Fetal alcohol

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Fetal Alcohol Syndrome: An Ophthalmologic Perspective

Disease Entity

Fetal Alcohol Syndrome (FAS) is an irreversible congenital condition that is a result of maternal alcohol use during pregnancy[1]. Classic signs include: abnormal facial features (short palpebral fissure, thin vermillion border, and smooth philtrum), growth retardation, and neurobehavioral impairment[2]. These signs range greatly in severity, and can include any mix of the classic signs. FAS is a syndrome that falls under a larger group of conditions known as Fetal Alcohol Spectrum Disorder (FASD). FASD includes Alcohol-Related Neurodevelopmental Disorder (ARND), Alcohol-Related Birth Defects (ARBD), partial-Fetal Alcohol Syndrome (pFAS), and FAS, which is considered the most severe syndrome.

Etiology

Alcohol is a known CNS teratogen that causes reduced brain volume and irregular brain and facial structure[3]. Though there are many hypotheses, the exact mechanism by which alcohol induces CNS and structural changes is still unclear3[3]. Some proposed mechanisms include: direct cytotoxic effect to embryonic cells (specifically the anterior neural ridge which organizes the prosencephalon), epigenetic changes leading to disrupted neural plasticity, and disruption of retinoic acid-based cell signaling[3][4][5][6].

Epidemiology

One CDC study showed FAS occurring in 0.3 out of 1000 children from 7-9 years old[7]. More recent studies have shown FAS to have a prevalence as high as 98.5 per 1,000 in certain US populations8-10[8][9][10].

Ocular Specific Pathology

Up to 90% of newborns with maternal alcohol misuse during pregnancy have ocular damage or abnormality[11] [12]. Both periocular and intraocular structures are affected13[13].

Periocular[13][14] [15][16]

  • Short horizontal palpebral fissures (decreased distance between the medial eye canthi and lateral eye canthi) commonly found and easy to measure[15].
  • Telecanthus (increased distance between the medial eye canthi) is commonly found in FAS[15][17].
  • Epicanthus (vertical fold of skin on the lateral nose), with one study finding up to 80% of infants exposed to alcohol having epicanthus[15][18].
  • Microphthalmia (abnormally small eyes) is commonly found in FAS and can aid in diagnosis of FAS[12][15][19].
  • Strabismus (abnormal alignment of eyes) is non-specific, but commonly found in FAS[12].
  • Blepharoptosis (drooping of upper eyelid) is non-specific, but can be seen in some FAS patients[12].

Intraocular

Optic nerve hypoplasia was found in up to 48% of Swedish children with FAS[11][15][20].

  • Small optic discs[21]
  • Decreased vision
  • Decreased number of optic nerve axons


Increased tortuosity of the retinal vessels was found in up to 49% of Swedish children with FAS[12][15][21]. Fundus abnormalities including optic nerve hypoplasia and tortuosity of the retinal vessels seems to remain unchanged throughout childhood and adolescence[21].

Decreased visual acuity

  • Attributed to optic nerve hypoplasia and increased tortuosity of retinal vessels.
  • In one study, up to 65% of FAS children had decreased visual acuity[11].
  • More than half of FAS children with visual impairment had severe acuity < 0.2[11].

Eye movement (motor control and executive function)[22]

  • Children with FASD had elongated reaction times, excessive direction errors, and no express saccades[22].
  • Possible dysfunction of frontal lobes[22]
  • Eye movement tasks could be another possible tool for assessing FAS in children as well as measuring executive function in FAS patients[22].

Primary Prevention

There is no known safe limit of alcohol consumption during pregnancy. Both quantity and pattern (binge) of drinking are more likely important factors in the teratogenic effects. Pregnant women and reproductive- aged women without reliable contraception should be advised to abstain from alcohol.

Detection through ophthalmologic exam

FAS often get missed in newborns and neonates, and is sometimes diagnosed as late as early adulthood. Early detection and diagnosis leads to significantly less comorbidities and symptoms in later life of FAS patients[23]. With rising prevalence of FAS, there is an opportunity for ophthalmology to drastically reduce the morbidity of FAS patients through a thorough eye exam. Some studies suggest a full ophthalmic exam in all children who are suspected of having FAS[15]. This includes: inspection of periocular features (supplemented with morphometric analysis if needed), visual acuity (with visual evoked potentials), slit lamp exam, and ophthalmoscopic exam (particularly the optic disc looking for optic disc hypoplasia and tortuosity of retinal vessels)[15][24]. In addition, ocular abnormalities seem to remain unchanged and persistent throughout childhood and adolescence, increasing the odds of diagnosing FAS[25]. Providing an FAS diagnosis earlier through eye exam could help provide earlier management of problems and reduce both ocular comorbidities (vision loss) and cognitive/neurobehavioral comorbidities.

