Elevated Second-Trimester Maternal Serum Inhibin A Levels in Asian Pregnancies with Fetal Down Syndrome and Other Chromosomal Abnormalities

Hsu, Jenn-J.; Chiang, Chih Kang; Hsieh, Ching-C.; Hsieh, T’sang-T.

doi:10.1159/000068070

Cited by 10 publications

(4 citation statements)

References 37 publications

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“…Other studies have reported similar results, that the median MoMs of the maternal serum quadruple test of normal Asian fetuses were higher than those of Western populations [ 17 – 19 ]. Thus, we recommend not using the WF model as a standard cutoff in quadruple screening for our and other Asian populations.…”

Section: Discussionsupporting

confidence: 61%

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

et al. 2021

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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 β-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.

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Section: Discussionsupporting

confidence: 61%

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

et al. 2021

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“…[46][47][48] There appears to be no consistent pattern in the serum markers for cases of trisomy 13, with the exception of a slight reduction in uE3 levels. 49 Levels of inhibin A were unaffected in one case of trisomy 13 studied by Hsu et al (0.89 MoM) 50 and four cases studied by Watanabe et al (1.14 MoM) 51 but were increased in six cases studied by Cuckle et al (2.22 MoM). 48 Further study of inhibin A levels in cases of trisomy 13 is needed.…”

Section: Inhibin-related Moleculesmentioning

confidence: 85%

“…54 Maternal serum inhibin A levels were increased (median ¼ 1.70 MoM) in one other sex chromosome abnormality, 47,XYY, studied. 50 Triploidy, or three copies of the haploid chromosome set, can originate from either maternal or paternal errors in meiosis. Type I triploidy results from an extra set of paternal chromosomes and is characterized by a large cystic placenta and fetal loss early in gestation.…”

Section: Inhibin a Levels In Other Fetal Abnormalitiesmentioning

confidence: 99%

Clinical Application of Inhibin A Measurement: Prenatal Serum Screening for Down Syndrome

Lambert-Messerlian¹,

Canick²

2004

Semin Reprod Med

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Inhibin A is secreted in significant quantities by the corpus luteum and fetoplacental unit, suggesting a role in fertility and pregnancy. Negative feedback regulation of follicle-stimulating hormone during pregnancy is one expected function of inhibin A, but the complete repertoire of actions of this hormone in pregnancy, including paracrine and autocrine actions, is yet to be fully understood. Inhibin A levels have been carefully described throughout normal pregnancy and studied in association with maternal and fetal complication such as intrauterine growth restriction, preterm labor or delivery, and preeclampsia. The first clinical application of inhibin A measurement in pregnancy has been its use as a second-trimester maternal serum marker for Down syndrome. Our laboratory was among the first, in 1998, to implement Quad marker screening, inhibin A measurement in conjunction with alpha-fetoprotein, unconjugated estriol, and human chorionic gonadotropin, to assess patients' risk of having a Down syndrome baby. The test performance of the Quad test has been validated by several large studies, detecting about 80% of Down syndrome pregnancies at a 5% false-positive rate. The present review describes Down syndrome and the use of inhibin A in second-trimester prenatal screening. We also address the method used for inhibin A measurement, the biology of inhibin A in Down syndrome pregnancy, and the effects of covariates and other fetal abnormalities on inhibin A levels.

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“…We use as an example a meta-analysis on studies of inhibin-A as a screening marker for Down’s syndrome, which summarized the results of 20 studies. 4–25 Figure 1 shows this plot in a standard format. There is a vertical line designating no difference (ie.…”

mentioning

confidence: 99%

Presentation of meta-analysis plots

Wald

Bestwick

2015

J Med Screen

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Meta-analysis (forest) plots are widely used to show the results from multiple individual randomized trials or observational studies that address the same question, including the assessment of screening markers. They show the between study spread of results and provide a summary estimate of the results from all the studies combined. We here illustrate the advantage of ordering study results by the magnitude of the effect and including a vertical shaded band encompassing the summary 95% confidence interval of the summary estimate to emphasize the uncertainty of the estimate in a way that is more prominent than only displaying a ''diamond'' around its value.Keywords meta-analysis plots, forest plots, inhibin-A, antenatal screening for Down's syndrome Meta-analysis (forest) plots 1 are widely used to present data from randomized trials (eg. on anti-platelet treatment 2 ) and observational studies (eg. studies on antenatal screening markers 3 ) as a simple way of illustrating the results from multiple individual studies that address the same question. Such plots are often used to assess the discriminatory value of possible screening markers. The plots typically show a summary estimate of the results from all the studies combined, presented as a ''diamond'', with the width of the diamond representing the 95% confidence interval of the summary estimate based on all the results combined. It is customary to produce a central vertical line designating ''no effect'', either at 1 for measures such as relative risk estimates, or at zero for absolute differences. We here illustrate the advantage of ordering study results by the magnitude of the effect and including a vertical shaded band encompassing the summary 95% confidence interval to emphasize the uncertainty in the summary estimate in a more prominent way.We use as an example a meta-analysis on studies of inhibin-A as a screening marker for Down's syndrome, which summarized the results of 20 studies.4-25 Figure 1 shows this plot in a standard format. There is a vertical line designating no difference (ie. a multiple of the median [MoM] for unaffected pregnancies of 1.00) and a separate vertical line through the summary estimate of the observed median MoM value in Down's syndrome pregnancies (1.93), so that it is possible to see whether the individual studies have confidence intervals that include the summary estimate (although this is too strict a test, because it ignores the uncertainty around the overall summary estimate). The size of the squares showing the estimate from each study reflects the statistical ''weight'' of that study, ie. the relative contribution of that study to the summary estimate. When combining relative risks (or odds ratios) or relative differences as in our example, it is best to present the horizontal axis on a doubling (log scale) because the confidence intervals for each individual study and the confidence interval for the summary estimate are then expected to be symmetrical about the point estimate.It is usual to present the result...

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Elevated Second-Trimester Maternal Serum Inhibin A Levels in Asian Pregnancies with Fetal Down Syndrome and Other Chromosomal Abnormalities

Cited by 10 publications

References 37 publications

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

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

Clinical Application of Inhibin A Measurement: Prenatal Serum Screening for Down Syndrome

Presentation of meta-analysis plots

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