There were no clinically significant differences noted between the groups with regard to gestational age at delivery or birth weight. The mean gestational age at delivery was 39.1 ± 2.7 weeks for all patients, 39.1 ± 2.5 weeks for group 1, 39.0 ± 3.1 weeks for group 2, and 38.7 ± 3.7 weeks for group 3. The mean birth weight was 3,348 ± 538 g for all patients, 3,341 ± 531 g for group 1, 3,385 ± 557 g for group 2, and 3,331 ± 588 g for group 3.
As anticipated, advancing maternal age was significantly associated with an increased risk for miscarriage (adjOR 2.0, 95% CI 1.5–2.6; adjOR 2.4, 95% CI 1.6–3.6, for ages 35–39 years and ≥ 40 years, respectively) and chromosomal abnormalities (adjOR 4.0, 95% CI 2.5–6.3; adjOR 9.9, 95% CI 5.8–17.0). Advancing maternal age was also significantly associated with fetal/neonatal congenital anomalies (adjOR 1.4, 95% CI 1.1–1.8; adjOR 1.7, 95% CI 1.2–2.4), gestational diabetes (adjOR 1.8, 95% CI 1.5–2.1; adjOR 2.4, 95% CI 1.9–3.1), placenta previa (adjOR 1.8, 95% CI 1.3–2.6; adjOR 2.8, 95% CI 1.6–4.6), and cesarean delivery (adjOR 1.6, 95% CI 1.5–1.7; adjOR 2.0, 95% CI 1.8–2.3). Patients aged 35–39 years were at increased risk for macrosomia (adjOR 1.4, 95% CI 1.1–1.8). In addition, age greater than 40 years at delivery was significantly associated with placental abruption (adjOR 2.3, 95% CI 1.3–3.8), preterm delivery (adjOR 1.4, 95% CI 1.1–1.7), low birth weight (adjOR 1.6, 95% CI 1.3–2.1), and perinatal mortality (adjOR 2.2, 95% CI 1.1–4.5). No statistically significant differences were noted among the groups for threatened abortion, gestational hypertension, preeclampsia, preterm labor, preterm PROM, and assisted vaginal delivery.
The impact that the decision to delay childbearing has on maternal and perinatal outcomes becomes increasingly relevant as more and more women postpone having children until they are over the age of 35. There are numerous reports in the literature assessing the effect of advancing maternal age on pregnancy outcomes, but results are varied.2–31 The majority of studies are optimistic with regard to maternal and neonatal outcomes.2,3,33 Unlike the majority of other studies, the study described here is a contemporary, large, prospective study of unselected patients with singletons, which was conducted over a narrow period of time with approximately 98% ascertainment of outcome data. Most importantly, potential confounding factors to the relationship between advancing maternal age and the obstetric outcomes, including race, parity, BMI, education, marital status, smoking, pre-existing medical conditions, previous adverse pregnancy outcomes, use of assisted conception, and patient's study site, were considered separately.
Our investigation found that both maternal and perinatal outcomes are favorable for women of advancing maternal age. For the most part, patients aged 35 and older deliver at term with birth weights comparable to infants born to women aged less than 35 years at delivery. We did not find a statistically significant association between maternal age 35 or older and increased risk for threatened abortion, gestational hypertension, preeclampsia, preterm labor, preterm PROM, and operative vaginal delivery. Nonetheless, advancing maternal age is statistically associated with a small number of adverse outcomes even after controlling for race, parity, BMI, education, marital status, smoking, pre-existing medical conditions, previous adverse pregnancy outcomes, use of assisted reproductive care, and patient's study site. As would be expected, maternal age greater than 35 years and maternal age 40 years and older at delivery are both associated with an increased risk for miscarriage (adjORs 2.0 and 2.4, respectively) and for chromosomal abnormalities (adjORs 4.0 and 9.9, respectively). Ages 35–39 years were associated with a statistically significant increased risk for fetal/neonatal congenital anomalies, gestational diabetes, placenta previa, macrosomia, and cesarean delivery. The clinical significance of these associations in practice is less clear because, although P was < .05, the adjOR was not greater than 2.0. That is, while women aged 35–39 years were significantly more likely to experience one of these outcomes statistically, the level of increased risk was not overly large and should be interpreted cautiously. Maternal age 40 years and older at delivery, on the other hand, was an independent risk factor for gestational diabetes (adjOR 2.4), placenta previa (adjOR 2.8), placental abruption (adjOR 2.3), cesarean delivery (adjOR 2.0), and perinatal mortality (adjOR 2.2). The magnitude of these odds ratios would suggest that these findings are not only statistically significant, but also are likely to be clinically meaningful. Increased risks for fetal/neonatal congenital anomalies, preterm delivery, and low birth weight were statistically associated with age 40 years and older, but the clinical significance of these associations is less clear because the adjOR was not greater than 2.0.
