Combined association of early exposure to long-chain n-3 polyunsaturated fatty acids, mercury and selenium with cognitive performance in 1-year-old infants

Abstract

BackgroundPrevious studies on long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) and infant neurodevelopment did not consider effect modifications of mercury (Hg) and selenium (Se). ObjectivesTo examine the joint association of prenatal LCn3PUFAs, Hg and Se with infant cognitive performance, and to explore whether DNA methylation may explain this potential association. MethodsA total of 484 newborns were enrolled from the Shanghai Birth Cohort with available data on cord blood LCn3PUFA, nail Hg and Se during 2015–2016. Cord blood LCn3PUFA concentrations were assessed by gas chromatography, and nail Hg and Se concentrations were measured using clippings collected within 6 months of birth by inductively coupled plasma mass spectrometry. Five aspects of infant neurodevelopment (communication, gross motor, fine motor, problem-solving, and personal-social skills) were assessed using the Age and Stage Questionnaire (ASQ) at ages 6 and 12 months. Multivariable-adjusted generalized estimating equations models were performed to examine the associations between cord blood LCn3PUFA concentrations and ASQ test scores, and these associations were stratified by nail Hg and Se levels. Epigenome-wide DNA methylation in cord blood was compared in a random subgroup consisting of 19 infants from the highest and 21 from the lowest decile of LCn3PUFA concentrations. ResultsLCn3PUFAs were not significantly associated with any ASQ test scores. However, in the subgroup with lower Hg (<median 0.13 ppm) and higher Se (≥median 0.87 ppm) levels, infants with higher LCn3PUFA concentrations had higher ASQ scores indicating better performance in gross motor skills [quartile 4 vs. 1: mean difference = 7.78; 95% confidence interval=(3.47, 12.09); Ptrend<0.01; Pinteraction = 0.03]. Additionally, twenty CpG sites were differentially methylated when comparing high to low LCn3PUFA groups. ConclusionThe association of prenatal LCn3PUFA concentrations with infant neurodevelopment, particularly gross motor skills, may be observed among infants with high Se and low Hg levels.