Prenatal Exposure to Stress, Alterations in Fetal Brain Development Related to Neurodevelopmental Outcomes

Prenatal Exposure to Stress, Alterations in Fetal Brain Development Related to Neurodevelopmental Outcomes

A rising variety of research have indicated that psychological misery skilled by the mom — within the type of stress, anxiousness, or melancholy — is related to alterations in fetal mind growth.  These research have been difficult to do and infrequently depend on imaging carried out after supply; nonetheless, latest advances in magnetic resonance imaging (MRI) methods have allowed researchers to make use of MRI throughout being pregnant to look at fetal mind growth. 

In a earlier research from researchers on the Children’s National Hospital in Washington, DC, Wu and colleagues (2020) used these methods to look at fetal mind growth in a bunch of women with wholesome pregnancies.  They noticed that stress, anxiousness, or melancholy skilled by the mom throughout being pregnant — even when signs didn’t attain the severity of a psychiatric dysfunction — have been related to adjustments in fetal mind growth, together with decreased quantity of the left hippocampus and elevated cortical gyrification (folding) within the frontal and temporal lobes. 

While these findings are in line with earlier analysis trying on the affect of maternal psychological misery on fetal growth, we all know a lot much less about how these adjustments have an effect on long-term neurodevelopmental outcomes in youngsters.  In a latest report, Wu and colleagues study the affiliation between fetal mind growth and neurodevelopment at 18 months of age and decide whether or not fetal mind growth mediates the affiliation between prenatal maternal psychological misery and toddler neurodevelopmental outcomes.

Study Population.  Healthy mother-infant dyads have been prospectively recruited right into a longitudinal observational cohort research between January 2016 to October 2020 on the Children’s National Hospital in Washington, DC.  Because this research was designed to characterize fetal mind growth in wholesome pregnancies over the second and third trimesters of being pregnant, the women had low-risk pregnancies and weren’t particularly recruited primarily based on historical past of psychological health points.  In addition, it ought to be famous that the research inhabitants was largely composed of women with excessive socioeconomic {and professional} standing and with out the most important psychosocial stressors noticed in different populations.

Measurements of Prenatal Stress.  Participants accomplished validated, self-report questionnaires between 24 and 40 weeks of gestation to measure maternal stress (Perceived Stress Scale [PSS]), anxiousness (Spielberger State Anxiety Inventory [SSAI] and Spielberger Trait Anxiety Inventory [STAI]), and melancholy (Edinburgh Postnatal Depression Scale [EPDS]) have been accomplished on the identical day as every MRI go to.

Fetal MRI Assessments.  Using third-dimensional, reconstructed T2-weighted MRI scans, the researchers measured fetal mind volumes and cortical folding at two time factors throughout the second and third trimesters (between 24 and 40 weeks’ gestation).  Fetal mind creatine and choline have been used as a measure of mind metabolism and have been  quantified utilizing proton magnetic resonance spectroscopy.

Assessment of Children and Parenting.  Infant neurodevelopment at 18 months was measured utilizing the Bayley Scales of Infant and Toddler Development III and the Infant-Toddler Social and Emotional Assessment.  Parenting stress within the parent-child dyad was measured utilizing the Parenting Stress Index-Short Form at 18 months.

The research included 97 mother-infant dyads (imply [SD] maternal age, 34.79 [5.64] years) who underwent a complete of 184 fetal MRI visits (87 contributors with two fetal research every). Psychological misery within the mom was related to a number of completely different adjustments in fetal mind structure and metabolism.  Maternal anxiousness was related to smaller left hippocampal quantity within the fetus. Maternal anxiousness and stress have been additionally related to elevated fetal cortical gyrification within the frontal and temporal lobes.  Elevated maternal melancholy was related to decreased creatine and choline ranges within the fetal mind.

In 18-month previous youngsters, prenatal maternal stress was related to decrease scores of toddler cognitive efficiency.  This affiliation was mediated by fetal left hippocampal quantity.  Exposure to prenatal maternal stress was additionally related to decrease scores on measures of social-emotional efficiency, a discovering which was mediated by the diploma of fetal cortical native gyrification and sulcal depth.  In addition, maternal stress, anxiousness and melancholy throughout being pregnant have been positively related to parenting stress reported at 18 months. 

Moving Forward

The authors observe that stress-related signs at the moment are acknowledged as the most typical complication of being pregnant, affecting roughly 1 of each 4 women, together with these with wholesome pregnancies.  While sure populations — for instance, these with being pregnant issues and people coping with extra anxious residing circumstances — could expertise even increased ranges of stress, even people perceived to be at low threat for stress expertise stress-related signs throughout being pregnant. 

While the present research and former analysis have documented that psychological misery skilled by the mom throughout being pregnant is related to alterations in fetal mind growth, the findings of this research go one step additional and hyperlink alterations in fetal mind growth with long-term results on neurodevelopment.  Previous research have documented that publicity to emphasize throughout being pregnant can have an effect on fetal growth and is related to adjustments within the little one’s mind,  together with alterations in regional mind volumetric development (e.g., amygdala, hippocampus, cerebellum, and cortical grey matter volumes), cortical folding, metabolism, microstructure, and practical connectivity.  However, most of those research have been carried out in older youngsters, so it’s not potential to parse out the consequences of in utero publicity to emphasize from different exposures occurring after beginning.  The power of this research is that neuroimaging is carried out throughout being pregnant, in order that we will rule out the affect of exposures occurring after beginning on mind growth and construction.  

While the authors hypothesize that these adjustments in mind construction could predict future neurodevelopmental issues, we can not rule out the likelihood that the kid is uncovered to different components after beginning that contribute to worse outcomes.  For instance, moms with melancholy throughout being pregnant usually tend to have postpartum melancholy.  Exposure to emphasize throughout being pregnant could negatively have an effect on outcomes; nonetheless, we additionally know that postpartum melancholy (within the absence of melancholy throughout being pregnant) may additionally negatively have an effect on youngsters’s cognitive and socioemotional growth.    

Future research are wanted to raised perceive the connections between early publicity to emphasize and alterations in youngsters’s neurodevelopment and subsequent vulnerability to neurodevelopmental issues.  And importantly we have to take a look at outcomes in additional racially and socioeconomically various populations in order that we will higher perceive the connection between different sorts of hostile exposures and little one neurodevelopment.  

This research raises issues, but it surely additionally factors to alternatives for intervention.  Would methods designed to lower stress throughout being pregnant have a optimistic affect on little one neurodevelopment? Rather than ready for social-emotional or cognitive issues in youngsters to come up, may we institute interventions after beginning that promote cognitive and social-emotional growth?  The authors observe that figuring out biomarkers at (and even earlier than) the time of supply related worse neurodevelopmental outcomes  could help in growing early focused interventions which mitigate the consequences of prenatal publicity to emphasize.


Ruta Nonacs, MD PhD


Wu Y, Lu YC, Jacobs M, et al. Association of Prenatal Maternal Psychological Distress With Fetal Brain Growth, Metabolism, and Cortical Maturation. JAMA Netw Open. 2020;3(1):e1919940. 

Wu Y, Espinosa KM, Barnett SD, Kapse A, Quistorff JL, Lopez C, Andescavage N, Pradhan S, Lu YC, Kapse Okay, Henderson D, Vezina G, Wessel D, du Plessis AJ, Limperopoulos C.  Association of Elevated Maternal Psychological Distress, Altered Fetal Brain, and Offspring Cognitive and Social-Emotional Outcomes at 18 Months.  JAMA Netw Open. 2022 Apr 1;5(4):e229244. Free PMC article.



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