Skip to main content Accessibility help
×
Home

Prenatal maternal bereavement and mortality in the first decades of life: a nationwide cohort study from Denmark and Sweden

  • Y. Yu (a1), S. Cnattingius (a2), J. Olsen (a1) (a3) (a4), E. T. Parner (a5), M. Vestergaard (a6), Z. Liew (a4), N. Zhao (a7) and J. Li (a3)...

Abstract

Background

The loss of a close relative is one of the most stressful life events. In pregnancy, this experience has been associated with a higher risk of fetal death and under-five mortality, but little is known about potential effects on long-term mortality in offspring. We examined the association between prenatal maternal bereavement and mortality in a cohort of 5.3 million children followed until up to 37 years of age.

Method

The population-based cohort study included 5 253 508 live singleton births in Denmark (1973–2004) and Sweden (1973–2006). Children born to mothers who lost a child, spouse, sibling, or parent during or 1 year before pregnancy were categorized as exposed.

Results

Prenatal maternal bereavement was associated with a 10% increased all-cause mortality risk in offspring [mortality rate ratio (MRR) 1.10, 95% confidence interval (CI) 1.03–1.18]. The association was the most pronounced for children of mothers who lost a child/spouse (MRR 1.28, 95% CI 1.14–1.44) and was stronger during the first 10 years of life. Prenatal maternal bereavement may have stronger effects on natural causes of death in offspring, including infectious/parasitic disease (MRR 1.86, 95% CI 1.07–3.23), endocrine/nutritional/metabolic diseases (MRR 3.23, 95% CI 2.02–5.17), diseases of nervous system (MRR 3.36, 95% CI 2.47–4.58), and congenital malformations (MRR 1.39, 95% CI 1.08–1.80). No excess mortality risk in offspring was observed for unnatural causes of death.

Conclusion

Prenatal maternal bereavement was associated with an increased long-term mortality risk in offspring, particularly for selected natural causes of diseases and medical conditions. Our results support the fetal programming hypothesis that prenatal stress may contribute to ill health from physical diseases later in life.

Copyright

Corresponding author

*Address for correspondence: Y. Yu, MSc, Section for Epidemiology, Department of Public Health, Aarhus University, Artholins Alle 2, DK 8000 Aarhus C, Denmark. (Email: yoyu@ph.au.dk)

