Introduction
Maternal psychosocial stress, resulting from acute stressors during pregnancy such as financial and economic instability and lack of social support Reference Coussons-Read1 and/or lifetime experiences of bias and discrimination, Reference Collins and David2 can have adverse effects on fetal growth. The effect of maternal stress on fetal growth and development is thought to operate, in part, through disruption to the hypothalamic–pituitary–adrenal (HPA) axis Reference Coussons-Read1 which, in turn, leads to dysregulation of maternal–fetal pathways involved in energy balance and fat accrual. Reference Entringer, Buss and Rasmussen3,Reference Entringer, Buss and Wadhwa4
Prior studies have linked maternal psychosocial stress to delivery of both small- Reference Staneva, Bogossian, Pritchard and Wittkowski5–Reference Preis, Mahaffey, Pati, Heiselman and Lobel7 and large-for-gestational-age newborns. Reference Entringer, Buss and Rasmussen3,Reference Mélançon, Bernard and Forest8 As discussed in a 2018 meta-analysis Reference Lima, El Dib and Rodrigues6 and a 2015 review Reference Staneva, Bogossian, Pritchard and Wittkowski5 and subsequent empirical studies in both developing Reference Ae-Ngibise, Wylie and Boamah-Kaali9 and developed settings, Reference Preis, Mahaffey, Pati, Heiselman and Lobel7 experiences of maternal stress and anxiety during pregnancy are associated with preterm delivery and smaller newborn size based on birthweight-for-gestational-age. Reference Staneva, Bogossian, Pritchard and Wittkowski5,Reference Lima, El Dib and Rodrigues6 At the other end of the spectrum, other studies have found positive associations of maternal stress with newborn size. For example, in a study of 5721 predominantly white mother/offspring pairs in Canada, Melancon et al. observed that women who reported intermediate to high levels of stress during pregnancy, based on the Measure of Psychological Stress (MS-9), had a 1.2- to 1.8-fold greater risk of delivering a macrosomic newborn. Reference Mélançon, Bernard and Forest8 Similarly, Entringer et al. found that higher prenatal stress, as determined by cortisol levels, was associated with higher infant adiposity at 6 months of age among 67 diverse mother/child dyads in southern California. Reference Entringer, Buss and Rasmussen3
Beyond differences in sociodemographic characteristics of the study samples and method of assessing maternal psychosocial stress, one contributing factor to the inconsistency in study findings is use of relatively crude weight- and length-based indices as proxies for neonatal body composition, which precludes assessment of fat vs. fat-free mass (FFM). Given that there is likely variation in body composition among infants of similar weight and length, direct assessments of body composition in newborns allow for more precise insight into potential consequences of maternal prenatal stress on fetal growth and development.
To address gaps in the literature, we investigated associations of maternal psychosocial stress, based on responses to the Edinburgh Postpartum Depression Scale (EPDS) and Cohen’s Perceived Stress Scale (PSS) during pregnancy, with air displacement plethysmography (ADP) assessed fat and FFM, as well as standardized weight- and length-based indices of body size that are commonly used as proxies for adiposity (body mass index [BMI]-for-age, weight-for-length, weight-for-age) and lean mass (length-for-age). Secondarily, we sought to determine whether the relationship between maternal psychosocial stress and neonatal body composition are modified by race/ethnicity. We hypothesized that higher maternal psychosocial stress would be associated with higher neonatal adiposity but not lean mass, and that this relationship differs by race/ethnicity. Specifically, we hypothesized that mothers identifying as non-Hispanic Black would experience higher maternal psychosocial stress, as measured by the EPDS and PSS questionnaires, and therefore deliver smaller-framed newborns with higher neonatal adiposity.
Methods
Study population
Mother/newborn pairs were participants of the ongoing Healthy Start pre-birth cohort, recruited from prenatal obstetric clinics at the University of Colorado Hospital between 2010 and 2014 during the first trimester of pregnancy. Data were collected at three in-person research visits: early pregnancy (median of gestational 17 weeks), mid-pregnancy (median of gestational 27 weeks), and delivery. Reference Starling, Brinton and Glueck10 The initial study population was 1,410 mother/newborn pairs. All mothers provided written informed consent.
