Saturday, May 15, 2021

Possible effects of the COVID-19 vaccine on pregnancy and fertility. Part I.

 Copyright 2021 Robert Clark


I.)Maternal Fevers and birth defects.

 It is dismaying that the CDC has not been made clear the extent of the fevers that arise after the COVID vaccine shot. The CDC has put on its web site that fever can result after the shot but it has not emphasized the high prevalence: 15% to 30%, or perhaps as high as 50% for women is high prevalence.

 I think the CDC just putting that fevers can arise on its web site has not made this extent commonly known. Even if doctors or average citizens have heard the vaccine particularly the 2nd shot can cause a fever they would not be aware of its prevalence, or that the flu-like symptoms that arise can be so severe as to wipe you out, to the extent you can't go to work the next day.

 Most people would think it's just like the flu-vaccine. No, the flu-vaccine does not require hospitals to stagger their vaccination times for their staff to insure not too many people get knocked out on the same day.

 My guess is few doctors are aware the prevalence of fevers is as high as it is after the 2nd shot of the COVID vaccine. I certainly don't believe most OB-GYN's are aware of it. But that's where the problem comes in: maternal fevers in pregnancy are strongly associated with an increased chance of birth defects.

 I'm suggesting because of the potential danger of birth defects that can arise from these fevers when they occur in the pregnant mother, every time any health official comes on TV, every time any health agency puts out any update of any nature on COVID-19, every time any newspaper, TV news show, news web site, social media company says anything at all about COVID-19 or its vaccine, it should be accompanied by an advisory that pregnant mothers experiencing a fever after taking the vaccine should take it very seriously because of the potential of causing birth defects and so it should be reported both to their OB-GYN and to the CDC.

 In short, maternal fevers in the 1st trimester are linked to an increased chance of a very serious form of birth defect known as neural tube defect. These include spina bifida, anencephaly, and encephalocele.

 The naturally occurring fevers in the 1st trimester are at about 68%. But judging by the number of fevers seen in the COVID vaccine trials, there would be an additional ~15% vaccine caused fevers. So if you add the 15% COVID vaccine fevers to the number of natural fevers, the maternal fevers could be bumped up to the 21­­­‒23% range. And actually three separate sources put the number of fevers in pregnant woman after the 2nd shot of the vaccine as ~30%, which would mean the number of maternal fevers in the first trimester would shoot up to the 36­­­‒38% range, an increase by a factor of 6. I simply can not believe that knowing the strong association of maternal fevers to birth defects that most OB-GYN's would be at ease with maternal fevers shooting up this high.

 This article gives the number of fevers, albeit in their small sample size as 32%:

ORIGINAL RESEARCH: OBSTETRICS|ARTICLES IN PRESS
COVID-19 vaccine response in pregnant and lactating women: a cohort study
Kathryn J. Gray, MD PhD, Evan A. Bordt, PhD, Caroline Atyeo, BS, Michal A. Elovitz, MD, Galit Alter, PhD, Andrea G. Edlow, MD, MSc
Open Access Published:March 25, 2021 DOI:https://doi.org/10.1016/j.ajog.2021.03.023
COVID-19 vaccine response in pregnant and lactating women: a cohort study - American Journal of Obstetrics & Gynecology (ajog.org)

  

 This report also puts the number of fevers in pregnant women as ~30%:

COVID-19 vaccine safety update
Advisory Committee on Immunization Practices (ACIP)
March 1, 2021
Tom Shimabukuro, MD, MPH, MBA
CDC COVID-19 Vaccine Task Force
Vaccine Safety Team



 And this recently published article also puts the number of fevers in pregnant women after the vaccine as ~35% after dose 2:

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons
List of authors.
Tom T. Shimabukuro, M.D., et al.
April 21, 2021
DOI: 10.1056/NEJMoa2104983

 So according to this article after you add on the ‒ 8% naturally occurring fevers, the number or maternal fevers could balloon to the range of 41 ‒ 43% in the first trimester. According to this data, it's particularly bad for the Moderna vaccine at 46% fevers in pregnant women after the 2nd dose. This would mean adding the naturally occurring fevers, the number of maternal fevers for those getting the Moderna shot would balloon to 52 ‒ 54% range.

 The CDC makes it seem like the COVID shot is just like the flu-shot. No, after the flu-shot perhaps 1­­­‒2% of people will get fever. But with the COVID vaccine shot a radically larger proportion of people will get flu-like symptoms such as high fever after the 2nd shot that are so severe it will keep them off work for a day or so. In fact this is so common that some hospitals have to stagger the days their staff get the vaccine to insure not too many people call in sick the same day after their shot:

Second COVID Shot Packs the Big Punch
— First dose also worse for those with previous COVID, but "small price to pay" for protection
by Kristina Fiore, Director of Enterprise & Investigative Reporting, MedPage Today February 11, 2021
https://www.medpagetoday.com/special-reports/exclusives/91157
(May need free registration.)

