Combined maternal risk factors and the Quadruple test to predict late-onset preeclampsia in pregnant Thai women.

BACKGROUND: This study aimed to evaluate the predictive power of a model combining maternal risk factors and the Quadruple screen test for late-onset preeclampsia (PE). METHODS: All pregnant women that received the Quadruple test for Down syndrome at 15+ 0-20+ 6 weeks' gestation were recruited. Maternal serum α-fetoprotein, ß-human chorionic gonadotropin, unconjugated estriol, and inhibin A were measured as multiples of the median. A logistic regression model was used to identify predictors associated with late-onset PE with severe features. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the model's predictive ability. RESULTS: Fifty-five of the 2,000 pregnant women had PE, and 31 of 55 women had late-onset PE. Multivariate analysis identified maternal age ≥ 35 years, inhibin A, history of previous PE, history of infertile, cardiac disease, chronic hypertension, and thyroid disease as significant risk factors. The area under the curve of the receiver operating characteristic curve was 0.78. The likelihood ratio to predict late-onset PE was 49.4 (total score > 60). CONCLUSIONS: Our model combining serum inhibin A with maternal risk factors was useful in predicting late-onset PE. Close monitoring of these patients is recommended.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening.

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays. The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Ethnic-specific reference range affects the efficacy of quadruple test as a universal screening for Down syndrome in a developing country.

OBJECTIVE: To evaluate the efficacy of the quadruple test for potential use as a Thai national policy for Down syndrome (DS) screening and establish an accurate equation for risk estimation of Down syndrome based on gestational age, weight and the ethnic-specific reference range of our population. METHODS: A prospective study was conducted on singleton pregnancies at 14 to 21 weeks of gestation to evaluate the efficacy of quadruple DS screening using the automatically calculated Western European descent factor (WF) in our population and the impact of screening using a specific Thai ethnic factor as well as to establish an equation for the risk estimation of DS based on gestational age, weight and a local Thai ethnic factor to correct for the impact of ethnic factor on the screening efficacy. RESULTS: Of a total of 5,515 women, 12 cases of DS and 8 cases of other aneuploidies were found. The detection rate, false positive rate and specificity were 75.0%, 9.1% and 90.9%, respectively, by automatic calculation with the widely used WF; the screening efficacy was lower when used in Asian populations than in other studies. The best-fitted regression equation of serum quadruple screening of AFP, free ß-hCG, uE3 and inhibin A was established by adjustment for gestational age (GA) in days, maternal weight and our Thai-specific ethnic reference range which was created for this study. Calculations with our Thai-specific ethnic model gave a better detection rate of 83.3%, a false positive rate of 9.6% and specificity of 90.4%. CONCLUSION: The serum quadruple test had a lower detection rate than expected when the risk estimation was based on the WF reference range. The serum quadruple test using WF had significantly different levels when corrected with our ethnic-specific factor. Using our local ethnic specific model could increase the detection rate of DS screening in Thailand with a minimal increase in false positive rates. Our findings indicate that DS screening should be adjusted with an appropriate individual ethnic factor when used for national screening.

Risk of Severe Maternal Morbidity or Death in Relation to Prenatal Biochemical Screening: Population-Based Cohort Study.

OBJECTIVE: This study aimed to examine whether prenatal biochemical screening analytes are associated with an increased risk of severe maternal morbidity (SMM) or maternal mortality. STUDY DESIGN: This population-based cohort study includes all women in Ontario, Canada, who underwent prenatal screening from 2001 to 2011. Increasing fifth percentiles of the multiple of the median (MoM) for alphafetoprotein (AFP), total human chorionic gonadotropin, unconjugated estriol (uE3), dimeric inhibin-A (DIA), and pregnancy-associated plasma protein A were evaluated. An abnormally high concentration (>95th percentile MoM) for each analyte, individually and combined, was also evaluated. The main outcome assessed was the adjusted relative risk (aRR) of SMM or maternal mortality from 20 weeks' gestation up to 26 weeks thereafter. RESULTS: Among 748,972 pregnancies, 11,177 resulted in SMM or maternal mortality (1.5%). Except for uE3, the aRR of SMM or maternal mortality increased in association with increasing fifth percentiles of the MoM for all analytes. AFP (aRR: 2.10; 95% confidence interval [CI]: 1.97-2.25) and DIA (aRR: 2.33; 95% CI: 1.98-2.74) > 95th versus ≤ 5th percentile of the MoM were especially associated with SMM or death. CONCLUSION: Women with abnormally high concentrations of certain prenatal biochemical analytes may be at a higher risk of SMM or death in pregnancy or postpartum.

