average PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy according to NLE and PSS stratums did not yield any significant association (Supplementary Fig.\u0026nbsp;1a-1f). However, the effect of PM\u003csub\u003e2.5\u003c/sub\u003e on chronic PPD appeared to be in the positive direction among mothers with low PSS across the different EPDS threshold (Supplementary Fig.\u0026nbsp;1b, 1d, and 1f), consistent with the above findings for prevalent PPD.\u003c/p\u003e\n\u003cp\u003eThe associations between PM\u003csub\u003e2.5\u003c/sub\u003e exposure and new-onset PPD according to NLE and PSS stratum were assessed (Fig.\u0026nbsp;3). Each 5-µg/m³ increase in average PM\u003csub\u003e2.5\u003c/sub\u003e during pregnancy was associated with a 371% increase in the risk of new-onset PPD (EPDS ≥ 13) in mothers with high NLE (RR: 4.71, 95%CI: 1.72–12.92) (Fig.\u0026nbsp;3e) and a 358% increase among those with a low PSS scores (RR: 4.58, 95%CI: 1.83–11.49) (Fig.\u0026nbsp;3f). Similar findings were observed using an EPDS ≥ 12 in mothers with high NLE (RR: 4.66, 95%CI: 1.80–12.10) Fig.\u0026nbsp;3c) and among those with low PSS (RR: 2.67, 95%CI: 1.27–5.64) (Fig.\u0026nbsp;3d). Increased risk of new-onset PPD per 5-µg/m³ increase in average PM\u003csub\u003e2.5\u003c/sub\u003e was also observed among mothers with high NLE (RR: 3.34, 95%CI: 1.36–8.21) (Fig.\u0026nbsp;3a), and with high PSS (RR: 4.77, 95%CI: 1.04–21.81) using an EPDS ≥ 10, although the association was borderline among those with a low PSS (RR: 1.83, 95%CI: 0.99–3.40) (Fig.\u0026nbsp;3b).\u003c/p\u003e\n\u003cp\u003eFinally, we assessed whether the association between average PM\u003csub\u003e2.5\u003c/sub\u003e level during pregnancy and depression depended on stress (Supplementary Table\u0026nbsp;1). Indeed, a statistically significant interaction was observed between the average PM\u003csub\u003e2.5\u003c/sub\u003e level and PSS on new-onset PPD (p = 0.035) using an EPDS ≥ 13 as well as between average PM\u003csub\u003e2.5\u003c/sub\u003e level and NLE on new-onset PPD o using an EPDS ≥ 12 (P = 0.005). A similar finding was observed between average PM\u003csub\u003e2.5\u003c/sub\u003e level and PSS on prevalent PPD using an EPDS ≥ 12 (Supplementary Table\u0026nbsp;1).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study assessed the modifying role of prenatal psychosocial stress on the association between prenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure and postpartum depression in Mexico, using three EPDS cut-offs (\u0026ge;\u0026thinsp;13, \u0026ge;\u0026thinsp;12, and \u0026ge;\u0026thinsp;10). We observed that PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy was consistently associated with increased risk of new-onset PPD across all thresholds. Among mothers with a low PSS, the effect of PM\u003csub\u003e2.5\u003c/sub\u003e on prevalent PPD was stronger independently of the EPDS threshold used. Similar findings were observed for new-onset PPD among mothers with a high NLE and a low PSS across all the three EPDS cut-offs. These findings indicate that PM\u003csub\u003e2.5\u003c/sub\u003e exposure during pregnancy is a consistent environmental risk factor for PPD, independently of the EPDS threshold used. Whether using a lower threshold (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;10) to capture milder symptoms or a higher cut-off to identify cases with more marked symptomatology, the association between PM\u003csub\u003e2.5\u003c/sub\u003e and new-onset PPD remained consistent. More importantly, the findings indicate that prenatal stress, particularly high exposure to NLE and low PSS may heighten the effect of ambient air pollution on new-onset PPD at 6 months postpartum, regardless of the cut-off used. However, we observed no statistically significant association between depression that began during pregnancy and persisted to six months postpartum (i.e., chronic PPD), suggesting that PM\u003csub\u003e2.5\u003c/sub\u003e may not play a significant role in the continuation of pre-existing depressive symptoms. The fact that PM\u003csub\u003e2.5\u003c/sub\u003e was positively associated with prevalent PPD which included both new and old cases of probable depression suggests that PM\u003csub\u003e2.5\u003c/sub\u003e may contribute more to the incidence of new cases or exacerbate existing symptoms enough to meet the minimal EPDS threshold, which was evident when considering new-onset PPD, which includes only new cases of PPD at 6 months postpartum.