These are my notes from reading Lise Elliot’s What’s Going On in There?.

“Prenatal Influences on the Developing Brain”.

This chapter goes through all the things that can affect the development of the fetus – mostly negatively. Nutrition (lack of), alcohol, drugs, chemicals, infections, stress, etc etc. On a more positive note there is a section about folic acid and how it helps prevent neural tube defects.

A few interesting facts I learned:

• There is enough folic acid in normal multivitamins for the needs of pregnant women. There is no evidence that the extra amount in specialist pills is useful (or unsafe, for that matter).
• A woman needs about 300 kcal extra per day during pregnancy, and 500–600 during breastfeeding.

Teratogens and birth defects

Life in the womb is characterised by lack of stimulation: dark, warm, confining, quiet. This seems to be important for early brain development: premature babies have a high risk of mental and neurological problems. Preterm babies who stay in a “womblike” environment stay healthier and develop faster.

The fatigue and nausea that many women experience may be another way to protect the embryo / fetus. The mother feels most miserable during the baby’s most vulnerable phase, and this keeps her from risky physical activities, and from spoiled and exotic foods.

But the womb is not immune from the outside world. Almost every drug, chemical, hormone, or infectious agent will cross from mother’s blood into the placenta to some extent. Substances that can cause fetal malformations are called teratogens. These are difficult to identify, because it’s a question of probabilities. The baseline probability of some kind of defect is 2–3%. Thalidomide, one of the worst teratogens known, caused malformations in 20% of exposed fetuses.

Most birth defects (65%) occur without any identifiable cause. Another 20–25% are linked to defects in chromosomes or genes – some inherited, some spontaneous. Known environmental or disease agents are responsible for 10%.

Teratogens are likely to have the worst effect during the first 3–4 months of pregnancy, when the organ systems are forming, but the nervous system is more sensitive because its development goes on throughout the entire pregnancy. The effects of teratogens on the brain are hard to identify, because brain damage can be caused by smaller amounts of teratogens than other congenital abnormalities. Also the effects on the brain tend to be more subtle and may even not be evident until in later childhood.

Very few drugs and chemicals have been tested for these effects so the general approach is “better safe than sorry” and pregnant women are advised to avoid heavy exposure to anything suspect. It also makes sense because many teratogens have a cumulative effect: the risk of one exposure is low, but exposure to one thing increases the damage done by others. For example, smoking increases the probability of other teratogens causing damage.

The flip side of this approach is that it sometimes leads to excessive worry and the stress of avoiding endless minimal risks may be more damaging than the risks themselves. A significant minority of parents even choose to terminate pregnancies because of their fears about such risks. A large number of such abortions took place in the US after the Chernobyl accident, even though the amount of radiation reaching the US was too small to measurably increase any risk.

Neural tube defects

One of the most important phases of brain development is the closure of the neural tube (from day 22 to day 28). If this fails in the spinal cord, it leads to spina bifida (part of the spinal cord developing outside the vertebrae). If this fails at the top end, the result is anencephaly (most of the brain fails to develop). The symptoms of spina bifida range from none to severe (paralysis); anencephaly is lethal.

Neural tube defects (NTDs) occur in 0.1% of pregnancies in the US. The rate of NTDs may be much higher because many miscarried fetuses have NTD, but this normally goes undetected.

NTDs are caused by several factors combined: genetic, ethnic, nutritional, chemical, etc. There have even been reports of seasonal variation. NTDs are more common when the pregnant mother has diabetes or epilepsy. Some drugs are known or suspected to be a risk; so is high body temperature (whether due to fever or a sauna).

Most NTDs can be detected early in the 2nd trimester by blood test, amniocentesis or ultrasound. When the neural tube fails to close, a certain protein present in the fluid in the ventricles leaks into the amniotic fluid and to the mother’s blood. The blood test is performed between 16–18 weeks of pregnancy, and if positive, it is followed up with other methods. All the methods together are able to detect ca 93% of NTDs during the 1st half of pregnancy.

Folic acid

The risk of NTDs is lowered significantly by folic acid (vitamin B9). The original study found 60% reduced risk for first-time NTDs, and 76% for women who had already had a pregnancy with NTD.

