Download PDF
CC BY-NC-ND 4.0 · Geburtshilfe Frauenheilkd 2019; 79(11): 1176-1182
DOI: 10.1055/a-0960-0939
GebFra Science
Review/Übersicht
Georg Thieme Verlag KG Stuttgart · New York

Maternal Overweight, Inflammation and Neurological Consequences for the Preterm Child: Results of the ELGAN Study

Article in several languages: English | deutsch
Lars Brodowski
2   Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany
,
Wolfgang Büter
1   Kinderklinik, Medizinische Hochschule Hannover, Hannover, Germany
,
Fabian Kohls
2   Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany
,
Peter Hillemanns
2   Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany
,
Constantin von Kaisenberg
2   Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany
,
Olaf Dammann
2   Frauenklinik, Medizinische Hochschule Hannover, Hannover, Germany
3   Public Health & Community Medicine, Tufts University School of Medicine, Boston, MA, USA
› Author Affiliations
Further Information

Publication History

received 20 March 2019
revised 25 May 2019

accepted 21 June 2019

Publication Date:
11 November 2019 (online)

Also available at
   Permissions and Reprints

Abstract

Maternal overweight and obesity are prenatal risk factors for obstetrical complications, preterm birth, neonatal morbidity as well as cognitive and behavioural developmental disorders in children. Paediatric morbidity and mortality as well as child development disorders are significantly associated with maternal obesity. Particularly in the neurodevelopmental and psychiatric area, it is becoming increasingly clear that, in children of mothers with an increased body mass index (BMI), there is a high correlation with childhood cognitive disabilities, attention disorders, and diseases on the autistic spectrum. The ELGAN (Extremely Low Gestational Age Newborn) study is a multicentre study which has been supported since 2000 by the National Institutes of Health (NIH) and whose objective is to research predictors for neonatal brain damage and neurological-cognitive sequelae in premature infants. The areas of focus are the connection between maternal overweight and obesity and pregnancy complications, APGAR scores and systemic inflammatory markers. In this overview, our aim is to summarise the work in this area and discuss it critically on the basis of current literature. We will examine the hypothesis whether maternal overweight and obesity in terms of a chronic inflammatory state is associated with neonatal inflammation which in turn is associated with an unfavourable development prognosis.

