Literature Review
- mfulk78
- Oct 13
- 5 min read
FOR THOSE THAT MISSED THIS LAST WEEK:
Which is why I suspect that Dr. Makary and the FDA posted this information:
"“The FDA is taking action to make parents and doctors aware of a considerable body of evidence about potential risks associated with acetaminophen,” said FDA Commissioner Marty Makary, M.D., M.P.H. “Even with this body of evidence, the choice still belongs with parents. The precautionary principle may lead many to avoid using acetaminophen during pregnancy, especially since most low-grade fevers don’t require treatment. It remains reasonable, however, for pregnant women to use acetaminophen in certain scenarios.”
Evidence in recent years has suggested a correlation between acetaminophen use during pregnancy and subsequent diagnosis of conditions like autism and ADHD. Multiple large-scale cohort studies, including the Nurses’ Health Study II and the Boston Birth Cohort, find this association. Some studies have described that the risk may be most pronounced when acetaminophen is taken chronically throughout pregnancy.
It is important to note that while an association between acetaminophen and neurological conditions has been described in many studies, a causal relationship has not been established and there are contrary studies in the scientific literature. It is also noted that acetaminophen is the only over-the-counter drug approved for use to treat fevers during pregnancy, and high fevers in pregnant women can pose a risk to their children. Additionally, aspirin and ibuprofen have well-documented adverse impacts on the fetus."(FDA.gov)
Here is more from the excellent Egorova article:
Pregnancy is an exquisite dance between two biological systems, mother and child, linked by a placenta that must both connect and protect. Nature equips this dyad with dual defenses: mechanical barriers like the placenta and amniotic membranes, and immunologic intelligence that recognizes and regulates friend from foe. When a virus like influenza enters this delicate equilibrium, the consequences ripple far beyond a transient fever.
The influenza A virus (IAV) rarely infects the fetus directly, but the placenta is not immune to its reach. In severe cases, the virus has been isolated from placental and amniotic tissues, where it can incite placentitis, an inflammatory degeneration of the amniotic cells, trophoblasts, decidua, and vascular linings. This inflammation can weaken the structural integrity of the maternal-fetal interface, occasionally leading to miscarriage or preterm labor, which is associated with ASD.
Interestingly, studies reveal that the maternal decidua, the uterine lining that nourishes early pregnancy, is a more permissive environment for viral replication than the placenta itself. From this foothold, influenza can spread into the fetal membranes, triggering cell death and cytokine storms that compromise fetal growth. What we see clinically as “pregnancy loss” may, in fact, begin as a microscopic war at the maternal–fetal frontier. the authors state: "It should be noted that, in general, in humans, seasonal influenza viruses do not cause viremia in non-pregnant women". (Egorova et al 2021)
Because direct human evidence is ethically elusive, scientists turn to animal models. Ferrets, pigs, and mice, each biologically closer to us than we might imagine, have illuminated this path. In most cases, when influenza is introduced through the respiratory tract, the virus remains confined there. Only when it breaches into the bloodstream, called viremia, does it access the placenta or fetus. This suggests that viral load and maternal immune status are the gatekeepers between containment and catastrophe.
Even when the virus never touches fetal tissue, its signals do. Maternal immune activation, characterized by elevations in pro inflammatory cytokine interleukins (IL-1β, IL-6, IL-17) and TNF-α, can cross the immature blood–brain barrier and rewire developmental programming. IL-6, in particular, stands out as a master conductor, altering placental signaling, modifying fetal synapse formation, and changing neurotransmitter balance in the developing brain.
Animal and human studies converge on one truth: it is the inflammatory echo, not the infection itself (same reason given above for Covid and death), that may alter neurodevelopmental outcomes. Elevated maternal cytokines have been linked to increased risks of autism spectrum disorder, ADHD, cerebral palsy, and psychosis-like behaviors. The same immune molecules that protect can also, in excess, sculpt the brain in unintended ways.
Pregnancy’s hormonal orchestra, dominated by progesterone, estrogen, and glucocorticoids, adds another layer of complexity. These hormones have long been known to shift the immune system toward a Th2-dominant, anti-inflammatory state to preserve fetal tolerance. Yet this adaptation comes at a price: dampened viral defenses and altered inflammatory tone.
Beyond inflammation lies another mechanism, autoimmunity. Maternal antibodies that mistake fetal neural proteins for viral targets may cross the placenta and subtly alter brain development. Experimental models show that these antibodies can induce psychosis-like behaviors, motor abnormalities, and changes in sensorimotor gating in offspring, phenotypes reminiscent of schizophrenia or autism. While human data remain preliminary, this “maternal antibody hypothesis” underscores the fine line between protection and misdirected aggression. Obesity and metabolic disease also raise maternal autoantibodies targeting specific brain networks linked to ASD phenotypes. (Ramirez Cellis et al., 2021)
"Similar to other viruses, like Zika virus and cytomegalovirus, in the case of influenza A, the activation of proinflammatory cytokines (IL-6, IL-1b, TNF-a, and IFN-b) in the mother can induce neuroinflammation in the fetus. The expression of these factors can be triggered, in part, by the human leukocyte antigen DRB14. Additionally, hypoxia likely plays a role in neurodegeneration, as increased expression of hypoxic-inducible factor-1a (HIF-1a) is observed during inflammation. Moreover, maternal viral infection has been shown to lead to a reduction in the volume of the prefrontal, frontal, cingulate, insular, parietal, and temporo-auditory cortices in some cases, which can result in disturbances in exploratory behavior and social interaction in adulthood." (Egorova et al 2021)
Influenza-induced inflammation can constrict placental blood flow, leading to relative hypoxia, another potential insult to fetal brain development. Think of Rick Johnson's fructose and uric acid work here. Many routes are potentially leading to the same broken immunometabolic place. Meanwhile, the maternal microbiome, which interacts closely with immune tone, may amplify, buffer or worsen these inflammatory cascades. Each system: immune, endocrine, microbial, interlocks in a dynamic web that shapes the intrauterine environment. (Egorova et al 2021)
There is so much information here covered in the past 5 years of newsletters for those wanting to go deeper and farther.
The maternal immune system is not merely a shield; it is a sculptor of the human brain.
At this point, I remain humbled by the volume of information that must be read and understood to gain a foothold on the genesis of ASD.
Dr. M
Images below from Zhao et. al. 2023
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