Alas, I lapsed into the sixth deadly sin due to a combination of leftover Halloween candy and a discovery of cookie butter. It's pretty easy to stuff my face while reading medical articles and typing this week's blog.
Maternal Covid Infection Associated With Neurodevelopmental Disabilities in Offspring
This retrospective cohort study from Massachusetts provides strong evidence that SARS-CoV-2 infection of a pregnant person carries with it an association with neurodevelopmental disabilities, including autism, in the offspring of that pregnancy. The lay press reported the findings quickly, but it's important to realize that a) this association is entirely expected, based on animal studies and experience in humans with other viruses like influenza, and b) at this point it is just an association, not proving causality, and the study design as a retrospective cohort dependent on database registries leaves it open to error. Having said that, let's dig a little deeper.
The cohort was comprised of all births at 2 academic and 6 community hospitals within a single medical system in Massachusetts from March 1, 2020, to May 31, 2021. The children's records were queried for any neurodevelopmental disability diagnostic codes up to 36 months of age. The timing of the cohort is important. It was early in the pandemic, at a time when the less reliable home testing kits weren't used as frequently and those home antigen tests during pregnancy were likely to be confirmed by PCR, assuming the women were receiving prenatal care. Also, the population in general was highly motivated to be tested for covid; in other words, ascertainment of covid episodes during pregnancy likely were more reliable than what we commonly see later in the pandemic and beyond. It's also important to note that vaccination wasn't available for much of the study period. Only 8% of mothers in the non-infected group had received at least 1 covid vaccine, compared to 2% of mothers who had been infected - the differences in vaccination rates most likely are due to socioeconomic factors.
Here's what the investigators found. Of a little over 18,000 live births in the cohort, 861 mothers (4.8% of the cohort of live births), were diagnosed with SARS-CoV-2 infection during pregnancy. By age 36 months, 140 (16%) of children exposed to maternal infection had received at least one neurodevelopmental disability diagnosis, compared to 1680 (a little less than 10%) in the unexposed birth group.
Now comes the hard part, trying to correct for all those other maternal factors that are associated with increased neurodevelopmental disabilities in infants. Known risk factors such as male sex, preterm birth, Hispanic ethnicity, and public insurance status had higher rates of disabilities in this cohort, lending support to the accuracy of the overall findings. Also supportive of the findings was an association with infection during the third trimester, an important time for fetal neurodevelopment.
After performing a multivariate analysis to correct for multiple confounding risk factors, the association with maternal covid infection during pregnancy remained significant independent of these risks. Unfortunately, one very important risk factor for autism and similar disabilities, genetics, couldn't be analyzed. This would likely require a prospective study with sibling controls.
Note that we aren't talking about vertical transmission of the virus from mother to fetus, such as occurs with CMV and toxoplasmosis. Vertical transmission of SARS-CoV-2 from mother to fetus is rare, although I did participate in the care of one such newborn early in the pandemic. The biologic plausibility of maternal viral infection without vertical transmission causing neurodevelopmental disability is supported by many animal studies and likely involves some sort of maternal immune activation that interferes with the developing newborn brain.
These findings shouldn't change practice now. First, we don't know if the findings would persist in an era where almost everyone has some form of immune experience with SARS-CoV-2. Second, we don't know the effect vaccination might have on this process. And again, remember we're talking about association rather than causation.
Respiratory Vaccines Are Good
In my August 24 posting I commented on the Vaccine Integrity Project's systematic review of respiratory vaccine effectiveness and safety. Now that report is fully available in a new publication this past week. It doesn't contain any substantially new material or conclusions, but it's a lot easier to evaluate the numbers in print than it is with the August slides and oral presentations. Vaccines for covid, RSV, and influenza all had significant benefit against a variety of outcomes in children and adults. (I'm not showing data for covid, the report didn't contain any nice tables or graphs for pediatric covid.)
Here is a forest plot for RSV vaccine effectiveness for preventing hospitalizations in various settings:
And for influenza vaccinations:
This should be the go-to study for any provider needing to explain respiratory vaccine benefits and risks to patients and families.
Wikipedia Under Attack
Some of you probably saw that Elon Musk and others are developing "non-woke" alternatives to Wikipedia. Regular readers of this blog certainly will have noticed I frequently link to Wikipedia articles, not with respect to medical issues but rather to whatever little quirks and digressions I find myself exploring in a particular week. I certainly haven't perceived any liberal or conservative bias in the postings. In fact, I would expect less bias in a publication that can be edited by multitudes online; any mistakes or biases tend to get corrected pretty quickly. Wikipedia even has its own entry on ideological bias in its pages.
I decided to look at a medically-related post, in this case ivermectin. Early in the pandemic I followed this topic very closely; all of us were desperate for any intervention that seem beneficial, at the same time worried about just trying something that could end up useless or, worse, harmful. It turns out that Wikipedia has a separate post specifically for ivermectin during the pandemic. I read through everything, it was very reasonable and didn't even mention the President's wild ravings about what he thought was a wonderful drug for covid. I found no bias, unless you count the bias where more credit is given to bonafide clinical trials published in a peer-reviewed journal compared to some podcaster's unsubstantiated opinion. Musk's new Grokipedia has an identically titled post that I reviewed. I found it to be credible in some areas but extremely opinionated in others to the extent that I felt that the content obscured the fact that the drug was ineffective.
Asymptomatic Bird Flu?
Influenza A H5N1, the "bird flu" that's been plaguing our dairy cow and poultry industry plus several humans in the US for a while now, hasn't been closely studied beyond symptomatic people mostly exposed to infected animals or cow milk. A recent review sheds more light on asymptomatic H5N1 infections. Investigators from the CDC looked for studies with molecular evidence of infection with or without serologic confirmation (note that some asymptomatic people with influenza never show seroconversion). They found a handful of cases, including a couple with both molecular and serologic evidence of infection,
H5N1 continues to lurk out there, waiting perhaps for some genetic reassortment that facilitates human spread. As an aside, I noted that the CDC article utilized the services of a medical librarian to find these articles, and I recalled that librarians have been cut from CDC recently.
H5N1 continues to infect animals and humans around the globe, perhaps waiting for that unfortunate reassortment that will facilitate human to human transmission. We need CDC and its librarians to help keep us safe.
WRIS
Winter respiratory infection season hasn't hit us yet, though the lay press has latched onto a mild upturn in respiratory illnesses in the past week. We should be a bit more wary of tracking accuracy this year due to the double wammy hit to CDC of funding cuts and now the federal shutdown, but I think we'll see significantly more respiratory illness starting in the next few weeks.
In my meanderings around the web, I noted a map on POPHIVE showing RSV queries in Google by state. Web searching activity has been advocated by many as one way to assess disease activity. RSV usually begins in the South, especially in Florida, so I was a little surprised to see a lot of Google RSV searches in places like Maine and the northern midwest and mountain states.
We'll see if those states start RSV season a little early.
Cookie Butter
About a week ago I happened on a recipe for "Holiday Rocky Road" by one of my favorite chefs, Sohla El-Waylly. She has some unusual cooking ideas, plus she is very entertaining. If you want to have a smile plus see how to gorge yourself on chocolate, cookie butter, and other goodies, take a look at her recipe video.
Bon Appetit!