This cohort study aims to determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.
Key Points
Question
What are the long-term mortality risks in women with adverse pregnancy outcomes?
Findings
In a national cohort study of more than 2 million women in Sweden, women who experienced any of 5 major adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes) had increased mortality risks that remained elevated more than 40 years later. These findings were not explained by shared familial factors.
Meaning
All major adverse pregnancy outcomes should now be recognized as long-term risk factors for premature mortality in women.
Abstract
Importance
Women with adverse pregnancy outcomes, such as preterm delivery or preeclampsia, have higher future risks of cardiometabolic disorders; however, little is known about their long-term mortality risks. A better understanding of such risks is needed to facilitate early identification of high-risk women and preventive actions.
Objective
To determine long-term mortality risks associated with 5 major adverse pregnancy outcomes in a large population-based cohort of women.
Design, Setting, and Participants
This national cohort study in Sweden used the Swedish Medical Birth Register, containing prenatal and birth information for nearly all deliveries in Sweden since 1973, to identify women who had a singleton delivery during 1973 to 2015. All 2 195 667 such women with information for pregnancy duration and infant birth weight were included in the study. Data were analyzed from March to September 2023.
Exposure
Adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes), identified from nationwide birth records.
Main Outcome and Measures
All-cause and cause-specific mortality through December 31, 2018. Cox regression was used to compute hazard ratios (HRs) for mortality associated with specific adverse pregnancy outcomes, adjusted for other maternal factors. Cosibling analyses assessed for confounding by shared familial (genetic or environmental) factors.
Results
In 56 million person-years of follow-up to a median (IQR) age of 52 (42-61) years, 88 055 women (4%) died (median [IQR] age at death, 59 [50-67] years). All 5 adverse pregnancy outcomes were independently associated with increased mortality. Across the entire follow-up (≤46 years after delivery), adjusted HRs for all-cause mortality associated with specific adverse pregnancy outcomes were as follows: gestational diabetes, 1.52 (95% CI, 1.46-1.58); preterm delivery, 1.41 (95% CI, 1.37-1.44); small for gestational age, 1.30 (95% CI, 1.28-1.32); other hypertensive disorders, 1.27 (95% CI, 1.19-1.37); and preeclampsia, 1.13 (95% CI, 1.10-1.16). All HRs remained significantly elevated even 30 to 46 years after delivery. These effect sizes were only partially (0%-45%) reduced after controlling for shared familial factors in cosibling analyses. Women who experienced multiple adverse pregnancy outcomes had further increases in risk. Several major causes of death were identified, including cardiovascular and respiratory disorders and diabetes.
Conclusions and Relevance
In this large national cohort study, women who experienced any of 5 major adverse pregnancy outcomes had increased mortality risks that remained elevated more than 40 years later. Women with adverse pregnancy outcomes need early preventive evaluation and long-term follow-up for detection and treatment of chronic disorders associated with premature mortality.
Introduction
Adverse pregnancy outcomes, including preterm delivery, delivery of a small for gestational age infant, preeclampsia, other hypertensive disorders, and gestational diabetes, have been associated with higher future risks of cardiometabolic disorders.1,2,3,4,5,6,7,8,9,10 However, little is known about long-term mortality risks in women who experience adverse pregnancy outcomes. Nearly 30% of all women experience an adverse pregnancy outcome during their reproductive years.2,11 A better understanding of long-term mortality risks in this large and growing population of women is needed to facilitate early identification of high-risk women, timely preventive actions, and long-term clinical care.
Most prior research has focused on a single adverse pregnancy outcome in relation to future mortality. For example, women with preterm delivery were found to have a 1.4-fold higher mortality up to 44 years later compared with women who delivered at full term, including increased cardiovascular, respiratory, and diabetes mortality, after adjusting for other maternal factors.12 Women with preeclampsia also have been reported to have a 1.2- to 2-fold higher mortality during 25 to 36 years of follow-up.13,14 A recent study suggested that preterm delivery, preeclampsia, and gestational diabetes were each associated with 1.1- to 1.3-fold mortality risks up to 50 years later, based on assessment of only 1 pregnancy per woman.15 To our knowledge, no studies have examined multiple adverse pregnancy outcomes across each woman’s reproductive life in relation to future mortality. Such studies could help elucidate the relative effects of specific adverse pregnancy outcomes on subsequent mortality, which may further improve clinical risk assessment and preventive interventions.
To address these knowledge gaps, we conducted a national cohort study of more than 2 million women in Sweden. The goals of this study were to (1) examine long-term mortality risks associated with 5 major adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, and gestational diabetes) using prospectively ascertained data in a large population-based cohort; (2) assess changes in such risks across the life course with up to 46 years of follow-up after delivery; and (3) assess for potential confounding by unmeasured shared genetic or environmental factors in families using cosibling analyses. We hypothesized that women who experienced any of these 5 major adverse pregnancy outcomes would have long-term increased mortality risks and that such risks would be only partially explained by shared familial factors.
Methods
Study Population
The Swedish Medical Birth Register contains prenatal and birth information for nearly all deliveries in Sweden since 1973.16 Using this registry, we identified 2 201 352 women who had a singleton delivery during 1973 to 2015. Singleton deliveries were chosen to improve internal comparability, given the higher prevalence and different causes of adverse pregnancy outcomes in multiple-gestation pregnancies. We excluded 5685 women (0.3%) who had missing information for pregnancy duration or infant birth weight, leaving 2 195 667 women (99.7% of the original cohort) for inclusion in the study. This study was approved by the Regional Ethical Review Board in Lund, Sweden. Participant consent was not required because this study used only pseudonymized registry-based secondary data.
Adverse Pregnancy Outcome Ascertainment
Five major adverse pregnancy outcomes were identified from the Medical Birth Register.4 Preterm delivery (gestational age <37 completed weeks) was based on maternal report of last menstrual period in the 1970s and ultrasonography estimation starting in the 1980s and onward (>70% of the cohort). Small for gestational age was defined by infant birth weight lower than the 10th percentile for gestational age. Preeclampsia, other hypertensive disorders, and gestational diabetes were identified from diagnostic codes in the Medical Birth Register (eTable 1 in Supplement 1). Preeclampsia and other hypertensive disorders were examined separately to provide more specific results for these disorders and to facilitate comparability with previously reported risk estimates.
