Journal of Pediatrics, 92(1):64-67

The photograph at left shows the brain of an infant girl who died at 6 weeks. The mother was categorized as a chronic alcoholic. The child’s head circumference was 27 centimeters at birth and did not grow at all during her 6 weeks of life (normal head circumference is approximately 35 centimeters - about 13 and 3/4 inches).

Readily observable is a massive sheet of tissue that covered the left cerebral hemisphere. Microscopic investigations showed some areas of the left cortex were "uniformly thinned and disorganized." There was an increased cell density in the second layer of the superficial cortical layers (top of the brain) and decreased cell density in the third layer, demonstrating errors in the migration process of brain cells. The researchers also found that in scattered areas of the cortex the neurons showed "bizarre arrangements."

Case number 2 was a male infant born at term and died at 10 weeks due to a sudden cardiac arrest (see picture at right). The mother's alcohol drinking included   up to a gallon of wine at a time several times a week. The child had hydrocephalus (excess water in the brain) and typical facial features of fetal alcohol syndrome (FAS). The cerebellum (which controls coordination and movement) was "extremely small and poorly shaped (see picture at right)." The brainstem (responsible for processes such as breathing and body temperature) was also grossly malformed.

Case number 3 was stillborn at the 29th week of pregnancy. The mother reported drinking alcohol beverages at approximately weekly intervals, sometimes consuming at least five "drinks" at one time. The child had most of the features of FAS, including short palpebral fissures, flat midface, cleft lip and palate. The testicles were also absent. The cerebrum appeared normal except for overly large ventricles (the ventricles are fluid cavities in the brain which help maintain constant pressure). The researchers stated the brainstem and cerebellum were "unfortunately lost" prior to microscopic study.

Case number 4 was a premature infant born about two months early. The mother reported drinking alcohol three or four times each week, sometimes consuming at least five "drinks" at one time. The child suffered respiratory distress and died three days after birth. Although the brain weight of the infant was normal and no features of FAS were apparent, there was the similar smooth covering of the left cerebral hemisphere as shown in the picture of the first infant.

In a discussion of these observations, the researchers stated:

Fetal Alcohol Syndrome (FAS)
Occurs After One Binge Drinking Episode

Fetal Alcohol Syndrome
Occurs at Moderate Alcohol Levels

10% risk of having abnormal or FAS child
if drinking ranged from 1 to 2 ounces of absolute alcohol per day (2-4 drinks)

19% risk of having abnormal FAS child
if drinking ranged above 2 ounces of alcohol daily (more than 4 drinks)

The figures above show the serious problem posed by drinking mothers. These figures are not 10% and 19% increased risk figures for having an abnormal or FAS child but are the actual risk figures. In other words, the study showed that if the mother drank 2-4 drinks daily - she had a 1 in 10 chance of having an abnormal or FAS child and if she drank more than 4 drinks daily she had nearly a 1 in 5 chance of having an abnormal or FAS child. Previous reports have suggested that in chronic alcoholic women (usually more than 5-6 drinks daily) the risk of producing a clinically abnormal child (not necessarily a complete FAS) may be 40% or more. Also, the researchers stated that the observation that drinking behavior in the immediate prerecognition of pregnancy period is more strongly related to fetal outcome suggests that the quantity and timing of alcohol intake in the earliest stages of pregnancy have important implications for fetal growth and development.

The researchers concluded,

Dr. James W. Hanson
Dysmorphology Unit, Department of Pediatrics, University of Washington
Journal of Pediatrics, 92(3):457-460

Attention Deficit & Distractibility Increase
when Mothers Consumed Alcohol During Pregnancy

Neurobehavioral Toxicology and Teratology, 8:717-725, 1986

Attention, distraction and impulsive behavior problems were found to occur more often in a study of 475 young school age children whose mothers drank moderate amounts of alcohol during pregnancy. The study, conducted by the University of Washington, used sensitive neurological test measures, called Continuous Performance Tasks (CPT), to determine endurance, persistence, organization, distractibility and impulsivity in this large group of 7 year old children.