\u003c/p\u003e \u003cp\u003eThe amplified effect of PM\u003csub\u003e2.5\u003c/sub\u003e on prevalent depression, particularly on new-onset PPD in mothers with a low PSS highlights the increase vulnerability of these mothers to the mental health effects of PM\u003csub\u003e2.5\u003c/sub\u003e. In this population, mothers with low perceived stress might not have established coping mechanisms, and therefore, be more overwhelmed by environmental stressors such as air pollution. Similarly, these mothers may live in environments with greater environmental hazards due to socioeconomics challenges and lack social support networks making them even more vulnerable to the effect of PM\u003csub\u003e2.5\u003c/sub\u003e. As shown in previous studies, exposure to higher levels of PM\u003csub\u003e2.5\u003c/sub\u003e may elicit a more pronounced biological stress response in these mothers, which may lead to over-activation of the HPA axis (\u003cspan additionalcitationids=\"CR51\" citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e), elevated cortisol (\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e), and release of pro-inflammatory cytokines like 1α (IL-1α), IL-1β, IL-6, and tumor necrosis factor-α(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e, \u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e), with subsequent downstream consequences on maternal mental health. Given that perceived stress is subjective, mothers with low PSS can still face significant stressors like PM\u003csub\u003e2.5\u003c/sub\u003e and other postpartum life challenges that make them more susceptible to the risk of these outcomes, if effective coping mechanisms or social support is lacking (\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e, \u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e). In this study, the NLE captured events that occurred in the past six months, while the PSS focused on stress that occurred in the last month during the third trimester of pregnancy. Although the NLE and PSS capture different dimensions of stress, it is possible that stressful events throughout the gestational period align more closely to the detrimental effect of PM\u003csub\u003e2.5\u003c/sub\u003e on new-onset PPD at six months postpartum, compared to perceived stress. The stronger effect of PM\u003csub\u003e2.5\u003c/sub\u003e on the risk of new-onset PPD in mothers with high NLE scores across all three threshold suggests that prolonged exposure to stressors like NLE may increase their susceptibility to air pollution, increasing the risk of new-onset PPD at 6 months. However, we observed that the effect of PM\u003csub\u003e2.5\u003c/sub\u003e on prevalent PPD at 6 months remained similar across different levels of NLE scores indicating that NLE do not act as an effect modifier in this relationship. The difference in the effect of PM\u003csub\u003e2.5\u003c/sub\u003e on prevalent PPD and new-onset PPD across NLE scores suggests that the combination of air pollution and NLE has a stronger influence on the later postpartum onset of depression rather than on depression that is persistence from pregnancy to 6 months postpartum. Overall, our findings highlight the interplay between environmental and psychosocial stressors, emphasizing pregnancy as a heightened period of susceptibility for postpartum mental health outcomes. This also highlights the need to account for air pollution and the need for well-characterized prenatal stressors when assessing the risk to postpartum maternal mental health outcomes.\u003c/p\u003e \u003cp\u003eWhile past analyses established the independent link between both prenatal stress (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e)and PM\u003csub\u003e2.5 (21, 22)\u003c/sub\u003e with PPD, there is a lack of studies assessing the role of prenatal stress on the association between prenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure and the risk of PPD. Given that both increased PM\u003csub\u003e2.5\u003c/sub\u003e and prenatal stress independently place significant psychological strain on individuals (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e), primarily by activating the HPA axis and triggering an inflammatory response, such disruption in the presence of the combined effect of prenatal stress and PM\u003csub\u003e2.5\u003c/sub\u003e may overwhelm stress regulation mechanisms, exacerbating the risk of PPD particularly new-onset PPD at 6 months as we see here.