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Research

In 1973, fifty years ago, two physicians from the University of Washington, Dr. Kenneth Jones and Dr. David Smith, published their research on the effects of prenatal alcohol exposure on the developing fetus. This was the start of awareness of FAS (FASD) in the U.S.*  Since then, there have been thousands of research articles on FASD published in mainstream journals. A sample of this research, by topic, is listed below.  

*Paul Lemoine MD, a French pediatrician, published the first research on FAS in 1968.

Recent Research/Reports

Mareckova, Klara, et al. Prenatal exposure to alcohol and its impact on reward processing and substance use in adulthood.Transl Psychiatry 14, 220 (2024). https://doi.org/10.1038/s41398-024-02941-9

"Overall, our findings, based on 30 years’ worth of data on a prenatal birth cohort, suggest that even relatively moderate exposure to alcohol during pregnancy, a critical sensitive period for brain development, might alter neural reward processing in the offspring and contribute to the intergenerational transmission of risk for substance use disorders."

 

Higher rates of alcohol related liver disease among women.

"This is a touchy topic," said Rachel Sayko Adams, a research associate professor at the Boston University School of Public Health. "There is no safe level of alcohol use," she said. "That's, like, new information that people didn't want to know." The World Health Organization and various studies have found that no amount of alcohol is safe for human health. Even light drinking has been linked to health concerns, like hypertension and coronary artery disease and an increased risk of breast and other cancers.

And when it does come up, said Stephanie Garbarino, a transplant hepatologist at Duke Health, it's often surprising how many patients are unaware how their drinking affects their health.

"Often, they didn't know there was anything wrong with what they're doing," she said. She is more frequently seeing younger patients with liver disease, including men and women in their 20s and 30s.

But women are also frequently the focus of gender-targeted advertising for alcoholic beverages. The growth of rosé sales and low-calorie wines, for example, has exploded in recent years. New research published by the International Journal of Drug Policy in February found that the "pinking of products is a tactic commonly used by the alcohol industry to target the female market."

When Canada published guidance in 2023 advising that drinking any more than two alcoholic beverages a week carried health risks, Koob sparked backlash when his comments to the Daily Mail suggested that U.S. guidelines might move in the same direction. The CDC report published in February suggested that an increase in alcohol taxes could help reduce excessive alcohol use and deaths. 

  • More info on alcohol use/alcohol marketing here.

  • Alcohol use among childbearing aged women in Maine      

  • Myths and Facts about alcohol use in pregnancy and FASD

FASD and sleep

Wilson, Donald, et al. Developmental alcohol exposure is exhausting: Sleep and the enduring consequences of alcohol exposure during development. Neurosci BioBehav Rev 2024 February 1 105567. 

doi: 10.1016/j.neubiorev.2024.105567.

Prenatal alcohol exposure is the leading nongenetic cause of human intellectual impairment. The long-term impacts of prenatal alcohol exposure on health and well-being are diverse, including neuropathology leading to behavioral, cognitive, and emotional impairments. Additionally negative effects also occur on the physiological level, such as the endocrine, cardiovascular, and immune systems. Among these diverse impacts is sleep disruption. In this review, we describe how prenatal alcohol exposure affects sleep, and potential mechanisms of those effects. Furthermore, we outline the evidence that sleep disruption across the lifespan may be a mediator of some cognitive and behavioral impacts of developmental alcohol exposure, and thus may represent a promising target for treatment.

FASD and stigma

Roozen, Sylvia, et al. Understanding the Social Stigma of Fetal Alcohol Spectrum Disorders: From Theory to Interventions. Foundations of Science (2022) 27:753–771 https://doi.org/10.1007/s10699-020-09676-y

Alcohol consumption during pregnancy can lead to fetal alcohol spectrum disorders (FASD). FASD is a spectrum of structural, functional, and neurodevelopmental problems with often lifelong implications, affecting communities worldwide. It is a leading preventable form of intellectual disabilities and therefore warrants effective prevention approaches. However, well-intended FASD prevention can increase stigmatization of individuals with FASD, women who consume or have consumed alcohol during pregnancy, and non-biolog- ical parents and guardians of individuals with FASD. This narrative review surveyed the literature on stigmatization related to FASD. Public stigma appears to be the most common form of stigma studied.

