Association Between Prenatal Stress and the Development of ADHD in Children

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Literature Review:

The Association Between Prenatal Stress and the Development of ADHD in Children

Abstract

Attention-deficit hyperactivity disorder (ADHD) is one of the most common diagnoses among children. Biological and environmental factors contribute to the development of ADHD symptoms. Although heredity is a major determinant of ADHD, other environmental factors are suggested to increase the risk of ADHD in children. In particular, increased prenatal stress has been linked to the development of a psychiatric disorder, specifically ADHD. Possible factors that may influence the relationship between maternal stress and ADHD diagnoses include gender differences, severity of maternal stress, and socioeconomic disadvantages. Additionally, explanations for the causal relationship include genetic and environmental influences, and the interaction of maternal stress and the DRD4 7/7 genotype in children. Thus, this review analyzed the relationship between prenatal stress and ADHD. Conclusively, prenatal stress was found to contribute to increased ADHD prognosis in children.

Keywords: prenatal stress, Attention-deficit hyperactivity disorder, ADHD

Introduction

Attention-deficit hyperactivity disorder (ADHD) is one of the most common behavioral diagnoses among young children. It is defined as a neuro-developmental disorder characterized by hyperactivity and/or inattention that continues for at least six months across several situations (Rodriguez & Bohlin, 2005).  The symptoms of ADHD can influence a child’s academic and social capabilities (Okano, Ji, Riley, & Wang, 2018). Although the prevalence of ADHD decreases with age, symptoms of ADHD continue throughout adulthood (Rodriguez & Bohlin, 2005). If left untreated, a child’s social and academic functioning can be severely affected by symptoms of ADHD (Grizenko, Shayan, Polotskaia, Ter-Stepanian, & Joober, 2008).

While the causes of ADHD are unknown, both environmental and genetic factors have been implicated. Though many studies have shown ADHD to be a heritable disorder, only 75-80% of ADHD symptoms are the result of genetic factors. Studies have suggested causal factors from pre-, peri-, and postnatal environments to play a role in ADHD (Grizenko et al., 2008). Findings have suggested that the implementation of intervention strategies to lower the stress a woman experiences during pregnancy can reduce the probability that a child will develop ADHD behaviors (Ronald, Pennell, & Whitehouse, 2011). Because prenatal stress is preventable, it is of public health significance to study the relationship between prenatal stress and symptoms of ADHD in children. Therefore, this review primarily investigates prenatal stress as a modifiable environmental factor to prevent the development of ADHD symptoms among children.

The diagnostic process of ADHD in children

The diagnostic process of ADHD includes diagnostic tests, patient history and parent interviews. In addition, behavior scales are used by clinical psychologists to measure the symptom severity of children. Clinical psychologists use the Diagnostic and Statistical Manual of Mental Disorder (DSM) when rating a child’s behavior. In addition, behavioral scales are useful in assessing ADHD behavior at school and at home. Teachers’ ratings of children are often more accurate when analyzing externalizing behaviors, such as aggression, because such behaviors create noticeable disturbances in the classroom, than internalizing behaviors, such as day dreaming, may not be identified as often. In addition, mothers are more likely to report inattentive behaviors rather than hyperactive behaviors (Mayfield et al., 2018).  These diagnostic processes are utilized in the following studies when evaluating children; therefore, it is important to understand how ADHD is identified and assessed.

Heritability of ADHD

Heritability is defined as how much of a trait is the result of genetic influences (Grimm, Kittel-Schneider, & Reif, 2018). Many studies have found ADHD to be highly heritable. Grimm et al. (2018) have estimated heritability of ADHD to be 76%. In addition, ADHD has been found to have a stronger heritability compared to other psychiatric disorders (Grimm et al., 2018). ADHD has also been found to have a higher prevalence among first-degree relatives (Grimm et al., 2018).  With heritability playing a partial role in ADHD, understanding the relationship between environmental factors and the development of ADHD among children is necessary.

Prenatal stress as an environmental factor

Many studies have found maternal stress to have a significant impact on a child’s development. Although several hypotheses have been formed, the mechanisms by which maternal stress causes developmental issues in children is still uncertain. Hypotheses that try to explain the onset of ADHD symptoms include, but are not limited to: the activation of the sympathetic nervous system, causing an increase in uterine artery resistance that triggers a decrease in the blood flow to the fetus; amplification of the fetal cortisol levels modifies the nervous system and dysregulates the hypothalamus-pituitary-adrenal (HPA) axis; and reduced inhibition of the frontal activity is caused by the catecholamine in the synaptic cleft in specific brain regions (Grizenko et al., 2012). Conclusively, it is biologically plausible that the development of ADHD is affected by prenatal stress.