For the present analysis, we excluded mothers who were missing responses to either questionnaire (n = 487), newborns missing birthweight data (n = 111), and those measured more than 2 days after delivery (n = 208). After exclusion, the analytic sample included 604 mother/newborn pairs (Supplementary Figure S1). In comparison to the overall sample, mothers in the present analysis had slightly more education (68.3% vs. 67.2% attended college); and the newborns had slightly higher birthweight (3136 vs. 3112 g), higher length z-score (−0.23 vs. −0.37 z-score), as well as lower fat mass (FM) (285 vs. 295 g) and higher FFM (2858 vs. 2833 g).
Exposure: maternal psychosocial stress during pregnancy
The exposures of interest were derived from responses to the Edinburgh Postnatal Depression Scale (EPDS) Reference Cox, Holden and Sagovsky11 and Cohen’s PSS Reference Yokokura, Silva and Fernandes12 questionnaires administered at median 17 and 27 gestational weeks. The EPDS is a validated 10-item questionnaire used to assess risk of postpartum depression (PPD) by querying the respondent’s feelings and level of satisfaction or dissatisfaction with regular activities and behaviors in the prior 7 days via a ranking scale from 0 to 3 (0 = As much as I always could, 1 = Not quite as much now, 2 = Definitely not as much now, 3 = Not at all). Although the EPDS is validated for assessing PPD, lower scores that do not reach the PPD diagnosis threshold (<13) can be interpreted as indications of maternal distress in clinical settings. Reference Khanlari, Barnett Am, Ogbo and Eastwood13 The PSS is a 10-item questionnaire used to assess the degree to which life situations are deemed unpredictable, uncontrollable, and overwhelming, with each answer scored on a scale of 0–4. The PSS has been shown to have high internal reliability in pregnant populations and has been validated for depressive and physical symptomatology of stress in non-pregnant populations. Reference Combs, Canu, Broman-Fulks, Rocheleau and Nieman14,Reference Nast, Bolten, Meinlschmidt and Hellhammer15 In the analysis, we considered EPDS and PSS as predictors of neonatal adiposity in separate models as these two constructs capture distinct but overlapping psychosocial pathways for which mutual adjustment may represent an overadjustment.
For the analysis, we took the average of the scores for the EPDS and PSS administered at 17 and 27 gestational weeks to capture psychosocial stress across the prenatal period. The recommended threshold for prenatal depression is EPDS score >12 or 13. Reference Cox, Holden and Sagovsky11 However, there were too few women with EPDS >12 (N = 20, 3.3%). Therefore, we employed a threshold of EPDS >6.5, corresponding with the fourth quartile of EPDS score in our sample. For PSS, we applied the commonly used threshold of >21 as an indicator of elevated stress. Reference Yokokura, Silva and Fernandes12,Reference Geslani and Gaebelein16
Outcome: neonatal body composition and anthropometry
The outcomes of interest were indicators of newborn size and body composition. For adiposity, we focused on ADP-assessed FM and percent fat mass (%FM), while also considering BMI-for-age z-score, weight-for-age z-score, weight-for-length z-score, standardized according to the World Health Organization Growth Standard for infants 0–2 years of age. 17 For newborn lean mass, we focused on ADP-assessed fat-free mass (FFM) and length-for-age z-score.
