Perspective Chapter: Autism Spectrum Disorder Neurophenotype with Preconceptional and Prenatal Alcohol Exposure – A Call for Industry Responsibility in Prevention

Abstract

Preconceptional and prenatal alcohol exposure is a widespread, costly, and preventable influence on neurodevelopment contributing to Autism Spectrum Disorder. Neurodevelopmental Disorder associated with Prenatal Alcohol Exposure is a heterogeneous neurophenotype that underscores the importance of etiology in diagnosis, treatment, and prevention. Expanding upon previously published clinical implications, this perspective elucidates a phenomenology describing neurophenotypic heterogeneity leading to a range of clinical neurophenotypes including Autism Spectrum Disorder as well as neurodevelopmental issues and neuropsychiatric problems. Given that ND-PAE affects up to 1 in 20 people, a pandemic-level public health response is warranted to prevent and treat preconceptional and prenatal alcohol exposure. Given the widespread use of alcohol during reproductive years, governmental enforcement of industry responsibility in consumer protection should include point of sales labeling and risk reduction advertising about the reproductive effects of alcohol products. Widespread dissemination of public health information by physicians and allied health professionals would help improve awareness that use of the solvent (alcohol) can cause reproductive health effects to gametes, zygotes, embryos, and fetuses. Improvements in screening for ND-PAE, nonjudgmental discussions with biological parents about preconceptional alcohol use, pregnancy planning through contraceptive access, and marketing mandates may reduce unintentional exposures prior to pregnancy recognition.

1. Introduction

Alcohol is a prevalent and potent neuroteratogen affecting as many as 1 in 20 Americans [1], and a worldwide cause of atypical neurodevelopment, particularly due to exposures in unplanned or mistimed pregnancies for “social drinkers” [2, 3]. Clinically, Neurodevelopmental Disorder associated with Prenatal Alcohol Exposure (ND-PAE) and Autism Spectrum Disorder (ASD) have overlapping clinical features [4], in part due to the symptom-based diagnostic paradigm of the Diagnostic and Statistical Manual of Psychiatric Disorders (DSM-5) [5], with few psychiatric symptoms being mutually exclusive to a single psychiatric condition. Since human neurodevelopment is complex and dependent on multifactorial processes, it is no wonder that we have such heterogeneity of expressed neurophenotypes. Alcohol as a solvent perhaps is perhaps the most quintessential neurodevelopmental teratogen known to mankind.

Effects of prenatal alcohol exposure (PAE) exist on a continuum, with milder cases exposed to as few as 7 drinks per week (1 serving per day on average) associated with attention deficits and as few as 4–5 consumed during the late 3rd to early 4th week post conception causing the full Fetal Alcohol Syndrome (FAS) [6]. Alcohol can affect human development at any point from preconceptionally (gametogenesis) to the first few weeks post conceptionally (neurulation and gastrulation through organogenesis) [7] through fetal development to birth. Lactation is also a time when the newborn and infant can be exposed to and affected by a mother’s use of alcohol [8]. Neurodevelopmental effects of PAE involve brain functions as well as sensorium (cranial nerves and sensory neurons), motor neurons, autonomic regulation, and neurotransmitter systems. These effects have been described in the DSM-5 as ND-PAE, yet there remains a lack of acknowledgement, understanding, and recognition in the psychiatric community for this diagnosis. Nonetheless, scholars are attempting to highlight the link between PAE and neuropsychiatric illness [9].

Neurodevelopmental complexity of symptoms associated with prenatal alcohol exposure can lead to an ASD-like phenotype, including social communication deficits, neurocognitive issues (e.g., executive functions), sensory integration problems (e.g., interoception, hypo/hypersensitivities), motor deficits, and emotional dysregulation. All of the body systems can be affected by PAE, including immune, endocrine, reproductive, metabolic, cardiovascular, urinary, gastrointestinal, and integumentary. Alcohol affects both the developing sperm up to 3 months preconceptionally (DNA histone modifications) as well as beginning as early as weeks 2–3 post-conception. Research implicates alcohol consumption during adolescence with epigenetic effects on gametes, leading to alterations in the hypothalamic stress response system [10].