\u003c/p\u003e \u003cp\u003eOur study has strengths and limitations. To our knowledge, this is the first study to examine whether the association between PM\u003csub\u003e2.5\u003c/sub\u003e and the risk of PPD differs according to prenatal stress levels. We used an EPDS\u0026thinsp;\u0026ge;\u0026thinsp;13 considered as a conservative threshold to identify postpartum women at risk for major depressive symptoms (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e), and compared our findings with two other proposed thresholds (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;10, EPDS\u0026thinsp;\u0026ge;\u0026thinsp;12) for screening PPD in Mexico to determine robustness of the associations. Data used in this study came from a well-defined longitudinal cohort study, with substantial sample size, and high spatial resolution of PM\u003csub\u003e2.5\u003c/sub\u003e exposure data that covers the whole pregnancy period. The study showed that prenatal stress particularly low PSS and high NLE exacerbated the effect of prenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure on PPD, especially new-onset PPD. However, our findings must be interpreted as an increased risk for PPD as the EPDS is a screening tool used to assess possible depression, instead of clinical depression per se. Furthermore, considering that the NLE scale and the PSS used in this study represent different periods of exposure during pregnancy, the results of our study must be interpreted accordingly. It is necessary to measure perceived stress throughout all trimesters of pregnancy for comparative purposes and to identify critical periods of vulnerability during pregnancy.\u003c/p\u003e"},{"header":"Conclusion and recommendation","content":"\u003cp\u003ePrenatal low perceived stress and high negative life events exacerbate the effect of prenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure on the risk of PPD, particularly new-onset PPD, across EPDS thresholds of \u0026ge;\u0026thinsp;10 to \u0026ge;\u0026thinsp;13. This highlights the robustness of our findings and the complex interplay between environmental and psychosocial factors, particularly among mothers facing psychosocial challenges. More longitudinal study is needed particularly using perceived stress collected across all trimesters of pregnancy to understand the interplay between environmental exposures and prenatal stress on PPD.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eAOD: Aerosol Optical Depth\u003c/p\u003e\n\u003cp\u003eBMI: Body mass index (BMI)\u003c/p\u003e\n\u003cp\u003eCRH: Corticotropin-releasing hormone\u003c/p\u003e\n\u003cp\u003eCRISYS: Crisis in Family Systems-Revised\u003c/p\u003e\n\u003cp\u003eEPDS: Edinburgh Postnatal Depression Scale\u003c/p\u003e\n\u003cp\u003eHPA: Hypothalamic-pituitary-adrenal\u003c/p\u003e\n\u003cp\u003eIMSS: Instituto Mexicano del Seguro Social\u003c/p\u003e\n\u003cp\u003eMODIS: Moderate Resolution Imaging Spectroradiometer\u003c/p\u003e\n\u003cp\u003eNLE: Negative life events\u003c/p\u003e\n\u003cp\u003ePM2.5: Ambient air pollution\u003c/p\u003e\n\u003cp\u003ePPD: Postpartum depression\u003c/p\u003e\n\u003cp\u003ePROGRESS: Programming Research in Obesity, Growth, Environment, and Social Stressors\u003c/p\u003e\n\u003cp\u003ePSS: Perceived stress score\u003c/p\u003e\n\u003cp\u003eSES: Socioeconomic status\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eEach participant signed a written informed consent before participating in the study. Approval was obtained from the institutional review boards at the Harvard School of Public Health, Icahn School of Medicine at Mount Sinai, the National Institute of Perinatology, and the Mexican National Institute of Public Health.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u0026nbsp;\u003c/strong\u003eThe data that support the findings of this study are available from the corresponding authors upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding and Acknowledgements:\u0026nbsp;\u003c/strong\u003eThis study was funded by the National Institutes of Health/National Institute of Environmental Health Sciences [R01 ES036725, R01 ES014930, R01 ES013744, P30 ES023515, R00\u0026nbsp;ES027496, R01 ES031117, and UL1TR004419] and the National Institute of Public Health/Ministry of Health of Mexico. We are grateful to the ABC (American British Cowdray Medical Center) in Mexico for providing research facilities.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions:\u0026nbsp;\u003c/strong\u003eConceptualization: LP, MN, EC, CHC. \u0026nbsp;Data curation and verification: IK, ACJ, IG-A. Funding acquisition: ROW, MT-J, LP. Methodology development: CHC, MN. Formal analysis: GJ. Supervision: LP. Original draft: GJ and LP. Writing-review and editing: All authors. Approval of final version: All authors.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eRussell G, Lightman S. The human stress response. Nat reviews Endocrinol. 