Pregnancy at Age 35 Years or Older

SUMMARY:

Advanced maternal age (AMA) was historically defined as women who will be ≥35 years at estimated date of delivery (EDD). There has been a continued upward trend in the mean age of pregnant individuals in the US and globally. AMA is associated with adverse maternal, fetal, neonatal adverse outcomes, with progressive age-related risks. ACOG in collaboration with SMFM, provide evidence-based clinical recommendations for obstetric care in this population. The document notes the fact that 35 years is an arbitrary threshold, and some outcomes may not be of concern until 40 years of age or later.

Associated Risks

• AMA is associated with higher risks for
  • Gestational diabetes | Preeclampsia | Labor dystocia | Cesarean delivery
  • Preterm birth | NICU admission | Low birth weight | Low 5-minute Apgar score
  • Pre-gestational chronic hypertension | Type 2 diabetes
• Risk for adverse outcomes increases continuously with advancing age
  • 35 to 39 years | 40 to 44 years | 45 to 49 years | ≥50 years

Preeclampsia

• Progressive risk with increasing age particularly >40 years
• Daily low-dose aspirin is recommended in patients ≥35 years old with at ≥1 other high/moderate risk factor
  • Initiate between 12 and 16 weeks and continue until delivery
  • High risk factors: History of preeclampsia | Multifetal gestation | Chronic hypertension | Diabetes | Kidney disease | Autoimmune disease
  • Moderate risk factors: Nulliparity | Obesity | Family history of preeclampsia | Black race | Lower income | Previous adverse pregnancy outcome
  • Black race and lower income are risk factors related to racism and health disparities

Multiple Gestation

• Twin birth doubles >35 years and triples >40 years vs <20 years
• Increased risk for multiple gestation with increasing age
  • Partly attributed to ovulation induction and assisted reproductive technology
• Increased risk for nearly all pregnancy related morbidities with multiple gestations
• Making the diagnosis
  • Determine number of fetuses: First trimester
  • Determine chorionicity:  Late first trimester or early second trimester

Chromosomal Abnormalities

• Prenatal genetic screening and diagnostic testing should be offered to all pregnant individuals regardless of age or risk of chromosomal abnormality
  • Prenatal genetic screening: Serum screening with or without nuchal translucency ultrasound | Cell-free DNA screening
  • Diagnostic testing: Chorionic villus sampling | Amniocentesis
• Age 35: Increased risk for chromosomal abnormalities
  • Risk of all chromosomal abnormalities: 1 in 84
  • Trisomy 21: 1 in 294
  • Trisomy 18: 1 in 1111
  • Trisomy 13: 1 in 2500
  • Sex chromosome aneuploidy: 1 in 285
  • Rare chromosomal abnormality: 1 in 270
• Age 40: Increased risk for chromosomal abnormalities
  • Risk of all chromosomal abnormalities: 1 in 40
  • Trisomy 21: 1 in 86
  • Trisomy 18: 1 in 333
  • Trisomy 13: 1 in 714
  • Sex chromosome aneuploidy: 1 in 196
  • Rare chromosomal abnormality: 1 in 270
• Decision about testing should be shared between patient and clinician based on values, availability, regardless of cost
  • If available, a genetic counselor may offer additional assistance

Note: Sex chromosome trisomies (XXX, XXY, XYY) increase with maternal age but rates of 45X (Turner syndrome) does not

Congenital Anomalies

• A detailed fetal anatomic ultrasound examination is recommended particularly for individuals without aneuploidy screening or testing
• Potential increased risk for congenital anomalies
  • Previous studies suggest higher risk of congenital cardiac disease | Cardiac malformations | Neural tube defects | Renal anomalies
  • Recent studies show conflicting results challenging the concept that maternal age alone is an independent risk factor for congenital anomalies

Birth Weight

• Ultrasound for growth assessment is recommended in the third trimester for patients ≥40 years
• Higher frequency of both small-for-gestational-age and large-for-gestational-age
  • Risk increases significantly in patients >40 years
  • Low birth weight partially attributed to preterm delivery
• No data regarding timing or frequency of ultrasound assessments
  • Depends on other comorbidities or pregnancy complications
• Insufficient evidence to recommend growth assessment ultrasonography for patients aged 35 to 39 years in the absence of other risk factors

Stillbirth

• Antenatal fetal surveillance is recommended for patients ≥40 years
• Higher risk for stillbirth with increasing maternal age >35 years and gestational age >37 weeks
• Antenatal surveillance
  • No data on timing or frequency of antenatal surveillance
• ≥40 years: Risk begins to increase and therefore reasonable to initiate surveillance between 32 and 36 weeks
• 35 to 39 years: Insufficient evidence to recommend antenatal fetal surveillance in the absence of other risk factors

Delivery

≥40 Years

• Delivery at 39w0d to 39w6d is recommended
• Induction of labor between 39w0d and 39w6d
  • No increased risk of adverse neonatal outcomes
  • Potential benefits: Decrease in cesarean delivery rate and hypertensive disorders in general population
  • ≥35 years

35 to 39 Years

• Insufficient evidence to recommend timing for delivery in the absence of other risk factors

Mode of Delivery

• Vaginal delivery is safe and appropriate if there are no other indications for cesarean delivery
• Higher rates of cesarean delivery with increasing age
  • Associated with increased maternal morbidity
• Advancing age alone is not an indication for cesarean delivery
• Counseling should include risks of cesarean delivery, individual comorbidities, and patient preferences

Health Inequities

• Obstetric care professionals should be aware of disproportionate rates of most adverse maternal and perinatal outcomes in Black and American Indian and Alaska Native individuals ≥35 years
• Maternal mortality rate is substantially higher among these populations and increases >35 years
• Preterm birth increases significantly more in the Black population ≥35 years as racism contributes to perpetuating these outcomes
• Obstetric care professionals should consider system-based and individual strategies to reduce racial and ethnic disparities in care and outcomes
• Advocate for anti-racist policies and practices

KEY POINTS

• Advanced maternal age is a risk factor for adverse outcomes with progressive risk >40 years
• Prenatal genetic screening and diagnostic testing should be offered to all pregnant individuals
• Be aware of disproportionate rates of adverse outcome in Black and American Indian and Alaska Native due to racism and health disparities
• For pregnant individuals ≥35 years
  • Daily low-dose aspirin in the setting of least one other moderate risk factor
  • First-trimester ultrasound given the increased rate of multiple gestation
  • Detailed fetal anatomic ultrasound given the potential increased risk of congenital abnormalities
• For pregnant individuals ≥40 years
  • Daily low-dose aspirin in the setting of at least one other moderate risk factor
  • Ultrasound for growth assessment in the 3rd trimester due to increased risk for both large-for-gestational age and small-for-gestational-age
  • Antenatal surveillance given the increased risk for stillbirth
  • Delivery at 39w0d to 39w6d due to increased risk of neonatal morbidity and stillbirth with advancing gestational age

Learn More – Primary Sources: 

ACOG Obstetric Care Consensus 11: Pregnancy at Age 35 Years or Older