Covariates
We considered covariates that could confound the relationship between maternal psychosocial stress during pregnancy and newborn size. We selected covariates based on prior knowledge of shared common causes (confounders) of maternal stress and neonatal body composition, as shown in the directed acyclic graph (DAG) depicted in Supplementary Figure S2. These included maternal age (16–24 years old, 25–29 years old, 30–34 years old, 35+ years old) which is a known correlate of prenatal stress and depression Reference Dhaliwal, Dabelea, Lee-Winn, Glueck, Wilkening and Perng18 as well as a newborn size Reference Di Gravio, Lawande and Potdar19 ; maternal education level (less than high school, high school/GED, associate’s degree/some college, 4-year college degree, graduate degree) and household income (<$40,000, $40,000–$70,000, >$70,000), and marital status (yes/no) as social factors that influence both perinatal women’s health status and neonatal outcomes. 20 Additionally, we conceptualized self-identified race/ethnicity (non-Hispanic White, non-Hispanic Black, Hispanic, other) as an effect modifier given documented differences in wide-ranging health outcomes across racial and ethnic strata. Reference Flanagin, Frey and Christiansen21 Additional confounders that we considered included parity, maternal diet quality, physical activity level, and pre-pregnancy BMI. Parity was defined as the woman’s number of previous live births (0, 1, 2, 3+). Maternal diet quality was measured by the healthy eating index (HEI) and classified into healthy diet (>57) and unhealthy diet (≤57) based on prior findings in this cohort Reference Shapiro, Kaar and Crume22,Reference Francis, Dabelea, Boyle, Jansson and Perng23 and physical activity levels were measured by estimated total energy expenditure according to the Pregnancy Physical Activity Questionnaire. Reference Harrod, Chasan-Taber and Reynolds24 Pre-pregnancy BMI was calculated as pre-pregnancy weight divided by height. Reference Collins and David2 In addition, we considered offspring sex as a precision covariate for neonatal body composition in light of sex differences in birth size. Reference Crawford, Doyle and Meadows25
Statistical analysis
Prior to formal analyses, we assessed univariate distributions of all variables to identify deviations from normality and missing values. Next, we conducted bivariate analyses to assess the correlation (Pearson’s R 2 and Spearman’s Rho) between EPDS and PSS, and of EPDS and PSS scores with background characteristics of the study participants to identify confounders for multivariable analyses. Here, we calculated the % (N) of participants who had scores above the threshold values for EPDS (>6.5) and PSS (>21) for each level of the covariate and used the chi-squared test to assess statistical significance.
For the primary analysis, we started by examining unadjusted associations of dichotomous and continuous EPDS and PSS scores with each newborn outcome using linear regression. In multivariable analysis, we adjusted for covariates that were associated with EPDS and PSS score in the bivariate analysis and are also known determinants of fetal growth: maternal age, race/ethnicity, maternal education level, marital status, pre-pregnancy BMI, and newborn sex.
To assess for effect modification by race/ethnicity, we entered a product term between the maternal stress indicators and race/ethnicity categorized as non-Hispanic White, Hispanic, non-Hispanic Black, and Other. Here, we considered evidence for a statistical interaction as P-interaction <0.05.
In sensitivity analyses, we re-ran all models after excluding infants born <37 weeks gestation, since preterm infants may have inherently different body composition than those born at term. Reference Ahmad, Nemet and Eliakim26 In light of prior evidence that diet quality Reference Shapiro, Kaar and Crume22 and physical activity levels Reference Harrod, Chasan-Taber and Reynolds24 during pregnancy influences neonatal body composition, we further adjusted for maternal HEI score (>57 vs. ≤57) and average maternal physical activity and compared the direction, magnitude, and precision of effect estimates before vs. after including these variables.
Across all analyses, we considered an alpha level of 0.05 for statistical significance. All analyses were completed using SAS (version 9.04, Cary, NC, USA).
Results
Table 1 shows background characteristics of the 604 mother/newborn pairs included in the study. Approximately a quarter (24.3%) of the women had an EPDS score >6.5, thereby meeting the threshold for potential prenatal depression, and 18.1% had a PSS score >21, meeting the threshold for elevated stress. Over half (54.6%) of women identified as non-Hispanic White and 26.2% identified as Hispanic. The majority of women (81.6%) were married or living with a partner. Almost half of the mothers (44.7%) were nulliparous, and 27.8% of mothers were categorized as overweight and 18.1% as obese.
