The impact of maternal obesity on childhood neurodevelopment

Abstract

There is growing clinical and experimental evidence to suggest that maternal obesity increases children’s susceptibility to neurodevelopmental and neuropsychiatric disorders. Given the worldwide obesity epidemic, it is crucial that we acquire a thorough understanding of the available evidence, identify gaps in knowledge, and develop an agenda for intervention. This review synthesizes human and animal studies investigating the association between maternal obesity and offspring brain health. It also highlights key mechanisms underlying these effects, including maternal and fetal inflammation, alterations to the microbiome, epigenetic modifications of neurotrophic genes, and impaired dopaminergic and serotonergic signaling. Lastly, this review highlights several proposed interventions and priorities for future investigation.

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Fig. 1: Potential mechanisms underlying the effects of maternal obesity on offspring neurodevelopment.

References

  1. 1.

    Branum AM, Kirmeyer SE, Gregory ECW. Prepregnancy body mass index by maternal characteristics and state: data from the birth certificate, 2014. Natl Vital- Stat Rep. 2016;65:1–11.

    PubMed  Google Scholar 

  2. 2.

    Johnson JL, Farr SL, Dietz PM, Sharma AJ, Barfield WD, Robbins CL. Trends in gestational weight gain: the Pregnancy Risk Assessment Monitoring System, 2000—2009. Am J Obstet Gynecol. 2015;212:806.e1–e8.

    Article  Google Scholar 

  3. 3.

    Rowlands I, Graves N, de Jersey S, McIntyre HD, Callaway L. Obesity in pregnancy: outcomes and economics. Semin Fetal Neonatal Med. 2010;15:94–99.

    PubMed  Article  Google Scholar 

  4. 4.

    Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115:290–6.

    Article  Google Scholar 

  5. 5.

    Godfrey KM, Reynolds RM, Prescott SL, Nyirenda M, Jaddoe VWV, Eriksson JG, et al. Influence of maternal obesity on the long-term health of offspring. Lancet Diabetes Endocrinol. 2017;5:53–64.

    PubMed  PubMed Central  Article  Google Scholar 

  6. 6.

    Coo H, Fabrigar L, Davies G, Fitzpatrick R, Flavin M. Are observed associations between a high maternal prepregnancy body mass index and offspring IQ likely to be causal? J Epidemiol Community Health. 2019;73:920–8.

    PubMed  Article  Google Scholar 

  7. 7.

    Huang L, Yu X, Keim S, Li L, Zhang L, Zhang J. Maternal prepregnancy obesity and child neurodevelopment in the Collaborative Perinatal Project. Int J Epidemiol. 2014;43:783–92.

    PubMed  Article  Google Scholar 

  8. 8.

    Pugh SJ, Richardson GA, Hutcheon JA, Himes KP, Brooks MM, Day NL, et al. Maternal Obesity and Excessive Gestational Weight Gain Are Associated with Components of Child Cognition. J Nutr. 2015;145:2562–9.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  9. 9.

    Pugh SJ, Hutcheon JA, Richardson GA, Brooks MM, Himes KP, Day NL, et al. Child academic achievement in association with pre-pregnancy obesity and gestational weight gain. J Epidemiol Community Health. 2016;70:534–40.

    PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Tanda R, Salsberry PJ, Reagan PB, Fang MZ. The Impact of Prepregnancy Obesity on Children’s Cognitive Test Scores. Matern Child Health J. 2013;17:222–9.

    PubMed  PubMed Central  Article  Google Scholar 

  11. 11.

    Torres-Espinola FJ, Berglund SK, García-Valdés LM, Segura MT, Jerez A, Campos D, et al. Maternal Obesity, Overweight and Gestational Diabetes Affect the Offspring Neurodevelopment at 6 and 18 Months of Age – A Follow Up from the PREOBE Cohort. PLOS ONE. 2015;10:e0133010.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  12. 12.

    Casas M, Chatzi L, Carsin A-E, Amiano P, Guxens M, Kogevinas M, et al. Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two Southern European birth cohort studies. Int J Epidemiol. 2013;42:506–17.

    PubMed  Article  Google Scholar 

  13. 13.

    Hinkle SN, Schieve LA, Stein AD, Swan DW, Ramakrishnan U, Sharma AJ. Associations between maternal prepregnancy body mass index and child neurodevelopment at 2 years of age. Int J Obes. 2012;36:1312–9.

    Article  CAS  Google Scholar 

  14. 14.

