Vaccination of Very Premature Infants by F. Yazbak, MD, FAAP

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March 13, 2007

Vaccination of Very Premature Infants

F. Yazbak, MD, FAAP

http://www.vaproject.org/yazbak/vaccination-of-very-premature-infants-200703

10.htm

According to the March of Dimes, 1 out of every 8 babies is born

prematurely in the United States.

Parents have been concerned about exposing their small and very small

premature infants to the many mandated pediatric vaccines too early. The

CDC, certain " vaccine experts " and pediatricians have always insisted that

small and frail infants can tolerate all vaccines and develop immunity,

just like full term and robust infants.

A recent study from a major vaccine research center strongly suggests that

the immune system of very small preemies does not indeed adequately respond

to vaccination during the first few months of life.

VAP urges a review of the vaccination schedule of premature infants and a

reassessment of its risks and benefits.

Doctor Yazbak's review of the new study raises other questions.

Vaccination of Very Premature Infants

By

F. Yazbak, MD, FAAP

(download pdf)

The number of infants born prematurely has been steadily increasing in the

United States. Very small and very premature infants are now surviving in

increasing numbers.

The CDC has decided that in the majority of cases, infants born

prematurely, regardless of birth weight, should be vaccinated with the same

dose(s), at the same chronological age and according to the same schedule

and precautions as full-term infants and children.

D’Angio et al of the Vaccine Research Unit at the University of Rochester

have reported that during the first six months of life, extremely preterm

infants mount lower antibody responses to vaccines than term infants.

Accordingly, the risks and benefits of the ever increasing number of

mandated pediatric vaccines from birth to six months, need to be carefully

re-examined for that specific group of infants.

------------------

When it comes to information about vaccines and vaccination research, it is

becoming extremely difficult, even for professionals, to sort out the facts.

On March 6, 2007, a good friend in New Zealand who is well aware of my

interest in MMR vaccination sent me a report originally filed by WMTW-TV

Channel 8 in Auburn, Maine. The station is the ABC affiliate covering the

greater Portland, ME area, a gorgeous part of New England, situated just

three hours away by car from my home.

The title of the news item was

“Vaccines Safe For Preemies, Study Says –

MMR, Chicken Pox Shots Work In Pre-Term Infants

Vaccines for measles-mumps-rubella and or chicken pox are effective

in extremely preterm infants, according to a new study .

The rest of the news report read:

“ Pediatricians had assumed they would work, even though preemies'

immune systems may not be fully developed.

" No one had formally researched the subject, " said study author Dr.

Carl D'Angio of the University of Rochester Medical Center. " I'm happy to

be able to reassure my colleagues and parents that it is OK. "

The study included 16 full-term and 16 extremely preterm infants

born between May 2002 and May 2005. It examined the antibody levels of the

diseases before and after vaccination. It was published in this month's

issue of Pediatrics.

The same number of infants in each group reached a level considered

protective.

" Now we can all breathe a sigh of relief. We were right, " D'Angio

said.”

http://www.wmtw.com/health/11172803/detail.html

It is entirely possible that an uninformed reader or young parent would

interpret the above jubilant report as proving that the MMR and chickenpox

vaccines were safe and effective in extremely preterm infants, like those

often seen on television with breathing tubes and IV lines in incubators.

In fact, the infants who participated in the investigational study – all 32

of them - were healthy and 15 months old when they were vaccinated.

Relative to the safety statement, the infants were just seen twice, 3 to 6

weeks apart, and “safety” was assessed “by parental recall of

vaccine-related adverse events and by active, prospective collection of

blood-draw-associated adverse events”.

It should be noted that all MMR vaccine safety studies conducted by the

vaccine industry have been notoriously short. Only two studies extended to

eight weeks.

***

A friend in Wales also sent me information about the same Rochester

University study that she had received via EurekAlert Science News Service.

http://www.eurekalert.org/pub_releases/2007-03/uorm-mcp030207.php

The tone of that news item was more restrained but its message was no less

decisive.

“MMR, chicken pox vaccines work for preemies”

“Vaccines for measles-mumps-rubella and varicella, or chicken pox,

are effective in extremely preterm infants, even though preemies' immune

systems are not as developed as full-term babies. This confirms a

long-held assumption by pediatricians and neonatologists across the country.”

