TY - JOUR
T1 - Periconception bisphenol and phthalate concentrations in women and men, time to pregnancy, and risk of miscarriage
AU - Blaauwendraad, Sophia M.
AU - Boxem, Aline J.
AU - Gaillard, Romy
AU - Kahn, Linda G.
AU - Lakuleswaran, Mathusa
AU - Sakhi, Amrit Kaur
AU - Bekkers, Eline L.
AU - Mo, Zixuan
AU - Spadacini, Larry
AU - Thomsen, Cathrine
AU - Steegers, Eric AP
AU - Mulders, Annemarie GMGJ
AU - Jaddoe, Vincent WV
AU - Trasande, Leonardo
N1 - Publisher Copyright: © 2025 The Authors
PY - 2025/8/1
Y1 - 2025/8/1
N2 - Background: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates might lead to adverse fertility and early pregnancy outcomes. Methods: This study was embedded in the Generation R Next Study, a population-based cohort study from preconception onwards. Urinary phthalate and bisphenol concentrations were assessed in the preconception period (938 women), defined as the period in which couples were actively trying to conceive, and early pregnancy (1,366 women and 1,202 men, mean gestational age at sampling 8·6 weeks). Time to pregnancy and miscarriage were assessed using questionnaires and ultrasounds. Subfertility was defined as the inability to conceive within 12 months or need for assisted reproductive technologies. Findings: Higher preconception urinary bisphenol S (BPS) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (mCOCH) concentrations in women were associated with longer time to pregnancy. Higher preconception mono-[(2-carboxymethyl)hexyl] phthalate, mono-2-ethyl-5-oxohexyl phthalate (mEOHP), mono-(7-carboxy-n-heptyl)phthalate (mCHpP), and mono benzyl phthalate (mBzBP) were associated with shorter time to pregnancy, and higher mono-2-ethyl-5-hydroxyhexyl phthalate (mEHHP), mEOHP, and mBzBP with lower odds of subfertility. In men, higher early pregnancy BPS, mCHpP, mono-4-methyl-7-hydroxyoctyl phthalate, mono-4-methyl-7-oxooctyl phthalate, and mono-ethyl phthalate were associated with shorter time to pregnancy or lower odds of subfertility. Higher preconception or early pregnancy BPS, phthalic acid, and mCHpP in women were associated with lower odds of miscarriage, whereas higher mono-carboxy-isoctyl phthalate, mCOCH, and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cxmPHxP) with higher odds of miscarriage (all p-values <0·05). Interpretation: Preconception and early pregnancy exposure to bisphenols and phthalates may affect couple fertility. Our results should be considered as hypothesis generating and replicated in future studies, possibly including repeated chemical measurements and mixture analysis.
AB - Background: Exposure to endocrine-disrupting chemicals such as bisphenols and phthalates might lead to adverse fertility and early pregnancy outcomes. Methods: This study was embedded in the Generation R Next Study, a population-based cohort study from preconception onwards. Urinary phthalate and bisphenol concentrations were assessed in the preconception period (938 women), defined as the period in which couples were actively trying to conceive, and early pregnancy (1,366 women and 1,202 men, mean gestational age at sampling 8·6 weeks). Time to pregnancy and miscarriage were assessed using questionnaires and ultrasounds. Subfertility was defined as the inability to conceive within 12 months or need for assisted reproductive technologies. Findings: Higher preconception urinary bisphenol S (BPS) and cyclohexane-1,2-dicarboxylic acid-monocarboxy isooctyl ester (mCOCH) concentrations in women were associated with longer time to pregnancy. Higher preconception mono-[(2-carboxymethyl)hexyl] phthalate, mono-2-ethyl-5-oxohexyl phthalate (mEOHP), mono-(7-carboxy-n-heptyl)phthalate (mCHpP), and mono benzyl phthalate (mBzBP) were associated with shorter time to pregnancy, and higher mono-2-ethyl-5-hydroxyhexyl phthalate (mEHHP), mEOHP, and mBzBP with lower odds of subfertility. In men, higher early pregnancy BPS, mCHpP, mono-4-methyl-7-hydroxyoctyl phthalate, mono-4-methyl-7-oxooctyl phthalate, and mono-ethyl phthalate were associated with shorter time to pregnancy or lower odds of subfertility. Higher preconception or early pregnancy BPS, phthalic acid, and mCHpP in women were associated with lower odds of miscarriage, whereas higher mono-carboxy-isoctyl phthalate, mCOCH, and mono-2-(propyl-6-carboxy-hexyl)-phthalate (cxmPHxP) with higher odds of miscarriage (all p-values <0·05). Interpretation: Preconception and early pregnancy exposure to bisphenols and phthalates may affect couple fertility. Our results should be considered as hypothesis generating and replicated in future studies, possibly including repeated chemical measurements and mixture analysis.
UR - http://www.scopus.com/inward/record.url?scp=105003922139&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2025.121712
DO - 10.1016/j.envres.2025.121712
M3 - Article
C2 - 40311909
AN - SCOPUS:105003922139
SN - 0013-9351
VL - 278
JO - Environmental Research
JF - Environmental Research
M1 - 121712
ER -