COVRAC Guest blog: Influenza vaccination during pregnancy

We are very grateful to COVRAC, the author of today's guest post, who can be found over at his Facebook page "Chillin' Out, Vaxin', Relaxin' All Cool.

Seasonal influenza disease is dangerous to both a pregnant mother and the fetus. This is generally not in dispute, even by the most staunch antivaxers. But get about three Facebook comments into a discussion over flu shots for pregnant women (perhaps one that goes something like this, and invariably your self-proclaimed educated opponent with tell you in no uncertain terms that influenza vaccine has never been studied in pregnancy.

Well, then. Let's go over the numerous studies of influenza vaccines in pregnant women that have, it is claimed, never been done.

These studies have allegedly never been done on seasonal influenza vaccine in pregnant women. If they had been done, they would clearly demonstrate it to be safe.
http://www.ajog.org/article/S0002-9378(04)02102-7/abstract
http://www.ncbi.nlm.nih.gov/pubmed/20715555

These were apparently never done on the H1N1 vaccine. It would also have been clearly demonstrated to be safe (if they had been done).
http://www.ncbi.nlm.nih.gov/pubmed/20832495
http://www.ncbi.nlm.nih.gov/pubmed/21596080
http://idsa.confex.com/idsa/2010/webprogram/Paper3534.html
http://www.ajog.org/article/S0002-9378(11)00775-7/abstract

This study which obviously was never done showed far less premature births in mothers vaccinated during pregnancy.
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000441;jsessionid=8B7B450C63F7196BE157DB7629B57432.ambra02

This other totally undone study looked specifically at miscarriages in women vaccinated in the first trimester, and did not find an increased risk.
http://idsa.confex.com/idsa/2011/webprogram/Paper30513.html

This one, which might look like a study showing decreased fetal deaths in the H1N1-vaccinated, is really just a bunch of fancy words meaning "404 page not found."
http://www.nejm.org/doi/full/10.1056/NEJMoa1207210

This study in the Canadia Medical Association Journal found that pregnancies during influenza season resulted in higher birth weight and less premature birth if the mother was vaccinated against influenza. But you can sooo tell it is CG and not real.
http://www.cmaj.ca/content/early/2012/02/21/cmaj.110754

These figments of your imagination show how influenza vaccination of pregnant mothers protects newborns from influenza.
http://archpedi.ama-assn.org/cgi/content/short/archpediatrics.2010.192
http://www.ncbi.nlm.nih.gov/pubmed/21058908
http://www.nejm.org/doi/full/10.1056/NEJMoa0708630

And finally, this indigestion-induced hallucination here from the American Journal of Obstetrics & Gynecology is a list of studies on the safety of influenza vaccine dating back to 1964. As Scrooge would say, "You may be an undigested bit of beef, a blot of mustard, a crumb of cheese, a fragment of an underdone potato."
http://www.influenza.org.nz/site_resources/Influenza/Influenza%202010/Safety_of_influenza_vaccination_during_pregnancy.pdf#page=2

Back to reality: These studies have, in fact, been done. An antivaxer will fall back to quoting a vaccine package insert, but it's evident that such a document does not reflect the entirety of the world's research on a given vaccine. Influenza vaccination in pregnancy has been studied in abundance. A flu shot is safe during pregnancy (without a known medical contraindication), does not cause miscarriage, and protects the health of pregnant women and their babies.

Pregnant women in the UK to be offered whooping cough vaccination

The British Department of Health announced last week, that starting from today, pregnant women will be offered the whooping cough vaccine to protect their new borns. The idea is that when vaccinated during pregnancy, the maternal antibodies will be passed through the placenta to the baby before birth and will protect the infant in the first couple of months of their lives, when they cannot yet be vaccinated. This move comes after nine infants, all under three months old, died of pertussis in the UK of 302 under 3 month olds who contracted the disease (yes, that is a mortality of 3 percent, 3 of 100). The HPA welcomes this move, after having received notification of 1230 whooping cough cases in August 2012 alone.

