Association between depression during pregnancy and preterm birth: Results from population cohorts and mouse experimental models methods
Aim. Evidence-backed execution summary for Association between depression during pregnancy and preterm birth: Results from population cohorts and mouse experimental models methods from Association between depression during pregnancy and preterm birth: Results from population cohorts and mouse experimental models.
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mouse
Subject model for the experiment.
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- confirm full cohort details in the source paper
Methods
We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), a screening tool, with a score ≥12 indicating elevated symptoms suggestive of depression. PTB was defined as d...
- Use
- We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), a screening tool, with a score ≥12 indicating elevated symptoms suggestive of depression. PTB was defined as d...
Establishment of a murine model for depression
The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are subjected to long-term exposure under unpredictable conditions, effectively replicating the diverse psychological pressures encountered in hu...
- Use
- The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are subjected to long-term exposure under unpredictable conditions, effectively replicating the diverse psychological pressures encountered in hu...
Open field test (OFT).
The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed before the modeling and on the weekends of the 2nd, 4th, and 6th weeks of the molding, and the mice were placed in the laboratory for 60 minutes...
- Use
- The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed before the modeling and on the weekends of the 2nd, 4th, and 6th weeks of the molding, and the mice were placed in the laboratory for 60 minutes...
Statistical analysis
Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses proceeded as follows: First, we described the demographic characteristics of the cohort. Second, we assessed the association between prenatal d...
- Use
- Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses proceeded as follows: First, we described the demographic characteristics of the cohort. Second, we assessed the association between prenatal d...
Statistical analysis
Software used for acquisition, scoring, statistics, or reporting.
- Use
- Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses proceeded as follows: First, we described the demographic characteristics of the cohort. Second, we assessed the association between prenatal d...
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Methods
We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), a screening tool, with a score ≥12 indicating elevated symptoms suggestive of depression. PTB was defined as delivery before 37 gestational weeks, confirmed by ultrasound. In parallel, a mouse model of depression was established using Chronic Unpredictable Mild Stress (CUMS) for 6 weeks prior to mating. PTB in mice was defined as delivery before 19 days of gestation.
Screening tools for depression during pregnancy
Assessment of depressive symptoms was conducted using the EPDS, a widely used screening tool for postpartum depression, which is equally applicable for screening depressive symptoms during pregnancy. It is crucial to note that the EPDS identifies symptoms suggestive of depression but is not a diagnostic tool for clinical depression. The scale gauged the severity of depressive symptoms over the past 7 days, comprising 10 items graded as "never," "occasionally," "often," and "always," corresponding to "0 points," "1 point," "2 points," and "3 points," respectively. The total score ranged from 0 to 30 points, with higher scores indicating more severe depressive symptoms. Participants were categorized into two groups based on their EPDS scores: women with elevated depressive symptoms (EPDS̴...
Establishment of a murine model for depression
The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are subjected to long-term exposure under unpredictable conditions, effectively replicating the diverse psychological pressures encountered in human daily life. This depression model extends over three months and is widely utilized in most experimental studies.Selection and Grouping of Mice A 6-week-old SPF-level C57BL/6 female mouse weighing 18.0-21.0 g was selected from the Department of Laboratory Animal Science, Kunming Medical University, and assigned an experimental unit use license number. The experimental animals were housed in a clean animal room with a maintained room temperature of 25 ± 1°C, humidity of 65 ± 5%, and a 12-hour cyclic alternating illuminati...
Behavioral tests
The SPT was utilized to assess hedonic deficiency in mice, with a decrease in sugar water preference indicative of anhedonia [ ]. Three days prior to commencing the experiment, the mice underwent training to acclimate to the sugar water test. Each mouse was group-housed in a single cage, with two water bottles provided simultaneously within each cage. Initially, both bottles contained 1% sucrose water. Subsequently, one bottle contained sucrose water, while the other contained distilled water, with the positioning of the bottles rotated every 4 hours to prevent bias. On the third day, food and water were withheld. At 9 am on the fourth day, each mouse was simultaneously given prequantified sucrose water and distilled water, and after 24 hours, all the water bottles were weighed. Throughout the modeling phase, measurements were taken on the 2nd, 4th, and 6th days according to the descr...
Open field test (OFT).
The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed before the modeling and on the weekends of the 2nd, 4th, and 6th weeks of the molding, and the mice were placed in the laboratory for 60 minutes before the start of the experiment to adapt to the laboratory environment. A single mouse was placed in the open field test chamber during observation, and the open field data were analyzed after the overall experiment.
