Ethnicity-Specific Normative Models of Quadruple Test as a Screening Test for Down Syndrome.

Background and Objectives: To establish normative models for median levels of serum biomarkers of the second trimester quad test (alpha-fetoprotein: AFP; free beta-human gonadotropins: hCG; inhibin-A; and unconjugated estriol: uE3) specific to Thai women and to compare multiples of the median (MoMs) derived from ethnicity-specific models and those derived from Caucasian models with ethnic correction. Materials and Methods: A cross-sectional study was undertaken in a tertiary, medical teaching center among low-risk pregnant Thai women between 14 and 21 weeks of gestation to measure the levels of the four serum biomarkers. The measured values of each biomarker were analyzed using the multivariable factorial polynomial technique for quantile regression as a function of gestational age and maternal weight. Results: The Thai-specific normative models for the four biomarkers were generated and available for use. The MoMs of all individuals generated from our models were significantly different from conventional (Caucasian) models with ethnic correction (Wilcoxon signed-rank test; p < 0.0001 for all biomarkers). The MoMs of AFP and hCG from both methods were in agreement, but those from Thai-specific models were significantly higher. However, those of inhibin-A and uE3 were markedly different and ethnic correction was unlikely to be useful. Conclusions: The Thai-specific normative models of the quad test as a function of gestational age and maternal weight were constructed using multivariable factorial polynomial models, better than simple quantile regression or log-linear regression used in earlier decades. The analysis of MoMs supports the use of ethnicity-specific models instead of Caucasian models with ethnic correction.

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.

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.

A cohort study of the association between maternal serum Inhibin-A and adverse pregnancy outcomes: a population-based study.

BACKGROUND: To compare the rates of adverse pregnancy outcomes between women with normal and abnormal inhibin-A levels. METHODS: Based on a prospective database of Down syndrome screening program, the consecutive records were comprehensively reviewed. Pregnancies were classified into three groups: normal, high (> 2 MoM) and low (< 0.5 MoM) inhibin-A levels. The pregnancies with medical diseases, chromosome abnormalities and fetal anomalies were excluded. The primary outcomes were the rates of preterm birth, preeclampsia, and fetal growth restriction (FGR). RESULTS: Of 6679 recruited pregnancies, 5080 met the inclusion criteria, including 4600, 205 and 275 pregnancies in the group of normal, high, and low inhibin-A levels respectively. The rates of preterm birth, preeclampsia and FGR were significantly higher in the group of high levels; (RR, 1.51, 95%CI: 1.01-2.26; 3.47, 95% CI: 2.13-5.65; 3.04, 95% CI: 1.99-4.65 respectively), whereas the rates of other adverse outcomes were comparable. However, the rate of spontaneous preterm birth among women with high inhibin-A was not significantly increased. Based on multivariate analysis, the preterm birth rate was not significantly associated with inhibin-A levels, but it was rather a consequence of preeclampsia and FGR. Low levels of serum inhibin-A were not significantly associated with any adverse outcomes. CONCLUSIONS: High levels of maternal serum inhibin-A in the second trimester are significantly associated with abnormal placentation, which increases the risk of preeclampsia and FGR with a consequence of indicated preterm birth but not a risk of spontaneous preterm birth. In contrast, low inhibin-A levels were not associated with any common adverse pregnancy outcomes.

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.

Association between unexplained thickened nuchal translucency and adverse pregnancy outcomes.

OBJECTIVE: To determine the association between unexplained increased nuchal translucency (INT) and adverse pregnancy outcomes. PATIENTS AND METHODS: The prospective database of our fetal down screening project was accessed to retrieve the records with NT measurement and complete follow-up. Pregnancies with pre-existing medical diseases, fetal chromosomal or structural abnormalities were excluded. The selected pregnancies were classified into the INT groups (> 95th percentile), the normal (< 95th percentile) group. RESULTS: Of 6026 available for analysis (INT:277; and normal: 5749), the abortion rate was significantly higher in the INT group, 18/277 (6.5%) versus 55/5749 (1.0%); p < 0.001. After excluding 73 cases ending-up with abortion, a total of 5953 women were analyzed for final pregnancy outcomes, including 260 (4.4%), and 5693 (95.6%) in the study group (INT), and the control group (normal NT), respectively. The rates of pre-eclampsia (7.3 vs. 4.1%; p: 0.018), preterm birth (12.7 vs. 8.4%; p: 0.023), fetal growth restriction (11.5 vs. 7.6%; p: 0.032), and low birth weight (16.5 vs. 10.0%; p: 0.002) were slightly, but significantly higher in the study group. CONCLUSIONS: INT in the first trimester is associated with significantly increased risk of abortion, fetal growth restriction, preterm birth, low birth weight and pre-eclampsia.

