Fetal Alcohol Spectrum Disorder: How to Recognize the Various Manifestations

ABSTRACT: Fetal alcohol spectrum disorder (FASD) can be identified at birth by the presence of 1 or more of the 3 diagnostic criteria for fetal alcohol syndrome (growth deficiency, facial features, and CNS involvement) and the disclosure of prenatal alcohol consumption. The fetal alcohol syndrome face diagnostic screening tool (short palpebral fissures, smooth philtrum, and thin upper lip) is useful in the assessment of children with suspected FASD. It becomes more difficult to identify FASD by facial features alone in adolescence. Identification in older children is primarily based on the presence of neurobehavioral patterns and cognitive difficulties in the school setting.

Each year, fetal alcohol spectrum disorder (FASD) affects about 40,000 infants born in the United States.¹ FASD is an umbrella term used to encompass the range of effects seen in infants and children whose birth mother drank alcohol or consumed alcoholcontaining products during pregnancy. These effects include a specific craniofacial phenotype, neurological impairment, behavioral abnormalities, and learning disabilities.^1,2

Because of the life-long insult to the child, prenatal alcohol exposure continues to be a substantial public health concern. The financial burden of FASD is also significant; the lifetime cost is estimated to be about $1.5 million per affected child.³ Thus, prevention by educating women of childbearing age on the teratogenic impact of alcohol consumption before and during pregnancy is essential.

Here I will provide an overview of the clinical and neurodevelopmental features and behaviors in children with FASD. I will also present a case study that illustrates the range of manifestations in 2 sisters with prenatal alcohol exposure.

ALCOHOL CONSUMPTION AND THE DEGREE OF FETAL IMPACT

No clearly defined dose-response relationship has been determined between the amount of maternal alcohol consumption during pregnancy and the potential degree of impairment to the newborn. Alcohol crosses the placental barrier into the amniotic fluid with ease and is a well-known teratogen. Prenatal alcohol exposure is currently the leading known cause of mental retardation and behavioral teratogenesis in humans and affects all socioeconomic groups, races, and ethnicities.⁴

Certain maternal factors and patterns of maternal alcohol consumption during pregnancy play roles in the degree of fetal impact. The risk of FASD is greater in older mothers, women of high parity, women of compromised nutritional status, and women who previously had a child with FASD. Mothers of African American or Native American ethnic background are at greater risk for having a child with FASD (see the CDC's State-Specific Weighted Prevalence Estimates of Alcohol Use Among Women Aged 18 – 44 Years).³

Maternal polymorphisms of alcohol dehydrogenase, the enzyme responsible for the metabolism of alcohol, also play a role in determining the rate of alcohol metabolism and the impact on the fetus. Whether the mother was a binge drinker (consumed 4 or more alcoholic drinks at one sitting) or drank 1 alcoholic drink per day is also a factor. Binge drinking seems to have a more deleterious effect on neurobehavioral development.²

SPECTRUM OF ALCOHOL-RELATED DISORDERS

Given the wide spectrum of potential outcomes, a number of medically defined conditions fall under the umbrella of FASD:

FAS is considered the most severe form of FASD. Patients with FAS have abnormalities in 3 areas: intrauterine and postnatal growth retardation, CNS abnormalities (eg, deficient brain growth, brain malformations, and neurofunctional anomalies), and a specific craniofacial phenotype.^1,2 Patients who do not meet the triad of diagnostic criteria for FAS may have one of the other FASDs. These diagnoses are based on a history of prenatal alcohol exposure in a child who has either intellectual disabilities and neurobehavioral concerns (alcoholrelated neurodevelopmental disorder) or congenital defects that involve cardiac, renal, auditory, or visual systems (alcohol-related birth defects).⁵

Surveillance data on FAS in the United States show a prevalence rate of 0.3 to 1.5 per 1000 live-born infants. The prevalence is highest in African Americans, American Indians, and Alaskan Natives.⁶