 But as the article notes this can even happen after the 1st shot if the person had COVID-19 before. Most distressingly, it might even be the case that if the person had an asymptomatic case, so they didn’t know they had it, they could still get these severe reactions after just the 1st shot.

 And in this video Dr. Kavita Patel being interviewed says the side effects for 1/3rd of the people after 2nd dose feels like they have the flu. She herself had to take off. While many people wouldn’t take off for say a cold, the flu is more debilitating and most people do take off work then:

 This discusses the Pfizer and Moderna COVID vaccines. But the Astrazeneca vaccine also results in a high number of flu-like symptoms:

“But it turns out the side effects were underestimated, and we found ourselves with almost a third of health workers in some departments presenting severe symptoms and having to go on sick leave.”
https://www.thelocal.fr/20210225/french-hospitals-pause-astrazeneca-vaccine-campaign-as-temporary-side-effects-leave-many-staff-needing-sick-leave/

 It should be noted though that for the Astrazeneca vaccine the greatest side effects occur after the first shot, not the second.

 But in addition to the CDC emphasizing the  high prevalence of the "flu" after the shot, it also needs to be emphasized the length of time for these severe flu-like symptoms of a day or so is just the average length of time. For some people, perhaps 1­­­‒2%, they will be wiped out by this “flu” with high fever for over a week, obviously, quite concerning for the elderly and pregnant mothers.

 The CDC has put it on their web site there is a chance of the fevers after the COVID-19 shot. Even still, most doctors are not aware of the extent of these fevers and certainly most average citizens don’t know it.

  But I’ll explain why it is extremely important that this be commonly known.

 To obstetricians a well-known contributing factor to a very serious birth-defect known as neural tube defect is fever during first trimester in the mother. In fact the chance of this occurring can be increased multiple times when the mother has a 1st trimester fever. These birth defects include spina bífida, anencephaly, and encephalocele. Spina bifida most people have heard of where the baby is born with the spinal cord partially protruding through the back. Anencephaly is not as well known by the public, but it's where the baby is born with only a partially formed brain. And encephalocele is where part of the brain extrudes through the back of the head, [1].

 But fevers can also cause other birth defects in the 1st trimester such as heart defects, cleft palate, and autism. And the increased chance of these with maternal fever extends also into the 2nd trimester, [2].

 With the controversy over a claimed connection between vaccines in children and autism, it should be required to inform women that the chance is increased for autism in the child if the mother contracts a fever due to the COVID vaccine, under the principle of informed consent.

 Quite concerning also is the chance of the baby suffering one of these birth defects grows larger in an additive fashion with multiple fevers, up to a factor of 2 times larger with 3 fevers, [3].

 And for the serious neural tube birth defects, the degree of the increased chance is no small number. We are used to hearing of some drug causing an increased chance of some adverse effect by, say, 20% or 30%, but with maternal fevers the chance of the baby having a neural tube birth defect increases by 300% higher, when the mothers are not on the protective folic acid.

 Given this you would think obstetricians would give a caution to be wary of the fevers for pregnant mothers after getting the vaccine shot.

 So why haven’t they? My opinion is it’s because the CDC has not emphasized the prevalence of fevers after the COVID-vaccine shot. They have given the impression the side-effects are just like the flu vaccine.

 The CDC has been aware of the increased chance of birth defects with maternal fevers for several years now:

Maternal Fever During Early Pregnancy May Be Linked to Birth Defects.
https://www.cdc.gov/ncbddd/birthdefects/features/kf-birthdefects-maternal-fever-during-pregnancy.html

 A food additive called folic acid can lower, though not eliminate, the size of the increased chance. The CDC puts out an advisory that all women of child bearing years whether or not they are pregnant or plan to become pregnant take the additive and has seen that it is also included as an additive in some foods.

 The reason why it is important that all women of child-bearing years take the protective folic acid is that frequently women can be pregnant and not know it, early on. Then the warning of the danger of the increased fevers due to the vaccine in the first trimester should be extended to all women in child-bearing years even those not knowingly pregnant.

 But a problem is most women still don’t take or get enough of the folic acid.

 Then most women will still have the increased chance of the birth defects with fevers, such as those that occur to a high percentage of times with the COVID-19 vaccine.

 Moreover, this increased chance of these devastating birth defects will be worse for black women. The reason is even fewer black women get the protective folic acid, only about 20%. Then when the increase in these birth defects is seen to be especially high in black women the CDC can claim all they want they didn't know, but the response in the black community will be that they were targeted.

