Advanced maternal age (AMA) is defined as childbearing in a woman over 35 years of age and is the cut-off age for a somewhat higher-risk pregnancy. Between 2014 and 2018 in the US, 230.7 per 1,000 women aged 34 to 44 experienced pregnancy complications. This trend is likely due to first-time moms delaying childbearing or to sub-fertility and those who have had babies in the past and desire more children.
Advanced maternal age (AMA) is reported to be associated with pregnancy complications including such as fetal growth restriction, preeclampsia, placental abruption, preterm birth and stillbirth.
In low‐risk women, the risk of adverse pregnancy – maternal and fetal – events increases with advancing maternal age even if adjusted for parity, onset of labor and gestational age.
Women aged over 40 have an increased risk of adverse fetal and maternal outcomes when pregnancy goes beyond 41 weeks. For this reason, induction of labor may be suggested before 41 weeks.
Women have benefited from advancements in infertility treatments such as reproductive technologies and this has created some unique risks because it is often undertaken after age 30.
Advanced maternal age associations
According to epidemiologic studies, AMA is reported to be associated with pregnancy complications including such as fetal growth restriction, preeclampsia, placental abruption, preterm birth and stillbirth.
More importantly, these increased risks appeared to be independent of other variables such as maternal comorbidities, such as diabetes, hypertension, and obesity. For example, there was a 100% increase in the number of pregnant women with pre-existing obesity in the US between 2015 and 2018.
Consequences of being high-risk
AMA is associated with an increased risk of Cesarean birth and stillbirth. Cesarean rates may be due to prior cesarean sections and a lower threshold to perform one in AMA women.
AMA is associated with an increase in emergency cesarean section, which is defined as fetal distress and/or arrest of labor, regardless of how many previous babies the woman had.
Literature review of high-risk pregnancies for older women
A review of literature on pregnancy risks in women over the age of 45 years found increased rates of hypertension before pregnancy, gestational diabetes mellitus, gestational hypertension and preeclampsia, and that these conditions can increase the risk of stillbirth independently. Placental dysfunction is deemed the most likely cause of stillbirths in high-income countries.
The majority of secondary outcomes in AMA women are small for gestational age infants, low birth weight infants, preterm birth, neonatal deaths, neonatal intensive care (NICU) admission, preeclampsia, placental abruption and GDM. However, only NICU admission and neonatal deaths had a significant correlation to increasing maternal age.
Stillbirths higher in AMA women with more than one baby
In first-time moms, the rate of stillbirth did not vary with maternal age but was more common in AMA women who had more than one baby. No studies have been able to distinguish between different causes of stillbirth, yet unexplained stillbirths were the most frequent classification in AMA. Congenital abnormalities are not considered the reason for stillbirth in AMA women.
As AMA is also associated with an increased risk of disorders such as placental abruption, preeclampsia and FGR, placental dysfunction and altered vascular function are the likely contributors.
Stillbirth is also more common in pregnancies when the father is between the age of 40 and 45, with a 50% increase in that rate in fathers over 45. Whether the combination of AMA and advanced paternal age combined further increases that risk is presently undetermined.
Another theory that may explain stillbirth is the reduced genetic quality of the older eggs. However, animal models have found relationships between older eggs and early placental growth, which may explain altered placental function.
Labor inductions and cesarean sections higher in AMA women
Women with AMA had more labor inductions and fewer spontaneous vaginal deliveries in comparison with women without AMA. The rate of cesarean section was 8.8% in women aged 18 to 34, 12.3% in women aged 35 to 39, and 16.3% in women aged over 40. This was primarily due to an increase in elective cesarean section.
There was an increase in cesarean sections due to fetal distress and arrest of labor that increased with age.
Composite adverse maternal outcome, primarily postpartum hemorrhage, was found in 4.6% of women aged 18 to 34, 5.0% of women aged 34 to 39 and 5.2% of women aged over 40.
Women with a higher gestational age and first-time mothers are more at risk for composite adverse perinatal or maternal outcomes, irrespective of maternal age.
Composite adverse perinatal outcome study
AMA is significantly associated with a higher incidence of composite adverse perinatal outcome (CAPO) after adjusting for the number of pregnancies, onset of labor and gestational age. AMA is also significantly associated with a higher incidence of composite adverse maternal outcome (CAMO) after the same adjustments.
One study in Denmark of 369,516 women addressed the CAPO by combining chromosomal abnormalities, congenital malformation, miscarriage, stillbirth and birth before 34 weeks of gestation.
The results were an increase in CAPO in women aged 35 to 39 years by 7%) and over 40 years by 10.8% in comparison with women aged 20 to 34 years who saw a 5.5% increase.