The official recommendation is that all women capable of becoming pregnant should consume 0.4 mg of folic acid every day. This amount is present in most standard multivitamin pills. Special prenatal pills contain a higher dose, which has not been proven more effective but appears to be safe. Folic acid is also present in many foods (leafy green vegetables, peas, beans, citrus fruits, liver, whole wheat bread) but these forms of folate are less easy to process by the body, and less stable when cooked, so some experts say it is hard to get the recommended 0.4 mg even with an excellent diet.

A problem with this recommendation is that many pregnancies are not planned. Because neural tube closure begins very early in the pregnancy (only 8 days after a missed period) many women will not be taking folic acid when it is actually needed. Many countries therefore require folic acid to be added to food. In the US it is added to all grains (flour, bread, pasta, rice, cereal). This extra amount is beneficial but small enough that women are still advised to take folic acid supplements before and during early pregnancy.

Nutrition

Unlike chemicals and drugs, general nutrition (getting enough calories) is less important during early pregnancy, and more important later, because the fetus requires less energy when it is small in size. From halfway through the pregnancy to about 2 years after birth, nutrition is very important for the growth and development of the brain. The earlier malnutrition begins, and the longer it lasts, the worse the effects. By comparison, starvation does not damage the brain in adults.

Babies of malnourished mothers are likely to be small. Within the normal range, birth weight and head size are not strongly related to later intelligence, but very small babies (birth weight less than 2 kg) have a higher risk of mental deficits. Optimally a pregnant woman should gain about 20% of her ideal pre-pregnancy weight, and bigger is generally better (up to a limit). A woman needs about 300 kcal extra per day during pregnancy, and 500–600 during breastfeeding.

When a pregnant mother is malnourished the placenta will not develop properly, which makes it even harder for the fetus to get the necessary nutrients. This sometimes happens in well-nourished mothers as well and is called intrauterine growth retardation. The problems are similar when there is more than one fetus competing for nourishment.

After birth, malnourishment leads to smaller brains, weaker dendrite growth and less myelin. Because neurons are produced early in the pregnancy, their number is not affected, but the number of glial cells (which produce myelin) is, because these are produced later.

Malnourishment often occurs together with other problems (the baby may be neglected, sick, abused, or just so hungry that it has no energy to learn), so it is hard to isolate the effects of malnutrition. However babies who are undernourished because of illness, but who are in a stimulating environment, do not suffer from mental deficits – a supportive environment can compensate for malnutrition. Also, children who are rescued early from malnutrition can recover most of their intellectual ability.

Chemicals and drugs

Nowadays drugs are assumed to be harmful in pregnancy, unless proven otherwise. For most of the known harmful medications, there are safer alternatives. Although over-the-counter medicines are generally less risky, it is best to avoid even those, unless absolutely needed. In particular, aspirin and ibuprofen are associated with pregnancy complications, and Tylenol is recommended instead.

Alcohol. Alcohol crosses the placenta easily, and will reach almost the same concentration in the fetus’s blood as in the mother’s. Prenatal exposure to high doses of alcohol causes fetal alcohol syndrome (face and head defects, growth and mental retardation, anomalies of internal organs), increases the risk of miscarriage, premature birth, and birth complications. In the brain, alcohol kills neurons and disrupts the migration of neurons and glia. Modest consumption (less than 2 drinks per day) appears to be harmless. As with most teratogens, there is probably a level below which alcohol has no effect on fetal development, but that level is not known.

Cigarettes. Smoking (including passive smoking) is one of the leading causes of low birth weight, and also increases the risk of miscarriage and premature birth. Nicotine interferes with the fetus’s breathing movements – this may also explain the higher risk of SIDS in babies born to smoking mothers. Nicotine also interferes with the neurotransmitter acetylcholine, affecting neuron structure.

Drugs. All of the widely abused drugs increase the probability of miscarriage and premature delivery, and to various sorts of behavioural problems.

Caffeine. Caffeine crosses the placenta and may even concentrate in the fetus. Caffeine has been found to be teratogenic in rodents, but does not appear to be a teratogen in humans.

Aspartame. In the body, aspartame breaks down into aspartate and phenylalanine (both normally present in the body) and methanol. The amount of methanol is minute. None of these appear to pose a risk.

MSG. High doses of glutamate overexcite neurons, which can damage or kill them. However glutamate does not cross the placenta well, and the amounts consumed are too small to be risky.

Both aspartate and glutamate pose a higher risk to infants and should be avoided in baby food.

