title: The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders.
abstract: The developing immune system and central nervous system in the fetus and child are extremely sensitive to both exogenous and endogenous signals. Early immune system programming, leading to changes that can persist over the life course, has been suggested, and other evidence suggests that immune dysregulation in the early developing brain may play a role in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. The timing of immune dysregulation with respect to gestational age and neurologic development of the fetus may shape the elicited response. This creates a possible sensitive window of programming or vulnerability. This review will explore the effects of maternal prenatal and infant nutritional status (from conception until early childhood) as well as maternal prenatal stress and anxiety on early programming of immune function, and how this might influence neurodevelopment. We will describe fetal immune system development and maternal-fetal immune interactions to provide a better context for understanding the influence of nutrition and stress on the immune system. Finally, we will discuss the implications for prevention of neurodevelopmental disorders, with a focus on nutrition. Although certain micronutrient supplements have shown to both reduce the risk of neurodevelopmental disorders and enhance fetal immune development, we do not know whether their impact on immune development contributes to the preventive effect on neurodevelopmental disorders. Future studies are needed to elucidate this relationship, which may contribute to a better understanding of preventative mechanisms. Integrating studies of neurodevelopmental disorders and prenatal exposures with the simultaneous evaluation of neural and immune systems will shed light on mechanisms that underlie individual vulnerability or resilience to neurodevelopmental disorders and ultimately contribute to the development of primary preventions and early interventions.
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University New York, NY, USA ; Institute of Human Nutrition, Columbia University New York, NY, USA.
authors.forename: Andrea Horvath
authors.initials: AH
authors.lastname: Marques
authors.forename: Thomas G
authors.initials: TG
authors.lastname: O'Connor
authors.forename: Christine
authors.initials: C
authors.lastname: Roth
authors.forename: Ezra
authors.initials: E
authors.lastname: Susser
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Bjørke-Monsen
keywords: anxiety; immunology; mental health; neurodevelopmental disorders; nutrition; programming; psychiatric disorders; stress
references.citation: Annu Rev Immunol. 2013;31:387-411
references.pmid: 23298207
references.citation: Nat Med. 2009 Jan;15(1):91-6
references.pmid: 19079257
references.citation: Brain Behav Immun. 2013 Aug;32:21-8
references.pmid: 23439080
references.citation: Int J Dev Biol. 2010;54(2-3):531-43
references.pmid: 19924635
references.citation: Schizophr Bull. 2011 Mar;37(2):284-90
references.pmid: 21134972
references.citation: Nat Rev Endocrinol. 2011 Feb;7(2):89-97
references.pmid: 21178998
references.citation: JAMA Psychiatry. 2013 Jun;70(6):573-81
references.pmid: 23894747
references.citation: Allergy. 2012 Jun;67(6):718-25
references.pmid: 22519427
references.citation: Pediatrics. 2012 Jul;130(1):e152-8
references.pmid: 22711729
references.citation: J Allergy Clin Immunol. 2009 Nov;124(5):954-60
references.pmid: 19748657