Gestational age and birth weight in the Medical Birth Register have been found to be highly reliable.17,18 Most chronic disorders in the Swedish registries also have high validity, with positive predictive values in the range of 85% to 95%,19 although to our knowledge, other diagnoses in the Medical Birth Register have not been formally validated. In the present cohort, 16% of women had 1 or more deliveries before the beginning of the Medical Birth Register in 1973, and thus outcomes were unavailable for those deliveries; however, as described herein, all analyses were adjusted for parity.
Mortality Ascertainment
The study cohort was followed up from first delivery through December 31, 2018 (maximum follow-up time, 46 years; median, 25 years). Deaths were identified using the Swedish Death Register, which includes all deaths and causes of death for all persons registered in Sweden since 1960, with compulsory reporting nationwide. Cause-specific mortality was examined for categories that had more than 500 total deaths, which included cardiovascular disease, any cancer, breast cancer, respiratory disorders, diabetes, and other causes combined (eTable 1 in Supplement 1).
Covariates
Other maternal characteristics that may be associated with adverse pregnancy outcomes and mortality were identified using the Medical Birth Register and national census data, which were linked using pseudonymous serial numbers. Maternal age is a strong predictor of mortality and a potential confounder and therefore was adjusted for in all analyses as the Cox model timescale (as described herein). Covariates included the following maternal factors, with all time-varying factors updated for each pregnancy: calendar year of delivery (continuous and categorical in 5-year groups), parity (1, 2, 3, 4, and ≥5; information on gravidity was unavailable), education level (≤9, 10-12, and >12 years), employment status (yes/no) and income (quartiles) in the year prior to delivery, country of maternal birth (Sweden/other), body mass index (BMI; calculated as weight in kilograms divided by height in meters squared and modeled as continuous and categorical [<18.5, 18.5-24.9, 25.0-29.9, and ≥30.0] variables simultaneously to allow for potential nonlinear effects), smoking status (0, 1-9, and ≥10 cigarettes/d), and prepregnancy hypertension or diabetes as identified from nationwide diagnoses (eTable 1 in Supplement 1).
Maternal BMI and smoking were assessed at the beginning of prenatal care starting in 1982 and were available for 56% and 67% of women, respectively. Data were more than 99% complete for all other variables. Missing data were multiply imputed with 20 imputations using all other covariates and mortality as predictors.20 As alternatives to multiple imputation, sensitivity analyses were performed that (1) restricted to women with complete data (N = 1 202 125) or (2) coded missing data for each variable as a separate category.
Statistical Analysis
Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% CIs for subsequent all-cause and cause-specific mortality associated with adverse pregnancy outcomes. These associations were examined across the maximum possible follow-up (≤46 years after delivery) and within narrower intervals of follow-up (<10, 10-19, 20-29, and 30-46 years) in separate analyses among women still living in Sweden at the beginning of the respective interval. Each adverse pregnancy outcome was modeled as a time-dependent variable to compare women who had ever vs never experienced the respective outcome, while adjusting for parity and other covariates. For example, if a woman’s first delivery had no adverse pregnancy outcomes and her second was preterm with preeclampsia, she entered the preterm and preeclampsia exposure categories at the date of her second delivery. If a woman’s first and second deliveries were both preterm, she entered the preterm delivery exposure category at the date of her first delivery.4
Maternal age was used as the Cox model time axis with age at first delivery as “time zero” (ie, each singleton delivery was included as a separate observation, with exposures updated for each delivery). Women were censored at emigration as determined by absence of a Swedish residential address in census data (n = 93 098 [4%]). Two adjusted Cox models were performed that (1) adjusted for maternal sociodemographic factors and parity, and (2) further adjusted for all other adverse pregnancy outcomes (ie, all adverse pregnancy outcomes were included in the same model to assess their independent associations with mortality). The proportional hazards assumption was assessed by testing for interaction between adverse pregnancy outcome status and follow-up time and examining log-log survival plots.21 Time interaction terms were statistically significant (P < .05) in models that included the entire follow-up period, but the departure from proportional hazards was minor, as illustrated in log-log plots (eFigure 1 in Supplement 1); thus, HRs from those models represent average HRs over time. Mortality rate differences and 95% CIs, attributable fraction in the exposed, and population attributable fraction were computed for each adverse pregnancy outcome. In addition, a sensitivity analysis was performed that was restricted to each woman’s first delivery instead of time-dependent modeling of all deliveries.
Cosibling analyses were performed to assess for potential confounding by unmeasured shared familial (genetic or environmental) factors.4,12 Shared environmental factors in families may include lifestyle factors such as diet and physical activity or ambient exposures such as passive smoking and air pollution. These analyses included all 1 188 948 women (54%) with at least 1 sister who had a singleton delivery (regardless of adverse pregnancy outcome status). Sisters were identified based on having the same birth mother and father in the Swedish Multigeneration Register using pseudonymous serial numbers to preserve confidentiality (71% were in sister pairs, 22% were in sister triples, and 7% were in sets of >3 sisters). Stratified Cox models were performed with a separate stratum for each unique set of sisters, with each stratum having its own baseline hazard function that reflects shared genetic and environmental factors, thus controlling for shared exposures within each family. In addition, these analyses were further adjusted for the same covariates as in the main analyses.4,12
Secondary analyses were performed to examine (1) associations between the total number of adverse pregnancy outcomes (0, 1, 2, or ≥3; ie, different adverse pregnancy outcomes in the same or different pregnancies, or the same adverse pregnancy outcome in different pregnancies) and mortality, adjusting for parity and other covariates; and (2) potential multiplicative or additive interactions between adverse pregnancy outcomes and maternal age at delivery or BMI (as continuous or categorical variables as defined in Table 1).22
Table 1. Baseline Maternal Characteristics by Ever Occurrence of an Adverse Pregnancy Outcome in Sweden, 1973-2015.
