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Correspondence: Angela Nash, PhD, APRN, CPNP-PC, PMHS, University of Texas Health Science Center at Houston School of Nursing, SON 747, 6901 Bertner Ave, Houston, TX 77030.
Prenatal alcohol exposure is the cause of fetal alcohol spectrum disorders (FASDs), the prevalence of which is similar to that of other developmental disabilities like Down syndrome and autism. Children, adolescents, and adults who live with the disabilities associated with prenatal alcohol exposure face extraordinary challenges throughout their lives. Pediatric providers need to be able to identify patients with FASD because early recognition and intervention is known to improve life outcomes for affected individuals. The purposes of this continuing education activity are to report what is known about the prevalence of FASDs; to detail the spectrum of problems experienced by affected individuals; and to suggest specific strategies for preventing, identifying, and managing FASDs in clinical practice.
). Many factors influence the severity of fetal alcohol spectrum disorders (FASDs); however, PAE is the necessary component, making FASDs completely preventable (
). FASD is an umbrella term describing the range of negative effects that can occur including physical and central nervous system (CNS) malformations, deficits in growth, and neurocognitive impairments (e.g., in behavior, self-regulation, and adaptive skills). Specific disorders include fetal alcohol syndrome (FAS), partial FAS, alcohol-related birth defects, and neurobehavioral disorder associated with PAE (ND-PAE;
). Although FASDs are permanent conditions, with early recognition and intervention specific symptoms are manageable, and affected individuals' life outcomes can be improved (
Interventions for Children with Fetal Alcohol Spectrum Disorders Research Consortium Interventions for children with fetal alcohol spectrum disorders (FASDs): Overview of findings for five innovative research projects.
Research in Developmental Disabilities.2009; 30: 986-1006
Pediatric providers need to be able to identify patients with FASD and manage their care. The purposes of this article are to report what is known about FASDs; to detail the spectrum of problems experienced by affected individuals; and to suggest specific strategies for preventing, identifying, and managing FASDs.
Pediatric providers need to be able to identify patients with FASD and manage their care.
Teratogenic Effects of Alcohol
The fetus is sensitive to alcohol's teratogenic effects throughout gestation. At 1 to 2 hours after maternal alcohol ingestion, the fetal blood alcohol concentration reaches a level equivalent to that of the mother, and the process of amniotic reuptake prolongs the time of PAE. Elimination of alcohol from the fetus is dependent on the mother's metabolic capacity, which varies considerably among pregnant women (
). Toxic byproducts of alcohol metabolism accumulate, disrupting the growth, division, and survival of cells throughout the body. Depending on the timing and severity of PAE, associated malformations can occur in the cardiac, skeletal, renal, ophthalmic, auditory, and neurologic systems (
Animal studies have consistently shown that moderate to heavy PAE induces negative effects on neurodevelopment, and several studies have suggested that low to moderate PAE can produce functional damage on the developing fetal brain without obvious effects on other systems (
). Experimental human studies to determine the impact of the dose, timing, and pattern of PAE on outcomes are not ethically feasible; however, case–control and cohort studies with humans have shown consistent associations between moderate to heavy PAE and poor neurodevelopmental outcomes (
). The evidence for adverse effects from low to moderate PAE from observational studies is less robust because of challenges in accurately measuring the dose, pattern, and timing of alcohol consumption from self-reports, controlling for the presence of confounding factors, and a lack of consensus on diagnostic criteria in the scientific literature (
). Despite these methodologic challenges, evidence on the magnitude of the problem and the spectrum of disabilities associated with PAE support advising all women of childbearing age that there is no known “safe” level of alcohol consumption during pregnancy and that abstinence is the healthiest choice (
Several maternal factors affect the severity of effects from PAE. These include the pattern of maternal drinking (timing, quantity, and frequency), genetics, and maternal health history (
). The pattern of drinking found to be most harmful to the fetus is binge drinking, defined as drinking enough to raise the blood alcohol content level to 0.08 g/dl (
). Although metabolism and other genetic factors cause variability, for most women this means drinking approximately four standard drinks and for adolescents, drinking approximately three standard drinks in about 2 hours (Figure 1;
