Correspondence
In Utero and Early-Life Conditions and Adult Health and Disease
N Engl J Med 2008; 359:1523-1524October 2, 2008
- Article
To the Editor:
In their article on the developmental origin of disease, Gluckman et al. (July 3 issue)1 state that “an altered long-term risk of disease is initially induced through adaptive responses that the fetus or infant makes to cues from the mother about her health or physical state.” This rather narrow definition and the overall focus of the review leave out adverse responses due to maternal exposures to environmental chemicals, occupational hazards, drugs, tobacco smoking, or infection. These factors are likely to make a very large contribution to adult diseases of developmental origin, and they have the advantage of being potentially preventable.2 Risk assessment of environmental hazards must therefore include the effects of developmental exposures to stimulate better protection of the most vulnerable life stages.
2 ReferencesPhilippe Grandjean, M.D., Ph.D.
Harvard School of Public Health, Boston, MA 02215
pgrand@hsph.harvard. edu Jerrold J. Heindel, Ph.D.
National Institute of Environmental Health Sciences, Research Triangle Park, NC 277091
Gluckman PD ,Hanson MA ,Cooper C ,Thornburg KL . Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 2008;359:61-73
Full Text | Web of Science | Medline2
Grandjean P ,Bellinger D ,Bergman A , et al. The Faroes statement: human health effects of developmental exposure to chemicals in our environment. Basic Clin Pharmacol Toxicol 2008;102:73-75
Web of Science | Medline
To the Editor:
The article by Gluckman et al. highlights an ongoing fundamental change in medical thinking known as the life-course approach to the development of disease. The “developmental model” of chronic diseases postulates that early-life events affect individual differences in vulnerability to lifestyle and environment. This concept is supported by studies of in utero or at-birth conditions on future diseases by the fact that differences in adult lifestyles only partially explain the development of diseases.1
Considering the aging of the worldwide population and the associated increase in the prevalence of chronic diseases, research on the initiating events of such diseases is valuable and necessary, but research on possible synergism or antagonism between in utero and childhood or adulthood conditions on elderly health could be as important for future public health policies. For example, the interaction between education — which has been found to be inversely associated with both multiple chronic conditions2 and Alzheimer's disease3 in the elderly population — and in utero environment might be a pioneering project in this growing research field.
3 ReferencesAlessandra Marengoni, M.D., Ph.D.
University of Brescia, 25123 Brescia, Italy
pgrand@hsph.harvard. edu Bengt Winblad, M.D., Ph.D.
Laura Fratiglioni, M.D., Ph.D.
Karolinska Institutet, 113 30 Stockholm, Sweden1
Gluckman P, Hanson M, eds. Developmental origins of health and disease. Cambridge, England: Cambridge University Press, 2006.
2
Marengoni A ,Winblad B ,Karp A ,Fratiglioni L . Prevalence of chronic diseases and multimorbidity among the elderly population in Sweden. Am J Public Health 2008;98:1198-1200
CrossRef | Web of Science | Medline3
Karp A ,Kareholt I ,Qiu C ,Bellander T ,Winblad B ,Fratiglioni L . Relation of education and occupation-based socioeconomic status to incident Alzheimer's disease. Am J Epidemiol 2004;159:175-183
CrossRef | Web of Science | Medline
To the Editor:
Gluckman et al. review evidence on the effects of fetal conditions on adult disease. However, an important potential player is being left out of their discussion. Prenatal inflammation, reflected by chorioamnionitis and the fetal inflammatory response syndrome, has been recognized as a fetal condition that contributes to disease in the perinatal period and beyond, mainly affecting the developing lung and brain.1,2 The evidence is increasing that prenatal exposure to inflammation in utero is related to disease, later in childhood, involving the affected organs and is associated with physician-diagnosed asthma,3 recurrent wheezing,3 autistic behavior,4 and adverse neurodevelopmental outcome.5 Experimental chorioamnionitis results in pathogenic programming of the fetal immune response, endotoxin tolerance, and crucial developmental changes, suggesting an important programming effect.1 Thus, accumulating evidence implies an important role of antenatal inflammation in fetal programming and subsequent disease development, the mechanisms of which need further investigation. Considering the immature stage of the exploration of these effects, we may well currently be looking at the tip of the iceberg, anticipating potential links with adult pulmonary and neurologic diseases like chronic obstructive pulmonary disease and dementia.