Likewise, Autism Spectrum Disorder (ASD) is a broad, umbrella term describing complex atypical neurodevelopment due to a wide array of multifactorial etiologies [11]. Williams and Lewis have developed a useful clinical screening tool for ASD [12]. As a neurophenotype [13], ASD has a wide range of symptoms which can be due to preconceptional epigenetic insults to gametes, in utero prenatal exposures to neuroteratogens, genetic (familial) hereditary anomalies, early neurologic birth traumas, and as yet unidentified causes [14]. The heterogeneity of ASD as well as the plethora of etiological factors are beyond the scope of this chapter. Given the range of unknown and otherwise as yet nonpreventable causes of ASD, any reductions in etiology due to a substance so ubiquitous as alcohol would reduce the societal burden of this otherwise complex, difficult to treat condition.

Since human neurodevelopment is multifactorial, with genetic, epigenetic, and environmental influences, exact etiological associations in each child difficult to elucidate. A proposed paradigm for atypical neurophenotypic development is described in Figure 1, which is adapted from Picci and Sherf [15]. The combination of preconceptional issues, genetics, epigenetics, and the prenatal environment are exacerbated by adverse childhood experiences (ACEs) and adolescent use of alcohol, tobacco and other drugs – which are cumulative effects to disrupt healthy neuronal development. This model shows prenatal alcohol exposure in the context of an individual zygote’s biological background of epigenetic and/or genetic factors, such as familial autism traits and/or predisposition to effects of prenatal alcohol exposure (e.g., CYP-450 enzyme expression in the mother or fetus). The first preventable hit to neurodevelopment is preconceptional or prenatal use of alcohol, whereas the model assumes that the epigenetic and genetic background of the zygote may not be changed. In order to effectively prevent the first hit, one must contracept if using alcohol and must stop using alcohol up to 3 months preconceptionally in order to prevent epigenetic influences on spermatogenesis. The second hit, ACEs, is currently identified by childhood screening for abuse and neglect, though beyond the scope of this chapter. Further alterations in neurodevelopment happen when adolescent use of substances such as alcohol, tobacco and other drugs, often triggering psychosis, mania, or other severe and persistent mental illness. Hence, the term “neurodevelopmental” may be best understood in the context of the neurological development of mental disorders.

Figure 1.

3-hit model of “neuro-develop-mental” damage.

Because DSM-5 is based on symptomatology, etiological factors of neurodevelopmental conditions are conceptualized by psychiatrists and mental health practitioners as secondary or inconsequential to diagnostic criteria and treatment paradigms. Co-morbidity of ASD and ND-PAE blurs the clinical picture, leaving psychiatrists, pediatricians, mid-level providers, and allied health professionals with a laundry list differential diagnoses and complex formulations. Individuals with prenatal alcohol exposure are at risk for many DSM-5 psychiatric and neurodevelopmental conditions [16]. Co-occurrence may be overlooked for affected children who may have been exposed prior to pregnancy recognition or who have preconceptional alcohol-induced epigenetic factors that would not show up on chromosomal karyotype or genetic microarray analysis [17]. Neurobiology, neuropsychiatry, neuroimaging, and neurogenetics may assist in clarifying clinically overlapping phenotypes (i.e., co-morbid ASD and ND-PAE) when prenatal alcohol exposure is known.

2. Alcohol’s impact on evolution, epigenetics, neurodevelopmental (functional) birth defects, and the etiology of ASD

The origins of the earliest fertile crescent agricultural settlements have been associated with the production of beer for feasting and celebrations as early as the pre-pottery neolithic age (PPNA) [18] approximately 11,500 to 11,000 years ago around the end of the last ice age. Homo sapiens is the only species to have fermented, distilled, and mass-produced alcohol for large scale population consumption and exposure to laboratory animals to study the effects. Alcohol is therefore the oldest and most pervasive recreationally used neurodevelopmental teratogen, affecting human neurodevelopment since the earliest known neolithic agricultural settlements. Hence, widespread use of our social drug of choice has influenced human evolution through preconceptional (epigenetic) and prenatal exposures since those ancient times. Alcohol metabolic variants have been found among Southeast Asian human populations [19], with their fermentation of rice and berry wines dating back to 6500 to 7000 BC [20]. Hence, alcohol’s transgenerational effects for 10,000 years on our evolution as a species may account for metabolic and phenotypic variance in human populations.