 The NEJM article has been cited to support the safety of the vaccine for pregnant women. But it is important note most of the completed pregnancies were for women getting the vaccine in the third trimester. But the danger of maternal fevers to birth defects is for the first and second trimesters. So the NEJM article can not address this key question.

 Tests for neural tube defects by either genetic markers, amniocenteses, or ultrasound can be done at about the 15th to 20th week of pregnancy. Women who were vaccinated in their first trimester in December or early January would now be in the time period for these types of tests to be done. It is imperative that such tests be done on all such pregnant women to insure this very serious type of birth defect does not occur at increased incidence after COVID vaccination.

II.)Possible Effect of COVID Vaccine on Infertility.

 As part of the justification being given for the safety of the vaccine in pregnancy, the animal studies Pfizer and Moderna did on pregnant rats have often been cited. The vaccine manufacturers have claimed that there were no statistically significant increases in infertility or birth defects in their rat studies. However, it is important to note there were increases in both infertility and birth defects in the rats for both the Pfizer and Moderna studies. 

 The claims of Pfizer and Moderna that these increases were not statistically significant, and therefore not "real", points out a major problem with medical studies that statisticians have complained about repeatedly in recent years. A difference in the data not being at the level of "statistical significance" does NOT mean it is nothing more than a random blip in the data, so not real. It just as well could be a real effect but the number of cases in the study is not sufficient for it to rise to statistical significance. 

 The issue is discussed in this article in the journal Nature:

COMMENT  20 MARCH 2019
Scientists rise up against statistical significance.
Valentin Amrhein, Sander Greenland, Blake McShane and more than 800 signatories call for an end to hyped claims and the dismissal of possibly crucial effects.
Valentin Amrhein, Sander Greenland & Blake McShane.

"When was the last time you heard a seminar speaker claim there was ‘no difference’ between two groups because the difference was ‘statistically non-significant’?

If your experience matches ours, there’s a good chance that this happened at the last talk you attended. We hope that at least someone in the audience was perplexed if, as frequently happens, a plot or table showed that there actually was a difference.

How do statistics so often lead scientists to deny differences that those not educated in statistics can plainly see? {emphasis added} For several generations, researchers have been warned that a statistically non-significant result does not ‘prove’ the null hypothesis (the hypothesis that there is no difference between groups or no effect of a treatment on some measured outcome)1. Nor do statistically significant results ‘prove’ some other hypothesis. Such misconceptions have famously warped the literature with overstated claims and, less famously, led to claims of conflicts between studies where none exists.

We have some proposals to keep scientists from falling prey to these misconceptions.

Pervasive problem

Let’s be clear about what must stop: we should never conclude there is ‘no difference’ or ‘no association’ just because a P value is larger than a threshold such as 0.05 or, equivalently, because a confidence interval includes zero. Neither should we conclude that two studies conflict because one had a statistically significant result and the other did not. These errors waste research efforts and misinform policy decisions."

https://www.nature.com/articles/d41586-019-00857-9

 In other words, for an observed large difference in the data, the difference should not be simply dismissed and regarded as not real just because it is not at the statistically significant level. The correct conclusion should be to do larger studies to determine if it is a real effect or not.

 A discussion of the Moderna rat study on the vaccines effect on fertility  appears on p. 50 to 51 of this report:

Assessment report
COVID-19 Vaccine Moderna.

https://www.ema.europa.eu/en/documents/assessment-report/covid-19-vaccine-moderna-epar-public-assessment-report_en.pdf

 Moderna noted in the rat study that fertility dropped from 93.2% for the controls to 84.1% for the vaccinated rats. That means infertility doubled for the vaccinated rats, from 6.8% for the controls to 15.9% for the vaccinated.

 Moderna asserts this is within the normal range but no statistical significance values are provided so we can judge that.

 Other odd statements in this passage: Moderna’s researchers noted that the vaccinated pregnant rats wound up with limited use of their hind legs, but Moderna did not consider that to be an adverse event. That the vaccinated pregnant rats loss the use of their hind legs obviously should be concerning. Moreover, the fact it was the hind legs effected suggests also it’s related to the pregnancy.

 Then beyond that, Moderna noted that babies from the vaccinated rats had an INCREASE in skeletal birth defects. The Moderna researchers assert this is not an adverse event because it’s a common birth defect in rats. But how much was it increased? By 10%? Was it doubled, was it tripled? We’re not given that information. And again, even if the difference is not statistically significant, it is possible that these increased numbers of birth defects are real effects and that can only be determined by looking at larger studies.

