A recently published epidemiological study in JAMA Pediatrics looked at the association between induction and enhancement of labor and the risk of autism. The researchers found a positive association, especially with males. The study has been variously reported in the popular press with causal interpretations not justified by the data.
The study itself is very robust – the authors looked at 625,042 live births, including 5,500 children with a diagnosis of autism. They found:
Compared with children born to mothers who received neither labor induction nor augmentation, children born to mothers who were induced and augmented, induced only, or augmented only experienced increased odds of autism after controlling for potential confounders related to socioeconomic status, maternal health, pregnancy-related events and conditions, and birth year. The observed associations between labor induction/augmentation were particularly pronounced in male children.
Although this is a large study, it is one study, and so the correlation needs to be independently confirmed. But if we assume the correlation is accurate, the next question is – what is the arrow of causation? Observational studies can only indicate an association. By themselves they cannot prove causation, although multiple observational studies may be able to triangulate to the most likely causal interpretation.
There are always three generic interpretations when A is associated with B: A causes B, B causes A, or C causes both A and B.
In the case of this study, either inducing/augmenting labor triggers autism in some children, children with autism are more likely to require induced labor, or some other factor(s) is a risk factor for both developing autism and needing to induce or augment labor. This current study does not contain data that can differentiate among these possibilities.
We can, however, explore plausibility. Inducing and augmenting labor includes a variety of generally safe procedures and medications. An unknown medication side effect, however, is always possible. Anything that adds stress to a newborn can also plausibly be a trigger for autism.
Twin studies and other genetic studies suggest that autism has a large genetic predisposition, but that genes are not 100% of the causal factors for autism. It may be that we simply do not yet have the full genetic picture. But it is also likely that the environment in the womb interacts with the genetic predisposition in determining the development of autism.
The environment of the womb could include delayed delivery, which results in induction, or some other factor that delays delivery. It is therefore plausible that either the delay in delivery itself, some other factor that delays delivery, or the procedures used to induce or augment labor when delivery is delayed can (separately or together) be an environmental trigger in genetically susceptible children.
It is also plausible that children who will become autistic may also be slow to deliver – that the delayed delivery is a symptom of, rather than a cause of, autism.
Evidence is mounting that autism begins in the womb, and not just from genetic evidence. Several studies, although individually small, have all shown that children with autism have significantly more brain cells, especially in their frontal cortex.
Other studies indicate that people with autism have abnormal networks in the brain, and specifically there is a deficit of connectivity between different parts of the brain, especially interhemispheric connectivity (the two sides of the brain do not talk to each other as robustly as a typical brain).
Clinically, the features of autism appear to be present starting at about 6 months. Such early presentation of clinical features is consistent with autism being a congenital disorder (i.e. present at birth).
Further, the specific changes in the autistic brain that research so far is demonstrating – changes in neuron number and connectivity – are the kinds of changes that occur during fetal development.
While there is still room for much further research, all the information we have at this time suggests that autism is something that occurs as the fetus is developing the womb, is primarily genetically determined, but may also be determined by factors present in the environment of the womb. The latest study identifies delivery as another possible factor, but it is not clear what role it is playing, and delayed delivery may simply be another symptom or marker of the underlying cause(s) of autism.
All of this is incompatible, of course, with theories about environmental triggers that cause autism in children older than 6 months. The MMR and other vaccines come to mind.
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