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    Maternal obesity and the fetal brain


    Applications to patient care

    • Preconception counseling of obese and overweight women may be appropriate to discuss risks and to encourage weight loss and adoption of a healthy diet prior to pregnancy.

    • Maternal preconception lifestyle change and weight loss may also reduce the risk for preeclampsia and gestational/pregestational diabetes, which have also been associated with iatrogenic prematurity and an increased risk for ASD and other neurodevelopmental morbidity in offspring.

    • Evidence is insufficient to recommend routine omega-3 or omega-6 fatty acid supplementation in obese pregnant women to reduce the risk of offspring neurodevelopmental morbidity.

    • Evidence is insufficient to recommend routine use of metformin in obese pregnant women to reduce the risk of offspring neurodevelopmental morbidity.



    1.         Flegal KM, Carroll MD, Kit BK, Ogden CL. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA. 2012;307(5):491-497.

    2.         Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA. 2014;311(8):806-814.

    3.         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(3):e290-296.

    4.         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(3):783-792.

    5.         Tanda R, Salsberry PJ, Reagan PB, Fang MZ. The impact of prepregnancy obesity on children's cognitive test scores. Matern Child Health J. 2012.

    6.         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 (Lond). 2012;36(10):1312-1319.

    7.         Heikura U, Taanila A, Hartikainen AL, et al. Variations in prenatal sociodemographic factors associated with intellectual disability: a study of the 20-year interval between two birth cohorts in northern Finland. Am J Epidemiol. 2008;167(2):169-177.

    8.         Neggers YH, Goldenberg RL, Ramey SL, Cliver SP. Maternal prepregnancy body mass index and psychomotor development in children. Acta Obstet Gynecol Scand. 2003;82(3):235-240.

    9.         Basatemur E, Gardiner J, Williams C, Melhuish E, Barnes J, Sutcliffe A. Maternal prepregnancy BMI and child cognition: a longitudinal cohort study. Pediatrics. 2013;131(1):56-63.

    10.       Krakowiak P, Walker CK, Bremer AA, et al. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics. 2012;129(5):e1121-1128.

    11.       Li M, Fallin MD, Riley A, et al. The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics. 2016;137(2):1-10.

    12.       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(9):688-692.

    13.       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(7):891-902.

    14.       Moss BG, Chugani DC. Increased risk of very low birth weight, rapid postnatal growth, and autism in underweight and obese mothers. AJHP. 2014;28(3):181-188.

    15.       Walker CK, Krakowiak P, Baker A, Hansen RL, Ozonoff S, Hertz-Picciotto I. Preeclampsia, placental insufficiency, and autism spectrum disorder or developmental delay. JAMA Pediatrics. 2015;169(2):154-162.

    16.       Bilder DA, Bakian AV, Viskochil J, et al. Maternal prenatal weight gain and autism spectrum disorders. Pediatrics. 2013;132(5):e1276-1283.

    17.       Gardner RM, Lee BK, Magnusson C, 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(3):870-883.

    18.       Suren P, Gunnes N, Roth C, et al. Parental obesity and risk of autism spectrum disorder. Pediatrics. 2014;133(5):e1128-1138.

    19.       Rodriguez A, Miettunen J, Henriksen TB, et al. Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts. Int J Obes (Lond). 2008;32(3):550-557.

    20.       Buss C, Entringer S, Davis EP, et al. Impaired executive function mediates the association between maternal pre-pregnancy body mass index and child ADHD symptoms. PLoS One. 2012;7(6):e37758.

    21.       Chen Q, Sjolander A, Langstrom N, 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(1):83-90.

    22.       Rodriguez A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J Child Psychol.Psychiatry. 2010;51(2):134-143.

    23.       Tanda R, Salsberry PJ. Racial differences in the association between maternal prepregnancy obesity and children's behavior problems. JDBP. 2014;35(2):118-127.

    24.       Brion MJ, Zeegers M, Jaddoe V, et al. Intrauterine effects of maternal prepregnancy overweight on child cognition and behavior in 2 cohorts. Pediatrics. 2011;127(1):e202-211.