references.citation: J Allergy Clin Immunol. 2007 Jan;119(1):81-8
references.pmid: 17208588
references.citation: J Immunol. 1994 May 15;152(10):4903-11
references.pmid: 8176211
references.citation: Brain Behav Immun. 2013 Jul;31:54-68
references.pmid: 22841693
references.citation: Immunol Invest. 2008;37(5):535-64
references.pmid: 18716937
references.citation: J Child Psychol Psychiatry. 2007 Mar-Apr;48(3-4):245-61
references.pmid: 17355398
references.citation: PLoS One. 2008 Apr 30;3(4):e2078
references.pmid: 18446208
references.citation: J Am Acad Child Adolesc Psychiatry. 2013 May;52(5):519-26
references.pmid: 23622853
references.citation: Pediatr Allergy Immunol. 2011 Sep;22(6):608-13
references.pmid: 21781174
references.citation: Glia. 2001 Nov;36(2):145-55
references.pmid: 11596123
references.citation: Brain Behav Immun. 1995 Mar;9(1):31-46
references.pmid: 7620209
references.citation: J Toxicol Environ Health B Crit Rev. 2008 Oct;11(8):660-80
references.pmid: 18821424
references.citation: Science. 2003 Feb 14;299(5609):1057-61
references.pmid: 12522256
references.citation: Chimerism. 2011 Jul;2(3):71-7
references.pmid: 22163064
references.citation: Biol Psychiatry. 2010 Jun 1;67(11):1026-32
references.pmid: 20188350
references.citation: Epidemiology. 2012 Mar;23(2):257-63
references.pmid: 22081060
references.citation: Pediatrics. 2013 Mar;131(3):e687-94
references.pmid: 23420914
references.citation: Br J Nutr. 2001 May;85 Suppl 2:S81-6
references.pmid: 11509094
references.citation: Pediatrics. 2003 Sep;112(3 Pt 1):e177-83
references.pmid: 12949309
references.citation: J Exp Med. 1999 Jul 19;190(2):157-67
references.pmid: 10432279
references.citation: Biol Reprod. 2009 May;80(5):1036-45
references.pmid: 19164169
references.citation: J Immunol. 2012 Sep 15;189(6):2869-78
references.pmid: 22869901
references.citation: JAMA. 2011 Oct 12;306(14):1566-73
references.pmid: 21990300
references.citation: Environ Sci Technol. 2010 Sep 15;44(18):7123-9
references.pmid: 20722423
references.citation: Arch Gen Psychiatry. 2010 Sep;67(9):889-94
references.pmid: 20819982
references.citation: Psychosom Med. 2012 Jul-Aug;74(6):635-41
references.pmid: 22753636
references.citation: Vet Immunol Immunopathol. 2009 Sep 15;131(1-2):17-24
references.pmid: 19362376
references.citation: Pediatrics. 2008 Nov;122(5):1142-52
references.pmid: 18977996
references.citation: Blood. 2010 Oct 14;116(15):2706-12
references.pmid: 20628146
references.citation: Am J Psychiatry. 2000 Mar;157(3):438-43
references.pmid: 10698821
references.citation: J Clin Invest. 1999 Jul;104(1):41-7
references.pmid: 10393697
references.citation: Vaccine. 2001 Dec 12;20(5-6):647-50
references.pmid: 11738729
references.citation: Lancet. 2001 Nov 10;358(9293):1602-7
references.pmid: 11716887
references.citation: Clin Rev Allergy Immunol. 2013 Oct;45(2):217-26
references.pmid: 23359064
references.citation: Ann N Y Acad Sci. 2004 Jun;1024:138-46
references.pmid: 15265778
references.citation: Pediatr Res. 2008 Mar;63(3):292-8
references.pmid: 18287968
references.citation: Cell Immunol. 1999 Sep 15;196(2):122-30
references.pmid: 10527564
references.citation: J Clin Invest. 2007 Jun;117(6):1637-46
references.pmid: 17549258
references.citation: Immunity. 1995 Dec;3(6):793-800
references.pmid: 8777724
references.citation: Int Rev Immunol. 2002 Nov-Dec;21(6):471-95
references.pmid: 12650238
references.citation: Biol Reprod. 2010 Sep;83(3):325-31
references.pmid: 20445129
references.citation: Psychoneuroendocrinology. 2011 Apr;36(3):426-36
