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Am J Perinatol 2009; 26(2): 107-112
DOI: 10.1055/s-0028-1090593
© Thieme Medical Publishers

Advanced Maternal Age. Part II: Long-Term Consequences

Anwar H. Nassar1 , Ihab M. Usta1
  • 1Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon
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Publication History

Publication Date:
19 November 2008 (online)

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ABSTRACT

In addition to the possible association between pregnancy in women with advanced maternal age and increased rates of obstetric and perinatal complications, those women and their children might suffer from long-term sequelae. In this review, the long-term consequences of delayed motherhood on the offspring and the possible association between advanced maternal age and the development of certain cancers are discussed.

KEYWORDS

Advanced maternal age - pregnancy - long-term consequences - cancer

REFERENCES

  • 1 Tarín J J. Aetiology of age-associated aneuploidy: a mechanism based on the “free radical theory of ageing”.  Hum Reprod. 1995;  10 1563-1565
    PubMedSearch in Google Scholar
  • 2 Aagesen L, Grinsted J, Mikkelsen M. Advanced grandmaternal age on the mother's side—a risk of giving rise to trisomy 21.  Ann Hum Genet. 1984;  48(Pt 4) 297-301
    CrossrefPubMedSearch in Google Scholar
  • 3 Papp Z, Váradi E, Szabó Z. Grandmaternal age at birth of parents of children with trisomy 21.  Hum Genet. 1977;  39 221-224
    PubMedSearch in Google Scholar
  • 4 Durkin M V, Kaveggia E G, Pendleton E, Neuhaüser G, Opitz J M. Analysis of etiologic factors in cerebral palsy with severe mental retardation. I. Analysis of gestational, parturitional and neonatal data.  Eur J Pediatr. 1976;  123 67-81
    CrossrefPubMedSearch in Google Scholar
  • 5 Monetti V C, Granieri E, Casetta I et al.. Risk factors for idiopathic generalized seizures: a population-based case control study in Copparo, Italy.  Epilepsia. 1995;  36 224-229
    CrossrefPubMedSearch in Google Scholar
  • 6 Gillberg C. Maternal age and infantile autism.  J Autism Dev Disord. 1980;  10 293-297
    PubMedSearch in Google Scholar
  • 7 Jayasekara R, Street J. Parental age and parity in dyslexic boys.  J Biosoc Sci. 1978;  10 255-261
    PubMedSearch in Google Scholar
  • 8 Gillberg C. Parental age in child psychiatric clinic attenders.  Acta Psychiatr Scand. 1982;  66 471-478
    PubMedSearch in Google Scholar
  • 9 Kinnell H G. Parental age in schizophrenia.  Br J Psychiatry. 1983;  142 204
    PubMedSearch in Google Scholar
  • 10 Gillberg C, Rasmussen P, Wahlström J. Minor neurodevelopmental disorders in children born to older mothers.  Dev Med Child Neurol. 1982;  24 437-447
    PubMedSearch in Google Scholar
  • 11 Cryan E, Byrne M, O'Donovan A, O'Callaghan E. A case-control study of obstetric complications and later autistic disorder.  J Autism Dev Disord. 1996;  26 453-460
    PubMedSearch in Google Scholar
  • 12 Bertranpetit J, Fañanás L. Parental age in schizophrenia in a case-controlled study.  Br J Psychiatry. 1993;  162 574
    CrossrefPubMedSearch in Google Scholar
  • 13 Fiaschi A, Coccia G, Rozza L, Benedetti M D, Bongiovanni L G, Tacconi A. Multifactorial etiological aspects of epilepsy.  Funct Neurol. 1986;  1 391-397
    PubMedSearch in Google Scholar
  • 14 Degen R. Epilepsy in children. An etiological study based on their obstetrical records.  J Neurol. 1978;  217 145-158
    PubMedSearch in Google Scholar
  • 15 Stein Z, Susser M. The risks of having children in later life: social advantage may make up for biological disadvantage.  BMJ. 2000;  320 1681-1682
    CrossrefPubMedSearch in Google Scholar
  • 16 Gross S J, Mettelman B B, Dye T D, Slagle T A. Impact of family structure and stability on academic outcome in preterm children at 10 years of age.  J Pediatr. 2001;  138 169-175
    CrossrefPubMedSearch in Google Scholar
  • 17 Fonteyn V J, Isada N B. Nongenetic implications of childbearing after age thirty-five.  Obstet Gynecol Surv. 1988;  43 709-720