Tail suspension test (TST).
The TST is generally used for screening antidepressants and for behavioral evaluation in animal models [ ]. The whole process of the experiment usually lasts 6 minutes, and the duration of immobility is generally evaluated as a state of despair in mice. This experiment was performed once before molding and once on the weekends of the 2nd, 4th, and 6th weeks of molding. With a homemade partition 50 cm from the ground, one side is open, the mouse is easy to observe, and the rest of the side is closed. To avoid interference from the external environment, the mouse tail is glued to the crossbar placed on the partition beforehand, and the amount of time it does not move is recorded. The mice were allowed to acclimatize to the environment for the first 2 min, and the immobility time was recorded for the last 4 min. The laboratory environment was kept quiet during the exper...
Mouse cage conception and pregnancy observation.
Successful depression induction required ≥30% decrease in sucrose preference vs. controls (P < 0.01), ≥ 40% increase in immobility time (FST/TST), and consistent weight divergence (>15%) by week 3. These thresholds align with published CUMS standards. Nine-week-old SPF-level C57BL/6 male mice and mature depressed models were carefully selected to establish successful mating pairs for mice and controls, aiming to enhance the pregnancy rate. Mating was conducted at a male-to-female ratio of 1:2, with male mice introduced into the cages at 18:00 on the day of mating and removed at 8:00 the following day. Subsequently, the female mice were directly observed for the presence of a vaginal plug using forceps, indicating successful mating. Mating usually occurred at night, and the identification of the vaginal plug marked the suspected pregnancy day. To pre...
Statistical analysis
Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses proceeded as follows: First, we described the demographic characteristics of the cohort. Second, we assessed the association between prenatal depressive symptoms (EPDS ≥12) and PTB using Cox proportional hazards models, which included Model 1: no adjustment for confounding factors; Model 2: adjusted for age, nationality, residence, marital status, education level, occupation status, annual family income, and pregnancy. Model 3: Adjust for all above plus pre-pregnancy BMI and parity. Third, a pre-planned analysis examined the dose-response relationship by categorizing depressive symptoms into mild, moderate, and severe levels. Fourth, we conducted pre-specified subgroup analyses to explore effect modification...
Measurement outputs
What raw and processed outputs should exist?
We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal D...
- Raw artifact
- Per-run gait capture with paw placement, timing, and stride features for each animal
- Processed artifact
- Cleaned gait metrics table and recovery trend summary across timepoints
- Reported as
- Group comparisons of gait indices, stride metrics, or recovery curves
Pregnant women receiving prenatal care at Kunming Medical University Affiliated Qujing Hospital from August 2020 to March 2022 constituted the study subjects. Inclusion criteria...
- Raw artifact
- Per-run gait capture with paw placement, timing, and stride features for each animal
- Processed artifact
- Cleaned gait metrics table and recovery trend summary across timepoints
- Reported as
- Group comparisons of gait indices, stride metrics, or recovery curves
Assessment of depressive symptoms was conducted using the EPDS, a widely used screening tool for postpartum depression, which is equally applicable for screening depressive symp...
- Raw artifact
- Per-run gait capture with paw placement, timing, and stride features for each animal
- Processed artifact
- Cleaned gait metrics table and recovery trend summary across timepoints
- Reported as
- Group comparisons of gait indices, stride metrics, or recovery curves
The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are s...
- Raw artifact
- Per-run gait capture with paw placement, timing, and stride features for each animal
- Processed artifact
- Cleaned gait metrics table and recovery trend summary across timepoints
- Reported as
- Group comparisons of gait indices, stride metrics, or recovery curves
Analysis plan
How should the outputs become interpretable results?
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
inferred from protocolPreprocessing / cleaning
The key strengths of our study include its prospective design, the combination of a human cohort with an experimental animal model, the use of a validated scale for depressive symptoms, and the adjustment for a comprehensive set of confounders across multiple statistical models.
from paperScoring or quantification
Quantify the primary readouts for this experiment: We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal D...; Pregnant women receiving prenatal care at Kunming Medical University Affiliated Qujing Hospital from August 2020 to March 2022 constituted the study subjects. Inclusion criteria...; Assessment of depressive symptoms was conducted using the EPDS, a widely used screening tool for postpartum depression, which is equally applicable for screening depressive symp...; The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are s....