One study examined epidemiologic data to determine which maternal variables were most influential on affected children's intelligence and behavior at age 7 years (
). Maternal physical characteristics associated with higher severity of FASD in the child included low body mass index, small head circumference, and maternal weathering (e.g., advanced age, poor nutrition, and smoking). Maternal environmental factors associated with higher severity included low socioeconomic status, low education level, rural residence, social isolation, and belonging to social groups that promote heavy drinking (
). A growing body of research has shown how alcohol leads to alterations in gene expression in key brain regions (e.g., vascular endothelial growth factor A, an important regulator of blood vessel formation and the corpus callosum;
). Advances in epigenetic research may enhance our ability to determine specific risk factors that predict FASD severity, demystifying the wide spectrum of deficits associated with PAE (
). The most easily identifiable manifestation on the spectrum is FAS, which includes physical (e.g., fetal alcohol facial phenotype) and CNS malformations, growth deficits, cognitive disabilities, and neurobehavioral impairment (behavior, self-regulation, and adaptive skills;
Olson, H. C., Ohlemiller, M. M., O'Connor, M. J., Brown, C. W., Morris, C. A., Damus, K. (2009). A call to action: Advancing essential services and research on fetal alcohol spectrum disorders. Washington, DC: US Department of Health and Human Services.
; Figure 2, Figure 3). Individuals with partial FAS have CNS abnormalities and functional deficits at the same level as FAS but may not meet all the specific criteria for FAS. Alcohol-related birth defects are diagnosed in individuals with a history of PAE and physical malformations in the absence of neurobehavioral problems (
). Alcohol-related neurodevelopmental disorder or the newly proposed mental health disorder ND-PAE are diagnosed in individuals with PAE who experience many of the cognitive, neurobehavioral, and adaptive functioning deficits associated with FAS but may or may not exhibit the typical dysmorphic characteristics (
Figure 3Lip–philtrum guide. University of Washington Lip–Philtrum Guides 1(A) and 2(B) are used to rank upper lip thinness and philtrum smoothness. The philtrum is the vertical groove between the nose and upper lip. The guides reflect the full range of lip thickness and philtrum depth, with Rank 3 representing the population mean. Ranks 4 and 5 reflect the thin lip and smooth philtrum that characterize the FAS facial phenotype. This guide is used for White patients and those of all other races with lips like Whites. A second Guide is available for African American patients and all other races with lips as full as African Americans.
FASDs affect people from all socioeconomic strata and are highly heterogeneous disorders that manifest uniquely in each individual. Children, adolescents, and adults who live with the disabilities associated with PAE face extraordinary challenges throughout their lives, and most require some level of external support (
). Affected children without the specific FAS physical criteria often remain undiagnosed or encounter challenges qualifying for the appropriate interventions and support (
). FASDs represent a tremendous public health burden, with estimated annual costs up to $4 billion (medical and psychiatric care, foster care, special education, supportive employment, social security benefits, juvenile and adult corrections, long-term care, lost productivity, prevention and research;
FASDs affect people from all socioeconomic strata and are highly heterogeneous disorders that manifest uniquely in each individual.
Epidemiology
Prevalence of Alcohol Use by Women
Drinking is very common in adolescents and women of childbearing age. A recent systematic review and meta-analysis estimated the global prevalence of alcohol use during pregnancy to be 9.8% (
Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis.
). Almost 50% of all U.S. pregnancies are unintended, and 80% of teen pregnancies are unintended, so PAE may occur before a woman is aware of the pregnancy (
Centers for Disease Control and Prevention Planning and implementing screening and brief intervention for risky alcohol use: A step-by-step guide for primary care practices.
Centers for Disease Control and Prevention & National Center on Birth Defects and Developmental Disabilities,
Atlanta, Georgia2014
). Most women decrease or abstain from drinking when they discover they are pregnant, but 9.3% of adults and 13.4% of adolescents report continued drinking throughout pregnancy (
Center for Behavioral Health Statistics and Quality. (2016). Key substance use and mental health indicators in the United States: Results from the 2015 national survey on drug use and health. Rockville, MD: Substance Abuse and Mental Health Services Administration.