| Characteristic | No. (%) | |||||
|---|---|---|---|---|---|---|
| All women (N = 2 195 667) | Preterm delivery (n = 194 751 [8.9%]) | Small for gestational age infant (n = 314 605 [14.3%]) | Preeclampsia (n = 132 543 [6.0%]) | Other hypertensive disorders (n = 34 186 [1.6%]) | Gestational diabetes (n = 36 269 [1.7%]) | |
| Age at first delivery, y | ||||||
| <20 | 119 076 (5.4) | 16 329 (8.4) | 20 027 (6.4) | 6759 (5.1) | 1418 (4.2) | 1859 (5.1) |
| 20-24 | 602 431 (27.4) | 58 301 (29.9) | 90 898 (28.9) | 36 879 (27.8) | 7966 (23.3) | 8797 (24.2) |
| 25-29 | 790 584 (36.0) | 64 634 (33.2) | 109 077 (34.7) | 46 754 (35.3) | 11 662 (34.1) | 11 856 (32.7) |
| 30-34 | 483 663 (22.0) | 38 379 (19.7) | 66 712 (21.2) | 28 479 (21.5) | 8519 (24.9) | 8595 (23.7) |
| 35-39 | 166 369 (7.6) | 14 009 (7.2) | 23 307 (7.4) | 11 017 (8.3) | 3639 (10.6) | 4020 (11.1) |
| ≥40 | 33 544 (1.5) | 3099 (1.6) | 4584 (1.5) | 2655 (2.0) | 982 (2.9) | 1142 (3.2) |
| Year of first delivery | ||||||
| 1973-1979 | 528 272 (24.1) | 42 646 (21.9) | 92 125 (29.3) | 51 021 (38.5) | 1817 (5.3) | 6031 (16.6) |
| 1980-1989 | 444 616 (20.2) | 46 315 (23.8) | 65 695 (20.9) | 27 365 (20.6) | 6926 (20.3) | 5060 (14.0) |
| 1990-1999 | 445 591 (20.3) | 42 426 (21.8) | 58 355 (18.5) | 19 738 (14.9) | 8668 (25.4) | 7625 (20.0) |
| 2000-2009 | 460 982 (21.0) | 40 717 (20.9) | 57 180 (18.2) | 20 278 (15.3) | 9601 (28.1) | 10 380 (28.6) |
| 2010-2015 | 316 206 (14.4) | 22 647 (11.6) | 41 250 (13.1) | 14 141 (10.7) | 7174 (21.0) | 18 557 (20.8) |
| Education, y | ||||||
| ≤9 | 305 054 (13.9) | 30 401 (15.6) | 54 082 (17.2) | 21 391 (16.1) | 2938 (8.6) | 6472 (17.8) |
| 10-12 | 971 890 (44.3) | 91 177 (46.8) | 144 549 (45.9) | 62 838 (47.4) | 15 085 (44.1) | 15 990 (44.1) |
| >12 | 918 623 (41.8) | 73 173 (37.6) | 115 974 (36.9) | 48 314 (36.5) | 16 163 (47.3) | 13 807 (38.1) |
| Employed | 1 894 994 (86.3) | 165 857 (85.2) | 264 748 (84.2) | 119 997 (90.5) | 31 121 (91.0) | 28 609 (78.9) |
| Income (quartile) | ||||||
| 1 (Highest) | 548 973 (25.0) | 44 134 (22.7) | 67 748 (21.5) | 26 942 (20.3) | 12 531 (36.7) | 10 545 (29.1) |
| 2 | 547 262 (24.9) | 46 520 (23.9) | 75 756 (24.1) | 33 549 (25.3) | 8520 (24.9) | 8587 (23.7) |
| 3 | 551 569 (25.1) | 49 411 (25.4) | 84 955 (27.0) | 39 390 (29.7) | 6696 (19.6) | 7552 (20.8) |
| 4 (Lowest) | 547 863 (25.0) | 54 686 (28.1) | 86 146 (27.4) | 32 662 (24.6) | 6439 (18.8) | 9585 (26.4) |
| Swedish born | 1 802 612 (82.1) | 160 656 (82.5) | 251 510 (79.9) | 114 766 (86.6) | 29 952 (87.6) | 25 929 (71.5) |
| BMI | ||||||
| <18.5 | 52 916 (2.4) | 5730 (2.9) | 10 816 (3.4) | 1509 (1.1) | 477 (1.4) | 542 (1.5) |
| 18.5-24.9 | 845 112 (38.5) | 68 996 (35.4) | 112 544 (35.8) | 32 402 (24.5) | 13 081 (38.3) | 11 010 (30.4) |
| 25.0-29.9 | 244 159 (11.1) | 20 876 (10.7) | 27 176 (8.6) | 15.127 (11.4) | 6.971 (20.4) | 6558 (18.1) |
| ≥30.0 | 92 217 (4.2) | 9194 (4.7) | 10 474 (3.3) | 8962 (6.8) | 4442 (13.0) | 5116 (14.1) |
| Unknown | 961 263 (43.8) | 89 955 (46.2) | 153 595 (48.8) | 74 543 (56.2) | 9215 (27.0) | 13 043 (36.0) |
| Smoking status by cigarettes/d | ||||||
| 0 | 1 258 162 (57.1) | 106 397 (54.4) | 150 527 (47.7) | 60 699 (45.6) | 26 701 (77.7) | 23 423 (64.2) |
| 1-9 | 154 526 (7.0) | 16 158 (8.3) | 29 052 (9.2) | 5971 (4.5) | 2390 (7.0) | 2614 (7.2) |
| ≥10 | 69 365 (3.2) | 8498 (4.3) | 15 518 (4.9) | 2575 (1.9) | 994 (2.9) | 1243 (3.4) |
| Unknown | 713 614 (32.7) | 63 698 (33.0) | 119 508 (38.2) | 63 298 (47.9) | 4101 (12.4) | 8989 (25.2) |
| Preexisting diagnoses | ||||||
| Hypertension | 2966 (0.1) | 718 (0.4) | 685 (0.2) | 884 (0.7) | 1212 (3.5) | 351 (1.0) |
| Diabetes | 10 045 (0.5) | 3058 (1.6) | 745 (0.2) | 1907 (1.4) | 517 (1.5) | 6119 (16.8) |
Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).
Data were analyzed from March to September 2023. All statistical tests were 2-sided and used a significance level of P < .05. All analyses were conducted using Stata, version 16.1 (StataCorp).
Results
Population Characteristics
A total of 667 774 women (30%) experienced at least 1 adverse pregnancy outcome, and 181 783 (8%) experienced at least 2 adverse pregnancy outcomes (not necessarily in the same pregnancy). The most common adverse pregnancy outcomes were delivery of a small for gestational age infant (10% of deliveries and 14% of all women during their reproductive years) and preterm delivery (5% of deliveries and 8% of all women). The most common pair of adverse pregnancy outcomes experienced by the same woman were small for gestational age and preterm delivery (31 822 women [1.4%]) (eTable 2 in Supplement 1).
Table 1 summarizes characteristics of women with specific adverse pregnancy outcomes. Women with preterm or small for gestational age delivery were more likely to be younger at first delivery, have low education level or income, and/or to smoke. Women with preeclampsia were more likely to have low education level or income, have high BMI, and/or smoke cigarettes. Women with other hypertensive disorders or gestational diabetes were more likely to be older at first delivery, have higher income or BMI, and/or to be a nonsmoker.
