Objective
This study aims to evaluate perceived lifetime stress, perceived stress during pregnancy, chronic hypertension, and their joint association with preeclampsia risk.
Study Design
This study includes 4314 women who delivered a singleton live birth at the Boston Medical Center from October 1998 through February 2008. Chronic hypertension was defined as hypertension diagnosed before pregnancy. Information regarding lifetime stress and perceived stress during pregnancy was collected by questionnaire. Preeclampsia was diagnosed by clinical criteria.
Results
Lifetime stress (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.6–2.9), perceived stress during pregnancy (OR, 1.7; 95% CI, 1.3–2.2), and chronic hypertension (OR, 10.4; 95% CI, 7.5–14.4) were each associated with an increased risk of preeclampsia. Compared to normotensive pregnancy with low lifetime stress, both normotensive pregnancy with high lifetime stress (OR, 2.1; 95% CI, 1.6–2.9) and pregnancy with chronic hypertension and low lifetime stress (OR, 10.2; 95% CI, 7.0–14.9) showed an increased risk of preeclampsia, while pregnancy with high lifetime stress and chronic hypertension yielded the highest risk of preeclampsia (OR, 21.3; 95% CI, 10.2–44.3). The joint association of perceived stress during pregnancy and chronic hypertension with preeclampsia was very similar to that of the joint association of lifetime stress and chronic hypertension with preeclampsia.
Conclusion
This finding indicates that high psychosocial stress and chronic hypertension can act in combination to increase the risk of preeclampsia up to 20-fold. This finding underscores the importance of efforts to prevent, screen, and manage chronic hypertension, along with those to reduce psychosocial stress, particularly among women with chronic hypertension.
Preeclampsia occurs in 5-7% of pregnancies, and is a major cause of maternal and fetal mortality and morbidity in both developed and developing countries. Onset early in pregnancy is associated with a poorer prognosis. For the fetus, preeclampsia may result in growth restriction, preterm birth, hypoxia, and death. For the mother, it may induce placental abruption with possible disseminated intravascular coagulation, end organ damage as a result of accelerated hypertension, stroke, and death. Women who have preeclampsia as a multipara, have it as a recurrent event, or develop it in the second trimester have been found to be at higher risk for hypertension and diabetes later in life. Worldwide, 10-15% of the half million maternal deaths that occur every year are associated with hypertensive disorders of pregnancy, mainly preeclampsia/eclampsia (PE/E). In Canada, PE/E was one of the leading causes of maternal death from 1997 through 2000, directly accounting for 21% of maternal deaths.
Previous studies have found that women with certain conditions, including nulliparity, a family history or self-history of preeclampsia, increased body mass index (BMI), multiple pregnancies, increased age, chronic hypertension, diabetes mellitus, renal and connective tissue diseases, work-related psychosocial strain during pregnancy, poor social status, coagulation abnormalities, and dyslipidemia are at increased risk for preeclampsia. Of note, chronic hypertension is a well-known risk factor for preeclampsia. Its prevalence in pregnant women varies from 1-5%; and the rates are higher in older, obese, and black women. It is estimated that 25% of women with preexisting hypertension will have PE/E during pregnancy. In Thailand, pregnant women with chronic hypertension had a 19.5-fold (95% confidence interval [CI], 2.4–155.7) increased risk of preeclampsia, compared with those without chronic hypertension. Previously, our study group found that chronic hypertension was associated with preeclampsia among black and white pregnant women. In short, data from different studies have consistently shown that chronic hypertension is a leading risk factor of PE/E.
In contrast, findings to date on psychosocial stress and PE/E have been inconsistent. Some studies found depression, anxiety, and other psychopathologies during pregnancy to be risk factors for adverse fetal and neonatal outcomes including preterm delivery, fetal growth restriction, and low Apgar scores. In addition, the mother’s anxiety during pregnancy is associated with an increased risk of asthma in the child. Indeed, accumulating evidence indicates that psychiatric disorders during pregnancy are related to an increased risk of preeclampsia. One prospective study indicated that women with depression, anxiety, or both had a 3.1-fold increased risk for preeclampsia, compared to those without. Another recent study by Qiu et al found that a positive history of maternal mood or anxiety disorder was associated with a 2.12-fold increased risk of preeclampsia. Four further studies observed an association of preeclampsia/gestational hypertension with job stress in working women, and another demonstrated that anxiety during early pregnancy increased the risk of preeclampsia >3-fold among 652 Finnish nulliparous women (odds ratio [OR], 3.2; 95% CI, 1.4–7.4). Likewise, both depression and perceived stress during pregnancy were associated with increased rates of preeclampsia.
