Abstract
Background
Metabolic Syndrome (MetS) can be considered as a consequence of a complex interplay between genetic and environmental factors and can be influenced by changes in the environment early in life. Prenatal stress (PS) exposure likely represents an important adverse intrauterine environment that may impact the biology of the developing organism. The aim of this study was to quantitatively synthesize the available data on the effects of PS on offspring’s obesity, estimated indirectly by body mass index (BMI) and body fat; blood pressure, plasma glucose and blood lipid concentrations (triglycerides and high-density lipoprotein cholesterol).
Methods
Literature searches for eligible studies on PubMed were conducted until October 8, 2018. Full text review yielded 24 publications for inclusion into the systematic review. Meta-analyses were performed for the outcomes BMI and body fat. 62 effect sizes from 19 studies together with relevant moderators were collected. Summary estimates were calculated by using random-effects model.
Results
The combined standardized mean difference (d) for the relation between BMI and PS indicated that despite significant heterogeneity, stress exposure of expectant mothers was associated with increased BMI of their offspring [d (95% CI) = 0.268 (0.191; 0.345)]. Both objective and subjective stress have been linked to increased overweight. Preliminary results of the relationship between PS and body fat suggested that the contribution of PS to body fat should be at least further considered [d (95% CI) = 0.167 (0.016; 0.317)]. Evidence from a limited number of published studies do not sustains an effect on blood pressure, glucose metabolism or circulating lipids, however these outcomes have only been scarcely investigated.
Conclusions
A direct association between PS and BMI was found and further studies are needed to confirm the relationship between maternal stress during gestation and body fat. Overall, findings suggest that PS could contribute to alterations to the post-natal offspring phenotype.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Kivimaki M, Steptoe A. Effects of stress on the development and progression of cardiovascular disease. Nat Rev Cardiol. 2018;15:215–29.
Chrousos GP. Stress and disorders of the stress system. Nat Rev Endocrinol. 2009;5:374–81.
Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995;311:171–4.
Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 2011;378:31–40.
Ozanne SE, Hales CN. Pre- and early postnatal nongenetic determinants of type 2 diabetes. Expert Rev Mol Med. 2002;4:1–14.
Bercovich E, Keinan-Boker L, Shasha SM. Long-term health effects in adults born during the Holocaust. Isr Med Assoc J. 2014;16:203–7.
Flory JD, Bierer LM, Yehuda R. Maternal exposure to the holocaust and health complaints in offspring. Dis Markers. 2011;30:133–9.
Painter RC, de Rooij SR, Bossuyt PM, Phillips DI, Osmond C, Barker DJ, et al. Blood pressure response to psychological stressors in adults after prenatal exposure to the Dutch famine. J Hypertens. 2006;24:1771–8.
Poggi Davis E, Sandman C. Prenatal exposure to stress and stress hormones influences child development. Infants Young Child. 2006;19:246–59.
Roseboom T, de Rooji S, Painter R. The Dutch famine and its long-term consequences for adult health. Early Hum Dev. 2006;82:485–91.
Christian LM, Franco A, Glaser R, Iams JD. Depressive symptoms are associated with elevated serum proinflammatory cytokines among pregnant women. Brain Behav Immun. 2009;23:750–4.
Gitau R, Cameron A, Fisk NM, Glover V. Fetal exposure to maternal cortisol. Lancet. 1998;352:707–8.
Edwards CR, Benediktsson R, Lindsay RS, Seckl JR. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet. 1993;341:355–7.
Meaney MJ, Szyf M, Seckl JR. Epigenetic mechanisms of perinatal programming of hypothalamic–pituitary–adrenal function and health. Trends Mol Med. 2007;13:269–77.
Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR. Glucocorticoid exposure in utero: new model for adult hypertension. Lancet. 1993;341:339–41.
Brown RW, Diaz R, Robson AC, Kotelevtsev YV, Mullins JJ, Kaufman MH, et al. The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development. Endocrinology. 1996;137:794–7.