Whooping cough is not a mild disease by any stretch of the imagination - the BBC has several testimonials from mothers of babies, but also older kids:

Nine year old Zara Mummery was seven when she caught whooping cough. One night she was coughing so much she stopped breathing.

"It was very frightening, but I remember that my mum brought me into the bathroom and she called the paramedics.

"She was just screaming on the phone 'my child's going to be dead, please come'."

Her mother Katrina said she couldn't get her daughter to breathe.

"It was like she froze. It was one of the most terrifying things any parent can go through, to think they have lost a child."

Zara spent a week in hospital on very strong antibiotics and is now fit and well.

 While the number of cases in the UK are increasing at an alarming rate,

it is worth remembering what the situation was like before the introduction of the vaccine. 

Before routine vaccination in 1957, whooping cough outbreaks in the UK were on a huge scale. It could affect up to 150,000 people and kill 300 in a single year.

What is already being remarked in vaccine-critical circles is that the dTaP/IPV booster vaccine, Repevax, is not recommended for use in pregnant women in the UK. The package information states:

Pregnancy

The effect of REPEVAX on embryo-foetal development has not been assessed. No teratogenic effect of vaccines containing diphtheria or tetanus toxoids, or inactivated poliovirus has been observed following use in pregnant women. Limited post-marketing information is available on the safety of administering REPEVAX to pregnant women.

In their FAQs for GPs, the reason for the recommendation despite this disclaimer is provided:

Why does the Patient Information Leaflet state that Repevax® should not be used in pregnancy?

This says that the vaccine is not recommended for use in pregnancy because of the routine exclusion of pregnant women from clinical trials, and not because of any specific safety concerns or evidence of harm in pregnancy. Use in pregnancy is not contraindicated.

The CDC recently published the reasoning behind their older recommendation to vaccinate pregnant women against pertussis, and, using data from VAERS and two smaller studies, found that vaccination during pregnancy is safe. There is good indication that vaccine-induced antibodies pass through the placenta and hence would protect the newborn.

This new recommendation could save lives - I'll tell my pregnant friends about it - you should, too.

Christmas is nigh - donate vaccines to UNICEF and get the t-shirt

I cannot believe that the first Christmas chocolate selection boxes have already made it into some stores. That means Christmas must be imminent, right? I guess any month is a good month to think of gifts, so let me advertise this fabulous idea (for which I am not getting any commission or anything, I just want to share the thrill of saving lives - feel free to donate any other way you see fit).

Measles kill more than 600 children every day (for example 100 in Pakistan since May), and those who survive may be left with disabilities such as blindness and brain damage. $24.30 can pay for vaccination of 81 children against measles. 100% of your donation will go to the U.S. Fund for UNICEF to support life-saving relief efforts for children. I have the shirt from last Christmas:

There are other fabulous ways to save lives - consider donating mosquito nets ($18.57 will get you the shirt and three people in malaria stricken areas an insecticide treated net):

$36.10 will buy 1000 deworming tablets and one dead worm will feature on your shirt:

You are anti-vaccine and you think that really all is needed to prevent disease is food and water? Put your money where your mouth is and provide a water pump ($500):

or 1200 vitamin enriched high energy biscuits ($59.96):

and if you want to give that very special present and money doesn't matter - consider getting your loved one a UNICEF Cargo Flight from Denmark to Kenia - at $300'000 it is a steal and the t-shirt you'll get will be a beautiful understatement of your generosity:

Check out all donation options and beautiful t-shirts illustrated by Christine and Justin Gignac on Threadless and tell us which choice you have made for your present :)

And Everything Stops for a Second...

The daily delusions, presented with the arrogance of ignorance and a degree from Google U, the smugness of those whose children are protected by herd immunity, afforded by the grace of having been born in a time when a lot of diseases are preventable by vaccines, are so tiresome to counter.

"No, by the time it is properly diagnosed, pertussis can not really be treated."
"No, SIDS did not disappear from Japan when the raised vaccination age to 2 years and stopped whole cell pertussis vaccination, instead, pertussis cases and fatalities soared."
"No, unvaccinated kids do not have the better immune systems."

