We Are Our Brains (8 page)

Heavy metals can also disrupt fetal brain development. The lead added to gasoline to reduce engine knocking entered the atmosphere, causing more children to be born with mental disabilities. The dangers of mercury became apparent only in the 1950s, when cats in the fishing villages around the Bay of Minamata in Japan started acting strangely and dying and fish began to swim in bizarre patterns. The fishermen had been selling their best fish and keeping the worst specimens for the family pantry. As a result of the fish's high organic mercury content—mercury that proved to come from a plastics factory—6 percent of the children in the surrounding villages had suffered serious brain damage before birth. The formation of their brain cells and the growth of brain tissue had been inhibited by the mercury, leading to mental disability. The adults in these villages also developed various forms of paralysis. A monument has now been erected in Minamata's environmental park, dedicated to all the life-forms in the Shiranui Sea that fell victim to this disaster. The park itself was built on twenty-seven tons of mercury-polluted sludge from the Bay of Minamata as well as dozens of sealed containers full of poisoned fish. The Japanese government never gave the victims proper financial compensation.

Disorders of sex development, or intersex, are also often caused by environmental factors during fetal development. They affect up to 2 percent of children, depending on how comprehensively you define such disorders and at what stage of life they are diagnosed. In 10 to 20 percent of cases, no chromosomal cause is found for atypical development of the sex organs, so one may conclude that the disorders are due to environmental chemicals. DDT, PCBs, dioxins, and many other substances present in the environment are now referred to as “endocrinal disrupters” because they can disrupt hormonal regulation of sexual differentiation. As far back as 1940, the pilots of planes spraying DDT were found to have reduced sperm counts. What's more, the effects of these substances on brain development have been demonstrated in many animal species. The possible impact of endocrinal disrupters on the process of sexual differentiation in the fetal brain—and thus on gender identity and sexual orientation (see
chapter 3
)—is a concern that has arisen only very recently.

Fortunately, the most severe developmental disorders that can arise early in pregnancy are rare. Examples of such serious birth defects include spina bifida (the risk of which is increased by taking antiepileptic drugs during pregnancy), anencephaly, which is the absence of a forebrain (often associated with exposure to pesticides), or missing limb parts. The latter type of defect occurred in great numbers during the late 1950s and early 1960s after the appearance of a now-notorious sedative drug called thalidomide that was prescribed for pregnant women. It led to a great number of children being born with teratological abnormalities, usually missing limb sections. The
thalidomide disaster made doctors more cautious about prescribing medication during the first three months of pregnancy.

These defects, however, are just the tip of the iceberg of the developmental brain disorders that can be caused by chemical substances during pregnancy, including after the first trimester. Microscopic abnormalities are far more common than classic teratological abnormalities. They occur later in pregnancy only, and the problems they cause manifest themselves much later in life. Children affected in this way appear to be completely healthy at birth, but the defects emerge later, when functional requirements are imposed on their brain systems. The children of pregnant women who smoke, for instance, are much more likely to have learning difficulties as well as behavioral problems in adolescence and reproductive problems in adulthood. These disorders are known as functional disorders or “behavioral-teratological disorders.”

Many chemical substances can reach the fetus and threaten its developing brain. Heavy metals in the environment, nicotine, alcohol, cocaine, and other addictive substances, as well as medication taken during pregnancy, can disrupt the rapid development of the brain. Children exposed before birth to the drugs taken by their mothers not only display withdrawal symptoms after birth but can also be left with permanent brain damage. I believe that all substances that affect the adult brain can also influence the development of the fetal brain. I have yet to see a single exception to this rule.

