
In a recent commentary, Dr. Lee Cohen, notes that over the past 15-20 years, now we have collected an unlimited amount of information on using antidepressants while pregnant. Data from multiple studies and meta-analyses have demonstrated no increased risk of major malformations in children exposed to antidepressants while pregnant, including the SSRIs, SNRIs, tricyclic antidepressants and bupropion.
While previous studies have focused totally on the chance of major malformations in children with prenatal exposure to antidepressants, newer studies have attempted to measure more subtle outcomes, specifically the impact of prenatal antidepressant exposure on brain development and performance. A recent prospective, population-based cohort study conducted within the Netherlands as a part of the Generation R Study investigates the association between intrauterine SSRI exposure and maternal depressive symptoms and structural brain development in offspring 7 to fifteen years of age.
On this study, all pregnant individuals with an expected delivery date between April 1, 2002, and January 31, 2006, were invited to participate. Maternal reports of SSRI use were verified using pharmacy records. To estimate the impact of depressive symptoms during and after pregnancy on brain development, moms were assessed while pregnant and at 2 and 6 months after delivery using the Temporary Symptom Inventory.
Brain morphology was assessed within the offspring, including global and cortical brain volumes, measured at three different time points between the ages of seven and 15 using magnetic resonance imaging (MRI).
What Did the Study Show?
The study included 3198 mother-child dyads. The mean (SD) age at intake was 31.1 (4.7) years. Children (1670 [52.2%] female) underwent brain imaging assessment between the ages of seven and 15 years of age, with a complete of 5624 scans.
Outcomes were assessed in five distinct groups of mother-infant dyads with different exposures:
- Maternal SSRI use while pregnant (n = 41; 80 scans),
- Maternal SSRI use only before pregnancy (n = 77; 126 scans),
- Prenatal depressive symptoms without prenatal SSRI use (n = 257; 477 scans),
- Postpartum depressive symptoms only (n = 74; 128 scans), and
- Non-exposed control individuals (n = 2749; 4813 scans).
When it comes to measurements of brain volumes, the researchers observed the next:
- In comparison with non-exposed controls, children prenatally exposed to SSRIs had lower cerebral gray matter volumes, particularly inside the corticolimbic circuit. These changes persevered as much as 15 years of age.
- Children prenatally exposed to SSRIs while pregnant also had lower cerebral white matter volumes; nonetheless, these volume differences diminished with age.
- Children exposed to SSRIs prenatally showed a steeper increase in volumes of the amygdala from 7 to fifteen years of age. These volumetric differences within the amygdala and fusiform seen in childhood didn’t persist until early adolescence
- Prenatal SSRI exposure was not related to changes in the amount or growth trajectory of the hippocampus.
Additionally they noted that exposure to maternal depression was related to changes in brain morphology:
- Children exposed to prenatal depressive symptoms had reduced rostral anterior cingulate gyrus volumes.
- Children exposed to postpartum depressive symptoms had reduced fusiform gyrus volumes.
SSRI use before conception was not related to any brain differences.
Strengths and Limitations of the Study
Overall this can be a well done and thoroughly constructed study. The potential nature of the study and the indisputable fact that it’s embedded inside a bigger study of kid development reduces the chance of selection bias. Participation within the Generation R study is obtainable to all pregnant moms and is just not specifically targeted to women with histories of psychiatric illness.
While older studies have often compared outcomes in antidepressant-exposed children to outcomes in healthy children born to moms without psychiatric illness, this study chosen more appropriate comparison groups to higher control for genetic and environmental aspects that could be more commonly related to using antidepressants and/or psychiatric illness. More specifically, they compared outcomes in antidepressant-exposed children to children born to women previously treated with SSRIs who elected to stop antidepressant treatment prior to conception. As well as, antidepressant-exposed children were in comparison with non-exposed children born to moms who experienced either prenatal or postpartum depression.
