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June 13, 2016

Breaking the Cycle of Obesity

Adequate folate levels in obese pregnant women may substantially reduce risk that their children will become overweight or obese

Adequate levels of the B vitamin folate in the blood of obese pregnant women appear to reduce by 43 percent the risk that their children would be overweight or obese up to nine years later, new research from the Johns Hopkins Bloomberg School of Public Health suggests.

Folate is an essential B vitamin and maternal folate deficiency around the time of conception is known to cause fetal neural tube defects.

The findings, published June 13 in JAMA Pediatrics, add to the growing evidence that the nutritional status of pregnant women may play an important long-term role in the metabolic health of their children.

“Half of mothers in the United States enter pregnancy either obese or overweight and maternal obesity is a major risk factor for childhood obesity, part of a vicious cycle fueling the current epidemic,” says the study’s principal investigator, Xiaobin Wang, MD, MPH, ScD, the Zanvyl Krieger Professor in Child Health at the Bloomberg School and director of the Center on the Early Life Origins of Disease. “What we have found in this study is that pregnant women with adequate levels of folate appear to be much less likely to pass obesity on to their children. It could help break an unhealthy cycle.”

Folate is a primary component of prenatal vitamins taken by many pregnant women. It is found in certain fruits and vegetables and, in the United States, bread, cereal, flour, cornmeal, pasta, rice and other grain products are fortified with folic acid (a synthetic form of folate).  Yet, some women aren’t getting enough or their bodies aren’t properly absorbing it, leading to insufficient folate levels in their blood. The Centers for Disease Control and Prevention says that one in four women of reproductive age in the U.S. have insufficient folate for preventing neural tube defects.

The researchers also determined that the level of folate associated with a reduced risk of passing obesity on to the next generation may be significantly higher than what is currently considered adequate for a pregnant woman. Folate levels under 10 nanomoles per liter have been the standard definition of deficiency based on the role it plays in a certain type of anemia. Wang’s new research suggests that pregnant, obese women need levels of 20 or more nanomoles per liter in their blood to begin to see a reduction in obesity rates in their children. However, much beyond the 20 nanomole range, the benefits of additional folate tapered off.

Complicating matters further, emerging research suggests too much folate in pregnant mothers may also be detrimental for child health. Preliminary research conducted by Wang and her colleagues and presented in May at the 2016 International Meeting for Autism Research suggested that excessive amounts of maternal folate – more than 59 nanomoles per liter – was associated with increased risk for autism in their offspring. 

“These findings are not contradictory,” Wang says. “They do, however, reflect the complexity of these nutritional questions and the importance of developing and getting evidence-based, more specific guidance out to expectant mothers. We hope that our work will stimulate more research to look into these complex nutritional issues in the future.” The work suggests that too little, and too much, may be detrimental to child health and that further focus should be on optimizing “adequate” levels in the context of maternal obesity, genetic background and diet, she says. 

For the study, researchers analyzed data from 1,517 mother-child pairs in the Boston Birth Cohort, a predominantly low-income minority population. The mothers were recruited at the time of their child’s birth and their children were followed for up to nine years from 2003 to 2014. Of the mother-child pairs, 29.2 percent of mothers were overweight and 25.1 percent were obese pre-pregnancy. A total of 590 children (38.9 percent) were overweight or obese by the ages of two to nine years old.

Wang and her colleagues found that obese mothers had significantly lower folate levels than normal weight mothers, but adequate maternal folate concentrations could mitigate the adverse effects of maternal obesity on the child’s risk of developing obesity. About a quarter of mothers in the cohort had folate levels below 20 nanomoles per liter (24 percent in normal weight mothers and 27 percent in obese mothers).

In the study, the researchers also linked inadequate folate levels in obese mothers to an increase in blood concentrations of insulin and leptin, two hormones related to metabolism, in their children. These findings lend further evidence that inadequate folate in mothers can lead to metabolic disorders in the offspring, the researchers say.

While all women who seek preconception and prenatal care should be encouraged to take folate supplements, Wang says, a wide range of blood folate levels in the study participants was observed.

“Given the important role of folate, it would be worthwhile for physicians to check folate levels in obese women.” she says. “This way, we hope to be able to ensure an optimal folate level in order to decrease adverse outcomes due to either too little or too much folate.”

Associations of Maternal Prepregnancy BMI and Plasma Folate Concentrations with Child Metabolic Health” was written by Guoying Wang, MD, PhD; Frank B. Hu, MD, PhD; Kamila B. Mistry, PhD, MPH; Cuilin Zhang, MD, PhD; Fazheng Ren, PhD; Yong Huo, MD; David Paige, MD; Tami Bartell, BS; Xiumei Hong, MD, PhD; Deanna Caruso, MS; Zhicheng Ji, BS; Zhu Chen, PhD; Yuelong Ji, MSPH; Colleen Pearson, BA; Hongkai Ji, PhD; Barry Zuckerman, MD; Tina L. Cheng, MD; and Xiaobin Wang, MD, ScD, MPH.

The Boston Birth Cohort (BBC) has been funded continuously by National Institutes of Health’s National Institute of Child Health and Human Development over the past 15 years (2R01 HD041702; R01 HD086013). The BBC was also supported by the National Institute of Environmental Health Sciences, and the National Institute of Allergy and Infectious Diseases, as well as the Health Resources and Services Administration’s Maternal and Child Health Bureau and the March of Dimes.

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Media contact for the Johns Hopkins School of Public Health: Stephanie Desmon at 410-955-7619 or sdesmon1@jhu.edu and Barbara Benham at 410-614-6029 or bbenham1@jhu.edu.