" The assumption has always been that it would be OK, that very

early babies would have enough immunity, but no one had formally researched

the subject, " said Carl D'Angio, M.D., associate professor of Pediatrics at

the University of Rochester Medical Center, and author of a paper on the

subject in Pediatrics this month. " I'm happy to be able to reassure my

colleagues and parents that it is OK. "

The Principal Investigator (PI) was again quoted as saying " Now we can all

breathe a sigh of relief. We were right, "

According to the news report, the study was funded by the National

Institute of Allergy and Infectious Diseases and the National Center for

Research Resources of the National Institutes of Health.

***

The Official Study Record

ClinicalTrials.gov

MMR and Varicella Vaccine in Premature Infants

This study has been completed.

Sponsored by:

University of Rochester

Information provided by:

University of Rochester

ClinicalTrials.gov Identifier:

NCT00156559

http://tinyurl.com/36v2l9

The purpose of the study was listed as follows:

“This research is designed to address the question, “Does the

relative deficit in vaccine immunogenicity in extremely premature infants

persist beyond the first 6 months of life?”

Immunogenicity is the ability of a vaccine to provoke an immune response

and result in immunity.

The above question, as stated, suggests that administration of one or

several vaccines once, twice or three times to very small (< 1lb) and very

premature (<28 wk gestation) infants during the first six months of life,

does not provoke immune responses and therefore does not protect from

illness. In a literal sense, all the administered antigens cannot be

referred to as “immunizations”.

If that is so, then a true re-evaluation of risks and benefits of

vaccinations administered in that population is in order and the statement

by some that infants without exception have the capacity to respond to an

enormous number of antigens (1) is invalid.

The PI goes on to describe the purpose of the study as follows:

“We propose to measure the immunogenicity of varicella and

mumps-measles-rubella vaccines in relatively healthy, 12-to-15 month-old

children born at <29 weeks gestation, when compared to full-term infants,

as measured by the relevant viral serologies.”

In fact the enrolled infants were not “relatively” healthy. They had to be

healthy.

Inclusion Criteria:

Subjects must meet all of the inclusion criteria to participate in

this study.

1.

Premature infant < 29 weeks’ gestation at birth or term infant

>/= 37 weeks’ gestation at birth.

2. Postnatal age < 16 months, 0 days.

3. Has not yet received MMR or varicella vaccines. (There are

no restrictions on the administration of other vaccines at the time of

MMR/varicella vaccination.)

4. Parental permission.

5. Agreement of primary care pediatrician/ health care provider.

6. Receives primary pediatric care within an approximate

25-mile radius of the University of Rochester.

7. Healthy status at enrollment.

Exclusion Criteria:

1.

Known immunodeficiency.

2. Systemic corticosteroid therapy at the time of MMR/varicella

vaccination.

3. Requiring oxygen therapy.

4. Clinically significant findings on review of medical history

and physical exam determined by the investigator or sub-investigator to be

sufficient for exclusion.

5. Any condition determined by the investigator that would

interfere with the evaluation of the vaccine or be a potential health risk

to the subject.

“Healthy status at enrollment”

According to the protocol “subjects will be approached at 9-12 months of

age for inclusion”. They included sixteen ex-very premature infants had to

be healthy, not only on the day they were vaccinated, but actually three to

six months earlier, when they were registered. In other words, when the

study was being conducted, those infants were the healthiest very small

infants around Rochester, New York.

It should be pointed out that pediatricians are constantly told that they

can and should vaccinate infants that are not in such pristine condition.

Obeying such directives, pediatricians insist on vaccinating small preemies

on oxygen and monitors, or who have colds and sniffles, on or close to

schedule. Some actually threaten recalcitrant parents with referral to

child protective agencies or exclusion from the practice.

The study

Study start: January 2004; Study completion: December 2005

Last follow-up: May 2005; Data entry closure: May 2005

Title: MMR and Varicella Vaccine Responses in Extremely Premature Infants

“Phase: IV

Population: 16 generally healthy premature infants born at < 29 weeks’

gestation, < 16 months old from the Rochester area 16 generally healthy 37

weeks’ gestation,³full-term infants born at < 16 months old from the

Rochester area

Number of Sites: University of Rochester

Study Duration: 1.5 – 8.5 months

Description of Agent or Intervention:

Subjects will make 2 study visits. The first, at 15 months of age,

will coincide with a routine well child visit. Subjects will have 2 mL of

blood drawn at the time of their routine, 15-month MMR, varicella, and

pneumococcal conjugate immunizations. At a second study visit 4-6 weeks

later, another 2 mL of blood will be drawn.

