Unconjugated Estriol Levels Research Articles

Early warning of low maternal unconjugated estriol level by prenatal screening for fetus with X-linked ichthyosis

Objective: To analyze the characteristic of prenatal serological screening in fetus with X-linked ichthyosis (XLI), and to explore the relationship between unconjugated estriol (uE3) levels and XLI. Methods: A total of 56 fetuses with Xp22.31 microdeletion indicated by prenatal diagnosis and 70 fetuses diagnosed with trisomy 21 and 26 fetuses with trisomy 18 in Henan Provincial People's Hospital and Affiliated Hospital of Weifang Medical College from September 2016 to June 2021 were collected. The multiples of median (MoM) values of uE3, alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) during the second trimester of pregnancy were retrospectively analyzed. Prenatal diagnosis was made by amniotic fluid karyotype analysis and genome copy number variant analysis, parent genetic verification and pathogenicity analysis were performed, and maternal and infant outcomes were followed up. Results: Of 56 pregnant women with fetal Xp22.31 microdeletion, 43 underwent serological screening during the second trimester of pregnancy, of which 42 were abnormal (39 male fetuses and 3 female fetuses). The median uE3 MoM value of 39 male fetuses [0.06 (0.00-0.21)] was lower than the normal value and significantly lower than that of fetuses with trisomy 21 [0.71 (0.26-1.27)] and fetuses with trisomy 18 [0.36 (0.15-0.84)], the difference was statistically significant (Z=99.96, P<0.001). While the MoM values of AFP and hCG were all within the normal range. Among the 56 fetuses carrying Xp22.31 microdeletion, 45 were male fetuses and 11 were female fetuses, and the deletion fragments all involved STS gene. Eighty-nine percent (50/56) were inherited from mother (49 cases) or father (1 case), and 11% (6/56) were de novo mutations. Follow-up showed 48 live births (38 males and 10 females) and 8 chose to terminate pregnancy (7 males and 1 female). Among the 38 male newborns, 37 presented with scaly skin changes from 1 to 3 months of age, and one had no clinical manifestations until 4 months after birth. Ten female newborns had no obvious clinical manifestations. Conclusions: The decrease levels of uE3 MoM on maternal serological screening is closely related to the higher risk of XLI in male fetuses. For pregnant women with low uE3 in serological screening or with family history of ichthyosis, in addition to chromosomal karyotype analysis, joint detection of genomic copy number variant analysis should be recommended.

Antenatal Antidepressant Prescription Associated With Reduced Fetal Femur Length but Not Estimated Fetal Weight

Antidepressants are among the most frequently prescribed medications during pregnancy and may affect fetal weight. Associations between antenatal antidepressant use and ultrasonographic measures of fetal development have rarely been examined. We hypothesized that the prescription of an antenatal antidepressant would be associated with lower estimated fetal weight (EFW). A retrospective analysis of routine ultrasonographic data extracted from electronic medical records was performed on a cohort of pregnant women with psychiatric diagnoses and grouped according to the presence of an antenatal antidepressant prescription (n = 32 antidepressant-prescribed and n = 44 antidepressant prescription-free). After stratifying for gestational age, comparisons included 13 ultrasonographic parameters, frequency of oligohydramnios and polyhydramnios and growth deceleration, and maternal serum protein markers assessed per routine care, including α-fetoprotein, free β-human chorionic gonadotropin, and unconjugated estriol levels, using t tests, nonparametric and Fisher tests, and effect sizes (ESs) were computed. No statistically significant EFW differences between groups at any time point were detected (P > 0.05). Antenatal antidepressant prescription was associated with lower femur length at weeks 33 to 40 (P = 0.046, ES = 0.75) and greater left ventricular diameter at weeks 25 to 32 (P = 0.04, ES = 1.18). No differences for frequency of oligohydramnios or polyhydramnios or growth deceleration were observed (P > 0.05). We did not detect group differences for maternal proteins (P > 0.05). Our evidence suggested a lack of association between antenatal antidepressant prescription and lower EFW but indicated an association with lower femur length and greater left ventricular diameter in mid-late gestation. Future research should examine the clinical implications of these findings.

