Gestational acrylamide exposure and biomarkers of fetal growth: Probing the mechanism underlying the association between acrylamide and reduced fetal growth.

• Acrylamide was positively associated with placental NGF and cord blood free T3. • Glycidamide was positively associated with cord blood free T3. • Acrylamide was negatively associated with cord blood TSH and free T4/T3. • Glycidamide was negatively associated with cord blood insulin and free T4/T3. • Insulin seemed to mediate the association between glycidamide and birth weight. Four epidemiological studies have shown a negative association between prenatal acrylamide exposure and birth size. In order to shed light on the possible underlying mechanism(s), we analysed associations between acrylamide biomarkers and biomarkers related to fetal growth. In newborns of the ENVIR ON AGE birth cohort (n ranges from 215 to 434), we investigated the association between prenatal acrylamide exposure (acrylamide and glycidamide hemoglobin adduct levels in cord blood) and thyroid hormones (TSH, T3, T4 and the ratio of T4 to T3 in cord plasma), insulin-related factors (cord plasma insulin and IGF1, and placental IGF2), neurotrophins (cord plasma BDNF, and placental NGF, NT3 and NT4), and cord plasma homocysteine and progesterone, using multiple linear regression analysis. In addition, we investigated whether the biomarkers mediated the associations between prenatal acrylamide exposure and birth outcomes. We observed lower cord plasma TSH (−10.2% [95% CI: −15.0, −4.3]) and higher placental NGF levels (10.0% [95% CI 3.7, 17.4]) for a twofold increase of acrylamide adducts, a decrease in the ratio of cord plasma free T4 and free T3 with higher acrylamide and glycidamide adducts of −2.9% (95% CI: −5.7, −0.1) and −3.9% (95% CI: −6.2, −1.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively, and higher cord plasma free T3 with increases in both acrylamide and glycidamide adducts of 2.8% (95% CI: 0.2, 5.6) and 3.6% (95% CI: 0.8, 6.6) for a twofold increase in acrylamide and glycidamide adduct levels, respectively. Additionally, a twofold increase in glycidamide adducts was associated with lower cord plasma insulin levels, particularly among newborns of non-smoking mothers (−11.2% [95% CI: −19.5, −0.1]). Cord plasma insulin seemed to mediate the association between glycidamide adducts and birth weight. A decrease in cord plasma insulin levels may be (a marker of) a mechanism by which gestational acrylamide exposure is associated with decreased fetal growth. The possible health consequences of the associations between gestational acrylamide exposure and thyroid hormones and neurotrophins warrant future study. [ABSTRACT FROM AUTHOR]