The past week has been particularly bad, with media outlets thoughtlessly spewing anti-vaccine dreck (hat tip to Seth Mnookin). Despite State after State reporting pertussis outbreaks or even epidemics, every day there was a chance to whack-a-mole-of-the-day... oh, there is another.

So tedious.

And then, everything stops for a second:

Francesca Marie McNally

February 24, 2012 - May 17, 2012
Resided in Franklin, MI

FRANCESCA MARIE McNALLY, May 17, 2012, of complications from Pertussis. Age 3 months.

Most precious angel of Sean and Veronica. Dearest younger sister of, and inspiration to, Duke and Stephen. Cherished granddaughter of Thomas and Debra McNally and Stephen and Frances Valentine. Great-granddaughter of Phyllis Lanesey, Mary Jane McNally, and the late Robert McNally, George Holt, Frank Lanesey, Joseph and Joan Craig, and Bernice and Stephen Valentine. Goddaughter of Tyler Wesorick and Erin Goward. Also survived by eight cousins and many aunts and uncles.

Memorial Mass Wednesday 11 a.m. at Shrine Chapel of Our Lady of Orchard Lake, 3535 Indian Trail, Orchard Lake. Visitation at church begins at 10 a.m.

In lieu of flowers family suggests memorials to C.S. Mott Children's Hospital, 301 E. Liberty, Suite 400, Ann Arbor, MI 48104. A.J. Desmond & Sons, 248-362-2500. 

My heart goes out to the McNally family. No one should have to bury a child. Let's whack another mole and save a life or three...

Unanswered question

So following my recent post about that paper by Miller and Goldman, which crudely correlates numbers of recommended vaccines with infant mortality rates in the US and any country with a lower IMR, I got mail. Gary Goldman wanted to discuss my criticism with me and explain why they were still right. He actually wanted me to call him, which I was initially tempted to do, but eventually didn't because I was put off by the twisting and turning email conversation. He did request that I keep our exchange private, however, he stopped writing me, so I thought I'd just bring one argument up here and see whether he will answer.

me on 13 May - I (for Germany) and the devine Prometheus (for the US) had asked this earlier:

I see that you are avoiding the most obvious question: why are there fewer and fewer infant deaths when more and more vaccines are given? I gave you the German numbers, where infant mortality dropped by 80% while the number of scheduled vaccines tripled. Every country I look at has the same temporal trend, although in the US it is not as pronounced as in Europe, most likely because of your crappy health system. I would really like to know what your thoughts on this are.

No response to that by Gary on the same day (while was responding to other points)

Me, in response, still 13 May (his points in italics):

I notice you are still avoiding the historical question and if I may make a prediction - you are going to avoid answering this question forever. I would really be interested in your reasoning.

14 May, Gary, at the very bottom of a looong email elaborating on a number of points entirely unrelated to any of my questions:

I am not able to address the specific historical factors concerning infant deaths in Germany upon which you rely to support your contention that no correlation exists. I have seen data where 90% of disease mortality declined prior to vaccinations and this was largely attributed to improved sanitation, nutrition, and water. Other
studies, more longitudinal, and in other populations are reasonably necessary to support the present trend we report.

Now this is really irritating, because we were talking the past 30 years, not "pre all vaccines". Therefore, me, a day later:

Dear Gary,

I should maybe specify

I am not able to address the specific historical factors concerning infant deaths in Germany upon which you rely to support your contention that no correlation exists.

Germany is, of course, not the only country in which infant mortality plummeted over the past 30 years, it did so in every developed country I looked at.

I have seen data where 90% of disease mortality declined prior to vaccinations and this was largely attributed to improved sanitation, nutrition, and water.

Yes, all anti-vaccine protagonists like to refer to such curves. However, I am not talking about disease mortality, and I am talking a period of 1981 to 2011, when sanitation, nutrition and water were not a problem at all in Germany (or any of the other developed countries in which infant mortality dropped over the same time period).

Other studies, more longitudinal, and in other populations are reasonably necessary to support the present trend we report.

But Gary, we already know that infant mortality plummeted while the number of vaccines was significantly increased. I don't think that the kind of crude and error/bias ridden correlation that you have published advance the field at all, or reasonable raises new questions.

