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Published in final edited form as: J Obstet Gynecol Neonatal Nurs. 2023 Dec 1;53(2):160–171. doi: 10.1016/j.jogn.2023.11.005

Relationships Among Number of Stressors, Perceived Stress, and Salivary Cortisol Levels During the Third Trimester of Pregnancy

Rebecca Salomon 1, Sandra Weiss 2
PMCID: PMC10939920  NIHMSID: NIHMS1946699  PMID: 38048897

Abstract

Objective

To examine relationships among the number of stressors, perceived stress, and salivary cortisol levels during the third trimester of pregnancy.

Design

Secondary analysis of cross-sectional data.

Setting

Participants’ homes.

Participants

Women during the third trimester of pregnancy (N = 73).

Methods

Participants provided saliva samples at four timepoints over 2 days for cortisol assay and completed questionnaires to assess stressors and perceived stress. We computed multiple linear regression models to examine the relationships among the number of stressors and perceived stress to cortisol awakening response, diurnal slope, and overall cortisol secretion. We also computed a multiple linear regression model to examine the relationship between perceived stress and the number of stressors.

Results

Greater perceived stress was associated with reduced overall cortisol secretion across the day (β= −0.41, p=.01). The number of stressors was associated with perceived stress (β= 0.48, p=.002) but not salivary cortisol measures.

Conclusion

Elevated perceived stress and the related cortisol alterations that we identified could represent salient targets for enhancing HPA axis function during the third trimester. Perceived stress may shape the relationship between exposure to stressors and cortisol response during pregnancy. Future research is warranted to confirm study results and to understand the implications for parturition and fetal development.

Keywords: Psychological stressors, cortisol, perceived stress, pregnancy


Researchers have repeatedly found associations between altered hypothalamic-pituitary adrenal (HPA) axis function during pregnancy and negative health outcomes for the pregnant woman and the fetus (Duthie & Reynolds, 2013) as well as specific consequences for the pregnant woman (Elrefaay & Weiss, 2023; Solano & Arch, 2020) or the developing fetus alone (Musana et al., 2022; Rakers et al., 2020; Weiss et al., 2023). Regulation of cortisol levels has salience during pregnancy because of the naturally occurring cortisol changes that are essential to prepare the fetus for birth (Duthie & Reynolds, 2013; Stoye et al., 2020). To address stress-related alterations that might lead to negative perinatal outcomes, we will need a better understanding of the differential impact of stressors and perceived stress on HPA axis function during pregnancy. We also need to determine whether stressors experienced during pregnancy are related to self-reported perceived stress.

Individuals may experience certain life events or situations as stressors, while perceived stress encompasses their affective and cognitive reactions to these stressors (Epel et al., 2018). In response to stress, the hypothalamus in our brain activates the HPA axis and the sympathetic nervous system. This activation prompts the release of corticotropin-releasing hormone and adrenocorticotropic hormone, which in turn stimulates the adrenal glands to release cortisol. Thus, when we face a stressor—which we may or may not register as perceived stress—our bodies undergo these physiological changes, measurable through cortisol levels (Miller et al., 2007; O’Connor et al., 2021). Typically, researchers examine three cortisol metrics: the surge in cortisol after morning awakening (cortisol awakening response [CAR]), the decline in cortisol across the day (diurnal slope), and overall cortisol secretion.

Callout 1

Currently, mixed evidence on the associations between the number of prenatal stressors encountered and these cortisol metrics exists. Peer et al. (2013) found no associations between number of stressors and measures of salivary cortisol, including CAR and nighttime cortisol levels. In another study, Schreier et al. (2015) reported a marginally significant association between number of stressors and salivary cortisol level at awakening, although they found no significant associations with other cortisol measures. Lastly, there was no association between number of stressors and CAR in a study conducted during the third trimester (Simon et al., 2016).

