Children whose depressed mothers took newer antidepressants while pregnant were not at increased risk of childhood asthma, according to a retrospective, population-based study in Denmark.

When restricting analyses to children born to mothers with depression, maternal antidepressant use did not increase asthma risk in offspring (HR 1.00, 95% CI 0.93-1.08), stated Xiaoqing Liu, MD, section for epidemiology, department of public health at Aarhus University in Denmark, and colleagues. Prenatal maternal depression was classified as "a diagnosis of depressive disorder or use of antidepressants 1 year before or during pregnancy."

The majority of women (80.8%) with prenatal maternal depression were prescribed serotonin reuptake inhibitors (or SSRIs). These "newer" drugs were not associated with an increased risk for asthma in offspring (HR 0.95, 95% CI 0.88-1.03), the authors reported in Pediatrics.

Risk for childhood asthma increased when women with prenatal depression were prescribed "older" antidepressants, such as tricyclic antidepressants or TCAs. In fact, TCAs accounted for 81% of prescriptions for "older" antidepressants and those women taking TCAs only were associated with a 28% increased risk in childhood asthma (95% CI 1.06-1.56).

In a separate interview with MedPage Today, Liu pointed out the "sparse" research on antidepressant use in pregnancy on asthma compared with the substantial research about the effect of the drugs on congenital malformation, pulmonary hypertension of the newborn, behavior problems, and autism disorder.

"The safety of antidepressant use during pregnancy has never been evaluated in randomized controlled trials," said Liu. "We hope our study will contribute knowledge to the safety of antidepressant use during pregnancy."

Peter Bernstein, MD, MPH, professor, clinical obstetrics & gynecology and women's health, and program director, Maternal-Fetal Medicine Fellowship at the Montefiore Medical Center/Albert Einstein College of Medicine in New York City, who was not affiliated with this study, described it as "reassuring" given all of the concerns about SSRIs and pregnancy. "There's more and more research coming out around SSRIs and poor neonatal outcomes, and so being able to essentially take them off the list as a risk factor for childhood asthma is really for me the most important point from this," he said.

Comparing offspring's outcomes in women taking antidepressants during pregnancy with those in women who were not depressed -- a different comparison than the one restricted only to depressed mothers -- the researchers found a significant increase in offspring's asthma risk associated with antidepressant use: HR 1.25 (95% CI 1.18-1.33). There was also a similar offspring asthma risk in depressed mothers not taking antidepressants compared with the nondepressed mothers (HR 1.25, 95% CI, 1.20-1.30).

Researchers noted other factors that may have contributed to a mother's prenatal depression. "Compared to mothers with no record of prenatal depression, mothers with prenatal depression were characterized as having more previous pregnancies, having lower income, being smokers, having a higher proportion of asthma history and giving birth in later calendar years," they wrote.

The study examined a cohort of 733,685 "live born singletons" born in Denmark from 1996 to 2007. A diagnosis of asthma (n=84,684) was identified by the Danish National Patient Register and the Danish National Prescription Registry as having "at least two prescriptions for antiasthmatic medications or one asthma hospital contact after 3 years of age from 1999 to 2010." In addition, 21,371 children were determined to have been born to mothers with prenatal depression, according to records from the Danish Psychiatric Central Register and the Danish National Patient Register.

Limitations of the study include the fact that while antidepressant use is classified as having been prescribed medication, it was unclear whether the patients actually took the medication. The authors also describe that since asthma is defined as a hospital diagnosis or prescription, it excludes the "milder" cases of asthma. They also wrote that since they did not account for confounding by "severity" of maternal depression, the risk of antidepressant use may be over or underestimated.

Bernstein also added that it was not even clear from the study whether depression itself was the reason for the greater risk of childhood asthma. "The question that comes up in my mind is: is it really the depression or is the depression a marker of something else?" he said.

"It doesn't clearly make sense to me why a woman who has depression would be more likely to have a child with asthma unless there's some genetic difference in women who have depression that predisposes their child to having asthma," Bernstein concluded.