Given the range of effects on developing limbic brain systems, some of our most severe mental illnesses can be traced to preconceptional and prenatal alcohol exposure. Many neuropsychiatric and neurodevelopmental conditions are reported to be familial and/or transmitted intergenerationally, most likely through epigenetic [21], multifactorial gene–environment interactions. Prenatal and preconceptional alcohol exposure result in genetic and epigenetic [22] variants, which also have been described in ASD [23], schizophrenia [24], as well as other neuropsychiatric conditions [25]. Further, genetic and epigenetic variants of serotonin, dopaminergic and norepinephrine metabolism may account for the clustering of mental health disorders such as schizophrenia and bipolar disorder in families with histories of alcohol abuse.

2.1 Epigenetics, teratogenicity, and neurodevelopmental (functional) birth defects

Neurodevelopmental teratogens are chemicals that cause functional birth defects in the developing zygote or embryo. In contrast to physical birth defects, functional (or neurodevelopmental) birth defects are those associated with changes in brain, central nervous system, sensorium, motor nerves, and somatosensory function [26]. Alcohol has long since been known to be a potent, prevalent and preventable neurodevelopmental teratogen leading to atypical social communication, neurocognitive processes, sensory integration and motor problems, and mood regulation/autonomic arousal. These children, adolescents, and young adults often have difficulty with adaptive functions (conceptual, social, and practical skills) despite a relatively normal intellect.

Neuroteratologists define functional birth defects as abnormalities in neurological, immune and endocrine systems, in contrast to physical anomalies such as phocomelia, cleft lip or palate, hypospadias or other structural malformations. Whereas structural problems may be identified at birth, functional abnormalities can take months or years to identify. Alcohol can cause physical birth defects but is more potent as a neurodevelopmental teratogen. An increased understanding of epigenetic effects on neurodevelopment may expand the definition of neuroteratogens to include chemicals that cause methylation effects in the gametes, not simply effects in the embryo, zygote and fetus.

Alcohol has long been described as a neurodevelopmental teratogen, affecting sperm beginning as early as 3 months preconceptionally (epigenetic) and within 2 to 3 weeks postconceptionally in the embryo (teratogenic). An array of de novo DNA damage (microdeletions, microinsertions, translocations) can happen as a result of alcohol’s effects on the gamete, conceptus, zygote, early embryo and fetus. Carefully designed animal studies and epidemiological human studies have provided clues to the neurodevelopmental teratogenicity of alcohol – leading to many different types of de novo microdeletions, insertions, translocations, and epigenetic mechanisms for atypical development.

An appreciation of the epigenetic influence on ND-PAE begins before conception and embryonic neurodevelopment. Spermatogenesis takes 3 months for sperm maturation, during which time the male gametes are susceptible to a father’s use of alcohol. Epigenetic effects mediated by histone protein methylation during spermatogenesis make the zygote and early embryo more susceptible to neuroteratogenic effects of prenatal alcohol exposure (i.e., maternal alcohol use) [27]. This epigenetic susceptibility of the zygote interacts with maternal factors (e.g., timing, duration, blood alcohol concentration, nutrition, metabolism, stress hormone secretion, other drug exposure) to worsen the prognosis.

2.2 ND-PAE as a preventable cause of ASD

Developmental deficits, executive functioning issues, neuropsychiatric sequelae, and adaptive functioning issues make ND-PAE a challenging, under-appreciated, and costly neurodevelopmental condition for the individual, family and society [28]. Given the association between prenatal alcohol exposure, neuroteratogenicity, and de novo genetic changes, our social drug of choice, alcohol may be the leading known and preventable cause of ASD. Gamete and embryonic exposure leading to microdeletions and insertions associated with autism features. As a solvent, alcohol is lipophilic – penetrating every barrier in the human body, from the blood–brain barrier to the maternal-fetal circulation, to the gut-circulatory system. Clinical overlap between symptoms necessitates a careful preconceptional and prenatal history to accurately identify patients with ND-PAE with or without comorbid ASD.