One test given, considered to be effective at assessing Attention Deficit Disorders, is called the AX-task. In this test the child sits at a computer screen that is flashing single letters at one second intervals. The child is asked to push a button when the letter "X" appears, but only when it was immediately preceded by the letter "A". The number of errors were then calculated for three different mother alcohol consumption levels (0-3 drinks daily, 3-4 drinks daily, & more than 4 drinks daily) to determine if there was any correlation between the amount of alcohol consumed and the number of errors the child made on the test.

The results showed that greater alcohol exposure resulted in far more errors on the AX task. The authors stated that, "The direction of the effect is as predicted, with poorer performance associated with higher (alcohol) exposure."

Tests of distraction were also conducted while the child was taking the CPT tests. There was an 8% distraction rate for the 0-3 drink exposure children, a 14% distraction rate for the 3-4 drink exposure children and a 46% distraction rate for the children whose mothers drank more than 4 drinks per day. Average reaction times were about twice as slow for the more than 3 drink exposure children. In conclusion the researchers stated,

Developmental Observations
of Children & Adolescents Exposed to Alcohol

A variety of neurological and school problems were detected among 500 children examined at numerous points in time, including day 1 and 2 of life, at 8 and 18 months, and then again at 4, 7 and 14 years. Mothers were primarily white, middle class, well-educated, married women at low risk for adverse pregnancy outcomes. Approximately 80% were drinking. The study, headed by Dr. Ann P. Streissguth, Department of Psychiatry and Behavioral Sciences, University of Washington, lists the following principal findings:

1. Effects of prenatal alcohol exposure are clearly obvious at all ages from birth to 7 years; they were detected on a variety of behavioral measures.
   
2. Among the most salient sequelae of exposure are neonatal habituation to light, time in error from the Wisconsin Motor Steadiness Battery at age 4, standardized WISC-R and WRAT-R arithmetic subtests at age 7, and academic adjustment rating by the second grade teacher.
   
3. For most outcomes, binge drinking has more serious consequences than steady drinking, and drinking early in pregnancy has more serious consequences than drinking in midpregnancy.
   
4. These alcohol effects cannot be explained away by any of 150 covariates considered, including parental education, nutrition, and smoking.
   
5. Profiles of alcohol-related scholastic and neurobehavioral deficit are shown by second grade. Data from teachers when the children reached age 11 revealed prenatal alcohol-related difficulties in classroom behavior, academic performance (particularly arithmetic), and information processing. At 14 years, continued prenatal alcohol effects on measures of attention and memory were observed, as well as on measures of phonological processing and numerical reasoning.

Reading Test Scores Lower
in Children Whose Mothers Drank Alcohol
During Last Trimester of Pregnancy

Neurotoxicology & Teratology, 13:357-367, 1991

Significant reductions in several areas of intellectual functioning were found in preschool children whose mothers drank during pregnancy. The study, conducted by the Emory University School of Medicine and Georgia Mental Health Institute, looked at 68 mother/child pairs, primarily low income and black, who were placed into three groups including: "never drank" (21 mothers), "stopped drinking" (22 mothers who stopped drinking just before the third trimester), and "continued to drink" (25 mothers who were exposed throughout pregnancy). The women did not use other drugs except for cigarette and marijuana use in about 12%. Average alcohol intake for both alcohol drinking groups was 2-3 drinks per day with approximately 21% of the women engaging in "binge" drinking episodes of more than 5 drinks per occasion.

Main results of the survey showed children’s head circumference was much lower in the drinking groups measuring 34.7 cm for the "never drank" - 33.3 cm for the "stopped drinking" - and 32.4 for the "continued to drink" (over 2 cm difference between the "never drank" and "continued to drink" groups). Scores for math and reading/decoding were also significantly lower for the alcohol exposed groups. Using the Kaufman Assessment Battery for Children, the researchers calculated a math score of 96.5 for the "never drank" group, 86.7 for the "stopped drinking" group and 84.8 for the "continued to drink" group (nearly a 12 point difference). Reading/decoding scores were significantly lower only for the "continued to drink" group dropping from 101.8 to 91.6 suggesting the importance of neurological growth in the "reading areas" of the developing brain during the last 3 months of pregnancy.

Also, the test of sequential processing skills was much lower for the alcohol groups which included subtests for hand movement and reciting numbers and word order, each of which is stated to require short term memory processing. Short term memory processing, often called encoding, is believed to be supported by the subcortical structures of the brain including the hippocampus, which are particularly susceptible to the effects of alcohol according to research in the Archives of Neurological Psychiatry Vol. 79(5):475-497.