What about you? What experiences have you had that have shaped your thinking and views?

Misrepresentation of scientific evidence and dodging of straight forward questions by anti-vaccinationists for example - you wrote many many words, totally side tracking - we were talking German vaccination schedule and how it is not what you wrote about - you have similar misrepresentations for other countries as well - then you write about varicella, which is a second year vaccine - this was not the topic at hand - and you come with "sanitation" when we are talking 1980ies Germany - that is rather lame, you know.

So, given that Germany had great sanitation in 1981 and we are talking infant mortality, not disease related mortality, and they had 9 recommended vaccine doses and 10'000 infant deaths then, while they have 21 to 28 recommended doses and under 2000 infant deaths now, how would number of recommended vaccines correlate with infant mortality at all? Can you give me even an idea, a reasonable notion how your idea would match, umm, reality?

Thanks

Catherina

I had to wait two days to get a response, signed by Miller and Goldman:

Dear Catherina,

Infant mortality rates in all developed nations, including Germany, were much higher in the 19th and early 20th centuries and have continued to decline mainly due to improvements in nutrition (including breastfeeding advocacy), sanitation, and access to healthcare. [This information is not a conspiracy of "anti-vaccine protagonists" as you suggest; it is well-documented in the medical and historical literature.] For example, nearly 300 per 1,000 German infants died in the mid 1800s. By 1950, the German IMR had dropped to 52/1,000—an 83% decline. By 1960, the German IMR had dropped another 33% to about 35 infant deaths per 1,000 live births. These dates and declines in IMR preceded the extensive increases in compulsory vaccinations required of German infants.

Furthermore, Germany’s IMR declined at a rate of 3% annually from 1960 to 1979 during a time when few infant vaccines were required. This rate of decline was much faster than the 2.4% annual "plummet" from 1980 to 2009 during a period when more infant vaccines were required.

Additionally, Germany and other developed nations continued to make medical advances at reducing neonatal mortality during periods of increasing vaccine requirements. For example, from 1970 to 1979 there was a 41% decline in U.S. neonatal mortality. From 1980 to 1989, there was an additional 27% decline in neonatal mortality. Neonatal mortality (deaths in the first 28 days of life) usually accounts for more than 50% of all infant deaths. From 1990 through 2010, neonatal mortality in Germany represented about 68% of all infant mortality. During that period, Germany’s neonatal mortality rate had declined by 55%. Such improvements to the neonatal mortality rate greatly reduce the infant mortality rate yet are unrelated to the number of vaccines administered to infants.

Sincerely,
Neil Z. Miller
Gary Goldman, PhD

So here is my question that I have not gotten an answer for in the past 2 weeks:

Dear Gary,

so if I understand you correctly, infant mortality is dependent on all sorts of factors (hygiene, nutrition, sanitation, access to health care) and still declining, but just not as fast as it would be if we didn't vaccinate. Despite all these factors, which obviously vary tremendously between countries, you decided to only crudely correlate vaccines to infant mortality?

Thank you for clarifying

Catherina

Infant mortality and vaccines

ETA 1.4.16: Gary Goldman and Neil Miller failed to disclose their conflicts of interest to Human and Experimental Toxicology.  The corrigendum is here.

oh goodness, here I wanted to go to bed early and then I stumbled over this latest "peer reviewed" paper in a journal "indexed by the National Library of Medicine" (see the anti-vaccine faction gloating at those fantastic quality indicators) and "proving" with an correlation co-efficient of 0.992 and a p of 0.0009 (so "sciencey") that:

Nations requiring the most vaccines tend to have the worst infant mortality rates

Authors of this little gem, in the journal Human & Experimental Toxicology, with the impressive impact factor of 1.307 and a proud ranking of 58th of 77 in the area of Toxicology (yes, that would put them into the bottom quarter) are Think Twice's own Neil Z. Miller and Medical Veritas' Gary S. Goldman. I wonder why Miller and Goldman didn't publish their paper in Medical Veritas (here is the link to the journal, please don't go blind), seeing that item 7 in their mission is: "Create a movement to address the adverse vaccine reactions and vaccine-related injuries afflicting children and adults". I guess that is because parents have clued in that "peer review" and being indexed on PubMed is a quality measure (although very obviously no guarantee for quality).