Despite public health warnings by the Centers for Disease Control and Prevention (CDC) for women to abstain from alcohol if pregnant or planning to be, and to contracept if using alcohol, the Fetal Alcohol Spectrum Disorder incidence has been reported to be as high as 1 in 20 grade school children in the United States. The simple fact that neuroteratogenic effects of prenatal alcohol exposure begins as early as the late 3rd to early 4th week post conception means that an unplanned pregnancy in a “social drinking” couple may be associated with exposure prior to pregnancy recognition. Recent reports indicate the convergence of two “perfect storm” situations: nearly 50% of pregnancies are mistimed or unplanned and drinking rates among childbearing age women has been steadily on the rise, exceeding that of males for some age groups.

Like other DSM-5 conditions, the diagnosis of Autism Spectrum Disorder (ASD) as a DSM-5 disorder is made based on symptoms rather than etiology, with a wide array of genetic and environmentally-acquired issues giving rise to the phenotypic expression. A number of neurodevelopmental teratogens have been identified in our human ecosystem, from petroleum derivatives, solvents, recreational substances, and pharmaceuticals. However, the heterogeneity of symptoms and difficulty with cause-effect clinical research has left large gaps in understanding etiology of autism spectrum disorder, outside of the known associated rare genetic disorders [29]. The American Academy of Child and Adolescent Psychiatry recommends genetic testing (chromosomes and a microarray) of individuals with ASD to rule out genetic variants associated with syndromic conditions. Findings may not be associated with any known clinical disorder because of the range of possible mutations that may lead to a phenotypic change.

3. A four domain clinical model

A previously published model describes four domains of clinical functioning impacting an individual’s adaptive functions. These domains may be scaffolded by family, school, therapeutic, or community supports to improve an individual’s adaptive functions. The clinical presentation may manifest as a plethora of externalizing neurobehavioral symptoms masking intrinsic neurodevelopmental deficit. This model can help elucidate the domains of functional deficits to help scaffold the child, adolescent, or young adult with appropriate systems of care to reduce their sensory overstimulation, social pragmatic issues, and/or frustration from neurocognitive issues to minimize outbursts. For example, a child may be having mood outbursts or rage due to hypersensitivity to crowded places (school bus, classroom, playground, lunchroom), people (facial expressions, voice tone, body odor, etc.), sounds (sirens, TV, voice frequency or volume, screechy noises, chalkboard, etc.), smells (food odors, body odor, smoke, decaying trash, sewer, public bathroom, etc.) (Figure 2).

Figure 2.

Four domain model of neurodevelopmental issues.

3.1 Social communication (social intellect)

Speech and language pragmatics, receptive and expressive language deficits, nonverbal cue recognition, facial expressions, body language, and a variety of other social communication issues can be affected by prenatal alcohol exposure. Social misperceptions, suspiciousness, feeling judged and scrutinized by peers, misunderstanding constructive criticism, personalizing negative comments, over-reacting to social slights are common consequences of the miswiring of neural networks important in social cognition. From an early age, social communication issues are tied to maladaptive attachment behaviors as the individual may lack a social smile, eye contact, and typical attachment behaviors. During early childhood and latency years, these deficits leave the individual vulnerable to social problems and negative peer interactions. By middle school, atypical social interactions leave the adolescent vulnerable to bullying and harassment by peers who misunderstand their social deficits and mood dysregulation or have outpaced them in their social and emotional functioning. Affected individuals’ atypical reactions to social slights may cause social disenfranchisement and maladaptive peer interactions (e.g., friends’ anger and/or hurt feelings, estrangement from social groups, fear responses in peers, etc.). Often, alexithymia (difficulty recognizing their own emotions and that of others) and poor social perceptions lead family and friends feeling they lack empathy and compassion. Socially awkward facial expressions and nonverbal cues may lead others (e.g., teachers, principals, administrators) to feel they are narcissistic, callous and unemotional. Because of lack of understanding social risk and subtleties of community safety, often these individuals are at risk of having predatory behavior perpetrated against them. Their social dysmaturity makes relationships with younger individuals feel more comfortable, which can lead to inappropriate interactions with peers.