Evidence of an Association

Three studies were selected to analyze the association between prenatal stress and ADHD.  The first study set out to determine if there was a relationship between the severity of maternal stress and the extent of ADHD symptomology in children. Participants included 203 children consisting of 32 girls and 171 boys between the ages 6 and 12. Participants were diagnosed with ADHD according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The children were assessed using a variety of clinical interviews and evaluations. In addition, parents completed the Child Behavior Checklist (CBCL). The study used the Kinney Medical and Gynecological Questionnaire to assess the stressful life events the mother encountered before, during and after pregnancy. Mothers were then divided into three groups: no stress, moderate stress, and severe stress. The level of ADHD symptoms present in children were calculated using CBCL scores. The study analyzed the level of stress the mother experienced in each trimester to determine if stress during a particular period altered the severity of ADHD symptoms in children. Grizenko et al. (2012) discovered an association between maternal stress and symptoms of ADHD in children. Additionally, the study found a relationship between increased stress during the third trimester and high CBCL scores (Grizenko et al., 2012). It was more likely that a mother would report symptoms of ADHD if they were to experience stress during the third trimester of pregnancy. The following research demonstrated limitations that should be addressed in future studies such as the use of the Kinney Medical and Gynecological Questionnaire, which relied on the mother to successfully recall the degree of stress she felt while pregnant. The dependence on the mother’s memory could have produced recall bias (Grizenko et al., 2012).

Similar to the previous study, another study investigated the association between prenatal maternal stress (PNMS) and ADHD behaviors in 2-year-olds (Ronald, Pennell, & Whitehouse, 2011). The sample consisted of 913 males and 833 females. Between the ages of 1 ½ and 5, child behavior was measured by the Child Behavior Checklist (CBCL). In addition, ADHD was diagnosed using the DSM-IV symptomology list. Maternal stress was measured at 18- and 34-weeks gestation by asking whether 10 stressful life events have occurred. Consistently, Ronald et al. (2011) discovered a significant relationship between prenatal maternal stress (PNMS) and ADHD behaviors in both males and females. Conclusively, PNMS is related to the development of ADHD-like behaviors in children. The mothers who reported higher levels of stress also reported more symptoms of ADHD. However, the study could experience attrition bias as underprivileged mothers were less likely to participate.

The final study examined whether a link between maternal psychosocial stress and the diagnosis of ADHD among children was present (Okano et al., 2018). The study consisted of 2140 pairs of mothers and children. Children who participated in the study were around 9.1 years old during the follow-up examination. Maternal stress was measured using three scales including the 4-item Perceived Stress Scale, experiences of daily stress during pregnancy, and the absence or presence of five major stressful happenings. The study also included environmental conditions, paternal involvement, social support, and whether pregnancy was expected. The child’s diagnosis of ADHD was based upon the International Classification of Diseases (ICD-9). The study found that as the level of maternal psychosocial stresses increased the likelihood of an ADHD diagnoses increased. Mothers who were single, smoked during pregnancy, had not completed high school, or had intrauterine complications during pregnancy were more likely to have children diagnosed with ADHD. Additionally, the study found that males had at higher risk of developing ADHD when the mother experienced stress during pregnancy. Although a limitation of this study was that the sample was not demographically diverse, therefore, results could not be generalizable to the entire population.

Explanations of the Causal Relationship

It is clear that maternal stress is positively associated with the development of ADHD in children. Many studies have addressed the risk that maternal stress can have on a child’s development, but there is still a debate as to whether maternal stress is considered an environmental risk factor or genetic risk factor. Although stressful situations may be considered an environmental risk factor, many studies have suggested that these “environmental” variables display genetic influences. It is possible that genes that influence the mother stress levels throughout pregnancy are also involved in the risk of a child developing ADHD in the future (Ronald et al., 2011). So, if a mother is more prone to experience higher degrees of stress, it is likely to have a negative impact on the child’s development. Thus, the nature of nurture is a possible explanation for the causal relationship between maternal stress and ADHD (Ronald et al., 2011).

