Maternal obesity and neurodevelopmental and psychiatric disorders in offspring.
There is a growing body of evidence from both human epidemiologic and animal studies that prenatal and lactational exposure to maternal obesity and high-fat diet are associated with neurodevelopmental and psychiatric disorders in offspring. These disorders include cognitive impairment, autism spectrum disorders, attention deficit hyperactivity disorder, cerebral palsy, anxiety and depression, schizophrenia, and eating disorders. This review synthesizes human and animal data linking maternal obesity and high-fat diet consumption to abnormal fetal brain development and neurodevelopmental and psychiatric morbidity in offspring. In addition, it highlights key mechanisms by which maternal obesity and maternal diet might impact fetal and offspring neurodevelopment, including neuroinflammation; increased oxidative stress, dysregulated insulin, glucose, and leptin signaling; dysregulated serotonergic and dopaminergic signaling; and perturbations in synaptic plasticity. Finally, the review summarizes available evidence regarding investigational therapeutic approaches to mitigate the harmful effects of maternal obesity on fetal and offspring neurodevelopment. © 2016 John Wiley & Sons, Ltd.
Division of Maternal-Fetal Medicine, Department of Ob/Gyn, Tufts Medical Center, Boston, MA, USA.|Mother Infant Research Institute, Tufts Medical Center, Boston, MA, USA.
Andrea G
AG
Edlow
D000818:Animals; D005260:Female; D006801:Humans; D065886:Neurodevelopmental Disorders / Q000209:etiology* / Q000517:prevention & control; D009765:Obesity; D011247:Pregnancy; D011248:Pregnancy Complications; D011296:Prenatal Diagnosis
Mol Autism. 2011 Aug 02;2:13
21810230
J Child Psychol Psychiatry. 2010 Feb;51(2):134-43
19674195
J Neuroinflammation. 2014 Sep 12;11:156
25212412
Semin Fetal Neonatal Med. 2010 Apr;15(2):70-6
19896913
Behav Brain Res. 2014 Jul 1;267:178-88
24667364
J Pediatr. 2013 Nov;163(5):1307-12
23932316
Acta Psychiatr Scand. 2004 Oct;110(4):257-63
15352926
Am J Epidemiol. 2008 Jan 15;167(2):169-77
18024987
Int J Dev Neurosci. 2009 Nov;27(7):627-33
19695321
Am J Psychiatry. 1998 Mar;155(3):355-64
9501745
FASEB J. 2009 Jun;23(6):1920-34
19158155
Neuroscience. 2002;112(4):803-14
12088740
Obesity (Silver Spring). 2013 Jan;21(1):E124-30
23505192
Neuroendocrinology. 1997 Sep;66(3):145-50
9380271
J Autism Dev Disord. 2011 Jul;41(7):891-902
20922473
Am J Epidemiol. 2013 Jul 15;178(2):209-20
23813699
Lancet Diabetes Endocrinol. 2015 Oct;3(10):778-86
26165398
Am J Physiol Regul Integr Comp Physiol. 2010 Sep;299(3):R711-22
20631295
Placenta. 2015 Aug;36(8):903-10
26145226
N Engl J Med. 2016 Feb 4;374(5):434-43
26840133
