Hostname: page-component-cd9895bd7-jkksz Total loading time: 0 Render date: 2024-12-26T09:29:50.195Z Has data issue: false hasContentIssue false
  • English
  • Français

The ‘Developmental Origins’ Hypothesis: relevance to the obstetrician and gynecologist

Part of: Sir David Barker Symposium

Published online by Cambridge University Press:  08 September 2015

A. J. Kermack ,
B. B. Van Rijn ,
F. D. Houghton ,
P. C. Calder ,
I. T. Cameron  and
N. S. Macklon
A. J. Kermack
Affiliation:
Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton, UK Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK Department of Obstetrics and Gynaecology, Complete Fertility Centre, Princess Anne Hospital, Southampton, UK
B. B. Van Rijn
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK Wilhelmina Children’s Hospital Birth Centre, UMCU, Utrecht, The Netherlands
F. D. Houghton
Affiliation:
Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, Southampton, UK Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK
P. C. Calder
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK
I. T. Cameron
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK
N. S. Macklon*
Affiliation:
Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, UK NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK Department of Obstetrics and Gynaecology, Complete Fertility Centre, Princess Anne Hospital, Southampton, UK
*
*Address for correspondence: Professor N. S. Macklon, Department of Obstetrics and Gynaecology (MP815), Princess Anne Hospital, University of Southampton, Coxford Road, Southampton, SO16 5YA, UK. (Email n.s.macklon@soton.ac.uk)
Get access Rights & Permissions [Opens in a new window]

Abstract

The recognition of ‘fetal origins of adult disease’ has placed new responsibilities on the obstetrician, as antenatal care is no longer simply about ensuring good perinatal outcomes, but also needs to plan for optimal long-term health for mother and baby. Recently, it has become clear that the intrauterine environment has a broad and long-lasting impact, influencing fetal and childhood growth and development as well as future cardiovascular health, non-communicable disease risk and fertility. This article looks specifically at the importance of the developmental origins of ovarian reserve and ageing, the role of the placenta and maternal nutrition before and during pregnancy. It also reviews recent insights in developmental medicine of relevance to the obstetrician, and outlines emerging evidence supporting a proactive clinical approach to optimizing periconceptional as well as antenatal care aimed to protect newborns against long-term disease susceptibility.

Keywords

developmental originsovaryplacentapregnancy
Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 6 , Issue 5: Themed Issue: David Barker commemorative meeting, September 2014; Prenatal Exposures and Health Outcomes , October 2015 , pp. 415 - 424
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Barker, DJ, Gluckman, PD, Godfrey, KM, et al. Fetal nutrition and cardiovascular disease in adult life. Lancet. 1993; 341, 938–941.Google Scholar
2. Ravelli, AC, van Der Meulen, JH, Osmond, C, Barker, DJ, Bleker, OP. Obesity at the age of 50 y in men and women exposed to famine prenatally. Am J Clin Nutr. 1999; 70, 811–816.CrossRefGoogle ScholarPubMed
3. Barker, DJ, Hales, CN, Fall, CH, et al. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993; 36, 62–67.CrossRefGoogle ScholarPubMed
4. 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.CrossRefGoogle ScholarPubMed
5. Stocks, J, Hislop, A, Sonnappa, S. Early lung development: lifelong effect on respiratory health and disease. Lancet Respir Med. 2013; 1, 728–742.CrossRefGoogle ScholarPubMed
