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Published online before print July 16, 2007, 10.1097/PSY.0b013e3180cac25d
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Psychosomatic Medicine 69:566-570 (2007)
© 2007 American Psychosomatic Society

ORIGINAL ARTICLES

Maternal Prenatal Pregnancy-Related Anxiety and Spontaneous Preterm Birth in Baltimore, Maryland

Suezanne T. Orr, PhD, Jerome P. Reiter, PhD, Dan G. Blazer, MD, PhD and Sherman A. James, PhD

From the Department of Health Education and Promotion (S.T.O.), College of Health and Human Performance, East Carolina University, Greenville, North Carolina; Institute of Statistics and Decision Sciences (J.P.R.), Duke University, Durham, North Carolina; Department of Psychiatry and Behavioral Sciences (D.G.B.), Duke University Medical Center, Durham, North Carolina; Terry Sanford Institute for Policy Studies (S.A.J.), Duke University, Durham, North Carolina.

Address correspondence and reprint requests to Suezanne T. Orr, Department of Health Education and Promotion, College of Health and Human Performance, East Carolina University, 200 Christenbury, Greenville, NC 27858. E-mail: orrs{at}ecu.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Objective: To focus on the relationship between pregnancy-related anxiety and spontaneous preterm birth. Psychosocial factors have been the subject of inquiries about the etiology of preterm birth; a factor of recent interest is maternal prenatal pregnancy-related anxiety (worries and concerns related to the pregnancy).

Methods: From 1991 to 1993, a total of 1820 women completed the study questionnaire during their first prenatal visit to clinics in Baltimore, Maryland. Pregnancy-related anxiety was assessed using six questions from the Prenatal Social Environment Inventory; scores ranged from 0 to 6. Data on pregnancy outcome and clinical and behavioral covariates were obtained from the women’s clinical records.

Results: After adjustment for covariates (first or second trimester bleeding, drug use, employment, prior poor pregnancy outcome, smoking, low body mass index, maternal education, age, and race), women with higher levels of pregnancy-related anxiety (scores of 5 or 6) had a significantly increased risk of spontaneous preterm birth compared with those with scores of ≤3.

Conclusions: If additional research confirms these results, then this finding may suggest the possibility of intervention to reduce maternal prenatal pregnancy-related worries and concerns, thereby reducing the risk of spontaneous preterm birth.

Key Words: anxiety • pregnancy • preterm birth

Abbreviations: PSEI = Prenatal Social Environment Inventory; CES-D = Center for Epidemiologic Studies Depression Scale; BMI = body mass index; OR = Odds Ratio.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Preterm birth (birth at <37 completed weeks of gestation) continues to be a major public health and medical problem in the United States. In 2003 to 2004, one in eight (12.5%) live births were preterm (1), and the rate of preterm birth has increased steadily over the past several decades. From 1990, the rate of preterm birth has increased 18% (1). Preterm birth is associated with a substantial risk of infant morbidity and mortality and also with childhood morbidity (2,3), and the high rate of preterm birth in the United States contributes to the high rate of infant mortality.

Despite the importance of preterm birth, its etiology and prevention are poorly understood. Psychosocial factors have been the subject of inquiries into the etiology of preterm birth. Prior research has focused on associations between psychosocial factors such as maternal exposure to stressors (4–9) and anxiety (4,10–14) with preterm birth. Although most prior research has identified associations between exposure to stressors with poor pregnancy outcomes (4–9), these findings have not been easily utilized to develop interventions to reduce the incidence of preterm birth. Some studies have not found significant associations between exposure to stressors and preterm birth (15).