Relations between second-trimester aneuploidy screening results and prediction of labour induction success in term pregnancies.

We aimed to assess whether the second-trimester maternal serum markers could be used for the prediction of labour induction success. This prospective study enrolled women planned labour induction at term. Women were assigned to one of two groups: vaginal prostaglandin or balloon dilatation. All patients were evaluated for Bishop score, maternal serum oestriol, human chorionic gonadotropin and progesterone at the time of second-aneuploidy screening. The total successful rate for induction of labour was 63.9% in both groups. Maternal serum oestriol multiple of median (MoM) values were significantly lower among the caesarean section group compared to the vaginal delivery group (p < .001). A MoM value of 0.74 for oestriol was associated with a sensitivity of 75.9%, specificity of 41.0%, a positive predictive value of 76.6% and a negative predictive value of 58.0% for a successful induction of labour. Oestriol had a good performance in the prediction of successful induction of labour at term.IMPACT STATEMENTWhat is already known on this subject? Induction of labour is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Previous studies have reported that a decreased progesterone/oestradiol ratio and increased maternal plasma oestriol levels are associated with successful labour. What the results of this study add? The results of this study showed that second-trimester oestriol multiple of median (MoM) value provide a significant contribution to the efforts of the prediction of successful induction of labour in term pregnancy, having a sensitivity of 69.8%, specificity of 92.4%, positive predictive value of 83.3% and negative predictive value of 82.5%.What the implications are of these findings for clinical practice and/or further research? This finding can be used as an additional method for prediction of labour induction as well as multiparity and Bishop score. This adds new valuable data to the literature which could be used for systematic reviews and for implementing guidelines and protocols on labour induction.

Evaluation of sporadic bovine alkaline phosphatase interference in the Beckman Access unconjugated estriol (uE3) assay affecting maternal serum screening results.

OBJECTIVES: Bovine alkaline phosphatase (BALP) mediated interference is a potential issue in the Beckman Access unconjugated estriol (uE3) assay. As the uE3 assay is a component of second trimester maternal serum screening characterizing this interference is essential for delivering accurate trisomy 18 and trisomy 21 risks. DESIGN AND METHODS: Residual serum samples (n = 517) were measured by two different lots of uE3 assay. Scavenger BALP (sBALP) was added to all samples to remove potential BALP dependent interference and assessed using both lots of uE3 reagent. RESULTS: BALP mediated interference was observed in similar frequency in both lots of reagent (~3%), although the patterns of positive and negative interference differed between the lots. Pretreatment with sBALP improved lot-to-lot comparison. The presence of BALP related interference was not related to the concentration of endogenous human alkaline phosphatase. The use of polyethylene glycol and sBALP treatment appeared to mitigate BALP mediated interference equally well, and resulted in concordance in measured uE3 concentrations between reagent lots. Additionally, heterophile antibody interference was observed in two samples affected with BALP interference, and the heterophile antibody interference was resolved by both PEG and heterophile antibody blocking reagent treatment, but not sBALP treatment. While the maternal screen numeric risk for affected samples changed, the risk classification changed from a negative to positive screen in two samples. CONCLUSIONS: Interference in the uE3 assay has the potential to affect maternal serum risk calculations in different reagent lots, and pretreatment of samples with scavenger BALP or PEG should be considered in cases of unexplained uE3 concentrations.

Quad test for fetal aneuploidy screening as a predictor of small-for-gestational age fetuses: a population-based study.

