ECEESPE2025 Oral Communications Oral Communications 16: Reproductive and Developmental Endocrinology Part 2 (6 abstracts)
Exposure to phthalates at the masculinization programming window is associated with longer anogenital distance and reduced birth weight in healthy children: A COPANA cohort study of 589 infants
Gylli Mola 1,2 , Margit Bistrup Fischer 1,2 , Emilie Zeuthen 1,2 , Hanne Frederiksen 1,2 , Jørgen Petersen 1,2 , Anders Juul 1,2,3 , Casper Hagen 1,2,3 & Anna-Maria Andersson 1,2
1Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 2International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; 3Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
JOINT3920
Background: Phthalates are used widely in several consumer products. Previous studies suggest that phthalate exposure during the male programming window (MPW), gestational week (GW) 8-14, may disrupt gonadal and genital development with persistent effects. Most consistently, prenatal exposure to phthalates has been associated with reduced anogenital distance (AGD) in human and animal studies.
Primary aim: Exploratory assessment of prenatal exposure to phthalates was associated with changes in reproductive parameters in infancy.
Design: Prospective, observational pregnancy and birth cohort; The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222).
Setting: Copenhagen University Hospital - Rigshospitalet (2020-2022).
Methods: Healthy, singleton pregnant women (n=685) were enrolled during the first trimester, and 589 (287 boys) infants were examined. Metabolites of 15 phthalates and two substitutes were measured by LC-MS/MS in maternal urine samples collected in the first trimester (GW 14.1±1.8 (mean±SD)). Third-trimester ultrasound (GW 29-34): Fetal AGD and estimated fetal weight (EFW). Child examination (boys, mean age 3.1 months; girls, mean age 3.5 months): AGD by TIDES method, penile width and length, anthropometrics.
Statistics: Linear regression adjusted for maternal age, BMI, education level, and parity. Non-normally distributed data were ln2-transformed.
Results: Prenatal exposure to several phthalates in the first trimester was associated with longer fetal and infant AGD (raw and adjusted for weight), Table 1. In addition, exposure was associated with increased penile width and length. Metabolites of five different phthalates were associated with reduced birth weight and length in boys.
| Phthalate (ln2) | Percent change | P value | Phthalate (ln2) | Percent change | P value | |
| Girls | Boys | |||||
| Fetal outcomes | ||||||
| Fetal AGD, mm | MEP | 21.3 | 0.018 | ΣDiBPm | -35.9 | 0.022 |
| ΣDiNPm | 39.1 | 0.005 | ΣDnBPm | -32.0 | 0.049 | |
| ΣDINCHm | 26.8 | 0.004 | ||||
| Fetal AGD/EFW, mm/g | MEP | 15.8 | 0.003 | MMP | 27.0 | 0.046 |
| MnHxP | 16.5 | 0.0007 | ||||
| ΣDiBPm | 14.5 | 0.033 | ||||
| ΣDnBPm | 23.2 | 0.003 | ||||
| ΣDINCHm | 12.7 | 0.021 | ||||
| EFW, g (ln2) | MnHxP | -1.1 | 0.046 | ΣDiBPm | -1.9 | 0.041 |
| ΣDnBPm | -2.1 | 0.022 | ||||
| Infant outcomes | ||||||
| AGDaf/ as, mm | ΣDINCHm | 40.3 | 0.009 | ΣDnBPm | 94.0 | 0.049 |
| AGDaf/ as per body weight, mm/kg | MnHxP | 3.8 | 0.041 | MBzP | 9.6 | 0.022 |
| ΣDEHTPm | 4.9 | 0.036 | ΣDiBPm | 12.6 | 0.019 | |
| ΣDINCHm | 5.4 | 0.016 | ΣDnBPm | 11.0 | 0.045 | |
| AGDac/ ap per body weight, mm/kg | ΣDEHTPm | 11.2 | 0.004 | MBzP | 12.1 | 0.044 |
| af=ano-fourchette. ac=ano-clitoral. as=ano-scrotal. ap=ano-penile. | ||||||
Conclusion: The results suggest endocrine-disrupting effects of phthalate exposure affecting early fetal development. We provide unique human data on phthalate exposure at MPW indicating androgenic effects. This may explain discrepancies with previous studies reporting reduced AGD after phthalate exposure in fetal life.
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