Semin Reprod Med 2009; 27(5): 391-402
DOI: 10.1055/s-0029-1237427
© Thieme Medical Publishers

Developmental Origins of Health and Disease: Environmental Exposures

James M. Swanson1 , Sonja Entringer2 , Claudia Buss2 , Pathik D. Wadhwa2
  • 1Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, California
  • 2Department of Psychiatry and Human Behavior, University of California, Irvine, School of Medicine, Irvine, California
Further Information

Publication History

Publication Date:
26 August 2009 (online)

ABSTRACT

The developmental origins of health and disease (DOHaD) approach has evolved over the past 20 years, and the current hypothesis proposes that fetal adaptations to intrauterine and maternal conditions during development shape structure and function of organs. Here we present a review of some environmental exposures that may trigger fetal maladaptations in these processes, including three examples: exposures to tobacco smoke, antidepressant medication, and folic acid deficits in the food supply. We provide a selected review of current research on the effects of each of these exposures on fetal development and birth outcomes, and use the DOHaD approach to suggest how these exposures may alter long-term outcomes. In the interpretation of this literature, we review the evidence of gene–environment interactions based on evaluation of biological pathways and evidence that some exposures to the fetus may be moderated by maternal and fetal genotypes. Finally, we use the design of the National Children's Study (now in progress) to propose how the DOHaD approach could be used to address questions that have emerged in this area that are relevant to reproductive medicine and subsequent health outcomes.