The prevalence of alcohol-related neurodevelopmental disorder is reportedly much higher than FAS, estimated at 1% (1 per 100 live births).^7,8

CLINICAL FEATURES AND OTHER MANIFESTATIONS

FASDs can be identified at birth by the presence of 1 or more of the 3 diagnostic criteria for FAS (growth deficiency, facial features, and CNS involvement) and the disclosure of prenatal alcohol consumption. However, it is important to consider other possible causes of prenatal and postnatal growth retardation, such as Russell-Silver syndrome and Fanconi syndrome, and conditions with a presentation similar to that of FASDs. For instance, the craniofacial features of Dubowitz syndrome and Noonan syndrome are similar to those of FASD.⁹ The clinical findings in children exposed to phenytoin in utero (fetal hydantoin syndrome) or valproic acid in utero (fetal valproate syndrome) and in children with toluene embryopathy also are similar to those in children exposed to alcohol in utero.^2,9

The FAS face diagnostic screening tool is used to assess the craniofacial phenotype in patients in whom an FASD is suspected.^10,11 The FAS face has 3 elements: short palpebral fissures, smooth philtrum, and thin upper lip. This tool accounts for ethnic variations, and the assessment of lip and philtrum must be done in a nonsmiling participant. Because of the natural maturation of the face that occurs with age, it is more difficult to identify FASD in adolescence and adulthood on the basis of facial features alone; only about 10% of adults with FASDs remain recognizable on the basis of the craniofacial phenotype.^10,12

Table 1 lists the various clinical features associated with FASDs. Given the wide spectrum of manifestations, FASD may not be recognized in a newborn. The phenotypic findings may be subtle and maternal alcohol consumption during pregnancy may not be confirmed because of denial or lack of inquiry.

Identification of FASD in older children is primarily based on the presence of neurobehavioral patterns and cognitive difficulties in the school setting.²Table 2 lists the neurodevelopmental features and behaviors associated with FASD at each stage of development. Secondary disabilities, including disrupted school experiences, problems with employment, alcohol and drug abuse, inappropriate sexual behaviors, difficulty with the law, mental illness, and the inability to live independently or function successfully in society, can be hallmarks of prenatal neurological insult.²

TREATMENT AND PROGNOSIS

Fetal Alcohol Spectrum Disorder: Online Resources

The effects of FASD are permanent. There is no cure.⁵ The goal of treatment is to manage associated birth defects, optimize nutritional growth, and identify developmental delays/learning disabilities early in life. This is accomplished with the aid of many specialists under the coordinated care of a pediatric primary care provider. Children with FASDs greatly benefit from early diagnosis and interventions that foster physical, occupational, speech, and language growth. Behavior and educational therapies with active parent/caregiver training are also essential treatment modalities.^2,13 Medications for attention-deficit/hyperactivity disorder (ADHD) may be of benefit.⁵

Living in a stable, nurturing home environment is crucial for children with FASDs. Given the instability of home environments in which alcohol abuse and risk-taking behaviors occur, many children with FASD are placed in foster care in an attempt to create a safe, structured home. The number of adopted children with FASDs is also high. A recent study cited that 52% of 71 children adopted from Eastern Europe had received a diagnosis of FASD.¹⁴

The neurobehavioral and psychological aspects of FASDs must be addressed throughout life, especially during adolescence and adulthood. Affected adolescents often have poor socialization skills, memory deficits, sleep disturbances, and ADHD behaviors (such as impulsiveness, aggressiveness, and distractibility).

