Delivery mode is associated with persistent changes of steroid hormone levels in boys at three months of age - a COPANA study of 508 healthy infants

Andrea Bogehave; Gylli Mola; Norus Emilie Zeuthen; Hanne Frederiksen; Karin Sundberg; Rom Ane Lilleore; Hanne Kristine Hegaard; Anders Juul; Casper P. Hagen; Fischer Margit Bistrup

doi:10.1530/endoabs.110.RC3.5

RC3.5

Prev Next

Section Contents Cite

Endocrine Abstracts (2025) 110 RC3.5 | DOI: 10.1530/endoabs.110.RC3.5

ECEESPE2025 Rapid Communications Rapid Communications 3: Metabolism and Aging (6 abstracts)

Delivery mode is associated with persistent changes of steroid hormone levels in boys at three months of age - a COPANA study of 508 healthy infants

Andrea Bøgehave ^1,2 , Gylli Mola ^1,2 , Emilie Zeuthen Norus ^1,2 , Hanne Frederiksen ^1,2 , Karin Sundberg ³ , Ane Lilleøre Rom ^4,5 , Hanne Kristine Hegaard ^4,6 , Anders Juul ^1,2,6 , Casper P. Hagen ^1,2,6 & Margit Bistrup Fischer ^1,2

Author affiliations

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; ³Center of Fetal Medicine and Pregnancy, Department of Obstetrics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; ⁴Department of Gynaecology, Fertility and Obstetrics, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark; ⁵Research Unit of Gynaecology and Obstetrics, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; ⁶Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

JOINT192

Background: Epidemiological studies suggest that delivery mode is associated with numerous long-term conditions, including atopy and asthma, potentially associated with altered levels of cortisol. Emergency caesarean section is associated with increased levels of cortisol in the umbilical cord, and animal studies suggests that perinatal stress cause persistent changes in hypothalamic-pituitary-adrenal (HPA) axis activity. However, human data on the long-term impact of delivery mode on steroid hormone profiles during infancy remain limited.

Objectives: To evaluate the association between delivery mode and circulating levels of steroid hormone metabolites in healthy infants at three months of age.

Design: Prospective, observational pregnancy and birth cohort; The Copenhagen Analgesic Study (COPANA) (ClinicalTrials.gov NCT04369222).

Setting

Copenhagen University Hospital – Rigshospitalet, Denmark (2020-2022).

Methods: Healthy, singleton pregnant women recruited early in pregnancy (n=685) and 589 infants (287 boys) were examined (age 3.31 months (0.67) mean (±SD)). Infants with available hormone values and information on delivery mode (n=508) were included and stratified according to delivery mode: 1) emergency caesarean section (ECS), n=50 (26 males), 2) vaginal delivery (VD), n=437 (207 males), 3) elective caesarean section (ELCS), n=21 (10 males). Steroid hormones: progesterone (PRO), 11-deoxycorticosterone (DOC), corticosterone (CORT), aldosterone (ALDO), 17alfa-hydroxypregnenolone (17-OHPreg), 17-hyroxyprogesterone (17-OHP), 11-deoxycortisol (11-DOC), cortisol, cortisone, dehydroepiandrosterone (DHEA), androstenedione (Adion), testosterone (T) and dihydrotestosterone (DHT) were analyzed (LC/MS-MS), and age-related standard deviation scores (SDS) were calculated. Statistics: Kruskal-Wallis (KW) and Mann-Whitney U (MWU) tests.

Results: In boys, ECS was associated with consistently lower levels of: CORT, 17-OHPreg, 17-OHP, 11-DOC and cortisol compared to both VD and ELSC at three months of age (Table 1). Delivery mode was not associated with steroid hormone levels in girls.

Table 1. Levels of steroid hormones at three months of age in boys (n=243) according to delivery mode
Hormone SDS	ECS (n=26)	VD (n=207)	ELCS (n=10)	KW P-value	Pairwise MWU P-value
	Median (IQR)	Median (IQR)	Median (IQR)		ECS/VD	VD/ELCS	ECS/ELCS
CORT	-0.64 (-1.87-1.64)	0.22 (-2.74-1.96)	0.68 (1.73-1.29)	0.034	0.026	0.239	0.023
17-OHPreg	-0.49 (-1.92-1.03)	-0.07 (-3.43-3.57)	0.56 (-1.70-2.19)	0.015	0.034	0.068	0.006
17-OHP	-0.38 (-1.77-1.01)	0.24 (-3.30-2.27)	0.55 (-0.88-1.53)	0.006	0.005	0.190	0.007
11-DOC	-0.46 (-1.99&unix2013;1.29)	0.17 (-2.93-2.71)	0.58 (-1.19-1.23)	0.026	0.013	0.376	0.031
Cortisol	-0.38 (-1.71&unix2013;1.79)	0.34 (-2.48-2.46)	0.81 (-0.67-1.60)	0.008	0.019	0.058	0.003

Conclusions: The present study suggests that delivery mode has long-term impact on HPA axis activity. Whether effects on steroid hormone levels contribute to adverse long-term health outcomes associated with delivery mode remains to be examined.