April 14, 2017

Director's Letter 
Carole Baggerly 
Director, GrassrootsHealth 

It is a personal decision. Do you research the latest health news? How much research do you read before you act? One article? 20 articles? 

Whatever your threshold for acceptance, there is now enough research reported for vitamin D and pregnancy. Many of the studies analyze preterm birth, in part because it is a condition that leads to future health problems - and it is very easily measurable. Babies either are or aren't born before 37 weeks. 

In this newsletter we are concentrating on research relating to how vitamin D in utero affects the future full life of the newborn. 

For those of you who have followed GrassrootsHealth you may know that we have done seminars where prominent vitamin D researchers have come to one place to present to the public. In one of those meetings, Toronto 2009, an audience member asked the presenter, "When should someone start measuring their vitamin D values and keeping above 40 ng/ml in order to best reduce the risk of cancer?"

The answer was "in utero." This was before Protect our Children NOW!, before much of the pregnancy research we have to date. At that time researchers knew that the most protective benefit for vitamin D is to have that protection your whole life - not just when cancer usually appears. A nd, this means that the best time to protect the future life is actually preconception, before pregnancy.

I have often remembered that answer as it shocked many in the crowd. There was a temporary silence in the full room. It was a new idea to many, and yet, now the research has shown that idea is here to stay.

Carole Baggerly 
Director, GrassrootsHealth 
A Public Health Promotion & Research Organization 
Moving Research into Practice NOW!
  Can vitamin D in pregnancy affect the future health of the child?

The role of vitamin D in pregnancy and lactation; emerging concepts by Carol Wagner et al. provides a thorough summary. The full paper is available for the public. Wagner discusses many aspects of vitamin D and pregnancy including the differences in vitamin D metabolism during pregnancy, as opposed to non-pregnant; the future effects on the baby; vitamin D's immune effects during pregnancy; and an overview of her randomized controlled trials with vitamin D and pregnancy.

The conclusion is that pregnant women should get their 25(OH)D serum level up to 40 ng/ml as early as possible in their pregnancy, and remain there throughout for an optimal pregnancy and fetus. Ideally, before they even get pregnant.

It is even better to have a 40 ng/ml or higher vitamin D level during preconception!  In a recent study published by Dr. Mirzakhani et al., they had zero instances of preeclampsia IF the woman came into her first visit with a vitamin D serum level of 40 ng/ml or above.

How does Vitamin D effect the immune system of the child?

You may not call it respiratory syncytial virus (RSV) when your child has cold-like symptoms, bronchitis, or pneumonia - but that is the virus which typically causes those conditions in the lungs. Since sickness in early life can be very serious, or even fatal, a set of researchers decided to study the role of vitamin D in utero on the incidence of these infections during the first year of life.

Mirjam E. Belderbos et al. enlisted mothers in a birth cohort in Utrecht, Netherlands. They studied 156 babies who were all born healthy and full term (37 weeks or later). Cord blood was taken at birth for study and a consultation was done with the parents between 1 and 3 weeks of age. Parents kept a daily log for one year to report any symptoms. If any cough or wheeze lasted for 2 days parents were instructed to get a sample via swab and send it to the lab. Physician reports were also used if the baby was brought to the doctor. 

Analyzing the number of infections by vitamin D serum level found that babies with cord blood less than 20 ng/ml were 6.2 times more likely to have an infection compared to babies with cord blood greater than or equal to 30 ng/ml. The study also found an association between vitamin D levels in the mother and the child as well as a clear seasonal variation in vitamin D levels - with those born in the summer having the highest levels. 

How does vitamin D effect brain development in the child?

Andrew Whitehouse et al. set out to determine whether vitamin D sufficiency in pregnancy during a critical time window of brain development had an effect on brain development during childhood. They studied behavioral, emotional and language development.

Vitamin D levels were measured for 743 women at 18 weeks pregnancy in Perth, Australia and their measurements were put into four different groups (6-18 ng/ml, 19-23 ng/ml, 24-28 ng/ml, 29-62 ng/ml). The children were then measured using industry standard checklists for behavior, emotional and language development at ages 2, 5, 8, 10, 14, and 17 years.

They did not find a significant difference in behavior and emotional difficulties. But, there was a significant difference in language impairment. Children whose mothers had vitamin D levels in the lowest group, 6- 18 ng/ml, were twice as likely to have difficulties in language development as compared to the children whose mothers had vitamin D levels in the highest group, between 29 and 62 ng/ml.

How does vitamin D effect future type 1 diabetes diagnosis 30 years later?