3.2 Neurocognitive (general intellect and executive functions)

Only 10–15% of individuals affected by prenatal alcohol exposure have intellectual disability (IQ at or below 75 per DSM-5) according to research by the National Institutes on Alcohol Abuse and Alcoholism. Executive functioning issues (organization, planning, time management, working memory, problem solving, visual spatial planning, etc.) are more common sequelae of prenatal alcohol exposure, with attention deficits associated with as little as 1 drink per day or up to 7 drinks per week. Hyperactivity and impulsivity (failure to inhibit unwanted behaviors) lead the individual to be seen as willful and destructive, immature or dysmature, and unable to self-regulate at home, in the classroom, and in the community. These subtle yet important neurodevelopmental functions leave the individual prone to learning challenges, academic failure, vocational problems, and difficulties transitioning into young adulthood. Often, their faulty ego strength masks their challenges, leading to a sense of “false bravado.” The resulting subconscious over-inflation of their strengths to hide their challenges can lead the individual to appear haughty, grandiose, narcissistic, and flamboyant. Faulty information processing combined with impulsivity, deficits in consequential thinking and understanding social risk may lead the individual to confabulate, steal, cheat, or be vulnerable to predatory behavior.

3.3 Sensory and motor (sensorium and kinesthetic intellect)

Our somatosensory, cranial nerves, and voluntary nervous systems are as intricately wired and vulnerable to the effects of prenatal alcohol exposure as our higher-level brain functions. In fact, the midline brain defects linked to prenatal alcohol exposure from the neural crest cell migration all the way to development of the brain, cranial nerves, somatosensory and motor neurons can be affected by alcohol. Hence, hyper- and hyposensitivities to noise, texture, temperatures, and even interoceptive signals can lead to sensory integration issues. Interoceptive deficits can cause difficulty accurately perceiving signals from the digestive system (e.g., normal digestive sensations from peristalsis, gas, bloating, indigestion, stomach aches, hunger cues), rectum and bladder (defecation and urination signals). These interoceptive signaling issues often lead to emotional outbursts due to lack of understanding of the source of the discomfort and/or frustration/embarrassment due to voiding accidents. Children with interoceptive deficits may have delays in bowel and bladder control, nocturia, fecal smearing (caused by overflow incontinence), somatosensory complaints, and heightened stress response or mood dysregulation caused by hypersensitivities to environmental stimuli.

3.4 Emotional regulation (emotional quotient)

Prenatal alcohol exposure affects the sympathetic and parasympathetic nervous system, leading to emotional dysregulation, autonomic arousal (fight or flight response), sleep–wake cycle disturbances, and a variety of mood problems. Often, affected individuals are irritable, easily frustrated, annoyed, and provoked into heightened stress response by facial expressions, sensory overstimulation, or unpreferred activities. Their emotional dysmaturity leads them to seem years younger than their chronological age, to revert to more primitive mood states during stressful situations, and to be overreactive to discomfort and distress. They are perceived as infants and toddlers as emotionally dysregulated, fussy, hyper-reactive, clingy, and easily fatigued.

4. Patient perspective

A Patient presents for an intake assessment, which includes a comprehensive childhood history questionnaire complete with questions about intendedness of pregnancy (mistimed or unplanned), prenatal exposures, paternal use of substances. A very careful preconceptional and prenatal history may reveal unintentional exposures to alcohol or other drugs prior to pregnancy recognition. The history also includes history of neglect, abuse, and other adverse childhood experiences; developmental milestones (speech/language delays, social relatedness, gross/fine motor deficits, coordination problems, sensory hypo- or hypersensitivities, toileting issues). During the assessment, we find that the birth mother drank two glasses of wine per day up until week 7 post conception at the point of pregnancy recognition. The mother is Asian with alcohol dehydrogenase (ADH) enzyme variant leading to rapid metabolism of alcohol into acetaldehyde, a highly neurotoxic metabolite. Therefore, she would have higher blood acetaldehyde levels during gastrulation, neurulation, other critical points during neurogenesis, and a majority of organogenesis. Whereas she may have stopped drinking at the point she learned she was pregnant, much of neurodevelopment had already occurred at the time she stopped drinking. Her child at age 10 presents with years of distress in school due to inattention, hyperactivity, impulsivity; learning disabilities; sleep–wake cycle dysregulation; difficulty with fine and gross motor as well as coordination and balance; social communication issues (i.e., speech/language issues, pragmatic difficulties, nonverbal facial expression recognition, and decreased empathy), and sensory disintegration. There is no family history of similar problems, he has a neurotypical younger brother, and he had a normal karyotype analysis with reflex microarray. A discussion with his parents about the etiology of their son’s neurodiversity helps convey a sense of responsibility on the part of the parents who had previously demeaned and demoralized the patient with statements like “You’re a bad seed. Why can’t you be like your brother? You need to try harder. You’re stupid!” as a way to motivate better behavior.

