Advertisement
JOGC

No-271-Delayed Child-Bearing

      Abstract

      Objective

      To provide an overview of delayed child-bearing and to describe the implications for women and health care providers .

      Options

      Delayed child-bearing, which has increased greatly in recent decades, is associated with an increased risk of infertility, pregnancy complications, and adverse pregnancy outcome . This guideline provides information that will optimize the counselling and care of Canadian women with respect to their reproductive choices .

      Outcomes

      Maternal age is the most important determinant of fertility, and obstetric and perinatal risks increase with maternal age .
      Many women are unaware of the success rates or limitations of assisted reproductive technology and of the increased medical risks of delayed child-bearing, including multiple births, preterm delivery, stillbirth, and Caesarean section . This guideline provides a framework to address these issues .

      Evidence

      Studies published between 2000 and August 2010 were retrieved through searches of PubMed and the Cochrane Library using appropriate key words (delayed child-bearing, deferred pregnancy, maternal age, assisted reproductive technology, infertility, and multiple births) and MeSH terms (maternal age, reproductive behaviour, fertility) . The Internet was also searched using similar key words, and national and international medical specialty societies were searched for clinical practice guidelines and position statements . Data were extracted based on the aims, sample, authors, year, and results .

      Values

      The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.

      Sponsor

      The Society of Obstetricians and Gynaecologists of Canada.

      Recommendations

      • 1.
        Women who delay child-bearing are at increased risk of infertility . Prospective parents, especially women, should know that their fecundity and fertility begin to decline significantly after 32 years of age . Prospective parents should know that assisted reproductive technologies cannot guarantee a live birth or completely compensate for age-related decline in fertility (II-2A).
      • 2.
        A fertility evaluation should be initiated after 6 months of unprotected intercourse without conception in women 35 to 37 years of age, and earlier in women > 37 years of age (II-2A).
      • 3.
        Prospective parents should be informed that semen quality and male fertility deteriorate with advancing age and that the risk of genetic disorders in offspring increases (II-2A).
      • 4.
        Women ≥ 35 years of age should be offered screening for fetal aneuploidy and undergo a detailed second trimester ultrasound examination to look for significant fetal birth defects (particularly cardiac defects) (II-1A).
      • 5.
        Delayed child-bearing is associated with increased obstetrical and perinatal complications . Care providers need to be aware of these complications and adjust obstetrical management protocols to ensure optimal maternal and perinatal outcomes (II-2A).
      • 6.
        All adults of reproductive age should be aware of the obstetrical and perinatal risks of advanced maternal age so they can make informed decisions about the timing of child-bearing (II-2A).
      • 7.
        Strategies to improve informed decision-making by prospective parents should be designed, implemented, and evaluated . These strategies should provide opportunity for adults to understand the potential medical, social, and economic consequences of child- bearing throughout the reproductive years (III-B).
      • 8.
        Barriers to healthy reproduction, including workplace policies, should be reviewed to optimize the likelihood of healthy pregnancies (III-C).

      Key Words

      Abbreviations:

      ART (assisted reproductive technology), OR (odds ratio), ICSI (intracytoplasmic sperm injection), IUI (intrauterine insemination), LBW (low birth weight), PTD (preterm delivery), SGA (small for gestational age)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Obstetrics and Gynaecology Canada
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      REFERENCES

