Biomarkers of preconception stress and the incidence of pregnancy loss
Open accessAbstract
STUDY QUESTION: Are biomarkers of preconception stress associated with pregnancy loss? SUMMARY ANSWER: Preconception stress, as measured by basal salivary cortisol and alpha-amylase concentrations, is not associated with pregnancy loss. WHAT IS KNOWN ALREADY: Many studies, most of which have been retrospective, have identified an association between stressful life events and perceived stress and miscarriage. STUDY DESIGN, SIZE, DURATION: A prospective pregnancy study with preconception enrollment was conducted between 2005 and 2009. Among the 344 women who became pregnant during the Longitudinal Investigation of Fertility and the Environment (LIFE) study, 337 (98%) had salivary biomarker data for analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples planning pregnancy were followed for up to 12 months as they tried to become pregnant and through pregnancy if it occurred. Participating women collected a basal saliva sample on the morning following enrollment and a second on the morning following their next menses to measure cortisol and alpha-amylase, biomarkers of stress. Women used home pregnancy tests on the day of expected menses. A pregnancy loss was defined as a negative pregnancy test following a positive pregnancy test, the onset of menses, or for pregnancies that survived to clinical recognition, recognition of the loss by a healthcare provider. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 337 couples, the median age of female and male partners was 29 and 31 years, respectively. Most of the women were non-Hispanic white (83%) and highly educated. There were 97 pregnancy losses reported among the 337 pregnancies. The median gestational age at loss was 6 weeks 5 days with only two losses occurring in the second trimester. Using Cox proportional hazards models, we found no clear pattern of association between two preconceptional biomarkers of stress (salivary cortisol and alpha-amylase concentrations) modeled both continuously or in tertiles and incident pregnancy loss after adjustment for confounders. LIMITATIONS REASONS FOR CAUTION: Our prior work suggests that women enrolled in the LIFE Study had lower stress levels than women in the general population. Owing to concerns regarding participant burden, we were unable to collect serial saliva measurements, which would have allowed us to examine the association between stress in early pregnancy and pregnancy loss. Further, with regard to the measurement of perceived stress, the Cohen's Perceived Stress Scale was only administered at baseline. While every attempt was made to ensure diversity in the cohort, non-Hispanic white women were over-represented, therefore it is possible that the results might not be generalizable to all women. WIDER IMPLICATIONS OF THE FINDINGS: In one of the largest studies in the USA to prospectively capture data on the incidence of early pregnancy loss, we found no clear association between two biomarkers of preconception stress (measured in saliva) and pregnancy loss. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contracts #N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: Not applicable.
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High alcohol consumption during the first trimester is associated with an increase in miscarriage risk (aOR 1.67; 95% CI 1.31-2.19).
“Our literature review found that alcohol use is also an important modifiable risk factor, as high alcohol consumption during the first trimester is associated with an increase in miscarriage risk (aOR 1·67; 95% CI 1·31-2·19; Table 6). 25,39,62-70”
From Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss (2021) · cites this paper as [66]
Table I (reproduced under Discussion; page unavailable) shows that drinking at least one alcoholic drink per day during pregnancy was more common among women with pregnancy loss than among those with live births (15% versus 2%). The paper does not report the claimed adjusted odds ratio or confidence interval for alcohol, and the table does not specify first-trimester consumption. (LLM, conf=0.84)
Experimental — accuracy not yet measuredHigh stress is associated with miscarriage risk (aOR 1.46; 95% CI 1.16-1.77).
“Our review of the evidence also found that high stress is associated with miscarriage risk (aOR 1·46; 95% CI 1·161·77; Table 6) 66,71,73-77”
From Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss (2021) · cites this paper as [66]
The Introduction says most prior studies reported an association between stress and miscarriage, supporting the broad background claim. But the Results report no statistically significant association for this paper’s preconception stress biomarkers, and its Table III does not give the cited aOR of 1.46 (95% CI 1.16–1.77). Page numbers were not provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAlcohol use is an important modifiable risk factor for miscarriage.
“Our literature review found that alcohol use is also an important modifiable risk factor, as high alcohol consumption during the first trimester is associated with an increase in miscarriage risk (aOR 1·67; 95% CI 1·31-2·19; Table 6). 25,39,62-70”
From Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss (2021) · cites this paper as [66]
The Introduction identifies alcohol consumption as a lifestyle factor investigated for miscarriage risk, and Table I (shown under Discussion; page unavailable) records more women drinking at least one drink per day during pregnancy in the pregnancy-loss group than in the live-birth group. The paper does not establish alcohol use as an important risk factor or report the cited first-trimester adjusted odds ratio of 1.67. (LLM, conf=0.83)
Experimental — accuracy not yet measured
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- Authors
- Lynch, C. D., Sundaram, R., & Buck Louis, G. M.
- Affiliations
- The Ohio State University (US)
- George Mason University (US)
- Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Building 6710B, Room 3232, Rockville, Bethesda, MD 20852-7004, USA
- Corresponding author
- Lynch, Courtney D
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-02-27
- Volume
- 33
- Issue
- 4
- Pages
- 728-735
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- PMC
- PMC6065502
- OpenAlex
- W2793991885
- Cited by
- 20
- References
- 40
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 2 · 2019: 1 · 2018: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Human Reproduction (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (#N01-HD-3-3355, N01-HD-3-3356, N01-HD-3358)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
- Keywords
- miscarriage, salivary cortisol, salivary amylase, stress biomarkers, perceived stress, life studies
- MeSH terms
- Abortion, Spontaneous, Adult, Female, Humans, Hydrocortisone, Male, Pregnancy, Prospective Studies, Saliva, Stress, Psychological, Biomarkers, Incidence, Salivary alpha-Amylases, Time-to-Pregnancy
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