ENGLISH
Among the various factors affecting a child’s postnatal condition, including the function of the visual system, changes caused by fetal alcohol spectrum disorders (FASD) are highly significant.
FASD encompasses a spectrum of abnormalities in body structure, growth retardation, neurological alterations, congenital anomalies, and cognitive as well as behavioral disorders. Globally, negative effects of prenatal alcohol exposure on the developing embryo and fetus affect 0.77% to 1.0% of live births. In Europe and North America, FASD prevalence rates range between 2% and 5% of the population [1-3]. They vary between countries and are also related to the accessibility of epidemiological methods. According to the Demographic Yearbook, over 305,000 live births were registered in Poland in 2022 [4]. Estimating that approximately 1% of these children might develop symptoms of FASD, the condition would affect 3,050 children, representing a numerically significant group. These children need ongoing multidisciplinary medical care and psychological attention, while also presenting significant social challenges that come with their associated costs. In highly developed countries, the economic index of FASD-related procedures shows that they require considerable financial resources extending across many years [5, 6]. Except for psychiatric costs, the expenses for healthcare are the highest during the early years of life of FASD children [6].
The authors of the present study found no information in the existing Polish ophthalmological literature regarding organic and psychological abnormalities induced by FASD. Therefore, the authors thought it appropriate to conduct a more detailed examination of health issues in children with FASD.
Prenatal alcohol exposure (PAE) is known to profoundly impact neurological development through several mechanisms including oxidative damage, apoptosis, modulation of gene expression, and interference with neuronal migration/axonal pathfinding [1]. Deficits in neuronal plasticity are believed to be the underlying cause of abnormal neurological development in human fetal alcohol spectrum disorders and in animal models [1, 7]. Brain developmental abnormalities are thought to result from alcohol-induced damage to glial cells [8]. Neurological changes linked to FASD have a negative impact on the child’s cognitive abilities, learning capacity, knowledge acquisition, interpersonal relationships, and social behavior. Neuroimaging uncovers abnormalities in brain architectonics, and visualizes the degree of cerebral cortical development and white matter microstructure, allowing assessment of the functional effects of damage to these structures [2, 7]. Exposure of the developing fetus to the effects of alcohol not only leads to neurodevelopmental disorders but also induces somatic changes and mental health deviations. The detrimental consequences of prenatal alcohol exposure on the growing embryo and fetus manifest as a series of physical abnormalities and behavioral neurocognitive deficits. Even though FASD presents with a broad range of distinct clinical symptoms, it is not always identified and diagnosed accurately at an early stage. This is likely due to several factors, including a lack of awareness about the disease; concerns about social stigmatization of FASD patients; the complexity of the diagnostic process, which can lead to underdiagnosis; variable severity of facial dysmorphia; and the potential overlap with other diagnoses [1]. Many individuals with milder FASD exhibit subtle subclinical neurodevelopmental defects that may go unnoticed during clinical observation.
In addition to the abnormalities mentioned above, the symptoms and clinical presentation of the disease include a range of manifestations observed from the neonatal period onward, such as low birth weight with slow weight gain and delayed growth, alcohol withdrawal symptoms in newborns (such as inarticulate sounds, crying, tremors, and seizures), hypersensitivity to stimuli, feeding problems, delayed sleep onset and intermittent sleep, thoracic structural anomalies causing flattened chest, developmental abnormalities of internal organs, damage to the organ of vision, impaired physical coordination, general developmental delays, cognitive issues, learning difficulties, poor school performance, and low IQ. A substantial proportion of these defects stems from cortical brain damage, which has an adverse effect on the visual cortex, also causing disruption in visual function [9, 10].
Physical damage to the growing fetus due to alcohol poisoning in FASD can lead to various abnormalities contributing in particular to the development of heart defects, liver disease, disorders in the urinary tract starting with the kidneys, and damage to the reproductive organs. These abnormalities are typically linked to intellectual, mental, and psychological defects stemming from damage to the central nervous system and other sensory organs, such as hearing.