BACKGROUND: To identify the relationship between quadruple test for aneuploidy screening (alpha-fetoprotein: AFP; free beta-human chorionic gonadotropin: b-hCG; unconjugated estriol: uE3 and inhibin-A: IHA) and fetal growth restriction and to construct predictive models for small-for-gestational-age (SGA) fetuses. METHODS: Women who underwent quadruple test for aneuploidy were followed-up for final outcomes. The multiples of the median (MoMs) of the four biochemical markers for the SGA group and those of normal fetuses were compared. The models for predicting SGA by the individual biomarkers and their combination were constructed using binary logistic regression analysis, and their diagnostic performances in predicting SGA were determined. RESULTS: Of 10,155 eligible pregnant women, 578 (5.7%) and 9577 (94.3%) had SGA and normal growth, respectively. High levels of AFP, b-hCG and IHA but low levels of uE3 significantly increased the risk of SGA. The constructed predictive equations had predictive performance for SGA, with areas under the receiver-operated characteristic curve of 0.724, 0.655, 0.597, 0.664 and 0.754 for AFP, b-hCG, uE3, IHA, and the combination, respectively. CONCLUSION: The quad test for aneuploidy screening could also be used as a predictor of SGA, without extra-effort and extra-cost.

Diagnostic accuracy of maternal serum multiple marker screening for early detection of gestational diabetes mellitus in the absence of a gold standard test.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse diabetic complications for both mother and child during pregnancy. The common Gold Standard (GS) for diagnosis of GDM is 75 g oral glucose tolerance test (OGTT) during 24-28 gestational weeks which seems a little late for any proper intervention. This study aimed to employ the Bayesian latent class models (LCMs) for estimating the early diagnostic power of combination of serum multiple marker in detecting GDM during 14-17 weeks of gestation. METHODS: Data from a sample of 523 pregnant women who participated in gestational diabetes screening tests at health centers affiliated to Shahid Beheshti University of Medical Sciences in Tehran, Iran from 2017 to 2018 were used. The beta-human chorionic gonadotropin (ß-hCG), unconjugated estriol (uE3), and alfa-fetoprotein (AFP) values were extracted from case records for all participants. The Bayesian LCMs were applied for estimating sensitivity, specificity, and area under receiver operating characteristic curve (AUC) of combining the three biomarkers' results in the absence of GS, adjusting for maternal age and body mass index. RESULTS: The mean (standard deviation) maternal age of the participants was 28.76 (±5.33) years. Additionally, the mean (standard deviation) BMI was 24.57 (±3.22) kg/m2. According to the Bayesian model, the cSensitivity, cSpecificity, and cAUC for the optimal composite diagnostic test were estimated as 94% (95% credible interval (CrI) [0.91-0.99]), 86% (95% CrI [0.80-0.92]), and 0.92 (95% CrI [0.87-0.98]), respectively. CONCLUSIONS: Overall, the findings revealed that the combination of uE3, AFP, and ß-hCG results might be considered as an acceptable predictor for detecting GDM with a rather high level of accuracy in the early second trimester of pregnancy without a GS.

Is maternal serum inhibin A a good predictor in preterm labor? - Experience from a community hospital in Taiwan.

BACKGROUND: We aimed to determine whether inhibin A could be a reliable and accurate predictor of preterm birth, and discuss the possible pathogenic processes of inhibin A leading to preterm birth. METHODS: A retrospective cohort study was conducted on consecutive singleton pregnant women who underwent the second-trimester quad screen test at a gestational age of 15-20 weeks at Keelung Chang-Gung Memorial Hospital from March 2011 to May 2015. Data including maternal characteristics and pregnancy outcomes were collected from an electric medical record database. Data regarding pregnancy terminations before a gestational age of 24 weeks and regarding pregnancies that involved chromosomal or congenital anomalies were excluded from this analysis. One-way analysis of variance was used to compare second-trimester α-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A in women with preterm deliveries versus those with term deliveries. RESULTS: Although a total of 935 women with singleton pregnancies were enrolled, pregnancy outcome and complete maternal data were obtained from only 770 (82.3%)of them. In total, 687 (89.2%) women delivered at or after 37 weeks of gestation and 83 (10.8%) women delivered before 37 weeks of gestation. The results showed that the inhibin A level was significantly increased in the preterm labor group (p = 0.009). A cutoff inhibin A value above 2.25 was identified statistical significantly in the preterm labor group. CONCLUSIONS: From our results, an inhibin A level above 2.25 multiples of the median in the quad screen test may be associated with preterm labor afterward. Closely monitoring for uterine contractions or cervical length measurement in the second trimester may be indicated in patients with unexplained elevated inhibin A levels.