REFERENCES

  • 1 Wadhwa P D, Buss C, Entringer S, Swanson J D. Developmental origins of health and disease: brief history of the approach and current focus on epigenetic mechanisms.  Semin Reprod Med. 2009;  27(5) 358-368
  • 2 Barker D J, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.  Lancet. 1986;  1(8489) 1077-1081
  • 3 Barker D J, Winter P D, Osmond C, Margetts B, Simmonds S J. Weight in infancy and death from ischaemic heart disease.  Lancet. 1989;  2(8663) 577-580
  • 4 Barker D J, Gluckman P D, Godfrey K M, Harding J E, Owens J A, Robinson J S. Fetal nutrition and cardiovascular disease in adult life.  Lancet. 1993;  341(8850) 938-941
  • 5 Bar-Oz B, Einarson T, Einarson A et al.. Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors.  Clin Ther. 2007;  29(5) 918-926
  • 6 Hales C N, Barker D J. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis.  Diabetologia. 1992;  35(7) 595-601
  • 7 Gluckman P, Hanson M. Developmental Origins of Health and Disease. Cambridge, United Kingdom; Cambridge University Press 2006
  • 8 Gluckman P D, Hanson M A, Beedle A S. Non-genomic transgenerational inheritance of disease risk.  Bioessays. 2007;  29(2) 145-154
  • 9 Jirtle R L, Skinner M R. Epigenetics: a window on gene dysregulation and disease.  Nature Genetics Reviews. 2007;  8(4) 253-263
  • 10 Waterland R A, Michels K B. Epigenetic epidemiology of the developmental origins hypothesis.  Annu Rev Nutr. 2007;  27 363-388
  • 11 Bala M, Strzeszynski L, Cahill K. Mass media interventions for smoking cessation in adults.  Cochrane Database Syst Rev. 2008;  (1) CD004704
  • 12 Messer K, Pierce J P, Zhu S H et al.. The California Tobacco Control Program's effect on adult smokers: (1) Smoking cessation.  Tob Control. 2007;  16(2) 85-90
  • 13 Rovniak L S, Johnson-Kozlow M F, Hovell M F. Reducing the gap between the economic costs of tobacco and funds for tobacco training in schools of public health.  Public Health Rep. 2006;  121(5) 538-546
  • 14 U.S. Department of Health and Human Services .The Health Consequences of Smoking: A Report of the Surgeon General. Atlanta, Georgia; U.S. Department of Health and Human Services, CDC, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health 2004
  • 15 U.S. Department of Health and Human Services .The Health Consequences of Involuntary Exposure to Tobacco Smoke. A Report of the Surgeon General—Executive Summary. Atlanta, GA; U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health 2006
  • 16 Simpson W J. A preliminary report on cigarette smoking and the incidence of prematurity.  Am J Obstet Gynecol. 1957;  73(4) 807-815
  • 17 Yerushalmy J. The relationship of parents' cigarette smoking to outcome of pregnancy—implications as to the problem of inferring causation from observed associations.  Am J Epidemiol. 1971;  93(6) 443-456
  • 18 Olsen J. Cigarette smoking in pregnancy and fetal growth. Does the type of tobacco play a role?.  Int J Epidemiol. 1992;  21(2) 279-284
  • 19 Herrmann M, King K, Weitzman M. Prenatal tobacco smoke and postnatal secondhand smoke exposure and child neurodevelopment.  Curr Opin Pediatr. 2008;  20(2) 184-190
  • 20 Stroud L R, Paster R L, Goodwin M S et al.. Maternal smoking during pregnancy and neonatal behavior: a large-scale community study.  Pediatrics. 2009;  123(5) e842-e848
  • 21 Aagaard-Tillery K M, Porter T F, Lane R H, Varner M W, Lacoursiere D Y. In utero tobacco exposure is associated with modified effects of maternal factors on fetal growth.  Am J Obstet Gynecol. 2008;  198(1) 61-66
  • 22 Lumley J, Oliver S S, Chamberlain C, Oakley L. Interventions for promoting smoking cessation during pregnancy.  Cochrane Database Syst Rev. 2004;  (4) CD001055
  • 23 Jaddoe V W, Verburg B O, de Ridder M A et al.. Maternal smoking and fetal growth characteristics in different periods of pregnancy: the generation R study.  Am J Epidemiol. 2007;  165(10) 1207-1215
  • 24 Li C Q, Windsor R A, Perkins L, Goldenberg R L, Lowe J B. The impact on infant birth weight and gestational age of cotinine-validated smoking reduction during pregnancy.  JAMA. 1993;  269(12) 1519-1524
  • 25 McCowan L M, Dekker G A, Chan E SCOPE consortium et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study.  BMJ. 2009;  338 b1081
  • 26 March of Dimes .Preconception health and healthcare. Available at: http://www.marchofdimes.com/professionals/19695_1171.asp Accessed July 2, 2009
  • 27 Toschke A M, Montgomery S M, Pfeiffer U, von Kries R. Early intrauterine exposure to tobacco-inhaled products and obesity.  Am J Epidemiol. 2003;  158(11) 1068-1074
  • 28 von Kries R, Bolte G, Baghi L, Toschke A M. GME Study Group . Parental smoking and childhood obesity—is maternal smoking in pregnancy the critical exposure?.  Int J Epidemiol. 2008;  37(1) 210-216
  • 29 Oken E, Levitan E B, Gillman M W. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis.  Int J Obes (Lond). 2008;  32(2) 201-210
