Demographics of study population and median concentrations of analytes in maternal and cord samples
The maternal, gestational, and neonatal characteristics of the study population are reported in . A total of 49 women with term pregnancies were included in this study. Of these, 38 were African-American, 3 were Hispanic, and 8 were Caucasian, non-Hispanic. Approximately 65% of the women had vaginal deliveries, while 32% were delivered by caesarean-section. The majority of the women, per design of the parent study, were nulliparous (90%) and, on average, young (mean age 20.5 years) with a self-reported pre-pregnancy body mass index (BMI) of mean 25.9 kg/m2. Mean gestational age at delivery was 39 weeks. Maternal and neonatal characteristics did not differ by whether the delivery was vaginal or by caesarean-section (data not shown).
Descriptive characteristics of the study sample
Analyte concentrations in maternal and cord samples
Medians for the sex steroids and proteins measured in both maternal and cord samples are presented in . For most steroid and protein measures, maternal concentrations were equivalent to or higher than cord concentrations, with the exception of A4, E3, P, and PRL, which were higher in the fetal circulation. The hormone and protein measures were analyzed by method of delivery (vaginal vs. Caesarean) and no significant differences were detected, except for higher cord E2 concentrations associated with vaginal deliveries (data not shown).
Median concentrations of hormones and proteins in maternal and mixed cord serum samples from uncomplicated pregnancies
Correlation between the same analyte in the maternal and cord circulation
Overall, the only analyte that showed moderate correlation between the maternal and cord circulations was T (r=0.47, p=0.006). A4, IGF-1, C-peptide, and leptin were weakly correlated between maternal and cord samples; all other hormones and proteins analyzed exhibited no correlation ().
Spearman correlations of maternal and mixed cord serum hormone and protein concentrations in uncomplicated pregnancies.
Patterns of correlation among analytes in the maternal and fetal circulation
The results in and demonstrate multiple, positive correlations between hormones and protein analytes in the maternal and fetal circulations, respectively. When comparing correlations among maternal and cord measures, several consistent patterns were evident. For the most part, the steroid sex hormones were moderately to highly correlated with each other. IGF-1, IGF-2, and IGFBP-3 were also correlated with each other (r=0.42–0.81) and, in general, with the estrogens.
Spearman correlations among hormone and protein concentrations in maternal serum from uncomplicated pregnancies
Spearman correlations among hormone and protein concentrations in mixed cord serum from uncomplicated pregnancies
There also were patterns that differed between the maternal and cord measures. Surprisingly, cord A4 was significantly correlated with all other cord measures (r=0.38–0.66), except PRL, IGF-2, and C peptide. P and PRL were correlated with members of the IGF axis in maternal samples but not at all in cord samples. Among angiogenic factors, maternal PLGF and sFlt-1 were associated with the maternal sex steroid hormones E2 and P (r=0.38–0.52) while, in the cord, sFlt-1 correlated with cord sex steroid hormones A4 and T (r=0.53–0.72).
Associations of pregnancy characteristics with maternal and cord analytes
Univariate analysis demonstrated that only a few maternal or neonatal characteristics were independently associated with any of the hormones or angiogenic factors (). Birth weight was positively correlated with cord T (r=0.44) and inversely correlated with maternal IGF-1 (r= −0.32) and IGFBP-3 (r= −0.31). Maternal pre-pregnancy weight (r=0.36), weight gain (r=0.39), and offspring birth weight (r=0.30) were correlated with maternal leptin. Maternal age was positively correlated with maternal IGF-2 (r=0.29) but inversely correlated with maternal C-peptide (r=−0.38). Placental weight was inversely correlated with maternal IGFBP-3 (r=−0.42) and birth length was positively correlated with maternal PlGF (r=0.29). When these same associations were examined in linear regression models including gestational age and additional maternal or neonatal characteristics associated with the analyte in univariate analyses, the only associations that remained significant were the inverse associations of maternal IGFBP-3 with placental weight and IGF-1 with birth weight, as well as the positive associations of maternal leptin with maternal weight and weight gain.
Associations with offspring gender also were evaluated in models including gestational age and maternal or neonatal characteristics that were significantly associated with the analyte in univariate analyses. Maternal A4 (p=0.07), E3 (p=0.07), P (p=0.01), sFlt-1 (p=0.04), and PlGF (p=0.03), as well as cord T (p=0.03) were all higher in pregnancies with males than females. For steroid hormones, maternal A4, E3, P, and cord T were approximately 21%, 84%, 68%, and 126% higher, respectively, in pregnancies with male compared to female offspring. Among angiogenic factors, maternal sFlt-1 and PlGF were 46% and 161% higher, respectively, in pregnancies with male compared to female offspring.
Although there was little diversity in the study population with respect to race, we conducted exploratory analyses of potential differences in hormone and protein concentrations between African-Americans and Caucasians, given prior findings that have shown racial differences particularly with steroid hormones. As with offspring gender, analyses including race were adjusted for gestational age and maternal or neonatal characteristics that were significantly associated with the analyte in univariate analysis. In the present data, maternal T (p=0.04) and A4 (p=0.04) were higher in African-Americans than Caucasians. Cord IGF-1 (p=0.06) was higher in Caucasians than in African-Americans. The few Hispanic individuals in this analysis had maternal A4 and T concentrations similar to those in Caucasians but cord IGF-1 levels were more similar to those in African-Americans. There were no differences in angiogenic factor measurements by race/ethnicity in this population.