CASE: Preterm labor in an older woman
G.S. is a 41-year-old G1P0 with a several-year history of infertility and a medical history of chronic hypertension. She undergoes in vitro fertilization (IVF) using her own oocytes, with transfer of two embryos. Early ultrasonography (US) confirms a diamniotic/dichorionic twin gestation. She undergoes chorionic villus sampling (CVS) during the first trimester, with normal fetal karyotypes noted.
For her chronic hypertension, the patient is treated with oral labetalol 200 mg twice daily, beginning in the first trimester. Results of a baseline comprehensive metabolic profile and complete blood count, and electrocardiogram are normal. Baseline 24-hour urine study results reveal no significant proteinuria and a normal creatinine clearance.
At 18 weeks’ gestation, US results show normal growth and amniotic fluid volume for each fetus, with no anomalies detected. Because of a gradual increase in the patient’s blood pressure, her labetalol dose is increased to 400 mg orally thrice daily. Her urine protein output remains negative on dipstick, and US every 4 weeks until 28 weeks’ gestation continues to show normal fetal growth and amniotic fluid volume.
At 33 weeks’ gestation, the patient presents with regular uterine activity. Nonstress tests for both fetuses are reactive. She is given a 1-L intravenous (IV) fluid bolus of lactated Ringers solution, as well as subcutaneous terbutaline sulfate every 15 minutes for four doses, without resolution of the uterine contractions. Her pulse has increased to 120 bpm.
How do you manage this patient’s care?
Nine times as many women aged 35 and older gave birth to their first child in 2012 than did women of the same age 40 years ago, according to the most recent data from the National Center for Health Statistics.1 The rate of first births for women aged 40 to 44 remained essentially stable during the 1970s and early 1980s but increased more than fourfold from 1985 through 2012—from 0.5 to 2.3 per 1,000 women.1 Clearly, more women are delaying childbearing to a later age by personal choice for reasons such as completion of education and career advancement.2
The path to late motherhood is not without thorns, however. Heightened risks associated with increasing maternal age include:
- fetal aneuploidy
- fetal malformation
- gestational diabetes
- chronic and gestational hypertension
- antepartum hemorrhage
- placenta previa
- prelabor rupture of membranes
- preterm labor.3,4
Women with advanced age at conception also are more likely to have a multifetal gestation because of the need for assisted reproduction and are more likely to require cesarean delivery5 as a result of abnormal placentation, fetal malpresentation, an abnormal pattern of labor, or increased use of oxytocin in labor. In addition, they are more likely to experience rupture of the sphincter, postpartum hemorrhage, and thromboembolism.3 Advanced maternal age also is associated with a higher risk of stillbirth throughout gestation, with the peak risk period reported to occur at 37 to 41 weeks.6
Maternal age-related risks of autosomal trisomies (especially Down syndrome) are well understood and have been quantified for singleton and twin gestations. TABLE 1 shows the risks at term for singleton and twin gestations for at least one chromosomally abnormal fetus by maternal age (40–46 years) and race.7
Aging and fertility
These combined result of aging of the ovary and uterus and an escalating risk of underlying medical comorbidities has a detrimental effect on fertility.8 Although assisted reproductive technologies are helpful, they cannot guarantee a live birth or completely compensate for an age-related decline in fertility.9
Many IVF programs refuse infertility treatment to women over age 43 or 44 who want to use their own oocytes. The reason: low pregnancy rates. The use of donor oocytes, however, increases the risks of gestational hypertension and preeclampsia. And if assisted reproductive technologies are needed, the risk for multifetal pregnancy increases.
Women of advanced maternal age are likely to have an older spouse or partner. There is no clearly accepted definition of advanced paternal age, but it is most often defined as an age of 40 years or older at the time of conception. Advanced paternal age has been associated with a higher risk for autism spectrum disorder and schizophrenia, as well as mutations in the FGFR2 and FGFR3 genes that result in skeletal dysplasias and craniosynostosis syndromes.10
Medical conditions are more common
Women of advanced maternal age have an increased rate of such prepregnancy chronic medical complications as diabetes, chronic hypertension, obesity, and renal and cardiac disease. Therefore, it is best to optimize control of these chronic illnesses prior to conception to minimize the risks of miscarriage, fetal anomalies, and gestational hypertension and preeclampsia.
Preeclampsia. Although daily low-dose (60–81 mg) aspirin has been used to reduce the risk of preeclampsia, current recommendations from the American College of Obstetricians and Gynecologists (ACOG) suggest that this therapy be reserved for women with a medical history of early-onset preeclampsia or those who have had preeclampsia in more than one pregnancy.11