        • Bushnick T.
        • Garner R.
        The children of older first-time mothers in Canada: their health and development.
        (Ottawa (ON): Statistics Canada; Available at:)
        • Royal College of Obstetricians and Gynaecologists
        RCOG statement on later maternal age.
        (Available at:)
        • Leridon H.
        Can assisted reproductive technology compensate for the natural decline in fertility with age? A model assessment.
        Hum Reprod. 2004; 19: 1548-1553
      1. Human Fertilisation and Embryology Authority, facts and figures 2006: fertility problems and treatment.
        (October 2008. London: HEFA)2010
        • Leader A.
        Pregnancy and motherhood: the biological clock.
        Sex Reprod Menopause. 2006; 4: 3-6
        • Hassold T.
        • Chiu D.
        Maternal age-specific rates of numerical chromosome abnormalities with special reference to trisomy.
        Hum Genet. 1985; 70: 11-17
        • Nybo Andersen A.
        • Wohlfahrt J.
        • Christens P.
        • Olsen J.
        • Melbye M.
        Maternal age and fetal loss: population based register linkage study.
        BMJ. 2000; 320: 1708-1712
        • Cleary-Goldman J.
        • Malone F.D.
        • Vidaver J.
        • et al.
        Impact of maternal age on obstetric outcome.
        Obstet Gynecol. 2005; 105: 983-990
        • Storeide O.
        • Veholmen M.
        • Eide M.
        • Bergsjø P.
        • Sandvei R.
        The incidence of ectopic pregnancy in Hordaland County, Norway 1976–1993.
        Acta Obstet Gynecol Scand. 1997; 76: 345-349
        • Luke B.
        • Brown M.B.
        Contemporary risks of maternal morbidity and adverse outcomes with increasing maternal age and plurality.
        Fertil Steril. 2007; 88: 283-293
        • Blickstein I.
        Motherhood at or beyond the edge of reproductive age.
        In J Fertil Womens Med. 2003; 48: 17-24
        • Frets R.C.
        Effect of advanced age on fertility and pregnancy in women.
        (Available at)
        http://www.uptodate.com
        Date: 2009
        Date accessed: October 28, 2011
        • Statistics Canada
        Births 2005. (Cat. No. 84F0210XIE). 2007.
        (Ottawa, Ministry of Industry)2007
        • Fell D.B.
        • Joseph K.S.
        • Dodds L.
        • Allen A.C.
        • Jangaard K.
        • Van den Hof M.
        Changes in maternal characteristics in Nova Scotia, Canada from 1988 to 2001.
        Can J Public Health. 2005; 96: 234-238
        • Statistics Canada
        The Daily.
        (Available at:)
        http://www.statcan.ca/Daily/English/020926/d020926c.htm
        Date: 2002
        Date accessed: October 3, 2011
        • Tough S.
        • Tofflemire K.
        • Benzies K.
        • Fraser-Lee N.
        • Newburn-Cook C.
        Factors influencing childbearing decisions and knowledge of perinatal risks among Canadian men and women.
        Matern Child Health J. 2007; 11: 189-198
        • Brehterick K.L.
        • Fairbroher N.
        • Avila L.
        • Harbord S.
        • Robinson W.P.
        • Karla L.
        Fertility and aging: do reproductive-aged Canadian women know what they need to know?.
        Fertil Steril. 2010; 93: 2162-2168
        • Committee on Gynecologic Practice of American College of Obstetricians and Gynecologists
        • Practice Committee of American Society for Reproductive Medicine
        Age-related fertility decline: a committee opinion.
        Fertil Steril. 2008; 90: 486-487
        • Faddy M.J.
        • Gosden R.G.
        • Gougeon A.
        • Richardson S.J.
        • Nelson J.F.
        Accelerated disappearance of ovarian follicles in mid-life: implications for forecasting menopause.
        Hum Reprod. 1992; 7: 1342-1346
        • Menken J.
        • Trussell J.
        • Larsen U.
        Age and infertility.
        Science. 1986; 233: 1389-1394
        • Laufer N.
        • Simon A.
        • Samueloff A.
        • Yaffe H.
        • Milwidsky A.
        • Gielchinsky Y.
        Successful spontaneous pregnancies in women older than 45 years.
        Fertil Steril. 2004; 81: 1328-1332
        • Dunson D.B.
        • Colombo B.
        • Baird D.D.