Background characteristics of 604 mother/newborn pairs in the Healthy Start study
a Counts may not add up to 604 due to missing values.
b According to a US birthweight reference (Oken et al. BMC Pediatrics 2003; 3:6).
BMI = body mass index.
Table 2 shows the newborn outcomes. The mean (SD) birthweight of the study sample was 3,136.1 g (437.1 g). Mean (SD) FM was 8.77% (3.82%) FM. Eighteen percent of the infants were small-for-gestational-age, 78.6% were appropriate-for-gestational-age, and 3.3% were large-for-gestational-age. Additional details on maternal and newborn characteristics are in Table 1 and Table 2.
Body composition and anthropometry among 604 newborns in the Healthy Start study
BMI = body mass index.
Table 3 shows bivariate associations of background characteristics with EPDS >6.5 and PSS >21. Younger maternal age, non-White race, lower educational attainment, being single, lower household income, and preterm delivery were associated with EPDS >6.5. On the other hand, none of the characteristics were associated with PSS score.
Bivariate associations of maternal Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) scores with background characteristics of 604 mother/newborn pairs
a Counts may not add up to 604 due to missing values.
b According to a US birthweight reference (Oken et al. BMC Pediatrics 2003; 3:6).
c Maternal EPDS and PSS scores are averaged across the first two pregnancy visits.
BMI = body mass index.
The two exposure variables, EPDS score and PSS score, had a moderate positive correlation; Pearson’s R 2 = 0.47 and Spearman’s correlation (Rho) = 0.46.
Table 4 shows unadjusted associations of EPDS and PSS, both as dichotomous indicators as well as continuously, with the neonatal outcomes. In general, EPDS – whether assessed dichotomously or continuously – was inversely associated with the neonatal outcomes. Mothers with EPDS scores >6.5 delivered newborns with 40.1 g (95% CI: 12.7, 67.4) lower FM and 0.97% (95% CI: 0.26, 1.62) lower %FM, compared to those who scored ≤6.5. Similarly, each 1-unit increment in EPDS score corresponded with 5.6 g (95% CI: 2.3, 9.0) lower neonatal FM. We observed similar associations with the weight- and length-based indicators of body size. On the other hand, PSS was not associated with any of the neonatal outcomes.
Unadjusted associations of maternal Edinburgh Postnatal Depression Scale (EPDS) and Perceived Stress Scale (PSS) scores with newborn body size and anthropometry among 604 mother/offspring pairs in the Healthy Start study
c Maternal EPDS and PSS scores are averaged across the first two pregnancy visits.
BMI = body mass index.
Table 5 shows results from multivariable analysis. Here, EPDS remained associated with higher neonatal FM and %FM. For example, after adjusting for maternal age, race/ethnicity, education level, marital status, pre-pregnancy BMI, and newborn sex, mothers with EPDS >6.5 vs. ≤6.5 delivered newborns with 35.3 g (95% CI: 6.6, 64.0) lower FM and 1.0% (95% CI: 0.0, 1.7) lower %FM. Although not statistically significant, we noted similar, albeit marginally significant, inverse associations of EPDS with lean mass indicators. Mothers who scored > vs. ≤ 6.5 on the EPDS questionnaire delivered newborns with 29.2 g (95% CI: −37.3, 95.7) lower FFM (P = 0.15) and 0.18 (95% CI: −0.03, 0.39) lower length z-score (P = 0.09).
Adjusted associations of maternal Edinburgh Postnatal Depression Scale (EPDS) score with newborn body size and anthropometry among 604 mother/offspring pairs in the Healthy Start study
c Maternal EPDS and PSS scores are averaged across the first two pregnancy visits.
BMI = body mass index.
Consistent with the unadjusted analysis, PSS was not significantly associated with the neonatal outcomes, though similar inverse associations were observed (Table 6).
Adjusted associations of maternal Perceived Stress Scale (PSS) score with newborn body size and anthropometry among 604 mother/offspring pairs in the Healthy Start study
c Maternal EPDS and PSS scores are averaged across the first two pregnancy visits.
BMI = body mass index.
