Association of psychological states, sleep patterns, vaccine, and pregnancy outcomes during the COVID-19 pandemic

Abstract

Objective

This study investigates the relationships among psychological state, sleep patterns, COVID-19 vaccination during the COVID-19 pandemic, with postpartum hemorrhage as the primary outcome, and other adverse pregnancy outcomes, mental health, and sleep quality as secondary outcomes.

Methods

A prospective cohort study was conducted from April 2022 to November 2022 at the First Affiliated Hospital of Sun Yat-sen University, including 260 pregnant women meeting the inclusion criteria in the obstetric department. The Depression Anxiety Stress Scales (DASS-21) was used to assess depression, anxiety, and stress; the Impact of Event Scale-Revised (IES-R) was utilized to evaluate psychological stress related to COVID-19, and the Pittsburgh Sleep Quality Index (PSQI) was employed to measure sleep quality; Participants were grouped based on their scores or vaccination status (vaccinated: n = 204; unvaccinated: n = 56), and the incidence of adverse pregnancy outcomes was compared among different groups.

Results

The primary outcome showed that the incidence of postpartum hemorrhage (PPH) differed significantly across depression subgroups (normal: 3.6%, mild: 15.0%, moderate-severe: 13.0%; χ²(2) = 9.450). Compared with the non-depression group, mild depression was significantly associated with an increased risk of PPH (OR = 4.19, 95% CI: 1.15–15.18, P = 0.006); moderate-to-severe depression was also significantly associated with an elevated risk of PPH (OR = 4.78, 95% CI: 1.39–16.40, P = 0.013). For secondary outcomes, no significant differences in adverse pregnancy outcomes were observed among groups stratified by anxiety, stress, COVID-19-related psychological stress, or sleep quality (all P > 0.05).In addition, pre-pregnancy inactivated COVID-19 vaccination was not associated with an elevated risk of PPH or other adverse pregnancy outcomes(P > 0.05).

Conclusion

COVID-19-related depressive symptoms are associated with an increased risk of postpartum hemorrhage. Pre-pregnancy COVID-19 vaccination showed no adverse effects on maternal mental health or pregnancy outcomes.

Background

The coronavirus disease 2019 (COVID-19) pandemic has garnered widespread global attention. Studies [1, 2] show that adverse pregnancy outcomes have been more prevalent during the pandemic. These outcomes include miscarriage, preterm birth (PTB), low birth weight (LBW), low Apgar scores, fetal death, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and pregnancy-related thyroid dysfunction. Furthermore, studies [3–9] also have indicated that pregnant women facing COVID-19 were at an increased risk of psychological issues such as anxiety, depression, stress, and insomnia. In addition, some studies [10, 11] suggest that antenatal psychological problems (stress, anxiety, depression) during the COVID-19 pandemic can increase the risk of adverse pregnancy outcomes, such as cesarean section (CS), PTB, and LBW. However, these conclusions are drawn from studies conducted mainly in the Polish and American populations. There is currently no relevant research on the Chinese population.

A key measure in China’s epidemic prevention strategy is the administration of COVID-19 vaccines, which are associated with the psychological status of pregnant women. Theoretical considerations suggest that vaccination during the pandemic may exert a complex influence on maternal mental health through multiple pathways. On one hand, vaccination can provide psychological protection by reducing the fear of infection and the burden of disease prevention. On the other hand, concerns regarding vaccine safety, the novelty of inactivated vaccines, and ambiguous public health information may conversely induce anxiety and stress.However, existing empirical evidence remains mixed: while some studies [12, 13]. In addition, the impact of COVID-19 vaccine administration on pregnancy outcomes is a highly debated topic. Large-scale retrospective cohort studies overseas have concluded that COVID-19 vaccine administration in pregnant women is safe and does not increase adverse pregnancy outcomes [14–18].However, the majority of international studies have focused on mRNA-based vaccines, whereas in China, the inactivated vaccine is the primary type administered, which may have different immunological and clinical profiles.Furthermore, the vast majority of vaccinated participants in the present study received their vaccines prior to conception. This distinction between pre-pregnancy and in-pregnancy vaccination is crucial for interpreting the psychological and clinical outcomes, as the context and potential psychological impacts of vaccination differ significantly across these two stages.

Despite the growing body of evidence, several critical gaps remain in the current literature. First, it remains unclear whether psychological distress and sleep quality during the pandemic are independently associated with adverse pregnancy outcomes among Chinese pregnant women. Second, the relationship between China-specific inactivated COVID-19 vaccines and maternal mental health as well as pregnancy outcomes has not been fully elucidated. Based on the aforementioned background, the primary aim of this study is to test the following hypotheses:

1. Psychological hypothesis: Higher levels of antenatal depression, anxiety, stress, and COVID-19-related psychological stress are associated with an increased likelihood of adverse pregnancy outcomes.

