Maternal Visceral Fat in Prediction of Gestational Diabetes Mellitus.

Objective: To determine the diagnostic performance of maternal abdominal visceral adipose tissue thickness, measured by ultrasound, in predicting gestational diabetes mellitus (GDM). Patients and methods: A prospective diagnostic study was conducted on low-risk pregnant women attending our antenatal care clinic. All underwent abdominal visceral adipose tissue (VAT) measurement by two-dimension transabdominal ultrasound twice, at late first trimester (gestational age: GA 11-14 weeks) and second trimester (GA 18-22 weeks). All patients underwent a two-step approach for screening and diagnosis of GDM between GA 24 and 28 weeks. Results: A total of 141 women were recruited into the study; including 32 (22.7%) women with GDM, and 109 (77.3%) women of non-GDM, between GA 24 and 28 weeks. The means VAT at the 1st, 2nd trimester and the difference of VAT of GDM group were 4.0 ± 0.27 cm, 5.7 ± 1.12 cm, and 1.6 ± 0.91 cm respectively. The means VAT at 1st, 2nd trimester and the difference of VAT of non-GDM group were 3.8 ± 1.01 cm, 5.4 ± 1.07 cm, and 1.6 ± 1.12 cm respectively. There were no significant differences of VAT measurements (1st, 2nd and the difference) between both groups. The VAT thickness was slightly greater in the GDM group but the mean differences between 1st and 2nd trimester were comparable between the two groups. The diagnostic performance of VAT, maternal age and body mass index (BMI) in predicting GDM was comparable. Conclusion: Measurement of maternal visceral adipose thickness in early pregnancy is not effective in predicting GDM among Thai women, which is different from most studies conducted on western women. However, a trend of higher VAT in the GDM group was noted.

Reference-range of arterial stiffness by cardio-ankle vascular index in normal pregnancy.

OBJECTIVE: To establish the arterial stiffness, represented by the cardio-ankle vascular index (CAVI) at various gestational ages among low-risk pregnant women. The second objective is to construct the reference range of mean arterial pressure and maternal heart rate during pregnancy. METHODS: This cross-sectional study was conducted on low risk pregnant Thai women, meeting the following inclusion criteria: 1) singleton pregnant women aged 18 years old or over; 2) gestational age between 11 and 40 weeks; 3) low-risk pregnancy without any underlying medical diseases; and 4) known final pregnancy outcomes. Pregnancy-induced hypertension, gestational diabetes and fetal growth restriction were excluded. The mean CAVI, mean arterial pressure (MAP), and heart rate were measured at each gestational age. RESULTS: A total of 329 measurements for each parameter were available for analysis. CAVI was significantly correlated with gestational age with the best fitted model: CAVI = 6.952 - 0.076(GA) + 0.001(GA)2; SD = 0.742 (R2 = 0.049; p-value < 0.001). The maternal age and pre-pregnancy BMI were correlated with CAVI. CAVI gradually increased with maternal age and decreased with increasing body mass index (BMI). The MAP and heart rate of normal pregnancy in each gestation were conducted. CONCLUSION: The reference range of CAVI in normal pregnancies as a function of gestational age and the model for predicting CAVI based on multiple regression analysis are constructed and presented. These reference ranges may be useful in predicting risk of cardiovascular disorders during pregnancy.

Performance of Serum Quad Test in Screening for Fetal Down Syndrome in a Large-Scale Unselected Population in a Developing Country.

Objective: To assess the effectiveness of Quad test in the detection of Down syndrome (DS) in routine practice among a large-scale population and to compare the effectiveness of Quad test based on the Western reference model (WM) and that based on Thai reference model (TM). Methods: Quad test was performed on 42,769 pregnancies at 14-21 weeks. The fetal risk of DS derived from Quad test was automatically computed based on WM and used in evaluating the effectiveness. Also, the fetal risk was calculated based on the TM. Results: Of 39,740 women with complete follow-ups including 74 fetuses with DS, with WM, the detection and false positive rates were 81.1% and 7.2%, respectively, whereas the detection and false positive rates with TM were 87.8%, and 6.8%, respectively. According to ROC curves, the performance of Quad test based on TM was slightly but significantly better than that based on WM (AUC of 0.959 vs. 0.940, p = 0.001). Conclusion: Quad test is highly effective in service settings and suitable for developing countries and the effectiveness is even higher when based on ethnicity-specific reference model.

