Duke Health Referring Physicians


Inflammation Not to Blame for Adverse Pregnancy Outcomes in Women With Depression

Although women with depression have elevated levels of inflammatory markers, inflammation does not appear to mediate the link between depression and adverse pregnancy outcomes, according to new research.

Emily S. Miller, MD, of the Division of Maternal Fetal Medicine at Northwestern University Feinberg School of Medicine in Chicago, IL, presented results from the prospective, observational study at the 37th Annual Pregnancy Meeting of the Society for Maternal Fetal Medicine held January 23 to 28, 2017, in Las Vegas, NV. Douglas Williamson, PhD, of the Department of Psychiatry and Behavioral Sciences at Duke University, was a coinvestigator of the study.

Among pregnant women, depression is a known risk factor for adverse pregnancy outcomes. However, the underlying mechanisms that drive this relationship are not well understood. Nonpregnant adults with depression tend to have high levels of serum inflammatory markers, indicating increased systemic inflammation.

A total of 731 pregnant women were enrolled in the study from 4 prenatal clinics. All women were screened for depression using the Center for Epidemiologic Studies Depression (CESD) scale. The women also underwent laboratory tests to measure their serum inflammatory cytokine levels between 12 and 21 weeks of gestation.

Only women with CESD scores strongly indicating the absence (< 16) or presence (≥ 23) of depressive symptoms were included. Those with CESD scores between 16 and 22 were excluded from the analysis.

The primary end point was the association between depressive symptoms and inflammatory cytokine levels. As a secondary end point, the researchers also evaluated the potential link between depressive symptoms and adverse pregnancy outcomes.

Among the 731 women screened for depression, 486 (66.5%) had scores below the threshold for depression and 128 (17.5%) had scores indicating depression (Table 1). Several baseline characteristics, including race/ethnicity, socioeconomic status, and psychiatric medication use, differed between the groups.

Table 1. Baseline Characteristics By Depression Screening Results

Characteristic Negative Result
(n = 486)
Positive Result
 (n = 128)
P Value
Maternal age, y 29.5 27.3 .001
Gestational age at CESD scoring, wk 16.6 16.0 .032
Race/ethnicity (n = 613), % < .001
Non-Hispanic white 63.2 38.3  
Non-Hispanic black 13.8 30.0  
Hispanic  16.7 29.1  
Other 6.4 2.4
Household income > $100,000 (n = 555), %  27.2 8.2 < .001
Public insurance (n = 594), %  28.8 56.4 < .001
College-level education (n = 613), % 46.3 13.4 < .001
Employed, % 70.8 46.9 < .001
Married (n = 613), % 61.9 28.4 < .001
BMI at first prenatal visit, kg/m²  25.3 27.2 .068
Any psychiatric medication use (n = 267), % 8.1 17.4 .030
Daily psychiatric medication use, % 6.6 14.5 .043

BMI = body mass index, CESD = Center for Epidemiologic Studies Depression.

In the comparison of cytokines, interleukin (IL) 6 was the only inflammatory marker that significantly differed between the groups (Table 2). The women who were depressed had a significantly higher mean serum IL-6 level than those with a negative result on depression screening (0.50 vs 0.48 pg/mL; P = .042).

Table 2. Inflammatory Markers Stratified By Depression Screening Results

Inflammatory Marker Negative Result
(n = 486)
Positive Result
(n = 128)
P Value
IFN-γ 3.0 3.13 .890
IL-10 0.30 0.30 .772
IL-13 2.35 2.32 .369
IL-6 0.48 0.50 .042
IL-8 1.81 1.81 .710
TNF-α 0.96 0.96 .438

IFN = interferon, IL = interleukin, TNF = tumor necrosis factor.

After controlling for the baseline differences between the groups, the relationship between depression and elevated IL-6 levels remained statistically significant (adjusted odds ratio 1.11; 95% confidence interval, 1.01-1.23).

Depression also predicted adverse pregnancy outcomes (Table 3). Compared with women who were not depressed, women with depressive symptoms were significantly more likely to give birth to small for gestational age infants (8.6% vs 15.3%; P = .003) and significantly more likely to experience intrauterine fetal demise (0.2% vs 3.6%; P = .001).

Table 3. Adverse Pregnancy Outcomes Stratified By Results on Depression Screening

Outcome Negative Result (n = 486), % Positive Result (n = 128), % P Value
Small for gestational age 8.6 15.3 .033
Intrauterine fetal demise 0.2 3.6 .001
Hypertensive disorders 12.5 18.8 .087
Preeclampsia 4.8 7.1 .332
Gestational hypertension 10.6 17.0 .123

Other adverse pregnancy outcomes, including hypertensive symptoms, gestational diabetes, and placental abruption, were similar in both groups.

However, despite IL-6 levels and adverse pregnancy outcomes both being linked to depression, they were not associated with each other. No statistically significant relationship was observed between IL-6 level and birth rate of small for gestational age infants (P = .150) or intrauterine fetal demise (P = .938).

Therefore, the researchers concluded that maternal inflammation does not appear to mediate the relationship between depression and adverse pregnancy outcomes. Future research may focus on other mediators that can be therapeutically targeted to improve pregnancy outcomes in women with depression.

Source: Miller ES, Grobman WA, Culhane J, et al. Does maternal inflammation mediate the relationship between antenatal depression and adverse pregnancy outcomes? Presented at: Society for Maternal-Fetal Medicine 37th Annual Pregnancy Meeting; January 23-28, 2017; Las Vegas, NV. Abstract 689.