2019;15(9):525\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRitter C, Hobfoll SE, Lavin J, Cameron RP, Hulsizer MR. Stress, psychosocial resources, and depressive symptomatology during pregnancy in low-income, inner-city women. Health Psychol. 2000;19(6):576.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLobel M, Cannella DL, Graham JE, DeVincent C, Schneider J, Meyer BA. Pregnancy-specific stress, prenatal health behaviors, and birth outcomes. Health Psychol. 2008;27(5):604.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaylor K, Compton S, Kolenic G. Financial Hardship Among Pregnant and Postpartum Women in the United States, 2013 to 2018. JAMA Network Open. 2021; 4 (10): e2132103. 2021.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlotiby A. Immunology of stress: a review article. J Clin Med. 2024;13(21):6394.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCoussons-Read ME. Effects of prenatal stress on pregnancy and human development: mechanisms and pathways. Obstetric Med. 2013;6(2):52\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRich-Edwards J, Mohllajee A, Kleinman K, Hacker M, Majzoub J, Wright R, et al. Elevated midpregnancy corticotropin-releasing hormone is associated with prenatal, but not postpartum, maternal depression. J Clin Endocrinol Metabolism. 2008;93(5):1946\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKendall-Tackett K. A new paradigm for depression in new mothers: the central role of inflammation and how breastfeeding and anti-inflammatory treatments protect maternal mental health. Int Breastfeed J. 2007;2:1\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchneider S, Freerksen N, Maul H, Roehrig S, Fischer B, Hoeft B. Risk groups and maternal-neonatal complications of preeclampsia\u0026ndash;current results from the national. German Perinat Qual Registry. 2011.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSargent IL, Borzychowski AM, Redman CW. Immunoregulation in normal pregnancy and pre-eclampsia: an overview. Reprod Biomed Online. 2006;13(5):680\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi P, Wang H, Feng J, Chen G, Zhou Z, Gou X et al. Association between perceived stress and prenatal depressive symptoms: moderating effect of social support. J Multidisciplinary Healthc. 2021:3195\u0026ndash;204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGokoel AR, Abdoel Wahid F, Zijlmans WC, Shankar A, Hindori-Mohangoo AD, Covert HH, et al. Influence of perceived stress on prenatal depression in Surinamese women enrolled in the CCREOH study. Reproductive health. 2021;18:1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing X, Liang M, Wang H, Song Q, Guo X, Su W, et al. Prenatal stressful life events increase the prevalence of postpartum depression: Evidence from prospective cohort studies. J Psychiatr Res. 2023;160:263\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZoubovsky SP, Williams MT, Hoseus S, Tumukuntala S, Riesenberg A, Schulkin J, et al. Neurobehavioral abnormalities following prenatal psychosocial stress are differentially modulated by maternal environment. Translational psychiatry. 2022;12(1):22.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeinstock M. Prenatal stressors in rodents: Effects on behavior. Neurobiol stress. 2017;6:3\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarchisella F, Creutzberg KC, Begni V, Sanson A, Wearick-Silva LE, Tractenberg SG, et al. Exposure to prenatal stress is associated with an excitatory/inhibitory imbalance in rat prefrontal cortex and amygdala and an increased risk for emotional dysregulation. Front Cell Dev Biology. 2021;9:653384.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePayne JL, Maguire J. Pathophysiological mechanisms implicated in postpartum depression. Front Neuroendocr. 2019;52:165\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQobadi M, Collier C, Zhang L. The effect of stressful life events on postpartum depression: Findings from the 2009\u0026ndash;2011 Mississippi pregnancy risk assessment monitoring system. Matern Child Health J. 2016;20:164\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeonard KS, Evans MB, Kjerulff KH, Downs DS. Postpartum perceived stress explains the association between perceived social support and depressive symptoms. Women's Health Issues. 2020;30(4):231\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDias JM, Kelty EC, Nicklas JM, Doucette JT, Levkoff SE, Seely EW. Perceived Stress and Early Postpartum Depressive Symptoms in Women with Recent GDM: Implications for Postpartum Lifestyle Programs. Matern Child Health J. 2025:1\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSheffield PE, Speranza R, Chiu Y-HM, Hsu H-HL, Curtin PC, Renzetti S, et al. Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning. PLoS ONE. 2018;13(4):e0195267.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBastain TM, Chavez T, Habre R, Hernandez-Castro I, Grubbs B, Toledo-Corral CM, et al. Prenatal ambient air pollution and maternal depression at 12 months postpartum in the MADRES pregnancy cohort. Environ Health. 2021;20:1\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun Y, Headon KS, Jiao A, Slezak JM, Avila CC, Chiu VY, et al. Association of Antepartum and Postpartum Air Pollution Exposure With Postpartum Depression in Southern California. JAMA Netw Open. 2023;6(10):e2338315\u0026ndash;e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNiedzwiecki MM, Rosa MJ, Solano-Gonz\u0026aacute;lez M, Kloog I, Just AC, Mart\u0026iacute;nez-Medina S, et al. Particulate air pollution exposure during pregnancy and postpartum depression symptoms in women in Mexico City. Environ Int. 2020;134:105325.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCadman T, Strandberg-Larsen K, Calas L, Christiansen M, Culpin I, Dadvand P, et al. Urban environment in pregnancy and postpartum depression: An individual participant data meta-analysis of 12 European birth cohorts. Environ Int. 2024;185:108453.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBolton JL, Huff NC, Smith SH, Mason SN, Foster WM, Auten RL, et al. Maternal stress and effects of prenatal air pollution on offspring mental health outcomes in mice. Environ Health Perspect. 2013;121(9):1075\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvarado-Esquivel C, Sifuentes-Alvarez A, Salas-Martinez C, Mart\u0026iacute;nez-Garc\u0026iacute;a S. Validation of the Edinburgh Postpartum Depression Scale in a population of puerperal women in Mexico. Clin Pract Epidemiol Mental Health. 2006;2:1\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlvarado-Esquivel C, Sifuentes-Alvarez A, Salas-Martinez C. Validation of the Edinburgh postpartum depression scale in a population of adult pregnant women in Mexico. J Clin Med Res. 2014;6(5):374.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtega L, Lartigue T, Figueroa ME. Prevalencia de depresi\u0026oacute;n, a trav\u0026eacute;s de la Escala de Depresi\u0026oacute;n Perinatal de Edinburgh (EPDS), en una muestra de mujeres mexicanas embarazadas. Perinatolog\u0026iacute;a y Reproducci\u0026oacute;n Humana. 2001;15(1):11\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMac\u0026iacute;as-Cort\u0026eacute;s EdC, Lima-G\u0026oacute;mez V, Asbun-Bojalil J. Exactitud diagn\u0026oacute;stica de la Escala de Depresi\u0026oacute;n Posnatal de Edimburgo: consecuencias del tamizaje en mujeres mexicanas. Gac Med Mex. 2020;156(3):202\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOquendo M, Lartigue T, Gonz\u0026aacute;lez-Pacheco I, M\u0026eacute;ndez S. Validez y seguridad de la Escala de Depresi\u0026oacute;n Perinatal de Edinburgh como prueba de tamiz para detectar depresi\u0026oacute;n perinatal. Perinatolog\u0026iacute;a y Reproducci\u0026oacute;n Humana. 2008;22(3):195\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcRae N, Bello G, Svensson K, Solano-Gonz\u0026aacute;lez M, Wright RJ, Niedzwiecki MM, et al. Blood manganese levels during pregnancy and postpartum depression: A cohort study among women in Mexico. Neurotoxicology. 2020;76:183\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSit DK, Wisner KL. Identification of postpartum depression. Clin Obstet Gynecol. 2009;52(3):456\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFellmeth G, Opondo C, Henderson J, Redshaw M, Mcneill J, Lynn F, et al. Identifying postnatal depression: Comparison of a self-reported depression item with Edinburgh Postnatal Depression Scale scores at three months postpartum. J Affect Disord. 2019;251:8\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFlom JD, Chiu Y-HM, Tamayo-Ortiz M, Schnaas L, Curtin PC, Wright RJ, et al. Subconstructs of the Edinburgh Postpartum Depression Scale in a postpartum sample in Mexico City. J Affect Disord. 2018;238:142\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCox JL, Holden JM, Sagovsky R. Detection of postnatal depression: development of the 10-item Edinburgh Postnatal Depression Scale. Br J psychiatry. 1987;150(6):782\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSit D, Rothschild AJ, Wisner KL. A review of postpartum psychosis. J women's health. 2006;15(4):352\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJust AC, Wright RO, Schwartz J, Coull BA, Baccarelli AA, Tellez-Rojo MM, et al. Using high-resolution satellite aerosol optical depth to estimate daily PM2. 