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Your Life. New to BabyCenter? Results from sensitivity analysis i. The results of this meta-analysis support the belief that psychological stress before and during pregnancy is associated with miscarriage. A view held by some medical practitioners and around three quarters of pregnant women, but most often dismissed by doctors and other health care professionals.
Psychological stress can influence well-being through associated health-impairing behaviors and through physiological responses which affect vascular, immune, metabolic or neuroendocrine functions Effects are difficult to assess as physiological responses to stress vary with its intensity and duration, and are contingent on the genetic vulnerability and life history of the affected individual Persistent stressors, which are perceived as uncontrollable, are the most damaging to physical and mental health However, as far as the authors are aware, different classes of stress do not systematically elicit differential physiological responses.
Because of the complexity of the mechanisms and the degree of individual variation in the response to stressors, accurate measurement and comparisons of the experience of stress between individuals or groups of individuals is challenging. Psychological stress is also likely to co-occur with other psychological factors such as anxiety and depression 27 and may be chronic, acute or transient.
A variety of relevant scales have been applied in specific studies, for example, the Perceived Stress Scale 28 , the Pre-natal Social Environment Inventory 29 and Index of Spousal Abuse 30 and others pertaining more generally to life events and stress symptoms, thus making simple comparisons between studies difficult. Retrospective reports, both from focal groups and controls, may be especially vulnerable to recall bias.
Even a small indicator of prospective miscarriage, or history of previous miscarriage, is likely to produce stress, therefore confounding the direction of effects.
In addition, many miscarriages are managed at home and never reported 7. Estimating miscarriage risk is further complicated by the difficulty in distinguishing the effect of stress from the effects of substances like alcohol, tobacco and caffeine which are taken to relieve stress. Based on the considerations described above, interpretation of the findings from this meta-analysis is subject to some caution; the included studies also vary by the types of stress under focus and their prospective or retrospective design.
The measures of stress vary between studies and do not always assess symptoms directly 8 , 13 and some scales do not specify cut-off points between high and low stress e. Perceived Stress Scale. Participant self-reports are often retrospective with an associated risk of recall bias, as authors generally acknowledge 11 , Whilst the NOS assessment provided a means to assess non-randomized studies, the scoring system itself is not without its drawbacks and criticisms Study quality is also variable: some offer limited detail on assessment 1 , 7 , 23 , on case selection procedures 1 and on timing of assessment in relation to outcome 1.
Therefore we propose the need for high quality research into an association between the experience of stress in a variety of contexts and miscarriage risk. In the present meta-analysis, on sub analysis, six studies with higher quality showed a significantly increased miscarriage risk in women suffering from psychological stress, but this was not found in the two studies with lower NOS scores.
An increased miscarriage risk was found on analysis of cohort and nested case-control but not in case-control studies. For case-controls, the variability is also much larger leading to an interval including 0. The explanation for this possibly relates to the smaller number of studies hence larger variability , or perhaps the increased level of heterogeneity intrinsic in case-controls.
However inclusion or exclusion of confounders did not affect the results. The association between psychological stress and miscarriage could result, at least in part, from activation of the hypothalamic-pituitary-adrenal axis by recruitment of hypothalamic neurones which secrete corticotrophin-releasing hormone, increasing pituitary secretion of adrenocorticotrophic hormone secretion and hence of adrenal cortisol This hormone has direct effects on decidual and placental metabolism but also interacts with progesterone signalling Stress-related early pregnancy failure could also result from suppression of the hypothalamic-pituitary-gonadal axis 32 — Since prolactin stimulates progesterone secretion, the reduced levels will decrease progesterone synthesis 37 , Stress also inhibits pituitary human chorionic gonadotropin secretion compounding the effect of prolactin on progesterone release from the corpus luteum 32 , 39 , These mechanisms are relevant because progesterone activity is crucial for the maintenance of pregnancy; low levels in early of gestation predicting miscarriage Among its multiple effects, this hormone contributes to the suppression of maternal immune response to the conceptus In summary, the result of this systematic review and meta-analysis support the belief that psychological stress, including life events and occupational stress, in pregnancy is associated with an increased risk of miscarriage and indicates a critical need for further high quality research into the relationship between miscarriage and stress experienced prior to pregnancy and in the early gestational period.
Taken together with the serious morbidities already known to be associated with stress pregnancy induced hypertension, preterm birth and low birth weight , this finding also highlights the need to include a structured psychological assessment in early pregnancy into routine antenatal care. This demonstration that stress contributes to early pregnancy failure could provide the basis for novel and effective interventions in this field. Twenty-five years later, the results of our meta-analysis, highlight the potential to identify and treat psychological factors which contribute to adverse pregnancy outcomes in the human.