Data from animal studies have indicated that in 14-day pregnant rats, chronic stress leads to increased adrenal weight and lower endothelium-derived relaxing factor release; likewise, in 20-day pregnant rats, chronic stress caused higher blood pressure, increased vasomotility and proteinuria, and lower endothelium-derived relaxing factor release. The animal data also imply that mental stress during pregnancy may increase the risk of hypertension-associated disorders. In contrast with these animal findings, there was no association between work stress, anxiety, depression, or pregnancy-related anxiety early in pregnancy and the development of gestational hypertension or preeclampsia later in pregnancy among a cohort of 3679 pregnant women in Amsterdam, The Netherlands. Two other prospective studies did not observe an association between depression or anxiety and hypertensive complications, and moreover, these studies also did not find a significant association between maternal psychopathology and preeclampsia.
To date, no study has examined the combined association of psychosocial stress and chronic hypertension with PE/E in a US urban minority population, in which both psychosocial risk factors and chronic hypertension are prevalent. The objectives of this study were to examine the individual and joint association of psychosocial stress and chronic hypertension with preeclampsia in an urban US population, and to explore whether the associations differ between black and nonblack women.
Materials and Methods
Study population and data collection
This study is part of an ongoing National Institutes of Health–funded case-control study on preterm birth, and includes women enrolled at the Boston Medical Center (BMC) from October 1998 through February 2008. The parent study (1998 through present) is also being conducted at the BMC, a large urban hospital with a predominantly minority, inner-city patient population. Case mothers were those who delivered singleton, live births occurring at <37 weeks of gestation, and controls were defined as mothers delivering at ≥37 weeks of gestation with birthweight appropriate for gestational age as defined by the National Center for Health Statistics/Centers for Disease Control and Prevention guidelines (birthweight 2500-4000 g). Pregnancies resulting in multiple births and newborns with major birth defects were excluded; a detailed description of the study population is available elsewhere. For this study, we collected epidemiologic data, clinical data, and maternal venous blood samples. In addition, placenta samples were sent for histopathology based on routine indications, including preterm birth. The institutional review boards of BMC; the Massachusetts Department of Public Health; Children’s Memorial Hospital in Chicago (now Ann and Robert H. Lurie Children’s Hospital of Chicago); and the Bloomberg School of Public Health, Johns Hopkins University approved the study protocol, and all participants gave written informed consent.
Definition of preeclampsia and other key variables
Preeclampsia and chronic hypertension
All of the following key outcomes were defined by physician diagnosis and confirmed by a review of prenatal care records in accordance with published clinical studies. Preeclampsia was defined according to the report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy, as systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg on at least 2 occasions, and proteinuria of at least 1+ by urine dipstick testing on ≥2 occasions, >20 weeks of gestation. In the present report, the preeclampsia group also included women with eclampsia. Women with gestational hypertension, defined as elevated blood pressure occurring >20 weeks of gestation without preexisting hypertension, and not associated with proteinuria or other systemic manifestations, were excluded from the analysis. Chronic hypertension was defined as persistent hypertension that is present before conception or during the first 20 weeks of gestation.
Variables of psychological stress
We examined the following variables: women’s perceived amount of general life stress, perceived stress during pregnancy, major stressful life events within 1 year prior to pregnancy, major stressful life events during pregnancy, any violence witnessed during pregnancy, father of baby involved in index pregnancy, father of baby supportiveness, family and friend supportiveness, whether pregnancy was desired, annual household income, and food supply. Information about psychological stress was collected by questionnaire. Lifetime stress and stress during pregnancy were defined, respectively, by responses to the following 2 questions: “How would you characterize the amount of stress in your life in general?” and “How would you characterize the amount of stress in your life during pregnancy?” Three options for response to these questions were provided: “not stressful,” “average stressful,” and “very stressful.” For the analyses, “not stressful” and “average stressful” were considered to be low stress, and “very stressful” was regarded as high stress; missing data indicate that the pregnant woman was not employed.