Alcohol

That alcohol can cause birth defects has been common knowledge for a very long time. The Phoenicians of Carthage apparently worried about the effects of alcohol on unborn children, to judge by their law banning the drinking of alcohol on one's wedding day. The English writer Henry Fielding warned of the effects of the British gin epidemic back in 1751, lamenting, “What must become of an infant who is conceived in gin?” It wasn't until 1968 that French scientists
established that drinking during pregnancy could impair fetal brain development—rather in the way that Gammas were bred by adding alcohol to the blood surrogate around the developing embryo in Aldous Huxley's
Brave New World
(1932). However, the French publication went unnoticed until it was rediscovered in 1973, with its finding dubbed “fetal alcohol syndrome” in English-language medical journals. To this day, a quarter of pregnant women have the occasional glass of alcohol, even though drinking while pregnant can cause children to be born with undersized brains and severe mental disabilities. It's also responsible for less severe damage, specifically learning and behavioral problems.

In early development, brain cells are created around the brain cavities. They then migrate to the cerebral cortex, where they ripen and sprout tissue to establish contact with other brain cells. This migratory process of fetal brain cells can be so severely disrupted by alcohol that the cells sometimes work their way through the cerebral membranes and end up outside the brain. Alcohol also permanently activates the stress axis of the unborn child's brain, increasing the risk of depression and phobia. In hospitals in the 1960s, alcohol was routinely administered intravenously to women at risk of giving birth prematurely. It inhibited contractions, enabling the baby to remain in the uterus longer. At the time, no one was concerned about alcohol coming into contact with a baby's brain. Whether or not this approach was harmful has never been established.

Smoking

The potential harm that can be caused to an unborn child when its mother smokes during pregnancy is frightening. Smoking is the most common cause of neonatal death. It doubles the risk of sudden infant death syndrome (SIDS). A mother who smokes increases her child's risk of premature birth, low birth weight, impaired brain development, disturbed sleep patterns, poorer school performance, and obesity later in life. Her smoking affects not only her own thyroid
function but also that of her child. Her children have a higher risk of ADHD, aggressive behavior, impulsiveness, speech defects, attention problems, and, in the case of boys, impaired testes development and reproductive disorders.

Around 12 percent of women still smoke during pregnancy. Despite the known dangers, very few are able to give up smoking at this stage. (Incidentally, trying to stop by using nicotine patches is also dangerous for the unborn child—animal studies have shown that nicotine has an extremely harmful effect on brain development. In other words, it's not just all of the substances in the smoke but also the nicotine itself that causes developmental brain disorders.) If all pregnant women in the Netherlands were to stop smoking, 30 percent fewer children would be born extremely prematurely, underweight births would decrease by 17 percent, and savings amounting to $33 million could be made in health care. Surely that's an effort worth making for your child?

Aspecific Effects

The functional teratological impact of medication sometimes comes to light by chance. Majid Mirmiran, a PhD student working at our institute in the 1980s, studied the question of whether the high level of REM sleep in fetuses—REM being the phase in which you dream the most—is important for normal brain development. During this stage of sleep, the brain is strongly activated, a pattern that starts already in the womb. Mirmiran carried out an experiment that inhibited REM sleep in rats by giving the rats either chlorimipramine (an antidepressant) or clonidine (a medicine used to combat high blood pressure and migraine). The experiment was conducted on two- to three-week-old rats at a stage at which the rats' brain development was comparable to fetal brain development in the second half of human pregnancy. After a short course of this treatment during their development, the adult animals had less REM and were more fearful.
Moreover, the sex drive in the grown male rats diminished, and they became hyperactive. In other words, a mere two weeks of exposure to these substances during their development caused permanent alterations in the brains and behavior of rats. A subsequent study in Groningen looked at children whose mothers had been prescribed clonidine eight years previously during their pregnancy as a “safe” medication for high blood pressure and migraine. The children proved to have severe sleep disorders; some were even sleepwalkers. One of the problems of functional teratological disorders, in other words, is that doctors must be able to determine, on the basis of animal studies, what disorders they need to look for in humans. What's more, the effects of the substances in question are aspecific. You can't tell from a condition that manifests itself long after birth, such as a sleep disorder, exactly what substance taken during pregnancy caused the brain damage in question. Other examples of aspecific symptoms of functional teratology are learning disorders (caused by alcohol, cocaine, smoking, lead, marijuana, DDT, antiepileptic drugs), depression, phobias and other psychiatric problems (diethylstilbestrol, smoking), transsexuality (phenobarbital, diphantoin), aggression (progestogens, smoking), impaired motor skills, and social and emotional problems.