Diagnosis

Clinical

FAS is diagnosed clinically and requires at least 2 of these findings: characteristic facial features (short palpebral fissure, thin vermillion border, smooth philtrum), signs of growth retardation (height and/or weight <10th percentile), clear evidence of brain involvement, or neurobehavioral involvement[26]. Documented maternal alcohol use is not needed for diagnosis, but can help provide evidence for FAS if positive[26].

Ocular Signs and Symptoms

The only ophthalmologic diagnostic criteria for FAS is short palpebral fissures. But, as discussed earlier, there are many periocular and intraocular signs that can point to a diagnosis of FAS. Ocular signs present earlier than signs of growth retardation, brain involvement, and neurobehavioral involvement and thus can be more useful in aiding the early diagnosis of FAS. Periocular signs include: short palpebral fissures, telecanthus, epicanthus, microphthalmia, strabismus, and blepharoptosis[13][14][15][16] . Intraocular signs include: optic nerve hypoplasia and tortuosity of retinal vessels[11][15][20][21]. Visual acuity can also be used to aid in diagnosis as FAS children tend to have reduced visual acuity[11]. Eye movement tasks could be another possible tool for assessing FAS in children as well as measuring executive function in FAS patients[22].

Comorbidities

One recent meta-analysis showed that the 5 most prevalent comorbidities of FAS were expressive language disorder, chronic otitis media, conduct disorder, receptive language disorder, and abnormal function of peripheral nervous system and special senses[27]. There also tends to be higher rates of mental disorders in people with FAS[28].

Differential Diagnosis[29]

Syndromes that may appear similar to FAS include: Williams Syndrome, DiGeorge Syndrome, Velocardiofacial Syndrome, Noonan Syndrome, Fetal Hydantoin Syndrome, Fetal Valproate, and Maternal PKU[29].

Management

General Treatment

Early detection and appropriate behavioral and special education are the most important factors for positive outcomes in children with FAS[23]. These therapies improve social and cognitive abilities and have an inverse relationship with time of diagnosis. Treatment is highly individualized and can include occupational therapists, speech therapists, and cognitive behavioral therapy for patients who suffer from anxiety and/or depression.

Medical Therapy

There are no specific medications approved to treat FAS, but appropriate medication can be used for related symptoms (e.g. stimulants for hyperactivity).

Complications

FAS is an irreversible congenital disorder that can only be prevented by decreasing alcohol quantity during the whole pregnancy. It is a lifelong disorder, and most treatment is symptomatic. Patients generally tend to have lower academic performance, difficulty reading social cues, and higher rates of incarceration[30].

Prognosis

Prognosis for FAS patients is poor with higher rates of alcohol/drug abuse, psychiatric disorders, unemployment, sexual misconduct, and disability[31][32]. One study also reported much lower average life expectancy for FAS patients at 34 years old with deaths reported due to suicide (15%), accidents (14%), poisoning by illegal drugs or alcohol (7%), diseases of the nervous and respiratory systems (8% each), and diseases of the digestive system (7%)[33].

Pictures

Fetal alcohol spectrum disorders [34]