Early pregnancy prediction of gestational diabetes mellitus risk using prenatal screening biomarkers in nulliparous women

AimsTo evaluate the clinical utility of first and second trimester prenatal screening biomarkers for early pregnancy prediction of gestational diabetes mellitus (GDM) risk in nulliparous women. MethodsWe conducted a population-based cohort study of nulliparous women participating in the California Prenatal Screening Program from 2009 to 2011 (n = 105,379). GDM was ascertained from hospital discharge records or birth certificates. Models including maternal characteristics and prenatal screening biomarkers were developed and validated. Risk stratification and reclassification were performed to assess clinical utility of the biomarkers. ResultsDecreased levels of first trimester pregnancy-associated plasma protein A (PAPP-A) and increased levels of second trimester unconjugated estriol (uE3) and dimeric inhibin A (INH) were associated with GDM. The addition of PAPP-A only and PAPP-A, uE3, and INH to maternal characteristics resulted in small, yet significant, increases in area under the receiver operating characteristic curve (AUC) (maternal characteristics only: AUC 0.714 (95% CI 0.703–0.724), maternal characteristics + PAPP-A: AUC 0.718 (95% CI 0.707–0.728), maternal characteristics + PAPP-A, uE3, and INH: AUC 0.722 (0.712–0.733)); however, no net improvement in classification was observed. ConclusionsPAPP-A, uE3, and INH have limited clinical utility for prediction of GDM risk in nulliparous women. Utility of other readily accessible clinical biomarkers in predicting GDM risk warrants further investigation.

Second-trimester maternal serum screening for fetal Down syndrome: As a screening test for hemoglobin Bart's disease: A prospective population-based study.

The purpose of this study is to determine the effectiveness of second-trimester maternal serum screening for Down syndrome as a screening test for fetal hemoglobin (Hb) Bart's disease among an unselected population. A secondary analysis of a large prospective database (20254 pregnancies) was conducted to compare the levels of maternal serum screening, alpha-fetoprotein (AFP), free beta-human chorionic gonadotropin, and unconjugated estriol between pregnancies with Hb Bart's disease and unaffected pregnancies. The median AFP levels were much higher among affected fetuses (1.96 vs 1.12 multiple of the median; P<.001), yielding a sensitivity of 81.6% and specificity of 86.4%. Thus, AFP measurement is effective in predicting fetal Hb Bart's disease among an unselected population when using a cutoff value of 1.5 multiple of the median. The serum free beta-human chorionic gonadotropin levels were slightly, but significantly, higher in the affected pregnancies, while the serum unconjugated estriol levels were minimally, but significantly, lower among the affected pregnancies. Second-trimester maternal serum AFP levels were significantly elevated in cases of fetal Hb Bart's disease. Pregnancies with unexplained elevated serum AFP levels in areas of high prevalence of Hb Bart's disease should always undergo a detailed ultrasound examination to detect any early signs of fetal anemia before development of hydrops fetalis.

Prediction of Gestational Diabetes Mellitus by Unconjugated Estriol Levels in Maternal Serum.

The aim of this study was to evaluate the association between maternal serum estriol levels, which are routinely measured in the first trimester of pregnancy, and adverse pregnancy outcomes including gestational diabetes. We performed a retrospective chart analysis of women who delivered between July 1, 2007, and December 31, 2009, at Kangnam CHA Medical Center in Seoul, Korea. Only patients with available estriol measurements during their pregnancies and complete follow-up data were included in the study. The effect of estriol on the incidence of adverse pregnancy outcomes was examined using multinomial logistic regression analysis with age and pre-pregnancy body mass index (BMI) as covariates. The total number of subjects was 1,553, the mean age was 32.9 ± 3.7 years, and the mean pre-pregnancy BMI was 21.2 ± 3.0 kg/m2. Unconjugated estriol > 95th percentile of the screened population or unconjugated estriol ≥ 2.0 MoM (Multiple of the Median) was significantly associated with an increased risk for developing gestational diabetes mellitus (GDM), after adjusting for age and pre-pregnancy maternal weight. High levels of unconjugated estriol in the maternal serum during the early second trimester of pregnancy are a useful predictor of GDM development.

Autism Spectrum Disorder Risk in Relation to Maternal Mid-Pregnancy Serum Hormone and Protein Markers from Prenatal Screening in California.