Noninvasive Prenatal Diagnosis of Beta-Thalassemia Disease by Using Digital PCR Analysis of Cell-Free Fetal DNA in Maternal Plasma.

INTRODUCTION: Prenatal diagnosis of thalassemia disease was usually based on invasive technique. Noninvasive diagnosis using cell-free fetal DNA (cff-DNA) was described with various laboratory techniques. The aim of this study was to identify the performance of dPCR for analyzing cff-DNA in maternal plasma to diagnose fetal beta-thalassemia diseases. METHODS: Thirty-five couples at risk of fetal beta-thalassemia disease caused by four common mutations of HBB were enrolled at 12-18 weeks. The dPCR assay was designed to detect and quantify paternally inherited beta-thalassemia allele (PIB) and maternally inherited beta-thalassemia allele (MIB) from cff-DNA in maternal plasma. RESULTS: Of 29 couples with different paternal/maternal mutations, all cases who inherited paternal mutation had detectable PIB-M. The MIB-mutant/wild-type (MIB-M/MIB-N) ratio in the mothers whose fetuses did not inherit maternal mutation was 0.87 ± 0.07 which was significantly lower than that of the mothers whose fetuses inherited maternal mutation, 1.01 ± 0.05. The sensitivity and specificity of MIB-M/MIB-N ratio >0.95 in predicting fetus inheriting maternal mutation were 100 and 92.3%, respectively. In four couples with same paternal/maternal mutation, IB-M/IB-N ratio of >0.95 correctly predicted the presence of an inheritance of at least one beta-thalassemia allele. In two couples with paternal Hb E/beta-thalassemia, the presence of PIB-M and the MIB-M/MIB-N ratio of >0.95 correctly predicted the presence of paternal/maternal mutations, respectively. CONCLUSIONS: The method of analyzing cff-DNA in maternal plasma by dPCR is efficient for prenatal diagnosis of beta-thalassemia.

Hydrops Fetalis Associated with Fetal Hemoglobin H-Pakse Disease.

INTRODUCTION: Hemoglobin H-Pakse (Hb H-PS) disease is a variant of non-deletional Hb H disease associated with various degrees of anemia. The disorder is rare but commonly seen in Southeast Asia. However, the prenatal course of Hb H-PS disease has never been published. The objective of this report was to describe prenatal diagnosis and management of Hb H-PS disease, which is theoretically much more critical in fetal life than adult life. CASE PRESENTATION: The prenatal courses of two fetuses affected by Hb H-PS were comprehensively explored. Both of them showed sonographic signs of fetal anemia at 19-20 weeks of gestation (increased cardiac size and increase middle cerebral artery peak systolic velocity [MCA-PSV]). On follow-up scans, both revealed frank hydropic signs at 22-24 weeks. One fetus died at 24 weeks, shortly before the scheduled intrauterine blood transfusion (IUT). The other one underwent IUT at 22 weeks, leading to completely reversed hydropic signs, which resulted in successful outcomes that ended with the delivery of a healthy baby at term. The fetus needed only one IUT, and the course of anemic status improved in late pregnancy. IUT in this case was possibly beneficial to adult life. CONCLUSION: Fetuses with Hb H-PS may be associated with hydrops fetalis, usually occurring at mid-pregnancy. The hydrops tends to improve in late gestation. If they can pass through this most critical period in utero without anemic insults in developing organs, good long-term prognosis can be expected. This successful prenatal diagnosis and intrauterine treatment may encourage care providers to pay more attention to fetal Hb H-PS disease, to prevent anemic hypoxia in developing organs and adult diseases of fetal origin.

DeepThal: A Deep Learning-Based Framework for the Large-Scale Prediction of the α+-Thalassemia Trait Using Red Blood Cell Parameters.