Statistical analysis
All analyses were conducted using software (SAS, version 8.0; SAS Institute Inc, Cary, NC). First, the sociodemographic and clinical variables were described, stratified by nonpreeclampsia and preeclampsia. The continuous and categorical variables were analyzed by t test and χ 2 test, respectively. Second, the distributions of variables related to psychological stress were presented, stratified by the nonpreeclampsia and preeclampsia groups. Third, the separate association of life stress, pregnancy stress, and either life or pregnancy stress combined with chronic hypertension relative to the risk of preeclampsia was analyzed before and after the adjustment of covariates using logistic regression models. Finally, the adjusted joint effects of life stress, pregnancy stress, and chronic hypertension on the risk of preeclampsia were evaluated for the entire study samples as well as for the population subgroups (black and nonblack mothers) using logistic regression models.
In the logistic regression models, the following covariates were included: marital status, maternal ethnicity, maternal education level, maternal active and passive smoking during pregnancy, maternal age, prepregnancy BMI, parity, drug use, and alcohol use.
Results
Altogether, 4314 mothers were included in the final analysis, including 3890 mothers without preeclampsia and 424 mothers with preeclampsia. The prevalence of preeclampsia was 9.9% in the study population. Table 1 shows the demographic and clinical characteristics of the study sample. As compared to those without preeclampsia, mothers with preeclampsia were older, had higher prepregnancy BMI, and had delivered babies with lower gestational age and/or lower birthweight (all P < .001). Mothers with preeclampsia were more likely to be black and primiparous, have a lower prevalence of active smoking, a higher prevalence of chronic hypertension, and a different distribution for education status than mothers without preeclampsia (all P < .01). Marital status and prevalence of passive smoking, illicit drug use, and alcohol drinking during pregnancy were similar between the 2 groups (all P > .05).
| Variable | Preeclampsia | No preeclampsia | P value |
|---|---|---|---|
| n | 424 | 3890 | |
| Maternal age, y (mean ± SD) | 29.3 ± 6.9 | 27.8 ± 6.4 | < .001 |
| Prepregnancy BMI, kg/m 2 (mean ± SD) | 28.2 ± 7.1 | 25.6 ± 6.0 | < .001 |
| Gestational age, wk (mean ± SD) | 35.3 ± 3.7 | 38.2 ± 3.2 | < .001 |
| Birthweight, g (mean ± SD) | 2332.3 ± 898.4 | 3015.9 ± 743.9 | < .001 |
| Maternal age distribution, n (%) | |||
| <20 y | 41 (9.7) | 453 (11.6) | < .001 |
| 20-29 y | 178 (42.0) | 2027 (52.1) | |
| 30-34 y | 109 (25.7) | 820 (21.1) | |
| ≥35 y | 96 (22.6) | 590 (15.2) | |
| Highest education completed, n (%) | |||
| Primary school | 28 (6.7) | 245 (6.4) | .022 |
| Middle school | 83 (19.9) | 1020 (26.5) | |
| High school | 168 (40.3) | 1317 (34.2) | |
| Some college | 88 (21.1) | 861 (22.4) | |
| ≥College degree | 50 (12.0) | 403 (10.5) | |
| Marital status, n (%) | |||
| Married | 270 (63.8) | 2549 (65.7) | .447 |
| Unmarried | 153 (36.2) | 1332 (34.3) | |
| Maternal ethnicity, n (%) | |||
| Black | 259 (61.1) | 1998 (51.4) | .002 |
| White | 39 (9.2) | 444 (11.4) | |
| Hispanic | 84 (19.8) | 968 (24.9) | |
| Other | 42 (9.9) | 480 (12.3) | |
| Parity, n (%) | |||
| 0 | 204 (48.1) | 1559 (40.1) | .001 |
| ≥1 | 220 (51.9) | 2331 (59.9) | |
| Maternal smoking, n (%) | |||
| Never | 361 (85.1) | 3061 (78.7) | < .001 |
| Intermittent | 34 (8.0) | 264 (6.8) | |
| Persistent | 29 (6.8) | 565 (14.5) | |
| Passive smoking, n (%) | |||
| No | 337 (79.5) | 2961 (76.1) | .121 |
| Yes | 87 (20.5) | 929 (23.9) | |
| Maternal illicit drug use, n (%) | |||
| No | 379 (89.4) | 3356 (86.3) | .074 |
| Yes | 45 (10.6) | 534 (13.7) | |
| Maternal alcohol use, n (%) | |||
| No | 415 (97.9) | 3736 (96.0) | .060 |
| Yes | 9 (2.1) | 154 (4.0) | |
| Preterm birth, n (%) | |||
| No | 167 (39.4) | 2964 (76.2) | < .001 |
| Yes | 257 (60.6) | 926 (23.8) | |
| Low birthweight delivery, n (%) | |||
| No | 208 (49.1) | 2506 (64.4) | < .001 |
| Yes | 216 (50.9) | 1384 (35.6) | |
| Chronic hypertension, n (%) | |||
| No | 318 (75.0) | 3787 (97.4) | < .001 |
| Yes | 106 (25.0) | 103 (2.6) | |
Table 2 presents the distribution of stress-related variables in the 2 groups. Women with preeclampsia had higher perceived levels of general stress in their lives, and higher perceived stress during pregnancy. They also had higher job-related stress during the first and second trimester compared to those without preeclampsia, and experienced more major stressful events within 1 year prior to pregnancy. The distributions of the other stress variables were similar in the 2 groups.