6. Suri, R, Lin, AS, Cohen, LS, Altshuler, LL. Acute and long-term behavioral outcome of infants and children exposed in utero to either maternal depression or antidepressants: a review of the literature. J Clin Psychiatry. 2014; 75, e1142–e1152.CrossRefGoogle ScholarPubMed
7. Godfrey, KM, Sheppard, A, Gluckman, PD, et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes. 2011; 60, 1528–1534.CrossRefGoogle ScholarPubMed
8. Sun, C, Denisenko, O, Sheth, B, et al. Epigenetic regulation of histone modifications and Gata6 gene expression induced by maternal diet in mouse embryoid bodies in a model of developmental programming. BMC Dev Biol. 2015; 15, 3.CrossRefGoogle Scholar
9. Lillycrop, KA, Burdge, GC. The effect of nutrition during early life on the epigenetic regulation of transcription and implications for human diseases. J Nutrigenet Nutrigenomics. 2011; 4, 248–260.Google ScholarPubMed
10. Watkins, AJ, Ursell, E, Panton, R, et al. Adaptive responses by mouse early embryos to maternal diet protect fetal growth but predispose to adult onset disease. Biol Reprod. 2008; 78, 299–306.CrossRefGoogle ScholarPubMed
11. Kwong, WY, Wild, AE, Roberts, P, Willis, AC, Fleming, TP. Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development. 2000; 127, 4195–4202.CrossRefGoogle ScholarPubMed
12. Dumoulin, JC, Land, JA, Van Montfoort, AP, et al. Effect of in vitro culture of human embryos on birthweight of newborns. Hum Reprod (Oxford, England). 2010; 25, 605–612.CrossRefGoogle ScholarPubMed
13. Eskild, A, Monkerud, L, Tanbo, T. Birthweight and placental weight; do changes in culture media used for IVF matter? Comparisons with spontaneous pregnancies in the corresponding time periods. Hum Reprod (Oxford, England). 2013; 28, 3207–3214.Google Scholar
14. Carrasco, B, Boada, M, Rodriguez, I, et al. Does culture medium influence offspring birth weight? Fertil Steril. 2013; 100, 1283–1288.Google Scholar
15. Lin, S, Li, M, Lian, Y, Chen, L, Liu, P. No effect of embryo culture media on birthweight and length of newborns. Hum Reprod (Oxford, England). 2013; 28, 1762–1767.CrossRefGoogle ScholarPubMed
16. Nohr, EA, Vaeth, M, Rasmussen, S, Ramlau-Hansen, CH, Olsen, J. Waiting time to pregnancy according to maternal birthweight and prepregnancy BMI. Hum Reprod (Oxford, England). 2009; 24, 226–232.CrossRefGoogle ScholarPubMed
17. Vanbillemont, G, Lapauw, B, Bogaert, V, et al. Birth weight in relation to sex steroid status and body composition in young healthy male siblings. J Clin Endocrinol Metab. 2010; 95, 1587–1594.CrossRefGoogle ScholarPubMed
18. Ramlau-Hansen, CH, Hansen, M, Jensen, CR, et al. Semen quality and reproductive hormones according to birthweight and body mass index in childhood and adult life: two decades of follow-up. Fertil Steril. 2010; 94, 610–618.Google Scholar
19. Zambrano, E, Rodriguez-Gonzalez, GL, Guzman, C, et al. A maternal low protein diet during pregnancy and lactation in the rat impairs male reproductive development. J Physiol. 2005; 563(Pt 1), 275–284.Google Scholar
20. Mamsen, LS, Lutterodt, MC, Andersen, EW, et al. Cigarette smoking during early pregnancy reduces the number of embryonic germ and somatic cells. Hum Reprod (Oxford, England). 2010; 25, 2755–2761.CrossRefGoogle ScholarPubMed
21. Baker, TG. A quantitative and cytological study of germ cells in human ovaries. Proceedings of the Royal Society of London. Series B, Biological Sciences 1963; 158(972), 417–433.Google Scholar
22. Fulton, N, Martins da Silva, SJ, Bayne, RA, Anderson, RA. Germ cell proliferation and apoptosis in the developing human ovary. J Clin Endocrinol Metab. 2005; 90, 4664–4670.CrossRefGoogle ScholarPubMed