Objectives: To develop a machine learning (ML)-based framework using red blood cell (RBC) parameters for the prediction of the α+-thalassemia trait (α+-thal trait) and to compare the diagnostic performance with a conventional method using a single RBC parameter or a combination of RBC parameters. Methods: A retrospective study was conducted on possible couples at risk for fetus with hemoglobin H (Hb H disease). Subjects with molecularly confirmed normal status (not thalassemia), α+-thal trait, and two-allele α-thalassemia mutation were included. Clinical parameters (age and gender) and RBC parameters (Hb, Hct, MCV, MCH, MCHC, RDW, and RBC count) obtained from their antenatal thalassemia screen were retrieved and analyzed using a machine learning (ML)-based framework and a conventional method. The performance of α+-thal trait prediction was evaluated. Results: In total, 594 cases (female/male: 330/264, mean age: 29.7 ± 6.6 years) were included in the analysis. There were 229 normal controls, 160 cases with the α+-thalassemia trait, and 205 cases in the two-allele α-thalassemia mutation category, respectively. The ML-derived model improved the diagnostic performance, giving a sensitivity of 80% and specificity of 81%. The experimental results indicated that DeepThal achieved a better performance compared with other ML-based methods in terms of the independent test dataset, with an accuracy of 80.77%, sensitivity of 70.59%, and the Matthews correlation coefficient (MCC) of 0.608. Of all the red blood cell parameters, MCH < 28.95 pg as a single parameter had the highest performance in predicting the α+-thal trait with the AUC of 0.857 and 95% CI of 0.816−0.899. The combination model derived from the binary logistic regression analysis exhibited improved performance with the AUC of 0.868 and 95% CI of 0.830−0.906, giving a sensitivity of 80.1% and specificity of 75.1%. Conclusions: The performance of DeepThal in terms of the independent test dataset is sufficient to demonstrate that DeepThal is capable of accurately predicting the α+-thal trait. It is anticipated that DeepThal will be a useful tool for the scientific community in the large-scale prediction of the α+-thal trait.

Outcomes of pregnancies complicated by haemoglobin H-constant spring and deletional haemoglobin H disease: A retrospective cohort study.

The objective of the study was to compare the maternal and foetal outcomes of pregnancies complicated by Hb H-constant spring (HbH-CS) disease/deletional HbH (HbH-del) disease and low-risk pregnancies. A retrospective cohort research was undertaken on singleton pregnancies with Hb H-CS and Hb H-del diseases. The controls were randomly selected with a control-to-case ratio of 10:1. A total of 55 cases of HbH-CS disease, 231 cases of HbH-del disease and 2860 controls were compared. The mean gestational age at delivery and birthweight were significantly lower in the HbH-CS group than in the HbH-del and control groups. The clinical course of Hb H-CS was more severe than that of HbH-del disease. The rates of preterm birth, foetal growth restriction and low birthweight were significantly increased in the HbH-CS and Hb H-del groups. These rates were significantly greater in the HbH-CS group than in the H-del group. The maternal outcomes were not significantly different among the three groups. In conclusion, pregnancy worsens the course of HbH disease, more noticeably in HbH-CS disease. Hb H disease significantly increases the risk of adverse foetal outcomes, more noticeably in the HbH-CS group. Pregnancy is relatively safe for women with HbH disease.

Effectiveness of ultrasound algorithm in prenatal diagnosis of hemoglobin Bart's disease among pregnancies at risk.

OBJECTIVE: To evaluate the effectiveness of ultrasound algorithm in diagnosis of fetal Hb Bart's disease among pregnancies at risk. METHODS: Pregnancies at risk underwent ultrasound for the first time at 12-14 weeks of gestation and serial ultrasound every 2-4 weeks until 24 weeks to identify pre-hydropic signs. The invasive procedure was omitted in case of no pre-hydropic signs. RESULTS: A total of 237 fetuses were recruited, including 53 affected and 184 unaffected fetuses. The algorithm has a sensitivity of 100% in the detection of fetal Hb Bart's disease with a false positive rate of 10.9%. Of the affected group, the mean gestational age at the time of diagnosis was 15.5 ± 2.6 week. 30.8% of all pregnancies at risk underwent invasive procedures. The algorithm had a 70% reduction in the rate of invasive procedures among pregnancies at risk without missing the affected cases. CONCLUSIONS: The algorithm is highly effective in the early detection of fetal Hb Bart's disease with a detection rate of 100%, and invasive diagnosis can be avoided in about 70% of cases. Thus, this algorithm should be used as a guideline for prenatal diagnosis of fetal Hb Bart's disease, especially in geographical areas of high prevalence.

First trimester genetic sonogram for screening fetal Down syndrome: A population-based study.

