A relatively new screening option is analysis of cell-free fetal DNA in maternal blood, which can be performed after 10 weeks’ gestation in singleton and multiple gestations. This directed analysis measures the relative proportions of chromosomes. The detection rate for fetal Down syndrome using cell-free fetal DNA is greater than 98%, with a false-positive rate of less than 0.5%. However, this screening is unreliable in triplet gestations.
Other screening options include US and biochemical screening to detect fetal aneuploidy and open neural tube defects during the second trimester. These options should be included in counseling of the patient.
Second and third trimesters
Gestational hypertension and preeclampsia are significant risks
Older pregnant women have an incidence of gestational hypertension and preeclampsia 2 to 4 times as high as that of patients younger than 30 years.13 The underlying risk for preeclampsia is further increased if coexisting medical disorders such as diabetes or chronic hypertension are present. Moreover, the risk for preeclampsia increases to 10% to 20% in twin gestations and 25% to 60% in triplet gestations. Le Ray and colleagues reported that, if oocyte donation is used with IVF in women older than age 43, the risk for preeclampsia triples.14
We previously studied 379 women aged 35 and older who had mild gestational hypertension remote from term, comparing them with their younger adult counterparts in a matched cohort design.15 Outpatient management produced similar maternal outcomes in both groups, but older women had a statistically insignificant increase in the rate of stillbirth (5 vs 0; P = .063).15
Gestational diabetes risk doubles
The rates of both diabetes mellitus and gestational diabetes increase with advanced maternal age. Data from the FASTER consortium included an adjusted odds ratio of 2.4 for gestational diabetes in women aged 40 or older, compared with a younger control group.4 This increased risk may be a consequence of greater maternal habitus as well as declining insulin sensitivity.
Diabetes increases the risks of macrosomia, cesarean birth, and gestational hypertension. Among women with pregestational diabetes, the risks of congenital heart disease and fetal neural tube defects increase threefold. Because of this increased risk, perinatal screening is indicated for both anomalies in older women.
Pulmonary complications increase
Another risk facing women of advanced maternal age—particularly those carrying a multiple gestation—is pulmonary edema, owing to the increased cardiac output, heart rate, and blood volume, the decreased systemic vascular resistance, and the physiologic anemia of pregnancy. These risks rise further in women who develop preterm labor that requires therapy and in those who develop gestational hypertension and/or preeclampsia. Judicious use of IV fluids, particularly those with lower sodium concentrations, can reduce the risk of pulmonary complications.
Women who develop pulmonary edema have an increased risk of peripartum cardiomyopathy.16
Preterm delivery is more common
Cleary-Goodman and colleagues noted an increased incidence of preterm delivery in women aged 40 and older, compared with women younger than age 35, but no increase in spontaneous preterm labor.4 Advanced maternal age appears to be associated with an increased risk of preterm birth largely as a consequence of underlying complications of fetal growth restriction and maternal disease, including hypertension. Because preterm birth is an important contributor to perinatal morbidity and mortality, steroids should be administered for fetal lung maturity whenever preterm labor is diagnosed before 34 weeks’ gestation.
Risk of placenta previa is 1.1%
Joseph and colleagues found the risk of placenta previa to be 1.1% in women aged 40 and older, compared with 0.3% in women aged 25 to 29 years.17 This increased risk likely is a consequence not only of maternal age but increased parity and a history of prior uterine surgery. If transabdominal US results are suspicious for placenta previa, transvaginal US is indicated for confirmation. Additional US assessment of the cord insertion site to the placenta also should be performed to rule out vasa previa.
Look for neonatal complications
Ziadeh and colleagues found that, although maternal morbidity was increased in older women, the overall neonatal outcome did not appear to be affected.18 However, we noted a higher rate of neonatal complications in women aged 40 or older, including higher NICU admission rates and more low-birth–weight infants.11
In addition, Odibo and colleagues found advanced maternal age to be an independent risk factor for intrauterine growth restriction (IUGR).19 In that study, the odds ratio for IUGR was 3.2 (95% confidence interval [CI], 1.9–5.4) for a maternal age of 40 years or older, compared with a control group. For that reason, they recommend routine screening for IUGR in all pregnant women of advanced age.
Stillbirth risk peaks at 37 to 41 weeks
In a review of more than 5.4 million singleton pregnancies without reported congenital anomalies, Reddy and colleagues found an association between advanced maternal age and stillbirth, with a higher risk of stillbirth at 37 to 41 weeks’ gestation.6 This effect of maternal age persisted despite adjusting for medical disease, parity, and race/ethnicity.
