The authors have declared that no competing interests exist.
Conceived and designed the experiments: CAG AHJ. Analyzed the data: CAG CAC AHJ. Contributed reagents/materials/analysis tools: CAG HLB RPH AHJ. Wrote the paper: CAG CAC LNCJ HLB RPH AHJ.
The number of women aged 45 and older who become pregnant is increasing. The objective of this study was to estimate the risk of medical and obstetric complications among women aged 45 and older.
The Nationwide Inpatient Sample was used to identify pregnant woman during admission for delivery. Deliveries were identified using International Classification of Diseases, Ninth Revision (ICD-9-CM) codes. Using ICD-9-CM codes, pre-existing medical conditions and medical and obstetric complications were identified in women at the time of delivery and were compared for women aged 45 years and older to women under age 35. Outcomes among women aged 35–44 were also compared to women under age 35 to determine if women in this group demonstrated intermediate risk between the older and younger groups. Logistic regression analyses were used to calculate odds ratios with 95% confidence intervals for pre-existing medical conditions and medical and obstetric complications for both older groups relative to women under 35. Multivariable logistic regression analyses were also developed for outcomes at delivery among older women, while controlling for pre-existing medical conditions, multiple gestation, and insurance status, to determine the effect of age on the studied outcomes.
Women aged 45 and older had higher adjusted odds for death, transfusion, myocardial infarction/ischemia, cardiac arrest, acute heart failure, pulmonary embolism, deep vein thrombosis, acute renal failure, cesarean delivery, gestational diabetes, fetal demise, fetal chromosomal anomaly, and placenta previa compared to women under 35.
Pregnant women aged 45 and older experience significantly more medical and obstetric complications and are more likely to die at the time of a delivery than women under age 35, though the absolute risks are low and these events are rare. Further research is needed to determine what associated factors among pregnant women aged 45 and older may contribute to these findings.
Advanced reproductive age, commonly defined as maternal age of 35 years or older at the time of delivery, has long been known to be a risk factor for fetal chromosomal abnormalities as well as for relatively common medical complications such as chronic hypertension, hypertensive disorders of pregnancy, and diabetes.
The fertility rate among women in their forties and fifties is low and risk for miscarriage among those who do become pregnant is high.
Prior studies of pregnancy outcomes among women in their forties and fifties have primarily focused on neonatal outcomes or common medical conditions. Many of these studies relied on data from single centers with sample sizes too small to determine if older women are at increased risk for death or severe medical morbidity. Using a national database, the objective of this study was to determine if healthy women aged 45 and older are at increased risk for death and severe medical and obstetric morbidity compared to women under 35.
The study was reviewed and approved by the Duke University Medical Center Institutional Review Board as exempt research. The Nationwide Inpatient Sample (NIS) from the Healthcare Cost and Utilization Project of the Agency for Healthcare Research and Quality (AHRQ) for years 2008 to 2010 was queried for all pregnancy-related discharges.
Using the NIS for the years 2008–2010, all records containing a delivery-related discharge were identified. An admission for delivery was defined as any discharge record that included a delivery code (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes 74.x [except 74.91] for cesarean delivery; and V27, 72.x, 73.x, and 650 for general delivery codes [not utilized to specify mode of delivery]). Deliveries were also identified by diagnosis-related group (DRG) codes. DRG codes 765 and 766 were utilized to identify cesarean deliveries and codes 767, 768, 774, and 775 for vaginal deliveries.