2. Sleep hypothesis: Poor sleep quality during pregnancy is associated with an increased risk of adverse pregnancy outcomes.

3. Vaccination hypothesis: COVID-19 vaccination among the Chinese population, predominantly administered pre-pregnancy, is not associated with an increased risk of adverse pregnancy outcomes or adverse maternal mental health outcomes.

Methods

Participants

This prospective cohort study enrolled pregnant women who underwent regular antenatal visits at the Obstetric Clinic of the First Affiliated Hospital, Sun Yat-sen University, between April 11 and November 23, 2022. Approval for the study was obtained from the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University (Number [2022]565). Informed consent was obtained from the participants.

Inclusion criteria for the study were gestational age between 24 and 28 weeks, age ≥ 18 years, and singleton pregnancy. Exclusion criteria for the study were non-Chinese nationality; invalid questionnaire due to patient-related issues (omissions or logical errors); pregestational diabetes mellitus, chronic hypertension; pregnant women with severe medical conditions: systemic lupus erythematosus or autoimmune diseases, malignant tumors; history of cognitive impairment, psychiatric disorders, or pre-existing psychological disorders; and individuals who underwent medical abortion.

A total of 483 pregnant women were recruited in this study, among whom 260 were finally included, with an overall loss-to-follow-up rate of 25.5% (123/483). The main reason for loss to follow-up was failure to successfully track pregnancy outcomes. Among the excluded participants (n = 100, non-loss to follow-up), 77 were excluded due to invalid questionnaires or missing key information, 1 due to pregestational diabetes mellitus, 7 due to chronic hypertension complicating pregnancy, 12 due to severe medical/surgical complications during pregnancy, 2 due to cognitive dysfunction or a history of psychiatric disorders, and 1 due to induction of labor with rivanol amniotic cavity injection or pharmacological induction.

Sample size calculation and statistical power analysis

Per Gorsuch (1983), an optimal item-to-participant ratio of 1:5 (minimum n = 100) is recommended. Guided by this, the present study’s questionnaire (17 indicators excluding demographics, 1 scale = 1 indicator) required a minimum of 85 valid samples.Accounting for 10.0% invalid questionnaires and 30.0% follow-up loss (OGTT participants delivering elsewhere), the correction coefficient was 1÷[ (1 − 10%)× (1 − 30%)] ≈ 1.587, leading to a corrected sample size of 135. Ultimately, 260 participants were enrolled, exceeding this requirement and aligning with conventional parameters (α = 0.05, two-tailed; β = 0.2, 80% power).

Statistical power analysis assumed core scales met acceptable internal consistency (Cronbach’s α ≥ 0.7). Post-collection reliability tests showed: DASS-21 (overall α = 0.956; depression = 0.906, anxiety = 0.858, stress = 0.906), IES-R (α = 0.954), and PSQI (α = 0.686).A clinically meaningful effect size was prespecified as an odds ratio (OR) ≥ 1.5 for the association between psychological factors and adverse pregnancy outcomes.

Measures

Demographic Data included Age, Pre-pregnancy BMI, Conception Method, and Parity. Pregnancy outcomes included GDM, HDP, PTB, PPH (Postpartum Hemorrhage), LBW, NA (Neonatal Asphyxia), Birth Defects, and Transfer to the NICU (neonatal intensive care unit).

Participants were requested to complete a questionnaire and provide the following information: Sociodemographic characteristics, including Educational Background, Occupation, Monthly Income, and Vaccination Status.COVID-19 Impact was assessed using the items: Daily Life (restricted /Normal), Knowledge Level (Excellent /Comparatively good /General), Quarantine Status (Underwent 14-day isolation /not isolated), Primary Concerns (Effectiveness of protective measures /antenatal check-ups / environmental safety at the delivery hospital /personal health / fetal health / inadequate family or nurse care capacity).

Psychological Stress, Depression, and Anxiety among pregnant women during the COVID-19 period were assessed using The Chinese revised version of the Depression Anxiety Stress Scales (DASS-21) [19, 20]. The scale consists of three subscales: depression, anxiety, and stress, each comprising seven items, with scores ranging from 0 to 3. Higher scores indicate higher levels of depression, anxiety, and stress.In accordance with the standardized scoring rules of the Depression Anxiety Stress Scales-21 (DASS-21), the severity of symptoms across the three dimensions (depression, anxiety, and stress) is categorized into 5 levels [21]. The specific cutoff scores for each severity level are detailed in Table 1.

Table 1.

