Advanced maternal age and the risk of antepartum stillbirth

A. Approximately 14.2% of women who give birth in the United States are 35 years of age or older, and 2.6% are age 40 or older.¹ Over the last 30 years, there has been a 36% increase in first births among women aged 35 to 39, and a 70% increase among women who are aged 40 to 45.

Stillbirth, defined as fetal death at 20 weeks or more, occurs at a rate of 6.2 per 1,000 US births. Epidemiological data have consistently implicated advanced maternal age (AMA) as one of the most important contributors to unexplained stillbirth.^2-5 Fretts and colleagues found that after controlling for many factors that occur more frequently in older women, such as hypertension, diabetes, abruption, and multiple gestation, AMA remained an independent risk factor for stillbirth.² Women aged 35 to 39 had a 1.9-fold increased risk of stillbirth compared with women younger than 30, while women 40 years or older had a 2.4-fold higher risk.

After adjusting for coexisting conditions, a recent meta-analysis demonstrated that AMA was associated with an increase of 65% in the odds of stillbirth, and the odds increased with increasing age, doubling for women age 40 or older (adjusted Odds Ratio [aOR], 2.29; 95% Confidence Interval [CI], 1.54-3.41).¹

Given the increased risk of stillbirth for women of AMA, should antepartum surveillance be routinely performed?

Antepartum surveillance is used for women deemed to be at increased risk for fetal death. While AMA has clearly been shown to be a significant risk factor for stillbirth at term, in the absence of other co-indications (eg, maternal or fetal complications), it has not routinely served as an indication for antepartum testing.

In an analysis of stillbirth by maternal age for nonanomalous singleton pregnancies in the United States, Reddy et al found that the risk of stillbirth for women 40 or older was higher at all gestational ages, but was particularly increased after 38 weeks' gestation.⁴ They demonstrated that older women have a magnitude of stillbirth risk usually seen with postdates, but that this occurs earlier in gestation. For example, for women younger than 35, the risk of stillbirth at 41 weeks is less than that of women aged 35 to 39 at 40 weeks and that of women 40 and older at 39 weeks.

Similarly, Bahtiyar et al used a mathematical model to show that the cumulative risk of stillbirth at 38 and 39 weeks in women aged 40 to 44 was similar to the stillbirth risk in women aged 25 to 29 at 41 and 42 weeks.⁵

Fretts et al performed a decision analysis of antepartum testing late in pregnancy for women who were at least age 35.⁶ Three strategies were compared: no testing, weekly testing starting at 37 weeks with induction after a positive test, and no testing with induction at 41 weeks. The analysis predicted that of the three, antepartum testing would be the most successful in reducing the number of unexplained stillbirths, although it was also associated with the highest induction rate. The model estimated that it would take approximately 863 antepartum tests and 71 additional inductions to prevent 1 unexplained stillbirth.