Researchers who investigated the relationship between perceived stress and salivary cortisol levels during pregnancy found similar inconclusive results. Simon et al. (2016) found perceived stress was associated with a lower, dampened CAR during the third trimester. In their scoping review, however, Rinne et al. (2023) reported that studies of women affected by stress during the prenatal period often reported null associations with cortisol or inconsistency in the direction of effects. Lazarides et al. (2020) suggested that the mixed associations between perceived stress and cortisol may be due to methodological differences across studies, particularly the mismatch between times when cortisol was acquired and stress was reported.

We found a scarcity of research concerning the relationship between the number of encountered stressors and perceived stress during pregnancy. People often assume that encountering stressors during pregnancy leads to greater feelings of stress. Despite this, researchers have conducted limited studies to verify this assumption. In recent literature, researchers have reported an association of specific stressors such as financial insecurity and intimate partner aggression/violence with greater perceived stress during pregnancy (Andhavarapu et al., 2021; Kashian et al., 2021). However, they have rarely studied whether the number of stressors a pregnant individual experiences is linked to their levels of psychological stress.

Despite the potential for deleterious effects of prenatal stress and stressors on HPA axis regulation, knowledge about the relationships among these important constructs is limited. Therefore, we sought to examine associations among the number of stressors, perceived stress, and salivary cortisol levels during the third trimester of pregnancy. Specifically, we assessed whether the number of self-reported stressors and perceived stress in women was associated with their cortisol levels in the third trimester of pregnancy and whether the number of stressors was related to perceived stress.

Methods

Design

In this secondary analysis, we used data from a longitudinal cohort study that was conducted to assess the effects of antenatal corticosteroids and maternal depression on stress regulation in infants during the first year of life (R01HD081188, PI: S. Weiss). The study reported here is a cross-sectional analysis of selected data acquired during participants’ third trimester of pregnancy.

We employed the integrative working model from the Unified View of Stress Measurement as the theoretical framework for our study (Epel et al., 2018). In this model, Epel et al. (2018) posit that stress is a complex construct with multiple layers of interactions that range from external events (stressors) to internal cognitive evaluations, emotional experiences, and physiological responses. The researchers emphasized the importance of distinguishing between these different components of stress to gain a comprehensive understanding. Accordingly, we conceptualized stress as a multi-faceted phenomenon that is best understood when delineated into distinct but interrelated components. Some of these components include stressors, perceived stress, and physiological responses.

Participants

Our participants were women at 24 to 34 weeks gestation, who were 18 years of age or older, and were fluent in English or Spanish. We excluded women with cognitive impairment, an adrenal or endocrine disorder, or who used a prescribed steroid medication (oral, inhalation, or topical). Additionally, we employed an exclusion criterion of being too psychologically or physically ill to participate, which was determined by the woman’s clinician; mental health problems (e.g., depression) alone did not preclude participation. We included 73 women whose salivary cortisol data were available in this analysis.

Procedures

The Institutional Review Board of the University of California, San Francisco provided approval for the parent study (IRB # 14–13516). The clinical research coordinator identified women who met criteria for participation and invited them to participate during a scheduled third trimester visit to the obstetric clinic. The coordinator provided the interested women with information about the study and we obtained informed consent before data collection. At the clinic visit or at a follow-up contact in their homes, researchers provided participants with self-report questionnaires on perceived stress, stressors experienced in their lives, demographic information, and training on methods for collecting salivary samples at home.

Measures

Salivary Cortisol

We asked participants to provide salivary samples for cortisol assay at four timepoints (waking, 45 minutes after waking, 4 pm, and bedtime) for 2 days and instructed them not to consume food, have alcohol or caffeine, exercise, or take any medications or drugs for 1 hour before their saliva sampling. We also provided written and pictorial instructions on when and how to collect saliva across the 2 sampling days and a brief checklist to document anything that may have affected the quality of their saliva or the time they provided each of the eight saliva samples. Research assistants contacted participants to provide answers to any questions and support them in collecting the samples.