references.pmid: 21041030
references.citation: Nutrients. 2013 Feb 06;5(2):424-40
references.pmid: 23389302
references.citation: Brain Behav Immun. 2008 Aug;22(6):933-40
references.pmid: 18308510
references.citation: Psychoneuroendocrinology. 2009 Apr;34(3):430-5
references.pmid: 19019559
references.citation: Baillieres Clin Obstet Gynaecol. 1992 Sep;6(3):417-38
references.pmid: 1446416
references.citation: Am J Clin Nutr. 2009 Feb;89(2):673S-7S
references.pmid: 19116320
references.citation: Ann N Y Acad Sci. 2004 Dec;1032:63-84
references.pmid: 15677396
references.citation: J Child Psychol Psychiatry. 2013 Feb;54(2):115-30
references.pmid: 23039359
references.citation: Am J Med Genet A. 2005 Jun 1;135(2):120-5
references.pmid: 15846825
references.citation: Am J Epidemiol. 1996 Mar 15;143(6):588-96
references.pmid: 8610676
references.citation: Environ Sci Technol. 2010 Dec 15;44(24):9550-6
references.pmid: 21090747
references.citation: Schizophr Bull. 2008 Nov;34(6):1054-63
references.pmid: 18682377
references.citation: Brain Behav Immun. 2007 Mar;21(3):343-50
references.pmid: 17029703
references.citation: Ann Nutr Metab. 2012;61 Suppl 1:8-17
references.pmid: 23343943
references.citation: N Engl J Med. 2007 Jul 12;357(2):135-42
references.pmid: 17625125
references.citation: Ann Nutr Metab. 2007;51(4):301-23
references.pmid: 17726308
references.citation: Brain Behav Immun. 2008 Jan;22(1):42-51
references.pmid: 17716859
references.citation: Cell. 1990 Sep 7;62(5):863-74
references.pmid: 1975515
references.citation: J Exp Med. 2007 Aug 6;204(8):1775-85
references.pmid: 17620362
references.citation: Trends Immunol. 2006 Sep;27(9):399-404
references.pmid: 16843067
references.citation: Semin Fetal Neonatal Med. 2013 Jun;18(3):129-135
references.pmid: 23415843
references.citation: Nutr Neurosci. 2011 Sep;14(5):216-25
references.pmid: 22005286
references.citation: Am J Clin Nutr. 2009 Feb;89(2):668S-72S
references.pmid: 19088150
references.citation: Transplantation. 2010 Sep 15;90(5):465-74
references.pmid: 20555306
references.citation: Curr Opin Allergy Clin Immunol. 2009 Oct;9(5):417-26
references.pmid: 19652594
references.citation: Brain Behav Immun. 2006 Jul;20(4):378-88
references.pmid: 16378711
references.citation: N Engl J Med. 1992 Dec 24;327(26):1832-5
references.pmid: 1307234
references.citation: Leuk Lymphoma. 2003 Nov;44(11):1881-91
references.pmid: 14738139
references.citation: Nat Rev Immunol. 2009 Jun;9(6):449-56
references.pmid: 19424277
references.citation: Curr Opin Clin Nutr Metab Care. 2012 Nov;15(6):605-13
references.pmid: 23075938
references.citation: Clin Sci (Lond). 2007 Jul;113(1):1-13
references.pmid: 17536998
references.citation: Neuroimmunomodulation. 2008;15(1):19-28
references.pmid: 18667796
references.citation: Dev Psychobiol. 2011 Apr;53(3):221-33
references.pmid: 21400485
references.citation: Environ Health Perspect. 2010 Jun;118(6):796-802
references.pmid: 20146964
references.citation: Dev Psychopathol. 2011 Nov;23(4):1139-47
references.pmid: 22018086
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 7;103(10):3938-42
references.pmid: 16495411
references.citation: Brain Behav Immun. 2011 May;25(4):604-15
references.pmid: 21195166
references.citation: Brain Behav Immun. 2012 Mar;26(3):393
references.pmid: 22001185
references.citation: Psychoneuroendocrinology. 2013 Sep;38(9):1630-8
references.pmid: 23433748
references.citation: Front Neuroendocrinol. 2013 Jan;34(1):47-64
references.pmid: 22796576
references.citation: N Engl J Med. 2000 Jul 6;343(1):37-49