Key words

preterm birth - obesity - pregnancy
 

  • References/Literatur

  • 1 Villamor E, Cnattingius S. Interpregnancy weight change and risk of adverse pregnancy outcomes: a population-based study. Lancet 2006; 368: 1164-1170
    CrossrefPubMedGoogle Scholar
  • 2 Cnattingius S, Villamor E, Johansson S. et al. Maternal obesity and risk of preterm delivery. JAMA 2013; 309: 2362-2370
    CrossrefPubMedGoogle Scholar
  • 3 Persson M, Johansson S, Villamor E. et al. Maternal overweight and obesity and risks of severe birth-asphyxia-related complications in term infants: a population-based cohort study in Sweden. PLoS Med 2014; 11: e1001648
    CrossrefPubMedGoogle Scholar
  • 4 Li M, Fallin MD, Riley A. et al. The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities. Pediatrics 2016; 137: e20152206
    CrossrefPubMedGoogle Scholar
  • 5 Aune D, Saugstad OD, Henriksen T. et al. Maternal body mass index and the risk of fetal death, stillbirth, and infant death: a systematic review and meta-analysis. JAMA 2014; 311: 1536-1546
    CrossrefPubMedGoogle Scholar
  • 6 Contu L, Hawkes CA. A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the Offspring. Int J Mol Sci 2017; 18: pii:E1093
    CrossrefPubMedGoogle Scholar
  • 7 Oostvogels AJJM, Hof MHP, Gademan MGJ. et al. Does maternal pre-pregnancy overweight or obesity influence offspringʼs growth patterns from birth up to 7years? The ABCD-study. Early Hum Dev 2017; 113: 62-70
    CrossrefPubMedGoogle Scholar
  • 8 van der Burg JW, Sen S, Chomitz VR. et al. The role of systemic inflammation linking maternal BMI to neurodevelopment in children. Pediatr Res 2016; 79: 3-12
    CrossrefPubMedGoogle Scholar
  • 9 Banik A, Kandilya D, Ramya S. et al. Maternal Factors that Induce Epigenetic Changes Contribute to Neurological Disorders in Offspring. Genes (Basel) 2017; 8: pii:E150
    CrossrefPubMedGoogle Scholar
  • 10 OʼShea TM, Allred EN, Dammann O. et al. ELGAN study Investigators. The ELGAN study of the brain and related disorders in extremely low gestational age newborns. Early Hum Dev 2009; 85: 719-725
    CrossrefPubMedGoogle Scholar
  • 11 Chen M, McNiff C, Madan J. et al. Maternal obesity and neonatal Apgar scores. J Matern Fetal Neonatal Med 2010; 23: 89-95
    CrossrefPubMedGoogle Scholar
  • 12 Madan JC, Davis JM, Craig WY. et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine 2009; 47: 61-64
    CrossrefPubMedGoogle Scholar
  • 13 van der Burg JW, Allred EN, Kuban K. et al. Maternal obesity and development of the preterm newborn at 2 years. Acta Paediatr 2015; 104: 900-903
    CrossrefPubMedGoogle Scholar
  • 14 van der Burg JW, Allred EN, McElrath TF. et al. Is maternal obesity associated with sustained inflammation in extremely low gestational age newborns?. Early Hum Dev 2013; 89: 949-955
    CrossrefPubMedGoogle Scholar
  • 15 Jensen ET, van der Burg JW, OʼShea TM. et al. Extremely Low Gestational Age Newborns Study Investigators. The Relationship of Maternal Prepregnancy Body Mass Index and Pregnancy Weight Gain to Neurocognitive Function at Age 10 Years among Children Born Extremely Preterm. J Pediatr 2017; 187: 50-57.e3
    CrossrefPubMedGoogle Scholar
  • 16 van der Burg JW, Jensen ET, van de Bor M. et al. Maternal obesity and attention-related symptoms in the preterm offspring. Early Hum Dev 2017; 115: 9-15
    CrossrefPubMedGoogle Scholar
  • 17 Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 2000; 894: i-xii 1–253
    PubMedGoogle Scholar
  • 18 Schienkiewitz A, Mensink GBM, Kuhnert R. et al. Übergewicht und Adipositas bei Erwachsenen in Deutschland. J Health Monitor 2017; 2: 21-28
    PubMedGoogle Scholar
  • 19 He Y, Pan A, Wang Y. et al. Prevalence of overweight and obesity in 15.8 million men aged 15–49 years in rural China from 2010 to 2014. Sci Rep 2017; 7: 5012