Data was weighted based on the NIS sampling design. Two-way chi-square tests incorporating NIS discharge weighting variables and survey codes generated cell frequencies and standard deviations for demographics, medical conditions and events, and pregnancy-related complications. Survey-weighted logistic regression analyses were used to compute odds ratios with 95% confidence intervals for age, race, medical conditions and events, and pregnancy-related complications among older women (age equal to or greater than 45) compared to younger women (under 35) as well as for women aged 35–44 compared to women younger than 35. To determine the effect of maternal age on medical and obstetric complications at delivery, a multivariable logistic regression model was created for the outcome of medical and obstetric complications among women aged 45 and older, or women aged 35–44, and each age group compared to women age less than 35, while controlling for pre-existing medical conditions, multiple gestation, and insurance status. By controlling for pre-existing medical conditions, we attempted to estimate the role of maternal age alone on medical and obstetric complications among healthy women. Race/ethnicity was not included in the final model as some states do not report race/ethnicity data, therefore there are a large number of entries in the NIS with missing race/ethnicity data
The number of births occurring to women aged 45 to 49 per 1000 total deliveries in the United States was determined from data obtained from the US Centers for Disease Control and Prevention’s (CDC) VitalStats for the years 1990 to 2010.
Finally, to determine the absolute risk of each outcome among women age 45 and older compared to the entire pregnant population, the population attributable risk (PAR) percent for each outcome was calculated.
During the years 2008–2010, there were an estimated 12,628,746 deliveries occurring in the United States within the NIS. Among these deliveries, 1,836,403 (14.5%) were to women age 35–44 and 23,807 (0.19%) were to women aged 45 and older, while 10,768,536 (85.3%) were to women less than 35. The median (quartile) age for the two older groups were 37 (36, 39) and 46 (45, 47) years, while for the younger group was 26 (22, 30) years. The racial/ethnic distribution of women at a delivery admission differed by age group. Using white women as the reference group, pregnant women aged 35–44 and women aged 45 and older were less likely to be black (OR 0.68, 95% CI 0.67, 0.69 and OR 0.80, 95% CI 0.76, 0.83, respectively), Hispanic (OR 0.76, 95% CI 0.76, 0.76 and OR 0.59, 95% CI 0.57, 0.62, respectively), or Native American (OR 0.57, 95% CI 0.56, 0.58, and OR 0.35, 95% CI 0.28, 0.44, respectively), and were more likely to be Asian/Pacific Islander (OR 1.84, 95% CI 1.83, 1.85 and OR 1.80, 95% CI 1.71, 1.89, respectively) compared to women less than 35. Race/ethnicity data was missing for 13.8% of women aged 35–44, 18.0% of women greater than 45, and 15.8% of the younger women (
Age<35, n = 10,768,536 | Age 35–44, n = 1,836,403 | Age≥45, n = 23,807 | |||
n (%) | n (%) | OR (95% CI)p-value | n (%) | OR (95% CI)p-value | |
Race/Ethnicity, n (%) | |||||
White | 4,681,697 (43.5) | 878,691 (47.8) | 1.0 | 11,146 (46.8) | 1.0 |
Black | 1,337,921 (12.4) | 170,568 (9.3) | 0.68 (0.67, 0.68) <0.0001 | 2565 (10.8) | 0.80 (0.76, 0.83) <0.0001 |
Hispanic | 2,119,897 (19.7) | 303,130 (16.5) | 0.76 (0.76, 0.76) <0.0001 | 3015 (12.7) | 0.59 (0.57, 0.62) <0.0001 |
Asian/Pacific Islander | 414,366 (3.8) | 143,919 (7.8) | 1.84 (1.83 1.85) <0.0001 | 1768 (7.4) | 1.80 (1.71, 1.89) <0.0001 |
Native American | 86,452 (0.8) | 9260 (0.5) | 0.57 (0.56, 0.58) <0.0001 | 74 (0.3) | 0.35 (0.28, 0.44) <0.0001 |
Other | 428,853 (4.0) | 77,900 (4.2) | 0.96 (0.95, 0.97) <0.0001 | 956 (4.0) | 0.93 (0.87, 0.99) 0.0001 |
Missing | 1,699,350 (15.8) | 252,935 (13.8) | – | 4283 (18.0) | – |
Age, yrs |
26.0 (22.0, 30.0) | 37.0 (36.0, 39.0) | – <0.0001 | 46.0 (45.0, 47.0) | – <0.0001 |
Length of stay, days |
2 (2, 3) | 2 (2, 3) | – <0.0001 | 3 (2, 4) | – <0.0001 |
Total charges, $ |
9792 (6648, 14,800) | 11,340 (7456, 17,298) | – <0.001 | 13,846 (8696, 22,296) | – <0.0001 |
Private insurance,n (%) |
4,953,527 (46.0) | 1,281,862 (69.8) | 2.71 (2.70, 2.72) <0.0001 | 16,974 (71.3) | 2.92 (2.83, 3.00) <0.0001 |
Median houseincome in ZIPcode of lowestquartile, n (%) |
3,021,833 (28.1) | 315,513 (17.2) | 0.53 (0.53, 0.53) <0.0001 | 3823 (16.1) | 0.49 (0.47, 0.51) <0.0001 |
Values are median (interquartile). Comparison by Wilcoxon Sign-Rank test.
