Despite the use of alcohol during pregnancy being the top preventable cause of birth defects and developmental disabilities worldwide, prevalence rates of fetal alcohol spectrum disorders (FASD) may be higher than previously believed. Recent studies in the US, for example, have found prevalence rates of 1.1%-2.5% for FAS and partial FAS (PFAS) combined, and rates of 2.4%-4.8% for the full spectrum of FASD. New guidelines published in Pediatrics present updated recommendations for the diagnosis of FASD.
In a 1996 report, the Institute of Medicine (IOM) defined 4 diagnostic categories of FASD, including FAS, PFAS, alcohol-related neurodevelopmental disorder (ARND), and alcohol-related birth defects (ARBD). The authors of the current paper, representing a variety of specialties, introduced diagnostic guidelines in 2005 based on the IOM categories. Because of advances in FASD research since that time, along with the combined expertise of the authors from assessing more than 10,000 children for FASD, they created an updated set of diagnostic guidelines.
“In the 11 years since our original diagnostic guidelines were published, significant headway has been made into specifically defining the cognitive and neurodevelopmental characteristics of affected children based on data-driven population-based studies, and a precise definition of the amount of prenatal alcohol exposure required to consider an FASD diagnosis,” lead author H. Eugene Hoyme, MD, told Neurology Advisor. Dr Hoyme is chief of genetics & genomic medicine at Sanford Health, professor of pediatrics at the University of South Dakota Sanford School of Medicine, senior advisor at the Center for Applied Genetics & Genomic Medicine, and professor of pediatrics and medicine at the University of Arizona College of Medicine.
The new guidelines include a step-by-step diagnostic algorithm for use in the clinical setting, as well as a special emphasis on neurobehavioral impairment. The criteria, which should ideally be applied in assessment by a multidisciplinary team led by a pediatrician or clinical geneticist/ dysmorphologist with the relevant expertise, cover the following aspects of diagnosis:
Assessment of maternal prenatal alcohol intake, the first step in the algorithm, is ideally based on the frequency, quantity, and timing of alcohol consumption during gestation. Considering the associated stigma, inquiries about alcohol intake should follow broader questions about the patient’s health and medical history. The authors note that “although certain circumstances permit the diagnosis of FAS or PFAS without firm documentation of gestational alcohol use… positive confirmation of alcohol exposure must be available for the diagnosis of ARND or ARBD to be assigned.”
Dysmorphology evaluation is the next step in assessment and includes evaluation of the presence or absence of prenatal growth restriction and the 3 cardinal facial characteristics of children with FASD. “If 2 of the 3 cardinal facial characteristics are present (short palpebral fissures, smooth philtrum, and/or thin vermilion border of the upper lip) the child is classified as having a positive dysmorphology facial evaluation for FASD,” the authors wrote. The new recommendations include added guidance for assessing the philtrum/lip in white children.
Neurodevelopmental assessment and neuropsychology evaluation is an essential diagnostic step considering that impairment of brain structure and/or function represents the primary fetotoxic effects of alcohol. While a conventional neurocognitive evaluation may not be feasible until the child is older than 3 years, the “cognitive and neurobehavioral phenotype of affected children evolves predictably over time… and can be correlated with areas of brain vulnerability,” according to the guidelines.
After those 3 key areas have been assessed, a case conference between the multidisciplinary team should take place before a diagnosis is assigned. In addition, because the facial phenotype associated with FAS may also be present in many other conditions, clinicians should “use a low threshold for ordering additional genetic testing of children with potential FASD,” they advise, and a “chromosome microarray has been shown to be the highest-yield diagnostic test when a genetic phenocopy of FASD is being considered.”
In summary, a diagnosis of fetal alcohol syndrome requires the presence of the following clinical features, according to Dr Hoyme: restricted growth in terms of height and/or weight; abnormal central nervous system structure or neurophysiology, e.g. small head circumference, structural brain malformations, or recurrent non-febrile seizures; and neurodevelopmental impairment. “Children with FASD can present with cognitive impairment alone, neurobehavioral abnormalities in the absence of cognitive impairment, or with a combination of both categories,” he said.
The authors note that not all experts in the field of FASD agree on universal diagnostic criteria; for example, others have advocated for the requirement of all 3 cardinal facial features vs 2 of 3. However, the current authors fear that approach could lead to underdiagnosis, and early detection is critical to help minimize the array of problems faced by children with FASD.
Hoyme HE, Kalberg WO, Elliott AJ, et al. Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. Pediatrics. 2016; doi:10.1542/peds.2015-4256.