Even though causative links may not have been established, there is good reason to want to have an idea of how many known or suspected risk factors are present in any child. If you are seeing a child early in the educational process, this information could help you determine how likely a future problem might be. Details about potential risks also help in formulating conclusions about the prognosis for recovery or improvement following treatment or therapy. Awareness of the potential impact of risk factors can lead to prevention of problems for future patients.

It is helpful to note the type, severity, and number of past occurrences that are potentially contributory to visual and learning difficulties. Although they might not be known to be causative, many past events are at least coincidental with learning difficulties. This is the concept of risk - that a child has a better than average chance of having a condition (e.g., reading disability) based on some historical event or medical condition. It is best thought of in epidemiological terms such as odds ratio or relative risk. If a child has a positive history of an exposure, then he or she is statistically more likely to have an unfavorable outcome. For example, if the odds ratio of a child having severe learning disabilities when the mother was on antidiabetic medications was 1.99, that would mean the child was twice as likely to have the disability as a child of a nondiabetic mother (all else being equal). In addition to the importance of singular events, there is evidence that the cumulative and interactive effects of multiple exposures may be even more significant.
 
 

A listing of some conditions reported to be risk factors for physical, physiological, or behavioral disorders that might eventually result in visual and learning and reading problems. Most of these factors have not been studied in sufficient depth to determine whether they cause learning delays. Some have been investigated only for their effects in the immediate postnatal period, or during infancy. Many have concentrated only on physical changes and have not looked at behavioral or learning outcomes at all.

MALE GENDER

Make the point that there really is a significant gender issue - males are selectively afflicted with most neurological, psychological and developmental disorders of childhood. The sex ratio is used to express the occurrence of conditions relative to gender and is calculated by dividing the number of males by the number of females and multiplying by 100. The sex ratios of important neurodevelopmental disorders range from 120 for seizure disorders and 130 for severe mental retardation to 219 for learning difficulties, 300 for hyperkinesis, 400 for stuttering and 430 for dyslexia.

The sex differences in neurodevelopmental disorders of childhood follow four distinct trends - males are more commonly affected; when females are affected, the manifestation is more severe; in females, genotype is the likely cause of the condition and thus the manifestations are more specific; in males, manifestations are more diverse owing to a stronger interaction between genotype and environmental factors (including many of the risks we're discussing).

NUTRITION

Low birth weight and learning problems are related.

During pregnancy, mother needs increased:     calories
                                                                                      minerals
                                                                                      water soluble vitamins
                                                                                      fat soluble vitamins

Chronic hypertension in the pregnant woman can exert a hazardous influence on the fetus by interfering with the blood supply and consequently with the oxygen and nutrient supply by preventing normal placental development or function.

When maternal famine occurs, i.e., when she gets decreased nutrition, it creates a significant reduction in the birth weight of the infant only if it happens during the last trimester.

Using a multivariate list of agents that are risks of growth failure, maternal weight and weight gain are 3X as significant as other factors. Maternal insufficiency is an important risk factor.

Identification and management of high-risk pregnancies is important!

Fetal Malnutrition
causes are multiple and subtle
studies show prolonged slow head growth in utero affects a child's later development and abilities, particularly perceptual performance and motor ability.
One area where treatment is available =
    Inborn errors of metabolism
        Inborn errors of metabolism more often than not impair development and behavior. Examples include PKU,
        galactosemia, maple syrup urine disease, and urea cycle enzyme deficiencies.

Prenatal management (two types):
    1. nutrient is administered - positive intervention
    2. nutrient is withheld - negative intervention

Postnatal management

Diabetes is another important issue. Pregnancy in an insulin dependent diabetic who is not well controlled may result in a macrosomic infant with multiple congenital anomalies. The risk of fatality and of CNS anomalies can be as much as 28X higher in infants born of diabetic mothers. The risk increases with the length of time the mother has had diabetes. If metabolic control is to be effective, the diabetic woman must control her disease meticulously from before conception until delivery, with particular emphasis on the first 2 months.

PRENATAL DRUGS

Pregnancy - period of -     excitement
                                                expectation
                                                stress

this gives an increased frequency of contact between pregnant women and physicians;  the probability of prescribing drugs increases.

An overwhelming number of drugs (both OTC and Rx) have not been tested for their teratogenic effects on a fetus.

Also now having to deal more and more with the problems of mothers who were on illicit drugs such as cocaine during pregnancy and the learning problems their children experience.