    25.       Ahlin K, Himmelmann K, Hagberg G, et al. Non-infectious risk factors for different types of cerebral palsy in term-born babies: a population-based, case-control study. BJOG. 2013;120(6):724-731.

    26.       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 Pediatrics. 2013;163(5):1307-1312.

    27.       Mehta SH, Kerver JM, Sokol RJ, Keating DP, Paneth N. The Association between Maternal Obesity and Neurodevelopmental Outcomes of Offspring. J Pediatrics. 2014;165(5):891-896.

    28.       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(12):NP196-201.

    29.       Shatrov JG, Birch SC, Lam LT, Quinlivan JA, McIntyre S, Mendz GL. Chorioamnionitis and cerebral palsy: a meta-analysis. Obstet Gynecol. 2010;116(2 Pt 1):387-392.

    30.       Dulloo AG, Jacquet J, Solinas G, Montani JP, Schutz Y. Body composition phenotypes in pathways to obesity and the metabolic syndrome. Int J Obes (Lond). 2010;34 Suppl 2:S4-17.

    31.       Rivera HM, Christiansen KJ, Sullivan EL. The role of maternal obesity in the risk of neuropsychiatric disorders. Front Neurosci. 2015;9:194.

    32.       Friis CM, Paasche Roland MC, Godang K, et al. Adiposity-related inflammation: effects of pregnancy. Obesity (Silver Spring). 2013;21(1):E124-130.

    33.       Challier JC, Basu S, Bintein T, et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta. 2008;29(3):274-281.

    34.       Ramsay JE, Ferrell WR, Crawford L, Wallace AM, Greer IA, Sattar N. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab. 2002;87(9):4231-4237.

    35.       van der Burg JW, Sen S, Chomitz VR, Seidell JC, Leviton A, Dammann O. The role of systemic inflammation linking maternal BMI to neurodevelopment in children. Pediatr Res. 2016;79(1-1):3-12.

    36.       Aye IL, Lager S, Ramirez VI, et al. Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways. Biol Reprod. 2014;90(6):129.

    37.       Elovitz MA, Brown AG, Breen K, Anton L, Maubert M, Burd I. Intrauterine inflammation, insufficient to induce parturition, still evokes fetal and neonatal brain injury. Int J Dev Neurosci. 2011;29(6):663-671.

    38.       Goines PE, Croen LA, Braunschweig D, et al. Increased midgestational IFN-gamma, IL-4 and IL-5 in women bearing a child with autism: A case-control study. Mol Autism. 2011;2:13.

    39.       Krakowiak P, Goines PE, Tancredi DJ, et al. Neonatal Cytokine Profiles Associated with Autism Spectrum Disorder. Biol Psychiatry. 2015.

    40.       Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun. 2011;25(1):40-45.

    41.       Bilbo SD, Tsang V. Enduring consequences of maternal obesity for brain inflammation and behavior of offspring. FASEB. 2010;24(6):2104-2115.

    42.       White CL, Pistell PJ, Purpera MN, 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(1):3-13.

    43.       Grayson BE, Levasseur PR, Williams SM, Smith MS, Marks DL, Grove KL. Changes in melanocortin expression and inflammatory pathways in fetal offspring of nonhuman primates fed a high-fat diet. Endocrinology. 2010;151(4):1622-1632.

    44.       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):156.

    45.       Smith SE, Li J, Garbett K, Mirnics K, Patterson PH. Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci. 2007;27(40):10695-10702.

    46.       Heerwagen MJ, Miller MR, Barbour LA, Friedman JE. Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am J Physiol Regul Integr Comp Physiol. 2010;299(3):R711-722.

    47.       Sen S, Iyer C, Meydani SN. Obesity during pregnancy alters maternal oxidant balance and micronutrient status. J Perinatol. 2014;34(2):105-111.