| Variable | Level | Preeclampsia, n (%) | No preeclampsia, n (%) | P value |
|---|---|---|---|---|
| n | 424 | 3890 | ||
| Life stress a | Low | 345 (81.4) | 3460 (88.9) | < .001 |
| High | 79 (18.6) | 430 (11.1) | ||
| Pregnancy stress b | Low | 310 (73.1) | 3126 (80.4) | < .001 |
| High | 114 (26.9) | 764 (19.6) | ||
| Job stress during first and second trimester | Low | 2925 (75.2) | 295 (69.6) | .009 |
| High | 816 (21.0) | 116 (27.4) | ||
| Missing | 149 (3.8) | 13 (3.1) | ||
| Job stress during third trimester | Low | 3190 (82.0) | 338 (79.7) | .507 |
| High | 533 (13.7) | 65 (15.3) | ||
| Missing | 167 (4.3) | 21 (5.0) | ||
| Event within 1 y c | No | 349 (82.3) | 3381 (86.9) | .009 |
| Yes | 75 (17.7) | 509 (13.1) | ||
| Event during pregnancy d | No | 325 (76.7) | 3026 (77.8) | .593 |
| Yes | 99 (23.3) | 864 (22.2) | ||
| Violence e | No | 410 (96.7) | 3695 (95.0) | .119 |
| Yes | 14 (3.3) | 195 (5.0) | ||
| Father involved f | Low | 101 (23.8) | 976 (25.1) | .566 |
| High | 323 (76.2) | 2914 (74.9) | ||
| Father supportive g | Low | 96 (22.6) | 967 (24.9) | .314 |
| High | 328 (77.4) | 2923 (75.1) | ||
| Family supportive h | Low | 27 (6.4) | 349 (9.0) | .071 |
| High | 397 (93.6) | 3541 (91.0) | ||
| Planned pregnancy i | Yes | 227 (53.5) | 2059 (52.9) | .812 |
| No | 197 (46.5) | 1831 (47.1) | ||
| Annual household income | <$15,000 | 132 (42.0) | 1216 (43.9) | .308 |
| $15,000-29,999 | 75 (23.9) | 726 (26.2) | ||
| ≥$30,000 | 107 (34.1) | 831 (30.0) | ||
| Food supply | Sufficient | 386 (91.0) | 3557 (91.4) | .779 |
| Insufficient | 38 (9.0) | 333 (8.6) |
a Amount of stress in mother’s life in general
b Amount of stress in mother’s life during pregnancy
c Major stressful events within 1 y prior to pregnancy
d Major stressful events during pregnancy
e Any violence witnessed during pregnancy
f Father of baby involved in index pregnancy
h Support from family and friends
The associations of chronic hypertension, life stress, pregnancy stress, and either general life stress or pregnancy stress with the risk of preeclampsia were evaluated for the entire study population ( Table 3 ). After adjusting for potential confounding variables, the risk of preeclampsia was increased by life stress (OR, 2.1; 95% CI, 1.6–2.9; P < .0001), stress during pregnancy (OR, 1.7; 95% CI, 1.3–2.2; P < .0001), and chronic hypertension (OR, 10.4; 95% CI, 7.5–14.4; P < .0001). Additionally, having either general life stress or pregnancy stress also increased the risk of preeclampsia (OR, 1.7; 95% CI, 1.3–2.1; P < .0001). Meanwhile, in the subanalyses based on maternal ethnicity (Appendix; Supplemental Table 1 ), the strength of the association between chronic hypertension, life stress, pregnancy stress, and either general life stress or pregnancy stress with the risk of preeclampsia among black mothers and nonblack mothers was highly similar to that of the entire study sample.