This study is a large report of pregnancy outcomes in patients 40 years and older, including outcomes for 1,364 patients in this age group. Gilbert et al14 reported on 24,032 cases but their study was limited by the fact that it was a retrospective study based on birth certificate and hospital discharge record data from the period 1992–1993. Bianco et al2 performed a study on 1,404 patients 40 years and older who delivered during the period 1988–1994. The latter study was limited by the fact that it was retrospective and studied a select population of patients with private medical insurance.
More recently, a birth certificate review from Sweden by Jacobsson et al34 reported pregnancy outcomes on a large cohort of older patients who delivered between 1987 and 2001. This study suggested an increased risk of developing severe preeclampsia with advancing maternal age but a decreased risk of developing mild preeclampsia. The authors could not explain this apparent contradiction. Rates of gestational hypertensive diseases in the control and study groups were lower than expected, calling into question the completeness of case ascertainment and so the applicability of the findings. In addition, the Swedish study disregarded outcome information on adverse events, including fetal loss, occurring before 28 weeks of gestation and did not control for use of in vitro fertilization. In contrast, our study did not suffer from the limitations of birth certificate studies and controlled for relevant confounding factors, including use of assisted conception. Furthermore, although our patients derived from those who were able to obtain prenatal care beginning in the first trimester, our patient population was diverse, coming from 15 medical centers throughout the United States. Therefore, our results more likely reflect the contemporary heterogeneous patient population in the United States.
An interesting aspect of this study was that we did not find advancing maternal age to be associated with a statistically significant increased risk for hypertensive complications of pregnancy such as gestational hypertension (adjOR 0.8 and 1.0, for women aged 35–39 and those aged ≥ 40 years, respectively) or preeclampsia (adjOR 0.9 and 1.1, for ages 35–39 and ≥ 40 years, respectively). These findings regarding hypertensive complications in pregnancy are in contrast to many other reports.2–5,7,14,18,21,23,25,26,28,30,35 Although there have been studies suggesting that advancing maternal age may not be associated with a statistically significant increased risk for hypertensive complications, these reports were limited by small numbers of patients.19,24,31 Our study controlled for covariates associated with gestational hypertension and preeclampsia, including parity, history of medical conditions, and use of assisted reproductive care. As a result, our findings suggest that although chronic hypertension is more common with advancing maternal age, age alone is not responsible for gestational hypertensive complications. It is important to note that our study did not include enough women older than 45 years and older than 50 years to draw any statistical conclusions about rates of gestational hypertension and preeclampsia in women of these age groups. The effect of egg donation on rates of gestational hypertensive complications also could not be discerned. Hypertensive complications of pregnancy may be more common in these patients. Seven percent of these women older than 45 years were diagnosed with gestational hypertension, while 11% had preeclampsia.
