Exposure to alcohol during pregnancy, makes a wide spectrum of disorders, the tip of the iceberg being the fetal alcohol syndrome (FAS); the amount of alcohol ingested ranging from occasional to chronic consumption. This syndrome is characterised by mental retardation, cranio-facial abnormalities, growth disorders, brain malformation (corpus callosum agenesis or hypopla-sia, hidrocephaly), cardiac and renal malformation, skeletal abnormalities, vision and hearing disorders. There is no treatment that can prevent the harmful effects of alcohol on fetus, the best measure in this regard is total avoidance of alcohol consumption during pregnancy.
Fetal alcohol syndrome (FAS) is a severe develop-mental disorder caused by fetal exposure to alcohol during prenatal period, with clinical features such as: cranio-facial malformations (sometimes even devel-opmental malformations of ventral induction, from 5 to 10 weeks) growth retardation (delay in intrauterine growth and failure to thrive postnatally, after birth), CNS dysfunction (cognitive impairment, learning disabilities or hyperactive behaviour).
Prenatal exposure to alcohol is of interest to public health for the following reasons: mental retardation is a major cause, fetal alcohol syndrome disorders are associated with physical and neurodevelopmental abnormalities. These occur in all socioeconomic groups and is found in all races and ethnicities.
The exact amount of alcohol that can cause this syndrome is unknown. It has been described consumer cases ranging from occasionally to chronic alcohol consumption. The alcohol consumed during pregnancy crosses the maternal-fetal barrier (area where the ex-change of nutrients takes place between mother and fetus) lowering thus the exchange of nutrients to the fetus, resulting in growth disturbance and normal fetal development. The metabolism of alcohol by the foetus depends on maternal liver detoxification because the activity of fetal alcohol dehydrohenase is <10% compared to the level of an adult. It was found that ethanol and its metabolite, acetaldehyde, prevents the growth and development of the foetus, inhibits protein syn-thesis and cell migration, cause DNA deletions, gets involved in intermediary metabolism of carbohydrates, proteins and lipids, decreases the transfer of glucose, amino acids, folic acid, zinc and other nutrients to the fetus through maternal-fetal barrier, preventing cell differentiation and growth (fig. 1).
In addition to FAS, alcohol consumption during pregnancy, can cause devastating effects same like an iceberg: miscarriage, placental abruption, premature birth, stillbirth, sudden infant death syndrome (fig. 2).
PATHOPHYSIOLOGY OF BRAIN MALFORMATIONS CORRESPONDENCE
Corpus callosum is a structure of white substance that connects the two cerebral hemispheres, making informations coordination and exchange of sensory stimulus between the cerebral hemispheres. The IQof patients varies greatly and can be normal. Symptoms of patients with agenesis of corpus callosum are very different from individual to individual, but there are some features, such as: visual disturbances, generalized weakness, inability to coordinate movements, slurred speech, swallowing disorder, delayed motor acquisi-tions, adaptation dificulty and social integration.Also seizures can occur, spasticity and mental retardation of varying grades. The absence of thalamic nucleus fusion determines attencion deficit and memory processing disorder in sleep. The result is an attencion deficit hy-perkinetic disorder (ADHD) and learning difficulties.
Normally, under focusing attention, basal nucleus cholinergic neurons of Meynert will produce an addi-tional inhibition of Mesh thalamic neurons reducing even more the thalamic filter for a better perception of the stimulus that captivate the attention. During the nonREM sleep Mesh thalamic neurons inhibits tha-lamic relay neurons increasing the capacity of thalamic filter (the brain does not respond to stimulus). During the REM sleep, cholinergic neurons from the latero-dorsal and pedunculo-pontin nucleus inhibits reticular neurons allowing brain stimulation by internal stimu-lus (from mnezic deposits). Relay nucleus plays a role in skin sensitivity, taste, hearing and visual.
Fig. 1. The effect of ethanol and its metabolite, acetaldehyde, during pregnancy
Fig. 2. Consequences during pregnancy, secondary to alcoholconsumption
The incidence of fetal alcohol syndrome in U.S is es-timated at 1-2 cases per 1000 live births rising to 4-5% in communities from South Africa, Russia etc. (4, 6).
American Institute of Medicine Guidelines con-tain three classes of diagnosis, namely (tabel I).