Additional medical concerns in these patients are seizure disorder, which is present in 10% to 20% of affected children, and an increased risk of malignancy, such as childhood acute myeloid leukemia.^15,16

HELPFUL RESOURCES

The CDC and other organizations, such the National Organization on Fetal Alcohol Syndrome, are invaluable resources for patients with FASD, their caregivers, and health care providers (Box). FASD Regional Training Centers funded by the CDC develop, implement, and evaluate educational curricula on FASD prevention, identification, and care and incorporate these curricula into medical training programs throughout the country. For more information on these centers or their location, visit the CDC Web site.17 A few books-Fetal Alcohol Syndrome: A Guide for Families and Communities by Streissguth,¹⁸The Challenge of Fetal Alcohol Syndrome: Overcoming Secondary Disabilities by Streissguth and Kanter,¹⁹ and ADHD and Fetal Alcohol Spectrum Disorders (FASD) by O'Malley and colleagues²⁰-also provide insightful advice on children with FASDs and their ongoing care and needs.

CASE - Two Sisters With a History of Fetal Alcohol Exposure

CLINICAL BACKGROUND

Two sisters, aged 10 and 13 years, are referred to the genetics clinic for evaluation of dysmorphic facial features and behaviorial problems in the older sibling (Photo A, on right) that began when she was in elementary school. The girls were placed in foster care 3 years earlier. They have been living with the same foster family whom they hope will adopt them. No prenatal, birth, early childhood, or medical history is known; however, it was reported that the biological mother was "drunk" when the older sibling was born.

The younger sibling (Photo A, on left) is thin, quiet, and cooperative. Her weight is 23.6 kg (3rd percentile); height, 128 cm (10th percentile); body mass index (BMI), 14.4 kg/m² (8th percentile); and head circumference, 51 cm (less than the 50th percentile). She has a round face with mid-face hypoplasia, short palpebral fissures, hypertelorism, a broad nasal bridge, tubular nose with anteverted nares, and a smooth philtrum. Her palate is intact and micrognathia is evident on profile view (Photo B). Her chest wall appears normal. A cardiac systolic ejection murmur is heard in the left upper sternal border, and a wide, fixed splitting second heart sound is present. Despite this finding, the patient reports no current symptoms or history of cardiovascular difficulties. Clinodactyly of both fifth fingers is noted.

The child is in 4th grade and attends regular classes. She has good grades and has not manifested any cognitive or behavioral problems.

The older sibling is quiet and reserved. She is notably larger than her sister in both height and weight. Her weight is 42 kg (25th to 50th percentile); height, 142 cm (less than the 3rd percentile); BMI, 20.8 kg/m² (89th percentile); and head circumference, 54 cm (50th percentile). She has an oval face with mid-face hypoplasia, short palpebral fissures, and a broad nasal bridge with a bulbous tip. A herpetic vesicular lesion is present on her upper lip. Her palate is intact. Her chest wall is normal; no cardiac murmur is heard. Like her sister, she also has bilateral fifth finger clinodactyly.

The teen is in 7th grade and has received C's and F's in her classes despite additional academic support. She admits to drinking alcohol and smoking cigarettes. She is having a tough time making friends at school and has been in fist fights with other kids. Her teachers are concerned about her impulsive behaviors and learning capability.

CASE DISCUSSION

Further inquiry with the present caregivers revealed that the biological mother drank beer and hard alcohol during her pregnancies. Although the salient diagnostic clues differ, the clinical findings and history of alcohol exposure in utero point to the presence of a fetal alcohol spectrum disorder (FASD). The younger sister has more pronounced phenotypic craniofacial features yet she seems to lack, at present, any of the cognitive or behavioral issues consistent with FASD. The older sibling has more subtle physical findings and appears to be manifesting neurobehavioral components associated with FASD. Both girls meet the criteria for postnatal growth retardation in that either their height or weight is the 10th percentile or less for age.

This case demonstrates the great overlap within the spectrum. To define the girls within a certain category of FASD would be difficult. This explains why researchers have been moving away from using classifications such as partial fetal alcohol syndrome in favor of the umbrella term "FASD." Most important for these children is that they receive the necessary resources for their ongoing care, including the assessment for secondary disabilities through school, psychological support, and a nuturing and supportive home environment with caregivers who understand the complexity of FASD. Because the younger child's cardiac findings indicate atrial septal defect (ASD), cardiology referral is important to monitor for cardiac compromise.

References:

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