Other chemicals. Based on current knowledge, pregnant women should avoid: organic solvents, oil-based paints, herbicides, pesticides, PCBs, vinyl chloride, carbon monoxide, hydrocarbons, mercury compounds, and other heavy metals (including cadmium, nickel and lead). The greatest risk occurs if any of these is inhaled or ingested.

Ionizing radiation

This includes X-rays and gamma rays. In adults radiation can lead to cancer; in a fetus it can lead to fetal death or birth defects, particularly in the brain. Exposure during the first 2 weeks after conception are generally lethal to the embryo. Between 2 and 8 weeks will likely damage other organs than the brain. Between 8 and 15 weeks (when neuron production is most intensive) brain damage is likely. After 15 weeks radiation continues to be dangerous but the risk of mental deficit is significantly lower.

Irradiation for treatment purposes (mainly cancer) is never advised during pregnancy – if it is necessary, abortion may be advised. Diagnostic irradiation should be used if necessary, but elective radiation (such as dental X-rays) should be postponed until after pregnancy.

Non-ionizing radiation

This catch-all term describes energy waves that may penetrate tissue but do not break apart biological molecules – light, microwaves, radio waves, ultrasound. The main factor limiting their safety is whether they raise the temperature of the fetus. They are generally considered safe as long as they don’t raise the temperature above 39°C. UV light does not penetrate deeply enough to harm a fetus.

Despite scare stories, exposure to microwave ovens, televisions, computer monitors, or low-frequency magnetic fields (from power lines) does not appear to be harmful. Evidence about MRI is mixed (women are recommended to avoid it during the first trimester), and for ultrasound the benefits far outweigh the possible minimal risk.

Infections

Several viruses are known to cause malformation of the brain or later mental deficits. As with all the other risk factors, the effects are greatest in early pregnancy.

Rubella (German measles): the woman may show no symptoms, while the fetus can be severely malformed. Luckily most women are immune by the time they are pregnant (due to earlier infection or immunization). A test is usually done at the first prenatal checkup.

Cytomegalovirus is a member of the herpes family. Again, adults often show no symptoms. This is the most common and most dangerous infection that a fetus can be exposed to. Luckily most of the population has already been infected before adulthood, and such recurring infections are less dangerous for the fetus. Most adults catch it from toddlers, so mothers in subsequent pregnancies are particularly susceptible. About 1 or 2 babies in 1000 is born with major brain or sensory damage due to CMV. No vaccine is available yet. Infection is spread via all bodily fluids, so pregnant women in contact with toddlers (own or others’) should be careful with hygiene.

Toxoplasmosis is a parasite often caught from animal feces (cats and mice), as well as raw meat, eggs and milk. Mothers’ symptoms are, again, often very mild. The chances of infecting the fetus are lower during the first 2 trimesters when it would do more damage. Still, 1 or 2 out of every 10,000 infants will be severely affected by toxoplasmosis – mental retardation, epilepsy, blindness, hearing loss. Avoid eating raw meat and eggs; wash hands and surfaces that have been in contact with these. Avoid all contact with cat litter.

Genital herpes can, in rare cases, be passed on to the fetus. Infection is more common during birth and can lead to severe brain damage. Antiviral drugs greatly lessen the severity of the infection.

Syphilis can cause severe damage to the fetus. Women are now routinely screened in early pregnancy, and penicillin is effective at blocking transmission.

Influenza is nowhere near as dangerous as the other diseases mentioned, but it is speculated that it may interfere with neuronal migration.

Hormones and stress

Most maternal hormones can influence the fetus in some way. Some cross the placenta and affect it directly. Thyroid hormone, for example, is crucial for neuron production, synapse formation and myelination. The fetus will start producing its own thyroid hormone halfway through gestation, but relies on the mother’s thyroid before that. Other hormones affect blood flow to the placenta.

Very high amounts of stress hormones are suspected to contribute to all sorts of problems: cleft lip and Down syndrome; newborn problems such as eczema, stomach ulcers and ear infections; even higher rates of miscarriage. These hormones can also interfere with almost every step of brain development. High levels of stress hormones in mothers may lead to higher levels of the same hormones in the baby, so babies born to stressed mothers are often fussier and more irritable.

Physical exercise leads to higher levels of some stress hormones, but lowers the levels of others. The current view is that exercise is safe for pregnant women, especially those who were physically active before pregnancy. (Avoid exercising in hot weather or at high altitude, and avoid scuba diving.)