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VOLUME 14 , ISSUE 4 ( July-August, 2022 ) > List of Articles


Prenatal Stress-induced Behavioral, Cognitive, and Psychopathological Modifications: A Mini Review of Literature

Grisilda Vidya Bernhardt, Kavitha Bernhardt, Sujatha Bhat, Pooja Shivappa, Janita RT Pinto

Keywords : Behavior, Cognition, Motor development, Prenatal stress

Citation Information : Bernhardt GV, Bernhardt K, Bhat S, Shivappa P, Pinto JR. Prenatal Stress-induced Behavioral, Cognitive, and Psychopathological Modifications: A Mini Review of Literature. J South Asian Feder Obs Gynae 2022; 14 (4):481-485.

DOI: 10.5005/jp-journals-10006-2072

License: CC BY-NC 4.0

Published Online: 22-08-2022

Copyright Statement:  Copyright © 2022; The Author(s).


Background: Prenatal stress (PNS) can influence the development of the progeny, which undergoes complex physiological changes during intrauterine and early postnatal life, thus causing them to experience far-reaching undesirable consequences. Prenatal stress is particularly a challenging issue because, by reacting to the mother's stress through a sequence of biological mechanisms, the fetus is placed under risk of several neurobiological variations that give rise to behavioral and emotional alterations in the offspring. Various studies have been conducted over the last two decades, not only on various stressors that give rise to negative emotions during pregnancy but also on their impact on offspring's mental health during the entire course of their development. Objective: This review aims at discussing various studies on the effect of prenatal stress in animal models and human subjects, and to explore some of the controversies arising in this field. Materials and methods: We searched PubMed and Scopus for English language abstracts published from 1992 to 2021. Search terms were related to prenatal stress, infant or child cognitive and motor development, and developmental psychopathology. Results and conclusion: A vast number of studies have reported negative neurobiological outcomes in the offspring subjected to PNS, although a clear understanding about the underlying biological mechanisms is not available. Methodological challenges do exist in PNS research which has not been successfully overcome. At present, however, there is a definite need to identify, advise, and support pregnant women with some degree of stress with a hope to minimize any adverse consequences in the progeny.