For the saliva collection, we asked participants to rinse their mouths with water 10 minutes before the sampling time and then to drool into a cryovial until 1 ml of saliva accumulated (Salimetrics, n.d.). Participants stored the samples in their home freezers until they gave them to a member of the research team for delivery to the lab for assay. We analyzed samples in duplicate using high sensitivity salivary cortisol enzyme immunoassay (ELISA). We used an assay with a lower limit of sensitivity of .007 μg/dl, a standard curve ranging from 0.012–3.0 μg/dl, an average intra-assay coefficient of variation of 4.6, and an average inter-assay coefficient of variation of 6%.

We calculated three well-established metrics of salivary cortisol from the cortisol concentrations determined by the lab: the CAR, the diurnal slope, and overall cortisol secretion. The CAR represents the expected initial surge in cortisol in the first 30 to 45 minutes after an individual wakes up. The diurnal slope is the linear change from awakening to bedtime. To measure overall cortisol secretion, we calculated the area under the curve (AUC) using Pruessner’s trapezoidal formula (Pruessner et al., 2003).

Stressors

We measured the number of stressors in a participant’s life using the Crisis in Family Systems Interview (CRISYS), a 50-item measure of different categories of stressors, including financial, legal, career, relationship, safety in the home and community, medical, housing, authority, and prejudice, that have occurred in the prior 6 months (Shalowitz et al., 1998). Items include potentially positive and negative events that can create strain or tension for an individual because of their demanding or challenging nature or their threat to safety or well-being. Researchers found that this multidimensional tool possesses content and construct validity and excellent test-retest reliability (Berry et al., 2001, 2006). For our analyses, we created a total score of the number of stressors reported by the participant. In our sample, we found a Cronbach's alpha of 0.84, which suggested good internal reliability of the self-report stressors measure.

Perceived Stress

We measured perceived stress with the Perceived Stress Scale (PSS-10), in which participants are asked to self-report their experiences of stress on 10 items over the past month (Cohen et al., 1983; Cohen & Williamson, 1988). We calculated the total score from the 10 items to create a stress score; higher scores indicated higher perceived stress (Taylor, 2015). Researchers used PSS-10 with pregnant women internationally and found good predictive validity and internal consistency (D’Anna-Hernandez et al., 2015; Lau et al., 2014). In our sample, we found that the PSS-10 had high internal consistency with a Cronbach's alpha of 0.875.

Demographic and Clinical Variables

Participants provided data on the following demographic variables: age, education, income, government assistance and race/ethnicity. We extracted one clinical variable, gestational age in weeks at time of cortisol sampling, from the electronic medical record.

Data Analyses

In preparation for our analyses, we examined the analytic assumptions for normality and linearity using the Shapiro-Wilks test for normality and scatter plots for linearity. Upon initial assessment, we found that salivary cortisol measures were not normally distributed and identified three outliers. In each case, we found a single value for three participants outside of the probable ranges demonstrated in the literature (Aardal & Holm, 1995; Ambroziak et al., 2015). We removed those three values, which were 15.11μg/dl, 7.72 μg/dl, and 4.44 μg/dl, and used the single value from the participant’s sample provided on the other day in place of the outlier score in these instances. After we addressed these outliers, the diurnal slope and area under the curve metrices were normally distributed as evidenced by non-significant Shapiro-Wilks tests and linearity on scatter plots. Although the CAR still had a significant Shapiro-Wilks test, we conducted a further examination of the q-q plot and skewness statistics and found that the distribution was approximately normal, and thus we accepted the normality assumption.

