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Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors.

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), ?4-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, ?4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, ?4-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.

SUBMITTER: Keelan JA

PROVIDER: S-EPMC3423422 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors.

Keelan Jeffrey A JA Mattes Eugen E Tan HaiWei H Dinan Andrew A Newnham John P JP Whitehouse Andrew J O AJ Jacoby Peter P Hickey Martha M

PloS one 20120820 8

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 ...[more]

PMID: 22916165

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Project description:ObjectiveNo validated biomarker at birth exists to predict which newborns will develop severe hyperbilirubinemia. This study's primary aim was to build and validate a prediction model for severe hyperbilirubinemia using umbilical cord blood bilirubins (CBB) and risk factors at birth in neonates at risk for maternal-fetal blood group incompatibility. This study's secondary aim was to compare the accuracy of CBB to the direct antigen titer.MethodsInclusion criteria for this prospective cohort study included: ≥35 weeks gestational age, mother with blood type O and/or Rh negative or positive antibody screen, and <24 hours of age. The primary outcome was severe hyperbilirubinemia, defined as phototherapy during the initial hospital stay. Secondary outcomes were a total serum bilirubin concentration >95th and >75th percentile during the initial hospital stay. The predictive performance and accuracy of the two tests (CBB and direct antigen titer) for each outcome was assessed using area under a receiver-operating characteristic curve (AUC), sensitivity, and specificity.ResultsWhen compared to neonates who did not receive phototherapy (n = 463), neonates who received phototherapy (n = 36) had a greater mean CBB ± standard deviation (2.5 ± 0.7 vs. 1.6 ± 0.4 mg/dL, p<0.001). For every 0.3 mg/dL increase in CBB, a neonate was 3.20 (95% confidence interval, 2.31-4.45), 2.10 (1.63-2.70), and 3.12 (2.44-3.99) times more likely to receive phototherapy or have a total serum bilirubin concentration >95th and >75th percentile, respectively. The AUC ± standard error (95% confidence interval) for CBB for phototherapy and a total serum bilirubin concentration >95th and >75th percentile was 0.89 ± 0.03 (0.82-0.95), 0.81 ± 0.04 (0.73-0.90), and 0.84 ± 0.02 (0.80-0.89), respectively. However, the AUC for gestational age and maternal Asian race for these outcomes was only 0.55 ± 0.05 (0.45-0.66), 0.66 ± 0.05 (0.56-0.76), and 0.57 ± 0.04 (0.05-0.64), respectively. When the CBB was combined with gestational age and maternal Asian race, the AUC for a total serum bilirubin concentration >95th percentile improved to 0.87 ± 0.03 (0.81-0.92) (p = 0.034 vs. the model with CBB only and p<0.001 vs. the model with clinical risk factors only). In a sub-group of subjects (n = 189), the AUC for the direct antigen titer for phototherapy was 0.64 ± 0.06 (0.52-0.77) with a 52% sensitivity and 77% specificity. In contrast, a CBB cut-point of 1.85 mg/dL was 92% sensitive and 70% specific for phototherapy with an AUC of 0.87 ± 0.04 (0.80-0.95).ConclusionCBB, in combination with gestational age and maternal race, may be a useful, non-invasive test to predict shortly after birth which neonates will develop severe hyperbilirubinemia.

