How Stress Pregnancy Outcomes Fetal Development

How Stress Affects Pregnancy Outcomes, Maternal Health and Fetal Development

How Stress Affects Pregnancy

In a recent review article in the journal Neuroscience & Biobehavioral Reviews, Lisa Christian discusses some biological mechanisms linking stress with maternal health, pregnancy outcomes and fetal development, focusing on peripheral immune markers, and stress reactivity and inflammatory processes during pregnancy.

Recent evidence indicates that maternal psychological and social stress is a significant and independent risk factor for a range of adverse reproductive outcomes including preterm birth. Very little empirical research to date, however, has examined the role of biological processes, if any, as mediators of the relationship between stress and preterm birth.

Preterm birth is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks’ gestational age. Preterm delivery affects 12–13% of birth in the US, versus 5–9% in other developed countries. Evidence accumulated over the last 2-3 decades indicates that psychological stress is associated with an increased risk of preterm birth after controlling for related traditional risk factors.

Stress experienced during pregnancy has also been linked to other pregnancy complications such as miscarriage, preeclampsia, low birth weight or major congenital malformations, and stress increases the risk of the child to develop diseases in the subsequent periods of life.

In the Neuroscience & Biobehavioral Reviews article, Lisa Christian from the Ohio State University Medical Center, Columbus, OH has outlined recent data linking stress with maternal and fetal health. Although previous research has focused almost exclusively on neuroendocrine mechanisms, several recent studies indicate that inflammatory processes may contribute to the association of psychosocial stress with preterm birth.

For example, high levels of proinflammatory cytokines in maternal serum and amniotic fluid including IL-6, IL-8, and TNF-alpha, have been causally implicated in risk of preterm delivery. As discussed by the author further research is needed to delineate effects of stress on adaptation of inflammatory processes across pregnancy at the level of circulating cytokines levels; inflammatory responses to in vivo and in vitro immune triggers and inflammatory responses in the context of psychosocial stressors.

Thus, stress-immune interactions research in the context of pregnancy has great potential for elucidating mechanisms underlying risk of adverse perinatal health outcomes, and this approach may provide a basis for individualized health care services.

SOURCE:  Neurosci Biobehav Rev 2012, 36:350. Epub 2011 Jul 19.

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Another 2012 review argues that the exposure to prenatal stress and pathogenic infections has been associated with an increased risk for neurodevelopmental disorders. The mechanisms by which these programing events occur likely involve complex interactions between the maternal hormonal milieu, the placenta, and the developing fetus. Despite the diverse biological processes involved, examination of common pathways in maternal stress and immune activation offers intriguing possibilities for elucidation of mechanistic insight.

Furthermore, it concludes that both maternal stress and immune activation serve as potentiating factors for alterations in offspring programing and increasing disease risk. This impressive coordination likely results from the multi-level reciprocal interactions found in these pathways where stress can serve as an immune activator and vice versa. Additionally, and perhaps even more intriguing are the seemingly temporal- and sex-specific effects of these fetal antecedents.

A 2013 study describes the effects of chronic social stress on the relationship between cortisol and the pro-inflammatory cytokines in a uniquely vulnerable population, pregnant women. The most significant finding of this study is that chronic stress related to minority status or low income was associated with elevated cortisol without a compensatory decrease in proinflammatory cytokine concentration; such a diminished negative feedback relationship between cortisol and proinflammatory cytokines is indicative of glucocorticoid resistance. Without cytokine glucocorticoid feedback, a pregnant woman’s ability to regulate inflammation is limited, potentially contributing to adverse maternal and infant outcomes.

A 2015 review yet again by Lisa Christian has focused on growing data linking stress to immune dysregulation during pregnancy, particularly inflammatory processes. An ultimate goal of this body of research is to quantify the impact of such immune-dysregulation on specific perinatal health outcomes, and ideally, develop targeted interventions. To-date, studies in pregnancy have focused largely on demonstrating and quantifying the impact of stress on immune function. Very limited data have linked stress, inflammation, and perinatal health within the same study.

Lisa Christian outlines the emerging evidence of stress-induced inflammation in pregnancy. Another factor is obesity as a principal driver of inflammation. Thus, more than 1/3 of women in the US are obese, and more than 1/2 of pregnant women are overweight or obese. Because adipocytes (fat cells) secrete proinflammatory cytokines, obesity is a primary driver of inflammation. Obesity can be conceptualized as a physiological stressor. Perinatal obesity increases risk of gestational hypertension and gestational diabetes via inflammatory pathways. Moreover, obesity-induced inflammation is transmitted to the child, potentially affecting their immune functioning, metabolism, and cognitive development.