23. Skinner, MK. Regulation of primordial follicle assembly and development. Hum Reprod Update. 2005; 11, 461–471.CrossRefGoogle ScholarPubMed
24. Vaskivuo, TE, Anttonen, M, Herva, R, et al. Survival of human ovarian follicles from fetal to adult life: apoptosis, apoptosis-related proteins, and transcription factor GATA-4. J Clin Endocrinol Metab. 2001; 86, 3421–3429.Google ScholarPubMed
25. Faddy, MJ, Gosden, RG, Gougeon, A, Richardson, SJ, Nelson, JF. Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause. Hum Reprod. 1992; 7, 1342–1346.Google Scholar
26. Barker, DJP. Fetal origins of coronary heart disease. BMJ 1995; 311, 171.CrossRefGoogle Scholar
27. Mark-Kappeler, CJ, Hoyer, PB, Devine, PJ. Xenobiotic effects on ovarian preantral follicles. Biol Reprod. 2011; 85, 871–883.CrossRefGoogle ScholarPubMed
28. Richardson, MC, Guo, M, Fauser, BC, Macklon, NS. Environmental and developmental origins of ovarian reserve. Hum Reprod Update. 2014; 20, 353–369.CrossRefGoogle ScholarPubMed
29. Rae, M, Palassio, S, Kyle, C, et al. Effect of maternal undernutrition during pregnancy on early ovarian development and subsequent follicular development in sheep fetuses. Reproduction (Cambridge, England). 2001; 122, 915–922.CrossRefGoogle ScholarPubMed
30. Rae, MT, Kyle, CE, Miller, DW, et al. The effects of undernutrition, in utero, on reproductive function in adult male and female sheep. Anim Reprod Sci. 2002; 72, 63–71.CrossRefGoogle ScholarPubMed
31. Mossa, F, Carter, F, Walsh, SW, et al. Maternal undernutrition in cows impairs ovarian and cardiovascular systems in their offspring. Biol Reprod. 2013; 88, 92.CrossRefGoogle ScholarPubMed
32. Ibanez, L, Potau, N, Enriquez, G, de Zegher, F. Reduced uterine and ovarian size in adolescent girls born small for gestational age. Pediatr Res. 2000; 47, 575–577.CrossRefGoogle ScholarPubMed
33. de Bruin, JP, Nikkels, PG, Bruinse, HW, et al. Morphometry of human ovaries in normal and growth-restricted fetuses. Early Hum Dev. 2001; 60, 179–192.CrossRefGoogle ScholarPubMed
34. Hart, R, Sloboda, DM, Doherty, DA, et al. Prenatal determinants of uterine volume and ovarian reserve in adolescence. J Clin Endocrinol Metab. 2009; 94, 4931–4937.CrossRefGoogle ScholarPubMed
35. Lem, AJ, Boonstra, VH, Renes, JS, et al. Anti-Müllerian hormone in short girls born small for gestational age and the effect of growth hormone treatment. Hum Reprod. 2011; 26, 898–903.Google Scholar
36. Shayeb, AG, Harrild, K, Bhattacharya, S. Birth weight and ovulatory dysfunction. BJOG. 2014; 121, 281–289.CrossRefGoogle ScholarPubMed
37. Ferreira, RV, Gombar, FM, da Silva Faria, T, et al. Metabolic programming of ovarian angiogenesis and folliculogenesis by maternal malnutrition during lactation. Fertil Steril. 2010; 93, 2572–2580.CrossRefGoogle ScholarPubMed
38. Hardy, R, Kuh, D. Social and environmental conditions across the life course and age at menopause in a British birth cohort study. BJOG. 2005; 112, 346–354.CrossRefGoogle Scholar
39. Gold, EB, Crawford, SL, Avis, NE, et al. Factors related to age at natural menopause: longitudinal analyses from SWAN. Am J Epidemiol. 2013; 178, 70–83.CrossRefGoogle ScholarPubMed
40. Bromberger, JT, Matthews, KA, Kuller, LH, et al. Prospective study of the determinants of age at menopause. Am J Epidemiol. 1997; 145, 124–133.CrossRefGoogle ScholarPubMed
41. Gold, EB, Bromberger, J, Crawford, S, et al. Factors associated with age at natural menopause in a multiethnic sample of midlife women. Am J Epidemiol. 2001; 153, 865–874.CrossRefGoogle Scholar
42. Xita, N, Tsatsoulis, A. Review: fetal programming of polycystic ovary syndrome by androgen excess: evidence from experimental, clinical, and genetic association studies. J Clin Endocrinol Metab. 2006; 91, 1660–1666.CrossRefGoogle ScholarPubMed