We examined prenatal screening markers and offspring autism spectrum disorder (ASD) using California statewide data on singleton births in 1996 and 2002. Second trimester levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and maternal serum alpha-fetoprotein (MSAFP) were compared between mothers of children with ASD (n = 2586) and of non-cases (n = 600,103). Adjusted odds ratios (AOR) were calculated by logistic regression. Lower uE3 (AOR for < 10th percentile vs. 25th-74th percentiles = 1.21, 95 % CI 1.06-1.37), and higher MSAFP (AOR = 1.21, 95 % CI 1.07-1.37 for > 90th percentile) were significantly associated with ASD. A U-shaped relationship was seen for hCG (AOR = 1.16, 95 % CI 1.02-1.32 for < 10th percentile; AOR = 1.19, 95 % CI 1.05-1.36 for > 90th percentile). Our results further support prenatal hormone involvement in ASD risk.

Association between isolated abnormal levels of maternal serum unconjugated estriol in the second trimester and adverse pregnancy outcomes

Objective: To determine the association between maternal serum unconjugated estriol (uE3) levels in the second trimester and adverse pregnancy outcomes.Patients and methods: The prospective database of our fetal Down screening program was assessed and reviewed for maternal serum uE3 levels. Pregnancies with medical diseases, abnormal levels of beta-human chorionic gonadotropin, alpha-fetoprotein and fetal chromosomal or structural abnormalities were excluded. The recruited women were categorized into three groups: high (>95th percentile), normal (5–95th percentile) and low (<5th percentile) uE3 levels.Results: Of 14 212 screened women, 9183 (high; 455, normal; 8271 and low; 457) levels group, were available for outcome analysis. The rates of most adverse outcomes, including preterm birth, low Apgar scores, fetal death, placental abruption, preeclampsia and gestational diabetes mellitus, of the high and normal groups were comparable. Nevertheless, low uE3 levels increased risk of fetal growth restriction (FGR) (RR: 2.36, 95% CI: 1.79–3.10) and low birth weight (LBW) (RR: 1.87, 95% CI: 1.45–2.39), but not preterm birth. Logistic regression analysis indicated that low uE3 level was an independent risk factor for FGR and LBW.Conclusions: High uE3 levels in the second trimester are not associated with poor outcomes, whereas low levels significantly increase risk of FGR and LBW but not other adverse outcomes.

Elevated Serum Level of IL-35 Associated with the Maintenance of Maternal-Fetal Immune Tolerance in Normal Pregnancy.

ObjectivesIL-35 is a novel inhibitory cytokine. In this study, we investigate the serum levels of inhibitory cytokines IL-35, IL-10 and TGF-β in both normal pregnancies and non-pregnant females, and whether IL-35 is associated with the pathogenesis of recurrent spontaneous abortion. We also try to elucidate the relationships of IL-35 with estrogen and alpha-fetoprotein (AFP).MethodsThe levels of IL-35, IL-10, TGF-β, estradiol (E2), unconjugated estriol (uE3) and AFP were analyzed in 120 normal pregnancies, 40 women suffering recurrent spontaneous abortion, 40 postpartum healthy women and 40 non-pregnant women by enzyme-linked immunosorbent assay (ELISA). The correlations between inhibitory cytokines, estrogen and AFP were assessed with the Spearman rank correlation coefficient.ResultsData are expressed as median and percentiles (Q1, Q3).The level of serum IL-35 in normal pregnancies was significantly higher than that in non-pregnant women [333.6 (59.32, 1391) pg/mL vs. 123.9 (8.763, 471.7) pg/mL; P < 0.001]. A significantly higher level of TGF-β was observed in the first trimester only as compared to non-pregnant women [473.4 (398.0, 580.5) pg/mL vs. 379.7 (311.0, 441.3) pg/mL, P < 0.01]. The difference in serum IL-10 level between pregnant women and non-pregnant women was not significant [8.602 (5.854, 12.89) pg/mL vs. 9.339 (5.691, 12.07) pg/mL; P > 0.05]. The level of serum IL-35 in recurrent spontaneous abortion was significantly lower than that in normal early pregnancy [220.4 (4.951, 702.0) pg/mL vs. 386.5 (64.37, 1355) pg/mL; P < 0.05]. The higher IL-35 level in first trimester pregnant women correlated with E2 (r = 0.3062, P < 0.01) and AFP (r = 0.3179, P < 0.01).ConclusionSerum levels of IL-35 increased in normal pregnancy and decreased in recurrent spontaneous abortion. Increased IL-35 correlated with estrogen and AFP levels in early pregnancy. IL-35 is becoming recognized as an active player in the maintenance of a successful pregnancy, but this is not the case for IL-10 or TGF-β.