Another psychosocial factor of interest is maternal anxiety. Findings on this topic have been controversial—some prior studies have suggested that maternal anxiety is associated with pregnancy outcomes (10,11,13), and others have reported no association between anxiety and pregnancy outcome (4,12). One factor of more recent interest is termed "pregnancy-related anxiety" (5,6,16), which refers to maternal worries and concerns related to the pregnancy such as worries about the health of the baby or labor and delivery (5,6). Only a few studies have explored the relationship between pregnancy-related anxiety and pregnancy outcome (5,6,15,16). In general, these studies have found significant associations between pregnancy-related anxiety with preterm birth outcomes. In one such study, Dole and colleagues constructed a measure of pregnancy-related anxiety using six items from the Prenatal Social Environment Inventory (PSEI) (17) and found a strong association between scores on this measure and preterm birth (15). This is a promising area for research on preterm birth because it may be possible to intervene with women who have high levels of pregnancy-related anxiety and relieve some of their worries and concerns, thereby reducing preterm birth.

In this study, we assessed the relationship between scores on the six items from the PSEI (used to measure pregnancy-related anxiety) and pregnancy outcome in a sample of women from Baltimore, Maryland. In addition, we chose spontaneous preterm birth as the outcome of interest. None of the prior studies on pregnancy-related anxiety and pregnancy outcome had focused on spontaneous preterm birth, using all preterm births instead. However, several prior studies have suggested that separating preterm births into homogeneous etiologic categories (spontaneous preterm births and medically indicated preterm births) might enhance research on preterm birth because the categories are likely etiologically distinct (18–20). Thus, in the present study, we sought to evaluate the association between pregnancy-related anxiety and spontaneous preterm birth. The main study hypothesis was that women with higher levels of pregnancy-related anxiety would have a greater risk of spontaneous preterm birth than those women with lower levels of pregnancy-related anxiety.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 
Women were enrolled in this study at the time of their first prenatal visit to four hospital-based prenatal clinics in Baltimore, Maryland, from 1991 to 1993. Each woman presenting for her first prenatal visit was approached by a trained research assistant, who invited her to participate and obtained informed consent. The Institutional Review Board of the Johns Hopkins School of Hygiene and Public Health approved the research. Women were eligible for inclusion in the study if they were ≥18 years of age. Fewer than five percent of the women who were asked to participate declined to do so. Each woman enrolled in the study completed a structured questionnaire as she waited to be seen in the clinic. The questionnaire assessed demographic factors and exposure to stressors. Thirty percent (n = 565) of the women initiated prenatal care during the first trimester, and 48% (n = 888) initiated prenatal care during the second trimester. The median number of weeks gestation at the time of the first prenatal visit was 16.

Pregnancy-related anxiety was measured using six items from the 41-item PSEI (17). The PSEI was developed over a decade ago to measure maternal exposure to psychosocial stressors among pregnant women. It primarily assesses exposure to chronic stressful life conditions in the past year but also includes several items to assess exposure to major stressful life changes (e.g., death, divorce). The PSEI measures exposure to stressors in areas that include family relationships, housing, employment, finances, neighborhood/housing, family health, parenting, and the current pregnancy. Items were identified for inclusion in the PSEI based on interviews with pregnant women. The PSEI was tested for temporal stability, internal consistency, and construct validity among a separate sample of pregnant women and performed adequately in these areas (17). The six items on the PSEI that are used to measure pregnancy-related anxiety ask the women if they experienced worries or concerns about, for example, the health of the baby; labor and delivery; or nausea with the current pregnancy. Women received 1 point for each affirmative response to the six items, so that scores could range from 0 (no pregnancy-related anxieties) to 6 (affirmative responses to all six items).

We conducted factor analysis to ascertain if pregnancy-related anxiety was an independent construct from depressive symptoms. We measured depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale (21). The two measures produced five different factors, using principal components analysis. Four of the factors were the usual four factor CES-D loadings (positive affect, negative affect, interpersonal, and somatic) (22), and the fifth factor was pregnancy-related anxiety. This analysis suggests that the CES-D and the pregnancy-related anxiety items are measuring distinct constructs and that the six items that measure pregnancy-related anxiety share much in common conceptually. We also assessed the internal consistency reliability of the six items used to measure pregnancy-related anxiety. The coefficient {alpha} was 0.52 and the Spearman-Brown coefficient was 0.49.

