Abstract
The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account.
Highlights
Median concentrations of TT were significantly (62%) higher in males compared to females (P,0.0001), as were free testosterone (FT) and bioavailable testosterone (BioT) levels (55–71%, P,0.0001); median Sex hormone binding globulin (SHBG) concentrations were modestly elevated in males (10.6%, P,0.0001)
This study of umbilical cord androgen concentrations measured by LC-MS/MS in an unselected population of male and female neonates is the largest to date and provides for the first time robust data on the relationship between fetal and obstetrics factors and circulating androgen and SHBG levels at birth
To the best of our knowledge, only three previous studies have applied this technology to the measurement of steroid levels in cord blood, none of which investigated the influence of key fetal or obstetric factors
Summary
Fetal androgen concentrations have been the subject of considerable interest over several decades due to their association with maternal metabolic disorders [1,2,3], later life cancer risk [4,5,6] and reproductive [7,8,9,10,11,12] and behavioral/neurodevelopmental problems [13,14,15,16,17,18]. Androgen concentrations in umbilical cord blood have been widely used as a marker of prenatal androgen exposure, with most published studies using radioimmunoassay (RIA) to measure steroid concentrations [1,3,5,8,11,19,20,21,22,23,24,25,26]. While androgen assays are sometimes tested and validated for use in female or pediatric samples, their suitability for umbilical cord blood analysis is usually unverified. Cord blood contains an abundance of unusual and potentially cross-reacting steroids and their conjugates, in addition to other interfering substances [32,33]; it is critical that steroid assays are properly validated prior to use in the analysis of cord blood
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