FASD is distinguished not only by abnormalities in the child’s overall physical structure but also by characteristic craniofacial changes. Notable among them are microcephaly, facial dysmorphia, microphthalmia, flattening of the midface, wide nasal bridge, short upturned nose, thin upper lip, absence of philtrum, mandibular underdevelopment, low-set malformed auricles, epicanthic fold, and short palpebral fissures. These changes, combined with other ophthalmic abnormalities, contribute to the spectrum of alterations seen in FASD and affect structures of varying importance for visual processes [2, 10-12]. Ophthalmic evaluation is an integral part of the diagnostic work-up for FASD. It is one of the primary examinations conducted to reach a diagnosis when there is suspicion of disease. Specialist ophthalmic assessment, adjusted to the age and cooperation ability of young patients, is essential for any child with suspected FASD referred to a medical practitioner. Ophthalmic diagnostic work-up comprises evaluation of visual acuity, refraction, and binocular vision, as well as biomicroscopy of the anterior segment of the eye and optical media, and ophthalmoscopy. Complementary diagnostic examinations, including imaging tests (radiology, ultrasound, magnetic resonance imaging, angiography, optical coherence tomography to evaluate individual internal ocular structures), electrophysiological assessment, perimetry, intraocular pressure measurements, photographic documentation of ocular lesions, tests to determine the need for corrective spectacles (or contact lenses), and other evaluations helpful in diagnosing FASD-induced ocular lesions, are also performed. The changes identified are numerous and affect the condition of the organ of vision to varying extents. Based on a total of 1,068 publications related to the topic, Tseng et al. identified 36 papers related to FASD, focusing specifically on the presence of ocular changes within this spectrum [13]. The study identified both structural and functional ocular abnormalities in children with FASD. Some of these changes were observable through direct visual assessment, while others required the use of specialized equipment. An increased distance between the inner corners of the eyes (telecanthus) was found in 31.7%, shortened palpebral fissures in 66.1%, and epicanthus in 53.5% of examined children. Visual acuity was reduced in 55.5% of the studied population of children with FASD. Additionally, 53.0% exhibited a disruption of binocular vision, with 33.0% of those affected showing impaired fixation ability. Changes in the ocular fundus manifested as an abnormal tortuous course of the retinal vessels in 50.5%, optic nerve hypoplasia in 30.2%, and small optic disc in 27.0% of children. Compared to the reference group, these changes occurred more frequently in the studied children with FASD [13].
Similar changes in the organ of vision were reported in other earlier publications, referenced by Ayoub et al. [12]. Based on the findings of these studies, children with FASD had a high prevalence of ophthalmic disorders, including inadequate visual acuity, optic nerve hypoplasia, retinal vascular abnormalities, visual perception problems, refractive defects, strabismus, and eyelid disorders.
In their study, Lyubasyuk et al. examined a subgroup of 53 children with FASD, aged 5-7 years, selected from a larger cross-sectional study involving 424 participants. They found a statistically significant association between FASD and the occurrence of strabismus, which was diagnosed in 11.9% of children. The authors propose that a high prevalence of strabismus in FASD children is associated with their distinctive facial structure consistent with the morphological characteristics of FASD. The authors did not find any correlation between reduced visual acuity, refractive errors, or the presence of one or more ophthalmic abnormalities in children with and without FASD [14].
FASD represents a broad spectrum of disorders. However, the clinical presentation in patients does not always encompass all symptoms. Children may exhibit selective deviations from the norm and abnormalities with an incomplete range of symptoms and varying clinical severity, forming distinct disease entities that make up FASD.
The most frequently reported changes are associated with fetal alcohol syndrome (FAS). FAS is characterized by a triad of symptoms including facial dysmorphia, growth abnormalities (low weight gain and growth deficiencies), and brain damage with associated dysfunctions. The study by Ribeiro et al., examining ocular changes in a group of 23 children with FAS, revealed prominent abnormalities similar to those observed in FASD [15]. Ptosis occurred in 16% and short palpebral fissures in 81% of the children. Epicanthic fold was noted in 27% of the eyes. A large distance between the inner canthi was observed in 13% of the children. Nystagmus was present in one, and unilateral cataract in another child. Refraction ranged from –23.0 to +6.5 diopters of spherical equivalent. The mean corrected visual acuity was 0.8+/–0.2. Analysis of photographic documentation also revealed changes in the eye fundus. In children with FAS, retinal vessels were characterized by tortuosity in 30%, optic nerve hypoplasia in 25%, and small optic nerve disc in 40% of the eyes.
Partial fetal alcohol syndrome (pFAS) includes some of the signs and symptoms of FAS. Children diagnosed within the spectrum of this syndrome exhibit two physical features associated with FAS: facial dysmorphia and growth retardation. However, these abnormalities are expressed to a lesser degree in pFAS compared to FAS. Ophthalmic disorders are part of the spectrum of FASD.
Children with alcohol-related neurodevelopmental disorders (ARND) often experience learning difficulties, particularly in mathematics, problems with memory retention, attention deficits, struggles with adaptation to school demands, potential communication issues, and atypical behaviors.
Alcohol-related birth defects (ARBO) is a term referring to another group of disorders within FASD, associated with the teratogenic effect of alcohol on the process of organogenesis. They can lead to developmental disorders in various internal organs, primarily affecting the heart, kidneys, bones, and hearing.