Information from obstetric and delivery records was used to classify each birth to women in the study as preterm (<37 weeks gestation) or full term (≥37 weeks), using the customary cut-point for preterm birth. The obstetricians caring for the women recorded their "best obstetric estimate" of gestational age at the time of delivery based on a) ultrasound(s) obtained during pregnancy, b) date of last menstrual period, c) when the fetal heart rate was first heard with a stethoscope, and d) fundal height. All preterm births were also classified into etiologically distinct groups as medically indicated or spontaneous. Prior research has suggested that using all preterm births is too heterogeneous as a dependent variable, and that it is preferable to focus on more etiologically homogeneous categories (18–20). "Medically indicated" preterm births were those births that occurred at <37 weeks in the absence of preterm labor or rupture of the chorioamniotic membranes, usually due to severe complications that threaten the health of the mother or infant (19). Medically indicated preterm births generally occur when the provider decides that continuing the pregnancy poses a significant risk to the mother or infant. "Spontaneous" preterm births are those births which occur at <37 weeks when a pregnant woman presents with either preterm, premature rupture of the chorioamniotic membranes, or preterm labor (19). We focused the analyses on the relatively homogeneous category of spontaneous preterm births and omitted medically indicated preterm births from the analyses.

Data on behavioral and clinical covariates were obtained from the clinical records of each woman in the sample by two trained abstractors. Smoking and drug use were the behavioral covariates of interest. Although underreporting of such behaviors may be problematic, the percentages of women reporting the behaviors were similar to those reported by other investigators (23,24). The clinical covariates of interest included a) prepregnancy body mass index (BMI) (weight (kg)/height (m2)); b) history of previous pregnancy outcomes (prior preterm or low birthweight birth, stillbirth, or fetal death); and c) course and complications of the current pregnancy (e.g., first or second trimester bleeding). All of the behavioral or clinical covariates were treated as dichotomies (i.e., as present or absent).

Unadjusted bivariate associations between pregnancy anxiety score and spontaneous preterm births were evaluated using odds ratios (ORs) and {chi}2 statistics. In addition, we estimated multiple logistic regressions of spontaneous preterm birth on pregnancy anxiety score and covariates which the literature suggested were associated with spontaneous preterm birth (2,25). The logistic regressions were estimated using the entire data set, after completing the missing values by multiple imputation (26,27). (Whereas overall, data were very complete, with <5% missing data, for BMI, data were missing for about 139 women. This was generally due to missing data on height, which precluded computing BMI. Multiple imputation allowed us to use the cases for whom data were missing on BMI.) Specifically, we filled in the missing data with plausible values generated with the MICE package in the statistical software Stata. This package randomly samples plausible values from a series of conditional regressions, which we specified to include an exhaustive set of variables partially related to the missing values. We did not include spontaneous preterm birth in the imputation models. We created five completed data sets in this manner and, in each data set, fit the logistic regression of spontaneous preterm birth on the covariates. We then averaged the point and variance estimates of the logistic regression coefficients from each completed data set using Rubin’s (26) combining rules, which are implemented automatically with MICE.

The adequacy of the logistic regression was investigated using case influence diagnostics (delete-one Cook’s distances and delete-one changes in deviance) and the Hosmer-Lemeshow test on the observed data (28). These did not show any problems with the model. No significant interactions were found between the exposure variable (i.e., pregnancy-related anxiety) and the covariates or among the covariates. There were some significant associations among the covariates; however, because of the large sample size, these did not inflate substantially the standard errors of the estimated coefficients.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 NOTES
 REFERENCES
 
Over 2000 women were enrolled in the study. Subsequently, approximately 15% of the women were eliminated from the sample post enrollment for reasons which included multiple pregnancy (due to its strong association with preterm birth); pregnancy loss (ectopic pregnancy, therapeutic or spontaneous abortion, stillbirth); moved from the area; or lost medical record. In addition, 41 women were excluded from these analyses because they had preterm births which were medically indicated (23), or for which an etiologic category could not be determined (18). The final sample for analysis consisted of 1820 women with either full-term (92.6%) or spontaneous preterm (7.4%) outcomes.

