Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study

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Abstract

Background: Identifying risk factors for adverse health outcomes in children is important. The intrauterine environment plays a pivotal role for health and disease across life.

Objectives: We conducted a comprehensive study to determine whether common psychosocial stress during pregnancy is a risk factor for a wide spectrum of pediatric diseases in the offspring.

Methods: The study was conducted using prospective data in a population-based sample of mothers with live singleton births ( n = 66,203; 71.4% of those eligible) from the Danish National Birth Cohort. We estimated the association between maternal stress during pregnancy (classified based on two a priori–defined indicators of common stress forms, life stress and emotional stress) and offspring diseases during childhood (grouped into 16 categories of diagnoses from the International Classification of Diseases, 10th Revision, based on data from national registries), controlling for maternal stress after pregnancy.

Results: Median age at end of follow-up was 6.2 (range, 3.6–8.9) years. Life stress (highest compared with lowest quartile) was associated with an increased risk of conditions originating in the perinatal period [odds ratio (OR) = 1.13; 95% confidence interval (CI): 1.06, 1.21] and congenital malformations (OR=1.17; CI: 1.06, 1.28) and of the first diagnosis of infection [hazard ratio (HR) = 1.28; CI: 1.17, 1.39], mental disorders (age 0–2.5 years: HR = 2.03; CI: 1.32, 3.14), and eye (age 0–4.5 years: HR = 1.27; CI: 1.06, 1.53), ear (HR = 1.36; CI: 1.23, 1.51), respiratory (HR = 1.27; CI; 1.19, 1.35), digestive (HR = 1.23; CI: 1.11, 1.37), skin (HR = 1.24; CI: 1.09, 1.43), musculoskeletal (HR = 1.15; CI: 1.01–1.30), and genitourinary diseases (HR = 1.25; CI; 1.08, 1.45). Emotional stress was associated with an increased risk for the first diagnosis of infection (HR = 1.09; CI: 1.01, 1.18) and a decreased risk for the first diagnosis of endocrine (HR = 0.81; CI; 0.67, 0.99), eye (HR = 0.84; CI; 0.71, 0.99), and circulatory diseases (age 0–3 years: HR = 0.63; CI: 0.42, 0.95).

Conclusions: Maternal life stress during pregnancy may be a common risk factor for impaired child health. The results suggest new approaches to reduce childhood diseases.

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Most cited references 74

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Stress and the individual. Mechanisms leading to disease.

B S McEwen, E STELLAR (1993)

This article presents a new formulation of the relationship between stress and the processes leading to disease. It emphasizes the hidden cost of chronic stress to the body over long time periods, which act as a predisposing factor for the effects of acute, stressful life events. It also presents a model showing how individual differences in the susceptibility to stress are tied to individual behavioral responses to environmental challenges that are coupled to physiologic and pathophysiologic responses. Published original articles from human and animal studies and selected reviews. Literature was surveyed using MEDLINE. Independent extraction and cross-referencing by us. Stress is frequently seen as a significant contributor to disease, and clinical evidence is mounting for specific effects of stress on immune and cardiovascular systems. Yet, until recently, aspects of stress that precipitate disease have been obscure. The concept of homeostasis has failed to help us understand the hidden toll of chronic stress on the body. Rather than maintaining constancy, the physiologic systems within the body fluctuate to meet demands from external forces, a state termed allostasis. In this article, we extend the concept of allostasis over the dimension of time and we define allostatic load as the cost of chronic exposure to fluctuating or heightened neural or neuroendocrine response resulting from repeated or chronic environmental challenge that an individual reacts to as being particularly stressful. This new formulation emphasizes the cascading relationships, beginning early in life, between environmental factors and genetic predispositions that lead to large individual differences in susceptibility to stress and, in some cases, to disease. There are now empirical studies based on this formulation, as well as new insights into mechanisms involving specific changes in neural, neuroendocrine, and immune systems. The practical implications of this formulation for clinical practice and further research are discussed.

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Developmental plasticity and human health.

