In vitro study finds digested formula, but not breast milk, is toxic to cells

Contact: Catherine Hockmuth chockmuth@ucsd.edu 858-822-1359 University of California – San Diego

Findings may help explain development of fatal condition in premature infants

             IMAGE:   This microscopic image of cells shows the effects of breast milk vs. infant formula digestion. Cells are alive and healthy after the digestion of breast milk (top row) with only…

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Free fatty acids created during the digestion of infant formula cause cellular death that may contribute to necrotizing enterocolitis, a severe intestinal condition that is often fatal and occurs most commonly in premature infants, according to a study by University of California, San Diego bioengineers. Their report, which was based on in vitro tests comparing the digestion of fresh human breast milk and nine different infant formulas, was published online in the journal Pediatric Research.

Scientists have long known that premature infants fed formula are more likely to develop necrotizing enterocolitis than those fed breast milk. The condition is the leading cause of death from gastrointestinal diseases in premature infants, but the underlying mechanism has not been understood.  Alexander Penn, a research scientist working in the Microcirculation Laboratory of bioengineering Professor Geert Schmid-Schönbein from the UC San Diego Jacobs School of Engineering, believes they have come closer to an answer.

Penn and others had previously determined that the partially digested food in a mature, adult intestine is capable of killing cells, due to the presence of free fatty acids which have a “detergent” capacity that damages cell membranes.  The intestines of healthy adults and older children have a mature mucosal barrier that may prevent damage due to free fatty acids. However, the intestine is leakier at birth, particularly for preterm infants, which could be why they are more susceptible to necrotizing enterocolitis.

Therefore, the researchers wanted to know what happens to breast milk as compared to infant formula when they are exposed to digestive enzymes.   They “digested,” in vitro, infant formulas marketed for full term and preterm infants as well as fresh human breast milk using pancreatic enzymes or fluid from an intestine. They then tested the formula and milk for levels of free fatty acids. They also tested whether these fatty acids killed off three types of cells involved in necrotizing enterocolitis: epithelial cells that line the intestine, endothelial cells that line blood vessels, and neutrophils, a type of white blood cell that is a kind of “first responder” to inflammation caused by trauma in the body.

             IMAGE:   This chart shows the high concentration of unbound (cytotoxic) free fatty acids (FFAs) (shown in white) created by the digestion of infant formula compared to the relatively small presence of…

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Overwhelmingly, the digestion of formula led to cellular death, or cytotoxicity – in less than 5 minutes in some cases – while breast milk did not. For example, digestion of formula caused death in 47 percent to 99 percent of neutrophils while only 6 percent of them died as a result of milk digestion.  The study found that breast milk appears to have a built-in mechanism to prevent cytotoxicity. The research team believes most food, like formula, releases high levels of free fatty acids during digestion, but that breast milk is digested in a slower, more controlled, process.

Currently, many neonatal intensive care units are moving towards formula-free environments, but breastfeeding a premature infant can be challenging or physically impossible and supplies of donor breast milk are limited. To meet the demand if insufficient breast milk is available, less cytotoxic milk replacements will need to be designed in the future that pose less risk for cell damage and for necrotizing enterocolitis, the researchers concluded.

This may be of benefit not only to premature infants, but also to full-term infants at higher risk for disorders that are associated with gastrointestinal problems and more leaky intestines, such as autism spectrum disorder. Dr. Sharon Taylor, a professor of pediatric medicine at UC San Diego School of Medicine and a pediatric gastroenterologist at Rady Children’s Hospital, San Diego, said the study offers more support to an already ongoing push by hospitals, including neonatal intensive care units, to encourage breastfeeding even in more challenging circumstances in the NICU. For patients who are too premature or frail to nurse, Dr. Taylor said hospital staff should provide consultation and resources to help mothers pump breast milk that can be fed to the baby through a tube.

The research was carried out in collaboration with Dr. Taylor, Karen Dobkins of the Department of Psychology, and Angelina Altshuler and James Small of the Department of Bioengineering at UC San Diego and was funded by the National Institutes of Health (NS071580 and GM85072).  The researchers conclude that breast milk has a significant ability to reduce cytotoxicity that formula does not have. One next step is to determine whether these results are replicated in animal studies and whether intervention can prevent free fatty acids from causing intestinal damage or death from necrotizing enterocolitis.