We calculated descriptive statistics on the sample and study variables. We transformed mother’s education into a binary variable in which 0 = less than college graduate and 1 = college graduate and above. We used a binary variable of self-reported income in the analysis in which 0 = below and 1 = above the income limits set by the Department of Housing and Urban Development (HUD) to qualify for housing assistance, as this limit is adjusted based on Median Family Income estimates and Fair Market Rent area definitions for each metropolitan area, parts of some metropolitan areas, and each non-metropolitan county (U.S. Department of Housing and Urban Development, 2023). Because of the small number of participants in specific racial and ethnic groups, we used a binary variable for self-reported race in the analysis in which 0 = White or European American, and 1 = non-White, which includes Black or African American, South and East Asian, or other. Similarly, we used a binary variable for self-reported ethnicity in which 0 = non-Hispanic/Latina, and 1 = Hispanic/Latina. We want to emphasize that we used the categories of race and ethnicity in this study as proxies for exposure to discrimination. However, race, as a social construct, lacks a biological foundation (Flanagin et al., 2021). Moreover, neither race nor ethnicity can wholly represent the intricacies of individual identity and experience or directly cause health differences between racial groups (Adkins-Jackson et al., 2021; Flanagin et al., 2021; Lett et al., 2022). Ascribing a biological basis to race can unintentionally perpetuate harmful stereotypes and neglect systemic issues (Flanagin et al., 2021). Thus, although we identified potential patterns and correlations in our data, we cannot adequately address the structural inequalities and experiences of racism that might influence health outcomes, specifically perceived stress and cortisol levels, in this study.

First, we calculated the bivariate correlations to examine relationships between each study variable and to identify potential covariates to include in the multivariate analysis. We then computed three multiple linear regression, with simultaneous entry of variables using the following three cortisol metrics as the dependent variables: CAR, diurnal slope, and overall cortisol secretion. We used the number of stressors and the perceived stress score as the independent variables in each of the regression models. In the correlation analyses, we found that maternal age, gestational week at the time of cortisol sample collection, and income were all significantly correlated with diurnal slope in the bivariate correlations. Therefore, we included these three variables in the multiple linear regression models to control for their effects on cortisol regulation. Finally, we computed a multiple linear regression with simultaneous entry of variables using perceived stress as the dependent variable and number of stressors was the independent variable. In the bivariate analyses, we did not find any potential covariates associated with perceived stress. However, we identified significant associations between the number of stressors and four variables: maternal age, race, education, and income. We adjusted for these four variables to clarify the unique variance for the number of stressors that may be associated with perceived stress.

To adjust for multiple comparisons, we applied the Bonferroni correction to all analyses by dividing the alpha level (0.05) by the number of tests (N = 3) being performed in the first set of models. By using this correction, we controlled the family-wise error rate and reduced the risk of making a Type I error. Thus, we set statistical significance at p < 0.017 for all analyses. We used SPSS version 26 (IBM, Armonk, NY) to complete all statistical analyses.

Callout 2

Results

We included a total of 73 participants in the analyses. Participants had an average age of 34.5 years, 58.9% identified as White, and approximately 21% identified as Hispanic/Latina. We collected salivary cortisol samples at an average of 31 weeks of gestation. We provide the descriptive characteristics of the sample in Table 1.

Table 1.

Sociodemographic Characteristics of Participants

Variable n %
Racial Identity
 White 43 58.9
 Black or African American 13 17.8
 Asian (South and East) 10 13.7
 Hawaiian/Pacific Islander 1 1.4
 Other or multiple identities 4 5.5
Ethnic Identity
 Not Hispanic/Latina 56 76.7
 Hispanic/Latina 15 20.1
Highest Education
 Elementary 5 6.8
 High school or GED 8 11.0
 Some college 11 15.1
 Associate degree 6 8.2
 College graduate 19 26.0
 Master's degree 10 13.7
 Professional degree 8 11.0
 PhD degree 5 6.8
Annual income
 <$15,000 10 13.7
 $15–20,999 6 8.2
 $21–30,999 8 11.0
 $31–50,999 1 1.4
 $51–75,999 2 2.7
 $76–100,999 1 1.4
 $101–149,999 9 12.3
 > $150,000 32 43.8
Government Assistance
 None 43 58.9
 Single form of assistance 8 10.1
 Multiple forms of assistance 20 27.4