Predictive value of abnormal second-trimester maternal serum triple screening markers for adverse pregnancy outcomes

To investigate the predictive value of abnormal multiples of the median (MoM) of second trimester maternal serum triple screening (STMSTS) markers for adverse pregnancy outcomes. 16 000 singleton pregnancies at 15⁺⁰ to 20⁺⁵ weeks' gestation who underwent STMSTS between July 2010 and January 2013 in the First Hospital of Jilin University were recruited. Maternal serum AFP, free β-hCG (F-β-hCG) and unconjugated estriol (uE3) levels were measured using time- resolved fluoroimmunoassay, and then converted to MoM. LifeCycle 3.2 software was used to calculate risk, and a risk value greater than 1 in 270 or 1 in 350 was considered as high risk for trisomy 21 syndrome (Down syndrome, DS) and trisomy 18 syndrome (Edwards syndrome, ES), respectively. MoM of AFP more than 2.5 was considered high risk for open neural tube defect (ONTD). Amniocentesis and karyotyping, ultrasound screening were advised for high risk women. AFP, F-β-hCG higher than 2.0 MoM or uE3 lower than 0.5 MoM was considered as abnormal, respectively. The MoM of STMSTS marker between women with adverse pregnancy outcome and with normal outcome was compared. (1) The median MoM of AFP, F-β-hCG and uE3 was 0.91 MoM, 0.94 MoM and 1.05 MoM, respectively. Of the 16 000 pregnant women, there was no statistical difference in the median MoM of triple screening marker at different weeks of gestation (P > 0.05). The positive rate of DS, ES and ONTD in women ≤35 years old (n = 14 972) was 4.03% (603/14 972), 0.36% (54/14 972) and 0.29% (44/14 972) respectively. And in women>35 years old (n = 1 028), the positive rate was 24.51% (252/1 028), 1.95% (20/1 028) and 0.78% (8/1 028), respectively. There was a statistically significant difference of positive rate between the two groups (P < 0.05). (2) 9 cases of DS, 1 case of ES and 1 case of ONTD were found in the high risk group, and 2 cases of DS in the low risk group. The detection rate of DS, ES and ONTD was 9/11, 1/1 and 1/1 respectively; and the positive predictive value was 1.05% (9/855), 1.35% (1/74) and 1.92% (1/52), respectively. (3)The incidence of adverse outcome (group 1) was 1.49 % ( 239/16 000). 7 760 pregnant women in this study were healthy during pregnancy, so were their fetuses (group 2). There were significant differences in the age at delivery, body weight and markers' MoM of STMSTS between the two groups (P < 0.01). (4) In group 1, the rate of abnormal MoM of AFP or F-β-hCG was 7.95% (19/239) and 23.85% (57/239), and the abnormal rate of MoM of uE3 was 4.18% (10/239). The rate of two abnormal MoM of markers was 5.02% (12/239); the rate that all three MoM were abnormal was 0.84% (2/239). However, in group 2, the rate of two abnormal MoM of markers was 0.14 % ( 11/7 760); and the rate that all three MoM were abnormal was 0. There was a significant difference of abnormal MoM of maternal serum marker between the two groups (P < 0.01). There is a relationship between abnormal marker of STMSTS and adverse outcomes. STMSTS show a high value in the detection of DS, ES and ONTD.

The effect of inherited thrombophilia on second trimester combined aneuploidy screening test markers.