    PubMedSearch in Google Scholar
  • 18 Perls T T, Alpert L, Fretts R C. Middle aged mothers live longer.  Nature. 1997;  389 133
    PubMedSearch in Google Scholar
  • 19 Bingley P J, Douek I F, Rogers C A, Gale E AM. Influence of maternal age at delivery and birth order on risk of type 1 diabetes in childhood: prospective population based family study.  BMJ. 2000;  321 420-424
    CrossrefPubMedSearch in Google Scholar
  • 20 Flood T M, Brink S J, Gleason R E. Increased incidence of type 1 diabetes in children of older mothers.  Diabetes Care. 1982;  5 571-573
    PubMedSearch in Google Scholar
  • 21 Metcalfe M A, Baum J D. Family characteristics and insulindependent diabetes.  Arch Dis Child. 1992;  67 731-736
    PubMedSearch in Google Scholar
  • 22 Bache I, Volund A, Bock T, Buschard K. Previous maternal abortion, longer gestation and younger maternal age decrease the risk of type 1 diabetes among male offspring.  Diabetes Care. 1999;  22 1063-1065
    PubMedSearch in Google Scholar
  • 23 Blom L, Dahlquist G, Nystrom L, Sandstrom A, Wall S. The Swedish childhood diabetes study—social and perinatal determinants for diabetes in childhood.  Diabetologia. 1989;  32 7-13
    PubMedSearch in Google Scholar
  • 24 Mayer E J, Hamman R F, Gay E C, Lezotte D C, Savitz D A, Klingensmith G J. Reduced risk of IDDM among breastfed children.  Diabetes. 1988;  37 1625-1632
    CrossrefPubMedSearch in Google Scholar
  • 25 Ziegler A G, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes. The 2year analysis of the German BABYDIAB study.  Diabetes. 1999;  48 460-468
    CrossrefPubMedSearch in Google Scholar
  • 26 St John J C, Cooke I D, Barratt C L. Mitochondrial mutations and male infertility.  Nat Med. 1997;  3 124-125
    PubMedSearch in Google Scholar
  • 27 Smits L J, Willemsen W N, Zielhuis G A, Jongbloet P H. Conditions at conception and risk of menstrual disorders.  Epidemiology. 1997;  8 524-529
    CrossrefPubMedSearch in Google Scholar
  • 28 Tarin J J, Brines J, Cano A. Long-term effects of delayed parenthood.  Hum Reprod. 1998;  13 2371-2376
    CrossrefPubMedSearch in Google Scholar
  • 29 Gavrilov L A, Gavrilova N S, Kroutko V N et al.. Mutation load and human longevity.  Mutat Res. 1997;  377 61-62
    PubMedSearch in Google Scholar
  • 30 Gavrilova N S, Gavrilov L A, Evdokushkina G N et al.. Evolution, mutations, and human longevity: European royal and noble families.  Hum Biol. 1998;  70 799-804
    PubMedSearch in Google Scholar
  • 31 Yip B H, Pawitan Y, Czene K. Parental age and risk of childhood cancers: a population-based cohort study from Sweden.  Int J Epidemiol. 2006;  35 1495-1503
    CrossrefPubMedSearch in Google Scholar
  • 32 Dockerty J D, Draper G, Vincent T, Rowan S D, Bunch K J. Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers.  Int J Epidemiol. 2001;  30 1428-1437
    CrossrefPubMedSearch in Google Scholar
  • 33 Moll A C, Imhof S M, Kuik D J et al.. High parental age is associated with sporadic hereditary retinoblastoma: the Dutch retinoblastoma register 1862–1994.  Hum Genet. 1996;  98 109-112
    PubMedSearch in Google Scholar
  • 34 Matsunaga E, Minoda K, Sasaki M S. Parental age and seasonal variation in the births of children with sporadic retinoblastoma: a mutation-epidemiologic study.  Hum Genet. 1990;  84 155-158
    PubMedSearch in Google Scholar
  • 35 Bradbury B D, Jick H. In vitro fertilization and childhood retinoblastoma.  Br J Clin Pharmacol. 2004;  58 209-211
    CrossrefPubMedSearch in Google Scholar
  • 36 Zhang Y, Cupples L A, Rosenberg L, Colton T, Kreger B E. Parental ages at birth in relation to a daughter's risk of breast cancer among female participants in the Framingham Study.  Cancer Causes Control. 1995;  6 23-29
    CrossrefPubMedSearch in Google Scholar
  • 37 Xue F, Colditz G A, Willett W C, Rosner B A, Michels K B. Parental age at delivery and incidence of breast cancer: a prospective cohort study.  Breast Cancer Res Treat. 2007;  104 331-340
    CrossrefPubMedSearch in Google Scholar
