COPANA - The Copenhagen Analgesic Study
2020 -
Background
Studies in animal models and in vitro have raised suspicions that some types analgesics (painkillers) may have an impact on the development of the fetal gonads. However, there are no human studies that specifically assess the effect of medication on gonadal development and sex differentiation.
Aims and Study Design
In COPANA we establish a longitudinal mother-child (and father) cohort with the main aim to investigate whether intake of mild analgesics during pregnancy is associated with early markers of effects on gonadal development and sex differentiation of the fetus. A total of 590 families (healthy mothers, biological fathers and their newborns) are included.
Mothers are recruited early in pregnancy and asked to report biweekly on medicine use through an electronic questionnaire. Blood and urine are collected during pregnancy from the mothers, from their children aged 3 months, and once from the father. Anogenital distance of male and female fetuses will be determined prenatally (by ultrasound) as well as postnatally. Around 3 months of age (during minipuberty) a detailed clinical examination of the child is performed, which incl. assessement of the external genitalia.
As secondary aims we will also investigate the associations of maternal use of anti-fungal medicine during pregnancy as well as maternal exposure to known or suspected endocrine disruptors to early markers of reproductive development.
Mothers are recruited early in pregnancy and asked to report biweekly on medicine use through an electronic questionnaire. Blood and urine are collected during pregnancy from the mothers, from their children aged 3 months, and once from the father. Anogenital distance of male and female fetuses will be determined prenatally (by ultrasound) as well as postnatally. Around 3 months of age (during minipuberty) a detailed clinical examination of the child is performed, which incl. assessement of the external genitalia.
As secondary aims we will also investigate the associations of maternal use of anti-fungal medicine during pregnancy as well as maternal exposure to known or suspected endocrine disruptors to early markers of reproductive development.
Status
Recruitment, sampling and examinations were completed by November 2022, followed by biochemical and chemical analyses of blood and urine samples collected from mother and child. Data analysis and publication of results from the COPANA study is still ongoing. A biobank of samples from the COPANA cohort has been established allowing for future analyses.
In 2024 a follow-up study of the COPANA children was initiated with focus on Neurobehavioral Development in Toddlers and Preschoolers - NeuroTOP.
The Research Team behind COPANA
COPANA is a collaboration between EDMaRC/Dept. of Growth and Reproduction at Rigshospitalet (Casper Hagen, Anders Juul, Margit Fischer, Gylli Mola, Anna-Maria Andersson, Hanne Frederiksen, Kristian Almstrup) and Department of Obstetrics and Section of fetal medicine at Rigshospitalet (Peter Damm, Karin Sundberg, Hanne Kristine Hegaard, Rikke Nue Møller, Ane Lilleøre Rom).
Key EDMaRC researchers in the project:
Casper Hagen (PI)
MD, PhD
MD, Post doc
Gylli Mola
MD, PhD-student
MDSc, Professor
MSc, PhD, Senior Researcher
Publications
Guttesen LF, Mola G, Frederiksen H, Sundberg K, Hegaard HK, Juul A, Hagen CP, Fischer MB. Associations of Maternal Polyendocrine Metabolic Ovarian Syndrome with Offspring Ovarian Activity in Minipuberty. Fertil Steril. 2026 Oct, 5:S0015-0282(26)01801-7. doi: 10.1016/j.fertnstert.2026.09.015
Fischer MB, Mola G, Sundberg K, Scheel L, Wraae KB, Rom AL, Frederiksen H, Anderson RA, Assens M, Andersson AM, Priskorn L, Petersen JH, Hegaard HK, Main KM, Kristensen DM, Juul A, Hagen CP. Fetal exposure to paracetamol is associated with altered markers of ovarian development and reduced uterine volume in girls: the COPANA study. Hum Reprod Open. 2026 Sep 8;2026(3):hoag073. doi: 10.1093/hropen/hoag073.
Mola G, Draskau MK, Jørgensen A, Chalmel F, Melau C, Evrard B, Mandrup K, Hegaard H, Hueg TK, Frederiksen H, Flück CE, Andersson AM, Juul A, Almstrup K, Fischer MB, Svingen T, Hagen CP. Prenatal antifungal exposure disrupts fetal steroidogenesis and is associated with persistent effects in children. Commun Med (Lond). 2026 Jul 31;6(1):473. doi: 10.1038/s43856-026-01815-z
Fischer MB, Mola G, Scheel L, Wraae KB, Rom AL, Frederiksen H, Johannsen TH, Almstrup K, Sundberg K, Hegaard HK, Juul A, Hagen CP. Cohort profile: The Copenhagen Analgesic Study-The COPANA cohort. Paediatr Perinat Epidemiol. 2024 May;38(4):370-381. doi: 10.1111/ppe.13058.
Fischer MB, Mola G, Priskorn L, Scheel L, Hegaard HK, Sundberg K, Frederiksen H, Andersson AM, Juul A, Hagen CP. Longitudinal Evaluation of Fetal and Infant AGD in Healthy Children: Association With Penile Size, Testosterone, and DHT. J Clin Endocrinol Metab. 2024 Nov 18;109(12):3087-3095. doi: 10.1210/clinem/dgae342.
Fischer MB, Mola G, Rom AL, Frederiksen H, Johannsen TH, Sundberg K, Hegaard HK, Juul A, Hagen CP. Ovarian and Uterine Morphology in Minipuberty: Associations With Reproductive Hormones: a COPANA Study of 302 Girls. J Clin Endocrinol Metab. 2025 Mar 17;110(4):1015-1022. doi: 10.1210/clinem/dgae678.