In 56 million person-years of follow-up, 88 055 women (4%) died, including 33 deaths within the first 7 days and 117 deaths within the first 28 days after delivery. The median (IQR) age at first delivery was 27 (24-31) years, at death was 59 (50-67) years, and at end of follow-up was 52 (42-61) years. The median (IQR) follow-up time in women who did not die was 26 (13-38) years. Mortality rates by specific adverse pregnancy outcomes are summarized in Table 2 and eTable 3 in Supplement 1 after further stratifying by maternal age or year of delivery. Cumulative mortality is shown in eFigure 2 in Supplement 1.
Table 2. Associations Between Adverse Pregnancy Outcomes From 1973 to 2015 and Subsequent All-Cause Mortality Through 2018 in Swedena.
| Adverse pregnancy outcome by time since delivery | No. of deaths | Rateb | Hazard ratio (95% CI) | Mortality rate difference (95% CI)e | AFe, % | PAF, % | |
|---|---|---|---|---|---|---|---|
| Reduced modelc | Full modeld | ||||||
| Up to 46 y after delivery | |||||||
| Preterm delivery | 9882 | 210.5 | 1.47 (1.44 to 1.51) | 1.41 (1.37 to 1.44) | 62.9 (58.5 to 67.2) | 29.9 | 4.8 |
| Small for gestational age | 17 701 | 207.9 | 1.31 (1.29 to 1.33) | 1.30 (1.28 to 1.32) | 60.1 (56.8 to 63.3) | 28.9 | 5.8 |
| Preeclampsia | 8903 | 227.3 | 1.17 (1.14 to 1.20) | 1.13 (1.10 to 1.16) | 75.6 (70.8 to 80.5) | 28.8 | 2.7 |
| Other hypertensive disorders | 777 | 128.0 | 1.38 (1.29 to 1.48) | 1.27 (1.19 to 1.37) | −29.2 (−38.3 to −20.1) | 8.6f | 0.2g |
| Gestational diabetes | 2227 | 271.2 | 1.77 (1.70 to 1.85) | 1.52 (1.46 to 1.58) | 116.0 (104.7 to 127.4) | 42.8 | 1.1 |
| <10 y After delivery | |||||||
| Preterm delivery | 873 | 56.8 | 1.81 (1.68 to 1.95) | 1.74 (1.61 to 1.88) | 27.6 (23.7 to 31.5) | 48.5 | 8.8 |
| Small for gestational age | 1278 | 42.9 | 1.18 (1.11 to 1.25) | 1.18 (1.11 to 1.25) | 11.5 (9.1 to 14.0) | 26.9 | 5.0 |
| Preeclampsia | 534 | 41.9 | 1.12 (1.03 to 1.23) | 1.05 (0.95 to 1.15) | 9.5 (5.8 to 13.1) | 22.6 | 1.8 |
| Other hypertensive disorders | 100 | 40.3 | 1.47 (1.21 to 1.80) | 1.38 (1.13 to 1.67) | 7.4 (−0.5 to 15.4) | 18.4 | 0.3 |
| Gestational diabetes | 197 | 62.8 | 1.72 (1.49 to 1.98) | 1.42 (1.23 to 1.64) | 30.3 (21.5 to 39.1) | 48.2 | 1.4 |
| 10-19 y After delivery | |||||||
| Preterm delivery | 1589 | 111.1 | 1.54 (1.46 to 1.63) | 1.48 (1.40 to 1.56) | 36.7 (30.9 to 42.4) | 33.0 | 5.9 |
| Small for gestational age | 2402 | 101.3 | 1.22 (1.16 to 1.27) | 1.21 (1.16 to 1.26) | 25.1 (20.8 to 29.4) | 24.8 | 4.7 |
| Preeclampsia | 1111 | 105.1 | 1.18 (1.11 to 1.26) | 1.12 (1.05 to 1.19) | 26.9 (20.6 to 33.3) | 25.6 | 2.2 |
| Other hypertensive disorders | 191 | 97.6 | 1.45 (1.26 to 1.68) | 1.35 (1.16 to 1.55) | 17.8 (3.9 to 31.7) | 18.2 | 0.3 |
| Gestational diabetes | 358 | 145.9 | 1.77 (1.59 to 1.96) | 1.54 (1.38 to 1.72) | 67.0 (51.8 to 82.2) | 45.9 | 1.3 |
| 20-29 y After delivery | |||||||
| Preterm delivery | 2686 | 255.7 | 1.43 (1.37 to 1.49) | 1.36 (1.30 to 1.42) | 67.3 (57.1 to 77.5) | 26.3 | 4.4 |
| Small for gestational age | 4560 | 187.8 | 1.30 (1.26 to 1.34) | 1.28 (1.24 to 1.32) | 65.9 (58.1 to 73.8) | 26.0 | 5.2 |
| Preeclampsia | 2134 | 251.9 | 1.15 (1.10 to 1.21) | 1.11 (1.06 to 1.16) | 58.1 (47.1 to 69.2) | 23.1 | 2.2 |
| Other hypertensive disorders | 268 | 216.7 | 1.34 (1.18 to 1.51) | 1.23 (1.09 to 1.40) | 18.8 (−7.3 to 44.9) | 8.7 | 0.1 |
| Gestational diabetes | 619 | 395.0 | 1.90 (1.75 to 2.06) | 1.66 (1.52 to 1.80) | 199.7 (168.4 to 230.9) | 50.5 | 1.4 |
| 30-46 y After delivery | |||||||
| Preterm delivery | 4734 | 699.3 | 1.42 (1.38 to 1.47) | 1.36 (1.31 to 1.41) | 161.2 (140.3 to 182.1) | 23.0 | 3.4 |
| Small for gestational age | 9461 | 692.8 | 1.35 (1.32 to 1.38) | 1.33 (1.30 to 1.36) | 155.2 (140.2 to 170.2) | 22.4 | 4.6 |
| Preeclampsia | 5124 | 693.6 | 1.18 (1.15 to 1.22) | 1.16 (1.12 to 1.20) | 142.9 (123.2 to 162.7) | 20.6 | 2.3 |
| Other hypertensive disorders | 218 | 552.5 | 1.42 (1.24 to 1.63) | 1.31 (1.14 to 1.49) | −11.2 (−84.7 to 62.4) | 2.0f | 0.0 |
| Gestational diabetes | 1053 | 1002.1 | 1.69 (1.59 to 1.79) | 1.44 (1.35 to 1.54) | 444.3 (383.5 to 505.2) | 44.3 | 1.0 |
Abbreviations: AFe, attributable fraction in the exposed; PAF, population attributable fraction.
