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ORIGINAL RESEARCH |
From the Departments of Psychiatry, Epidemiology, and Obstetrics, University of Washington, Seattle, Washington; and Health Information Solutions, Menlo Park, California.
Address reprint requests to: Rosemary H. Kelly, MD, Department of Psychiatry and Behavioral Sciences, University of Washington Medical Center, Box 356560, 1959 NE Pacific Street, Seattle, WA 98195-6560; E-mail: rhkelly{at}u.washington.edu.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: This population-based retrospective cohort analysis used linked hospital discharge and birth certificate data for 521,490 deliveries. Logistic regression analyses were conducted to assess the associations between maternal psychiatric and substance use hospital discharge diagnoses and LBW, VLBW, and preterm delivery while controlling for maternal demographic and medical characteristics.
RESULTS: Women with psychiatric diagnoses had a significantly higher risk of LBW (adjusted odds ratio [OR] 2.0; 95% confidence interval [CI] 1.7, 2.3), VLBW (OR 2.9; 95% CI 2.1, 3.9), and preterm delivery (OR 1.6; 95% CI 1.4, 1.9) compared with women without those diagnoses. Substance use diagnoses were also associated with higher risk of LBW (OR 3.7; 95% CI 3.4, 4.0), VLBW (OR 2.8; 95% CI 2.3, 3.3), and preterm delivery (OR 2.4; 95% CI 2.3, 2.6).
CONCLUSION: Maternal psychiatric and substance use diagnoses were independently associated with low birth weight and preterm delivery in the population of women delivering in California in 1995. Identifying pregnant women with current psychiatric disorders and increased monitoring for preterm and low birth weight delivery among this population may be indicated.
Approximately 11.6% of the 3.9 million infants delivered in the United States each year are preterm (< 37 weeks’ gestation), and 7.6% have low birth weight (< 2500 g).1 Because these adverse pregnancy outcomes constitute the leading causes of infant mortality and long-term childhood morbidity, public health efforts targeting identification of risk factors and intervention have been initiated.2–7
Prior studies have identified numerous sociodemographic and medical risk factors for these poor pregnancy outcomes, including nonwhite ethnicity, single marital status, parity, inadequate prenatal care, and preeclamp-sia.1,8–12 However, obstetric risk assessments predict only about half to two thirds of all adverse pregnancy outcomes,13 and the etiology of the majority of preterm births remains unexplained.12
Psychiatric disorders are prevalent among pregnant women. For instance, clinical and community-based studies reported that 9%–21% of pregnant women meet criteria for a depressive disorder,14–18 and 10%–20% suffer from substance abuse or dependence during pregnancy.19–21 Although recent research suggests that maternal depressive and anxiety symptoms and psychosocial stress during pregnancy are associated with low birth weight and preterm delivery,10, 22–29 few large-scale population-based investigations have examined maternal psychiatric disorders or diagnoses as predictors of these poor pregnancy outcomes. In addition, although population and community-based investigations have found that substance use disorders are associated with poor pregnancy outcomes,30–32 those studies did not comprehensively assess nonsubstance-related psychiatric disorders or dual diagnoses as independent risk factors.
The purpose of this study was to examine the associations between documented psychiatric, substance use, and dual diagnoses and low birth weight, very low birth weight, and preterm deliveries among women who delivered in California hospitals in 1995, while controlling for the potential confounding effects of established maternal demographic and medical risk factors. This study is unique in that it uses data from a large population of ethnically diverse pregnant women, examines psychiatric diagnoses rather than psychiatric symptoms or stress as a predictor of low birth weight and preterm delivery, and assesses the impact of comorbid psychiatric and substance use diagnoses on these obstetric outcomes.
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MATERIALS AND METHODS |
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Our study cohort included all women (N = 521,490) who gave birth to live-born singleton infants in California civilian hospitals reporting to the Office of Statewide Health Planning and Development in 1995 and their infants. Excluded were women with multiple gestation.
Psychiatric and substance use diagnoses were determined by ICD-9-CM diagnostic codes recorded on the maternal hospital discharge summary (a more complete discussion of diagnostic categories has been described previously).34 Diagnoses recorded either during a prenatal or delivery hospitalization were included. We categorized women into one of the following four predictor categories: (1) psychiatric diagnosis without substance use diagnosis, (2) substance use diagnosis without psychiatric diagnosis, (3) dual diagnosis (both psychiatric and substance use diagnoses), and (4) no psychiatric or substance use diagnosis. Psychiatric diagnoses included mood disorders, schizophrenia and other psychotic disorders, anxiety disorders, and somatoform, factitious, dissociative, sexual or gender identity, eating, sleep, impulse control, and adjustment disorders. In addition, women with the generic obstetric diagnosis of mental disorder of pregnancy (ICD-9 648.4) were included in the psychiatric diagnosis category. Substance use disorders included all ICD-9-CM substance-related disorders and the obstetrical diagnostic category substance use disorder of pregnancy (ICD-9 648.3). The following disorders were excluded: disorders of childhood, delirium, dementia, other cognitive disorders, diagnoses due to a general medical condition, and personality disorders.