    CrossrefPubMedGoogle Scholar
  • 20 Li LM, Rao KQ, Kong LZ. et al. Technical Working Group of China National Nutrition and Health Survey. [A description on the Chinese national nutrition and health survey in 2002]. Zhonghua Liu Xing Bing Xue Za Zhi 2005; 26: 478-484
    PubMedGoogle Scholar
  • 21 Blissing S, Roloff R, Girschick G. et al. [Neonatal results of prgenancies in overweight and obese mothers at the University of Würzburg Gynaecology Clinic–a comparison of the years 1980 and 2005]. Z Geburtshilfe Neonatol 2008; 212: 94-99
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Heslehurst N. Identifying ‘at risk’ women and the impact of maternal obesity on National Health Service maternity services. Proc Nutr Soc 2011; 70: 439-449
    CrossrefPubMedGoogle Scholar
  • 23 Flegal KM, Williamson DF. Incident CHD and excess body weight in the US population. Obesity (Silver Spring) 2010; 18: 1069 author reply 1069–1070
    PubMedGoogle Scholar
  • 24 Suitor CW. Perspectives on nutrition during pregnancy: Part I, Weight gain; Part II, Nutrient supplements. J Am Diet Assoc 1991; 91: 96-98
    CrossrefPubMedGoogle Scholar
  • 25 Schäfer-Graf U, Gembruch U, Louwen F. et al. Adipositas und Schwangerschaft. Frauenarzt 2017; 58: 22-27
    PubMedGoogle Scholar
  • 26 Shah TJ, Leik CE, Walsh SW. Neutrophil infiltration and systemic vascular inflammation in obese women. Reprod Sci 2010; 17: 116-124
    CrossrefPubMedGoogle Scholar
  • 27 Howe LR, Subbaramaiah K, Hudis CA. et al. Molecular pathways: adipose inflammation as a mediator of obesity-associated cancer. Clin Cancer Res 2013; 19: 6074-6083
    CrossrefPubMedGoogle Scholar
  • 28 Friis CM, Paasche Roland MC, Godang K. et al. Adiposity-related inflammation: effects of pregnancy. Obesity (Silver Spring) 2013; 21: E124-E130
    CrossrefPubMedGoogle Scholar
  • 29 Potvin S, Stip E, Sepehry AA. et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008; 63: 801-808
    CrossrefPubMedGoogle Scholar
  • 30 Hwang HS, Kwon JY, Kim MA. et al. Maternal serum highly sensitive C-reactive protein in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet 2007; 98: 105-109
    CrossrefPubMedGoogle Scholar
  • 31 Challier JC, Basu S, Bintein T. et al. Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 2008; 29: 274-281
    CrossrefPubMedGoogle Scholar
  • 32 Ramsay JE, Ferrell WR, Crawford L. et al. Maternal obesity is associated with dysregulation of metabolic, vascular, and inflammatory pathways. J Clin Endocrinol Metab 2002; 87: 4231-4237
    CrossrefPubMedGoogle Scholar
  • 33 Sacks GP, Seyani L, Lavery S. et al. Maternal C-reactive protein levels are raised at 4 weeks gestation. Hum Reprod 2004; 19: 1025-1030
    CrossrefPubMedGoogle Scholar
  • 34 Pendeloski KPT, Ono E, Torloni MR. et al. Maternal obesity and inflammatory mediators: A controversial association. Am J Reprod Immunol 2017; DOI: 10.1111/aji.12674.
    CrossrefPubMedGoogle Scholar
  • 35 Racusin D, Stevens B, Campbell G. et al. Obesity and the risk and detection of fetal malformations. Semin Perinatol 2012; 36: 213-221
    CrossrefPubMedGoogle Scholar
  • 36 Stothard KJ, Tennant PW, Bell R. et al. Maternal overweight and obesity and the risk of congenital anomalies: a systematic review and meta-analysis. JAMA 2009; 301: 636-650
    CrossrefPubMedGoogle Scholar
  • 37 Dai RX, He XJ, Hu CL. Maternal pre-pregnancy obesity and the risk of macrosomia: a meta-analysis. Arch Gynecol Obstet 2018; 297: 139-145
    CrossrefPubMedGoogle Scholar
  • 38 Sullivan EL, Grove KL. Metabolic imprinting in obesity. Forum Nutr 2010; 63: 186-194
    PubMedGoogle Scholar