Sapru, Saloni Mitchell, Kathleen McFadden, Tonya. Combining Physician Expertise and Women’s Lived Experience to Educate Health Professionals about Preventing Fetal Alcohol Spectrum Disorders. Maternal and Child Health Journal. October 2023. https://doi.org/10.1007/s10995-023-03786-2

"Combining physicians' expertise with mothers' personal stories of lived experiences of FASDs directed at residents, who are more reflective and open at this phase of their careers, moved them from a fact-based to an empathy-based approach to learning that is critical to address the stigma surrounding the women who may be using alcohol or struggling with an AUD during pregnancy.Collaboration between national organizations allowed this intervention to be widely implemented across the country."

Alcohol effect on prenatal development - results of new high resolution imaging.

Meombe Mbolle A, Thapa S, Bukiya AN, Jiang H. High-resolution imaging in studies of alcohol effect on prenatal development. Adv Drug Alcohol Res. 2023;3:10790. doi: 10.3389/adar.2023.10790. Epub 2023 Feb 1. PMID: 37593366; PMCID: PMC10433240.

Alcohol is capable of easily and rapidly passing from the mother’s bloodstream via the placenta into the developing fetal circulation where it penetrates through blood-brain barrier, and targets multiple critical fetal organs. 

Here are some of the findings from this review of studies on high resolution imaging on effects of prenatal alcohol exposure :

​Based on a pregnancy cohort study from 8 metropolitan areas in the United States, it was found:

  • every successive week of alcohol use led to an 8% increase in the risk of spontaneous abortion and did not correlate to the number of drinks consumed per week or to binge drinking.

  • This underscores the significant fact that no known amount of alcohol is safe during pregnancy.

  • Alcohol can directly target several mechanisms at different stages of gestation and enable teratogenic effects (birth defects)

Some of these  effects include:

  • disruption of neuronal cell survival, growth, and growth pathways leading to cell death in the early gestation period

  • brain cell abnormalites - microglial cells are considered immune sentinels that are capable of orchestrating a potent inflammatory response. The microglial cells account for 0.5–16.6% of the total cell population in the human brain

  • alteration of cardiac repair cells cells  

  • dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis , responsible for managing stress and anxiety, fight or flight response 

FASD and adaptive intelligence

Hammond, Leah, et al. Adaptive behavior, sleep, and physical activity in adolescents with fetal alcohol spectrum disorder. Research in Developmental Disabilities 131 (December 2022) 104366

  • Adaptive behavior describes an individual’s capacity to manage their everyday needs and encompasses abilities such as communication, social skills, personal care, and community use. Adaptive behavior deficits reflect an important clinical feature in FASD and are included in current diagnostic guidelines.

  • Adolescents with FASD displayed significant impairments to all domains of adaptive behavior and considerable sleep disturbance.

  • Worse sleep was associated with older age and sleep-related breathing disturbances were associated with poorer social adaptive behavior.

  • Participation in physical activity, particularly organized sport, was strongly associated with better adaptive behavior.

FASD and mental health 

Coles, Claire, et al. Prenatal alcohol exposure and mental health at midlife: A preliminary report on two longitudinal cohorts. Alcohol Clin Exp Res. 2022 Feb; 46(2): 232–242

 

No benefits to moderate drinking

Moderate Drinking Has No Health Benefits, Analysis of Decades of Research Finds  

Roni Caryn Rabin NYT April 4, 2023 

The review found that the methodology of many previous studies was flawed... In more recent decades, wine — and particularly red wine — developed a reputation for having health benefits after news stories highlighted its high concentration of a protective antioxidant called resveratrol, which is also found in blueberries and cranberries. But the moderate alcohol hypothesis has come under increasing criticism over the years as the alcohol industry’s role in funding research has come to light, and newer studies have found that even moderate consumption of alcohol — including red wine — may contribute to cancers of the breast, esophagus and head and neck, high blood pressure and a serious heart arrhythmia called atrial fibrillation.

FASD identificaiton and intervention

Glass, Leila, et al. Current Considerations for fetal alcohol spectrum disorders:identification to intervention. Curr Opin Psychiatry 2023, 36:000 – 000 DOI:10.1097/YCO.0000000000000862

FASD and suicidality

Flannigan, Katherine, et al. Suicidality and Associated Factors Among Individuals Assessed for Fetal Alcohol Spectrum Disorder Across the Lifespan in Canada. The Canadian Journal of Psychiatry / La Revue Canadienne de Psychiatrie 2022, Vol. 67(5) 361‐370

Mathews, Erin, et al. White matter abnormalities in fetal alcohol spectrum disorders: Focus on axon growth and guidance. Exp Biol Med (Maywood). 2021 Apr; 246(7): 812–821

