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Prenatal phthalate exposure and neurodevelopmental differences in twins at 2 years of age
Han Xiao1, Liqin Hu1, Tingting Tang2
1Institute of Maternal and Child Health, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
Insights
Prenatal phthalate exposure, particularly DEHP metabolites, is linked to neurodevelopmental differences in twins. These associations were stronger in monochorionic diamniotic twins, suggesting a critical exposure window during early pregnancy.
Area of Science:
- Environmental Health
- Developmental Psychology
- Toxicology
Background:
- Previous studies on prenatal phthalate exposure and singleton neurodevelopment yielded inconsistent results.
- Parental, obstetrical, and genetic factors may confound findings in singleton studies.
- A co-twin control design minimizes genetic and shared environmental influences.
Purpose of the Study:
- To investigate the association between prenatal phthalate exposure and neurocognitive development in twins.
- To identify specific phthalate metabolites and critical exposure windows affecting neurodevelopment.
- To leverage a co-twin control design to reduce confounding factors.
Main Methods:
- Utilized a co-twin control design with 97 mother-twin pairs from the Wuhan Twin Birth Cohort.
- Measured 14 phthalate metabolites in maternal urine across three trimesters.
- Assessed neurodevelopmental differences at age two using the Bayley Scales of Infant Development (Second Edition) and a multiple informant model.
Main Results:
- First-trimester exposure to MEOHP, MEHHP, and ∑DEHP showed significant positive associations with intra-twin differences in Mental Development Index (MDI).
- Associations between several phthalate metabolites (MEP, MiBP, MBP, MBzP, DEHP metabolites) and neurodevelopmental differences were stronger in monochorionic diamniotic (MCDA) twins compared to dichorionic diamniotic (DCDA) twins.
Conclusions:
- Prenatal phthalate exposure is significantly associated with neurodevelopmental disparities in MCDA twins.
- Findings highlight the susceptibility of MCDA twins to environmental exposures during gestation.
- Further validation in larger, longitudinal studies is recommended.
Background:
Previous studies of singletons evaluating prenatal phthalate exposure and early neurodevelopment reported mixed results and the associations could be biased by parental, obstetrical, and genetic factors.
Methods:
A co-twin control design was employed to test whether prenatal phthalate exposure was associated with children's neurocognitive development. We collected information from 97 mother-twin pairs enrolled in the Wuhan Twin Birth Cohort between March 2016 and October 2018. Fourteen phthalate metabolites were measured in maternal urine collected at each trimester. Neurodevelopmental differences in twins at the age of two were examined as the outcome of interest. Multiple informant model was used to examine the covariate-adjusted associations of prenatal phthalate exposure with mental development index (MDI) and psychomotor development index (PDI) scores assessed at 2 years of age based on Bayley Scales of Infant Development (Second Edition). This model also helps to identify the exposure window of susceptibility.
Results:
Maternal urinary levels of mono-2-ethyl-5-oxohexyl phthalate (MEOHP) (β = 1.91, 95% CI: 0.43, 3.39), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) (β = 1.56, 95% CI: 0.33, 2.79), and the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) (β = 1.85, 95% CI: 0.39, 3.31) during the first trimester showed the strongest and significant positive associations with intra-twin MDI difference. When stratified with twin chorionicity, the positive associations of monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), mono-n-butyl phthalate (MBP), monobenzyl phthalate (MBzP), individual DEHP metabolites, and ∑DEHP exposure during pregnancy with intra-twin neurodevelopmental differences were more significant in monochorionic diamniotic (MCDA) twins than those in dichorionic diamniotic (DCDA) twins.
Conclusions:
Neurodevelopmental differences in MCDA twins were strongly associated with prenatal phthalate exposure. Our findings warrant further confirmation in longitudinal studies with larger sample sizes.
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