Meta-Analysis Of Antenatal Depression And Adverse Birth Outcomes In US Populations, 2010–20

The US infant mortality rate of 5.67 per 1,000 live births is one of the highest rates among developed countries.^1,2 More than 21,000 infants died in 2018 alone.¹ Rates of infant mortality are higher among racial minority groups,³ with the mortality rate of Black infants almost twice as high as the rate of White infants in 2018,¹ demonstrating a clear health disparity. The leading causes of infant mortality and morbidity include preterm birth,^4,5 low birthweight,^6,7 and intrauterine growth restriction.⁸ Depression during pregnancy is another factor that affects detrimental birth outcomes and also exacerbates infant morbidity and mortality. A 2019 systematic review found that depression or elevated depressive symptoms during pregnancy are associated with higher likelihood of both hospitalization of infants and death of infants within the first year of life.⁹

Depression during pregnancy may contribute to detrimental birth outcomes through adverse conditions such as preterm birth, low birthweight, and intrauterine growth restriction.^10,11 However, research remains inconsistent regarding inverse associations between depression during pregnancy and birth outcomes. In fact, a recent study of 227 pregnant people indicated that those with depression were more likely than those without depression to have heavier babies.¹² These contradictory findings indicate that it is necessary to understand when and under which circumstances depression and elevated depressive symptoms during pregnancy might increase detrimental birth outcomes. A 2021 meta-analysis identified an association between antenatal pregnancy and adverse birth outcomes; however, the findings were not US specific, nor were racial or ethnic differences noted.¹³

Because of the fact that untreated depression increases risk for adverse birth outcomes, this study aimed to use a meta-analysis framework to examine recent trends in the US and determine whether racial and ethnic differences persist. The study was a follow-up to a systematic review and meta-analysis published in 2010,⁸ which reported on the association between depression and elevated depressive symptoms during pregnancy with the outcomes of preterm birth, low birthweight, and intrauterine growth restriction.

Study Data And Methods

Eligibility criteria, data sources, study selection, derivation of data, fidelity, and subgroup analyses were identified a priori. Measurement of depression during pregnancy, measurement of adverse birth outcomes (including preterm birth, low birthweight, and intrauterine growth restriction), and a focus on US populations directed the study design. Depression during pregnancy is often described using the term antenatal depression. To be consistent with the methodology of the 2010 study by Nancy Grote and colleagues,⁸ the research question used to guide this study was, “What is the relationship between antenatal depression and adverse birth outcomes including preterm birth, low birth weight, and intrauterine growth restriction?” For inclusivity in study design, all original research studies of depression during pregnancy and adverse birth outcomes in US populations published in peer-reviewed journals between January 2010 and December 2020 were examined for inclusion. Antenatal depression was operationalized as the measurement of depression during pregnancy (using a validated depression screening tool) or a formal clinical diagnosis (using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria). Preterm birth, low birthweight, and intrauterine growth restriction were operationalized as categorical measures based on electronic medical records. Both prospective and retrospective study designs were included. A full protocol of the study process is available from Shannon D. Simonovich on request. This study was registered with PROSPERO (CRD42020198904).

Search Strategy

Five databases—PubMed, CINAHL, APA PsycInfo, Academic Search Complete, and HealthSource Nursing Academic Edition—were searched to identify relevant original studies. Search terms used included combinations of the following keywords: (depression OR depressive OR depressed) AND (pregnancy OR pregnant OR antepartum OR prepartum OR antenatal OR prenatal) AND (((premature OR prematurity OR preterm) AND (labor OR birth OR childbirth OR obstetric)) OR gestational age OR birthweight OR birthweight OR growth restriction OR restricted growth OR growth retardation OR retarded growth). Search terms related to depression during pregnancy and birth outcomes were kept intentionally inclusive to ensure that we would capture all possible iterations represented in the literature.