Number of Stressors, Perceived Stress, and Cortisol Measures

Participants reported an average of 5.78 life stressors (SD = 5.09) in the past 6 months. The participants reported the following types of stressors most frequently: pregnancy (98.3%, n = 59), working (85%, n = 51), looking for a job (30%, n = 18), moving to a different location (28.3%, n = 17), and feeling unsafe due to events in the neighborhood (25%, n = 15). Participants’ perceived stress score was in the moderate range, with a mean of 15.26 out of a possible 40. This score exceeds the established norm for women of 13.7 (Cohen, 1994). Participants’ mean CAR was 0.01 μg/dl (SD= 0.16), the mean value for diurnal slope was 0.24 μg/dl (SD= 0.19) and the mean for AUC was 111.75 μg/dl (SD = 87.30). See Table 2.

Table 2.

Descriptive Statistics for Continuous Variables

Variable M SD Minimum Maximum
Mother’s Age 34.52 5.62 21 47
Gestational week when cortisol was collected 31.03 3.26 21.7 37.3
Stressors 5.78 5.09 1 31
Perceived stress 15.26 6.80 3 31
Cortisol awakening response (CAR) 0.01 0.16 −0.35 0.62
Diurnal slope 0.24 0.19 −0.28 0.78
Overall cortisol secretion (AUC) 111.75 87.30 −173.14 328.04

Relationships among Number of Stressors, Perceived Stress, and Salivary Cortisol Measures

In the bivariate analysis, the number of stressors had a significantly association with only one of the cortisol measures, diurnal slope (r= −0.32, p =.015; see Table 3). In the multiple linear regression model, the association was no longer significant. Perceived stress was negatively associated with AUC (r= −0.29, p=.018) in the bivariate analysis; however, this did not meet the threshold for significance after applying the Bonferroni correction for multiple comparisons (adjusted p-value threshold <.017). See Table 3. In the multiple linear regression model, increased perceived stress was significantly associated with a lower overall amount of cortisol secretion across the day (AUC; 𝖰= −0.41, p =.01). We can interpret the beta coefficient as indicating a moderate effect of perceived stress on cortisol secretion across the day (Acock, 2014). See Table 4. Perceived stress was not significantly associated with the other two cortisol measures – CAR or diurnal slope (see Supplementary Tables S1 and S2).

Table 3.

Correlations for Study Variables

Variable n 1 2 3 4 5 6 7 8 9 10 11
1. Mother’s age 71 --
2. Gestational week 64 −0.27 --
3. Mother's race 70 −0.30* −0.10 --
4. Mother's ethnicity 71 −0.20 0.14 −0.22 --
5. Educational level 72 0.49** −0.18 −0.31** −0.48** --
6. Income 69 0.59** −0.25 −0.41** −0.46** 0.85** --
7. Number of stressors 60 −0.36** 0.16 0.33* 0.31 −0.48** −0.52** --
8. Perceived stress 69 −0.11 −0.05 0.16 −0.04 −0.16 −0.22 0.43** --
9. Cortisol awakening response 73 −0.02 0.24 −0.12 0.01 −0.12 −0.13 0.08 −0.17 --
10. Diurnal slope 71 0.30* −0.33** −0.09 −0.15 0.19 0.31* −0.32* −0.18 −0.34** --
11. Overall cortisol secretion (AUC) 71 0.18 −0.09 −0.07 −0.18 0.06 0.16 −0.20 −0.29 0.46** 0.60** --

Note. n = number of participants included in correlation.. AUC = area under the curve.

*

p < .017.

**

p < .01.

Table 4.