    Mann JR, McDermott SW, Hardin J, Pan C, Zhang Z. Pre-pregnancy body mass index, weight change during pregnancy, and risk of intellectual disability in children. BJOG Int J Obstet Gynaecol. 2013;120:309–19.

    Article  CAS  Google Scholar 

  15. 15.

    Zhu Y, Yan H, Tang M, Fu Y, Hu X, Zhang F, et al. Impact of maternal prepregnancy body mass index on cognitive and metabolic profiles of singletons born after in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2019;112:1094–102.e2.

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Widen EM, Nichols AR, Kahn LG, Factor-Litvak P, Insel BJ, Hoepner L, et al. Prepregnancy obesity is associated with cognitive outcomes in boys in a low-income, multiethnic birth cohort. BMC Pediatr. 2019;19:1–10.

    Article  Google Scholar 

  17. 17.

    Nichols AR, Rundle AG, Factor-Litvak P, Insel BJ, Hoepner L, Rauh V, et al. Prepregnancy obesity is associated with lower psychomotor development scores in boys at age 3 in a low-income, minority birth cohort. J Dev Orig Health Dis. 2020;11:49–57.

    PubMed  Article  Google Scholar 

  18. 18.

    Rodriguez A, Miettunen J, Henriksen TB, Olsen J, Obel C, Taanila A, et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes. 2008;32:550–7.

    Article  CAS  Google Scholar 

  19. 19.

    Chen Q, Sjölander A, Långström N, Rodriguez A, Serlachius E, D’Onofrio BM, et al. Maternal pre-pregnancy body mass index and offspring attention deficit hyperactivity disorder: a population-based cohort study using a sibling-comparison design. Int J Epidemiol. 2014;43:83–90.

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Kong L, Norstedt G, Schalling M, Gissler M, Lavebratt C. The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity and Diabetes. Pediatrics. 2018; 142, https://doi.org/10.1542/peds.2018-0776.

  21. 21.

    Andersen CH, Thomsen PH, Nohr EA, Lemcke S. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry. 2018;27:139–48.

    PubMed  Article  Google Scholar 

  22. 22.

    Pugh SJ, Hutcheon JA, Richardson GA, Brooks MM, Himes KP, Day NL, et al. Gestational weight gain, prepregnancy body mass index and offspring attention-deficit hyperactivity disorder symptoms and behaviour at age 10. BJOG Int J Obstet Gynaecol. 2016;123:2094–103.

    Article  CAS  Google Scholar 

  23. 23.

    Daraki V, Roumeliotaki T, Koutra K, Georgiou V, Kampouri M, Kyriklaki A, et al. Effect of parental obesity and gestational diabetes on child neuropsychological and behavioral development at 4 years of age: the Rhea mother–child cohort, Crete, Greece. Eur Child Adolesc Psychiatry. 2017;26:703–14.

    PubMed  Article  Google Scholar 

  24. 24.

    Mina TH, Lahti M, Drake AJ, Räikkönen K, Minnis H, Denison FC, et al. Prenatal exposure to very severe maternal obesity is associated with adverse neuropsychiatric outcomes in children. Psychol Med. 2017;47:353–62.

    PubMed  Article  CAS  Google Scholar 

  25. 25.

    Fuemmeler BF, Zucker N, Sheng Y, Sanchez CE, Maguire R, Murphy SK et al. Pre-Pregnancy Weight and Symptoms of Attention Deficit Hyperactivity Disorder and Executive Functioning Behaviors in Preschool Children. Int J Environ Res Public Health. 2019; 16, https://doi.org/10.3390/ijerph16040667.

  26. 26.

    Robinson SL, Ghassabian A, Sundaram R, Trinh M-H, Lin T-C, Bell EM et al. Parental Weight Status and Offspring Behavioral Problems and Psychiatric Symptoms. J Pediatr. 2020, https://doi.org/10.1016/j.jpeds.2020.01.016.

  27. 27.

    Casas M, Forns J, Martínez D, Guxens M, Fernandez-Somoano A, Ibarluzea J, et al. Maternal pre-pregnancy obesity and neuropsychological development in pre-school children: a prospective cohort study. Pediatr Res. 2017;82:596–606.

    PubMed  Article  Google Scholar 

  28. 28.

    Li M, Fallin MD, Riley A, Landa R, Walker SO, Silverstein M et al. The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics. 2016; 137, https://doi.org/10.1542/peds.2015-2206.

  29. 29.

