Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure

Abstract

IMPORTANCE Several studies have examined the links between prenatal exposure to antidepressants and autism spectrum disorders (ASDs) in children, with inconsistent results, especially regarding the impact of the trimester of exposure. OBJECTIVE To perform a systematic review of the literature and a meta-analysis of published studies to assess the association between ASDs and fetal exposure to antidepressants during pregnancy for each trimester of pregnancy and preconception.DATA SOURCES PubMed, EMBASE, and PsycINFO databases up to May 2016 were searched in June 2016 for observational studies. For the meta-analyses, data were analyzed on RevMan version 5.2 using a random-effect model. For the review, studies were included if they had been published and were cohort or case-control studies, and for the meta-analysis, studies were included if they were published studies and the data were not derived from the same cohorts. STUDY SELECTIONWe included all the studies that examined the association between ASDs and antenatal exposure to antidepressants.DATA EXTRACTION AND SYNTHESIS Three reviewers independently screened titles and abstracts, read full-text articles, and extracted data. The quality of the studies was also assessed.MAIN OUTCOMES AND MEASURES Primary outcome was the association between antidepressants during pregnancy and ASDs. Secondary outcomes were the associations between antidepressants in each individual trimester or before pregnancy and ASDs. RESULTSOur literature search identified 10 relevant studies with inconsistent results. For prenatal exposure, the meta-analysis on the 6 case-control studies (117 737 patients) evidenced a positive association between antidepressant exposure and ASDs (odds ratio [OR], 1.81; 95% CI, 1.49-2.20). The association was weaker when controlled for past maternal mental illness (OR, 1.52; 95% CI, 1.09-2.12). A similar pattern was found whatever the trimester of exposure considered (first trimester: OR, 2.09, 95% CI,1.66-2.64; second: OR, 2.00, 95% CI, 1.55-2.59; and third: OR, 1.90, 95% CI, 1.20-3.02. Controlled for past maternal mental illness: first trimester: OR, 1.79; 95% CI, 1.27-2.52, second: OR, 1.67, 95% CI, 1.14-2.45; and third: OR, 1.54, 95% CI, 0.82-2.90). No association was found when the 2 cohort studies were pooled (772 331 patients) for the whole pregnancy (hazard ratio, 1.26; 95% CI, 0.91-1.74) or for the first trimester. In addition, preconception exposure to antidepressants was significantly associated with an increased risk for ASDs (OR controlled for past maternal illness, 1.77; 95% CI, 1.49-2.09). CONCLUSIONS AND RELEVANCEThere is a significant association between increased ASD risk and maternal use of antidepressants during pregnancy; however, it appears to be more consistent during the preconception period than during each trimester. Maternal psychiatric disorders in treatment before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for ASDs. Future studies should address the problem of this potential con...

The contribution of environmental exposure to the etiology of autism spectrum disorder

“…Evidence, both positive and negative, is mounting in relation to the role these risks play in the etiology of ASD. Several areas are now underpinned by relatively large bodies of evidence such as parental age and SSRI medication [58, 130–132], while others lines of inquiry have generated relatively little specific evidence such as smoking and alcohol use [145, 146, 150–154]. …”

“…SSRIs cross the placenta barrier, potentially triggering a cascade of adverse effects including reduced serotonin uptake, reduced uterine blood flow, and hypoxia resulting in brain damage. A systematic review of the literature aiming to assess the association between ASD and fetal exposure to antidepressants during pregnancy, from preconception and across each trimester of pregnancy, included ten studies with six case–control studies (117,737 patients) in a meta-analysis [130]. Findings revealed a positive association between SSRI exposure and ASD, consistent across all trimesters (OR 1.81; 95% CI 1.49–2.20), which while partially mitigated by controlling for past maternal mental illness (OR 1.52; 95% CI 1.09–2.12) remained significant.…”

“…Smoking exposes a developing fetus to many risks including thousands of potentially harmful chemicals and oxygen deprivation, collectively causing changes in neurotransmitter activity within the developing brain [138, 139]. Ethanol consumption during pregnancy can trigger multiple forms of neurodevelopmental damage, including fetal alcohol syndrome in cases of heavy drinking [130, 140, 141]. …”

Variations in Neurodevelopmental Outcomes in Children with Prenatal SSRI Antidepressant Exposure

“…In a meta‐analyses using four studies a significant association between first trimester SSRI exposure and ASD was reported (Brown et al, ), however the ability to account for confounding factors such as maternal mental illness and use of other psychotropic medication limited these findings. In another recent study Mezzacappa and colleagues (Mezzacappa et al, ) reported a significant association between increased ASD risk and maternal use of antidepressants during pregnancy. However, this association appeared to be more consistent when exposure occurred before conception rather than during pregnancy itself.…”

Maternal SSRI treatment during offspring development results in long-term behavioral, cellular, and neuroimaging disruptions

“…SSRIs are highly prescribed in pregnant women for mood disorders with prevalence of 5-13% (Cooper, Willy, Pont, & Ray, 2007). A recently published meta-analysis reported a significant case-control association between maternal antidepressant use and ASD risk in offspring, which remained when adjusted for maternal psychiatric history (Mezzacappa et al, 2017). Meta-analyzed cohort studies replicated the SSRI-ASD link, but not the independence from psychiatric history.…”