Advanced Maternal Age

Gabriel W. Briscoe, MD and Jason McCarthy, MD
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Subject: Advanced Maternal Age

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Basics

Description

  • No universal definition for advanced maternal age because effects of aging exist as a continuum rather than threshold.

  • Generally accepted definition is at least 35 years of age or estimated delivery date older than age 35.

  • Advanced maternal age has a significant independent association with decreased fertility as well as increase in fetal and obstetric complications (1,2).

Epidemiology

Incidence

  • Rate of live birth for older women has been rising significantly over past three decades, as people are delaying childbearing due to cultural and sociologic changes.

    • From 1990 to 2008, birth rate per 1,000 women age 35–44 years increased from 18.7 to 28.7 (3).

Prevalence

In 2008, about 15% of pregnancies occurred in women older than the age of 35 years (3). 

Etiology and Pathophysiology

  • Decline in fertility with age due to gradual decrease in quantity and quality of oocytes within the ovaries

    • As women age, there is a progressive loss of oocytes from fetal life through menopause (4).

  • Increased risk for aneuploidy and spontaneous abortion is due to changes in the meiotic spindle that predisposes to nondisjunction. However, no association has been found between nonaneuploid structural defects and maternal age (1,4).

  • Use of assisted reproductive techniques and ovulation induction has significantly contributed to increased rate of twin and triplet births, which further contributes to complications during pregnancy (1).

General Prevention

Premenopausal women not desiring pregnancy should be offered contraception. 

Diagnosis

History

  • As women age, they have increased rates of chronic illness that affect fertility and contribute to obstetrical complications. A careful history should be obtained at initial visit that pays special attention to factors that can affect fertility and pregnancy such as

    • Diabetes mellitus

    • Hypertension

    • Fibroids

    • Endometriosis

    • Sexually transmitted infections

    • Tubal disease

    • Heart disease

    • Renal dysfunction

    • Thyroid dysfunction

  • Women with chronic conditions may be on medications that are contraindicated during pregnancy. A careful review of medications should be performed and alternatives considered when applicable.

Physical Exam

Routine prenatal physical exams should be performed on patients with advanced maternal age. 

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • Standard prenatal laboratory tests and imaging should be performed on women of advanced maternal age.

  • American College of Obstetricians and Gynecologists recommend all women who present before 20 weeks should be offered aneuploidy screening and option of diagnostic testing, regardless of maternal age (5)[B]. Decision to test for genetic anomalies is personal and based on many factors including family history of birth defects, risk of pregnancy loss, and impact of abnormal findings.

    • 1st-trimester screening includes measurement of serum human chorionic gonadotropin (hCG or β-hCG) and pregnancy-associated plasma protein A (PAPP-A), usually combined with nuchal translucency measurement when available.

      • Large trials have demonstrated Down syndrome detection rates of 79–87% with false-positive rate of 5% (5).

    • Screening during 2nd trimester includes serum markers hCG, alpha fetoprotein (AFP), and unconjugated estriol.

      • When combined with a fourth marker, dimeric inhibin alpha, “quad” test has sensitivity for Down syndrome of up to 81% with 5% false-positive rate (5).

      • Some institutions may combine 1st- and 2nd-trimester markers into a single score (sequential testing). An integrated score may further increase sensitivity with lower false-positive rates (5)[B].

    • Noninvasive prenatal testing (NIPT) measuring cell-free fetal DNA circulating in maternal serum is a newer screening tool for fetal aneuploidy. It is indicated in singleton pregnancies for women at increased risk for aneuploidy, including maternal age older than 35 years at delivery (6).

    • NIPT may be used to screen for trisomy 21, trisomy 18, and, in some laboratories, trisomy 13 with detection rates of >98% with false-positive rates of less than 0.5% (6).

    • NIPT may be used as primary screening or as a follow-up screening test for women with positive 1st-trimester or 2nd-trimester test results (6).

  • Patients should be educated regarding the differences between screening and diagnostic tests for aneuploidy. Not all affected fetuses will be detected by screening. Some women may opt to have invasive testing (e.g., amniocentesis, chorionic villus sampling) without first undergoing screening. Pretest counseling should include a review of available screening and diagnostic modalities as well as discussion of the risks and benefits of each.

Follow-up tests & special considerations
  • Aneuploidy is often associated with major birth anatomic malformations, which can often be detected via sonogram. Abnormal findings on 2nd-trimester ultrasound merits further counseling and offer of invasive testing (5)[B].

  • Use of serum markers for aneuploidy screening in multiple gestation is less accurate than in singleton pregnancies (5,6)[B].

Diagnostic Procedures/Other

It should be noted that a positive screening test indicates increased risk for aneuploidy but is not diagnostic. Women with positive screen should be offered genetic counseling and invasive testing by chorionic villus sampling or amniocentesis for diagnostic karyotyping (5,6)[A]. 