In conclusion, the researchers stated,

Dr. Claire D. Coles, Human And Behavior Genetics Laboratory, Department Of Psychiatry, Emory University School of Medicine
Georgia Mental Health Institute, Atlanta, Georgia
Neurotoxicology And Teratology, 13:357-367, 1991

Language Skills Damage Easily from Light Social Drinking

Says da-da or equivalent, Jabbers expressively, Imitates words, Says 2 words, Names 1 object, Vocalizes 4 different syllables, Listens selectively to familiar words, Responds to verbal request, Inhibits on command, Shows shoes or other clothing or own toy.

Testing was given by a trained professional who was not aware of the mothers’ drinking habits. The researchers adjusted for known confounding variables such as social class, educational level, use of other drugs, etc. Results were considered significant at the p<0.05 level.

Early Memory Loss
Occurs When Offspring's Mother Exposed to Alcohol

Each different age group of alcohol exposed rats was first thoroughly taught the escape route to a semi-complex maze. The rats were then tested 24 hours later and then again after about 3 weeks to see if they still remembered their way out. All rats remembered their way out after this 24 hour period. However, what was interesting was that after a little over 3 weeks, only the older, 24 month old rats had a difficult time remembering their way out. In fact, the 2 year old alcohol exposed rats made an average of 18 errors in the maze, while the old rats not exposed to alcohol during pregnancy made on average only about 10 errors. The researchers stated this experiment clearly demonstrates damage to the long term memory centers of the aging rats that occurred sometime during their mothers alcohol exposed pregnancy and is believed to be extremely subtle since no other obvious effects were observed in biological examinations.

CHEM-TOX COMMENTS:
With the results of an experiment such as this, it provides a biological explanation as to why some adults could develop learning/memory problems at ages younger that what would normally be expected.

Attention Deficit Disorder (A.D.D.) Link
Brain Neurotransmitter Dopamine Lower After Alcohol Exposure

Brain Neurotransmitter Reduced After Alcohol Exposure

Abnormal Brain Area (in Basal Ganglia)
Found in Children Prenatally Exposed To Alcohol

In this present study, scientists from three California research universities including San Diego State University, University of California San Diego School of Medicine and the Scripps Research Institute, pooled their talents to investigate whether similar brain abnormalities would be present in non-FAS children whose mothers drank heavily during pregnancy.

In the present study, researchers investigated two 16 year old children (1 male, 1 female), who did not have FAS but whose mothers were considered "alcoholic" and drank heavily during pregnancy. Both children also had a history of behavior problems and cognitive impairments. Their IQ scores were 64 and 69.

Doctors stated results from the MRI scan of both children showed,

"...reduced volumes were found for the cerebrum and cerebellum. In addition, the proportional volume of the basal ganglia was reduced.....These results, taken in conjunction with our previous report of two FAS children, suggests that of the structures evaluate overall brain size and the volume of the basal ganglia are the most affected by a prenatal alcohol insult. Importantly, even in the absence of FAS, children exposed to alcohol in utero (during pregnancy) displayed proportionally smaller basal ganglia."

The authors further stated,

 "The role of the basal ganglia in the behavioral teratogenicity of alcohol needs to be clarified. If the two human cases reported here and the two previously reported, are typical of the larger population of children exposed to alcohol prenatally, we might expect to see some behavioral indications of the reduction in basal ganglia volume. In fact, some of the behavioral sequelae of FAS and prenatal alcohol exposure may be related to basal ganglia dysfunction. Gestational alcohol exposure has consistently been associated with perseverative behavior, difficulty with spatial memory, and understanding behavioral outcomes. Interestingly, the basal ganglia have been linked to the ability to change behavioral set, spatial memory, and goal-directed behavior. Thus, some of the behaviors in children with prenatal alcohol exposure may be the result of abnormal development of the basal ganglia."

In a follow-up study, the scientists studied 20 male mice exposed to alcohol during gestation. Autopsy results of the animals’ brains showed a smaller caudate-putamen area.

The authors stated,

"Interestingly, the caudate-putamen has been suggested to be part of a general learning system, in that lesions (damage) to this area can produce widespread learning and memory deficits (24)."