  • 38 English P B, Goldberg D E, Wolff C, Smith D. Parental and birth characteristics in relation to testicular cancer risk among males born between 1960 and 1995 in California.  Cancer Causes Control. 2003;  14 815-825
    CrossrefPubMedSearch in Google Scholar
  • 39 Møller H, Skakkebaek N E. Risks of testicular cancer and cryptorchidism in relation to socio-economic status and related factors: case-control studies in Denmark.  Int J Cancer. 1996;  66 287-293
    CrossrefPubMedSearch in Google Scholar
  • 40 Zhang Y, Graubard B I, Longnecker M P, Stanczyk F Z, Klebanoff M A, McGlynn K A. Maternal hormone levels and perinatal characteristics: implications for testicular cancer.  Ann Epidemiol. 2007;  17 85-92
    CrossrefPubMedSearch in Google Scholar
  • 41 Stewart A, Webb J, Hewitt D. A survey of childhood malignancies.  BMJ. 1958;  1 1495-1508
    PubMedSearch in Google Scholar
  • 42 Stark C R, Mantel N. Effects of maternal age and birth order on the risk of mongolism and leukemia.  J Natl Cancer Inst. 1966;  37 687-698
    PubMedSearch in Google Scholar
  • 43 Westergaard T, Andersen P K, Pedersen J B, Frisch M, Olsen J H, Melbye M. Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study.  J Natl Cancer Inst. 1997;  89 939-947
    CrossrefPubMedSearch in Google Scholar
  • 44 Neglia J P, Linet M S, Shu X O et al.. Patterns of infection and day care utilization and risk of childhood acute lymphoblastic leukaemia.  Br J Cancer. 2000;  82 234-240
    CrossrefPubMedSearch in Google Scholar
  • 45 Madigan M P, Ziegler R G, Benichou J, Byrne C, Hoover R N. Proportion of breast cancer cases in the United States explained by well-established risk factors.  J Natl Cancer Inst. 1995;  87 1681-1685
    CrossrefPubMedSearch in Google Scholar
  • 46 Rosner B, Colditz G A, Willet W C. Reproductive risk factors in a prospective study of breast cancer: the nurses' health study.  Am J Epidemiol. 1994;  139 819-835
    PubMedSearch in Google Scholar
  • 47 Kampert J B, Whittemore A S, Paffenbarger Jr R S. Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk.  Am J Epidemiol. 1988;  128 962-979
    PubMedSearch in Google Scholar
  • 48 Lagiou A, Lagiou P, Vassilarou D S, Stoikidou M, Trichopoulos D. Comparison of age at first full-term pregnancy between women with breast cancer and women with benign breast diseases.  Int J Cancer. 2003;  107 817-821
    CrossrefPubMedSearch in Google Scholar
  • 49 Sivaraman L, Conneely O M, Medina D, O'Malley B W. P53 is a potential mediator of pregnancy and hormone-induced resistance to mammary carcinogenesis.  Proc Natl Acad Sci U S A. 2001;  98 12379-12384
    CrossrefPubMedSearch in Google Scholar
  • 50 Russo J, Hu Y F, Silva I D, Russo I H. Cancer risk related to mammary gland structure and development.  Microsc Res Tech. 2001;  52 204-223
    CrossrefPubMedSearch in Google Scholar
  • 51 Russo J, Lynch H, Russo I H. Mammary gland architecture as a determining factor in the susceptibility of the human breast to cancer.  Breast J. 2001;  7 278-291
    CrossrefPubMedSearch in Google Scholar
  • 52 Lochen M L, Lund E. Childbearing and mortality from cancer of the corpus uteri.  Acta Obstet Gynecol Scand. 1997;  76 373-377
    PubMedSearch in Google Scholar
  • 53 Hinkula M, Pukkala E, Kyyronen P, Kauppila A. Grand multiparity and incidence of endometrial cancer: a population-based study in Finland.  Int J Cancer. 2002;  98 912-915
    CrossrefPubMedSearch in Google Scholar
  • 54 Lambe M, Wuu J, Weiderpass E, Hsieh C C. Childbearing at older age and endometrial cancer risk.  Cancer Causes Control. 1999;  10 43-49
    CrossrefPubMedSearch in Google Scholar
  • 55 Kvale G, Heuch I, Nilssen S. Reproductive factors and risk of cervical cancer by cell type. A prospective study.  Br J Cancer. 1988;  58 820-824
    PubMedSearch in Google Scholar
  • 56 Mogren I, Stenlund H, Hogberg U. Long-term impact of reproductive factors on the risk of cervical, endometrial, ovarian and breast cancer.  Acta Oncol. 2001;  40 849-854
    CrossrefPubMedSearch in Google Scholar
