Alcohol Abuse during Pregnancy and ADHD Symptoms

Research suggests that there is a relationship between maternal alcohol use during pregnancy and ADHD. Previous studies have found similar associations. Three different approaches were used to control for both measured and unmeasured confounding: statistical adjustment for covariates, a negative control comparison against maternal pre-pregnancy alcohol use, and comparison among differentially exposed siblings. For this proposal, data will be drawn from the Norwegian Mother and Child Cohort Study (MoBa), which recruited participants between 1999 and 2008. Self-reported measurements of alcohol use were obtained in week 30 of pregnancy.

This study will seek to identify the prevalence of ADHD symptoms among the cohort children up until the 5th grade. A stratified random sample of 120 children will be selected, and standardized ADHD measures will be administered to their parents and teachers. It is hypothesized that exposure to alcohol in the womb will increase the likelihood of children displaying ADHD symptoms during their elementary school years.

Introduction

Attention-deficit hyperactivity disorder (ADHD), usually characterized by inattention and hyperactivity-impulsivity, is the most common behavioral disorder in childhood. It typically manifests at an early age and affects approximately 5% of children worldwide. Many mothers continue to drink alcohol during pregnancy, a habit that is often linked to ADHD. Ethanol enhances the migration of nerve cells, an action hypothesized to be involved in behavioral difficulties in childhood. It also interferes with the production of neuroendocrine hormones, which may perturb brain growth. A positive association between maternal alcohol use during pregnancy and symptoms of ADHD in children has been reported in several studies. However, studies have not been directly conducted on children within this age group.

The aim of our study is to investigate whether maternal alcohol use during pregnancy is related to the incidence of ADHD in elementary school-aged children. Two measures of ADHD were administered for this study: the Conners Rating Scale-Revised (CRS-R) and the Child Behavior Checklist-Attention Problem (CBCL-AP) scale.

The Conners Rating Scales-Revised (CRS-R) is a thorough assessment of attention-deficit/hyperactivity disorder (ADHD). It involves paper-and-pencil screening questionnaires designed to be completed by parents and teachers to assist in evaluating children for ADHD. On the other hand, the CBCL-AP is a parent-rated questionnaire for assessing a wide range of child emotional and behavioral problems. We hypothesize that exposure to alcohol in the womb will increase the likelihood of children within this age range displaying ADHD symptoms.

Literature Review

Attention-deficit hyperactivity disorder (ADHD), characterized by inattention and/or hyperactivity-impulsivity, is the most common behavioral disorder in childhood. It manifests at an early age and affects approximately 5% of children worldwide. Maternal alcohol use during pregnancy has repeatedly been associated with the development of ADHD in offspring. Alcohol is considered one of the risk factors for ADHD.

Eilertsen et al.'s (2017) summary article reviewing maternal alcohol use during pregnancy and offspring ADHD found an overall positive association between maternal alcohol use during pregnancy and offspring ADHD symptoms. This association was only marginally attenuated after the inclusion of measured covariates. They found a weak, but potentially causal association with maternal alcohol use during pregnancy for offspring ADHD symptoms. However, no such effect was observed for clinical ADHD diagnosis.

A follow-up study by Gronimus, Ridout, Sandberg, and Santosh (2009) centered on maternal alcohol consumption. The study found that children exposed to alcohol in utero are 2.33 times more likely to have ADHD than non-exposed children. Those exposed to heavy alcohol consumption in utero are 2.27 times more likely to have ADHD than those exposed to mild consumption. Their meta-analysis suggests that children exposed to alcohol during pregnancy are at risk for ADHD. However, evidence is sparse, and it remains uncertain whether a causal association exists. Further research is needed into the dose-response relationship, timing of exposure, influence of genetic factors involved in maternal alcohol abuse, and the role of FASD in ADHD-like symptoms.

A similar study by Linnet et al. (2003) examined maternal lifestyle factors in the pregnancy risk of ADHD and associated behaviors. They found that alcohol is widely recognized as a teratogenic agent causing CNS dysfunction and impaired mental functioning, including fetal alcohol effect and fetal alcohol syndrome, which incorporates the core symptoms of ADHD.