Hyperactivity - A.D.D. and Behavior Disorders
Linked With Alcohol Exposure

"Our own clinical experience in a learning disorders unit, as well as other reports, both human and animal, suggest that perhaps more subtle manifestations of CNS dysfunction in the form of behavioral and learning difficulties might be significant but frequently overlooked problems in children exposed to ethanol (alcohol) in utero."

The intent of their research was to investigate the growth, cognitive function and school performance in a group of learning-disabled children of normal intelligence born to heavy drinking women. It is the recommendation of the physicians that children experiencing school failure should be evaluated for indications of prenatal exposure to alcohol. Cognitive performance was measured using the Stanford Binet form L-M , the Wechsler Pre-School and Primary Scale of Intelligence and the Wechsler Intelligence Scale for Children. Although all children had a mean full scale IQ of 98.2, there were other problems with school performance. Hyperactivity was evident in all but one of the patients’ school reports. Six were taking stimulant medication for their condition. The poorest scores on the intelligence tests were in the areas of coding, arithmetic, digit span memorization and information subtests. In conclusion the authors stated,

"Our findings provide further support for the belief that milder degrees of Central Nervous System dysfunction are frequently encountered in the offspring of alcoholic women, and suggest consideration of an expansion of the concept of fetal alcohol syndrome to include behavioral and learning deficits as manifestations of Central Nervous System involvement. An increasing body of evidence suggests a relationship between parental alcohol abuse and the development of disorders of activity and learning in their offsprings as, for example, in the symptom complex currently designated attention deficit disorder, this relationship is not exclusively mediated by social experience. Our data indicate a constellation of mild dysmorphic features of fetal alcohol syndrome, findings of hyperactivity and persistent school learning difficulties in children with normal intelligence born to heavy drinking mothers. Alcohol exposure in utero (during pregnancy) may be an important, preventable determinant of attention deficit syndromes in childhood."

Damage to Astrocyte Brain Cells
following "Realistic" Alcohol Exposures

Briefly, according to research By Dr. William Pardridge at University of California, Los Angeles, astrocytes serve a very important support role to our "thinking" primary brain cells called neurons, one of which is to literally pull nutrients from surrounding blood vessels and transport them to the neurons, almost like a vacuum cleaner. Another important role is to serve as the first stage to the "blood brain barrier" by attempting to detoxify toxic compounds that enter the blood, although the mechanism is far from fool-proof. Astrocytes are believed to be one of the first brain cells to develop in the fetus.

In their research to determine the effect of alcohol on astrocyte growth, Dr. L. A. Kennedy and colleagues at the College of Medicine, University of Saskatchewan, Canada placed approximately 600,000 newborn mouse brain cells into nutrient rich petri dishes to evaluate growth patterns after low level exposure to four alcohol concentrations (.0, .06, .12, .24 g/dl). These levels were chosen because they represent a range of alcohol levels to which the embryo and fetus might realistically be exposed in the uterus during periods of mild to severe states of maternal alcohol intoxication. After letting the cells establish themselves for 6 days, the researchers then exposed the brain cell groups to the varying alcohol levels for either 4 days (Experiment 1), 11 days (Experiment 2), 18 days (Experiment 3) and for the last brain cell group (Experiment 4) they waited 20 days before beginning a short 4 day exposure to the different alcohol levels.

The researchers stated the following results from their experiments,

 "There was a significant treatment related reduction in protein content (protein is used as a basis for building brain cells), in Experiments 1, 2 and 3 but not in the delayed exposure in Experiment 4. (Explained by the fact that the main growth period was already over in experiment 4). The glutamine synthetase enzyme level was reduced at all alcohol concentrations (even the lowest dose) and in a dose-dependent manner. For instance, in the cells exposed to alcohol for 18 days (Experiment 3), this important enzyme was about 20% less in the .24 g/dl alcohol exposure level than in the non-alcohol exposed culture.... It appears from these investigations that brief periods of ethanol (alcohol) exposure can be as damaging as longer exposures, if the exposure occurs within a rather narrow window, or critical period, of astrocyte development. Moreover, functional specialization of astrocytes (such as glutamine synthetase levels), appears to be more severely impaired by ethanol exposure, and at lower ethanol concentrations, than are either replication or growth."

Additional References