DASS-21 Score Cutoffs and Corresponding Symptom Severity

Symptom Severity	Depression (Score)	Anxiety (Score)	Stress (Score)
Normal	0–9	0–7	0–14
Mild	10–13	8–9	15–18
Moderate	14–20	10–14	19–25
Severe	21–27	15–19	26–33
Extremely Severe	≥ 28	≥ 20	≥ 34

The psychological impact of COVID-19 on pregnant women was assessed using The revised Impact of Event Scale (IES-R) [22]. The scale comprises 22 items, with scores ranging from 0 to 4. Severity levels are categorized based on total scores as normal (0–23), mild (24–32), moderate (33–36), and severe psychological impact (≥ 37). Sleep Quality was assessed using The Pittsburgh Sleep Quality Index (PSQI) [23]. A total score of 7 indicates “good sleep quality”, while a score exceeding seven is considered “poor sleep quality”.

Statistical analysis

SPSS version 25.0 was used to analyze the data. The scale was analyzed using parametric tests, and the scores were presented as mean ± standard deviation [24–26]. A higher Cronbach’s α coefficient indicates better internal consistency of the questionnaire. One-way analysis of variance was used for multiple group comparisons of continuous variables, followed by post multiple comparisons using the Least Significant Difference method or Tamhane’s T2 method if there was a significant difference. The chi-square or Fisher’s exact test was used to compare categorical variables. Pearson’s correlation coefficient was used to analyze the correlations between continuous variables. Multiple binary logistic regression analysis was performed to explore the associations between psychological status, sleep, vaccination and adverse pregnancy outcomes, with adjustment for confounding factors including age, pre-pregnancy body mass index, parity, household income, gestational age and educational level. To control for the inflation of type I error caused by multiple testing, the Benjamini-Hochberg false discovery rate (FDR) method was applied for correction stratified by each adverse pregnancy outcome. A two-tailed FDR-adjusted P value less than 0.05 was considered statistically significant.

Results

Baseline characteristics

Two hundred sixty valid questionnaires were obtained. The participants had an mean age of 32.11 ± 4.45 years and an mean pre-pregnancy BMI of 21.35 ± 3.02 kg/m². 13.8% of participants conceived through assisted reproductive technology, 74.6% were primiparous, and the mean gestational week at delivery was 38.87 ± 1.64 weeks. 70.0% of participants had a bachelor’s degree or higher, and 39.3% had a monthly income of more than 10,000 RMB. Additionally, 30.4% of participants reported that work and daily life were restricted because of the pandemic. None of the participants had been diagnosed with COVID-19 before or during pregnancy. In contrast, a small proportion (1.5%) had not been diagnosed with COVID-19 but had undergone a 14-day quarantine due to close contact exposure.

The psychological state of the participants

In this study, Cronbach’s α coefficients for the depression, anxiety, and stress subscales and the total DASS-21 scale were 0.906, 0.858, 0.893, and 0.956, respectively, indicating that the scales have high internal consistency. Anxiety and depression were more common among participants than stress, with prevalence rates of 53.5%, 36.5%, and 20.8%, respectively. There were 45.8%, 23.6%, and 7.7% of pregnant women who experienced moderate to severe anxiety, depression, and stress. Furthermore, 18.1% of the participants exhibited signs of all three conditions concurrently.

The Cronbach’s α coefficient of the IES-R scale was 0.954, indicating that the scales have high internal consistency. The mean ± standard deviation of participants’ scores on the IES-R was 19.86 ± 14.14. 38% of the participants were affected to varying degrees by the psychological impacts of COVID-19, with 15.0% experiencing severe psychological effects.

The Cronbach’s α coefficient of the PSQI scale was 0.686, which is below the commonly accepted threshold of 0.7 and thus indicates borderline internal consistency.The mean ± standard deviation of the scale scores was 6.25 ± 2.92. According to the assessment criteria, 71.0% of pregnant women had good sleep quality (≤ 7).

Correlation between DASS-21, IES-R, and PSQI Scores can be found in Table 2. There was a strong positive correlation (0.7 ≤ r) among the depression, anxiety, and stress subscale scores. The IES-R score exhibits a moderately strong positive correlation (0.5 ≤ r < 0.7) with the depression, anxiety, and stress subscale scores. The total score of PSQI demonstrates a moderate positive correlation (0.3 ≤ r < 0.5) with the depression, anxiety, and stress subscale scores and the IES-R score.

Table 2.

The Pearson Correlation Analysis of Each Item Scores

Items	Depression Score	Anxiety Score	Stress Score	IES-R Score	PSQI Score
Depression Score	1.000
Anxiety Score	0.833** (0.79–0.86)	1.000
Stress Score	0.866** (0.83–0.89 )	0.833** (0.79–0.86)	1.000
IES-R Score	0.584** (0.50–0.66)	0.575** (0.49–0.65)	0.649** (0.58–0.71)	1.000
PSQI Score	0.338** (0.23–0.44)	0.393** (0.29–0.49)	0.402** (0.30–0.50)	0.411** (0.31–0.51 )	1.000

^**P < 0.01; ^*P < 0.05; Values in parentheses are 95% confidence intervals (95% CI) calculated by Fisher’s Z transformation

Adverse pregnancy outcomes among participants with different psychological states

The incidence rates of adverse pregnancy outcomes among included pregnancies from highest to lowest: CS (46.15%; the national cesarean section rate in secondary and above hospitals in China was 44.1% in 2020 [27]), Transfer to NICU (20%), GDM (15.77%), LBW (8.46%), PTB (8.08%), PPH (7.31%), NA (3.46%), birth defect (3.08%), preeclampsia (2.60%), and GH (1.54%).