Patrick Bateson, David Barker, Timothy Clutton-Brock … (2004)

Many plants and animals are capable of developing in a variety of ways, forming characteristics that are well adapted to the environments in which they are likely to live. In adverse circumstances, for example, small size and slow metabolism can facilitate survival, whereas larger size and more rapid metabolism have advantages for reproductive success when resources are more abundant. Often these characteristics are induced in early life or are even set by cues to which their parents or grandparents were exposed. Individuals developmentally adapted to one environment may, however, be at risk when exposed to another when they are older. The biological evidence may be relevant to the understanding of human development and susceptibility to disease. As the nutritional state of many human mothers has improved around the world, the characteristics of their offspring--such as body size and metabolism--have also changed. Responsiveness to their mothers' condition before birth may generally prepare individuals so that they are best suited to the environment forecast by cues available in early life. Paradoxically, however, rapid improvements in nutrition and other environmental conditions may have damaging effects on the health of those people whose parents and grandparents lived in impoverished conditions. A fuller understanding of patterns of human plasticity in response to early nutrition and other environmental factors will have implications for the administration of public health.

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The Danish National Birth Cohort--its background, structure and aim.

J. Olsen, M Melbye, S. F. Olsen … (2001)

It is well known that the time from conception to early childhood has importance for health conditions that reach into later stages of life. Recent research supports this view, and diseases such as cardiovascular morbidity, cancer, mental illnesses, asthma, and allergy may all have component causes that act early in life. Exposures in this period, which influence fetal growth, cell divisions, and organ functioning, may have long-lasting impact on health and disease susceptibility. To investigate these issues the Danish National Birth Cohort (Better health for mother and child) was established. A large cohort of pregnant women with long-term follow-up of the offspring was the obvious choice because many of the exposures of interest cannot be reconstructed with sufficient validity back in time. The study needs to be large, and it is aimed to recruit 100,000 women early in pregnancy, and to continue follow-up for decades. The Nordic countries are better suited for this kind of research than most other countries because of their population-based registers on diseases, demography and social conditions, linkable at the individual level by means of the unique ID-number given to all citizens. Exposure information is mainly collected by computer-assisted telephone interviews with the women twice during pregnancy and when their children are six and 18 months old. Participants are also asked to fill in a self-administered food frequency questionnaire in mid-pregnancy. Furthermore, a biological bank has been set up with blood taken from the mother twice during pregnancy and blood from the umbilical cord taken shortly after birth. Data collection started in 1996 and the project covered all regions in Denmark in 1999. By August 2000. a total of 60,000 pregnant women had been recruited to the study. It is expected that a large number of gene-environmental hypotheses need to be based on case-control analyses within a cohort like this.

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Author and article information

Journal

Journal ID (nlm-ta): Environ Health Perspect

Journal ID (publisher-id): EHP

Title: Environmental Health Perspectives

Publisher: National Institute of Environmental Health Sciences

ISSN (Print): 0091-6765

ISSN (Electronic): 1552-9924

Publication date (Electronic): 21 July 2011

Publication date (Print): November 2011

Volume: 119

Issue: 11

Pages: 1647-1652

Affiliations

[1 ]Division of Clinical Psychology and Psychiatry, and

[2 ]Division of Clinical Psychology and Psychotherapy, Department of Psychology, University of Basel, Basel, Switzerland

[3 ]Department of Neurobehavioral Genetics, Institute of Psychobiology, University of Trier, Trier, Germany

[4 ]Department of Epidemiology, School of Public Health, University of California at Los Angeles, Los Angeles, California, USA

[5 ]The Danish Epidemiology Science Centre, Department of Epidemiology, Institute of Public Health, University of Aarhus, Aarhus, Denmark

[6 ]Division of Applied Statistics in Life Sciences, Department of Psychology, University of Basel, Basel, Switzerland

[7 ]National Centre of Competence in Research, Swiss Etiological Study of Adjustment and Mental Health (sesam), Basel, Switzerland

[8 ]Biostatistics and Computational Sciences, Department of Epidemiology and Public Health, Swiss Tropical and Public Health Institute, Basel, Switzerland

[9 ]Division of Clinical Psychology and Epidemiology, Department of Psychology, University of Basel, Basel, Switzerland

Author notes

Address correspondence to G. Meinlschmidt, University of Basel, Missionsstrasse 60/62, CH-4055 Basel, Switzerland. Telephone: 41-61-267-02-75. Fax: 41-61-267-06-59. E-mail: gunther.meinlschmidt@ 123456unibas.ch

Article

Publisher ID: ehp.1003253

DOI: 10.1289/ehp.1003253

PMC ID: 3226491

PubMed ID: 21775267

SO-VID: 534a48ca-0e22-4032-ab81-ebedbc42fa38

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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Stress during Pregnancy and Offspring Pediatric Disease: A National Cohort Study

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Most cited references 74

Stress and the individual. Mechanisms leading to disease.

Developmental plasticity and human health.

The Danish National Birth Cohort--its background, structure and aim.

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