No language or date restrictions were applied. We only included case-control, cohort retrospective or prospective and nested case-control studies for this review and for studies that reported similar or overlapping data, only the latest or those with a larger sample size were considered.
Only studies that included women who had miscarriage cases and women with ongoing pregnancy or live birth controls were considered for eligibility. Miscarriage or pregnancy loss occurring before the first 22 weeks gestation is defined as the natural death of an embryo or fetus before it is able to survive independently.
Three authors F. Disagreement was resolved by consensus or arbitration. The following information was recorded or coded for each article: country, year, study design, study population characteristics, total sample size, stress measurement methods of the studies, sample size related to our meta-analysis and outcome data. All the reviewers cross-checked the extracted data repeatedly and any disagreements were resolved by consensus.
Authors were contacted for further details if necessary. The quality of the included studies was assessed independently by three authors F. Different assessment items were applied to case-control and cohort studies, respectively. For each type of study, eight criteria were used in the assessment, namely 1 for cohort studies: representativeness of exposed cohort, selection of non-exposed cohort, ascertainment of exposure, outcome not present at baseline, comparability of cohorts, assessment of outcome, sufficient follow-up duration, and adequate follow-up; 2 for case-control studies: adequate definition of cases, representativeness of cases, selection of controls, definition of controls, comparability of cases and controls, ascertainment of exposure, same method of ascertainment for cases and controls, and non-response rate.
The total score for each study was obtained by summing up stars from each item. More than six stars indicate good quality, whereas 5—6 stars indicate acceptable quality. Disagreements were resolved by consensus. We firstly evaluated for the outliers, defining as that the individual ORs were more than 2 standard deviations from the mean of all the effect sizes, to see if replacement of extreme values is necessary.
DerSimonian and Laird random-effects model was employed, as our effect sizes were assumed to be sampled from a large number of possible sample sizes. Heterogeneity between studies was evaluated using homogeneity statistic Q , which follows a Chi-square distribution with a degree of freedom of n-1 where n is the total number of studies included Subgroup analysis was conducted to explore the sources of the heterogeneity, and sensitivity analysis was performed to examine the effect of excluding each study.
All authors approved the final version of the manuscript. Electronic supplementary material. Supplementary information accompanies this paper at doi Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
National Center for Biotechnology Information , U. Sci Rep. Published online May China Find articles by Fan Qu. China Find articles by Yan Wu. China Find articles by Yu-Hang Zhu. Brenda K. China Find articles by Fang-Fang Wang. Author information Article notes Copyright and License information Disclaimer.
Paul J Hardiman, Email: ku. Corresponding author. Received Aug 5; Accepted Mar This article has been cited by other articles in PMC. Associated Data Supplementary Materials Supplementary information. Abstract This systematic review and meta-analysis was designed to investigate whether maternal psychological stress and recent life events are associated with an increased risk of miscarriage.
Open in a separate window. Figure 1. Table 1 Characteristics of all studies included in the systematic review. First author, year published Country Year Design Total sample size Sample size related to our meta-analysis Exposures Reference group Stress measurement Effect estimates Matched or adjusted confounders NOS score Bashour H 1 Syria Case-control Psychological stress Women delivered normal babies at term Questionnaires the cases and controls were interviewed by trained midwives, using a structured questionnaire.
OR No 6 Boyles SH 8 USA — Nested case-control Life events Women maintained their pregnancy A modified life event inventory the participants were questioned about different categories of major life events, including death,debt burden, legal problems, and personal relationships. OR Tobacco use, cocaine use, alcohol use, prenatal care, living with the father 9 Brandt L, 12 Denmark — Cohort Work stress ND A questionnaire about stress-related job characteristics a questionnaire about the information on occupational status, job title, stress-related job characteristics, ergonomic work load, exposure to organic solvents, exposure to video display terminals, lifestyle factors, and health factors during pregnancy.
OR Previous pregnancies 6 Fenster L, 22 USA — Cohort Work stress Women maintained their pregnancy An abbreviated version of instrument the instrument is based on the concepts that job stress results from high psychological demands in combination with low control over those demands and that social support at work can ameliorate the effects of stressful work. OR Year of conception, maternal age, previous miscarriage and previous live birth, nausea 7 Meaney S 2 Ireland Cohort Psychological stress Women maintained their pregnancy Questionnaires and psychometric tests detailed lifestyle questionnaires, including common risk factors for miscarriage, and psychometric tests, including the Item Health Survey, the Maternity Social Support Scale, the Revised Life Orientation Test and the Perceived Stress Scale.
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