The first step in assessing the child or adolescent with ND-PAE is to assess and treat underlying sleep issues. Psychoeducation for the child and parent on the importance of adequate sleep for mental, physical, social and academic functioning; reviewing sleep hygiene; and providing information about natural sleep aids such as melatonin, magnesium 400 mg, lavender 500 mg or chamomile tea 30 minutes before sleep can be helpful to minimize medications. By improving sleep, we can reduce reliance on medications and improve the patient’s overall wellbeing. In the event these gentler approaches do not work, use of alpha adrenergic agonists like clonidine to down-regulate the sympathetic overdrive before sleep then the long-acting form (Clonidine ER 0.1 mg twice daily) to maintain sleep allows for a single medication to treat sleep, anxiety/heightened stress response, and ADHD symptoms. Other medications such as propranolol can be effective for sleep and anxiety but not necessarily for ADHD.

After the child is sleeping well, if regulation of mood is needed, an antiseizure medication such as lamotrigine or gabapentin can be helpful to reduce the seizure like irritability of the brain. Starting with a very low dose of lamotrigine 12.5 mg twice daily (or lamotrigine long acting 25 mg once daily after a meal) and gradually increasing by no more than a total of 25 mg per week until on 100–200 mg twice daily (depending on the age of the child) will reduce the frequency, duration, and intensity of the outbursts. It is necessary to have careful discussion with parents about the potential for rash and recommendation for them not to change any of their detergents, soaps, lotions or other hygiene products while the medication is being started and increased. In the event of poor response after a couple of months on the therapeutic dose, a transition to gabapentin or topiramate would be another choice to improve their symptoms.

Affected individuals have a hard time achieving Maslow’s Hierarchy (food clothing, shelter; safety/security; love, belonging and sense of community; and meaning/purpose); therefore self-actualization is as challenging as basic practical life skills, social aptitude and integration of academic skills into daily life. Beginning at young ages, developing a sense of purpose through hands-on experiences in nature and with farm animals or other meaningful activities can improve their self-esteem. These multisensory experiences desensitize children to environmental stimuli, enhance their self-esteem through accomplishments caring for animals, and improve social relationships through attachments with animals. Addressing adoptive parental rights and the affected individual’s rights to birth history exposure information will also improve outcomes for affected children by providing insight into etiology of their neurodevelopmental condition. Further, positive parenting approaches, self-regulation of adults around them, mindfulness, skill building and immersion in nature will create resiliency and a healthy sense of self.

5. The Industry’s responsibility

Whereas alcohol taxes are embedded in most governmental gross domestic profits, the industry seems immune to mandated responsibility for health consequences due to its products (beer, wine, or liquor) [30]. Social responsibility should account for more than prevention efforts [31]. The pharmaceutical industry is required to make reparations for damage from its products, yet the alcohol industry has no financial or legal accountability for ND-PAE or other medical problems. Like big tobacco was sued by states for the Medicaid and Medicare costs of people with emphysema, cancers, and other medical conditions [32], perhaps states should consider the inordinate costs associated with preterm labor, infant morbidity, developmental services for infants and toddlers, special education, juvenile and criminal justice, productive life years lost, and health/human services costs from adults with disabilities due to prenatal alcohol exposure.

6. Conclusions

While much is known about the effects of alcohol on embryogenesis (prior to pregnancy recognition) and methylation effects to gametes, the alcohol industry has bore little responsibility in prevention or treatment. A plethora of research indicates embryos are more vulnerable to the mother’s use of alcohol if the father also consumes alcohol during the 3 months preconceptionally. Little has been shared with the public about the implications of epigenetic methylation effects during spermatogenesis, likely due to the paucity of interest in the media. Further, the psychiatric community remains befuddled by the ND-PAE diagnosis, with clinicians using symptom clusters rather than etiology for diagnosis – largely based on the DSM-5 methodology. Clearly it would not be in the interest of alcohol manufacturers and distributers to have truth in labeling and advertising its product to include the warnings about epigenetic and early pregnancy effects. However, in the interest of public health, strong consistent messaging and warnings at every point of purchase as well as in marketing of alcohol would improve the knowledge of alcohol consumers and hopefully the use of contraceptives to prevent inadvertent exposures. Likewise, messaging in hospitals, health care facilities, physician offices, pregnancy test kits, and contraceptive packaging may improve the likelihood that couples would contracept if using alcohol and avoid alcohol if pregnant or planning to be, which is the 2016 revised CDC guidelines [33].

