Risk of stillbirth and miscarriage

Kortekaas et al found that the absolute risk of having a stillbirth at ages 35-39 was 0.22%, meaning then that 2.2 pregnant people out of 1 000 in this age group will experience a stillbirth.⁵

The rate of spontaneous miscarriage (pregnancy loss before 20 weeks) increases with age. The increased risk of miscarriage in older pregnant people is related to both egg quality and an increase in pre-existing medical conditions.²

A 2019 study by Magnus et al found that the risk of miscarriage was:⁶

• 17% at <20 years
• 11% at 20-24 years
• 10% at 25-29 years
• 11% at 30-34 years
• 17% at 35-39 years
• 33% at 40-44 years
• 57% at >45 years.

Risks of aneuploidy and congenital abnormalities

The risks of aneuploidy and congenital anomalies also increase with maternal age and despite antenatal screening, they likely contribute to the increased rate of stillbirth. These are the age-related rates of an embryo having Down syndrome at 10 weeks of pregnancy:^2,3,4

The rates of having a baby with Down syndrome at term are not as high as the chances at 10 weeks, mostly because these pregnancies have higher rates of miscarriage and stillbirth and won’t all reach the term period.²

Additional risks associated with AMA

AMA is also associated with the risk of higher ectopic pregnancy (eight times greater than women between the ages of 15- to 19-years), gestational diabetes mellitus (1.62 incidence rate) and gestational hypertension (increased relative risk of 1.2).⁴

What do women fear most when getting pregnant at an older age?

There are numerous reasons why women opt for delaying motherhood. Focusing on their careers, education, and travel are some of the main reasons given by some women, while others did not feel that they were ready to have get married or have children until they were older. Fear of infertility was one of the main reasons for deciding to become pregnant. Furthermore, advances in reproductive technology have extended the reproductive window of women, with a corresponding increase incidence of AMA.^4,7

In a small study involving pregnant women between 35- to 44-years (mean of 37.6 years) participants raised the following concerns:⁷

• Risks associated with pregnancy >35-years (interestingly, their fear of the risks decreased with advancing gestational weeks. An uncomplicated pregnancy and favourable screening results may contribute to this decrease)
• Foetal health and well-being (particularly genetic abnormalities)
• Waiting for screening results
• Bed rest and limited physical activities due to pregnancy complications (eg morning sickness)
• That this might be their last opportunity to have a biological child, contributed to feelings of anxiety/depression.

Managing pregnant women of AMA

1. Healthcare providers’ opinion

According to the participants in the study by Bayrampour et al, clinicians’ views, reactions to and interpretations of the risks associated with their late pregnancies play a role in how they themselves understand, react, assess and manage their risks. Participants also indicated that they do not want to be reminded of the risks constantly. Women may also intuit clinicians’ reactions and body language and taken together with information about their risks, will react in a certain manner (eg uncertain/vulnerable or optimistic).⁷

2. Pre-conception counselling should include supplementation

According to Glick et al, pregnant women of AMA should be encouraged to optimise their health when preparing for pregnancy, stop smoking and drinking alcohol, start physical activity, achieve normal body weight, take folic acid supplements, and stabilise comorbidities (eg gestational diabetes and hypertension).⁴

The American Academy of Family Physicians’ position paper on preconception care states that all women of reproductive age should be advised to take a daily supplement (prenatal or multivitamin), or 400mcg to 800mcg of folic acid daily, and to consume a balanced, healthy diet of folate-rich foods.⁸ 

Folic acid supplementation should start prior to conception and continue through 12 weeks of pregnancy. A higher dose of preconception folic acid (4mg starting one month prior to attempting pregnancy and continuing through the first three months of pregnancy) is recommended for women at high risk of pregnancy complications.⁸

Similarly, the World Health Organization’s 2020 maternal and perinatal guidelines recommend antenatal multiple micronutrient supplements that include iron, folic acid, as well as vitamin D for all pregnant women and adolescent girls.⁹

More recently (2022), the authors of an expert review that focused on the importance of nutrition in pregnancy and lactation, state that evidence supports the benefit of comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy). Comprehensive nutritional supplementation is associated with improved birth outcomes, stressed Marshall et al.¹⁰

Well-nourished women who consume an adequate diet may not require additional multivitamin supplementation, but in the absence of comprehensive evaluation by a dietitian, routine supplementation is encouraged.¹⁰

3. Low-dose aspirin prophylaxis

The United States Preventive Services Task Force – endorsed by the American College of Obstetricians and Gynaecologists – state that AMA is considered a moderate risk factor for pre-eclampsia. Thus, low-dose aspirin prophylaxis is recommended only when another moderate risk factor (nulliparity, obesity, family history of pre-eclampsia in mother or sister, African American race, low socioeconomic status, previous pregnancy with small gestational age infant, stillbirth, or interval >10 years between pregnancies) exists or in the presence of other high-risk factors.

4. Invasive diagnostic procedures

Women should be encouraged and counselled to undergo aneuploidy screening testing (preferably the cell free DNA testing) along with a detailed ultrasound and amniocentesis.

5. Preimplantation genetic testing

More research is needed regarding the benefit of preimplantation genetic testing in reducing miscarriage rates.

6. Induction of labour

Given the increased risk for stillbirth women of AMA, and particularly in very advanced maternal age (>40-years), it is reasonable to offer them induction of labour or elective caesarean delivery at 39 weeks’ gestation.

7. Prenatal screening for anxiety and depression

There is evidence that antenatal anxiety can increase the odds of postnatal depression. Therefore, identification of women with anxiety is crucial so that effective interventions can be targeted appropriately. Prenatal screening should also include screening for both depression and anxiety.⁷

References

1. Patel R, Moffatt JD, Mourmoura E, et al. Effect of reproductive ageing on pregnant mouse uterus and cervix. The Journal of Physiology, 2017.
2. Dekker R. Evidence on: Pregnancy at Age 35 and Older. https://evidencebasedbirth.com/advanced-maternal-age/
3. Jolly M, Sebrine N, Harris J, Robinson S and Regan L. The risks associated with pregnancy in women aged 35 years or older. Hum Reprod, 2000.
4. Glick I, Kadish E, Rottenstreich M. Management of Pregnancy in Women of Advanced Maternal Age: Improving Outcomes for Mother and Baby. Int J Womens Health, 2021.
5. Kortekaas JC, Kazemier BM, Keulen JKJ, et al. Risk of adverse pregnancy outcomes of late‐and postterm pregnancies in advanced maternal age: A national cohort study. Acta Obstet Gynecol Scand, 2020.
6. Magnus MC, Wilcox AJ, Morkel N-H, et al. Role of maternal age and pregnancy history in risk of miscarriage: prospective register-based study. BMJ,
7. Bayrampour H, Heaman M, Duncan KA and Tough S. Advanced maternal age and risk perception: A qualitative study. Pregnancy and Childbirth, 2012.
8. American Academy of Family Physicians. Preconception Care (Position Paper), 2016. https://www.aafp.org/about/policies/all/preconception-care.html
9. Nutritional interventions update: multiple micronutrient supplements during pregnancy. https://www.who.int/publications/i/item/9789240007789
10. Marshall NE, Abrams B, Barbour LA, et al. The importance of nutrition in pregnancy and lactation: lifelong consequences. American Journal of Obstetrics & Gynecology, 2022.