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  1. Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 2008;32(6):1073–1086. DOI: 10.1016/j.neubiorev.2008.03.002.
  2. Maccari S, Darnaudery M, Morley-Fletcher S, et al. Prenatal stress and long-term consequences: implications of glucocorticoid hormones. Neurosci Biobehav Rev 2003;27(1–2):119–127. DOI: 10.1016/s0149-7634(03)00014-9.
  3. Parker VJ, Douglas AJ. Stress in early pregnancy: maternal neuro-endocrine-immune responses and effects. J Reprod Immunol 2010;85(1):86–92. DOI: 10.1016/j.jri.2009.10.011.
  4. Slattery DA, Neumann ID. No stress please! Mechanisms of stress hyporesponsiveness of the maternal brain. J Physiol 2008;586(2):377–385. DOI: 10.1113/jphysiol.2007.145896.
  5. Rakers F, Rupprecht S, Dreiling M, et al. Transfer of maternal psychosocial stress to the fetus. Neurosci Biobehav Rev 2017. DOI: 10.1016/j.neubiorev.2017.02.019.
  6. Schneider ML, Moore CF, Kraemer GW, et al. The impact of prenatal stress, fetal alcohol exposure, or both on development: perspectives from a primate model. Psychoneuroendocrinology 2002 27(1):285–298. DOI: 10.1016/s0306-4530(01)00050-6.
  7. Son GH, Geum D, Chung S, et al. Maternal stress produces learning deficits associated with impairment of NMDA receptor-mediated synaptic plasticity. J Neurosci 2006;26(12):3309–3318. DOI: 10.1523/JNEUROSCI.3850-05.2006.
  8. Paris JJ, Frye CA. Juvenile offspring of rats exposed to restraint stress in late gestation have impaired cognitive performance and dysregulated progestogen formation. Stress 2011;14(1):23–32. DOI: 10.3109/10253890.2010.512375.
  9. Paris JJ, Brunton PJ, Russell JA, et al. Immune stress in late pregnant rats decreases length of gestation and fecundity, and alters later cognitive and affective behaviour of surviving pre-adolescent offspring. Stress 2011;14(6):652–664. DOI: 10.3109/10253890.2011.628719.
  10. Lemaire V, Koehl M, Le Moal M, et al. Prenatal stress produces learning deficits associated with an inhibition of neurogenesis in the hippocampus. Proc Natl Acad Sci USA 2000;97(20):11032–11037. DOI: 10.1073/pnas.97.20.11032.
  11. Koo JW, Park CH, Choi SH, et al. The postnatal environment can counteract prenatal effects on cognitive ability, cell proliferation, and synaptic protein expression. FASEB J 2003;17(11):1556–1558. DOI: 10.1096/fj.02-1032fje.
  12. Kim H, Lee M-H, Chang H-K, et al. Influence of prenatal noise and music on the spatial memory and neurogenesis in the hippocampus of developing rats. Brain Dev 2006;28(2):109–114. DOI: 10.1016/j.braindev.2005.05.008.
  13. Gue M, Bravard A, Meunier J, et al. Sex differences in learning deficits induced by prenatal stress in juvenile rats. Behav Brain Res 2004;150(1–2):149–157. DOI: 10.1016/S0166-4328(03)00250-X.
  14. Wu J, Song T-B, Li Y-J, et al. Prenatal restraint stress impairs learning and memory and hippocampal PKCbeta1 expression and translocation in offspring rats. Brain Res 2007;1141:205–213. DOI: 10.1016/j.brainres.2007.01.024.
  15. Yang J, Han H, Cao J, et al. Prenatal stress modifies hippocampal synaptic plasticity and spatial learning in young rat offspring. Hippocampus 2006;16(5):431–436. DOI: 10.1002/hipo.20181.
  16. Bernhardt LK, Bairy KL, Madhyastha S. Neuroprotective role of N-acetylcysteine against Learning deficits and Altered brain neurotransmitters in rat pups subjected to prenatal stress. Brain Sci 2018;8(7):120. DOI: 10.3390/brainsci8070120.
  17. Brunton PJ, Russell JA. Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: sex-specific effects. J Neuroendocrinol 2010;22(4):258–271. DOI: 10.1111/j.1365-2826.2010.01969.x.
  18. Jarvis S, Moinard C, Robson SK, et al. Programming the offspring of the pig by prenatal social stress: neuroendocrine activity and behaviour. Horm Behav 2006;49(1):68–80. DOI: 10.1016/j.yhbeh.2005.05.004.
  19. Abe H, Hidaka N, Kawagoe C, et al. Prenatal psychological stress causes higher emotionality, depression-like behavior, and elevated activity in the hypothalamo-pituitary-adrenal axis. Neurosci Res 2007;59(2):145–151. DOI: 10.1016/j.neures.2007.06.1465.