McTernan CL, Draper N, Nicholson H, Chalder SM, Driver P, Hewison M, et al. Reduced placental 11beta-hydroxysteroid dehydrogenase type 2 mRNA levels in human pregnancies complicated by intrauterine growth restriction: an analysis of possible mechanisms. J Clin Endocrinol Metab. 2001;86:4979–83.
Drake AJ, Liu L, Kerrigan D, Meehan RR, Seckl JR. Multigenerational programming in the glucocorticoid programmed rat is associated with generation-specific and parent of origin effects. Epigenetics. 2011;6:1334–43.
Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279–89.
Littleton HL, Bye K, Buck K, Amacker A. Psychosocial stress during pregnancy and perinatal outcomes: a meta-analytic review. J Psychosom Obstet Gynaecol. 2010;31:219–28.
Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993;36:62–7.
Phillips DI, Barker DJ, Hales CN, Hirst S, Osmond C. Thinness at birth and insulin resistance in adult life. Diabetologia. 1994;37:150–4.
van Montfoort N, Finken MJ, le Cessie S, Dekker FW, Wit JM. Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis. Eur J Endocrinol. 2005;153:811–7.
Reynolds RM. Corticosteroid-mediated programming and the pathogenesis of obesity and diabetes. J Steroid Biochem Mol Biol. 2010;122:3–9.
Entringer S. Impact of stress and stress physiology during pregnancy on child metabolic function and obesity risk. Curr Opin Clin Nutr Metab Care. 2013;16:320–7.
Virk J, Li J, Vestergaard M, Obel C, Kristensen JK, Olsen J. Prenatal exposure to bereavement and type-2 diabetes: a Danish longitudinal population based study. PLoS ONE. 2012;7:e43508.
Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62:1006–12.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.
Alder J, Fink N, Bitzer J, Hosli I, Holzgreve W. Depression and anxiety during pregnancy: a risk factor for obstetric, fetal and neonatal outcome? A critical review of the literature. J Matern Fetal Neonatal Med. 2007;20:189–209.
Littleton HL, Breitkopf CR, Berenson AB. Correlates of anxiety symptoms during pregnancy and association with perinatal outcomes: a meta-analysis. Am J Obstet Gynecol. 2007;196:424–32.
Wells JC. The thrifty phenotype hypothesis: thrifty offspring or thrifty mother? J Theor Biol. 2003;221:143–61.
Tellechea ML, Mensegue MF, Pirola CJ. The association between high fat diet around gestation and metabolic syndrome-related phenotypes in rats: a systematic review and meta-analysis. Sci Rep. 2017;7:5086.
Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.
Bhat SK, Beilin LJ, Robinson M, Burrows S, Mori TA. Contrasting effects of prenatal life stress on blood pressure and body mass index in young adults. J Hypertens. 2015;33:711–9.
Chatterjee A, Thompson JW, Svensson K, Tamayo YO, Wright R, Wright R, et al. Maternal antenatal stress has little impact on child sleep: results from a prebirth cohort in Mexico City. Sleep Health. 2018;4:397–404.
Christensen JS, Hjortebjerg D, Raaschou-Nielsen O, Ketzel M, Sorensen TIA, Sorensen M. Pregnancy and childhood exposure to residential traffic noise and overweight at 7 years of age. Environ Int. 2016;94:170–6.
Dancause KN, Veru F, Andersen RE, Laplante DP, King S. Prenatal stress due to a natural disaster predicts insulin secretion in adolescence. Early Hum Dev. 2013;89:773–6.
Dancause KN, Laplante DP, Hart KJ, O’Hara MW, Elgbeili G, Brunet A, et al. Prenatal stress due to a natural disaster predicts adiposity in childhood: the Iowa Flood Study. J Obes. 2015;2015:570541.
Dixon B, Rifas-Shiman SL, James-Todd T, Ertel K, Krieger N, Kleinman KP, et al. Maternal experiences of racial discrimination and child weight status in the first 3 years of life. J Dev Orig Health Dis. 2012;3:433–41.