January 2022 The CDC  Alcohol Consumption and Binge Drinking During Pregnancy Among Adults Aged 18–49 Years United States, 2018–2020   

In the U.S. 1 in 7 pregnant adults reported drinking at least one alcoholic drink in the last 30 days, 5.2% reported binge drinking - four or more drinks on at least one occasion in the last 30 days. This is an increase of 2 percentage points from 2019 data, in which 11.5% of pregnancies were alcohol exposed. In New England (Region 1) the rate of reported alcohol use among pregnant adults was 1 in 6, 16.4%. This was the second highest rate in the country - Region 9 was 16.7%.

Flannigan, Katherine, et al. Responding to the Unique Complexities of Fetal Alcohol Spectrum Disorder. Frontiers in Psychology. January 2022. Volume 12. doi: 10.3389/fpsyg.2021.778471

Flannigan, K and Temple, V. Difficulties in Daily Living Experienced by Adolescents, Transition-Aged Youth, and Adults With Fetal Alcohol Spectrum Disorder. May 2020. Alcoholism Clinical and Experimental Research 44(1) DOI: 10.1111/acer.14385

 

FASD and Choline supplementation

Ernst, Abigial M., et al. Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder. Nutrients 2022, 14, 688. https://doi.org/10.3390/nu14030688

Jacobson, Sandra W., et al. Efficacy of maternal choline supplementation during pregnancy in mitigating adverse effects of prenatal alcohol exposure on growth and cognitive function: A randomized, double-blind, placebo-controlled clinical trial. Alcohol Clin Exp Res. 2018 July ;42(7): 1327–1341. doi:10.1111/acer.13769

Prenatal Alcohol Exposure

U.S. Prevalence of Alcohol Use Among Pregnant Adults by Region  CDC January 2022

CDC Maine Rate of Alcohol Use Among Women Aged 18-44 

CDC Maine Rate of Binge Drinking Among Women Aged 18-44

Maine PRAMS Data Alcohol Use During Last Trimester

Concurrent Drug Use and Alcohol Use 

Page, Kimberly, et al. Prevalence of Marijuana Use in Pregnant Women with Concurrent Opioid Use Disorder or Alcohol use in Pregnancy. Addiction Science & Clinical Practice (2022) 17:3

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8734065/#CR46

Bakhireva, Ludmila, et al. Prevalence of Alcohol Use in Pregnant Women with Substance Use Disorder. Drug Alcohol Depend.2018 June 01;187:305-310

 doi:10.1016/j.drugalcdep.2018.02.025

Jarlenski, Marian, et al. Polysubstance use among US women of reproductive age who use opioids for nonmedical reasons. Am J Public Health. 2017 August; 107(8): 1308–1310

 

Prevalence of FASD

May PA, et al. Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities. JAMA. 2018 Feb 6;319(5):474-482

Bell, Carl C, et al. Prevalence of Neurodevelopmental Disorders Among Low-income African Americans at a Clinic on Chicago's South Side. Psychiatr Serv. 2015 May 1;66(5):539-42

Nakhoul, Marie R., et al. Fetal Alcohol Exposure: The Common Toll. J Alcohol Drug Depend 2017 Feb:5(1):257

A comprehensive review combining the molecular as well as the gross physiological and anatomical effects of prenatal alcohol exposure.

Chasnoff, Ira, et al. Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics. 2015 Feb;135(2):264-70

Smith, Vincent, et al. Caring for Patients with Prenatal  Alcohol Exposure: A Needs Assessment. J Popul Ther Clin Pharmacol Vol 24(1):e25-e39; January 27, 2017

"Prenatal alcohol exposure (PAE) is the United States’ most common preventable cause of birth defects and intellectual and developmental disabilities collectively referred to as Fetal Alcohol Spectrum Disorders (FASD). This study was designed to identify gaps in pediatric providers’ knowledge and practices regarding FASD patient identification, diagnosis, management and referral, and to inform needs-based FASD resource development."