    Varcin KJ, Newnham JP, Whitehouse AJO. Maternal pre-pregnancy weight and autistic-like traits among offspring in the general population. Autism Res. 2019;12:80–88.

    PubMed  Article  Google Scholar 

  30. 30.

    Getz KD, Anderka MT, Werler MM, Jick SS. Maternal Pre-pregnancy Body Mass Index and Autism Spectrum Disorder among Offspring: A Population-Based Case–Control Study. Paediatr Perinat Epidemiol. 2016;30:479–87.

    PubMed  PubMed Central  Article  Google Scholar 

  31. 31.

    Windham GC, Anderson M, Lyall K, Daniels JL, Kral TVE, Croen LA, et al. Maternal Pre-pregnancy Body Mass Index and Gestational Weight Gain in Relation to Autism Spectrum Disorder and other Developmental Disorders in Offspring. Autism Res. 2019;12:316–27.

    PubMed  Article  PubMed Central  Google Scholar 

  32. 32.

    Dodds L, Fell DB, Shea S, Armson BA, Allen AC, Bryson S. The Role of Prenatal, Obstetric and Neonatal Factors in the Development of Autism. J Autism Dev Disord. 2011;41:891–902.

    PubMed  Article  PubMed Central  Google Scholar 

  33. 33.

    Shen Y, Dong H, Lu X, Lian N, Xun G, Shi L, et al. Associations among maternal pre-pregnancy body mass index, gestational weight gain and risk of autism in the Han Chinese population. BMC Psychiatry. 2018;18:1–7.

    Article  CAS  Google Scholar 

  34. 34.

    Bilder DA, Bakian AV, Viskochil J, Clark EAS, Botts EL, Smith KR, et al. Maternal Prenatal Weight Gain and Autism Spectrum Disorders. Pediatrics. 2013;132:e1276–83.

    PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Reynolds LC, Inder TE, Neil JJ, Pineda RG, Rogers CE. Maternal obesity and increased risk for autism and developmental delay among very preterm infants. J Perinatol. 2014;34:688–92.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  36. 36.

    Gardner RM, Lee BK, Magnusson C, Rai D, Frisell T, Karlsson H, et al. Maternal body mass index during early pregnancy, gestational weight gain, and risk of autism spectrum disorders: Results from a Swedish total population and discordant sibling study. Int J Epidemiol. 2015;44:870–83.

    PubMed  PubMed Central  Article  Google Scholar 

  37. 37.

    Rodriguez A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J Child Psychol Psychiatry. 2010;51:134–43.

    PubMed  Article  PubMed Central  Google Scholar 

  38. 38.

    Van Lieshout RJ, Robinson M, Boyle MH. Maternal Pre-Pregnancy Body Mass Index and Internalizing and Externalizing Problems in Offspring. Can J Psychiatry. 2013;58:151–9.

    PubMed  Article  PubMed Central  Google Scholar 

  39. 39.

    Robinson M, Zubrick SR, Pennell CE, Lieshout RJV, Jacoby P, Beilin LJ, et al. Pre-pregnancy maternal overweight and obesity increase the risk for affective disorders in offspring. J Dev Orig Health Dis. 2013;4:42–48.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  40. 40.

    Nohr EA, Vaeth M, Baker JL, Sørensen TI, Olsen J, Rasmussen KM. Combined associations of prepregnancy body mass index and gestational weight gain with the outcome of pregnancy. Am J Clin Nutr. 2008;87:1750–9.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  41. 41.

    Wang S, Sun Q, Zhai L, Bai Y, Wei W, Jia L. The Prevalence of Depression and Anxiety Symptoms among Overweight/Obese and Non-Overweight/Non-Obese Children/Adolescents in China: A Systematic Review and Meta-Analysis. Int J Environ Res Public Health. 2019;16. https://doi.org/10.3390/ijerph16030340.

  42. 42.

    Crisham Janik MD, Newman TB, Cheng YW, Xing G, Gilbert WM, Wu YW. Maternal Diagnosis of Obesity and Risk of Cerebral Palsy in the Child. J Pediatr. 2013;163:1307–12.

    PubMed  Article  PubMed Central  Google Scholar 

  43. 43.

    Villamor E, Tedroff K, Peterson M, Johansson S, Neovius M, Petersson G, et al. Association Between Maternal Body Mass Index in Early Pregnancy and Incidence of Cerebral Palsy. JAMA. 2017;317:925–36.

    PubMed  Article  PubMed Central  Google Scholar 

  44. 44.