  20. Bosch OJ, Müsch W, Bredewold R, et al. Prenatal stress increases HPA axis activity and impairs maternal care in lactating female offspring: implications for postpartum mood disorder. Psychoneuroendocrinology 2007;32(3):267–278. DOI: 10.1016/j.psyneuen.2006.12.012.
  21. Zagron G, Weinstock M. Maternal adrenal hormone secretion mediates behavioural alterations induced by prenatal stress in male and female rats. Behav Brain Res 2006;175(2):323–328. DOI: 10.1016/j.bbr.2006.09.003.
  22. Zuena AR, Mairesse J, Casolini P, et al. Prenatal restraint stress generates two distinct behavioral and neurochemical profiles in male and female rats. PLoS One 2008;3(5):e2170. DOI: 10.1371/journal.pone.0002170.
  23. Zohar I, Weinstock M. Differential effect of prenatal stress on the expression of corticotrophin-releasing hormone and its receptors in the hypothalamus and amygdala in male and female rats. J Neuroendocrinol 2011;23(4):320–328. DOI: 10.1111/j.1365-2826.2011.02117.x.
  24. Bernhardt LK, Bairy KL, Madhyastha S. N-acetylcysteine for gestational stress-induced behavioral toxicity. Res J Pharmaceutical, Biol Chem Sci 2014;5(6):513–520.
  25. Nishio H, Kasuga S, Ushijima M, et al. Prenatal stress and postnatal development of neonatal rats—sex-dependent effects on emotional behavior and learning ability of neonatal rats. Int J Dev Neurosci 2001;19(1):37–45. DOI: 10.1016/s0736-5748(00)00070-8.
  26. Schneider ML, Coe CL. Repeated social stress during pregnancy impairs neuromotor development of the primate infant. J Dev Behav Pediatr 1993;14(2):81–87. PMID: 8473528.
  27. Bernhardt LK, Bairy KL, Madhyastha S. N-Acetylcysteine reverses late gestational stress induced maternal oxidative damage. Int J Pharm Pharm Sci 2015;7(1):165–168.
  28. Bernhardt LK, Madhyastha S, Bairy L, et al. Status of the brain antioxidant system at different growing periods after prenatal stress and N-acetyl cysteine administration. Folia Neuropathol 2017;55(1):38–48. DOI: 10.5114/fn.2017.66712.
  29. Kinsella MT, Monk C. Impact of maternal stress, depression and anxiety on fetal neurobehavioral development. Clin Obstet Gynecol 2009;52(3):425–440. DOI: 10.1097/GRF.0b013e3181b52df1.
  30. Van den Bergh BRH, Marcoen A. High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8-and 9-year-olds. Child Dev 2004;75(4):1085–1097. DOI: 10.1111/j.1467-8624.2004.0072.
  31. O'Connor TG, Heron J, Golding J, et al. Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis. J Child Psychol Psychiatry 2003;44(7):1025–1036. DOI: 10.1111/1469-7610.00187.
  32. Huizink AC, Dick DM, Sihvola E, et al. Chernobyl exposure as stressor during pregnancy and behaviour in adolescent offspring. Acta Psychiatr Scand 2007;116(6):438–446. DOI: 10.1111/j.1600-0447.2007.01050.x.
  33. Barker ED, Maughan B. Differentiating early-onset persistent versus childhood-limited conduct problem youth. Am J Psychiatry 2009;166(8):900–908. DOI: 10.1176/appi.ajp.2009.08121770.
  34. Talge NM, Neal C, Glover V. Antenatal maternal stress and long-term effects on child neurodevelopment: how and why? J Child Psychol Psychiatry 2007;48(3–4):245–261. DOI: 10.1111/j.1469-7610.2006.01714.x.
  35. Wadhwa PD. Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology 2005;30(8):724–743. DOI: 10.1016/j.psyneuen.2005.02.004.
  36. O'Connor TG, Heron J, Golding J, et al. Maternal antenatal anxiety and children's behavioural/emotional problems at 4 years. Report from the Avon Longitudinal Study of Parents and Children. Br J Psychiatry 2002;180(6):502–508. DOI: 10.1192/bjp.180.6.502.
  37. Van den Bergh BRH, Van Calster B, Smits T, et al. 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 2007;33(3):536–545. DOI: 10.1038/sj.npp.1301450.
  38. Huizink AC, Robles de Medina PG, Mulder EJ, et al. Stress during pregnancy is associated with developmental outcome in infancy. J Child Psychol Psychiatry 2003;44(6):810–818. DOI: 10.1111/1469-7610.00166.
  39. Bergman K, Sarkar P, O'Connor TG, et al. Maternal stress during pregnancy predicts cognitive ability and fearfulness in infancy. J Am Acad Child Adolesc Psychiatry 2007;46(11):1454–1463. DOI: 10.1097/chi.0b013e31814a62f6.
  40. Laplante DP, Brunet A, Schmitz N, et al. Project Ice Storm: prenatal maternal stress affects cognitive and linguistic functioning in 5½-year-old children. J Am Acad Child Adolesc Psychiatry 2008;47(9):1063–1072. DOI: 10.1097/CHI.0b013e31817eec80.