Summary of Regression for The Number of Stressors and Perceived Stress on Overall Cortisol Secretion (AUC)

Variables Unstandardized regression coefficient
Standardized coefficient
Test statistics
95% CI for B
B SE β t p
Intercept 287.18 164.20 1.75 0.09 [−44.20, 618.55]
Number of stressors −2.52 2.86 −0.15 −0.88 0.38 [−8.30, 3.25]
Perceived stress −5.44 2.01 −0.41 −2.71 0.01 [−9.49, −1.38]

Note. n = 48. R2 = 0.4. E (5, 42) = 2.69. Model controlled for participant’s age, gestational age, and income. AUC = area under the curve

Relationship between Number of Stressors and Perceived Stress

We found that the number of stressors had a positive, moderate association with perceived stress (r = 0.43, p =.001) in the bivariate analysis. See Table 3. In the multiple linear regression model, the number of stressors retained a significant, moderate association with perceived stress (𝖰= 0.48, p =.002). In other words, as participants reported a higher number of stressors, they also reported higher perceived stress. None of the covariates that we considered in the model (i.e., maternal age, race, ethnicity, education, and income) were significantly associated with perceived stress. See Table 5.

Table 5.

Summary of Regression for the Number of Stressors on Perceived Stress

Variables Unstandardized regression coefficient
Standardized coefficient
Test statistics
95% CI for B
B SE β t p
Intercept 6.53 6.24 1.05 0.30 [−5.97, 19.06]
Number of stressors 0.58 0.19 0.44 3.04 0.004 [0.20, 0.97]

Note. n = 57. R2 = 0.27. E (6, 49) = 3.02. Model controlled for participant’s age, race, education, income.

Discussion

Higher levels of perceived stress were related to a lower overall amount of cortisol secretion over the course of a day in the third trimester of pregnancy, a pattern characteristic of dysregulation. While we found no association between the number of stressors participants reported and their cortisol response, there was a significant association between the number of stressors and perceived stress. Taken as a whole, we can interpret these findings to suggest that perception of stressors among pregnant women, trans men, and gender non-conforming individual may exert a significant influence on how those stressors affect cortisol response.

The cortisol metrics we calculated align with expected cortisol changes across pregnancy and with existing research. Cortisol levels naturally rise closer to childbirth, and the average cortisol level for our participants, sampled around 28 weeks gestation, was lower than levels reported for individuals at 36 weeks gestation (Kivlighan et al., 2008). The average CAR for our sample matches findings from previous studies for salivary cortisol measurements taken during similar gestational weeks (Harville et al., 2007) and is lower than the CAR reported for those at 36 weeks (Cheng & Pickler, 2010). Finally, the average AUC in our sample aligns with findings from studies conducted at a comparable gestational period (Peterson et al., 2020) and is greater than values reported for cortisol measurements at 25 weeks gestation (Suglia et al., 2010).

Our findings regarding relationships between the number of stressors and salivary cortisol align with prior research. While researcher presented varied findings in the literature, Peer et al. (2013) found no association between the number of stressors and the CAR or overall cortisol secretion. Similarly, Schreier et al. (2015) reported no associations between number of stressors and diurnal slope or overall cortisol secretion. Researchers in both of those studies used the same measure as we did to quantify the number of stressors for their participants.

The number of stressors reported over the past 6 months may not be associated with salivary cortisol during the third trimester for a few reasons. It is possible that only particular stressors are biologically salient and that their effects are lost when the effects of all stressors are combined. For example, researchers found that social evaluative stressors had a larger effect on cortisol levels than other stressors in acute stressor situations (Dickerson & Kemeny, 2004; Woody et al., 2018). Alternatively, the effect of stressors may depend on the way in which they are appraised or the traits of the people who are experiencing them. For instance, Xin et al. (2017) found that individual cortisol response to stressors was associated with various personality traits.

Notably, we found that that greater perceived stress was associated with reduced overall cortisol concentration across the day for participants. Researchers attributed stress-related deficiency of cortisol to a number of mechanisms, including decreased synthesis at various timepoints during the circadian cycle or in response to stressors, downregulation of glucocorticoid receptors, and enhanced negative feedback inhibition of cortisol secretion (Herman et al., 2016; Karin et al., 2020; Russell & Lightman, 2019).