Comparison by Chi-Square.
Median house income $1–$38,999.
The absolute number of births to women aged 45 to 49 from 1990 to 2010 was obtained from the CDC’s VitalStats.
The birth rate among women aged 45 to 49 per 1000 women in that age group remained unchanged from 1980 to 1991 at 0.2 per 1000 women in that age group, per year, but increased to 0.7 per 1000 women by 2010, representing a 3.5-fold increase in the live birth rate among women 45 to 49 during the last 10 years (
Age<35, n = 10,768,536 | Age 35–44, n = 1,836,403 | Age≥45, n = 23,807 | |||
Condition, n (%) | n (%) | n (%) | OR (95% CI) p-value | n (%) | OR (95% CI) p-value |
Cardiomyopathy | 4337 (0.04) | 1388 (0.08) | 1.91 (1.79, 2.03) <0.0001 | 19 (0.08) | 2.10 (1.34, 3.27) 0.002 |
Valvular heart disease | 31,897 (0.3) | 11,814 (0.6) | 2.17 (2.12, 2.22) <0.0001 | 233 (1.0) | 3.33 (2.93, 3.79) <0.0001 |
Congenital heart disease | 10,675 (0.1) | 1814 (0.1) | 1.01 (0.96, 1.06) 0.72 | 14 (0.06) | 0.62 (0.37, 1.04) 0.07 |
Conduction disorder | 70,696 (0.7) | 12,202 (0.7) | 1.03 (1.01, 1.05) 0.006 | 287 (1.2) | 1.90 (1.69, 2.13) <0.0001 |
History of myocardialinfarction | 1013 (0.01) | 1029 (0.06) | 5.93 (5.44, 6.47) <0.0001 | 35 (0.1) | 15.67 (11.19, 21.94) <0.0001 |
Asthma | 355,290 (3.3) | 55,471 (3.0) | 0.92 (0.91, 0.93) <0.0001 | 855 (3.6) | 1.10 (1.03, 1.18) 0.006 |
Diabetes (non-gestational) | 95,515 (0.9) | 38,107 (2.1) | 2.41 (2.38, 2.44) <0.0001 | 734 (3.1) | 3.66 (3.40, 3.94) <0.0001 |
Thyroid disorder | 211,421 (2.0) | 86,848 (4.7) | 2.48 (2.46, 2.50) <0.0001 | 1658 (7.0) | 3.75 (3.57, 3.94) <0.0001 |
Systemic lupus erythem. | 11,224 (0.1) | 3087 (0.2) | 1.61 (1.54, 1.67) <0.0001 | 39 (0.2) | 1.58 (1.15, 2.16) 0.004 |
Rheumatoid arthritis/collagenvascular disease | 11,226 (0.1) | 4130 (0.2) | 2.15 (2.07, 2.23) <0.0001 | 45 (0.2) | 1.83 (1.37, 2.45) <0.0001 |
Thrombophilia/APS | 48,262 (0.4) | 15,962 (0.9) | 1.94 (1.90, 1.97) <0.0001 | 293 (1.2) | 2.76 (2.45, 3.09) <0.0001 |
Anemia | 1,179,067 (10.9) | 173,538 (9.4) | 0.84 (0.84, 0.85)<0.0001 | 2737 (11.5) | 1.05 (1.01, 1.10) 0.010 |
Thrombocytopenia | 95,316 (0.9) | 19,046 (1.0) | 1.17 (1.15, 1.19) <0.0001 | 335 (1.4) | 1.61 (1.44, 1.79) <0.0001 |
Drug use | 149,339 (1.4) | 16,149 (0.9) | 0.63 (0.62, 0.64) <0.0001 | 152 (0.6) | 0.46 (0.40, 0.54)<0.0001 |
Alcohol use | 11,159 (0.1) | 2882 (0.2) | 1.51 (1.45, 1.58) <0.0001 | 50 (0.2) | 2.08 (1.57, 2.74) <0.0001 |
Tobacco | 723,357 (6.7) | 70,907 (3.9) | 0.56 (0.55, 0.56) <0.0001 | 656 (2.7) | 0.39 (0.36, 0.42) <0.0001 |