43. Hague, WM, Adams, J, Rodda, C, et al. The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives. Clin Endocrinol (Oxf). 1990; 33, 501–510.Google Scholar
44. Dumesic, DA, Patankar, MS, Barnett, DK, et al. Early prenatal androgenization results in diminished ovarian reserve in adult female Rhesus monkeys. Hum Reprod. 2009; 24, 3188–3195.Google Scholar
45. Wu, XY, Li, ZL, Wu, CY, et al. Endocrine traits of polycystic ovary syndrome in prenatally androgenized female Sprague-Dawley rats. Endocr J. 2010; 57, 201–209.CrossRefGoogle ScholarPubMed
46. La Marca, A, Broekmans, FJ, Volpe, A, Fauser, BC, Macklon, NS. Anti-Müllerian hormone (AMH): what do we still need to know? Hum Reprod. 2009; 24, 2264–2275.Google Scholar
47. Diamanti-Kandarakis, E, Bourguignon, JP, Giudice, LC, et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr Rev. 2009; 30, 293–342.Google Scholar
48. Andersen, HR, Vinggaard, AM, Rasmussen, TH, Gjermandsen, IM, Bonefeld-Jorgensen, EC. Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. Toxicol Appl Pharmacol. 2002; 179, 1–12.Google Scholar
49. Shanle, EK, Xu, W. Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action. Chem Res Toxicol. 2011; 24, 6–19.CrossRefGoogle ScholarPubMed
50. Hruska, KS, Furth, PA, Seifer, DB, Sharara, FI, Flaws, JA. Environmental factors in infertility. Clin Obstet Gynecol. 2000; 43, 821–829.CrossRefGoogle ScholarPubMed
51. Matikainen, TM, Moriyama, T, Morita, Y, et al. Ligand activation of the aromatic hydrocarbon receptor transcription factor drives Bax-dependent apoptosis in developing fetal ovarian germ cells. Endocrinology. 2002; 143, 615–620.CrossRefGoogle ScholarPubMed
52. Lutterodt, MC, Sørensen, KP, Larsen, KB, et al. The number of oogonia and somatic cells in the human female embryo and fetus in relation to whether or not exposed to maternal cigarette smoking. Hum Reprod. 2009; 24, 2558–2566.CrossRefGoogle ScholarPubMed
53. Hoffmann, D, Hoffmann, I. The changing cigarette, 1950–1995. J Toxicol Environ Health. 1997; 50, 307–364.Google Scholar
54. Fowler, PA, Childs, AJ, Courant, F, et al. In utero exposure to cigarette smoke dysregulates human fetal ovarian developmental signalling. Hum Reprod (Oxford, England). 2014; 29, 1471–1489.CrossRefGoogle ScholarPubMed
55. Motejlek, K, Palluch, F, Neulen, J, Grummer, R. Smoking impairs angiogenesis during maturation of human oocytes. Fertil Steril. 2006; 86, 186–191.CrossRefGoogle ScholarPubMed
56. Erler, C, Novak, J. Bisphenol A exposure: human risk and health policy. J Pediatr Nurs. 2010; 25, 400–407.CrossRefGoogle ScholarPubMed
57. Manikkam, M, Guerrero-Bosagna, C, Tracey, R, Haque, MM, Skinner, MK. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One. 2012; 7, e31901.Google Scholar
58. Mok-Lin, E, Ehrlich, S, Williams, PL, et al. Urinary bisphenol A concentrations and ovarian response among women undergoing IVF. Int J Androl. 2010; 33, 385–393.Google Scholar
59. Lewis, RM, Cleal, JK, Hanson, MA. Review: placenta, evolution and lifelong health. Placenta. 2012; 33(Suppl.), S28–S32.CrossRefGoogle ScholarPubMed
60. Kaiser, J. Reproductive biology. Gearing up for a closer look at the human placenta. Science (New York, NY). 2014; 344, 1073.CrossRefGoogle Scholar
61. Constancia, M, Hemberger, M, Hughes, J, et al. Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature. 2002; 417, 945–948.Google Scholar
62. Freathy, RM, Mook-Kanamori, DO, Sovio, U, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010; 42, 430–435.Google Scholar
63. Horikoshi, M, Yaghootkar, H, Mook-Kanamori, DO, et al. New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism. Nat Genet. 2013; 45, 76–82.Google Scholar