    Pan C, Deroche CB, Mann JR, McDermott S, Hardin JW. Is Prepregnancy Obesity Associated With Risk of Cerebral Palsy and Epilepsy in Children? J Child Neurol. 2014;29:NP196–201.

    PubMed  Article  PubMed Central  Google Scholar 

  45. 45.

    Razaz N, Tedroff K, Villamor E, Cnattingius S. Maternal Body Mass Index in Early Pregnancy and Risk of Epilepsy in Offspring. JAMA Neurol. 2017;74:668–76.

    PubMed  PubMed Central  Article  Google Scholar 

  46. 46.

    Schaefer CA, Brown AS, Wyatt RJ, Kline J, Begg MD, Bresnahan MA, et al. Maternal Prepregnant Body Mass and Risk of Schizophrenia in Adult Offspring. Schizophr Bull. 2000;26:275–86.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  47. 47.

    Kawai M, Minabe Y, Takagai S, Ogai M, Matsumoto H, Mori N, et al. Poor maternal care and high maternal body mass index in pregnancy as a risk factor for schizophrenia in offspring. Acta Psychiatr Scand. 2004;110:257–63.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  48. 48.

    Mackay E, Dalman C, Karlsson H, Gardner RM. Association of Gestational Weight Gain and Maternal Body Mass Index in Early Pregnancy With Risk for Nonaffective Psychosis in Offspring. JAMA Psychiatry. 2017;74:339–49.

    PubMed  Article  PubMed Central  Google Scholar 

  49. 49.

    Ou X, Thakali KM, Shankar K, Andres A, Badger TM. Maternal Adiposity Negatively Influences Infant Brain White Matter Development. Obes Silver Spring Md. 2015;23:1047–54.

    Article  CAS  Google Scholar 

  50. 50.

    Verdejo-Román J, Björnholm L, Muetzel RL, Torres-Espínola FJ, Lieslehto J, Jaddoe V, et al. Maternal prepregnancy body mass index and offspring white matter microstructure: results from three birth cohorts. Int J Obes. 2019;43:1995–2006.

    Article  CAS  Google Scholar 

  51. 51.

    Li X, Andres A, Shankar K, Pivik RT, Glasier CM, Ramakrishnaiah RH, et al. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers. Int J Obes 2005. 2016;40:1931–4.

    CAS  Google Scholar 

  52. 52.

    Salzwedel AP, Gao W, Andres A, Badger TM, Glasier CM, Ramakrishnaiah RH et al. Maternal Adiposity Influences Neonatal Brain Functional Connectivity. Front Hum Neurosci. 2019; 12, https://doi.org/10.3389/fnhum.2018.00514.

  53. 53.

    Song JW, Chung KC. Observational studies: cohort and case-control studies. Plast Reconstr Surg. 2010;126:2234–42.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  54. 54.

    Kong L, Chen X, Gissler M, Lavebratt C. Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review. Int J Obes. 2020, https://doi.org/10.1038/s41366-020-0609-4.

  55. 55.

    Hariri N, Thibault L. High-fat diet-induced obesity in animal models. Nutr Res Rev. 2010;23:270–99.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  56. 56.

    Page KC, Jones EK, Anday EK. Maternal and postweaning high-fat diets disturb hippocampal gene expression, learning, and memory function. Am J Physiol-Regul Integr Comp Physiol. 2014;306:R527–37.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  57. 57.

    White CL, Pistell PJ, Purpera MN, Gupta S, Fernandez-Kim S-O, Hise TL, et al. Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: contributions of maternal diet. Neurobiol Dis. 2009;35:3–13.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  58. 58.

    Fusco S, Spinelli M, Cocco S, Ripoli C, Mastrodonato A, Natale F et al. Maternal insulin resistance multigenerationally impairs synaptic plasticity and memory via gametic mechanisms. Nat Commun. 2019; 10, https://doi.org/10.1038/s41467-019-12793-3.

  59. 59.

    Kim DW, Glendining KA, Grattan DR, Jasoni CL. Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus. Int J Dev Neurosci. 2016;53:18–25.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  60. 60.

    Mucellini AB, Laureano DP, Silveira PP, Sanvitto GL. Maternal and post-natal obesity alters long-term memory and hippocampal molecular signaling of male rat. Brain Res. 2019;1708:138–45.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  61. 61.

    Wolfrum C, Peleg-Raibstein D. Maternal overnutrition leads to cognitive and neurochemical abnormalities in C57BL/6 mice. Nutr Neurosci. 2019;22:688–99.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  62. 62.

