High-fat diet, obesity during pregnancy harms stem cells in developing fetus

Physician-scientists at OHSU Doernbecher Children’s Hospital reveal a high-fat diet and obesity during pregnancy compromise the blood-forming, or hematopoietic, stem cell system in the fetal liver responsible for creating and sustaining lifelong blood and immune system function.

The life-long burden of a western-style diet on the heart and circulatory system have long been appreciated. However, prior to this study, no one had considered whether the developing blood stem cells might be similarly vulnerable to prenatal high-fat diet and/or maternal obesity. The findings are published in the journal Molecular Metabolism.

“Our results offer a model for testing whether the effects of a high-fat diet and obesity can be repaired through dietary intervention, a key question when extrapolating this data to human populations,” said Daniel L. Marks, M.D., Ph.D., co-investigator and professor of pediatric endocrinology in the OHSU School of Medicine and Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital.

Several years ago, Marks and colleagues developed a mouse model that closely mimics the high-fat, high-simple-sugar diet currently consumed by many young women of childbearing age. Their subsequent research demonstrated that maternal overnutrition in mice significantly reduced the size of the fetal liver.

Armed with this information, Marks partnered with another stem cell expert, Peter Kurre, M.D., co-investigator on the current study and professor of pediatric oncology in the OHSU School of Medicine and the Papé Family Pediatric Research Institute at OHSU Doernbecher Children’s Hospital.

Together, they discovered that the complex changes that occur as a result of maternal high-fat diet and obesity put significant constraints on the growth and expansion of blood stem cells in the fetal liver, which ultimately compromises the developing immune system.

Being very overweight, which is usually defined as having a body mass index (BMI) of more than 30, is increasingly common. Around 15-20% of pregnant women are now in this category. Your BMI is a measurement of how overweight you are and is calculated using your weight and height.

Before you get pregnant you can use the BMI healthy weight calculator to work out if you are overweight. But once you’re pregnant this may not be accurate.

The best way to protect your health and your baby’s wellbeing is to lose weight before you become pregnant. By reaching a healthy weight, you increase your chances of conceiving naturally and reduce your risk of the problems associated with being overweight in pregnancy.

Contact your GP for advice on how to lose weight. Your doctor may be able to refer you to a specialist weight-loss clinic. Find out more about losing weight before you become pregnant.

If you get pregnant before losing weight, try not to worry - good antenatal care can help minimise any risks to you and your baby.
During pregnancy

If you are very overweight and you are pregnant, don’t try to lose weight during your pregnancy as this may not be safe. Although there are risks associated with being obese during pregnancy, there is no evidence that losing weight while you’re pregnant will reduce these risks.

The best way to protect your health and your baby’s health is to go to all your antenatal appointments so that the midwife, doctor and any other health professionals can keep an eye on you both. They can manage the risks that you might face due to your weight, and act to prevent - or deal with - any problems.

It’s also important to eat a healthy, balanced diet and get some physical activity every day. You should be offered referral to a dietitian or other health professional for personalised advice on healthy eating and how to be physically active during your pregnancy. Being physically active in pregnancy will not harm your baby.

High-fat diet, obesity during pregnancy harms stem cells in developing fetus “In light of the spreading western-style, high-fat diet and accompanying obesity epidemic, this study highlights the need to better understand the previous unrecognized susceptibility of the stem and progenitor cell system,” Kurre said. “These findings may provide broad context for the rise in immune disease and allergic disposition in children.”

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The study, “Maternal high-fat diet and obesity compromise fetal hematopoiesis,” was funded by Friends of Doernbecher and by the Oregon Clinical Translational Research Institute at OHSU. Research reported in this press release] was supported by National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR000128

Kurre and Marks also are members of the OHSU Knight Cancer Institute and Oregon Stem Cell Center at OHSU.

Pregnancy, or the desire to become pregnant, often inspires women to take better care of themselves -  quitting smoking, for example, or eating more nutritiously.

But now many women face an increasingly common problem: obesity, which affects 36 percent of women of childbearing age. In addition to hindering conception, obesity -  defined as a body mass index above 30 -  is linked to a host of difficulties during pregnancy, labor and delivery.

These range from gestational diabetes, hypertension and pre-eclampsia to miscarriage, premature birth, emergency cesarean delivery and stillbirth.

The infants of obese women are more likely to have congenital defects, and they are at greater risk of dying at or soon after birth. Babies who survive are more likely to develop hypertension and obesity as adults.

To be sure, most babies born to overweight and obese women are healthy. Yet a recently published analysis of 38 studies found that even modest increases in a woman’s pre-pregnancy weight raised the risks of fetal death, stillbirth and infant death.

Personal biases and concerns about professional liability lead some obstetricians to avoid obese patients. But Dr. Sigal Klipstein, chairwoman of the committee on ethics of the American College of Obstetricians and Gynecologists, says it is time for doctors to push aside prejudice and fear. They must take more positive steps to treat obese women who are pregnant or want to become pregnant.

OHSU researchers who contributed to this research include: Kurre, Marks, Ashley N. Kamimae-Lanning, Stephanie M. Krasnow, Natalya A. Goloviznina, Xinxia Zhu, Quinn R. Roth-Carter, Peter R. Levasseur, Sophia Jeng, Shannon K. McWeeney.

ABOUT OHSU DOERNBECHER CHILDREN’S HOSPITAL

High-fat diet, obesity during pregnancy harms stem cells in developing fetus OHSU Doernbecher Children’s Hospital ranks among the nation’s Best Children’s Hospitals,* is one of 21 members of the Children’s Oncology Group’s Phase 1 and Pilot Consortium, and ranks 39th for NIH awards to children’s hospitals and their university-affiliated Department of Pediatrics.** Nationally recognized physicians and nurses provide a full range of specialty and subspecialty care to tens of thousands of children annually, resulting in 200,000 discharges, surgeries, transports and outpatient visits annually in a patient- and family-centered environment. OHSU Doernbecher providers also travel throughout Oregon and Southwest Washington, providing specialty care to more than 3,000 children at more than 200 outreach clinics in 15 locations. Using state-of-the-art, secure two-way video and audio communication, OHSU Doernbecher’s Telemedicine Network connects pediatric intensivists and neonatologists to emergency room physicians statewide to help evaluate time-critical pediatric patient needs and assist with treatment plans.

* U.S. News & World Report 2014-15 Best Children’s Hospitals

** Children’s Hospital Association

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Tamara Hargens-Bradley
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