Chronic hypertension | 167,232 (1.5) | 79,841 (4.3) | 2.91 (2.88, 2.93) <0.0001 | 1855 (7.8) | 5.45 (5.20, 5.72) <0.0001 |
Chronic renal failure | 3694 (0.03) | 1330 (0.07) | 2.14 (2.01, 2.28) <0.0001 | 29 (0.1) | 3.67 (2.55, 5.29) <0.0001 |
(abbreviations: APS = antiphospholipid antibody syndrome).
Women in both of the older age groups (35–44 and 45 and older) were more likely to die during an admission in which a delivery occurred compared to women under 35 (OR 2.07, 95% CI 1.78, 2.40 and OR 9.90, 95% CI 5.60, 15.98, respectively), with the highest risk for death occurring among women age 45 and older (
Age<35, n = 10,768,536 | Age 35–44, n = 1,836,403 | Age≥45, n = 23,807 | |||
Condition, n (%) | n (%) | n (%) | OR (95% CI) p-value | n (%) | OR (95% CI) p-value |
Death | 682 (0.006) | 234 (0.01) | 2.07 (1.78, 2.40) <0.0001 | 14 (0.06) | 9.90 (5.60, 15.98) <0.0001 |
Mechanical ventilation | 6858 (0.06) | 2145 (0.1) | 1.86 (1.78, 1.96) <0.0001 | 25 (0.1) | 1.69 (1.14, 2.50) 0.009 |
Transfusion | 108,643 (1.0) | 22,470 (1.2) | 1.21 (1.20, 1.23) <0.0001 | 590 (2.5) | 2.46 (2.27, 2.68) <0.0001 |
Myocardial infarction/ischemia | 223 (0.002) | 151 (0.008) | 4.05 (3.29, 4.98) <0.0001 | 11 (0.05) | 21.38 (11.46, 39.88) <0.0001 |
Cardiac arrest/ventricularfibrillation | 618 (0.006) | 220 (0.01) | 2.07 (1.80, 2.42) <0.0001 | 15 (0.06) | 10.84 (6.48, 18.14) <0.0001 |
Acute heart failure | 3196 (0.03) | 1336 (0.07) | 2.47 (2.31, 2.63) <0.0001 | 57 (0.2) | 8.42 (6.48, 10.93) <0.0001 |
Pneumonia | 10,488 (0.1) | 2684 (0.1) | 1.68 (1.61, 1.75) <0.0001 | 52 (0.2) | 2.56 (1.95, 3.36) <0.0001 |
Pulmonary edema | 1507 (0.01) | 545 (0.03) | 2.19 (1.98, 2.42) <0.0001 | 11 (0.05) | 3.29 (1.80, 6.03) 0.0001 |
Pulmonary embolism | 2749 (0.03) | 841 (0.05) | 1.83 (1.69, 1.98) <0.0001 | 29 (0.1) | 5.01 (3.47, 7.23) <0.0001 |
Deep vein thrombosis | 4726 (0.04) | 1599 (0.09) | 2.02 (1.91, 2.14) <0.0001 | 49 (0.2) | 4.38 (3.26, 5.89) <0.0001 |
Stroke/cerebrovascular disorders | 3120 (0.03) | 1000 (0.05) | 1.87 (1.74, 2.01) <0.0001 | – |
– |
Sepsis | 5612 (0.05) | 1182 (0.06) | 1.31 (1.23, 1.40) <0.0001 | 25 (0.1) | 2.21 (1.49, 3.27) <0.0001 |
Influenza | 3232 (0.03) | 497 (0.03) | 1.14 (1.05, 1.23) 0.002 | 11 (0.05) | 1.37 (0.76, 2.50) 0.297 |
Acute renal failure | 5155 (0.04) | 1643 (0.09) | 1.86 (1.76, 1.97)<0.0001 | 73 (0.3) | 6.38 (5.06, 8.04) <0.0001 |
There were less than 10 subjects with stroke/cerebrovascular disorders among women age 45 and older. The NIS does not allow the reporting of the number of subjects of any cell with 10 or less subjects.