). This may be due to a lack of knowledge of the potential adverse effects of PAE or may indicate the need for professional intervention for substance use disorder. Approximately 20% of women report binge drinking, which is the pattern of drinking associated with the highest risk for FASDs (
Estimating the exact prevalence of FASDs in the general population is challenging, and a range of estimates exist based on the method used. Passive surveillance systems involve reviewing existing records (birth certificates, clinical records, registries of children with developmental disabilities) in a particular geographic area for probable or documented cases (
reports prevalence estimates for FAS at 0.3 infants of every 1,000 live births. This is considered to be a low estimate, because it is based on passive surveillance methods (
The active case–ascertainment surveillance method involves in-person physical examinations, cognitive behavioral testing, and interviewing the mothers of all children in a large population or geographic area to identify cases (
). Estimates from active surveillance with certain high-risk populations around the world have resulted in very high rates, which can bias estimates for the general population (
). A recent study that used active case–ascertainment methods with a middle class community selected to represent the general U.S. demographic resulted in much higher rates than previously accepted estimates (
). A consented sample of 70.5% of all first graders in public and private schools received examinations (physical, dysmorphology, development, and neurocognitive), and their mothers were interviewed (
). In this sample the prevalence of FAS was 6 to 9 cases per 1,000 births, and the prevalence of FASDs was estimated at 24 to 48 cases per 1,000 births (
). Although not generalizable, this study suggests that FASDs are more common than older estimates predicted.
A systematic review and meta-analysis of prevalence studies that used rigorous methods to reduce bias estimated the global prevalence of FAS in the general population to be about 1.5 cases per 1,000 births (
Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis.
). No global estimates exist for the prevalence of FASDs, but the prevalence ratio of FASDs to FAS is considered to be around 10 to 1, or about 15 cases of FASDs per 1,000 births worldwide (
Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis.
). Because of their role in developmental surveillance, primary care physicians (PCPs) are the most appropriate team members to identify and refer patients with signs and symptoms of FASDs for diagnostic evaluation (
). The continuum of conditions under the umbrella of FASDs can be recognized and the interventions benefit individuals of any age, but early (<age 6 years) identification, diagnosis, and therapy result in the best outcomes for affected patients (
In a pediatric medical home, complete histories should routinely include history of known or suspected PAE and/or other risk factors (e.g., siblings with FASDs, patient in foster care or adopted;
). Parental concerns or FASD signs and symptoms (e.g., growth deficits, CNS abnormalities, behavioral/developmental issues, or the cardinal FAS facial characteristics) identified during a routine health maintenance visit should trigger the gathering of data on FASD-specific characteristics, including (a) height and/or weight ≤ 10th percentile, (b) smooth philtrum, (c) thin upper lip, (d) short palpebral fissures, (e) CNS abnormalities (e.g., microcephaly or focal neurologic deficits) and/or impaired neurobehavioral functioning (cognition, self-regulation, and adaptive functioning), and (f) PAE. If one or more of these characteristics are present, a referral to FASD diagnostic and developmental services, as well as to a genetics specialist (to rule out potential differential diagnoses), should be considered. If FASD-specific services are unavailable, referral to a developmental pediatrician is recommended. Referral for early childhood or school-based developmental services can be done as soon as FASD is suspected (
). If one or more (a through f) are present, referral to an FASD clinic or the best available professionals should be considered for help with diagnosis and referral for early childhood or school-based services (
). If impaired neurobehavioral functioning is the presenting issue and the patient has a history of more than minimal PAE, ND-PAE should be considered and the appropriate referrals made (
). This diagnosis is the most frequently missed because of the absence of the specific physical characteristics. The diagnostic process for ND-PAE is complex because of the many potential interacting factors (e.g., genetic, environmental, or other toxic exposures), variability of PAE (dose, duration, and timing), and potential interactions among other factors (prenatal and postnatal environments, genetics, and exposure to other toxic substances). Therefore, it is important to refer these patients to diagnostic professionals with FASD experience (
). Other documents that contribute to the diagnostic process include a review of school records (if the child is school aged), birth information, and any psychological or developmental examinations. The AAP recommends considering referral to an FASD clinic and genetics specialist if PAE is suspected but not confirmed, even if none of the data points are identified (
). Factors that contribute to missed diagnoses or misdiagnosis include (a) a lack of awareness of FASDs, (b) a lack of physical stigmata, (c) an unknown history of PAE, and (d) high rates of co-occurring mental health disorders associated with FASDs (
). One study examined a random sample of 547 foster or adopted children ages 4 through 18 years who had been referred to a children's mental health center for behavioral problems (
). Few (6.6%) of the children came to the clinic with a prior FASD diagnosis. A team of FASD experts conducted a comprehensive diagnostic assessment. Of the 547 children, about 30% met the diagnostic criteria for an FASD, and 86.5% of those had been misdiagnosed or had never received an FASD diagnosis. Almost all (94%) of the children had one or more co-occurring mental health diagnoses. After the comprehensive assessment, the mental health diagnoses changed significantly. In particular, previously undiagnosed or unaddressed learning and/or communication disorders were identified. This resulted in significant alterations in treatment (psychotropic medicine and therapies;
). The study shows how underrecognized FASDs are in certain high-risk populations and implies that the therapeutic plan and potential outcomes for many children would significantly change with broader identification and referral of FASDs.