To determine whether inherited thrombophilia affects components of second trimester combined aneuploidy screening test. A case-control study was performed between 1 December 2010 and 1 February 2012, at a tertiary referral hospital. Singleton pregnancies with inherited thrombophilia that underwent second trimester (16-19(+6) week) combined aneuploidy screening test were included in the study. Maternal serum alfa fetoprotein, unconjugated estriol, human chorionic gonadotropin levels and multiple of median (MoM) levels were compared between the study group and controls. Within the study period, 18,943 women with singleton pregnancies had a combined second trimester aneuploidy screening test at our institution. Among these, 26 women met the criteria of thrombophilia. A control group that comprised 275 women with similar gestational age was generated, using a 1:1 ratio. Unconjugated estriol MoM levels were significantly lower in women with inherited thrombophilia (p=0.02). But there was no statistically significant difference for unconjugated estriol levels, human chorionic gonadotropin, alfa fetoprotein and their MoM levels. Our study suggest that in patients with hereditary thrombophilia a new correction factor should be used, when calculating unconjugated estriol MoM value, which is one of the markers of second trimester aneuploidy screening test.

Involvement and alteration of the Sonic Hedgehog pathway is associated with decreased cholesterol level in trisomy 18 and SLO amniocytes

BackgroundTrisomy 18 and Smith–Lemli–Opitz syndrome are two polymalformative conditions in which a cholesterol defect has been noted. When they occur prenatally, they are associated with a decreased maternal unconjugated estriol (uE3) level. Cholesterol plays an essential role in the Sonic Hedgehog pathway, allowing Shh protein maturation leading to its maximal activity. Many malformations in these two syndromes occur in Shh dependent tissues. We thus sought to assess whether a cholesterol defect could affect the Shh pathway and explain some of the observed malformations. Materials and methodsWe selected 14 cases of trisomy 18 and 3 cases of SLO in which the maternal uE3 level was decreased and reported malformations were observed after fetopathological examination. We correlated the number of malformations with maternal uE3 level. We then carried out cholesterol concentrations in separate culture media consisting of trisomy 18, SLO and control amniocytes. Finally, we analyzed the Shh pathway by testing the gene expression of several Shh components: GLI transcription factors, BMP2, BMP4, TGFβ1, COL1A1 and COL1A2. Results and discussionThere was an inverse correlation between phenotypic severity and maternal uE3 levels in SLO and trisomy 18. The cholesterol levels in the amniocyte culture media were correlated with maternal uE3 levels and were significantly lower in T18 and SLO amniocytes, reflecting cholesterol defects. There was an alteration in the Shh pathway since expression of several genes was decreased in T18 and SLO amniocytes. However, these cholesterol defects were not solely responsible for the altered Shh pathway and the malformations observed.

Population-based biomarker screening and the development of severe preeclampsia in California

The purpose of this study was to examine the relationship between second-trimester maternal serum biomarkers and the development of early- and late-onset severe preeclampsia in euploid pregnancies. Included were 136,139 pregnancies that obtained second-trimester prenatal screening through the California Prenatal Screening Program with live births in 2006-2008. We identified severe preeclampsia diagnoses from hospital discharge records. We used log binomial regression to examine the association between abnormal second-trimester maternal serum biomarkers and the development of severe preeclampsia. Approximately 0.9% of all women (n= 1208) in our sample experienced severe preeclampsia; 329 women at <34 weeks' gestation and 879 women ≥34 weeks' gestation. High levels of alpha fetoprotein (AFP), human chorionic gonadotropin, inhibin (multiple of the median, ≥95th percentile), and low unconjugated estriol (multiple of the median, ≤5th percentile), were associated with severe preeclampsia (relative risk, 2.5-11.7). Biomarkers were more predictive of early-onset severe preeclampsia (relative risk, 3.8-11.7). One in 9.5 pregnancies with combined high AFP, inhibin, and low unconjugated estriol levels experienced severe early-onset preeclampsia compared with 1 in 680.5 pregnancies without any abnormal biomarkers. The risk of the development of severe preeclampsia increases for women with high second-trimester AFP, human chorionic gonadotropin, inhibin, and/or low unconjugated estriol; this is especially true for early-onset severe preeclampsia. When abnormal biomarkers co-occur, risk dramatically increases. Although the screening value of second-trimester biomarkers is low, abnormal biomarkers, especially when occurring in combination, appear to indicate placental dysfunction that is associated with the development of severe preeclampsia.