        Changes with age in the first level and duration of fertility in the menstrual cycle.
        Hum Reprod. 2002; 17: 1399-1403
        • Peters H.
        Intrauterine gonadal development.
        Fertil Steril. 1976; 27: 493-500
        • Pellestor F.
        • Andreo B.
        • Arnal F.
        • Humeau C.
        • Demaille J.
        Maternal aging and chromosomal abnormalities: new data drawn from in vitro unfertilized human oocytes.
        Hum Genet. 2003; 112: 195-203
        • Fretts R.
        • Wilkins-Haug L.
        • Barss V.
        Management of infertility and pregnancy in women of advanced age.
        (UpToDate; Available at:)
        http://www.uptodate.com
        Date: 2009
        Date accessed: October 3, 2011
        • Balasch J.
        Ageing and infertility: an overview.
        Gynecol Endocrinol. 2010; 26: 855-860
        • Toner J.P.
        • Grainger D.A.
        • Frazier L.M.
        Clinical outcomes among recipients of donated eggs: an analysis of the U.S. national experience, 1996–1998.
        Fertil Steril. 2002; 78: 1038-1045
        • Stolwijk A.M.
        • Zielhuis G.A.
        • Sauer M.V.
        • Hamilton C.J.
        • Paulson R.J.
        The impact of the woman's age on the success of standard and donor in vitro fertilization.
        Fertil Steril. 1997; 67: 702-710
        • Sauer M.V.
        • Paulson R.J.
        • Lobo R.A.
        Reversing the natural decline in human fertility. An extended clinical trial of oocyte donation to women of advanced reproductive age.
        JAMA. 1992; 268: 1275-1279
        • Paulson R.J.
        • Hatch I.E.
        • Lobo R.A.
        • Sauer M.V.
        Cumulative conception and live birth rates after oocyte donation: implications regarding endometrial receptivity.
        Hum Reprod. 1997; 12: 835-839
        • Millar W.J.
        • Wadhera S.
        • Nimrod C.
        Multiple births: trends and patterns in Canada 1974–1990.
        Health Rep. 1992; 4: 223-250
        • Bissonnette F.
        • Cohen J.
        • Collins J.
        • et al.
        Incidence and complications of multiple gestation in Canada: proceedings of an expert meeting.
        Reprod Biomed Online. 2007; 14: 773-790
        • Helmerhorst F.M.
        • Perquin D.A.M.
        • Donker D.
        • Keirse M.J.N.C.
        Perinatal outcome of singletons and twins after assisted conception: a systematic review of controlled studies.
        BMJ. 2004; 328: 261-268
        • Bower C.
        • Hansen M.
        Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews.
        Reprod Fertil Dev. 2005; 17: 329-333
        • Fisher J.
        • Stocky A.
        Maternal perinatal mental health and multiple births: implications for practice.
        Twin Res. 2003; 6: 506-513
        • Cook R.
        • Bradley S.
        • Golombok S.
        A preliminary study of parental stress and child behaviour in families with twins conceived by in-vitro fertilization.
        Hum Reprod. 1998; 13: 3244-3246
        • Ellison M.A.
        • Hall J.E.
        Social stigma and compounded losses: quality-of-life issues for multiple-birth families.
        Fertil Steril. 2003; 80: 405-414
        • Toriello H.V.
        • Meck J.M.
        • Professional Practice and Guidelines Committee
        Statement on guidance for genetic counseling in advanced paternal age.
        Genet Med. 2008; 10: 457-460
        • Eskenazi B.
        • Wyrobek A.J.
        • Sloter E.
        • et al.
        The association of age and semen quality in healthy men.
        Hum Reprod. 2003; 18: 447-454
        • Araujo A.B.
        • Mohr B.A.
        • McKinlay J.B.
        Changes in sexual function in middle- aged and older men: longitudinal data from the Massachusetts Male Aging Study.
        J Am Geriatr Soc. 2004; 52: 1502-1509
        • Risch N.
        • Reigh E.W.
        • Wishnick M.W.
        • McCarthy J.G.
        Spontaneous mutation and parental age in humans.
        Am J Hum Genet. 1987; 41: 218-248
        • Crow J.F.
        The high spontaneous mutation rate: is it a health risk?.
        Proc Natl Acad Sci USA. 1997; 94: 8380-8386
        • Crow J.F.