 The Pfizer study on vaccinated pregnant rats is discussed here:

Assessment
Comirnaty

  The Pfizer researchers claim there were no observed difference in "fertility index" but the observed doubling in pre-implantation loss does amount to an increase in the pregnancy loss in the rats, i.e., an increase in infertility.

 The researchers assert it is within the normal range, i.e., not statistically significant, but again whether this is a real effect or not can only be determined by doing the study with a larger sample size.

 The phrasing in this passage also leads me to believe there was an increase in birth defects which the Pfizer researchers also say is not statistically significance. But again the validity of this claim can only be ascertained on a larger sample size.

 Note, even though both Moderna and Pfizer researchers assert no statistically significant difference in infertility, the size of the increase in both studies being doubled argues very strongly this is not coincidental, i.e., that it is a real effect.

 Because of the importance of this issue, these studies on vaccinated rats need to be published so they can be subjected to independent review, that is, by those not paid by the vaccine manufacturers, even if just a preprint on Medrxiv.com. 

 Other independent researchers need to confirm their validity. One key thing to check is to see if in future reproductive cycles, if the infertile rats had continue difficulty completing a pregnancy. If so, that would be alarming, since that would suggest the difference could be permanent. 

 The UK public health agency and WHO do not advise pregnant women in general to get the vaccine unless they are at high risk of getting COVID because of the lack of information either for or against its safety for pregnant women.

 But in the U.S., the CDC advises pregnant women consult with their doctor before getting the vaccine. Then both must be fully informed, including being made aware of the results of these studies.

 Even if it shown though the rat differences in infertility are real, that still would not mean that has to be the case in humans.

 For humans, fertility is usually determined over a year. However, the importance of answering this question about an effect on fertility is so great I suggest doing studies on the shorter time scale of 5 months since the vaccines have been released. Has there been a change in the number of pregnancies among those couples wanting to get pregnant when one or both members of the couple have been vaccinated?

 III. Could the vaccine induce auto-immune response within the placenta?

 Some scientists have argued that there is sufficient similarity of the spike protein to the syncytin proteins in the placenta that there could be cross-reactivity against the natural syncytins by the immune system in combating the COVID spike protein.

 This won't happen with B-cells which are very discriminating in the proteins they attack. However, T-cells are not nearly as discriminating. Still, E. Nirenberg argues against this possibility on the grounds the amino acid sequence where the synctins coincide with the COVID spike protein is too short:

Dec 3 
Written By Edward Nirenberg
Are COVID-19 Vaccines Going To Cause Infertility?

 However, to Nirenbergs credit he does mention in an addendum there is a known scenario where a similarly short amino acids sequence caused cross-reaction of rheumatic fever T-cells against normal heart muscle proteins.

 In an upcoming Part II, I'll discuss the evidence for and against the possibility the COVID vaccine could cause cross-reactivity with the synctin proteins of the placenta.


  Robert Clark


REFERENCES.

1.)Birth Defects Res. 2018 Mar 1; 110(4): 342–351.
Published online 2017 Nov 2. doi: 10.1002/bdr2.1147
Maternal report of fever from cold or flu during early pregnancy and the risk for noncardiac birth defects, National Birth Defects Prevention Study, 1997–2011
Dorothy Kim Waller,1 Syed Shahrukh Hashmi,2 Adrienne T. Hoyt,3 Hao T. Duong,4 Sarah C. Tinker,5 Michael Shayne Gallaway,6 Richard S. Olney,7 Richard H. Finnell,8 Jacqueline Tauber Hecht,2 Mark A. Canfield,3 and the National Birth Defects Prevention Study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831519/

2.)Mol Psychiatry. 2018; 23(3): 759–766.
Published online 2017 Jun 13. doi: 10.1038/mp.2017.119
Prenatal fever and autism risk
M Hornig,1,2,* M A Bresnahan,2,3 X Che,1 A F Schultz,1 J E Ukaigwe,1 M L Eddy,1 D Hirtz,4 N Gunnes,5 K K Lie,5 P Magnus,5 S Mjaaland,5 T Reichborn-Kjennerud,5,6 S Schjølberg,5 A-S Øyen,5,7 B Levin,8 E S Susser,2,3 C Stoltenberg,5,9 and W I Lipkin1,2,10
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5822459/

3.)Autism Res. 2017 Nov; 10(11): 1878–1890.
Published online 2017 Aug 11. doi: 10.1002/aur.1841
Prenatal exposure to fever is associated with Autism Spectrum Disorder in the Boston Birth Cohort
Martha Brucato,1,2,3 Christine Ladd-Acosta,1,3,* Mengying Li,4 Deanna Caruso,4 Xiumei Hong,4 Jamie Kaczaniuk,3 Elizabeth A. Stuart,5 M. Daniele Fallin,3,5,6 and Xiaobin Wang4,6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5685874/

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