Int J Dev Neurosci. 2012 Apr;30(2):75-81
22239918
Endocrinology. 2011 Aug;152(8):3192-201
21652728
Int J Dev Neurosci. 1997 Oct;15(6):711-6
9402221
Mol Cell Endocrinol. 2001 May 25;177(1-2):125-34
11377828
FASEB J. 2010 Jun;24(6):2104-15
20124437
Psychosom Med. 2016 Sep;78(7):861-6
27136499
Circulation. 2012 Mar 20;125(11):1381-9
22344037
Endocrinology. 2010 Apr;151(4):1622-32
20176722
Placenta. 2014 Mar;35(3):171-7
24484739
Horm Behav. 2015 Nov;76:153-61
25913366
PLoS One. 2015 Sep 04;10(9):e0137309
26340264
CNS Spectr. 2009 Jul;14(7):372-83
19773713
PLoS One. 2013 Jun 25;8(6):e67791
23825686
Int J Obes (Lond). 2009 Feb;33(2):257-66
19125163
Metab Brain Dis. 2013 Dec;28(4):721-5
24043569
Horm Behav. 2015 Nov;76:143-52
26145566
J Biol Chem. 1999 Dec 3;274(49):34893-902
10574963
Neurochem Int. 2010 Oct;57(3):235-47
20538025
Int J Epidemiol. 2014 Feb;43(1):83-90
24058000
Am J Clin Nutr. 2008 Jun;87(6):1750-9
18541565
Neurobiol Dis. 2009 Jul;35(1):3-13
19374947
PLoS One. 2014 Feb 18;9(2):e88661
24558408
BJOG. 2012 Feb;119(3):283-90
22168897
Can J Psychiatry. 2012 Jul;57(7):422-8
22762297
Behav Brain Res. 2012 Aug 1;233(2):398-404
22633920
Int J Obes (Lond). 2012 Oct;36(10):1312-9
22964791
Front Neurosci. 2015 Jun 18;9:194
26150767
Best Pract Res Clin Obstet Gynaecol. 2015 Apr;29(3):438-48
25497183
Obesity (Silver Spring). 2007 Apr;15(4):986-93
17426334
Pediatrics. 2016 Feb;137(2):e20152206
26826214
Nat Rev Neurosci. 2013 Jun;14(6):401-16
23674053
Pediatr Res. 2016 Jan;79(1-1):3-12
26375474
J Clin Endocrinol Metab. 2002 Sep;87(9):4231-7
12213876
Physiol Behav. 2015 Dec 1;152(Pt B):363-71
26066731
Pediatrics. 2011 Jan;127(1):e202-11
21187310
Schizophr Bull. 2000;26(2):275-86
10885630
Eur J Obstet Gynecol Reprod Biol. 2013 Jul;169(1):39-44
23453296
J Child Psychol Psychiatry. 2005 Apr;46(4):385-93
15819647
Pediatrics. 2011 Jun;127(6):1034-42
21606152
Nutr Neurosci. 2013 May;16(3):96-103
23006985
Am J Obstet Gynecol. 2013 Aug;209(2):136.e1-9
23659985
J Dev Behav Pediatr. 2014 Feb-Mar;35(2):118-27
24509056
Int J Dev Neurosci. 2011 Oct;29(6):663-71
21382466
Neuroscience. 2011 Mar 10;176:225-36
21187125
Br J Psychiatry. 1998 Jul;173:11-53
9850203
BJOG. 2016 Jan;123(2):180-9
26840378
Metabolism. 2005 Apr;54(4):500-7
15798958
Pediatrics. 2013 Nov;132(5):e1276-83
24167172
Neurobiol Dis. 2014 Jul;67:79-87
24686304
Acta Obstet Gynecol Scand. 2003 Mar;82(3):235-40
12694119
Curr Opin Clin Nutr Metab Care. 2006 Jul;9(4):388-94
16778567
Endocrinology. 2010 Oct;151(10):4756-64
20685869
BMC Pregnancy Childbirth. 2014 Apr 26;14:148
24767604
Br J Nutr. 2007 Oct;98(4):843-51
17697422
J Child Neurol. 2014 Dec;29(12):NP196-201
24334343
J Perinatol. 2014 Sep;34(9):688-92
24811227