        Age and sex effects on human mutation rates: an old problem with new complexities.
        J Radiat Res. 2006; 47: B72-B82
        • Hook E.B.
        Paternal age and effects on chromosomal and specific locus mutations and on other genetic outcomes in offspring.
        in: Mastroianni L. Paulsen C.A. Aging, reproduction, and the climacteric. Plenum Press, New York1986: 117-145
        • Summers A.M.
        • Langlois S.
        • Wyatt P.
        • et al.
        Prenatal screening for fetal aneuploidy. SOGC clinical practice guideline no. 187, February 2007.
        J Obstet Gynaecol Can. 2007; 29: 146-161
        • Wennerholm U.B.
        • Bergh C.
        • Hamberger L.
        • et al.
        Incidence of congenital malformations in children born after ICSI.
        Hum Reprod. 2000; 15: 944-948
        • Allen V.M.
        • Wilson R.D.
        • Cheung A.
        • SOGC Genetics Committee
        • SOGC Reproductive Endocrinology Infertility Committee
        Pregnancy outcomes after assisted reproductive technology. SOGC Clinical Practice Guideline N0.173, March 2006.
        J Obstet Gynaecol Can. 2006; 28: 220-250
        • Gianaroli L.
        • Magli M.C.
        • Munne S.
        • Fiorentino A.
        • Montanaro N.
        • Ferraretti A.P.
        Will preimplantation genetic diagnosis assist patients with a poor prognosis to achieve pregnancy?.
        Hum Reprod. 1997; 12: 1762-1767
        • Mastenbroek S.
        • Twisk M.
        • van Echten-Arends J.
        • et al.
        In vitro fertilization with preimplantation genetic screening.
        N Engl J Med. 2007; 357: 9-17
        • Kolevzon A.
        • Gross R.
        • Reichenberg A.
        Prenatal and perinatal risk factors for autism: a review and integration of findings.
        Arch Pediatr Adolesc Med. 2007; 161: 326-333
        • Reefhuis J.
        • Honein M.A.
        Maternal age and non-chromosomal birth defects, Atlanta—1968–2000: teenager or thirty-something, who is at risk?.
        Birth Defects Res A Clin Mol Teratol. 2004; 70: 572-579
        • Hollier L.M.
        • Leveno K.J.
        • Kelly M.A.
        • MCIntire D.D.
        Maternal age and malformations in singleton births.
        Obstet Gynecol. 2000; 96: 701-706
        • Jacobsson B.
        Advanced maternal age and adverse perinatal outcome.
        Obstet Gynecol. 2004; 104: 727-733
        • Jolly M.
        • Sebire N.
        • Harris J.
        • Robinson S.
        • Regan L.
        The risks associated with pregnancy in women aged 35 years or older.
        Hum Reprod. 2000; 15: 2433-2437
        • Ozalp S.
        • Tanir H.M.
        • Sener T.
        • Yazan S.
        • Keskin A.E.
        Health risks for early (< or =19) and late (> or = 35) childbearing.
        Arch Gynecol Obstet. 2003; 268: 172-174
        • Joseph K.S.
        • Allen A.C.
        • Dodds L.
        • Turner L.A.
        • Scott H.
        • Liston R.
        The perinatal effects of delayed childbearing.
        Obstet Gynecol. 2005; 105: 1410-1418
        • Canadian Institute of Health Information
        In due time: why maternal age matters.
        (Ottawa: Canadian Institute of Health Information; Available at:)
        • Smith K.E.
        • Buyalos R.P.
        The profound impact of patient age on pregnancy outcome after early detection of fetal cardiac activity.
        Fertil Steril. 1996; 65: 35-40
        • Spandorfer S.D.
        • Davis O.K.
        • Barmat L.I.
        • Chung P.H.
        • Rosenwaks Z.
        Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss.
        Fertil Steril. 2004; 81: 1265-1269
        • Hook E.B.
        Rates of chromosome abnormalities at different maternal ages.
        Obstet Gynecol. 1981; 58: 282
        • Bell J.S.
        • Campbell D.M.
        • Graham W.J.
        • Penney G.C.
        • Ryan M.
        • Hall M.H.
        Can obstetric complications explain the high levels of obstetric interventions and maternity service use among older women? A retrospective analysis of routinely collected data.
        BJOG. 2001; 108: 910-918
        • Newcomb W.W.
        • Rodriguez M.
        • Johnson J.W.
        Reproduction in the older gravida. A literature review.
