There is no shortage of debate about what may contribute to autism. Vaccines have been repeatedly studied and ruled out as a cause, while researchers continue to look at other possible effects, including acetaminophen use during pregnancy and exposure to chemicals found in plastics.
Now, a major new study adds another question to the debate: Could some commonly prescribed drugs affect fetal brain development when taken during pregnancy?
The researchers looked at health records from more than six million children and their mothers, focusing on drugs that may interfere with the body’s cholesterol-making pathway – a process that plays an important role in early brain development. Their findings show an association with higher rates of autism diagnosis, but do not prove that the drugs caused autism.
Medications included several antidepressants, antipsychotics, blood pressure medications, beta-blockers, and statins.
For pregnant patients, the message is not to stop the medication. It is to discuss the findings with a doctor and consider the benefits and risks of treatment.
Posted on Molecular Psychiatrythe study used files from the Epic Cosmos database.
The final analysis included 6,135,213 children born between 2014 and 2023 who had linked maternal health records and at least 18 months of follow-up.
The researchers focused on 15 drugs described as sterol biosynthesis inhibitor drugs, or SBIMs. These drugs can interfere with the process the body uses to make cholesterol and related molecules.
The drugs studied were:
Aripiprazole, atorvastatin, bupropion, buspirone, cariprazine, fluoxetine, haloperidol, metoprolol, nebivolol, pravastatin, propranolol, rosuvastatin, sertraline, simvastatin and trazodone.
These drugs treat many different conditions, including depression, anxiety, psychosis, high blood pressure, heart problems, and high cholesterol. What they may share is an effect on the sterol production pathway.
Among the children included in the study, 234,971, or 3.8%, had been diagnosed with autism.
About 700,000 mothers were prescribed at least one of the drugs during pregnancy.
In the raw data, autism was diagnosed in:
- 5% of children in the drug-exposed group
- 3.7% of children in the unexposed group
After the researchers adjusted for factors such as maternal age, diabetes, preeclampsia, race, ethnicity, social vulnerability, year of birth and reported tobacco or alcohol use, exposure to at least one of the drugs was associated with a 47% higher relative rate of autism diagnosis.
This does not mean that a child had a 47% chance of being autistic. It means that autism diagnoses occurred more often over time in the exposed group than in the comparison group.
The absolute difference in raw data was about 1.3 percentage points.
The strongest pattern was seen in mothers who prescribed more than one of the identified drugs.
Compared to no exposure, the adjusted relative rate of autism diagnosis was:
- 1.47 times higher with at least one drug
- 1.81 times higher with two or more
- 2.23 times higher with three or more
- 2.33 times higher with four or more
The researchers estimated that each additional drug was associated with an additional 33% increase in relative risk.
This dose-like pattern may support the possibility of a biological effect. However, patients taking multiple medications may also have more serious or complex health conditions, which could independently affect pregnancy and childhood.
Cholesterol isn’t just linked to heart health. It is also necessary for cell growth, hormone production and brain development.
During pregnancy, the developing brain needs cholesterol and related sterols to build cells and form nerve connections.
The researchers were particularly interested in drugs that might block enzymes involved in cholesterol production. When this pathway is disrupted, the body can produce less cholesterol while accumulating other compounds that can become highly reactive.
The authors suggest that this imbalance could affect the development of brain cells.
This theory is biologically plausible, but has not been proven in human pregnancies.
The magnitude of the association varied by medication.
Cariprazine had the highest adjusted hazard ratio at 2.59, followed by aripiprazole at 2.18 and pravastatin at 1.95.
Other estimates ranged from 1.35 for metoprolol to 1.86 for trazodone.
These numbers should not be used to rank drugs from safest to most dangerous.
Some drugs were prescribed to hundreds of thousands of patients, while others were used in much smaller groups. The drugs also treat very different conditions, making direct comparisons difficult.
One of the biggest challenges is separating the effects of a drug from the effects of the condition being treated.
For example, people taking antipsychotics or antidepressants may have serious mental health conditions. These conditions may be linked to genetics, stress, health behaviors, access to care, and family factors that may also affect developmental outcomes.
When the researchers adjusted for maternal mental health diagnoses, the associations for several psychiatric medications became weaker.
The adjusted estimate for aripiprazole decreased from 2.18 to 1.31.
The authors said the mother’s mental health conditions did not fully explain the results. However, medical record studies cannot capture every difference between patients who need medication and those who do not.
The study was based on prescription and medical record data.
The researchers were unable to confirm:
- Whether a prescription was filled
- Whether the medicine was taken
- The dose used
- The exhibition quarter
- How long the treatment continued
- It was identified if treatment was stopped after pregnancy
The study also could not independently confirm each autism diagnosis.
Some children, especially those born later in the study period, may have been too young to receive a diagnosis before follow-up ended. Autism is often not formally recognized until preschool or later.
Families with more frequent contact with the health care system may also have greater access to developmental screening, which could affect diagnosis rates.
The proportion of pregnant patients prescribed at least one of the drugs increased from 4.6% in 2014 to 16.8% in 2023.
This increase may in part reflect the growing recognition that untreated disease during pregnancy can also be harmful.
Severe depression, anxiety, psychosis, high blood pressure, and heart disease can all pose risks to the pregnant patient and the baby. In many cases, medication remains the safest option.
What should pregnant patients do?
Patients should not suddenly stop antidepressants, antipsychotics, statins, beta-blockers, or other prescription drugs because of this study.
Abruptly stopping treatment can cause withdrawal, relapse, or dangerous changes in blood pressure, mood, or heart function.
Instead, patients can ask their doctor:
- Is this medicine still necessary?
- Is the current dose the lowest effective dose?
- Do they need a lot of medication?
- Is there an alternative with stronger pregnancy safety data?
- What are the risks of leaving the condition untreated?
The correct answer will depend on the person, the drug and the disease being treated.
The researchers are calling for more studies that will monitor the exact dose, timing and duration of exposure to the drug.
They also want researchers to look at whether genetics make some babies more vulnerable and whether combining several sterol-blocking drugs creates a cumulative effect.
This study is large and the biological theory is worth investigating. But it’s still an observational study and can’t prove that the drugs caused autism.
For now, the findings should lead to more research and more careful prescribing – not panic, guilt or abrupt changes in necessary medical care