Women aged 35–44 and women aged 45 and older were also more likely to experience obstetric complications compared to women less than 35. Older women had higher odds of cesarean delivery, gestational diabetes, preelampsia/pregnancy-associated hypertensive disorders, multiple gestation, preterm labor, placental abruption, fetal growth restriction (women aged 45 and older only), fetal demise, cervical incompetence, fetal chromosomal anomalies, macrosomia, premature rupture of the membranes, placenta previa and postpartum hemorrhage (
Age<35, n = 10,768,536 | Age 35–44, n = 1,836,403 | Age≥45, n = 23,807 | |||
Condition, n (%) | n (%) | n (%) | OR (95% CI) p-value | n (%) | OR (95% CI) p-value |
Cesarean delivery | 3,266,518 (30.3) | 762,142 (41.5) | 1.62 (1.61, 1.62) <0.0001 | 12,438 (52.2) | 2.51 (2.44, 2.57) <0.0001 |
Operative vaginal delivery | 685,601 (6.4) | 105,358 (5.7) | 0.89 (0.88, 0.90) <0.0001 | 1284 (5.4) | 0.83 (0.79, 0.88) <0.0001 |
Multiple gestation | 205,158 (1.9) | 58,610 (3.2) | 1.69 (1.67, 1.71) <0.0001 | 2984 (12.5) | 7.35 (7.08, 7.65) <0.0001 |
Gestational diabetes | 513,260 (4.8) | 198,295 (10.8) | 2.42 (2.41, 2.44) <0.0001 | 3533 (14.8) | 3.50 (3.37, 3.62) <0.0001 |
Prex, eclamp, gest HTN | 781,124 (7.3) | 146,668 (8.0) | 1.11 (1.10, 1.12) <0.0001 | 3438 (14.4) | 2.17 (2.09, 2.25) <0.0001 |
Preterm labor | 880,375 (8.2) | 167,966 (9.1) | 1.16 (1.15, 1.17) <0.0001 | 3361 (14.1) | 1.91 (1.84, 1.98) <0.0001 |
Placental abruption | 112,550 (1.0) | 23,033 (1.2) | 1.21 (1.19, 1.22) <0.0001 | 486 (2.0) | 1.97 (1.80, 2.15) <0.0001 |
Fetal growth restriction | 234,163 (2.2) | 36,964 (2.0) | 0.92 (0.91, 0.93) <0.0001 | 784 (3.3) | 1.53 (1.42, 1.64) <0.0001 |
Fetal demise | 41,590 (0.4) | 9257 (0.5) | 1.30 (1.27, 1.33) <0.0001 | 232 (1.0) | 2.53 (2.22, 2.89) <0.0001 |
Cervical incompetence | 64,664 (0.6) | 20,492 (1.1) | 1.90 (1.87, 1.93) <0.0001 | 354 (1.5) | 2.52 (2.27, 2.81) <0.0001 |
Fetal chromosomal anomalies | 6533 (0.06) | 4328 (0.2) | 3.87 (3.73, 4.03) <0.0001 | 174 (0.7) | 12.10 (10.40, 14.07) <0.0001 |
Macrosomia | 262,449 (2.4) | 57,275 (3.1) | 1.28 (1.27, 1.30) <0.0001 | 640 (2.7) | 1.10 (1.02, 1.19) 0.016 |
Premature ROM | 394,220 (3.7) | 74,152 (4.0) | 1.10 (1.09, 1.11) <0.0001 | 1183 (5.0) | 1.38 (1.30, 1.46) <0.0001 |
Placenta previa | 53,312 (0.5) | 25,165 (1.4) | 2.86 (2.81, 2.90) <0.0001 | 562 (2.4) | 5.03 (4.63, 5.48) <0.0001 |
Postpartum hemorrhage | 274,359 (2.5) | 46,762 (2.5) | 0.99 (0.98, 1.01) 0.233 | 854 (3.6) | 1.40 (1.31, 1.51) <0.0001 |