The underlying cause of these abnormalities is always unequivocal: they stem from maternal consumption of alcohol during pregnancy, irrespective of the quantity and frequency of alcoholic beverages consumed. The diversity of symptoms and the mother’s concealment of alcohol consumption during pregnancy can delay accurate diagnosis and initiation of appropriate medical management.
Ethanol, which crosses the placenta, reaches the developing fetus in the uterus unhindered, causing irreversible damage to tissues and organs. The amount of alcohol consumed by the mother during pregnancy, the duration of fetal exposure to toxins, the mother’s age and overall health, and the trimester of pregnancy all influence the specific manifestations of the disorder. Fetal pathologies resulting from alcohol exposure may emerge later in a child’s life or in adulthood, leading to a range of health effects of varying severity [16-18]. These differences were highlighted in the study by Gyllencreutz et al. The authors examined the organ of vision in children who were several years old and then followed up over a period of more than a dozen years [18]. Visual acuity in children, determined with the LogMAR chart, was 0.2/0.2 in the right and left eyes, respectively, and reached 0.05/0.0 after 13 to 19 years. The refractive range of the right eye relative to the left eye was +0.88/+1.25 (–8.75 to +4.75/–9.38 to +5.25) Dsph in childhood and –0.25/–0.25 (–12.0 to +2.75/–13.25 to +2.63) Dsph in adulthood. Astigmatism was found to be the most common refractive error, affecting 40% of children and 47% of adults. Over the years of follow-up, the prevalence of stereoscopic vision disorders increased to 67% in children and 73% in adults. In adulthood, 43% of patients exhibited changes in the organ of vision which were less common in children (40%), including tortuosity of the retinal vessels, which occurred in 27% of individuals in childhood and 37% in adulthood, and optic nerve hypoplasia, which was also diagnosed slightly more often in adults with FASD. The authors conclude that ophthalmic symptoms, such as refractive defects, strabismus and ocular fundus abnormalities, are prevalent in children with FASD and continue into early adulthood. Facial features characteristic of FAS typically diminish with age, which makes it less likely to detect the classic dysmorphia of FAS in adults. This publication also highlights the value of ophthalmic examination in FASD, both in childhood and early adulthood.
The diagnostic work-up for FASD requires collaboration among medical professionals from various specialties as well as good communication with the mother/parents of a child suspected of alcohol exposure in utero. Before the physical examination, a comprehensive medical history should be obtained, covering the course of the pregnancy, the health of the newborn, and prior medical management. The diagnostic work-up incorporates an evaluation of the specific health deficits present. In the process of differential diagnosis, it is crucial to first assess the child for other congenital defects or genetically determined diseases that are not linked to maternal alcohol consumption during pregnancy. The evaluation should take into account the potential effects of intrauterine infections caused by various pathogens, congenital complications, zoonoses, as well as conditions like attention deficit hyperactivity disorder (ADHD), as its symptoms in childhood can resemble those seen in FASD.
Currently, there are no standardized screening tools available for FASD. Screening relies primarily on tests administered by primary care physicians, mid-level medical staff, social workers, and psychologists. The results of these tests dictate the initiation of a specialist diagnostic work-up for FASD and establish the timeline for the commencement of such assessment. Okulicz-Kozaryn et al. proposed screening tests for FASD in Poland, thoroughly addressing all issues relevant to this condition [19]. The recommendations include suggestions for repeated check-ups, the extent of which should be adjusted to the specific needs of each child, considering identified dysfunctions and any newly reported issues. The recommendations apply to children aged 4, between 6 and 7 years (the period of starting school), at approximately 11-12 and around 18 years of age.
The complexity of the clinical presentation underscores the importance of engaging an interdisciplinary team of specialists in the identification, assessment, and treatment of the disorder. Prevention of fetal damage involves pregnant women’s abstinence from consuming alcohol.
The “FASD Eye Code” proposed by Arving et al. and Avyub et al. might serve as a valuable supplementary diagnostic tool for FASD, assisting in the identification and diagnosis of ophthalmic abnormalities in individuals suspected of having FASD [12, 20].
There is no causal treatment for ophthalmic abnormalities stemming from FASD-induced irreversible fetal damage. Abstinence from alcohol is a key strategy for preventing FASD. Regardless of the stage of pregnancy, there is no safe amount of alcohol for a pregnant woman. Medical management in children with FASD involves long-term rehabilitation encompassing both physical interventions (physical therapy, exercise programs) and psychological support. Ophthalmic treatment, both surgical and conservative, focuses on enhancing the function of the visual organ. It may involve eyelid surgery, management of strabismus, and correction of existing refractive defects to improve vision. Children with FASD require regular ophthalmological follow-up. Treatment involves addressing existing dysfunctions and preventing secondary disorders that may arise due to inadequate or absent medical care.