        J Reprod Med. 1991; 36: 839-845
        • Hollander D.
        • Breen J.L.
        Pregnancy in the older gravida: how old is old?.
        Obstet Gynecol Surv. 1990; 45: 106-112
        • Seoud M.A.
        • Nassar A.H.
        • Usta I.M.
        • Melhem Z.
        • Kazma A.
        • Khalil A.M.
        Impact of advanced maternal age on pregnancy outcome.
        Am J Perinatol. 2002; 19: 1-8
        • Edge V.
        • Laros Jr, R.K.
        Pregnancy outcome in nulliparous women aged 35 or older.
        Am J Obstet Gynecol. 1993; 168: 1881-1884
        • Gilbert W.M.
        • Nesbitt T.S.
        • Danielsen B.
        Childbearing beyond age 40: pregnancy outcome in 24 032 cases.
        Obstet Gynecol. 1999; 93: 9-14
        • Bianco A.
        • Stone J.
        • Lynch L.
        • Lapinski R.
        • Berkowitz G.
        • Berkowitz R.L.
        Pregnancy outcome at age 40 and older.
        Obstet Gynecol. 1996; 87: 917-922
        • Salihu H.M.
        • Shumpert M.N.
        • Aliyu M.H.
        • Kirby R.S.
        • Alexander G.R.
        Smoking- associated fetal morbidity among older gravidas: a population study.
        Acta Obstet Gynecol Scand. 2005; 84: 329-334
        • Salihu H.M.
        • Shumpert M.N.
        • Aliyu M.H.
        • Alexander M.R.
        • Kirby R.S.
        • Alexander G.R.
        Stillbirths and infant deaths associated with maternal smoking among mothers aged > or = 40 years: a population study.
        Am J Perinatol. 2004; 21: 121-129
        • Aliyu M.H.
        • Salihu H.M.
        • Wilson R.E.
        • Alio A.P.
        • Kirby R.S.
        The risk of intrapartum stillbirth among smokers of advanced maternal age.
        Arch Gynecol Obstet. 2008; 278: 39-45
        • Luke B.
        • Brown M.B.
        Elevated risks of pregnancy complications and adverse outcomes with increasing maternal age.
        Hum Reprod. 2007; 22: 1264-1272
        • Paulson R.J.
        • Boostanfar R.
        • Saadat P.
        • et al.
        Pregnancy in the sixth decade of life. Obstetric outcomes in women of advanced reproductive age.
        JAMA. 2002; 288: 2320-2323
        • Casey B.M.
        • Lucas M.J.
        • Mcintire D.D.
        • Leveno K.J.
        Pregnancy outcomes in women with gestational diabetes compared with the general obstetric population.
        Obstet Gynecol. 1997; 90: 869-873
        • Miller D.A.
        • Chollet J.A.
        • Goodwin T.M.
        Clinical risk factors for placenta previa–placenta accreta.
        Am J Obstet Gynecol. 1997; 177: 210-214
        • Hack M.
        • Flannery D.J.
        • Schluchter M.
        • Cartar L.
        • Borawski E.
        • Klein N.
        Outcomes in young adulthood for very-low-birth-weight infants.
        N Engl J Med. 2002; 346: 149-157
        • McCormick M.C.
        • Richardson D.K.
        Premature infants grow up.
        N Engl J Med. 2002; 346: 197-198
        • Hack M.
        • Fanaroff A.A.
        Outcomes of children of extremely low birthweight and gestational age in the 1990s.
        Early Hum Dev. 1999; 53: 193-218
        • Cnattingius S.
        • Forman M.R.
        • Berendes H.W.
        • Isotalo L.
        Delayed childbearing and risk of adverse perinatal outcome. A population-based study.
        JAMA. 1992; 268: 886-890
        • Tough S.C.
        • Newburn-Cook C.
        • Johnston D.W.
        • Svenson L.W.
        Delayed childbearing and its impact on population rate changes in lower birth weight, multiple birth, and preterm delivery.
        Pediatrics. 2002; 109: 399-403
        • Huang L.
        • Sauve R.
        • Birkett N.
        • Fergusson D.
        • van Walraven C.
        Maternal age and risk of stillbirth: a systematic review.
        CMAJ. 2008; 178: 165-172
        • Fretts R.C.
        • Usher R.H.
        Fetal death in women in the older reproductive age group.
        Contemp Rev Obstet Gynecol. 1997; 9: 173-177
        • Bateman B.T.
        • Simpson L.L.
        Higher rate of stillbirth at the extremes of reproductive age: a large nationwide sample of deliveries in the United States.
        Am J Obstet Gynecol. 2006; 194: 840-845
        • Reddy U.M.