Entringer S, Wust S, Kumsta R, Layes IM, Nelson EL, Hellhammer DH, et al. Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. Am J Obstet Gynecol. 2008;199:498–7.
Farewell CV, Thayer ZM, Tracer DP, Morton S. Prenatal stress exposure and early childhood BMI: exploring associations in a New Zealand context. Am J Hum Biol. 2018;30:e23116.
Guxens M, Tiemeier H, Jansen PW, Raat H, Hofman A, Sunyer J, et al. Parental psychological distress during pregnancy and early growth in preschool children: the generation R study. Am J Epidemiol. 2013;177:538–47.
Hohwu L, Li J, Olsen J, Sorensen TI, Obel C. Severe maternal stress exposure due to bereavement before, during and after pregnancy and risk of overweight and obesity in young adult men: a Danish National Cohort Study. PLoS ONE. 2014;9:e97490.
Hohwu L, Zhu JL, Graversen L, Li J, Sorensen TI, Obel C. Prenatal parental separation and body weight, including development of overweight and obesity later in childhood. PLoS ONE. 2015;10:e0119138.
Ingstrup KG, Schou AC, Ajslev TA, Pedersen P, Sorensen TI, Nohr EA. Maternal distress during pregnancy and offspring childhood overweight. J Obes. 2012;2012:462845.
Ji C, Li Y, Cui L, Cai J, Shi J, Cheng FW, et al. Prenatal earthquake exposure and midlife uric acid levels among Chinese adults. Arthritis Care Res. 2017;69:703–8.
Li J, Olsen J, Vestergaard M, Obel C, Baker JL, Sorensen TI. Prenatal stress exposure related to maternal bereavement and risk of childhood overweight. PLoS ONE. 2010;5:e11896.
Liu GT, Dancause KN, Elgbeili G, Laplante DP, King S. Disaster-related prenatal maternal stress explains increasing amounts of variance in body composition through childhood and adolescence: Project Ice Storm. Environ Res. 2016;150:1–7.
Sandel M, Sheward R, Ettinger de Cuba S, Coleman S, Heeren T, Black MM, et al. Timing and duration of pre- and postnatal homelessness and the health of young children. Pediatrics. 2018;142:e20174254.
Taal HR, de Jonge LL, Tiemeier H, van Osch-Gevers L, Hofman A, Verhulst FC, et al. Parental psychological distress during pregnancy and childhood cardiovascular development. The Generation R Study. Early Hum Dev. 2013;89:547–53.
van Dijk AE, van EM, Stronks K, Gemke RJ, Vrijkotte TG. The association between prenatal psychosocial stress and blood pressure in the child at age 5-7 years. PLoS ONE. 2012;7:e43548.
van Dijk AE, van Eijsden M, Stronks K, Gemke RJ, Vrijkotte TG. The relation of maternal job strain and cortisol levels during early pregnancy with body composition later in the 5-year-old child: the ABCD study. Early Hum Dev. 2012;88:351–6.
van Dijk AE, van Eijsden M, Stronks K, Gemke RJ, Vrijkotte TG. No associations of prenatal maternal psychosocial stress with fasting glucose metabolism in offspring at 5–6 years of age. J Dev Orig Health Dis. 2014;5:361–9.
Wang R, An C, Wang J, Wang Y, Song M, Li N, et al. Earthquake experience at different trimesters during pregnancy is associated with leukocyte telomere length and long-term health in adulthood. Front Psychiatry. 2017;8:208.
Weyde KV, Krog NH, Oftedal B, Magnus P, White R, Stansfeld S, et al. A longitudinal study of road traffic noise and body mass index trajectories from birth to 8 years. Epidemiology. 2018;29:729–38.
Wu S, Gennings C, Wright RJ, Wilson A, Burris HH, Just AC, et al. Prenatal stress, methylation in inflammation-related genes, and adiposity measures in early childhood: the Programming Research in Obesity, Growth Environment and Social Stress Cohort Study. Psychosom Med. 2018;80:34–41.