Stigma and FASD

Corrigan, Patrick, W. et al. The Public Stigma of Birth Mothers of Children with Fetal Alcohol Spectrum Disorders. Alcohol Clin Exp Res 2017 Jun;41(6):1166-1173. doi: 10.1111/acer.13381

Flannigan, Katherine, et al. Responding to the Unique Complexities of Fetal Alcohol Spectrum Disorder. Front Psychol 2022 Jan 25;12:778471. doi: 10.3389/fpsyg.2021.778471

American Academy of Pediatrics

Screening for Prenatal Alcohol Exposure: An Implementation Guide for Pediatric Primary Care Providers

Genetic Vulnerability of Fetus

Hemingway Astley, Susan J., et al. Twin study confirms virtually identical prenatal alcohol exposures can lead to markedly different fetal alcohol spectrum disorder outcomes - fetal genetics influences fetal vulnerability. Advances in Pediatric Research. 2019;5:23

FASD 

Hagan, Joseph Jr., et al. Neurobehavioral disorder associated with prenatal alcohol exposure. Pediatrics2016 Oct;138(4):e20151553     ND-PAE

Glass, Leila, et al. Academic Difficulties in Children with Prenatal Alcohol Exposure: Presence, Profile, and Neural Correlates. Alcohol Clin Exp Res. 2017 May ; 41(5): 1024-1034 doi:10.1111/acer.13366

Glass, Leila, M.S. and Mattson, Sarah N. PhD.  Fetal Alcohol Spectrum Disorders: A Case Study. J Pediatr Neuropsychol. 2017 June ; 3(2): 114–135. doi:10.1007/s40817-016-0027-7

Jirikowic,Tracy, et al. Prevalence and patterns of sensory processing behaviors in a large clinical sample of children with prenatal alcohol exposure. Research in Developmental Disabilities. 2020 May;100:103617.doi:10.1016/j.ridd.2020.103617

Astley, Susan, J., et al. The essential role of growth deficiency in the diagnosis of fetal alcohol spectrum disorder.Advances in Pediatric Research. 2016;3:9

McLachlanan, K., et al. Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.Alcohol.2016 June ; 53: 9–18. doi:10.1016/j.alcohol.2016.03.003

Jirikowic, Tracy, et al. Regulatory Behaviors and Stress Reactivity Among Infants at High Risk for Fetal Alcohol Spectrum Disorders: An Exploratory Study. Journal of Mental Health Research in Intellectual Disabilities. 9:3; 171-188. DOI: 10.1080/19315864.2016.1183246

James, Jan  E., et al. Sleep health issues for children with FASD: Clinical considerations. Int J Pediatr. 2010; 2010:1–7

 

McLaughlin, Susan A., et al. Listening Difficulties in Children With Fetal Alcohol Spectrum Disorders: More Than a Problem of Audibility. J Speech Lang Hear Res. 2019 May 21;62(5):1532-1548. doi: 10.1044/2018_JSLHR-H-18-0359

 

Stephen, Julia M., et al. Delays in auditory processing identified in preschool children with FASD. Alcohol Clin Exp Res. 2012;36(10):1720-1727

Rachappa, Mallikarjuna and Nalawade, Triveni. Alcohol, It’s Effect on Dental Structures and the Role of a Dentist. J Alcohol Drug Depend. 2014 Jan;2(4):166. DOI: 10.4172/2329-6488.1000166

Chen, Maida Lynn, et al. Sleep problems in children with fetal alcohol spectrum disorders. J Clin Sleep Med. 2012 Aug 15;8(4):421-9

Bell, Stephanie H., et al.The remarkably high prevalence of epilepsy and seizure history in fetal alcohol spectrum disorders. Alcohol Clin Exp Res. 2010 Jun;34(6):1084-9

Chasnoff, Ira, et al. Misdiagnosis and missed diagnoses in foster and adopted children with prenatal alcohol exposure. Pediatrics. 2015 Feb;135(2):264-70

Khazan, Olga.When ADHD Isn't What It Seems. The Atlantic. January 15, 2015

(Ira Chasnoff interview)

Jarlenski, Marian, et al. Polysubstance use among US women of reproductive age who use opioids for nonmedical reasons. Am J Public Health. 2017 August; 107(8): 1308–1310

Nutritional Supplementation and FASD (Choline)

"Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions.

These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories."

Jeffrey Wozniak PhD 2015 FASD Choline Supplementation Webinar Video

 

Active Study on Choline Supplementation as a Neurodevelopmental Intervention in Fetal Alcohol Spectrum Disorders Study (CHOLINE4) 2022

This is a randomized, double-blind controlled trial of choline supplementation in children with Fetal Alcohol Spectrum Disorders (FASD). The study is comparing two administration durations (3 months vs. 6 months) of choline. The primary outcome measures are cognitive measures.