Medical Home Management
The PCP has an essential role in identifying and managing FASDs (
). A PCP who suspects an FASD should assess the child for comorbid conditions and secondary disabilities, understanding that many variables can compound an individual's presentation. These variables include (a) PAE severity and timing; (b) maternal health; (c) birth complications; (d) exposure to poor parenting or role models; and (e) the child's experience(s) of abuse, neglect, trauma, toxic stress, or other adverse experiences (
). As soon as the diagnosis is made, the next health maintenance visit should be scheduled, and the child should be identified as having special health care needs. The medical home should coordinate comprehensive continuing care and facilitate referrals to diagnostic, mental health, early childhood developmental services and educational services (
). Awareness of the problems experienced by affected individuals should inform pediatric PCPs' care planning and management.
Physical Problems
The physical problems associated with FASDs manifest early and are the most readily identifiable. These can include miscarriage or fetal demise; prematurity, low birth weight, and sudden infant death syndrome; CNS abnormalities (e.g., microcephaly, reduced brain volume, and malformations of the corpus callosum); congenital heart defects (e.g., malformations in the outflow tract such as transposition of the great arteries); abnormalities of the kidney (e.g., renal hypoplasia or hydronephrosis) and/or optic system (e.g., small palpebral fissures, hypertelorism, strabismus, optic nerve hypoplasia, or tortuosity of retinal vessels); and/or auditory processing delays. Besides the cardinal facial features (small palpebral fissures, smooth philtrum, and thin upper lip), other possible facial abnormalities include micrognathia, cleft palate, and maxillary hypoplasia (
Neurobehavioral problems associated with FASDs can range from subtle to severe and typically vary in presentation as a child grows. Affected children's IQ scores can range from very low to normal, but adolescents and adults tend to have lower academic achievement scores than their IQ scores would suggest (
). Table 3 details typical neurocognitive, behavioral, and adaptive functioning problems that FASD-affected children experience by developmental phase.
Table 3Typical FASD neurobehavioral problems by developmental phase
SAMHSA Fetal Alcohol Spectrum Disorders Center for Excellence Tools for success curriculum: Working with youth with fetal alcohol spectrum disorders (FASD) in the juvenile justice system.
Substance Abuse and Mental Health Services Administration. Center for Substance Abuse Prevention,
Rockville, MD2007
Note. Although considerable variation exists among affected children from all categories of severity, when compared with control subjects, those with FASDs perform poorly on all cognitive and behavioral tests. The poorest performers have more dysmorphology (
Individuals with FASDs experience comorbid conditions at much higher rates than the general population. A systematic review and meta-analysis of studies reporting cause of death and comorbidity of FASDs identified 428 comorbid conditions, including congenital malformations, genetic abnormalities, and mental and behavioral disorders (
). The most prevalent conditions (pooled prevalence > 67%) included disorders of special senses and the peripheral nervous system, conduct disorders, expressive and receptive language disorders, developmental deficiencies, and chronic serous otitis media. Other conditions (affecting > 50%) included hearing loss, retinal malformations, substance abuse and/or dependence, and attention deficit hyperactivity disorder (
). Little evidence supports the use of specific medications for this population, yet these children often present to PCPs after being prescribed multiple psychotropic medicines (
). The PCP should evaluate children taking these medications for effect, appropriateness, and potential interactions and refer for psychological intervention, because most patients receive more benefit from intense forms of mental health and family therapy than from medication.