    Ding Q, Zhao Y, Yang Y, Chen Z. Cognitive Impairment Due to Leptin Withdrawal in Rat Offspring of Dams with Maternal Diet-Induced Obesity. Med Sci Monit Int Med J Exp Clin Res. 2018;24:6208–17.

    CAS  Google Scholar 

  63. 63.

    Zhu C, Han T-L, Zhao Y, Zhou X, Mao X, Qi H, et al. A mouse model of pre-pregnancy maternal obesity combined with offspring exposure to a high-fat diet resulted in cognitive impairment in male offspring. Exp Cell Res. 2018;368:159–66.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  64. 64.

    Winther G, Elfving B, Müller HK, Lund S, Wegener G. Maternal High-fat Diet Programs Offspring Emotional Behavior in Adulthood. Neuroscience. 2018;388:87–101.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  65. 65.

    Sullivan EL, Grayson B, Takahashi D, Robertson N, Maier A, Bethea CL, et al. Chronic Consumption of a High-Fat Diet during Pregnancy Causes Perturbations in the Serotonergic System and Increased Anxiety-Like Behavior in Nonhuman Primate Offspring. J Neurosci. 2010;30:3826–30.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  66. 66.

    Thompson JR, Valleau JC, Barling AN, Franco JG, DeCapo M, Bagley JL et al. Exposure to a High-Fat Diet during Early Development Programs Behavior and Impairs the Central Serotonergic System in Juvenile Non-Human Primates. Front Endocrinol. 2017; 8, https://doi.org/10.3389/fendo.2017.00164.

  67. 67.

    Desai RA, Manley M, Desai MM, Potenza MN. Gender differences in the association between body mass index and psychopathology. CNS Spectr. 2009;14:372–83.

    PubMed  PubMed Central  Article  Google Scholar 

  68. 68.

    Winther G, Eskelund A, Bay-Richter C, Elfving B, Müller HK, Lund S, et al. Grandmaternal high-fat diet primed anxiety-like behaviour in the second-generation female offspring. Behav Brain Res. 2019;359:47–55.

    PubMed  Article  PubMed Central  Google Scholar 

  69. 69.

    Sarker G, Litwan K, Kastli R, Peleg-Raibstein D. Maternal overnutrition during critical developmental periods leads to different health adversities in the offspring: relevance of obesity, addiction and schizophrenia. Sci Rep. 2019; 9, https://doi.org/10.1038/s41598-019-53652-x.

  70. 70.

    Braff DL, Geyer MA. Sensorimotor gating and schizophrenia. Human and animal model studies. Arch Gen Psychiatry. 1990;47:181–8.

    PubMed  Article  CAS  Google Scholar 

  71. 71.

    Peleg-Raibstein D, Sarker G, Litwan K, Krämer SD, Ametamey SM, Schibli R, et al. Enhanced sensitivity to drugs of abuse and palatable foods following maternal overnutrition. Transl Psychiatry. 2016;6:e911.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  72. 72.

    Buffington SA, Prisco GVD, Auchtung TA, Ajami NJ, Petrosino JF, Costa-Mattioli M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell. 2016;165:1762–75.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  73. 73.

    Derntl B, Habel U. Deficits in social cognition: a marker for psychiatric disorders? Eur Arch Psychiatry Clin Neurosci. 2011;261(Suppl 2):S145–9.

    PubMed  Article  Google Scholar 

  74. 74.

    Kang SS, Kurti A, Fair DA, Fryer JD. Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J Neuroinflammation. 2014;11:1–12.

    Article  CAS  Google Scholar 

  75. 75.

    Niculescu MD, Lupu DS. High fat diet-induced maternal obesity alters fetal hippocampal development. Int J Dev Neurosci. 2009;27:627–33.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  76. 76.

    Tozuka Y, Wada E, Wada K. Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring. FASEB J. 2009;23:1920–34.

    PubMed  Article  CAS  Google Scholar 

  77. 77.

    Stachowiak EK, Srinivasan M, Stachowiak MK, Patel MS. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life. Metab Brain Dis. 2013;28:721–5.

    PubMed  Article  CAS  Google Scholar 

  78. 78.

    Graf AE, Lallier SW, Waidyaratne G, Thompson MD, Tipple TE, Hester ME, et al. Maternal high fat diet exposure is associated with increased hepcidin levels, decreased myelination, and neurobehavioral changes in male offspring. Brain Behav Immun. 2016;58:369–78.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  79. 79.

