Selin Acar

Prenatal selective serotonin reuptake inhibitor use and the risk of autism spectrum disorder in children: A systematic review and meta-analysis

OBJECTIVE To determine whether an up-to-date systematic review and meta-analysis of observational studies would support the previously suggested associations regarding prenatal selective serotonin reuptake inhibitor (SSRI) use and the risk for autism spectrum disorders (ASD) in children. METHODS PubMed/MEDLINE, Cochrane Central Register of Controlled Trials and Reprotox databases were searched; observational studies with an exposed and unexposed group were included. RESULTS The meta-analysis of case-control studies demonstrated a significantly increased risk of ASD in the children whose mothers were prenatally exposed to SSRIs during different exposure time windows (except third trimester). The qualitative review of the cohort studies suggested inconsistent findings. CONCLUSIONS The significant association between preconception-only SSRI exposure and ASD in the children and negative/inconsistent findings among cohort studies weaken the significant associations detected in this meta-analysis. We suggest that confounding by indication still cannot be ruled out regarding prenatal SSRI exposure and ASD in children.

Maternal SSRI discontinuation, use, psychiatric disorder and the risk of autism in children: a meta‐analysis of cohort studies

We undertook an exclusive meta-analysis of cohort studies investigating the possible link between prenatal selective serotonin reuptake inhibitor (SSRI) exposure and autism spectrum disorders (ASD) in children to further investigate our previous suggestion of confounding by indication. The point estimates regarding the following cohorts were extracted and pooled: (1) pregnant women who discontinued SSRI until 3 months before pregnancy; (2) pregnant women who were exposed to SSRI during pregnancy; and (3) pregnant women with maternal psychiatric disorder but no exposure to SSRI during pregnancy. Although the pooled point estimate of the first cohort showed a trend for increase, it did not reach significance. The pooled point estimates of the latter cohorts showed a significant association with ASD which strengthens our previous suggestion of confounding by indication. Future studies should be adequately designed to differentiate whether the previously suggested association is a result of maternal psychiatric disorder or SSRI exposure or both.

Prenatal Antidepressant Use and Risk of Autism Spectrum Disorders in Children

To the Editor The register-based cohort study by Boukhris et al1 investigating the association between prenatal antidepressant use and risk of autism spectrum disorders (ASD) in the offspring was interesting. The authors reported a significant increase in risk of ASD in children whose mothers were exposed to antidepressants and selective serotonin reuptake inhibitors (SSRIs) in the second and/or third trimesters of their pregnancy. However, we believe that the study suffers from incomplete reporting and discussion of the results, which may lead to significant misinterpretations. First, a hazard ratio regarding the ASD risk in children who were exposed to antidepressants and/or SSRIs anytime during pregnancy is missing. We expected this to be reported, as all previous cohort studies did,2-4 because an insignificant hazard ratio would change the whole discussion. Second, the authors did not assess, report, and discuss the risk estimate of SSRI-only exposures and ASD in children for the first trimester. This is very important because an insignificant hazard ratio would not be consistent with the preclinical findings, which suggests an association of early disruption of serotonergic system and ASD.5 The authors referred to this theory to explain the significance they detected for the later trimesters, but did not discuss first-trimester exposures, where the fetus may be regarded as even more vulnerable to the possible effects of SSRIs because of the possible immaturity of the blood-brain barrier. Third, it is difficult to understand why the authors clustered “second and/or third trimester” exposures in the same group rather than forming and assessing the “second and third trimester” and the “second or third trimester” exposures separately. It is likely that the pregnant women who used antidepressants during 2 trimesters would be different than the women who used them for only 1 trimester with regard to the severity of maternal depression, the most important confounder. Lastly, while the authors report a hazard ratio for antidepressant exposures during second and/or third trimester after restricting the analysis to the mothers with depression, they did not give such an estimate for SSRI-only exposures. An insignificant hazard ratio would be interesting. Therefore, without assessing and discussing the points above, it is too early to make a suggestion for “further research specifically assessing the risk of ASD associated with antidepressant types and dosages during pregnancy.”1 We believe that the shadow of the severity of maternal depression may not be prominent but is still there.

Pregnancy outcomes after maternal betahistine exposure: A case series

OBJECTIVE To investigate the pregnancy outcomes of women who were exposed to betahistine during their pregnancies. METHODS We identified and evaluated the outcomes of 27 pregnant women who were referred to Terafar (Teratology Information Service, Izmir, Turkey) for a teratological risk assessment. RESULTS Of 24 pregnancies with known outcomes, 21 resulted in live births (including two pairs of twins) whereas two ended with miscarriage and three with elective terminations. Among the 20 live births for whom the malformation details were available, there were 17 normal outcomes, one major and two minor congenital malformations. CONCLUSIONS Despite a number of limitations, this case series may be of value regarding counseling pregnant women with inadvertent betahistine exposure. Further epidemiological studies with larger sample sizes and control groups are necessary to draw more definite conclusions.