Maternal age, ethnicity, insurance, education, marital status, parity, and adequacy of prenatal care were determined from the birth record data file. The insurance category Medi-Cal included Medi-Cal (California’s Medicaid program), Medicare, and other government programs. Outpatient prenatal care utilization was categorized from birth certificate data using the Kotelchuck Adequacy of Prenatal Care Utilization Index.35 "Inadequate" prenatal care is defined as initiation of prenatal care after month 4 of pregnancy or less than 50% of recommended visits were completed. "Intermediate," "Adequate," and "Adequate Plus" are defined as care initiated by the fourth month of pregnancy, and 50%–79%, 80%–109%, or 110% or more, respectively, of recommended visits were completed. Maternal diabetes (gestational and established) and hypertension (preexisting, eclampsia, and preeclampsia) were determined by ICD-9-CM diagnostic codes in the hospital discharge file.
Birth weight was obtained from infant birth records. For 54 women, birth weight data were missing for their infants. Consistent with prior reports,1,9 we categorized birth weight less than 1500 g as very low birth weight (VLBW), less than 2500 g as low birth weight (LBW), and 2500 grams or more as normal birth weight. Preterm delivery was defined as infant gestational age less than 37 weeks1 as recorded on the birth certificate. For 18,012 (3.4%) of births, gestational age data were missing or recorded as over 900 days.
Demographic and outcome differences among the cohorts were assessed using 
2 tests, with P < .05 denoting statistically significant differences. Multivariable logistic regression was used to examine the independent association between diagnostic category and each outcome while adjusting for confounding factors. Three logistic regression models were constructed, one for each study outcome (LBW, VLBW, and preterm delivery). Each model had four exposure levels (psychiatric diagnosis, substance use diagnosis, psychiatric and substance use diagnoses, and the reference category of no psychiatric or substance use diagnosis). A covariate was considered a confounder if it changed the unadjusted odds ratio (OR) between diagnostic category and outcome by 10%.36 The following ten covariates were examined as potential confounders: maternal age, maternal ethnicity, insurance, marital status, education, parity, adequacy of prenatal care, gestational diabetes, preexisting diabetes, and hypertension. The following variables met the criteria for confounders: ethnicity, marital status, and adequacy of prenatal care. As an alternative, each model was also run including all ten covariates as potential confounders. Adjusted ORs and 95% confidence intervals (CI) for each study outcome were calculated. The statistical software package SPSS 10.0 (SPSS Inc., Chicago, IL) was used for all data analyses.37
We tested for effect modification between maternal demographic factors (age, ethnicity, insurance source, education, and marital status) and diagnostic category, and no covariates met criteria for effect modification.
We were unable to verify that psychiatric and substance use diagnoses documented at delivery were preexisting or preceded pregnancy outcome. Thus, in one subanalysis we examined the adjusted risk of VLBW, LBW, and preterm delivery among women with diagnoses documented during a prenatal hospitalization (n = 2020) relative to women without diagnoses, excluding women who were diagnosed only at delivery (n = 12,443).
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RESULTS |
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. Overall, 14,463 (2.8%) women had a documented psychiatric or substance use diagnosis; 1856 (0.4%) women had a psychiatric diagnosis, 5519 (1.0%) had a substance use diagnosis, and 7088 (1.4%) had a dual diagnosis. Women with psychiatric or substance use diagnoses or both were significantly more likely than the reference group to be black or white, insured by Medi-Cal, single, and to have had more than three prior deliveries, and inadequate prenatal care (Table 1). Of the 14,463 women with diagnoses, 13,279 (92%) were documented at delivery hospitalization, 2020 (14%) were documented during a prenatal hospitalization, and 836 (6%) had both a prenatal and a delivery diagnosis documented.
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presents the frequency of VLBW, LBW, and preterm delivery by diagnostic category. A higher percentage of women with psychiatric, substance use, or both diagnoses delivered VLBW and LBW infants compared with the reference group (Table 2). Psychiatric diagnoses were associated with a 154-g lower mean infant birth weight, substance use diagnoses with a 355-g decrease, and dual diagnoses with a 272-g decrease compared with mean birth weight in the reference group. In addition, a higher percentage of women with psychiatric and/or substance use diagnoses delivered a preterm infant.
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). The nearly three-fold higher risk of delivering a VLBW infant among women with psychiatric diagnoses (OR 2.9; 95% CI 2.1, 3.9) was essentially equal to the risk of VLBW among women with substance use diagnoses (OR 2.8; 95% CI 2.3, 3.3). Other predictors with risk elevations comparable to psychiatric and substance use diagnoses included black race, inadequate prenatal care, and adequate plus prenatal care (which most likely indicates that women with high-risk pregnancies had more prenatal care utilization) (Table 3). When we used less stringent criteria for confounding and adjusted for all ten covariates in the logistic regression models, the adjusted OR and 95% CI remained essentially unchanged for all diagnostic categories. In addition, to control for a history of preterm delivery as a possible confounder of our findings, we reran the regression models on nulliparous women only (n = 206,365 or 40% of the population) and found similar results.