Chorioamnionitis | 287,531 (2.7) | 35,583 (1.9) | 0.72 (0.71, 0.72) <0.0001 | 453 (1.9) | 0.70 (0.64, 0.77) <0.0001 |
Age 35–44, Adjusted OR |
Age≥45, Adjusted OR |
|
Death | 1.92 (1.65, 2.24) <0.0001 | 7.48 (4.40, 12.2) <0.0001 |
Mechanical ventilation | 1.71 (1.62, 1.80) <0.0001 | 1.12 (0.75, 1.69) 0.58 |
Transfusion | 1.30 (1.28, 1.32) <0.0001 | 2.00 (1.82, 2.18) <0.0001 |
Myocardial infarction/ischemia | 2.43 (1.94, 3.05) <0.0001 | 9.09 (4.69, 17.60) <0.0001 |
Cardiac arrest/ventricular fibrillation | 1.88 (1.61, 2.21) <0.0001 | 7.94 (4.68, 13.48) <0.0001 |
Acute heart failure | 1.76 (1.63, 1.90) <0.0001 | 5.09 (3.76, 6.89) <0.0001 |
Pneumonia | 1.68 (1.61, 1.76) <0.0001 | 1.82 (1.38, 2.40) <0.0001 |
Pulmonary edema | 1.75 (1.58, 1.94) <0.0001 | 1.36 (0.74, 2.51) 0.33 |
Pulmonary embolism | 1.70 (1.57, 1.85) <0.0001 | 3.39 (2.33, 4.92) <0.0001 |
Deep vein thrombosis | 1.83 (1.73, 1.94) <0.0001 | 3.22 (2.39, 4.35) <0.0001 |
Stroke/cerebrovascular disorders |
1.7 (1.5, 1.9) <0.0001 | – (–, –) – |
Sepsis | 1.32 (1.23, 1.40) <0.0001 | 1.76 (1.19, 2.61) 0.005 |
Influenza | 1.15 (1.06, 1.25) 0.0008 | 1.10 (0.60, 2.00) 0.76 |
Acute renal failure | 1.55 (1.46, 1.64) <0.0001 | 3.44 (2.67, 4.44) <0.0001 |
Cesarean delivery | 1.57 (1.56, 1.57) <0.0001 | 2.10 (2.05, 2.16) <0.0001 |
Operative vaginal delivery | 0.89 (0.88, 0.90) <0.0001 | 0.88 (0.83, 0.93) <0.0001 |
Gestational diabetes | 2.34 (2.32, 2.35) <0.0001 | 3.02 (2.91, 3.13) <0.0001 |
Prex, eclamp, gestational hypertension | 1.01 (1.004, 1.02) 0.0008 | 1.65 (1.59, 1.71) <0.0001 |
Preterm labor | 1.07 (1.06, 1.07) <0.0001 | 1.12 (1.07, 1.16) <0.0001 |
Abruption | 1.23 (1.21, 1.25) <0.0001 | 1.81 (1.65, 1.98) <0.0001 |
Fetal growth restriction | 0.89 (0.88, 0.90) <0.0001 | 1.18 (1.10, 1.27) <0.0001 |
Fetal demise | 1.24 (1.21, 1.27) <0.0001 | 2.08 (1.83, 2.37) <0.0001 |
Cervical incompetence | 1.69 (1.66, 1.71) <0.0001 | 1.39 (1.25, 1.55) <0.0001 |
Fetal chromosomal anomaly | 3.79 (3.64, 3.94) <0.0001 | 11.74 (10.07, 13.68) <0.0001 |
Macrosomia | 1.22 (1.21, 1.23) <0.0001 | 1.09 (1.01, 1.18) 0.029 |
Premature rupture of membranes | 1.10 (1.09, 1.11) <0.0001 | 1.24 (1.17, 1.32) <0.0001 |
Placenta previa | 2.83 (2.79, 2.88) <0.0001 | 4.45 (4.09, 4.85) <0.0001 |
Postpartum hemorrhage | 1.01 (1.005, 1.03) 0.0037 | 1.31 (1.22, 1.40) <0.0001 |
Chorioamnionitis | 0.73 (0.72, 0.74) <0.0001 | 0.73 (0.66, 0.80) <0.0001 |