OBJECTIVE: To evaluate the performance of first trimester sonomarkers in the detection of fetal Down syndrome among Thai pregnant women. MATERIALS AND METHODS: Pregnant women at 11-13+6 weeks' gestation underwent ultrasound examination for assessment of nuchal translucency (NT), nasal bone (NB), tricuspid regurgitation (TR), and abnormal ductus venosus (aDV) Doppler waveforms. The women were followed up for final outcomes. Fetal abnormalities other than trisomy 21 were excluded. The performances of each sonomarker and their combinations in predicting fetal Down syndrome were calculated. RESULTS: A total of 7820 pregnant women meeting the inclusion criteria were available for analysis, including 20 cases with fetal Down syndrome and 7800 unaffected cases. Of the four sonomarkers, NT, as a single sonomarker, had the highest detection rate (55.0% at a false positive rate of about 5%), whereas the remaining single sonomarkers had low detection rate (15-20%). The combination of all sonomarkers had the highest detection rate of 70% but the false positive rate was as high as 10.8%. The combination of NT and NB had a detection rate of 60% with an acceptable false positive rate of 6.9%, whereas the other combinations yielded relatively high false positive rates. CONCLUSION: The first trimester genetic sonogram in screening for Down syndrome among Asian women is acceptably effective and may be offered to some selected groups of the population. NT is the best sonomarker with a detection rate of 55% at 5% false positive rate and its combination with NB can improve performance with minimal increase in false positive rate.

A comparison of pregnancy outcomes after second-trimester amniocentesis between cases with penetration of the placenta and nonpenetration.

OBJECTIVE: To compare the fetal loss rate associated with second-trimester amniocentesis between the procedures with penetration and nonpenetration of the placenta, as a primary outcome and to compare the rates of adverse pregnancy outcomes including preterm birth, fetal growth restriction and low birth weight, as secondary outcomes. METHOD: A retrospective cohort study was conducted on women undergoing second-trimester amniocentesis. Our prospective database of amniocentesis, from January 1989 to December 2018, was accessed to retrieve the records meeting the inclusion criteria consisting of singleton pregnancies, gestational age of 16-22 weeks, and known obstetric outcomes. The patients were categorized into two groups: placental penetration and nonpenetration. The rates of fetal loss, including abortion (<24 weeks of gestation) and fetal death in utero (>24 weeks of gestation), and other adverse pregnancy outcomes were compared between the two groups. RESULTS: A total of 21,566 procedures were performed during the study period. Of them, 8601 were excluded due to chromosomal/structural abnormalities, various underlying medical diseases and incomplete data or unavailability of final outcomes. Finally, 12,965 cases were available for analysis including 4692 (36.2%) in the group of placental penetration and 8273 (63.8%) in the group of nonpenetration. The abortion rate after amniocentesis trended to be increased in the placental penetration group (0.6 versus 0.4%, p = .064; RR: 1.60, 95%CI 0.97-2.64). Likewise, the fetal loss rate trended to be increased in the placental penetration group (1.0 versus 0.7%, p = .121; RR: 1.35 95%CI 0.92-1.98). Interestingly, preterm birth rate was significantly increased in the placental penetration group (13.8 versus 12.6%, p = .043; RR: 1.10 95%CI 1.00-1.20). CONCLUSION: Fetal loss rate was slightly increased, but not statistically significant, among the procedures with placental penetration. However, penetration of the placenta was slightly but significantly associated with an increase in rates of preterm birth.

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.

Comparisons of pregnancy outcomes between twin pregnancies with and without second-trimester amniocentesis.

OBJECTIVE: To assess the amniocentesis-related pregnancy loss rate and preterm birth rate among twin pregnancies undergoing amniocentesis. METHODS: A retrospective cohort study was conducted at a tertiary center. The study group included twin pregnancies undergoing amniocentesis during 16 to 22 weeks of gestation. The control group was those not undergoing amniocentesis. All amniocenteses were performed by the MFM specialists. The main outcomes were the rate of pregnancy loss (before 24 weeks) and preterm birth. RESULTS: A total of 332 cases in the study group and 1188 controls were analyzed. The percentages of maternal age ≥35 years, high parity, and cases complicated with medical diseases were significantly higher in the study group. The pregnancy loss rate after the procedure tended to be higher, but not significant, in the study group (3.0% vs 2.2% P = .383). Likewise, the rate of preterm birth in the study group was higher, but not significant (70.5% vs 66.0% P = .130). Logistic regression analysis to adjust confounding factors showed no significance of amniocentesis on pregnancy loss and preterm birth. CONCLUSION: Though amniocentesis in twin pregnancies has theoretical risk of pregnancy loss, it is relatively safe when performed by maternal-fetal medicine specialists. This information is useful for counseling, especially when performed by experienced hands.