references.pmid: 10882768
references.citation: J Clin Endocrinol Metab. 2002 Feb;87(2):675-81
references.pmid: 11836303
references.citation: Curr Psychiatry Rep. 2011 Dec;13(6):467-75
references.pmid: 21927805
references.citation: J Clin Invest. 1984 Aug;74(2):657-61
references.pmid: 6611355
references.citation: Chest. 2011 Mar;139(3):640-647
references.pmid: 21362650
references.citation: Clin Perinatol. 2008 Dec;35(4):643-63, v
references.pmid: 19026332
references.citation: Pediatr Allergy Immunol. 2010 Feb;21(1 Pt 1):14-21
references.pmid: 19490478
references.citation: Immunol Allergy Clin North Am. 2009 May;29(2):247-64
references.pmid: 19389580
references.citation: Behav Brain Res. 2009 Dec 7;204(2):313-21
references.pmid: 19136031
references.citation: Soc Sci Med. 2013 Nov;97:325-30
references.pmid: 23557675
references.citation: Brain Behav Immun. 2013 Feb;28:196-206
references.pmid: 23207108
references.citation: Dev Neurosci. 2009;31(4):285-92
references.pmid: 19546565
references.citation: Proc Nutr Soc. 2010 Feb;69(1):1-10
references.pmid: 19968902
references.citation: J Affect Disord. 2004 May;80(1):65-73
references.pmid: 15094259
references.citation: Brain Behav Immun. 2010 Aug;24(6):881-97
references.pmid: 20230889
references.citation: Schizophr Bull. 2000;26(2):287-95
references.pmid: 10885631
references.citation: Proc Natl Acad Sci U S A. 2012 May 15;109(20):E1312-9
references.pmid: 22529357
references.citation: Vaccine. 2004 Jan 2;22(3-4):511-9
references.pmid: 14670334
references.citation: Prog Neurobiol. 2010 Mar;90(3):285-326
references.pmid: 19857543
references.citation: Ann N Y Acad Sci. 1998 May 1;840:45-50
references.pmid: 9629235
references.citation: Schizophr Bull. 2009 Sep;35(5):959-72
references.pmid: 18408229
references.citation: Cell. 1986 Nov 7;47(3):349-57
references.pmid: 3490311
references.citation: Birth Defects Res A Clin Mol Teratol. 2005 Oct;73(10):679-89
references.pmid: 16240378
references.citation: Psychosom Med. 2011 Oct;73(8):656-63
references.pmid: 21949424
references.citation: JAMA. 1993 Feb 17;269(7):898-903
references.pmid: 8426449
references.citation: Ann N Y Acad Sci. 2009 Oct;1179:1-18
references.pmid: 19906229
references.citation: Am J Clin Nutr. 2012 Jul;96(1):80-9
references.pmid: 22648721
references.citation: J Obstet Gynaecol Can. 2009 Sep;31(9):875-881
references.pmid: 19941713
references.citation: Adv Immunol. 2012;115:73-111
references.pmid: 22608256
references.citation: Am J Epidemiol. 1998 Feb 1;147(3):213-6
references.pmid: 9482494
references.citation: Curr Opin Rheumatol. 1998 Nov;10(6):564-71
references.pmid: 9812217
references.citation: Adv Nutr. 2011 Sep;2(5):377-95
references.pmid: 22332080
references.citation: J Immunol. 2004 Sep 1;173(5):2909-12
references.pmid: 15322146
references.citation: Biol Psychiatry. 2011 Mar 15;69(6):520-5
references.pmid: 21126730
references.citation: Psychosom Med. 2013 Jun;75(5):449-52
references.pmid: 23576771
references.citation: Nat Immunol. 2005 Jan;6(1):73-9
references.pmid: 15592472
references.citation: Am J Reprod Immunol. 1996 Nov;36(5):248-55
references.pmid: 8955500
references.citation: Nature. 2012 Nov 29;491(7426):717-23
references.pmid: 23051753
references.citation: Dev Psychobiol. 2013 Mar;55(2):145-55
references.pmid: 22315044
references.citation: Pediatrics. 1962 Apr;29:539-49
references.pmid: 14473162
references.citation: J Hum Lact. 2013 May;29(2):163-70
references.pmid: 23458952
references.citation: Science. 2013 Mar 1;339(6123):1222002