Adverse pregnancy outcomes were compared among different psychological severity groups based on scores from the DASS-Depression, DASS-Anxiety, DASS-Stress, IES-R, and PSQI scales. As shown in Table 3, there were significant differences in the incidence of postpartum hemorrhage (PPH) among groups with different depression severities (P < 0.05), with the highest incidence in the mild depression group, followed by the moderate-to-severe depression group, and the lowest incidence in the non-depression group. Multiple binary logistic regression analysis showed that after FDR adjustment, compared with the non-depression group, mild depression was significantly associated with an increased risk of PPH (OR = 4.19, 95% CI: 1.15–15.18, P = 0.006); moderate-to-severe depression was also significantly associated with an elevated risk of PPH (OR = 4.78, 95% CI: 1.39–16.40, P = 0.013). In addition, no statistically significant differences were observed in the incidence of other adverse pregnancy outcomes across all groups stratified by other psychological status assessments, including the DASS-Anxiety scale, DASS-Stress scale, IES-R scale, and PSQI scale (relevant data are presented in Tables 4, 5, 6 and 7).

Table 3.

Association between DASS-depression Groups and Adverse Pregnancy Outcomes

adverse pregnancy outcomes	DASS-depression groups			x2	P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Normal Depression Group)
	normal	mild	moderate or severe			mild	moderate or severe
N (%)	166 (63.8)	40 (15.4)	54 (20.8)
GDM	25 (15.1)	8 (20)	8 (14.8)	0.639	0.288/0.288	1.73 (0.63–4.74)	1.92 (0.67–5.47)
GH /pre-eclampsia	8 (4.8)	0	3 (5.6)	1.931	0.997/0.997	Not estimable	1.85 (0.35–9.77)
CS	79 (47.6)	19 (47.5)	22 (40.7)	0.804	0.743/0.743	0.88 (0.42–1.86)	0.79 (0.40–1.57)
PTB	14 (8.4)	3 (7.5)	4 (7.4)	0.074	0.999/0.999	Not estimable	Not estimable
PPH	6 (3.6)	6 (15)	7 (13)	9.450	0.006/0.013	4.19(1.15–15.18)	4.78 (1.39–16.40)
Birth defects	3 (1.8)	1 (2.5)	4 (7.4)	3.906	0.786/0.170	1.45(0.10–20.67)	4.99 (0.79–31.50)
LBW	13 (7.8)	3 (7.5)	6 (11.1)	0.737	0.461/0.611	0.33(0.02–6.63)	1.79 (0.19–16.90)
Transfer to NICU	33 (19.9)	8 (20)	11 (20.4)	0.006	0.918/0.918	1.05 (0.41–2.69)	0.86 (0.36–2.05)
NA	4 (2.4)	2 (5.0)	3 (5.6)	2.078	0.431/0.336	2.13(0.32–14.20)	3.35 (0.62–18.07)

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Table 4.

Association between DASS–anxiety Groups and Adverse Pregnancy Outcomes

adverse pregnancy outcomes	DASS-anxiety groups			x2	P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Normal Anxiety Group)
	normal	mild	moderate or severe			mild	moderate or severe
N (%)	121 (46.5)	20 (7.7)	119 (45.8)
GDM	20 (16.5)	3 (15)	17 (14.3)	0.102	0.814/0.921	0.83 (0.19–3.63)	1.04 (0.46–2.36)
GH /pre-eclampsia	5 (4.1)	1 (5.0)	5 (4.2)	0.014	0.799/0.800	1.49 (0.07–31.63)	1.24(0.24–6.37)
CS	59 (49.2)	9 (7.5)	52 (43.3)	0.220	0.689/0.689	0.81 (0.29–2.25)	0.78(0.45–1.35)
PTB	11 (9.1)	0	10 (8.4)	0.337	0.999/1.000	Not estimable	Not estimable
PPH	5 (4.1)	1 (5.0)	13 (10.9)	4.256	0.891/0.130	1.18 (0.11–12.56)	2.88 (0.9–9.20)
Birth defects	1 (0.8)	1 (5.0)	6 (5.0)	3.906	0.445/0.166	3.36(0.15–75.68)	9.44(0.74–120.18)
LBW	10 (8.3)	0	12 (10.1)	0.366	0.998/0.998	Not estimable	1.58 (0.47–5.37)
Transfer to NICU	22 (18.2)	4 (20)	26 (21.8)	0.140	0.456/0.683	1.64 (0.44–6.13)	1.16 (0.57–2.38)
NA	3 (2.5)	1 (5.0)	5 (4.2)	0.376	0.348/0.535	3.46 (0.23–51.87)	1.64 (0.36–7.43)

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Table 5.