Estriol serum levels in new and chronic users of vaginal estriol cream: A prospective observational study.

AIMS: To quantify estriol serum concentrations in "new" and "chronic users" of topical estriol cream using quantitative liquid chromatography tandem mass spectrometry. METHODS: In this singlecentre prospective observational study, postmenopausal women with urogynaecological complaints were enrolled: 40 had not used topical estriol previously ("new users") and 50 had been applying estriol cream for more than 12 weeks ("chronic users"). In "new users," serum estriol levels were measured at baseline and after 12 weeks use. Estriol cream 1 mg/g was used daily for 3 weeks, then twice weekly with applicator (group 1A) or digitally (group 1B) or three times per week digitally (group 1C). "Chronic users" applied the cream twice (n = 7) or three (n = 43) times per week. Serum samples were taken in the morning after using cream the previous night. The main outcome measures were estriol serum concentrations in "new" and "chronic users" of estriol cream. RESULTS: Baseline serum estriol concentrations were less than 5 pmol/L in all 40 "new users." At 12 weeks, the 12-hour serum estriol levels ranged from less than 5 to 494 pmol/L (median 22.8; Interquartile range [IQR] 9.2-108.5). Seven "new users" had levels more than 100 pmol/L. Most of the 50 "chronic users" also had 12-hour levels less than 100 pmol/L (median 15.1 pmol/L [IQR 2.7-33.9]: three had levels more than 100 pmol/L. CONCLUSIONS: This study reports serum estriol concentrations in a large number of "new" and "chronic users" of vaginal estriol cream, employing a novel highly sensitive and specific technique. Overall, the results are reassuring: 87% had 12-hour estriol levels less than 100 pmol/L.

Association between Maternal Serum Hormones along the Maternal-Fetal Hypothalamic-Pituitary-Adrenal Axis and Successful Vaginal Delivery Measured Prior to Labor Induction.

OBJECTIVE: This study aimed to evaluate if maternal serum hormones along the maternal-fetal hypothalamic-pituitary-adrenal (HPA) axis, when drawn prior to labor induction, differed between women who delivered vaginally and those who underwent cesarean. STUDY DESIGN: This was a prospective observational study at a single perinatal center performed from August 2017 to May 2018. Nulliparous women with uncomplicated singleton pregnancies ≥39 weeks had maternal serum collected prior to induction. Corticotrophin-releasing hormone (CRH) was measured by ELISA; dehydroepiandrosterone sulfate (DHEA-S), cortisol, estriol (E3) estradiol (E2), and progesterone (P4) were measured by chemiluminescent reaction. Mean analyte concentrations as well as three ratios (E2/P4, E3/P4, and E2/E3) were compared between women who had a vaginal versus cesarean delivery. Logistic regression was used to model the relationship between CRH and the odds of vaginal birth. We estimated that a sample size of 66 would have 90% power to detect a 25% difference in mean CRH levels assuming a vaginal:cesarean ratio of 2:1 with a baseline CRH concentration of 140 (standard deviation = 36) pg/mL. RESULTS: Of the 88 women who had their serum analyzed, 27 (31%) underwent cesarean. Mean maternal serum CRH levels were similar between the vaginal delivery and cesarean groups (122.6 ± 95.2 vs. 112.3 ± 142.4, p = 0.73). Similarly, there were no significant differences in any other maternal serum analytes or ratios. Logistic regression showed a nonsignificant odds ratio for successful vaginal birth (p = 0.69) even when evaluating only the 16 women who had a cesarean for an arrest disorder (p = 0.08). CONCLUSION: In low-risk nulliparous women undergoing full-term labor induction, there were no differences noted in a broad array of other maternal-fetal HPA-axis hormones between women who had a vaginal or cesarean delivery.

Prenatal sex hormones and behavioral outcomes in children.