Each adverse pregnancy outcome was modeled time dependently to compare women who had ever vs never experienced the respective outcome.
Mortality rate per 100 000 person-years.
Adjusted for maternal age, year of delivery, parity, education, employment, income, country of origin, body mass index, smoking, and prior history of hypertension or diabetes.
Adjusted for the same covariates as in the reduced model and adverse pregnancy outcomes.
Mortality rate difference per 100 000 person-years comparing women with vs without the respective adverse pregnancy outcome.
Preventable fraction among the exposed.
Population preventable fraction.
Adverse Pregnancy Outcomes and All-Cause Mortality
Across the entire follow-up time (≤46 years after delivery), all 5 adverse pregnancy outcomes were independently associated with higher mortality. After adjusting for all other adverse pregnancy outcomes and covariates, the HRs for all-cause mortality associated with specific adverse pregnancy outcomes were as follows: gestational diabetes, 1.52 (95% CI, 1.46-1.58); preterm delivery, 1.41 (95% CI, 1.37-1.44); small for gestational age, 1.30 (95% CI, 1.28-1.32); other hypertensive disorders, 1.27 (95% CI, 1.19-1.37); and preeclampsia, 1.13 (95% CI, 1.10-1.16). The HRs from the full model were only moderately lower than those not adjusted for other adverse pregnancy outcomes (Table 2).
The HRs associated with preterm delivery were highest in the first 10 years after delivery and then subsequently declined, whereas those associated with other adverse pregnancy outcomes remained overall stable or increased with additional follow-up time (Table 2). All HRs from the full model remained significantly elevated even 30 to 46 years after delivery: gestational diabetes, 1.44 (95% CI, 1.35-1.54); preterm delivery, 1.36 (95% CI, 1.31-1.41); small for gestational age, 1.33 (95% CI, 1.30-1.36); other hypertensive disorders, 1.31 (95% CI, 1.14-1.49); and preeclampsia, 1.16 (95% CI, 1.12-1.20). Figure 1 shows adjusted HRs for all-cause mortality by time since delivery for specific adverse pregnancy outcomes.
Figure 1. Adjusted Hazard Ratios (HRs) for All-Cause Mortality Associated With Adverse Pregnancy Outcomes by Time Since Delivery.
For all adverse pregnancy outcomes except other hypertensive disorders, the mortality rate differences (ie, excess deaths) increased with additional follow-up to older ages. Across the entire follow-up, gestational diabetes was associated with the most excess deaths (116 per 100 000 person-years), whereas small for gestational age and preterm delivery accounted for the largest percentages of deaths in this population (nearly 6% and 5%, respectively) (Table 2).
Cosibling Analyses
Cosibling analyses to control for unmeasured shared familial (genetic or environmental) factors resulted in only partial attenuation of most HRs (Table 3). Across the entire follow-up, the adjusted HR for all-cause mortality associated with gestational diabetes was 1.52 (95% CI, 1.46-1.58) in the primary analysis vs 1.46 (95% CI, 1.28-1.66) in the cosibling analysis, with preterm delivery was 1.41 (95% CI, 1.37-1.44) vs 1.37 (95% CI, 1.28-1.45), with small for gestational age was 1.30 (95% CI, 1.28-1.32) vs 1.22 (95% CI, 1.16-1.28), with other hypertensive disorders was 1.27 (95% CI, 1.19-1.37) vs 1.39 (95% CI, 1.18-1.63), and with preeclampsia was 1.13 (95% CI, 1.10-1.16) vs 1.07 (95% CI, 1.01-1.13). The main effect sizes (ie, adjusted HR −1) were 0% to 45% lower in the cosibling analyses compared with the main analyses.
Table 3. Cosibling Analyses of Adverse Pregnancy Outcomes From 1973 to 2015 and Subsequent All-Cause Mortality Through 2018 in Swedena.
| Adverse pregnancy outcome by time since delivery | No. of deaths | Hazard ratio (95% CI)b |
|---|---|---|
| Up to 46 y after delivery | ||
| Preterm delivery | 4519 | 1.37 (1.28-1.45) |
| Small for gestational age | 7915 | 1.22 (1.16-1.28) |
| Preeclampsia | 3753 | 1.07 (1.01-1.13) |
| Other hypertensive disorders | 364 | 1.39 (1.18-1.63) |
| Gestational diabetes | 995 | 1.46 (1.28-1.66) |
| <10 y After delivery | ||
| Preterm delivery | 843 | 1.57 (1.13-2.16) |
| Small for gestational age | 1232 | 0.96 (0.73-1.25) |
| Preeclampsia | 481 | 1.35 (0.88-2.01) |
| Other hypertensive disorders | 103 | 1.55 (0.63-3.81) |
| Gestational diabetes | 190 | 1.39 (0.68-2.86) |
| 10-19 y After delivery | ||
| Preterm delivery | 1110 | 1.44 (1.18-1.74) |
| Small for gestational age | 1664 | 1.13 (0.95-1.32) |
| Preeclampsia | 721 | 1.17 (0.92-1.45) |
| Other hypertensive disorders | 148 | 1.83 (1.11-3.04) |
| Gestational diabetes | 224 | 1.19 (0.78-1.81) |
| 20-29 y After delivery | ||
| Preterm delivery | 1435 | 1.39 (1.21-1.59) |
| Small for gestational age | 2432 | 1.23 (1.10-1.37) |
| Preeclampsia | 1135 | 0.97 (0.83-1.12) |
| Other hypertensive disorders | 99 | 1.71 (1.16-2.61) |
| Gestational diabetes | 311 | 1.41 (1.05-1.87) |
| 30-46 y After delivery | ||
| Preterm delivery | 1131 | 1.35 (1.21-1.50) |
| Small for gestational age | 2587 | 1.23 (1.14-1.33) |
| Preeclampsia | 1416 | 1.09 (0.98-1.21) |
| Other hypertensive disorders | 14 | 1.10 (0.70-1.72) |
| Gestational diabetes | 270 | 1.38 (1.10-1.74) |
Each adverse pregnancy outcome was modeled time dependently to compare women who had ever vs never experienced the respective outcome.
Adjusted for shared familial (genetic and/or environmental) factors and additionally for maternal age, year of delivery, parity, education, employment, income, country of origin, body mass index, smoking, prior history of hypertension or diabetes, and adverse pregnancy outcomes.