Aging (Albany NY). 2016 May;8(5):899-916
27070252
Am J Obstet Gynecol. 2016 May;214(5):623.e1-623.e10
26945603
Physiol Behav. 2014 Jan 17;123:236-42
23085399
JAMA. 2014 Feb 26;311(8):806-14
24570244
Physiol Behav. 2011 May 3;103(2):164-72
21241725
Biol Reprod. 2014 Jun;90(6):129
24759787
J Public Health (Oxf). 2015 Sep;37(3):419-26
25174039
Child Psychiatry Hum Dev. 2009 Dec;40(4):517-26
19404733
Nutr J. 2005 May 12;4:17
15890076
J Pediatr. 2014 Nov;165(5):891-6
25155965
PLoS One. 2013 Nov 13;8(11):e79200
24236109
Med Hypotheses. 2014 Jun;82(6):654-61
24685108
PLoS One. 2014 Apr 11;9(4):e94498
24727836
Arch Gen Psychiatry. 2006 Jul;63(7):824-30
16818872
Paediatr Perinat Epidemiol. 2016 Sep;30(5):479-87
27239935
Can J Psychiatry. 2013 Mar;58(3):151-9
23461886
J Abnorm Psychol. 2013 Aug;122(3):720-32
24016012
Int J Epidemiol. 2015 Jun;44(3):870-83
26045508
Neuroreport. 1996 Nov 4;7(15-17):2635-8
8981437
JAMA Psychiatry. 2014 Jan;71(1):81-90
24285382
Pediatrics. 2013 Jan;131(1):56-63
23230067
J Clin Invest. 2004 Dec;114(12):1752-61
15599400
Behav Pharmacol. 2012 Sep;23(5-6):582-92
22797467
Eur J Obstet Gynecol Reprod Biol. 2016 Jun;201:203-8
27160501
Psychoneuroendocrinology. 2012 Jul;37(7):956-69
22133515
Pediatrics. 2012 May;129(5):e1121-8
22492772
Obstet Gynecol. 2010 Aug;116(2 Pt 1):387-92
20664400
Am J Physiol Regul Integr Comp Physiol. 2014 Apr 15;306(8):R527-37
24523341
Am J Clin Nutr. 2011 Dec;94(6 Suppl):1980S-1985S
21613560
Pediatrics. 2014 May;133(5):e1128-38
24709932
Prim Care Companion CNS Disord. 2014;16(2):null
25133052
FASEB J. 2009 Jan;23(1):271-8
18827021
Am J Obstet Gynecol. 2006 Jun;194(6):1537-45
16731069
FASEB J. 2011 Jul;25(7):2167-79
21427213
Stress. 2013 Sep;16(5):540-8
23786443
Br J Nutr. 2007 Jan;97(1):176-81
17217574
JAMA. 2016 Jun 7;315(21):2284-91
27272580
Acta Paediatr. 1997 Sep;86(9):969-74
9343277
Int J Obes (Lond). 2008 Mar;32(3):550-7
17938639
Am J Health Promot. 2014 Jan-Feb;28(3):181-8
23875984
Neuroreport. 2007 Jan 22;18(2):137-40
17301678
Placenta. 2008 Mar;29(3):274-81
18262644
Arch Gen Psychiatry. 2001 Jan;58(1):48-52
11146757
Int J Epidemiol. 2014 Jun;43(3):783-92
24569381
BJOG. 2013 May;120(6):724-31
23418811
Neuroscience. 2004;123(2):429-40
14698750
Int J Eat Disord. 1999 May;25(4):375-87
10202648
Int Heart J. 2015;56(1):110-5
25503654
Neuroscience. 2014 Jan 3;256:53-60
24157927
Int J Dev Neurosci. 2013 Dec;31(8):731-9
24071008
PLoS One. 2012;7(6):e37758
22719848
Psychiatry Res. 2008 Sep 30;160(3):263-70
18710786
J Nutr. 1998 Dec;128(12):2505-11
9868200
JAMA Pediatr. 2015 Feb;169(2):154-62
25485869
Matern Child Health J. 2013 Feb;17(2):222-9
22350633
J Neurosci. 2010 Mar 10;30(10):3826-30
20220017
J Physiol. 2016 Mar 1;594(5):1483-99
26662841