Maternal Stress & Fetal Programming. Prenatal Stress & Programming of the Brain Prenatal stress (animal model) Hippocampus Site of learning & memory formation.

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Presentation transcript:

Maternal Stress & Fetal Programming

Prenatal Stress & Programming of the Brain Prenatal stress (animal model) Hippocampus Site of learning & memory formation Stress down-regulates glucocorticoid receptors Loss of negative feedback; overactive HPA axis Amygdala Site of anxiety and fear Stress up-regulates glucocorticoid receptors Accentuated positive feedback; overactive HPA axis Welberg LAM, Seckl JR. Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 2001;13:

Allostasis: Maintain Stability through Change McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

Allostastic Load: Wear and Tear from Chronic Stress McEwen BS. Protective and damaging effects of stress mediators. N Eng J Med. 1998;338:171-9.

Stressed vs. Stressed Out Stressed Increased cardiac output Increased available glucose Enhanced immune functions Growth of neurons in hippocampus & prefrontal cortex Stressed Out Hypertension & cardiovascular diseases Glucose intolerance & insulin resistance Infection & inflammation Atrophy & death of neurons in hippocampus & prefrontal cortex

Rethinking Preterm Birth

Racial & Ethnic Disparities Very Preterm Births < 32 Weeks Percent of Live Singleton Births Year 2010 Goal NCHS 2006

Allostasis & Allostatic Load McEwen BS, Lasley EN. The end of stress: As we know it. Washington DC: John Henry Press. 2002

Rethinking Preterm Birth Vulnerability to preterm delivery may be traced to not only exposure to stress & infection during pregnancy, but host response to stress & infection (e.g. stress reactivity & inflammatory dysregulation) patterned over the life course (early programming & cumulative allostatic load)

Life Course Perspective Lu MC, Halfon N. Racial and ethnic disparities in birth outcomes: a life-course perspective. Matern Child Health J. 2003;7:13-30.

Childhood conditions and persistent bacterial vaginosis Cammack et al* found: Associations of childhood sexual assault, and lack of parental home ownership to be associated with bacterial vaginosis No effect of education after controlling for the above. BV has a 2x increased risk of preterm birth and even higher risk for early preterm birth. Am J Obstet Gynecol 2011:204:431

Barker Hypothesis Birth Weight and Insulin Resistance Syndrome Odds ratio adjusted for BMI Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (Syndrome X): Relation to reduced fetal growth. Diabetologia 1993;36:62-67.

Preterm Birth & Maternal Ischemic Heart Disease Kaplan-Meier plots of cumulative probability of survival without admission or death from ischemic heart disease after first pregnancy in relation to preterm birth Smith et al Lancet 2001;357:

Eggs and Sperm are created in the middle of pregnancy (18-20 weeks) Means that conditions of the grandmother during her pregnancy affects the earliest “elements” of her grandchildren.

Life Course Perspective Lu MC, Halfon N. Racial and ethnic disparities in birth outcomes: a life-course perspective. Matern Child Health J. 2003;7:13-30.