Association between DASS-Stress Groups and Adverse Pregnancy Outcomes

adverse pregnancy outcomes	DASS-stress groups			x2	P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Normal Stress Group)
	normal	mild	moderate or severe			mild	moderate or severe
N (%)	208 (80.0)	36 (13.8)	16 (6.2)
GDM	31 (14.9)	8 (22.2)	2 (12.5)	1.375	0.707/0.937	1.21 (0.45–3.26)	1.07(0.2–5.23)
GH /pre-eclampsia	7 (3.4)	4 (11.1)	0	4.066	0.297/0.998	2.31 (0.48–11.13)	Not estimable
CS	93 (44.7)	18 (50.0)	9 (56.3)	1.045	0.671/0.451	1.18 (0.55–2.53)	1.572(0.51–4.49)
PTB	14 (6.7)	4 (11.1)	3 (18.8)	3.723	0.999/0.999	Not estimable	Not estimable
PPH	15 (7.2)	2 (5.6)	2 (12.5)	1.094	0.724/0.236	0.76 (0.15–3.70)	2.78(0.46–16.77)
Birth defects	8 (3.8)	0	0	0.842	0.998/0.998	Not estimable	Not estimable
LBW	18 (8.7)	3 (8.3)	1 (6.3)	0.069	0.289/0.246	0.20 (0.01–3.87)	0.02 (0.00–1.35)
Transfer to NICU	39 (18.8)	11 (30.6)	2 (12.5)	3.173	0.144/0.279	1.92(0.80–4.60)	0.40(0.08–2.03)
NA	7 (3.4)	2 (5.6)	0	0.835	0.705/0.998	1.40 (0.24–8.12)	Not estimable

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Table 6.

Comparison of the incidence of adverse pregnancy outcomes based on the IES-R scale

adverse pregnancy outcomes	groups with varying degrees of psychological impact of COVID-19		x2		P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Normal Psychological Impact Group)
	normal	mild	moderate or severe			mild	moderate or severe
N (%)	160 (61.2)	51 (19.6)	49 (19.2)
GDM	27(16.9)	5 (9.8)	9(18.4)	1.763	0.139/0.869	0.41 (0.13–1.33)	1.08 (0.41–2.86)
GH /pre-eclampsia	8 (5.0)	1 (2.0)	2 (4.0)	0.885	0.080/0.976	0.06 (0.00–1.48)	0.97 (0.14–6.67)
CS	75 (46.9)	23 (45.1)	22 (44.9)	0.087	0.656/0.690	0.986(0.42–1.76)	0.87 (0.43–1.77)
PTB	14 (8.8)	6 (11.8)	1 (2.0)	3.436	0.997/0.999	Not estimable	Not estimable
PPH	9 (5.6)	5 (9.8)	5 (10.2)	1.745	0.289/0.314	1.96 (0.56–6.86)	1.90 (0.54–6.67)
Birth defects	5 (3.1)	1 (2.0)	2 (4.1)	0.380	0.899/0.877	0.86 (0.09–8.50)	1.16 (0.19–7.16)
LBW	13 (8.1)	7 (13.7)	2 (4.1)	3.061	0.791/0.342	0.74 (0.08–6.68)	0.22(0.01–5.08)
Transfer to NICU	33 (20.6)	13 (25.5)	6 (12.2)	2.842	0.955/0.178	0.98 (0.43–2.23)	0.50(0.19–1.37)
NA	5 (3.1)	4 (7.8)	0	4.741	0.323/0.997	2.09 (0.48–9.08)	Not estimable

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Table 7.

Comparison of the incidence of adverse pregnancy outcomes based on the PSQI scale

adverse pregnancy outcomes	sleep quality groups		x2	P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Good Sleep Quality Group)
	good	poor
N (%)	43 (16.5)	217 (83.5)
GDM	7 (16.3)	34 (15.7)	0.010	0.687	1.67(0.23–1.94)
GH /pre-eclampsia	1 (2.3)	10 (4.6)	0.462	0.774	0.37(0.02–7.73)
CS	23 (53.5)	97(44.7)	1.115	0.671	1.32(0.64–2.71)
PTB	5 (11.6)	16 (7.4)	0.875	0.999	Not estimable
PPH	1 (2.3)	18 (8.3)	1.888	0.945	0.25(0.03–2.13)
Birth defects	0 (0)	8(3.7)	1.636	0.997	Not estimable
LBW	6 (16.0)	16 (7.4)	2.006	0.698	5.77(0.51–65.07)
Transfer to NICU	11 (25.6)	41 (18.9)	1.003	0.711	1.38(0.57–3.30)
NA	2 (4.7)	7 (3.2)	0.218	0.900	1.25(0.23–6.79)

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Post-hoc power analysis was additionally performed for the primary outcome of postpartum hemorrhage (PPH). Compared with the normal reference group, the observed adjusted OR for the mild depression group was 4.19, with an achieved statistical power of 72% (α = 0.05, two-tailed). For the moderate-to-severe depression group versus the normal group, the observed adjusted OR was 4.78, with an achieved power of 78% (α = 0.05, two-tailed). Although these values are slightly below the conventional 80% threshold, the large observed effect sizes (OR > 3.9) allowed for the detection of statistically significant associations with PPH, supporting the robustness of the main study findings.