Absent cavum with intact septum pellucidum and corpus callosum may indicate midline brain abnormalities

In a recent publication of a series of cases of absence of a visible cavum detected prenatally, Malinger et al.1 concluded that this finding is not always associated with callosal anomalies and may represent a variation of normal development with good postnatal outcome. Although this may be true in a proportion of cases, we would like to point out that absence of fluid in the cavum, with intact septum pellucidum and corpus callosum, potentially indicates subtle midline brain abnormalities that may have significant implications for perinatal management and postnatal neurological development. A 28-year-old woman presented for screening ultrasound at 19 + 4 weeks' gestation following isolated low unconjugated estriol level (0.29 multiples of the median) on serum screening for Down syndrome. Transvaginal sonography demonstrated absence of fluid within the cavum septi pellucidi but normal ventricular and callosal appearance. Follow-up ultrasound at 21 + 4 weeks confirmed these findings. Karyotyping performed on cultured amniocytes was normal. Smith–Lemli–Opitz syndrome was excluded by normal amniotic fluid 7-dehydrocholesterol level. A follow-up scan at 23 weeks showed no fluid within the cavum septi pellucidi (Figure 1). Transvaginal visualization of the corpus callosum demonstrated normal length, with possible subtle dysmorphic appearance of the splenium (Figure 2). A male infant was delivered by Cesarean section at 41 weeks after three failed inductions. Apgar scores were 3, 5 and 7 at 1, 5 and 10 min, respectively, and cord pH was 7.09. Respiratory effort was poor and he was transferred to the nursery due to mild respiratory distress. His blood glucose on arrival was < 1 mmol/L. He required two boluses of D10W and remained on D10W infusion for 48 h to achieve stabilization before discharge. He was readmitted at 11 days of age with persistent hyperbilirubinemia, low blood glucose level and weight loss. A diagnosis of cortisol deficiency, growth hormone deficiency and hypothyroidism was made, as well as, subsequently, diabetes insipidus. The adrenal insufficiency explained the prenatally detected low unconjugated estriol. Optic nerve hypoplasia was apparent on ophthalmological examination. Magnetic resonance imaging at 10 months of age showed vestigial prechiasmatic optic nerves and optic chiasm, as well as complete absence of pituitary tissue. There was posterior callosal dysgenesis. At the time of writing, he was 2 years old and was being followed for global developmental delay, hypotonia, panhypopituitarism, optic hypoplasia associated with visual impairment and symptomatic seizures. We believe that this case illustrates the need for caution in interpreting the significance of subtle midline intracranial abnormalities in the fetal brain, particularly when there is an aberration in development of the septum pellucidum. It has been well documented that visualization of the cavum septi pellucidi is a reliable means of confirming integrity of midline intracranial anatomy on screening ultrasound examination2. However, the septum pellucidum itself has not been well characterized histopathologically during fetal life, and pathogenesis in development is not well understood3. A hypothetical etiological association between septal agenesis and other midline brain anomalies has been postulated4. This is ascribed to possible vascular incidents which would explain the associated findings in embryologically disparate events. It could be extrapolated that an anomaly involving midline brain development, specifically development of the septum pellucidum, could be associated with other midline brain abnormalities. This case illustrates the importance of awareness of the possibility of pituitary and chiasmatic abnormalities, which may be difficult to detect with antenatal imaging and may result in significant clinical neonatal morbidity and developmental disability. D. Pugash*†, S. Langlois‡, P. Power§ and M. Demos¶ †Radiology, University of British Columbia, Ultrasound 1 T48, BC Women's Hospital, 4500 Oak St., Vancouver, British Columbia V6H 3 N1, Canada; ‡Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; §Medical Genetics, British Columbia Women's Hospital, Vancouver, British Columbia, Canada; ¶Pediatrics and Neurology, University of British Columbia, Vancouver, British Columbia, Canada *Correspondence. (e-mail: dpugash@cw.bc.ca)

The analysis of second-trimester triple screening for Down syndrome in Chinese normal singleton pregnancies

