In the United States, autism is an alarmingly common condition. At baseline, the risk of having a child with autism is about 1.5%, and one in 68 children carries the diagnosis. This amounts to a total of more than 1 million young Americans with autism. Autism is more common in boys than girls, with a 5:1 male-female predominance. Twenty years ago, the causes of autism weren’t well understood, and a damaging article published in the Lancet suggested autism was caused by childhood vaccinations. Fortunately, that article has since been discredited, and scientists now have a much better understanding of what causes autism.
Currently, researchers agree that autism is a multifactorial condition, resulting from a combination of genetic and environmental risk factors, with a heavy emphasis on the former. Evidence for the genetic basis of autism is longstanding and strong. About 40% of children diagnosed with autism will have identifiable gene mutations. Because a multitude of genes control brain development, many different genetic alternations can cause autism. Some examples of genetic mutations associated with autism include 11q23 and 19q13 deletions; ANKRD11, STXBP1, DYRK1A, and SHANK3 mutations; mitochondrial disorders; and expansions of the FMR gene (fragile X). For families who have one child with autism, the risk of having a second child with the disorder increases by 20%. Amongst identical twins, if one child has autism, then the sibling has a 36-95% chance of having autism.
What causes the genetic mutations underlying autism? As people age, their reproductive cells (sperm and eggs) are more prone to genetic mishaps. Because sperm are produced every day, they are particularly susceptible to genetic errors. A very large 2015 study funded by Autism Speaks supports the parental age-mutation hypothesis as a primary cause of autism. Researchers analyzed a database containing information on nearly six million children from Denmark, Israel, Norway, Sweden and Western Australia; more than 30,000 of these children had autism. Increasing paternal and maternal age were both associated with autism. However, the single most powerful causative factor associated with autism was paternal age, which makes sense, biologically speaking. Constant sperm production opens the doorway for frequent genetic mistakes, especially as men age. The correlation between increasing paternal age and the risk of autism has been duplicated across multiple studies over time. In the Autism Speaks study, dads in their 40s had a 28% increased risk of having a child with autism, and for dads over 50 the risk went up by 66% (which is still a low number, given the baseline rate of 1.5%). Maternal-paternal age gaps of more than 10 years were also associated with an increased risk of autism in this study, but the reasons behind this finding remain a mystery. Interestingly, autism rates were 18% higher amongst teen mothers, perhaps due to birth complications or underlying genetic factors.
Anecdotally speaking, when I was living in NYC during my pediatrics residency, it seemed no female Manhattanites (or very few of them) had children before the age of 40. In the city, women tended to have careers first and children later. Studies have shown that increasing levels of education for women correspond to an increased risk of autism in children; the effect is dose dependent, meaning the more education a woman has, the more likely it is that her child will have autism. In my opinion, this probably correlates more with maternal/paternal age than access to medical providers, diagnoses, or services. Perhaps this helps to explain why the rate of autism is so high in New Jersey, where a whopping 1/41 children are currently diagnosed with autism. Incidentally, Alabama has the lowest rate of autism in the US.
Along with genetic mutations, certain environmental factors increase the risk of autism. Pregnancy-related problems, such as chronic maternal illnesses, gestational diabetes, infections, bleeding, hypoxic-ischemic events, prematurity, and low birth weight have all been associated with autism. The seizure medication valproate is known to cause autism, as well as spina bifida and other congenital anomalies. Severe maternal hypothyroidism is also problematic, probably because thyroid hormone influences brain development.
Some studies have shown a link between autism and prenatal exposure to organophosphate pesticides; however, there is no hard evidence suggesting that eating organically prepared food decreases the risk of autism. Studies from North Carolina, Pennsylvania, and California have demonstrated a connection between prenatal air pollution and autism. Other toxic chemicals, such as cyanide, methylene chloride, methanol, and arsenic have been proposed as causative agents.
On a hopeful note, some large studies have recently demonstrated that taking folic acid and/or prenatal multivitamins decreases the risk of having a child with autism; yet these results haven’t been duplicated across all studies. Regular fish consumption during pregnancy (though not the high mercury kind) has been shown to promote optimal brain development for babies and may also help to avoid autism.
Because spontaneous genetic mutations can occur in people of all ages, autism isn’t 100% preventable; but the odds can potentially be shifted in the right direction by following the steps outlined below:
- Avoid unplanned pregnancy by using reliable methods of contraception. Women who have unplanned pregnancies are less likely to take folic acid or prenatal vitamins before and after conception.
- Women trying to get pregnant should do the following:
-Eat two to three servings of fish weekly to promote healthy brain development in the womb (the consumption of high-mercury fish, like king mackerel, marlin, orange roughy, shark, swordfish, tilefish, ahi tuna, and bigeye tuna should be limited).
–Take prenatal vitamins with folic acid. Even if future studies don’t support a definitive role for folic acid in autism prevention, taking vitamins before conception decreases the risk of neural tube defects, like spina bifida.
-Get excellent prenatal care and lead a healthy a lifestyle. These measures help to avoid illness and other complications during pregnancy. Future mothers should absolutely receive immunizations that prevent illness before, during and after pregnancy, such as Tdap and flu vaccines.
- If possible, women should avoid having children during the teen years or after age 40. From the standpoint of autism prevention, the best time to have children is in the 20s and 30s. Discussing family planning strategies with male partners will also be helpful (see tip #5, below).
- Men should try to have children before they turn 40. In my opinion, men planning to have children should not keep cellphones in their pants pockets, due to the risk of damaging sperm. Yes, I’m serious. Numerous studies have shown that radiofrequency radiation, the type of low-frequency radiation emitted by cellphones, iPads, and laptop computers, causes stress at the cellular level and isn’t healthy for sperm. If you aren’t convinced, visit PubMed through Google, and use the site to perform a quick search. Type in “radiofrequency radiation and sperm,” and see what pops up.
- Individuals planning to have children later in life, following a long career path, should consider banking eggs and sperm in their 20s and 30s. For women, simply getting pregnant in the 40s can be difficult. Furthermore, the risk of having a baby with genetic disorders significantly increases as women age, particularly after age 40.
- If you’re a woman selecting sperm from a bank, choose wisely. Don’t choose sperm from male donors over age 40.
- In case there is something to the parental age-gap hypothesis, consider procreating with someone close to your own age.
- Consider genetic screening prior to conception to rule out any recessive conditions that could cause autism. Individuals who carry recessive genetic conditions associated with autism may be candidates for in vitro fertilization and preimplantation diagnosis.
- Women should review the risks of baseline medications with their doctors. Seizure medications like valproate may need to be stopped or replaced with alternative treatments during pregnancy.
- If possible, avoid exposure to air pollution, pesticides, or other toxic chemicals before conception.
Dr. Allison Beitel's Pedi Blog 