A cohort study by Knopik et al. (2006) investigated the maternal alcohol use disorder and offspring ADHD. Their findings suggest that children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin has an AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD.

Mick, Biederman, Faraone, Sayer, and Kleinman (2002) scrutinized ADHD and maternal smoking, alcohol, and drug use during pregnancy. The study found that ADHD cases were 2.5 times more likely to have been exposed to alcohol in utero than were the non-ADHD control subjects.

Lastly, Ware et al. (2014) examined the interaction between prenatal alcohol exposure and ADHD on parent-rated adaptive behavior in four groups: children with prenatal alcohol exposure and ADHD (AE+), children with prenatal alcohol exposure without ADHD (AE-), children with ADHD, and control children (CON). They concluded that the significant interaction between ADHD and prenatal alcohol exposure was significant only for the Communication domain.
This proposal will seek to determine whether maternal alcohol use during pregnancy is related to offspring ADHD in children whose mothers consumed alcohol during their pregnancy, compared to children whose mothers did not. The Conner's Rating Scale-Revised (CRS-R) and the Child Behavior Checklist-Attention Problem (CBCL-AP) scale will be administered to parents and teachers during the fall break. This timing will allow enough time for the teachers to become acquainted with the children, ensuring more reliable results.

Definitions

Attention-Deficit/Hyperactivity Disorder (ADHD), according to the DSM-5 manual, is defined as a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with functioning or development. This is characterized by:

Inattention, in which an individual often fails to give close attention to detail, has difficulty sustaining attention in tasks or play activities, does not seem to listen when spoken to directly, does not follow through on instructions, and fails to finish schoolwork, chores, or duties. This is inconsistent with the individual's developmental level and negatively impacts their social and academic/occupational activities.

Hyperactivity and impulsivity represent the second characteristic of ADHD. This includes frequently fidgeting with hands or feet, often leaving one's seat when it is expected to stay put, running around or climbing in inappropriate situations, inability to play or engage in leisure activities quietly, and acting as if "driven by a motor". Other symptoms include talking excessively, blurting out answers before a question is completed, difficulty waiting one's turn (e.g. while waiting in line), and frequently interrupting or intruding on others. These symptoms must have persisted for at least 6 months to a degree that is inconsistent with the individual's developmental level and that negatively impacts their social and academic/occupational activities.

The Conners Rating Scales-Revised (CRS-R) are paper and pencil screening questionnaires, which parents and teachers can fill out, that assist in evaluating children for ADHD.

The CBCL Attention Problem (CBCL-AP) subscale is often used as a diagnostic tool for ADHD. It has been proven to possess strong discriminatory power for detecting the disorder in children.

Method

This proposal will seek to determine whether maternal alcohol use during pregnancy is related to offspring ADHD. Specifically, the study will compare children whose mothers consumed alcohol during their pregnancy to those whose mothers did not.

Participants

Participants in this study included 250 children (fifth graders): 127 males and 123 females from 232 mothers. These participants were representatives of the subjects recruited to the Norwegian Mother and Child Birth Cohort Study between 1999 and 2008. All participants in this study were volunteers. Written informed consent was obtained from all participants upon recruitment.

Materials

Self-reported measurements of alcohol use were obtained in week 30 during the pregnancy. Mothers rated offspring ADHD symptoms at five years on two measures that were used for this study. These measures are the Conners Rating Scale-Revised (CRS-R) and the Child Behavior Checklist-Attention Problem (CBCL-AP) scale. The Conners Rating Scales-Revised (CRS-R) are paper and pencil screening questionnaires designed to be completed by parents and teachers to assist in evaluating children for attention-deficit/hyperactivity disorder (ADHD). They are used as part of a comprehensive examination and are designed to be easily administered and scored to assist in determining whether children between the ages of three and 17 years might suffer from ADHD. CBCL-AP is a parent-rated questionnaire for assessing a wide range of child emotional and behavioral problems. The CBCL Attention Problem (CBCL-AP) subscale, one of the eight empirically derived clinical syndrome subscales of the CBCL-AP, is frequently used as a diagnostic tool for ADHD and has strong discriminatory power for detecting ADHD in children.

