Untreated depression during pregnancy is associated with an increased risk for preterm birth and low birth weight ― two of the leading causes of mortality and morbidity in infants ― results of a new meta-analysis suggest.

“Although this does not mean that treating depression with antidepressants will reduce these risks, this is an important piece of information for clinicians and women to take into account in the decision-making process around management of depression,” said lead author Alexander Jarde, PhD, postdoctoral fellow, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada.

Interestingly, the analysis showed that the odds of preterm birth reported in studies by authors receiving support from pharmaceutical companies were significantly higher than the odds reported in studies by authors who did not receive such support.

The study was published online June 8 in JAMA Psychiatry.

Researchers performed an exhaustive literature search for randomized and nonrandomized studies reporting adverse neonatal outcomes in pregnant women with untreated depression in comparison with pregnant women without depression. Studies assessed depression using either a clinical interview/diagnosis or a screening tool or scale.

The authors “rigorously” excluded the confounding effects of antidepressant use, said Dr Jarde.

Primary Outcomes

The primary outcomes were preterm birth before 37 weeks’ gestation or 32 weeks’ gestation, being small for gestational age (birth weight < 10th percentile for sex and gestation), being large for gestational age (birth weight > 90th percentile for sex and gestational age), low birth weight (< 2500 g), and admission to the neonatal intensive care unit.
The analysis included 23 studies. None of the studies reported preterm birth before 32 weeks’ gestation or being large for gestational age. Only one study reported being small for gestational age, and two reported admission to the neonatal intensive care.

The researchers found that in comparison with pregnant women who were without depression, those with untreated depression had a significantly increased risk for both birth before 37 weeks (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.25 – 1.94; 14 studies) and low birth weight (OR, 1.96; 95% CI, 1.24 – 3.10; 8 studies).

A subgroup analysis did not find any significant differences for preterm births between studies assessing depression using a clinical diagnosis or interview (40% of studies) and those using self-reporting questionnaires. However, there was a trend to an increased risk among women with more severe depression.

For low birth weight, subgroup analyses showed a significant increased risk in term infants, which would be about the equivalent of being small for gestational age. For this outcome, analyses also suggested that there was a significant difference between the results of studies of high or acceptable quality (5 or more points on the modified Newcastle-Ottawa scale) and the results of studies of low quality (4 or less points on this scale).

Role of Funding

The researchers also looked at the role of the study authors’ conflicts of interest (COI) ― whether they had direct or indirect funding by, or links to, pharmaceutical companies.

“This difference remained after removing low-quality studies from the analyses and does not seem to be explained by severity of depression,” noted Dr Jarde.

Although there was a trend toward a significant difference in low birth weight outcome between studies reporting and those not reporting COI, this disappeared when low-quality studies were removed.

The authors were unable to explain why COI seemed to affect preterm birth but not low birth weight.

A previous systematic review did not find the same increased risks for preterm birth and low birth weight as did the current study. “Unfortunately, although we did explore this contradiction, we have not found a satisfactory explanation for this yet,” said Dr Jarde.

Related Factors

How might untreated depression during pregnancy affect gestation and birth weight? According to Dr Jarde, it might not be the depression itself, but related factors.

“It’s challenging to isolate the effects of depression alone,” he said. “Depression can be accompanied by other risk factors for preterm birth and low birth weight, such as smoking, anxiety, and low socioeconomic status.”

From an obstetrics point of view, the results suggest that women with untreated depression might benefit from surveillance for preterm birth and small infant size, said Dr Jarde.

He stressed that when deciding on how to manage depression during pregnancy, many factors should be taken into consideration. Such factors, he said, should include each woman’s characteristics, for example, the severity of her depression, her treatment history, and her personal preference.

He also emphasized the need for more rigorous studies that carefully measure and report important risk factors to better understand the risks associated with depression during pregnancy.

The use of antidepressants during pregnancy has been increasing during the past few decades, with 3% to 8% of pregnant women being prescribed or having used antidepressants.

Important Counterpoint

For a comment, Medscape Medical News reached Nada Stotland, MD, professor of psychiatry, Rush University, Chicago, who is former president of the American Psychiatric Association.

She commended the authors for conducting such a study, because there is very little information available on the impact of untreated depression during pregnancy.

“All we ever hear about is the impact of medications in pregnancy,” said Dr Stotland.

Depression is “extremely painful,” she noted, and it is difficult for women and their physicians to know what to do when it occurs during a pregnancy. “While this study doesn’t give us the answers, it provides us with some counterpoint to the idea that taking medications is bad and harmful to the pregnancy.”

Some pregnant women feel guilty or selfish if they take a medication. “This is, again, a counterpoint to that,” said Dr Stotland.

It is important for women whose depression is effectively controlled by an antidepressant to not stop taking the medication during pregnancy, she said. “There’s a very strong likelihood that they’ll succumb to a recurrence or exacerbation of their depression, and it’s important for them to know that taking medication might be a good thing.”

Determining the impact of untreated depression during pregnancy is difficult, inasmuch as studies cannot randomly assign women to not receive treatment, said Dr Stotland. “So I give the authors all the more credit for that.”

That untreated depression causes problems during pregnancy makes sense, said Dr Stotland. “Depression causes you to lose your appetite, it causes you to not be able to sleep, it causes you either to be agitated and moving around too much or to be torpid and lying around, and none of these things, as we know, is good for pregnancy.”

As well, “Depression makes you feel helpless and hopeless,” she added, “so why go to the doctor? Why get checkups? Why take care of yourself?”

Dr Stotland noted that psychotherapy is “quite effective” for depression during pregnancy but that it is not as available as it should be.