5 ReferencesJasper V. Been, M.D.
Boris W. Kramer, M.D., Ph.D.
Luc J.I. Zimmermann, M.D., Ph.D.
Maastricht University Hospital, 6202 AZ Maastricht, the Netherlands
jasper.been@mumc. nl 1
Kramer BW . Antenatal inflammation and lung injury: prenatal origin of neonatal disease. J Perinatol 2008;28:Suppl 1:S21-S27
CrossRef | Web of Science | Medline2
Romero R ,Gotsch F ,Pineles B ,Kusanovic JP . Inflammation in pregnancy: its roles in reproductive physiology, obstetrical complications, and fetal injury. Nutr Rev 2007;65:S194-202
CrossRef | Web of Science | Medline3
Kumar R ,Yu Y ,Story RE , et al. Prematurity, chorioamnionitis, and the development of recurrent wheezing: a prospective birth cohort study. J Allergy Clin Immunol 2008;121:878-884
CrossRef | Web of Science | Medline4
Limperopoulos C ,Bassan H ,Sullivan NR , et al. Positive screening for autism in ex-preterm infants: prevalence and risk factors. Pediatrics 2008;121:758-765
CrossRef | Web of Science | Medline5
Redline RW ,Minich N ,Taylor HG ,Hack M . Placental lesions as predictors of cerebral palsy and abnormal neurocognitive function at school age in extremely low birth weight infants (<1 kg). Pediatr Dev Pathol 2007;10:282-292
CrossRef | Web of Science | Medline
Author/Editor Response
We are pleased with the interest in our review, particularly, as noted, concerning the relevance of developmental exposures (environmental toxins, smoking, and alcohol consumption), intermediary phenotypes (chronic low-grade inflammation), and health outcomes (aging and cognitive decline). Although we focused on metabolic, cardiovascular, and bone disease, the areas most developed, we have little doubt that developmental plasticity and epigenetic change have much greater involvement in the etiology of human disease than has previously been considered. We would urge further research to clarify the involved epigenetic mechanisms, to develop risk-prediction tools that might be applied throughout the life course, and to delineate preventive and interventional strategies.
Peter D. Gluckman, M.D., D.Sc.
University of Auckland, Auckland 1023, New Zealand
pd.gluckman@auckland. ac. nz Mark A. Hanson, D.Phil.
Cyrus Cooper, M.D.
University of Southampton, Southampton SO16 6YD, United Kingdom- Citing Articles (3)
Citing Articles
1
M Gantert, J V Been, A W D Gavilanes, Y Garnier, L J I Zimmermann, B W Kramer. (2010) Chorioamnionitis: a multiorgan disease of the fetus?. Journal of Perinatology 30, S21-S30
CrossRef2
Steffen Kunzmann, Kerstin Glogger, Jasper V. Been, Suhas G. Kallapur, Ilias Nitsos, Timothy J. Moss, Christian P. Speer, John P. Newnham, Alan H. Jobe, Boris W. Kramer. (2010) Thymic changes after chorioamnionitis induced by intraamniotic lipopolysaccharide in fetal sheep. American Journal of Obstetrics and Gynecology 202:5, 476.e1-476.e9
CrossRef3
Jasper V. Been, Ingrid G.I.J.G. Rours, René F. Kornelisse, Valéria Lima Passos, Boris W. Kramer, Tom A.J. Schneider, Ronald R. de Krijger, Luc J.I. Zimmermann. (2009) Histologic chorioamnionitis, fetal involvement, and antenatal steroids: effects on neonatal outcome in preterm infants. American Journal of Obstetrics and Gynecology 201:6, 587.e1-587.e8
CrossRef