Heroin use may be associated with:
        increased rate of prematurity
        increased number of SGA infants
        hyperactivity
        LD
as infants the children are irritable and hyperactive, and in early childhood they are distractible and inattentive.

Cocaine use may be associated with:
        intrauterine growth retardation
        decreased head circumference
        prematurity
        anemia

One additional example –
emphasizes the point that our society doesn't know all of the potential neurotoxic effects of drugs
Isotretinoin, marketed as Accutane for severe cystic acne, has also been used widely for the treatment of regular acne. Despite a category X FDA rating, it has been used by childbearing women, resulting in children born with MR and/or developing LD.
 

TRAUMA

Mainly preventable, obstetrical trauma.
Very difficult to derive good statistics due to many covariants and confounding factors.
Breech presentation =  increased problems
    5% died first week; increased morbidity
Breech presentation children also have about a 5X prevalence of hyperkinesis and LD compared to vertex presentations.

Prolonged labor shows up more commonly in the histories of kids with learning problems.

Intracranial vascular injury and hemorrhage can result in significant consequences including motor abnormalities (like CP), seizures, LD, and MR.

Long term meaning of short term changes ??? Unclear.
 

OBSTETRIC MEDICATIONS

Address three questions:
    1) do the effects of medication last past the peri-natal period?
    2) can the effects be identified in cognitive tasks or attention?
    3) can the cognitive effects be identified as LD or visual-perceptual disorders?

Most behavioral studies of the effects of drugs used in childbirth are concentrated in the newborn period. very few address children over 1 year and few of those address subtle visual, perceptual, cognitive or behavioral developmental areas.

Drug effects on neonates
    with few exceptions, drugs used in obstetric anesthesia and analgesia rapidly cross the placenta.
    Inducers: can give contractions too strong and sustained for safety of the mother and child

Study of about 2000 infants: inhalation anesthetics & oxytocin related to psychomotor deficits (1st year)
LD:     higher incidence of pregnancy and birth complications
          higher frequency of induction
          meds used in general, particularly inhalation anesthesia

While prenatal and perinatal complications are found more frequently in the histories of children with LD, they provide neither a necessary nor a sufficient explanation.

Fact remains, drug-related deficits in neonatal responsiveness suggest the possibility of deficits in responsiveness or learning at later ages. Concern stems from a lack of knowledge about the effects of a given agent on the fetus or newborn even though the effects may be known on an adult. The immaturity of the CNS increases its vulnerability to insult.
 

LOW BIRTH WEIGHT

Studied frequently -     prototypic risk group
                                         easily identified
                                         increasing numbers of survivors

about 7% of surviving infants
at risk for a variety of intellectual tasks
diverse population

Definition: 2500 G or less (5 1/2 lb.)
                < 1500 Very Low Birth Weight (VLBW)
                < 1000 Extremely Low Birth Weiht (ELBW)

VLBW can result in mothers with treatable conditions. The risk of VLBW deliveries in black women is significantly increased if they have essential hypertension or a urinary tract infection. The risk is higher in white women who have essential hypertension, a urinary tract infection, pregnancy-induced hypertension, or diabetes. Also higher in any woman who receives inadequate prenatal care.

Mean IQ is lower than average, but still within normal range
Higher incidence of learning problems
Failure in school/special class placement; found in 30% of LBW children with IQ over 100
    found in 36% of LBW children with IQ over 90

Motor Development
    LBW infants score: lower on motor development in infancy and preschool years
    lower on motor development than same kids mental scores
    Visual-motor integration (eye-hand coordination) is an area that has been a very consistent problem for the LBW child !!

Consideration: overwhelming role played by social factors!
    Social factors, i.e., the environment - most reliable predictors of later outcomes

Summary of what we know about LBW:
    1] decreased intellectual functioning is associated with LBW, may be associated with social factors
    2] social factors are more important
    3] school performance is not as good for LBW - with social implications
    4] visual-motor integration decreased
 
 

INFECTIONS

A growing number of infections are now recognized as important causes of fetal damage when the disease affects the mother during pregnancy - some of these infections can damage the developing nervous system of the child, resulting in a variety of clinical findings such as MR, LD, seizures, CP, microcephaly, and hydrocephaly. The damage appears to be due to direct effects of the infectious agents on the brain tissue. In most cases there is also damage to other organs, particularly included would be the visual system, e.g., neural tube ® colobomas.