Adverse Pregnancy Outcomes and Cause-Specific Mortality
A total of 12 328 deaths (14%) were attributed to cardiovascular disease, 42 971 (49%) to cancer (including 9686 to breast cancer), 3107 (4%) to respiratory disorders, 1117 (1%) to diabetes, and 28 530 (32%) to other causes. All 5 major adverse pregnancy outcomes were associated with substantially higher (1.5- to 2.5-fold) mortality from cardiovascular disease compared with women without the respective adverse pregnancy outcome (Figure 2). Women with preterm or small for gestational age delivery also had more than 2-fold higher respiratory mortality and 1.1- to 1.2-fold higher cancer mortality. Diabetes mortality was elevated more than 2-fold in women with preterm delivery or preeclampsia and 25-fold in those with gestational diabetes (Figure 2 and eTable 4 in Supplement 1).
Figure 2. Adjusted Hazard Ratios (HRs) for Cause-Specific Mortality Associated With Adverse Pregnancy Outcomes.
OHD indicates other hypertensive disorders; SGA, small for gestational age.
Secondary Analyses
Women who experienced multiple adverse pregnancy outcomes had further increases in mortality risk (eTable 5 in Supplement 1). For example, at 30 to 46 years after delivery, the adjusted HRs for mortality associated with 1, 2, or 3 or more adverse pregnancy outcomes were 1.27 (95% CI, 1.24-1.30), 1.56 (95% CI, 1.50-1.63), and 1.84 (95% CI, 1.73-1.95), respectively, compared with women who never experienced an adverse pregnancy outcome.
In analyses of interactions with either maternal age or BMI, a few weakly negative interactions were found between adverse pregnancy outcomes and older maternal age or high BMI in relation to all-cause mortality but no statistically significant positive interactions (eAppendix and eTables 6-8 in Supplement 1). In sensitivity analyses that assessed alternative approaches for missing data or were restricted to each woman’s first delivery, all results were similar to the main findings, and the conclusions were unchanged (eAppendix in Supplement 1).
Discussion
This study extends prior evidence by examining long-term mortality associated with 5 major adverse pregnancy outcomes across each woman’s reproductive life in a large national cohort. The findings suggest that all 5 adverse pregnancy outcomes are independently associated with higher mortality risks that persist more than 40 years later. Women who experienced multiple adverse pregnancy outcomes had further increases in risk. Cosibling analyses suggested that these findings were only partially explained by genetic or environmental factors that may be shared determinants of adverse pregnancy outcomes and early mortality within families.
To our knowledge, this is the largest study to date to examine multiple adverse pregnancy outcomes in the same cohort in relation to long-term mortality and the first to assess for potential unmeasured familial confounding. Most studies have focused on a single adverse pregnancy outcome, thus precluding within-cohort comparisons of risks. For example, in the same Swedish cohort, we previously found that women who delivered preterm or extremely preterm had 1.7- and 2.2-fold higher mortality, respectively, within the next 10 years compared with those who delivered full term and that those risks remained significantly elevated (1.3- and 1.6-fold, respectively) up to 44 years after delivery.12 A study of nearly 1 million women in Israel reported that those who delivered a low–birth weight infant had 2-fold higher mortality during 17 years of follow-up compared with those who had a normal–birth weight infant.23 Other studies also have reported increased cardiovascular24,25,26,27,28,29,30 and diabetes-related31 mortality in women who delivered a low–birth weight infant. Studies in Norway13 and Israel14 suggested that women with preeclampsia had 1.2- or 2-fold higher all-cause mortality with up to 25 or 36 years of follow-up, respectively. However, multiple adverse pregnancy outcomes have seldom been examined within the same cohort. A US study of 46 551 women who delivered in 1959 to 1966 reported that preterm delivery, preeclampsia, and gestational diabetes were each associated with 1.1- to 1.3-fold mortality up to 50 years later, but assessed only 1 pregnancy per woman.15
In the present study, women who experienced any of 5 major adverse pregnancy outcomes had long-term higher mortality risks, which remained significantly elevated (1.1- to 1.5-fold) even 30 to 46 years after delivery. Gestational diabetes was associated with the most excess deaths (mortality rate differences), whereas small for gestational age and preterm delivery accounted for the largest proportion of deaths (population attributable fraction) and together may have accounted for 5% to 10% of all deaths across several decades of follow-up. All 5 adverse pregnancy outcomes were associated with multiple important causes of death, such as cardiovascular or respiratory disorders, diabetes, or cancer.
Pregnancy has been considered a “natural stress test” that may yield valuable information for understanding future health risks.32 In prior research, a key unanswered question is to what extent adverse pregnancy outcomes might unmask preexistent risks vs elicit new risks.33 Adverse pregnancy outcomes may be, at least partly, a signal for preexisting or latent health risks. However, in cosibling analyses, we found that most findings persisted after controlling for familial (genetic or environmental) exposures that may be shared determinants of adverse pregnancy outcomes and premature mortality. Adverse pregnancy outcomes share common features, including abnormal placentation, inflammation, and microvascular dysfunction, that suggest overlapping pathophysiology.33 Small for gestational age, for example, may result from poor placental implantation or vascular insufficiency, mechanisms that are also shared with preterm delivery and hypertensive disorders.34,35 Interventions to interrupt these subclinical processes soon after an adverse pregnancy outcome may be key to preventing future development of chronic disorders that are associated with early mortality.
The present findings suggest that all 5 major adverse pregnancy outcomes should now be recognized as independent risk factors for premature mortality. Adverse pregnancy outcomes are currently underrecognized as long-term risk factors, especially in primary care where most women receive their care.36 Pregnancy complications should be routinely tracked in electronic health records to facilitate transition of patients from obstetric to primary care clinics. Women with adverse pregnancy outcomes need early preventive evaluation and long-term clinical follow-up for timely detection and treatment of cardiometabolic and other chronic disorders associated with premature mortality. In this study, the estimated deaths associated with adverse pregnancy outcomes were modest, albeit with an increasing trend as women reached older ages. Nonetheless, adverse pregnancy outcomes can provide an early window for identifying at-risk women, thus enabling earlier preventive actions to improve their long-term health.4
Strengths and Limitations
A key strength of the present study is its large national cohort design with up to 46 years of follow-up. The availability of highly complete birth, death, and time-varying covariate data from national registries helped minimize potential selection and ascertainment biases. The large sample size enabled high statistical power for simultaneous evaluation of 5 major adverse pregnancy outcomes. The results were controlled for multiple potential confounders, as well as unmeasured shared familial factors using cosibling analyses.
