Mütterliches Übergewicht, Inflammation und neurologische Konsequenzen für das frühgeborene Kind: Ergebnisse der ELGAN-Studie

Zusammenfassung

Mütterliches Übergewicht und Adipositas sind pränatale Risikofaktoren für geburtshilfliche Komplikationen, Frühgeburt, neonatale Morbidität sowie kognitive und verhaltensauffällige Entwicklungsstörungen bei Kindern. Die kindliche Morbidität und Mortalität sowie Störungen der Kindesentwicklung sind signifikant mit maternaler Adipositas assoziiert. Besonders im entwicklungsneurologischen und -psychiatrischen Bereich wird zunehmend klar, dass es bei Kindern von Müttern mit erhöhtem Body-Mass-Index eine hohe Korrelation zu kindlichen kognitiven Einschränkungen, Aufmerksamkeitsstörungen und Erkrankungen aus dem autistischen Spektrum gibt. Die ELGAN-(Extremely Low Gestational Age Newborn-)Studie ist eine seit 2000 von den National Institutes of Health (NIH) geförderte multizentrische Studie, deren Ziel es ist, Prädiktoren für neonatale Hirnschäden und neurologisch-kognitive Folgen bei Frühgeborenen zu erforschen. Schwerpunkte sind der Zusammenhang zwischen mütterlichem Übergewicht und Adipositas und Schwangerschaftskomplikationen, Apgar-Werten und systemischen Inflammationsmarkern. In dieser Übersichtsarbeit verfolgen wir das Ziel, die Arbeiten in diesem Bereich zusammenzufassen und auf Basis der aktuellen Literatur kritisch zu diskutieren. Geprüft wird die Hypothese, ob mütterliches Übergewicht und Adipositas im Sinne eines chronischen Inflammationsstatus mit einer neonatalen Inflammationssituation zusammenhängen, die wiederum mit einer ungünstigen Entwicklungsprognose assoziiert ist.

Schlüsselwörter

Frühgeburt - Adipositas - Schwangerschaft

• 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
• 2 Cnattingius S, Villamor E, Johansson S. et al. Maternal obesity and risk of preterm delivery. JAMA 2013; 309: 2362-2370
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 11 Chen M, McNiff C, Madan J. et al. Maternal obesity and neonatal Apgar scores. J Matern Fetal Neonatal Med 2010; 23: 89-95
• 12 Madan JC, Davis JM, Craig WY. et al. Maternal obesity and markers of inflammation in pregnancy. Cytokine 2009; 47: 61-64
• 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
• 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
• 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
• 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
• 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
• 18 Schienkiewitz A, Mensink GBM, Kuhnert R. et al. Übergewicht und Adipositas bei Erwachsenen in Deutschland. J Health Monitor 2017; 2: 21-28
• 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
• 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
• 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
• 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
• 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
• 24 Suitor CW. Perspectives on nutrition during pregnancy: Part I, Weight gain; Part II, Nutrient supplements. J Am Diet Assoc 1991; 91: 96-98
• 25 Schäfer-Graf U, Gembruch U, Louwen F. et al. Adipositas und Schwangerschaft. Frauenarzt 2017; 58: 22-27
• 26 Shah TJ, Leik CE, Walsh SW. Neutrophil infiltration and systemic vascular inflammation in obese women. Reprod Sci 2010; 17: 116-124
• 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
• 28 Friis CM, Paasche Roland MC, Godang K. et al. Adiposity-related inflammation: effects of pregnancy. Obesity (Silver Spring) 2013; 21: E124-E130
• 29 Potvin S, Stip E, Sepehry AA. et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008; 63: 801-808
• 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
• 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
• 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
• 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
• 34 Pendeloski KPT, Ono E, Torloni MR. et al. Maternal obesity and inflammatory mediators: A controversial association. Am J Reprod Immunol 2017;
• 35 Racusin D, Stevens B, Campbell G. et al. Obesity and the risk and detection of fetal malformations. Semin Perinatol 2012; 36: 213-221
• 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
• 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
• 38 Sullivan EL, Grove KL. Metabolic imprinting in obesity. Forum Nutr 2010; 63: 186-194
• 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
• 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
• 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
• 42 Rowlands I, Graves N, de Jersey S. et al. Obesity in pregnancy: outcomes and economics. Semin Fetal Neonatal Med 2010; 15: 94-99
• 43 Williams CB, Mackenzie KC, Gahagan S. The effect of maternal obesity on the offspring. Clin Obstet Gynecol 2014; 57: 508-515
• 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
• 45 Basatemur E, Gardiner J, Williams C. et al. Maternal prepregnancy BMI and child cognition: a longitudinal cohort study. Pediatrics 2013; 131: 56-63
• 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
• 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
• 48 Walstab J, Bell R, Reddihough D. et al. Maternal antecedents to cerebral palsy in preterm infants. Dev Med Child Neurol 2002; 44: 498
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 57 Leviton A. Preterm birth and cerebral palsy: is tumor necrosis factor the missing link?. Dev Med Child Neurol 1993; 35: 553-558
• 58 Dammann O, Leviton A. Maternal intrauterine infection, cytokines, and brain damage in the preterm newborn. Pediatr Res 1997; 42: 1-8
• 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
• 60 Dammann O, OʼShea TM. Cytokines and perinatal brain damage. Clin Perinatol 2008; 35: 643-663
• 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
• 62 Buka SL, Tsuang MT, Torrey EF. et al. Maternal cytokine levels during pregnancy and adult psychosis. Brain Behav Immun 2001; 15: 411-420
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 71 Dammann O, Leviton A. Intermittent or sustained systemic inflammation and the preterm brain. Pediatr Res 2014; 75: 376-380
• 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
• 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
• 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
• 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