Preeclampsia is a major complication in pregnancy.1 As the etiology of this complication is largely unknown,2 psychological aspects or aspects related to the nervous system also have to be considered.3 Preeclampsia has been regarded as a pregnancy-specific disease, but recent data on overall sympathetic overactivity in preeclampsia may imply that the autonomic nervous system and perhaps central nervous system also may contribute to the risk for this disorder.4
Little is known about the impact of psychosocial factors on subsequent preeclampsia. Strenuous work may increase the risk of preeclampsia,5,6 but the general stress of living may not.7
Therefore, we conducted a prospective study to assess the impact of depression and anxiety in early pregnancy on the subsequent risk for preeclampsia.
Materials and Methods
A cohort of 652 consecutive, healthy white, pregnant nulliparous women were enrolled at their first prenatal visit between 8–17 (median 12) weeks' gestation. All women in this population-based study came from a defined geographical area of Helsinki. The women gave their informed written consent and were then screened during the same visit for depression and anxiety by a structured questionnaire. The subjects were studied at about 1-month intervals at prenatal clinics and gave birth at the Helsinki City Maternity Hospital. Data from the questionnaires were stored in a database and completed with pertinent information on pregnancy outcome.
Of the 652 women, 15 were excluded because of a prior elevated risk for preeclampsia; five of them had essential hypertension, five had gestational diabetes, and five had twins. In addition, 14 women were excluded from the final analysis, nine because of spontaneous abortion, three because of termination of pregnancy, and two because of second-trimester fetal death; none of these had preeclampsia. The remaining 623 patients at low risk for preeclampsia comprised the study population, with the outcome of pregnancy known in all cases.
Of the 623, 23 (3.7%) women delivered before 37 weeks' gestation, and of these, 18 experienced spontaneous preterm delivery. In the remaining five, cause of prematurity was induction of labor due to severe preeclampsia (n = 3), cholestasis of pregnancy (n = 1), or fetal hydrops (n = 1).
Depression was measured by a Finnish modification for population studies8,9 of the shortened version of the Beck Depression Inventory,10,11 a widely used self-rating scale for depression with established reliability and validity.12,13 Results with the shortened 13-item Beck Depression Inventory have a high correlation with those in the original long Beck Depression Inventory. Both introductory questions and one positive choice answer were added for each item to the Finnish modification.8 Because these additional positive choices measure self-confidence and do not affect the scoring of depression, they are therefore more suitable for population screening than is the original Beck Depression Inventory, which was developed for psychiatric patients.14 As the majority of the subjects with depressive disorders may not be diagnosed by the primary and occupational health services, and therefore may not receive appropriate treatment, the Social Insurance Institution in Finland developed a 14-item questionnaire (13 items for depression and one for anxiety) for population screening.8,9 An example of the Finnish modification of the shortened 13-item Beck Depression Inventory is the following item of the questionnaire: “How do you feel?” “I am feeling quite optimistic and good” (4); “I do not feel sad” (0); “I feel sad or blue” (1); “I am blue or sad all the time and I cannot snap out of it” (2); “I am so sad or unhappy that I cannot stand it” (3). The first choice (4) measures self-confidence (only in the Finnish version), and the remaining three are from the original shortened Beck Depression Inventory.10 This Finnish modification has good reliability and validity and is used widely for screening of Finnish populations.8,9 We defined depression as a score of 3 or more, with lower scores considered as normal.
It is known that the majority of depressed persons also have anxiety.15 There are, however, no questions for perceived anxiety in the original or shortened version of Beck Depression Inventory. That is why one question regarding anxiety was developed. Anxiety was assessed as a dichotomous variable (0 for normal and 1–3 indicating presence of anxiety) with the following question: “Are you tense or distressed?” The choices were “I believe I have good nerves and do not become distressed easily” (0); “I do not feel tense or distressed” (0); “I become distressed quite easily” (1); “I become very easily anxious, tense and distressed” (2); “I feel myself all the time anxious and tense as if I had lost my nerves” (3). Positive answers (1–3) to this question were associated with an increased risk of anxiety among Finnish farmers.16
Gestational age was determined by the last menstrual period and by ultrasound at 16 to 20 weeks. Preeclampsia was defined as elevated blood pressure (BP) (more than 140/100 mmHg) and proteinuria (0.3 g during 24 hours or more) after 20 weeks' gestation. The potentially confounding variables studied were age, smoking, alcohol consumption, marital status, and social class based on the woman's profession (five categories include academic white-collar (9%), nonacademic white-collar (34%), skilled laborer (40%), nonskilled laborer (7%), and unclassified (10%). Bacterial vaginosis was assessed at the first prenatal visit by Gram stain as described previously.17
With a prevalence of 30% of mild depression among pregnant Finnish women, it was calculated that about 200 women with depression and 400 without were needed for the study for it to have an 80% power to detect a difference of 6% (10% compared with 4%) in incidence of preeclampsia between the groups at P < .05. All variables were treated as categoric. The χ2 test was used for testing differences, with P < .05 considered statistically significant. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with SAS (SAS Institute, Inc., Cary, NC) including multiple logistic regression analysis. All statistical tests were two sided.
