Advanced Maternal Age (AMA)

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Check out the new ACOG/SMFM Obstetric Care Consensus #11, Pregnancy at Age 35 Years or Older.

Why do we care about age in pregnancy? 

• Maternal age 

• CDC data (2020): continuing upward trend in the mean age of pregnant people in the US 

  • 19% of all pregnancies are currently in people 35 and older 

  • Mean age of people having their first birth in 2020 was 27.1, compared to 21.4 in 1970 

• Pregnancies in patients that are older are associated with higher risks, even if they come into the pregnancy as healthy individuals 

• Definition 

• Advanced maternal age: women who are 35 years or older at estimated date of delivery.

  • Why 35?

    • Selected based on evidence of declining fertility and concern surrounding increased risk for genetic abnormalities in babies born to those who are over the age of 35 

    • This has been a historical figure that we have used – this threshold is pretty arbitrary 

• Some risks associated with older age may not influence outcomes until even later in life (ie. 40 and older) 

  • The risk is on a continuum - there is no jump in risk just because someone hits 35 

  • More recent studies will stratify risk by age group, so for example, will divide out patients by age in 5 year increments (ie. 35-39, 40-44, etc).

Risks of AMA Status

• Pregnancy risks

• Compared to those of younger age, patients who are >35 at time of delivery are at higher risk of

• Gestational diabetes,

• Preeclampsia,

• Labor dystocia, and

• Cesarean delivery  

• Fetal/neonatal risks 

• Increased risk of preterm delivery

• Increased risk of NICU admission, low birth weight 

• These risks are on a continuum, with risks increasing progressively with advanced age, particularly in those older than 40 at the time of delivery 

• When looking at cohort studies, women 45-54 were at the highest risk of overall complications 

• Chronic medical disorders 

• More prevalent in individuals >35 years of age 

• Include things like obesity, hypertension, diabetes - studies show that pregnant people 35 or older are 2-4x more likely to have cHTN and nearly twice as likely to have T2DM as pregnant people 25-29 years old 

  • These are also risk factors for poor outcomes.

Considerations in pregnancy care for=patients older than age 35:

• Prevention of Preeclampsia 

• There is increased risk of preeclampsia in pregnancy patients older than 35 

• In one large meta-analysis, the risk of preeclampsia progressively increased with increasing age.

• However, the difference was only statistically significant in women aged 40 years and older 

• In USPSTF systematic review, there was reduction in risk of preeclampsia, preterm birth, small for gestational age, and perinatal mortality in individuals at increased risk of preeclampsia who took low-dose aspirin prophylaxis. 

• Recommendation: start low-dose aspirin (81 mg/day) ideally between 12-16 weeks of gestation, and continue daily until delivery in those at high-risk of preeclampsia 

  • Those who are 35 or older are at moderate risk of preeclampsia, so it is reasonable for those who are 35 or older with one high risk factor or at least one additional moderate risk factor to start low-dose aspirin therapy 

• Other moderate risk factors:

• Nulliparity

• Obesity (BMI >30)

• Family history of preeclampsia

• Black race (as proxy for underlying racism)

• Lower income

• Personal history factors (ie. low birth weight, previous adverse pregnancy outcome)

• IVF  

•  High risk factors 

• History of preeclampsia

• Multifetal gestation

• Chronic hypertension

• Pregestational diabetes,

• Chronic kidney disease

• Autoimmune disease

• Genetic Screening 

• Over time, there is decrease in oocyte and oocyte quality 

• Decline accelerates in 4th decade of life likely due to myriad of hormonal changes regulating the ovaries 

• Individual’s fertility will decline with increasing age 

• Frequency of aneuploidy will increase with age 

• However, not all aneuploidies or genetic abnormalities increase with age:

  • Sex chromosome trisomies and other trisomies increase with age 

  • However, sex chromosome monosomies and copy number variants seem to be independent of maternal age at pregnancy 

• Pregnant individuals should be aware of these risks and therefore, clinicians should be ready to discuss prenatal genetic testing (both screening and diagnostic) 

• There is conflicting data about increased risk of major congenital anomaly affecting the fetus in patients who are 35 years of age or older.

  • However, a detailed fetal anatomic survey should be done.

ACOG/SMFM OBSTETERIC CARE CONSENSUS #11

• Growth abnormalities 

  • Both large for gestational age and small for gestational age occurs in neonates at higher frequencies as maternal age increases.

    • Most of this data is for patients who are age 40 or above 

  • Insufficient evidence to recommend ultrasound for growth assessment in third trimester for individuals 35-39 years of age in absence of other risk factors 

  • But given the data for individuals age 40 and above, SMFM and ACOG recommend a growth ultrasound in the third trimester 

    • However, there is no data to guide timing or frequency of ultrasound assessments in individuals 40 or older 

• Prevention of stillbirth 

• We know there is increased risk of stillbirth with advancing age in pregnancy:

• In 2013, the stillbirth rate in the US was 6.0/1000 pregnancies that extended beyond 20 weeks of gestation 

  • For women 40-44: 10.1/1000 births 

  • For women >45: 13.8 /1000 births 

  • Risk of stillbirth at 37-41 weeks was 1/382 pregnancies for those 35-39, 1/267 in women 40 and older 

• However, the benefit of antenatal fetal surveillance to reduce the risk of stillbirth in this population remains unknown.

  • ACOG and SMFM have established guidance that suggests surveillance for conditions where stillbirth occurs more frequently than 0.8/1000 

  • Therefore, for those who will be 40 or older at time of delivery, antenatal surveillance is reasonable.

  • Reasonable to initiate some time between 32- 36 weeks of gestation 

  • Insufficient evidence for those 35-39 years of age

• Regarding delivery 

• Rate of stillbirth at 39 weeks in women 40 or older is nearly the same as rate of stillbirth of women aged 25-29 who are beyond 41 weeks gestation 

  • Therefore, delivery in well-dated pregnancies at 39 weeks of gestation or later for individuals 40 or older should be considered 

• Evidence for elevated stillbirth risk in individuals aged 35-39 is not sufficient to support a clear recommendation regarding timing of delivery beyond routine practice 

• Health equity 

• There is currently inequity in terms of maternal mortality and perinatal outcomes in patients who identify as non-Hispanic Black, as well as those that identify as American Indian and Alaskan Native 

• Maternal mortality 

• CDC Pregnancy Mortality Surveillance System data shows that maternal mortality trends determined a pregnancy related mortality ratio of 3.2 for non-Hispanic Black women compared to non-Hispanic White women 

• Ratio increased to 4.9 for non-Hospanic Black women between ages 35-39 

• 3.6 for women aged 40 years and older 

• Fetal outcomes 

• Preterm birth, SGA, stillbirth occur more frequently in some racial and ethnic groups that are disproportionately affected by social and structural barriers to care 

• Infant mortality rate for non-Hispanic black and American Indian/Alaska Native infants are 10.7/1000 live births and 7.9/1000 live births respectively 

• This is double the rate of non-Hispanic white infants 

• It is unclear the best strategy to overcome these inequities, but: 

• Ob/Gyns and other professionals should consider systems-based and individual strategies to reduce racial and ethnic disparities in care and outcomes 

• Systems: internal assessment of barriers and facilitators to providing equitable care, implementing unconscious bias and communication training, advocating for patient input in decision making