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

Karen C Schliep; Stefanie N Hinkle; Keewan Kim; Lindsey A Sjaarda; Robert M Silver; Joseph B Stanford; Alexandra Purdue-Smithe; Torie Comeaux Plowden; Enrique F Schisterman; Sunni L Mumford

doi:10.1093/humrep/deac172

Mental Health and Psychosocial Care Infertility Distress

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

Schliep KC, Hinkle SN, Kim K, Sjaarda LA, Silver RM, Stanford JB, Purdue-Smithe A, Plowden TC, Schisterman EF, Mumford SL

Published September 30, 2022 Human Reproduction (Oxford, England), 37(10), 2264-2274

DOI 10.1093/humrep/deac172 PMID 35972454 PMC PMC9802052

RRM Academy Synopsis

Early pregnancy stress is linked to loss in women with a prior loss

Higher stress in early pregnancy went with a higher risk of loss, hazard ratio 1.69, among women with one or two earlier losses. The study was a secondary analysis of a randomized trial of 797 pregnant women. The estimate was higher for very early losses found by an hCG test.

Key Findings

Among 797 women with an hCG-confirmed pregnancy, 188 pregnancies ended in loss: 55 hCG-detected losses and 133 clinically recognized losses.
In women with a prior loss, high versus low weekly stress (above versus at or below the median) gave a hazard ratio of 1.69 (95% CI: 1.13, 2.54) for any loss.
For hCG-detected loss in the same women, the hazard ratio was 2.16 (95% CI: 1.04, 4.46).
For clinical loss in the same women, the hazard ratio was 1.58 (95% CI: 0.96, 2.60). The interval includes no difference, and the authors call the relationship null.
Sorting stress into quartiles showed no clear dose-response effect.

Interpretation

This study was a secondary analysis of a randomized trial, following 797 pregnant women with daily stress diaries and urine hCG testing from before conception. Among women with a prior pregnancy loss, higher perceived stress early in pregnancy was linked with a higher risk of loss. The authors note they relied on self-reported stress alone, without biomarkers of stress. The findings support larger studies of stress and pregnancy loss.

RRM Context

The authors describe pregnancy loss as largely unexplained. Most earlier studies enrolled women at a first prenatal visit, missing early losses. This trial followed women from before conception with daily diaries and urine samples, counting losses found only by hCG. Restorative reproductive medicine looks for each cause of loss in a couple, evaluating before treating. Among women with a prior loss, the paper links perceived stress with loss, a potential cause worth evaluating.

Our editorial summary of this paper, not the article's abstract.

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 Interests

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

#NCT00467363.

Read the guide

Miscarriage and Recurrent Pregnancy Loss: The Workup Most Women Never Get

Topics

Mental Health and Psychosocial Care › Infertility Distress › Anxiety and Depression in Infertility · Lifestyle and Environment › Stress and Allostatic Load › Stress and Ovulation · Pregnancy › Early Pregnancy › Miscarriage

Karen C Schliep, Stefanie N Hinkle, Keewan Kim, Lindsey A Sjaarda, Robert M Silver, Joseph B Stanford, Alexandra Purdue-Smithe, Torie Comeaux Plowden, Enrique F Schisterman, Sunni L Mumford

K Schliep, S Hinkle, K Kim, L Sjaarda, Bob Silver, Rob Silver, Bobby Silver, R Silver, Joe Stanford, Joey Stanford, J Stanford, Alex Purdue-Smithe, A Purdue-Smithe, T Plowden, E Schisterman, S Mumford

PMID 35972454 35972454 DOI 10.1093/humrep/deac172 10.1093/humrep/deac172 Schliep et al. 2022, Schliep 2022

Keywords

Biomarkers, Caffeine