Of the 623, 28 women (4.5%) developed proteinuric preeclampsia, with three requiring delivery before 37 weeks.
The mean Beck score for the whole study population was 2.0 (range 0–17). Depression (mean Beck score 4.5, range 3–17) was detected in 185 (30%) women and anxiety in 99 (16%) (Table 1).
In univariate analysis, depression was associated with increased (OR 2.5; 95% CI 1.2, 5.3) risk for preeclampsia as was anxiety (OR 3.2; 95% CI 1.4, 7.1). Risk for preeclampsia did not further increase with Beck scores higher than 3. Of the potentially confounding variables, maternal age over 30 years was associated with increased (OR 3.4; 95% CI 1.3, 8.8) risk for preeclampsia, but smoking, alcohol consumption, marital and socioeconomic status, or bacterial vaginosis were not.
When multiple logistic regression analysis was applied, depression was still associated with 2.5-fold (95% CI 1.1, 5.4) and anxiety 3.2-fold (95% CI 1.4, 7.4) risk for preeclampsia when the data were adjusted for the six potentially confounding factors. Either depression or anxiety or both were associated with a 3.1-fold (95% CI 1.4, 6.9) risk for preeclampsia. Depression together with bacterial vaginosis (n = 44) was associated with a 5.3-fold risk (95% CI 1.8, 15.0) for preeclampsia (n = 7) as compared with the group of women who had neither depression nor bacterial vaginosis. The remaining variables showed no such synergistic effect.
This study suggests that depression and anxiety in early pregnancy may be associated with subsequent preeclampsia. In our study, healthy nulliparous women had undergone normal first trimesters and were then screened for depression with the aid of well-established questionnaires suitable for population screening.8,13,14 Depression and anxiety were assessed at a median 12 weeks' gestation, clearly before any clinical signs of preeclampsia occurred. The fact that depression (mean Beck score 4.5) was detected in 30% of these women and anxiety in 16% is in accordance with previous data in which, during pregnancy, up to 38% of women have shown depressive symptoms and 12% have shown symptoms of anxiety.18–21 Our mean Beck score of 2.0 in all pregnant women studied is also in accordance with prevalence of depressive symptoms (mean Beck score 1.9) in the normal nonpregnant female population in Finland.9
Vasoconstriction in preeclampsia may develop early in pregnancy.2,22 Indeed, increased uterine artery resistance in maternal anxiety23 could be a primary manifestation or even the cause of preeclampsia. The synergistic association of depression with bacterial vaginosis for subsequent risk of preeclampsia was an unexpected finding. It has, however, been shown that inflammatory changes may enhance the risk for subsequent preeclampsia.24,25 Furthermore, it is known that black pregnant women often have bacterial vaginosis26 as well as preeclampsia27 when compared with white women. Another explanation may be that bacterial vaginosis serves as a marker of low socioeconomic status, at least in the United States,26 but this is not necessarily the case in our population. Furthermore, it is known that depressive symptoms are more common in pregnant women of low economic status.28
Depression and anxiety during pregnancy could prove harmful through altered excretion of vasoactive hormones or other neuroendocrine transmitters,4,29–32 which in turn may increase the risk for hypertension.33 It is also possible that depression may trigger such vascular changes and eventually induce preeclampsia. However, the precise biochemical mechanism(s) remain unknown.
The limitations of this study may be that mood was assessed only once in early pregnancy, and that no information was available on family history or on biochemical parameters. Furthermore, the size of our series was not sufficient to assess whether the degree of depression was associated with the magnitude of the risk for preeclampsia. However, we consider that the strengths of this study are its prospective nature, enrollment of only nulliparous women, and early assessment (before any signs of preeclampsia) of depression and anxiety.
Our results indicate that women showing depression are at increased risk for subsequent preeclampsia and need extra social and psychological support and close follow-up for symptoms of preeclampsia.
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