    48.       Sullivan EL, Riper KM, Lockard R, Valleau JC. Maternal high-fat diet programming of the neuroendocrine system and behavior. Horm Behav. 2015;76:153-161.

    49.       Murabayashi N, Sugiyama T, Zhang L, et al. Maternal high-fat diets cause insulin resistance through inflammatory changes in fetal adipose tissue. Eur J Obstet Gynecol Reprod Biol. 2013;169(1):39-44.

    50.       Sullivan EL, Nousen EK, Chamlou KA. Maternal high fat diet consumption during the perinatal period programs offspring behavior. Physiol Behav. 2014;123:236-242.

    51.       Hauguel-de Mouzon S, Lepercq J, Catalano P. The known and unknown of leptin in pregnancy. Am J Obstet Gynecol. Jun 2006;194(6):1537-1545.

    52.       Desai M, Li T, Ross MG. Fetal hypothalamic neuroprogenitor cell culture: preferential differentiation paths induced by leptin and insulin. Endocrinology. 2011;152(8):3192-3201.

    53.       Couce ME, Burguera B, Parisi JE, Jensen MD, Lloyd RV. Localization of leptin receptor in the human brain. Neuroendocrinology. 1997;66(3):145-150.

    54.       Sullivan EL, Grayson B, Takahashi D, 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(10):3826-3830.

    55.       Ishikawa J, Ishikawa A, Nakamura S. Interferon-alpha reduces the density of monoaminergic axons in the rat brain. Neuroreport. 2007;18(2):137-140.

    56.       Jarskog LF, Xiao H, Wilkie MB, Lauder JM, Gilmore JH. Cytokine regulation of embryonic rat dopamine and serotonin neuronal survival in vitro. Int J Dev Neurosci. 1997;15(6):711-716.

    57.       Naef L, Gratton A, Walker CD. Exposure to high fat during early development impairs adaptations in dopamine and neuroendocrine responses to repeated stress. Stress. 2013;16(5):540-548.

    58.       Naef L, Moquin L, Dal Bo G, Giros B, Gratton A, Walker CD. Maternal high-fat intake alters presynaptic regulation of dopamine in the nucleus accumbens and increases motivation for fat rewards in the offspring. Neuroscience. 2011;176:225-236.

    59.       Vucetic Z, Kimmel J, Totoki K, Hollenbeck E, Reyes TM. Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology. 2010;151(10):4756-4764.

    60.       Aguilar-Valles A, Jung S, Poole S, Flores C, Luheshi GN. Leptin and interleukin-6 alter the function of mesolimbic dopamine neurons in a rodent model of prenatal inflammation. Psychoneuroendocrinology. 2012;37(7):956-969.

    61.       Penfold NC, Ozanne SE. Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions. Horm Behav. 2015;76:143-152.

    62.       Desai N, Roman A, Rochelson B, et al. Maternal metformin treatment decreases fetal inflammation in a rat model of obesity and metabolic syndrome. Am J Obstet Gynecol. 2013;209(2):136 e131-139.

    63.       Field SS. Interaction of genes and nutritional factors in the etiology of autism and attention deficit/hyperactivity disorders: a case control study. Medical hypotheses. 2014;82(6):654-661.

    64.       Haghiac M, Yang XH, Presley L, 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(9):e0137309.

    65.       Lyall K, Munger KL, O'Reilly EJ, Santangelo SL, Ascherio A. Maternal dietary fat intake in association with autism spectrum disorders. Am J Epidemiol. 2013;178(2):209-220.

    66.       Sarbattama S. BMI-based prenatal vitamins to ameliorate oxidative stress in obese pregnancy. http://grantome.com/grant/NIH/K23-HD074648-01A1. Accessed April 12, 2016.



    Andrea G Edlow, MD, MSc
    Dr Edlow is an attending physician in the Division of Maternal-Fetal Medicine, Department of Ob-Gyn, Tufts Medical Center, Boston, ...
    Larissa H Mattei, BA
    Ms Mattei is a fourth-year medical student at Tufts University School of Medicine, Boston, Massachusetts.


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