While we have considerable data on the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, most of this research focuses on the risk of congenital malformations in exposed children.  We have far less information regarding the long-term effects of SSRI antidepressants on neurodevelopmental outcomes in exposed children. A recent study looks at executive functioning in children at six years of age, measuring the impact of exposure to SSRIs, as well as exposure to maternal depressive symptoms.  

In this longitudinal prospective study, researchers assessed executive functioning in 139 children (77 girls and 62 boys) at six years of age.  In this cohort, 51 children had been exposed to SSRIs during pregnancy; 88 were not exposed. Executive functioning (EF) was obtained through maternal reports using the Behavior Rating Inventory of EF (BRIEF).  Depressive symptoms in the mother were obtained from the 2nd trimester to 6?years postpartum using the Hamilton Depression Rating Scale (HAM-D) and the Beck Depression Inventory.  

Higher levels of depressive symptoms in the mother (at all time points: second trimester, third trimester, 3 and 6?months postpartum, and at 3 and 6?years) were associated with poorer executive functioning skills in children at 6?years of age.  Maternal depressive symptoms at three years of age were most strongly correlated with poor executive functioning at six years of age.

Compared to women not treated with SSRIs during pregnancy, SSRI treated mothers had higher levels of depressive symptoms at all time points (second trimester to 6?years).  Prenatal SSRI exposure did not affect executive functioning, even after controlling for maternal education and depressive symptoms at 3?years postpartum.

These findings are consistent with multiple previous studies which have demonstrated that maternal depressive symptoms can lead to delays in cognitive development, behavioral problems, poor school performance, and lower IQ.  

And the data regarding prenatal exposure to SSRIs are reassuring, as SSRI exposure was not associated with worse executive functioning.  

The authors also raise an interesting possibility, questioning whether prenatal exposure to SSRis may actually have a beneficial effect.  This is based on the finding that when they looked at the SSRI-exposed children, they found that executive functioning was similar in those exposed to low vs. high levels of maternal depressive symptoms. The authors comment that SSRIs, either because they question whether SSRI exposure may confer some sort of  biological or developmental benefit which mitigates the negative effects of exposure to maternal depression during the perinatal period and beyond.  

Looking Beyond the Perinatal Period

What this study clearly shows is that we need to extend our focus well beyond the postpartum period and the first year of life.  This study suggests that exposure to maternal depressive symptoms at three years of age have the greatest impact on later executive functioning.  

Maternal depression is not restricted to the perinatal period.  For many women, depression is a recurrent or chronic illness. In a recent report, researchers followed a group of 1807 French mothers and noted that about a third of the women had depressive symptoms that persisted throughout the first five years of their child’s life.  Other studies from Australia and Canada have shown similarly high rates of depression in mothers of young children.

In an editorial accompanying the Australian study, Meltzer-Brody and Brandon urge a broader approach to how we take care of the mental health needs of mothers:

One of the most important ways in which we can address the neglect of maternal mental health is by examining the delivery of our healthcare services to children and families and finding ways to incorporate psychosocial and mental health assessment and intervention across mother–child units. It is extremely naive to believe that mothers can provide optimal care for their children without having adequate support and treatment for the widely prevalent societal and mental health concerns that challenge women during their reproductive years. Second, if we are to mitigate the intergenerational consequences of violence against women, we must take an active stance against intimate partner violence. Across healthcare settings, we can only optimize mother and child outcomes through tireless advocacy, careful assessment and immediate intervention.

Ruta Nonacs, MD PhD

A 6-year longitudinal study: Are maternal depressive symptoms and Selective Serotonin Reuptake Inhibitor (SSRI) antidepressant treatment during pregnancy associated with everyday measures of executive function in young children?

Hutchison SM, Mâsse LC, Brain U, Oberlander TF.  Early Hum Dev. 2018 Nov 14;128:21-26.

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