In any case - Miller and Goldman took a list of countries and looked at the number of vaccines they schedule for infants and they also looked at infant mortality. And then they correlated one with the other, a fail safe way to find causal relationships: Storks deliver babies p=0.008.

There are a number of things wrong with this procedure - first of all, the way Miller and Goldman are counting vaccines is completely arbitrary and riddled with mistakes.

Arbitrary: they count number of vaccines in US bins (DTaP is one, hib is separate) and non-specific designations (some "polio" is still given as OPV in Singapore), rather than antigens. If they did that, Japan, still giving the live bacterial vaccine BCG, would immediately go to the top of the list. That wouldn't fit the agenda, of course. But if you go by "shot" rather than by antigen, why are DTaP, IPV, hepB and hib counted as 4 shots for example in Austria, when they are given as Infanrix hexa, in one syringe?

Mistakes: The German childhood vaccination schedule recommends DTaP, hib, IPV AND hepB, as well as PCV at 2, 3 and 4 months, putting them squarely into the 21 - 23 bin. The fourth round of shots is recommended at 11 to 14 months, and MenC, MMR and Varicella are recommended with a lower age limit of 11 months, too, which means that a number of German kids will fall into the highest bin, at least as long as you count the Miller/Goldman way.

Then, they neatly put those arbitrarily counted doses into bins. Binning (i.e. grouping numbers before correlating them to something) always makes me suspicious. I don't have the time to check each country's vaccination schedule - I assume there will be mistakes in many claims, but I am guessing that if we plotted the infant mortality against the actual number of recommended vaccines, the correlation would be less good than engineered in this paper, i.e. the dose count above is probably not all that "arbitrary".

Then I noticed that the authors totally ignore historical trends. For example, in the early 1980ies, Germany's infant mortality was about 5 times as high (10000 infants died per year) than it is today (2000 died in 2009 with approximately the same birth rate), however (in Miller's and Goldman's twisted logic), the vaccination schedule contained far fewer vaccines in the first year (essentially just DT and polio, since the whole cell pertussis was not given between 1974 and 1991, the aP not yet introduced, the MMR given in year 2, no hib, nor hepB, nor PCV given either), while Germany was already very much a "developed country".

ETA: a similar point is made by Prometheus on Science based Medicine for the declining infant mortality rate in the US.

If I believed that one factor could ever explain something as complex as infant mortality, I would go and look at the relationship of maternity leave:

Japan, for example, generally gives 14 weeks at an average of 40% of a woman's salary and mothers are also entitled to childcare leave for their new baby's first year. Childcare laws dictate that in the first year of her baby's life, a mother may take two 30-minute breaks per day to care for her child (anyone else think breastfeeding?). She may also take time off any time during the baby's first year with one month's notice.

In Sweden, all working parents are entitled to up to 16 months of paid parental leave, Norway is similarly generous. Read the table and weep, US American parents!

In the bottom countries, the USA gives 0 months of parental leave, the FMLA offers some (up to 12 weeks) generally unpaid leave under very specific conditions. Heck - Botswana and Chad have better rules. Australia has 18 weeks (not months, like Norway) at minimal wage, but then, Canada, third worst in infant mortality has up to a year of parental leave at almost $2000 a month and that is where my crude correlation fails (although, if I binned some countries...a cunning plan).

ETA: Dr. Gorski picks up on some other flaws of this study - read his post.

In general, several large studies/meta-analyses NOT cited by Miller and Goldman, have indicated that if vaccines have anything to do with infant death, then as a protective factor, as this German study and meta-analysis and this large study from the UK.

To prevent SIDS (specified 10 May after comment):

put your baby "back to sleep"
do not smoke
breastfeed if at all possible (easier in countries with 18 months of paid maternity leave)
avoid loose bedding and soft mattresses or sofas
do not bed share when intoxicated, or smoker, or taking medicine that may make you drowsy, but keep your baby in your room
keep the sleep environment cool and don't overdress your baby

That is it.