Elina Hyppönen et al. wanted to find out how vitamin D in very early childhood would effect health later in life. In this case over 12,000 women in Oulu and Lapland, Northern Finland were enrolled in a birth cohort in 1966. The recommended dose of vitamin D for infants at the time was 2000 IU D per day. During that first year of life data was collected on how much vitamin D the children received and if any rickets was experienced.

After year one, 10,821 children had complete data. 30 years later, in 1997-1998, a follow up survey was sent to these participants. The main outcome they were searching for was whether this individual had been diagnosed with type 1 diabetes. For this group, 81 people had been diagnosed with type 1 diabetes, at a median age of 14 years. The conclusion was that the children who received regular supplementation of at least 2000 IU/day had an 80% lower risk of type 1 diabetes at 30 years old than the children who received less.
Vitamin D and Asthma Health Disparities

Recent Presentation by:

Scott Weiss, MD, MS 
Professor of Medicine, Harvard Medical School, Boston, MA 
Talk is 20 minutes, starting at 4 hours 25 minutes into the recording.
Listen to Talk

Health Disparity in African Americans

African Americans have the highest prevalence of asthma in the US. They also have greater severity with their asthma, and more hospitalizations due to asthma. Weiss reported two out of the three studies on vitamin D and asthma showed a positive correlation, and led to the creation of VDAART.
What is VDAART?

VDAART, Vitamin D Antenatal Asthma Reduction Trial, is a randomized controlled study to determine the relationship of vitamin D in pregnant women to asthma and allergies in their children, with a secondary outcome to look at conditions of pregnancy and whether those were reduced with vitamin D supplementation. The treatment group received 4400 IU vitamin D/day and the control group received 400 IU vitamin D/day.

Initial results for the 3 year arm were presented at the Vitamin D Workshop in 2016 and can be found here. The results were negative, meaning that vitamin D did not seem to affect the rate of asthma or allergies in 3 year olds. The results were 6.1% reduction in incidence of asthma or recurrent wheeze with 4400 IU/day as compared to 400 IU day, but had to be reported as "insignificant" because the statistical P-value was .051. 

The P-value is a probability, it is a percentage. In this calculation the P-value was .051, which means that there is a 5.1% chance that this result (6.1% reduction in asthma with 4400 IU vitamin D/day) was due to chance - not the actual treatment. In a different wording, that means you are 94.9% sure it was NOT chance! The scientific community has agreed that P=.05 or less is an accepted amount for study results to have "significance" and anything higher than P=.05 is "not statistically significant." There is no middle ground, it is black or white. 

What have they done since then? The study is continuing and the 6 year arm of the trial will be finished in January 2018 and results will be provided afterwards.

Weiss focused his presentation on some considerations brought to light since presenting at the Vitamin D Workshop in 2016. One important point is that his first analysis did not take into consideration the vitamin D level at the beginning of trial - and this had a huge effect - not for the treatment group, their levels of vitamin D were still raised, but with the control group. There was a group within the control group that entered with a vitamin D level of 30 ng/ml, the same level as what many in the treatment group achieved after three years.

Also, he reported that an editorial in JAMA said the study was underpowered. So, the team did an analysis with two different studies (both considered underpowered) - and found a 30% reduction in asthma incidence that was sufficiently powered. It is worth noting that this is roughly the same amount of effect found in observational studies.

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The role of vitamin D in pregnancy and lactation: emerging concepts
Carol L. Wagner et al.
Medical University of South Carolina 
Women's Health
March 2015

Early pregnancy vitamin D status and risk of preeclampsia
Hooman Mirzakhani et al.
Brigham and Women's Hospital
The Journal of Clinical Investigation
November 14, 2016

Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis
Mirjam E. Belderbos et al.
University Medical Center
Utrecht, Netherlands
June 2011

Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development
Andrew Whitehouse et al.
University of Western Australia
March 2012

Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study
Elina Hyppönen et al. 
Institute of Child Health
November 2001

High Prevalence of Vitamin D deficiency among Inner-City African American Youth with Asthma in Washington, DC
Robert Freishtat et al.
The Journal of Pediatrics
June 2010

Vitamin D Insufficiency and Severe Asthma Exacerbations in Puerto Rican Children
John Brehm et al.
American Journal of Respiratory and Critical Care Medicine
July 2012

Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents
Peter Gergen et al.
The American Journal of Clinical Nutrition
April 2013

The Vitamin D Antenatal Asthma Reduction Trial (VDAART): rationale, design, and methods of a randomized, controlled trial of vitamin D supplementation in pregnancy for the primary prevention of asthma and allergies in children
A. Litonjua et al.
Brigham and Women's Hospital, Boston 
Contemporary Clinical Trials
May 2014

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