Chemicals in common consumer products may play a role in pre-term births : phthalates

2009 study posted for filing

Contact: Laura Bailey baileylm@umich.edu 734-647-1848 University of Michigan

ANN ARBOR, Mich.—A new study of expectant mothers suggests that a group of common environmental contaminants called phthalates, which are present in many industrial and consumer products including everyday personal care items, may contribute to the country’s alarming rise in premature births.

Researchers at the University of Michigan School of Public Health found that women who deliver prematurely have, on average, up to three times the phthalate level in their urine compared to women who carry to term.

Professors John Meeker, Rita Loch-Caruso and Howard Hu of the SPH Department of Environmental Health Sciences and collaborators from the National Institute of Public Health in Mexico and the U.S. Centers for Disease Control and Prevention analyzed data from a larger study directed by Hu, which follows a cohort of Mexican women recruited during pre-natal visits at one of four clinics of the Mexican Institute of Social Security in Mexico City.

Meeker and colleagues looked at data from 60 women: 30 who carried to term and 30 who delivered prematurely (defined as less than 37 weeks gestation). They analyzed urine samples collected during the third trimester and compared them to the control group who carried to term. They found significantly higher phthalate metabolite levels in the women who delivered prematurely.

Premature birth is a significant risk factor for many health problems in childhood that can persist into adulthood, Meeker says. In the United States, premature births have increased by more than 30 percent since 1981 and by 18 percent since 1990. In 2004, premature births accounted for 12.8 percent of live births nationwide.

Premature births, he says, account for one-third of infant deaths in the United States, making it the leading cause of neonatal mortality. Being born too early can also lead to chronic health problems such as blindness, deafness, cerebral palsy, low IQ and more.

Phthalates are commonly used compounds in plastics, personal care products, home furnishings (vinyl flooring, carpeting, paints, etc.) and many other consumer and industrial products. The toxicity varies by specific phthalates or their breakdown products, but past studies show that several phthalates cause reproductive and developmental toxicity in animals.

A couple of human studies have reported associations between phthalates and gestational age, but this is the first known study to look at the relationship between phthalates and premature births, Meeker says.

“We looked at these commonly used compounds found in consumer products based on the growing amount of animal toxicity data and since national human data show that a large proportion of the population are unknowingly exposed,” Meeker said. “One of the problems for consumers is that you don’t know exactly which products contain phthalates because the products do not have to be labeled accordingly.”

Meeker says the U-M study is a stepping stone to larger and more detailed studies examining the role of phthalates and premature births. The researchers hope to examine a larger population of pregnant women to corroborate these initial study findings, and conduct experimental lab studies to further explore the biological mechanisms of how phthalates work in the body.

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The study, “Urinary Phthalate Metabolites in Relation to Preterm Birth in Mexico City,” is available online at: http://www.ehponline.org/docs/2009/0800522/abstract.html. It will appear in a later printed issue of Environmental Health Perspectives.

For more on Meeker: http://www.sph.umich.edu/iscr/faculty/profile.cfm?uniqname=meekerj

Loch-Caruso: http://www.sph.umich.edu/iscr/faculty/profile.cfm?uniqname=rlc

Hu: http://www.sph.umich.edu/iscr/faculty/profile.cfm?uniqname=howardhu

EHS: http://www.sph.umich.edu/ehs/

The University of Michigan School of Public Health has been working to promote health and prevent disease since 1941, and is consistently ranked among the top five public health schools in the nation

45th Health Research Report 09 NOV 2008 – Reconstruction

Editors Top Five:

1. Selenium may slow march of AIDS

2. Vitamin B1 could reverse early-stage kidney disease in diabetes patients

3. Persistent pollutant may promote obesity

4. Broccoli compound targets key enzyme in late-stage cancer

5. Down’s symptoms may be treatable in the womb

In this issue:

1. Inhaled corticosteroids raise pneumonia risk for lung disease sufferers

2. Stanford/Packard study shows no benefit from drug widely used to prevent premature births

3. US infant formula safe from melamine, says FDA

4. Vitamin K linked to insulin resistance in older men

5. Down’s symptoms may be treatable in the womb

6. Selenium may slow march of AIDS

7. Fast food a potential risk factor for Alzheimer’s

8. Despite “Apology Laws,” Physicians May Not Communicate Medical Errors

9. Broccoli compound targets key enzyme in late-stage cancer

10. Persistent pollutant may promote obesity

11. Calcium and vitamin D may not be the only protection against bone loss

12. A little wine boosts omega-3 in the body: Researchers find a novel mechanism for a healthier heart

13. Flu vaccine linked to reduced illness, impairment of academic performance among college students (Read WHOLE article),,,

14. Eating eggs when pregnant affects breast cancer in offspring

15. Vitamin D found to fight placental infection

16. Interferon as long-term treatment for hepatitis C not effective, report HALT-C researchers

17. Updated standards to reduce metal contaminants in prescription drugs

18. Breaking the silence after a study ends

19. Vitamin B1 could reverse early-stage kidney disease in diabetes patients

20. Statin warning for pregnant women

21. Pine bark reduces inflammatory marker CRP in osteoarthritis

 

Health Technology Research Synopsis

45th Issue Date 09 NOV 2008

Compiled By Ralph Turchiano

www.healthresearchreport.me www.vit.bz

www.youtube.com/vhfilm http://www.facebook.com/engineeringevil

www.engineeringevil.com

 

 

 

Study examines risk of poor birth outcomes following H1N1 vaccination

CHICAGO – In studies examining the risk of adverse outcomes after receipt of the influenza A(H1N1) vaccine, infants exposed to the vaccine in utero did not have a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction; while in another, study researchers found a small increased risk in adults of the nervous system disorder, Guillain-Barre syndrome, during the 4 to 8 weeks after vaccination, according to 2 studies in the July 11 issue of JAMA.

In the first study, Björn Pasternak, M.D., Ph.D., of the Statens Serum Institut, Copenhagen, Denmark and colleagues investigated whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of major birth defects, preterm birth, and fetal growth restriction. According to background information in the article, the 2009 influenza A(H1N1) pandemic put pregnant women at increased risk of illness, death, and poor pregnancy outcomes. “Pregnant women were among the main target groups prioritized for vaccination against influenza A(H1N1)pdm09, and an estimated 2.4 million women were vaccinated during pregnancy in the United States alone. However, assessment of the fetal safety of H1N1 vaccination in pregnancy has been limited to a few pharmacovigilance reports and descriptive cohort studies.”

The registry-based study included all live-born singleton infants in Denmark delivered between November 2, 2009, and September 30, 2010. The researchers estimated the prevalence odds ratios of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy. Following exclusions, a group of 53,432 live-born infants was identified with 6,989 (13.1 percent) exposed to the vaccine during pregnancy.

In a propensity score-matched analysis of 330 infants exposed to the vaccine in the first trimester of pregnancy and 330 unexposed, there were 18 infants (5.5 percent) diagnosed with a major birth defect among those exposed compared with 15 (4.5 percent) among the unexposed.  Among infants exposed to the H1N1 vaccine in the first trimester, 31 (9.4 percent) were born preterm compared with 24 (7.3 percent) among the unexposed. Preterm birth occurred in 302 of 6,543 infants (4.6 percent) with second- or third-trimester exposure, compared with 295 of 6,366 unexposed infants (4.6 percent). “Taking gestational age into account, there was no increased risk of small size for gestational age associated with vaccination in the first (25 [7.6 percent] exposed vs. 31 [9.4 percent] unexposed) or the second or third trimester (641 [9.7 percent] exposed vs. 657 [9.9 percent] unexposed),” the researchers write.

“In conclusion, this nationwide cohort study in Denmark found no significant associations between exposure to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in pregnancy and risk of adverse fetal outcomes including major birth defects, preterm birth, and growth restriction. Although the data provide robust evidence of safety with respect to outcomes associated with second- or third-trimester exposure, results from analyses of first-trimester exposure should be viewed as preliminary and need confirmation. Further research also needs to address risk of specific birth defects as well as effectiveness of H1N1 vaccination in pregnancy