Another possible explanation for the causal relationship between maternal stress and later development of ADHD is the influence of the DRD4 7/7 genotype (Grizenko et al., 2012). A child’s DRD4 7/7 genotype can interact with the stress levels experienced by the mother during pregnancy. The DRD4 7/7 genotype and maternal stress interaction could produce an increased risk of the development and severity of ADHD symptoms in children (Grizenko et al., 2012).

Overall, the following research has provided possible explanations for the causal relationship between maternal stress and ADHD in children, but additional research should be done. Findings have suggested that there is a gene-environment interaction when assessing maternal stress and the development of ADHD. The environmental situations that a mother encounters during pregnancy can influence the offspring’s genes, which puts the offspring at a greater risk for developing a psychiatric disorder later in life. Conversely, the stress that is felt by the mother during pregnancy can interact with a child’s genotype which can influence the course and severity of ADHD symptoms. This interaction demonstrates a relationship between maternal stress and severity of ADHD symptoms in children. Although there are several possible explanations for the causal relationship between maternal stress and symptoms of ADHD, including but not limited to gene-environment interaction and a child’s DRD4 7/7 genotype, but more research must be conducted in order to further explain the causal relationship.

Factors Influencing the Relationship between Maternal Stress and ADHD in Children

Impact of Severity of Maternal Stress

Research has found an association between the severity of maternal stress and ADHD symptoms in children (Grizenko et al., 2008). Mothers who experienced moderate to severe stress during pregnancy had children with higher CBCL scores and experienced more ADHD symptoms than children with mothers that experienced minimal amounts of stress (Grizenko et al., 2008). In addition to these findings, it appears that increased stress during the third trimester is associated with higher CBCL scores (Grizenko et al., 2008). Further, a possible explanation for the inflated CBCL scores is that when a mother experiences a stressful life event in the third trimester, it may continue after the child is born, disturbing the relationship between the mother and child (Grizenko et al., 2008).

Gender Differences in Children with ADHD

It has been shown that there are gender differences in the development of ADHD in children. Research has found that males are more likely to develop ADHD symptoms than females (Rodriguez & Bohlin, 2005). A possible explanation for this phenomenon is that male fetuses’ are more sensitive to calamity compared to girls (Rodriguez & Bohlin, 2005). Further, other research has explained gender differences in the development of hyperactive behavior as the result of the overproduction and later pruning of dopamine receptor masses in males (Rodriguez & Bohlin, 2005). Although an association has been found between gender differences and the development of ADHD, it is rarely the leading focus of research. Therefore, future research should concentrate on the influence that gender differences has on the development of psychiatric disorders in children.

Socioeconomic Status of Mothers

Research has found an association between behavioral symptoms of ADHD and socioeconomic disadvantage (Russell, Ford, Rosenberg, & Kelly, 2014). It is more common for those who come from a low socioeconomic status (SES) background to be diagnosed with ADHD. Mothers living in low SES neighborhoods are subject to more stress and adversity. Understanding stress, adversity and ADHD requires more research, but studies have indicated that hardships and stressful environments, such as discrimination, poverty, crowded households and family chaos can alter a person’s stress response. Further, if a mother is exposed to these types of stressful environments during pregnancy, it could influence the child’s neurobehavioral development, which could have an impact on the development of ADHD symptoms. Hence, it is evident that low socioeconomic status influences the relationship between maternal stress and children with ADHD.

Conclusions

All three studies demonstrated consistency in their results, in that each study found a relationship between prenatal stress and ADHD symptoms in children. Although research has found a significant relationship between two variables, the mechanism and specific determinants remain unknown. Genetic influences, postnatal environmental influences, and elevated self-report data are possible reasons for this relationship and require further research.

Future Directions

Previous studies have demonstrated a significant association between prenatal stress and symptoms of ADHD, as mentioned above. The majority of these studies used the same measurements, such as the CBCL to identify ADHD symptoms in children. Additionally, the studies included a wide range of ages when conducting research. In total, all results demonstrated the presence of a relationship between maternal stress and ADHD symptoms in children.

Future studies should use the same scales for measuring prenatal stress and criteria for diagnosing children with ADHD for consistency, and all children should be observed by an experienced child psychiatrist. Additionally, research should gather data on the mother’s stress levels before, during and after pregnancy instead of using memories to recall the stress they experienced. Also, different developmental periods should be assessed, and participants should be followed for longer durations to further understand the relationship. All studies analyzed did not follow up with children more than once. Future research should address these limitations by using a longitudinal research design. Researchers should recruit pregnant women and record the mother’s stress levels throughout the pregnancy, therefore eliminating recall bias. Moreover, a longitudinal research design would allow researchers to follow up with children more than once so that the children could be evaluated during different developmental periods.