Optimal cutoff of mean corpuscular volume (MCV) for screening of alpha-thalassemia 1 trait.

AIM: To identify the optimal cutoff of mean corpuscular volume (MCV) for screening of alpha-thalassemia 1 trait. METHODS: The database of pregnant women who attended antenatal care clinic at Department of Obstetrics and Gynecology, Chiang Mai University during January 1st, 2015 to December 31st, 2017 was accessed and reviewed. A total of 1264 cases who had MCV ≤80 fL and met the inclusion criteria were enrolled to the study. Cases with hemoglobin level ≤10.0 gm/dL, iron deficiency anemia, chronic medical diseases and other types of thalassemia trait except alpha-thalassemia 1 trait were excluded. RESULTS: After exclusion, 438 cases were available for analysis. Of them, 139 were alpha-thalassemia 1 trait. Based on the receiver operating characteristic curves, the best cutoff value of MCV for screening of alpha-thalassemia 1 trait was ≤76.15 fL, giving 100% sensitivity, and 60.9% specificity with the area under curve of 0.925. Compared to the conventional cutoff (≤80 fL), the new cutoff gave much less false positive tests (117 vs 299 cases), whereas capability to detect alpha-thalassemia 1 trait was the same. CONCLUSION: With the new MCV cutoff (≤76.15 fL) as a secondary cutoff for screening alpha-thalassemia 1 carrier, a substantial number of positive cases requiring DNA analysis could be avoided without compromising the detection efficacy.

Chorionic villous sampling-related complications: a cohort study.

Purpose: To compare the adverse pregnancy outcomes between the pregnant women undergoing chorionic villous sampling (CVS) and those without CVS.Materials and methods: A cohort study was conducted on low risk pregnancies attending Chiang Mai University Hospital between years 2003 and 2017 and identify the database of women undergoing CVS (study group) and control group. Each case in study group was matched for 10 cases of the control by maternal age and year of procedure.Results and conclusions: Of 1384 pregnancies undergoing CVS, 776 cases met criteria and were matched with 7760 controls. The gestational age at delivery and actual birth weight were significantly different between two groups (38.02 versus 38.96 weeks, p value <.001 and 3025 versus 3092 g, p value .001). Moreover, CVS group had significantly higher preterm birth (9.4 versus 7.3%, p value .037; RR 1.287, 95% CI 1.017-1.629). However, there was no significant difference in fetal loss rate before 24 weeks (1.16 versus 1.9%, p value .14), small for gestational age (SGA); SGA (4 versus 4%, p value .948) and low birth weight (LBW); LBW (8.9 versus 8.0%, p value .41). Pregnancies undergoing CVS tend to deliver earlier and has significantly higher preterm birth. However, the incidences of fetal loss, SGA and LBW are not significantly increased.

First-trimester serum biomarker screening for fetal Down syndrome as a predictor of preterm delivery: a population-based study.

Objective: To examine the relationship between the first-trimester serum biomarker levels (pregnancy-associated plasma protein A:PAPP-A; and free beta-human chorionic gonadotropin: b-hCG) and preterm birth; and to create the predictive models for preterm birth in case of strong correlation.Methods: Secondary analysis on a large prospective database of singleton pregnancies undergoing first-trimester serum screening with complete follow-up for pregnancy outcomes. The multiples of medians (MoM) of the biomarkers were compared between the group of term and preterm/early preterm birth. Predictive models were developed based on adjusted MoMs and logistic regression analysis, and then diagnostic performances in predicting preterm birth were assessed.Results: Of 24,611 pregnancies eligible for analysis, 1908 (7.8%) and 500 (2.0%) had preterm and early preterm birth, respectively. Medians MoMs of both biomarkers were significantly lower in preterm and early preterm birth group. The predictive models were constructed. Performance in predicting preterm birth of these models yielded the area-under-ROC-curve of 0.560, 0.652, and 0.653 for b-hCG, PAPP-A, and combined biomarkers, respectively. In predicting early preterm birth, the areas-under-the-curve were found to be 0.551, 0.675, and 0.674 for b-hCG, PAPP-A, and combined biomarkers, respectively.Conclusion: The routine first-trimester serum screening of fetal Down syndrome could also be used as a tool of risk identification of preterm birth. We could take advantage of the screening by incorporating the predictive models into the Down syndrome screening software to report the preterm risk in the same test without extra effort and extra cost.