Pregnancy Outcomes among Women with Intermittent Asthma: A Retrospective Cohort Study.

BACKGROUND: It is already known that asthma strongly increases risks of poor pregnancy outcomes. We wonder whether intermittent asthma, the least severe form but accounting for the majority of cases, increases such adverse outcomes or not. Therefore, we conducted this study to compare adverse pregnancy outcomes between pregnancies with intermittent asthma and low-risk pregnancies (controls). METHODS: The full medical records of pregnancies with intermittent asthma were comprehensively reviewed and low-risk pregnancies were randomly recruited as controls with a ratio of 10:1. The obstetric outcomes were compared between both groups, and the outcomes in the active subgroup of intermittent asthma (defined as at least one asthmatic attack during pregnancy) were also compared with the controls. RESULTS: Of 364 study cases and 3640 controls, the rates of poor outcomes (preterm birth, preeclampsia, fetal growth restriction etc.) were not significantly different. However, cases with active disease slightly, but significantly, increased the risk of low birth weight. Moreover, mean gestational age was significantly lower in the study group. CONCLUSIONS: A new insight gained from this study is that intermittent asthma is not associated with poor pregnancy outcomes, but cases with asthmatic attack during pregnancy tended to increase the risk of preterm birth and low birth weight. This information is important for counseling and the planning of antepartum management.

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.

How to correct the impact of ethnicity on effectiveness of the second trimester maternal serum screen of fetal Down syndrome?

Objectives: To compare the performance of second trimester maternal serum screen (MSS) for fetal Down syndrome in Thai population between the conventional method using Caucasian reference ranges with ethnic factor correction (CRR-EC) and the method using specific Thai reference ranges (TRRs). Methods: A prospective database of the MSS project was accessed. The concentrations of alpha fetoprotein (AFP), beta-hCG, and uE3 were converted to their multiple of medians (MoMs) by two methods; CRR-EC for Asian women and TRR. The detection rate and false positive rate derived from the two methods were compared. Results: Of 20,229 cases, 35 women had fetal Down syndrome. The detection rates of both methods were comparable, whereas the false-positive rate of TRR was significantly lower (8.8 versus 11.7%; p < .001). The improvement was mainly caused by more accuracy of the MoMs of beta-hCG, not AFP/uE3, based on TRR. Conclusions: The effectiveness of MSS could be improved by using our own reference ranges instead of using ethnic factor correction. With TRR, the false-positive rate or the number of invasive diagnoses could be significantly decreased without compromise of the detection rate. To improve MSS performance, each population should use its own reference ranges.

Factors Associated with Successful Trial of Labor after Cesarean Section: A Retrospective Cohort Study.

OBJECTIVE: To determine the effectiveness of trial of labor after cesarean section (TOLAC) and the factors associated with a successful TOLAC. MATERIALS AND METHODS: A retrospective cohort study was conducted on consecutive singleton pregnancies with a previous single low-transverse cesarean section planned for TOLAC at a tertiary teaching hospital. The potential risk factors of a successful TOLAC were compared with those associated with a failed TOLAC. A simple audit system used in the first two years was also taken into account in the analysis as a potential factor for success. RESULTS: During the study period, 2,493 women were eligible for TOLAC and 704 of them were scheduled for TOLAC, but finally 592 underwent TOLAC. Among them, 355 (60%) had a successful vaginal birth and 237 (40%) had a failed TOLAC. The independent factors associated with the success rate included the audit system, prior vaginal birth, low maternal BMI, and lower birth weight or gestational age, whereas induction of labor and recurring indications in previous pregnancy significantly increased the risk of having a failed TOLAC. Strikingly, the strongest predictor of a successful TOLAC was the audit system with OR of 6.4 (95%CI: 3.9-10.44), followed by a history of vaginal birth in previous pregnancies (OR: 3.2; 95%CI: 1.87-5.36). CONCLUSION: The simple audit system had the greatest impact on the success rate of TOLAC, instead of the less powerful obstetrical factors as reported in previous reports. The audit system is the only potential factor that could be strengthened to improve the success rate.