Problems in accurately diagnosing prenatal alcohol exposure as an etiological basis for autism spectrum stems from lack of understanding and recognition by geneticists, dysmorphologists, developmental pediatricians, neurologists, psychiatrists, and “mid-level providers” (nurses, physician assistants) and allied health professionals (social workers, speech/language pathologists, occupational therapists, physical therapists, applied behavioral analysts) who commonly see these children in practice. Additionally, research on the effects of prenatal alcohol exposure tend to be published in obscure research journals read by a paucity of clinicians (e.g., Alcohol Health and Research). Lack of appreciation for the numbers of affected children (1 in 20) by policymakers and legislatures may stem from financial incentives to overlook the influence of alcohol on many of our social ills (such as prenatal/preconceptional brain damage leading to the pipeline to prison). Political campaigns all the way back to our first President George Washington have been funded by the very drug causing many of these problems; therefore, it presents an ethical conundrum for policymakers and legislators.

A neurodevelopmental approach to diagnosis and treatment enables specificity in surveillance efforts, improved prognosis through the life course, and prevention through preconceptional approaches. While neurodevelopment is multifactorial, distinguishing ND-PAE co-occurring with ASD (i.e., as an etiological subtype for some affected individuals, like genetic causes) would enable improved specificity of surveillance and targeted clinical trials of therapies for the underlying neurodevelopmental lesions, leading to improved treatment efficacy and clinical prognosis (i.e., possibly reducing the burden of severe and persistent mental illness such as schizophrenia for the individual). Elucidating etiology (i.e., prenatal alcohol exposure) identifies the individuals who may suffer from underlying cardiac defects, susceptibility to seizure disorders, metabolic anomalies, propensity to CYP-450 enzyme variants, and a variety of other underlying contraindications to certain medications. From a public health perspective, distinguishing prenatal alcohol exposure as a preventable cause of ASD would help improve policy and prevention efforts, given the concerns raised by policy makers and legislators about the impact of ASD on productive life years lost.

To appropriately prevent unintentional prenatal alcohol exposure prior to pregnancy recognition, public health approaches must include preconception health, pregnancy planning and contraception for alcohol consumers. A comprehensive, holistic approach to treatment for alcohol-exposed children, similar to the well accepted guidelines for ASD, may reduce the need for medication and improve prognosis. The clinical, public health, and therapeutic implications of this perspective will hopefully help motivate policy makers, legislators, educators, and mental health professionals to work proactively in consort with childbearing alcohol consumers, affected children, and parents to create lasting change.

Acknowledgments

I would like to recognize the contribution of my mentors from the University of North Carolina at Chapel Hill - Dr. Robert C. Cefalo, past Chairman of the Department of Obstetrics and Gynecology and Dr. Kathleen K. Sulik of the UNC Bowles Center for Alcohol Studies. Their insights into preconception health and teratology helped highlight the need for contraception and careful family planning for alcohol consumers to prevent alcohol exposure prior to pregnancy recognition.

Conflict of interest

The author declares no conflict of interest.

Notes/thanks/other declarations

I would especially like to thank my children who have tolerated “good enough mothering” while growing up on an inclusive green care farm animal sanctuary. They have been great traveling companions during international conferences in Toronto, Canada; Vienna, Austria; and Shanghai, China. My advocacy in raising awareness about ND-PAE in the psychiatric community are supported by my outpatient clinical practice, Therapeutic & Learning Centers, P-LLC (www.susandrich.com) and my nonprofit 501c3, 7th Generation Foundation, Inc. (www.7thGenerationFoundationInc.org).

Nomenclature

Neurodevelopmental DisorderAtypical NeurodevelopmentFunctional Birth DefectNeurophenotypePreconception HealthEpigeneticsMethylation