Across a substantial body of research, investigators found that higher levels of burnout, chronic stress, and adversity can increase negative feedback inhibition in the HPA axis to reduce cortisol exposure (Bunea et al., 2017; Herman et al., 2016; Lennartsson et al., 2015; Miller et al., 2007). Eventually, cortisol production and release habitually reduce. Researchers described reduced cortisol concentration as a marker of allostatic load, which represents the cumulative physical and mental burden of chronic stress and life events (Badanes et al., 2011; Sterling, 2012). Some proposed that allostatic overload occurs when environmental challenges exceed the individual ability to cope (Guidi et al., 2021). Given our focus in this study on recent stress perception rather than chronic stress perception, the role of repeated or persistent perception of stress in reduced cortisol amounts remains an open question. This question becomes particularly pertinent when considering pregnancy. If pregnant women with heightened stress exhibit reduced cortisol as a sign of such a hypoactive HPA axis, it could pose detrimental effects for the woman (Bunea et al., 2017; Wichmann et al., 2017) and the fetus (Karakash et al., 2016). Lower than expected amounts of cortisol exposure across the day might also negatively influence fetal neurodevelopment, as researchers have found that increased cortisol near term played a significant mechanistic role in lung and brain development, among other important organ systems (Busada & Cidlowski, 2017; Glynn et al., 2016; Pofi & Tomlinson, 2020).

In the past 10 years, researchers have not explored the relationship between perceived stress and overall cortisol secretion. Thus, our novel findings have important implications for the well-being of pregnant patients and their infants and warrant further research to confirm stability in other samples and potential underlying mechanisms.

Although we found a significant association between the number of stressors and perceived stress, only perceived stress was associated with cortisol response. Based on these findings, we could hypothesize that perceived stress might shape the relationship between exposure to stressors during pregnancy and cortisol response. The cortico-limbic system, which includes the hippocampus, prefrontal cortex and amygdala, plays a central role in regulating the HPA axis. How individuals interpret stressors in the environment, as threats or not, can determine HPA axis activation (Herman et al., 2016; Tafet, 2022). Recently, researchers identified three distinct factors of perceived stress among pregnant women: feelings of emotional distress, perceived inability to cope with stressors, and negative frame of mind regarding one’s situation and ability to handle problems (Musana et al., 2020). Considering these factors, we might conclude that the effect of stressors, regardless of their severity or persistence, could be minimal if an individual does not feel substantial emotional distress from them, believes they can cope effectively with them, and does not view them negatively. This interpretation is supported by prior research in which investigators reported a robust relationship between cognitive appraisal and cortisol response to stressors (Helbig & Backhaus, 2017; Kerr et al., 2020).

Due to the cross-sectional nature of this research, we must also consider the possibility of the inverse direction of our findings. HPA axis dysregulation could create a physiologic state that influences stress perception, an idea consistent with theories of embodied cognition (Schultz & Vögele, 2015). Researchers previously demonstrated that increased cortisol can be mood-protective during acute stress (referece). If cortisol has a mood-protective role in late pregnancy, this could account for our observation that greater total cortisol output was associated with less perceived stress, while reduced cortisol output correlates with more stress. However, given the robust evidence that links higher cortisol during pregnancy and depressive mood states (Orta et al., 2018; Seth, Lewis & Galbally, 2016), this interpretation seems less plausible.

Callout 3

Limitations

We recognize potential limitations in our study. First, given the cross-sectional design, we captured data at a single timepoint, so we cannot directly prove that perceived stress causes HPA axis dysregulation. Additionally, our focus on the third trimester limits generalizations to the entire pregnancy, and our modest sample size might not have been large enough to detect certain associations. Further, our measurement of the number of stressors did not consider the severity or how long-lasting these stressors were, which are factors that other researchers have found to be associated with differential HPA axis response (Epstein et al., 2021; Lam et al., 2019). Moreover, while participants reported a wide range in the number of stressors, the average number of stressors was low. This limited our ability to distinguish participants who may have experienced a very high burden of stressors from those who did not. These measurement concerns may have contributed to our inability to find an association between stressors and salivary cortisol. Finally, there is limited literature available from the past ten years to which we could relate our findings. The paucity of recent literature on cortisol in pregnancy and the relationship between stressors and cortisol supports the need for further research in these areas.