Study Selection

The initial search in July 2020 identified 1,907 abstract records. All abstracts were extracted to Endnote and uploaded to RAYYAN for review. Two authors independently reviewed each of these abstracts. A total of 377 full-text articles were each independently reviewed by two authors, using a Qualtrics survey for data extract, yielding a total of nine studies with adequate data for inclusion in this systematic review and meta-analysis. Online appendix 1 contains the PRISMA flowchart for the full systematic review process.¹⁴ Studies were excluded if they did not meet inclusion criteria. They were excluded if they measured lifetime history of depression or postpartum depression rather than depression during pregnancy, and also if they did not report the necessary data to calculate odds ratios. A subsequent literature search using these study criteria was conducted in February 2021 to examine publications from July 2020 to December 2020, resulting in an additional 158 abstract reviews and 26 full-text reviews; this systematic review added zero new studies.

Methodological Quality Assessment

After completion of the search strategy, the nine full texts under consideration for inclusion in the meta-analysis were assessed for quality using the National Heart, Lung, and Blood Institute’s Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.¹⁵ Each study was assessed following these standardized criteria, with an overall sample of articles with low risk of bias.

Analysis

Meta-analysis was performed using RevMan 5.4.1 software. A random effects model was used to calculate pooled odds ratios and 95% confidence intervals of included studies. For each individual study, weights were determined based upon the standard error, with studies having smaller standard errors given more weight than studies having large standard errors. The weights adjust for the different sample sample sizes in each study. In separate statistical models, the main analyses tested whether antenatal depression increased the odds of preterm birth and low birthweight. Intrauterine growth restriction was not analyzed, as the included studies did not examine this outcome. To examine potential differences in the relationship between depression during pregnancy and adverse birth outcomes by race and ethnicity, a priori subgroup analyses were planned to examine the effect of antenatal depression on preterm birth and low birthweight among Black and Latine populations. Heterogeneity was evaluated using chi-square test and tau-square statistics. Funnel plots were used to identify publication bias.

Limitations

The strength of a meta-analysis is its ability to summarize the collective knowledge to date around a topic of interest in comparison to individual studies. Although this study of depression during pregnancy and adverse birth outcomes in the US during the period 2010–20 had several strengths in its implications for health policy and services, a few limitations remain. First, eight of the nine articles in the meta-analysis were based on elevated depressive symptoms captured using validated depression screening tools; only one article used a formal clinical diagnosis as the measure of depression. Second, the studies identified in this search did not contain updated findings related to intrauterine growth restriction. Given the tremendous risk of intrauterine growth restriction on infant outcomes, the lack of these data is worrisome. Third, this study sought to perform an updated search and meta-analysis for the US with specific context by race and ethnicity. There were a limited number of studies that presented findings stratified by race, and thus we were able to identify only three studies for the subgroup analyses of African American pregnant people and inadequate data for a subgroup analysis for Hispanic or Latine pregnant people. It is imperative that future studies disaggregate findings by race and ethnicity instead of simply adjusting for race, to better identify sound pathways to address racial disparities in birth outcomes. Finally, there may be studies that did not find any association between antenatal depression and adverse birth outcomes during our review time frame that were never published. Accordingly, it is important to note publication bias as a possible limitation of the meta-analysis.

Study Results

Nine articles were ultimately included in this systematic review and meta-analysis.^16–24Exhibit 1 describes the study characteristics of these nine studies published in the US during 2010–20, describing the association between depression during pregnancy and associated adverse birth outcomes, including preterm birth (eight studies) and low birthweight (four studies). (Full characteristics of studies included in the meta-analysis are in appendix 2.)¹⁴ Among these studies, sample sizes ranged from 90 to 14,175, with a mean of 3,412 participants. Six studies included pregnant people from multiple racial and ethnic backgrounds, with two studies focusing on African American people and one study focusing on Puerto Rican and Dominican people. Across the nine studies, measurement of antenatal depression included three screening instruments—the Edinburgh Postnatal Depression Scale (five studies), Center for Epidemiologic Studies Depression Scale (two studies), and nine-item Patient Health Questionnaire (one study)—as well as a formal clinical diagnosis of depression (one study). Depression measurement cut points used in each study are described in exhibit 1.

