Prenatal Stress and Its Effects on the Fetus and the Child: Possible Underlying Biological Mechanisms
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Many prospective studies have shown that if a mother is depressed, anxious or stressed while pregnant, this increases the risk for her child having a wide range of adverse outcomes including emotional problems, symptoms of attention deficit hyperactivity disorder (ADHD) or impaired cognitive development. Although genetics and postnatal care clearly affect these outcomes, evidence for a prenatal causal component also is substantial. Prenatal anxiety/depression may contribute 10–15 % of the attributable load for emotional/behavioural outcomes.
The mechanisms underlying these changes are just starting to be explored. One possible mediating factor is increased exposure of the fetus to cortisol, as has been shown in animal studies. However, the human hypothalamic–pituitary–adrenal (HPA) axis which makes cortisol functions differently in human pregnancy from in most animals. The maternal HPA axis becomes gradually less responsive to stress as pregnancy progresses. And there is only a weak, if any, association between a mother’s prenatal mood and her cortisol level, especially later in pregnancy. Cytokines are alternative possible mediators. An additional explanation is that stress or anxiety causes increased transfer of maternal cortisol across the placenta to the fetus. The placenta plays a crucial role in moderating fetal exposure to maternal factors and presumably in preparing the fetus for the environment in which it is going to find itself. There is some evidence in both rat models and in humans that prenatal stress can reduce placental 11β-HSD2, the enzyme which metabolises cortisol to inactive cortisone. The level of cortisol in the amniotic fluid, surrounding the baby in the womb, has been shown to be inversely correlated with infant cognitive development. However, several other biological systems are likely to be involved. Serotonin is another possible mediator of prenatal stress induced programming effects on offspring neurocognitive and behavioural development. The role of epigenetic changes in mediating alterations in offspring outcome following prenatal stress is likely to be important and starting to be explored.
KeywordsPrenatal stress Fetus Programming Neurodevelopment Cortisol HPA Placenta 11β-HSD2
- Baibazarova E, van de Beek C, Cohen-Kettenis PT, Buitelaar J, Shelton KH, van Goozen SH (2013) Influence of prenatal maternal stress, maternal plasma cortisol and cortisol in the amniotic fluid on birth outcomes and child temperament at 3 months. Psychoneuroendocrinology 38:907–915PubMedCrossRefGoogle Scholar
- Braithwaite EC, Ramchandani PG, O’Connor TG, van Ijzendoorn MH, Bakermans-Kranenburg MJ, Glover V, Netsi E, Evans J, Meaney MJ, Murphy SE (2013) No moderating effect of 5-HTTLPR on associations between antenatal anxiety and infant behavior. J Am Acad Child Adolesc Psychiatry 52:519–526PubMedCentralPubMedCrossRefGoogle Scholar
- Class QA, Abel KM, Khashan AS, Rickert ME, Dalman C, Larsson H, Hultman CM, Langstrom N, Lichtenstein P, D’Onofrio BM (2013) Offspring psychopathology following preconception, prenatal and postnatal maternal bereavement stress. Psychol Med 44:1–14Google Scholar
- Hompes T, Izzi B, Gellens E, Morreels M, Fieuws S, Pexsters A, Schops G, Dom M, Van Bree R, Freson K, Verhaeghe J, Spitz B, Demyttenaere K, Glover V, Van den Bergh B, Allegaert K, Claes S (2013) Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. J Psychiatr Res 47:880–891PubMedCrossRefGoogle Scholar
- Jansson T, Powell TL (2007) Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches. Clin Sci (Lond) 113:1113Google Scholar
- Ponder KL, Salisbury A, McGonnigal B, Laliberte A, Lester B, Padbury JF (2011) Maternal depression and anxiety are associated with altered gene expression in the human placenta without modification by antidepressant use: implications for fetal programming. Dev Psychobiol 53:711–723PubMedCentralPubMedCrossRefGoogle Scholar
- Salaria S, Chana G, Caldara F, Feltrin E, Altieri M, Faggioni F, Domenici E, Merlo-Pich E, Everall IP (2006) Microarray analysis of cultured human brain aggregates following cortisol exposure: implications for cellular functions relevant to mood disorders. Neurobiol Dis 23:630–636PubMedCrossRefGoogle Scholar
- Van den Bergh BR, Van Calster B, Smits T, Van Huffel S, Lagae L (2008) Antenatal maternal anxiety is related to HPA-axis dysregulation and self-reported depressive symptoms in adolescence: a prospective study on the fetal origins of depressed mood. Neuropsychopharmacology 33:536–545PubMedCrossRefGoogle Scholar