64. Thornburg, KL, Challis, JR. How to build a healthy heart from scratch. Adv Exp Med Biol. 2014; 814, 205–216.CrossRefGoogle ScholarPubMed
65. Musa, MG, Torrens, C, Clough, GF. The microvasculature: a target for nutritional programming and later risk of cardio-metabolic disease. Acta Physiologica (Oxford, England). 2014; 210, 31–45.CrossRefGoogle ScholarPubMed
66. Lewis, RM, Demmelmair, H, Gaillard, R, et al. The placental exposome: placental determinants of fetal adiposity and postnatal body composition. Ann Nutr Metab. 2013; 63, 208–215.CrossRefGoogle ScholarPubMed
67. Zhu, MJ, Du, M, Ford, SP. Cell Biology Symposium: impacts of maternal obesity on placental and gut inflammation and health. J Anim Sci. 2014; 92, 1840–1849.Google Scholar
68. Lewis, RM, Cleal, JK, Ntani, G, et al. Relationship between placental expression of the imprinted PHLDA2 gene, intrauterine skeletal growth and childhood bone mass. Bone. 2012; 50, 337–342.CrossRefGoogle ScholarPubMed
69. Keverne, EB. Genomic imprinting, action, and interaction of maternal and fetal genomes. Proc Natl Acad Sci U S A. 2015; 112, 6834–6840.Google Scholar
70. Sebire, NJ, Jolly, M, Harris, JP, et al. Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London. Int J Obes Relat Metab Disord. 2001; 25, 1175–1182.Google Scholar
71. Landon, MB, Spong, CY, Thom, E, et al. A multicenter, randomized trial of treatment for mild gestational diabetes. N Engl J Med. 2009; 361, 1339–1348.CrossRefGoogle ScholarPubMed
72. Jansson, N, Pettersson, J, Haafiz, A, et al. Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol. 2006; 576(Pt 3), 935–946.Google Scholar
73. Li, Y, Hadden, C, Singh, P, et al. GDM-associated insulin deficiency hinders the dissociation of SERT from ERp44 and down-regulates placental 5-HT uptake. Proc Natl Acad Sci U S A. 2014; 111, E5697–E5705.CrossRefGoogle Scholar
74. Jansson, N, Rosario, FJ, Gaccioli, F, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab. 2013; 98, 105–113.CrossRefGoogle ScholarPubMed
75. Jansson, T, Powell, TL. IFPA 2005 award in placentology lecture. Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? – a review. Placenta. 2006; 27(Suppl. A), S91–S97.Google Scholar
76. Edwards, CR, Benediktsson, R, Lindsay, RS, Seckl, JR. Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet. 1993; 341, 355–357.CrossRefGoogle ScholarPubMed
77. Novakovic, B, Gordon, L, Robinson, WP, Desoye, G, Saffery, R. Glucose as a fetal nutrient: dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation. J Nutr Biochem. 2013; 24, 282–288.Google Scholar
78. Marseille-Tremblay, C, Ethier-Chiasson, M, Forest, JC, et al. Impact of maternal circulating cholesterol and gestational diabetes mellitus on lipid metabolism in human term placenta. Mol Reprod Dev. 2008; 75, 1054–1062.CrossRefGoogle ScholarPubMed
79. Challier, JC, Basu, S, Bintein, T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta. 2008; 29, 274–281.CrossRefGoogle ScholarPubMed
80. Zhu, MJ, Du, M, Nathanielsz, PW, Ford, SP. Maternal obesity up-regulates inflammatory signaling pathways and enhances cytokine expression in the mid-gestation sheep placenta. Placenta. 2010; 31, 387–391.CrossRefGoogle ScholarPubMed
81. Barker, DJ, Thornburg, KL. Placental programming of chronic diseases, cancer and lifespan: a review. Placenta. 2013; 34, 841–845.Google Scholar
82. Alwasel, SH, Abotalib, Z, Aljarallah, JS, et al. Secular increase in placental weight in Saudi Arabia. Placenta. 2011; 32, 391–394.Google Scholar
83. Barker, DJ, Bull, AR, Osmond, C, Simmonds, SJ. Fetal and placental size and risk of hypertension in adult life. BMJ (Clinical research ed). 1990; 301, 259–262.Google Scholar