Background and objectives. The study aimed to compare the α fetoprotein (AFP), total β-human chorionic gonadotropin (hCG), and unconjugated estriol (uE3) levels in the second-trimester triple screening for Down syndrome with different regions, and to analyse the related factors that influenced the screening performance. Materials and methods. The study was conducted between February 2007 and November 2010 in Beijing Tongren Hospital, P. R. China. Data derived from 7,647 normal singleton pregnancies between 14 and 21 weeks of gestation were examined. The regressed median values in different gestational ages were compared with earlier published data from other regions. The distribution of median values and multiples of median (MoM) of AFP, hCG and uE3 according to maternal age and weight in normal pregnancies were described. Statistic parameters for AFP, hCG, and uE3 (based on log10 MoM values) were compared with earlier published data from other studies. Results. There were significantly increasing trends for AFP (p < 0.001) and uE3 (p < 0.001), and a significantly decreasing trend for hCG (p < 0.001) in the second trimester. There were significantly decreasing trends with increasing maternal weight for all the markers and their MoMs (p < 0.001). The distribution of the log10 MoM marker values were Gaussian for the three parameters. Conclusions. Ethnic and laboratory variance should be taken into account in the second trimester triple screening for Down syndrome. The parameters of maternal serum markers should be calculated using local data, and the algorithm modified to match the screening achievable for the local population.

Second trimester maternal serum markers and a predictive model for predicting fetal hemoglobin Bart’s disease

Objective: To compare the levels of maternal serum α-fetoprotein (AFP), unconjugated estriol (uE3) and free β-human chorionic gonadotropin (free β-hCG) between pregnancies with fetal Hb Bart’s disease and unaffected pregnancies. Methods: 148 pregnancies at risk of fetal Hb Bart’s disease scheduled for cordocentesis at 18 to 22 weeks were prospectively recruited into the study. AFP, uE3 and free β-hCG concentrations were measured before cordocentesis and the final fetal diagnosis of Hb Bart’s disease was based on fetal Hb typing using high-performance liquid chromatography. Results: AFP and free β-hCG were significantly higher whereas uE3 was lower in women with fetal Hb Bart’s disease than those with unaffected fetuses (1.94 MoM, 1.38 MoM and 0.81 MoM respectively). Hb Bart’s predictive model; probability = 1/1+e−[2.876 + 1.333(AFP) − 6.310(uE3)], effectively predicted fetal Hb Bart’s disease (AUC ROC 0.91, 95% CI 0.84–0.97) with 61.5% sensitivity and 98.1% specificity using a cut-off probability at greater than 0.5. Conclusions: In triple test, serum AFP and hCG levels are significantly higher while serum uE3 is significantly lower in pregnancies with fetal Hb Bart’s disease. Hb Bart’s predictive model included AFP and uE3 is relatively effective and may be helpful in Hb Bart’s prenatal screening.

Risk of bronchopulmonary dysplasia by second-trimester maternal serum levels of α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol

Although maternal serum alpha-fetoprotein (AFP), human chorionic gonandotrophin (hCG), and estriol play important roles in immunomodulation and immunoregulation during pregnancy, their relationship to the development of bronchopulmonary dysplasia (BPD) in young infants is unknown despite BPD being associated with pre- and postnatal inflammatory factors. The objective of this population-based study was to examine whether second trimester levels of AFP, hCG, and unconjugated estriol (uE3) were associated with an increased risk of BPD. We found that these serum biomarkers were associated with an increased risk of BPD. Risks were especially high when AFP and/or hCG levels were above the 95th percentile and/or when uE3 levels were below the 5th percentile (relative risks (RRs) 3.1 to 6.7). Risks increased substantially when two or more biomarker risks were present (RRs 9.9 to 75.9). Data suggested that pregnancies which had a biomarker risk and yielded an offspring with BPD were more likely to have other factors present that suggested early intrauterine fetal adaptation to a stress including maternal hypertension and asymmetric growth restriction.