    Janthakhin Y, Rincel M, Costa A-M, Darnaudéry M, Ferreira G. Maternal high-fat diet leads to hippocampal and amygdala dendritic remodeling in adult male offspring. Psychoneuroendocrinology. 2017;83:49–57.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  80. 80.

    Arikkath J. Molecular mechanisms of dendrite morphogenesis. Front Cell Neurosci. 2012; 6, https://doi.org/10.3389/fncel.2012.00061.

  81. 81.

    Hatanaka Y, Wada K, Kabuta T. Maternal high-fat diet leads to persistent synaptic instability in mouse offspring via oxidative stress during lactation. Neurochem Int. 2016;97:99–108.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  82. 82.

    Contu L, Nizari S, Heath CJ, Hawkes CA. Pre- and Post-natal High Fat Feeding Differentially Affects the Structure and Integrity of the Neurovascular Unit of 16-Month Old Male and Female Mice. Front Neurosci. 2019; 13, https://doi.org/10.3389/fnins.2019.01045.

  83. 83.

    Stolp HB, Dziegielewska KM. Review: Role of developmental inflammation and blood–brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases. Neuropathol Appl Neurobiol. 2009;35:132–46.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  84. 84.

    Jiang NM, Cowan M, Moonah SN, Petri WA. The Impact of Systemic Inflammation on Neurodevelopment. Trends Mol Med. 2018;24:794–804.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  85. 85.

    Kim S, Kim H, Yim YS, Ha S, Atarashi K, Tan TG, et al. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature. 2017;549:528–32.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  86. 86.

    Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA, et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol. 2014;10:643–60.

    PubMed  Article  CAS  Google Scholar 

  87. 87.

    Kuban KCK, O’Shea TM, Allred EN, Fichorova RN, Heeren T, Paneth N, et al. The Breadth and Type of Systemic Inflammation and the Risk of Adverse Neurological Outcomes in Extremely Low Gestation Newborns. Pediatr Neurol. 2015;52:42–48.

    PubMed  Article  Google Scholar 

  88. 88.

    Das UN. Is obesity an inflammatory condition? Nutrition. 2001;17:953–66.

    PubMed  Article  CAS  Google Scholar 

  89. 89.

    Zaretsky MV, Alexander JM, Byrd W, Bawdon RE. Transfer of Inflammatory Cytokines Across the Placenta. Obstet Gynecol. 2004;103:546–50.

    PubMed  Article  CAS  Google Scholar 

  90. 90.

    Challier JC, Basu S, Bintein T, Minium J, Hotmire K, Catalano PM, et al. Obesity in Pregnancy Stimulates Macrophage Accumulation and Inflammation in the Placenta. Placenta. 2008;29:274–81.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  91. 91.

    Edlow AG, Glass RM, Smith CJ, Tran PK, James K, Bilbo S. Placental macrophages: a window into fetal microglial function in maternal obesity. Int J Dev Neurosci. 2019;77:60–68.

    PubMed  Article  CAS  Google Scholar 

  92. 92.

    Collado MC, Laitinen K, Salminen S, Isolauri E. Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk. Pediatr Res. 2012;72:77–85.

    PubMed  Article  CAS  Google Scholar 

  93. 93.

    Panagos P, Vishwanathan R, Penfield-Cyr A, Matthan N, Shivappa N, Wirth M, et al. Breastmilk from obese mothers has pro-inflammatory properties and decreased neuroprotective factors. J Perinatol J Calif Perinat Assoc. 2016;36:284–90.

    CAS  Google Scholar 

  94. 94.

    Lauritzen L, Brambilla P, Mazzocchi A, Harsløf LBS, Ciappolino V, Agostoni C. DHA Effects in Brain Development and Function. Nutrients 2016; 8, https://doi.org/10.3390/nu8010006.

  95. 95.

    Ozawa Y, Sasaki M, Takahashi N, Kamoshita M, Miyake S, Tsubota K. Neuroprotective Effects of Lutein in the Retina. Curr Pharm Des. 2012;18:51–56.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  96. 96.

    Cowan M, Petri WAJ. Microglia: immune regulators of neurodevelopment. Front Immunol. 2018; 9, https://doi.org/10.3389/fimmu.2018.02576.

  97. 97.

    Glendining KA, Fisher LC, Jasoni CL. Maternal high fat diet alters offspring epigenetic regulators, amygdala glutamatergic profile and anxiety. Psychoneuroendocrinology. 2018;96:132–41.