5 geographical distribution in Mexico City. Environ Sci Technol. 2015;49(14):8576\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Y, Zhang T, Zhu Z, Gong W, Xia X. PM2. 5 concentration estimation with 1-km resolution at high coverage over urban agglomerations in China using the BPNN-KED approach and potential application. Atmos Res. 2021;258:105628.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang W, Zheng F, Zhang W, Yang X. Estimating Ground-Level Hourly PM 2.5 Concentrations Over North China Plain with Deep Neural Networks. J Indian Soc Remote Sens. 2021;49:1839\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerry CA, Quinn KA, Portillo N, Shalowitz MU. Reliability and validity of the Spanish version of the Crisis in Family Systems\u0026ndash;Revised. Psychol Rep. 2006;98(1):123\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShalowitz MU, Berry CA, Rasinski KA, Dannhausen-Brun CA. A new measure of contemporary life stress: development, validation, and reliability of the CRISYS. Health Serv Res. 1998;33(5 Pt 1):1381.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ey Ortiz MT, T\u0026eacute;llez-Rojo MM, Trejo-Valdivia B, Schnaas L, Osorio-Valencia E, Coull B, et al. Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment. Environ Int. 2017;98:191\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVallejo MA, Vallejo-Slocker L, Fern\u0026aacute;ndez-Abascal EG, Ma\u0026ntilde;anes G. Determining factors for stress perception assessed with the Perceived Stress Scale (PSS-4) in Spanish and other European samples. Front Psychol. 2018;9:37.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983:385\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCampbell RK, Tamayo-Ortiz M, Cantoral A, Schnaas L, Osorio-Valencia E, Wright RJ, et al. Maternal prenatal psychosocial stress and prepregnancy BMI associations with fetal iron status. Curr Developments Nutr. 2020;4(2):nzaa018.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eL\u0026oacute;pez Romo H. AMAI advances: Distribution of socioeconomic levels in urban Mexico. Mexican Association of Marketing Research and Public Opinion Agencies: Mexico City, Mexico, 2006. Social Investigations Institute, SC [Online]. Available at: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp//www.amai.org\u003c/span\u003e\u003cspan address=\"http://www.amai.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e2006.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRosa MJ, Just AC, Kloog I, Pantic I, Schnaas L, Lee A, et al. Prenatal particulate matter exposure and wheeze in Mexican children: effect modification by prenatal psychosocial stress. Ann Allergy Asthma Immunol. 2017;119(3):232\u0026ndash;7. e1.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIslam T, Urman R, Gauderman WJ, Milam J, Lurmann F, Shankardass K, et al. Parental stress increases the detrimental effect of traffic exposure on children's lung function. Am J Respir Crit Care Med. 2011;184(7):822\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhlers NE, Weiss SJ. Exposure to particulate matter, prenatal depressive symptoms and HPA axis dysregulation. Heliyon. 2021;7(6).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThomson EM, Filiatreault A, Gu\u0026eacute;nette J. Stress hormones as potential mediators of air pollutant effects on the brain: rapid induction of glucocorticoid-responsive genes. Environ Res. 2019;178:108717.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu S, Yin Y, Du L. Blood\u0026ndash;brain barrier dysfunction in the pathogenesis of major depressive disorder. Cell Mol Neurobiol. 2022;42(8):2571\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJia Z, Wei Y, Li X, Yang L, Liu H, Guo C, et al. Exposure to ambient air particles increases the risk of mental disorder: findings from a natural experiment in Beijing. Int J Environ Res Public Health. 2018;15(1):160.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcoba EF. Social support and mental health: the mediating role of perceived stress. Front Psychol. 2024;15:1330720.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivera Rivera NY, McGuinn L, Osorio-Valencia E, Martinez-Medina S, Schnaas L, Wright RJ, et al. Changes in depressive symptoms, stress and social support in Mexican women during the COVID-19 pandemic. Int J Environ Res Public Health. 2021;18(16):8775.