Objectives:

Primary: We propose to measure the immunogenicity of routinely

administered varicella and mumps-measles-rubella vaccines in relatively

healthy, 12-to-15 month-old children born at <29 weeks gestation

(premature), when compared to that in full-term infants…

Safety will be assessed by parental recall of vaccine-related adverse

events and by active, prospective collection of blood-draw-associated

adverse events.

Schematic of Study Design:

Subjects will be approached at 9-12 months of age for inclusion, and

will consent at this time or at Visit 1”

--------------

The study was published in the March 2007 issue of PEDIATRICS. (1)

A Medline abstract is available at http://tinyurl.com/36bfne

RESULTS: Preterm children had lower mumps and rubella geometric

mean titers than did term children before vaccine, and nearly all children

were seronegative for each of the 4 vaccine antigens before immunization.

Measles, mumps, rubella, and varicella geometric mean titers were similar

between groups after vaccine. All children were seropositive for measles

after vaccine, whereas 13 of 14 preterm and 11 of 13 term children were

seropositive for mumps, 13 of 14 preterm and 13 of 13 term children were

seropositive for rubella, and 11 of 16 preterm and 9 of 15 term children

were seropositive for varicella.

CONCLUSIONS: Preterm children mounted antibody responses that were

similar to those of term children after measles-mumps-rubella and varicella

vaccines at 15 months of age.

The CDC has long recommended the administration of the first dose of MMR

and chickenpox vaccines at the age of one year and parents are cajoled and

coerced to comply. This study does not guarantee that the risk taken by

having 4 live attenuated virus vaccines administered simultaneously to

small children is warranted. Indeed, as noted, even vaccination at 15

months of age did not result in full protection against rubella, mumps and

chicken pox.

It is not clear why the investigators proposed to examine the immunogenic

response between 12 and 15 months but actually waited to vaccinate the

children until they were 15 to 16 months old. This is certain to raise

questions.

The timing of the vaccinations brings out another indirectly related but

yet very important point.

According to the American Academy of Pediatrics, the “routine” pediatric

visit at which the MMR and chickenpox (and other) vaccines are administered

should be scheduled at the age of twelve months. Why then was that

“routine visit” actually “scheduled” at age 15 months in Rochester, the

site of a major vaccine center?

--------------

The Principal Investigator is a member of the Department of Pediatrics at

the University of Rochester. He is presently finishing a similar study on

the pneumococcal conjugate vaccine and is in the process of studying the

influenza vaccine. All 32 infants in this study also received a dose of

pneumococcal conjugate vaccine at the age of 15 months.

The University of Rochester’s Vaccine Research Unit is renowned.

“The vaccine research effort at the University of Rochester Medical

Center brings together a rare combination of resources that covers the

gamut from basic research, to vaccine testing, to improving and measuring

the availability of vaccines to people who need them most…. All vaccines

depend on our knowledge of the basic workings of the immune system…

More recently, research done more than a decade ago by a trio of

University virologists has become crucial to two promising vaccines

designed to prevent cervical cancer. A vaccine to prevent this type of

cancer, which kills more than 250,000 women around the globe every year, is

expected to become available within a year, thanks in large part to

technology developed at the University. The vaccine targets a group of

viruses known as human papillomaviruses (HPV), which cause cervical cancer.

On the applied side, the University’s Vaccine and Treatment

Evaluation Unit has had a hand in testing dozens of new vaccine candidates,

including nearly every new vaccine to be approved in the last three

decades. The unit is part of a network that the Federal government turns

to for protecting the nation against infectious threats…

Just as important as creating or testing the vaccines, is getting

them to the people who need them most. Here again, University doctors are

part of virtually every large national network created to monitor the

effectiveness of vaccines. The Rochester community finds itself one of the

best vaccinated and best monitored in the world, and researchers worldwide

have a grasp on just how well vaccines work, thanks to research by

Rochester doctors.”

http://www.urmc.rochester.edu/pr/current_research/bird_flu/research.cfm

Funding for vaccine research at the University of Rochester Medical Center

is provided by the National Institutes of Health and has almost doubled in

five years (see graph).

NIH Funding Continues to Grow at URMC

For parents in the autism community, the University of Rochester will

always be remembered as the place that produced the Pichichero Thimerosal

study. (2) Most of us are still scratching our heads about that study’s

methodology and conclusions.

More recently, the University of Rochester Vaccine Research Unit offered to

the world (and Merck coffers) the gift of the Human Papilloma Virus (HPV)

vaccine.