This study also had certain limitations. Despite controlling for multiple maternal factors and shared familial exposures in cosibling analyses, residual confounding by maternal smoking, BMI, or other factors during pregnancy is still possible. We lacked information on behavioral factors such as physical activity and diet. Future studies could help delineate important mediating factors, which were not the focus of the present analysis. During the study period, Sweden had no national consensus on gestational diabetes screening37; underdetection may potentially influence results toward the null hypothesis by including certain women with gestational diabetes in the comparison group. This study will need replication in other countries when feasible, including racially diverse populations to explore for potential heterogeneity of findings. The present findings may have even higher public health importance in US racial and ethnic minority populations that have more restricted access to postpartum care and higher rates of adverse pregnancy outcomes and mortality.33,38
Conclusions
In this large national cohort study, women who experienced any of 5 major adverse pregnancy outcomes (preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders, or gestational diabetes) had increased mortality risks that remained elevated more than 40 years later. Several important causes of death were identified, including cardiovascular and respiratory disorders and diabetes. All 5 major adverse pregnancy outcomes should now be recognized as long-term risk factors for premature mortality. Women with adverse pregnancy outcomes need early preventive actions and long-term follow-up for timely detection and treatment of chronic disorders associated with early mortality.
eAppendix. Secondary Analyses
eTable 1. ICD codes used in the analyses
eTable 2. Prevalence of combinations of adverse pregnancy outcomes
eTable 3. Mortality rates by adverse pregnancy outcome, stratified by maternal age or year of delivery
eTable 4. Associations between adverse pregnancy outcomes and cause-specific mortality
eTable 5. Associations between number of adverse pregnancy outcomes and all-cause mortality
eTable 6. Interactions between preterm delivery and maternal age at delivery in relation to all-cause mortality
eTable 7. Interactions between gestational diabetes and maternal age at delivery in relation to all-cause mortality
eTable 8. Interactions between small for gestational age and maternal body mass index in relation to all-cause mortality
eFigure 1. Log-log plots for associations between adverse pregnancy outcomes and all-cause mortality at 0-46 years of follow-up
eFigure 2. Cumulative mortality at 0-46 years of follow-up associated with specific adverse pregnancy outcomes
Data Sharing Statement
References
- 1.Søndergaard MM, Hlatky MA, Stefanick ML, et al. Association of adverse pregnancy outcomes with risk of atherosclerotic cardiovascular disease in postmenopausal women. JAMA Cardiol. 2020;5(12):1390-1398. doi: 10.1001/jamacardio.2020.4097 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Fraser A, Nelson SM, Macdonald-Wallis C, et al. Associations of pregnancy complications with calculated cardiovascular disease risk and cardiovascular risk factors in middle age: the Avon Longitudinal Study of Parents and Children. Circulation. 2012;125(11):1367-1380. doi: 10.1161/CIRCULATIONAHA.111.044784 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Grandi SM, Filion KB, Yoon S, et al. Cardiovascular disease-related morbidity and mortality in women with a history of pregnancy complications. Circulation. 2019;139(8):1069-1079. doi: 10.1161/CIRCULATIONAHA.118.036748 [DOI] [PubMed] [Google Scholar]
- 4.Crump C, Sundquist J, McLaughlin MA, et al. Adverse pregnancy outcomes and long term risk of ischemic heart disease in mothers: national cohort and co-sibling study. BMJ. 2023;380:e072112. doi: 10.1136/bmj-2022-072112 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Crump C, Sundquist J, Howell EA, McLaughlin MA, Stroustrup A, Sundquist K. Pre-term delivery and risk of ischemic heart disease in women. J Am Coll Cardiol. 2020;76(1):57-67. doi: 10.1016/j.jacc.2020.04.072 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Crump C, Sundquist J, McLaughlin MA, Dolan SM, Sieh W, Sundquist K. Pre-term delivery and long-term risk of heart failure in women: a national cohort and co-sibling study. Eur Heart J. 2021;ehab789. doi: 10.1093/eurheartj/ehab789 [DOI] [PubMed] [Google Scholar]
- 7.Crump C, Sundquist J, Sundquist K. Preterm delivery and long-term risk of stroke in women: a national cohort and cosibling study. Circulation. 2021;143(21):2032-2044. doi: 10.1161/CIRCULATIONAHA.120.052268 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Crump C, Sundquist J, Sundquist K. Preterm delivery and long-term risk of hypertension in women. JAMA Cardiol. 2022;7(1):65-74. doi: 10.1001/jamacardio.2021.4127 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Wu P, Gulati M, Kwok CS, et al. Preterm delivery and future risk of maternal cardiovascular disease: a systematic review and meta-analysis. J Am Heart Assoc. 2018;7(2):e007809. doi: 10.1161/JAHA.117.007809 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Wu P, Haththotuwa R, Kwok CS, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497. doi: 10.1161/CIRCOUTCOMES.116.003497 [DOI] [PubMed] [Google Scholar]
- 11.Rich-Edwards JW, Fraser A, Lawlor DA, Catov JM. Pregnancy characteristics and women’s future cardiovascular health: an underused opportunity to improve women’s health? Epidemiol Rev. 2014;36(1):57-70. doi: 10.1093/epirev/mxt006 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Crump C, Sundquist J, Sundquist K. Preterm delivery and long term mortality in women: national cohort and co-sibling study. BMJ. 2020;370:m2533. doi: 10.1136/bmj.m2533 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Irgens HU, Reisaeter L, Irgens LM, Lie RT. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. BMJ. 2001;323(7323):1213-1217. doi: 10.1136/bmj.323.7323.1213 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Funai EF, Friedlander Y, Paltiel O, et al. Long-term mortality after preeclampsia. Epidemiology. 2005;16(2):206-215. doi: 10.1097/01.ede.0000152912.02042.cd [DOI] [PubMed] [Google Scholar]