Secondary Disabilities
Although a person with FAS may have severe CNS malformations and neurobehavioral and cognitive impairments, these same challenges often make them more easily identifiable by PCPs. FASDs have been called the “invisible disability” because affected individuals (especially those with ND-PAE) may seem typical in appearance, so their deficits and behaviors are frequently misunderstood or misinterpreted as willful or defiant (
). The cognitive, adaptive, and social deficits associated with FASDs (Table 3) may prompt them to develop maladaptive behaviors, leading to a pattern of life-long physical, mental, social, and behavioral challenges. Adverse environmental conditions (e.g., frequent changes in caretaker placement, victimization, etc.) exacerbate the problems. These factors can lead to the development of secondary disabilities in adolescence and adulthood, including educational disruption, legal trouble, difficulty securing or keeping a job, confinement in psychiatric institutions or jail, inappropriate sexual behavior, and substance use disorders (
). Most individuals with FASDs need ongoing social support and mental health services.
Individuals with signs of FASDs must be identified early so they can receive a diagnosis and interventions to prevent secondary disabilities. Secondary disabilities and negative life outcomes have been shown to be mitigated by a loving and stable family; positive role models; predictable, structured routines; and clear, reasonable expectations (
). Additional factors that can reduce the odds of negative life outcomes in affected individuals include early diagnosis (before age 6 years), a high percentage of life in a nurturing stable home environment, having basic needs met, few changes in caretakers, a lack of victimization, and eligibility for social and educational services (
NOFAS Web site Multiple links to resources on education, interventions, criminal justice Parent and birth mother suppor Videos of affected individuals Patient education and training
Note. AAP, American Academy of Pediatrics; NIAAA, National Institute on Alcohol Abuse and Alcoholism; NOFAS, National Organization on Fetal Alcohol Syndrome; SBIRT, Screening, Brief Intervention and Referral to Treatament.
Although there is no cure for FASDs, it is widely accepted that early identification and referral to appropriate interventions mitigate the chances of secondary disabilities (
). Although no medications have been specifically approved to treat FASDs, medications targeting an individual's specific symptoms can be helpful and are often prescribed; however, these children often respond differently than children without PAE (
). Evidence-based interventions for people with an FASD involve providing parent education, support, and skills; addressing social skills; addressing specific learning challenges around mathematics, executive functioning skills, and self-regulation; and developing strategies to address challenging behaviors (
Interventions for Children with Fetal Alcohol Spectrum Disorders Research Consortium Interventions for children with fetal alcohol spectrum disorders (FASDs): Overview of findings for five innovative research projects.
Research in Developmental Disabilities.2009; 30: 986-1006
). Most research around interventions for those with an FASD focuses on young children. Unfortunately, research targeting adolescents or adults with FASDs is lacking (
Education of children and adolescents requires a team approach (teachers; parents; administrators; health care and community providers; medical, developmental, and mental health services;
). Parents and teachers should recognize that students with FASDs are capable of learning, but they tend to function at lower levels than their similarly aged peers. Structure, consistency, brevity, variety, and repetition are keys to working with affected students (
). Parents and educators need to be concrete, simple, specific, and consistent with their instructions. These students have difficulty generalizing learning from one situation to another and do best with predictable routines. Memory problems may necessitate frequent repetition and re-teaching. Supervision is important for teaching appropriate behavior because they tend to be naïve and easily victimized (
). See the BOX for Web links to educational resources.
