We have long been concerned about the impact of prenatal stress on fetal development and subsequent risk for developmental problems and psychiatric morbidity.  Various studies have demonstrated an association between maternal depression and anxiety during pregnancy and increased risk for psychiatric morbidity in exposed children. It is important to recognize that many women experience multiple psychological and medical adversities during pregnancy.   It is not known how being exposed to a greater number of adversities during pregnancy affects risk for subsequent psychopathology in exposed children.  

A recent study examined whether exposure to multiple adversities during pregnancy is associated with increasing risk of psychiatric morbidity in adolescents.  Using data from the 2014 Ontario Child Health Study (OCHS), Faltyn and colleagues examined the association between several different prenatal risk factors (maternal hypertension, diabetes mellitus, bleeding during pregnancy, influenza infection, urinary tract infection, thyroid disease, and depression/anxiety) and adolescent psychiatric illness. This list of exposures reflects the most common pregnancy-associated complications. Prenatal adversities were retrospectively reported by mothers at the time their children were assessed (12 to 17 years after exposure).

A total of 2219 adolescents between the ages of 12 and 17 years were assessed using the Mini-International Neuropsychiatric Interview for Children and Adolescents.  In unadjusted analyses, as the number of prenatal adversities increased, so did risk for attention deficit hyperactivity disorder (ADHD), social anxiety disorder, and generalized anxiety disorder (GAD) in the exposed children.  The researchers did not observe any statistically significant associations between prenatal adversity and risk for major depressive disorder, separation anxiety disorder, specific phobia, conduct disorder, or oppositional defiant disorder.

After accounting for potential confounding variables (e.g., adolescent sex, age, socioeconomic status, maternal age), each additional adversity was associated with an increase in risk for ADHD (OR 1.29, 95% CI: 1.03–1.60), social anxiety disorder (OR 1.35, 95% CI: 1.01–1.79), and GAD (OR 1.27, 95% CI: 1.05–1.55).  For example, in a mother who experienced three of the above listed adversities, her child would have about a two-fold increased risk of having ADHD, GAD or social phobia compared to children born to mothers who did not experience adversity.   

This study has some limitations.  For one, this study relied on retrospective reporting, which may not be 100% accurate, especially when accounting for events that are perceived to be less severe. In addition, this study did not assess for other prenatal exposures previously associated with increased risk of psychopathology in children — for example, smoking and use of alcohol or other substances.  Nonetheless this study includes one of the largest groups of adolescents in which psychiatric morbidity was assessed using a structured diagnostic interview. 

The findings of this study suggest that increased risk of anxiety and ADHD in children may be prenatally programmed after the fetus is exposed to multiple insults during pregnancy.  It has been hypothesized that exposures occurring during critical windows of fetal development can permanently impact how the child’s nervous system is “programmed” to function.  Research in both animal and human populations support the Fetal Programming Hypothesis, which asserts that experiences during pregnancy may modulate the normal course of development such that adverse experiences during this period may result in permanent alterations to the physiology, neurodevelopment, and behavior of the child which persist into adulthood.

What we consider to be a relevant exposure in terms of fetal programming is evolving.  Previous studies have focused on more extreme insults, such as malnutrition (for example, the Dutch famine of 1944 to 1945), severe illness in the mother (the 1918 influenza pandemic), and life-threatening events or natural disasters (the Queensland flood, 9/11 attacks in New York City).  This study suggests that common pregnancy complications, such as hypertension or urinary tract infection, may carry some degree of risk, especially when multiple adversities occur concurrently.  


Ruta Nonacs, MD PhD


Faltyn M, Savoy C, Krzeczkowski JE, Ferro MA, Colman I, Van Lieshout RJ.  Exploring Links Between Prenatal Adversity and Adolescent Psychiatric Risk in a Canadian Population-Based Sample.  J Dev Behav Pediatr. 2021 Feb 3.  


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