- 15.Hinkle SN, Schisterman EF, Liu D, et al. Pregnancy complications and long-term mortality in a diverse cohort. Circulation. 2023;147(13):1014-1025. doi: 10.1161/CIRCULATIONAHA.122.062177 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.National Medical Birth Register. Swedish National Board of Health and Welfare . Accessed March 10, 2024. https://www.socialstyrelsen.se/en/statistics-and-data/registers/national-medical-birth-register/
- 17.Cnattingius S, Ericson A, Gunnarskog J, Källén B. A quality study of a medical birth registry. Scand J Soc Med. 1990;18(2):143-148. doi: 10.1177/140349489001800209 [DOI] [PubMed] [Google Scholar]
- 18.Cnattingius S, Källén K, Sandström A, et al. The Swedish Medical Birth Register during five decades: documentation of the content and quality of the register. Eur J Epidemiol. 2023;38(1):109-120. doi: 10.1007/s10654-022-00947-5 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Ludvigsson JF, Andersson E, Ekbom A, et al. External review and validation of the Swedish national inpatient register. BMC Public Health. 2011;11:450. doi: 10.1186/1471-2458-11-450 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Rubin DB. Multiple Imputation for Nonresponse in Surveys. Wiley; 1987. doi: 10.1002/9780470316696 [DOI] [Google Scholar]
- 21.Grambsch PM. Goodness-of-fit and diagnostics for proportional hazards regression models. Cancer Treat Res. 1995;75:95-112. doi: 10.1007/978-1-4615-2009-2_5 [DOI] [PubMed] [Google Scholar]
- 22.VanderWeele TJ. Causal interactions in the proportional hazards model. Epidemiology. 2011;22(5):713-717. doi: 10.1097/EDE.0b013e31821db503 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Grisaru-Granovsky S, Gordon ES, Haklai Z, et al. Delivery of a very low birth weight infant and increased maternal risk of cancer and death: a population study with 16 years of follow-up. Cancer Causes Control. 2015;26(11):1593-1601. doi: 10.1007/s10552-015-0653-x [DOI] [PubMed] [Google Scholar]
- 24.Smith GD, Whitley E, Gissler M, Hemminki E. Birth dimensions of offspring, premature birth, and the mortality of mothers. Lancet. 2000;356(9247):2066-2067. doi: 10.1016/S0140-6736(00)03406-1 [DOI] [PubMed] [Google Scholar]
- 25.Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet. 2001;357(9273):2002-2006. doi: 10.1016/S0140-6736(00)05112-6 [DOI] [PubMed] [Google Scholar]
- 26.Smith GD, Sterne J, Tynelius P, Lawlor DA, Rasmussen F. Birth weight of offspring and subsequent cardiovascular mortality of the parents. Epidemiology. 2005;16(4):563-569. doi: 10.1097/01.ede.0000164790.96316.c0 [DOI] [PubMed] [Google Scholar]
- 27.Davey Smith G, Hart C, Ferrell C, et al. Birth weight of offspring and mortality in the Renfrew and Paisley study: prospective observational study. BMJ. 1997;315(7117):1189-1193. doi: 10.1136/bmj.315.7117.1189 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Smith GD, Harding S, Rosato M. Relation between infants’ birth weight and mothers’ mortality: prospective observational study. BMJ. 2000;320(7238):839-840. doi: 10.1136/bmj.320.7238.839 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Davey Smith G, Hyppönen E, Power C, Lawlor DA. Offspring birth weight and parental mortality: prospective observational study and meta-analysis. Am J Epidemiol. 2007;166(2):160-169. doi: 10.1093/aje/kwm054 [DOI] [PubMed] [Google Scholar]
- 30.Li CY, Chen HF, Sung FC, et al. Offspring birth weight and parental cardiovascular mortality. Int J Epidemiol. 2010;39(4):1082-1090. doi: 10.1093/ije/dyq045 [DOI] [PubMed] [Google Scholar]
- 31.Li CY, Sung FC, Hsieh PC, Lee MD, Lu TH, Chen HF. Offspring birth weight and risk of mortality from diabetes in mothers. J Epidemiol Community Health. 2011;65(9):775-779. doi: 10.1136/jech.2009.100644 [DOI] [PubMed] [Google Scholar]
- 32.Williams D. Pregnancy: a stress test for life. Curr Opin Obstet Gynecol. 2003;15(6):465-471. doi: 10.1097/00001703-200312000-00002 [DOI] [PubMed] [Google Scholar]
- 33.Lane-Cordova AD, Khan SS, Grobman WA, Greenland P, Shah SJ. Long-term cardiovascular risks associated with adverse pregnancy outcomes: JACC review topic of the week. J Am Coll Cardiol. 2019;73(16):2106-2116. doi: 10.1016/j.jacc.2018.12.092 [DOI] [PubMed] [Google Scholar]
- 34.Siddiqui N, Hladunewich M. Understanding the link between the placenta and future cardiovascular disease. Trends Cardiovasc Med. 2011;21(7):188-193. doi: 10.1016/j.tcm.2012.05.008 [DOI] [PubMed] [Google Scholar]
- 35.Valdiviezo C, Garovic VD, Ouyang P. Preeclampsia and hypertensive disease in pregnancy: their contributions to cardiovascular risk. Clin Cardiol. 2012;35(3):160-165. doi: 10.1002/clc.21965 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Gogineni VSM, Manfrini D, Aroda SH, et al. Variations in awareness of association between adverse pregnancy outcomes and cardiovascular risk by specialty. Cardiol Ther. 2021;10(2):577-592. doi: 10.1007/s40119-021-00220-y [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Lindqvist M, Persson M, Lindkvist M, Mogren I. No consensus on gestational diabetes mellitus screening regimes in Sweden: pregnancy outcomes in relation to different screening regimes 2011 to 2012, a cross-sectional study. BMC Pregnancy Childbirth. 2014;14:185. doi: 10.1186/1471-2393-14-185 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Minehart RD, Bryant AS, Jackson J, Daly JL. Racial/ethnic inequities in pregnancy-related morbidity and mortality. Obstet Gynecol Clin North Am. 2021;48(1):31-51. doi: 10.1016/j.ogc.2020.11.005 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
eAppendix. Secondary Analyses
eTable 1. ICD codes used in the analyses
eTable 2. Prevalence of combinations of adverse pregnancy outcomes
eTable 3. Mortality rates by adverse pregnancy outcome, stratified by maternal age or year of delivery
eTable 4. Associations between adverse pregnancy outcomes and cause-specific mortality
eTable 5. Associations between number of adverse pregnancy outcomes and all-cause mortality
eTable 6. Interactions between preterm delivery and maternal age at delivery in relation to all-cause mortality
eTable 7. Interactions between gestational diabetes and maternal age at delivery in relation to all-cause mortality
eTable 8. Interactions between small for gestational age and maternal body mass index in relation to all-cause mortality
eFigure 1. Log-log plots for associations between adverse pregnancy outcomes and all-cause mortality at 0-46 years of follow-up
eFigure 2. Cumulative mortality at 0-46 years of follow-up associated with specific adverse pregnancy outcomes
Data Sharing Statement