references.pmid: 23449594
references.citation: JAMA. 2001 Jun 20;285(23):2981-6
references.pmid: 11410096
references.citation: Nat Genet. 2003 Mar;33 Suppl:245-54
references.pmid: 12610534
references.citation: Neuron. 2009 Oct 15;64(1):25-7
references.pmid: 19840544
references.citation: Vaccine. 2003 Jul 28;21(24):3365-9
references.pmid: 12850341
references.citation: Early Hum Dev. 2003 Nov;74(2):125-38
references.pmid: 14580752
references.citation: N Engl J Med. 1999 Nov 11;341(20):1485-90
references.pmid: 10559448
references.citation: Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):705-8
references.pmid: 8570620
references.citation: J Leukoc Biol. 2011 Oct;90(4):703-16
references.pmid: 21873457
references.citation: Dev Psychobiol. 2008 Sep;50(6):579-87
references.pmid: 18683180
references.citation: Pediatrics. 2004 Apr;113(4):733-7
references.pmid: 15060220
references.citation: Allergy. 2008 Nov;63(11):1473-80
references.pmid: 18925884
references.citation: Int Immunol. 1992 Feb;4(2):243-52
references.pmid: 1377947
references.citation: Blood. 2003 Jun 15;101(12):5076-83
references.pmid: 12609834
references.citation: Arch Dis Child. 1992 Aug;67(8):1003-7
references.pmid: 1520001
references.citation: Autoimmun Rev. 2013 Aug;12(10):976-89
references.pmid: 23542507
references.citation: Arch Gen Psychiatry. 2004 Aug;61(8):774-80
references.pmid: 15289276
references.citation: Cleve Clin J Med. 2009 Apr;76 Suppl 2:S23-6
references.pmid: 19376977
references.citation: Trends Immunol. 2012 Aug;33(8):421-7
references.pmid: 22609148
references.citation: J Trace Elem Med Biol. 2013 Jul;27(3):174-83
references.pmid: 23395294
references.citation: J Child Psychol Psychiatry. 2011 Feb;52(2):119-29
references.pmid: 20854366
references.citation: Schizophr Bull. 2000;26(2):257-73
references.pmid: 10885629
references.citation: Neuropsychopharmacology. 2008 Feb;33(3):536-45
references.pmid: 17507916
references.citation: Am J Respir Crit Care Med. 2010 Jul 1;182(1):25-33
references.pmid: 20194818
references.citation: Environ Health Perspect. 2006 Apr;114(4):477-83
references.pmid: 16581533
references.citation: Mol Psychiatry. 2005 Mar;10(3):239-50
references.pmid: 15685252
references.citation: Environ Health. 2010 Aug 23;9:51
references.pmid: 20731829
references.citation: Br J Nutr. 2006 Oct;96(4):774-90
references.pmid: 17010239
references.citation: Mucosal Immunol. 2010 Jul;3(4):326-33
references.pmid: 20485330
references.citation: Dev Neurobiol. 2012 Oct;72(10):1327-34
references.pmid: 22911883
references.citation: Thyroid. 2011 Aug;21(8):879-90
references.pmid: 21745103
references.citation: Am J Epidemiol. 2011 May 1;173(9):990-7
references.pmid: 21389042
references.citation: Epidemiol Psichiatr Soc. 2005 Oct-Dec;14(4):194-7
references.pmid: 16396427
references.citation: Teratology. 2002 Jul;66(1):33-9
references.pmid: 12115778
references.citation: Pharmacol Ther. 2011 May;130(2):226-38
references.pmid: 21334376
references.citation: J Child Psychol Psychiatry. 2003 Sep;44(6):810-8
references.pmid: 12959490
references.citation: Neuropharmacology. 2013 Jan;64:550-65
references.pmid: 22841917
references.citation: J Clin Invest. 2003 Jun;111(11):1747-55
references.pmid: 12782677
references.citation: Pharmacol Ther. 2011 Oct;132(1):96-110
references.pmid: 21704074
references.citation: Psychoneuroendocrinology. 2012 Jun;37(6):818-26
references.pmid: 22001010
references.citation: Clin Exp Immunol. 2003 Mar;131(3):498-505
references.pmid: 12605704
references.citation: Physiol Behav. 1998 Feb 1;63(3):397-402