Implications

Social interventions remain essential for pregnant women, pregnant trans men, and pregnant gender non-conforming individuals who experience ongoing stressors. However, based on data from this study, we recommend interventions for the management of stress symptoms during pregnancy. Strategies that reduce psychological distress and enhance coping skills may be especially helpful in regulating cortisol (Urizar et al., 2019). Alternatively, if researchers find in subsequent studies that reduced cortisol in the third trimester intensifies the perception of stress, we recommend developing interventions such as biological therapies that directly foster optimal cortisol output throughout the day.

Because optimal cortisol levels in late pregnancy are critical to fetal lung and brain development (Busada & Cidlowski, 2017; Glynn et al., 2016; Pofi & Tomlinson, 2020), understanding the nuanced relationship between perceived stress, the number of stressors, and cortisol levels is essential. From this knowledge, researchers and clinicians might derive significant advances in prenatal care, optimizing both maternal well-being and fetal development outcomes. While immediate clinical or policy changes are premature, given the exploratory nature of this study, there is an undeniable need for further research in this area. Ultimately, the insights gained from such studies may enhance prenatal care and ensure positive outcomes for both pregnant individuals and their infants.

Conclusion

We found that pregnant women with greater perceived stress during their third trimester of pregnancy had reduced cortisol concentrations. Pregnant women pregnant trans men, or pregnant gender non-conforming individuals who experience greater stress but have difficulty mounting an adequate neuroendocrine response may be at particular risk for stress-related disorders and adverse birth outcomes. Targeting the elevated perceived stress and related cortisol alterations identified in this study could be effective strategies to enhance HPA axis function during the third trimester. More research is needed to explore the potential causal mechanisms linking perceived stress and reduced cortisol concentration, including understanding the roles of neuroendocrine secretion, glucocorticoid receptors, and the HPA axis’s negative feedback inhibition. Using insights from further studies, researchers and clinicians can craft effective clinical interventions to improve outcomes for pregnant women, pregnant trans men, or pregnant gender non-conforming individuals and their future children.

Declaration of Generative AI and AI-assisted Technologies in the Writing Process

During the preparation of this work the authors used OpenAI's GPT-3.5 and GPT-4 language models to receive suggestions on refining the language and framing of certain sections. After using this tool, the authors reviewed and edited the content as needed and take full responsibility for the content of the publication.

Supplementary Material

1

Precis.

The number of stressors was related to perceived stress, but only perceived stress was associated with cortisol levels in the third trimester.

Callouts.

  1. The precise connections among the quantity of stressors, the perception of stress, and the functioning of the hypothalamic-pituitary-adrenal axis during pregnancy remain unclear.

  2. Elevated perceived stress and the related cortisol alterations identified in this study could represent salient targets for enhancing HPA axis function during the third trimester.

  3. Pregnant women who experience greater stress levels but have difficulty mounting an adequate neuroendocrine response might face heightened vulnerability to stress-related conditions and adverse birth outcomes.

Funding

The original research from which the data for this article were derived was funded by the National Institute of Child Health and Human Development (NIH, R01 HD081188, S. Weiss, PI). This secondary analysis was conducted by Rebecca Salomon as a postdoctoral fellow supported by a training grant (T32 NR016920) from the National Institute of Nursing Research at the National Institutes of Health.

Footnotes

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Disclosure

The authors report no conflicts of interest or relevant financial relationships.

Contributor Information

Rebecca Salomon, School of Nursing, University of North Carolina Chapel Hill, Chapel Hill, NC..

Sandra Weiss, School of Nursing, University of California San Francisco, San Francisco CA..

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