Maria Assens1, Hanne Frederiksen2, Jørgen Holm Petersen3, Torben Larsen4, Niels E Skakkebæk2, Anders Juul2, Anna-Maria Andersson2, Katharina M Main2. 1. Department of Growth and Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: mariaassens@dadlnet.dk. 2. Department of Growth and Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark. 3. Department of Growth and Reproduction and EDMaRC, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, 2100 Copenhagen, Denmark; Section for Biostatistics, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5, 1014 Copenhagen, Denmark. 4. Department of Obstetrics and Gynecology, Holbaek Hospital, University of Copenhagen, Smedelundsgade 60, 4300 Holbaek, Denmark.
Abstract
BACKGROUND: Biobank serum samples from longitudinal mother-child cohorts have been used to estimate prenatal exposures to endocrine disrupting chemicals (EDCs). However, the knowledge about variations in serum concentrations of non-persistent chemicals during pregnancy is limited. OBJECTIVE: To describe the within- and between-person variations in serum concentrations of non-persistent chemicals and changes over trimesters, including phthalate metabolites, parabens, phenols, and UV filters. DESIGN: Longitudinal study with repeated blood samples from 128 healthy pregnant women during pregnancy. SETTING: Population based study at a University Hospital in Copenhagen 1999-2001. METHODS: 503 repetitive prenatal serum samples from 128 pregnant women taken at approximately gestational week 12, 20, 30 and 40 were analyzed for 7 UV filters, 32 metabolites of 15 phthalate diesters, 8 phenols and 7 parabens by LC-MS/MS. RESULTS: Ten of 32 phthalate metabolites from six out of 15 phthalate diesters, two of seven parabens, two of eight phenols and three of seven UV filters were measurable in more than half of the serum samples. Of these chemicals, mono‑ethyl phthalate (MEP), mono‑iso‑nonyl phthalate (MiNP), mono‑iso‑decyl phthalate (MiDP), 4‑methylbenzophenone (4‑MBP), 4‑hydroxybenzoephenone (4‑HBP) and n‑propyl paraben (nPrP) had intra-class correlation coefficients (ICC) above 0.4 in both adjusted and unadjusted analyses (0.427-0.795), indicating low within-person variation. The serum concentration of UV filters 4‑MBP and 4‑HBP significantly increased throughout pregnancy, also after adjusting for seasonal variation (4‑HBP: effect estimates 0.142-0.437, p < 0.001. 4‑MBP: effect estimates 0.156-0.458, p < 0.002.). CONCLUSION: MEP, MiNP, MiDP, 4‑MBP, 4‑HBP and nPrP were measurable in >50% of serum samples and showed low within-person variation. Thus, it is possible with acceptable accuracy to evaluate maternal exposure during pregnancy for these non-persistent chemicals using one or more biobank serum samples. The here presented adjusted ICC values can in addition be applied as adjustment of residual variation in future studies that evaluate outcomes related to prenatal exposures.
BACKGROUND: Biobank serum samples from longitudinal mother-child cohorts have been used to estimate prenatal exposures to endocrine disrupting chemicals (EDCs). However, the knowledge about variations in serum concentrations of non-persistent chemicals during pregnancy is limited. OBJECTIVE: To describe the within- and between-person variations in serum concentrations of non-persistent chemicals and changes over trimesters, including phthalate metabolites, parabens, phenols, and UV filters. DESIGN: Longitudinal study with repeated blood samples from 128 healthy pregnant women during pregnancy. SETTING: Population based study at a University Hospital in Copenhagen 1999-2001. METHODS: 503 repetitive prenatal serum samples from 128 pregnant women taken at approximately gestational week 12, 20, 30 and 40 were analyzed for 7 UV filters, 32 metabolites of 15 phthalate diesters, 8 phenols and 7 parabens by LC-MS/MS. RESULTS: Ten of 32 phthalate metabolites from six out of 15 phthalate diesters, two of seven parabens, two of eight phenols and three of seven UV filters were measurable in more than half of the serum samples. Of these chemicals, mono‑ethyl phthalate (MEP), mono‑iso‑nonyl phthalate (MiNP), mono‑iso‑decyl phthalate (MiDP), 4‑methylbenzophenone (4‑MBP), 4‑hydroxybenzoephenone (4‑HBP) and n‑propyl paraben (nPrP) had intra-class correlation coefficients (ICC) above 0.4 in both adjusted and unadjusted analyses (0.427-0.795), indicating low within-person variation. The serum concentration of UV filters 4‑MBP and 4‑HBP significantly increased throughout pregnancy, also after adjusting for seasonal variation (4‑HBP: effect estimates 0.142-0.437, p < 0.001. 4‑MBP: effect estimates 0.156-0.458, p < 0.002.). CONCLUSION: MEP, MiNP, MiDP, 4‑MBP, 4‑HBP and nPrP were measurable in >50% of serum samples and showed low within-person variation. Thus, it is possible with acceptable accuracy to evaluate maternal exposure during pregnancy for these non-persistent chemicals using one or more biobank serum samples. The here presented adjusted ICC values can in addition be applied as adjustment of residual variation in future studies that evaluate outcomes related to prenatal exposures.