| Variable | Preeclampsia, n (%) | No preeclampsia, n (%) | OR (95% CI) | P value |
|---|---|---|---|---|
| Life stress | ||||
| Low | 345 (9.1) | 3460 (90.9) | 1.0 | – |
| High | 79 (15.5) | 430 (84.5) | 2.1 (1.6–2.9) | < .0001 |
| Pregnancy stress | ||||
| Low | 310 (9) | 3126 (91) | 1.0 | – |
| High | 114 (13) | 764 (87) | 1.7 (1.3–2.2) | < .0001 |
| Either life or pregnancy stress | ||||
| Low | 301 (8.9) | 3063 (91.1) | 1.0 | – |
| High | 123 (12.9) | 827 (87.1) | 1.7 (1.3–2.1) | < .0001 |
| Chronic hypertension | ||||
| No | 318 (7.7) | 3787 (92.3) | 1.0 | – |
| Yes | 106 (50.7) | 103 (49.3) | 10.4 (7.5–14.4) | < .0001 |
Table 4 and Supplemental Table 2 present the joint association between stress and chronic hypertension in the entire study population, and in the black and nonblack subgroups. Mothers with both chronic hypertension and high stress had a high risk of preeclampsia. Normotensive mothers with high life stress, and chronic hypertensive mothers with either low or high life stress, had an increased risk of preeclampsia as compared with normotensive mothers with low life stress. Notably, the combination of high life stress and chronic hypertension yielded the highest risk of preeclampsia (OR, 21.3; 95% CI, 10.2–44.3; P < .0001). Hypertensive mothers with both life stress and pregnancy stress also had a markedly high increased risk of preeclampsia (OR, 21.5; 95% CI, 9.6–48.0; P < .0001). The joint effect of stress during pregnancy with chronic hypertension or having either general life stress or pregnancy stress with chronic hypertension on preeclampsia was very similar ( Table 4 ). The mothers with chronic hypertension and high stress during pregnancy had 18.5-fold (95% CI, 10.0–34.4) increased risk of preeclampsia, compared with normotensive mothers with low stress during pregnancy. Additionally, the joint effects of psychological stress and chronic hypertension on preeclampsia were also observed among black mothers and nonblack mothers, respectively, though there was no association of chronic hypertension and stress during pregnancy on preeclampsia among black mothers (Appendix; Supplemental Table 2 ).
| Variable | Preeclampsia, n (%) | No preeclampsia, n (%) | OR (95% CI) | P value | |
|---|---|---|---|---|---|
| Hypertension | |||||
| Life stress | |||||
| No | Low | 262 (7.2) | 3370 (92.8) | 1.0 | – |
| High | 56 (11.8) | 417 (88.2) | 2.1 (1.6–2.9) | < .0001 | |
| Yes | Low | 83 (48.0) | 90 (52.0) | 10.4 (7.3–14.9) | < .0001 |
| High | 23 (63.9) | 13 (36.1) | 21.3 (10.2–44.3) | < .0001 | |
| Stress during pregnancy | |||||
| No | Low | 235 (7.2) | 3044 (92.8) | 1.0 | – |
| High | 83 (10.0) | 743 (90.0) | 1.7 (1.3–2.2) | < .0001 | |
| Yes | Low | 75 (47.8) | 82 (52.2) | 10.2 (7.0–14.9) | < .0001 |
| High | 31 (59.6) | 21 (40.4) | 18.5 (10.0–34.4) | < .0001 | |
| Any one of life and pregnancy stress | |||||
| No | Low | 230 (7.2) | 2983 (92.8) | 1.0 | – |
| High | 88 (9.9) | 804 (90.1) | 1.6 (1.3–2.2) | < .0001 | |
| Yes | Low | 71 (47.0) | 80 (53.0) | 10.0 (6.8–14.6) | < .0001 |
| High | 35 (60.3) | 23 (39.7) | 18.8 (10.4–33.7) | < .0001 | |
| Both life and pregnancy stress | |||||
| No | Low | 230 (7.2) | 2983 (92.8) | 1.0 | – |
| High | 51 (12.5) | 356 (87.5) | 2.3 (1.7–3.3) | < .0001 | |
| Yes | Low | 71 (47.0) | 80 (53.0) | 10.0 (6.8–14.6) | < .0001 |
| High | 19 (63.3) | 11 (36.7) | 21.5 (9.6–48.0) | < .0001 | |
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