Fetal Down syndrome screening models for developing countries; Part I: Performance of Maternal Serum Screening.

BACKGROUND: To identify the performance of fetal Down syndrome (DS) screening for developing countries. METHODS: A prospective study on MSS (maternal serum screening) with complete follow-ups (n = 41,924) was conducted in 32 network hospitals in the northern part of Thailand. Various models of MSS were tested for performance. RESULTS: MSS based on Caucasian reference range resulted in very high false positive rate (FPR; 13%) in our country, compared to the rate of 7.8% with our own (Thai) reference range, whereas the detection rate was comparable. As individual screening, C-S (contingent first trimester screening including PAPP-A, and free beta-hCG, classified as a) high risk [> 1:30], indicated for invasive diagnosis; b) intermediate risk [1:30-1500], indicated for STS; and c) low risk [< 1:1500], need no further tests.) was the most effective model (sensitivity 84.9%, FPR 7.7%) but nearly one-third needed the second trimester test (STS) because of intermediate results. Additionally, about one-third had their first visits in the second trimester and had no chance of FTS (first trimester screening). C-S plus STS had a sensitivity of 82.4% and FPR 8.1% whereas independent first and second trimester screening model (I-S) gave the sensitivity of 78.4% and FPR of 7.5% but was much more convenient and practical. CONCLUSION: C-S plus STS was the most effective models while I-S model was also effective and may be better for developing countries because of its simplicity and feasibility.

Prenatal diagnosis and management of homozygous hemoglobin constant spring disease.

OBJECTIVE: To describe fetal management of homozygous hemoglobin constant spring (Hb CS). METHODS: Six fetuses with homozygous Hb CS disease undergoing intrauterine transfusion (IUT) were comprehensively reviewed. Additionally, when combined with 8 cases previously reported, a total of 14 cases were analyzed. RESULTS: The first clues of diagnosis were hydropic changes suggesting fetal anemia. Increased cardiothoracic diameter ratio (CTR) was the most sensitive sonographic marker but slowly changed after IUT, whereas MCA-PSV was the most sensitive in response to IUT. Pre-IUT Hb varied from 1.1% to 6.8%. Gestational age at diagnosis was 17-29 (22.8 ± 3.3) weeks. Rates of adverse obstetric outcomes were relatively high; preterm birth: 35.7%, low birthweight: 42.9%, and fetal growth restriction: 28.6%. All showed good response to IUT with disappearance of hydropic signs and all survived without short-term complications. Their anemia gradually improved in childhood and transfusion independent. CONCLUSION: Homozygous Hb CS can cause severe fetal anemia. Early diagnosis and IUT can improve neonatal outcomes, probably preventing adult diseases caused by fetal programming.

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.

Borderline hemoglobin A2 levels in northern Thai population: HBB genotypes and effects of coinherited alpha-thalassemia.

INTRODUCTION: Identification of beta-thalassemia carrier in prenatal screening relies on the elevated Hb A2 level. Borderline Hb A2 levels pose a diagnostic challenge. We determined the HBB genotypes in subjects with borderline Hb A2 in northern Thailand and studied the effects of coinherited alpha0-thalassemia on Hb A2 levels. METHODS: Blood samples with Hb A2 3.1-10.0% from 2193 samples submitted for prenatal thalassemia screening were selected. Information on HBB genotypes and coinherited alpha0-thalassemia were collected. All samples with unknown HBB genotypes underwent an automated DNA sequencing. The Hb A2 levels were compared according to the coinherited alpha0-thalassemia. RESULTS: HBB mutations were found in 298 (98.7%) of 302 samples with Hb A2 4.0-10.0%. In the 106 samples with Hb A2 3.1-3.9%, six had HBB mutations; four Hb Dhonburi [codon 126 (T > G)], one CAP site mutation [CAP + 1 (A > C)] and one beta0-thalassemia [codon 41/42 (-TTCT)] with a coinherited HBD mutation [nt-77 (T > C)]. The Hb A2 levels in beta-thalassemia carriers with and without coinherited alpha0-thalassemia were not significantly different. CONCLUSIONS: HBB mutations in northern Thais with borderline Hb A2 levels comprise an unstable variant Hb Dhonburi and CAP + 1 (A > C) mutation. Coinherited HBD mutation lowers Hb A2 and can cause a misidentification of a beta-thalassemia carrier.