references.pmid: 9469733
references.citation: J Epidemiol Community Health. 2001 Aug;55(8):537-46
references.pmid: 11449010
references.citation: Viral Immunol. 2005;18(1):41-78
references.pmid: 15802953
references.citation: Brain Behav Immun. 1996 Sep;10(3):221-34
references.pmid: 8954595
references.citation: Br J Nutr. 2012 Oct 28;108(8):1443-54
references.pmid: 22348468
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 30;104(5):1637-42
references.pmid: 17244711
references.citation: Am J Obstet Gynecol. 1993 Oct;169(4):858-65
references.pmid: 8238139
references.citation: J Epidemiol Community Health. 2010 Jul;64(7):636-42
references.pmid: 19828512
references.citation: Proc Natl Acad Sci U S A. 2007 Dec 11;104(50):19966-70
references.pmid: 18077428
references.citation: Lancet. 2011 Jun 11;377(9782):2007-12
references.pmid: 21640375
references.citation: Neuron. 2009 Oct 15;64(1):61-78
references.pmid: 19840550
references.citation: Matern Child Health J. 2001 Jun;5(2):127-34
references.pmid: 11573838
references.citation: Arch Gen Psychiatry. 1996 Jan;53(1):25-31
references.pmid: 8540774
references.citation: Eur J Immunol. 2005 Feb;35(2):383-90
references.pmid: 15682453
references.citation: Nat Med. 2004 Aug;10(8):801-5
references.pmid: 15286781
references.citation: J Pediatr. 2013 Apr;162(4):832-838.e3
references.pmid: 23140881
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 26;110(9):3507-12
references.pmid: 23401516
references.citation: J Clin Invest. 2010 May;120(5):1603-16
references.pmid: 20424322
references.citation: Nat Med. 2006 Sep;12(9):1065-74
references.pmid: 16892062
references.citation: Front Behav Neurosci. 2009 Aug 24;3:14
references.pmid: 19738918
references.citation: Psychoneuroendocrinology. 2013 Jul;38(7):1112-21
references.pmid: 23265310
references.citation: PLoS One. 2009 Nov 16;4(11):e7845
references.pmid: 19924280
references.citation: Trends Mol Med. 2011 Jul;17(7):389-94
references.pmid: 21482187
references.citation: J Physiol. 2004 Jul 1;558(Pt 1):263-75
references.pmid: 15133062
references.citation: N Engl J Med. 2013 Jan 31;368(5):425-35
references.pmid: 23363496
references.citation: Int J Dev Biol. 2010;54(2-3):421-30
references.pmid: 19876825
references.citation: Lancet. 1991 Jul 20;338(8760):131-7
references.pmid: 1677062
references.citation: Proc Nutr Soc. 2012 Feb;71(1):154-65
references.pmid: 22124338
references.citation: Clin Exp Immunol. 2010 Jan;159(1):65-72
references.pmid: 19860744
references.citation: Immunol Rev. 2011 May;241(1):20-38
references.pmid: 21488887
references.citation: Eur J Pharmacol. 2011 Sep;668 Suppl 1:S16-32
references.pmid: 21816150
references.citation: Nat Immunol. 2011 Mar;12(3):189-94
references.pmid: 21321588
references.citation: Front Neuroendocrinol. 2012 Aug;33(3):267-86
references.pmid: 22982535
references.citation: Mol Cell Neurosci. 2013 Mar;53:69-76
references.pmid: 23069728
references.citation: Immunol Rev. 1997 Feb;155:105-17
references.pmid: 9059886
references.citation: Biol Psychiatry. 2011 Nov 15;70(10):906-7
references.pmid: 22018354
references.citation: J Autism Dev Disord. 2010 Dec;40(12):1423-30
references.pmid: 20414802
references.citation: J Psychiatr Res. 2009 Jul;43(11):962-9
references.pmid: 19552919
references.citation: Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):11032-7
references.pmid: 11005874
references.citation: Immunol Today. 1993 Jul;14(7):353-6
references.pmid: 8363725
references.citation: Br J Nutr. 2011 Jul;106(2):183-95
references.pmid: 21486513