Papers of the Month
By Nancy Lamontagne
Baby teeth may link autism and heavy metals
NIEHS grantees reported that baby teeth from children with autism contain more lead and lower amounts of the essential nutrients zinc and manganese compared with baby teeth from children without autism. The new findings suggest that autism risk may be influenced by differences in early life exposure to metals and how a child’s body processes them.
The researchers studied twins to help control genetic influences and explore environmental contributors. Participants included 32 pairs of twins and 12 individual twins. The twins had one sibling with autism, both siblings with autism, or neither with autism. The researchers used a method called laser ablation-inductively coupled plasma mass spectrometry to analyze the metal uptake in the teeth’s growth rings, which correspond to different developmental periods, including the prenatal period.
Analyses of the baby teeth revealed that the children with autism exhibited higher lead levels in the prenatal period and in the first five months after birth compared with children without autism. The children with autism also exhibited lower zinc levels during the third trimester and lower manganese levels both prenatally and after birth, with the highest deficiency seen four months after birth. The researchers said that replication in larger studies is necessary to confirm the connection between metal uptake and autism.
Arora M, Reichenberg A, Willfors C, Austin C, Gennings C, Berggren S, Lichtenstein P, Anckarsater H, Tammimies K, Bolte S. 2017. Fetal and postnatal metal dysregulation in autism. Nat Commun 8:15493.
Pesticides for flower harvest linked to neurobehavioral effects in children
A study, funded in part by NIEHS, found that changes in short-term neurological behaviors in children were associated with the peak pesticide spraying season before the Mother’s Day flower harvest. The findings are among the first to suggest that in children who are not flower workers, a peak period of pesticide use may temporarily affect neurobehavior.
To find out if insecticides commonly used to treat flowers for pests affected the neurobehavior of children, the researchers examined 308 children, 4 to 9 years old, who participated in the Secondary Exposure to Pesticides among Children and Adolescents study. The children lived in flower farming communities in Ecuador, but they did not actually work on the farms. The researchers conducted behavioral and blood tests on the children twice — before the time of peak Mother’s Day flower production and between 63 and 100 days after harvest.
Organophosphate insecticides exert their toxicity by inhibiting the enzyme acetylcholinesterase (AChE), which regulates the neurotransmitter acetylcholine. The blood tests showed that AChE activity was lower in children examined sooner after Mother’s Day than in those examined later, indicating that the pesticides were reaching the children. Children tested closer to Mother's Day also exhibited lower performance for most neurobehavioral areas, including attention and inhibitory control, visuospatial processing, and sensory motor skills, compared with children examined later.
The researchers noted that because the study collected and analyzed data for distinct groups of children at specific points in time, future work needs to assess exposure before, during, and after the peak periods.
Suarez-Lopez JR, Checkoway H, Jacobs DR Jr, Al-Delaimy WK, Gahagan S. 2017. Potential short-term neurobehavioral alterations in children associated with a peak pesticide spray season: The Mother's Day flower harvest in Ecuador. Neurotoxicology 60:125−133.
Phthalate exposure may impair thyroids of young girls
An NIEHS grantee and colleagues found that early childhood exposures to certain phthalates were associated with reduced thyroid function in 3-year-old girls. The study is among the first to examine the link between phthalate exposure and thyroid function in children over time.
The study included 229 inner city mothers and their children enrolled in the Mothers and Newborns Study. To assess phthalate exposure, the researchers measured metabolites produced when the body breaks down five different phthalates in urine samples from women in late pregnancy and from their children at age 3 years. They also assessed thyroid function by measuring the children's thyroxine (FT4) thyroid hormone and thyroid-stimulating hormone at age 3 years.
The researchers found lower levels of FT4 were associated with the presence of metabolites for di-n-butyl phthalate, di-isobutyl phthalate, butylbenzyl phthalate, and diethyl phthalate in girls. Conversely, no associations between FT4 and child phthalate metabolites were seen in boys at age 3 years.
Previous studies have shown links between prenatal exposure to phthalates and risk for lower IQ at age 7 years, as well as mental and motor development problems in preschool children. Because thyroid hormones are necessary for normal brain development, the researchers said the new results may support the hypothesis that lower levels of thyroid hormones are involved in the association between early life phthalate exposure and neurodevelopmental problems.
Morgenstern R, Whyatt RM, Insel BJ, Calafat AM, Liu X, Rauh VA, Herbstman J, Bradwin G, Factor-Litvak P. 2017. Phthalates and thyroid function in preschool age children: Sex specific associations. Environ Int 106:11−18.
Prenatal inflammation associated with later neurological problems
Researchers supported in part by NIEHS identified genes whose expression levels are associated with both prenatal inflammation and later neurocognitive impairment. Results from the study of preterm infants suggested that the prenatal environment could affect neurodevelopment in ways that persist into later childhood.
Using umbilical cord tissue obtained from 43 babies born before 28 weeks of gestation, the researchers identified 445 genes with expression levels linked to inflammation in the womb. They examined the function of these genes and whether expression levels in umbilical cord tissue could predict neurocognitive function at 10 years of age. The inflammation-associated genes that showed decreased expression also significantly enhanced biological processes related to brain development and growth. The researchers also found that six of the 445 identified genes predicted neurocognitive impairment at age 10 years.
By identifying genes associated with neurodevelopmental problems, the work may eventually lead to improved detection of neurocognitive deficits and earlier intervention for children who are at risk. According to the authors, future research is needed to identify the underlying mechanisms.
Tilley SK, Joseph RM, Kuban KCK, Dammann OU, O'Shea TM, Fry RC. 2017. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes. PLoS One 12(5):e0176953.