The demographic, behavioral, and clinical characteristics of the sample are shown in Table 1. Eighty-one percent of the women were aged ≥20 years, and 19% were aged 18 to 19 years. About one-third of the women had less than a high school education. Thirty percent of the women were employed outside of the home and about one-fourth of the women were either married or living with a man who was like a husband to them. About three-fourths of the women were African-American and the rest were Caucasian. Fewer than 10% of the women reported drug use (8.9%) during the pregnancy; about a third reported smoking cigarettes during the pregnancy. Eighty percent of the women initiated prenatal care during the first or second trimester. Nineteen percent had low BMI (<21) and 27% had a prior poor pregnancy outcome.


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  		TABLE 1. Selected Demographic, Behavioral, Psychosocial and Clinical Characteristics of the Sample (n = 1820)

 

Scores on the pregnancy anxiety items ranged from 0 to 6 (median = 2.0). Approximately 28% of the women scored ≥4 on the six items, although only 1.8% had a score of 6. A score of ≥4 was used to indicate increased pregnancy-related anxiety (corresponding to approximately the upper 25% of scores). In unadjusted bivariate analysis, women scoring ≥4 had approximately 1.5 times the risk of spontaneous preterm birth as women scoring <4 on the pregnancy-related anxiety items (p = .01).

The logistic regression model compared anxiety scores of 4, 5, or 6 (separately) with scores of <4. This model fits essentially as well as the model with separate indicators for each anxiety score (likelihood ratio test, p = .42) while facilitating interpretation. The ORs for 4, 5, and 6 are nearly identical in the two models (i.e., a model comparing scores of 4, 5, or 6 with scores of <4, and a model comparing each level of scores from 1 to 6 with a score of 0). Other variables included in the logistic regression model were bleeding during the first or second trimester, drug use, employment outside of the home, prior poor pregnancy outcome, smoking, BMI, race, age, and education. We used dichotomous versions of age (<20 years and at least 20 years) and education (<12 years and at least 12 years). Actual values of age and education were not measured in the data and hence were unavailable for analysis.

As shown in Table 2, the adjusted OR for a score of 4 was 1.15 (95% Confidence Interval (CI): 0.70, 1.90); for a score of 5, the OR was 1.70 (95% CI: 1.01, 2.87); and for a score of 6 on the anxiety measure, the OR was 2.73 (95% CI: 1.03, 7.27). Other variables associated with spontaneous preterm birth in the logistic regression model were low BMI, previous poor pregnancy outcome, and Black race. Finally, the model was replicated not using multiple imputation for missing data, and the conclusions were essentially unchanged.


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  		TABLE 2. Logistic Regression Model for the Associations Between Spontaneous Preterm Birth with Pregnancy-Related Anxiety and Behavioral, Clinical, and Demographic Variables

 


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
NOTES
 REFERENCES
 
Our results suggest that high levels of maternal prenatal worries and concerns about pregnancy (pregnancy-related anxiety) are significantly associated with an increased risk of spontaneous preterm birth, even after adjustment for traditional risk factors for preterm outcomes such as prior poor pregnancy outcome, low BMI, bleeding, smoking, and race. Women with the highest levels of pregnancy-related anxiety (scores of 5 or 6) had an increased risk of spontaneous preterm birth compared with women with lower levels of pregnancy-related anxiety. In addition, our data suggest that a score of 6 (the highest possible score) is associated with an almost three-fold increase in risk of spontaneous preterm birth compared with women with scores of <4.

We were concerned that worry about the outcome of the current pregnancy might be influenced by the presence of risks for preterm birth, such as prior poor pregnancy outcomes, behavioral risks for the current pregnancy such as drug use, or complications of the current pregnancy, such as first or second trimester bleeding. These risks for preterm birth may have occurred before the women completed the study questionnaire, and may have influenced their responses. However, this seems to not be the case. First, the ORs for pregnancy-related anxiety were adjusted for potential confounding by each of these factors. Also, we replicated the logistic regression models excluding (separately) women with a prior poor pregnancy outcome, bleeding or spotting with the current pregnancy, or drug use with the current pregnancy. The adjusted ORs for these models were not weakened compared with those from the models that included these women. Thus, we are reassured that our results are not due to the inclusion of women with these risks in the analyses.