Participants were divided into vaccinated and unvaccinated groups to compare adverse pregnancy outcomes. No statistically significant difference was found between the vaccinated and unvaccinated groups in the incidence of all adverse pregnancy outcomes (Table 8).

Table 8.

Impact of Vaccination on Adverse Pregnancy Outcomes

adverse pregnancy outcomes	vaccinated groups n = 204	unvaccinated groups n = 56	x2	P(FDR-adjusted)	Adjusted OR, 95% CI (Reference: Unvaccinated Group)
GDM	31 (15.2)	10 (17.9)	0.234	0.628	0.82 (0.38–1.77)
GH /pre-eclampsia	11 (5.4)	0	3.153	0.076	Not estimable
CS	94 (46.1)	26 (46.4)	0.002	0.963	0.99 (0.56–1.76)
PTB	18 (8.8)	3 (5.4)	0.711	0.399	1.71 (0.48–6.06)
PPH	15 (7.4)	4 (7.1)	0.003	0.957	1.04 (0.33–3.29)
Birth defects	6 (2.9)	2 (3.6)	0.059	0.809	0.80 (0.15–4.24)
LBW	19 (9.3)	3 (5.4)	0.888	0.346	1.81 (0.51–6.43)
Transfer to NICU	39 (19.1)	13 (23.2)	0.461	0.497	0.78 (0.39–1.55)
NA	8 (3.9)	1 (0.4)	0.600	0.439	2.25 (0.27–18.83)

Not estimable due to zero events in the group, leading to unstable effect size calculation.P values were adjusted for multiple comparisons using the False Discovery Rate (FDR) method

OR Odds Ratio, CI Confidence Interval

Discussion

The COVID-19 pandemic could lead to an increase in psychological problems. This study found that participants exhibited different degrees of depression, stress, and anxiety symptoms, among which anxiety symptoms were the most common. 38.0% of participants experienced psychological effects attributable to the COVID-19 pandemic, with 15.0% reporting severe impact. Additionally, 29.0% of pregnant women faced issues related to poor sleep quality. This study also revealed a positive correlation between psychiatric disorders and sleep disturbances. It is important to note that antenatal depression may increase the risk of PPH (mild vs. normal: OR = 4.19, 95% CI: 1.15–15.18; moderate or severe vs. normal: OR = 4.78, 95% CI:1.39–16.40 ), while vaccination has no adverse effects on mental health and adverse pregnancy outcomes.

The prevalence of anxiety symptoms in the second trimester of pregnancy in China before the COVID-19 epidemic was 17.4%, and the prevalence of depression symptoms was 24.0% [28]. This study indicates a significant increase in the prevalence of anxiety (53.5%), depression (36.5%), and stress (20.8%) symptoms among pregnant women during the COVID-19 pandemic. Moreover, more than half of the pregnant women with depression, anxiety, and stress symptoms were moderate or above. In this study, 18.0% of the respondents experienced a mild or severe psychological impact, suggesting that COVID-19 was associated with significant psychological distress among pregnant women, consistent with the findings of Aman Dule et al.‘s study [29]. This highlights the urgent need for routine perinatal mental health screening (e.g., DASS-21, IES-R) during public health emergencies like the COVID-19 pandemic—targeted interventions for high-risk groups (e.g., depressed pregnant women) may help reduce adverse outcomes such as PPH. The current study showed that 29.0% had poor sleep quality. Moreover, a study that used the PSQI scale to assess sleep quality during the epidemic showed that 37.6% of the participants had poor sleep quality [30]. Günkaya et al. conducted a cross-sectional study on postpartum mothers who gave birth during the first wave of the COVID-19 pandemic and found that although the risk of postpartum depression (mean EPDS score = 3.93) was below the clinical cutoff (≥ 13), maternal psychological burden persisted, and sleep quality remained poor (mean PSQI score = 7.04, exceeding the cutoff of 5 for poor sleep) [31]. Notably, these outcomes were not significantly alleviated even after the relaxation of strict quarantine measures. Although no significant association was found between sleep quality and adverse pregnancy outcomes, the low reliability of the PSQI (Cronbach’s α = 0.686) may limit the robustness and interpretability of these null findings.This indicates that the impact of the pandemic on perinatal mental and physical health may span the entire pregnancy-postpartum continuum, rather than being limited to a single stage. Such continuity emphasizes the importance of establishing a comprehensive and continuous perinatal health management system during public health emergencies, rather than focusing solely on isolated stages.