84. Eriksson, JG, Kajantie, E, Osmond, C, Thornburg, K, Barker, DJ. Boys live dangerously in the womb. Am J Hum Biol. 2010; 22, 330–335.Google Scholar
85. Bille, C, Andersen, AM. Preconception care. BMJ (Clinical research ed). 2009; 338, b22.Google Scholar
86. Crozier, SR, Robinson, SM, Godfrey, KM, Cooper, C, Inskip, HM. Women’s dietary patterns change little from before to during pregnancy. J Nutr. 2009; 139, 1956–1963.Google Scholar
87. Kermack, AJ, Finn-Sell, S, Cheong, YC, et al. Amino acid composition of human uterine fluid: association with age, lifestyle and gynaecological pathology. Hum Reprod. 2015; 30, 917–924.Google Scholar
88. Twigt, JM, Bolhuis, ME, Steegers, EA, et al. The preconception diet is associated with the chance of ongoing pregnancy in women undergoing IVF/ICSI treatment. Hum Reprod (Oxford, England). 2012; 27, 2526–2531.Google Scholar
89. Fleming, TP, Lucas, ES, Watkins, AJ, Eckert, JJ. Adaptive responses of the embryo to maternal diet and consequences for post-implantation development. Reprod Fertil Dev. 2011; 24, 35–44.Google Scholar
90. Cerf, M. High fat programming of β-Cell failure. In The islets of Langerhans (ed. Islam MS), 2010; pp. 77–89. Springer: The Netherlands.CrossRefGoogle Scholar
91. Yang, Z, Huffman, SL. Nutrition in pregnancy and early childhood and associations with obesity in developing countries. Matern Child Nutr. 2013; 9, 105–119.Google Scholar
92. Setia, S, Sridhar, MG. Changes in GH/IGF-1 axis in intrauterine growth retardation: consequences of fetal programming? Horm Metab Res. 2009; 41, 791–798.CrossRefGoogle ScholarPubMed
93. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet. 1991; 338, 131–137.Google Scholar
94. Boxmeer, JC, Brouns, RM, Lindemans, J, et al. Preconception folic acid treatment affects the microenvironment of the maturing oocyte in humans. Fertil Steril. 2008; 89, 1766–1770.Google Scholar
95. Boxmeer, JC, Macklon, NS, Lindemans, J, et al. IVF outcomes are associated with biomarkers of the homocysteine pathway in monofollicular fluid. Hum Reprod (Oxford, England). 2009; 24, 1059–1066.Google Scholar
96. Harvey, NC, Holroyd, C, Ntani, G, et al. Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess (Winchester, England). 2014; 18, 1–190.Google ScholarPubMed
97. Lewis, S, Lucas, RM, Halliday, J, Ponsonby, AL. Vitamin D deficiency and pregnancy: from preconception to birth. Mol Nutr Food Res. 2010; 54, 1092–1102.Google Scholar
98. McGrath, J. Does ‘imprinting’ with low prenatal vitamin D contribute to the risk of various adult disorders? Med Hypotheses. 2001; 56, 367–371.Google Scholar
99. Calder, PC. Mechanisms of action of (n-3) fatty acids. J Nutr. 2012; 142, 592S–599S.Google Scholar
100. Calder, PC. Very long chain omega-3 (n-3) fatty acids and human health. Eur J Lipid Sci Technol. 2014; 116, 1280–1300.Google Scholar
101. Calder, PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2014; 1851: 469–484.Google Scholar
102. Haggarty, P. Fatty acid supply to the human fetus. Annu Rev Nutr. 2010; 30, 237–255.CrossRefGoogle Scholar
103. Al, MD, van Houwelingen, AC, Kester, AD, et al. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr. 1995; 74, 55–68.Google Scholar
104. Al, MD, van Houwelingen, AC, Hornstra, G. Relation between birth order and the maternal and neonatal docosahexaenoic acid status. Eur J Clin Nutr. 1997; 51, 548–553.Google Scholar
105. TSO. Scientific Advisory Committee on Nutrition/Committee on Toxicity: Advice on Fish Consumption: Benefits and Risks, 2004. TSO, London, UK.Google Scholar
106. European Food Safety Authority. Scientific opinion on dietarty reference values for fats, including saturated fatty acids, polyunsaturated fatty acids, monounsaturated fatty acids, trans fatty acids and cholesterol. EFSA J. 2010; 8, 1461.Google Scholar