    PubMed  Article  CAS  Google Scholar 

  98. 98.

    Grissom NM, Herdt CT, Desilets J, Lidsky-Everson J, Reyes TM. Dissociable Deficits of Executive Function Caused by Gestational Adversity are Linked to Specific Transcriptional Changes in the Prefrontal Cortex. Neuropsychopharmacology. 2015;40:1353–63.

    PubMed  Article  CAS  Google Scholar 

  99. 99.

    Edlow AG, Guedj F, Pennings JLA, Sverdlov D, Neri C, Bianchi DW. Males are from Mars, and females are from Venus: sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity. Am J Obstet Gynecol. 2016;214:623.e1–623.e10.

    Article  Google Scholar 

  100. 100.

    McKee SE, Zhang S, Chen L, Rabinowitz JD, Reyes TM. Perinatal high fat diet and early life methyl donor supplementation alter one carbon metabolism and DNA methylation in the brain. J Neurochem. 2018;145:362–73.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  101. 101.

    Autry AE, Monteggia LM. Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders. Pharm Rev. 2012;64:238–58.

    PubMed  Article  CAS  Google Scholar 

  102. 102.

    Tozuka Y, Kumon M, Wada E, Onodera M, Mochizuki H, Wada K. Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring. Neurochem Int. 2010;57:235–47.

    PubMed  Article  CAS  Google Scholar 

  103. 103.

    Wu A, Ying Z, Gomez-Pinilla F. The interplay between oxidative stress and brain-derived neurotrophic factor modulates the outcome of a saturated fat diet on synaptic plasticity and cognition. Eur J Neurosci. 2004;19:1699–707.

    PubMed  Article  Google Scholar 

  104. 104.

    Santacruz A, Collado MC, García-Valdés L, Segura MT, Martín-Lagos JA, Anjos T, et al. Gut microbiota composition is associated with body weight, weight gain and biochemical parameters in pregnant women. Br J Nutr. 2010;104:83–92.

    PubMed  Article  CAS  Google Scholar 

  105. 105.

    Soderborg TK, Borengasser SJ, Barbour LA, Friedman JE. Microbial transmission from mothers with obesity or diabetes to infants: an innovative opportunity to interrupt a vicious cycle. Diabetologia. 2016;59:895–906.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  106. 106.

    Galley JD, Bailey M, Dush CK, Schoppe-Sullivan S, Christian LM. Maternal Obesity Is Associated with Alterations in the Gut Microbiome in Toddlers. PLOS ONE. 2014;9:e113026.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  107. 107.

    Ma J, Prince AL, Bader D, Hu M, Ganu R, Baquero K, et al. High-fat maternal diet during pregnancy persistently alters the offspring microbiome in a primate model. Nat Commun. 2014;5:1–11.

    CAS  Google Scholar 

  108. 108.

    Kennedy PJ, Murphy AB, Cryan JF, Ross PR, Dinan TG, Stanton C. Microbiome in brain function and mental health. Trends Food Sci Technol. 2016;57:289–301.

    Article  CAS  Google Scholar 

  109. 109.

    Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. J Med Microbiol. 2005;54:987–91.

    PubMed  Article  Google Scholar 

  110. 110.

    Jiang H, Zhang X, Yu Z, Zhang Z, Deng M, Zhao J, et al. Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. 2018;104:130–6.

    PubMed  Article  Google Scholar 

  111. 111.

    Prehn-Kristensen A, Zimmermann A, Tittmann L, Lieb W, Schreiber S, Baving L et al. Reduced microbiome alpha diversity in young patients with ADHD. PLoS ONE. 2018; 13, https://doi.org/10.1371/journal.pone.0200728.

  112. 112.

    Sanguinetti E, Guzzardi MA, Tripodi M, Panetta D, Selma-Royo M, Zega A, et al. Microbiota signatures relating to reduced memory and exploratory behaviour in the offspring of overweight mothers in a murine model. Sci Rep. 2019;9:1–12.

    Article  CAS  Google Scholar 

  113. 113.

    Money KM, Stanwood GD. Developmental origins of brain disorders: roles for dopamine. Front Cell Neurosci. 2013; 7, https://doi.org/10.3389/fncel.2013.00260.

  114. 114.

    Gugusheff JR, Bae SE, Rao A, Clarke IJ, Poston L, Taylor PD, et al. Sex and age-dependent effects of a maternal junk food diet on the mu-opioid receptor in rat offspring. Behav Brain Res. 2016;301:124–31.

