Background
Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation.
Objective
This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes.
Study Design
This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits: between 6 and 14 weeks’ gestation and between 22 and 30 weeks’ gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. The frequencies of adverse pregnancy outcomes (hypertensive disorders of pregnancy, abruption, cesarean delivery, preterm birth [ie, <37 weeks’ gestation], small for gestational age neonates, neonatal intensive care unit admission, and maternal readmission) were compared with depression trajectories across gestation in bivariable and multivariable analyses. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks’ gestation.
Results
Of the 8784 women who completed the 2 antenatal Edinburgh Postpartum Depression Scale screens, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptom trajectories across gestation. Compared with women with improved or stable depressive symptoms, those with worsened symptoms were more likely to experience preterm birth (8.3% vs 7.4% vs 9.9%, respectively; P =.018). After controlling for potential confounders, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10–2.57).
Conclusion
Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.
Introduction
Perinatal depression is one of the most common complications of pregnancy, affecting at least 1 of 7 American women, with a disproportionate impact on women with adverse social determinants of health. Perinatal depression can have debilitating effects on the mother if left untreated. Depression not only does incur serious maternal risks but also has been associated with adverse perinatal outcomes, including preeclampsia, placental abruption, cesarean delivery, preterm birth, fetal growth restriction, , , , low Apgar scores, neonatal intensive care (NICU) admission, and maternal postpartum readmission. These complications are responsible for most neonatal morbidities and mortalities across the United States and are an enormous economic burden to the healthcare system. Moreover, untreated perinatal depression is independently associated with long-term adverse neurodevelopmental consequences in offspring with effects particularly pronounced in socioeconomically disadvantaged populations.
Why was this study conducted?
Data examining the association between antenatal depressive symptoms and adverse pregnancy outcomes are often cross-sectional and yielded conflicting results. This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with adverse pregnancy outcomes independent of depression status.
Key findings
Women whose depressive symptoms worsened during pregnancy had an increased odds of preterm birth (ie, <37 weeks’ gestation).
What does this add to what is known?
These findings indicated that depressive symptoms can change as pregnancy progresses and that worsening symptoms may be associated with more frequent adverse pregnancy outcomes. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depression as a strategy to prevent preterm birth.
Data regarding the relationships between antenatal depression and adverse pregnancy outcomes have yielded conflicting results. The inconsistent findings were likely because of the pervasive use of a cross-sectional design in these studies. Growth curve mixture modeling data demonstrated that antenatal depressive symptoms are often not static across gestation. Thus, results of analyses assessing the exposure of depression early in gestation may differ from those assessing this same exposure occurring in the third trimester of pregnancy. Furthermore, depressive sympto2m trajectories, rather than an overt diagnostic categorization of depression, may better reflect the evolution of an underlying physiological dysregulation. As this evolving pathophysiology may contribute to the risk of adverse pregnancy outcomes, the analyses of depressive symptom trajectories may be a more biologically appropriate framework for the analyses of adverse pregnancy outcomes.
This study aimed to identify whether differing antenatal depressive symptom trajectories are associated with adverse pregnancy outcomes independent of initial depression status. Based on extant associations of perinatal depression in the literature, we hypothesized that a worsened antenatal depressive symptom trajectory would be associated with an increased risk of adverse pregnancy outcomes, including hypertensive disorders of pregnancy, placental abruption, cesarean delivery, preterm birth, small-for-gestational-age (SGA) births, low Apgar score, NICU admission, and maternal postpartum readmission.
Materials and Methods
The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (nuMoM2b) was a prospective cohort study designed to identify maternal characteristics predictive of adverse pregnancy outcomes. Women were enrolled from geographically diverse hospitals affiliated with 8 clinical centers. Women were eligible for inclusion if they were nulliparous and had a singleton gestation between 6 0/7 and 13 6/7 weeks’ gestation. Women were excluded if they were <13 years of age, had ≥3 previous spontaneous abortions, had a suspected fatal fetal malformation or known aneuploidy, conceived using a donor oocyte, had a multifetal reduction, or planned to terminate the pregnancy.
The women underwent a series of surveys and interviews at various time points in pregnancy. Pertinent to this analysis, sociodemographic characteristics and an assessment of medical comorbidities were assessed at visit 1 (between 6 0/7 and 13 6/7 weeks’ gestation). Antenatal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS) administered at study visit 1 and again at study visit 3 (between 22 0/7 and 29 6/7 weeks’ gestation). Detailed interviews to assess medication use were performed at study visit 1, study visit 2 (between 16 0/7 and 21 6/7 weeks’ gestation; note that the EPDS was not obtained at this study visit), study visit 3, and after delivery. Pregnancy outcomes were collected after delivery via medical record abstraction.
For this analysis, women were classified into 3 groups by their depressive symptom trajectory: “improved,” “stable,” or “worsened.” These groups were defined by a change in the EPDS score between visit 1 and visit 3 by at least 1 standard deviation (4 points, as defined by a previous large epidemiologic cohort study ). Adverse pregnancy outcomes examined included gestational diabetes mellitus, preeclampsia, placental abruption, cesarean delivery, preterm birth (ie, <37 weeks’ gestation), etiology of preterm birth (ie, spontaneous or medically indicated), SGA birthweight (<10th percentile at delivery defined using Alexander norms ), 5-minute Apgar score of <7, NICU admission, and postpartum maternal hospital readmission. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks’ gestation.