In addition to these classes, can be used another two categories, when maternal exposure to alcohol is present and other causes are excluded :
- (ARBD – alcohol-related birth defects)
- (ARND – alcohol-related neurodevelop-mental disorders)
The clinical picture of FAS includes:
- cranio-facial anomalies: short palpebral fis-sure, flat midface hypoplasia, flattened nose root, short nose, epicantus, thin upper lip, micrognathia, long philtrum and indistinct, microphthalmia, stra-bismus, short neck;
- CNS abnormalities: microcephaly, mental retar-dation, cognitive impairment, developmental delay, infant irritability, hyperactivity in childhood, attention deficit, seizures, incomplete or delayed myelination, agenesis or hypoplasia of the corpus callosum, hydrocephalus;
- skeletal abnormalities: radioulnar synostosis, flexion contracture, camptodactily, aberrant palmar crease, clinodactily, scoliosis, dislocated joints;
- other major birth defects: palatoschizis/ogi-val palate, heart and/or kidney malformations;
- functional disorders: refractive disorders (my-opia, astigmatism), optic disc hypoplasia, hearing loss;
- growth failure: small for gestational age (<10 per-centile for weight or length), postnatal growth deficiency.
As treatment, the most important is prevention, avoiding maternal exposure to alcohol during preg-nancy. Treatment for these patients also includes cor-rection of associated congenital defects, treatment of cognitive and behavioral deficiencies with psychoac-tive drugs and special education.
In terms of prognosis this is reserved, most pa-tients are having mental health problems (95%); near school age these patients abuse or the become addicted to alcohol, drugs, they failure school, have behavioral disorders with delinquency (60%), have in-napropiate sexual behavioral (52%) and at about adult age are unable to live independently (82%) and have trouble finding or keeping a job (70%). (7)
Patient R.W., aged 1 year and 3 months from rural areas is hospitalised for fever, refusing food and
vomiting onset of aproximately 2 days. Insignificant family history.
Living and working conditions: 7 persons in a room, both parents smokers, drinking alcohol occasionally, comes from a poor socio-economic environment. Cohabitants and separated parents are now both unemployed. Of physiological and pathological personal history: mother – 17 years and 9 months, primiparous with hospitaliza-tion in 7 months of pregnancy for infection urinary tract, spontaneous birth at 39 weeks, cranial presentation with fetal hypotrophy, birth weight 2500 g, length 47 cm, Ap-gar score 9/8. He presented moderate respiratory distress.
The patient had multiple admissions in Brasov Children’s Hospital for: acute pneumonia, acute en-terocolitis, acute dehydration syndrome, anemia defi-ciency, urinary tract infections with E.Coli, Klebsiella, microcephaly, hydrocephalus, hypoplasia of the optic disc, agenesis of the corpus callosum and septum pel-lucidum, severe psychomotor retardation, protein-en-ergy malnutrition, social case.
Clinical examination: poor general condition, weight 6300g on admission in hospital, length 71 cm, head circumference 44 cm, thoracic perimeter of 45 cm, hypotrophy stature weighted with an index of 0.68 (9250g ideal weight for age), a facies dismorfic with: microcephaly, small palpebral fissure, epicanthal folds, flattened nose root, flat midface hypoplasia, short nose, long philtrum and deleted, thin upper lip, ogival palate, micrognathia, short neck, intermittent horizontal nystagmus, skin and pale mucous membranes with capillary staining of 4 seconds, elastic abdominal skin fold reduced, pharyngeal hyperemia, dental eruption, underrepresented fat on the chest, abdomen and limbs; flared torax at base, nasal obstruction, serous rhinorrhea, stetacustic lung – transmission bilateral rales, oliguria due to dehydration, not keeping his head, cooing.
From investigations: leukocytosis with lymphocy-tosis, anemia, electrolyte disturbances, urea increased secondary to dehydration, ear drops reaction to ENT examination, thoracic cervical spine radiography, functional thoraco-lumbar kyphosis; x-ray fist delayed bone age; ophthalmologic exam hypoplasia of optic disc; cranial CT: agenesis of corpus callosum, agenesis of septum pellucidum, triventricular hydrocephalus making monoventricular aspect, without clear signs of front fusion, without thalamic nucleus fusion.
Based on history, clinical examination and labo-ratory investigations, it been established the fol-lowing diagnoses: severe psychomotor retardation developmental malformation (agenesis of corpus callosum and agenesis of septum pellucidum triven-tricular hydrocephalus), optic disc hypoplasia, pro-tein-energy malnutrition grade II, acute dehydration syndrome,nacute nasopharyngitis, deficiency anemia.
The presence of these diagnoses made us orient to FETAL ALCOHOL SYNDROME.
Diagnosis of fetal alcohol syndrome was support-ed positive on:
- history: patient born at 39 weeks, fetal hypotrophy, presented moderate respiratory distress, comes from a poor socio-economic environment, presence of maternal exposure to alcohol during preganancy;
- clinical: staturo-ponderal hypotrophy, with weight and length below the percentile of 3% for the age; facies dysmorphic presence (fig. 3 , fig. 4, fig. 5); hypoton, with diminished reactivity, severe psychomotor retarda-tion, (not being able to hold his head, cooing) (fig. 6)
- laboratory: fist radiography that showed delayed bone age; optic disc hypoplasia at eye examination (fig. 7a, fig. 7b); cranial CT scan which revealed: agenesis of corpus callosum and septum pellucidum, triventricular hydrocephalus making monoventricular aspect. (fig. 8)
According to diagnosis guidelines of American Institute of Medicine for FAS, this case was classi-fied as class I diagnosis due to positive maternal ex-posure to alcohol, presence of cranio-cerebral facial abnormalities characteristic to prenatal and postnatal growth retardation and central nervous system neuro-development abnormalities.