This approach helps to attenuate the contribution of some confounding aspects, but it surely is unlikely to completely account for all confounding variables. More specifically, we cannot conclude that the mother who elects to stop antidepressants while pregnant is clinically or genetically comparable to women who elect to keep up treatment. Notably, on this study, the researchers observed that girls using SSRIs while pregnant had higher levels of depressive symptoms and were more more likely to even be taking benzodiazepines compared with the reference group, a finding that implies a more severe depression or comorbidity in women who elect to keep up treatment with antidepressants while pregnant.
Moreover, other aspects that will potentially have antagonistic developmental outcomes within the child, similar to increased BMI and smoking, are more common in women with psychiatric illness. Although the study was in a position to control for educational level and socioeconomic status, other necessary variables, including BMI, smoking, comorbid psychiatric diagnoses, weren’t considered.
Since it is just not possible to do a randomized controlled trial where an identical groups of ladies are treated with antidepressants or placebo, there isn’t a such thing as an ideal study.
What Does This Study Tell Us? How Can We Use This Information?
The findings of the present study suggest that SSRI exposure while pregnant could also be related to changes in brain morphology. Specifically, the authors observed altered developmental trajectories in brain regions related to emotional regulation within the offspring. Within the comparison group — women who stopped SSRIs prior to pregnancy — didn’t exhibit any differences in brain morphology in comparison with non-exposed controls.
Of note, in addition they observed that maternal depression (without exposure to SSRIs) was also related to changes in brain morphology, although the particular changes were distinct from those related to antidepressant exposure.
One explanation of those findings is that SSRIs (versus associated genetic or environmental aspects) may alter brain development and/or morphology. Nevertheless, we cannot exclude the likelihood that the ladies who elect to take antidepressants while pregnant have more severe psychiatric illness or comorbidity and it’s the underlying illness (versus the treatment itself) that affects brain development.
It’s interesting to notice that while some changes persevered into adolescence, others (reduced white matter volumes) didn’t, suggesting a developmental delay somewhat than a everlasting structural change. Further studies are required to follow these findings into maturity.
Most significantly, the present study measured structural changes but didn’t assess function or evidence of psychopathology. We must consider this study together with other studies exploring clinical outcomes. For instance, a recent study from Suarez and colleagues analyzed data from nearly 150,000 children with prenatal antidepressant exposure in two healthcare databases and located no association between prenatal exposure to antidepressants and risk for neurodevelopmental disorders. That is the biggest study so far examining neurodevelopmental outcomes in children exposed to antidepressants while pregnant. Antidepressant use in pregnancy itself doesn’t increase the chance of neurodevelopmental disorders in children. There are, nonetheless, other aspects more common in women who take antidepressants while pregnant that will increase the chance of getting a baby with a neurodevelopmental disorder.
Does This Study Change What We Recommend?
Concerns regarding the consequences of fetal exposure to antidepressants is acceptable provided that about 15% of ladies experience depression while pregnant. For some women, psychotherapy could also be an efficient treatment option on this setting. Nevertheless, a considerable number of ladies don’t reply to psychotherapy alone or have severe depressive symptoms and should require treatment with an antidepressant.
While this study suggests the likelihood that SSRIs may affect fetal brain development, the study also clearly shows that maternal depression — whether it while pregnant or the postpartum period — also alters brain development. The choice to make use of antidepressants while pregnant involves weighing the risks related to exposure to a selected medication against the risks related to untreated depression within the mother.
The present study adds to our understanding of the consequences of antidepressant exposure on fetal brain development; nonetheless, the knowledge remains to be incomplete. At this point, it could be premature to limit antidepressant treatment while pregnant based on this study. Further research on the functional implications of those findings is warranted.
Ruta Nonacs, MD PhD
Koc D, Tiemeier H, Stricker BH, Muetzel RL, Hillegers M, El Marroun H. Prenatal Antidepressant Exposure and Offspring Brain Morphologic Trajectory. JAMA Psychiatry. 2023 Aug 30:e233161.
Talati A. Maternal Depression, Prenatal SSRI Exposure, and Brain Trajectories in Childhood. JAMA Psychiatry. 2023 Aug 30.