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"environmental-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"enhe","sideBox":"Learn more about [Environmental Health](http://ehjournal.biomedcentral.com)","snPcode":"12940","submissionUrl":"https://submission.nature.com/new-submission/12940/3","title":"Environmental Health","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Air pollution, postpartum depression, prenatal stress","lastPublishedDoi":"10.21203/rs.3.rs-8523355/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8523355/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePostpartum depression (PPD) is a global health issue that can lead to high levels of maternal morbidity. We previously found that ambient air pollution (PM\u003csub\u003e2.5\u003c/sub\u003e) during pregnancy is associated with PPD. However, the modifying role of psychosocial stress on this relationship is unclear.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe measured pregnancy stress in the PROGRESS cohort (n\u0026thinsp;=\u0026thinsp;475 mothers) using negative life events (NLE) and perceived stress score (PSS). We assessed the modifying role of NLE and PSS on the association between prenatal PM\u003csub\u003e2.5\u003c/sub\u003e exposure and PPD at 6 months. Daily residence level PM\u003csub\u003e2.5\u003c/sub\u003e estimates generated from a spatiotemporal model was averaged over pregnancy. PPD was assessed using the Edinburgh Postnatal Depression Scale (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;13) and categorized as chronic depression (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;13 during pregnancy and at 6 months), new-onset PPD (EPDS\u0026thinsp;\u0026lt;\u0026thinsp;13 during pregnancy and EPDS\u0026thinsp;\u0026ge;\u0026thinsp;13 at 6 months), or prevalent PPD (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;13 at 6 months, regardless of EPDS score during pregnancy). Modified Poisson regression evaluated the association between PM\u003csub\u003e2.5\u003c/sub\u003e and PPD, stratified by NLE and PSS scores, dichotomized around the median (low/high). We repeated the analyses with other proposed EPDS cut-offs for Mexico (EPDS\u0026thinsp;\u0026ge;\u0026thinsp;10 and \u0026ge;\u0026thinsp;12).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eEach 5-\u0026micro;g/m\u0026sup3; increase in average pregnancy PM\u003csub\u003e2.5\u003c/sub\u003e exposure was associated with 129% higher risk of prevalent PPD among mothers with low PSS (RR: 2.29, 95% CI: 1.17\u0026ndash;4.47). The risk of new-onset PPD at 6 months per 5-\u0026micro;g/m\u0026sup3; increase in PM\u003csub\u003e2.5\u003c/sub\u003e during pregnancy quadrupled among mothers with low PSS (RR: 4.58, 95% CI: 1.83\u0026ndash;11.49) and high NLE (RR: 4.71, 95% CI: 1.72\u0026ndash;12.92) scores. Similar findings were observed with an EPDS\u0026thinsp;\u0026ge;\u0026thinsp;10 or EPDS\u0026thinsp;\u0026ge;\u0026thinsp;12 cut-off.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe risk of PPD from PM\u003csub\u003e2.5\u003c/sub\u003e exposure was enhanced in mothers with low PSS or high NLE scores, especially new-onset PPD, regardless of the EPDS threshold used. These findings suggest that well-characterized stress phenotyping during pregnancy may help identify which women are at-risk for depression.\u003c/p\u003e","manuscriptTitle":"Air pollution and postpartum depression: the interplay with prenatal stress","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 11:18:16","doi":"10.21203/rs.3.rs-8523355/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-27T14:14:29+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-20T23:03:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"25407892444452277219584213162591400510","date":"2026-01-30T15:12:45+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-30T14:34:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-07T08:55:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-07T08:51:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"Environmental Health","date":"2026-01-05T16:08:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"environmental-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"enhe","sideBox":"Learn more about [Environmental Health](http://ehjournal.biomedcentral.com)","snPcode":"12940","submissionUrl":"https://submission.nature.com/new-submission/12940/3","title":"Environmental Health","twitterHandle":"@bmc","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2f979756-25e5-468a-bde6-bd92f1526b74","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-30T00:23:11+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-02 11:18:16","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8523355","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8523355","identity":"rs-8523355","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}