  • 57 Bjorge T, Kravdal O. Reproductive variables and risk of uterine cervical cancer in Norwegian registry data.  Cancer Causes Control. 1996;  7 351-357
    CrossrefPubMedSearch in Google Scholar
  • 58 Guo W D, Hsing A W, Li J Y, Chen J S, Chow W H, Blot W J. Correlation of cervical cancer mortality with reproductive and dietary factors, and serum markers in China.  Int J Epidemiol. 1994;  23 1127-1132
    CrossrefPubMedSearch in Google Scholar
  • 59 Biswas L N, Manna B, Maiti P K, Sengupta S. Sexual risk factors for cervical cancer among rural Indian women: a case-control study.  Int J Epidemiol. 1997;  26 491-495
    PubMedSearch in Google Scholar
  • 60 Merrill R M, Fugal S, Novilla L B, Raphael M C. Cancer risk associated with early and late maternal age at first birth.  Gynecol Oncol. 2005;  96 583-593
    CrossrefPubMedSearch in Google Scholar
  • 61 Greggi S, Parazzini F, Paratore M P et al.. Risk factors for ovarian cancer in central Italy.  Gynecol Oncol. 2000;  79 50-54
    CrossrefPubMedSearch in Google Scholar
  • 62 Adami H O, Lambe M, Persson I, Ekbom A, Hsieh C C, Trichopoulos D. Parity, age at first childbirth, and risk of ovarian cancer.  Lancet. 1994;  344 1250-1254
    CrossrefPubMedSearch in Google Scholar
  • 63 Whiteman D C, Siskind V, Purdie D M, Green A C. Timing of pregnancy and the risk of epithelial ovarian cancer.  Cancer Epidemiol Biomarkers Prev. 2003;  12 42-46
    PubMedSearch in Google Scholar
  • 64 Whittemore A S, Harris R, Itnyre J. Characteristics relating to ovarian cancer risk: collaborative analysis of 12 US case-control studies: II. Invasive epithelial ovarian cancers in white women. Collaborative ovarian cancer group.  Am J Epidemiol. 1992;  136 1184-1203
    PubMedSearch in Google Scholar
  • 65 Kune G A, Kune S, Watson L F. Children, age at first birth, and colorectal cancer risk. Data from the Melbourne Colorectal Cancer Study.  Am J Epidemiol. 1989;  129 533-542
    PubMedSearch in Google Scholar
  • 66 Broeders M J, Lambe M, Baron J A, Leon D A. History of childbearing and colorectal cancer risk in women aged less than 60: an analysis of Swedish routine registry data 1960–1984.  Int J Cancer. 1996;  66 170-175
    CrossrefPubMedSearch in Google Scholar
  • 67 Troisi R, Schairer C, Chow W H, Schatzkin A, Brinton L A, Fraumeni Jr J F. Reproductive factors, oral contraceptive use, and risk of colorectal cancer.  Epidemiology. 1997;  8 75-79
    PubMedSearch in Google Scholar
  • 68 McMichael A J, Potter J D. Reproduction, endogenous and exogenous sex hormones, and colon cancer: a review and hypothesis.  J Natl Cancer Inst. 1980;  65 1201-1207
    PubMedSearch in Google Scholar
  • 69 Peters R K, Pike M C, Chang W WL, Mack T M. Reproductive factors and colon cancers.  Br J Cancer. 1990;  61 741-748
    PubMedSearch in Google Scholar
  • 70 Cantor K P, Lynch C F, Johnson D. Reproductive factors and risk of brain, colon, and other malignancies in Iowa (United States).  Cancer Causes Control. 1993;  4 505-511
    CrossrefPubMedSearch in Google Scholar
  • 71 Negri E, Ron E, Franceschi S et al.. Risk factors for medullary thyroid carcinoma: a pooled analysis.  Cancer Causes Control. 2002;  13 365-372
    CrossrefPubMedSearch in Google Scholar
  • 72 Ji B T, Hatch M C, Chow W H et al.. Anthropometric and reproductive factors and the risk of pancreatic cancer: a case-control study in Shanghai, China.  Int J Cancer. 1996;  66 432-437
    CrossrefPubMedSearch in Google Scholar
  • 73 Fernandez E, La Vecchia C, D'Avanzo B, Negri E. Menstrual and reproductive factors and pancreatic cancer risk in women.  Int J Cancer. 1995;  62 11-14
    CrossrefPubMedSearch in Google Scholar
  • 74 Skinner H G, Michaud D S, Colditz G A et al.. Parity, reproductive factors, and the risk of pancreatic cancer in women.  Cancer Epidemiol Biomarkers Prev. 2003;  12 433-438
    PubMedSearch in Google Scholar

Anwar H NassarM.D. 

Department of Obstetrics and Gynecology, American University of Beirut Medical Center

PO Box 113-6044/B36, Hamra 110 32090, Beirut, Lebanon

Email: an21@aub.edu.lb