An important limitation of this research is the lower-than-desirable reliability of the six items used to measure pregnancy-related anxiety. This is likely due to the small number of items that comprise the measure. Problems with reliability as, for example, demonstrated by the lower coefficient {alpha} might be interpreted to mean that the six items may have permitted misclassification of some women on the exposure variable (i.e., pregnancy-related anxiety). This would suggest that the true association between pregnancy-related anxiety and spontaneous preterm birth might be stronger than we report, because random misclassification error on the exposure variable would tend to bias the OR toward 1.0. Thus, the association we observed may be conservative.

A final potential limitation of our study is that residual confounding may exist. We controlled for many potential confounding variables (guided by the literature on preterm birth), but, as with all observational studies, the results may be affected by unobserved confounders.

Our findings are consistent with the limited literature about pregnancy-related anxiety and pregnancy outcome (5,6,16). The few prior studies on this topic have reported significant associations between pregnancy-related anxiety and pregnancy outcome, although ours is the first study of which we are aware to focus on spontaneous preterm birth as the outcome of interest. It is notable that, whereas prior research has identified associations between pregnancy-related anxiety and pregnancy outcomes, inconsistent findings have been reported for the associations between other measures of anxiety and pregnancy outcome. Part of this inconsistency may arise from the variety of measures used for both anxiety and for the various pregnancy outcomes studied (4,10,12,13). For example, many older studies about anxiety and pregnancy outcome group a variety of complications and poor outcomes into "abnormal outcome," which is different from preterm birth or more specific indicators. Thus, there remains a need for additional research about anxiety and preterm birth. Anxiety is the most common mental disorder among women (29). Future research about anxiety and preterm birth should use valid and reliable measures of anxiety disorders and should focus specifically on preterm birth or spontaneous preterm birth outcomes. Future research could also seek to identify biologic pathways through which anxiety is associated with preterm birth outcomes (30). Such research may help to identify new etiologic factors for preterm birth.

If additional research confirms our findings, then this might suggest an avenue for intervention to reduce spontaneous preterm birth. Anxiety is a treatable condition (31). Women with high levels of worries and concerns about pregnancy (scores of 5 or 6) could receive supportive interventions to reduce some of their worries, to ascertain if this might reduce their risk of spontaneous preterm births. There is precedence for psychosocial interventions for women at increased risk of poor pregnancy outcome by virtue of psychosocial risk (32,33). Even brief prenatal telephone interventions by nurses have been shown to confer benefits on women with psychosocial risk (32). Psychosocial interventions have been shown to be most efficacious when delivered to pregnant women with increased psychosocial risk, and not all pregnant women (32,34). To score 5 or 6 on the pregnancy-related anxiety measure, a woman would have reported being worried or concerned about labor and delivery, nausea, bleeding or pain early in pregnancy, and the health of the baby. These concerns lend themselves to educational interventions. For example, pregnant women could receive information from their healthcare providers about the signs and symptoms of a normal pregnancy and the process of labor and delivery to reduce their worries and concerns about pregnancy, and ultimately their risk of spontaneous preterm birth outcomes. Such interventions could be delivered as part of preconception care, or early during the pregnancy, to reduce anxieties about pregnancy early in pregnancy. Reducing pregnancy-related anxiety among women may be a strategy to reduce the risk of spontaneous preterm birth in the United States. Because the rates of preterm birth have been increasing in the United States for the past several decades (1), it is imperative to develop strategies to intervene with women to reduce psychosocial risk factors and thereby reduce preterm birth outcomes. Our research may ultimately lead to such strategies.


   NOTES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
REFERENCES
 
Data collection and instrument development for this study were supported by Grant 1 R01-HD-25754 from the National Institute of Child Health and Human Development, National Institutes of Health.

Received for publication October 10, 2006; revision received April 2, 2007.

DOI:10.1097/PSY.0b013e3180cac25d


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 NOTES
 REFERENCES
 

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