Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

<div><p>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.</p> </div

Total testosterone (TT), Δ⁴-androstenedione (A4), dehydroepiandrostenedione (DHEA) and SHBG concentrations, plus calculated free testosterone (FT) and bioavailable testosterone (BioT) levels in umbilical cord serum samples from male and female neonates.

<p>Concentrations of all analytes were significantly different between the sexes (<i>P</i><0.0001, Mann-Whitney test) with the exception of A4.</p

Linear regression analysis of the relationships between gestational age at delivery and cord blood androgen and SHBG concentrations in 803 neonates (males and females combined).

<p>The linear regression coefficients (R²) are indicated on each graph. All correlations remained statistically significant (<i>P</i><0.0001) after controlling for obstetric factors.</p

Effects of labor on androgen and SHBG concentrations.

<p>A) SHBG, A4 and DHEA concentrations are significantly increased with labor (n = 83 no labor, 718 with labor); B) TT and FT, but not BioT, levels are significantly reduced with labor. Data shown are median ± interquartile range (IQR). Note that the FT values have been multiplied by 100 to allow presentation on the same graph. *, <i>P</i><0.05; **, <i>P</i><0.01; ***, <i>P</i><0.0005 by Kruskal Wallis test.</p

Linear regression analysis of cord androgen and SHBG concentrations in 803 neonates (males and females combined).

<p>The linear regression coefficients (R²) are indicated on each graph. All correlations were statistically significant (A, B and D: <i>P</i><0.0001; C: <i>P</i><0.0005) and remained significant after controlling for multiple maternal and obstetric factors in multiple regression analysis.</p

Demographic and obstetric characteristics of the study cohort by fetal sex.

a<p>Mean+/−SD;</p>b<p>income <$24,000 per annum;</p>c<p>smoking defined as one or more cigarettes per day;</p>d<p>includes both elective and in-labor sections;</p>e<p>all deliveries excluding elective Cesarean-section deliveries;</p>f<p>stage 1 and 2 labor combined;</p>g<p>the number of pregnancies included for each category or variable are indicated in parentheses;</p>h<p>NS,</p><p>not significant (<i>P</i>>0.05 by Mann-Whitney U-test for group median comparisons or Fisher's Exact test for categorical variables).</p