  • 30 Leonardi-Bee J, Smyth A, Britton J, Coleman T. Environmental tobacco smoke and fetal health: systematic review and meta-analysis.  Arch Dis Child Fetal Neonatal Ed. 2008;  93(5) F351-F361
  • 31 Eskenazi B, Castorina R. Association of prenatal maternal or postnatal child environmental tobacco smoke exposure and neurodevelopmental and behavioral problems in children.  Environ Health Perspect. 1999;  107(12) 991-1000
  • 32 Braun J M, Kahn R S, Froehlich T, Auinger P, Lanphear B P. Exposures to environmental toxicants and attention deficit hyperactivity disorder in U.S. children.  Environ Health Perspect. 2006;  114(12) 1904-1909
  • 33 Perera F P, Rauh V, Whyatt R M et al.. A summary of recent findings on birth outcomes and developmental effects of prenatal ETS, PAH, and pesticide exposures.  Neurotoxicology. 2005;  26(4) 573-587
  • 34 Wenten M, Li Y F, Lin P C et al.. In utero smoke exposure, glutathione S-transferase P1 haplotypes, and respiratory illness-related absence among schoolchildren.  Pediatrics. 2009;  123(5) 1344-1351
  • 35 Shi M, Wehby G L, Murray J C. Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects.  Birth Defects Res C Embryo Today. 2008;  84(1) 16-29
  • 36 Hirschhorn J N. Genomewide association studies—illuminating biologic pathways.  N Engl J Med. 2009;  360(17) 1699-1701
  • 37 Shi M, Christensen K, Weinberg C R et al.. Orofacial cleft risk is increased with maternal smoking and specific detoxification-gene variants.  Am J Hum Genet. 2007;  80(1) 76-90
  • 38 Wang X, Zuckerman B, Pearson C et al.. Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight.  JAMA. 2002;  287(2) 195-202
  • 39 Tsai H J, Liu X, Mestan K et al.. Maternal cigarette smoking, metabolic gene polymorphisms, and preterm delivery: new insights on GxE interactions and pathogenic pathways.  Hum Genet. 2008;  123(4) 359-369
  • 40 Yu Y, Tsai H J, Liu X et al.. The joint association between F5 gene polymorphisms and maternal smoking during pregnancy on preterm delivery.  Hum Genet. 2009;  124(6) 659-668
  • 41 Kahn R S, Khoury J, Nichols W C, Lanphear B P. Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors.  J Pediatr. 2003;  143(1) 104-110
  • 42 Neuman R J, Lobos E, Reich W, Henderson C A, Sun L W, Todd R D. Prenatal smoking exposure and dopaminergic genotypes interact to cause a severe ADHD subtype.  Biol Psychiatry. 2007;  61(12) 1320-1328
  • 43 Obel C, Linnet K M, Henriksen T B et al.. Smoking during pregnancy and hyperactivity-inattention in the offspring—comparing results from three Nordic cohorts.  Int J Epidemiol. 2009;  38(3) 698-705
  • 44 Swanson J M, Kinsbourne M, Nigg J et al.. Etiologic subtypes of attention-deficit/hyperactivity disorder: brain imaging, molecular genetic and environmental factors and the dopamine hypothesis.  Neuropsychol Rev. 2007;  17(1) 39-59
  • 45 Cole J A, Modell J G, Haight B R, Cosmatos I S, Stoler J M, Walker A M. Bupropion in pregnancy and the prevalence of congenital malformations.  Pharmacoepidemiol Drug Saf. 2007;  16(5) 474-484
  • 46 Källén B, Otterblad Olausson P. Antidepressant drugs during pregnancy and infant congenital heart defect.  Reprod Toxicol. 2006;  21(3) 221-222
  • 47 Bellantuono C, Migliarese G, Gentile S. Serotonin reuptake inhibitors in pregnancy and the risk of major malformations: a systematic review.  Hum Psychopharmacol. 2007;  22(3) 121-128
  • 48 Gentile S, Bellantuono C. Selective serotonin reuptake inhibitor exposure during early pregnancy and the risk of fetal major malformations: focus on paroxetine.  J Clin Psychiatry. 2009;  70(3) 414-422
  • 49 Chambers C D, Hernandez-Diaz S, Van Marter L J et al.. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn.  N Engl J Med. 2006;  354(6) 579-587
  • 50 Chambers C D, Johnson K A, Dick L M, Felix R J, Jones K L. Birth outcomes in pregnant women taking fluoxetine.  N Engl J Med. 1996;  335(14) 1010-1015
  • 51 Moses-Kolko E L, Bogen D, Perel J et al.. Neonatal signs after late in utero exposure to serotonin reuptake inhibitors: literature review and implications for clinical applications.  JAMA. 2005;  293(19) 2372-2383
  • 52 Koren G, Boucher N. Adverse effects in neonates exposed to SSRIs and SNRI in late gestation—Motherisk Update 2008.  Can J Clin Pharmacol. 2009;  16(1) e66-e67
  • 53 Toh S, Mitchell A A, Louik C, Werler M M, Chambers C D, Hernández-Díaz S. Selective serotonin reuptake inhibitor use and risk of gestational hypertension.  Am J Psychiatry. 2009;  166(3) 320-328
  • 54 Oberlander T F, Warburton W, Misri S, Aghajanian J, Hertzman C. Effects of timing and duration of gestational exposure to serotonin reuptake inhibitor antidepressants: population-based study.  Br J Psychiatry. 2008;  192(5) 338-343
  • 55 Tan K S, Thomson N C. Asthma in pregnancy.  Am J Med. 2000;  109(9) 727-733
  • 56 Bakhireva L N, Schatz M, Chambers C D. Effect of maternal asthma and gestational asthma therapy on fetal growth.  J Asthma. 2007;  44(2) 71-76