Adjusted OR for each condition while controlling for: insurance status, multiple gestation, chronic hypertension, chronic renal failure, cardiomyopathy, valvular heart disease, cardiac conduction disorders, history of myocardial infarction or chronic ischemia, asthma, diabetes, thyroid disorders, systemic lupus erythematosus/collagen vascular disease, rheumatoid arthritis, thrombophilia/APS, anemia, thrombocytopenia, drug use, alcohol use, and tobacco use.
There were less than 10 subjects with stroke/cerebrovascular disorders among women age 45 and older. The NIS does not allow the reporting of the number of subjects of any cell with 10 or less subjects.
To determine the contribution of adverse outcomes among women aged 45 and older to the entire pregnant population at delivery, the population attributable risk (PAR) percent was calculated for each adverse outcome studied. Pregnancies to women aged 45 and over represented 0.19% of all pregnancies between the years 2008 and 2010 but 1.32% of all deaths of pregnant women at an admission for delivery occurred in women age 45 and older (
Population attributable risk percent, PAR% |
|
Death | 1.32 |
Mechanical ventilation | 0.09 |
Transfusion | 0.26 |
Myocardial infarction/ischemia | 2.68 |
Cardiac arrest/ventricular fibrillation | 1.58 |
Acute heart failure | 1.06 |
Pneumonia | 0.21 |
Pulmonary edema | 0.35 |
Pulmonary embolism | 0.62 |
Deep vein thrombosis | 0.58 |
Stroke/cerebrovascular disorders |
- |
Sepsis | 0.18 |
Influenza | 0.11 |
Acute renal failure | 0.88 |
Cesarean delivery | 0.12 |
Operative vaginal delivery | −0.03 |
Gestational diabetes | 0.31 |
Prex, eclamp, gestational hypertension | 0.18 |
Preterm labor | 0.13 |
Abruption | 0.17 |
Fetal growth restriction | 0.10 |
Fetal demise | 0.27 |
Cervical incompetence | 0.23 |
Fetal chromosomal anomaly | 1.39 |
Macrosomia | 0.01 |
remature rupture of membranes | 0.06 |
Placenta previa | 0.81 |
Postpartum hemorrhage | 0.08 |
Chorioamnionitis | −0.05 |
Population attributable risk percent was calculated using the equation: PAR = Pe (RRe–1)/[1+ Pe (RRe–1)], where PAR = Population attributable risk, Pe = prevalence of the exposure, and RRe = relative risk of disease due to the exposure.
There were less than 10 subjects with stroke/cerebrovascular disorders among women age 45 and older. The NIS does not allow the reporting of the number of subjects of any cell with 10 or less subjects, thus a PAR% value was not calculated.