Project description:BackgroundUmbilical cord blood could serve as useful source of blood markers enabling more efficient and reliable prenatal and neonatal diagnostics. MicroRNAs (miRNAs) are ubiquitous in body fluids where they were used for detecting and monitoring various physiological and pathological conditions. In this descriptive study, we aimed to identify changes in miRNA expression profiles associated with basic maternal somatic and epidemiological characteristics.MethodsStudy is based on 24 mothers from the Pilot phase of CELSPAC: TNG (Central European Longitudinal Studies of Parents and Children: The Next Generation) study. Cord blood was collected at time of delivery and global miRNA profiling was performed using microRNA Ready-to-use PCR Human Panel I+II TaqMan microarrays. Expression profiles were statistically evaluated in relation to maternal age, BMI, pregnancy weight gain, blood type, Rh factor status, allergies during pregnancy, addictive substance abuse and smoking status.ResultsWe analyzed expression of 752 human mature miRNAs in 24 samples of umbilical cord blood. For all maternal characteristics tested we described a specific signature of significantly deregulated miRNAs (P < 0.05). Analysis revealed seven miRNA associated with maternal age (three increased and four decreased in women younger than 35 years), 14 miRNAs associated with BMI status (five miRNAs increased and nine miRNAs decreased in women with BMI > 25) and nine miRNAs associated with maternal weight gain during pregnancy (eight miRNAs increased, and one miRNA decreased in women with weight gain < 12 kg). Additionally, 17 miRNAs correlated to blood type (two miRNAs decreased in blood type A, 11 increased in blood type B, two miRNAs increased in blood type AB and two miRNAs increased in blood type 0) and 17 miRNAs to Rh status of mother. We also detected seven miRNAs deregulated in umbilical cord blood of women with allergy (four increased and three decreased in women with allergy), four miRNAs associated to addictive substance abuse status (two up- and two downregulated in women with addictive substance abuse) and eight miRNAs associated with maternal cigarette smoking during pregnancy.ConclusionsWe successfully described differences in miRNA profiles in umbilical cord blood associated with basic characteristics connected with mother. Our data suggest that miRNAs in umbilical cord blood are detectable and associated with a wide range of maternal characteristics. These results indicate that miRNAs could potentially serve, and should be studied, as biomarkers for screening and diagnosis of pregnancy-associated complications and pathologies.

Project description:BACKGROUND:Investigators have hypothesized that omega-3 fatty acid supplementation may modulate the immune response. However, available evidence is conflicting. We performed this study to investigate the effect of prenatal eicosapentaenoic acid (EPA)- and docosahexaenoic acid (DHA)-rich fish oil supplementation on maternal and fetal cytokine production. METHODS:This study is a secondary analysis of a randomized controlled trial designed to assess whether prenatal EPA- or DHA-rich fish oil supplementation would prevent perinatal depressive symptoms among women at risk. Enrolled participants received EPA-rich fish oil (1060 mg EPA plus 274 mg DHA), DHA-rich fish oil (900 mg DHA plus 180 mg EPA) or soy oil placebo. Maternal venous blood was collected at enrollment (12-20 weeks gestation) and after supplementation (34-36 weeks gestation). Umbilical cord blood was collected at delivery. We analyzed stored plasma specimens for 16 human cytokines using multiplex immunoassays. Maternal and cord blood cytokine levels were compared among the treatment groups. Associations of serum DHA and EPA with maternal and cord blood cytokines were explored via regression analysis. RESULTS:We enrolled 126 women, of whom 118 completed the trial. Prenatal supplementation with EPA-rich fish oil significantly lowered maternal IL6, IL15, and TNFα concentrations. However, supplementation with DHA-rich fish oil had no significant effect on maternal cytokine profiles. Maternal serum DHA fraction was significantly associated with IL1α, and maternal serum DHA and EPA fractions were significantly associated with IL 10 concentrations after supplementation. Compared with placebo, supplementation with EPA- or DHA-rich fish oils had no significant effect on cord blood cytokine concentrations. CONCLUSIONS:Prenatal supplementation with EPA-rich fish oil significantly reduced levels of several inflammatory cytokines in maternal plasma, while prenatal DHA-rich fish oil had no significant effect on cytokine concentrations. Supplementation with EPA- and DHA- rich fish oil had no significant effect on umbilical cord blood cytokine concentrations. TRIAL REGISTRATION:Clinical Trial Registration: registration number NCT00711971 7/7/2008.

Dataset Information

Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors.

Publications

Androgen concentrations in umbilical cord blood and their association with maternal, fetal and obstetric factors.

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