Zadzinska E, Rosset I. Pre-natal and perinatal factors affecting body mass index in pre-pubertal Polish children. Ann Hum Biol. 2013;40:477–84.
Mirzababaei A, Djafarian K, Mozafari H, Shab-Bidar S. The long-term prognosis of heart diseases for different metabolic phenotypes: a systematic review and meta-analysis of prospective cohort studies. Endocrine. 2019;63:439–62.
Deng G, Yin L, Liu W, Liu X, Xiang Q, Qian Z. et al. Associations of anthropometric adiposity indexes with hypertension risk: a systematic review and meta-analysis including PURE-China. Medicine. 2018;97:e13262
Jayedi A, Rashidy-Pour A, Khorshidi M, Shab-Bidar S. Body mass index, abdominal adiposity, weight gain and risk of developing hypertension: a systematic review and dose-response meta-analysis of more than 2.3 million participants. Obes Rev. 2018;19:654–67.
Tate EB, Wood W, Liao Y, Dunton GF. Do stressed mothers have heavier children? A meta-analysis on the relationship between maternal stress and child body mass index. Obes Rev. 2015;16:351–61.
Stettle N, Stallings VA, Troxel AB, Zhao J, Schinnar R, Nelson SE, et al. Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation. 2005;111:1897–903.
Singhal A, Cole TJ, Fewtrell M, Deanfield J, Lucas A. Is slower early growth beneficial for long-term cardiovascular health? Circulation. 2004;109:1108–13.
Stettler N, Zemel BS, Kumanyika S, Stallings VA. Infant weight gain and childhood overweight status in a multicenter, cohort study. Pediatrics. 2002;109:194–9.
Cao-Lei L, de Rooij SR, King S, Matthews SG, Metz GAS, Roseboom TJ, et al. Prenatal stress and epigenetics. Neurosci Biobehav Rev. 2017. pii: S0149-7634(16)30726-6. https://doi.org/10.1016/j.neubiorev.2017.05.016. [Epub ahead of print].
Jensen PC, Monk C, Champagne FA. Epigenetic effects of prenatal stress on 11beta-hydroxysteroid dehydrogenase-2 in the placenta and fetal brain. PLoS ONE. 2012;7:e39791.
Glover V, O’Donnell KJ, O’Connor TG, Fisher J. Prenatal maternal stress, fetal programming, and mechanisms underlying later psychopathology—a global perspective. Dev Psychopathol. 2018;30:843–54.
Entringer S, Epel ES, Kumsta R, Lin J, Hellhammer DH, Blackburn EH, et al. Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proc Natl Acad Sci USA. 2011;108:E513–8.
Acknowledgements
This study was partially supported by grants PICT-2015-1567, PICT 2016-2727 (Agencia Nacional de Promoción Científica Tecnológica) and PIP 2015-2017 No. 11220150100163 (Consejo Nacional de Investigaciones Científicas y Técnicas). ALB, AMG, and MLT are members of Consejo Nacional de Investigaciones Científicas y Técnicas.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
About this article
Cite this article
Burgueño, A.L., Juarez, Y.R., Genaro, A.M. et al. Systematic review and meta-analysis on the relationship between prenatal stress and metabolic syndrome intermediate phenotypes. Int J Obes 44, 1–12 (2020). https://doi.org/10.1038/s41366-019-0423-z
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41366-019-0423-z
This article is cited by
-
The relation between prenatal stress, overweight and obesity in children diagnosed according to BMI and percentage fat tissue
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity (2022)
-
Overweight and obesity at age 19 after pre-natal famine exposure
International Journal of Obesity (2021)
-
Meta-analytic evidence for increased low-grade systemic inflammation and oxidative stress in hypothyroid patients. Can levothyroxine replacement therapy mitigate the burden?
Endocrine (2021)