**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

#### *Perspective Chapter: Autism Spectrum Disorder Neurophenotype with Preconceptional… DOI: http://dx.doi.org/10.5772/intechopen.108820*

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 "midlevel 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.

#### *Perspective Chapter: Autism Spectrum Disorder Neurophenotype with Preconceptional… DOI: http://dx.doi.org/10.5772/intechopen.108820*

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.

### **Acknowledgements**

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.