Abnormal sex hormone levels in utero have been associated with child behavioral problems, but it is unclear if normal variation in prenatal sex hormones is associated with subsequent behavior in childhood. We assessed maternal sex hormones, including serum estrone (E1), estradiol (E2), estriol (E3), free testosterone (FT), and total testosterone (TT), during early pregnancy (gestational week 6-21 (mean = 11.1)) and evaluated child behavior at ages 4-5 using the Behavioral Assessment System for Children (BASC-2) and Social Responsiveness Scale (SRS-2) in 404 mother/child pairs (211 girls, 193 boys) within The Infant Development and Environment Study, a multi-site pregnancy cohort study. Associations between hormones and composite scores were evaluated using multiple linear regressions in both sexes combined, and separate models assessed effect modification by sex with the addition of interaction terms. A 10-fold increase in maternal FT or TT was associated in both sexes with a 4.3-point (95 % CI: 0.5, 8.2) or 4.4-point (0.8, 8.0) higher BASC-2 internalizing composite T score, respectively. In addition, a 10-fold increase in FT or TT was associated with a 3.8-point (0.04, 7.5) or 4.0-point (0.5, 7.5) higher behavioral symptoms index composite score. In models evaluating effect modification by sex, a 10-fold increase in E1 was associated with a 4.3-point (1.2, 7.4) decrease in adaptive skills composite score in girls only (interaction p = 0.04). We observed associations between testosterone and internalizing behaviors and behavioral symptoms index in both sexes, as well as a female-specific association between E1 and adaptive skills. Sex hormones during pregnancy may play a key role in influencing later-life behavior, and additional studies should further examine different periods of susceptibility to hormonal signals.

In utero and postnatal programing of dehydroepiandrosterone sulfate (DHEAS) in young adult women.

Fetal adrenal-derived OH-DHEAS is the primary precursor for maternal estriol, an abundant, human, placental estrogen. We measured maternal pregnancy estriol as a marker of fetal adrenal function + placenta capacity to synthesize estriol. We hypothesized that maternal estriol is directly correlated with the adrenal hormone, DHEAS, in young adult women. We tested this hypothesis in a subset of women in the Child Health and Development Studies (351 of 470 eligible). 176 of these had serum samples collected at ages 27-30 for DHEAS assays, archived maternal pregnancy serum for estriol assays, and childhood growth data. In regression analyses, both maternal estriol and accelerated growth in middle childhood were independently, directly associated with DHEAS (+19% for quartile 4 versus quartile 1 of estriol, 95%CI=+ 2%, +36% and +12% for quartile 4 versus quartile 1 for middle childhood growth, 95%CI= +3%, +21%). Adrenal function may be programmed in utero and middle childhood with long-term consequences.

A-FABP and oestrogens are independently involved in the development of breast cancer.

We previously reported that postmenopausal obese women exhibit increased levels of circulating adipocyte fatty acid binding protein (A-FABP), which is associated with breast cancer (BC) development. In postmenopause, increased oestrogen levels are reported to be associated with increased BC risk. Herein, we assessed if oestrogens, including oestrone (E1), oestradiol (E2) and oestriol (E3), are associated with A-FABP in the obesity-related BC development. We collected 249 serum samples from women with or without BC and measured serum levels of E1, E2, E3 and A-FABP. Considering all subjects, E1 and E2 but not E3 levels were significantly higher in pre- than in postmenopause individuals. E3 and E1 levels were higher in non-obese than in obese women. When samples were separated by BC status, E2 levels were significantly higher, while E1 and E3 levels were significantly lower in postmenopausal obese than non-obese women without BC. These differences based on body mass index (BMI) were not observed among women with BC. E3 levels were higher in obese women with BC than those without. A-FABP levels were significantly higher in postmenopausal obese women regardless of BC status. In addition, A-FABP was not associated with E1, E2 or E3. Altogether, our data suggest that A-FABP is independently regulated by obesity and menopausal status compared to oestrogens, thus playing a unique role in the development of BC.

What you need to know about maternal-fetal medicine.