from paperStatistical comparison
The key strengths of our study include its prospective design, the combination of a human cohort with an experimental animal model, the use of a validated scale for depressive s...; This study also has limitations. First, depressive symptoms were assessed using the EPDS, a screening tool, and were measured only once during early pregnancy; repeated assessme...; The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed befor...; Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses pro...
from paperReporting output
Report representative outputs alongside summary comparisons for We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal D..., Pregnant women receiving prenatal care at Kunming Medical University Affiliated Qujing Hospital from August 2020 to March 2022 constituted the study subjects. Inclusion criteria..., Assessment of depressive symptoms was conducted using the EPDS, a widely used screening tool for postpartum depression, which is equally applicable for screening depressive symp..., The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are s....
inferred from protocolStructured statistical methods
The key strengths of our study include its prospective design, the combination of a human cohort with an experimental animal model, the use of a validated scale for depressive s...; This study also has limitations. First, depressive symptoms were assessed using the EPDS, a screening tool, and were measured only once during early pregnancy; repeated assessme...; The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed befor...; Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses pro...
source structuredSource and audit
What supports the facts on this page?
Evidence quotes (8)
We recruited 1,466 women during their first-trimester routine visits at Qujing Hospital. Depressive symptoms were assessed using the Chinese version of the Edinburgh Postnatal Depression Scale (EPDS), a screening tool, with a score ≥12 indicating elevated symptoms suggestive of depression. PTB was defined as delivery before 37 gestational weeks, confirmed by ultrasound. In parallel, a mouse model of depression was established using Chronic Unpredictable Mild Stress (CUMS) for 6 weeks prior to mating. PTB in mice was defined as delivery before 19 days of gestation.
Assessment of depressive symptoms was conducted using the EPDS, a widely used screening tool for postpartum depression, which is equally applicable for screening depressive symptoms during pregnancy. It is crucial to note that the EPDS identifies symptoms suggestive of depression but is not a diagnostic tool for clinical depression. The scale gauged the severity of depressive symptoms over the past 7 days, comprising 10 items graded as "never," "occasionally," "often," and "always," corresponding to "0 points," "1 point," "2 points," and "3 points," respectively. The total score ranged from 0 to 30 points, with higher scores indicating more severe depressive symptoms. Participants were categorized into two groups based on their EPDS scores: women with elevated depressive symptoms (EPDS ≥ 12) and women without elevated depressive symptoms (EPDS < 12) using 12 points as the cutoff value. Scores of 12-13, 14-18, and 19-30 indicated mild, moderate, and major depressive symptoms, respectively [ - ]. To ensure data quality, all questionn...
The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are subjected to long-term exposure under unpredictable conditions, effectively replicating the diverse psychological pressures encountered in human daily life. This depression model extends over three months and is widely utilized in most experimental studies.Selection and Grouping of Mice A 6-week-old SPF-level C57BL/6 female mouse weighing 18.0-21.0 g was selected from the Department of Laboratory Animal Science, Kunming Medical University, and assigned an experimental unit use license number. The experimental animals were housed in a clean animal room with a maintained room temperature of 25 ± 1°C, humidity of 65 ± 5%, and a 12-hour cyclic alternating illumination method for the circadian rhythm (light time from 7 am to 19 pm). After one week of adaptive rearing, all mice underwent open field experiments. Mice with poor spontaneous movement were eliminated based on the open field experiment score, the sample size in the CUMS group was larger than in the co...
The SPT was utilized to assess hedonic deficiency in mice, with a decrease in sugar water preference indicative of anhedonia [ ]. Three days prior to commencing the experiment, the mice underwent training to acclimate to the sugar water test. Each mouse was group-housed in a single cage, with two water bottles provided simultaneously within each cage. Initially, both bottles contained 1% sucrose water. Subsequently, one bottle contained sucrose water, while the other contained distilled water, with the positioning of the bottles rotated every 4 hours to prevent bias. On the third day, food and water were withheld. At 9 am on the fourth day, each mouse was simultaneously given prequantified sucrose water and distilled water, and after 24 hours, all the water bottles were weighed. Throughout the modeling phase, measurements were taken on the 2nd, 4th, and 6th days according to the described protocol, and the sugar water preference rate was calculated as a percentage of total water consumption (1% sugar water consumption/total water consumption × 100%).