Eligible: Children ages 30 to 72 months

For more information about participating in this study

Jeff Wozniak, University of Minnesota

For more information about previous choline studies

Collaborator:National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Ernst, A., et al. Prenatal and Postnatal Choline Supplementation in Fetal Alcohol Spectrum Disorder Nutrients. 2022 Feb; 14(3): 688

2022 Feb 6. doi: 10.3390/nu14030688

Dr. Carl Bell MD

Northeast Conference on Fetal Alcohol Spectrum Disorders 2017 

Colby College, Maine

Dr. Bell presented on the use of choline supplementation in the treatment of FASD, prenatally and in early childhood.

Jacobson, Sandra, et al. Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Alcohol Clin Exp Res. 2018 Jul;42(7):1327-1341

Kable, J.A., et al.The Impact of Micronutrient Supplementation in Alcohol Exposed Pregnancies on Information Processing Skills in Ukranian Infants. Alcohol 2015 Nov;49(7):647-656

Coles, Claire D., et al. Dose and Timing of Prenatal Alcohol Exposure and Maternal Nutritional Supplements: Developmental Effects on 6-Month-Old Infants. Matern Child Health J. 2015 Dec;19(12):2605-14

NIH/NIAAA Current Study 

Fetal Alcohol Spectrum Disorders (FASD) in Adults: Health and Behavior

Principal Investigators: Claire Coles, Ph.D. (Emory University, Atlanta, Georgia), Therese Grant Ph.D. (University of Washington, Seattle, Washington)This current NIH/NIAAA-funded research addresses the deficit of research on adults with FASD with the following Specific Aims: 1) Establish a registry of 500 individuals, older than 30 years of age, with known alcohol exposure/FASD diagnosis or who are matched controls who will respond to a health survey, and who will be available for future studies; 2) Evaluate in depth current physical health, mental health, and functional status among affected individuals (FAS or FASD) and controls (120 from Seattle and 120 from Atlanta);  with the goal of refining diagnostic criteria for FASD in this age group and determining the persistence and severity of disability associated with PAE. and 3) Assess immune status in collaboration with Dr. Weinberg (University of British Columbia) and identify outcomes associated with health indicators. 07/01/17 through 06/30/22

Advances in Research on Fetal Alcohol Spectrum Disorders.NIAAA Spectrum Fall 2020 12(3)

FASD  Interventions

 

Carmichael Olson, Heather and Montague, Rachel A. An Innovative Look at Early Intervention for Children Affected by Prenatal Alcohol Exposure. Prenatal Alcohol Use and FASD: Diagnosis, Assessment and New Directions in Research and Multimodal Treatment, 2011, 64-107

Paley, Blair, Ph.D, O'Connor, Mary J. Ph.D. Behavioral Interventions for Children and Adolescents With Fetal Alcohol Spectrum Disorders. Alcohol Res Health. 2011; 34(1): 64–75

Petrenko, Christie L. M. PhD. Positive Behavioral Interventions and Family Support for Fetal Alcohol Spectrum Disorders. Curr Dev Disord Rep. 2015 Sep; 2(3): 199–209

Jirikowic,Tracy, et al. Children and Youth with Fetal Alcohol Spectrum Disorders: Summary of Intervention Recommendations after Diagnosis. Intellect Dev Disabil. 2010 Oct;48(5):330-44

Petrenko, Christie L. M., et al.The Association Between Parental Attributions of Misbehavior and Parenting Practices in Caregivers Raising Children with Prenatal Alcohol Exposure: A Mixed-Methods Study. Res Dev Disabil. 2016 Dec;59:255-267

“Caregivers who attributed their child's misbehavior to underlying neurodevelopmental disabilities were more likely to use antecedent strategies and feel more confident in managing their child's behavior. Parents who attributed their child's misbehavior to willful disobedience were more likely to rely on consequence strategies and feel more ineffective.”

FASD Sensory Processing Disorder     Occupational Therapy

Jirikowic, Tracy L. et al. Prevalence and Patterns of Sensory Processing Behaviors in A Large Clinical Sample of Children with Prenatal Alcohol Exposure. Research in Developmental Disabilities 2020;(100)

Fjeldsted, Brenda and  Xue, Lin. Sensory Processing in Young Children with Fetal Alcohol Spectrum Disorder. Phys Occup Ther Pediatr​2019;39(5):553-565

Franklin, Laureen, et al. Children with Fetal Alcohol Spectrum Disorders: Problem Behaviors and Sensory Processing. Am J Occup Ther​. May-Jun 2008;62(3):265-73

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