木瓜直播

Infants exposed to fluoxetine (Prozac) in their mother's first trimester of pregnancy had small but significant increased risks of major malformations and cardiovascular malformations, a small systematic review and meta-analysis found.

Using pooled data from 16 studies, Chinese researchers found statistically significant increased risks of both major malformations (RR 1.18, 95% CI 1.08-1.29) and cardiovascular malformations (RR 1.36, 95% CI 1.17-1.59) on infants exposed to fluoxetine during the first trimester, reported Shan-Yan Gao, MD, of Shenjing Hospital of China Medical University, and colleagues.

However, there were no significant increased risks linked to use of the drug in the first trimester for other system-specific malformations, including the nervous system, eye, urogenital system, digestive system, or musculoskeletal system, the authors wrote in the

They characterized fluoxetine as "the most commonly prescribed SSRIs [sic] during the first trimester," and added that in the past five years, a "growing body of cohort studies" have found links between fluoxetine use and the risk of malformations.

Various found on the between use of the drug and both major malformations and cardiovascular malformations in the infant.

But they cited limitations to prior meta-analyses, including the use of case-cohort studies, inaccurate information, unclear adjustments made for confounders and no other evidence for other system-specific malformations.

"The present study is the most comprehensive and current meta-analysis of published cohort studies," the authors wrote. "The results ... suggest healthcare providers and their patients should carefully consider risk-benefit analyses before proceeding with fluoxetine therapy ... during the first trimester."

They examined 16 cohort studies that enrolled a total of 6,562,262 pregnant women. These studies defined the exposure as fluoxetine use and exposure period as the first trimester and who had a comparison group that included pregnant women not exposed to any antidepressants and/or teratogens. Seven of the studies were from Europe and six were from North America. There was no indication of publication bias. Data from 12 studies covered major malformations and cardiovascular malformations in infants with first-trimester fluoxetine exposure.

In addition to the findings for those large classes of defects, data from seven studies showed significant increased risk for certain subtypes of cardiovascular malformation: septal defects (RR 1.38, 95% CI 1.19-1.61) and non-septal defects (RR 1.39, 95% CI 1.12-1.73).

The authors said that most selective serotonin reuptake inhibitors have a short half-life of approximately 1 day, but fluoxetine has a longer half-life (up to 4 days) and "is known to cross the human placenta because high concentrations of fluoxetine in umbilical cord blood," though they added that "the exact biological mechanism that causes fluoxetine-induced congenital malformations is unknown."

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