Vitamin B6 supplementation in pregnant women with nausea and vomiting

ObjectiveTo determine whether supplementation with vitamin B6 improves nausea and/or vomiting in pregnancy. MethodsThis experimental study was conducted with 60 pregnant women experiencing nausea and/or vomiting prior to the 12th gestational week. Of these women, 30 were treated daily with 10mg and the remaining 30 with 1.28mg of pyridoxine hydrochloride for 2weeks. The primary outcome was the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score in each group at the end of treatment. ResultsThe women experiencing nausea and/or vomiting in pregnancy had significantly lower levels of circulating vitamin B6 (P=0.007) compared with those without this symptom. Vitamin B6 supplementation significantly increased plasma vitamin B6 concentration (P<0.05 in both groups). There were no significant differences in PUQE score or in plasma concentration levels of protein, dopamine, serotonin, unconjugated estriol, and ghrelin after supplementation between the 2 groups at baseline, but there was a significantly lesser decrease in PUQE score and a greater increase in vitamin B6 level and vitamin B6 concentration to plasma protein concentration ratios in group 1 than in group 2 after supplementation (P<0.05 for all). ConclusionAlthough the high-supplementation group had a greater decrease in PUQE score in comparison to the low-supplementation group, the difference is unlikely to affect the severity of symptoms.

Possible association of medications during pregnancy with low estriol level of the triple antenatal screening test

Objective: Our purpose was to reach the reasons of isolated low levels of maternal serum unconjugated estriol (uE3) levels (≤0.3 multiples of the median (MoM)) in the triple-marker screen with special emphasis on maternal diseases and medications used for them. Methods: Single center retrospective cross-sectional analysis. Of 13,367 non-smoking women with identified singleton pregnancies screened for triple test, during 3-year period (2007–2009), a group of women with isolated low serum uE3 levels (≤0.3 MoM) (n = 14) were selected as the study group. Results: Of these 14 women, no one gave birth with ichthyosis. Five patients had, isolated very low uE3 levels (<0.01 MoM). Of these women, one had umbilical cord knot, one was on corticosteroid and three were on propylthiouracil treatment. So, there was history of maternal drug intake in 28.5% of cases with isolated low uE3 (≤0.3 MoM). This rate increases to 80% in cases with very low uE3 levels (<0.01 MoM). Conclusions: Maternal diseases and medications used during pregnancy can affect fetus and antenatal screening test results. This is important during counseling of patients and to perform the appropriate antenatal and postnatal evaluation of the mother and fetus with multidisciplinary approach.

Prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3) presenting as apparent isochromosome 18q in a fetus with holoprosencephaly

Objective To present prenatal diagnosis and molecular cytogenetic characterization of a derivative chromosome der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). Materials, Methods, and Results A 32-year-old woman was referred for genetic counseling of prenatally detected isochromosome 18q [i(18q)]. She had undergone amniocentesis at 19 gestational weeks because of a trisomy 18 risk of 1/39 derived from abnormally low levels of maternal serum unconjugated estriol, inhibin A, α-fetoprotein, and total β-human chorionic gonadotropin. Amniocentesis revealed a karyotype of 46,XX,i(18)(q10). Parental karyotypes were normal. Prenatal ultrasound showed alobar holoprosencephaly. Repeated amniocentesis was requested and performed at 21 gestational weeks. Array-comparative genomic hybridization analyses revealed a 14-Mb deletion of 18p11.32-p11.21, a 37.8-Mb duplication of 18q12.1-q22.1, and a 6.9-Mb duplication of 18q22.3-q23. Metaphase fluorescence in situ hybridization study showed the absence of an 18q12.1-specific probe signal in one arm and the absence of an 18q22.2-specific probe signal in the other arm of the derivative chromosome. Quantitative fluorescent polymerase chain reaction analysis determined a paternal origin of the derivative chromosome. The cytogenetic result was 46,XX,der(18;18)(q10;q10)del(18)(q11.1q12.1)del(18)(q22.1q22.3). The fetus postnatally manifested cebocephaly. Conclusion Concomitant monosomy 18p and trisomy 18q can be associated with holoprosencephaly and abnormal maternal serum screening results. Array-comparative genomic hybridization, fluorescence in situ hybridization, and quantitative fluorescent polymerase chain reaction are useful in genetic counseling of prenatally detected isochromosomes by providing information on the origin and genetic components of the isochromosome.

PP-214. Perinatal outcome of women with isolated low unconjugated estriol levels in the maternal triple-marker screening

PP-214. Perinatal outcome of women with isolated low unconjugated estriol levels in the maternal triple-marker screening