    PubMed  Article  CAS  Google Scholar 

  115. 115.

    Kepser L-J, Homberg JR. The neurodevelopmental effects of serotonin: a behavioural perspective. Behav Brain Res. 2015;277:3–13.

    PubMed  Article  CAS  Google Scholar 

  116. 116.

    Kim T-W, Park H-S. Physical exercise improves cognitive function by enhancing hippocampal neurogenesis and inhibiting apoptosis in male offspring born to obese mother. Behav Brain Res. 2018;347:360–7.

    PubMed  Article  Google Scholar 

  117. 117.

    BMI-based Vitamins in Obese Pregnant Women - Full Text View - ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02802566 (accessed 14 Apr 2020).

  118. 118.

    Haghiac M, Yang X, Presley L, Smith S, Dettelback S, Minium J, et al. Dietary Omega-3 Fatty Acid Supplementation Reduces Inflammation in Obese Pregnant Women: A Randomized Double-Blind Controlled Clinical Trial. PLOS ONE. 2015;10:e0137309.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  119. 119.

    Penfield-Cyr A, Monthe-Dreze C, Smid MC, Sen S. Maternal BMI, Mid-pregnancy Fatty Acid Concentrations, and Perinatal Outcomes. Clin Ther. 2018;40:1659–1667.e1.

    PubMed  Article  CAS  Google Scholar 

  120. 120.

    Lu D-Y, Tsao Y-Y, Leung Y-M, Su K-P. Docosahexaenoic Acid Suppresses Neuroinflammatory Responses and Induces Heme Oxygenase-1 Expression in BV-2 Microglia: Implications of Antidepressant Effects for Omega-3 Fatty Acids. Neuropsychopharmacology. 2010;35:2238–48.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

  121. 121.

    Patrick RP, Ames BN. Vitamin D and the omega-3 fatty acids control serotonin synthesis and action, part 2: relevance for ADHD, bipolar disorder, schizophrenia, and impulsive behavior. FASEB J. 2015;29:2207–22.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  122. 122.

    Matsui F, Hecht P, Yoshimoto K, Watanabe Y, Morimoto M, Fritsche K, et al. DHA Mitigates Autistic Behaviors Accompanied by Dopaminergic Change in a Gene/Prenatal Stress Mouse Model. Neuroscience. 2018;371:407–19.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  123. 123.

    Brei C, Stecher L, Brunner S, Ensenauer R, Heinen F, Wagner PD, et al. Impact of the n-6:n-3 long-chain PUFA ratio during pregnancy and lactation on offspring neurodevelopment: 5-year follow-up of a randomized controlled trial. Eur J Clin Nutr. 2017;71:1114–20.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  124. 124.

    Ostadrahimi A, Salehi-Pourmehr H, Mohammad-Alizadeh-Charandabi S, Heidarabady S, Farshbaf-Khalili A. The effect of perinatal fish oil supplementation on neurodevelopment and growth of infants: a randomized controlled trial. Eur J Nutr. 2018;57:2387–97.

    PubMed  Article  CAS  Google Scholar 

  125. 125.

    Asemi Z, Samimi M, Tabassi Z, Naghibi Rad M, Rahimi Foroushani A, Khorammian H, et al. Effect of daily consumption of probiotic yoghurt on insulin resistance in pregnant women: a randomized controlled trial. Eur J Clin Nutr. 2013;67:71–74.

    PubMed  Article  CAS  PubMed Central  Google Scholar 

  126. 126.

    Brantsaeter AL, Myhre R, Haugen M, Myking S, Sengpiel V, Magnus P, et al. Intake of probiotic food and risk of preeclampsia in primiparous women: the Norwegian Mother and Child Cohort Study. Am J Epidemiol. 2011;174:807–15.

    PubMed  PubMed Central  Article  Google Scholar 

  127. 127.

    Halkjaer SI, Nilas L, Carlsen EM, Cortes D, Halldórsson TI, Olsen SF, et al. Effects of probiotics (Vivomixx®) in obese pregnant women and their newborn: study protocol for a randomized controlled trial. Trials. 2016;17:491.

    PubMed  PubMed Central  Article  CAS  Google Scholar 

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LT performed the literature review. LT and BTK co-wrote the paper. LT created the Table and Figure.

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Tong, L., Kalish, B.T. The impact of maternal obesity on childhood neurodevelopment. J Perinatol (2020). https://doi.org/10.1038/s41372-020-00871-0

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