We did not observe consistent evidence of a statistical interaction with maternal stress indicators, with all P-interaction >0.05, except for weight-for-length z-score. However, beta estimates within strata of race/ethnicity category did not markedly differ across strata. Therefore, we do not present stratified results.
Excluding newborns delivered <37 weeks did not change findings; therefore, we included all infants in the presentation of results to avoid collider stratification bias due to study sample selection based on an intermediate variable. Reference Ananth and Schisterman27 The inclusion of HEI score and maternal physical activity level in multivariable models did not result in marked differences in the direction, magnitude, or precision of estimates. For example, after additional adjustment for these variables, mothers with EPDS scores > vs. ≤6.5 delivered newborns with 37.0 g (95% CI: 8.2, 65.7) lower FM, and 0.18 (95% CI: −0.03, 0.39) lower length-for-age z-score.
Discussion
Summary of main findings
In this analysis of 604 mother/newborn pairs, higher maternal psychosocial stress during pregnancy, based on our internal definition of being in the highest quartile of EPDS score during pregnancy, was associated with the delivery of smaller newborns that have less FM, and marginally lower FFM and length at birth. On the other hand, the women’s score for Cohen’s PSS was not associated with any neonatal outcomes.
Our findings of an inverse relationship of EPDS, an assessment of prenatal depression, with neonatal adiposity and lean mass were counter to our hypothesis, as well as some of the existing literature of mother/offspring pairs in comparable settings. For example, in an analysis of 227 multi-ethnic mother/offspring pairs in New York, Ecklund-Flores et al. reported that prenatal depression according to the Center for Epidemiologic Studies Depression Scale (CESD) was associated with higher birthweight, an association that the authors hypothesized may result from higher heart rate among depressed women and thus enhanced placental perfusion. Reference Ecklund-Flores, Myers, Monk, Perez, Odendaal and Fifer28 However, our findings do fall in line with other published studies, including several papers included in a 2012 review that identified associations of maternal depression during pregnancy on low birthweight in offspring, Reference Davalos, Yadon and Tregellas29 as well as recent empirical studies. For instance, in an analysis of 1377 Chinese mother/infant dyads, Li et al. found that EPDS score ≥12 corresponded with over twice the odds of low birthweight. Reference Li, Gao and Dai30 Similarly, in a study of 353 mother/offspring pairs in rural Ghana, Ae-Ngibise et al. reported that maternal experiences of negative life events, a determinant of maternal depression, Reference Jin, Shen, Xing and Wang31 corresponded with delivery of low birthweight and small-for-gestational-age neonates. Reference Ae-Ngibise, Wylie and Boamah-Kaali9
In addition to the inverse relationship between EPDS and indicators of adiposity, we noted marginal inverse associations with FFM and length-for-age z-score. These findings suggest that maternal depression not only affects fetal fat accretion, but may also influence lean mass accrual and length gain in utero, both of which serve as bellwethers for future FFM and linear growth. Reference Berglund, Lewis, Michaelsen, Mølgaard, Renault and Carlsen32 Importantly, these associations were independent of key sociodemographic and lifestyle confounders previously identified as determinants of neonatal body composition. Reference Shapiro, Kaar and Crume22,Reference Harrod, Chasan-Taber and Reynolds24
There are several mechanisms by which maternal depression may hinder fetal growth. During pregnancy, the placenta acts as a buffer against negative exposures the mother experiences. However, maternal stress specifically can increase cortisol levels and inflammation, impacting the placenta’s buffering activity and can alter the physiological programming of the HPA axis, responsible for fetal development and fat accrual. Reference Coussons-Read1 Second, it is also possible that maternal depression may affect fetal growth and development through lifestyle behaviors and shorter gestation length, Reference Christian, Franco, Glaser and Iams33 though we were able to account for these variables in our analysis and did not observe evidence that these factors were driving the observed inverse association.
