Advanced Maternal Age

Basics

Description

  • The cutoff age for advanced maternal age (AMA) is not uniformly defined.
  • Delayed childbearing is traditionally defined as pregnancy occurring in women aged ≥35 years.
  • AMA is a growing trend within high-income countries.
  • At a time when women are delaying childbearing, the availability of assisted reproductive technologies for older women has allowed women to extend their reproductive options.
  • Maternal age is the most important determinant of fertility, and obstetric and perinatal risks increase with maternal age (1).
  • After 35 years of age, fecundity decreases, and the chance of miscarriage, spontaneous abortion, pregnancy complications, and adverse pregnancy outcomes increases (2).

Epidemiology

Incidence
Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries.

  • In 2014, 9% of first births in the United States were to women ≥35 years of age, which is a 23% increase from 2000 (3).
  • In the United States, there were 743 births to women ages ≥50 years in 2014, an increase from 677 births in 2013.

Prevalence

  • In 2014, 9% of first births in the United States were to women >35 years of age, which is a 23% increase from 2000 (3).
  • In 2016, the birth rate for women 45 to 49 years old was 0.9/1,000 women, the highest rate for this age group since 1963 (4).

Etiology and Pathophysiology

  • Some obstetric complications in older women appear to be related to the aging process alone, whereas others are related to coexisting factors, which are less likely to be observed in younger women.
  • Observational studies have consistently demonstrated a decline in pregnancy rates with advancing maternal age (2).
  • Cycles that result in pregnancy are less likely to progress to live births because of higher rates of aneuploidy and spontaneous abortion among older women (1,2).
  • Recent studies of AMA pregnancies identified signs of accelerated placental aging, altered nutrient transport, and vascular function compared to a control group (5).

Risk Factors

  • There are important differentials in the risk for women 35 to 39, 40 to 45, and >45 years (4).
  • For women aged 40 to 44 years, the likelihood for most adverse outcomes is increased compared with women aged 35 to 39 years (4).
  • Women ≥45 years of age are at highest risk for a broad range of adverse outcomes during delivery hospitalizations (4).

General Prevention

  • All adults of reproductive age should be aware of the obstetrical and perinatal risks of AMA, so they can make informed decisions about the timing of childbearing (1,2)[A].
  • Women not desiring pregnancy should be offered contraception and counseling.
  • 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.
  • Many women are unaware of the success rates or limitations of assisted reproductive technology and of the increased medical risks of delayed childbearing.

Commonly Associated Conditions

  • Maternal age is an independent factor associated with adverse pregnancy outcome.
  • AMA is reported to be associated with a range of pregnancy complications including fetal growth restriction, preeclampsia, placental abruption, preterm birth, and stillbirth (5).
    • These risks appear to be independent of maternal comorbidities.
    • The rate of spontaneous abortions, ectopic pregnancies, and stillbirths increases exponentially with age.
  • The risk of fetal aneuploidy increases with maternal age.
  • 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 (6).
  • Pregnancy risks in women >45 years have increased rates of preexisting hypertension and pregnancy complications, such as gestational diabetes mellitus, gestational hypertension, and PE (5).
  • AMA is associated with an increased risk of cesarean birth (5).

Diagnosis

History

A careful history should be obtained at initial visit that pays special attention to factors that can affect fertility and pregnancy.

  • The prevalence of medical and surgical illness, such as cancer; cardiovascular, renal, and autoimmune disease; and obesity increases with advancing age.
  • The two most common medical problems complicating pregnancy are hypertension and diabetes, both of which are increased in older women.
  • Smoking has been associated with increased perinatal morbidity and stillbirth in all ages, but the risk is particularly high in older smokers.

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)

  • Standard prenatal laboratory tests and imaging should be performed on women of AMA.
  • American College of Obstetricians and Gynecologists recommends all women who present before 20 weeks should be offered aneuploidy screening and option of diagnostic testing, regardless of maternal age (6)[C].
  • Noninvasive prenatal testing detecting cell-free fetal DNA in maternal blood is becoming the preferred test due to higher sensitivity and lower false-positive rate and is safer than invasive testing.
  • There are no large randomized trials that have examined the efficacy of routine antepartum testing in women age ≥35 years. There remains no consensus on the management of late pregnancy for these women.