References

Hide All
Alexander, GR, Kogan, M, Martin, J, Papiernik, E (1998). What are the fetal growth patterns of singletons, twins, and triplets in the United States? Clinical Obstetrics and Gynecology 41, 115125.
Alexander, GR, Salihu, HM (2005). Perinatal outcomes of singleton and multiple births in the United States. In Multiple Pregnancy: Epidemiology, Gestation, and Perinatal Outcome, pp. 39. CRC Press: Boca Raton, FL.
Barker, DJ, Eriksson, JG, Forsen, T, Osmond, C (2002). Fetal origins of adult disease: strength of effects and biological basis. International Journal of Epidemiology 31, 12351239.
Class, QA, Khashan, AS, Lichtenstein, P, Langstrom, N, D'Onofrio, BM (2013). Maternal stress and infant mortality: the importance of the preconception period. Psychological Science 24, 13091316.
Class, QA, Mortensen, PB, Henriksen, TB, Dalman, C, D'Onofrio, BM, Khashan, AS (2015). Preconception maternal bereavement and infant and childhood mortality: a Danish population-based study. Psychosomatic Medicine 77, 863869.
Cottrell, EC, Seckl, JR (2009). Prenatal stress, glucocorticoids and the programming of adult disease. Frontiers in Behavioral Neuroscience 3, 19.
Donovan, SJ, Susser, E (2011). Commentary: advent of sibling designs. International Journal of Epidemiology 40, 345349.
Drake, AJ, Tang, JI, Nyirenda, MJ (2007). Mechanisms underlying the role of glucocorticoids in the early life programming of adult disease. Clinical Science 113, 219232.
Eurostat (1998). European shortlist causes of death (http://ec.europa.eu/eurostat/ramon/documents/cod_1998/cod_1998_pdf.zip). Accessed 17 November 2015.
Fowden, AL, Sibley, C, Reik, W, Constancia, M (2006). Imprinted genes, placental development and fetal growth. Hormone Research 65 (Suppl. 3), 5058.
Gitau, R, Cameron, A, Fisk, NM, Glover, V (1998). Fetal exposure to maternal cortisol. Lancet 352, 707708.
Glover, V (2015). Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms. In Perinatal Programming of Neurodevelopment (ed. M. C. Antonelli), pp. 269283. Springer: New York.
Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL (2008). Effect of in utero and early-life conditions on adult health and disease. New England Journal of Medicine 359, 6173.
Guldin, MB, Li, J, Pedersen, HS, Obel, C, Agerbo, E, Gissler, M, Cnattingius, S, Olsen, J, Vestergaard, M (2015). Incidence of suicide among persons who had a parent who died during their childhood: a population-based cohort study. JAMA Psychiatry 72, 12271234.
Hansen, D, Lou, HC, Olsen, J (2000). Serious life events and congenital malformations: a national study with complete follow-up. Lancet 356, 875880.
Heron, M (2013). Deaths: leading causes for 2010. National vital Statistics Reports 62, 197.
Kapoor, A, Dunn, E, Kostaki, A, Andrews, MH, Matthews, SG (2006). Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. Journal of Physiology 572, 3144.
Kapoor, A, Kostaki, A, Janus, C, Matthews, SG (2009). The effects of prenatal stress on learning in adult offspring is dependent on the timing of the stressor. Behavioural Brain Research 197, 144149.
Khashan, AS, Abel, KM, McNamee, R, Pedersen, MG, Webb, RT, Baker, PN, Kenny, LC, Mortensen, PB (2008). Higher risk of offspring schizophrenia following antenatal maternal exposure to severe adverse life events. Archives of General Psychiatry 65, 146152.
Khashan, AS, McNamee, R, Abel, KM, Mortensen, PB, Kenny, LC, Pedersen, MG, Webb, RT, Baker, PN (2009). Rates of preterm birth following antenatal maternal exposure to severe life events: a population-based cohort study. Human Reproduction 24, 429437.
Krozowski, Z (1999). The 11beta-hydroxysteroid dehydrogenases: functions and physiological effects. Molecular and Cellular Endocrinology 151, 121127.
Laszlo, KD, Li, J, Olsen, J, Vestergaard, M, Obel, C, Cnattingius, S (2016). Maternal bereavement and the risk of preterm delivery: the importance of gestational age and of the precursor of preterm birth. Psychological Medicine 46, 11631173.
Laszlo, KD, Svensson, T, Li, J, Obel, C, Vestergaard, M, Olsen, J, Cnattingius, S (2013). Maternal bereavement during pregnancy and the risk of stillbirth: a nationwide cohort study in Sweden. American Journal of Epidemiology 177, 219227.
Li, J, Laursen, TM, Precht, DH, Olsen, J, Mortensen, PB (2005). Hospitalization for mental illness among parents after the death of a child. New England Journal of Medicine 352, 11901196.
Li, J, Olsen, J, Vestergaard, M, Obel, C (2010). Attention-deficit/hyperactivity disorder in the offspring following prenatal maternal bereavement: a nationwide follow-up study in Denmark. European Child and Adolescent Psychiatry 19, 747753.