The frequency of each adverse pregnancy outcome was compared across trajectory categories using Mann-Whitney U and chi-square analyses for continuous and categorical variables, respectively. Multivariable logistic regression analyses were performed to assess whether various categories of depressive symptom trajectory were independently associated with each adverse pregnancy outcome. For multivariable analyses, women with worsened symptom trajectories were compared with women with either improved or stable symptom trajectories. Variables that significantly ( P <.05) differed by trajectory in bivariable analyses were included in multivariable regression analyses. Multivariable analyses used a generalized linear model using a binomial distributional assumption and a logit link to generate adjusted relative risks (aRRs). These models controlled for a positive baseline screen status for depression (ie, an EPDS score of ≥13) to allow the assessment of whether depressive symptom trajectory was associated with adverse pregnancy outcomes independent of the overt categorization of baseline depression. Psychiatric medication use was considered a priori to be an important potential confounder. Reported medications were categorized on the basis of whether a psychiatric indication for their use exists. Sensitivity analyses were performed to assess whether the reported indication for use was a psychiatric diagnosis and to include only psychiatric medications taken throughout the pregnancy (ie, initiated at visit 1 and continued through delivery). A Breslow-Day test for homogeneity was used to identify whether there were differences in the magnitude of the association between depressive symptom trajectory and preterm birth after stratification by depression screen status at baseline.
All tests were 2 tailed, and a P value of <.05 was used to define statistical significance. Analyses were conducted using Stata (version 15.0; StataCorp LLC, College Station, TX). Each site’s local institutional review board approved the parent study, and all participants gave written informed consent for the use of their data.
Results
Of the 10,038 women in the nuMoM2b cohort, 9685 completed the EPDS screen at visit 1, and 8784 (88% of the cohort) completed the EPDS screen at 2 visits, representing the analyzable sample. Of women who completed EPDS screens at 2 time points, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptoms. Of the 980 women with worsened depressive symptoms, only 277 (28%) had an EPDS score of ≥13.
The sociodemographic and medical characteristics of women, stratified by depressive symptom trajectory, are shown in Table 1 . There were differences in maternal age, race and ethnicity, education obtained, insurance, relationship status, household income, endorsement of the pregnancy as planned, body mass index at visit 1, and substance use histories between depressive symptom trajectory groups. Notably, there was no difference in the frequencies of psychiatric medication use, psychiatric medication use for a reported psychiatric indication, or use of a psychiatric medication throughout pregnancy among the depressive symptom trajectory groups ( Table 2 ). Women who had improved symptom trajectories had a higher median EPDS score and were more likely to have a positive EPDS screen at visit 1 than women who had stable or worsened symptom trajectories.
| Characteristic | Depressive symptoms improved (n=1141) | Depressive symptoms remained stable (n=6663) | Depressive symptoms worsened (n=980) | P value |
|---|---|---|---|---|
| Sociodemographic characteristics | ||||
| Maternal age (y) | 25 (21–30) | 28 (23–31) | 26 (21–31) | .012 |
| Race and ethnicity | .075 | |||
| Non-Hispanic White | 594 (52.1) | 4347 (65.2) | 534 (54.5) | |
| Non-Hispanic Black | 203 (17.8) | 742 (11.1) | 174 (17.8) | |
| Hispanic | 226 (19.8) | 985 (14.8) | 175 (17.9) | |
| Asian | 50 (4.4) | 268 (4.0) | 41 (4.2) | |
| Other | 68 (6.0) | 321 (4.8) | 56 (5.7) | |
| Education | <.001 | |||
| Degree work beyond college | 179 (15.1) | 1689 (25.4) | 196 (20.0) | |
| Completed college | 245 (21.5) | 2028 (30.4) | 232 (23.7) | |
| Associates or technical degree | 135 (11.8) | 669 (10.0) | 97 (9.9) | |
| Some college | 262 (23.0) | 1193 (17.9) | 196 (20.0) | |
| High school or GED | 176 (15.4) | 683 (10.3) | 135 (13.8) | |
| Less than high school grad | 144 (12.6) | 400 (6.0) | 124 (12.7) | |
| Public insurance | 430 (38.1) | 1581 (23.9) | 342 (35.2) | .024 |
| Current partner or significant other | 113 (9.9) | 285 (4.3) | 66 (6.7) | <.001 |
| Household income | .002 | |||
| <100% FPL | 215 (24.3) | 746 (13.3) | 148 (19.2) | |
| 100%–200% FPL | 154 (17.4) | 732 (13.1) | 135 (17.5) | |
| >200% FPL | 515 (58.3) | 4115 (73.6) | 488 (63.3) | |
| Clinical characteristics | ||||
| Gravidity category | .934 | |||
| 1 | 846 (74.2) | 5029 (75.5) | 727 (74.2) | |
| 2 | 214 (18.8) | 1246 (18.7) | 181 (18.5) | |
| ≥3 | 81 (7.1) | 388 (5.8) | 72 (7.4) | |
| Pregnancy planned | 596 (52.3) | 2428 (36.5) | 473 (48.3) | .008 |
| BMI at visit 1 (kg/m 2 ) | 24.9 (21.8–29.3) | 24.5 (21.9–28.8) | 25.2 (22.3–30.1) | .021 |
| Obesity | 252 (22.4) | 1383 (21.1) | 245 (25.3) | .150 |
| Tobacco use (3 mo before pregnancy) | 296 (25.9) | 1057 (15.9) | 202 (20.6) | <.001 |
| Alcohol use (3 mo before pregnancy) | 708 (72.2) | 4382 (76.9) | 624 (72.9) | .585 |
| Drug use | ||||
| Any previous use of illegal drugs | 450 (39.4) | 2236 (33.6) | 357 (36.4) | .089 |
| Problem use (n=3400) | 52 (11.7) | 148 (6.7) | 29 (8.2) | .031 |
| Medical comorbidities | ||||
| Chronic hypertension | 32 (2.9) | 163 (2.5) | 22 (2.3) | .392 |
| Diabetes mellitus | 22 (2.0) | 88 (1.4) | 17 (1.8) | .621 |
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