Pregnancies to women aged 45 and older represented 0.19% of all deliveries in the years 2008–2010.
In this study, while controlling for insurance status, multiple gestation and pre-existing medical conditions, we were able to demonstrate that pregnant women aged 45 years and older are at increased risk for death as well as serious medical and obstetrical complications during pregnancy and childbirth compared to women under age 35 at delivery. Women in an intermediate age category of 35–44 were also at risk for death and severe morbidity compared to younger women, though most of the rates were lower than that seen in women aged 45 and older. Furthermore, the number of deliveries to women 45 and over and the birth rate among women over 45 are both increasing in the United States. As the number of deliveries to women 45 and over and the birth rate among women over 45 are both increasing in the United States, these findings are important. As the numbers of women over 45 who become pregnant are likely to continue to increase, these women and their physicians should be aware of the increased risk of death and significant morbidity, though recognize that the absolute risk for death or severe morbidity among women age 45 and older remains low.
The fertility rate, defined as the rate of childbearing in a population, declines markedly with advancing maternal age.
The American Society for Reproductive Medicine (ASRM) recently recommended that the experimental label be removed from egg freezing.
Most studies of pregnancy outcomes among women in their forties and fifties have focused on neonatal outcomes or relatively common maternal medical conditions such as diabetes and hypertension. Among those studies reporting maternal medical and obstetric complications, most have been small, single-center case series, where maternal death and severe maternal medical morbidity had not been able to be studied, and thus these studies have suggested favorable outcomes in this age group.
Hoffman reported on neonatal outcomes among 3953 pregnant women aged 40 and older and found that these women had increased risk for fetal death, preterm delivery, and low birth weight compared to women under 35.
There are potential limitations with our study. The NIS relies on accurate medical coding at discharge. For pre-existing medical conditions, the condition may not have been coded, especially if that condition was not active at the time of a woman’s admission for delivery. Therefore, it is possible that some pre-existing medical conditions that are more common among older women may have not been coded or were less likely to be coded among younger subjects even if present. By controlling for pre-existing medical conditions, we attempted to estimate the role of age alone on the risk for medical and obstetric complications at delivery, but if the pre-existing medical condition was present and not coded, we may have overestimated the effect of age for the studied adverse outcomes. Nonetheless, using the NIS, we were able to identify medical and obstetric complications that were more common among older women compared to younger women during pregnancy and at the time of childbirth.
Next, our study did not identify all maternal deaths occurring during the years 2008–2010. Maternal mortality is defined by the Centers for Disease Control and Prevention as a maternal death occurring during pregnancy or within forty-two days from delivery.
It is unclear why older women are at increased risk for death and severe medical morbidity in pregnancy compared to younger women, although the prevalence and mortality from many of these medical conditions increases with age in the non-pregnant population. Furthermore, population studies reporting risk factors for myocardial infarction and other myocardial disorders, stroke, renal failure, pulmonary embolism and respiratory distress syndrome in pregnancy have demonstrated higher rates of these complications among women over age 35.
The calculation of population attributable risk for death or adverse medical and obstetric outcomes among women aged 45 and older allows for an estimate of the burden of these complications to the entire pregnant population. Pregnancies to women aged 45 and older represented only 0.19% of all pregnancies but accounted for 1–2.5% of the deaths or severe adverse cardiac outcomes that occur among all pregnant women. Thus, the odds of death or severe medical morbidity such as cardiac complications among women aged 45 and older is significant, but still rare.
In summary, the number of births to women aged 45 and older is increasing and women aged 45 and older are at risk for death and severe medical and obstetric morbidity during pregnancy. Women in this age group should be counseled concerning these risks prior to becoming pregnant but then recognize that the absolute risk for these adverse events is low as they occur rarely. With oocyte cryopreservation no longer being considered experimental, more and more women in this age group will likely seek infertility services and the number of pregnancies to women age 45 and older will likely continue to increase.