  41. Buss C, Davis EP, Shahbaba B, et al. Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci USA 2012;109(20):E1312–E1319. DOI: 10.1073/pnas.1201295109.
  42. Entringer S, Kumsta R, Hellhammer DH, et al. Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Horm Behav 2009;55(2):292–298. DOI: 10.1016/j.yhbeh.2008.11.006.
  43. Obel C, Henriksen TB, Secher NJ, et al. Psychological distress during early gestation and offspring sex ratio. Hum Reprod 2007;22(11):3009–3012. DOI: 10.1093/humrep/dem274.
  44. Glover V. Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done. Best Pract Res Clin Obstet Gynaecol 2014;28(1):25–35. DOI: 10.1016/j.bpobgyn.2013.08.017.
  45. DiPietro JA, Hilton SC, Hawkins M, et al. Maternal stress and affect influence fetal neurobehavioral development. Dev Psychol 2002;38(5):659–668. PMID: 12220045.
  46. Groome LJ, Swiber MJ, Bentz LS, et al. Maternal anxiety during pregnancy: effect on fetal behavior at 38 to 40 weeks of gestation. J Dev Behav Pediatrics 1995;16(6):391–396. PMID: 8746547.
  47. Obel C, Hedegaard M, Henriksen TB, et al. Psychological factors in pregnancy and mixed-handedness in the offspring. Dev Med Child Neurol 2003;45(8):557–561. DOI: 10.1017/s0012162203001014.
  48. DiPietro JA, Novak MFSX, Costigan KA, et al. Maternal psychological distress during pregnancy in relation to child development at age two. Child Dev 2006;77(3):573–587. DOI: 10.1111/j.1467-8624.2006.00891.x.
  49. McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 2008;583(2–3):174–185. DOI: 10.1016/j.ejphar.2007.11.071.
  50. Seckl JR, Holmes MC. Mechanisms of disease: glucocorticoids, their placental metabolism and fetal'programming'of adult pathophysiology. Nat Clin Pract Endocrinol Metabolism 2007;3(6):479–488. DOI: 0.1038/ncpendmet0515.
  51. McIntosh LJ, Sapolsky RM. Glucocorticoids may enhance oxygen radical-mediated neurotoxicity. Neurotoxicology 1995;17(3–4):873–882. PMID: 9086511.
  52. Li J, Olsen J, Vestergaard M, et al. Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark. Eur Child Adolesc Psychiatry 2010;19(10):747–753. DOI: 10.1007/s00787-010-0113-9.
  53. Kinney DK, Munir KM, Crowley DJ, et al. Prenatal stress and risk for autism. Neurosci Biobehav Rev 2008;32(8):1519–1532. DOI: 10.1016/j.neubiorev.2008.06.004.
  54. Kinney DK, Miller AM, Crowley DJ, et al. Autism prevalence following prenatal exposure to hurricanes and tropical storms in Louisiana. J Autism Dev Disord 2008;38(3):481–488. DOI: 10.1007/s10803-007-0414-0.
  55. Grizenko N, Shayan YR, Polotskaia A, et al. Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. J Psychiatry Neurosci 2008;33(1):10–16. PMID: 18197267.
  56. Beversdorf DQ, Manning SE, Hillier A, et al. Timing of prenatal stressors and autism. J Autism Dev Disord 2005;35(4):471–478. DOI: 10.1007/s10803-005-5037-8.
  57. Rodrigues A-J, Leão P, Carvalho M, et al. Potential programming of dopaminergic circuits by early life stress. Psychopharmacology 2011;214(1):107–120. DOI: 10.1007/s00213-010-2085-3.
  58. van Os J, Selten JP. Prenatal exposure to maternal stress and subsequent schizophrenia. The May 1940 invasion of The Netherlands. Br J Psychiatry 1998;172(4):324–326. DOI: 10.1192/bjp.172.4.324.
  59. Murray RM, Sham P, Van Os J, et al. A developmental model for similarities and dissimilarities between schizophrenia and bipolar disorder. Schizophr Res 2004;71(2–3):405–416. DOI: 10.1016/j.schres.2004.03.002.
  60. Susser ES, Lin SP. Schizophrenia after prenatal exposure to the Dutch Hunger Winter of 1944-1945. Arch Gen Psychiatry 1992;49(12):983–988. DOI: 10.1001/archpsyc.1992.01820120071010.
  61. Imamura Y, Nakane Y, Ohta Y, et al. Lifetime prevalence of schizophrenia among individuals prenatally exposed to atomic bomb radiation in Nagasaki City. Acta Psychiatr Scand 1999;100(5):344–349. DOI: 10.1111/j.1600-0447.1999.tb10877.x.
  62. Selten J-P, Cantor-Graae E, Nahon D, et al. No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel. Schizophr Res 2003;63(1–2): 131–135. DOI: 10.1016/s0920-9964(02)00375-4.
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