  • 39 Koletzko B, Girardet JP, Klish W. et al. Obesity in children and adolescents worldwide: current views and future directions–Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2002; 35 (Suppl. 02) S205-S212
    CrossrefPubMedGoogle Scholar
  • 40 Oken E, Taveras EM, Kleinman KP. et al. Gestational weight gain and child adiposity at age 3 years. Am J Obstet Gynecol 2007; 196: 322.e1-322.e8
    CrossrefPubMedGoogle Scholar
  • 41 Catalano PM, Ehrenberg HM. The short- and long-term implications of maternal obesity on the mother and her offspring. BJOG 2006; 113: 1126-1133
    CrossrefPubMedGoogle Scholar
  • 42 Rowlands I, Graves N, de Jersey S. et al. Obesity in pregnancy: outcomes and economics. Semin Fetal Neonatal Med 2010; 15: 94-99
    CrossrefPubMedGoogle Scholar
  • 43 Williams CB, Mackenzie KC, Gahagan S. The effect of maternal obesity on the offspring. Clin Obstet Gynecol 2014; 57: 508-515
    CrossrefPubMedGoogle Scholar
  • 44 Van Lieshout RJ. Role of maternal adiposity prior to and during pregnancy in cognitive and psychiatric problems in offspring. Nutr Rev 2013; 71 (Suppl. 01) S95-S101
    CrossrefPubMedGoogle Scholar
  • 45 Basatemur E, Gardiner J, Williams C. et al. Maternal prepregnancy BMI and child cognition: a longitudinal cohort study. Pediatrics 2013; 131: 56-63
    CrossrefPubMedGoogle Scholar
  • 46 Andersen CH, Thomsen PH, Nohr EA. et al. Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children. Eur Child Adolesc Psychiatry 2018; 27: 139-148
    CrossrefPubMedGoogle Scholar
  • 47 Wang Y, Tang S, Xu S. et al. Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis. Sci Rep 2016; 6: 34248
    CrossrefPubMedGoogle Scholar
  • 48 Walstab J, Bell R, Reddihough D. et al. Maternal antecedents to cerebral palsy in preterm infants. Dev Med Child Neurol 2002; 44: 498
    PubMedGoogle Scholar
  • 49 Crisham Janik MD, Newman TB, Cheng YW. et al. Maternal diagnosis of obesity and risk of cerebral palsy in the child. J Pediatr 2013; 163: 1307-1312
    CrossrefPubMedGoogle Scholar
  • 50 Forthun I, Wilcox AJ, Strandberg-Larsen K. et al. Maternal Prepregnancy BMI and Risk of Cerebral Palsy in Offspring. Pediatrics 2016; 138: pii:e20160874
    PubMedGoogle Scholar
  • 51 Villamor E, Tedroff K, Peterson M. et al. Association Between Maternal Body Mass Index in Early Pregnancy and Incidence of Cerebral Palsy. JAMA 2017; 317: 925-936
    CrossrefPubMedGoogle Scholar
  • 52 Pan C, Deroche CB, Mann JR. et al. Is prepregnancy obesity associated with risk of cerebral palsy and epilepsy in children?. J Child Neurol 2014; 29: NP196-NP201
    CrossrefPubMedGoogle Scholar
  • 53 Xiao D, Qu Y, Huang L. et al. Association between maternal overweight or obesity and cerebral palsy in children: A meta-analysis. PLoS One 2018; 13: e0205733
    CrossrefPubMedGoogle Scholar
  • 54 Zhang J, Peng L, Chang Q. et al. Maternal obesity and risk of cerebral palsy in children: a systematic review and meta-analysis. Dev Med Child Neurol 2019; 61: 31-38
    CrossrefPubMedGoogle Scholar
  • 55 van der Burg JW, OʼShea TM, Kuban K. et al. Are Extremely Low Gestational Age Newborns Born to Obese Women at Increased Risk of Cerebral Palsy at 2 Years?. J Child Neurol 2018; 33: 216-224
    CrossrefPubMedGoogle Scholar
  • 56 Reynolds LC, Inder TE, Neil JJ. et al. Maternal obesity and increased risk for autism and developmental delay among very preterm infants. J Perinatol 2014; 34: 688-692
    CrossrefPubMedGoogle Scholar
  • 57 Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the missing link?. Dev Med Child Neurol 1993; 35: 553-558
    PubMedGoogle Scholar
  • 58 Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997; 42: 1-8
    CrossrefPubMedGoogle Scholar