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). Likewise, limiting the analysis to prenatal substance use diagnoses (n = 697) relative to the reference group, this group had a significantly higher risk of LBW (adjusted OR 4.6; 95% CI 3.8, 5.6), VLBW (adjusted OR 4.0; 95% CI 2.7, 6.0), and preterm delivery (adjusted OR 2.2; 95% CI 1.8, 2.8). Compared with women with no diagnoses, women with prenatal dual diagnoses (n = 611) had a substantially higher risk of LBW (adjusted OR 5.5; 95% CI 4.5, 6.9), VLBW (adjusted OR 5.9; 95% CI 4.1, 8.4), and preterm delivery (adjusted OR 3.4; 95% CI 2.8, 4.2). |
DISCUSSION |
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Furthermore, the risk of VLBW delivery was equal in magnitude among women with psychiatric and substance use diagnoses. Although maternal substance abuse is a well-established risk factor for low birth weight,30–32 our study suggests that psychiatric disorders may be equally as important when considering the risk of VLBW delivery.
Our risk estimates are corroborated by those of smaller prospective studies. For example, among lower-income women with less education, a high level of depressive symptoms was associated with a 100–150-g lower infant birth weight.28 Also, among a cohort of pregnant inner city women, depressive symptoms were associated with a four-fold higher risk of LBW, and a 3.4-fold increased risk of preterm delivery.25 Given that the latter study involved a high-risk homogenous sample, it is not surprising that the adjusted risks are somewhat higher than those we found. Kaye et al31 reported that infants of drug abusing women weighed an average of 423 g less than controls, an effect similar in magnitude to our results.
Our findings underscore the importance of improved detection of psychiatric and substance use disorders in the obstetric sector. Once identified, increased monitoring for preterm and LBW delivery among women with psychiatric and substance use disorders could enhance timely interventions and improve birth outcomes. Furthermore, clinical research into the development and impact of interventions targeting women with antenatal psychiatric disorders is necessary.
There are several considerations in interpreting the results of this study. For psychiatric and substance use diagnoses documented only at the time of hospital delivery, we were unable to confirm that the disorders preceded outcome ascertainment. It is possible that obstetric providers were more likely to diagnose psychiatric conditions at delivery among women with LBW or preterm delivery, or that psychiatric disorders developed in response to these outcomes. However, when we limited our analyses to women with documented prenatal diagnoses (ie, diagnosis recorded before outcome ascertainment), significant positive associations between psychiatric, substance use, and dual diagnoses and LBW, VLBW, and preterm delivery remained.
We were unable to validate diagnoses or obstetric outcomes by structured clinical interviews, other validated instruments, or chart review. An additional concern is that only 2.8% of women delivering had a documented psychiatric or substance use diagnosis, whereas prior community-based studies documented rates of 9%–21% for depression alone. Psychiatric and substance use diagnoses have been shown to be significantly under-recorded in the California hospital discharge data file,38 as well as significantly underdetected and undertreated in obstetric practices.14,18,20 However, in the current study, the inclusion of psychiatric and substance use disorders in the reference group would have underestimated the strength of the true association between these disorders and LBW and preterm delivery; thus, the risk estimates reported may be conservative.
A potential limitation of this investigation is that unmeasured confounders could have biased our risk estimates. Although we were unable to control for maternal smoking, as previously discussed, our risk estimates are corroborated by smaller prospective studies that controlled for maternal smoking.25,26,28 Furthermore, among women with psychiatric disorders, smoking might be a mediator of poor pregnancy outcome,39–41 occurring along the causal pathway, rather than a confounder of the relationship between psychiatric illness and poor outcome. Although we controlled for the most prevalent maternal medical risk factors in pregnancy (diabetes and hypertension),1 we were unable to control for other factors, such as prior obstetric complications, infection, poor nutrition, or medication exposure. However, our analyses did adjust for high numbers of prenatal care visits, which most likely indicated medically high-risk pregnancies.
Several potential mechanisms might explain a positive association between maternal psychiatric disturbance and LBW and preterm delivery.22,23,42 Indirect mechanisms might mediate the effect of psychiatric disorders on these adverse outcomes. For example, women with psychiatric and substance use disorders might be more likely to engage in poor health behaviors, such as inadequate diet, poor weight gain, or smoking,10,39–41,43 or might be less likely to receive adequate prenatal care.34 Among high-risk populations such as homeless women, a psychiatric history is associated with more severe and longstanding homelessness, which in turn is a strong predictor of preterm and LBW delivery.44 In addition, research suggests that maternal stress and depression directly affect neuroendocrine parameters,42,45–47 uterine blood flow and contractility,5,48,49 and other physiologic responses that might play a role in preterm labor,48 newborn neurobehavioral function,50 and other poor pregnancy outcomes.
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Footnotes |
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Received September 27, 2001. Received in revised form February 11, 2002. Accepted March 7, 2002.
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