Parental Support
PCPs should play an active role in educating and supporting parents to become experts about and advocates for their FASD-affected child. Parents have four basic needs: receiving a diagnosis, accepting the child's deficits and processing emotions, developing a new understanding of their child's behavior, and receiving support from a knowledgeable community (
PCPs should be aware that an FASD is a diagnosis of both the mother and child. Alcohol use during pregnancy is a complex issue, and birth mothers often endure tremendous guilt when they learn that their child's problems are related to their drinking (
). Mothers report that they drank before they were aware of the pregnancy, they were not aware that PAE is harmful, or they were addicted to alcohol and unable to stop independently (
). PCPs have a powerful role in supporting the recovery and parental role of biological mothers of children with FASDs. See the BOX for birth mother resources.
PCPs have a powerful role in supporting the recovery and parental role of biological mothers of children with FASDs.
Prevention
Alcohol Screening and Brief Intervention
Over 30 years of evidence shows that universal screening using validated tools is an effective method for identifying individuals at risk for having an alcohol-exposed pregnancy and provides the opportunity for clear and consistent messaging about the risks associated with alcohol use (
). For this reason, the U.S. Preventive Services Task Force and many other organizations recommend alcohol screening and brief interventions as part of routine clinical practice (
Centers for Disease Control and Prevention Planning and implementing screening and brief intervention for risky alcohol use: A step-by-step guide for primary care practices.
Centers for Disease Control and Prevention & National Center on Birth Defects and Developmental Disabilities,
Atlanta, Georgia2014
Centers for Disease Control and Prevention Planning and implementing screening and brief intervention for risky alcohol use: A step-by-step guide for primary care practices.
Centers for Disease Control and Prevention & National Center on Birth Defects and Developmental Disabilities,
Atlanta, Georgia2014
Centers for Disease Control and Prevention Planning and implementing screening and brief intervention for risky alcohol use: A step-by-step guide for primary care practices.
Centers for Disease Control and Prevention & National Center on Birth Defects and Developmental Disabilities,
Atlanta, Georgia2014
). PCPs who identify risky alcohol use have the privilege of influencing behavior change through brief interventions (short conversations designed to stimulate a patient's own motivation for changing). Screening forms the basis for informed medical decision making and care planning. The whole process of screening and advice typically takes just a few minutes, is inexpensive, and is reimbursable in many cases (
Centers for Disease Control and Prevention Planning and implementing screening and brief intervention for risky alcohol use: A step-by-step guide for primary care practices.
Centers for Disease Control and Prevention & National Center on Birth Defects and Developmental Disabilities,
Atlanta, Georgia2014
). When repeated routinely over time, screening reinforces knowledge around preventing FASDs. Waiting until a woman or adolescent is aware that she is pregnant (which may be well into her first trimester) to advise her to discontinue drinking alcohol can preclude an opportunity for prevention (
National Task Force on Fetal Alcohol Syndrome and Fetal Alcohol Effect Prevention Report Writing Group Reducing alcohol-exposed pregnancies: A report of the national task force on fetal alcohol syndrome and fetal alcohol effect.
Centers for Disease Control and Prevention,
Atlanta, GA2009
). To provide a safety net for newborns and identify women in need of intervention, some researchers have advocated for universal screening of mothers and newborns for PAE via biomarkers. Biomarkers currently under study include fatty acid ethyl esters (products of ethanol metabolism) and microRNAs (tiny RNAs that repress protein translation;
). High levels of these biomarkers correlate with moderate to heavy drinking. Although promising, biomarkers are not supported for use in clinical practice at this time. A systematic review of studies that used biomarkers found that the methodologic quality of studies was generally poor, the diagnostic accuracy of PAE biomarkers varied widely across studies, and participant recruitment from high-risk populations limited the generalizability of the findings (
Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis.
). Individuals with FASDs have a wide variety of comorbid conditions and secondary disabilities for which health care providers can provide intervention. Well-informed PCPs can reduce this burden significantly through early identification, referral to services, and advocating for families.
Center for Behavioral Health Statistics and Quality. (2016). Key substance use and mental health indicators in the United States: Results from the 2015 national survey on drug use and health. Rockville, MD: Substance Abuse and Mental Health Services Administration.
Olson, H. C., Ohlemiller, M. M., O'Connor, M. J., Brown, C. W., Morris, C. A., Damus, K. (2009). A call to action: Advancing essential services and research on fetal alcohol spectrum disorders. Washington, DC: US Department of Health and Human Services.
Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: A systematic review and meta-analysis.
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