Administration of glucocorticoids during pregnancy is an established practice for reducing morbidity and mortality of fetuses at risk of preterm delivery However, exposure to exogenous glucocorticoids in utero has been linked to suppressed hypothalamic-pituitary-adrenal (HPA) axis activity in animals and human neonates. Because of its role in regulating the stress response, suppression of HPA axis activity is associated with adverse cardiovascular and mental health outcomes. Yet no evidence is available regarding the ongoing effects of corticosteroids as the preterm infant develops. Our primary aim is to determine whether preterm infants who are exposed to antenatal corticosteroids show persistent evidence of a suppressed stress response system during their first year of life, in contrast to preterm and full term infants who are not exposed. Effects will be examined across 3 regulatory components of the stress response: hormonal (cortisol level), autonomic (heart rate variability), and affective (emotional regulation).
Our second aim i s to determine whether maternal depression may moderate any effect of corticosteroids on the infant's stress response. Mothers of preterm infants have a high incidence of depression, which has been linked to less emotional availability/responsiveness to infant distress. The interaction between a mother's diminished ability to help regulate infant distress and poor self-regulation by the infant could gie rise to severe impairments in stress regulation. In this cohort study, 230 women will be recruited during their 3rd trimester of pregnancy. 75% of the women will be at risk of preterm delivery but will vary in whether a course of corticosteroids has been prescribed or not. 25% of the women will be expected to deliver at term. At the time of consent, women will complete measures of depression and stress/adversity and will provide salivary samples for cortisol assay. They will complete these same procedures at 6 and 12 months postpartum. Infants will receive a standardized caregiving `stressor' while in the NICU. At 6 and 12 month home visits, another well-established infant stressor (the `Still Face Procedure') will be administered. Infant salivary cortisol, heart rate variability, and emotional distress will be measured before and after these `stressors' in the NICU and at home. To control for their effects, data on infant birth weight, gestational age, and neonatal morbidity as well as maternal cortisol level, stress, adversity, and emotional availability will also be acquired. Data will be analyzed using latent growth modeling procedures. Findings are critical for informed prenatal decision-making, for identifying infants and mothers at greatest risk, and for providing care that will prevent stress-related illness among preterm children.

Public Health Relevance

There is some evidence that fetal exposure to corticosteroids may impair the stress response system of preterm infants and that infants with mothers who have postpartum depression may be particularly vulnerable to the drug's effects. This study will examine the effects of corticosteroids on stress hormones, heart rate and emotional distress of preterm infants as they manage stress during their first year of life. Findings may improve decision-making regarding use of corticosteroids during pregnancy and identify mothers who need special support to assure development of a healthy stress response system for infants exposed to these drugs.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Project (R01)
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Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
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Lee, Karen
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University of California San Francisco
Other Health Professions
Schools of Nursing
San Francisco
United States
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