Additionally, chemical substances are thought to contribute to developmental disorders in which diverse factors play a role, like schizophrenia, autism, SIDS, and ADHD. Depending on her baby's genetic background, a woman who smokes during pregnancy can increase the chances of her child developing ADHD by a factor of nine. The risk of ADHD is also increased when adrenal cortex hormones are administered during pregnancy to promote lung development in babies at risk of being born prematurely. This procedure has been found to impair brain development, potentially causing not only ADHD but also a smaller brain, impaired motor skills, and a lower IQ. These hormones are now administered much more sparingly.

Dilemma

One of the dilemmas confronted by doctors is that patients with schizophrenia, depression, or epilepsy often continue to need treatment during pregnancy, because the mother's condition is potentially harmful to her child. Unfortunately, taking antipsychotics like chlorpromazine during pregnancy has been shown to cause motor disorders in children, and some antiepileptics increase the risk of spina bifida or transsexuality. It's best to treat epilepsy during pregnancy with a single drug (rather than a combination) together with folic acid. Some antiepileptics are more harmful than others: Valproic acid has been shown to impair verbal IQ more than other epilepsy medications. Around 2 percent of pregnant women take antidepressants even when they have only mild depression. Such drugs don't appear to increase the risk of serious birth defects, though the children born to these mothers are somewhat underweight and slightly premature, score somewhat less well on the post-birth Apgar test, and have subtle motor disorders. However, these disadvantages must be weighed against the problems that can result from a mother being stressed and depressed during pregnancy, such as impaired cognitive performance, attention, and language development. When a mother is fearful during pregnancy, she can permanently activate her baby's stress axis, thus increasing the risk of phobia, impulsiveness, ADHD, and depression later in life. If at all possible, it's worth considering treating depression in pregnant women with alternative therapies, like light therapy, transcranial magnetic stimulation, massage, acupuncture, or online therapy. Clearly, doctors treating such patients need to do a lot of careful thinking.

Mechanisms

Brain cells are created with incredible rapidity in the womb and shortly after birth, and this process continues, somewhat more
slowly, until around the fourth year of life. Brain maturation goes on much longer; in the case of the prefrontal cortex, it continues right up to the age of twenty-five. Every facet of brain cell development can be disrupted by chemical substances during pregnancy. Disturbances to the migration of brain cells can lead to heterotopias, a condition in which groups of cells making their way to the cerebral cortex end up in the wrong part of the brain. They get trapped in the white matter, the fiber connections, as they journey to the cerebral cortex (
fig. 20
), a location where they can't function properly. Substances that are regularly taken by pregnant women, such as benzodiazepines, can induce this condition. Drinking during pregnancy also causes malformations and malfunctions of nerve cell fibers. Smoking and drinking during pregnancy alter the receptors for nicotine, and smoking cannabis can alter the dopamine receptors in the fetal brain.

Conclusions

Addictive substances, medication, and environmental substances can permanently disrupt fetal brain development, leading to learning and behavioral disorders in later life. Congenital defects of this kind are known as functional or behavioral-teratological defects.

Tracing the connection between these disorders and the effects of chemical substances is difficult due to the length of time between the child's exposure to such substances in the womb and their effects, which may only be manifested when the child goes to school or—in the case of reproductive problems—perhaps twenty or thirty years later. Moreover, the conditions caused by these substances, like learning and sleep disorders, are so aspecific that they can't be used to identify the substance that caused the brain damage during pregnancy. On top of that, a single substance can produce different symptoms depending on the stage of development at which the child was exposed to it. All of this is complicated by the fact that doctors, especially in the absence of reliable animal studies, don't know what disorders
they should be looking for. With women who may require drug treatment during pregnancy, it's essential to discuss potential problems at an early stage so that if a pregnancy is planned, the safest drug or alternative therapy can be prescribed.