Although we did not find any significant associations of the women’s PSS score with newborn body composition, we noted that the relationships followed the same inverse trend as observed for EPDS. It is possible that questionnaire-based indicators of psychosocial stress may not completely capture the stress mothers experience during pregnancy. Additionally, the null findings with respect to PSS could be due to the relatively low PSS scores in this study sample, which may make it more difficult to detect associations with offspring outcomes.
Finally, we did not find evidence of effect modification by race/ethnicity. This was unexpected given an established literature, primarily focused on Black Americans, indicating that chronic stress related to experiences of racial bias and discrimination is associated with adverse pregnancy and birth outcomes. Reference Collins and David2 The lack of racial/ethnic differences in the relationship between maternal psychosocial stress and newborn outcomes could be because most mothers in our study sample identified as Hispanic or non-Hispanic White. There is evidence documenting more favorable health and pregnancy outcomes among Latinas, despite having more risk factors for adverse outcomes, due to strong social support within their communities – a phenomena known as the Latina paradox. Reference McGlade, Saha and Dahlstrom34 Future studies in populations with a higher proportion of other racial/ethnic groups are warranted.
Strengths and limitations
The primary strength of this study is the use of ADP-measured neonatal body composition, which allows for precise assessment of neonatal fat and FFM. Using these measures in conjunction with the standardized weight and length measurements provides a more accurate and holistic assessment of newborn body composition. Additional strengths include the relatively large study sample, rich covariate data to control for confounding, and prospective study design.
Limitations of this study include potential lack of generalizability to mother/newborn pairs in other geographic regions, those who cannot afford private prenatal care, or those with markedly different sociodemographic composition.
Conclusion
Maternal psychosocial stress, as measured by the EPDS, was associated with delivery of smaller newborns with lower FM, FFM, and birth length. These results add to the growing body of knowledge regarding the effect of maternal stress and newborn body composition and emphasize a need to identify resources to help women cope with stress during pregnancy which, in turn, can improve not only the woman’s well-being but also that of her infant.
Supplementary material
The supplementary material for this article can be found at https://doi.org/10.1017/S2040174423000223
Acknowledgments
We thank the Healthy Start study project coordinator, Mercedes Martinez. The authors’ responsibilities were as follows – KEB: analyzed the data, performed the statistical analyses; KEB and WP: wrote the manuscript, had primary responsibility for the final content; KEB, WP, and SKD: designed the research and developed the plan for analysis; DD: oversaw the study and provided the data necessary for research; WP, SKD, and DD: provided critical feedback; and all authors: read and approved the final manuscript. None of the authors reported a conflict of interest related to the study. This work was supported by the National Institutes of Health (R01DK076648 and UH3OD023248). Additionally, SKD is supported by NIH/NCATS Colorado CTSA (Grant Number TL1 TR002533) and WP is supported by the Center for Clinical and Translational Sciences Institute (KL2-TR002534).
Financial support
The Healthy Start study is funded by the National Institutes of Health (NIH) R01DK076648 and UH3OD023248. Satvinder K. Dhaliwal is supported by NIH/NCATS Colorado CTSA Grant Number TL1 TR002533. Dr Perng is supported by the Center for Clinical and Translational Sciences Institute via KL2-TR002534. The funder/sponsor did not participate in the work.
Competing interests
None.
Ethical standard
All procedures of the study protocol were performed according to the Declaration of Helsinki 35 of 1975, revised in 2008, and was approved by the Colorado Multiple Institutional Review Board (IRB #09-0563).
Clinical trial registry
The Healthy Start study is registered as an observational study at clinicaltrials.gov (NCT #002273297).
Article summary
Mothers with higher levels of psychosocial stress delivered shorter newborns with less fat mass.
What is known on this subject
Maternal psychosocial stress has been linked to adverse neonatal outcomes regarding birth size and body composition. However, prior research has not considered differences in fat mass vs fat-free mass, an important distinction to make when assessing risk factors for future health outcomes, such as obesity.
What this study adds
This study assesses body composition using a variety of standardized weight- and length-based indices in addition to measures of fat mass and fat-free mass using air displacement plethysmography.