Treatment

General Measures

  • Advanced maternal age has significant increased risks to both mother and fetus (1,2).

  • Women older than 35 years are at higher risk of

    • Ectopic pregnancy

    • Gestational diabetes

    • Placenta previa

    • Abruptio placentae

    • Cesarean delivery

    • Maternal mortality

  • The fetus of a mother older than 35 years is at increased risk of

    • Miscarriage

    • Chromosomal abnormalities

    • Congenital anomalies

    • Preterm delivery

    • Perinatal mortality and neonatal death

  • Patients may minimize risks by treating preexisting conditions and should be counseled to optimize their well-being with healthy diet, exercise, and to avoid smoking.

Issues for Referral

Due to increased impairment of fertility, women older than 35 years desiring pregnancy should receive an expedited evaluation for treatment after 6 months of failed attempts to conceive. Women older than 40 years should be evaluated immediately (4)[C]. 

Ongoing Care

Follow-up Recommendations

Patient Monitoring

  • Prenatal care for patients of advanced maternal age should follow same course and timeline as for younger women.

  • Closer monitoring or referral to maternal–fetal medicine may be warranted should complications arise.

Patient Education

  • Providers should discuss the potential consequences of delayed childbearing, including increased risk for infertility or developing chronic medical conditions, which might complicate pregnancy.

  • There is a misconception that advances in assisted reproductive technology can compensate for age-related decline in fertility. Women should be counseled that age is the single most important determinant of fertility, and assisted reproductive technology cannot reverse the effects of age (1).

Prognosis

Although advanced maternal age imposes increased risk to obstetric patients affecting both prenatal course and pregnancy outcome, the majority of patients will deliver at term without adverse maternal or perinatal outcomes (1,2). 

References

Balasch  J, Gratacós  E. Delayed childbearing: effects of fertility and the outcome of pregnancy. Fetal Diagn Ther.  2011;29(4):263–273.  []
Cleary-Goldman  J, Malone  FD, Vidaver  J, et al. Impact of maternal age on obstetric outcome. Obstet Gynecol.  2005;105(5 pt 1):983–990.  []
Ventura  SJ, Curtin  SC, Abma  JC, et al. Estimated pregnancy rates and rates of pregnancy outcomes for the United States, 1990–2008. Natl Vital Stat Rep.  2012;60(7):1–21.  []
American College of Obstetricians and Gynecologists Committee on Gynecologic Practice; Practice Committee of the American Society for Reproductive Medicine. Female age-related fertility decline. Committee Opinion No. 589. Obstet Gynecol.  2014;123(3):719–721.  []
ACOG Committee on Practice Bulletins. ACOG Practice Bulletin No. 77: screening for fetal chromosomal abnormalities. Obstet Gynecol.  2007;109(1):217–227.  []
American College of Obstetricians and Gynecologists Committee on Genetics. Committee Opinion No. 545: noninvasive prenatal testing for fetal aneuploidy. Obstet Gynecol.  2012;120(6):1532–1534.  []

Codes

ICD09

  • V23.81 Supervision of high-risk pregnancy with elderly primigravida

  • V23.82 Supervision of high-risk pregnancy with elderly multigravida

  • 659.50 Elderly primigravida, unspecified as to episode of care or not applicable

  • 659.60 Elderly multigravida, unspecified as to episode of care or not applicable

ICD10

  • O09.519 Supervision of elderly primigravida, unspecified trimester

  • O09.529 Supervision of elderly multigravida, unspecified trimester

  • O09.511 Supervision of elderly primigravida, first trimester

  • O09.521 Supervision of elderly multigravida, first trimester

  • O09.512 Supervision of elderly primigravida, second trimester

  • O09.513 Supervision of elderly primigravida, third trimester

  • O09.522 Supervision of elderly multigravida, second trimester

  • O09.523 Supervision of elderly multigravida, third trimester

SNOMED

  • 416413003 advanced maternal age gravida (finding)

  • 443460007 Multigravida of advanced maternal age (finding)

Clinical Pearls

  • Advanced maternal age is independently associated with decreased fertility as well as increased obstetric and fetal complications.

  • Although majority of patients of advanced maternal age will have normal pregnancy and delivery, older women are more likely to have developed chronic medical conditions which can complicate prenatal and perinatal outcomes.

  • Risk of chromosomal abnormalities increases with maternal age, especially as women progress though their 30s. An individual older woman is more likely to have a true positive screen than a younger woman because prevalence of chromosomal abnormality is higher. Regardless of maternal age, all pregnant women should have the option of aneuploidy screening and diagnostic testing.

  • Patients should be counseled regarding possible consequences of delayed childbearing.

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