From the Journals

High maternal lead levels linked to children’s obesity



Children born to mothers with high blood levels of lead have an increased risk of being overweight or obese, particularly if their mothers are also overweight, according to new research.

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Adequate maternal plasma levels of folate, however, mitigated this risk.

“When considered simultaneously, maternal lead exposure, rather than early childhood lead exposure, contributed to overweight/obesity risk in a dose-response fashion across multiple developmental stages (preschool age, school age and early adolescence) and amplified intergenerational overweight/obesity risk (additively with maternal overweight/obesity),” Guoying Wang, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and associates, reported in JAMA Network Open.

“These findings support the hypothesis that the obesity epidemic could be related to environmental chemical exposures in utero and raise the possibility that optimal maternal folate supplementation may help counteract the adverse effects of environmental lead exposure,” the authors wrote.

The prospective urban, low-income cohort study, which ran from 2002 to 2013, involved 1,442 mother-child pairs who joined the study when the children were born and attended follow-up visits at Boston Medical Center. The mean age of the mothers was 29 years, and the children were, on average, 8 years old at follow-up. Half the children were male; 67% of mothers were black, and 20% were Latina.

The researchers collected maternal blood samples within 24-72 hours after birth to measure red blood cell lead levels and plasma folate levels. Children’s whole-blood lead levels were measured during the first lead screening of their well child visits, at a median 10 months of age. Researchers tracked children’s body mass index Z-score and defined overweight/obesity as exceeding the 85th national percentile for their age and sex.

Detectable lead was present in all the mothers’ blood samples. The median maternal red blood cell lead level was 2.5 mcg/dL, although black mothers tended to have higher lead exposure than that of other racial groups. Median maternal plasma folate level was 32 nmol/L. Children’s blood lead levels were a median 1.4 mcg/dL, and their median BMI Z-score was 0.78.

Children whose mothers had red blood cell lead levels of 5.0 mcg/dL or greater (16%) had 65% greater odds of being overweight or obese compared with children whose mothers’ lead level was less than 2 mcg/dL, after adjustment for maternal education, race/ethnicity, smoking status, parity, diabetes, hypertensive disorder, preterm birth, fetal growth, and breastfeeding status (odds ratio [OR], 1.65; 95% confidence internal [CI], 1.18-2.32). Only 5.2% of children had whole-blood lead levels of 5 mcg/dL or greater.

“Mothers with the highest red blood cell lead levels were older and multiparous, were more likely to be black and nonsmokers, had lower plasma folate levels and were more likely to have prepregnancy overweight/obesity and diabetes,” the authors reported.

The dose-response association did not lose significance when the researchers adjusted for children’s blood lead levels, maternal age, cesarean delivery, term births only, and black race. Nor did it change in a subset of children when the researchers adjusted for children’s physical activity.

The strength of the association increased when mothers also had a BMI greater than the average/healthy range. Children were more than four times more likely to be overweight or obese if their mothers were overweight or obese and had lead levels greater than 5.0 mcg/dL, compared with nonoverweight mothers with levels below 2 mcg/dL (OR, 4.24; 95% CI, 2.64-6.82).

Among children whose mothers were overweight/obese and had high blood lead levels, however, high folate levels appeared protective against obesity. These children had a 41% lower risk of being overweight or obese, compared with others in their group, if their mothers had plasma folate levels of at least 20 nmol/L (OR, 0.59 CI, 0.36-0.95; P = .03).

According to an invited commentary, “approximately 140,000 new chemicals and pesticides have appeared since 1950,” with “universal human exposure to approximately 5,000 of those,” wrote Marco Sanchez-Guerra, PhD, of the National Institute of Perinatology in Mexico City, and coauthors Andres Cardenas, PhD, of the University of California, Berkeley, and Citlalli Osorio-Yáñez, PhD, of the National Autonomous University of Mexico in Mexico City. Yet fewer than half of those chemicals have been tested for safety or toxic effect, the editorialists wrote, and scientists know little of their potential reproductive harm.

Dr. Sanchez-Guerra, Dr. Cardenas, and Dr. Osorio-Yáñez agreed with the study authors that elevated lead exposures, especially from gasoline before lead was removed in the United States in 1975, may partly explain the current epidemic of obesity.

“Identifying preventable prenatal causes of obesity is a cornerstone in the fight against the obesity epidemic,” the editorialists said. While most recommendations center on changes to diet and physical activity, environmental factors during pregnancy could be involved in childhood obesity as well.

“The study by Wang et al. opens the door to new questions about whether adequate folate intake might modify the adverse effects of other chemical exposures,” they continued, noting other research suggesting a protective effect from folate against health effects of air pollution exposure. “These efforts could yield substantial public health benefits and represent novel tools in fighting the obesity epidemic,” they concluded.

The research was funded by the National Institutes of Health and the U.S. Department of Health and Human Services. Neither the study authors nor the editorialists had industry financial disclosures.

SOURCES: Wang G et al. JAMA Netw Open. 2019;2(10):e1912343. doi: 10.1001/jamanetworkopen.2019.12343; Sanchez-Guerra M et al. JAMA Netw Open. 2019;2(10):e1912334. doi: 10.1001/jamanetworkopen.2019.12334.

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