The field of pediatric Surgery now encompasses fetal Surgery. The purpose of this article is to review aspects of antepartum care pertinent to the fetal and pediatric surgeon. We summarize antepartum screening, methods to assess the fetus, gestational disorders and variants of umbilical cord insertion sites and the placenta.

Second Trimester Serum Biomarker Screen for Fetal Aneuploidies as a Predictor of Preterm Delivery: A Population-Based Study.

OBJECTIVE: To determine the association between second-trimester serum Down syndrome screening (alpha-fetoprotein [AFP] free beta-human chorionic gonadotropin [b-hCG] unconjugated estriol [uE3]) and preterm birth and to create predictive models for preterm birth. METHODS: Secondary analysis on a prospective database of pregnancies undergoing second-trimester screen with complete follow-up. The multiples of medians (MoM) of the biomarkers were compared between the group of term, preterm (< 37 weeks), early preterm (< 34 weeks), and very early preterm (< 32 weeks) delivery. Predictive models were developed based on adjusted MoMs and logistic regression and diagnostic performances in predicting preterm birth were determined. RESULTS: Of 20,780 pregnancies, 1,554 (7.5), 363 (1.7), and 158 (0.8%) had preterm, early preterm, and very early preterm birth respectively. High levels of AFP and b-hCG but low levels of uE3 were significantly associated with higher rates of preterm, early preterm and very early preterm delivery. The predictive models had diagnostic performance in predicting preterm birth with the areas under the ROC curve of 0.688, 0.534, 0.599, and 0.718 for AFP, b-hCG, uE3, and combined biomarkers respectively. CONCLUSION: The second trimester Down syndrome screening could also be used as a tool of risk identification of preterm birth in the same test, without extra-effort and extra-cost.

Predictors of Steroid Hormone Concentrations in Early Pregnancy: Results from a Multi-Center Cohort.

Objectives To identify factors predicting maternal sex steroid hormone concentrations in early pregnancy. Methods The Infant Development and the Environment Study recruited healthy pregnant women from academic medical centers in four US cities. Gold standard liquid chromatography-tandem mass spectrometry was used to measure maternal sex steroids concentrations (total testosterone [TT], free testosterone [FT], estrone [E1], estradiol [E2], and estriol [E3] concentrations) in serum samples from 548 women carrying singletons (median = 11.7 weeks gestation). Women completed questionnaires on demographic and lifestyle characteristics. Results In multivariable linear regression analyses, hormone concentrations varied in relation to maternal age, body mass index (BMI), race, and parity. Older mothers had significantly lower levels of most hormones; for every year increase in maternal age, there was a 1-2% decrease in E1, E2, TT, and FT. By contrast, each unit increase in maternal BMI was associated 1-2% lower estrogen (E1, E2, E3) levels, but 1-2% higher androgen (TT, FT) concentrations. Hormone concentrations were 4-18% lower among parous women, and for each year elapsed since last birth, TT and FT were 1-2% higher (no difference in estrogens). Androgen concentrations were 18-30% higher among Black women compared to women of other races. Fetal sex, maternal stress, and lifestyle factors (including alcohol and tobacco use) were not related to maternal steroid concentrations. Conclusions for Practice Maternal demographic factors predict sex steroid hormone concentrations during pregnancy, which is important given increasing evidence that the prenatal endocrine environment shapes future risk of chronic disease for both mother and offspring.

Associations of serum markers screening for Down's syndrome with pregnancy outcomes: A Chinese retrospective cohort study.

BACKGROUND: We examined the associations between Down's serum screening analytes and pregnancy outcomes in Chinese women. METHODS: A retrospective cohort study of 2470 pregnant women was conducted. Maternal serum triple tests (AFP, fß-hCG, uE3), maternal characteristics and pregnancy outcomes were recorded from our prenatal screening and hospitalization information system, respectively. RESULTS: The elevated concentration of uE3 in the early-second trimester was associated with increased risk of LGA infants and macrosomia, decreased risk of PE and small SGA infants (for LGA: OR: 1.34, 95% CI: 1.09-1.65; for macrosomia: OR:1.39, 95% CI: 1.08-1.78; for PE: OR: 0.61, 95% CI: 0.40-0.95; for SGA: OR: 0.35, 95% CI: 0.25-0.49). The increased ratio of AFP/uE3 was associated with reduced risk of GDM in the study populations (BMI ≥ 25; OR: 0.96, 95% CI: 0.0.93-1.00). The higher ratio of AFP/fß-hCG + uE3 associated with increased risk of SGA infants and ICP in these subjects (BMI ≥ 25) was also observed (for SGA: OR: 1.11, 95% CI: 1.03-1.18; for ICP: OR: 1.27, 95% CI: 1.06-1.53). CONCLUSIONS: Down's serum screening analytes were associated with pregnancy outcomes in Chinese population and might provide an alternative tools for risk estimates on these unfavorable outcomes.