Follow-Up Tests & Special Considerations

  • Women who undergo 1st-trimester screening should be offered 2nd-trimester assessment for open fetal defects (by ultrasonography, MSAFP screening, or both) and ultrasound screening for other fetal structural defects (6)[A].
  • Women with a positive screening test result for fetal aneuploidy should be offered further detailed counseling and testing (6)[A].

Test Interpretation

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 (3,6)[A].

Treatment

General Measures

  • A fertility evaluation should be initiated after 6 months of unprotected intercourse without conception in women 35 to 37 years of age, earlier in women >37 years of age, and immediately in women >40 years of age (1,2).
  • Care providers need to be aware of the increased obstetrical and perinatal complications associated with delayed childbearing and adjust obstetrical management protocols to ensure optimal outcomes (2).
  • The optimum gestational age for delivery of women of advancing age is unclear. Risk of stillbirth at 39 weeks in women >40 years is approximately the same as for women in their mid-20s at 41 weeks. For this reason, many favor induction around 39 weeks and certainly by 40 weeks in AMA women.

Issues For Referral

Given the magnitude of risk present, consultation with a maternal–fetal medicine specialist for women ≥45 years may be indicated.

Ongoing Care

Follow-up Recommendations

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

Patient Education

The experience of pregnancy at an AMA may impact subsequent health as the woman continues to age.

Prognosis

Although AMA 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 (2,6).

Codes

ICD-10

  • 009.511 Supervision of elderly primigravida, first trimester
  • O09.512 Supervision of elderly primigravida, second trimester
  • O09.513 Supervision of elderly primigravida, third trimester
  • O09.519 Supervision of elderly primigravida, unspecified trimester
  • O09.521 Supervision of elderly multigravida, first trimester
  • O09.522 Supervision of elderly multigravida, second trimester
  • O09.523 Supervision of elderly multigravida, third trimester
  • O09.529 Supervision of elderly multigravida, unspecified trimester

ICD-9

  • 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
  • V23.81 Supervision of high-risk pregnancy with elderly primigravida
  • V23.82 Supervision of high-risk pregnancy with elderly multigravida

SNOMED

  • 416413003 advanced maternal age gravida (finding)
  • 443460007 Multigravida of advanced maternal age (finding)

Clinical Pearls

  • Obstetric and perinatal risks increase with AMA.
  • Although majority of patients of AMA will have normal pregnancy and delivery, older women are more likely to have developed chronic medical conditions, which can complicate prenatal and perinatal outcomes.
  • Preconceptional counseling is recommended for all couples when of advanced reproductive age.
  • All adults of reproductive age should be aware of the obstetrical and perinatal risks of AMA, so they can make informed decisions about the timing of childbearing.
  • Prenatal screening for all chromosome abnormalities and a second-trimester ultrasound should be offered as standard of care for all women.

Authors

Nicole E. Tafuri, DO
Rebecca Lauters, MD

Bibliography

  1. 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. [PMID:24553169]
  2. Johnson JA, Tough S. No-271-delayed child-bearing. J Obstet Gynaecol Can. 2017;39(11):e500–e515. [PMID:29080737]
  3. Mathews TJ, Hamilton BE. Mean Age of Mothers Is on the Rise: United States, 2000–2014. Hyattsville, MD: National Center for Health Statistics; 2016. NCHS Data Brief, No. 232. http://www.cdc.gov/nchs/data/databriefs/db232.pdf. Accessed January 14, 2019.
  4. Sheen JJ, Wright JD, Goffman D, et al. Maternal age and risk for adverse outcomes. Am J Obstet Gynecol. 2018;219(4):390.e1–390.e15. [PMID:30153431]
  5. Lean SC, Derricott H, Jones RL, et al. Advanced maternal age and adverse pregnancy outcomes: a systematic review and meta-analysis. PLoS One. 2017;12(10):e0186287. [PMID:29040334]
  6. Committee on Practice Bulletins—Obstetrics, Committee on Genetics, and the Society for Maternal–Fetal Medicine. Practice Bulletin No. 163: screening for fetal aneuploidy. Obstet Gynecol. 2016;127(5):e123–e137. [PMID:26938574]

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