Design and Procedure

The Conners Rating Scale-Revised (CRS-R) was administered to teachers and parents of the children in this sample. Symptoms of ADHD at 5 years of age were assessed by maternal report. The scale consists of 12 four-point items, which were summed to a score ranging from 12 to 48. The Child Behavior Checklist-Attention Problem (CBCL-AP) scale was also used, and this included six three-point items summed to a score ranging from 6 to 18. Both measures were standardized to zero mean and unit variance prior to analyses. This assessment was scored to determine the percentage of children in the sample who met the criteria for ADHD, compared with other children whose mothers did not consume any alcohol during pregnancy.

Measurements of Maternal Alcohol Use

Alcohol use was measured using the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) designed to identify harmful patterns of usage. The scale consists of three five-point items measuring drinking frequency, quantity, and binge drinking, summed to a score ranging from 0 to 12. The questionnaire was administered around week 30 in pregnancy, and mothers reported on their use pre-pregnancy and during the first trimester. Both measurements were standardized to zero mean and unit variance prior to analysis.

Statistical Analysis:

To facilitate comparisons across analyses of ADHD symptoms, we restricted the sample to mothers with two or more birth records in MoBa, comprising 300 mothers and 250 children. Symptoms were modelled using linear multilevel regression models with random intercepts for mothers, allowing for residual correlations (familial dependence) in responses of siblings. The two outcome measures were analyzed separately.

A crude estimate of the association with the outcome measures was obtained by including maternal alcohol use during pregnancy as a fixed effect in the models. We used maternal alcohol use before the pregnancy as a negative control, and we also compared siblings differentially exposed to alcohol during pregnancy.

It is hypothesized that there will be a higher rate of ADHD in children whose mothers consumed alcohol during their pregnancy compared to children whose mothers did not. ADHD symptoms, measured by the CPRS-R scale, were associated with maternal alcohol use during pregnancy, even under our most stringent control, indicating a possible causal effect. A positive association was found between maternal alcohol use during pregnancy and offspring ADHD symptoms, which remained after controlling for the covariates. This pattern was replicated across both ADHD symptom measures. The results conform to other findings and suggest that maternal alcohol use during pregnancy is related to ADHD.

References

1. Eilertsen, E. M., Gjerde, L. C., Reichborn-Kjennerud, T., Ørstavik, R. E., Knudsen, G. P., Stoltenberg, C., . . . Ystrom, E. (2017). Maternal alcohol use during pregnancy and offspring attention-deficit hyperactivity disorder (ADHD): A prospective sibling control study. International Journal of Epidemiology, 46(5), 1633-1640.
2. Gronimus, R., Ridout, D., Sandberg, S., & Santosh, P. (2009). Maternal alcohol consumption. London Journal of Primary Care, 2(1), 28-35.
3. Knopik, V. S., Heath, A. C., Jacob, T., Slutske, W. S., Bucholz, K. K., Madden, P. A., . . . Martin, N. G. (2006). Maternal alcohol use disorder and offspring ADHD: Disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine, 36(10), 1461.
4. Linnet, K. M., Dalsgaard, S., Obel, C., Wisborg, K., Henriksen, T. B., Rodriguez, A., . . . Jarvelin, M. (2003). Maternal Lifestyle Factors in Pregnancy Risk of Attention Deficit Hyperactivity Disorder and Associated Behaviors: Review of the Current Evidence. American Journal of Psychiatry,160(6), 1028-1040.
5. Mick, E., Biederman, J., Faraone, S. V., Sayer, J., & Kleinman, S. (2002). Case-Control Study of Attention-Deficit Hyperactivity Disorder and Maternal Smoking, Alcohol Use, and Drug Use During Pregnancy. Journal of the American Academy of Child & Adolescent Psychiatry, 41(4), 378-385.
6. Ware, A. L., Glass, L., Crocker, N., Deweese, B. N., Coles, C. D., Kable, J. A., . . . Mattson, S. N. (2014). Effects of Prenatal Alcohol Exposure and Attention-Deficit/Hyperactivity Disorder on Adaptive Functioning. Alcoholism: Clinical and Experimental Research, 38(5), 1439-1447.

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