Papers of the Month
By Sara Amolegbe
Fluoride exposure in the womb may lower IQ in children
A new NIEHS-funded study suggests that fluoride consumption during pregnancy may be linked to lower IQ scores in children. According to the authors, it is the first study to estimate fluoride exposure in a large birth cohort, including communities that receive fluorinated water in line with recommendations to prevent tooth decay.
Examining a large existing prospective cohort of 600 mother-child pairs from six Canadian cities, the team measured fluoride in the urine of women throughout their pregnancies and estimated the fluoride in their water by matching their residence with their city water source. They also used a survey to estimate fluoride consumption from tap water and beverages made with tap water, like coffee and tea.
Women living in areas with fluorinated tap water had significantly higher urine fluoride concentrations compared with women who drank nonfluorinated water. When examining estimated overall fluoride intake during pregnancy, they found that a 1 milligram higher daily estimated intake of fluoride among pregnant women was associated with a 3.66-point lower IQ score in children ages 3 to 4. Based only on urine measurements, a 1 milligram per liter increase in maternal urinary fluoride was associated with a 4.49-point lower IQ score only in boys. There was no significant association between maternal urine measurements and IQ in girls, which indicated potential differences between effects from exposure on boys and girls.
Because lowered IQ was observed at fluoride levels typically found in North American cities, the authors suggested that the study might raise concerns about exposures to fluoride during pregnancy, even among pregnant women exposed to optimally fluorinated water.
Citation: Green R, Lanphear B, Hornung R, Flora D, Martinez-Mier EA, Neufeld R, Ayotte P, Muckle G, Till C. 2019. Association between maternal fluoride exposure during pregnancy and IQ scores in offspring in Canada. JAMA Pediatr 173(10):940–948.
Methods to study chemical mixtures in the environment
NIEHS grantees demonstrated how modern statistical methods can be used to address a range of distinct questions about exposures to mixtures of chemicals in the environment. According to the authors, no single method can answer all mixtures questions, but with a well-defined research question and appropriate use of statistical approaches, scientists can explore complex relationships between environmental mixtures and adverse health outcomes.
The researchers evaluated the impact of exposure to a mixture of persistent organic pollutants (POPs) on leukocyte telomere length (LTL), a potential mechanism of underlying risk of developing cancer. With information on 18 POPs and LTLs among 1,003 U.S. adults, the researchers used unsupervised methods, which recognize patterns, to identify common exposure sources and shared behaviors among similarly exposed participants. They also employed supervised learning techniques, which focus on relationships between known variables, to identify potentially toxic agents, synergistic activities among the mixture’s components, and to estimate the overall mixture effect.
The researchers showed that results using unsupervised and supervised approaches might not be directly comparable but were generally consistent with each other and with biologically driven results. Using different approaches, they observed an overall mixture effect on LTLs but no interactions among chemicals that would amplify the effects. They also identified individual chemicals that were toxic across the different analyses, including specific forms of polychlorinated biphenyls and furans. The researchers suggested their methods could be used as a toolbox to guide method selection based on specific research questions about mixtures.
Citation: Gibson EA, Nunez Y, Abuawad A, Zota AR, Renzetti S, Devick KL, Gennings C, Goldsmith J, Coull BA, Kioumourtzoglou MA. 2019. An overview of methods to address distinct research questions on environmental mixtures: an application to persistent organic pollutants and leukocyte telomere length. Environ Health 18(1):76.
Simple urine test identifies colon cancer in mice
NIEHS grantees developed a simple and sensitive test that produces a color change in urine when colon cancer is present in mice. According to the authors, this test has potential for use in low-resource settings for rapid detection of colon cancer.
The early stage technology uses ultra-small gold nanoclusters (AuNCs) connected to a protein carrier called neutravidin. The researchers designed the nanosensors to be disassembled by specific tumor enzymes known as matrix metalloproteinases (MMPs), which help promote the growth and spread of tumors. MMP enzymes are produced in colon tumors, so they can serve as a biological marker that cancer is present.
The researchers injected the AuNC nanosensors into mice and found that when the nanosensors were broken up by MMPs, they passed through the kidney and were released in the urine. They found that urine from tumor-bearing mice became bright blue in less than one hour, exhibiting a 13-fold increase in blue color signal compared with urine samples from healthy mice. They also found that the nanosensors were eliminated completely by mice — both with and without cancer — through excretion within four weeks of injection and with no evidence of toxicity.
According to the authors, engineered nanosensors that indicate the presence of different enzymes may be translatable to a range of diseases in which enzyme activity can serve as a biomarker, including other cancers and infectious diseases.
Citation: Loynachan CN, Soleimany AP, Dudani JS, Lin Y, Najer A, Bekdemir A, Chen Q, Bhatia SN, Stevens MM. 2019. Renal clearable catalytic gold nanoclusters for in vivo disease monitoring. Nat Nanotechnol 14(9):883–890.
Phthalates linked to preterm birth in Puerto Rico
Among a group of pregnant women in Puerto Rico, exposure to two phthalates, di-n-butyl phthalate (DBP) and di-isobutyl phthalate (DiBP), was linked to reduced gestational age at delivery and increased odds of preterm birth, according to an NIEHS-funded study.
The researchers took urine samples from 1,090 women in Puerto Rico at approximately 20, 24 and 28 weeks of pregnancy and measured for markers of different phthalate chemicals. Exposure to phthalates could occur through drinking water sources, diet, and use of consumer products.
Researchers found that higher urinary concentrations of DBP metabolites in women translated into 42% greater odds of having a preterm birth compared with women with lower exposures. Higher urinary concentrations of DiBP metabolites were associated with 32% greater odds of having a preterm birth. On average, women with DBP exposure levels in the highest 25% of the population had a pregnancy that was 1.55 days shorter than women whose exposure was in the lowest 25%. Associations were highest for urinary concentrations measured at the second study visit, near the end of the second trimester.
According to the authors, results from a limited number of other studies have been inconsistent, but this most recent work represents one of the largest and most detailed prospective cohort studies to investigate these associations to date. The authors suggest that phthalate exposures may be contributing to elevated rates of preterm birth found in Puerto Rico.
Citation: Ferguson KK, Rosen EM, Rosario Z, Feric Z, Calafat AM, McElrath TF, Velez Vega C, Cordero JF, Alshawabkeh A, Meeker JD. 2019. Environmental phthalate exposure and preterm birth in the PROTECT birth cohort. Environ Int 132:105099.
(Sara Amolegbe is a research and communication specialist for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)