The present study found that both mild and moderate-to-severe antenatal depression were significantly associated with an increased risk of postpartum hemorrhage (PPH). Currently, limited evidence is available directly linking antenatal depression to the subsequent risk of PPH. Notably, a meta-analysis published in 2024 reported that women who experienced PPH had a significantly elevated risk of developing postpartum depression or anxiety, especially among those with a history of depression or anxiety [32].

These findings suggest a potential bidirectional association between depression and PPH: antenatal depression may increase the risk of PPH, while PPH itself may further predispose women to adverse postpartum psychological outcomes, forming a potential vicious cycle. Our study provides novel prospective evidence from the prenatal psychological perspective to support this potential pathway.

Meanwhile, no significant association was identified between inactivated COVID‑19 vaccination and adverse pregnancy outcomes such as PPH in this study, which is consistent with the findings of a retrospective cohort study published in 2025 [33]. This study included 610 pregnant women (280 of whom received inactivated vaccines) and confirmed that inactivated vaccination during pregnancy does not increase the risk of adverse pregnancy outcomes, providing real‑world evidence for the safety of COVID‑19 vaccination in pregnancy.

Notably, most existing studies and meta-analyses have explored the associations of psychological factors or vaccination with PPH separately. This study simultaneously evaluated the independent relationships of antenatal depressive symptoms, pre-pregnancy COVID-19 vaccination, and PPH within a single cohort during the COVID-19 pandemic, thereby complementing existing evidence on multiple determinants of PPH.

The results of this study also indicate a positive correlation between psychological issues and sleep disturbances, suggesting that improving psychological states can enhance sleep quality. Additionally, good sleep quality can effectively alleviate symptoms of depression, anxiety, and stress [34]. This bidirectional association further supports integrating mental health and sleep management into routine antenatal care—simple interventions (e.g., sleep hygiene education, brief psychological counseling) could yield dual benefits for maternal mental and sleep health.

A previous study reported that experiencing stress during pregnancy was significantly associated with a higher risk of preterm and small for gestational age births [35]. The severity of depression was negatively correlated with gestational age and birth weight [36]. In this study, antenatal depression was associated with increased PPH risk, a relationship underpinned by two key mechanisms: (1) Hypothalamic-pituitary-adrenal (HPA) axis hyperactivation elevates cortisol levels, suppressing oxytocin receptor expression and placental prostaglandin synthesis to induce uterine atony—the leading cause of PPH [37, 38]; (2) Immune dysregulation in depression promotes proinflammatory cytokine (e.g., TNF-α, IL-6) release, damaging vascular endothelium and disrupting coagulation function [39, 40]. However, this study did not detect relevant biomarkers; these mechanisms are merely speculative and still require validation through subsequent studies.This study did not find associations between anxiety, stress, psychological impacts of COVID-19, sleep quality, and adverse pregnancy outcomes. Notably, these null findings may be constrained by study limitations: our sample size was relatively small (n = 260), with underpowered subgroups, which could have reduced the ability to detect subtle associations. The discrepancies between the results of this study and previous research may be attributed to factors such as differences in participant samples, study designs, confounding variables, and chance effects. Future confirmatory research should employ larger, diverse cohorts and measure intermediate indicators (e.g., cortisol levels, cytokine profiles) to validate the mechanistic links between antenatal depression and PPH.

This study suggests that vaccination does not have adverse effects on the mental health of pregnant women. However, other researchers have proposed that pregnant women who receive vaccinations have a lower incidence of psychological disorders, such as stress, depression, anxiety, and insomnia, compared to those who are unvaccinated [13]. Our null finding may relate to our sample’s vaccination timing: most participants received the vaccine pre-pregnancy (not during pregnancy), which differs from the in-pregnancy vaccination populations in prior studies.Due to the small number of participants with COVID-19 vaccination during pregnancy, stratified analyses by vaccination timing were not conducted, which represents a limitation of this study.Given the study’s relatively limited sample size, we acknowledge that the study may be underpowered to detect subtle differences or establish definitive non-inferiority regarding mental health outcomes; thus, the conclusions should be tempered by the potential for a type II error.Subgroup analyses of unvaccinated participants (n = 56) were limited by small sample size and low statistical power; accordingly, these findings should be interpreted as exploratory rather than conclusive. This study revealed that vaccination does not increase the risk of adverse pregnancy outcomes. Before January 2022, China’s National Health Commission had categorized pregnant women as a contraindication group for vaccine administration. Therefore, in this study, most pregnant women received the COVID-19 vaccine before pregnancy. A few pregnant women received the vaccine before discovering their pregnancy. Hence, the results of this study can only suggest the impact of pre-pregnancy COVID-19 vaccine administration on mental health and adverse pregnancy outcomes. Multiple large-scale systematic reviews and meta-analyses have indicated that COVID-19 vaccination during pregnancy (regardless of vaccine type, dosage, or gestational week) is not significantly associated with an increased risk of adverse perinatal outcomes.A meta-analysis of 39 studies further demonstrated that the overall risk of adverse perinatal outcomes was comparable between vaccinated and unvaccinated groups [41].