107. Lauritzen, L, Hansen, HS, Jorgensen, MH, Michaelsen, KF. The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Prog Lipid Res. 2001; 40, 1–94.Google Scholar
108. Agostoni, C, Riva, E, Trojan, S, Bellu, R, Giovannini, M. Docosahexaenoic acid status and developmental quotient of healthy term infants. Lancet. 1995; 346, 638.CrossRefGoogle ScholarPubMed
109. Bakker, EC, Hornstra, G, Blanco, CE, Vles, JS. Relationship between long-chain polyunsaturated fatty acids at birth and motor function at 7 years of age. Eur J Clin Nutr. 2009; 63, 499–504.Google Scholar
110. Helland, IB, Smith, L, Saarem, K, Saugstad, OD, Drevon, CA. Maternal supplementation with very-long-chain n-3 fatty acids during pregnancy and lactation augments children’s IQ at 4 years of age. Pediatrics. 2003; 111, e39–e44.Google Scholar
111. Miles, EA, Calder, PC. Omega-6 and omega-3 polyunsaturated fatty acids and allergic diseases in infancy and childhood. Curr Pharm Des. 2014; 20, 946–953.Google Scholar
112. Olsen, SF, Sorensen, JD, Secher, NJ, et al. Randomised controlled trial of effect of fish-oil supplementation on pregnancy duration. Lancet. 1992; 339, 1003–1007.Google Scholar
113. Olsen, SF, Secher, NJ. A possible preventive effect of low-dose fish oil on early delivery and pre-eclampsia: indications from a 50-year-old controlled trial. Br J Nutr. 1990; 64, 599–609.Google Scholar
114. Mazza, D, Chapman, A, Michie, S. Barriers to the implementation of preconception care guidelines as perceived by general practitioners: a qualitative study. BMC Health Serv Res. 2013; 13, 36.CrossRefGoogle Scholar
115. Larsson, M. A descriptive study of the use of the Internet by women seeking pregnancy-related information. Midwifery. 2009; 25, 14–20.Google Scholar
116. Martyn, CN, Barker, DJ, Osmond, C. Mothers’ pelvic size, fetal growth, and death from stroke and coronary heart disease in men in the UK. Lancet. 1996; 348, 1264–1268.Google Scholar
117. Eriksson, J, Forsen, T, Tuomilehto, J, Osmond, C, Barker, D. Fetal and childhood growth and hypertension in adult life. Hypertension. 2000; 36, 790–794.CrossRefGoogle ScholarPubMed
118. Barker, DJ, Thornburg, KL, Osmond, C, Kajantie, E, Eriksson, JG. The surface area of the placenta and hypertension in the offspring in later life. Int J Dev Biol. 2010; 54, 525–530.Google Scholar
119. Eriksson, JG, Kajantie, E, Thornburg, KL, Osmond, C, Barker, DJ. Mother’s body size and placental size predict coronary heart disease in men. Eur Heart J. 2011; 32, 2297–2303.CrossRefGoogle ScholarPubMed
120. Barker, DJ, Gelow, J, Thornburg, K, et al. The early origins of chronic heart failure: impaired placental growth and initiation of insulin resistance in childhood. Eur J Heart Fail. 2010; 12, 819–825.Google Scholar
121. van Abeelen, AF, de Rooij, SR, Osmond, C, et al. The sex-specific effects of famine on the association between placental size and later hypertension. Placenta. 2011; 32, 694–698.CrossRefGoogle ScholarPubMed
122. Barker, DJ, Osmond, C, Forsen, TJ, et al. Foetal and childhood growth and asthma in adult life. Acta Paediatr. 2013; 102, 732–738.Google Scholar
123. Barker, DJ, Thornburg, KL, Osmond, C, Kajantie, E, Eriksson, JG. The prenatal origins of lung cancer. II. The placenta. Am J Hum Biol. 2010; 22, 512–516.Google Scholar
124. Barker, DJ, Osmond, C, Thornburg, KL, Kajantie, E, Eriksson, JG. The shape of the placental surface at birth and colorectal cancer in later life. Am J Hum Biol. 2013; 25, 566–568.Google Scholar
125. Barker, DJ, Osmond, C, Thornburg, KL, Kajantie, E, Eriksson, JG. The intrauterine origins of Hodgkin’s lymphoma. Cancer Epidemiol. 2013; 37, 321–323.Google Scholar