Plasma progesterone, estradiol, and unconjugated estriol concentrations in twin pregnancies: Relation with cervical length and preterm delivery.

INTRODUCTION: The aim of this study was to examine the association between plasma hormone concentrations, cervical length, and preterm delivery in twin pregnancies, including the effect of progesterone treatment. MATERIAL AND METHODS: This study included 191 women pregnant with twins from a randomized placebo-controlled trial. A baseline blood sample was collected at 18-24 weeks before treatment with vaginal progesterone (n = 95) or placebo pessaries (n = 96), and 167 (87.4%) women had a second sample collected after 4-8 weeks of treatment. At baseline, 155 (81.2%) women had their cervical length measured. Progesterone, estradiol, and unconjugated estriol concentration was measured, and the association between hormone concentrations, cervical length, and gestational age at delivery was examined. Hormone concentrations were compared in the placebo and progesterone group. Statistical analysis included Spearman's rho, Mann-Whitney U test, Cuzick's test for trends, and linear regression analyses. RESULTS: A short cervical length was associated with preterm delivery. Cervical length and hormone concentrations were not associated (Spearman's rho; progesterone -.05, estradiol .04, estriol .08). Decreasing gestational age at delivery was associated with higher progesterone and estradiol concentrations at baseline (P trend; progesterone 0.04, estradiol 0.02) but not in the second sample or in the weekly change between samples. Progesterone treatment did not increase the progesterone concentration. CONCLUSIONS: Plasma concentrations of progesterone, estradiol, and unconjugated estriol at 18-24 weeks are not associated with cervical length or preterm delivery in twin pregnancies. Vaginal progesterone treatment does not increase the circulating progesterone concentration in twin pregnancies. Cervical length, but not hormone concentration, is predictive of preterm delivery in twin gestations.

Prenatal diagnosis of chromosomal polymorphisms: most commonly observed polymorphism on Chromosome 9 have associations with low PAPP-A values.

INTRODUCTION: To identify the prevalence and types of fetal chromosomal polymorphisms in pregnant women and to examine possible associations with screening test parameters. MATERIALS AND METHODS: Fetal chromosomal polymorphism rate was investigated in pregnant women who had been implemented for invasive prenatal test in a tertiary reference center in Thrace Region of Turkey. Fetal chromosomal polymorphisms were determined and their effects on screening tests' parameters were investigated. Possible differences in the first and second-trimester screening test parameters between women; with fetal chromosomal polymorphism who had screening test results (Group 1) and those with a normal karyotype (Group 2) were evaluated. RESULTS: Fetal chromosomal polymorphism prevalence was 5.3% (n = 101). The most common polymorphisms were identified on chromosome 9, 1, and 16 [54.5% (n = 55); 8.9% (n = 9), and 6.9% (n = 7), respectively]. The most common polymorphic variant was 9qh+ (n = 23; 22.8%). Among the screening test parameters, significantly lower pregnancy-associated plasma protein-A (PAPP-A) (p = .028) and higher unconjugated estriol (uE3) (p = .019) values were found in Group 1. In patients having fetuses with polymorphic variants on chromosome 9, a significantly lower PAPP-A values were observed compared to women with other fetal polymorphic variants (p = .048) or women having fetuses with normal karyotype (p = .007). CONCLUSIONS: Lower PAPP-A and higher uE3 levels were observed in women having fetuses with chromosomal polymorphisms, which might affect screening test results. Lower PAPP-A levels were apparent in women having fetuses with polymorphism on chromosome 9.