Antenatal Depression And Preterm Birth

Eight studies examined the association between depression during pregnancy and preterm birth, with odds ratios ranging from 0.99 to 16.39 (exhibit 2).^{16–19,21–24} Meta-analysis of the studies’ data found that depression during pregnancy was significantly associated with preterm birth (odds ratio: 1.46; 95% confidence interval: 1.20, 1.78). A subgroup analysis of studies that stratified results by race also found a significant relationship between depression during pregnancy and preterm birth in African American people (OR: 2.33; 95% CI: 1.37, 3.98) (data not shown).

Antenatal Depression And Low Birthweight

Four studies examined the association between depression during pregnancy and low birthweight, with odds ratios ranging from 1.44 to 4.44 (exhibit 3).^16,18–20 Meta-analysis of the studies’ data found that depression during pregnancy was significantly associated with low birthweight (OR: 1.90; 95% CI: 1.31, 2.74). A subgroup analysis of studies that stratified results by race also found a significant relationship between depression during pregnancy and low birthweight in African American people (OR: 2.47; 95% CI: 1.31, 4.65) (data not shown).

Discussion

This updated systematic review and meta-analysis of antenatal depression and adverse birth outcomes in US populations during the period 2010–20 found that pregnant people with depression were 1.46 times more likely to give birth preterm than people without depression. These findings are consistent with those of past studies.⁸ In addition, among the studies in this meta-analysis, people with depression during pregnancy were 1.90 times more likely to deliver a low-birthweight infant. Although people with depression during pregnancy in the US are at increased risk for preterm birth and low birthweight, the risks are greater for African American people. Subgroup analyses demonstrated that African American people with depression during pregnancy are 2.33 times more likely to give birth preterm and 2.47 times more likely to deliver a low-birthweight infant than African American people without depression.

Our updated meta-analysis aligns with previous findings that antenatal depression adversely affects birth outcomes. Given this harmful association, universal screening for depression during pregnancy remains a priority to promote early diagnosis and treatment to minimize harm to the maternal-infant dyad.⁸ The American College of Obstetricians and Gynecologists recommends that all pregnant people be screened for depression and anxiety during both pregnancy and the postpartum period, using a validated screening instrument.²⁵ However, universal depression screening remains scarce across the US. For universal perinatal depression screening to be successful, states can employ policy mandate strategies, and payers must provide adequate reimbursement.^25,26 These policy shifts are small steps to ensure the effectiveness of universal depression screening as a preventive strategy to improve delivery outcomes for mothers and babies. To determine the effectiveness of universal depression screening, well-designed studies are needed to examine the relationship between depression screening during pregnancy, with and without treatment, and subsequent birth outcomes. In addition to depression screening options in pregnancy, depression treatment options must also be implemented. Universal depression screening creates an opportunity to provide access to more equal care and to address disparities. Our study indicates that antenatal depression is associated with a greater risk for preterm birth and low birthweight for African American people. A universal depression screening approach would ensure that African American people received early assessment, referral, and treatment options at the same rate as White people. Policy changes should reflect this increased risk and specifically target strategies with a health equity approach.

Conclusion

Identifying and treating childbearing people with untreated antenatal depression must become a policy and practice priority in the US. In this study we found a persistent association between antenatal depression and adverse birth outcomes, and we further described associations between antenatal depression in Black pregnant people and preterm birth and low birthweight. Past studies have identified the “perinatal depression treatment cascade” as a major public health issue and have presented the reality that fewer than half of perinatal people are asked about mental health.²⁷ Early identification and treatment of depression during pregnancy are essential recommendations to improve practice guidelines and patient safety bundles.

ACKNOWLEDGMENTS

The authors acknowledge Nadia Quad and Heysel Serra of the Maternal Child Health Initiative Research Collaborative for their contributions to this project over the summer of 2020.

NOTES

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