Prospectively assessed perceived stress associated with early pregnancy losses among women with history of pregnancy loss

Abstract

Study question: What is the association between perceived stress during peri-conception and early pregnancy and pregnancy loss among women who have experienced a prior pregnancy loss?

Summary answer: Daily perceived stress above the median is associated with over a 2-fold risk of early pregnancy loss among women who have experienced a prior loss.

What is known already?: Women who have experienced a pregnancy loss may be more vulnerable to stress while trying to become pregnant again. While prior research has indicated a link between psychological stress and clinically confirmed miscarriages, research is lacking among a pre-conceptional cohort followed prospectively for the effects of perceived stress during early critical windows of pregnancy establishment on risk of both hCG-detected pregnancy losses and confirmed losses, while considering important time-varying confounders.

Study design, size, duration: Secondary data analysis of the EAGeR trial (2007-2011) among women with an hCG-detected pregnancy (n = 797 women).

Participants/materials, setting, methods: Women from four US clinical centers enrolled pre-conceptionally and were followed ≤6 cycles while attempting pregnancy and, as applicable, throughout pregnancy. Perceived stress was captured via daily diaries and end-of-month questionnaires. Main outcome measures include hCG-detected and clinically recognized pregnancy losses.

Main results and the role of chance: Among women who had an hCG-confirmed pregnancy, 188 pregnancies (23.6%) ended in loss. Women with high (>50th percentile) versus low (≤50th percentile) peri-implantation or early pregnancy weekly perceived stress had an elevated risk of experiencing any pregnancy loss (hazard ratio (HR): 1.69, 95% CI: 1.13, 2.54) or clinical loss (HR: 1.58, 95% CI: 0.96, 2.60), with higher risks observed for women experiencing an hCG-detected loss (HR: 2.16, 95% CI: 1.04, 4.46). Models accounted for women's age, BMI, employment, marital status, income, education, race, parity, prior losses, exercise and time-varying nausea/vomiting, caffeine, alcohol and smoking.

Limitations, reasons for caution: We were limited in our ability to clearly identify the mechanisms of stress on pregnancy loss due to our sole reliance on self-reported perceived stress, and the lack of biomarkers of different pathways of stress.

Wider implications of the findings: This study provides new insight on early pregnancy perceived stress and risk of pregnancy loss, most notably hCG-detected losses, among women with a history of a prior loss. Our study is an improvement over past studies in its ability to account for time-varying early pregnancy symptoms, such as nausea/vomiting, and lifestyle factors, such as caffeine, alcohol and smoking, which are also risk factors for psychological stress and pregnancy loss.

Study funding/competing interest(s): This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland (Contract numbers: HHSN267200603423, HHSN267200603424, HHSN267200603426, HHSN275201300023I). Additionally, K.C.S. was supported by the National Institute on Aging of the National Institutes of Health under Award Number K01AG058781. The authors have no conflicts of interest to disclose.

Trial registration number: #NCT00467363.

Keywords: epidemiology; mental health pregnancy loss; miscarriage; perceived stress; preconception cohort; psychological stress; recurrent pregnancy loss; spontaneous abortion; time-varying confounding factors.

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Variations in perceived stress during early pregnancy (Weeks 2–8). (a) Boxplot of perceived stress via daily preconception and pregnancy diaries recorded via a Likert scale: 0 = no stress, 1 = little stress, 2 = moderate stress and 3 = a lot of stress. The length of the box represents the interquartile range (the distance between the 25th and 75th percentiles). The symbol in the box interior represents the group mean. The horizontal line in the box interior represents the group median. The vertical lines (whiskers) issuing from the box extend to the group minimum and maximum values. (b) Mean ± SD variations in pregnancy perceived stress. Comparisons were made with the use of linear mixed models to account for repeated measures within women.

Figure 2.

Variations in perceived stress during later pregnancy (Weeks 9–36). (a) Boxplot of perceived stress via monthly questionnaires during pregnancy passive follow-up recorded via a Likert scale: 0 (no stress) to 10 (maximum stress). The length of the box represents the interquartile range (the distance between the 25th and 75th percentiles). The symbol in the box interior represents the group mean. The horizontal line in the box interior represents the group median. The vertical lines (whiskers) issuing from the box extend to the group minimum and maximum values. (b) Mean ± SD variations in pregnancy perceived stress. Comparisons were made with the use of linear mixed models to account for repeated measures within women.

Figure 3.

Hazard ratio of pregnancy loss, high (>median) versus low (≤median) perceived stress.