  • 57 Holmes L B, Harvey E A, Coull B A et al.. The teratogenicity of anticonvulsant drugs.  N Engl J Med. 2001;  344(15) 1132-1138
  • 58 Adab N, Tudur S C, Vinten J, Williamson P, Winterbottom J. Common antiepileptic drugs in pregnancy in women with epilepsy.  Cochrane Database Syst Rev. 2004;  (3) CD004848
  • 59 Meador K J, Penovich P, Baker G A et al.. Antiepileptic drug use in women of childbearing age.  Epilepsy Behav. 2009;  , May 26 (Epub ahead of print)
  • 60 Meador K J, Baker G A, Browning N NEAD Study Group et al. Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs.  N Engl J Med. 2009;  360(16) 1597-1605
  • 61 U.S. Preventive Services Task Force . Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement.  Ann Intern Med. 2009;  150(9) 626-631
  • 62 Honein M A, Paulozzi L J, Mathews T J, Erickson J D, Wong L Y. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects.  JAMA. 2001;  285(23) 2981-2986
  • 63 Abramsky L, Dolk H. EUROCAT Folic Acid Working Group . Should Europe fortify a staple food with folic acid?.  Lancet. 2007;  369(9562) 641-642
  • 64 Busby A, Abramsky L, Dolk H et al.. Preventing neural tube defects in Europe: a missed opportunity.  Reprod Toxicol. 2005;  20(3) 393-402
  • 65 Charles D H, Ness A R, Campbell D, Smith G D, Whitley E, Hall M H. Folic acid supplements in pregnancy and birth outcome: re-analysis of a large randomised controlled trial and update of Cochrane review.  Paediatr Perinat Epidemiol. 2005;  19(2) 112-124
  • 66 Bukowski R, Malone F D, Porter F T et al.. Preconceptional folate supplementation and the risk of spontaneous preterm birth: a cohort study.  PLoS Med. 2009;  6(5) e1000061
  • 67 Edison R J, Berg K, Remaley A et al.. Adverse birth outcome among mothers with low serum cholesterol.  Pediatrics. 2007;  120(4) 723-733
  • 68 Steffen K M, Cooper M E, Shi M et al.. Maternal and fetal variation in genes of cholesterol metabolism is associated with preterm delivery.  J Perinatol. 2007;  27(11) 672-680
  • 69 Ehn N L, Cooper M E, Orr K et al.. Evaluation of fetal and maternal genetic variation in the progesterone receptor gene for contributions to preterm birth.  Pediatr Res. 2007;  62(5) 630-635
  • 70 Gluckman P D, Hanson M A, Cooper C, Thornburg K L. Effect of in utero and early-life conditions on adult health and disease.  N Engl J Med. 2008;  359(1) 61-73
  • 71 Larsen W J, Sherman L S, Potter S S, Scott W S. Human Embryology. Philadelphia, PA; Churchill Livingstone 2001
  • 72 Lee J H, Hart S RL, Skalnik D G. Histone deacetylase activity is required for embryonic stem cell differentiation.  Genesis. 2004;  38(1) 32-38
  • 73 Reik W. Stability and flexibility of epigenetic gene regulation in mammalian development.  Nature. 2007;  447(7143) 425-432
  • 74 Rasmussen T P. Embryonic stem cell differentiation: a chromatin perspective.  Reprod Biol Endocrinol. 2003;  1 100
  • 75 Santos F, Dean W. Epigenetic reprogramming during early development in mammals.  Reproduction. 2004;  127(6) 643-651
  • 76 Mackay J, Eriksen M. The Tobacco Atlas. Brighton, United Kingdom; World Health Organization 2002
  • 77 Waterland R A, Jirtle R L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation.  Mol Cell Biol. 2003;  23(15) 5293-5300
  • 78 Dolinoy D C, Weidman J R, Waterland R A, Jirtle R L. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.  Environ Health Perspect. 2006;  114(4) 567-572
  • 79 Meaney M J, Szyf M. Environmental programming of stress responses through DNA methylation: life at the interface between a dynamic environment and a fixed genome.  Dialogues Clin Neurosci. 2005;  7(2) 103-123
  • 80 Ravelli G P, Stein Z A, Susser M W. Obesity in young men after famine exposure in utero and early infancy.  N Engl J Med. 1976;  295(7) 349-353
  • 81 Gluckman P D, Hanson M A. Living with the past: evolution, development, and patterns of disease.  Science. 2004;  305(5691) 1733-1736
  • 82 McGowan P O, Sasaki A, D'Alessio A C et al.. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse.  Nat Neurosci. 2009;  12(3) 342-348
  • 83 McGowan P O, Sasaki A, Huang T C et al.. Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain.  PLoS One. 2008;  3(5) e2085
  • 84 McMinn J, Wei M, Schupf N et al.. Unbalanced placental expression of imprinted genes in human intrauterine growth restriction.  Placenta. 2006;  27(6–7) 540-549
  • 85 Tycko B. Imprinted genes in placental growth and obstetric disorders.  Cytogenet Genome Res. 2006;  113(1–4) 271-278
  • 86 Haig D. Genetic conflicts in human pregnancy.  Q Rev Biol. 1993;  68(4) 495-532
  • 87 Swanson J D, Wadhwa P M. Developmental origins of child mental health disorders.  J Child Psychol Psychiatry. 2008;  49(10) 1009-1019

James M SwansonPh.D. 

Professor of Pediatrics Director, UC Irvine Child Development Center, University of California, Irvine, School of Medicine

19722 MacArthur Boulevard, Irvine, CA 92612-4480

Email: jmswanso@uci.edu

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