See “How Cow Warts, Clergy Sex Surveys Moved Along Cancer Vaccine” at

http://www.urmc.rochester.edu/pr/current_research/Cervical_Cancer_Vaccine/

“The creation of a successful vaccine against cervical cancer,

approved today by the U.S. Food and Drug Administration, is the culmination

of research that occurred thanks not only to scientists and physicians, but

also to generous farmers and veterinarians, priests and nuns willing to

tell all – and some very patient cows”(Thursday June 8, 2006)

On Tuesday February 8, 2007, the University of Rochester Medical Center

published “Preventing V.D. as Valentine’s Day Approaches”.

It started:

“With Valentine’s Day just around the corner, the world’s largest

study of a vaccine to protect against genital herpes – a disease that

infects approximately one of every four women and men in the nation – takes

on special significance for Rochester-area women and their male companions.

Doctors and nurses are recruiting women in the Rochester area who

don’t have genital herpes to help test a vaccine against the sexually

transmitted disease. So far, 237 women locally have joined the study,

making Rochester one of the lead sites nationally. But more female

participants ages 18 to 30 are needed to effectively test the vaccine.”

The statement ended “Men are not part of the study because previous studies

have shown that the vaccine does not work in men.”

That alone may have ruined the Valentine's Day in Rochester.

http://www.urmc.rochester.edu/pr/news/story.cfm?id=1365

--------------

Discussion

All clinical trials of pediatric vaccines only enroll healthy infants and

children and everyone makes certain that the infant or child is healthy at

the time the vaccine is administered.

There are no studies where sick or “slightly sick” infants are vaccinated.

It is therefore strange that pediatricians are asked to vaccinate less than

perfectly healthy infants and even stranger that they insist to do so.

In the recent Rochester study, the 16 ex-small preemies and the 16 normal

infants used as controls received the MMR and chickenpox vaccines at the

age of 15 months. In real life, the CDC recommends that these two vaccines

be administered at 12 months of age when the ex-preemies are often more

vulnerable.

“In the majority of cases, infants born prematurely, regardless of

birth weight, should be vaccinated at the same chronological age and

according to the same schedule and precautions as full-term infants and

children. Birth weight and size are not factors in deciding whether to

postpone routine vaccination of a clinically stable premature infant,

except for hepatitis B vaccine. The full recommended dose of each vaccine

should be used. Divided or reduced doses are not recommended”. (3)

In the case of live virus vaccines such as MMR, a follow-up period of 3 to

6 weeks is not long enough to evaluate safety.

One can only wonder why small very premature infants need the rubella, the

mumps and the chickenpox vaccines at the age of twelve months.

Conclusions

The single most important conclusion that anyone can draw from

“Measles-mumps-rubella and varicella vaccine responses in extremely preterm

infants” is that extremely premature infants have a relative deficit in

vaccine immunogenicity until the age of 6 months.

The issues that have been identified in this report will tend to compromise

the significance of the study findings and their relevance to pediatric

practice.

--------------

Footnote:

“The Rochester community finds itself one of the best vaccinated and

best monitored in the world…”

http://www.urmc.rochester.edu/pr/current_research/bird_flu/research.cfm

The United States Congress passed the Children's Health Act of 2000 and

mandated the establishment of centers of excellence in autism research. In

response, the Institutes of the NIH Autism Coordinating Committee have

implemented the STAART (Studies to Advance Autism Research and Treatment)

network program.

One of the eight US Autism Research Centers of Excellence is located at the

University of Rochester. Rodier, Ph.D., is the Director of the

Center and Hyman, M.D., FAAP is the Co-director.

According to Dr. Hyman, about 50% of Rochester area families with preschool

children on the autistic spectrum use a gluten free and casein free diet.

http://www.nimh.nih.gov/autismiacc/rochesterautism.cfm

References:

1. D'Angio CT, Boohene PA, Mowrer A, Audet S, Menegus MA,

Schmid DS, Beeler JA. Measles-mumps-rubella and varicella vaccine responses

in extremely preterm infants. Pediatrics. 2007 Mar;119(3):e574-9

2. Pichichero ME, Cernichiari E, Lopreiato J, Treanor J.

Mercury concentrations and metabolism in infants receiving vaccines

containing thiomersal: a descriptive study. Lancet. 2002 Nov

30;360(9347):1737-41.

3. Atkinson WL et al General Recommendations on Immunization

CDC - MMWR February 8, 2002 / 51(RR02);1-36

F. Yazbak, MD, FAAP

Falmouth, Massachusetts

2007