References

  1. Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Cmaj 2005;172:S1-S21.
  2. Astley SJ. Comparison of the 4-digit diagnostic code and the Hoyme diagnostic guidelines for fetal alcohol spectrum disorders. Pediatrics 2006;118:1532-45.
  3. 3.0 3.1 3.2 Goodlett CR, Horn KH, Zhou FC. Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Experimental Biology and Medicine 2005;230:394-406.
  4. Sulik KK. Genesis of Alcohol-Induced Craniofacial Dysmorphism. Experimental Biology and Medicine 2005;230:366-75.
  5. Varadinova M, Boyadjieva N. Epigenetic mechanisms: A possible link between autism spectrum disorders and fetal alcohol spectrum disorders. Pharmacological research 2015;102:71-80.
  6. Deltour L, Ang HL, Duester G. Ethanol inhibition of retinoic acid synthesis as a potential mechanism for fetal alcohol syndrome. The FASEB journal 1996;10:1050-7.
  7. Fox DJ, Pettygrove S, Cunniff C, et al. Fetal alcohol syndrome among children aged 7–9 years—Arizona, Colorado, and New York, 2010. MMWR Morbidity and mortality weekly report 2015;64:54.
  8. May PA, Baete A, Russo J, et al. Prevalence and characteristics of fetal alcohol spectrum disorders. Pediatrics 2014;134:855-66.
  9. May PA, Gossage JP, Kalberg WO, et al. Prevalence and epidemiologic characteristics of FASD from various research methods with an emphasis on recent in‐school studies. Developmental disabilities research reviews 2009;15:176-92.
  10. May PA, Chambers CD, Kalberg WO, et al. Prevalence of fetal alcohol spectrum disorders in 4 US communities. Jama 2018;319:474-82.
  11. 11.0 11.1 11.2 11.3 11.4 11.5 Strömland K. Ocular abnormalities in the fetal alcohol syndrome. Acta Ophthalmologica Supplement 1985;171:1-50.
  12. 12.0 12.1 12.2 12.3 12.4 Strömland K. Ocular involvement in the fetal alcohol syndrome. Survey of ophthalmology 1987;31:277-84.
  13. 13.0 13.1 13.2 Strömland K, Pinazo-Durán MD. Ophthalmic involvement in the fetal alcohol syndrome: clinical and animal model studies. Alcohol and alcoholism 2002;37:2-8.
  14. 14.0 14.1 Astley SJ, Clarren SK. A fetal alcohol syndrome screening tool. Alcoholism: Clinical and experimental research 1995;19:1565-71.
  15. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 Abdelrahman A, Conn R. Eye abnormalities in fetal alcohol syndrome. The Ulster medical journal 2009;78:164.
  16. 16.0 16.1 Ribeiro I, Vale P, Tenedorio P, Rodrigues P, Bilhoto M, Pereira H. Ocular manifestations in fetal alcohol syndrome. European journal of ophthalmology 2007;17:104-9.
  17. Astley SJ, Clarren SK. Measuring the facial phenotype of individuals with prenatal alcohol exposure: correlations with brain dysfunction. Alcohol and Alcoholism 2001;36:147-59.
  18. Manning MA, Hoyme HE. Fetal alcohol spectrum disorders: a practical clinical approach to diagnosis. Neuroscience & Biobehavioral Reviews 2007;31:230-8.
  19. Sokol RJ, Clarren SK. Guidelines for use of terminology describing the impact of prenatal alcohol on the offspring. Alcoholism: Clinical and Experimental Research 1989;13:597-8.
  20. 20.0 20.1 20 Hug TE, Fitzgerald KM, Cibis GW. Clinical and electroretinographic findings in fetal alcohol syndrome. Journal of American Association for Pediatric Ophthalmology and Strabismus 2000;4:200-4.
  21. 21.0 21.1 21.2 21.3 Hellström A, Chen Y, Strömland K. Fundus morphology assessed by digital image analysis in children with fetal alcohol syndrome. Journal of pediatric ophthalmology and strabismus 1997;34:17-23.
  22. 22.0 22.1 22.2 22.3 22.4 Green CR, Munoz DP, Nikkel SM, Reynolds JN. Deficits in eye movement control in children with fetal alcohol spectrum disorders. Alcoholism: clinical and experimental research 2007;31:500-11.
  23. 23.0 23.1 O'Connor MJ, Frankel F, Paley B, et al. A controlled social skills training for children with fetal alcohol spectrum disorders. Journal of consulting and clinical psychology 2006;74:639.
  24. Strömland K. Visual impairment and ocular abnormalities in children with fetal alcohol syndrome. Addiction biology 2004;9:153-7.
  25. Strömland K, Hellström A. Fetal alcohol syndrome—an ophthalmological and socioeducational prospective study. Pediatrics 1996;97:845-50.
  26. 26.0 26.1 Hoyme HE, Kalberg WO, Elliott AJ, et al. Updated clinical guidelines for diagnosing fetal alcohol spectrum disorders. Pediatrics 2016;138:e20154256.
  27. Popova S, Lange S, Shield K, et al. Comorbidity of fetal alcohol spectrum disorder: a systematic review and meta-analysis. The Lancet 2016;387:978-87.
  28. Weyrauch D, Schwartz M, Hart B, Klug MG, Burd L. Comorbid mental disorders in fetal alcohol spectrum disorders: a systematic review. Journal of Developmental & Behavioral Pediatrics 2017;38:283-91.
  29. 29.0 29.1 Sharpe TT, Alexander M, Hutcherson J, et al. Report from the CDC. Physician and allied health professionals' training and fetal alcohol syndrome. Journal of Women's Health 2004;13:133-9.
  30. Jones K. Successfully raising resilient foster children with fetal alcohol syndrome: What works. Envision: The Manitoba Journal of Child Welfare 2004;3:1-18.
  31. Rangmar J, Hjern A, Vinnerljung B, Strömland K, Aronson M, Fahlke C. Psychosocial outcomes of fetal alcohol syndrome in adulthood. Pediatrics 2015;135:e52-e8.
  32. Streissguth AP, Bookstein FL, Barr HM, Sampson PD, O'MALLEY K, Young JK. Risk factors for adverse life outcomes in fetal alcohol syndrome and fetal alcohol effects. Journal of Developmental & Behavioral Pediatrics 2004;25:228-38.
  33. Thanh NX, Jonsson E. Life expectancy of people with fetal alcohol syndrome. Journal of Population Therapeutics and Clinical Pharmacology 2016;23.
  34. Williams JF, Smith VC, Abuse CoS. Fetal alcohol spectrum disorders. Pediatrics 2015;136:e1395-e406.