Gestational Diabetes a Risk Factor for Postpartum Depression

Nancy A. Melville

January 23, 2017

Gestational diabetes appears to be an independent risk factor for postpartum depression (PPD) in first-time mothers, new research shows.

Results of a large, population-based study showed that even in the absence of a history of depression, gestational diabetes significantly increased the risk for PPD. The investigators, led by Michael E. Silverman, PhD, assistant professor of psychiatry at the Icahn School of Medicine at Mount Sinai in New York Cty, also found that women with a history of depression are 20 times more likely to experience PPD than their counterparts without a depression history. A history of maternal depression in conjunction with gestational diabetes further increased the likelihood of PPD.

"Most practitioners think of these as two isolated and very different conditions, but we now understand gestational diabetes and postpartum depression should be considered together," Dr Silverman said in a release.

"While having diabetes increases PPD risk for all women, for those women who have had a past depressive episode, having diabetes during pregnancy makes it 70% more likely that they will develop PPD," he added.

The study was published online January 18 in Depression and Anxiety.

Largest Study to Date

The investigators point out that PPD can have a negative impact on women and child development. They note that to date, no study has examined how a history of maternal depression interacts with known risk factors.

To examine the impact of a history of depression on PPD and pre- and perinatal risk factors, the researchers analyzed data from a prospective cohort study of births of a first child between 1997 and 2008 in the Swedish Medical Birth Register.

In addition to information on virtually all births in Sweden, the registry has included, since 2000, data on hospital outpatient care.

The study, which is the largest of its kind to date, showed that among 707,701 women who had a live singleton birth during the study period, there were 4397 cases of PPD within the first year of delivery.

For PPD, the study included diagnoses of the condition as well as major depressive disorder, unspecified episodic mood disorder, or depressive disorder that occurred within the first year post partum.

A history of prepregnancy depression dramatically increased the risk for PPD, with 1154 cases per 10,000 patients among those with a history of depression compared to only 42 cases per 10,000 patients among those without a history (relative risk [RR], 21.03; 95% confidence interval [CI], 19.72 - 22.42).

Women with gestational diabetes had a significantly increased risk for PPD, regardless of whether they had a history of depression (RR 1.70; 95% CI, 1.36 - 2.13). Women older than 35 years also were at increased risk for PPD regardless of depression history in comparison with compared women aged 25 to 29 years (RR, 1.25; 95% CI, 1.13 - 1.37).

The risk for PPD was also significantly increased among women who had a history of depression as well as pregestational diabetes in comparison with those without pregestational diabetes (RR, 1.49; 95% CI, 1.01 - 2.21) as well as with preterm delivery of 32 to 36 weeks' gestation (RR 1.20; 95% CI, 1.06 - 1.36).

Surprise Finding

The increased risk with gestational diabetes was a surprise, as were the findings on pregestational diabetes, Dr Silverman, told Medscape Medical News.

"It was a surprise that pregestational diabetes was only an issue with a depression history. I say this because there is a well-understood link between depression and diabetes, so women with no history of depression who have diabetes represent what seems to be a postpartum-resilient population," he added.

Among women with no history of depression, other risk factors for PPD included younger age (15 to 19 years and 20 to 24 years; RR, 2.14; 95% CI, 1.79 - 2.57), cesarean delivery (RR, 1.64; 95% CI, 1.07 - 2.50); instrument-assisted delivery (RR, 1.23; 95% CI, 1.09 - 1.38); and moderate (less than 32 weeks' gestation) preterm delivery risk (RR, 1.36; 95% CI, 1.05 - 1.75).

Previous studies have reported inconclusive findings regarding the link between preterm delivery and PPD. The association in the new research may reflect the study's design, which included following women for a full year after delivery. This allowed the investigators to capture later depression diagnoses, they note.

Although a history of depression is a well-known risk factor of PPD, the authors were surprised by the magnitude of the increased risk.

"We were surprised not only to the extent that a history of depression predicts postpartum depression but moreso by how few postpartum depression cases occurred without a history of depression. That is, postpartum depression without a depression history is far rarer than we, and I think anyone, expected," Dr Silverman said.

Although the dramatic hormonal fluctuations of pregnancy and childbirth are commonly attributed to PPD, the authors point to another possible mechanism, inflammation, which is associated with many of the risk factors.

"We know there is a strong relationship between inflammatory cytokines and depression ― even for those who are otherwise medically healthy ― and between the cytokines and diabetes, diabetes and depression during pregnancy are independently associated with obstetric complications, preterm birth, and neonatal complications, among other things," said Dr Silverman.

"Obviously, association does not imply causality, but we do know that inflammatory cytokines have profound effects on hormonal and neurotransmitter metabolism in brain areas that regulate emotion, such as the HPA axis," he said.

More Research Needed

More research is needed to determine the role of the mechanisms in PPD, the authors note.

The findings underscore the need for clinicians to take note of the risk factors for PPD while women are still pregnant, Dr Silverman said.

"While depressed women don't always return for postpartum care, which includes depression screenings, pregnant women represent a medically captured population," he said.

"Based on these new findings, we believe the vast majority of women who will develop postpartum depression can be captured before they give birth by asking about their history of depression and monitoring for diabetes."

He added that the role of clinicians with respect to PPD can be compared to their role regarding tobacco use.

"The reason a doctor asks if you smoke is because they know you are 20 times more likely to get cancer if you do. Given it's the same for depression history and postpartum depression, we believe Ob/Gyns should now do the same for depression history," he said.

"These women can be identified, and interventions can be administered before the depression occurs and before something potentially catastrophic occurs."

Promise of New Therapeutic Agents

Commenting on the findings for Medscape Medical News, Emily S. Miller, MD, MPH, an assistant professor in the Division of Maternal Fetal Medicine, Northeastern University Feinberg School of Medicine, Chicago, Illinois, said the study's strengths include its use of a large population.

"This is an important study, as [the authors] were able to identify risk factors for postpartum depression in a large epidemiologic evaluation," she said. "The large sample along with their very specific definition of depression adds to our understanding of risk factors for postpartum depression."

In a previous study published in 2016 in the Archives of Women's Mental Health, Dr Miller and colleagues evaluated a smaller cohort of 305 women and did not see an association between gestational diabetes and PPD. She said the larger size of the new study likely explains the difference.

"The most notable limitation in our study was sample size, and so we were insufficiently powered to identify small effect sizes such as the RR of 1.70."

Dr Miller's current research focuses on the role inflammation, and she echoed the theories on the possible relationships with PPD.

"Pregestational diabetes is associated with increased levels of inflammation, which has a causal relationship with depression," she said.

"Similarly, the underlying proinflammatory milieu that may contribute to the development of gestational diabetes may also contribute to the evolution of depression antenatally or post partum.

"While the underlying molecular mechanisms that lead to this causation are incompletely defined, it holds promise as we look forward toward new therapeutic agents that can improve depression symptoms, particularly in women with established high levels of inflammation."

The study received grant support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Coauthor Henrik Larsson, PhD, has served as a speaker for Eli Lilly and Shire. Dr Miller has disclosed no relevant financial relationships.

Depress Anxiety. Published online January 18, 2017. Abstract

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