Conclusions

Antenatal depressive symptoms are independently associated with an increased risk of PPH. Pre-pregnancy inactivated COVID-19 vaccination is not associated with adverse pregnancy outcomes such as PPH. Routine screening and targeted intervention for antenatal depression may be beneficial in reducing the risk of PPH.

Limitations

Firstly, the results may not represent the overall population’s psychological condition, as only collecting completed questionnaires may lead to underestimating the severity of adverse psychological conditions. No quantitative analysis of selection bias was performed for lost-to-follow-up participants in this study, and there remains a potential risk of self-selection bias, as pregnant women who are more concerned about their own mental health were more likely to participate in the present study.Secondly, self-reported questionnaires are only one assessment tool; a comprehensive evaluation combining other clinical manifestations, physical examinations, and medical assessments is required to accurately determine whether pregnant women have issues with depression, anxiety, stress, and sleep disorders. This method may also be subject to recall bias.Additionally, the exclusion of pregnant women with a prior psychiatric history may further restrict the external validity of the results, as this criterion could potentially underestimate the true strength of the association between psychological distress and adverse pregnancy outcomes.Thirdly, during the study period, there were relatively few reported cases of COVID-19 infection nationwide, and we did not collect sufficient data from pregnant women infected with COVID-19 for in-depth analysis. Fourthly, factors such as residual confounding bias and the failure to adjust for socioeconomic-related variables may have an impact on the observed relationships between psychological conditions, vaccination, and pregnancy outcomes.Lastly, the sample size in this study is relatively small, which may have implications for the reliability of the results. Larger samples and multi-center cohort studies are needed to verify the relationship between psychological conditions and vaccination.

Novelty statements

This study successfully elucidates the associations between prenatal psychological distress, vaccination status, and adverse pregnancy outcomes. Unlike previous domestic studies conducted during the COVID-19 pandemic that mainly focused on the prevalence and influencing factors of perinatal mental health problems, the present study takes postpartum hemorrhage (PPH) as the primary outcome and systematically explores the relationship between multi-dimensional psychological status (depression, anxiety, stress, post-traumatic stress, and sleep quality) and adverse pregnancy outcomes. In addition, as a prospective cohort study, this study further analyzes the combined effects of inactivated COVID-19 vaccination and psychological status on maternal and infant outcomes, which has rarely been involved in previous relevant studies. Moreover, a comprehensive psychological evaluation system including multiple scales was adopted to reflect the real psychological status of pregnant women during the pandemic more comprehensively. Unlike previous studies that have primarily focused on COVID-19 infection itself, our findings highlight the impacts of pandemic-related mental health challenges and vaccination decisions on maternal and fetal health outcomes. Collectively, these results provide valuable evidence for clinical prenatal care and public health strategies, informing the development of targeted interventions tailored to the unique psychological needs of pregnant women during infectious disease outbreaks.

Abbreviations

DASS-21

Depression Anxiety Stress Scales

IES-R

Impact of Event Scale-Revised

PSQI

Pittsburgh Sleep Quality Index

PPH

Postpartum Hemorrhage

COVID-19

The Coronavirus Disease 2019

PTB

Preterm Birth

LBW

Low Birth Weight

GDM

Gestational Diabetes Mellitus

HDP

Hypertensive Disorders of Pregnancy

CS

Cesarean Section

NA

Neonatal Asphyxia

NICU

Neonatal Intensive Care Unit

Authors’ contributions

Shiqin Cai, Lixia Shen, and Lisha Ye wrote the main manuscript text.Shaofeng Zhang and Jingwan Huang help collect data.Haitian Chen is responsible for the overall concept of the article and communication with the journal, while Caixia Zhu handles data analysis, manuscript writing, and revisions.

Funding

Not applicable.

Data availability

The data used in this study is based on primary survey data collected by the author. These data are held securely and are available upon request. Interested parties should contact the author directly for access to the data.This study was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University (Approval Number: [2022]565). All procedures performed in this study were in compliance with the ethical principles of the Declaration of Helsinki.

Declarations

Ethics approval and consent to participate

This single-center prospective cohort study was approved by the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University (Approval No.: LS[2022]565). All procedures involving human participants were conducted in accordance with the ethical standards of the institutional research committee and the 1964 Helsinki Declaration and its subsequent amendments. Written informed consent was obtained from all participants prior to study entry and data collection.

Consent for publication

Informed consent was obtained from all participants.

Competing interests

The authors declare no competing interests.