Photo Credit – CDC
#17,845
We've long known that pregnancy and flu can be a bad combination, with historical accounts and studies following the last four influenza pandemics (1918, 1957, 1968, and 2009) all showing distinct increases in maternal mortality, the number stillborns, and evidence of impaired fetal development.
The best records come from the most recent, and mildest, of these flu pandemics (2009).
- In the fall of 2009 we learned that pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).
- In 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study where pregnant women who were admitted to the hospital with an H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.
- And in 2019, in Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09 found that women admitted to the ICU with H1N1 were more likely to deliver preterm infants, low birth weight infants, and infants with low Apgar scores than women in the other groups.
- In 2014's Pregnancy, Influenza & Elevated Psychosis Risks In Adult Offspring, researchers reported `. . . The results suggest that maternal influenza exposure may increase the risk for offspring to develop bipolar disorder with psychotic features'.
- In 2017, in Molecular Psy.: Increased Autism Risk Linked To Prenatal Fever, we saw a study suggesting maternal fever in the 2nd trimester was linked to a 40% increased risk of autism.
- In 2019's JAMA Psych: Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero we looked at an impressively large, multi-decade study published in JAMA Psychiatry on the risks of developing neuropsychiatric disease later in life that found (emphasis mine).
- `. . . those people whose mothers had been hospitalized for any infection during pregnancy had a 79 percent higher risk of being diagnosed with autism and a 24 percent increased risk of being diagnosed with depression.'
- And in 2022, in Systematic Review & Meta-Analysis: First-Trimester Influenza Infection Increases the Odds of Non-Chromosomal Birth Defects, researchers found:
- . . . maternal influenza was associated with increased odds of developing any type of birth defects (OR: 1.5, CI: 1.30–1.70). Moreover, newborns were more than twice as likely to be diagnosed with neural tube defects (OR: 2.48, CI: 1.95–3.14) or cleft lip and palate (OR: 2.48, CI: 1.87–3.28). We also found increased odds of developing congenital heart defects (OR: 1.63, CI: 1.27–2.09).
All of which brings us to a new review article published in Current Issues in Molecular Biology, which examines the growing evidence of maternal influenza infection's impact on the neurodevelopment of the offspring.
This is a lengthy article, which looks not only at outcomes but at some of the possible mechanisms behind those outcomes (see graphic below). More work is obviously needed, but the evidence of harm to the developing fetus is compelling.
Due to its length, I've only posted the abstract and some brief excerpts. Follow the link to read the review in its entirety. I'll have a brief postscript after the break.
Maternal Influenza and Offspring Neurodevelopment
Marya Egorova 1, Vladimir Egorov 1,2 and Yana Zabrodskaya 1,3,*
Curr. Issues Mol. Biol. 2024, 46(1), 355-366; https://doi.org/10.3390/cimb46010023 (registering DOI)Published: 2 January 2024
Abstract
This review examines the complex interactions between maternal influenza infection, the immune system, and the neurodevelopment of the offspring. It highlights the importance of high-quality studies to clarify the association between maternal exposure to the virus and neuropsychiatric disorders in the offspring. Additionally, it emphasizes that the development of accurate animal models is vital for studying the impact of infectious diseases during pregnancy and identifying potential therapeutic targets. By drawing attention to the complex nature of these interactions, this review underscores the need for ongoing research to improve the understanding and outcomes for pregnant women and their offspring
(SNIP)
Prospects
Influenza infection during pregnancy presents a complex and clinically important issue. Understanding the mechanisms of interaction between the mother, the virus, and the immune system, at both systemic and local levels, is crucial for enhancing prevention and treatment strategies and warrants further investigation [1]. It is important not to overlook the identification and examination of the influence of other factors on the development of pregnancy complications, including those of a neuropsychiatric nature, for which high-quality epidemiological studies are necessary [12].
(SNIP)
In terms of future studies, investigating the relationship between infection and innate and adaptive immune responses in schizophrenia using animal models and large-scale serological studies in patients at different stages of the disease will be beneficial. Standardized and more sensitive testing technologies, including improved non-invasive methods, are required to assess central neuroinflammation in humans and animals [104,105]. Additionally, the development of next-generation genetic, immunological, and bioinformatics technologies may shed light on the relationship between influenza and psychosis [44].
It is evident that numerous factors can influence the development of neurological complications in offspring due to maternal influenza infection. Primarily, this effect is directly caused by the pathogen and the mother’s immune response to the infection. It is important to consider that pregnant women comprise a special group with limited options for therapeutic drug use. The establishment of appropriate models to study the mechanisms of neurological complications resulting from influenza in offspring will likely lead to the identification of potential therapeutic targets to mitigate the risk of complications. However, currently, the only way to protect both the mother and her offspring from illness and serious complications is through influenza vaccination, which is also permitted during pregnancy.
While influenza is undoubtedly of greatest risk to high risk individuals - the elderly, very young children, those with significant comorbidities, and those who are pregnant - it isn't exactly benign for healthy adults.
Increasingly we are learning that influenza can have similar (albeit usually milder) long-term sequelae to COVID (see The Lancet: Long-term Outcomes Following Hospital Admission for COVID-19 Versus Seasonal Influenza).
There are strong links between influenza infection and cardiovascular events like heart attacks and strokes (see also Eur. Resp.J.: Influenza & Pneumonia Infections Increase Risk Of Heart Attack and Stroke).
But we've also seen evidence suggesting that repeated influenza infections may be linked to an increase risk of developing Parkinson's later in life (see 2017's Nature Comms: Revisiting The Influenza-Parkinson's Link).
In early 2023, in Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks, we also looked at a study published in Cell Neuron which found a statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.
And at an AAIC Meeting in 2020 (see Flu & Pneumonia Shots Appear To Reduce Dementia Risk In Elderly, researchers presented evidence suggesting:
● At least one flu vaccination was associated with a 17% reduction in Alzheimer’s incidence. More frequent flu vaccination was associated with another 13% reduction in Alzheimer’s incidence.
● Vaccination against pneumonia between ages 65 and 75 reduced Alzheimer’s risk by up to 40% depending on individual genes.
While the current flu vaccine is nowhere near as effective as we'd like it to be, and the promise of a universal flu vaccine remains elusive (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine), there is evidence to suggest the benefits of vaccination may extend beyond simply reducing the risk of influenza infection.
I view getting a yearly flu shot like always wearing a seat belt in an automobile. It doesn't guarantee a good outcome in a wreck, but it certainly increases your odds of walking away.
And for me - now that I've entered that dreaded `elderly' demographic - that is an extra bit of insurance worth having.