Li, J, Olsen, J, Vestergaard, M, Obel, C, Kristensen, JK, Virk, J (2012). Prenatal exposure to bereavement and type-2 diabetes: a Danish longitudinal population based study. PLoS ONE 7, e43508.
Li, J, Precht, DH, Mortensen, PB, Olsen, J (2003). Mortality in parents after death of a child in Denmark: a nationwide follow-up study. Lancet 361, 363367.
Li, J, Vestergaard, M, Cnattingius, S, Gissler, M, Bech, BH, Obel, C, Olsen, J (2014). Mortality after parental death in childhood: a nationwide cohort study from three nordic countries. PLoS Medicine 11, e1001679.
Li, J, Vestergaard, M, Obel, C, Cnattingus, S, Gissler, M, Olsen, J (2011). Cohort profile: the nordic perinatal bereavement cohort. International Journal of Epidemiology 40, 11611167.
Li, J, Yang, H, Guldin, MB, Vedsted, P, Vestergaard, M (2015). Increased utilisation of primary healthcare in persons exposed to severe stress in prenatal life: a national population-based study in Denmark. BMJ Open 5, e005657.
Marinescu, IP, Foarfa, MC, Pirlog, MC, Turculeanu, A (2014). Prenatal depression and stress – risk factors for placental pathology and spontaneous abortion. Romanian Journal of Morphology and Embryology 55, 11551160.
Mulder, EJ, Robles de Medina, PG, Huizink, AC, Van den Bergh, BR, Buitelaar, JK, Visser, GH (2002). Prenatal maternal stress: effects on pregnancy and the (unborn) child. Early Human Development 70, 314.
Nielsen, NM, Hansen, AV, Simonsen, J, Hviid, A (2011). Prenatal stress and risk of infectious diseases in offspring. American Journal of Epidemiology 173, 990997.
Office for National Statistics (2012). Statistical bulletin: live births, stillbirths and infant deaths, babies born in 2009 in England and Wales (http://www.ons.gov.uk/ons/dcp171778_266305.pdf). Accessed 17 November 2015.
Patin, V, Lordi, B, Vincent, A, Thoumas, JL, Vaudry, H, Caston, J (2002). Effects of prenatal stress on maternal behavior in the rat. Developmental Brain Research 139, 18.
Plana-Ripoll, O, Liu, X, Momen, NC, Parner, E, Olsen, J, Li, J (2016). Prenatal exposure to maternal stress following bereavement and cardiovascular disease: a nationwide population-based and sibling-matched cohort study. European Journal of Preventive Cardiology 23, 10181028.
Skodol, AE, Shrout, PE (1989). Use of DSM-III axis-IV in clinical practice: rating etiologically significant stressors. American Journal of Psychiatry 146, 6166.
Stroebe, M, Schut, H, Stroebe, W (2007). Health outcomes of bereavement. Lancet 370, 19601973.
Virk, J, Li, J, Lauritsen, J, Olsen, J (2013). Risk of childhood injuries after prenatal exposure to maternal bereavement: a danish national cohort study. BMJ Open 3, e002357.
Wadhwa, PD (2005). Psychoneuroendocrine processes in human pregnancy influence fetal development and health. Psychoneuroendocrinology 30, 724743.
Wainstock, T, Lerner-Geva, L, Glasser, S, Shoham-Vardi, I, Anteby, EY (2013). Prenatal stress and risk of spontaneous abortion. Psychosomatic Medicine 75, 228235.
Welberg, LA, Seckl, JR (2001). Prenatal stress, glucocorticoids and the programming of the brain. Journal of Neuroendocrinology 13, 113128.
Wisborg, K, Barklin, A, Hedegaard, M, Henriksen, TB (2008). Psychological stress during pregnancy and stillbirth: prospective study. British Journal of Obstetrics and Gynaecology 115, 882885.
Wolfe, I, Macfarlane, A, Donkin, A, Marmot, M, Viner, R (2014). Why children die: death in infants, children, and young people in the UK – Part A. Royal College of Paediatrics and Child Health (http://www.rcpch.ac.uk/sites/default/files/page/Death%20in%20infants,%20children%20and%20young%20people%20in%20the%20UK.pdf). Accessed 17 November 2015.
Yu, Y, Qin, G, Cnattingius, S, Gissler, M, Olsen, J, Zhao, N, Li, J (2016). Mortality in children aged 0–9 years: a nationwide cohort study from three nordic countries. PLoS ONE 11, e0146669.
Zhu, JL, Olsen, J, Sorensen, HT, Li, J, Nohr, EA, Obel, C, Vestergaard, M, Olsen, MS (2013). Prenatal maternal bereavement and congenital heart defects in offspring: a registry-based study. Pediatrics 131, e1225e1230.

Keywords

Type Description Title
WORD
Supplementary materials

Yu supplementary material
Figure S1 and Table S1

 Word (71 KB)
71 KB

Prenatal maternal bereavement and mortality in the first decades of life: a nationwide cohort study from Denmark and Sweden

  • Y. Yu (a1), S. Cnattingius (a2), J. Olsen (a1) (a3) (a4), E. T. Parner (a5), M. Vestergaard (a6), Z. Liew (a4), N. Zhao (a7) and J. Li (a3)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed