Criteria for neurocognitive impairment include evidence of 1 of the following: global impairment, executive dysfunction, deficits in learning, memory problems, or trouble with visual–spatial reasoning. These criteria may be assessed by standardized testing, clinical observation, or, more often, clinical history. To ensure the integrity of the diagnostic criteria for ND-PAE, findings based on clinical observation or history are best if based on specific examples of impairment and documented in the medical record.

For global deficits, comprehensive standardized testing results are the gold standard. This might require referral for testing or coordination with school psychologists. However, for diagnosis it is important to recognize that not all affected children perform in the range of intellectual disability. Clinical research has found that 86% of individuals with any of the FASDs have an IQ in the low average or borderline ranges.¹⁷ The important point is that the child under consideration is functioning below what would be expected relative to his or her peers.

Even if global delay or impairment is not present, specific deficits can indicate neurocognitive impairment consistent with ND-PAE. Impairment in executive function often presents as poor planning skills, inflexibility, or difficulty with behavior inhibition.¹⁸ Impaired learning or specific learning disabilities often manifest in the areas of math, visual–spatial reasoning, or abstract academic material. Finally, memory problems might be seen as problems remembering recently learned materials or repeatedly making the same mistake.¹⁹ These particular types of learning and memory problems often lead caregivers and educators to mistakenly assume the child is being defiant or willfully disobeying rather than having genuine difficulty, the “can’t vs won’t” error.^2,20,21

Impaired self-regulation might include difficulty regulating mood or behavior, attention deficits, or poor impulse control. Early signs of mood and behavior regulation problems might include sleep problems or severe reactions to discomfort for infants and extended tantrums for toddlers.^22–25 For older children, increased incidence of externalizing behaviors and severe reactions to stress are most common.^3,26,27 However, increased levels of anxiety and depression have been documented.²⁷ Attention problems are often associated with prenatal alcohol exposure. Children with ND-PAE can have particular difficulty shifting attention, resulting in behavior problems. Poor impulse control is an additional impairment.^28,29 These difficulties in all areas of self-regulation are particularly challenging for the entire family of a child with ND-PAE. The sleep problems and mood lability with frequent behavior outbursts, typically caused by frustration with task shifting, are often the presenting complaints to a pediatrician.^30–32

Adaptive functioning is the ability to acquire daily skills for personal and social sufficiency. Impairment in adaptive functioning can occur in communication, social communication and interaction, daily living skills, or motor skills for very young children. Adaptive functioning is an area of special concern of children with ND-PAE because these impairments are pervasive across domains and situations as children age.³ Therefore, meeting this criterion requires impairment across 2 domains of adaptive functioning. Although most language milestones (eg, babbling, first words, and syntax) are acquired on schedule,³³ individuals with ND-PAE might exhibit communication problems such as difficulty in understanding figurative language (eg, understanding idioms, jokes, or sarcasm) and social communication conventions (eg, how to effectively enter a conversation).^30,34 Socially, they can be overly friendly with strangers, be at high risk of bullying, have difficulty learning social rules through experience (eg, how to join a group on the playground), or be highly susceptible to manipulation by others.³⁵ Because of attention and memory problems, a child with ND-PAE might initially learn daily skills such as hygiene or house rules, yet maintaining those skills and organizing daily activities present a challenge.^36,37 Finally, motor skills can be impaired at the fine motor level (eg, poor writing skills) or gross motor level (eg, poor coordination or balance).^7,38

Unlike FAS, which can be diagnosed when information about history of prenatal alcohol exposure is unavailable, diagnosing other conditions along the continuum of FASDs, including ND-PAE, requires a confirmed history of in utero exposure. There are clear and strong research human and animal data documenting adverse neurodevelopmental outcomes from moderate to heavy levels of prenatal exposure to alcohol³⁶ and adverse reproductive (eg, prematurity) effects from even very low exposure levels.³⁹ Linking adverse neurodevelopmental outcomes to in utero exposure at these lower levels remains a challenge but can be revealed with more sensitive testing.⁴⁰ Despite clear evidence for the association between prenatal exposure to alcohol and the wide profile of strengths and weaknesses that might be observed across children with ND-PAE, the specificity of the profile is not yet known. Therefore, the criterion of more than minimal gestational exposure is required for the ND-PAE diagnosis. More than minimal exposure is defined as maternal consumption of ≥13 drinks per month during pregnancy (ie, any 30-day period of pregnancy). The “More than minimal” criterion is not intended to denote a threshold for safe consumption of alcohol during pregnancy. It is simply an acknowledgment of ongoing controversy about low levels of exposure and an attempt make sure the diagnosis was not overused because the base rate of drinking any alcohol among women of childbearing years is relatively high.⁵

Suggestions for obtaining a prenatal history of alcohol exposure are presented in the Appendix.

The primary care pediatrician needs to be aware that there is no known level of alcohol use during pregnancy that has been established as safe. The US surgeon general still advises that women who are pregnant, or are considering pregnancy, should abstain from consuming alcohol.⁴¹ Primary care pediatricians will want to provide this important health message to their adolescent patients and mothers-to-be and obtain information on prenatal exposure to alcohol for all patients.

The diagnosis of ND-PAE encompasses the behavioral, developmental, and mental health aspects of FASDs. Other diagnoses along the spectrum, such as FAS or pFAS, focus on structural and neurophysiological central nervous system abnormalities (eg, microcephaly or neurologic soft signs). Physical features such as facial dysmorphia or growth restrictions (either prenatal or postnatal) are required for FAS and pFAS. Thus, for children with both physical findings and behavioral findings consistent with ND-PAE, it is appropriate that a comorbid diagnosis of FAS or pFAS also be used.³

As mentioned, a majority of children with any of the FASDs score in the low range of normative intellectual functioning.¹⁵ The history of more than minimal in utero exposure to alcohol will be a major decision point between children with ND-PAE comorbid with intellectual disability and children with intellectual disability due to another etiology. However, deficits specific to ND-PAE are recognized. For example, even with repeated experience and an IQ within normal limits, the memory and learning impairments of a child with ND-PAE may mean that he or she has difficulty with previously learned skills, such as finding his or her locker at school on a routine basis despite repeated instructions and practice^48,49 or forgetting how to tie his or her shoes, despite previous mastery, and having to relearn that skill entirely. This is different from regression of emerging skills seen in some children with autism.³³

Finally, children with intellectual disability without prenatal alcohol exposure tend to have lowered functioning across all neurocognitive domains. In contrast, individuals with ND-PAE tend to have specific difficulty with nonverbal aspects of cognition such as visual–motor skills, learning and memory for recently learned skills, and executive functioning, resulting in behavioral problems.^3,49 Cognitive impairment coupled with behavioral problems should prompt clinicians to consider a diagnosis of ND-PAE.

Current research demonstrates differences in manifestations of attention-deficit/hyperactivity disorder (ADHD) and FASDs. Behaviorally, children with FASDs have higher rates of social behavioral problems resulting from difficulties in social cognition and emotional processing.⁵⁰ They might also be more likely to have problems dealing with overstimulation than children with simple ADHD.⁵¹ In contrast, children with ADHD due to etiology not attributable to alcohol have difficulty with focus and sustained attention.⁵² Medication for symptoms of ADHD can result in unexpected outcomes in children with a history of prenatal alcohol exposure.^53,54 Stimulant medications are often ineffective for children with prenatal alcohol exposure.^27,33 Care should be given to investigate whether in utero exposure to alcohol contributes to attention problems for any child because treatment and management plans could differ.²

Children who experience early trauma (including physical events, psychological events, and abuse or neglect) often display serious behavioral problems, receiving a mental health diagnosis of conduct disorder, oppositional defiant disorder, anxiety, or depression. Because of overlap between these other behavioral disorders and ND-PAE, at a general level (especially for the self-regulation component) it is important for a clinician to consider these as both differential and comorbid diagnoses. Until additional data are available about the validity and reliability of all childhood behavior disorders, including ND-PAE, this will continue to be a tricky diagnostic issue. Furthermore, for some children a history of early trauma, abuse, neglect, or parental loss will be the only presenting problem because children with prenatal exposure to alcohol are at higher risk for these negative events. Therefore, it is particularly important to obtain prenatal exposure history in these situations.^18,55 Such early trauma has been shown to drastically worsen the effects of prenatal alcohol exposure and must be taken into account.⁵⁵

Children with diagnoses of conduct disorder, oppositional defiant disorder, or even posttraumatic stress disorder (PTSD) are often aggressive without appropriate provocation, whereas children with ND-PAE might have behavioral outbursts caused by situational frustrations they experience when interacting with others or by their own neurodevelopmental limitations.³⁵ Furthermore, children with other early trauma diagnoses might have inappropriate social interactions but tend to withdraw from others as self-protection, whereas children with ND-PAE are more likely to be overly friendly, seeking out companionship and social acceptance, although often in an inappropriate manner.^35,56

A special issue regarding ND-PAE and early trauma is that among children in the child welfare system and children adopted internationally. Researchers have found disproportionately high rates of children with FASDs, including diagnoses without physical features such as ND-PAE, in these populations.^57–60 Because these children also often experience early trauma, separation, and poor early caregiving, they are at elevated risk for a comorbid diagnosis of reactive attachment disorder or PTSD after abandonment.^61–64 Obtaining information about, and documenting, possible prenatal exposures for all who have a current or history of involvement with the child welfare system is prudent clinical practice. Such information can inform assessments and evaluation at older ages.

Finally, although prenatal alcohol exposure does occur in various contexts and varying levels, the presence of ongoing alcohol or substance abuse in the home confers additional risk. Families with substance abuse problems are more likely to suffer from multiple forms of trauma, antisocial behavior, financial instability, and poverty.¹⁸ These factors can lead to additional comorbid conditions in a child with ND-PAE.

The evidence base for pharmacologic treatment in this population is limited,^53,69,70 with no medications indicated specifically for ND-PAE. Studies on human and animal models are inconclusive at this time, and more data are needed for proper guidance. However, findings from small pilot studies suggest that ADHD stimulant medication can improve hyperactive symptoms but not attention and impulsivity.^71,72 And another small study found that neuroleptics can be more beneficial than psychostimulants for improving social skills.⁵⁶ A poor or adverse clinical response to stimulants (ie, ineffective clinical response or significant side effects) can occur, and clinicians should plan to adjust medications as necessary. Such medication failure also might be an indicator to consider a diagnosis under the umbrella of FASDs.

By definition ND-PAE is a behavioral or mental health diagnosis, and therefore such patients will benefit from referral to specialties that can address these needs.^3,73,74 In addition, academic problems are a natural sequela of these primary disabilities. An overview of interventions developed specifically for these children found that effective interventions include explicit teaching techniques, repetitive presentation, and caregiver instructions about specific strengths and weaknesses associated with prenatal alcohol exposure.^73,75,76 As with many aspects of ND-PAE, additional systematic research is needed to develop new intervention strategies and to get a clearer picture of the long-term effectiveness of available programs.^{24,73,74,77,78} However, a sample of currently available evidence-based and evidence-informed interventions are described in the online Supplemental Information.

It is important to remember that all aspects of the ND-PAE diagnosis (ie, neurocognition, self-regulation, and adaptive behavior) are developmental processes, and the type of specialty needed might change across development. For younger children, allied health referrals, such as physical or occupational therapies, might be most appropriate. Early intervention might focus on general developmental skills for the infant or preschooler. Occupational therapy is often recommended for fine motor impairments, sensory integration problems, and emerging self-regulation problems.⁷⁹ For older school-age children, several evidence-based interventions targeting specific skills and adapted for children with FASDs are available and can be recommended to school-age children. Several of these interventions are described in the online Supplemental Information.⁷³ More information on such interventions is available at the National Organization on Fetal Alcohol Syndrome (www.NOFAS.org).

Older children with ND-PAE might need more traditional mental health services and can begin to benefit from modified insight-based therapies.^27,80 Referral to a psychiatrist or psychologist can be appropriate. Referral for substance abuse evaluation or treatment also might be warranted.^15,27 For the medical home provider, however, it is most effective to provide background information on the strengths and weaknesses of a child with ND-PAE in addition to child specific symptoms when making such a referral.

Of special note for this population is that many affected children and adolescents do not qualify for special education under standard criteria, yet they still need services.^17,81 This gap must be addressed at the individual patient or student level. Psychoeducational testing (by school personnel or private psychologists) might be required for diagnostic confirmation and treatment planning. Creative solutions and closely engaging with the family, school, and community by the pediatric medical home can facilitate meaningful results (see the AAP FASD Toolkit at www.aap.org/fasd).^82,83

Parental education about ND-PAE, and even about FASDs in general, is particularly effective.⁸⁴ For parents there might be fears about stigma or the legal implications of the child’s diagnosis. It is important that clinicians ask the difficult questions to screen for prenatal alcohol exposure when they suspect a child might have been prenatally exposed to alcohol.

Caregivers appreciate information about how the behavioral difficulties they experienced with their child were directly related to their child’s exposure to alcohol in utero.^17,73,84 Instruction on the use of explicit explanations that avoid idioms or other figurative language, the value of routines, and the need to relearn some skills and obtain repeated instruction is a practical technique. Furthermore, such instruction provides reassurance and support.^64,73 It often helps to explain to parents that structural brain abnormalities and the resulting neurobehavioral manifestations their child has (eg, problems with poor problem solving and executive dysfunction) might make him or her less responsive to pharmacotherapy than other children with a developmental disability. The pediatric medical home is an ideal setting to provide such education and reassurance that the child’s primary care pediatrician will be available to work with the family to address problems as they arise.⁶⁵ It is especially helpful for the clinician to explain that the vulnerabilities of a child with ND-PAE might not be readily recognizable by others. For example, the child’s good structural language skills and friendly nature can give a false impression of competence, and forgetting previously learned material might give a false impression of a defiant or oppositional disorder.⁷⁴ Additionally, the medical home provider caring for the child with ND-PAE can help explain how the needs of the child change across development and provide anticipatory care.