        • Ko C.W.
        • Willinger M.
        Maternal age and the risk of stillbirth throughout pregnancy in the United States.
        Am J Obstet Gynecol. 2006; 195: 764-770
        • Canterino J.C.
        • Ananth C.V.
        • Smulian J.
        • Harrigan J.T.
        • Vintzileos A.M.
        Maternal age and risk of fetal death in singleton gestations: USA, 1995–2000.
        J Matern Fetal Neonatal Med. 2004; 15: 193-197
        • Bahtiyar M.O.
        • Funai E.F.
        • Rosenberg V.
        • et al.
        Stillbirth at term in women of advanced maternal age in the United States: when could the antenatal testing be initiated?.
        Am J Perinatol. 2008; 25: 301-304
        • Delbaere I.
        • Verstraelen H.
        • Goetgeluk S.
        • et al.
        Perinatal outcome of twin pregnancies in women of advanced age.
        Hum Reprod. 2008; 23: 2145-2150
        • Martin J.A.
        • Hamilton B.E.
        • Sutton P.D.
        • et al.
        Division of Vital Statistics Births: final data for 2006. National vital statistics reports Hyattsville, MD.
        Natl Center Health Stat. 2009; 57
        • Callaway L.K.
        • Lust K.
        • McIntyre H.D.
        Pregnancy outcomes in women of very advanced maternal age.
        Aust N Z J Obstet Gynaecol. 2005; 45: 12-16
        • Lin H.C.
        • Xirasagar S.
        Maternal age and the likelihood of a maternal request for cesarean delivery: a 5-year population-based study.
        Am J Obstet Gynecol. 2005; 192: 848-855
        • Main D.M.
        • Main E.K.
        • Moore 2nd., D.H.
        The relationship between maternal age and uterine dysfunction: a continuous effect throughout reproductive life.
        Am J Obstet Gynecol. 2000; 182: 1312-1320
        • Smith G.C.
        • Cordeaux Y.
        • White I.R.
        • et al.
        The effect of delaying childbearing on primary Cesarean section rates.
        PLoS Med. 2008; 5: E144
        • Greenberg M.B.
        • Cheng Y.W.
        • Sullivan M.
        • Norton M.E.
        • Hopkins L.M.
        • Caughey A.B.
        Does length of labor vary by maternal age?.
        Am J Obstet Gynecol. 2007; 197 (e1-7): 428
        • Bujold E.
        • Hammoud A.O.
        • Hendler I.
        • et al.
        Trial of labor in patients with a previous cesarean section: does maternal age influence the outcome?.
        Am J Obstet Gynecol. 2004; 190: 1113-1118
        • Shipp T.D.
        • Zelop C.
        • Repke J.T.
        • Cohen A.
        • Caughey A.B.
        • Lieberman E.
        The association of maternal age and symptomatic uterine rupture during a trial of labor after prior cesarean delivery.
        Obstet Gynecol. 2002; 99: 585-588
        • Public Health Agency of Canada
        Special report on maternal mortality and severe morbidity in Canada enhanced surveillance: the path to prevention.
        (Available at:)
        • Chang J.
        • Elam-Evans L.D.
        • Berg C.J.
        • et al.
        Pregnancy-related mortality surveillance—United States, 1991–1999.
        MMWR Surveill Summ. 2003; 52: 1-8
        • Department of Health, Welsh Office, Scottish Office Department of Health, Department of Health and Social Services, Northern Ireland
        Why Mothers Die. Report on Confidential Enquiries into Maternal Deaths in the United Kingdom, 1997–1999.
        (London: The Stationary Office)2001
        • Australia Institute of Health and Welfare
        Report on Maternal Deaths in Australia, 1994–96.
        (AIHW Cat. No. PER 13. Canberra: Australia Institute of Health and Welfare)2000
        • Health Canada
        Canadian Perinatal Health Report, 2003.
        (Ottawa: Minister of Public Works and Government Services)2003
        • Stein Z.
        • Susser M.
        The risks of having children later in life: social advantage may make up for biologic disadvantage.
        BMJ. 2000; 320: 1681-1682
        • Woolf S.H.
        • Battista R.N.
        • Angerson G.M.
        • Logan A.G.
        • Eel W.
        • Canadian Task Force on Preventive Health Care
        New grades for recommendations from the Canadian Task Force on Preventive Health Care.
        CMAJ. 2003; 169: 207-208