Two recent studies have examined the relationship between use of serotonergic antidepressants during pregnancy and subsequent diagnosis of autism and other psychiatric disorders in offspring. In one retrospective cohort study of Canadian women receiving public prescriptions for 2 or more serotonergic antidepressants during pregnancy, the relationship between drug exposure and child autism spectrum disorder (ASD) (identified after the age of 2 years old) was examined (See abstract). In utero serotonergic exposure was not associated with ASD in the child.
However, in this study a statistical approach was applied to balance group differences between exposed and unexposed groups in the following areas: maternal age, parity, neighborhood income, quintile, rural residence, medical and psychiatric diagnoses, and health service use before and during pregnancy. In a second study conducted in Sweden, the relationship between antidepressant use in the first trimester and preterm birth, small gestational age, ASD, and attention deficit/hyperactivity disorder among offspring was examined (See abstract). After accounting for confounding factors, first trimester exposure to antidepressants, compared with no exposure was associated with a small increased risk of preterm birth, but no increased risk of small for gestational age, ASD, or attention-deficit/hyperactivity disorder. The findings from both studies contradict previous findings where blood and platelet serotonin levels are high in approximately one third of patients with ASD, suggesting the implication of serotonin in ASD (McNamara et al., 2008; Yang et al., 2014).
Additionally, two recent meta-analyses reported a significant association between antenatal antidepressant exposure and ASDs (Rais et al., 2014; Man et al., 2015). A recent meta-analysis included ten studies on antenatal exposure to antidepressants in each individual trimester of pregnancy, or before pregnancy and ASD (See abstract). A positive association was detected 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). The same pattern was found in each trimester when controlled for past maternal mental illness.
The results suggest that while there is a significant association between increased ASD risk and maternal use of antidepressants during pregnancy, treatment for maternal psychiatric disorders before pregnancy rather than antenatal exposure to antidepressants could have a major role in the risk for ASDs. Previous studies have not examined the influence of serotonergic antidepressant use for treatment of maternal psychiatric disorders prior to pregnancy and this may explain some of the inconsistency in reports on the association between antenatal antidepressant use and ASD. Future studies should address the problem of this potential confound.
>> Brown HK et al. JAMA. 2017;317(15):1544-1552.
>> Sujan AC et al. JAMA. 2017;317(15):1553-1562.
>> Mezzacappa A et al. JAMA Pediatr. 2017
References:
Brown HK, Ray JG, Wilton AS, Lunsky Y, Gomes T, Vigod SN. Association Between Serotonergic Antidepressant Use During Pregnancy and Autism Spectrum Disorder in Children. JAMA. 2017;317(15):1544-1552.
Man KK, Tong HH, Wong LY, Chan EW, Simonoff E, Wong IC. Exposure to selective serotonin reuptake inhibitors during pregnancy and risk of autism spectrum disorder in children: a systematic review and meta-analysis of observational studies. Neurosci Biobehav Rev. 2015;49:82-9.
Mcnamara IM, Borella AW, Bialowas LA, Whitaker-azmitia PM. Further studies in the developmental hyperserotonemia model (DHS) of autism: social, behavioral and peptide changes. Brain Res. 2008;1189:203-14.
Mezzacappa A, Lasica PA, Gianfagna F, et al. Risk for Autism Spectrum Disorders According to Period of Prenatal Antidepressant Exposure: A Systematic Review and Meta-analysis. JAMA Pediatr. 2017
Rais TB, Rais A. Association Between Antidepressants Use During Pregnancy and Autistic Spectrum Disorders: A Meta-analysis. Innov Clin Neurosci. 2014;11(5-6):18-22.
Sujan AC, Rickert ME, Öberg AS, et al. Associations of Maternal Antidepressant Use During the First Trimester of Pregnancy With Preterm Birth, Small for Gestational Age, Autism Spectrum Disorder, and Attention-Deficit/Hyperactivity Disorder in Offspring. JAMA. 2017;317(15):1553-1562.
Yang CJ, Tan HP, Du YJ. The developmental disruptions of serotonin signaling may involved in autism during early brain development. Neuroscience. 2014;267:1-10.