As differential diagnosis were considered the fol-lowing genetic syndromes (tabel II) (8).
Facies dismorfic with: 1. Flattened nose bridge. 2. Epi-canthal folds. 3. Short nose. 4. Short palpebral fissure. 5. Long philtrum. 6. Micrognathia. 7. Short neck.
Facies dismorfic (profile): 1. Flattened nose bridge. 2. Short nose. 3. Long philtrum. 4. Micrognathia
Severe psychomotor retardation (1 year and 3 months) – not holding his head, not being able to sit.
Normal ophtalmoscopic image of an normal eye, average diameter of the optic nerve papilla (1500 microns) and normal diameter of retinal veins near the optic nerve papilla (120-150 microns)
Fundus photo view at our patient where the diameter of retinal vein near the optic nerve papilla is normal and papilla is small, pale and has blurred contour plan.
Fig. 8. CT scan:
1. Absence of septum pellucidum. 2. Ventricle III ascending (indirect sign of corpus callosum absence). 3. Occipital horns of lateral ven-tricles are parallel (indirect sign of corpus callosum absence). 4. The absence of corpus callosum. 5. The absence of brain scythe.
- Alcohol consumption during pregnancy is a real risk factor for fetal alcohol syndrome, low birth weight, congenital defects. The confirmation of alcohol consumption is difficult to obtain from parents and the amount is very subjective. The average con-sumption of occasionally alcohol among pregnant women is 12.2% (1 in 8 women) and among pregnant women with excessive alcohol consumption is 1.9%. At a total number of 10,000 births, the FAS in-cidence in different ethnic groups is 29.9 at native americans, 0.8 hispanics, 0.3 for asians (1, 2)
- The diagnosis for this patient was established early despite the young age, mostly are diagnosed at school age when mental retardation becomes obvious. Diagnosis was made possible due to the gravity of the case, meeting the evident criteria of fetal alcohol syn-drome class I.
- In our case the mother is unmarried, minor, eight classes graduate, having therefore risk for alco-hol consumption. Centers for Disease Control and Prevention (CDC) analyzed in a study the fact that between 2001 and 2005 the highest percentage of alcohol consumption during pregnancy was found in women aged 35-44 years (17.7%) with higher education (14.4%), employed (13.7%) and unmarried (13.4%) (1, 2).
- Patient with this syndrome involves a high cost with various intercurrent disease requiring therapy, antiepileptic treatment and cognitive stimulation adapted to disease complications: hearing loss, visual disturbances, mental retardation. In the U.S about $2 million is spent on patient living with fetal alcohol syndrome and annualy $321 millions are used for the care of these patients. (2)
- Variable disorders in all metabolic lines affects the somatic development, generates persistent gaps so that children with FAS have significantly a decrease below average in terms of weight, height and head circumference.
- The clear moment of developmental malforma-tions suggests that alcohol ocurred in the first 5-10 weeks of pregnancy.
- Mental retardation is a cause of maternal expo-sure to alcohol.
- The more maternal exposure to alcohol is ear-lier in pregnancy, the more the risk of developmental malformations of ventral induction; the weeks 5-10 (3) are higher for fetal survival and long term progno-sis is more reserved.
- Excessive costs of fetal alcohol syndrome complications, cause the need of information approved by the media, schools and medical services regarding the effects of alcohol on pregnancy.
The most important and efficient treatment re-mains prevention.
- Bailey BA, Sokol RJ. Pregnancy and alcohol use: evidence and recommendations for prenatal care. Clin Obst.et Gy-necol 2008;51:436–44.
- Centers for disease control and preventions, http://www. cdc.gov/ncbddd/fasd/index.html
- Engel J. Jr. and Pedley TA. Epilepsy: A Comprehensive Textbook. Lippincott-Raven Publishers, Philadelphia 1997.
- May PA, Brooke L, Gossage JP, et al. Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province. Am J Public Health. Dec 2000;90 (12):1905-12
- Sampson P.D. ET AL. Teratology 56:317 – 326 (1997)
- Stratton K, Howe C, Battaglia F. Fetal Alcohol Syndrome: Diagnosis, Epidemiology, Prevention, and Treatment. National Academy Press; 1996
- Streissguth, A. (1997). Fetal Alcohol Syndrome: A Guide for Families and Communities. Baltimore: Brookes Pub-lishing.
- Taybi H. Handbook of Syndromes and Metabolic Disor-ders: Radiologic and Clinical Manifestations. Philadelphia, PA: Mosby-Year Book; 1998
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