Other findings in our study are consistent with previous studies. It is well established that advancing maternal age is associated with an increased risk for miscarriage and fetal chromosomal abnormalities.5 In patients aged 40 years and older, the higher incidence of antepartum complications such as miscarriage, gestational diabetes, placenta previa, and placental abruption have been documented in the literature.2,13,14,21,23,30,36,37 The increased incidence of miscarriage is thought to be secondary to the increased risk of chromosomal abnormalities in these pregnancies. The increased risk of gestational diabetes and placenta previa may be secondary to the relationship between aging and progressive vascular endothelial damage.2,23,38 Studies regarding an increased risk for perinatal mortality in women of advanced maternal age have been controversial.2,3,11,14,21,26,28,31,39 In this study, the increased risk of perinatal mortality was not statistically significant for patients aged 35–39 years (adjOR 1.1). Age 40 years and older was associated with a statistically significant increased risk of perinatal loss (adjOR 2.2). There were only 119 stillbirths and 37 neonatal demises in total. As a result, we could not draw any meaningful conclusions about the etiology or timing of perinatal mortality in women of advancing maternal age. The reason that advanced-maternal-age patients may be at increased risk of perinatal mortality is unknown.40 The failure of uterine vasculature to adapt to the increased hemodynamic demands of pregnancy as women age is a proposed explanation.23
As with prior literature, this study demonstrated that women aged 40 years and older are at increased risk for cesarean delivery.2,13,14,21,22,26–28,30,31 Older women may be at increased risk for abnormalities of the course of labor, perhaps secondary to the physiology of aging. It is possible that decreased myometrial efficiency occurs with aging.2,12 Nonetheless, maternal age alone may be a factor influencing physician decision making.24 It is uncertain whether the increased rates of cesarean delivery are due to a real increase in the prevalence of obstetric complications or whether there is a component of iatrogenic intervention secondary to both physician and patient attitudes toward pregnancy in this older patient population.2,5,41–43
It is important to note that the findings of this study may not be generalized to every advanced-maternal-age obstetric patient in the United States. Although the FASTER trial patient population was unselected, meaning that patients were not excluded based on any confounding factors such as race, parity, BMI, education, marital status, smoking, pre-existing medical conditions, previous adverse pregnancy outcomes, and use of assisted reproductive care, there may have been significant patient or provider self-selection. Patients could only enroll in the study if they started antepartum care in the first trimester and if they received care at a facility participating in the FASTER trial.
In summary, the majority of women of advanced maternal age deliver at term without maternal or perinatal adverse outcomes. Advancing maternal age does not appear to be associated with hypertensive complications such as gestational hypertension and preeclampsia. Nonetheless, as women become older, they become increasingly prone to perinatal complications above and beyond the medical complications concomitant with aging. This study better defines the importance of both counseling and following patients for specific adverse outcomes associated with advancing maternal age. Patients aged 35 years and older are at an increased risk for miscarriage and fetal chromosomal abnormalities, many of which may be diagnosed prenatally. Age 40 years and older is an independent risk factor for gestational diabetes, placenta previa, placental abruption, cesarean delivery, and perinatal mortality. The role of routine antenatal surveillance in women aged 40 years and older requires further investigation because these women seem to be at increased risk for perinatal mortality, including stillbirth. Although the likelihood of adverse outcomes increases along with maternal age, patients and obstetric care providers can be reassured that overall maternal and fetal outcomes are favorable in this patient population.
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The following is a list of the members of the FASTER Research Consortium: K. Welch, ms, R. Denchy, ms (Columbia University, New York, NY); F. Porter, md, M. Belfort, md, B. Oshiro, md, L. Cannon, bs, K. Nelson, bsn, C. Loucks, rnc, A. Yoshimura (University of Utah, and IHC Perinatal Centers, Salt Lake City, Provo, and Ogden, UT); D. Luthy, md, S. Coe, ms (Swedish Medical Center, Seattle, WA); J. Esler, bs (William Beaumont Medical Center, Royal Oak, MI); G. Hankins, md, R. Bukowski, md, phd, J. Lee, ms (UTMB, Galveston, TX); R. Berkowitz, md, Y. Kharbutli, ms (Mount Sinai Medical Center, New York, NY); I. Merkatz, md, S. Carter, ms, S. Gross, md (Montefiore Medical Center, Bronx, NY); J. Hobbins, md, L. Schultz, rn (University of Colorado Health Science Center, Denver, CO); M. Paidas, md, J. Borsuk, ms (NYU Medical Center, New York, NY); B. Isquith, ms, B. Berlin, ms (Tufts University, Boston, MA); J. Canick, phd, G. Messerlian, phd, C. Duquette, rdms (Brown University, Providence, RI); R. Baughman, ms (University of North Carolina, Chapel Hill, NC); K. Dukes, phd, L. Sullivan, phd, T. Tripp, ma, D. Emig, mph, N. Tibbetts (DM-STAT Inc, Medford, MA).© 2005 The American College of Obstetricians and Gynecologists