The OFT can detect spontaneous locomotion and exploratory behavior in mice, and the effect is significant [, ]. In this experiment, an open field experiment was performed before the modeling and on the weekends of the 2nd, 4th, and 6th weeks of the molding, and the mice were placed in the laboratory for 60 minutes before the start of the experiment to adapt to the laboratory environment. A single mouse was placed in the open field test chamber during observation, and the open field data were analyzed after the overall experiment.
The TST is generally used for screening antidepressants and for behavioral evaluation in animal models [ ]. The whole process of the experiment usually lasts 6 minutes, and the duration of immobility is generally evaluated as a state of despair in mice. This experiment was performed once before molding and once on the weekends of the 2nd, 4th, and 6th weeks of molding. With a homemade partition 50 cm from the ground, one side is open, the mouse is easy to observe, and the rest of the side is closed. To avoid interference from the external environment, the mouse tail is glued to the crossbar placed on the partition beforehand, and the amount of time it does not move is recorded. The mice were allowed to acclimatize to the environment for the first 2 min, and the immobility time was recorded for the last 4 min. The laboratory environment was kept quiet during the experiment.
Successful depression induction required ≥30% decrease in sucrose preference vs. controls (P < 0.01), ≥ 40% increase in immobility time (FST/TST), and consistent weight divergence (>15%) by week 3. These thresholds align with published CUMS standards. Nine-week-old SPF-level C57BL/6 male mice and mature depressed models were carefully selected to establish successful mating pairs for mice and controls, aiming to enhance the pregnancy rate. Mating was conducted at a male-to-female ratio of 1:2, with male mice introduced into the cages at 18:00 on the day of mating and removed at 8:00 the following day. Subsequently, the female mice were directly observed for the presence of a vaginal plug using forceps, indicating successful mating. Mating usually occurred at night, and the identification of the vaginal plug marked the suspected pregnancy day. To prevent oversight and false pregnancy, the body weight of pregnant mice was monitored daily. Suspected pregnancies were confirmed if the body weight of the mice increased by more than 2 g within 10 days, and these mice were then individually housed and given special care. Nonpregnant mice underwe...
Statistical analysis of the population cohort and animal experiments was performed using R language software (version 4.2.0) and GraphPad Prism (version 9.0.0). The analyses proceeded as follows: First, we described the demographic characteristics of the cohort. Second, we assessed the association between prenatal depressive symptoms (EPDS ≥12) and PTB using Cox proportional hazards models, which included Model 1: no adjustment for confounding factors; Model 2: adjusted for age, nationality, residence, marital status, education level, occupation status, annual family income, and pregnancy. Model 3: Adjust for all above plus pre-pregnancy BMI and parity. Third, a pre-planned analysis examined the dose-response relationship by categorizing depressive symptoms into mild, moderate, and severe levels. Fourth, we conducted pre-specified subgroup analyses to explore effect modification by age, trimester of enrollment, socioeconomic status, education, residence, occupation, and marital status. If sufficient data are available from the cohort, pre-specified subgroup analyses will be conducted to examine the association between depressive symptoms and PTB across strata defined by ma...
Machine-readable layer
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"text": "The CUMS model is currently the most widely used, reliable, and effective rodent model for depression [ ]. By employing various environmental and physical stimuli, animals are subjected to long-term exposure under unpredictable conditions, effectively replicating the diverse psychological pressures encountered in human daily life. This depression model extends over three months and is widely utilized in most experimental studies.Selection and Grouping of Mice A 6-week-old SPF-level C57BL/6 female mouse weighing 18.0-21.0 g was selected from the Department of Laboratory Animal Science, Kunming Medical University, and assigned an experimental unit use license number. The experimental animals were housed in a clean animal room with a maintained room temperature of 25 ± 1°C, humidity of 65 ± 5%, and a 12-hour cyclic alternating illuminati..."
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"text": "Successful depression induction required ≥30% decrease in sucrose preference vs. controls (P < 0.01), ≥ 40% increase in immobility time (FST/TST), and consistent weight divergence (>15%) by week 3. These thresholds align with published CUMS standards. Nine-week-old SPF-level C57BL/6 male mice and mature depressed models were carefully selected to establish successful mating pairs for mice and controls, aiming to enhance the pregnancy rate. Mating was conducted at a male-to-female ratio of 1:2, with male mice introduced into the cages at 18:00 on the day of mating and removed at 8:00 the following day. Subsequently, the female mice were directly observed for the presence of a vaginal plug using forceps, indicating successful mating. Mating usually occurred at night, and the identification of the vaginal plug marked the suspected pregnancy day. To pre..."
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"datePublished": "2026",
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