Cytomegalovirus = most frequent cause of congenital infection in US // hematogenous spread from the mother
    can be fatal with large organ difficulties.
    usually combined MR and high tone deafness.
    often chorioretinitis

Rubella = usually epidemics every 6-7 years. Fortunately, in US, with widespread use of vaccine - no epidemic since 1964.
    In 1983, for example, 934 cases, which resulted in 4 cases of CRS.
    significant mortality rate. significant damage to CNS.
    cardiac damage. ocular effects - cataracts, microphthalmia, glaucoma, chorioretinitis.
    can't be vaccinated during pregnancy - vaccine is made from live virus.
    language problems. frequently some degree of deafness.  also over half have visual perceptual and motor planning problems.

Herpes = Genital (Type 2) HSV is #2 cause of STD in U.S.
    90-95% of newborn infections are due to Type 2 virus,
    60% die/50%+ of the survivors have significant neurological sequelae.
    Born normally, get heavy dose of HS passing through the birth canal. Identify high risk mothers; herpes status
    at the time of delivery - is she still shedding the virus?

Varicella = Varicella (chickenpox) and Herpes Zoster (shingles) are caused by the same virus.
    15% of women of child bearing age are susceptible.
    infection in the first 16 weeks => cataracts, MR.,
            encephalopathy, microcephaly, club feet, badly scarred extremities
    last four days - lesions then or the day after - 10-30% of kids die of disseminated infection (placental transfer)
        because he/she gets infected but doesn't stick around long enough to get the antibodies (born too soon).

Syphilis = Spirochete crosses the placenta and grows in the tissue of the child. Results in MR., paresis if CNS is affected
    can occur at any time during the pregnancy.
    Other signs - rash, chorioretinitis, iritis, Hutchinson’s teeth, deafness

Toxoplasmosis = Parasitic; can be congenital or acquired; wide range of symptoms -
    from severe generalized infection with fatality to asymptomatic forms.
    Findings = chorioretinitis, anemia, seizures, decreased IQ with microcephaly

In summary, some maternal infections affect CNS and give brain damage. LD, visual perceptual problems, ocular disease, etc. are among the defects produced by these infections. The affected children, unfortunately, are often multiply handicapped.
 

ENVIRONMENTAL TOXINS

Of the many industrial chemicals to find their way into the environment, a substantial number are demonstrated neurotoxins at high doses. It is reasonable to ask which of these agents can pass through the maternal placenta and reach the developing gamete, embryo, or fetus, and what the effects might be. Altered behavior or performance on the part of the developing child is one possible result or neurotoxicity at lesser doses.

If the effects are immediate and dramatic - discovery is easy
If less dramatic - effects are evasive

Lead - oldest and best studied neurotoxin
    gives     decreased IQ.
                    speech processing
                    attention
                    classroom behavior

younger kids are more susceptible to lead exposure
lead based paints - chips on floor and off toys
lead does cross placenta

Lead story may be paralleled by other chemicals =
    several candidates: cadmium
                                         methyl mercury
                                         estrogen-like substances - pesticides/organic solvents
 

ALCOHOL AND SMOKING

The old assumption that the placenta protected the embryo from toxic substances has been dispelled, for it is clear that the placenta could be viewed better as a sieve than a wall. Most common drugs - including both alcohol and nicotine - readily cross and circulation levels in the fetal blood are often similar to those in maternal blood.

Animal research has established a causal link between parental exposure to alcohol or nicotine and offspring effects, such as delayed development, hyperactivity, and learning decrements. Human studies, however, are clouded with methodological problems.

Is there a relationship between alcohol and/or nicotine exposure in utero and subsequent LD in offspring after consideration of other related variables?

What do we know?

It is known that smoking is related to =
    placental abnormalities
    SGA ( about 200 G lighter)
    20-40% of incidence of LBW can be explained by smoking and the decrease in BW is directly related to
        the number of cigarettes smoked
    also, the rates of spontaneous abortion and perinatal mortality are 2X higher
    associated with retarded reading at age 7 & 11
    if only fathers smoke, problem is about ½ size

Fetal alcohol syndrome [or also called fetal alcohol effect]
    growth deficiency, dysmorphic facial characteristics (small palpebral fissures, flat bridges), CNS dysfunction
    and often a major malfunction such as a heart defect
    height, weight, and head circumference decreased at first but catch up by 18 months and stay even at ages 4, 7, 14
    memory and attention problems observed frequently
    Risk: 1/3 of chronic alcoholic mothers

FAS clinical observations:
Hyperactivity (#1); distractible; decreased gross motor; poor fine motor; learning problems; uninhibited; socially engaging
Cognitive, behavioral, communicative, and socialization difficulties may well persist throughout adulthood