  • 59 Dammann O, Leviton A, Allred EN. What explains away the increased risk of histological chorioamnionitis in African-American mothers of very-low-birthweight infants?. Paediatr Perinat Epidemiol 2000; 14: 20-29
    CrossrefPubMedGoogle Scholar
  • 60 Dammann O, OʼShea TM. Cytokines and perinatal brain damage. Clin Perinatol 2008; 35: 643-663
    CrossrefPubMedGoogle Scholar
  • 61 Cai Z, Lin S, Pang Y. et al. Brain injury induced by intracerebral injection of interleukin-1beta and tumor necrosis factor-alpha in the neonatal rat. Pediatr Res 2004; 56: 377-384
    CrossrefPubMedGoogle Scholar
  • 62 Buka SL, Tsuang MT, Torrey EF. et al. Maternal cytokine levels during pregnancy and adult psychosis. Brain Behav Immun 2001; 15: 411-420
    CrossrefPubMedGoogle Scholar
  • 63 Brown AS, Hooton J, Schaefer CA. et al. Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry 2004; 161: 889-895
    CrossrefPubMedGoogle Scholar
  • 64 Maffoni S, De Giuseppe R, Stanford FC. et al. Folate status in women of childbearing age with obesity: a review. Nutr Res Rev 2017; 30: 265-271
    CrossrefPubMedGoogle Scholar
  • 65 Kapadia MZ, Park CK, Beyene J. et al. Weight Loss Instead of Weight Gain within the Guidelines in Obese Women during Pregnancy: A Systematic Review and Meta-Analyses of Maternal and Infant Outcomes. PLoS One 2015; 10: e0132650
    CrossrefPubMedGoogle Scholar
  • 66 Tieu J, Shepherd E, Middleton P. et al. Dietary advice interventions in pregnancy for preventing gestational diabetes mellitus. Cochrane Database Syst Rev 2017; (01) CD006674
    PubMedGoogle Scholar
  • 67 Koletzko B, Cremer M, Flothkötter M. et al. Diet and Lifestyle Before and During Pregnancy – Practical Recommendations of the Germany-wide Healthy Start – Young Family Network. Geburtsh Frauenheilk 2018; 78: 1262-1282
    Article in Thieme ConnectPubMedGoogle Scholar
  • 68 Koletzko B, Godfrey KM, Poston L. et al. EarlyNutrition Project Systematic Review Group. Nutrition During Pregnancy, Lactation and Early Childhood and its Implications for Maternal and Long-Term Child Health: The Early Nutrition Project Recommendations. Ann Nutr Metab 2019; 74: 93-106
    CrossrefPubMedGoogle Scholar
  • 69 McElrath TF, Hecht JL, Dammann O. et al. Pregnancy Disorders That Lead to Delivery Before the 28th Week of Gestation: An Epidemiologic Approach to Classification. Am J Epidemiol 2008; 168: 980-989
    CrossrefPubMedGoogle Scholar
  • 70 McElrath TF, Allred EN, Boggess KA. et al. Maternal antenatal complications and the risk of neonatal cerebral white matter damage and later cerebral palsy in children born at an extremely low gestational age. Am J Epidemiol 2009; 170: 819-828
    CrossrefPubMedGoogle Scholar
  • 71 Dammann O, Leviton A. Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res 2014; 75: 376-380
    CrossrefPubMedGoogle Scholar
  • 72 McElrath TF, Fichorova RN, Allred EN. et al. Blood protein profiles of infants born before 28 weeks differ by pregnancy complication. Am J Obstet Gynecol 2011; 204: 418.e1-418.e12
    CrossrefPubMedGoogle Scholar
  • 73 Faupel-Badger JM, Fichorova RN, Allred EN. et al. Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries less than 28 weeks of gestation. Am J Reprod Immunol 2011; 66: 488-494
    CrossrefPubMedGoogle Scholar
  • 74 Hecht JL, Fichorova RN, Tang VF. et al. Relationship Between Neonatal Blood Protein Concentrations and Placenta Histologic Characteristics in Extremely Low GA Newborns. Pediatr Res 2011; 69: 68-73
    CrossrefPubMedGoogle Scholar
  • 75 Leviton A, Joseph RM, Allred EN. et al. The risk of neurodevelopmental disorders at age 10 years associated with blood concentrations of interleukins 4 and 10 during the first postnatal month of children born extremely preterm. Cytokine 2018; 110: 181-188
    CrossrefPubMedGoogle Scholar