Thus, with ADHD being a long-term psychiatric disorder, future research should continue to measure the development and severity of ADHD symptoms. Lastly, a diverse set of participants should be examined so that the data can be generalizable to the entire population.  In total, further research should address the limitations that prior research encountered, as it may impact the identification and understanding of risk factors involved in the development of ADHD symptoms.

Other environmental factors may implicate the following studies, and therefore, further research should analyze the impact of other possible factors, in addition to prenatal stress, on ADHD.  Previous studies have found environmental factors, such as maternal smoking, drug or alcohol consumption during pregnancy, low socioeconomic status, and family discord to be associated with developmental cases (Freitag et al., 2012). These account for possible environmental explanations for the development of ADHD, and therefore, additional research is necessary.

Overall, current research has found a modest, yet significant, relationship between prenatal stress and ADHD outcomes in children.  All studies demonstrated prenatal stress to be an important risk factor that can influence ADHD cases; however, other environmental variables may also contribute to the development of ADHD in children and should be considered in future studies.  Conclusively, prenatal stress should be monitored in order to decrease the likelihood of ADHD cases in children.

References

Freitag, C. M., Hänig, S., Schneider, A., Seitz, C., Palmason, H., Retz, W., & Meyer, J. (2012). Biological and psychosocial environmental risk factors influence symptom severity and psychiatric comorbidity in children with ADHD. Journal of Neural Transmission (Vienna, Austria : 1996), 119(1), 81–94. https://doi.org/10.1007/s00702-011-0659-9

Grimm, O., Kittel-Schneider, S., & Reif, A. (2018). Recent developments in the genetics of attention-deficit hyperactivity disorder. Psychiatry and Clinical Neurosciences, 72(9), 654–672. https://doi.org/10.1111/pcn.12673

Grizenko, N., Fortier, M. E., Zadorozny, C., Thakur, G., Schmitz, N., Duval, R., & Joober, R. (2012). Maternal stress during pregnancy, ADHD symptomatology in children and genotype: Gene-environment interaction. Journal of the Canadian Academy of Child and Adolescent Psychiatry, 21(1), 9–15.

Grizenko, N., Shayan, Y. R., Polotskaia, A., Ter-Stepanian, M., & Joober, R. (2008). Relation of maternal stress during pregnancy to symptom severity and response to treatment in children with ADHD. Journal of Psychiatry and Neuroscience. https://doi.org/10.1093/ije/dyq025

Mayfield, A. R., Parke, E. M., Barchard, K. A., Zenisek, R. P., Thaler, N. S., Etcoff, L. M., & Allen, D. N. (2018). Equivalence of mother and father ratings of ADHD in children. Child Neuropsychology : A Journal on Normal and Abnormal Development in Childhood and Adolescence, 24(2), 166–183. https://doi.org/10.1080/09297049.2016.1236186

Okano, L., Ji, Y., Riley, A. W., & Wang, X. (2018). Maternal psychosocial stress and children’s ADHD diagnosis: a prospective birth cohort study. Journal of Psychosomatic Obstetrics and Gynecology, 0(0), 1–9. https://doi.org/10.1080/0167482X.2018.1468434

Rodriguez, A., & Bohlin, G. (2005). Are maternal smoking and stress during pregnancy related to ADHD symptoms in children? Journal of Child Psychology and Psychiatry and Allied Disciplines, 46(3), 246–254. https://doi.org/10.1111/j.1469-7610.2004.00359.x

Ronald, A., Pennell, C. E., & Whitehouse, A. J. O. (2011). Prenatal maternal stress associated with ADHD and autistic traits in early childhood. Frontiers in Psychology, 1(JAN), 1–8. https://doi.org/10.3389/fpsyg.2010.00223

Russell, G., Ford, T., Rosenberg, R., & Kelly, S. (2014). The association of attention deficit hyperactivity disorder with socioeconomic disadvantage: alternative explanations and evidence. Journal of Child Psychology and Psychiatry, and Allied Disciplines, 55(5), 436–445. https://doi.org/10.1111/jcpp.12170

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